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Answers and Critiques Item 1 Answer: B Bibliography Cnossen MC, Scholten AC, Lingsma HF, et al. Predictors of major depres- Educational Objective: Screen for depression in mili- sion and posttraumatic stress disorder following traumatic brain tary service members with persistent posttraumatic brain injury: a systematic review and meta-analysis. J Neuropsychiatry Clin Neurosci. 2017;29:206-224. [PMID: 28193126] doi:10.1176/appi. injury symptoms. neuropsych.16090165

Item 1 Answer: B Bibliography Cnossen MC, Scholten AC, Lingsma HF, et al. Predictors of major depres- Educational Objective: Screen for depression in mili- sion and posttraumatic stress disorder following traumatic brain tary service members with persistent posttraumatic brain injury: a systematic review and meta-analysis. J Neuropsychiatry Clin Neurosci. 2017;29:206-224. [PMID: 28193126] doi:10.1176/appi. injury symptoms. neuropsych.16090165 This patient should be screened for depression (Option B). He is a returning military service member with a history of Item 2 Answer: B mild traumatic brain injury (TBI) and persistent posttrau- matic headaches. Although headache is the most common Educational Objective: Treat cognitive dysfunction in symptom after a mild TBI, persons with this diagnosis multiple sclerosis. 1 also may experience other symptoms, such as dizziness, cs) The most appropriate management is to refer the patient for memory or cognitive impairment, insomnia, and mood and sc cognitive rehabilitation (Option B). Cognitive deficits are = anxiety disorders. The incidence of mild TBI in military ser- c common in patients with multiple sclerosis (MS) and can wn vice personnel is high. Falls, vehicular accidents, and head tems often be life-impairing, especially for those who are employed o trauma from explosions and weaponry are common mech- in positions that have high cognitive demand. Typical find- = wn anisms of injury. Those with mild TBI sustained during = ings include deficits in short-term memory and processing <x active military duty appear to be particularly susceptible speed, although almost any domain can be impaired. Non- to posttraumatic stress disorder (PTSD) and depression. pharmacologic interventions, such as cognitive rehabilitative Given the high prevalence of depression and the increased and accommodative strategies (such as creating checklists to risk for suicide in returning military personnel with mild overcome memory deficits) and physical exercise programs, TBI, screening for depression is mandatory. The nine-item have shown benefit for improving and/or maintaining cogni- Patient Health Questionnaire (PHQ-9) is a validated and tive performance in patients with MS. widely used depression screening tool for detection of Depressive symptoms are frequently encountered in depression. Its benefits include brevity and ease of use. Mil- patients with chronic medical disease either as a result of itary personnel who screen positive for depression should the illness itself (such as hypothyroidism) or as a response be asked about suicidal ideation and intent. Screening for to the disability caused by the illness. Depression commonly PTSD using tools such as the Primary Care PTSD Screen accompanies many medical conditions, including neuro- and the PTSD Checklist should also occur. logic conditions (multiple sclerosis, Parkinson disease), can- Besides headaches, the patient reports no neurologic cer, heart failure, and HIV infection. For initial acute therapy, symptoms and has a normal examination. Head CT per- guidelines recommend either cognitive behavioral therapy formed immediately after the injury was normal. There is no or second-generation antidepressants such as venlafaxine need for repeat neuroimaging with brain MRI (Option A). (Option A). Therapeutic response can be objectively mea- Electroencephalography (Option C) is not indicated in sured with the Patient Health Questionnaire 9 (PHQ-9) for the assessment of patients with mild TBI or posttraumatic depression. This patient’s score on the PHQ-9 is 4, and her headaches, and the patient reports no events suspicious for answers are not indicative of active depression. Thus, her seizure. current venlafaxine dose is appropriate. Although erythrocyte sedimentation rate measurement Referral to a psychiatrist (Option C) is indicated for (Option D) is helpful in the evaluation of headaches poten- patients with severe depression, failure of initial therapy, tially related to giant cell arteritis (GCA), development of complex psychiatric comorbidities, and high suicide risk. headaches due to GCA in someone under the age of 50 years This patient has no indication for a psychiatric referral. would be highly unlikely. Clinical trials of pharmacologic therapies, such as meman- The Montreal Cognitive Assessment (Option E) is useful tine (Option D), donepezil, and methylphenidate (Option E), to in evaluating patients with mild cognitive impairment or treat MS-related cognitive dysfunction have not shown efficacy. dementia but is not useful in evaluating patients with mild Therefore, these medications should not be initiated. TBI or posttraumatic headaches. This patient neither reports nor exhibits any cognitive impairment.

This patient should be screened for depression (Option B). He is a returning military service member with a history of Item 2 Answer: B mild traumatic brain injury (TBI) and persistent posttrau- matic headaches. Although headache is the most common Educational Objective: Treat cognitive dysfunction in symptom after a mild TBI, persons with this diagnosis multiple sclerosis. 1 also may experience other symptoms, such as dizziness, cs) The most appropriate management is to refer the patient for memory or cognitive impairment, insomnia, and mood and sc cognitive rehabilitation (Option B). Cognitive deficits are = anxiety disorders. The incidence of mild TBI in military ser- c common in patients with multiple sclerosis (MS) and can wn vice personnel is high. Falls, vehicular accidents, and head tems often be life-impairing, especially for those who are employed o trauma from explosions and weaponry are common mech- in positions that have high cognitive demand. Typical find- = wn anisms of injury. Those with mild TBI sustained during = ings include deficits in short-term memory and processing <x active military duty appear to be particularly susceptible speed, although almost any domain can be impaired. Non- to posttraumatic stress disorder (PTSD) and depression. pharmacologic interventions, such as cognitive rehabilitative Given the high prevalence of depression and the increased and accommodative strategies (such as creating checklists to risk for suicide in returning military personnel with mild overcome memory deficits) and physical exercise programs, TBI, screening for depression is mandatory. The nine-item have shown benefit for improving and/or maintaining cogni- Patient Health Questionnaire (PHQ-9) is a validated and tive performance in patients with MS. widely used depression screening tool for detection of Depressive symptoms are frequently encountered in depression. Its benefits include brevity and ease of use. Mil- patients with chronic medical disease either as a result of itary personnel who screen positive for depression should the illness itself (such as hypothyroidism) or as a response be asked about suicidal ideation and intent. Screening for to the disability caused by the illness. Depression commonly PTSD using tools such as the Primary Care PTSD Screen accompanies many medical conditions, including neuro- and the PTSD Checklist should also occur. logic conditions (multiple sclerosis, Parkinson disease), can- Besides headaches, the patient reports no neurologic cer, heart failure, and HIV infection. For initial acute therapy, symptoms and has a normal examination. Head CT per- guidelines recommend either cognitive behavioral therapy formed immediately after the injury was normal. There is no or second-generation antidepressants such as venlafaxine need for repeat neuroimaging with brain MRI (Option A). (Option A). Therapeutic response can be objectively mea- Electroencephalography (Option C) is not indicated in sured with the Patient Health Questionnaire 9 (PHQ-9) for the assessment of patients with mild TBI or posttraumatic depression. This patient’s score on the PHQ-9 is 4, and her headaches, and the patient reports no events suspicious for answers are not indicative of active depression. Thus, her seizure. current venlafaxine dose is appropriate. Although erythrocyte sedimentation rate measurement Referral to a psychiatrist (Option C) is indicated for (Option D) is helpful in the evaluation of headaches poten- patients with severe depression, failure of initial therapy, tially related to giant cell arteritis (GCA), development of complex psychiatric comorbidities, and high suicide risk. headaches due to GCA in someone under the age of 50 years This patient has no indication for a psychiatric referral. would be highly unlikely. Clinical trials of pharmacologic therapies, such as meman- The Montreal Cognitive Assessment (Option E) is useful tine (Option D), donepezil, and methylphenidate (Option E), to in evaluating patients with mild cognitive impairment or treat MS-related cognitive dysfunction have not shown efficacy. dementia but is not useful in evaluating patients with mild Therefore, these medications should not be initiated. TBI or posttraumatic headaches. This patient neither reports nor exhibits any cognitive impairment. e In patients with multiple sclerosis, cognitive rehabili- tative and accommodative strategies (such as creating ¢ Military personnel with mild traumatic brain injury checklists to overcome memory deficits) and physical symptoms should be screened for depression and exercise programs have shown benefit for improving posttraumatic stress disorder. and/or maintaining cognitive performance.

e In patients with multiple sclerosis, cognitive rehabili- tative and accommodative strategies (such as creating ¢ Military personnel with mild traumatic brain injury checklists to overcome memory deficits) and physical symptoms should be screened for depression and exercise programs have shown benefit for improving posttraumatic stress disorder. and/or maintaining cognitive performance. 117

Answers and Critiques Bibliography Bibliography Goverover Y, Chiaravalloti ND, O’Brien AR, et al. Evidenced-based cognitive Bhattacharyya S. Spinal cord disorders: myelopathy. Am J Med. 2018;131(11): rehabilitation for persons with multiple sclerosis: an updated review of 1293-97. [PMID: 29605415] doi:10.1016/j-amjmed.2018.03.009 the literature from 2007 to 2016. Arch Phys Med Rehabil. 2018;99:390- 407. [PMID: 28958607] doi: 10.1016/j.apmr.2017.07.021 Item 4 Answer: B Educational Objective: Diagnose generalized tonic-clonic Item 3 Answer: D seizures. Educational Objective: Evaluate myelopathy. The most likely diagnosis is generalized tonic-clonic seizures The most appropriate diagnostic test to perform next is MRI (GTCS) (Option B). Although this patient’s first two seizures of the thoracic spine (Option D). Myelopathy (any disor- were unwitnessed, the third event was characterized by an ictal der involving the spinal cord) arises from extrinsic (external cry, whole-body stiffening and falling down, rhythmic synchro- compression) and intrinsic (intramedullary) pathologic causes. nous limb jerking, and subsequent postictal lethargy and ster- > Corticospinal tract injury results in spastic paresis or paralysis, = torous respirations (slow, deep, snoring-like breathing due to wn with weakness, hyperreflexia, muscle spasticity, and extensor = upper airway obstruction); these features characterize a GTCS. @ plantar responses. There is often loss of sensation at or below = Generalized convulsive status epilepticus (Option A) is wn the site of injury. This patient has signs of thoracic myelopathy defined as a GTCS lasting more than 5 minutes, or two GTCS Q = on examination, with bilateral patellar hyperreflexia, extensor occurring within 5 minutes of each other without a return to ty plantar responses, and a sensory level at approximately T3 baseline mental status. Convulsive status epilepticus is diagnosed (=) eae (below the nipple line). These examination findings suggest clinically. This patient’s clonic activity lasted 2 minutes with an =. <— a thoracic cord localization, and thus the most specific test to 8-minute postictal period of impaired alertness and does not <= order would be MRI of the thoracic spine. Determining the © meet the definition of generalized convulsive status epilepticus. an location and mechanism of injury is crucial for rapidly deciding The postictal period of confusion and impaired alertness is not on the accurate site, type of neuroimaging required, and the accounted for as part of seizure duration, although the layperson kind of specialty consultation (such as neurosurgical) needed. may inadvertently include it when interviewed about the event. CT myelography (Option A) is not the most appropriate Myoclonic seizures (Option C) typically include jerking choice in this situation. Although this imaging modality could or shaking that lasts less than 1 second and may occur in potentially reveal a compressive cord cause, it is not clear from the clusters, resulting in a patient falling down. However, unlike patient’s history that the cause is compressive in nature. Whereas this patient’s seizure, there is no postictal lethargy or con CT myelography is sensitive to compressive causes, intrinsic cord fusion after myoclonic seizures, and 2-minute duration of pathology can be missed. Noncompressive myelopathy is pos- shaking would be unusually long for this seizure type. sible in this patient and can be caused by many inflammatory, Psychogenic nonepileptic spells/events (PNES) (Option infectious, metabolic, vascular, and genetic disorders. Inflam- D) may be considered in the differential diagnosis. PNES matory causes are most common, including multiple sclerosis, are most often related to posttraumatic stress disorder or neuromyelitis optica, and sarcoidosis. Finally, CT myelography is conversion disorder. Patients often have a history of military invasive and thus should not be used as first-line therapy. combat, sexual or physical abuse, chronic medical illness, or MRI of the brain (Option B) is incorrect. The patient's prominent life stressors. PNES often mimic GTCS, but cer- neurologic examination cannot be explained bya brain lesion. tain features help distinguish the diagnoses. PNES findings No brain localization can result in a distinct spinal sensory may include asynchronous flailing of variable limbs, side-to level as seen in this patient. Further, the bilateral findings in side head shaking, pelvic thrusting, and prolonged duration the lower extremities would require bilateral brain lesions, (>5 minutes or even hours). Event capture during video EEG which, although they may occur, are less likely than a single monitoring usually is required to confirm the diagnosis. lesion in the spinal cord and would likely result in far greater GTCS are a better fit for this patient’s symptoms. neurologic sequelae than that seen in this patient. A lumbosacral spine MRI (Option C) would not be an appropriate diagnostic test in this situation because the e Generalized tonic-clonic seizures are characterized by an patient has signs of upper motor neuron dysfunction and a abrupt loss of consciousness and falling down, whole- thoracic sensory deficit, which cannot occur in disorders of body stiffening, rhythmic synchronous limb jerking, and the lumbosacral spine. subsequent postictal lethargy and stertorous respirations.

Bibliography Bibliography Goverover Y, Chiaravalloti ND, O’Brien AR, et al. Evidenced-based cognitive Bhattacharyya S. Spinal cord disorders: myelopathy. Am J Med. 2018;131(11): rehabilitation for persons with multiple sclerosis: an updated review of 1293-97. [PMID: 29605415] doi:10.1016/j-amjmed.2018.03.009 the literature from 2007 to 2016. Arch Phys Med Rehabil. 2018;99:390- 407. [PMID: 28958607] doi: 10.1016/j.apmr.2017.07.021 Item 4 Answer: B Educational Objective: Diagnose generalized tonic-clonic Item 3 Answer: D seizures. Educational Objective: Evaluate myelopathy. The most likely diagnosis is generalized tonic-clonic seizures The most appropriate diagnostic test to perform next is MRI (GTCS) (Option B). Although this patient’s first two seizures of the thoracic spine (Option D). Myelopathy (any disor- were unwitnessed, the third event was characterized by an ictal der involving the spinal cord) arises from extrinsic (external cry, whole-body stiffening and falling down, rhythmic synchro- compression) and intrinsic (intramedullary) pathologic causes. nous limb jerking, and subsequent postictal lethargy and ster- > Corticospinal tract injury results in spastic paresis or paralysis, = torous respirations (slow, deep, snoring-like breathing due to wn with weakness, hyperreflexia, muscle spasticity, and extensor = upper airway obstruction); these features characterize a GTCS. @ plantar responses. There is often loss of sensation at or below = Generalized convulsive status epilepticus (Option A) is wn the site of injury. This patient has signs of thoracic myelopathy defined as a GTCS lasting more than 5 minutes, or two GTCS Q = on examination, with bilateral patellar hyperreflexia, extensor occurring within 5 minutes of each other without a return to ty plantar responses, and a sensory level at approximately T3 baseline mental status. Convulsive status epilepticus is diagnosed (=) eae (below the nipple line). These examination findings suggest clinically. This patient’s clonic activity lasted 2 minutes with an =. <— a thoracic cord localization, and thus the most specific test to 8-minute postictal period of impaired alertness and does not <= order would be MRI of the thoracic spine. Determining the © meet the definition of generalized convulsive status epilepticus. an location and mechanism of injury is crucial for rapidly deciding The postictal period of confusion and impaired alertness is not on the accurate site, type of neuroimaging required, and the accounted for as part of seizure duration, although the layperson kind of specialty consultation (such as neurosurgical) needed. may inadvertently include it when interviewed about the event. CT myelography (Option A) is not the most appropriate Myoclonic seizures (Option C) typically include jerking choice in this situation. Although this imaging modality could or shaking that lasts less than 1 second and may occur in potentially reveal a compressive cord cause, it is not clear from the clusters, resulting in a patient falling down. However, unlike patient’s history that the cause is compressive in nature. Whereas this patient’s seizure, there is no postictal lethargy or con CT myelography is sensitive to compressive causes, intrinsic cord fusion after myoclonic seizures, and 2-minute duration of pathology can be missed. Noncompressive myelopathy is pos- shaking would be unusually long for this seizure type. sible in this patient and can be caused by many inflammatory, Psychogenic nonepileptic spells/events (PNES) (Option infectious, metabolic, vascular, and genetic disorders. Inflam- D) may be considered in the differential diagnosis. PNES matory causes are most common, including multiple sclerosis, are most often related to posttraumatic stress disorder or neuromyelitis optica, and sarcoidosis. Finally, CT myelography is conversion disorder. Patients often have a history of military invasive and thus should not be used as first-line therapy. combat, sexual or physical abuse, chronic medical illness, or MRI of the brain (Option B) is incorrect. The patient's prominent life stressors. PNES often mimic GTCS, but cer- neurologic examination cannot be explained bya brain lesion. tain features help distinguish the diagnoses. PNES findings No brain localization can result in a distinct spinal sensory may include asynchronous flailing of variable limbs, side-to level as seen in this patient. Further, the bilateral findings in side head shaking, pelvic thrusting, and prolonged duration the lower extremities would require bilateral brain lesions, (>5 minutes or even hours). Event capture during video EEG which, although they may occur, are less likely than a single monitoring usually is required to confirm the diagnosis. lesion in the spinal cord and would likely result in far greater GTCS are a better fit for this patient’s symptoms. neurologic sequelae than that seen in this patient. A lumbosacral spine MRI (Option C) would not be an appropriate diagnostic test in this situation because the e Generalized tonic-clonic seizures are characterized by an patient has signs of upper motor neuron dysfunction and a abrupt loss of consciousness and falling down, whole- thoracic sensory deficit, which cannot occur in disorders of body stiffening, rhythmic synchronous limb jerking, and the lumbosacral spine. subsequent postictal lethargy and stertorous respirations. ¢ Generalized convulsive status epilepticus is defined as a

Bibliography Bibliography Goverover Y, Chiaravalloti ND, O’Brien AR, et al. Evidenced-based cognitive Bhattacharyya S. Spinal cord disorders: myelopathy. Am J Med. 2018;131(11): rehabilitation for persons with multiple sclerosis: an updated review of 1293-97. [PMID: 29605415] doi:10.1016/j-amjmed.2018.03.009 the literature from 2007 to 2016. Arch Phys Med Rehabil. 2018;99:390- 407. [PMID: 28958607] doi: 10.1016/j.apmr.2017.07.021 Item 4 Answer: B Educational Objective: Diagnose generalized tonic-clonic Item 3 Answer: D seizures. Educational Objective: Evaluate myelopathy. The most likely diagnosis is generalized tonic-clonic seizures The most appropriate diagnostic test to perform next is MRI (GTCS) (Option B). Although this patient’s first two seizures of the thoracic spine (Option D). Myelopathy (any disor- were unwitnessed, the third event was characterized by an ictal der involving the spinal cord) arises from extrinsic (external cry, whole-body stiffening and falling down, rhythmic synchro- compression) and intrinsic (intramedullary) pathologic causes. nous limb jerking, and subsequent postictal lethargy and ster- > Corticospinal tract injury results in spastic paresis or paralysis, = torous respirations (slow, deep, snoring-like breathing due to wn with weakness, hyperreflexia, muscle spasticity, and extensor = upper airway obstruction); these features characterize a GTCS. @ plantar responses. There is often loss of sensation at or below = Generalized convulsive status epilepticus (Option A) is wn the site of injury. This patient has signs of thoracic myelopathy defined as a GTCS lasting more than 5 minutes, or two GTCS Q = on examination, with bilateral patellar hyperreflexia, extensor occurring within 5 minutes of each other without a return to ty plantar responses, and a sensory level at approximately T3 baseline mental status. Convulsive status epilepticus is diagnosed (=) eae (below the nipple line). These examination findings suggest clinically. This patient’s clonic activity lasted 2 minutes with an =. <— a thoracic cord localization, and thus the most specific test to 8-minute postictal period of impaired alertness and does not <= order would be MRI of the thoracic spine. Determining the © meet the definition of generalized convulsive status epilepticus. an location and mechanism of injury is crucial for rapidly deciding The postictal period of confusion and impaired alertness is not on the accurate site, type of neuroimaging required, and the accounted for as part of seizure duration, although the layperson kind of specialty consultation (such as neurosurgical) needed. may inadvertently include it when interviewed about the event. CT myelography (Option A) is not the most appropriate Myoclonic seizures (Option C) typically include jerking choice in this situation. Although this imaging modality could or shaking that lasts less than 1 second and may occur in potentially reveal a compressive cord cause, it is not clear from the clusters, resulting in a patient falling down. However, unlike patient’s history that the cause is compressive in nature. Whereas this patient’s seizure, there is no postictal lethargy or con CT myelography is sensitive to compressive causes, intrinsic cord fusion after myoclonic seizures, and 2-minute duration of pathology can be missed. Noncompressive myelopathy is pos- shaking would be unusually long for this seizure type. sible in this patient and can be caused by many inflammatory, Psychogenic nonepileptic spells/events (PNES) (Option infectious, metabolic, vascular, and genetic disorders. Inflam- D) may be considered in the differential diagnosis. PNES matory causes are most common, including multiple sclerosis, are most often related to posttraumatic stress disorder or neuromyelitis optica, and sarcoidosis. Finally, CT myelography is conversion disorder. Patients often have a history of military invasive and thus should not be used as first-line therapy. combat, sexual or physical abuse, chronic medical illness, or MRI of the brain (Option B) is incorrect. The patient's prominent life stressors. PNES often mimic GTCS, but cer- neurologic examination cannot be explained bya brain lesion. tain features help distinguish the diagnoses. PNES findings No brain localization can result in a distinct spinal sensory may include asynchronous flailing of variable limbs, side-to level as seen in this patient. Further, the bilateral findings in side head shaking, pelvic thrusting, and prolonged duration the lower extremities would require bilateral brain lesions, (>5 minutes or even hours). Event capture during video EEG which, although they may occur, are less likely than a single monitoring usually is required to confirm the diagnosis. lesion in the spinal cord and would likely result in far greater GTCS are a better fit for this patient’s symptoms. neurologic sequelae than that seen in this patient. A lumbosacral spine MRI (Option C) would not be an appropriate diagnostic test in this situation because the e Generalized tonic-clonic seizures are characterized by an patient has signs of upper motor neuron dysfunction and a abrupt loss of consciousness and falling down, whole- thoracic sensory deficit, which cannot occur in disorders of body stiffening, rhythmic synchronous limb jerking, and the lumbosacral spine. subsequent postictal lethargy and stertorous respirations. ¢ Generalized convulsive status epilepticus is defined as a ¢ Myelopathy may result in spastic paresis or paralysis, generalized tonic-clonic seizure (GTCS) lasting more than with weakness, hyperreflexia, muscle spasticity, 5 minutes, or two GTCSs occurring within 5 minutes of

¢ Generalized convulsive status epilepticus is defined as a ¢ Myelopathy may result in spastic paresis or paralysis, generalized tonic-clonic seizure (GTCS) lasting more than with weakness, hyperreflexia, muscle spasticity, 5 minutes, or two GTCSs occurring within 5 minutes of extensor plantar responses, and often loss of sensation each other without a return to baseline mental status. at or below the site of injury. Bibliography ¢ MRI is the preferred initial imaging test for most patients Pack AM. Epilepsy overview and revised classification of seizures and epi- with findings of myelopathy. lepsies. Continuum (Minneap Minn). 2019;25:306-21. [PMID: 30921011] doi: 10.1212/CON.0000000000000707 118

Answers and Critiques Item 5 Answer: C Item 6 Answer: A Educational Objective: Treat secondary idiopathic Educational Objective: Prevent chronic tension-type intracranial hypertension. headache.

Item 5 Answer: C Item 6 Answer: A Educational Objective: Treat secondary idiopathic Educational Objective: Prevent chronic tension-type intracranial hypertension. headache. The most appropriate next step in management is to dis- The patient has tension-type headache and should be treated continue doxycycline (Option C). The patient’s history with amitriptyline (Option A). The most prevalent primary head- and examination findings are classic for idiopathic intra- ache condition, tension-type headache is defined as a headache cranial hypertension (IIH). Increased intracranial pres- disorder that, unlike migraine, is mild to moderate in intensity sure in the absence of any vascular or space-occupying and not associated with nausea or severe sensory or neurologic lesion is the hallmark of IIH (also known as pseudotumor symptoms. Annual population prevalence in the United States is cerebri). Headaches, visual symptoms, and intracranial approximately 40% for episodic (<15 days monthly) tension-type noises (pulsatile tinnitus) are the most common present- headache and 2.5% for its chronic (15 or more days monthly) ing symptoms of IIH. Head pain is nonspecific, and neck counterpart. Despite its high population prevalence, tension-type wn ao pain is common. Vision may be blurred or periodically headache comprises only 3% of outpatient headache consul- = a dim in brief episodes known as visual obscurations. Find- tations, most likely because of its nondisabling nature. Pain is ~ typically bilateral, nonpulsatile, and mild to moderate in intensity = ings on neurologic examination include papilledema and Ss) occasionally ophthalmoplegia, typically sixth nerve palsy. without aggravation by physical activity. Acetaminophen, aspirin, s = Contrast-enhanced brain MRI may reveal widening of the NSAIDs, and caffeine-containing compounds are typically effec- c

The most appropriate next step in management is to dis- The patient has tension-type headache and should be treated continue doxycycline (Option C). The patient’s history with amitriptyline (Option A). The most prevalent primary head- and examination findings are classic for idiopathic intra- ache condition, tension-type headache is defined as a headache cranial hypertension (IIH). Increased intracranial pres- disorder that, unlike migraine, is mild to moderate in intensity sure in the absence of any vascular or space-occupying and not associated with nausea or severe sensory or neurologic lesion is the hallmark of IIH (also known as pseudotumor symptoms. Annual population prevalence in the United States is cerebri). Headaches, visual symptoms, and intracranial approximately 40% for episodic (<15 days monthly) tension-type noises (pulsatile tinnitus) are the most common present- headache and 2.5% for its chronic (15 or more days monthly) ing symptoms of IIH. Head pain is nonspecific, and neck counterpart. Despite its high population prevalence, tension-type wn ao pain is common. Vision may be blurred or periodically headache comprises only 3% of outpatient headache consul- = a dim in brief episodes known as visual obscurations. Find- tations, most likely because of its nondisabling nature. Pain is ~ typically bilateral, nonpulsatile, and mild to moderate in intensity = ings on neurologic examination include papilledema and Ss) occasionally ophthalmoplegia, typically sixth nerve palsy. without aggravation by physical activity. Acetaminophen, aspirin, s = Contrast-enhanced brain MRI may reveal widening of the NSAIDs, and caffeine-containing compounds are typically effec- c optic nerve sheaths, an empty sella, or flattening of the pos- tive acute treatments for tension-type headache, and many wn i o terior optic globes. Magnetic resonance venography may patients self-medicate successfully. Nonpharmacologic treat- = reveal unilateral or bilateral stenoses of the intracranial ments have gained popularity as alternative interventions for 2] = transverse sinuses or may have normal results. Approxi- tension-type headaches in recent years. Psychological treatment «f

optic nerve sheaths, an empty sella, or flattening of the pos- tive acute treatments for tension-type headache, and many wn i o terior optic globes. Magnetic resonance venography may patients self-medicate successfully. Nonpharmacologic treat- = reveal unilateral or bilateral stenoses of the intracranial ments have gained popularity as alternative interventions for 2] = transverse sinuses or may have normal results. Approxi- tension-type headaches in recent years. Psychological treatment «f mately 90% of persons with IIH are women of childbearing strategies, such as relaxation training and cognitive behavioral age with an elevated BMI. IIH has been associated with therapies, are evidence-based and should be considered for all kidney failure, endocrine disorders, and the use of tetracy- patients with tension-type headache. Available options for pre- clines, retinoic acid, and progesterone or estrogen supple- vention of tension-type headache are more limited. Amitriptyline ments. Discontinuation of any potential offending agent is is the only agent shown to be effective in controlled trials; venla- the first step in management. faxine and mirtazapine have more limited data. There is no indication for beginning prednisone in the Due to potential for habituation and medication over- setting of I[H (Option A). Both initiation and withdrawal use, guidelines recommend that butalbital (Option B) be of glucocorticoids have been associated with the develop- avoided in the management of primary headache disorders, ment of ITH; therefore, they are not recommended for ITH such as migraine and tension-type headache. treatment. Many with tension-type headaches also will exhibit Topiramate (Option B) may be helpful in certain cases pericranial and cervical muscle tenderness on examination. of ITH associated with elevated BMI but is considered a This finding became the basis for the development of this second-line agent to acetazolamide because its carbonic specific headache diagnostic category. Despite this associa- anhydrase effect, which is thought to be helpful in lowering tion, evidence suggests muscle relaxants such as cycloben- intracranial pressure, is weaker. For this patient, stopping zaprine (Option C) are ineffective in this condition. doxycycline is the first step in management. Onabotulinum toxin A (Option D) is indicated in the Exposure to excessive doses of vitamin A has been management of chronic migraine, but studies in tension- associated with the development of ITH, but similar reports type headache have been negative. have not been seen with vitamin D supplementation. There Topiramate (Option E) is a first-line preventive treatment is no indication to discontinue vitamin D in this patient for episodic migraine (<15 days monthly) and has evidence of (Option D). benefit in chronic migraine (15 or more days monthly). How- ever, it has no evidence of benefit in tension-type headache.

mately 90% of persons with IIH are women of childbearing strategies, such as relaxation training and cognitive behavioral age with an elevated BMI. IIH has been associated with therapies, are evidence-based and should be considered for all kidney failure, endocrine disorders, and the use of tetracy- patients with tension-type headache. Available options for pre- clines, retinoic acid, and progesterone or estrogen supple- vention of tension-type headache are more limited. Amitriptyline ments. Discontinuation of any potential offending agent is is the only agent shown to be effective in controlled trials; venla- the first step in management. faxine and mirtazapine have more limited data. There is no indication for beginning prednisone in the Due to potential for habituation and medication over- setting of I[H (Option A). Both initiation and withdrawal use, guidelines recommend that butalbital (Option B) be of glucocorticoids have been associated with the develop- avoided in the management of primary headache disorders, ment of ITH; therefore, they are not recommended for ITH such as migraine and tension-type headache. treatment. Many with tension-type headaches also will exhibit Topiramate (Option B) may be helpful in certain cases pericranial and cervical muscle tenderness on examination. of ITH associated with elevated BMI but is considered a This finding became the basis for the development of this second-line agent to acetazolamide because its carbonic specific headache diagnostic category. Despite this associa- anhydrase effect, which is thought to be helpful in lowering tion, evidence suggests muscle relaxants such as cycloben- intracranial pressure, is weaker. For this patient, stopping zaprine (Option C) are ineffective in this condition. doxycycline is the first step in management. Onabotulinum toxin A (Option D) is indicated in the Exposure to excessive doses of vitamin A has been management of chronic migraine, but studies in tension- associated with the development of ITH, but similar reports type headache have been negative. have not been seen with vitamin D supplementation. There Topiramate (Option E) is a first-line preventive treatment is no indication to discontinue vitamin D in this patient for episodic migraine (<15 days monthly) and has evidence of (Option D). benefit in chronic migraine (15 or more days monthly). How- ever, it has no evidence of benefit in tension-type headache. e Increased intracranial pressure in the absence of any vascular or space-occupying lesion is the hallmark of ¢ Nonpharmacologic treatment strategies, such as relaxa- idiopathic intracranial hypertension. tion training and cognitive behavioral therapy, should be considered for all patients with tension-type headache. e Idiopathic intracranial hypertension is associated with use of tetracyclines, retinoic acid, and progesterone or e Amitriptyline is the only agent that has been shown to estrogen supplements; discontinuation of any potential be effective in the prevention of tension-type headache offending agent is the first step in management. in controlled clinical trials.

e Increased intracranial pressure in the absence of any vascular or space-occupying lesion is the hallmark of ¢ Nonpharmacologic treatment strategies, such as relaxa- idiopathic intracranial hypertension. tion training and cognitive behavioral therapy, should be considered for all patients with tension-type headache. e Idiopathic intracranial hypertension is associated with use of tetracyclines, retinoic acid, and progesterone or e Amitriptyline is the only agent that has been shown to estrogen supplements; discontinuation of any potential be effective in the prevention of tension-type headache offending agent is the first step in management. in controlled clinical trials. Bibliography Bibliography Wall M. Update on idiopathic intracranial hypertension. Neurol Clin. 2017 Jensen RH. Tension-type headache—The normal and most prevalent head- Feb;35(1):45-57. [PMID: 27886895] doi: 10.1016/j-ncl.2016.08.004. ache. Headache. 2018;58:339-345. [PMID: 28295304] doi:10.1111/head.13067 119

Answers andCritiques — Item 7 Answer: C Item 8 Answer: A Educational Objective: Treat aneurysmal subarachnoid Educational Objective: Treat peroneal mononeuropathy. hemorrhage with nimodipine. The most appropriate next step in management is to avoid leg The most appropriate treatment is oral nimodipine (Option C). crossing (Option A). This patient has focal mononeuropathy The patient has had a subarachnoid hemorrhage (SAH) due to of the peroneal nerve. Foot drop can be caused by injury to the a ruptured aneurysm in the posterior communicating artery peroneal nerve, sciatic nerve, or lumbar L5 nerve root or by that has now been occluded to prevent neurologic decline a central nervous system lesion. In this patient, the distribu- from aneurysmal rebleeding. Treatment of SAH focuses on tion of motor and sensory deficits and the electromyography prevention of early (<48 hours) and late neurologic complica finding of focal slowing of peroneal nerve conduction around tions. Within the first 48 hours, a major cause of morbidity is the fibular neck points toward an injury of the peroneal nerve aneurysmal rebleeding; early surgical exclusion of the ruptured around its most common site of compression around the

Item 7 Answer: C Item 8 Answer: A Educational Objective: Treat aneurysmal subarachnoid Educational Objective: Treat peroneal mononeuropathy. hemorrhage with nimodipine. The most appropriate next step in management is to avoid leg The most appropriate treatment is oral nimodipine (Option C). crossing (Option A). This patient has focal mononeuropathy The patient has had a subarachnoid hemorrhage (SAH) due to of the peroneal nerve. Foot drop can be caused by injury to the a ruptured aneurysm in the posterior communicating artery peroneal nerve, sciatic nerve, or lumbar L5 nerve root or by that has now been occluded to prevent neurologic decline a central nervous system lesion. In this patient, the distribu- from aneurysmal rebleeding. Treatment of SAH focuses on tion of motor and sensory deficits and the electromyography prevention of early (<48 hours) and late neurologic complica finding of focal slowing of peroneal nerve conduction around tions. Within the first 48 hours, a major cause of morbidity is the fibular neck points toward an injury of the peroneal nerve aneurysmal rebleeding; early surgical exclusion of the ruptured around its most common site of compression around the =] aneurysm and blood pressure control are the foundations of fibular neck. There is no electromyographic or clinical evi- = dence of injury affecting a more proximal site, and no upper 7 early treatment. The target blood pressure for patients following = SAH is not well defined, but guidelines suggest a systolic blood motor neuron findings support a central cause. Most peroneal oO = wn pressure of less than 160 mm Hg as reasonable. Late complica- mononeuropathies are caused by compression due to fre- gy tions include elevated intracranial pressure from obstructive quent crossing of legs, weight loss, or trauma. In addition to | 2. hydrocephalus, cerebral edema, seizures, and cerebral vaso advising the patient to avoid crossing his legs, stretching exer- (=) cises to maintain range of motion and use of an ankle orthosis spasm. Cerebral vasospasm with resultant cerebral ischemia = =. and neurologic worsening may develop beginning near day to compensate for foot drop may be considered. 2 < 5. Nimodipine should be started as early as possible once the Pain from sciatic neuropathy, another condition that om wn patient is stabilized to improve neurologic outcomes. Nimodip may sometimes present with isolated foot drop, may be ine was thought to prevent cerebral artery vasospasm, but aggravated by prolonged standing (Option B). However, no evidence for this effect is lacking. However, nimodipine does evidence suggests that this patient has sciatica or that avoid- improve clinical outcomes in patients with SAH and is recom- ance of prolonged standing would benefit this patient. mended in all patients as soon as possible following diagnosis. There is no reason to stop simvastatin (Option C). Intravenous dexamethasone (Option A) is not effective Although myalgia is common with statin use, myopathy is in reducing cerebral edema following a SAH. In patients rare. This patient has no muscle-related symptoms, and the undergoing craniotomy, dexamethasone may be used on a creatine kinase level is normal. If a statin-related myopathic case-by-case basis to reduce surgery-related edema, but this process was present, the pattern of muscle weakness would is not indicated after coiling. be proximal and symmetric, which is not consistent with The patient has no acute indications for lowering blood this patient’s findings. pressure with intravenous labetalol (Option B) now that the This patient’s BMI is 27. Although he might realize other ruptured cerebral aneurysm has been secured and her systolic health benefits from weight loss, losing weight (Option D) is blood pressure is less than the 160 mm Hg guideline suggested a risk factor for peroneal mononeuropathy and is not indi- target. Patients with a treated aneurysm may require blood pres- cated in this patient. sure augmentation if there is any evidence of vasospasm detected with surveillance transcranial Doppler ultrasonography. Oral verapamil (Option D) is not appropriate because it ¢ Most peroneal mononeuropathies are caused by com-

=] aneurysm and blood pressure control are the foundations of fibular neck. There is no electromyographic or clinical evi- = dence of injury affecting a more proximal site, and no upper 7 early treatment. The target blood pressure for patients following = SAH is not well defined, but guidelines suggest a systolic blood motor neuron findings support a central cause. Most peroneal oO = wn pressure of less than 160 mm Hg as reasonable. Late complica- mononeuropathies are caused by compression due to fre- gy tions include elevated intracranial pressure from obstructive quent crossing of legs, weight loss, or trauma. In addition to | 2. hydrocephalus, cerebral edema, seizures, and cerebral vaso advising the patient to avoid crossing his legs, stretching exer- (=) cises to maintain range of motion and use of an ankle orthosis spasm. Cerebral vasospasm with resultant cerebral ischemia = =. and neurologic worsening may develop beginning near day to compensate for foot drop may be considered. 2 < 5. Nimodipine should be started as early as possible once the Pain from sciatic neuropathy, another condition that om wn patient is stabilized to improve neurologic outcomes. Nimodip may sometimes present with isolated foot drop, may be ine was thought to prevent cerebral artery vasospasm, but aggravated by prolonged standing (Option B). However, no evidence for this effect is lacking. However, nimodipine does evidence suggests that this patient has sciatica or that avoid- improve clinical outcomes in patients with SAH and is recom- ance of prolonged standing would benefit this patient. mended in all patients as soon as possible following diagnosis. There is no reason to stop simvastatin (Option C). Intravenous dexamethasone (Option A) is not effective Although myalgia is common with statin use, myopathy is in reducing cerebral edema following a SAH. In patients rare. This patient has no muscle-related symptoms, and the undergoing craniotomy, dexamethasone may be used on a creatine kinase level is normal. If a statin-related myopathic case-by-case basis to reduce surgery-related edema, but this process was present, the pattern of muscle weakness would is not indicated after coiling. be proximal and symmetric, which is not consistent with The patient has no acute indications for lowering blood this patient’s findings. pressure with intravenous labetalol (Option B) now that the This patient’s BMI is 27. Although he might realize other ruptured cerebral aneurysm has been secured and her systolic health benefits from weight loss, losing weight (Option D) is blood pressure is less than the 160 mm Hg guideline suggested a risk factor for peroneal mononeuropathy and is not indi- target. Patients with a treated aneurysm may require blood pres- cated in this patient. sure augmentation if there is any evidence of vasospasm detected with surveillance transcranial Doppler ultrasonography. Oral verapamil (Option D) is not appropriate because it ¢ Most peroneal mononeuropathies are caused by com- does not reduce the risk of vasospasm or improve neurologic pression due to frequent crossing of legs, weight loss,

=] aneurysm and blood pressure control are the foundations of fibular neck. There is no electromyographic or clinical evi- = dence of injury affecting a more proximal site, and no upper 7 early treatment. The target blood pressure for patients following = SAH is not well defined, but guidelines suggest a systolic blood motor neuron findings support a central cause. Most peroneal oO = wn pressure of less than 160 mm Hg as reasonable. Late complica- mononeuropathies are caused by compression due to fre- gy tions include elevated intracranial pressure from obstructive quent crossing of legs, weight loss, or trauma. In addition to | 2. hydrocephalus, cerebral edema, seizures, and cerebral vaso advising the patient to avoid crossing his legs, stretching exer- (=) cises to maintain range of motion and use of an ankle orthosis spasm. Cerebral vasospasm with resultant cerebral ischemia = =. and neurologic worsening may develop beginning near day to compensate for foot drop may be considered. 2 < 5. Nimodipine should be started as early as possible once the Pain from sciatic neuropathy, another condition that om wn patient is stabilized to improve neurologic outcomes. Nimodip may sometimes present with isolated foot drop, may be ine was thought to prevent cerebral artery vasospasm, but aggravated by prolonged standing (Option B). However, no evidence for this effect is lacking. However, nimodipine does evidence suggests that this patient has sciatica or that avoid- improve clinical outcomes in patients with SAH and is recom- ance of prolonged standing would benefit this patient. mended in all patients as soon as possible following diagnosis. There is no reason to stop simvastatin (Option C). Intravenous dexamethasone (Option A) is not effective Although myalgia is common with statin use, myopathy is in reducing cerebral edema following a SAH. In patients rare. This patient has no muscle-related symptoms, and the undergoing craniotomy, dexamethasone may be used on a creatine kinase level is normal. If a statin-related myopathic case-by-case basis to reduce surgery-related edema, but this process was present, the pattern of muscle weakness would is not indicated after coiling. be proximal and symmetric, which is not consistent with The patient has no acute indications for lowering blood this patient’s findings. pressure with intravenous labetalol (Option B) now that the This patient’s BMI is 27. Although he might realize other ruptured cerebral aneurysm has been secured and her systolic health benefits from weight loss, losing weight (Option D) is blood pressure is less than the 160 mm Hg guideline suggested a risk factor for peroneal mononeuropathy and is not indi- target. Patients with a treated aneurysm may require blood pres- cated in this patient. sure augmentation if there is any evidence of vasospasm detected with surveillance transcranial Doppler ultrasonography. Oral verapamil (Option D) is not appropriate because it ¢ Most peroneal mononeuropathies are caused by com- does not reduce the risk of vasospasm or improve neurologic pression due to frequent crossing of legs, weight loss, outcomes after aneurysmal SAH. In case series of patients with or trauma.

=] aneurysm and blood pressure control are the foundations of fibular neck. There is no electromyographic or clinical evi- = dence of injury affecting a more proximal site, and no upper 7 early treatment. The target blood pressure for patients following = SAH is not well defined, but guidelines suggest a systolic blood motor neuron findings support a central cause. Most peroneal oO = wn pressure of less than 160 mm Hg as reasonable. Late complica- mononeuropathies are caused by compression due to fre- gy tions include elevated intracranial pressure from obstructive quent crossing of legs, weight loss, or trauma. In addition to | 2. hydrocephalus, cerebral edema, seizures, and cerebral vaso advising the patient to avoid crossing his legs, stretching exer- (=) cises to maintain range of motion and use of an ankle orthosis spasm. Cerebral vasospasm with resultant cerebral ischemia = =. and neurologic worsening may develop beginning near day to compensate for foot drop may be considered. 2 < 5. Nimodipine should be started as early as possible once the Pain from sciatic neuropathy, another condition that om wn patient is stabilized to improve neurologic outcomes. Nimodip may sometimes present with isolated foot drop, may be ine was thought to prevent cerebral artery vasospasm, but aggravated by prolonged standing (Option B). However, no evidence for this effect is lacking. However, nimodipine does evidence suggests that this patient has sciatica or that avoid- improve clinical outcomes in patients with SAH and is recom- ance of prolonged standing would benefit this patient. mended in all patients as soon as possible following diagnosis. There is no reason to stop simvastatin (Option C). Intravenous dexamethasone (Option A) is not effective Although myalgia is common with statin use, myopathy is in reducing cerebral edema following a SAH. In patients rare. This patient has no muscle-related symptoms, and the undergoing craniotomy, dexamethasone may be used on a creatine kinase level is normal. If a statin-related myopathic case-by-case basis to reduce surgery-related edema, but this process was present, the pattern of muscle weakness would is not indicated after coiling. be proximal and symmetric, which is not consistent with The patient has no acute indications for lowering blood this patient’s findings. pressure with intravenous labetalol (Option B) now that the This patient’s BMI is 27. Although he might realize other ruptured cerebral aneurysm has been secured and her systolic health benefits from weight loss, losing weight (Option D) is blood pressure is less than the 160 mm Hg guideline suggested a risk factor for peroneal mononeuropathy and is not indi- target. Patients with a treated aneurysm may require blood pres- cated in this patient. sure augmentation if there is any evidence of vasospasm detected with surveillance transcranial Doppler ultrasonography. Oral verapamil (Option D) is not appropriate because it ¢ Most peroneal mononeuropathies are caused by com- does not reduce the risk of vasospasm or improve neurologic pression due to frequent crossing of legs, weight loss, outcomes after aneurysmal SAH. In case series of patients with or trauma. reversible cerebral vasoconstriction syndrome (a rare condition that can be triggered by medications, such as amphetamines Bibliography or selective serotonin reuptake inhibitors), verapamil has been Hobson-Webb LD, Juel VC. Common entrapment neuropathies. Continuum (Minneap Minn). 2017;23:487-511. [PMID: 28375915] doi:10.1212/CON. associated with a reduction in neurologic adverse events. 0000000000000452

reversible cerebral vasoconstriction syndrome (a rare condition that can be triggered by medications, such as amphetamines Bibliography or selective serotonin reuptake inhibitors), verapamil has been Hobson-Webb LD, Juel VC. Common entrapment neuropathies. Continuum (Minneap Minn). 2017;23:487-511. [PMID: 28375915] doi:10.1212/CON. associated with a reduction in neurologic adverse events. 0000000000000452 e A target systolic blood pressure of less than 160 mm Hg Item 9 Answer: B is recommended for patients in the acute phase fol- Educational Objective: Diagnose focal impaired lowing subarachnoid hemorrhage. awareness seizures. e The use of nimodipine is associated with improved The most likely diagnosis is focal impaired awareness sei- long-term neurologic outcomes in patients with zures (also known as complex partial or focal dyscognitive aneurysmal subarachnoid hemorrhage. seizures) (Option B). These seizures are characterized by the sudden onset of staring or arrested speech (seizure-related aphasia) or behavior, lasting at least 30 but up to 90 seconds Bibliography during which the patient is unaware and unresponsive. Epi- Lawton MT, Vates GE. Subarachnoid hemorrhage. N Engl J Med. 2017; 377:257-266. [PMID: 28723321] doi:10.1056/NEJMcp1605827 sodes are followed by a short period of postictal somnolence 120

be ele or confusion. When focal seizures (with or without impaired with photophobia, phonophobia, and nausea lasting 6 to awareness) involve the frontal lobe, specifically the motor 8 hours) that are unrelated to the tumor. Because the cortex, contralateral limb twitching and stiffness can be seen patient’s throbbing headache can occur on either side of during the seizure, with transient weakness immediately her head, and the tingling is on the incorrect side of the after the seizure (Todd paralysis). Postictal aphasia can occur body in relationship to the meningioma, the meningioma is with a seizure emanating from the dominant hemisphere. most likely an incidental finding in this patient. Episodes usually occur weekly or monthly. Brain biopsy (Option A) is not indicated based on the Focal aware seizures (Option A) may have some of the classic imaging characteristics of a meningioma. Repeat same features described in this patient, such as arrest of speech imaging in 3 to 6 months, or at any time if the patient’s and behavior, focal contralateral limb twitching and stiffness, symptoms or examination findings change, could be consid- and postseizure focal weakness. However, by definition, aware- ered. If the MRI appearance is changing or becomes atypical, ness and memory are retained in focal aware seizures. biopsy could be considered. Absence seizures (Option C) can present with staring Dexamethasone therapy (Option B) is not indicated for nn rt} and confusion, but they are typically shorter in duration this patient. There is no evidence of mass effect or cerebral =

or confusion. When focal seizures (with or without impaired with photophobia, phonophobia, and nausea lasting 6 to awareness) involve the frontal lobe, specifically the motor 8 hours) that are unrelated to the tumor. Because the cortex, contralateral limb twitching and stiffness can be seen patient’s throbbing headache can occur on either side of during the seizure, with transient weakness immediately her head, and the tingling is on the incorrect side of the after the seizure (Todd paralysis). Postictal aphasia can occur body in relationship to the meningioma, the meningioma is with a seizure emanating from the dominant hemisphere. most likely an incidental finding in this patient. Episodes usually occur weekly or monthly. Brain biopsy (Option A) is not indicated based on the Focal aware seizures (Option A) may have some of the classic imaging characteristics of a meningioma. Repeat same features described in this patient, such as arrest of speech imaging in 3 to 6 months, or at any time if the patient’s and behavior, focal contralateral limb twitching and stiffness, symptoms or examination findings change, could be consid- and postseizure focal weakness. However, by definition, aware- ered. If the MRI appearance is changing or becomes atypical, ness and memory are retained in focal aware seizures. biopsy could be considered. Absence seizures (Option C) can present with staring Dexamethasone therapy (Option B) is not indicated for nn rt} and confusion, but they are typically shorter in duration this patient. There is no evidence of mass effect or cerebral = (less than 15 seconds), are more frequent (occurring multi- edema on brain MRI. There is no herniation on neurologic ae ple times per day), and do not have associated postictal focal examination. = 1S) weakness or confusion. They may occur as the only seizure Prophylactic administration of antiepileptic drugs is sc = type in school-age children and are often confused with generally not indicated in patients with meningioma in © attention-deficit disorder. the absence of seizures. Therefore, starting levetiracetam 2 o Myoclonus is the defining seizure manifestation of (Option C) is not indicated. = myoclonic seizures (Option D). When describing symptoms, Surgical resection of the lesion (Option E) is not indicated wn = patients will usually use words like “spasms,” “jerks,” or for this patient given the absence of a history of neurologic <

(less than 15 seconds), are more frequent (occurring multi- edema on brain MRI. There is no herniation on neurologic ae ple times per day), and do not have associated postictal focal examination. = 1S) weakness or confusion. They may occur as the only seizure Prophylactic administration of antiepileptic drugs is sc = type in school-age children and are often confused with generally not indicated in patients with meningioma in © attention-deficit disorder. the absence of seizures. Therefore, starting levetiracetam 2 o Myoclonus is the defining seizure manifestation of (Option C) is not indicated. = myoclonic seizures (Option D). When describing symptoms, Surgical resection of the lesion (Option E) is not indicated wn = patients will usually use words like “spasms,” “jerks,” or for this patient given the absence of a history of neurologic < “shakes.” Myoclonic seizures may have twitching of the arms deterioration (e.g., symptoms, focal findings, drug-resistant and legs, but this is usually bilateral and last 1 second or less. seizures), a normal neurologic examination, and brain MRI Myoclonic seizures may result in dropping objects and also can results that show a typical meningioma appearance without result in falls. Awareness is maintained during the seizures. edema or mass effect.

“shakes.” Myoclonic seizures may have twitching of the arms deterioration (e.g., symptoms, focal findings, drug-resistant and legs, but this is usually bilateral and last 1 second or less. seizures), a normal neurologic examination, and brain MRI Myoclonic seizures may result in dropping objects and also can results that show a typical meningioma appearance without result in falls. Awareness is maintained during the seizures. edema or mass effect. ¢ Focal seizures with impaired awareness are character- ¢ Meningiomas are benign dural-based tumors that ized by arrest of speech or behavior and staring without require no management in asymptomatic patients and responsiveness. are usually followed clinically. ¢ Focal aware seizures may be associated with arrest of ¢ In patients with asymptomatic meningioma, prophy- speech and behavior and focal motor symptoms, but lactic administration of antiepileptic drugs is generally awareness, responsiveness, and memory are retained. not indicated in the absence of seizures. Bibliography Bibliography Pack AM. Epilepsy overview and revised classification of seizures and epilep- Strowd RE 3rd, Blakeley JO. Common histologically benign tumors of the brain. sies. Continuum (Minneap Minn). 2019;25:306-21. [PMID: 30921011] Continuum (Minneap Minn). 2017 Dec 1;23(6, Neuro-oncology):1680-708. doi: 10.1212/CON.0000000000000707

Bibliography Bibliography Pack AM. Epilepsy overview and revised classification of seizures and epilep- Strowd RE 3rd, Blakeley JO. Common histologically benign tumors of the brain. sies. Continuum (Minneap Minn). 2019;25:306-21. [PMID: 30921011] Continuum (Minneap Minn). 2017 Dec 1;23(6, Neuro-oncology):1680-708. doi: 10.1212/CON.0000000000000707 Item 11 Answer: C Item 10 Answer: D Educational Objective: Diagnose Creutzfeldt-Jakob Educational Objective: Manage asymptomatic disease. meningioma. The most appropriate diagnostic test to perform on the cere- The most appropriate management is serial brain MRI brospinal fluid (CSF) is real-time quaking-induced conver. (Option D). This patient most likely has a meningioma, sion assay (Option C). This patient has signs, symptoms, a benign tumor that is outside of the brain tissue (extra- and MRI findings concerning for Creutzfeldt-Jakob (CJD) axial) but inside the skull (intradural), arising from the dura disease. MRI is one of the most sensitive diagnostic tools for (meninges). On noncontrast images, meningiomas may CJD, typically showing a pattern of increased intensity in be hypointense or isointense and thus not readily seen. the diffusion-weighted sequence in the basal ganglia and The term benign is used with caution in neurology because various cortical regions. CJD is a prion-related disorder that a histologically benign tumor may still be neurologically often presents with rapidly progressive dementia. The cause morbid because of location and size. No acute treatment of CJD is an abnormally folded prion protein, which occurs is necessary in this case because the patient does not have by a spontaneous mutation (85%), is acquired by exposure to a history of worrisome focal neurologic symptoms, has a a transmissible protein. or is an inherited genetic mutation. normal neurologic examination, and shows a clear and Prion diseases have no known therapy. Time from disease stable pattern of migraine headaches (throbbing headache onset to death is approximately 12 months in as many as

Item 11 Answer: C Item 10 Answer: D Educational Objective: Diagnose Creutzfeldt-Jakob Educational Objective: Manage asymptomatic disease. meningioma. The most appropriate diagnostic test to perform on the cere- The most appropriate management is serial brain MRI brospinal fluid (CSF) is real-time quaking-induced conver. (Option D). This patient most likely has a meningioma, sion assay (Option C). This patient has signs, symptoms, a benign tumor that is outside of the brain tissue (extra- and MRI findings concerning for Creutzfeldt-Jakob (CJD) axial) but inside the skull (intradural), arising from the dura disease. MRI is one of the most sensitive diagnostic tools for (meninges). On noncontrast images, meningiomas may CJD, typically showing a pattern of increased intensity in be hypointense or isointense and thus not readily seen. the diffusion-weighted sequence in the basal ganglia and The term benign is used with caution in neurology because various cortical regions. CJD is a prion-related disorder that a histologically benign tumor may still be neurologically often presents with rapidly progressive dementia. The cause morbid because of location and size. No acute treatment of CJD is an abnormally folded prion protein, which occurs is necessary in this case because the patient does not have by a spontaneous mutation (85%), is acquired by exposure to a history of worrisome focal neurologic symptoms, has a a transmissible protein. or is an inherited genetic mutation. normal neurologic examination, and shows a clear and Prion diseases have no known therapy. Time from disease stable pattern of migraine headaches (throbbing headache onset to death is approximately 12 months in as many as 121

80% of patients with CJD. The rapid cognitive decline seen with high baseline headache frequency. The development of with this disorder is associated with myoclonus, gait prob MOH often coincides with the transformation of episodic CONT. lems, visual compromise, and interruption of the circadian forms of migraine or tension-type headache (occurring rhythm. The real-time quaking-induced conversion assay is <15 days per month) into their chronic subtypes (15 or more the most sensitive and specific test for prion proteins in the days monthly). Treatment of MOH is to wean overused acute CSF It uses recombinant prion protein and thioflavin T, a medications, initiate migraine preventive medication, and fluorescent dye, to detect prion protein present in the CSF provide new acute medications limited in use to 10 or fewer despite its being present in only small quantities. The prion days per month. protein in the CSF induces the recombinant prion protein Guidelines suggest butalbital compounds be avoided in to change shape and form fibrils that bind thioflavin T and patients with primary headache (Option A). In those with begin to fluoresce. The quantity of fluorescence is measured migraine, opioids are associated with a 44% increase and in real time. butalbital compounds with a 70% increase in the risk of

80% of patients with CJD. The rapid cognitive decline seen with high baseline headache frequency. The development of with this disorder is associated with myoclonus, gait prob MOH often coincides with the transformation of episodic CONT. lems, visual compromise, and interruption of the circadian forms of migraine or tension-type headache (occurring rhythm. The real-time quaking-induced conversion assay is <15 days per month) into their chronic subtypes (15 or more the most sensitive and specific test for prion proteins in the days monthly). Treatment of MOH is to wean overused acute CSF It uses recombinant prion protein and thioflavin T, a medications, initiate migraine preventive medication, and fluorescent dye, to detect prion protein present in the CSF provide new acute medications limited in use to 10 or fewer despite its being present in only small quantities. The prion days per month. protein in the CSF induces the recombinant prion protein Guidelines suggest butalbital compounds be avoided in to change shape and form fibrils that bind thioflavin T and patients with primary headache (Option A). In those with begin to fluoresce. The quantity of fluorescence is measured migraine, opioids are associated with a 44% increase and in real time. butalbital compounds with a 70% increase in the risk of aad CSF 14-3-3 protein (Option A) and total tau proteins headache progression. Both medications should be avoided = wv (Option D), although elevated in CJD, lack sufficient sensi- in patients with recurrent primary headache disorders, par- = tivity and specificity for diagnosis of this disease. They can ticularly those already diagnosed with MOH. © = w also be elevated in other diseases that cause neurodegenera This patient’s headache history is compatible with me = tion or neuronal loss. migraine and subsequent development of MOH. There is no 2. Ordering polymerase chain reaction assay (Option B) evidence that verapamil is helpful in either headache disor- (=) =e for herpes simplex virus would be of low yield in this case der (Option B). =. because the symptoms have been noted for 6 months. Her- Amitriptyline is indicated for the preventive treatment =) fe pes encephalitis is characterized by headache, fever, and of migraine; there is no need to discontinue this medication © ~n neck stiffness, symptoms not present in this patient. The in the setting of MOH (Option C). Most preventive options patient also lacks the MRI brain findings that are charac- for migraine are rendered less effective or ineffective in the teristic of herpes encephalitis, including hyperintensity on presence of MOH. Resolving MOH often restores the ther- T2-weighted fluid-attenuated inversion recovery sequences apeutic benefits of pharmacologic prevention of migraine. in the bilateral temporal lobes.

aad CSF 14-3-3 protein (Option A) and total tau proteins headache progression. Both medications should be avoided = wv (Option D), although elevated in CJD, lack sufficient sensi- in patients with recurrent primary headache disorders, par- = tivity and specificity for diagnosis of this disease. They can ticularly those already diagnosed with MOH. © = w also be elevated in other diseases that cause neurodegenera This patient’s headache history is compatible with me = tion or neuronal loss. migraine and subsequent development of MOH. There is no 2. Ordering polymerase chain reaction assay (Option B) evidence that verapamil is helpful in either headache disor- (=) =e for herpes simplex virus would be of low yield in this case der (Option B). =. because the symptoms have been noted for 6 months. Her- Amitriptyline is indicated for the preventive treatment =) fe pes encephalitis is characterized by headache, fever, and of migraine; there is no need to discontinue this medication © ~n neck stiffness, symptoms not present in this patient. The in the setting of MOH (Option C). Most preventive options patient also lacks the MRI brain findings that are charac- for migraine are rendered less effective or ineffective in the teristic of herpes encephalitis, including hyperintensity on presence of MOH. Resolving MOH often restores the ther- T2-weighted fluid-attenuated inversion recovery sequences apeutic benefits of pharmacologic prevention of migraine. in the bilateral temporal lobes. ¢ Medication overuse headache can result from the use ¢ Creutzfeldt-Jakob disease is a prion-related disorder of triptans, ergot alkaloids, opioids, or combination that often presents with rapidly progressive dementia. analgesics for 10 or more days per month or simple

¢ Medication overuse headache can result from the use ¢ Creutzfeldt-Jakob disease is a prion-related disorder of triptans, ergot alkaloids, opioids, or combination that often presents with rapidly progressive dementia. analgesics for 10 or more days per month or simple e The real-time quaking-induced conversion assay is analgesics for 15 or more days per month. the most sensitive and specific test for prion proteins e Treatment of medication overuse headache is to wean in the cerebrospinal fluid. overused acute medications, initiate migraine preven- tive medication, and provide new acute medications Bibliography limited in use to 10 or fewer days per month. Mead S, Rudge P. CJD mimics and chameleons. Pract Neurol. 2017;17:113-21. [PMID: 28153848] doi:10.1136/practneurol-2016-001571 Bibliography Chen P, Wang S. Medication overuse and medication overuse headache: risk factors, comorbidities, associated burdens and nonpharmacologic and pharmacologic treatment approaches. Curr Pain Headache Rep. 2019;23(8): Item 12 Answer: D 60. [PMID: 31346781] doi: 10.1007/s11916-019-0796-7.

the most sensitive and specific test for prion proteins e Treatment of medication overuse headache is to wean in the cerebrospinal fluid. overused acute medications, initiate migraine preven- tive medication, and provide new acute medications Bibliography limited in use to 10 or fewer days per month. Mead S, Rudge P. CJD mimics and chameleons. Pract Neurol. 2017;17:113-21. [PMID: 28153848] doi:10.1136/practneurol-2016-001571 Bibliography Chen P, Wang S. Medication overuse and medication overuse headache: risk factors, comorbidities, associated burdens and nonpharmacologic and pharmacologic treatment approaches. Curr Pain Headache Rep. 2019;23(8): Item 12 Answer: D 60. [PMID: 31346781] doi: 10.1007/s11916-019-0796-7. Educational Objective: Treat medication overuse headache. Item 13 Answer: B The most appropriate next step in management is to discon- Educational Objective: Evaluate depression as a cause tinue sumatriptan (Option D). The patient has a history of of cognitive impairment. headaches meeting criteria for episodic migraine and has likely now developed medication overuse headache (MOH). The most appropriate test to perform next is depression MOH is defined as headache occurring on at least 15 days per screening (Option B). This patient’s findings on the Mini-Cog month in a patient with a pre-existing headache disorder test suggest cognitive impairment, and further investigation exposed to regular overuse for more than 3 months of one or is warranted. Assessment for a reversible cause of cognitive more drugs taken for acute and/or symptomatic treatment of impairment is the initial recommended strategy and should headache. Use of triptans, ergot alkaloids, opioids, or com- include evaluation for depression and sleep disorders, con- bination analgesics for 10 or more days per month or simple sideration of medication adverse effects and alcohol use, analgesics for 15 or more days per month constitutes medi- basic laboratory studies, and basic neuroimaging (MRI or cation overuse. Affected patients often report daily or near- CT without contrast). The symptoms of depression in geri- daily headache that is refractory to numerous treatments. atric patients can differ slightly from those in the general MOH is more common in midlife, in women, and in persons population, and depression symptoms can be misattributed

Educational Objective: Treat medication overuse headache. Item 13 Answer: B The most appropriate next step in management is to discon- Educational Objective: Evaluate depression as a cause tinue sumatriptan (Option D). The patient has a history of of cognitive impairment. headaches meeting criteria for episodic migraine and has likely now developed medication overuse headache (MOH). The most appropriate test to perform next is depression MOH is defined as headache occurring on at least 15 days per screening (Option B). This patient’s findings on the Mini-Cog month in a patient with a pre-existing headache disorder test suggest cognitive impairment, and further investigation exposed to regular overuse for more than 3 months of one or is warranted. Assessment for a reversible cause of cognitive more drugs taken for acute and/or symptomatic treatment of impairment is the initial recommended strategy and should headache. Use of triptans, ergot alkaloids, opioids, or com- include evaluation for depression and sleep disorders, con- bination analgesics for 10 or more days per month or simple sideration of medication adverse effects and alcohol use, analgesics for 15 or more days per month constitutes medi- basic laboratory studies, and basic neuroimaging (MRI or cation overuse. Affected patients often report daily or near- CT without contrast). The symptoms of depression in geri- daily headache that is refractory to numerous treatments. atric patients can differ slightly from those in the general MOH is more common in midlife, in women, and in persons population, and depression symptoms can be misattributed 122

Answers and Critiques to aging or chronic illness; therefore, depression might not first-line therapy of intravenous lorazepam. Intravenous fos- be identified as readily in older patients. Depression in older phenytoin is indicated for second-line therapy. Fosphenytoin adults may also be confused with cognitive dysfunction and can cause acute bradycardia and hypotension. Intravenous is itself a risk factor for cognitive dysfunction. Older adults valproic acid or levetiracetam are reasonable alternatives, with depression are often treated with pharmacotherapy, provided that he is not already taking maximum doses of and psychotherapy may also be considered as primary treat- levetiracetam at home. Fosphenytoin, valproate, and leveti- ment or as adjunctive therapy. racetam have similar efficacy as second-line agents. The diagnosis of Alzheimer disease is often established A head CT (Option A) can be considered acutely in the by finding impairment in two cognitive domains (memory, emergency department, especially if an obvious cause of attention, language, visuospatial impairment, and executive seizure is not found. However, obtaining a head CT should functioning) with a compatible history of functional decline not delay rapid intravenous treatment for CSE. and supportive neuroimaging findings. Decreased cerebro- Immediate continuous EEG (Option B) is not indicated spinal fluid AB,, and increased tau and phosphorylated tau at this point, because the diagnosis can be confirmed clini- w ry levels are highly specific for Alzheimer disease, but testing is cally, and the delay in treatment would increase this patient's 5

to aging or chronic illness; therefore, depression might not first-line therapy of intravenous lorazepam. Intravenous fos- be identified as readily in older patients. Depression in older phenytoin is indicated for second-line therapy. Fosphenytoin adults may also be confused with cognitive dysfunction and can cause acute bradycardia and hypotension. Intravenous is itself a risk factor for cognitive dysfunction. Older adults valproic acid or levetiracetam are reasonable alternatives, with depression are often treated with pharmacotherapy, provided that he is not already taking maximum doses of and psychotherapy may also be considered as primary treat- levetiracetam at home. Fosphenytoin, valproate, and leveti- ment or as adjunctive therapy. racetam have similar efficacy as second-line agents. The diagnosis of Alzheimer disease is often established A head CT (Option A) can be considered acutely in the by finding impairment in two cognitive domains (memory, emergency department, especially if an obvious cause of attention, language, visuospatial impairment, and executive seizure is not found. However, obtaining a head CT should functioning) with a compatible history of functional decline not delay rapid intravenous treatment for CSE. and supportive neuroimaging findings. Decreased cerebro- Immediate continuous EEG (Option B) is not indicated spinal fluid AB,, and increased tau and phosphorylated tau at this point, because the diagnosis can be confirmed clini- w ry levels are highly specific for Alzheimer disease, but testing is cally, and the delay in treatment would increase this patient's 5 usually unnecessary (Option A). Such testing might be con- morbidity and mortality. = sidered in atypical situations, such as early onset disease, or Rectal administration of diazepam (Option D) is a = es) when the diagnosis otherwise remains in doubt. reasonable option for CSE and is used frequently in the cs < Genetic testing for the apolipoprotein-E ¢4 (APOE ¢4) home or in an ambulance. However, this patient has intra- ro]

usually unnecessary (Option A). Such testing might be con- morbidity and mortality. = sidered in atypical situations, such as early onset disease, or Rectal administration of diazepam (Option D) is a = es) when the diagnosis otherwise remains in doubt. reasonable option for CSE and is used frequently in the cs < Genetic testing for the apolipoprotein-E ¢4 (APOE ¢4) home or in an ambulance. However, this patient has intra- ro] (Option C) allele is not recommended in the evaluation of venous access, which provides more rapid and predictable w eo o cognitive impairment. The APOE é4 allele is a risk factor for absorption. = Alzheimer disease but is not causative. wn < Routine screening for neurosyphilis with a rapid plas- 4 min reagin (RPR) test in a patient with cognitive impairment ¢ Convulsive status epilepticus is a medical emergency

(Option C) allele is not recommended in the evaluation of venous access, which provides more rapid and predictable w eo o cognitive impairment. The APOE é4 allele is a risk factor for absorption. = Alzheimer disease but is not causative. wn < Routine screening for neurosyphilis with a rapid plas- 4 min reagin (RPR) test in a patient with cognitive impairment ¢ Convulsive status epilepticus is a medical emergency is not indicated. Guidelines recommend that RPR testing and empiric therapy is indicated without awaiting with VDRL (Option D) or RPR testing by itself be reserved diagnostic studies that would delay treatment. for high-risk patients based on sexual history. In these situ- e First-line therapy for convulsive status epilepticus is ations, screening for HIV infection may also be appropriate. intravenous lorazepam; second-line therapy is intra- venous fosphenytoin, valproic acid, or levetiracetam.

is not indicated. Guidelines recommend that RPR testing and empiric therapy is indicated without awaiting with VDRL (Option D) or RPR testing by itself be reserved diagnostic studies that would delay treatment. for high-risk patients based on sexual history. In these situ- e First-line therapy for convulsive status epilepticus is ations, screening for HIV infection may also be appropriate. intravenous lorazepam; second-line therapy is intra- venous fosphenytoin, valproic acid, or levetiracetam. e Assessment for a reversible cause of cognitive impairment Bibliography should include consideration of medication adverse Glauser T, Shinnar S, Gloss D, et al. Evidence-Based Guideline: Treatment of effects, alcohol use, sleep apnea, and depression. Convulsive Status Epilepticus in Children and Adults: Report of the Guideline Committee of the American Epilepsy Society. Epilepsy Curr. 2016 Jan-Feb;16:48-61. [PMID: 26900382] Bibliography Petersen RC, Lopez O, Armstrong MJ, et al. Practice guideline update sum- mary: mild cognitive impairment: report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Item 15 Answer: C Academy of Neurology. Neurology. 2018;90:126-35. [PMID: 29282327] doi:10.1212/WNL.0000000000004826 Educational Objective: Diagnose optic neuritis.

e Assessment for a reversible cause of cognitive impairment Bibliography should include consideration of medication adverse Glauser T, Shinnar S, Gloss D, et al. Evidence-Based Guideline: Treatment of effects, alcohol use, sleep apnea, and depression. Convulsive Status Epilepticus in Children and Adults: Report of the Guideline Committee of the American Epilepsy Society. Epilepsy Curr. 2016 Jan-Feb;16:48-61. [PMID: 26900382] Bibliography Petersen RC, Lopez O, Armstrong MJ, et al. Practice guideline update sum- mary: mild cognitive impairment: report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Item 15 Answer: C Academy of Neurology. Neurology. 2018;90:126-35. [PMID: 29282327] doi:10.1212/WNL.0000000000004826 Educational Objective: Diagnose optic neuritis. The most likely diagnosis is optic neuritis (Option C). The Item 14 Answer: C patient has pain with eye movement, unilateral visual defi- cit, and an afferent pupillary defect in the left eye. These are Educational Objective: Treat convulsive status classic findings of optic neuritis, an inflammation of the epilepticus with a second-line therapy. optic nerve. The lack of funduscopic examination findings in The most appropriate management is to administer intrave- this patient does not rule out this diagnosis. Acute papillitis nous fosphenytoin (Option C). This patients meets the clin- (flared appearance of the optic disc caused by inflammatory ical criteria for convulsive status epilepticus (CSE), defined changes) is only seen when the inflammatory changes occur as a generalized tonic-clonic seizure lasting greater than at the optic nerve head, and optic disc pallor is only seen 5 minutes, or two generalized tonic-clonic seizures occur- as a chronic change—occurring weeks to months after an ring within 5 minutes of each other and without a return to acute optic neuritis event. This patient may have a clinically baseline mental status. CSE is a medical emergency. Empiric isolated syndrome (CIS). CIS is a first symptomatic episode therapy is indicated without awaiting results of electroen- compatible with demyelination or multiple sclerosis (MS). cephalography (EEG), imaging, serum studies, or lumbar The cumulative 5-year incidence of clinically definite MS is puncture because a longer duration of CSE is strongly linked 30% followinga first episode of demyelinating optic neuritis. to worse outcomes. Securing the airway and obtaining intra- Central retinal artery occlusion (Option A) is not a venous access are the first steps in CSE management. If point- likely diagnosis in this case. Although central retinal artery of-care glucose testing is not available, thiamine should be occlusions are typically unilateral in nature, they are pain given, followed by intravenous glucose. This patient has failed less, acute in onset (as opposed to this patient’s subacute

The most likely diagnosis is optic neuritis (Option C). The Item 14 Answer: C patient has pain with eye movement, unilateral visual defi- cit, and an afferent pupillary defect in the left eye. These are Educational Objective: Treat convulsive status classic findings of optic neuritis, an inflammation of the epilepticus with a second-line therapy. optic nerve. The lack of funduscopic examination findings in The most appropriate management is to administer intrave- this patient does not rule out this diagnosis. Acute papillitis nous fosphenytoin (Option C). This patients meets the clin- (flared appearance of the optic disc caused by inflammatory ical criteria for convulsive status epilepticus (CSE), defined changes) is only seen when the inflammatory changes occur as a generalized tonic-clonic seizure lasting greater than at the optic nerve head, and optic disc pallor is only seen 5 minutes, or two generalized tonic-clonic seizures occur- as a chronic change—occurring weeks to months after an ring within 5 minutes of each other and without a return to acute optic neuritis event. This patient may have a clinically baseline mental status. CSE is a medical emergency. Empiric isolated syndrome (CIS). CIS is a first symptomatic episode therapy is indicated without awaiting results of electroen- compatible with demyelination or multiple sclerosis (MS). cephalography (EEG), imaging, serum studies, or lumbar The cumulative 5-year incidence of clinically definite MS is puncture because a longer duration of CSE is strongly linked 30% followinga first episode of demyelinating optic neuritis. to worse outcomes. Securing the airway and obtaining intra- Central retinal artery occlusion (Option A) is not a venous access are the first steps in CSE management. If point- likely diagnosis in this case. Although central retinal artery of-care glucose testing is not available, thiamine should be occlusions are typically unilateral in nature, they are pain given, followed by intravenous glucose. This patient has failed less, acute in onset (as opposed to this patient’s subacute 123

Answers and Critiques onset), and often responsible for altitudinal defects, which worsening of memory, language, and visuospatial abilities. are those in the upper or lower portion of vision in the eye Alzheimer disease is associated with hippocampal atrophy CONT. rather than diffuse or central. on MRI. The patient lacks both memory loss and structural Giant cell arteritis (GCA) (Option B) is an unlikely cause changes on MRI, making this diagnosis unlikely. of this patient’s visual deficit given his young age (peak The most prominent feature of behavioral-variant fron- incidence of GCA is between 70 and 80 years of age), normal tal temporal dementia (FTD) (Option B) is an alteration in erythrocyte sedimentation rate, and absence of headache or personality and behavior that typically develops years before jaw claudication. Patients with GCA involving the ophthal- the onset of cognitive impairment. Many patients with mic artery note an abrupt partial field defect or temporary behavioral-variant FTD have frontotemporal lobe atrophy curtain effect (a moving dark shadow) in the field of vision visible on imaging, which is not apparent in this patient’s of one eye. MRI. Orbital cellulitis (infection of the fat and muscle cells Two major signs of vascular cognitive impairment

onset), and often responsible for altitudinal defects, which worsening of memory, language, and visuospatial abilities. are those in the upper or lower portion of vision in the eye Alzheimer disease is associated with hippocampal atrophy CONT. rather than diffuse or central. on MRI. The patient lacks both memory loss and structural Giant cell arteritis (GCA) (Option B) is an unlikely cause changes on MRI, making this diagnosis unlikely. of this patient’s visual deficit given his young age (peak The most prominent feature of behavioral-variant fron- incidence of GCA is between 70 and 80 years of age), normal tal temporal dementia (FTD) (Option B) is an alteration in erythrocyte sedimentation rate, and absence of headache or personality and behavior that typically develops years before jaw claudication. Patients with GCA involving the ophthal- the onset of cognitive impairment. Many patients with mic artery note an abrupt partial field defect or temporary behavioral-variant FTD have frontotemporal lobe atrophy curtain effect (a moving dark shadow) in the field of vision visible on imaging, which is not apparent in this patient’s of one eye. MRI. Orbital cellulitis (infection of the fat and muscle cells Two major signs of vascular cognitive impairment Pd of the orbit) (Option D) is a vision-threatening eye infection (Option D) are early gait impairment and personality or P=| wn requiring immediate intravenous antibiotics and ophthal- mood changes. Brain imaging is a critical component sup- = mology evaluation. Characteristic findings include ocular porting the diagnosis of vascular cognitive impairment. MRI @o typically displays a pattern of diffuse and confluent changes = wn pain and eyelid swelling with erythema as well as pain with <3) = eye movements, proptosis, and less frequently, ophthalmo- in the white matter of the brain, cerebral microhemor- Qa plegia with diplopia. Orbital cellulitis is an unlikely cause rhages, and cortical infarcts. Although the cognitive profiles oO =. given the absence of fever, swelling, erythema, proptosis, of TES and vascular cognitive impairment overlap, and this =. pain on palpation of the orbit, or elevated leukocyte count. patient’s slow gait and mood changes could be consistent 2 ij with this diagnosis, the brain MRI shows no evidence of @o 172) cerebrovascular disease. ¢ Classic findings of optic neuritis include pain with eye movement, unilateral visual deficit, and an afferent pupillary defect. e Traumatic encephalopathy syndrome is a progressive neurodegenerative syndrome associated with repetitive e The cumulative 5-year incidence of clinically definite head trauma. multiple sclerosis is 30% following a first episode of demyelinating optic neuritis. ¢ Clinical features supporting the diagnosis of traumatic encephalopathy syndrome include emotional dysreg- Bibliography ulation, behavior change, and motor disturbance with Bennett JL. Optic neuritis. Continuum (Minneap Minn). 2019;25(5):1236- parkinsonian features. 64. [PMID: 31584536] doi:10.1212/CON.0000000000000768

Pd of the orbit) (Option D) is a vision-threatening eye infection (Option D) are early gait impairment and personality or P=| wn requiring immediate intravenous antibiotics and ophthal- mood changes. Brain imaging is a critical component sup- = mology evaluation. Characteristic findings include ocular porting the diagnosis of vascular cognitive impairment. MRI @o typically displays a pattern of diffuse and confluent changes = wn pain and eyelid swelling with erythema as well as pain with <3) = eye movements, proptosis, and less frequently, ophthalmo- in the white matter of the brain, cerebral microhemor- Qa plegia with diplopia. Orbital cellulitis is an unlikely cause rhages, and cortical infarcts. Although the cognitive profiles oO =. given the absence of fever, swelling, erythema, proptosis, of TES and vascular cognitive impairment overlap, and this =. pain on palpation of the orbit, or elevated leukocyte count. patient’s slow gait and mood changes could be consistent 2 ij with this diagnosis, the brain MRI shows no evidence of @o 172) cerebrovascular disease. ¢ Classic findings of optic neuritis include pain with eye movement, unilateral visual deficit, and an afferent pupillary defect. e Traumatic encephalopathy syndrome is a progressive neurodegenerative syndrome associated with repetitive e The cumulative 5-year incidence of clinically definite head trauma. multiple sclerosis is 30% following a first episode of demyelinating optic neuritis. ¢ Clinical features supporting the diagnosis of traumatic encephalopathy syndrome include emotional dysreg- Bibliography ulation, behavior change, and motor disturbance with Bennett JL. Optic neuritis. Continuum (Minneap Minn). 2019;25(5):1236- parkinsonian features. 64. [PMID: 31584536] doi:10.1212/CON.0000000000000768 Bibliography Item 16 Answer: C Bailes JE, Origenes AK, Alleva JT. Chronic traumatic encephalopathy. Dis Mon. 2019;65(10):100855. [PMID: 30878141] doi:10.1016/j.disamonth. Educational Objective: Diagnose traumatic 2019.02.008

Bibliography Item 16 Answer: C Bailes JE, Origenes AK, Alleva JT. Chronic traumatic encephalopathy. Dis Mon. 2019;65(10):100855. [PMID: 30878141] doi:10.1016/j.disamonth. Educational Objective: Diagnose traumatic 2019.02.008 encephalopathy syndrome.

Bibliography Item 16 Answer: C Bailes JE, Origenes AK, Alleva JT. Chronic traumatic encephalopathy. Dis Mon. 2019;65(10):100855. [PMID: 30878141] doi:10.1016/j.disamonth. Educational Objective: Diagnose traumatic 2019.02.008 encephalopathy syndrome. The patient meets the proposed criteria for traumatic Item 17 Answer: 8B encephalopathy syndrome (TES) (Option C). TES is the pro- Educational Objective: Diagnose corticobasal gressive neurodegenerative syndrome associated with repet- degeneration. itive head trauma. This clinical syndrome is associated with the pathological diagnosis referred to as chronic traumatic The most likely diagnosis is corticobasal degeneration encephalopathy. Proposed clinical diagnostic criteria for TES (Option B), one of the Parkinson-plus syndromes. Cortico- include symptoms for longer than 2 years, no other neuro- basal degeneration is characterized by severely asymmetric logic disorder more likely to account for all of the clinical parkinsonism, fixed dystonia, myoclonus, cortical sensory features, history of repetitive head trauma exposure, pro- deficits, apraxia, and cognitive deficits. Parkinson-plus syn- gressive course, delayed symptom onset, and cognitive dys- dromes share some features of Parkinson disease but are function confirmed by objective decline on formal neuro- distinguished by faster progression than in Parkinson dis- psychological testing. Supportive features include emotional ease, additional features that are atypical for Parkinson dis- dysregulation, behavior change, and motor disturbance with ease, and lack of typical response to levodopa. This patient’s parkinsonian features. Diagnosis is supported by abnor- symptoms and physical examination findings are consistent mal neuroimaging findings on PET, single-photon emission with corticobasal degeneration. Both symmetry and extreme tomography, structural MRI, or diffusion-tensor imaging. asymmetry of clinical deficits are among the red flags for A common but nonspecific finding includes generalized atypical Parkinson-plus syndromes. cerebral atrophy. Amyotrophic lateral sclerosis (ALS) (Option A) can pres- Alzheimer disease (Option A) is a memory-predominant ent with weakness, atrophy, spasticity, and hyperreflexia. dementia. Its typical presentation includes an insidious Because it also causes asymmetry and rapid progression,

The patient meets the proposed criteria for traumatic Item 17 Answer: 8B encephalopathy syndrome (TES) (Option C). TES is the pro- Educational Objective: Diagnose corticobasal gressive neurodegenerative syndrome associated with repet- degeneration. itive head trauma. This clinical syndrome is associated with the pathological diagnosis referred to as chronic traumatic The most likely diagnosis is corticobasal degeneration encephalopathy. Proposed clinical diagnostic criteria for TES (Option B), one of the Parkinson-plus syndromes. Cortico- include symptoms for longer than 2 years, no other neuro- basal degeneration is characterized by severely asymmetric logic disorder more likely to account for all of the clinical parkinsonism, fixed dystonia, myoclonus, cortical sensory features, history of repetitive head trauma exposure, pro- deficits, apraxia, and cognitive deficits. Parkinson-plus syn- gressive course, delayed symptom onset, and cognitive dys- dromes share some features of Parkinson disease but are function confirmed by objective decline on formal neuro- distinguished by faster progression than in Parkinson dis- psychological testing. Supportive features include emotional ease, additional features that are atypical for Parkinson dis- dysregulation, behavior change, and motor disturbance with ease, and lack of typical response to levodopa. This patient’s parkinsonian features. Diagnosis is supported by abnor- symptoms and physical examination findings are consistent mal neuroimaging findings on PET, single-photon emission with corticobasal degeneration. Both symmetry and extreme tomography, structural MRI, or diffusion-tensor imaging. asymmetry of clinical deficits are among the red flags for A common but nonspecific finding includes generalized atypical Parkinson-plus syndromes. cerebral atrophy. Amyotrophic lateral sclerosis (ALS) (Option A) can pres- Alzheimer disease (Option A) is a memory-predominant ent with weakness, atrophy, spasticity, and hyperreflexia. dementia. Its typical presentation includes an insidious Because it also causes asymmetry and rapid progression, 124

__Answers and Critiques ALS is sometimes considered in the differential diagnosis gene sequencing. The recently approved drugs inotersen and of corticobasal degeneration. However, ALS is characterized patisiran have slowed the progression of hereditary amyloid by muscle weakness and other upper motor neuron signs neuropathy and improved quality of life. (hyperreflexia, spasticity, and extensor plantar response) Anti-muscle-specific kinase antibody (Option B) is spe- that are absent in this patient. cific for a variant of myasthenia gravis. This condition is not Multiple system atrophy (Option C) is another Par- associated with neuropathy or autonomic dysfunction. kinson-plus syndrome that presents with symmetric par- Myotonic dystrophy (Option C) can cause multisystem kinsonism, severe dysautonomia (orthostatic hypotension organ involvement, but its neuromuscular presentation is in and urinary incontinence), cerebellar ataxia, and early falls. the form of myopathy. It does not cause significant neuropathy. These features are not present in this patient. Serum GQ1b antibody (Option D) is specific for the This patient’s rapid clinical course, severely asymmetric Miller-Fisher variant of Guillain-Barré syndrome, a sub- parkinsonism, fixed dystonia, myoclonus, and early cogni- acute demyelinating neuropathy characterized by ophthal- tive deficits are all inconsistent with idiopathic Parkinson moplegia, ataxia, and areflexia. The patient’s findings are not wn o disease (Option D). consistent with the Miller-Fisher variant of Guillain-Barré |

ALS is sometimes considered in the differential diagnosis gene sequencing. The recently approved drugs inotersen and of corticobasal degeneration. However, ALS is characterized patisiran have slowed the progression of hereditary amyloid by muscle weakness and other upper motor neuron signs neuropathy and improved quality of life. (hyperreflexia, spasticity, and extensor plantar response) Anti-muscle-specific kinase antibody (Option B) is spe- that are absent in this patient. cific for a variant of myasthenia gravis. This condition is not Multiple system atrophy (Option C) is another Par- associated with neuropathy or autonomic dysfunction. kinson-plus syndrome that presents with symmetric par- Myotonic dystrophy (Option C) can cause multisystem kinsonism, severe dysautonomia (orthostatic hypotension organ involvement, but its neuromuscular presentation is in and urinary incontinence), cerebellar ataxia, and early falls. the form of myopathy. It does not cause significant neuropathy. These features are not present in this patient. Serum GQ1b antibody (Option D) is specific for the This patient’s rapid clinical course, severely asymmetric Miller-Fisher variant of Guillain-Barré syndrome, a sub- parkinsonism, fixed dystonia, myoclonus, and early cogni- acute demyelinating neuropathy characterized by ophthal- tive deficits are all inconsistent with idiopathic Parkinson moplegia, ataxia, and areflexia. The patient’s findings are not wn o disease (Option D). consistent with the Miller-Fisher variant of Guillain-Barré | Progressive supranuclear palsy (Option E) is a Parkinson- syndrome. = ‘= plus syndrome characterized by symmetric parkinsonism, pos- oO tural instability with early falls, and vertical oculomotor deficit. sc e Amyloid neuropathy manifests as progressive painful = This patient’s normal eye movements and severe asymmetry cs

Progressive supranuclear palsy (Option E) is a Parkinson- syndrome. = ‘= plus syndrome characterized by symmetric parkinsonism, pos- oO tural instability with early falls, and vertical oculomotor deficit. sc e Amyloid neuropathy manifests as progressive painful = This patient’s normal eye movements and severe asymmetry cs are inconsistent with progressive supranuclear palsy. axonal polyneuropathy with predominant involvement wn aww o of small fibers (pain and temperature) and multiorgan = dysautonomia. wn 4 e Corticobasal degeneration is a Parkinson-plus syndrome <= e Amyloidosis is diagnosed by tissue biopsy, and familial characterized by severely asymmetric parkinsonism, amyloidosis is confirmed with the addition of transthyre- fixed dystonia, myoclonus, cortical sensory deficits, tin gene sequencing. apraxia, and cognitive deficits.

are inconsistent with progressive supranuclear palsy. axonal polyneuropathy with predominant involvement wn aww o of small fibers (pain and temperature) and multiorgan = dysautonomia. wn 4 e Corticobasal degeneration is a Parkinson-plus syndrome <= e Amyloidosis is diagnosed by tissue biopsy, and familial characterized by severely asymmetric parkinsonism, amyloidosis is confirmed with the addition of transthyre- fixed dystonia, myoclonus, cortical sensory deficits, tin gene sequencing. apraxia, and cognitive deficits. e Parkinson-plus syndromes share some features of Bibliography Parkinson disease but are distinguished by faster pro- Adams D, Cauquil C, Labeyrie C. Familial amyloid polyneuropathy. Curr gression, additional atypical features, and lack of Opin Neurol. 2017;30:481-489. [PMID: 28678039] doi:10.1097/WCO. 0000000000000476 response to levodopa.

e Parkinson-plus syndromes share some features of Bibliography Parkinson disease but are distinguished by faster pro- Adams D, Cauquil C, Labeyrie C. Familial amyloid polyneuropathy. Curr gression, additional atypical features, and lack of Opin Neurol. 2017;30:481-489. [PMID: 28678039] doi:10.1097/WCO. 0000000000000476 response to levodopa. Bibliography Item 19 Answer: A McFarland NR. Diagnostic approach to atypical parkinsonian syndromes. Educational Objective: Evaluate a first (new-onset) Continuum (Minneap Minn). 2016;22:1117-42. [PMID: 27495201] doi:10.1212/ CON.0000000000000348 seizure. The most appropriate management for this patient is a brain

Bibliography Item 19 Answer: A McFarland NR. Diagnostic approach to atypical parkinsonian syndromes. Educational Objective: Evaluate a first (new-onset) Continuum (Minneap Minn). 2016;22:1117-42. [PMID: 27495201] doi:10.1212/ CON.0000000000000348 seizure. The most appropriate management for this patient is a brain Item 18 Answer: A MRI without contrast (Option A). For any patient with a first seizure, obtaining a detailed history is crucial to distinguish Educational Objective: Diagnose amyloid neuropathy. seizures from other causes of symptoms. Making the distinc- The most appropriate diagnostic test to perform next is tion between seizure and nonseizure events and first-time abdominal fat pad biopsy (Option A). Progressive painful versus recurrent episodes is key in selecting the proper man axonal polyneuropathy with predominant involvement of agement. The patient likely had a first (new-onset) seizure, small fibers (pain and temperature) and multiorgan dysau- and neuroimaging is indicated for all adult patients with tonomia is concerning for amyloidosis. Primary amyloidosis a first-time seizure. CT of the head is adequate initially to is associated with monoclonal proteins, whereas familial rapidly exclude emergent pathology, including hemorrhage, amyloidosis is secondary to transthyretin gene mutation. but MRI is required and preferred in most patients. Because When low ECG voltage accompanies increased myocardial temporal lobe epilepsy is common, MRI sequences focusing wall thickness on echocardiogram, amyloidosis should be on the hippocampus and temporal lobes are useful. Outpa- considered. Bilateral involvement of carpal tunnel syndrome tient electroencephalography (EEG) also is recommended in and, particularly, recurrence of related symptoms after patients with a first seizure (and has already been scheduled decompression surgery is suggestive of amyloid neurop- in this case). A single routine EEG is only 40% to 50% sen- athy. Other common symptoms include sluggish pupils, sitive in the diagnosis of seizure, but the yield can increase hypohidrosis, orthostatic hypotension, gastrointestinal dys- to 80% to 90% with repeated studies, prolonged studies, and motility, and urinary and erectile dysfunction. Although studies that capture sleep. hereditary amyloidosis is more common in African Ameri- Followinga first seizure, contrast-enhanced CT (Option cans, it should be considered in all patients and regardless of B) or MRI may be deferred unless infection, tumor, or vascu- family history. Amyloidosis is diagnosed by tissue biopsy and lar lesions are suspected. These imaging procedures are not familial amyloidosis by additional testing with transthyretin indicated in this patient.

Item 18 Answer: A MRI without contrast (Option A). For any patient with a first seizure, obtaining a detailed history is crucial to distinguish Educational Objective: Diagnose amyloid neuropathy. seizures from other causes of symptoms. Making the distinc- The most appropriate diagnostic test to perform next is tion between seizure and nonseizure events and first-time abdominal fat pad biopsy (Option A). Progressive painful versus recurrent episodes is key in selecting the proper man axonal polyneuropathy with predominant involvement of agement. The patient likely had a first (new-onset) seizure, small fibers (pain and temperature) and multiorgan dysau- and neuroimaging is indicated for all adult patients with tonomia is concerning for amyloidosis. Primary amyloidosis a first-time seizure. CT of the head is adequate initially to is associated with monoclonal proteins, whereas familial rapidly exclude emergent pathology, including hemorrhage, amyloidosis is secondary to transthyretin gene mutation. but MRI is required and preferred in most patients. Because When low ECG voltage accompanies increased myocardial temporal lobe epilepsy is common, MRI sequences focusing wall thickness on echocardiogram, amyloidosis should be on the hippocampus and temporal lobes are useful. Outpa- considered. Bilateral involvement of carpal tunnel syndrome tient electroencephalography (EEG) also is recommended in and, particularly, recurrence of related symptoms after patients with a first seizure (and has already been scheduled decompression surgery is suggestive of amyloid neurop- in this case). A single routine EEG is only 40% to 50% sen- athy. Other common symptoms include sluggish pupils, sitive in the diagnosis of seizure, but the yield can increase hypohidrosis, orthostatic hypotension, gastrointestinal dys- to 80% to 90% with repeated studies, prolonged studies, and motility, and urinary and erectile dysfunction. Although studies that capture sleep. hereditary amyloidosis is more common in African Ameri- Followinga first seizure, contrast-enhanced CT (Option cans, it should be considered in all patients and regardless of B) or MRI may be deferred unless infection, tumor, or vascu- family history. Amyloidosis is diagnosed by tissue biopsy and lar lesions are suspected. These imaging procedures are not familial amyloidosis by additional testing with transthyretin indicated in this patient. 125

Answers and Critiques — Levetiracetam (Option C) would be indicated for this Inclusion body myositis (Option C) is a late-onset (after patient if epilepsy was suspected (i.e., if the seizure recur- age 50 years) sporadic inflammatory myopathy diagnosed CONT. rence risk was determined to be at least 60%). Determining more often in men than in women. Symptoms involve asym- seizure recurrence risk for this patient would first require metric weakness predominantly in quadriceps and bulbar brain MRI and EEG to detect the presence of any significant muscles and distal upper extremities. Involvement of extra- abnormality that would support a diagnosis of epilepsy. ocular muscles and multiorgan involvement is not expected. Unlike in children, a seizure in adults is not enough of McArdle disease (Option D), an autosomal recessive an indication for lumbar puncture (Option D). Other signs disorder causing myophosphorylase deficiency, is a meta- of meningitis, such as neck stiffness, fever, altered mental bolic myopathy associated with isolated exercise-induced status, or headache, are indications for lumbar puncture; weakness, cramps, and myoglobinuria. Ophthalmople- this patient does not have these signs. gia and multiorgan involvement are not expected in this condition. > = e Neuroimaging with brain MRI and electroencephalog- w = raphy are recommended for all adults with a first e Mitochondrial myopathy is associated with fluctuating © = wr (new-onset) seizure. weakness, ophthalmoplegia, multiorgan symptoms, see) and family history in female relatives. ~~ 2. Bibliography (=) = Krumholz A, Wiebe S, Gronseth GS, et al. Evidence-based guideline: Bibliography =A Management of an unprovoked first seizure in adults: Report of the Gorman GS, Chinnery PF, DiMauro §, et al. Mitochondrial diseases. Nat Rev ao] Guideline Development Subcommittee of the American Academy of Dis Primers. 2016;2:16080. [PMID: 27775730] doi:10.1038/nrdp.2016.80 i= Neurology and the American Epilepsy Society. Neurology. 2015;84:1705- @o wn 13. [PMID: 25901057] doi: 10.1212/ WNL.0000000000001487

Levetiracetam (Option C) would be indicated for this Inclusion body myositis (Option C) is a late-onset (after patient if epilepsy was suspected (i.e., if the seizure recur- age 50 years) sporadic inflammatory myopathy diagnosed CONT. rence risk was determined to be at least 60%). Determining more often in men than in women. Symptoms involve asym- seizure recurrence risk for this patient would first require metric weakness predominantly in quadriceps and bulbar brain MRI and EEG to detect the presence of any significant muscles and distal upper extremities. Involvement of extra- abnormality that would support a diagnosis of epilepsy. ocular muscles and multiorgan involvement is not expected. Unlike in children, a seizure in adults is not enough of McArdle disease (Option D), an autosomal recessive an indication for lumbar puncture (Option D). Other signs disorder causing myophosphorylase deficiency, is a meta- of meningitis, such as neck stiffness, fever, altered mental bolic myopathy associated with isolated exercise-induced status, or headache, are indications for lumbar puncture; weakness, cramps, and myoglobinuria. Ophthalmople- this patient does not have these signs. gia and multiorgan involvement are not expected in this condition. > = e Neuroimaging with brain MRI and electroencephalog- w = raphy are recommended for all adults with a first e Mitochondrial myopathy is associated with fluctuating © = wr (new-onset) seizure. weakness, ophthalmoplegia, multiorgan symptoms, see) and family history in female relatives. ~~ 2. Bibliography (=) = Krumholz A, Wiebe S, Gronseth GS, et al. Evidence-based guideline: Bibliography =A Management of an unprovoked first seizure in adults: Report of the Gorman GS, Chinnery PF, DiMauro §, et al. Mitochondrial diseases. Nat Rev ao] Guideline Development Subcommittee of the American Academy of Dis Primers. 2016;2:16080. [PMID: 27775730] doi:10.1038/nrdp.2016.80 i= Neurology and the American Epilepsy Society. Neurology. 2015;84:1705- @o wn 13. [PMID: 25901057] doi: 10.1212/ WNL.0000000000001487 Item 21 Answer: B Item 20 Answer: E Educational Objective: Diagnose focal dystonia of the Educational Objective: Diagnose mitochondrial vocal cords. myopathy. The most likely diagnosis is dystonia (Option B). This patient The most likely diagnosis is mitochondrial myopathy (Option has focal dystonia of the vocal cords, also known as laryn- E). Mitochondrial diseases are a group of genetic disorders geal dystonia or vocal cord spasmodic dysphonia. Dystonia caused by dysfunction of the mitochondria and may present is characterized by sustained or intermittent muscle con- as myopathies, neuropathies, and multisystemic diseases tractions that are slow, repetitive, and directional. It can be with maternal inheritance. Maternal inheritance is a unique generalized or focal and can involve isolated body parts, such and distinctive feature of mitochondrial DNA. Mitochondrial as the vocal cords, face, or neck. In this patient, persistent disorders can present with a wide range of fluctuating symp- worsening of movements with certain sounds, resolution toms, including weakness, autonomic dysfunction, gastroin- of spasms with different tasks (such as singing), and direct testinal motility disorders, chronic pain, vision and hearing observation of slow and sustained pulling of vocal cords disorders, and cardiovascular disease. In this patient, fluc- support a diagnosis of dystonia. tuating weakness, ophthalmoplegia, multiorgan symptoms, Chorea (Option A) is characterized by random flowing and family history in female relatives should prompt consid- movements. Sustained and patterned movements on direct eration of mitochondrial myopathy. observation and isolated involvement of vocal cords do not Acid maltase deficiency (Pompe disease) (Option A), an support a diagnosis of chorea. autosomal recessive disorder, can present in adulthood. This Functional disorders (Option C) can present with condition may be associated with progressive rather than variability, distractibility, and inconsistency with organic fluctuating weakness in proximal and respiratory muscles. It disorders. This patient’s symptoms are not variable or incon- is diagnosed by assessing acid maltase activity in leukocytes sistent, and observation of involuntary movements of vocal and genetic testing for the acid o-glucosidase gene. cords in a pattern typical for dystonia rules out functional Becker muscular dystrophy (Option B) is an X-linked disorder. Dystonia is sometimes misdiagnosed as a func- recessive disorder characterized by dystrophinopathy asso- tional disorder because of clinical features, such as task ciated with progressive weakness and cardiomyopathy. dependency or sensory tricks (difficulty speaking but ability The clinical course is milder than that of related Duchenne to sing and movement or touch that interrupts dystonia, also muscular dystrophy, and these patients are sometimes seen known as geste antagoniste). in an adult clinic. Because of X-linked transmission, this Myoclonus (Option D) is characterized by fast jerky condition is not expected in a female patient even though movements that can involve various body parts. Slow move- female carriers of dystrophin gene may develop hyperCKe- ments and isolated involvement of vocal cords are inconsis- mia or nocturnal cramps. In addition, a fluctuating course, tent with myoclonus. ophthalmoplegia, and multiorgan involvement (except for Vocal tics (Option E) usually present as sudden utterances the heart) are not expected in this disorder. or words, including repetition of others’ words (echolalia) or

Item 21 Answer: B Item 20 Answer: E Educational Objective: Diagnose focal dystonia of the Educational Objective: Diagnose mitochondrial vocal cords. myopathy. The most likely diagnosis is dystonia (Option B). This patient The most likely diagnosis is mitochondrial myopathy (Option has focal dystonia of the vocal cords, also known as laryn- E). Mitochondrial diseases are a group of genetic disorders geal dystonia or vocal cord spasmodic dysphonia. Dystonia caused by dysfunction of the mitochondria and may present is characterized by sustained or intermittent muscle con- as myopathies, neuropathies, and multisystemic diseases tractions that are slow, repetitive, and directional. It can be with maternal inheritance. Maternal inheritance is a unique generalized or focal and can involve isolated body parts, such and distinctive feature of mitochondrial DNA. Mitochondrial as the vocal cords, face, or neck. In this patient, persistent disorders can present with a wide range of fluctuating symp- worsening of movements with certain sounds, resolution toms, including weakness, autonomic dysfunction, gastroin- of spasms with different tasks (such as singing), and direct testinal motility disorders, chronic pain, vision and hearing observation of slow and sustained pulling of vocal cords disorders, and cardiovascular disease. In this patient, fluc- support a diagnosis of dystonia. tuating weakness, ophthalmoplegia, multiorgan symptoms, Chorea (Option A) is characterized by random flowing and family history in female relatives should prompt consid- movements. Sustained and patterned movements on direct eration of mitochondrial myopathy. observation and isolated involvement of vocal cords do not Acid maltase deficiency (Pompe disease) (Option A), an support a diagnosis of chorea. autosomal recessive disorder, can present in adulthood. This Functional disorders (Option C) can present with condition may be associated with progressive rather than variability, distractibility, and inconsistency with organic fluctuating weakness in proximal and respiratory muscles. It disorders. This patient’s symptoms are not variable or incon- is diagnosed by assessing acid maltase activity in leukocytes sistent, and observation of involuntary movements of vocal and genetic testing for the acid o-glucosidase gene. cords in a pattern typical for dystonia rules out functional Becker muscular dystrophy (Option B) is an X-linked disorder. Dystonia is sometimes misdiagnosed as a func- recessive disorder characterized by dystrophinopathy asso- tional disorder because of clinical features, such as task ciated with progressive weakness and cardiomyopathy. dependency or sensory tricks (difficulty speaking but ability The clinical course is milder than that of related Duchenne to sing and movement or touch that interrupts dystonia, also muscular dystrophy, and these patients are sometimes seen known as geste antagoniste). in an adult clinic. Because of X-linked transmission, this Myoclonus (Option D) is characterized by fast jerky condition is not expected in a female patient even though movements that can involve various body parts. Slow move- female carriers of dystrophin gene may develop hyperCKe- ments and isolated involvement of vocal cords are inconsis- mia or nocturnal cramps. In addition, a fluctuating course, tent with myoclonus. ophthalmoplegia, and multiorgan involvement (except for Vocal tics (Option E) usually present as sudden utterances the heart) are not expected in this disorder. or words, including repetition of others’ words (echolalia) or 126

Answers and Critiques obscenities (coprolalia), that disrupt otherwise normal speech. removal or lumbar drainage, a permanent ventricular shunt Tics often start in childhood, are associated with premoni- should not be pursued. tory urges, and are transiently suppressible. In this patient, the absence of these features and sustained pulling on direct observation make tics an unlikely diagnosis. e The characteristic findings of normal pressure hydro- cephalus are gait changes, urinary incontinence, and cognitive impairment. e Dystonia is characterized by sustained or intermittent e In patients with normal pressure hydrocephalus, the muscle contractions that are slow, repetitive, and most predictive test for improvement with ventricular directional. shunting is gait assessment before and after high vol- e Dystonia can be generalized or focal and can involve ume cerebrospinal fluid removal. isolated body parts, such as the vocal cords, face, or wn neck. Bibliography 5st) = Yamada S, Ishikawa M, Miyajima M, et al. Timed up and go test at tap test and shunt surgery in idiopathic normal pressure hydrocephalus. = Bibliography Neurol Clin Pract. 2017;7:98-108. [PMID: 29185546] doi:10.1212/CPIJ. i Albanese A, Di Giovanni M, Lalli S. Dystonia: diagnosis and management. 0000000000000334 w Eur J Neurol. 2019;26:5-17. [PMID: 30035844] doi:10.1111/ene.13762 sc & Co wn

obscenities (coprolalia), that disrupt otherwise normal speech. removal or lumbar drainage, a permanent ventricular shunt Tics often start in childhood, are associated with premoni- should not be pursued. tory urges, and are transiently suppressible. In this patient, the absence of these features and sustained pulling on direct observation make tics an unlikely diagnosis. e The characteristic findings of normal pressure hydro- cephalus are gait changes, urinary incontinence, and cognitive impairment. e Dystonia is characterized by sustained or intermittent e In patients with normal pressure hydrocephalus, the muscle contractions that are slow, repetitive, and most predictive test for improvement with ventricular directional. shunting is gait assessment before and after high vol- e Dystonia can be generalized or focal and can involve ume cerebrospinal fluid removal. isolated body parts, such as the vocal cords, face, or wn neck. Bibliography 5st) = Yamada S, Ishikawa M, Miyajima M, et al. Timed up and go test at tap test and shunt surgery in idiopathic normal pressure hydrocephalus. = Bibliography Neurol Clin Pract. 2017;7:98-108. [PMID: 29185546] doi:10.1212/CPIJ. i Albanese A, Di Giovanni M, Lalli S. Dystonia: diagnosis and management. 0000000000000334 w Eur J Neurol. 2019;26:5-17. [PMID: 30035844] doi:10.1111/ene.13762 sc & Co wn Item 23 Answer: B in if)

Item 23 Answer: B in if) Item 22 Answer: A = Educational Objective: Assess “return to play” in c Educational Objective: Diagnose normal pressure following mild traumatic brain injury in athletes. L—4 hydrocephalus. The patient has fully recovered from her mild traumatic The most appropriate next step is removal of a large volume brain injury (TBI) and may be advised to return to play of cerebrospinal fluid (CSF) (Option A) coupled with gait (Option B). The terms mild TBI and concussion are often assessment. The patient has signs and symptoms of normal used interchangeably. Concussion has been defined as a pressure hydrocephalus (NPH) (gait changes, urinary incon- clinical syndrome of biomechanically induced alteration of tinence, and cognitive impairment). Gait impairment, the brain function. Altered brain function is most commonly most prominent feature, is characterized by shuffling short described by affected subjects as being confused or dazed, step length and often problems with starting ambulation with 10% reporting transient loss of consciousness. Next (hesitation). The feet can appear as though they are stuck to to accidents, sporting activities represent the second most the ground, which is described as a “magnetic” gait. In addi- common source of TBI in young adults. In men, football and tion, this patient’s MRI of the brain shows communicating hockey result in most cases of mild TBI, whereas in women, (nonobstructive) hydrocephalus. NPH is treated by a ventric- the most common cause is soccer. When TBI is suspected, uloperitoneal shunt placed by a neurosurgeon. Before treat- athletes must be immediately removed from play and sub- ment is attempted, a test that predicts response to shunting jected to standardized sideline assessment tools. Guidelines is necessary. This test assesses the patient’s gait after removal recommend continued avoidance of contact sports until of 30 to 50 mL of CSF. The patient’s walking is timed imme 10 days after the trauma or until the patient has been asymp- diately before and after lumbar puncture. An objective mea- tomatic while taking no medication for a period of 7 days. sure of gait improvement is the Timed Up and Go test (TUG), This patient meets both time-based criteria, is asymptomatic which measures the amount of time necessary to rise from with normal findings on neurologic examination, and may a chair, walk 3 meters, turn, return to the chair, and sit. An be cleared to return to play. improvement in time by more than 5 seconds is predictive of Although brain MRI (Option A) is more diagnostically a positive response to CSF shunting. accurate than head CT in the setting of subacute or chronic Placement of a lumboperitoneal shunt (Option B) is headache, a patient without symptoms or abnormal exam- another surgical option for treatment but should not precede ination findings after a mild TBI does not require imaging testing for response to shunting. before return to play. Gait disturbance is the clinical symptom most amenable There are many published indications for head CT to ventricular shunting. The longer cognitive impairment (Option C) in the setting of acute head injury, such as has been present and the more pronounced the memory age greater than 60 years, progressive headache, seizure, problem, the less certain is the response to shunting. repeated vomiting after the trauma, persistent drowsiness If response to high-volume CSF removal is uncertain, or amnesia, focal deficits, and certain dangerous mecha- assessment for gait improvement after placement ofa lum- nisms of injury. This patient, however, sustained the TBI bar drain (Option C) by a neurosurgeon can be pursued. 10 days ago and had none of these indications, so head CT is CSF diversion through a ventriculoperitoneal shunt unnecessary.

Item 22 Answer: A = Educational Objective: Assess “return to play” in c Educational Objective: Diagnose normal pressure following mild traumatic brain injury in athletes. L—4 hydrocephalus. The patient has fully recovered from her mild traumatic The most appropriate next step is removal of a large volume brain injury (TBI) and may be advised to return to play of cerebrospinal fluid (CSF) (Option A) coupled with gait (Option B). The terms mild TBI and concussion are often assessment. The patient has signs and symptoms of normal used interchangeably. Concussion has been defined as a pressure hydrocephalus (NPH) (gait changes, urinary incon- clinical syndrome of biomechanically induced alteration of tinence, and cognitive impairment). Gait impairment, the brain function. Altered brain function is most commonly most prominent feature, is characterized by shuffling short described by affected subjects as being confused or dazed, step length and often problems with starting ambulation with 10% reporting transient loss of consciousness. Next (hesitation). The feet can appear as though they are stuck to to accidents, sporting activities represent the second most the ground, which is described as a “magnetic” gait. In addi- common source of TBI in young adults. In men, football and tion, this patient’s MRI of the brain shows communicating hockey result in most cases of mild TBI, whereas in women, (nonobstructive) hydrocephalus. NPH is treated by a ventric- the most common cause is soccer. When TBI is suspected, uloperitoneal shunt placed by a neurosurgeon. Before treat- athletes must be immediately removed from play and sub- ment is attempted, a test that predicts response to shunting jected to standardized sideline assessment tools. Guidelines is necessary. This test assesses the patient’s gait after removal recommend continued avoidance of contact sports until of 30 to 50 mL of CSF. The patient’s walking is timed imme 10 days after the trauma or until the patient has been asymp- diately before and after lumbar puncture. An objective mea- tomatic while taking no medication for a period of 7 days. sure of gait improvement is the Timed Up and Go test (TUG), This patient meets both time-based criteria, is asymptomatic which measures the amount of time necessary to rise from with normal findings on neurologic examination, and may a chair, walk 3 meters, turn, return to the chair, and sit. An be cleared to return to play. improvement in time by more than 5 seconds is predictive of Although brain MRI (Option A) is more diagnostically a positive response to CSF shunting. accurate than head CT in the setting of subacute or chronic Placement of a lumboperitoneal shunt (Option B) is headache, a patient without symptoms or abnormal exam- another surgical option for treatment but should not precede ination findings after a mild TBI does not require imaging testing for response to shunting. before return to play. Gait disturbance is the clinical symptom most amenable There are many published indications for head CT to ventricular shunting. The longer cognitive impairment (Option C) in the setting of acute head injury, such as has been present and the more pronounced the memory age greater than 60 years, progressive headache, seizure, problem, the less certain is the response to shunting. repeated vomiting after the trauma, persistent drowsiness If response to high-volume CSF removal is uncertain, or amnesia, focal deficits, and certain dangerous mecha- assessment for gait improvement after placement ofa lum- nisms of injury. This patient, however, sustained the TBI bar drain (Option C) by a neurosurgeon can be pursued. 10 days ago and had none of these indications, so head CT is CSF diversion through a ventriculoperitoneal shunt unnecessary. (Option D) is the definitive treatment of NPH. However, in Neuropsychological testing (Option D) is valuable in the the absence of a clear response to either high-volume CSF assessment of patients remaining symptomatic after a mild

Item 22 Answer: A = Educational Objective: Assess “return to play” in c Educational Objective: Diagnose normal pressure following mild traumatic brain injury in athletes. L—4 hydrocephalus. The patient has fully recovered from her mild traumatic The most appropriate next step is removal of a large volume brain injury (TBI) and may be advised to return to play of cerebrospinal fluid (CSF) (Option A) coupled with gait (Option B). The terms mild TBI and concussion are often assessment. The patient has signs and symptoms of normal used interchangeably. Concussion has been defined as a pressure hydrocephalus (NPH) (gait changes, urinary incon- clinical syndrome of biomechanically induced alteration of tinence, and cognitive impairment). Gait impairment, the brain function. Altered brain function is most commonly most prominent feature, is characterized by shuffling short described by affected subjects as being confused or dazed, step length and often problems with starting ambulation with 10% reporting transient loss of consciousness. Next (hesitation). The feet can appear as though they are stuck to to accidents, sporting activities represent the second most the ground, which is described as a “magnetic” gait. In addi- common source of TBI in young adults. In men, football and tion, this patient’s MRI of the brain shows communicating hockey result in most cases of mild TBI, whereas in women, (nonobstructive) hydrocephalus. NPH is treated by a ventric- the most common cause is soccer. When TBI is suspected, uloperitoneal shunt placed by a neurosurgeon. Before treat- athletes must be immediately removed from play and sub- ment is attempted, a test that predicts response to shunting jected to standardized sideline assessment tools. Guidelines is necessary. This test assesses the patient’s gait after removal recommend continued avoidance of contact sports until of 30 to 50 mL of CSF. The patient’s walking is timed imme 10 days after the trauma or until the patient has been asymp- diately before and after lumbar puncture. An objective mea- tomatic while taking no medication for a period of 7 days. sure of gait improvement is the Timed Up and Go test (TUG), This patient meets both time-based criteria, is asymptomatic which measures the amount of time necessary to rise from with normal findings on neurologic examination, and may a chair, walk 3 meters, turn, return to the chair, and sit. An be cleared to return to play. improvement in time by more than 5 seconds is predictive of Although brain MRI (Option A) is more diagnostically a positive response to CSF shunting. accurate than head CT in the setting of subacute or chronic Placement of a lumboperitoneal shunt (Option B) is headache, a patient without symptoms or abnormal exam- another surgical option for treatment but should not precede ination findings after a mild TBI does not require imaging testing for response to shunting. before return to play. Gait disturbance is the clinical symptom most amenable There are many published indications for head CT to ventricular shunting. The longer cognitive impairment (Option C) in the setting of acute head injury, such as has been present and the more pronounced the memory age greater than 60 years, progressive headache, seizure, problem, the less certain is the response to shunting. repeated vomiting after the trauma, persistent drowsiness If response to high-volume CSF removal is uncertain, or amnesia, focal deficits, and certain dangerous mecha- assessment for gait improvement after placement ofa lum- nisms of injury. This patient, however, sustained the TBI bar drain (Option C) by a neurosurgeon can be pursued. 10 days ago and had none of these indications, so head CT is CSF diversion through a ventriculoperitoneal shunt unnecessary. (Option D) is the definitive treatment of NPH. However, in Neuropsychological testing (Option D) is valuable in the the absence of a clear response to either high-volume CSF assessment of patients remaining symptomatic after a mild 127

Answers and Critiques ~ TBI, but this patient has returned to baseline and needs no Lumbar disk herniation (Option C) is an unlikely cause such testing. for this patient's weakness. Lumbar disk herniations typi Vestibular therapy (Option E) may be valuable in the cally result in radiculopathy or cauda equina syndrome, nei- management of patients with persistent posttraumatic diz- ther of which would result in complete plegia of all muscles ziness or gait imbalance. This patient exhibits no symptoms in both lower extremities. Further, such pathology would or signs of ongoing vestibular dysfunction. also likely result in sensory deficits, which this patient is not experiencing. e For athletes who sustain a mild traumatic brain injury, guidelines recommend continued avoidance of contact e Spinal cord infarction can occur as a consequence of sports until 10 days after the trauma or until the patient hypotension during cardiovascular or aortic surgery. has been asymptomatic while taking no medication for e Anterior infarction of the spinal cord typically results Pp a period of 7 days. in acute, bilateral, flaccid paralysis. = wn

e For athletes who sustain a mild traumatic brain injury, guidelines recommend continued avoidance of contact e Spinal cord infarction can occur as a consequence of sports until 10 days after the trauma or until the patient hypotension during cardiovascular or aortic surgery. has been asymptomatic while taking no medication for e Anterior infarction of the spinal cord typically results Pp a period of 7 days. in acute, bilateral, flaccid paralysis. = wn = Bibliography Bibliography @ Mullally WJ. Concussion. Am J Med. 2017 Aug;130(8):885-92. Epub 2017 May Romi F, Naess H. Spinal cord infarction in clinical neurology: a review of el wn wy 11. [PMID: 28502817] doi: 10.1016/j-amjmed.2017.04.016 characteristics and long-term prognosis in comparison to cerebral = infarction. Eur Neurol. 2016;76:95-8. [PMID: 27487411] a. oO =e Item 24 Answer: D =. Item 25 Answer: C 2 S Educational Objective: Diagnose spinal cord infarction. o Educational Objective: Prevent cognitive impairment. wn The most likely diagnosis is spinal cord infarction (Option D). The most common clinical presentation of a spinal The most important measure to help this patient prevent cord infarction involves the anterior spinal artery. Pro- dementia is to begin a regular program of physical exercise longed hypotension during cardiovascular or aortic sur (Option C). With the growth of the aging population, the gery can result in lack of perfusion to watershed regions prevalence of mild cognitive impairment and dementia is of the spinal cord. In this patient, the infarction likely increasing. However, the incidence of dementia is declining occurred as a consequence of hypoperfusion to the spinal with the control of vascular risk factors (diabetes melli- cord vasculature in the anterior arterial vascular distri- tus, hypertension, hyperlipidemia). Adjustments to diet will bution in the setting of repair of an aortic dissection. mitigate many of the risk factors for developing cognitive The midportion of the thoracic spinal cord is especially decline. Diets rich in fruits and vegetables, unsaturated fats, prone to hypoperfusion infarction where the anterior fish and whole-grain cereal products are being studied and spinal artery from above meets the radicular artery of show some promise for increasing brain health. However, Adamkiewicz from below. Hypoperfusion in the anterior these benefits have not been confirmed. Exercise is the most arterial vascular distribution of the cord typically inter important modifiable lifestyle factor to prevent the onset of rupts both descending motor pathways and the anterior cognitive impairment. Results from systematic reviews sug- horn cells in the gray matter of the cord, resulting in gest that exercise training is associated with moderate pos- acute, bilateral, flaccid (low tone, hyporeflexia) paralysis. itive effects for global cognition, logical memory, inhibitory If sensation is impaired, it will not involve the posterior control, and divided attention. Even exercise that is initiated columns (vibration, position) because of separate vascular in mid to late life can still provide benefits. The 2018 Physical supply to the posterior cord. Activity Guidelines for Americans recommend that adults Guillain-Barré syndrome (Option A) is not a likely diag- perform at least 150 to 300 minutes per week of moderate- nosis. This inflammatory polyradiculopathy is typified by a intensity exercise. Other options include 75 to 150 minutes subacute onset with progressive ascending paralysis. This per week of vigorous-intensity aerobic activity or equivalent patient’s acute onset of symptoms is not consistent with the combinations of moderate- and vigorous-intensity exercise. subacute ascending paralysis typical of Guillain-Barré syn- Although evidence suggests that higher educational drome. Guillain-Barré syndrome also typically occurs as a attainment and mid-life intellectual and social activities postinfectious syndrome, and this patient did not experience lead to more late-life cognitive reserve, there is insufficient a preceding infection. evidence to support or refute the use of any individual cog- Idiopathic transverse myelitis (Option B) is an unlikely nitive intervention strategy (Option A) in the prevention of explanation for the patient’s symptoms. Although this entity cognitive impairment. could potentially result in a similar set of findings on exam- There is no role for donepezil (Option B) or any other ination, the time course of an acute onset and the association pharmacologic agent in preventing cognitive decline in of the patient’s symptoms with concurrent aortic surgery patients with normal cognitive function. make a vascular cause far more likely than an inflammatory In patients with MCI, use of vitamin E 2000 U daily myelitis, which would have a more subacute onset and is (Option D) is ineffective for reducing progression to Alzhei- typically a postinfectious phenomenon. mer disease. In the absence of a specific vitamin deficiency,

= Bibliography Bibliography @ Mullally WJ. Concussion. Am J Med. 2017 Aug;130(8):885-92. Epub 2017 May Romi F, Naess H. Spinal cord infarction in clinical neurology: a review of el wn wy 11. [PMID: 28502817] doi: 10.1016/j-amjmed.2017.04.016 characteristics and long-term prognosis in comparison to cerebral = infarction. Eur Neurol. 2016;76:95-8. [PMID: 27487411] a. oO =e Item 24 Answer: D =. Item 25 Answer: C 2 S Educational Objective: Diagnose spinal cord infarction. o Educational Objective: Prevent cognitive impairment. wn The most likely diagnosis is spinal cord infarction (Option D). The most common clinical presentation of a spinal The most important measure to help this patient prevent cord infarction involves the anterior spinal artery. Pro- dementia is to begin a regular program of physical exercise longed hypotension during cardiovascular or aortic sur (Option C). With the growth of the aging population, the gery can result in lack of perfusion to watershed regions prevalence of mild cognitive impairment and dementia is of the spinal cord. In this patient, the infarction likely increasing. However, the incidence of dementia is declining occurred as a consequence of hypoperfusion to the spinal with the control of vascular risk factors (diabetes melli- cord vasculature in the anterior arterial vascular distri- tus, hypertension, hyperlipidemia). Adjustments to diet will bution in the setting of repair of an aortic dissection. mitigate many of the risk factors for developing cognitive The midportion of the thoracic spinal cord is especially decline. Diets rich in fruits and vegetables, unsaturated fats, prone to hypoperfusion infarction where the anterior fish and whole-grain cereal products are being studied and spinal artery from above meets the radicular artery of show some promise for increasing brain health. However, Adamkiewicz from below. Hypoperfusion in the anterior these benefits have not been confirmed. Exercise is the most arterial vascular distribution of the cord typically inter important modifiable lifestyle factor to prevent the onset of rupts both descending motor pathways and the anterior cognitive impairment. Results from systematic reviews sug- horn cells in the gray matter of the cord, resulting in gest that exercise training is associated with moderate pos- acute, bilateral, flaccid (low tone, hyporeflexia) paralysis. itive effects for global cognition, logical memory, inhibitory If sensation is impaired, it will not involve the posterior control, and divided attention. Even exercise that is initiated columns (vibration, position) because of separate vascular in mid to late life can still provide benefits. The 2018 Physical supply to the posterior cord. Activity Guidelines for Americans recommend that adults Guillain-Barré syndrome (Option A) is not a likely diag- perform at least 150 to 300 minutes per week of moderate- nosis. This inflammatory polyradiculopathy is typified by a intensity exercise. Other options include 75 to 150 minutes subacute onset with progressive ascending paralysis. This per week of vigorous-intensity aerobic activity or equivalent patient’s acute onset of symptoms is not consistent with the combinations of moderate- and vigorous-intensity exercise. subacute ascending paralysis typical of Guillain-Barré syn- Although evidence suggests that higher educational drome. Guillain-Barré syndrome also typically occurs as a attainment and mid-life intellectual and social activities postinfectious syndrome, and this patient did not experience lead to more late-life cognitive reserve, there is insufficient a preceding infection. evidence to support or refute the use of any individual cog- Idiopathic transverse myelitis (Option B) is an unlikely nitive intervention strategy (Option A) in the prevention of explanation for the patient’s symptoms. Although this entity cognitive impairment. could potentially result in a similar set of findings on exam- There is no role for donepezil (Option B) or any other ination, the time course of an acute onset and the association pharmacologic agent in preventing cognitive decline in of the patient’s symptoms with concurrent aortic surgery patients with normal cognitive function. make a vascular cause far more likely than an inflammatory In patients with MCI, use of vitamin E 2000 U daily myelitis, which would have a more subacute onset and is (Option D) is ineffective for reducing progression to Alzhei- typically a postinfectious phenomenon. mer disease. In the absence of a specific vitamin deficiency, 128

Answers and Critiques there is no role for herbal or vitamin supplementation to Discontinuing glatiramer acetate and initiating natal- prevent cognitive decline in adults without cognitive impair- izumab (Option D) is not indicated. The patient does not ment. have any new disease activity, and results of her MRI show stable lesions. e Physical exercise is the most important modifiable lifestyle factor to prevent the onset of cognitive e Depression is very common in patients with multiple impairment. sclerosis, and clinicians should be vigilant for the signs of depression, and if present, screen for e Medications, vitamin, and herbal supplements do not prevent cognitive decline in healthy people or in suicidality.

impairment. sclerosis, and clinicians should be vigilant for the signs of depression, and if present, screen for e Medications, vitamin, and herbal supplements do not prevent cognitive decline in healthy people or in suicidality. patients with mild cognitive impairment. Bibliography Kalb R, Feinstein A, Rohrig A, Sankary L, Willis A. Depression and suicidal- 7) Bibliography a ity in multiple sclerosis: red flags, management strategies, and ethical = Kivipelto M, Mangialasche F, Ngandu T. Lifestyle interventions to prevent considerations. Curr Neurol Neurosci Rep. 2019 Aug 28;19(10):77. doi: cognitive impairment, dementia and Alzheimer disease. Nat Rev Neurol. 10.1007/s11910-019-0992-1. PMID: 31463644 = 2018;14(11):653-66. [PMID: 30291317] doi:10.1038/s41582-018-0070-3 = 1S) cs = ltem 26 Answer: C Item 27 Answer: D 4] 7) td Educational Objective: Screen for depression in a Educational Objective: Prevent deep venous thrombosis a

patients with mild cognitive impairment. Bibliography Kalb R, Feinstein A, Rohrig A, Sankary L, Willis A. Depression and suicidal- 7) Bibliography a ity in multiple sclerosis: red flags, management strategies, and ethical = Kivipelto M, Mangialasche F, Ngandu T. Lifestyle interventions to prevent considerations. Curr Neurol Neurosci Rep. 2019 Aug 28;19(10):77. doi: cognitive impairment, dementia and Alzheimer disease. Nat Rev Neurol. 10.1007/s11910-019-0992-1. PMID: 31463644 = 2018;14(11):653-66. [PMID: 30291317] doi:10.1038/s41582-018-0070-3 = 1S) cs = ltem 26 Answer: C Item 27 Answer: D 4] 7) td Educational Objective: Screen for depression in a Educational Objective: Prevent deep venous thrombosis a patient with multiple sclerosis. following acute stroke. = wn = The most appropriate management is to screen for depression 4 The most appropriate management is venous thromboem- (Option C). This patient presents with signs of depression, bolism (VTE) prophylaxis (Option D). Patients with acute including low energy, lack of interest in activities, and poor stroke, including patients with intracerebral hemorrhage sleep. Major depression is very common in patients with (ICH), are at increased risk for VTE. In patients with acute multiple sclerosis (MS) and likely occurs in approximately stroke, guidelines recommend intermittent pneumatic com- 50% of patients during their lifetime. Approximately 10% of pression beginning the day of hospital admission. Intermit- patients with MS have experienced persistent thoughts of tent pneumatic compression is superior to either knee-high suicide. Furthermore, the suicide rate for patients with MS or thigh-high compression stockings in the prevention of and depression is elevated compared with that of patients VTE. After 24 hours, if there is no evidence of hematoma with depression only. MS-related depression is likely mul- expansion, then subcutaneous pharmacoprophylaxis (typ- tifactorial, involving the emotional response to dealing with ically, low-molecular-weight heparin) is recommended for a chronic disease, the consequence of demyelinating lesions VTE prophylaxis. and inflammatory cytokines on neurotransmitter function, Dysphagia is a common complication of stroke and is and the adverse effects of treatments (such as interferon a major risk factor for developing aspiration pneumonia. A beta). Clinicians should be vigilant for the signs of depres- bedside water swallowing test is often a sufficient screening sion, and if present, screen for suicidality. If suicidal ideation test for dysphagia until more sophisticated diagnostic test- is present, the lethality of the ideation should be evaluated. ing, such as video fluoroscopy, can assess the severity of dys- Clinicians should have a low threshold for initiating antide- phagia. This patient should not begin oral feeding (Option A) pressants and offering referrals to psychiatry or psychology following a positive bedside dysphagia screening test until for counseling. Referral to a psychiatrist is indicated for further evaluation is completed. patients with severe depression, failure of initial therapy, Routine placement of a bladder catheter (Option B) in complex psychiatric comorbidities, and high suicide risk. acutely ill hospitalized patients is not recommended. Indica- Initiation of modafinil (Option A) is not indicated. tions for bladder catheterization have been established and Although this patient reports low energy, and fatigue is a include conditions such as acute or chronic urinary reten- common symptom in MS, fatigue is not the only potential tion, treatment of significant pressure injury complicated cause of her presenting symptoms. Patients with MS who are by urinary incontinence, and need for hourly urine output experiencing fatigue should be evaluated for depression and measurements. This patient has no indication for bladder sleep disturbances before initiation of treatment for fatigue. catheterization. Measuring this patient’s serum 25-hydroxy vitamin D A 2018 systematic review found that supplemental level (Option B) is not the most appropriate next step in oxygen (Option C) in patients with normal oxygen satur- management. Although the patient has a history of vitamin ation as measured by pulse oximetry increases mortality D deficiency, and optimization of vitamin D levels may have in patients with stroke. The American Heart Association/ some benefit in patients with MS, the patient’s presenting American Stroke Association recommends oxygen to main- symptom of depression is not a symptom commonly associ- tain an oxygen saturation of 94% or greater. Other guidelines ated with vitamin D deficiency, and deficiency is unlikely in recommend against starting oxygen therapy in patients at or a patient taking supplementation. above 93% saturation and discontinuing oxygen if saturation

patient with multiple sclerosis. following acute stroke. = wn = The most appropriate management is to screen for depression 4 The most appropriate management is venous thromboem- (Option C). This patient presents with signs of depression, bolism (VTE) prophylaxis (Option D). Patients with acute including low energy, lack of interest in activities, and poor stroke, including patients with intracerebral hemorrhage sleep. Major depression is very common in patients with (ICH), are at increased risk for VTE. In patients with acute multiple sclerosis (MS) and likely occurs in approximately stroke, guidelines recommend intermittent pneumatic com- 50% of patients during their lifetime. Approximately 10% of pression beginning the day of hospital admission. Intermit- patients with MS have experienced persistent thoughts of tent pneumatic compression is superior to either knee-high suicide. Furthermore, the suicide rate for patients with MS or thigh-high compression stockings in the prevention of and depression is elevated compared with that of patients VTE. After 24 hours, if there is no evidence of hematoma with depression only. MS-related depression is likely mul- expansion, then subcutaneous pharmacoprophylaxis (typ- tifactorial, involving the emotional response to dealing with ically, low-molecular-weight heparin) is recommended for a chronic disease, the consequence of demyelinating lesions VTE prophylaxis. and inflammatory cytokines on neurotransmitter function, Dysphagia is a common complication of stroke and is and the adverse effects of treatments (such as interferon a major risk factor for developing aspiration pneumonia. A beta). Clinicians should be vigilant for the signs of depres- bedside water swallowing test is often a sufficient screening sion, and if present, screen for suicidality. If suicidal ideation test for dysphagia until more sophisticated diagnostic test- is present, the lethality of the ideation should be evaluated. ing, such as video fluoroscopy, can assess the severity of dys- Clinicians should have a low threshold for initiating antide- phagia. This patient should not begin oral feeding (Option A) pressants and offering referrals to psychiatry or psychology following a positive bedside dysphagia screening test until for counseling. Referral to a psychiatrist is indicated for further evaluation is completed. patients with severe depression, failure of initial therapy, Routine placement of a bladder catheter (Option B) in complex psychiatric comorbidities, and high suicide risk. acutely ill hospitalized patients is not recommended. Indica- Initiation of modafinil (Option A) is not indicated. tions for bladder catheterization have been established and Although this patient reports low energy, and fatigue is a include conditions such as acute or chronic urinary reten- common symptom in MS, fatigue is not the only potential tion, treatment of significant pressure injury complicated cause of her presenting symptoms. Patients with MS who are by urinary incontinence, and need for hourly urine output experiencing fatigue should be evaluated for depression and measurements. This patient has no indication for bladder sleep disturbances before initiation of treatment for fatigue. catheterization. Measuring this patient’s serum 25-hydroxy vitamin D A 2018 systematic review found that supplemental level (Option B) is not the most appropriate next step in oxygen (Option C) in patients with normal oxygen satur- management. Although the patient has a history of vitamin ation as measured by pulse oximetry increases mortality D deficiency, and optimization of vitamin D levels may have in patients with stroke. The American Heart Association/ some benefit in patients with MS, the patient’s presenting American Stroke Association recommends oxygen to main- symptom of depression is not a symptom commonly associ- tain an oxygen saturation of 94% or greater. Other guidelines ated with vitamin D deficiency, and deficiency is unlikely in recommend against starting oxygen therapy in patients at or a patient taking supplementation. above 93% saturation and discontinuing oxygen if saturation 129

muapae ane Eee. is at or above 96%. This patient has no indication for supple- mental oxygen therapy. CONT. e Patients with evidence of dementia symptoms for less than 3 years should have advanced neuroimaging with noncontrast CT or MRI. e Patients with acute stroke, including patients with intracerebral hemorrhage, are at increased risk for ¢ MRI of the brain supports the diagnosis of Alzheimer venous thromboembolism. disease when it shows evidence of decreased volume ¢ Venous thromboembolism prevention should be initiated of the hippocampi out of proportion to rest of the for patients with acute stroke on the day of hospital brain.

is at or above 96%. This patient has no indication for supple- mental oxygen therapy. CONT. e Patients with evidence of dementia symptoms for less than 3 years should have advanced neuroimaging with noncontrast CT or MRI. e Patients with acute stroke, including patients with intracerebral hemorrhage, are at increased risk for ¢ MRI of the brain supports the diagnosis of Alzheimer venous thromboembolism. disease when it shows evidence of decreased volume ¢ Venous thromboembolism prevention should be initiated of the hippocampi out of proportion to rest of the for patients with acute stroke on the day of hospital brain. admission. Bibliography Oh ES, Rabins PV. Dementia. Ann Intern Med. 2019;171:ITC33-ITC48. Bibliography [PMID: 31476229] doi: 10.7326/AITC201909030 Pd Schtinemann HJ, Cushman M, Burnett AE, et al. American Society of = wn Hematology 2018 guidelines for management of venous thromboembo- = lism: prophylaxis for hospitalized and nonhospitalized medical patients. @ Blood Adv. 2018;2:3198-3225. [PMID: 30482763] doi:10.1182/bloodad- Item 29 Answer: A = wn vances.2018022954 gy Educational Objective: Treat gait dysfunction in = a. multiple sclerosis. (=) = Item 28 Answer: D The intervention most likely to improve this patient’s ambu- =. 2 latory function is dalfampridine (Option A). Maintenance of Educational Objective: Evaluate dementia with a mobility in MS patients is essential to maintaining quality J neuroimaging. “ of life. An active healthy lifestyle is necessary to help stave off Either a brain MRI or a head CT without contrast (Option D) future disability. Physical and occupational therapy can pro- should be done in the evaluation of dementia. Guidelines rec- vide gait safety training and improve balance and endurance. ommend that patients with evidence of dementia symptoms Assistive devices, such as braces, canes, walkers, and elec- for less than 3 years should have advanced neuroimaging with trostimulatory walk-assist devices, can provide additional noncontrast CT or MRI. Neuroimaging can identify conditions benefit. This patient’s left leg findings are consistent with that may be remediable or modifiable, such as cerebrovascu- injury to the corticospinal tract froma prior relapse. Dalfam- lar disease, hemorrhage, tumor, and abscess. Neuroimaging pridine, an oral voltage-gated potassium channel antagonist, can also support the diagnoses of specific dementias, such can improve gait speed and endurance in patients with as Alzheimer disease, Creutzfeldt-Jakob disease, and hydro- relapsing-remitting multiple sclerosis (MS) with ambulatory cephalus. MRI of the brain supports the diagnosis of Alzhei- dysfunction. Dalfampridine cannot induce healing or remy- mer disease when it shows evidence of decreased volume of elination. However, this medication likely improves neuro- the hippocampi out of proportion to rest of the brain. This nal conduction, allowing signals to be processed through patient likely has Alzheimer disease, and although a head CT the corticospinal tract more efficiently and thus leading to is acceptable, brain MRI would be better to define the level of improvements in gait in those with injury to this tract. Dal- atrophy in the hippocampi for this diagnosis. fampridine has a rare risk of seizures and should not be used An amyloid-specific PET scan (Option A) uses '8F- in patients with known epilepsy or with kidney impairment. fluorodeoxyglucose (FDG) to detect amyloid plaques. Amy- Initiation of modafinil (Option B) would not be an loid PET scanning is not routinely recommended in the appropriate intervention at this time. This medication has evaluation of dementia. However, this imaging modality can potential benefit for those with fatigue related to MS, but it help differentiate frontotemporal dementia from Alzheimer has no demonstrated efficacy for improvement in gait. disease when the correct diagnosis is not clinically apparent. MS spasticity is due to corticospinal tract damage, An amyloid PET scan, although FDA-approved, is not cov- resulting in increased muscle tone, painful muscle cramps, ered by insurance. spasms, and contractures. The use of muscle relaxants, such When the MRI is normal and the diagnosis is in ques- as tizanidine (Option C), baclofen, cyclobenzaprine, and the tion or a non-Alzheimer disease process is being considered, benzodiazepines, may be helpful. However, this patient is a functional fluorodeoxyglucose PET scan (Option B) can be not reporting painful muscle spasms or cramps, and these used to look for the Alzheimer disease pattern of decreased drugs are not proven to improve gait function. brain function in the bilateral parietal and temporal regions. Altering the patient’s disease-modifying therapy, However, it is typically not an appropriate assessment until such as switching to natalizumab (Option D) or ocreli- structural lesions in the brain are assessed by either MRI of zumab (Option E), would not be appropriate in this set- the brain or head CT. ting. Although these disease-modifying therapies have high A head CT with contrast (Option C) is not necessary efficacy, none have demonstrated benefit for symptomatic unless there is concern for infection, inflammation, or neo- improvement for long-standing neurologic deficits. The ben- plasm, which would typically be accompanied by focal neur- efit of these disease-modifying therapies is in prevention— ologic findings on examination. reducing risk for future relapses, MRI activity, or disability

admission. Bibliography Oh ES, Rabins PV. Dementia. Ann Intern Med. 2019;171:ITC33-ITC48. Bibliography [PMID: 31476229] doi: 10.7326/AITC201909030 Pd Schtinemann HJ, Cushman M, Burnett AE, et al. American Society of = wn Hematology 2018 guidelines for management of venous thromboembo- = lism: prophylaxis for hospitalized and nonhospitalized medical patients. @ Blood Adv. 2018;2:3198-3225. [PMID: 30482763] doi:10.1182/bloodad- Item 29 Answer: A = wn vances.2018022954 gy Educational Objective: Treat gait dysfunction in = a. multiple sclerosis. (=) = Item 28 Answer: D The intervention most likely to improve this patient’s ambu- =. 2 latory function is dalfampridine (Option A). Maintenance of Educational Objective: Evaluate dementia with a mobility in MS patients is essential to maintaining quality J neuroimaging. “ of life. An active healthy lifestyle is necessary to help stave off Either a brain MRI or a head CT without contrast (Option D) future disability. Physical and occupational therapy can pro- should be done in the evaluation of dementia. Guidelines rec- vide gait safety training and improve balance and endurance. ommend that patients with evidence of dementia symptoms Assistive devices, such as braces, canes, walkers, and elec- for less than 3 years should have advanced neuroimaging with trostimulatory walk-assist devices, can provide additional noncontrast CT or MRI. Neuroimaging can identify conditions benefit. This patient’s left leg findings are consistent with that may be remediable or modifiable, such as cerebrovascu- injury to the corticospinal tract froma prior relapse. Dalfam- lar disease, hemorrhage, tumor, and abscess. Neuroimaging pridine, an oral voltage-gated potassium channel antagonist, can also support the diagnoses of specific dementias, such can improve gait speed and endurance in patients with as Alzheimer disease, Creutzfeldt-Jakob disease, and hydro- relapsing-remitting multiple sclerosis (MS) with ambulatory cephalus. MRI of the brain supports the diagnosis of Alzhei- dysfunction. Dalfampridine cannot induce healing or remy- mer disease when it shows evidence of decreased volume of elination. However, this medication likely improves neuro- the hippocampi out of proportion to rest of the brain. This nal conduction, allowing signals to be processed through patient likely has Alzheimer disease, and although a head CT the corticospinal tract more efficiently and thus leading to is acceptable, brain MRI would be better to define the level of improvements in gait in those with injury to this tract. Dal- atrophy in the hippocampi for this diagnosis. fampridine has a rare risk of seizures and should not be used An amyloid-specific PET scan (Option A) uses '8F- in patients with known epilepsy or with kidney impairment. fluorodeoxyglucose (FDG) to detect amyloid plaques. Amy- Initiation of modafinil (Option B) would not be an loid PET scanning is not routinely recommended in the appropriate intervention at this time. This medication has evaluation of dementia. However, this imaging modality can potential benefit for those with fatigue related to MS, but it help differentiate frontotemporal dementia from Alzheimer has no demonstrated efficacy for improvement in gait. disease when the correct diagnosis is not clinically apparent. MS spasticity is due to corticospinal tract damage, An amyloid PET scan, although FDA-approved, is not cov- resulting in increased muscle tone, painful muscle cramps, ered by insurance. spasms, and contractures. The use of muscle relaxants, such When the MRI is normal and the diagnosis is in ques- as tizanidine (Option C), baclofen, cyclobenzaprine, and the tion or a non-Alzheimer disease process is being considered, benzodiazepines, may be helpful. However, this patient is a functional fluorodeoxyglucose PET scan (Option B) can be not reporting painful muscle spasms or cramps, and these used to look for the Alzheimer disease pattern of decreased drugs are not proven to improve gait function. brain function in the bilateral parietal and temporal regions. Altering the patient’s disease-modifying therapy, However, it is typically not an appropriate assessment until such as switching to natalizumab (Option D) or ocreli- structural lesions in the brain are assessed by either MRI of zumab (Option E), would not be appropriate in this set- the brain or head CT. ting. Although these disease-modifying therapies have high A head CT with contrast (Option C) is not necessary efficacy, none have demonstrated benefit for symptomatic unless there is concern for infection, inflammation, or neo- improvement for long-standing neurologic deficits. The ben- plasm, which would typically be accompanied by focal neur- efit of these disease-modifying therapies is in prevention— ologic findings on examination. reducing risk for future relapses, MRI activity, or disability 130

Answers and Critiques progression. Altering this patient’s disease-modifying ther- patients because of their propensity to cause or worsen apy would thus not help improve his gait, which has been delirium. They should not be started in this patient. affected for 1 year. Studies of hospitalized patients with acute delirium have documented a mean of three precipitating causes of delir- ium per patient in two thirds of carefully evaluated patients. e In patients with multiple sclerosis with ambulatory While holding the oxycodone is appropriate, careful evalu dysfunction, dalfampridine can improve gait speed ation of other causes of delirium should be undertaken. No and endurance. additional treatment (Option E) is not the best option. e The benefit of disease-modifying therapies is reducing risk for future relapses, MRI activity or disability pro- e Withdrawal from alcohol or other abused drugs and gression, not symptomatic improvement of existing from prescribed medications can precipitate delirium. disability. wn rf Bibliography 3 Bibliography > Marcantonio ER. Delirium in hospitalized older adults. N Engl J Med. 2017; Shi J, Wu X, Chen Y. Study on dalfampridine in the treatment of multiple 377:1456-66. [PMID: 29020579] doi: 10.1056/NEJMcp1605501 = be sclerosis mobility disability: a meta-analysis. PLoS One. 2019;14(9): rs) e0222288. Published 2019 Sep 12. [PMID: 31513613] doi:10.1371/journal. 3 pone.0222288 = Item 31 Answer: D co wn Pu Educational Objective: Treat cluster headache. 7) Item 30 Answer: C = ” The most appropriate management is subcutaneous = Educational Objective: Treat delirium in a hospitalized << sumatriptan (Option D). The clinical presentation is clas- patient. sic for episodic cluster headache, the most common of the The most appropriate next step in management is the addition trigeminal autonomic cephalalgias (TACs). Male gender and of paroxetine (Option C). The patient shows signs of delirium, tobacco use are risk factors for cluster headache. Diagnos- such as fluctuations in mentation, nighttime sleeplessness, tic criteria require one to eight daily episodes lasting 15 to and hallucinations. Treatment of delirium involves identifying 180 minutes when untreated. The pain is unilateral and and treating its underlying causes. In the elderly, medications severe and orbital, supraorbital, or temporal in location. are a common precipitating cause of delirium in hospital Associated features must include at least one ipsilateral ized patients. Sedating medications, including opioids, can cranial autonomic feature (lacrimation, nasal stuffiness or precipitate or worsen delirium, and holding or reducing the rhinorrhea, conjunctival injection, ptosis, miosis) and/or patient’s overall dose of oxycodone is a reasonable first step a sense of restlessness or agitation. Cluster headache has in addressing her delirium. Withdrawal of alcohol and drugs a cyclical nature in which periods of recurrent headache such as benzodiazepines, opioids, and antidepressants can activity are interrupted by months to years of headache also precipitate delirium. Antidepressant medications should remission. Many of the attacks are nocturnal, and some may be gradually tapered to avoid discontinuation syndrome. Dis- be provoked by alcohol ingestion. When cluster headache continuation symptoms can occur with any selective sero- (or any TAC) is suspected, brain MRI is necessary to rule tonin reuptake inhibitor but is most commonly reported out structural mimics. Subcutaneous sumatriptan and 100% with paroxetine. The most common symptoms are dizziness, oxygen inhalation are both effective for cluster headache and fatigue, and headache. Other commonly reported symptoms indicated as first-line treatments of attacks. are agitation, anxiety, and insomnia. Symptoms may start Carbamazepine (Option A) is a first-line treatment for from 1 to 7 days following abrupt discontinuation of antide- trigeminal neuralgia, but the length of this patient’s episodes pressant medications. Paroxetine should be reintroduced. and the presence of autonomic features are not compatible Other classes of drugs that have been implicated in pre- with this diagnosis. cipitating delirium in hospitalized patients include benzodiaz Several headache conditions are uniquely responsive to epines and drugs with anticholinergic properties. Drugs with indomethacin (Option B), but cluster headache is not among anticholinergic properties are associated with well-known them. Chronic paroxysmal hemicrania is a TAC related to adverse effects, particularly in the elderly, yet are commonly cluster headache that is indomethacin responsive, but epi- prescribed. Frequently reported central nervous system adverse sodes are shorter in duration (2-30 minutes) and higher in effects include memory impairment, confusion, and hallucina- frequency (5-20 per day) compared with cluster headache. tions. First-generation antihistamines, such as diphenhydra- Hemicrania continua and primary cough headache are other mine (Option A), are often prescribed to induce sedation and examples of indomethacin-responsive headache disorders. sleep in the elderly. However, these drugs have anticholinergic Carotid angiography and magnet resonance angiogra- properties and, according to the American Geriatrics Society, phy (MRA) of the head and neck (Option C) are preferred are among the drugs to be avoided in the elderly. options in the evaluation of cervical artery dissections. Sedative hypnotic drugs, such as lorazepam (Option Although the differential diagnosis of a headache with pto- B) and zolpidem (Option D), should be avoided in older sis and miosis (partial Horner syndrome) includes carotid

progression. Altering this patient’s disease-modifying ther- patients because of their propensity to cause or worsen apy would thus not help improve his gait, which has been delirium. They should not be started in this patient. affected for 1 year. Studies of hospitalized patients with acute delirium have documented a mean of three precipitating causes of delir- ium per patient in two thirds of carefully evaluated patients. e In patients with multiple sclerosis with ambulatory While holding the oxycodone is appropriate, careful evalu dysfunction, dalfampridine can improve gait speed ation of other causes of delirium should be undertaken. No and endurance. additional treatment (Option E) is not the best option. e The benefit of disease-modifying therapies is reducing risk for future relapses, MRI activity or disability pro- e Withdrawal from alcohol or other abused drugs and gression, not symptomatic improvement of existing from prescribed medications can precipitate delirium. disability. wn rf Bibliography 3 Bibliography > Marcantonio ER. Delirium in hospitalized older adults. N Engl J Med. 2017; Shi J, Wu X, Chen Y. Study on dalfampridine in the treatment of multiple 377:1456-66. [PMID: 29020579] doi: 10.1056/NEJMcp1605501 = be sclerosis mobility disability: a meta-analysis. PLoS One. 2019;14(9): rs) e0222288. Published 2019 Sep 12. [PMID: 31513613] doi:10.1371/journal. 3 pone.0222288 = Item 31 Answer: D co wn Pu Educational Objective: Treat cluster headache. 7) Item 30 Answer: C = ” The most appropriate management is subcutaneous = Educational Objective: Treat delirium in a hospitalized << sumatriptan (Option D). The clinical presentation is clas- patient. sic for episodic cluster headache, the most common of the The most appropriate next step in management is the addition trigeminal autonomic cephalalgias (TACs). Male gender and of paroxetine (Option C). The patient shows signs of delirium, tobacco use are risk factors for cluster headache. Diagnos- such as fluctuations in mentation, nighttime sleeplessness, tic criteria require one to eight daily episodes lasting 15 to and hallucinations. Treatment of delirium involves identifying 180 minutes when untreated. The pain is unilateral and and treating its underlying causes. In the elderly, medications severe and orbital, supraorbital, or temporal in location. are a common precipitating cause of delirium in hospital Associated features must include at least one ipsilateral ized patients. Sedating medications, including opioids, can cranial autonomic feature (lacrimation, nasal stuffiness or precipitate or worsen delirium, and holding or reducing the rhinorrhea, conjunctival injection, ptosis, miosis) and/or patient’s overall dose of oxycodone is a reasonable first step a sense of restlessness or agitation. Cluster headache has in addressing her delirium. Withdrawal of alcohol and drugs a cyclical nature in which periods of recurrent headache such as benzodiazepines, opioids, and antidepressants can activity are interrupted by months to years of headache also precipitate delirium. Antidepressant medications should remission. Many of the attacks are nocturnal, and some may be gradually tapered to avoid discontinuation syndrome. Dis- be provoked by alcohol ingestion. When cluster headache continuation symptoms can occur with any selective sero- (or any TAC) is suspected, brain MRI is necessary to rule tonin reuptake inhibitor but is most commonly reported out structural mimics. Subcutaneous sumatriptan and 100% with paroxetine. The most common symptoms are dizziness, oxygen inhalation are both effective for cluster headache and fatigue, and headache. Other commonly reported symptoms indicated as first-line treatments of attacks. are agitation, anxiety, and insomnia. Symptoms may start Carbamazepine (Option A) is a first-line treatment for from 1 to 7 days following abrupt discontinuation of antide- trigeminal neuralgia, but the length of this patient’s episodes pressant medications. Paroxetine should be reintroduced. and the presence of autonomic features are not compatible Other classes of drugs that have been implicated in pre- with this diagnosis. cipitating delirium in hospitalized patients include benzodiaz Several headache conditions are uniquely responsive to epines and drugs with anticholinergic properties. Drugs with indomethacin (Option B), but cluster headache is not among anticholinergic properties are associated with well-known them. Chronic paroxysmal hemicrania is a TAC related to adverse effects, particularly in the elderly, yet are commonly cluster headache that is indomethacin responsive, but epi- prescribed. Frequently reported central nervous system adverse sodes are shorter in duration (2-30 minutes) and higher in effects include memory impairment, confusion, and hallucina- frequency (5-20 per day) compared with cluster headache. tions. First-generation antihistamines, such as diphenhydra- Hemicrania continua and primary cough headache are other mine (Option A), are often prescribed to induce sedation and examples of indomethacin-responsive headache disorders. sleep in the elderly. However, these drugs have anticholinergic Carotid angiography and magnet resonance angiogra- properties and, according to the American Geriatrics Society, phy (MRA) of the head and neck (Option C) are preferred are among the drugs to be avoided in the elderly. options in the evaluation of cervical artery dissections. Sedative hypnotic drugs, such as lorazepam (Option Although the differential diagnosis of a headache with pto- B) and zolpidem (Option D), should be avoided in older sis and miosis (partial Horner syndrome) includes carotid 131

Answers and Critiques artery dissection, this diagnosis is unlikely with a pattern of thrombolytic therapy. Acute treatment to lower it is therefore daily, brief, episodic headaches over a span of 2 weeks. not indicated. Providing no additional therapy (Option D) for this patient is not the best option because thrombectomy may ¢ Trigeminal autonomic cephalalgias are characterized result in improved neurologic outcomes. by severe pain localized to the periorbital or temporal areas and associated with autonomic features, such as nasal congestion or rhinorrhea and ptosis or miosis; ¢ Patients eligible for alteplase should receive alteplase cluster headache is the most common subtype. even if mechanical thrombectomy is being considered. e Subcutaneous sumatriptan and oxygen inhalation are e In patients who meet eligibility requirements, effective treatments of cluster headache and are indi- thrombectomy after thrombolysis is associated with

cluster headache is the most common subtype. even if mechanical thrombectomy is being considered. e Subcutaneous sumatriptan and oxygen inhalation are e In patients who meet eligibility requirements, effective treatments of cluster headache and are indi- thrombectomy after thrombolysis is associated with cated as first-line treatments of attacks. improved neurologic outcomes. > = wa Bibliography Bibliography = @o Hoffmann J, May A. Diagnosis, pathophysiology, and management of cluster Powers WJ, Rabinstein AA, Ackerson T, et al; American Heart Association = wa headache. Lancet Neurol. 2018 Jan;17(1):75-83. [PMID: 29174963] doi: Stroke Council. 2018 Guidelines for the Early Management of rot) 10.1016/S1474-4422(17)30405-2. Patients With Acute Ischemic Stroke: A Guideline for Healthcare = Professionals From the American Heart Association/American Stroke Qu Association. Stroke. 2018;49:e46-e110. [PMID: 29367334] doi:10.1161/ (=) STR.0000000000000158 re Item 32 Answer: A = 2 Educational Objective: Evaluate a patient with acute <= @ ischemic stroke for thrombectomy. Item 33 Answer: E wn

cated as first-line treatments of attacks. improved neurologic outcomes. > = wa Bibliography Bibliography = @o Hoffmann J, May A. Diagnosis, pathophysiology, and management of cluster Powers WJ, Rabinstein AA, Ackerson T, et al; American Heart Association = wa headache. Lancet Neurol. 2018 Jan;17(1):75-83. [PMID: 29174963] doi: Stroke Council. 2018 Guidelines for the Early Management of rot) 10.1016/S1474-4422(17)30405-2. Patients With Acute Ischemic Stroke: A Guideline for Healthcare = Professionals From the American Heart Association/American Stroke Qu Association. Stroke. 2018;49:e46-e110. [PMID: 29367334] doi:10.1161/ (=) STR.0000000000000158 re Item 32 Answer: A = 2 Educational Objective: Evaluate a patient with acute <= @ ischemic stroke for thrombectomy. Item 33 Answer: E wn Educational Objective: Manage drug-related orthostatic The most appropriate management is CT angiography of the hypotension in Parkinson disease. brain (Option A). The patient is seen because of an acute ischemic stroke within 3 hours of onset and was appropri- The most appropriate next step to prevent additional falls is ately treated with intravenous alteplase. Patients eligible for to increase the dosage of carbidopa (Option E). Patients with alteplase should receive alteplase even if mechanical throm- Parkinson disease and falls, such as this patient, should be bectomy is being considered. She has had a large stroke, assessed for postural imbalance, impaired stepping, freezing with a National Institutes of Health Stroke Scale score of 18, of gait, and orthostatic hypotension. This patient’s history of and has examination findings consistent with a large-vessel lightheadedness on standing and substantial drop in stand- (middle cerebral or intracranial carotid artery) occlusion, ing blood pressure suggests orthostatic hypotension as the including aphasia. A large-vessel occlusion is associated likely cause of his fall. Examination reveals no freezing of with lower rates of neurologic improvement and recanali- gait or postural impairment, findings that are often noted zation with alteplase; treatment with thrombectomy after in more advanced Parkinson disease. Orthostatic hypoten- thrombolysis is indicated and associated with improved sion in Parkinson disease can be due to disease-related neurologic outcomes. In patients with a large-vessel occlu- autonomic dysfunction, comorbidities (such as diabetic sion, thrombectomy should be considered within 6 hours autonomic neuropathy). or a peripheral effect of levodopa. after symptom onset if noncontrast CT of the head shows Symptom onset after initiation of levodopa therapy should no extensive infarction. Thrombectomy can be considered alert clinicians to this potential drug-related adverse effect. in select patients not treated with thrombolysis in a 6- to Carbidopa blocks the adverse effects of levodopa outside 24-hour time-of-onset window. A large-vessel occlusion can the brain and is always administered in combination with be identified only with vascular imaging; CT angiography is levodopa. However, in patients with severe peripheral side indicated in patients with a suspicion of a large-vessel occlu- effects of levodopa, such as orthostatic hypotension, higher sion on the basis of examination. carbidopa doses can alleviate these symptoms. Intravenous heparin (Option B) is not appropriate Droxidopa (Option A) and fludrocortisone (Option because the patient has received intravenous thrombolysis, B) can be used for symptomatic management of neuro- and any antithrombotic agent should be held within the genic orthostatic hypotension and would be the appropriate first 24 hours in order to reduce hemorrhagic complica- next options if additional carbidopa is ineffective. However, tions. The patient likely has new-onset atrial fibrillation unlike carbidopa, these medications are associated with risk and in the long term should receive anticoagulation for for supine hypertension; therefore, a carbidopa trial should stroke prevention; in the acute setting, however, anticoag- be prioritized. ulation is not associated with a reduced risk for stroke and Gabapentin (Option C) can improve neuropathic pain is associated with a higher risk for hemorrhagic transfor- and paresthesia but has no role in improving autonomic mation of ischemic stroke. neuropathy or preventing falls. Intravenous labetalol (Option C) should not be admin- Dopamine agonists, such as pramipexole (Option D), istered because the patient's blood pressure is less than can cause orthostatic hypotension and are likely to aggra- the recommended threshold of 180/105 mm Hg following vate the risk for falls in this patient. This drug would have

Educational Objective: Manage drug-related orthostatic The most appropriate management is CT angiography of the hypotension in Parkinson disease. brain (Option A). The patient is seen because of an acute ischemic stroke within 3 hours of onset and was appropri- The most appropriate next step to prevent additional falls is ately treated with intravenous alteplase. Patients eligible for to increase the dosage of carbidopa (Option E). Patients with alteplase should receive alteplase even if mechanical throm- Parkinson disease and falls, such as this patient, should be bectomy is being considered. She has had a large stroke, assessed for postural imbalance, impaired stepping, freezing with a National Institutes of Health Stroke Scale score of 18, of gait, and orthostatic hypotension. This patient’s history of and has examination findings consistent with a large-vessel lightheadedness on standing and substantial drop in stand- (middle cerebral or intracranial carotid artery) occlusion, ing blood pressure suggests orthostatic hypotension as the including aphasia. A large-vessel occlusion is associated likely cause of his fall. Examination reveals no freezing of with lower rates of neurologic improvement and recanali- gait or postural impairment, findings that are often noted zation with alteplase; treatment with thrombectomy after in more advanced Parkinson disease. Orthostatic hypoten- thrombolysis is indicated and associated with improved sion in Parkinson disease can be due to disease-related neurologic outcomes. In patients with a large-vessel occlu- autonomic dysfunction, comorbidities (such as diabetic sion, thrombectomy should be considered within 6 hours autonomic neuropathy). or a peripheral effect of levodopa. after symptom onset if noncontrast CT of the head shows Symptom onset after initiation of levodopa therapy should no extensive infarction. Thrombectomy can be considered alert clinicians to this potential drug-related adverse effect. in select patients not treated with thrombolysis in a 6- to Carbidopa blocks the adverse effects of levodopa outside 24-hour time-of-onset window. A large-vessel occlusion can the brain and is always administered in combination with be identified only with vascular imaging; CT angiography is levodopa. However, in patients with severe peripheral side indicated in patients with a suspicion of a large-vessel occlu- effects of levodopa, such as orthostatic hypotension, higher sion on the basis of examination. carbidopa doses can alleviate these symptoms. Intravenous heparin (Option B) is not appropriate Droxidopa (Option A) and fludrocortisone (Option because the patient has received intravenous thrombolysis, B) can be used for symptomatic management of neuro- and any antithrombotic agent should be held within the genic orthostatic hypotension and would be the appropriate first 24 hours in order to reduce hemorrhagic complica- next options if additional carbidopa is ineffective. However, tions. The patient likely has new-onset atrial fibrillation unlike carbidopa, these medications are associated with risk and in the long term should receive anticoagulation for for supine hypertension; therefore, a carbidopa trial should stroke prevention; in the acute setting, however, anticoag- be prioritized. ulation is not associated with a reduced risk for stroke and Gabapentin (Option C) can improve neuropathic pain is associated with a higher risk for hemorrhagic transfor- and paresthesia but has no role in improving autonomic mation of ischemic stroke. neuropathy or preventing falls. Intravenous labetalol (Option C) should not be admin- Dopamine agonists, such as pramipexole (Option D), istered because the patient's blood pressure is less than can cause orthostatic hypotension and are likely to aggra- the recommended threshold of 180/105 mm Hg following vate the risk for falls in this patient. This drug would have 132

«SWE and Grivigaes been an appropriate option if the falls were related to motor this patient’s myoclonic seizures, a typical duration of 1 to symptoms of Parkinson disease, such as shuffling and freez- 3 minutes. Also, unlike myoclonic seizures, GTCS are char- CONT. ing, rather than orthostatic hypotension. In addition, it is acterized by altered awareness and post-event confusion. important to ensure levodopa therapy is optimized before Tonic seizures (Option D) are also short, lasting only considering adding other medications. a few seconds, and are associated with generalized muscle stiffening. Tonic seizures are typically painful if awareness is retained, although awareness is typically altered and leads to e Patients with Parkinson disease and falls should be falling. Tonic seizures typically occur in patients with neuro- assessed for postural imbalance, impaired stepping, logic developmental disabilities and epilepsies with multiple freezing of gait, and orthostatic hypotension. seizure types; this patient is an otherwise neurologically e In patients with Parkinson disease who experience healthy adult with brief episodes of myoclonus without

been an appropriate option if the falls were related to motor this patient’s myoclonic seizures, a typical duration of 1 to symptoms of Parkinson disease, such as shuffling and freez- 3 minutes. Also, unlike myoclonic seizures, GTCS are char- CONT. ing, rather than orthostatic hypotension. In addition, it is acterized by altered awareness and post-event confusion. important to ensure levodopa therapy is optimized before Tonic seizures (Option D) are also short, lasting only considering adding other medications. a few seconds, and are associated with generalized muscle stiffening. Tonic seizures are typically painful if awareness is retained, although awareness is typically altered and leads to e Patients with Parkinson disease and falls should be falling. Tonic seizures typically occur in patients with neuro- assessed for postural imbalance, impaired stepping, logic developmental disabilities and epilepsies with multiple freezing of gait, and orthostatic hypotension. seizure types; this patient is an otherwise neurologically e In patients with Parkinson disease who experience healthy adult with brief episodes of myoclonus without severe peripheral side effects of levodopa, such as impairment of consciousness. wo orthostatic hypotension, higher carbidopa doses can a Ej alleviate these symptoms. e Characteristic clinical findings of myoclonus are brief me: (<1 second), “shock-like” involuntary movements - Bibliography ws) caused by muscular contractions. =) Seppi K, Ray Chaudhuri K, Coelho M, et al; the collaborators of the e Parkinson’s Disease Update on Non-Motor Symptoms Study Group on e Myoclonus and retained awareness are the defining © behalf of the Movement Disorders Society Evidence-Based Medicine wn Committee. Update on treatments for nonmotor symptoms of manifestations of myoclonic seizures. ed o Parkinson’s disease-an evidence-based medicine review. Mov Disord. > 2019;34:180-98. [PMID: 30653247] doi:10.1002/mds.27602 wn Bibliography = <x Baykan B, Wolf P. Juvenile myoclonic epilepsy as a spectrum disorder: A focused review. Seizure. 2017;49:36-41. [PMID: 28544889] doi:10.1016/ Item 34 Answer: C j.seizure.2017.05.011

severe peripheral side effects of levodopa, such as impairment of consciousness. wo orthostatic hypotension, higher carbidopa doses can a Ej alleviate these symptoms. e Characteristic clinical findings of myoclonus are brief me: (<1 second), “shock-like” involuntary movements - Bibliography ws) caused by muscular contractions. =) Seppi K, Ray Chaudhuri K, Coelho M, et al; the collaborators of the e Parkinson’s Disease Update on Non-Motor Symptoms Study Group on e Myoclonus and retained awareness are the defining © behalf of the Movement Disorders Society Evidence-Based Medicine wn Committee. Update on treatments for nonmotor symptoms of manifestations of myoclonic seizures. ed o Parkinson’s disease-an evidence-based medicine review. Mov Disord. > 2019;34:180-98. [PMID: 30653247] doi:10.1002/mds.27602 wn Bibliography = <x Baykan B, Wolf P. Juvenile myoclonic epilepsy as a spectrum disorder: A focused review. Seizure. 2017;49:36-41. [PMID: 28544889] doi:10.1016/ Item 34 Answer: C j.seizure.2017.05.011 Educational Objective: Diagnose myoclonic seizures.

severe peripheral side effects of levodopa, such as impairment of consciousness. wo orthostatic hypotension, higher carbidopa doses can a Ej alleviate these symptoms. e Characteristic clinical findings of myoclonus are brief me: (<1 second), “shock-like” involuntary movements - Bibliography ws) caused by muscular contractions. =) Seppi K, Ray Chaudhuri K, Coelho M, et al; the collaborators of the e Parkinson’s Disease Update on Non-Motor Symptoms Study Group on e Myoclonus and retained awareness are the defining © behalf of the Movement Disorders Society Evidence-Based Medicine wn Committee. Update on treatments for nonmotor symptoms of manifestations of myoclonic seizures. ed o Parkinson’s disease-an evidence-based medicine review. Mov Disord. > 2019;34:180-98. [PMID: 30653247] doi:10.1002/mds.27602 wn Bibliography = <x Baykan B, Wolf P. Juvenile myoclonic epilepsy as a spectrum disorder: A focused review. Seizure. 2017;49:36-41. [PMID: 28544889] doi:10.1016/ Item 34 Answer: C j.seizure.2017.05.011 Educational Objective: Diagnose myoclonic seizures. The most likely diagnosis is myoclonic seizures (Option C), Item 35 Answer: E which typically have very short duration (<1 second) with Educational Objective: Manage elevated blood pressure retained awareness. Characteristic clinical findings of myoc- in a patient with ischemic stroke. lonus are brief, “shock-like” involuntary movements caused by muscular contractions (positive myoclonus) or inhibi- The most appropriate immediate action is no further inter- tions (negative myoclonus, [e.g., asterixis]). Positive myoc- vention or treatment (Option E). The patient has had a minor lonus is the defining seizure manifestation of myoclonic sei- ischemic stroke (National Institutes of Health Stroke Scale zures. When describing symptoms, patients will usually use score of 3) due to high-grade stenosis of the middle cerebral words like “twitches”, “spasms,” “jerks,” or even “shakes.” artery. He is receiving the most appropriate medical ther Patients are often described as “clumsy” before establishing apy, including dual antiplatelet agents and a high-intensity the diagnosis of myoclonic seizure, since suddenly dropping statin. In the long term, the patient will require control of items is a common symptom. Myoclonic seizures are con- hypertension. A target blood pressure less than 130/80 mm sidered generalized seizures, which involve the entire body. Hg is considered a reasonable therapeutic target for most They may occur more often on awakening, and recording an patients. In the first 48 hours, however, and especially in electroencephalogram (EEG) after a period of sleep may help patients with symptomatic intracranial stenosis, lowering capture evidence of the seizure for diagnostic confirmation. blood pressure is associated with neurologic worsening. Myoclonus should not be confused with myoclonic seizures; Furosemide, chlorthalidone, and lisinopril (Options A-C) myoclonus is a single muscle group twitch that may be focal are not appropriate because blood pressure lowering in the or generalized, but which may or may not represent a sei- acute setting is associated with neurologic worsening. Acute zure. For example, benign myoclonus of sleep, the so-called lowering of blood pressure is indicated if clinical findings sug- hypnic jerks commonly experienced when falling asleep, are gest end-organ damage, including active ischemic coronary normal; unlike with a myoclonic seizure, the EEG pattern disease, heart failure, aortic dissection, or hypertensive enceph would be normal during the myoclonic event. alopathy. Treatment in the acute setting is also indicated in Focal motor aware seizures (Option A), previously patients who are receiving intravenous alteplase, to maintain known as complex partial seizures, typically originate in the the blood pressure less than 180/105 mm Hg. In others, treat- frontal lobe, where the motor cortex controls contralateral ment is indicated if blood pressure exceeds 220/120 mm Hg. In limb movement. By definition, the shaking of these sei- these patients, it might be reasonable to lower blood pressure zures is rhythmic, repetitive, and unilateral. Similar to JME, by 15% during the first 24 hours after onset of stroke. patients with focal motor seizures are alert and responsive. Intracranial stenting (Option D) of symptomatic intra- Generalized tonic-clonic seizures (GTCS) (Option B) cranial arterial stenosis is not appropriate because it is are typically characterized by abrupt loss of consciousness, associated with a high risk for procedural stroke and no whole body stiffening followed by shaking, and, unlike long-term reduction in risk for subsequent stroke. Stenting

The most likely diagnosis is myoclonic seizures (Option C), Item 35 Answer: E which typically have very short duration (<1 second) with Educational Objective: Manage elevated blood pressure retained awareness. Characteristic clinical findings of myoc- in a patient with ischemic stroke. lonus are brief, “shock-like” involuntary movements caused by muscular contractions (positive myoclonus) or inhibi- The most appropriate immediate action is no further inter- tions (negative myoclonus, [e.g., asterixis]). Positive myoc- vention or treatment (Option E). The patient has had a minor lonus is the defining seizure manifestation of myoclonic sei- ischemic stroke (National Institutes of Health Stroke Scale zures. When describing symptoms, patients will usually use score of 3) due to high-grade stenosis of the middle cerebral words like “twitches”, “spasms,” “jerks,” or even “shakes.” artery. He is receiving the most appropriate medical ther Patients are often described as “clumsy” before establishing apy, including dual antiplatelet agents and a high-intensity the diagnosis of myoclonic seizure, since suddenly dropping statin. In the long term, the patient will require control of items is a common symptom. Myoclonic seizures are con- hypertension. A target blood pressure less than 130/80 mm sidered generalized seizures, which involve the entire body. Hg is considered a reasonable therapeutic target for most They may occur more often on awakening, and recording an patients. In the first 48 hours, however, and especially in electroencephalogram (EEG) after a period of sleep may help patients with symptomatic intracranial stenosis, lowering capture evidence of the seizure for diagnostic confirmation. blood pressure is associated with neurologic worsening. Myoclonus should not be confused with myoclonic seizures; Furosemide, chlorthalidone, and lisinopril (Options A-C) myoclonus is a single muscle group twitch that may be focal are not appropriate because blood pressure lowering in the or generalized, but which may or may not represent a sei- acute setting is associated with neurologic worsening. Acute zure. For example, benign myoclonus of sleep, the so-called lowering of blood pressure is indicated if clinical findings sug- hypnic jerks commonly experienced when falling asleep, are gest end-organ damage, including active ischemic coronary normal; unlike with a myoclonic seizure, the EEG pattern disease, heart failure, aortic dissection, or hypertensive enceph would be normal during the myoclonic event. alopathy. Treatment in the acute setting is also indicated in Focal motor aware seizures (Option A), previously patients who are receiving intravenous alteplase, to maintain known as complex partial seizures, typically originate in the the blood pressure less than 180/105 mm Hg. In others, treat- frontal lobe, where the motor cortex controls contralateral ment is indicated if blood pressure exceeds 220/120 mm Hg. In limb movement. By definition, the shaking of these sei- these patients, it might be reasonable to lower blood pressure zures is rhythmic, repetitive, and unilateral. Similar to JME, by 15% during the first 24 hours after onset of stroke. patients with focal motor seizures are alert and responsive. Intracranial stenting (Option D) of symptomatic intra- Generalized tonic-clonic seizures (GTCS) (Option B) cranial arterial stenosis is not appropriate because it is are typically characterized by abrupt loss of consciousness, associated with a high risk for procedural stroke and no whole body stiffening followed by shaking, and, unlike long-term reduction in risk for subsequent stroke. Stenting 133

Answers and Critiques can be considered on a case-by-case basis if the patient weakness is not typical. This patient does not exhibit signs has additional infarcts despite adherence to best medical of myeloneuropathy. CONT. therapy.

Answers and Critiques can be considered on a case-by-case basis if the patient weakness is not typical. This patient does not exhibit signs has additional infarcts despite adherence to best medical of myeloneuropathy. CONT. therapy. e Hypothyroid myopathy is associated with proximal e Inpatients not eligible for thrombolytic therapy, the blood symmetric weakness, myalgia, and cramps without pressure (BP) threshold for initiating antihypertensive sensory loss or upper motor neuron signs, and muscle therapy is greater than 220/120 mm Hg; reduction of BP mounding after percussion (myoedema). by 15% during the first 24 hours may then be reasonable. e Myopathy may be the only manifestation of hypothy- roidism. Bibliography Powers WJ, Rabinstein AA, Ackerson T, et al; American Heart Association Bibliography Stroke Council. 2018 Guidelines for the Early Management of > Patients With Acute Ischemic Stroke: A Guideline for Healthcare Sindoni A, Rodolico C, Pappalardo MA, et al. Hypothyroid myopathy: a pecu- = wn Professionals From the American Heart Association/American Stroke liar clinical presentation of thyroid failure. Review of the literature. Rev = Association. Stroke. 2018;49:e46-e110. [PMID: 29367334] doi:10.1161/ Endocr Metab Disord. 2016;17:499-519. [PMID: 27154040] doi:10.1007/ © STR.0000000000000158 $11154-016-9357-0 = wn pe) s 2. a Item 36 Answer: C Item 37 Answer: D ae a2 Educational Objective: Diagnose hypothyroid myopathy. Educational Objective: Diagnose statin-induced 2 < myopathy. © The most likely cause of this patient’s findings is hypo- wn thyroidism, and the most likely diagnosis is hypothyroid The most likely diagnosis is statin-induced myopathy myopathy (Option C). The clinical presentation of proximal (Option D). The incidence of statin-induced muscle symp- symmetric weakness, myalgia, and cramps without sen- toms is no greater than 1%, and the incidence of myopathy sory loss or upper motor neuron signs is consistent with a and rhabdomyolysis is less than 0.1%. Statin-induced myo- myopathy. In this patient, the finding of muscle mounding pathy manifests as unexplained muscle pain or weakness after percussion (myoedema) strongly suggests hypothyroid- with an increase in the creatine kinase (CK) level up to ism. The diagnosis of primary hypothyroidism is made by 10 times the upper limit of normal (ULN). Statin-induced measuring serum thyroid-stimulating hormone level and, rhabdomyolysis is a more severely symptomatic form of if elevated, measuring the level of serum free thyroxine myopathy with CK levels typically greater than 40 times (T,). Clinical symptoms and signs can be nonspecific, often the ULN. Most patients experience statin-induced myopathy resulting in a delayed diagnosis. If asked, most patients do within the first year of therapy after a dose increase or the have muscular symptoms (stiffness, myalgias, cramps, easy addition of an interacting drug. Most drugs that interact with fatigability), and muscle symptoms may be the predomi- statins increase the statin blood concentration and the risk nant or the only clinical manifestation of hypothyroidism. of myopathy/rhabdomyolysis. The typical clinical presenta- If measured, serum creatine kinase is elevated in many tion consists of symmetric muscle pain and weakness, but patients with hypothyroidism, but the degree of elevation nonspecific lower back pain has been reported as a feature of does not always correlate with the severity of muscle symp- statin-induced myopathy. The serum CK level should be toms. Other features that may be seen with hypothyroid measured in patients taking a statin who develop mus- myopathy include goiter, ptosis, enlarged muscle bulk, and cle pain or weakness. Delay in making the diagnosis (and delayed relaxation of deep tendon reflexes (Woltman sign). stopping the statin) can lead to rhabdomyolysis and possi- Copper deficiency (Option A) can lead to myeloneuro- bly acute kidney injury. Discontinuation of the statin most pathy associated with large-fiber sensory deficit, ataxia, and commonly results in a rapid resolution of symptoms and brisk reflexes. In this patient, proximal weakness, intact sen- normalization of the serum CK level. sory examination, and absence of upper motor neuron signs Immune-mediated necrotizing myopathy (IMNM) (such as the extensor plantar response and hyperreflexia) are (Option A) presents acutely or subacutely with more severe inconsistent with copper deficiency. proximal muscle pain and extremely high CK levels. The Hypokalemia (Option B) can be associated with muscle vast majority of patients on statins with muscle pain do not weakness and cramps. However, this patient’s myoedema is have IMNM. This patient with mild symptoms and modest not a typical feature of hypokalemia. Hypokalemic periodic elevation of CK is unlikely to have IMNM. paralysis is a rare genetic disorder associated with episodic Polymyalgia rheumatica (Option B) is an inflammatory weakness. disorder associated with pain and stiffness of the neck, Vitamin D deficiency (Option D) can be associated with shoulder, and hip girdle. The erythrocyte sedimentation rate myalgia and proximal weakness. Myoedema is not a feature is invariably elevated but the CK level is normal. of vitamin D deficiency. Proximal lumbosacral radiculoneuropathy (Option C) Vitamin E deficiency (Option E) can cause myelopathy is associated with subacute painful involvement of the lum- and peripheral neuropathy, but myopathy with proximal bosacral plexus followed by resolution of pain and onset of

e Hypothyroid myopathy is associated with proximal e Inpatients not eligible for thrombolytic therapy, the blood symmetric weakness, myalgia, and cramps without pressure (BP) threshold for initiating antihypertensive sensory loss or upper motor neuron signs, and muscle therapy is greater than 220/120 mm Hg; reduction of BP mounding after percussion (myoedema). by 15% during the first 24 hours may then be reasonable. e Myopathy may be the only manifestation of hypothy- roidism. Bibliography Powers WJ, Rabinstein AA, Ackerson T, et al; American Heart Association Bibliography Stroke Council. 2018 Guidelines for the Early Management of > Patients With Acute Ischemic Stroke: A Guideline for Healthcare Sindoni A, Rodolico C, Pappalardo MA, et al. Hypothyroid myopathy: a pecu- = wn Professionals From the American Heart Association/American Stroke liar clinical presentation of thyroid failure. Review of the literature. Rev = Association. Stroke. 2018;49:e46-e110. [PMID: 29367334] doi:10.1161/ Endocr Metab Disord. 2016;17:499-519. [PMID: 27154040] doi:10.1007/ © STR.0000000000000158 $11154-016-9357-0 = wn pe) s 2. a Item 36 Answer: C Item 37 Answer: D ae a2 Educational Objective: Diagnose hypothyroid myopathy. Educational Objective: Diagnose statin-induced 2 < myopathy. © The most likely cause of this patient’s findings is hypo- wn thyroidism, and the most likely diagnosis is hypothyroid The most likely diagnosis is statin-induced myopathy myopathy (Option C). The clinical presentation of proximal (Option D). The incidence of statin-induced muscle symp- symmetric weakness, myalgia, and cramps without sen- toms is no greater than 1%, and the incidence of myopathy sory loss or upper motor neuron signs is consistent with a and rhabdomyolysis is less than 0.1%. Statin-induced myo- myopathy. In this patient, the finding of muscle mounding pathy manifests as unexplained muscle pain or weakness after percussion (myoedema) strongly suggests hypothyroid- with an increase in the creatine kinase (CK) level up to ism. The diagnosis of primary hypothyroidism is made by 10 times the upper limit of normal (ULN). Statin-induced measuring serum thyroid-stimulating hormone level and, rhabdomyolysis is a more severely symptomatic form of if elevated, measuring the level of serum free thyroxine myopathy with CK levels typically greater than 40 times (T,). Clinical symptoms and signs can be nonspecific, often the ULN. Most patients experience statin-induced myopathy resulting in a delayed diagnosis. If asked, most patients do within the first year of therapy after a dose increase or the have muscular symptoms (stiffness, myalgias, cramps, easy addition of an interacting drug. Most drugs that interact with fatigability), and muscle symptoms may be the predomi- statins increase the statin blood concentration and the risk nant or the only clinical manifestation of hypothyroidism. of myopathy/rhabdomyolysis. The typical clinical presenta- If measured, serum creatine kinase is elevated in many tion consists of symmetric muscle pain and weakness, but patients with hypothyroidism, but the degree of elevation nonspecific lower back pain has been reported as a feature of does not always correlate with the severity of muscle symp- statin-induced myopathy. The serum CK level should be toms. Other features that may be seen with hypothyroid measured in patients taking a statin who develop mus- myopathy include goiter, ptosis, enlarged muscle bulk, and cle pain or weakness. Delay in making the diagnosis (and delayed relaxation of deep tendon reflexes (Woltman sign). stopping the statin) can lead to rhabdomyolysis and possi- Copper deficiency (Option A) can lead to myeloneuro- bly acute kidney injury. Discontinuation of the statin most pathy associated with large-fiber sensory deficit, ataxia, and commonly results in a rapid resolution of symptoms and brisk reflexes. In this patient, proximal weakness, intact sen- normalization of the serum CK level. sory examination, and absence of upper motor neuron signs Immune-mediated necrotizing myopathy (IMNM) (such as the extensor plantar response and hyperreflexia) are (Option A) presents acutely or subacutely with more severe inconsistent with copper deficiency. proximal muscle pain and extremely high CK levels. The Hypokalemia (Option B) can be associated with muscle vast majority of patients on statins with muscle pain do not weakness and cramps. However, this patient’s myoedema is have IMNM. This patient with mild symptoms and modest not a typical feature of hypokalemia. Hypokalemic periodic elevation of CK is unlikely to have IMNM. paralysis is a rare genetic disorder associated with episodic Polymyalgia rheumatica (Option B) is an inflammatory weakness. disorder associated with pain and stiffness of the neck, Vitamin D deficiency (Option D) can be associated with shoulder, and hip girdle. The erythrocyte sedimentation rate myalgia and proximal weakness. Myoedema is not a feature is invariably elevated but the CK level is normal. of vitamin D deficiency. Proximal lumbosacral radiculoneuropathy (Option C) Vitamin E deficiency (Option E) can cause myelopathy is associated with subacute painful involvement of the lum- and peripheral neuropathy, but myopathy with proximal bosacral plexus followed by resolution of pain and onset of 134

Answers and Critiques marked asymmetric weakness with atrophy and weight loss. sleep-wake cycle. Unless patients are at risk of harm to It is often associated with diabetes, even when glucose levels themselves or others, antipsychotic agents such as queti- are well controlled. The patient’s symptoms do not match apine (Option C) should be avoided because psychoactive those of proximal lumbosacral radiculopathy. and sedating medications can contribute to the development of delirium. Scheduled morphine administration (Option D) is ¢ Statin-induced myopathy is rare and manifests as likely to overtreat the patient’s pain and lead to sedation. unexplained proximal muscle pain or weakness with It is important to treat pain, but pain should be managed an increase in serum creatine kinase level. using the least sedating agents possible in patients at risk e Discontinuation of the statin most commonly results for delirium. in a rapid resolution of muscle symptoms and nor- malization of the serum creatine kinase level. e Identifying and correcting sensory impairments, wn a including providing patients with their visual and 3 Bibliography Newman CB, Preiss D, Tobert JA, et al; American Heart Association Clinical hearing aids, is effective in the prevention of delirium. = Lipidology, Lipoprotein, Metabolism and Thrombosis Committee, a Joint = Committee of the Council on Atherosclerosis, Thrombosis and rs) Bibliography sc Vascular Biology and Council on Lifestyle and Cardiometabolic Health; Marcantonio ER. Delirium in hospitalized older adults. N Engl J Med. = Council on Cardiovascular Disease in the Young; Council on Clinical ec Cardiology; and Stroke Council. Statin safety and associated adverse 2017;377:1456-66. [PMID: 29020579] doi: 10.1056/NEJMcp1605501 wr oT events: a scientific statement from the American Heart Association. a Arterioscler Thromb Vasc Biol. 2019;39:e38-e81. [PMID: 30580575] = doi:10.1161/ATV.0000000000000073 4) Item 39 Answer: B = < Educational Objective: Prevent venous thromboembo- C) Item 38 Answer: E lism in patients with primary brain tumors. Educational Objective: Prevent delirium in a Mechanical prophylaxis (Option B) is the most appropriate hospitalized patient. venous thromboembolism (VTE) prophylaxis immediately This patient’s glasses and hearing aids should be provided to following cranial surgery. Patients with primary and malig- him to prevent delirium (Option E). Delirium is a potentially nant brain tumors, as with most patients with cancer, are preventable syndrome associated with other medical disor: hypercoagulable and predisposed to VTE. The perioperative ders, the adverse effects of medication, or drug withdrawal. risk associated with glioma approaches 25% in some studies It is common in hospitalized patients, and elderly patients and prophylaxis should begin on admission to the hos such as this one are at higher risk postsurgery. Delirium pital. Guidelines recommend pharmacologic VTE prophy- is associated with increases in morbidity, medical com laxis over mechanical prophylaxis in acutely or critically ill plications, hospital length of stay, and rate of discharge to patients. In situations in which pharmacologic prophylaxis long-term care facilities; prevention is more effective than cannot be given, such as immediately prior to or following treatment of delirium, especially in at-risk patients. Iden neurosurgery, guidelines recommend mechanical prophy- tifying and correcting sensory impairments, including laxis over no prophylaxis. Mechanical prophylaxis choices providing patients with their visual and hearing aids, is for patients undergoing cranial surgery include either inter- an environmental modification that has been shown to be mittent pneumatic compression or graduated compression effective in the prevention of delirium. stockings. However, not all guidelines support the use of Early mobilization prevents delirium, so the patient compression stockings for VTE prophylaxis. The differing does not need bedrest (Option A) outside of physical therapy. recommendations relate to the quality of evidence and val- Checking vital signs every 2 hours would entail awak- ues assigned to benefits and harms. Recent guidelines rec- ening the patient throughout the night (Option B). Because ommend continuation of mechanical prophylaxis following altered circadian rhythm is a component of the clinical cranial surgery for 30 days or until the patient is mobile syndrome of delirium, promoting a normal sleep-wake cycle or discharged, whichever is sooner. The addition of low- by limiting interruptions during nocturnal sleeping hours, molecular-weight heparin (LMWH) starting 24 to 48 hours minimizing light and noise at night, and opening curtains after cranial surgery and continued for 7 days after surgery and encouraging activity during the daytime is an import- is also suggested for patients whose risk of VTE outweighs ant element in the prevention of delirium. Finally, frequent their risk of bleeding. monitoring of vital signs may provide early detection of In the immediate perioperative period neither LMWH changes in clinical status but will not prevent delirium. (Option A) nor unfractionated heparin (UFH) (Option C) is No medication is currently approved by the FDA for recommended because of the risk of intracerebral bleeding. the management of delirium, so the use of these agents for When anticoagulation can be safely initiated, guidelines such an indication is off-label. Furthermore. there is no suggest LMWH over UF unless there is significant renal strong evidence that any particular drug is useful for delir impairment (creatinine clearance < 30 mL/min). Studies ium prevention. Melatonin may assist in maintaining the evaluating the effectiveness of long-term prophylaxis with

marked asymmetric weakness with atrophy and weight loss. sleep-wake cycle. Unless patients are at risk of harm to It is often associated with diabetes, even when glucose levels themselves or others, antipsychotic agents such as queti- are well controlled. The patient’s symptoms do not match apine (Option C) should be avoided because psychoactive those of proximal lumbosacral radiculopathy. and sedating medications can contribute to the development of delirium. Scheduled morphine administration (Option D) is ¢ Statin-induced myopathy is rare and manifests as likely to overtreat the patient’s pain and lead to sedation. unexplained proximal muscle pain or weakness with It is important to treat pain, but pain should be managed an increase in serum creatine kinase level. using the least sedating agents possible in patients at risk e Discontinuation of the statin most commonly results for delirium. in a rapid resolution of muscle symptoms and nor- malization of the serum creatine kinase level. e Identifying and correcting sensory impairments, wn a including providing patients with their visual and 3 Bibliography Newman CB, Preiss D, Tobert JA, et al; American Heart Association Clinical hearing aids, is effective in the prevention of delirium. = Lipidology, Lipoprotein, Metabolism and Thrombosis Committee, a Joint = Committee of the Council on Atherosclerosis, Thrombosis and rs) Bibliography sc Vascular Biology and Council on Lifestyle and Cardiometabolic Health; Marcantonio ER. Delirium in hospitalized older adults. N Engl J Med. = Council on Cardiovascular Disease in the Young; Council on Clinical ec Cardiology; and Stroke Council. Statin safety and associated adverse 2017;377:1456-66. [PMID: 29020579] doi: 10.1056/NEJMcp1605501 wr oT events: a scientific statement from the American Heart Association. a Arterioscler Thromb Vasc Biol. 2019;39:e38-e81. [PMID: 30580575] = doi:10.1161/ATV.0000000000000073 4) Item 39 Answer: B = < Educational Objective: Prevent venous thromboembo- C) Item 38 Answer: E lism in patients with primary brain tumors. Educational Objective: Prevent delirium in a Mechanical prophylaxis (Option B) is the most appropriate hospitalized patient. venous thromboembolism (VTE) prophylaxis immediately This patient’s glasses and hearing aids should be provided to following cranial surgery. Patients with primary and malig- him to prevent delirium (Option E). Delirium is a potentially nant brain tumors, as with most patients with cancer, are preventable syndrome associated with other medical disor: hypercoagulable and predisposed to VTE. The perioperative ders, the adverse effects of medication, or drug withdrawal. risk associated with glioma approaches 25% in some studies It is common in hospitalized patients, and elderly patients and prophylaxis should begin on admission to the hos such as this one are at higher risk postsurgery. Delirium pital. Guidelines recommend pharmacologic VTE prophy- is associated with increases in morbidity, medical com laxis over mechanical prophylaxis in acutely or critically ill plications, hospital length of stay, and rate of discharge to patients. In situations in which pharmacologic prophylaxis long-term care facilities; prevention is more effective than cannot be given, such as immediately prior to or following treatment of delirium, especially in at-risk patients. Iden neurosurgery, guidelines recommend mechanical prophy- tifying and correcting sensory impairments, including laxis over no prophylaxis. Mechanical prophylaxis choices providing patients with their visual and hearing aids, is for patients undergoing cranial surgery include either inter- an environmental modification that has been shown to be mittent pneumatic compression or graduated compression effective in the prevention of delirium. stockings. However, not all guidelines support the use of Early mobilization prevents delirium, so the patient compression stockings for VTE prophylaxis. The differing does not need bedrest (Option A) outside of physical therapy. recommendations relate to the quality of evidence and val- Checking vital signs every 2 hours would entail awak- ues assigned to benefits and harms. Recent guidelines rec- ening the patient throughout the night (Option B). Because ommend continuation of mechanical prophylaxis following altered circadian rhythm is a component of the clinical cranial surgery for 30 days or until the patient is mobile syndrome of delirium, promoting a normal sleep-wake cycle or discharged, whichever is sooner. The addition of low- by limiting interruptions during nocturnal sleeping hours, molecular-weight heparin (LMWH) starting 24 to 48 hours minimizing light and noise at night, and opening curtains after cranial surgery and continued for 7 days after surgery and encouraging activity during the daytime is an import- is also suggested for patients whose risk of VTE outweighs ant element in the prevention of delirium. Finally, frequent their risk of bleeding. monitoring of vital signs may provide early detection of In the immediate perioperative period neither LMWH changes in clinical status but will not prevent delirium. (Option A) nor unfractionated heparin (UFH) (Option C) is No medication is currently approved by the FDA for recommended because of the risk of intracerebral bleeding. the management of delirium, so the use of these agents for When anticoagulation can be safely initiated, guidelines such an indication is off-label. Furthermore. there is no suggest LMWH over UF unless there is significant renal strong evidence that any particular drug is useful for delir impairment (creatinine clearance < 30 mL/min). Studies ium prevention. Melatonin may assist in maintaining the evaluating the effectiveness of long-term prophylaxis with 135

Answers and Critiques LMWH in patients with glioma show a trend toward fewer neurosurgical clipping versus endovascular coiling has sim- episodes of VTE but more episodes of intracerebral hemor ilar success at occlusion of the aneurysm, and the choice of CONT. rhage; therefore, long-term therapy is not recommended for one modality over another is dictated by aneurysm shape most patients with glioma. and location and by operator experience. Providing no VTE prophylaxis (Option D) is not the Because it is invasive, catheter-based angiography best option because it places the patient at increased (Option C) is not routinely indicated for imaging of aneur- risk for VTE. All guidelines agree that acutely ill medical ysms unless further treatment is planned on the basis of patients, patients with active cancer, surgical patients, features that could help predict rupture. CT angiography and selected patients with identifiable risk factors should (Option D) is also incorrect because an additional test is not receive VTE prophylaxis during hospitalization. likely to reveal a change in the size of the aneurysm, and CT is associated with risks from radiation and contrast medium.

LMWH in patients with glioma show a trend toward fewer neurosurgical clipping versus endovascular coiling has sim- episodes of VTE but more episodes of intracerebral hemor ilar success at occlusion of the aneurysm, and the choice of CONT. rhage; therefore, long-term therapy is not recommended for one modality over another is dictated by aneurysm shape most patients with glioma. and location and by operator experience. Providing no VTE prophylaxis (Option D) is not the Because it is invasive, catheter-based angiography best option because it places the patient at increased (Option C) is not routinely indicated for imaging of aneur- risk for VTE. All guidelines agree that acutely ill medical ysms unless further treatment is planned on the basis of patients, patients with active cancer, surgical patients, features that could help predict rupture. CT angiography and selected patients with identifiable risk factors should (Option D) is also incorrect because an additional test is not receive VTE prophylaxis during hospitalization. likely to reveal a change in the size of the aneurysm, and CT is associated with risks from radiation and contrast medium. p> e Perioperative mechanical venous thromboembolism = prophylaxis is a reasonable option for patients under- wn e Risk for rupture at 5 years is low for unruptured = going cranial surgery. intracranial arterial aneurysms less than 7 mm in the © a ¢ Subcutaneous low-molecular-weight heparin added posterior circulation and less than 12 mm in the ante- ro) | to mechanical venous thromboembolism prophylaxis rior circulation. 2. is reasonable 24 to 48 hours following resection of e Annual noninvasive imaging is recommended in patients (a) a primary brain tumors for patients whose risk of VTE with an unruptured aneurysm. =a 2 outweighs their risk of bleeding. i © Bibliography wn Bibliography Thompson BG, Brown RD Jr, Amin-Hanjani S, et al; American Heart Association Stroke Council, Council on Cardiovascular and Stroke National Institute for Health and Care Excellence. Venous thromboembo- Nursing, and Council on Epidemiology and Prevention. Guidelines for lism in over 16s: reducing the risk of hospital-acquired deep vein throm- the Management of Patients With Unruptured Intracranial Aneurysms: A bosis or pulmonary embolism. https: //www.nice.org.uk/guidance/ng89. Guideline for Healthcare Professionals From the American Heart Accessed May 2, 2020. Association/American Stroke Association. Stroke. 2015;46:2368-400. [PMID: 26089327] doi:10.1161/STR.0000000000000070

p> e Perioperative mechanical venous thromboembolism = prophylaxis is a reasonable option for patients under- wn e Risk for rupture at 5 years is low for unruptured = going cranial surgery. intracranial arterial aneurysms less than 7 mm in the © a ¢ Subcutaneous low-molecular-weight heparin added posterior circulation and less than 12 mm in the ante- ro) | to mechanical venous thromboembolism prophylaxis rior circulation. 2. is reasonable 24 to 48 hours following resection of e Annual noninvasive imaging is recommended in patients (a) a primary brain tumors for patients whose risk of VTE with an unruptured aneurysm. =a 2 outweighs their risk of bleeding. i © Bibliography wn Bibliography Thompson BG, Brown RD Jr, Amin-Hanjani S, et al; American Heart Association Stroke Council, Council on Cardiovascular and Stroke National Institute for Health and Care Excellence. Venous thromboembo- Nursing, and Council on Epidemiology and Prevention. Guidelines for lism in over 16s: reducing the risk of hospital-acquired deep vein throm- the Management of Patients With Unruptured Intracranial Aneurysms: A bosis or pulmonary embolism. https: //www.nice.org.uk/guidance/ng89. Guideline for Healthcare Professionals From the American Heart Accessed May 2, 2020. Association/American Stroke Association. Stroke. 2015;46:2368-400. [PMID: 26089327] doi:10.1161/STR.0000000000000070 Item 40 Answer: E Educational Objective: Manage a low-risk intracranial Item 41 Answer: B aneurysm. Educational Objective: Diagnose mild cognitive impairment. The most appropriate management is serial magnetic resonance angiography (Option E). This patient has an The patient has the typical clinical history, cognitive screen- unruptured intracranial arterial aneurysm that is less than ing results, and imaging findings of Alzheimer disease. How- 12 mm in the anterior circulation (anterior cerebral, middle ever, his functional status is independent in all instrumental cerebral, and internal carotid arteries). Such aneurysms are and basic activities of daily living. The diagnosis of mild cog- associated with a low risk for rupture at 5 years. Aneurysms nitive impairment (MCI) (Option B) includes patients with that are less than 7 mm in the posterior circulation (posterior clear symptoms of cognitive decline who do not meet criteria communicating and basilar arteries) have a similarly low for dementia. The formal criteria for MCI are a subjective risk for rupture. Factors associated with increased risk for report (from either the patient or a witness) of a decline in rupture include rapid growth detected over serial imaging, cognitive abilities with relative preservation of day-to-day active tobacco use, and uncontrolled hypertension. Other function and evidence of cognitive impairment on cognitive predictors of aneurysmal rupture that should prompt surgi- testing. Because of wide variability in the risk of progres- cal consideration include a previous aneurysmal subarach- sion, steps should be taken to confirm the underlying cause noid hemorrhage, rapid aneurysm growth, or the presence of the symptoms. In patients with cognitive impairment of cranial nerve palsy. Annual noninvasive imaging is rec- lasting more than 3 months, evaluation should include labo- ommended in patients with an unruptured aneurysm. CT ratory testing for potentially reversible conditions. Examples or MRI angiography can be considered for serial imaging include assessment for medication adverse events, sleep because they are both noninvasive, with CT usually per- apnea, depression, and other common medical conditions formed in patients who cannot undergo MRI. Additional and an MRI without contrast. noninvasive testing on a yearly basis should be performed MRI of the brain supports the diagnosis of Alzheimer to track aneurysm growth, which may be a predictor for disease (Option A) when it shows evidence of decreased rupture. volume of the hippocampi, although this is a nonspecific Aneurysm clipping and coiling (Options A and B) are finding. When seen in MCI, decreased hippocampal volume not indicated because this patient’s risk for rupture is low, predicts a higher likelihood of progression to Alzheimer and the associated neurologic disability and morbidity with dementia. Because of his independence in activities of daily intervention are high. In patients with a ruptured aneurysm, living, this patient does not have Alzheimer dementia.

Item 40 Answer: E Educational Objective: Manage a low-risk intracranial Item 41 Answer: B aneurysm. Educational Objective: Diagnose mild cognitive impairment. The most appropriate management is serial magnetic resonance angiography (Option E). This patient has an The patient has the typical clinical history, cognitive screen- unruptured intracranial arterial aneurysm that is less than ing results, and imaging findings of Alzheimer disease. How- 12 mm in the anterior circulation (anterior cerebral, middle ever, his functional status is independent in all instrumental cerebral, and internal carotid arteries). Such aneurysms are and basic activities of daily living. The diagnosis of mild cog- associated with a low risk for rupture at 5 years. Aneurysms nitive impairment (MCI) (Option B) includes patients with that are less than 7 mm in the posterior circulation (posterior clear symptoms of cognitive decline who do not meet criteria communicating and basilar arteries) have a similarly low for dementia. The formal criteria for MCI are a subjective risk for rupture. Factors associated with increased risk for report (from either the patient or a witness) of a decline in rupture include rapid growth detected over serial imaging, cognitive abilities with relative preservation of day-to-day active tobacco use, and uncontrolled hypertension. Other function and evidence of cognitive impairment on cognitive predictors of aneurysmal rupture that should prompt surgi- testing. Because of wide variability in the risk of progres- cal consideration include a previous aneurysmal subarach- sion, steps should be taken to confirm the underlying cause noid hemorrhage, rapid aneurysm growth, or the presence of the symptoms. In patients with cognitive impairment of cranial nerve palsy. Annual noninvasive imaging is rec- lasting more than 3 months, evaluation should include labo- ommended in patients with an unruptured aneurysm. CT ratory testing for potentially reversible conditions. Examples or MRI angiography can be considered for serial imaging include assessment for medication adverse events, sleep because they are both noninvasive, with CT usually per- apnea, depression, and other common medical conditions formed in patients who cannot undergo MRI. Additional and an MRI without contrast. noninvasive testing on a yearly basis should be performed MRI of the brain supports the diagnosis of Alzheimer to track aneurysm growth, which may be a predictor for disease (Option A) when it shows evidence of decreased rupture. volume of the hippocampi, although this is a nonspecific Aneurysm clipping and coiling (Options A and B) are finding. When seen in MCI, decreased hippocampal volume not indicated because this patient’s risk for rupture is low, predicts a higher likelihood of progression to Alzheimer and the associated neurologic disability and morbidity with dementia. Because of his independence in activities of daily intervention are high. In patients with a ruptured aneurysm, living, this patient does not have Alzheimer dementia. 136

Answers and Critiques Traumatic encephalopathy syndrome (TES) (Option C) Decompressive craniotomy (Option B) can be consid is the progressive neurodegenerative syndrome associated ered in this setting, and it would certainly be a more defin- with repetitive head trauma. Supportive clinical features itive measure. However, the other acute measures are a include emotional dysregulation, behavior change, and necessary bridge to emergent surgery. These measures are motor disturbance with parkinsonian features. Global brain temporizing but can be life-saving. atrophy may be seen on brain imaging. This patient does not Intravenous 0.9% saline (Option D) is likely to increase have the clinical or imaging characteristics of TES. ICP and should not be used. The likelihood of vascular cognitive impairment (Option D) increases with age and is associated with systemic vascu- lar risk factors and a history of stroke. In vascular cognitive e Emergency treatment of increased intracranial pres- impairment, MRIs typically display a pattern of diffuse and sure with impending herniation and death include confluent changes in the white matter of the brain. This elevation of the head of the bed, hyperventilation, patient’s lack of risk factors and MRI are not supportive of dexamethasone (for patients with peritumoral wn rt} vascular cognitive impairment. edema), and osmotic diuresis with hypertonic saline s

confluent changes in the white matter of the brain. This elevation of the head of the bed, hyperventilation, patient’s lack of risk factors and MRI are not supportive of dexamethasone (for patients with peritumoral wn rt} vascular cognitive impairment. edema), and osmotic diuresis with hypertonic saline s or mannitol. = + rs) e The diagnosis of mild cognitive impairment requires a Bibliography | subjective report of a decline in cognitive abilities Phillips KA, Fadul CE, Schiff D. Neurologic and medical management of 3 cs with relative preservation of day-to-day function and brain tumors. Neurol Clin. 2018;36(3):449-466. [PMID: 30072065] doi:10.1016/j.ncl.2018.04.004 2 evidence of cognitive impairment on cognitive testing. o = A) & Bibliography L—§ Item 43 Answer: A Petersen RC, Lopez O, Armstrong MJ, et al. Practice guideline update sum- mary: mild cognitive impairment: report of the Guideline Development, Educational Objective: Treat Alzheimer disease. Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2018;90:126-35. The most appropriate treatment is an acetylcholinesterase inhibitor, such as donepezil (Option A). One tool used to categorize dementia into levels of severity is the Mini-

or mannitol. = + rs) e The diagnosis of mild cognitive impairment requires a Bibliography | subjective report of a decline in cognitive abilities Phillips KA, Fadul CE, Schiff D. Neurologic and medical management of 3 cs with relative preservation of day-to-day function and brain tumors. Neurol Clin. 2018;36(3):449-466. [PMID: 30072065] doi:10.1016/j.ncl.2018.04.004 2 evidence of cognitive impairment on cognitive testing. o = A) & Bibliography L—§ Item 43 Answer: A Petersen RC, Lopez O, Armstrong MJ, et al. Practice guideline update sum- mary: mild cognitive impairment: report of the Guideline Development, Educational Objective: Treat Alzheimer disease. Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2018;90:126-35. The most appropriate treatment is an acetylcholinesterase inhibitor, such as donepezil (Option A). One tool used to categorize dementia into levels of severity is the Mini- Item 42 Answer: C Mental State Examination (MMSE) score. Mild dementia is often associated with a MMSE score of 20 to 23, mod- Educational Objective: Treat brain edema and erate dementia a score of 10 to 19, and severe dementia a herniation. score <10. This patient is in a mild stage of dementia due The patient has a brainstem tumor with associated acute to Alzheimer disease (AD), given her abnormal test score hemorrhage and edema, leading to herniation. Brain hernia- and her functional dependence with her finances. AD is tion inevitably leads to death if unrecognized or not properly the most common memory-predominant dementia and treated. It manifests as an abrupt decline in mental status, is also the most common cause of dementia. The typical unreactive dilated pupils, and motor weakness with flexor presentation of AD is that of an insidious worsening of or extensor posturing. This patient also demonstrates the memory, language, and visuospatial abilities. Manifestations Cushing response (bradycardia and hypertension), a sign include forgetfulness, frequent repetition of questions or of elevated intracranial pressure (ICP). Emergent treatment statements, word-finding difficulties, hesitation in speech, includes elevation of the head of the bed to 30 degrees, and navigational problems. The acetylcholinesterase inhibi- hyperventilation (usually with mechanical ventilation) to tors donepezil, rivastigmine, and galantamine are approved an arterial Pco, of 20 to 25 mm Hg (2.7-3.3 kPa), infusion of for treating mild-to-moderate dementia in patients with either hypertonic saline or mannitol (Option C), and admin AD and have demonstrated modest benefits in cognitive istration of dexamethasone (for patients with peritumoral performance, stabilizing progression of symptoms, and edema). Mannitol is a diuretic that reduces brain edema by functional loss. Because of their possible adverse effects on osmotically transferring water from brain tissue into the cir conduction, acetylcholinesterase inhibitors should be used culation, where it is renally excreted. The impact of mannitol with caution or avoided in patients with bradycardia or on ICP is evident within minutes and peaks in 1 hour. These other conduction abnormalities. The most common adverse treatments can be life-saving and often are used as a bridge effects are gastrointestinal issues, which result in discontin- to emergent surgery. uation of the medication in nearly 20% of patients. Addi- Bevacizumab (Option A) is an antiangiogenic agent that tional adverse effects include syncope, agitation, nocturnal is used in the treatment of a variety of tumors, including cramps, and vivid dreams. Donepezil should be used with tumors metastatic to the brain. Antiangiogenic agents may caution in patients with a history of seizures. reduce ICP by a number of mechanisms including inhibiting Supplements such as Ginkgo biloba (Option B) and angiogenesis and minimizing vasogenic edema. However, high-dose vitamin E (Option C) have not shown clinical these agents take weeks or months to have an effect and are benefit in studies. Therapy with Ginkgo biloba is also limited not a good option in an emergency situation. because there is no standardization of dose or regulation of

Item 42 Answer: C Mental State Examination (MMSE) score. Mild dementia is often associated with a MMSE score of 20 to 23, mod- Educational Objective: Treat brain edema and erate dementia a score of 10 to 19, and severe dementia a herniation. score <10. This patient is in a mild stage of dementia due The patient has a brainstem tumor with associated acute to Alzheimer disease (AD), given her abnormal test score hemorrhage and edema, leading to herniation. Brain hernia- and her functional dependence with her finances. AD is tion inevitably leads to death if unrecognized or not properly the most common memory-predominant dementia and treated. It manifests as an abrupt decline in mental status, is also the most common cause of dementia. The typical unreactive dilated pupils, and motor weakness with flexor presentation of AD is that of an insidious worsening of or extensor posturing. This patient also demonstrates the memory, language, and visuospatial abilities. Manifestations Cushing response (bradycardia and hypertension), a sign include forgetfulness, frequent repetition of questions or of elevated intracranial pressure (ICP). Emergent treatment statements, word-finding difficulties, hesitation in speech, includes elevation of the head of the bed to 30 degrees, and navigational problems. The acetylcholinesterase inhibi- hyperventilation (usually with mechanical ventilation) to tors donepezil, rivastigmine, and galantamine are approved an arterial Pco, of 20 to 25 mm Hg (2.7-3.3 kPa), infusion of for treating mild-to-moderate dementia in patients with either hypertonic saline or mannitol (Option C), and admin AD and have demonstrated modest benefits in cognitive istration of dexamethasone (for patients with peritumoral performance, stabilizing progression of symptoms, and edema). Mannitol is a diuretic that reduces brain edema by functional loss. Because of their possible adverse effects on osmotically transferring water from brain tissue into the cir conduction, acetylcholinesterase inhibitors should be used culation, where it is renally excreted. The impact of mannitol with caution or avoided in patients with bradycardia or on ICP is evident within minutes and peaks in 1 hour. These other conduction abnormalities. The most common adverse treatments can be life-saving and often are used as a bridge effects are gastrointestinal issues, which result in discontin- to emergent surgery. uation of the medication in nearly 20% of patients. Addi- Bevacizumab (Option A) is an antiangiogenic agent that tional adverse effects include syncope, agitation, nocturnal is used in the treatment of a variety of tumors, including cramps, and vivid dreams. Donepezil should be used with tumors metastatic to the brain. Antiangiogenic agents may caution in patients with a history of seizures. reduce ICP by a number of mechanisms including inhibiting Supplements such as Ginkgo biloba (Option B) and angiogenesis and minimizing vasogenic edema. However, high-dose vitamin E (Option C) have not shown clinical these agents take weeks or months to have an effect and are benefit in studies. Therapy with Ginkgo biloba is also limited not a good option in an emergency situation. because there is no standardization of dose or regulation of 137

Answers and Cr itiques _ content by the FDA. High-dose vitamin E has been associ- Restless legs syndrome (Option D) is unlikely because ated with an increase in all-cause mortality and heart failure the patient reports no subjective discomfort or making vol- in some studies. untary movements to relieve an urge. In addition, restless leg Memantine (Option D) is an N-methyl-p-aspartate symptoms occur at night and with rest but when patients receptor antagonist that is FDA-approved for use in AD as an are awake. adjunct to an acetylcholinesterase inhibitor in the moderate Vivid dreams (Option E) are not associated with invol- to severe stage of dementia due to AD. There is no evidence untary movements (acting out) during sleep. Vivid dreams of benefit in the mild stage of AD dementia. Memantine has are experienced sporadically by most people. In a patient fewer adverse effects than acetylcholinesterase inhibitors with RBD, vivid dreams may trigger a pronounced or violent and is not associated with adverse cardiovascular effects. The reaction as patients act out an escape or fight. most commonly reported side effect is dizziness.

content by the FDA. High-dose vitamin E has been associ- Restless legs syndrome (Option D) is unlikely because ated with an increase in all-cause mortality and heart failure the patient reports no subjective discomfort or making vol- in some studies. untary movements to relieve an urge. In addition, restless leg Memantine (Option D) is an N-methyl-p-aspartate symptoms occur at night and with rest but when patients receptor antagonist that is FDA-approved for use in AD as an are awake. adjunct to an acetylcholinesterase inhibitor in the moderate Vivid dreams (Option E) are not associated with invol- to severe stage of dementia due to AD. There is no evidence untary movements (acting out) during sleep. Vivid dreams of benefit in the mild stage of AD dementia. Memantine has are experienced sporadically by most people. In a patient fewer adverse effects than acetylcholinesterase inhibitors with RBD, vivid dreams may trigger a pronounced or violent and is not associated with adverse cardiovascular effects. The reaction as patients act out an escape or fight. most commonly reported side effect is dizziness. > e Rapid eye movement sleep behavior disorder is caused = ¢ The acetylcholinesterase inhibitors donepezil, riv- 7) by loss of normal paralysis during the rapid eye move- = astigmine, and galantamine are approved for treating ment phase of sleep, leading to violent movements @ eae 17) mild to moderate dementia in patients with and shouting. oy Alzheimer disease. = ¢ RBD has a strong association with neurodegenerative Qa. ¢ Memantine is used as an adjunct to an acetylcho- disorders including Parkinson disease, multiple system ie) =e linesterase inhibitor in the moderate to severe stage of atrophy, and dementia with Lewy bodies and may S. 2 Alzheimer disease. precede these disorders by decades. <= @ n” Bibliography Bibliography Oh ES, Rabins PV. Dementia. Ann Intern Med. 2019;171:ITC33-ITC48. Dauvilliers Y, Schenck CH, Postuma RB, et al. REM sleep behaviour disorder. [PMID: 31476229] doi: 10.7326/AITC201909030 Nat Rev Dis Primers. 2018;4:19. [PMID: 30166532] doi:10.1038/s41572- 018-0016-5

> e Rapid eye movement sleep behavior disorder is caused = ¢ The acetylcholinesterase inhibitors donepezil, riv- 7) by loss of normal paralysis during the rapid eye move- = astigmine, and galantamine are approved for treating ment phase of sleep, leading to violent movements @ eae 17) mild to moderate dementia in patients with and shouting. oy Alzheimer disease. = ¢ RBD has a strong association with neurodegenerative Qa. ¢ Memantine is used as an adjunct to an acetylcho- disorders including Parkinson disease, multiple system ie) =e linesterase inhibitor in the moderate to severe stage of atrophy, and dementia with Lewy bodies and may S. 2 Alzheimer disease. precede these disorders by decades. <= @ n” Bibliography Bibliography Oh ES, Rabins PV. Dementia. Ann Intern Med. 2019;171:ITC33-ITC48. Dauvilliers Y, Schenck CH, Postuma RB, et al. REM sleep behaviour disorder. [PMID: 31476229] doi: 10.7326/AITC201909030 Nat Rev Dis Primers. 2018;4:19. [PMID: 30166532] doi:10.1038/s41572- 018-0016-5 Item 44 Answer: C Item 45 Answer: B Educational Objective: Diagnose rapid eye movement Educational Objective: Treat epilepsy in an elderly sleep behavior disorder. patient with a history of seizure medication-related rash.

Item 44 Answer: C Item 45 Answer: B Educational Objective: Diagnose rapid eye movement Educational Objective: Treat epilepsy in an elderly sleep behavior disorder. patient with a history of seizure medication-related rash. The most likely diagnosis is rapid eye movement sleep The most appropriate seizure management is to initiate behavior disorder (RBD) (Option C). This movement disor- gabapentin (Option B). This elderly patient likely has a der is caused by loss of normal paralysis during the rapid lamotrigine-related rash. Lamotrigine may cause a mor- eye movement phase of sleep, leading to violent move- biliform rash, which most commonly resolves with dis- ments and shouting as patients respond to their dreams. continuation of the drug but sometimes may be severe Patients are often unaware of the movements; these are and life-threatening. This patient’s rash is likely not a typically reported by their bed partners. RBD is some- serious rash based on the lack of mucosal involvement, times brought to attention as a result of injuries sustained lymphadenopathy, and systemic features, including fever. by patients or their bed partners during sleep. RBD has Reassuring laboratory findings include the absence of a strong association with neurodegenerative disorders eosinophilia and normal aminotransaminase levels. Mor- caused by synuclein accumulation, including Parkinson billiform reactions are the most common drug reactions disease, multiple system atrophy, and dementia with Lewy and are most likely a type IV delayed hypersensitivity bodies, and may precede these disorders by decades. In reaction. As such, the rash appears in the first or second this patient, the report by his wife, sleep study findings, week after drug exposure. Patients develop pink papules and clinical evidence of a parkinsonian disorder (likely and macules that coalesce symmetrically to form plaques. multiple system atrophy given the associated ataxia and The papules are often dense and monomorphic and are dysautonomia) suggest RBD. accompanied by varying degrees of pruritus beginning on Hypnic myoclonus (Option A) or sleep starts are phys- the trunk and progressing distally across the limbs. Palms iologic rapid jerky movements experienced at sleep onset. and soles are usually spared. Treatment involves cessation Movements consist of simple jerks and may be associated of the causative agent, systemic and/or topical glucocorti- with a subjective sense of falling from a height. coids, and oral H1 antihistamines. Any patient taking an Periodic limb movement disorder (Option B) is a com- antiepileptic drug should be counseled to stop their medi- mon movement disorder characterized by brief triple flexion cation and to contact their clinician if a rash develops, and movements of the legs that repeat in 20-second periods seek emergency care if fevers, skin pain, blisters, pustules, during sleep. This disorder is not associated with vocaliza- or mucous membrane involvement is present, indicating tion or complex behavior, such as punching or jumping out serious and potentially life-threating conditions such as of bed, and thus is not a likely diagnosis in this patient. Stevens-Johnson syndrome/toxic epidermal necrolysis.

The most likely diagnosis is rapid eye movement sleep The most appropriate seizure management is to initiate behavior disorder (RBD) (Option C). This movement disor- gabapentin (Option B). This elderly patient likely has a der is caused by loss of normal paralysis during the rapid lamotrigine-related rash. Lamotrigine may cause a mor- eye movement phase of sleep, leading to violent move- biliform rash, which most commonly resolves with dis- ments and shouting as patients respond to their dreams. continuation of the drug but sometimes may be severe Patients are often unaware of the movements; these are and life-threatening. This patient’s rash is likely not a typically reported by their bed partners. RBD is some- serious rash based on the lack of mucosal involvement, times brought to attention as a result of injuries sustained lymphadenopathy, and systemic features, including fever. by patients or their bed partners during sleep. RBD has Reassuring laboratory findings include the absence of a strong association with neurodegenerative disorders eosinophilia and normal aminotransaminase levels. Mor- caused by synuclein accumulation, including Parkinson billiform reactions are the most common drug reactions disease, multiple system atrophy, and dementia with Lewy and are most likely a type IV delayed hypersensitivity bodies, and may precede these disorders by decades. In reaction. As such, the rash appears in the first or second this patient, the report by his wife, sleep study findings, week after drug exposure. Patients develop pink papules and clinical evidence of a parkinsonian disorder (likely and macules that coalesce symmetrically to form plaques. multiple system atrophy given the associated ataxia and The papules are often dense and monomorphic and are dysautonomia) suggest RBD. accompanied by varying degrees of pruritus beginning on Hypnic myoclonus (Option A) or sleep starts are phys- the trunk and progressing distally across the limbs. Palms iologic rapid jerky movements experienced at sleep onset. and soles are usually spared. Treatment involves cessation Movements consist of simple jerks and may be associated of the causative agent, systemic and/or topical glucocorti- with a subjective sense of falling from a height. coids, and oral H1 antihistamines. Any patient taking an Periodic limb movement disorder (Option B) is a com- antiepileptic drug should be counseled to stop their medi- mon movement disorder characterized by brief triple flexion cation and to contact their clinician if a rash develops, and movements of the legs that repeat in 20-second periods seek emergency care if fevers, skin pain, blisters, pustules, during sleep. This disorder is not associated with vocaliza- or mucous membrane involvement is present, indicating tion or complex behavior, such as punching or jumping out serious and potentially life-threating conditions such as of bed, and thus is not a likely diagnosis in this patient. Stevens-Johnson syndrome/toxic epidermal necrolysis. 138

Answers and Critiques Gabapentin has a low incidence of rash and other allergic the risk of major bleeding. Triple therapy for acute stroke reactions and also has good evidence of efficacy in focal cannot be recommended. epilepsy in older adults; thus, it is the most appropriate Ticagrelor monotherapy (Option D) is not appropriate replacement for lamotrigine. because ticagrelor has not been established to be effective In addition to lamotrigine, phenobarbital, phenytoin, at reducing the risk for ischemic stroke after TIA. The Acute and carbamazepine (Options A, C, and D) are all known Stroke or Transient Ischemic Attack Treated with Aspi to cause rash. The rash may be severe and life-threatening rin or Ticagrelor and Patient Outcomes (SOCRATES) trial and occur at an incidence high enough that these drugs showed no superiority of ticagrelor compared with aspirin should be avoided, especially in patients with prior drug in patients with TIA. rash (owing to cross-reactivity), unless no other good medi- cation options are available. e In patients who have experienced a transient ischemic attack, adding clopidogrel to aspirin for 21 days has wn rf e Lamotrigine may cause a morbilliform rash, which been shown to be effective in reducing the risk for = most commonly resolves with discontinuation of the subsequent stroke compared with monotherapy with A 3 drug but sometimes may be severe and life-threatening. either agent alone. ‘= Oo e Gabapentin is a first-line medication for treating epi- e In patients treated with dual antiplatelet therapy fol- sc & lepsy in older adults; it has a low incidence of rash and lowing a transient ischemic attack or minor stroke, co ” other allergic reactions and good evidence of efficacy. aspirin should be continued following discontinuation Den o of clopidogrel at 21 days. = 2) Bibliography Se << Mani R, Monteleone C, Schalock PC, et al. Rashes and other hypersensitivity Bibliography reactions associated with antiepileptic drugs: A review of current litera- ture. Seizure. 2019;71:270-278. [PMID: 31491658] Prasad K, Siemieniuk R, Hao Q, et al. Dual antiplatelet therapy with aspirin and clopidogrel for acute high risk transient ischaemic attack and minor ischaemic stroke: a clinical practice guideline. BMJ. 2018;363:k5130. [PMID: 30563885] doi:10.1136/bmj.k5130 Item 46 Answer: B Educational Objective: Treat an acute transient ischemic attack with antiplatelet agents. Item 47 Answer: 8B Educational Objective: Evaluate suspected subarachnoid The most appropriate treatment is aspirin and clopidogrel hemorrhage with lumbar puncture. (Option B). The patient sustained a high-risk transient ische- mic attack (TIA) and has no evidence of extracranial inter- The most appropriate next step in management is lumbar nal carotid artery stenosis. Two trials examined the role puncture (Option B). The patient is seen 24 hours after sud- of aspirin combined with clopidogrel versus monotherapy den onset of severe headache (thunderclap headache). Thun- (with either aspirin or clopidogrel) in TIA and minor stroke derclap headache is defined as a severe attack of headache initiated within 12 to 24 hours from onset. The studies used pain developing abruptly and reaching maximum intensity either 21 or 90 days of aspirin and clopidogrel versus single within 1 minute. Although occasionally of primary origin. antiplatelet agents and, overall, demonstrated a small but thunderclap headache is a medical emergency that warrants significant reduction in risk of recurrence at 90 days for immediate diagnostic evaluation. Thunderclap headache has the combination therapy. The American Heart Association a broad differential diagnosis; the most serious is aneurys Guidelines endorse a treatment duration of 21 days. The risk mal subarachnoid hemorrhage (SAH). A small proportion of hemorrhagic complications appeared to increase beyond (less than 5%) of patients with aneurysmal SAH will have a 30 days; duration between 30 to 90 days of aspirin and clopi- CT scan of the head that is negative for bleeding and require dogrel in minor stroke or TIA is commonly used in patients a lumbar puncture to rule out this condition. In patients with intracranial atherosclerosis as the underlying stroke with SAH, results on lumbar puncture performed 12 to cause. Following that time, clopidogrel is discontinued, and 24 hours after symptom onset will reveal elevated eryth aspirin therapy is maintained. rocyte counts and xanthochromia (yellow color caused by Adding apixaban to aspirin (Option A) is not indi- breakdown of red blood cells). If lumbar puncture is per cated because the patient does not have atrial fibrillation formed within 12 hours of symptom onset, it may be chal- or any other indication for anticoagulation. In patients with lenging to distinguish a traumatic process from the acute acute stroke or TIA, direct oral anticoagulants have not been presence of erythrocytes from aneurysmal bleeding because established as effective at reducing the risk for subsequent xanthochromia may not yet have developed. adverse outcomes. Cerebral catheter angiography (Option A) is not appro- Adding dipyridamole to aspirin and clopidogrel priate because SAH has not been confirmed and an invasive (Option C) therapy may be harmful in patients with acute diagnostic test is not yet indicated. If evidence suggests SAH, ischemic stroke. Such therapy has not been found to reduce vascular imaging is indicated to first evaluate for an aneur- the risk or severity of recurrent stroke but does increase ysm; usually this is done with a less invasive test, such as CT

Gabapentin has a low incidence of rash and other allergic the risk of major bleeding. Triple therapy for acute stroke reactions and also has good evidence of efficacy in focal cannot be recommended. epilepsy in older adults; thus, it is the most appropriate Ticagrelor monotherapy (Option D) is not appropriate replacement for lamotrigine. because ticagrelor has not been established to be effective In addition to lamotrigine, phenobarbital, phenytoin, at reducing the risk for ischemic stroke after TIA. The Acute and carbamazepine (Options A, C, and D) are all known Stroke or Transient Ischemic Attack Treated with Aspi to cause rash. The rash may be severe and life-threatening rin or Ticagrelor and Patient Outcomes (SOCRATES) trial and occur at an incidence high enough that these drugs showed no superiority of ticagrelor compared with aspirin should be avoided, especially in patients with prior drug in patients with TIA. rash (owing to cross-reactivity), unless no other good medi- cation options are available. e In patients who have experienced a transient ischemic attack, adding clopidogrel to aspirin for 21 days has wn rf e Lamotrigine may cause a morbilliform rash, which been shown to be effective in reducing the risk for = most commonly resolves with discontinuation of the subsequent stroke compared with monotherapy with A 3 drug but sometimes may be severe and life-threatening. either agent alone. ‘= Oo e Gabapentin is a first-line medication for treating epi- e In patients treated with dual antiplatelet therapy fol- sc & lepsy in older adults; it has a low incidence of rash and lowing a transient ischemic attack or minor stroke, co ” other allergic reactions and good evidence of efficacy. aspirin should be continued following discontinuation Den o of clopidogrel at 21 days. = 2) Bibliography Se << Mani R, Monteleone C, Schalock PC, et al. Rashes and other hypersensitivity Bibliography reactions associated with antiepileptic drugs: A review of current litera- ture. Seizure. 2019;71:270-278. [PMID: 31491658] Prasad K, Siemieniuk R, Hao Q, et al. Dual antiplatelet therapy with aspirin and clopidogrel for acute high risk transient ischaemic attack and minor ischaemic stroke: a clinical practice guideline. BMJ. 2018;363:k5130. [PMID: 30563885] doi:10.1136/bmj.k5130 Item 46 Answer: B Educational Objective: Treat an acute transient ischemic attack with antiplatelet agents. Item 47 Answer: 8B Educational Objective: Evaluate suspected subarachnoid The most appropriate treatment is aspirin and clopidogrel hemorrhage with lumbar puncture. (Option B). The patient sustained a high-risk transient ische- mic attack (TIA) and has no evidence of extracranial inter- The most appropriate next step in management is lumbar nal carotid artery stenosis. Two trials examined the role puncture (Option B). The patient is seen 24 hours after sud- of aspirin combined with clopidogrel versus monotherapy den onset of severe headache (thunderclap headache). Thun- (with either aspirin or clopidogrel) in TIA and minor stroke derclap headache is defined as a severe attack of headache initiated within 12 to 24 hours from onset. The studies used pain developing abruptly and reaching maximum intensity either 21 or 90 days of aspirin and clopidogrel versus single within 1 minute. Although occasionally of primary origin. antiplatelet agents and, overall, demonstrated a small but thunderclap headache is a medical emergency that warrants significant reduction in risk of recurrence at 90 days for immediate diagnostic evaluation. Thunderclap headache has the combination therapy. The American Heart Association a broad differential diagnosis; the most serious is aneurys Guidelines endorse a treatment duration of 21 days. The risk mal subarachnoid hemorrhage (SAH). A small proportion of hemorrhagic complications appeared to increase beyond (less than 5%) of patients with aneurysmal SAH will have a 30 days; duration between 30 to 90 days of aspirin and clopi- CT scan of the head that is negative for bleeding and require dogrel in minor stroke or TIA is commonly used in patients a lumbar puncture to rule out this condition. In patients with intracranial atherosclerosis as the underlying stroke with SAH, results on lumbar puncture performed 12 to cause. Following that time, clopidogrel is discontinued, and 24 hours after symptom onset will reveal elevated eryth aspirin therapy is maintained. rocyte counts and xanthochromia (yellow color caused by Adding apixaban to aspirin (Option A) is not indi- breakdown of red blood cells). If lumbar puncture is per cated because the patient does not have atrial fibrillation formed within 12 hours of symptom onset, it may be chal- or any other indication for anticoagulation. In patients with lenging to distinguish a traumatic process from the acute acute stroke or TIA, direct oral anticoagulants have not been presence of erythrocytes from aneurysmal bleeding because established as effective at reducing the risk for subsequent xanthochromia may not yet have developed. adverse outcomes. Cerebral catheter angiography (Option A) is not appro- Adding dipyridamole to aspirin and clopidogrel priate because SAH has not been confirmed and an invasive (Option C) therapy may be harmful in patients with acute diagnostic test is not yet indicated. If evidence suggests SAH, ischemic stroke. Such therapy has not been found to reduce vascular imaging is indicated to first evaluate for an aneur- the risk or severity of recurrent stroke but does increase ysm; usually this is done with a less invasive test, such as CT 139

Answers and Critiques angiography. Noninvasive vascular imaging will also allow for Myasthenia gravis (Option D) can cause bulbar weak- evaluation of other causes of thunderclap headache, such as ness. This is often associated with extraocular and sym- CONT. reversible cerebral vasoconstriction syndrome (RCVS). RCVS metric proximal limb muscle weakness. However, isolated manifests as multifocal distal arterial narrowing on imaging. bulbar and neck weakness can be seen in the setting of Magnetic resonance venography of the brain (Option C) myasthenia gravis, particularly in patients with anti-muscle- is not indicated because the patient has no historical features specific kinase antibody. Presence of upper motor neuron or risk factors for dural sinus thrombosis, such as a hyper- signs is inconsistent with this diagnosis. coagulable state or oral contraceptive use; SAH is the initial Neuromyelitis optica (Option E) is a central nervous possible diagnosis of highest risk. If SAH is ruled out, venous system demyelinating disorder that can cause various neu- imaging should be considered, particularly if CT findings sug- rologic deficits, including bulbar and sensorimotor deficits, gest thrombosis (hyperdensity on noncontrast CT of the head). and upper motor neuron signs. Normal findings on MRI Oral sumatriptan (Option D) should not be admin- would rule out this entity. > istered because the patient has an atypical presentation J wn for migraine, and sumatriptan may worsen outcomes in = patients with aneurysmal SAH or RCVS. e Amyotrophic lateral sclerosis often begins as asym- @o metric distal extremity weakness or with bulbar = wn r+) symptoms, such as dysphagia, dysarthria, or tongue = a. e Thunderclap headache is a severe headache that weakness. (eo) reaches maximum intensity within 1 minute and me e In patients with suspected amyotrophic lateral sclerosis, =. is a medical emergency that warrants immediate 2 cervical cord compression, vitamin B,, and copper < evaluation with a head CT scan. oO deficiencies, HIV infection, Lyme disease, hyperpar- wn ¢ Patients with suspected subarachnoid hemorrhage but athyroidism, and thyrotoxicosis must be excluded. a normal head CT scan require a lumbar puncture.

angiography. Noninvasive vascular imaging will also allow for Myasthenia gravis (Option D) can cause bulbar weak- evaluation of other causes of thunderclap headache, such as ness. This is often associated with extraocular and sym- CONT. reversible cerebral vasoconstriction syndrome (RCVS). RCVS metric proximal limb muscle weakness. However, isolated manifests as multifocal distal arterial narrowing on imaging. bulbar and neck weakness can be seen in the setting of Magnetic resonance venography of the brain (Option C) myasthenia gravis, particularly in patients with anti-muscle- is not indicated because the patient has no historical features specific kinase antibody. Presence of upper motor neuron or risk factors for dural sinus thrombosis, such as a hyper- signs is inconsistent with this diagnosis. coagulable state or oral contraceptive use; SAH is the initial Neuromyelitis optica (Option E) is a central nervous possible diagnosis of highest risk. If SAH is ruled out, venous system demyelinating disorder that can cause various neu- imaging should be considered, particularly if CT findings sug- rologic deficits, including bulbar and sensorimotor deficits, gest thrombosis (hyperdensity on noncontrast CT of the head). and upper motor neuron signs. Normal findings on MRI Oral sumatriptan (Option D) should not be admin- would rule out this entity. > istered because the patient has an atypical presentation J wn for migraine, and sumatriptan may worsen outcomes in = patients with aneurysmal SAH or RCVS. e Amyotrophic lateral sclerosis often begins as asym- @o metric distal extremity weakness or with bulbar = wn r+) symptoms, such as dysphagia, dysarthria, or tongue = a. e Thunderclap headache is a severe headache that weakness. (eo) reaches maximum intensity within 1 minute and me e In patients with suspected amyotrophic lateral sclerosis, =. is a medical emergency that warrants immediate 2 cervical cord compression, vitamin B,, and copper < evaluation with a head CT scan. oO deficiencies, HIV infection, Lyme disease, hyperpar- wn ¢ Patients with suspected subarachnoid hemorrhage but athyroidism, and thyrotoxicosis must be excluded. a normal head CT scan require a lumbar puncture. Bibliography Bibliography Brown RH, Al-Chalabi A. Amyotrophic lateral sclerosis. N Engl J Med. 2017; Lawton MT, Vates GE. Subarachnoid hemorrhage. N EnglJ Med. 2017;377: 377:162-72. [PMID: 28700839] doi:10.1056/NEJMra1603471 257-266. [PMID: 28723321] doi:10.1056/NEJMcp1605827

Bibliography Bibliography Brown RH, Al-Chalabi A. Amyotrophic lateral sclerosis. N Engl J Med. 2017; Lawton MT, Vates GE. Subarachnoid hemorrhage. N EnglJ Med. 2017;377: 377:162-72. [PMID: 28700839] doi:10.1056/NEJMra1603471 257-266. [PMID: 28723321] doi:10.1056/NEJMcp1605827 Item 49 Answer: B Item 48 Answer: A Educational Objective: Treat spinal cord compression Educational Objective: Diagnose amyotrophic lateral due to metastatic disease in a patient with a poor prognosis. sclerosis. The most appropriate treatment is glucocorticoids and radio- The most likely diagnosis is amyotrophic lateral sclerosis (ALS) therapy (Option B). Neoplastic epidural spinal cord com- (Option A). ALS often begins as asymmetric distal extrem- pression (ESCC) develops in approximately 2.5% of patients ity weakness or with bulbar symptoms, such as dysphagia, with metastatic cancer. Lung, breast, and prostate cancer, dysarthria, or tongue weakness. The clinical course is rapid, multiple myeloma, and lymphoma are the most common progressive, and irreversible. In this patient, the presence of types of cancer that cause ESCC in adults. Emergent use of both lower motor neuron findings, such as atrophy and fas- high-dose glucocorticoids is the first step. Systematic reviews ciculations, and upper motor neuron signs, such as hyperre- of the evidence suggest that surgical decompression followed flexia, clonus, and brisk jaw jerk, suggest ALS. In patients with by radiotherapy is most beneficial for patients younger than these findings, diagnosis can be confirmed with electromyo- 65 years who have a single area of compression, paraple- graphic evidence of lower motor neuron signs in at least two gia with a duration of less than 48 hours, and a predicted (probable ALS) or more (definite ALS) regions. An alternative survival of greater than 6 months. In patients not meeting cause should be ruled out by cervical spine neuroimaging and these criteria, such as this patient, surgical intervention may assessment for thyroid and parathyroid dysfunction, copper be of little benefit, and radiotherapy alone may be used. and vitamin B,, deficiency, HIV infection, and Lyme disease. Furthermore, certain radiosensitive tumor types, such as Chronic inflammatory demyelinating polyradiculoneur- leukemia, lymphoma, myeloma, and germ cell tumors, may opathy (Option B) often presents with symmetric proximal not require initial surgical decompression and instead may and distal motor and sensory deficits and diffuse areflexia. be treated urgently with radiation therapy. Bulbar weakness and hyperreflexia are atypical for this entity. Emergent treatment of ESCC is usually indicated Inflammatory myopathies, such as inclusion body myo- because the most important indicator of long-term neur sitis (Option C), can present with neck extension weak- ologic function is the neurologic function at the time of ness, but upper motor neuron signs would not be expected. decompression (Options A, C, D). Neurologic function is Creatine kinase is often highly elevated in inflammatory rarely regained as a result of therapy, but further deteriora- myopathies, but its mild elevation can be seen in many neuro- tion may be prevented. In properly selected patients, clinical muscular disorders, including ALS. trials have shown the superiority of surgical decompression

Item 49 Answer: B Item 48 Answer: A Educational Objective: Treat spinal cord compression Educational Objective: Diagnose amyotrophic lateral due to metastatic disease in a patient with a poor prognosis. sclerosis. The most appropriate treatment is glucocorticoids and radio- The most likely diagnosis is amyotrophic lateral sclerosis (ALS) therapy (Option B). Neoplastic epidural spinal cord com- (Option A). ALS often begins as asymmetric distal extrem- pression (ESCC) develops in approximately 2.5% of patients ity weakness or with bulbar symptoms, such as dysphagia, with metastatic cancer. Lung, breast, and prostate cancer, dysarthria, or tongue weakness. The clinical course is rapid, multiple myeloma, and lymphoma are the most common progressive, and irreversible. In this patient, the presence of types of cancer that cause ESCC in adults. Emergent use of both lower motor neuron findings, such as atrophy and fas- high-dose glucocorticoids is the first step. Systematic reviews ciculations, and upper motor neuron signs, such as hyperre- of the evidence suggest that surgical decompression followed flexia, clonus, and brisk jaw jerk, suggest ALS. In patients with by radiotherapy is most beneficial for patients younger than these findings, diagnosis can be confirmed with electromyo- 65 years who have a single area of compression, paraple- graphic evidence of lower motor neuron signs in at least two gia with a duration of less than 48 hours, and a predicted (probable ALS) or more (definite ALS) regions. An alternative survival of greater than 6 months. In patients not meeting cause should be ruled out by cervical spine neuroimaging and these criteria, such as this patient, surgical intervention may assessment for thyroid and parathyroid dysfunction, copper be of little benefit, and radiotherapy alone may be used. and vitamin B,, deficiency, HIV infection, and Lyme disease. Furthermore, certain radiosensitive tumor types, such as Chronic inflammatory demyelinating polyradiculoneur- leukemia, lymphoma, myeloma, and germ cell tumors, may opathy (Option B) often presents with symmetric proximal not require initial surgical decompression and instead may and distal motor and sensory deficits and diffuse areflexia. be treated urgently with radiation therapy. Bulbar weakness and hyperreflexia are atypical for this entity. Emergent treatment of ESCC is usually indicated Inflammatory myopathies, such as inclusion body myo- because the most important indicator of long-term neur sitis (Option C), can present with neck extension weak- ologic function is the neurologic function at the time of ness, but upper motor neuron signs would not be expected. decompression (Options A, C, D). Neurologic function is Creatine kinase is often highly elevated in inflammatory rarely regained as a result of therapy, but further deteriora- myopathies, but its mild elevation can be seen in many neuro- tion may be prevented. In properly selected patients, clinical muscular disorders, including ALS. trials have shown the superiority of surgical decompression 140

in optimizing ambulation. However, it is unlikely that this Bibliography patient with a limited life span will benefit from surgical Rae-Grant A, Day GS, Marrie RA, et al. Practice guideline recommendations C ONT. summary: disease-modifying therapies for adults with multiple sclero- intervention regardless of whether it is combined with glu- sis. Report of the Guideline Development, Dissemination, and cocorticoids and/or radiation therapy. Implementation Subcommittee of the American Academy of Neurology. Neurology 2018;90(17);777-88. [PMID: 29686116] doi: 10.1212/WNL. 0000000000005347. e In patients with metastatic spinal compression, surgical decompression should be reserved for patients younger Item 51 Answer: A than 65 years with a single area of compression, para- plegia for less than 48 hours, and a predicted survival Educational Objective: Treat acute migraine with a of longer than 6 months. triptan.

e In patients with metastatic spinal compression, surgical decompression should be reserved for patients younger Item 51 Answer: A than 65 years with a single area of compression, para- plegia for less than 48 hours, and a predicted survival Educational Objective: Treat acute migraine with a of longer than 6 months. triptan. This patient has episodic migraine without aura and should Bibliography w be treated with an oral triptan such as zolmitriptan (Option @ George R, Jeba J, Ramkumar G, et al. Interventions for the treatment of = A). Migraine is thought to be a manifestation of a central ner- metastatic extradural spinal cord compression in adults. Cochrane = Database Syst Rev. 2015:CD006716. [PMID: 26337716] vous system that is biologically hypersensitive and prone to = episodes of disabling headache. Once initiated, the migraine Oo attack may possess not only the phases of aura and headache, s S but also of prodrome and postdrome. Prodromal or premon- CS Item 50 Answer: B 2 itory symptoms may precede these other phases by hours @ Educational Objective: Manage secondary progressive or sometimes days and, given that timing, they occasionally = wy multiple sclerosis in a nonambulatory patient. may be confused for a triggering influence. After severe = =f attacks, postdrome is quite common and often described as The most appropriate change is to discontinue the interferon a “headache hangover.” Evidence-based guidelines recom- beta-1b (Option B) in this patient. His multiple sclerosis mend several simple and combination analgesic agents as (MS) would be characterized currently as secondary pro- first-line therapies for acute migraine. Aspirin administered gressive with progression but no activity. American Academy alone or in combination with acetaminophen and caffeine, of Neurology guidelines recommend discontinuation of all ibuprofen, naproxen sodium, and dissolvable diclofenac disease-modifying therapy in patients with secondary pro- potassium are all supported by strong evidence. Triptans are gressive MS who have been nonambulatory for more than migraine-specific selective agonists at 5-hydroxytryptamine 2 years and who have had no relapsing activity during that 1B and 1D receptors with direct impact on trigeminovascu- same period. This patient has been nonambulatory for more lar activation associated with migraine attacks. Guidelines than 2 years, has no evidence of MS activity within the past recommend the use of triptans (such as zolmitriptan) in 2 years on a recent MRI, and has not had any relapses for patients with moderate to severe migraine who have not 6 years. This recommendation is based on data from clinical responded to NSAID therapy over a series of at least three trials in patients with progressive forms of MS that show migraine attacks. Current evidence suggests that all oral a lack of benefit from disease-modifying drugs in patients triptans possess nearly similar clinical efficacy. of any age with high degrees of disability and no relapsing In the absence of aura, there is no indication to dis- activity. Additionally, patients older than 65 years are more continue estrogen-containing oral contraceptives (OCPs) prone to infectious complications from disease-modifying (Option B). There appears to be no significant increase in therapy, which results in a risk-to-benefit ratio that does not stroke risk from OCPs in patients with migraine without favor treatment. aura. Courses of intravenous glucocorticoids (Option A) are In the presence of a stable clinical pattern of migraine only used as an acute treatment of MS relapses and are not and a normal neurologic examination, guidelines recom- indicated as disease-modifying therapy. mend against brain MRI (Option C). A clinical trial of natalizumab (Option C) in patients Neither fexofenadine nor loratadine have any demon- with secondary progressive MS was unsuccessful, so this strated benefit in migraine management, so there would be therapy cannot be recommended. no indication for switching agents (Option D). Ocrelizumab (Option D) is approved only for patients with relapsing-remitting MS and primary progressive MS and has not been approved for patients with secondary ¢ Guidelines recommend the use of triptans in patients progressive MS. with moderate to severe migraine who have not responded to appropriate NSAID therapy over a series

This patient has episodic migraine without aura and should Bibliography w be treated with an oral triptan such as zolmitriptan (Option @ George R, Jeba J, Ramkumar G, et al. Interventions for the treatment of = A). Migraine is thought to be a manifestation of a central ner- metastatic extradural spinal cord compression in adults. Cochrane = Database Syst Rev. 2015:CD006716. [PMID: 26337716] vous system that is biologically hypersensitive and prone to = episodes of disabling headache. Once initiated, the migraine Oo attack may possess not only the phases of aura and headache, s S but also of prodrome and postdrome. Prodromal or premon- CS Item 50 Answer: B 2 itory symptoms may precede these other phases by hours @ Educational Objective: Manage secondary progressive or sometimes days and, given that timing, they occasionally = wy multiple sclerosis in a nonambulatory patient. may be confused for a triggering influence. After severe = =f attacks, postdrome is quite common and often described as The most appropriate change is to discontinue the interferon a “headache hangover.” Evidence-based guidelines recom- beta-1b (Option B) in this patient. His multiple sclerosis mend several simple and combination analgesic agents as (MS) would be characterized currently as secondary pro- first-line therapies for acute migraine. Aspirin administered gressive with progression but no activity. American Academy alone or in combination with acetaminophen and caffeine, of Neurology guidelines recommend discontinuation of all ibuprofen, naproxen sodium, and dissolvable diclofenac disease-modifying therapy in patients with secondary pro- potassium are all supported by strong evidence. Triptans are gressive MS who have been nonambulatory for more than migraine-specific selective agonists at 5-hydroxytryptamine 2 years and who have had no relapsing activity during that 1B and 1D receptors with direct impact on trigeminovascu- same period. This patient has been nonambulatory for more lar activation associated with migraine attacks. Guidelines than 2 years, has no evidence of MS activity within the past recommend the use of triptans (such as zolmitriptan) in 2 years on a recent MRI, and has not had any relapses for patients with moderate to severe migraine who have not 6 years. This recommendation is based on data from clinical responded to NSAID therapy over a series of at least three trials in patients with progressive forms of MS that show migraine attacks. Current evidence suggests that all oral a lack of benefit from disease-modifying drugs in patients triptans possess nearly similar clinical efficacy. of any age with high degrees of disability and no relapsing In the absence of aura, there is no indication to dis- activity. Additionally, patients older than 65 years are more continue estrogen-containing oral contraceptives (OCPs) prone to infectious complications from disease-modifying (Option B). There appears to be no significant increase in therapy, which results in a risk-to-benefit ratio that does not stroke risk from OCPs in patients with migraine without favor treatment. aura. Courses of intravenous glucocorticoids (Option A) are In the presence of a stable clinical pattern of migraine only used as an acute treatment of MS relapses and are not and a normal neurologic examination, guidelines recom- indicated as disease-modifying therapy. mend against brain MRI (Option C). A clinical trial of natalizumab (Option C) in patients Neither fexofenadine nor loratadine have any demon- with secondary progressive MS was unsuccessful, so this strated benefit in migraine management, so there would be therapy cannot be recommended. no indication for switching agents (Option D). Ocrelizumab (Option D) is approved only for patients with relapsing-remitting MS and primary progressive MS and has not been approved for patients with secondary ¢ Guidelines recommend the use of triptans in patients progressive MS. with moderate to severe migraine who have not responded to appropriate NSAID therapy over a series e Disease-modifying therapy should be discontinued in of at least three migraine attacks.

This patient has episodic migraine without aura and should Bibliography w be treated with an oral triptan such as zolmitriptan (Option @ George R, Jeba J, Ramkumar G, et al. Interventions for the treatment of = A). Migraine is thought to be a manifestation of a central ner- metastatic extradural spinal cord compression in adults. Cochrane = Database Syst Rev. 2015:CD006716. [PMID: 26337716] vous system that is biologically hypersensitive and prone to = episodes of disabling headache. Once initiated, the migraine Oo attack may possess not only the phases of aura and headache, s S but also of prodrome and postdrome. Prodromal or premon- CS Item 50 Answer: B 2 itory symptoms may precede these other phases by hours @ Educational Objective: Manage secondary progressive or sometimes days and, given that timing, they occasionally = wy multiple sclerosis in a nonambulatory patient. may be confused for a triggering influence. After severe = =f attacks, postdrome is quite common and often described as The most appropriate change is to discontinue the interferon a “headache hangover.” Evidence-based guidelines recom- beta-1b (Option B) in this patient. His multiple sclerosis mend several simple and combination analgesic agents as (MS) would be characterized currently as secondary pro- first-line therapies for acute migraine. Aspirin administered gressive with progression but no activity. American Academy alone or in combination with acetaminophen and caffeine, of Neurology guidelines recommend discontinuation of all ibuprofen, naproxen sodium, and dissolvable diclofenac disease-modifying therapy in patients with secondary pro- potassium are all supported by strong evidence. Triptans are gressive MS who have been nonambulatory for more than migraine-specific selective agonists at 5-hydroxytryptamine 2 years and who have had no relapsing activity during that 1B and 1D receptors with direct impact on trigeminovascu- same period. This patient has been nonambulatory for more lar activation associated with migraine attacks. Guidelines than 2 years, has no evidence of MS activity within the past recommend the use of triptans (such as zolmitriptan) in 2 years on a recent MRI, and has not had any relapses for patients with moderate to severe migraine who have not 6 years. This recommendation is based on data from clinical responded to NSAID therapy over a series of at least three trials in patients with progressive forms of MS that show migraine attacks. Current evidence suggests that all oral a lack of benefit from disease-modifying drugs in patients triptans possess nearly similar clinical efficacy. of any age with high degrees of disability and no relapsing In the absence of aura, there is no indication to dis- activity. Additionally, patients older than 65 years are more continue estrogen-containing oral contraceptives (OCPs) prone to infectious complications from disease-modifying (Option B). There appears to be no significant increase in therapy, which results in a risk-to-benefit ratio that does not stroke risk from OCPs in patients with migraine without favor treatment. aura. Courses of intravenous glucocorticoids (Option A) are In the presence of a stable clinical pattern of migraine only used as an acute treatment of MS relapses and are not and a normal neurologic examination, guidelines recom- indicated as disease-modifying therapy. mend against brain MRI (Option C). A clinical trial of natalizumab (Option C) in patients Neither fexofenadine nor loratadine have any demon- with secondary progressive MS was unsuccessful, so this strated benefit in migraine management, so there would be therapy cannot be recommended. no indication for switching agents (Option D). Ocrelizumab (Option D) is approved only for patients with relapsing-remitting MS and primary progressive MS and has not been approved for patients with secondary ¢ Guidelines recommend the use of triptans in patients progressive MS. with moderate to severe migraine who have not responded to appropriate NSAID therapy over a series e Disease-modifying therapy should be discontinued in of at least three migraine attacks. patients with secondary progressive MS who have been e In the absence of aura, there is no indication to dis- nonambulatory for more than 2 years and who have continue estrogen-containing oral contraceptives in

e Disease-modifying therapy should be discontinued in of at least three migraine attacks. patients with secondary progressive MS who have been e In the absence of aura, there is no indication to dis- nonambulatory for more than 2 years and who have continue estrogen-containing oral contraceptives in had no relapsing activity during that same period. patients with migraine headaches. 141

wa sa dle Bibliography Bibliography Pringsheim T, Davenport WJ, Marmura MJ, et al. How to apply the AHS Rosness TA, Engedal K, Chemali Z. (2016). Frontotemporal dementia: an evidence assessment of the acute treatment of migraine in adults to your updated clinician's guide. J Geriatr Psychiatry Neurol. 2016 Sep;29(5):271- patient with migraine. Headache. 2016:56:1194-200. [PMID: 27322907] 80. [PMID: 27502302] doi.org/10.1177/0891988716654986. doi:10.1111/head.12870

Bibliography Bibliography Pringsheim T, Davenport WJ, Marmura MJ, et al. How to apply the AHS Rosness TA, Engedal K, Chemali Z. (2016). Frontotemporal dementia: an evidence assessment of the acute treatment of migraine in adults to your updated clinician's guide. J Geriatr Psychiatry Neurol. 2016 Sep;29(5):271- patient with migraine. Headache. 2016:56:1194-200. [PMID: 27322907] 80. [PMID: 27502302] doi.org/10.1177/0891988716654986. doi:10.1111/head.12870 Item 53 Answer: D Item 52 Answer: D Educational Objective: Treat dementia with Lewy Educational Objective: Treat the symptoms of bodies. frontotemporal dementia pharmacologically. The most appropriate treatment is rivastigmine (Option D). This patient most likely has behavioral-variant frontotem- This patient has dementia with Lewy bodies, which is poral dementia and should be treated with a selective characterized by parkinsonian motor features (particularly > serotonin reuptake inhibitor (SSRI) (Option D). The most gait problems and slowness of movements), visual hallu- S 72) prominent feature of behavioral-variant frontotempo- cinations, rapid eye movement sleep behavior disorder, = o ral dementia is an alteration in personality and behavior and frequent fluctuations in attention. Because Parkinson a that typically develops years before the onset of cogni- disease is a progressive neurodegenerative disorder, cog- Py) = tive impairment. Because these behaviors often manifest nitive symptoms frequently develop at some point in the 2. a as obsessive-compulsive tendencies, impulsivity, apathy, disease course. When dementia occurs well after the motor = and impaired judgment, patients with this disorder are symptoms, it is considered Parkinson disease dementia. a. 2 often misdiagnosed as having bipolar disorder, obsessive- When dementia and motor symptoms develop within 1 to = © compulsive disorder, and depression. Although there are 2 years of each other, it is classified as dementia with Lewy wn no FDA-approved pharmacologic treatments for fronto- bodies. The best diagnostic tools remain the clinical history temporal dementia, SSRIs have shown effectiveness in and examination. Although not FDA approved for patients treating some of its symptoms, especially by decreasing the with dementia with Lewy bodies, both rivastigmine and frequency of compulsive behaviors. Consequently, SSRIs donepezil (acetylcholinesterase inhibitors) can improve are considered first-line treatment of the behavioral dis- cognition, global function, and activities of daily living. turbances of frontotemporal dementia and should be used Evidence suggests that even if patients do not improve with before any agents with a sedative effect. acetylcholinesterase inhibitors, they are less likely to deter- Acetylcholinesterase inhibitors (donepezil, rivastigmine, iorate while taking them. and galantamine) (Option A) and NMDA receptor antagonists Although clonazepam (Option A) does have efficacy (memantine) (Option C) are not FDA approved for the treat- in treating rapid eye movement sleep behavior disorder in ment of frontotemporal dementia and have little evidence dementia with Lewy bodies, it should be used at the lowest of benefit. In fact, they may actually increase behavioral effective dose and after or in conjunction with melatonin, problems. Additionally, an increase in acetylcholine can lead up to 12 mg nightly. This patient has had only a few instances to delirium, which in the setting of a patient with behavioral- of movements in his sleep over the last few years, which variant frontotemporal dementia can increase dangerous, would not warrant pharmacologic treatment. Melatonin is impulsive behavior. preferred because of its safety profile. Atypical antipsychotic agents (Option B), such as Haloperidol (Option B) is an antipsychotic drug, and risperidone, aripiprazole, and olanzapine, are not an FDA- patients with dementia with Lewy bodies are more likely approved treatment of dementia. Current evidence does not to have severe sensitivity to antipsychotics. Haloperidol, a support the routine use of haloperidol or second-generation first-generation antipsychotic, is also more likely to cause antipsychotic agents to treat delirium in adult inpatients. extrapyramidal side effects. Diagnosing dementia with Additionally, atypical antipsychotic agents can increase the Lewy bodies as early as possible is important because risk of death from cardiac arrhythmia or aspiration pneu- the behavioral problems associated with this condition monia in patients with dementia and thus should be avoided frequently result in the use of antipsychotic agents. If an in these patients unless absolutely necessary. antipsychotic medication is required to maintain safety of the patient or people around them, one with a lower risk for extrapyramidal side effects (e.g., quetiapine) is ¢ The most prominent feature of behavioral-variant preferred. frontotemporal dementia is an alteration in personal- There is no clear evidence that memantine (Option C) ity and behavior that typically develops years before has efficacy in dementia with Lewy bodies, so this agent the onset of cognitive impairment. should not be used for this patient.

Item 53 Answer: D Item 52 Answer: D Educational Objective: Treat dementia with Lewy Educational Objective: Treat the symptoms of bodies. frontotemporal dementia pharmacologically. The most appropriate treatment is rivastigmine (Option D). This patient most likely has behavioral-variant frontotem- This patient has dementia with Lewy bodies, which is poral dementia and should be treated with a selective characterized by parkinsonian motor features (particularly > serotonin reuptake inhibitor (SSRI) (Option D). The most gait problems and slowness of movements), visual hallu- S 72) prominent feature of behavioral-variant frontotempo- cinations, rapid eye movement sleep behavior disorder, = o ral dementia is an alteration in personality and behavior and frequent fluctuations in attention. Because Parkinson a that typically develops years before the onset of cogni- disease is a progressive neurodegenerative disorder, cog- Py) = tive impairment. Because these behaviors often manifest nitive symptoms frequently develop at some point in the 2. a as obsessive-compulsive tendencies, impulsivity, apathy, disease course. When dementia occurs well after the motor = and impaired judgment, patients with this disorder are symptoms, it is considered Parkinson disease dementia. a. 2 often misdiagnosed as having bipolar disorder, obsessive- When dementia and motor symptoms develop within 1 to = © compulsive disorder, and depression. Although there are 2 years of each other, it is classified as dementia with Lewy wn no FDA-approved pharmacologic treatments for fronto- bodies. The best diagnostic tools remain the clinical history temporal dementia, SSRIs have shown effectiveness in and examination. Although not FDA approved for patients treating some of its symptoms, especially by decreasing the with dementia with Lewy bodies, both rivastigmine and frequency of compulsive behaviors. Consequently, SSRIs donepezil (acetylcholinesterase inhibitors) can improve are considered first-line treatment of the behavioral dis- cognition, global function, and activities of daily living. turbances of frontotemporal dementia and should be used Evidence suggests that even if patients do not improve with before any agents with a sedative effect. acetylcholinesterase inhibitors, they are less likely to deter- Acetylcholinesterase inhibitors (donepezil, rivastigmine, iorate while taking them. and galantamine) (Option A) and NMDA receptor antagonists Although clonazepam (Option A) does have efficacy (memantine) (Option C) are not FDA approved for the treat- in treating rapid eye movement sleep behavior disorder in ment of frontotemporal dementia and have little evidence dementia with Lewy bodies, it should be used at the lowest of benefit. In fact, they may actually increase behavioral effective dose and after or in conjunction with melatonin, problems. Additionally, an increase in acetylcholine can lead up to 12 mg nightly. This patient has had only a few instances to delirium, which in the setting of a patient with behavioral- of movements in his sleep over the last few years, which variant frontotemporal dementia can increase dangerous, would not warrant pharmacologic treatment. Melatonin is impulsive behavior. preferred because of its safety profile. Atypical antipsychotic agents (Option B), such as Haloperidol (Option B) is an antipsychotic drug, and risperidone, aripiprazole, and olanzapine, are not an FDA- patients with dementia with Lewy bodies are more likely approved treatment of dementia. Current evidence does not to have severe sensitivity to antipsychotics. Haloperidol, a support the routine use of haloperidol or second-generation first-generation antipsychotic, is also more likely to cause antipsychotic agents to treat delirium in adult inpatients. extrapyramidal side effects. Diagnosing dementia with Additionally, atypical antipsychotic agents can increase the Lewy bodies as early as possible is important because risk of death from cardiac arrhythmia or aspiration pneu- the behavioral problems associated with this condition monia in patients with dementia and thus should be avoided frequently result in the use of antipsychotic agents. If an in these patients unless absolutely necessary. antipsychotic medication is required to maintain safety of the patient or people around them, one with a lower risk for extrapyramidal side effects (e.g., quetiapine) is ¢ The most prominent feature of behavioral-variant preferred. frontotemporal dementia is an alteration in personal- There is no clear evidence that memantine (Option C) ity and behavior that typically develops years before has efficacy in dementia with Lewy bodies, so this agent the onset of cognitive impairment. should not be used for this patient. ¢ Selective serotonin reuptake inhibitors have shown Zolpidem (Option E) is a nonbenzodiazepine y-amino-

Item 53 Answer: D Item 52 Answer: D Educational Objective: Treat dementia with Lewy Educational Objective: Treat the symptoms of bodies. frontotemporal dementia pharmacologically. The most appropriate treatment is rivastigmine (Option D). This patient most likely has behavioral-variant frontotem- This patient has dementia with Lewy bodies, which is poral dementia and should be treated with a selective characterized by parkinsonian motor features (particularly > serotonin reuptake inhibitor (SSRI) (Option D). The most gait problems and slowness of movements), visual hallu- S 72) prominent feature of behavioral-variant frontotempo- cinations, rapid eye movement sleep behavior disorder, = o ral dementia is an alteration in personality and behavior and frequent fluctuations in attention. Because Parkinson a that typically develops years before the onset of cogni- disease is a progressive neurodegenerative disorder, cog- Py) = tive impairment. Because these behaviors often manifest nitive symptoms frequently develop at some point in the 2. a as obsessive-compulsive tendencies, impulsivity, apathy, disease course. When dementia occurs well after the motor = and impaired judgment, patients with this disorder are symptoms, it is considered Parkinson disease dementia. a. 2 often misdiagnosed as having bipolar disorder, obsessive- When dementia and motor symptoms develop within 1 to = © compulsive disorder, and depression. Although there are 2 years of each other, it is classified as dementia with Lewy wn no FDA-approved pharmacologic treatments for fronto- bodies. The best diagnostic tools remain the clinical history temporal dementia, SSRIs have shown effectiveness in and examination. Although not FDA approved for patients treating some of its symptoms, especially by decreasing the with dementia with Lewy bodies, both rivastigmine and frequency of compulsive behaviors. Consequently, SSRIs donepezil (acetylcholinesterase inhibitors) can improve are considered first-line treatment of the behavioral dis- cognition, global function, and activities of daily living. turbances of frontotemporal dementia and should be used Evidence suggests that even if patients do not improve with before any agents with a sedative effect. acetylcholinesterase inhibitors, they are less likely to deter- Acetylcholinesterase inhibitors (donepezil, rivastigmine, iorate while taking them. and galantamine) (Option A) and NMDA receptor antagonists Although clonazepam (Option A) does have efficacy (memantine) (Option C) are not FDA approved for the treat- in treating rapid eye movement sleep behavior disorder in ment of frontotemporal dementia and have little evidence dementia with Lewy bodies, it should be used at the lowest of benefit. In fact, they may actually increase behavioral effective dose and after or in conjunction with melatonin, problems. Additionally, an increase in acetylcholine can lead up to 12 mg nightly. This patient has had only a few instances to delirium, which in the setting of a patient with behavioral- of movements in his sleep over the last few years, which variant frontotemporal dementia can increase dangerous, would not warrant pharmacologic treatment. Melatonin is impulsive behavior. preferred because of its safety profile. Atypical antipsychotic agents (Option B), such as Haloperidol (Option B) is an antipsychotic drug, and risperidone, aripiprazole, and olanzapine, are not an FDA- patients with dementia with Lewy bodies are more likely approved treatment of dementia. Current evidence does not to have severe sensitivity to antipsychotics. Haloperidol, a support the routine use of haloperidol or second-generation first-generation antipsychotic, is also more likely to cause antipsychotic agents to treat delirium in adult inpatients. extrapyramidal side effects. Diagnosing dementia with Additionally, atypical antipsychotic agents can increase the Lewy bodies as early as possible is important because risk of death from cardiac arrhythmia or aspiration pneu- the behavioral problems associated with this condition monia in patients with dementia and thus should be avoided frequently result in the use of antipsychotic agents. If an in these patients unless absolutely necessary. antipsychotic medication is required to maintain safety of the patient or people around them, one with a lower risk for extrapyramidal side effects (e.g., quetiapine) is ¢ The most prominent feature of behavioral-variant preferred. frontotemporal dementia is an alteration in personal- There is no clear evidence that memantine (Option C) ity and behavior that typically develops years before has efficacy in dementia with Lewy bodies, so this agent the onset of cognitive impairment. should not be used for this patient. ¢ Selective serotonin reuptake inhibitors have shown Zolpidem (Option E) is a nonbenzodiazepine y-amino- effectiveness in treating some of the symptoms of butyric acid receptor agonist used for sleep induction and maintenance. Sedative-hypnotic drugs such as zolpidem frontotemporal dementia, especially compulsive may worsen cognitive impairment and fall risks in patients behaviors. with dementia. Its use is not appropriate in this case.

effectiveness in treating some of the symptoms of butyric acid receptor agonist used for sleep induction and maintenance. Sedative-hypnotic drugs such as zolpidem frontotemporal dementia, especially compulsive may worsen cognitive impairment and fall risks in patients behaviors. with dementia. Its use is not appropriate in this case. 142

_ Answers and Critiques e In patients with dementia with Lewy bodies, both e Myasthenia gravis is an autoimmune disease of the rivastigmine and donepezil (acetylcholinesterase postsynaptic neuromuscular junction associated with inhibitors) can improve cognition, global function, antibodies to the postsynaptic acetylcholine receptors. and activities of living. e Indications for thymectomy in myasthenia gravis ¢ Melatonin is preferred therapy for rapid eye movement include the presence of thymoma and the need to min- sleep behavior disorder in patients with dementia with imize immunotherapy requirements in patients with- Lewy bodies. out thymoma who have active disease and positivity for acetylcholine receptor antibodies, are younger than Bibliography 65 years, and are within 3 years of diagnosis. McKeith IG, Boeve BE, Dickson DW, et al. Diagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB Consortium. Neurology. 2017;:89:88-100. [PMID: 28592453] doi:10.1212/ Bibliography wn wo WNL.0000000000004058 Gilhus NE, Tzartos S, Evoli A, et al. Myasthenia gravis. Nat Rev Dis Primers. = 2019;5:30. [PMID: 31048702] doi:10.1038/s41572-019-0079-y = = .

e In patients with dementia with Lewy bodies, both e Myasthenia gravis is an autoimmune disease of the rivastigmine and donepezil (acetylcholinesterase postsynaptic neuromuscular junction associated with inhibitors) can improve cognition, global function, antibodies to the postsynaptic acetylcholine receptors. and activities of living. e Indications for thymectomy in myasthenia gravis ¢ Melatonin is preferred therapy for rapid eye movement include the presence of thymoma and the need to min- sleep behavior disorder in patients with dementia with imize immunotherapy requirements in patients with- Lewy bodies. out thymoma who have active disease and positivity for acetylcholine receptor antibodies, are younger than Bibliography 65 years, and are within 3 years of diagnosis. McKeith IG, Boeve BE, Dickson DW, et al. Diagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB Consortium. Neurology. 2017;:89:88-100. [PMID: 28592453] doi:10.1212/ Bibliography wn wo WNL.0000000000004058 Gilhus NE, Tzartos S, Evoli A, et al. Myasthenia gravis. Nat Rev Dis Primers. = 2019;5:30. [PMID: 31048702] doi:10.1038/s41572-019-0079-y = = . Item 54 Answer: E i =] <

e In patients with dementia with Lewy bodies, both e Myasthenia gravis is an autoimmune disease of the rivastigmine and donepezil (acetylcholinesterase postsynaptic neuromuscular junction associated with inhibitors) can improve cognition, global function, antibodies to the postsynaptic acetylcholine receptors. and activities of living. e Indications for thymectomy in myasthenia gravis ¢ Melatonin is preferred therapy for rapid eye movement include the presence of thymoma and the need to min- sleep behavior disorder in patients with dementia with imize immunotherapy requirements in patients with- Lewy bodies. out thymoma who have active disease and positivity for acetylcholine receptor antibodies, are younger than Bibliography 65 years, and are within 3 years of diagnosis. McKeith IG, Boeve BE, Dickson DW, et al. Diagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB Consortium. Neurology. 2017;:89:88-100. [PMID: 28592453] doi:10.1212/ Bibliography wn wo WNL.0000000000004058 Gilhus NE, Tzartos S, Evoli A, et al. Myasthenia gravis. Nat Rev Dis Primers. = 2019;5:30. [PMID: 31048702] doi:10.1038/s41572-019-0079-y = = . Item 54 Answer: E i =] < Educational Objective: Treat myasthenia gravis with Item 55 Answer: 8B ts°] wn” tho thymectomy. Educational Objective: Evaluate psychiatric side effects Q

Educational Objective: Treat myasthenia gravis with Item 55 Answer: 8B ts°] wn” tho thymectomy. Educational Objective: Evaluate psychiatric side effects Q of antiepileptic drugs. = wn The most appropriate treatment is thymectomy (Option E). = Myasthenia gravis is an autoimmune disease of the post- Levetiracetam should be discontinued for this patient x

of antiepileptic drugs. = wn The most appropriate treatment is thymectomy (Option E). = Myasthenia gravis is an autoimmune disease of the post- Levetiracetam should be discontinued for this patient x synaptic neuromuscular junction associated with antibod- (Option B). Suicide in patients with epilepsy is estimated to ies to the postsynaptic acetylcholine receptors. Onset most be three times higher than in patients without epilepsy. This commonly occurs in the third decade of life in women and risk remains elevated in patients with or without known after age 50 years in men. Ptosis and diplopia are the first psychiatric disease, although psychiatric conditions are manifestations in two thirds of patients. Diagnosis is based underdiagnosed in patients with epilepsy. Although antie on clinical, serologic, and EMG findings. In this patient with pileptic drugs (AEDs) have been associated with increased early-onset and active myasthenia gravis (<3 years’ duration), risk of suicidality, the increased risk cannot be explained thymectomy provides the best chance of avoiding or mini- by medication use alone. Other identified risk factors for mizing long-term immunotherapy. Indications for thymec- suicide among patients with epilepsy include male gender tomy in myasthenia gravis include the presence of thymoma and high seizure frequency. Many antiepileptic drugs have and the need to minimize immunotherapy requirements in mood-altering properties. Changes in therapy or dosages patients without thymoma who have active disease, have may result in unintended behavioral or psychiatric conse positivity for acetylcholine receptor antibodies, are younger quences. Examples include the discontinuation of AEDs than 65 years, and are within 3 years of diagnosis. with mood-stabilizing effects (carbamazepine, lamotrigine, Eculizumab (Option A) is a monoclonal antibody tar- valproic acid) or introduction of AEDs with adverse psychi- geting the complement system that is FDA approved for atric manifestations (topiramate, gabapentin, levetiracetam). managing refractory myasthenia gravis in patients who are All AEDs carry a warning about worsening depression and not responding to other immunosuppressive treatments and suicidality, and all patients must be screened and monitored are positive for acetylcholine receptor antibodies. However, for these symptoms. For such screening, the Patient Health this medication would not fulfill the patient’s goal of mini- Questionnaire-2 is effective and easy to use. If a patient mizing immunosuppressive medications. provides a positive response to either of the two questions Immune checkpoint inhibitors, such as ipilimumab (“Over the past 2 weeks, have you felt down, depressed, (Option B), have shown promise in management of certain or hopeless?” and “Over the past 2 weeks, have you felt malignancies, but their use is associated with increased little interest or pleasure in doing things?”), further inves- incidence of neuromuscular adverse effects, including myas- tigation for depression is warranted. Although all seizure thenia gravis, neuropathy, and myopathy. These medications medications carry a warning about suicidal ideation, it is are not indicated for treatment of myasthenia gravis. important to identify the agents with the highest risk. Leve Plasma exchange (Option C) is an appropriate treat- tiracetam carries a higher incidence of causing or worsening ment for managing myasthenic crisis or as a bridge therapy depression, anxiety, and suicidal ideation than other seizure for patients with severe generalized weakness or bulbar medications. A recent retrospective review of AED use and symptoms. This patient does not show signs of severe weak- side effects for 4085 adult patients started on a new AED ness or impending myasthenic crisis. regimen found that psychiatric and behavioral side effects Reducing prednisone dose (Option D) in this patient occur significantly more frequently in patients taking leve- without an alternative immunomodulatory strategy is likely tiracetam and zonisamide than any other AED. On the other to aggravate the clinical symptoms and is not appropriate. hand, carbamazepine, clobazam, gabapentin, lamotrigine,

synaptic neuromuscular junction associated with antibod- (Option B). Suicide in patients with epilepsy is estimated to ies to the postsynaptic acetylcholine receptors. Onset most be three times higher than in patients without epilepsy. This commonly occurs in the third decade of life in women and risk remains elevated in patients with or without known after age 50 years in men. Ptosis and diplopia are the first psychiatric disease, although psychiatric conditions are manifestations in two thirds of patients. Diagnosis is based underdiagnosed in patients with epilepsy. Although antie on clinical, serologic, and EMG findings. In this patient with pileptic drugs (AEDs) have been associated with increased early-onset and active myasthenia gravis (<3 years’ duration), risk of suicidality, the increased risk cannot be explained thymectomy provides the best chance of avoiding or mini- by medication use alone. Other identified risk factors for mizing long-term immunotherapy. Indications for thymec- suicide among patients with epilepsy include male gender tomy in myasthenia gravis include the presence of thymoma and high seizure frequency. Many antiepileptic drugs have and the need to minimize immunotherapy requirements in mood-altering properties. Changes in therapy or dosages patients without thymoma who have active disease, have may result in unintended behavioral or psychiatric conse positivity for acetylcholine receptor antibodies, are younger quences. Examples include the discontinuation of AEDs than 65 years, and are within 3 years of diagnosis. with mood-stabilizing effects (carbamazepine, lamotrigine, Eculizumab (Option A) is a monoclonal antibody tar- valproic acid) or introduction of AEDs with adverse psychi- geting the complement system that is FDA approved for atric manifestations (topiramate, gabapentin, levetiracetam). managing refractory myasthenia gravis in patients who are All AEDs carry a warning about worsening depression and not responding to other immunosuppressive treatments and suicidality, and all patients must be screened and monitored are positive for acetylcholine receptor antibodies. However, for these symptoms. For such screening, the Patient Health this medication would not fulfill the patient’s goal of mini- Questionnaire-2 is effective and easy to use. If a patient mizing immunosuppressive medications. provides a positive response to either of the two questions Immune checkpoint inhibitors, such as ipilimumab (“Over the past 2 weeks, have you felt down, depressed, (Option B), have shown promise in management of certain or hopeless?” and “Over the past 2 weeks, have you felt malignancies, but their use is associated with increased little interest or pleasure in doing things?”), further inves- incidence of neuromuscular adverse effects, including myas- tigation for depression is warranted. Although all seizure thenia gravis, neuropathy, and myopathy. These medications medications carry a warning about suicidal ideation, it is are not indicated for treatment of myasthenia gravis. important to identify the agents with the highest risk. Leve Plasma exchange (Option C) is an appropriate treat- tiracetam carries a higher incidence of causing or worsening ment for managing myasthenic crisis or as a bridge therapy depression, anxiety, and suicidal ideation than other seizure for patients with severe generalized weakness or bulbar medications. A recent retrospective review of AED use and symptoms. This patient does not show signs of severe weak- side effects for 4085 adult patients started on a new AED ness or impending myasthenic crisis. regimen found that psychiatric and behavioral side effects Reducing prednisone dose (Option D) in this patient occur significantly more frequently in patients taking leve- without an alternative immunomodulatory strategy is likely tiracetam and zonisamide than any other AED. On the other to aggravate the clinical symptoms and is not appropriate. hand, carbamazepine, clobazam, gabapentin, lamotrigine, 143

Answers and Critiques oxcarbazepine, phenytoin, and valproic acid were signifi- A head CT scan (Option B) or MRI of the brain should cantly associated with a decreased risk of psychiatric and be reserved for patients with focal findings on the neurologic CONT. behavioral side effects. Therefore, levetiracetam is the drug examination that suggest an intracerebral process for acute that should be discontinued in this patient. delirium, such as ischemic stroke or hemorrhage. Lamotrigine and valproic acid (Options A and D) are Lumbar puncture with cerebrospinal fluid analysis mood stabilizers. Because this patient has bipolar disorder, (Option C) is essential for the evaluation of suspected cen- discontinuation of these agents is not advised. tral nervous system infection, particularly when directed by Quetiapine (Option C) would have a positive impact on focal findings or meningismus. However, nothing suggests a behavioral and psychiatric symptoms and thus should not be central nervous infection in this patient. discontinued in this patient. e The leading causes of delirium are fluid and electro-

oxcarbazepine, phenytoin, and valproic acid were signifi- A head CT scan (Option B) or MRI of the brain should cantly associated with a decreased risk of psychiatric and be reserved for patients with focal findings on the neurologic CONT. behavioral side effects. Therefore, levetiracetam is the drug examination that suggest an intracerebral process for acute that should be discontinued in this patient. delirium, such as ischemic stroke or hemorrhage. Lamotrigine and valproic acid (Options A and D) are Lumbar puncture with cerebrospinal fluid analysis mood stabilizers. Because this patient has bipolar disorder, (Option C) is essential for the evaluation of suspected cen- discontinuation of these agents is not advised. tral nervous system infection, particularly when directed by Quetiapine (Option C) would have a positive impact on focal findings or meningismus. However, nothing suggests a behavioral and psychiatric symptoms and thus should not be central nervous infection in this patient. discontinued in this patient. e The leading causes of delirium are fluid and electro- > e Levetiracetam has a higher incidence of causing or lyte disturbances, infection, drug toxicity, metabolic = 7) worsening depression, anxiety, and suicidal ideation disturbances, and sensory/environmental distur- = than other seizure medications. bances. @o = wn ¢ The top three classes of drugs most commonly impli- r°3) = Bibliography cated in precipitating delirium are opioids, benzodi- a. Chen B, Choi H, Hirsch LJ, et al. Psychiatric and behavioral side effects of (=) antiepileptic drugs in adults with epilepsy. Epilepsy Behav. 2017:76:24-31. azepines, and drugs with anticholinergic properties. me [PMID: 28931473] =. <2 Bibliography ij @o Setters B, Solberg LM. Delirium. Prim Care. 2017;44(3):541-59. [PMID: 28797379] wn Item 56 Answer: D doi:10.1016 /j-_pop.2017.04.010

> e Levetiracetam has a higher incidence of causing or lyte disturbances, infection, drug toxicity, metabolic = 7) worsening depression, anxiety, and suicidal ideation disturbances, and sensory/environmental distur- = than other seizure medications. bances. @o = wn ¢ The top three classes of drugs most commonly impli- r°3) = Bibliography cated in precipitating delirium are opioids, benzodi- a. Chen B, Choi H, Hirsch LJ, et al. Psychiatric and behavioral side effects of (=) antiepileptic drugs in adults with epilepsy. Epilepsy Behav. 2017:76:24-31. azepines, and drugs with anticholinergic properties. me [PMID: 28931473] =. <2 Bibliography ij @o Setters B, Solberg LM. Delirium. Prim Care. 2017;44(3):541-59. [PMID: 28797379] wn Item 56 Answer: D doi:10.1016 /j-_pop.2017.04.010 Educational Objective: Diagnose the cause of delirium.

> e Levetiracetam has a higher incidence of causing or lyte disturbances, infection, drug toxicity, metabolic = 7) worsening depression, anxiety, and suicidal ideation disturbances, and sensory/environmental distur- = than other seizure medications. bances. @o = wn ¢ The top three classes of drugs most commonly impli- r°3) = Bibliography cated in precipitating delirium are opioids, benzodi- a. Chen B, Choi H, Hirsch LJ, et al. Psychiatric and behavioral side effects of (=) antiepileptic drugs in adults with epilepsy. Epilepsy Behav. 2017:76:24-31. azepines, and drugs with anticholinergic properties. me [PMID: 28931473] =. <2 Bibliography ij @o Setters B, Solberg LM. Delirium. Prim Care. 2017;44(3):541-59. [PMID: 28797379] wn Item 56 Answer: D doi:10.1016 /j-_pop.2017.04.010 Educational Objective: Diagnose the cause of delirium. Urinalysis (Option D) is the most appropriate additional Item 57 Answer: C diagnostic test. The patient’s sleeplessness and agitation Educational Objective: Diagnose chorea gravidarum. suggest that he has developed a hyperactive delirium. His age and dementia diagnosis place him at increased risk The most appropriate diagnostic test is a pregnancy test for delirium; preexisting cognitive impairment is the major (Option C) to diagnose chorea gravidarum. Chorea presents predisposing factor for delirium. The evaluation of delirium as random, nonrepetitive, flowing, dance-like movements can be very difficult in patients who cannot provide a helpful that are not suppressible. Subacute onset of chorea is indic- history to focus the evaluation. A single cause of delirium ative of an acquired cause, whereas a more insidious course is unusual, found in only about one-third of hospitalized would be suggestive of neurodegenerative causes. Pregnancy patients; a mean of three causes of delirium is found in the should be considered as a potential cause of chorea in a balance of patients. The leading causes of delirium are fluid young woman. Chorea can emerge early in pregnancy as a and electrolyte disturbances, infection (most commonly result of gestational hormonal changes and usually abates urinary tract and pneumonia), metabolic disturbances, after childbirth. A history of rheumatic fever and antiphos- sensory/environmental disturbances, and drug toxicity. The pholipid antibodies are risk factors for chorea gravidarum. top three classes of drugs most commonly implicated in Other acquired causes of acute or subacute chorea include precipitating delirium are opioids, benzodiazepines, and medications, autoimmune disorders, endocrine disorders, drugs with anticholinergic properties. Intracerebral pro- and paraneoplastic syndromes. cesses are uncommon causes of acute onset delirium and Huntington disease (Option A), the most common neu- are usually clinically apparent. Based on these findings, a rodegenerative cause of chorea, is a slowly progressive auto- practical strategy can be developed for the evaluation of somal dominant condition caused by a trinucleotide repeat delirium in the absence of suggestive symptoms or findings. expansion in the huntingtin gene. Cognitive and mood A careful review of medications should be the first step. symptoms often precede chorea. The rapid progression of Serum electrolytes, serum creatinine, and blood urea nitro- chorea, the absence of a family history of Huntington dis- gen levels may detect hyponatremia and suggest deficits in ease, and the patient’s normal cognition makes Huntington intravascular volume not detected on physical examination. disease unlikely. A urinalysis and urine culture should also be obtained. If Chorea-acanthocytosis is a neurodegenerative disor- the cause remains obscure, it is reasonable to consider chest der. Detection of acanthocytes on a peripheral blood smear radiography. (Option B) helps with diagnosis. This patient’s subacute Arterial blood gas analysis (Option A) should be course makes this diagnosis unlikely. reserved for patients at risk for hypoxia or hypercarbia, Wilson disease should be considered in all patients such as patients with chronic cardiopulmonary diseases younger than 40 years with involuntary movements. Mea- or findings that point toward an acute cardiopulmonary surement of serum ceruloplasmin (Option D) or 24-hour event. urine copper excretion can be diagnostic. The subacute

Urinalysis (Option D) is the most appropriate additional Item 57 Answer: C diagnostic test. The patient’s sleeplessness and agitation Educational Objective: Diagnose chorea gravidarum. suggest that he has developed a hyperactive delirium. His age and dementia diagnosis place him at increased risk The most appropriate diagnostic test is a pregnancy test for delirium; preexisting cognitive impairment is the major (Option C) to diagnose chorea gravidarum. Chorea presents predisposing factor for delirium. The evaluation of delirium as random, nonrepetitive, flowing, dance-like movements can be very difficult in patients who cannot provide a helpful that are not suppressible. Subacute onset of chorea is indic- history to focus the evaluation. A single cause of delirium ative of an acquired cause, whereas a more insidious course is unusual, found in only about one-third of hospitalized would be suggestive of neurodegenerative causes. Pregnancy patients; a mean of three causes of delirium is found in the should be considered as a potential cause of chorea in a balance of patients. The leading causes of delirium are fluid young woman. Chorea can emerge early in pregnancy as a and electrolyte disturbances, infection (most commonly result of gestational hormonal changes and usually abates urinary tract and pneumonia), metabolic disturbances, after childbirth. A history of rheumatic fever and antiphos- sensory/environmental disturbances, and drug toxicity. The pholipid antibodies are risk factors for chorea gravidarum. top three classes of drugs most commonly implicated in Other acquired causes of acute or subacute chorea include precipitating delirium are opioids, benzodiazepines, and medications, autoimmune disorders, endocrine disorders, drugs with anticholinergic properties. Intracerebral pro- and paraneoplastic syndromes. cesses are uncommon causes of acute onset delirium and Huntington disease (Option A), the most common neu- are usually clinically apparent. Based on these findings, a rodegenerative cause of chorea, is a slowly progressive auto- practical strategy can be developed for the evaluation of somal dominant condition caused by a trinucleotide repeat delirium in the absence of suggestive symptoms or findings. expansion in the huntingtin gene. Cognitive and mood A careful review of medications should be the first step. symptoms often precede chorea. The rapid progression of Serum electrolytes, serum creatinine, and blood urea nitro- chorea, the absence of a family history of Huntington dis- gen levels may detect hyponatremia and suggest deficits in ease, and the patient’s normal cognition makes Huntington intravascular volume not detected on physical examination. disease unlikely. A urinalysis and urine culture should also be obtained. If Chorea-acanthocytosis is a neurodegenerative disor- the cause remains obscure, it is reasonable to consider chest der. Detection of acanthocytes on a peripheral blood smear radiography. (Option B) helps with diagnosis. This patient’s subacute Arterial blood gas analysis (Option A) should be course makes this diagnosis unlikely. reserved for patients at risk for hypoxia or hypercarbia, Wilson disease should be considered in all patients such as patients with chronic cardiopulmonary diseases younger than 40 years with involuntary movements. Mea- or findings that point toward an acute cardiopulmonary surement of serum ceruloplasmin (Option D) or 24-hour event. urine copper excretion can be diagnostic. The subacute 144

Answers and Critiques course of symptoms and absence of tremor and dystonia in in the management of primary headache disorders. Effi- this patient make Wilson disease unlikely. cacy of hydrocodone in acute migraine has not been estab- Spinal fluid analysis (Option E) is not a priority in the lished. When compared with medications indicated in acute clinical evaluation of isolated chorea without encephalopa- migraine (NSAIDs, triptans), opioid drugs carry increased thy. Acquired causes should first be ruled out with serologies risks of habituation, addiction, and development of medica- and, if needed, brain MRI. Rarely, spinal fluid analysis may tion overuse headache. be considered to assess for autoimmune or paraneoplastic causes. e Typical aura does not affect choice of acute migraine therapy, although triptans are contraindicated in the e Subacute onset of chorea is indicative of an acquired setting of brainstem or hemiplegic auras. cause, whereas a more insidious course would be sug- e In the presence of a stable clinical pattern of migraine gestive of neurodegenerative causes. ” and a normal neurologic examination, brain imaging o e Pregnancy should be considered as a potential cause = is not indicated. = of chorea in a young woman. = Bibliography o

course of symptoms and absence of tremor and dystonia in in the management of primary headache disorders. Effi- this patient make Wilson disease unlikely. cacy of hydrocodone in acute migraine has not been estab- Spinal fluid analysis (Option E) is not a priority in the lished. When compared with medications indicated in acute clinical evaluation of isolated chorea without encephalopa- migraine (NSAIDs, triptans), opioid drugs carry increased thy. Acquired causes should first be ruled out with serologies risks of habituation, addiction, and development of medica- and, if needed, brain MRI. Rarely, spinal fluid analysis may tion overuse headache. be considered to assess for autoimmune or paraneoplastic causes. e Typical aura does not affect choice of acute migraine therapy, although triptans are contraindicated in the e Subacute onset of chorea is indicative of an acquired setting of brainstem or hemiplegic auras. cause, whereas a more insidious course would be sug- e In the presence of a stable clinical pattern of migraine gestive of neurodegenerative causes. ” and a normal neurologic examination, brain imaging o e Pregnancy should be considered as a potential cause = is not indicated. = of chorea in a young woman. = Bibliography o Bibliography Charles A. Migraine. N Engl J Med 2017 Aug 10;377(6):553-61. [28792865] sc = doi: 10.1056/NEJMcp1605502. 3] Miyasaki J, Aldakheel A. Movement disorders in pregnancy. Continuum (Minneap Minn). 2014 Feb;20(1 Neurology of Pregnancy):148-161. [PMID: wn Ph 24492816] doi: 10.1212/01.CON.0000443842.18063.a9. o = wn Item 59 Answer: A iS = Item 58 Answer: D Educational Objective: Treat levodopa-induced Educational Objective: Treat acute migraine. dyskinesia.

Bibliography Charles A. Migraine. N Engl J Med 2017 Aug 10;377(6):553-61. [28792865] sc = doi: 10.1056/NEJMcp1605502. 3] Miyasaki J, Aldakheel A. Movement disorders in pregnancy. Continuum (Minneap Minn). 2014 Feb;20(1 Neurology of Pregnancy):148-161. [PMID: wn Ph 24492816] doi: 10.1212/01.CON.0000443842.18063.a9. o = wn Item 59 Answer: A iS = Item 58 Answer: D Educational Objective: Treat levodopa-induced Educational Objective: Treat acute migraine. dyskinesia. The most appropriate step in management is subcutaneous The most appropriate next step in treatment is amantadine sumatriptan (Option D). The patient’s migraine meets Inter- (Option A). This patient with Parkinson disease has levodopa- national Classification of Headache Disorders, 3rd edition, induced dyskinesia. Patients with Parkinson disease may diagnostic criteria for migraine with aura. Aura may occur in develop medication-related complications after a few years 20% to 30% of patients with migraine. It frequently precedes of treatment with levodopa. One example is the “wearing- pain but also occurs during or without head discomfort. Aura off” phenomenon before each dose of medication due to symptoms involve positive (e.g., paresthesia) and negative progressive loss of the ability to store and release dopa- (e.g., scotomata) neurologic phenomena developing gradu- mine for extended periods. As a result, motor and nonmotor ally and evolving over a period of 5 to 60 minutes. Resolution symptoms recur before the next dose of levodopa. Another is gradual and complete. Typical aura involves any combi- complication is emergence of choreiform dyskinesia that nation of homonymous visual, hemisensory, or language peaks after each dose of levodopa and is caused by hypersen- symptoms. This patient has a typical migraine-associated sitization of dopamine receptors in the brain. Amantadine, aura. The presence of typical aura does not affect choice of a glutamate N-methyl-p-aspartate receptor antagonist, is an acute migraine therapy, although triptans are contraindicated efficacious treatment for levodopa-induced dyskinesia and in the setting of brainstem or hemiplegic auras. Given this should be offered next. Reducing the levodopa dose is patient’s migraine with typical aura and the severe migraine another strategy to improve dyskinesia but would lead to present on awakening with rapidly developing vomiting, sub- recurrence of the wearing-off problem in this patient, which cutaneous sumatriptan is an appropriate therapeutic choice. was previously experienced as end-of-dose slowness and Brain MRI (Option A) is the preferred brain imaging anxiety. study in patients with chronic headaches and any red flags Deep-brain stimulation (Option B) is a surgical therapy concerning for secondary headaches. This patient presents that involves the delivery of electrical stimulation to key with a stable pattern of episodic headaches meeting criteria brain targets, such as the subthalamic nucleus and the glo- for migraine with aura. No red flags are present, and both bus pallidus interna. This mode of treatment is indicated for the headaches and aura symptoms can alternate locations, patients who continue to benefit from levodopa but experi- reducing concerns for a focal lesion. In the presence of a ence motor fluctuations or have a refractory tremor. It can be stable clinical pattern of migraine and a normal neurologic effective for levodopa-induced motor complications that are examination, guidelines suggest that brain imaging is not refractory to medical management. However, in this patient, indicated. amantadine should be tried first because it is effective and Head CT (Option B) is only indicated in evaluation of noninvasive. acute severe headache. Because this patient has a more epi- Typical strategies to address end-of-dose wearing-off sodic headache, head CT is not indicated. phenomenon include increasing the dose of levodopa or Guidelines recommend against using opioid agents, adding a catechol-O-methyltransferase inhibitor (entacapone such as hydrocodone (Option C) or butalbital products, [Option C]), a dopamine agonist (ropinirole [Option D)),

The most appropriate step in management is subcutaneous The most appropriate next step in treatment is amantadine sumatriptan (Option D). The patient’s migraine meets Inter- (Option A). This patient with Parkinson disease has levodopa- national Classification of Headache Disorders, 3rd edition, induced dyskinesia. Patients with Parkinson disease may diagnostic criteria for migraine with aura. Aura may occur in develop medication-related complications after a few years 20% to 30% of patients with migraine. It frequently precedes of treatment with levodopa. One example is the “wearing- pain but also occurs during or without head discomfort. Aura off” phenomenon before each dose of medication due to symptoms involve positive (e.g., paresthesia) and negative progressive loss of the ability to store and release dopa- (e.g., scotomata) neurologic phenomena developing gradu- mine for extended periods. As a result, motor and nonmotor ally and evolving over a period of 5 to 60 minutes. Resolution symptoms recur before the next dose of levodopa. Another is gradual and complete. Typical aura involves any combi- complication is emergence of choreiform dyskinesia that nation of homonymous visual, hemisensory, or language peaks after each dose of levodopa and is caused by hypersen- symptoms. This patient has a typical migraine-associated sitization of dopamine receptors in the brain. Amantadine, aura. The presence of typical aura does not affect choice of a glutamate N-methyl-p-aspartate receptor antagonist, is an acute migraine therapy, although triptans are contraindicated efficacious treatment for levodopa-induced dyskinesia and in the setting of brainstem or hemiplegic auras. Given this should be offered next. Reducing the levodopa dose is patient’s migraine with typical aura and the severe migraine another strategy to improve dyskinesia but would lead to present on awakening with rapidly developing vomiting, sub- recurrence of the wearing-off problem in this patient, which cutaneous sumatriptan is an appropriate therapeutic choice. was previously experienced as end-of-dose slowness and Brain MRI (Option A) is the preferred brain imaging anxiety. study in patients with chronic headaches and any red flags Deep-brain stimulation (Option B) is a surgical therapy concerning for secondary headaches. This patient presents that involves the delivery of electrical stimulation to key with a stable pattern of episodic headaches meeting criteria brain targets, such as the subthalamic nucleus and the glo- for migraine with aura. No red flags are present, and both bus pallidus interna. This mode of treatment is indicated for the headaches and aura symptoms can alternate locations, patients who continue to benefit from levodopa but experi- reducing concerns for a focal lesion. In the presence of a ence motor fluctuations or have a refractory tremor. It can be stable clinical pattern of migraine and a normal neurologic effective for levodopa-induced motor complications that are examination, guidelines suggest that brain imaging is not refractory to medical management. However, in this patient, indicated. amantadine should be tried first because it is effective and Head CT (Option B) is only indicated in evaluation of noninvasive. acute severe headache. Because this patient has a more epi- Typical strategies to address end-of-dose wearing-off sodic headache, head CT is not indicated. phenomenon include increasing the dose of levodopa or Guidelines recommend against using opioid agents, adding a catechol-O-methyltransferase inhibitor (entacapone such as hydrocodone (Option C) or butalbital products, [Option C]), a dopamine agonist (ropinirole [Option D)), 145

Answers and Critiques or a monoamine oxidase type B inhibitor (selegiline Repeating head CT (Option D) is not appropriate [Option E]). All of these strategies, however, can aggravate because the patient has not had any change in examina the dyskinesia and should be avoided in this patient. tion findings and has not yet reached the posttreatment time window of 24 hours, at which point repeat imaging is indicated. e Amantadine is an efficacious treatment for levodopa- induced dyskinesia. ¢ Treatments for end-of-dose wearing-off phenomenon e Any change in neurologic status following intravenous include increasing the dose of levodopa or adding a thrombolytic therapy for acute ischemic stroke should catechol-O-methyltransferase inhibitor, a dopamine prompt repeat imaging to assess for intracerebral agonist, or a monoamine oxidase type B inhibitor. bleeding.

include increasing the dose of levodopa or adding a thrombolytic therapy for acute ischemic stroke should catechol-O-methyltransferase inhibitor, a dopamine prompt repeat imaging to assess for intracerebral agonist, or a monoamine oxidase type B inhibitor. bleeding. e Patients with a stroke should receive a formal swallow ed Bibliography = evaluation before any oral intake. wn Homayoun H. Parkinson disease. Ann Intern Med. 2018;169:ITC33-ITC48. = [PMID: 30178019] doi:10.7326/AITC201809040 @o =e Bibliography A) Powers WJ, Rabinstein AA, Ackerson T, et al; American Heart Association m& = Stroke Council. 2018 Guidelines for the Early Management of Qa. Patients With Acute Ischemic Stroke: A Guideline for Healthcare (2) Item 60 Answer: E Professionals From the American Heart Association/American Stroke me Association. Stroke. 2018;49:e46-e110. [PMID: 29367334] doi:10.1161/ =. Educational Objective: Manage acute ischemic stroke STR.0000000000000158 2 fe treated with thrombolysis. oO vn The most appropriate next step is to perform a swallow eval Item 61 Answer: 8B uation (Option E) for dysphagia. She had an acute ischemic Educational Objective: Diagnose nonconvulsive status stroke treated appropriately with intravenous alteplase. She epilepticus. was not eligible for thrombectomy, given the absence of a large vessel occlusion. The patient’s neurologic status has The most appropriate next step in management is to initi not changed since she received treatment, but she should ate immediate continuous electroencephalography (EEG) continue to have neurologic checks and blood pressure mon- (Option B). This patient has coma of unexplained etiol- itoring once every hour for the first 24 hours. Any change in ogy, and left-sided extremity twitching. In this patient with neurologic status should prompt repeat imaging to ensure altered mental status and continuous focal motor seizures that there is not symptomatic intracerebral hemorrhage. in the setting of critical illness, the diagnosis is most likely which would also require reversal. Oral medications can be nonconvulsive status epilepticus (NCSE). NCSE should be considered after a formal dysphagia evaluation to minimize suspected whena patient, particularly a critically ill patient, the risk of aspiration pneumonia. has altered mental status with an unclear cause. NCSE is Atorvastatin (Option A) and other statins have not characterized as electrical seizure activity without clinically been shown to reduce the risk of recurrent stroke when evident seizure activity. Patients with NCSE may manifest administered within 30 days but can be considered after rhythmic twitching of one or more muscle groups but these a dysphagia evaluation has been completed, especially in findings are often subtle and can be missed. NCSE requires those patients with an atherosclerotic stroke subtype. This continuous (24-hour) EEG confirmation for diagnosis. patient most likely had a cardioembolic stroke, and the Additional brain imaging (Option A) will not estab- need for statin therapy will be determined by measurement lish the diagnosis of NCSE. Because the patient's CT of the of lipid levels. head has excluded new structural intracranial pathologies, Intravenous heparin (Option B) is not effective in acute additional imaging is unlikely to be helpful. MRI may reveal ischemic stroke of cardioembolic etiology; in this patient indirect signs of potentially harmful, neuronal hyperactivity it is contraindicated because she received thrombolysis. but has no role in management. Oral anticoagulation in patients with atrial fibrillation can Unlike evidence for convulsive status epilepticus (CSE), be restarted closer to hospital discharge if there are no evidence does not clearly favor empiric treatment for NCSE. hemorrhagic complications. A direct acting anticoagulant Initiation of intravenous fosphenytoin (Option C) would be will be a better choice than restarting warfarin because of considered only after EEG confirmed the diagnosis of NCSE, superior effectiveness, standard dosing, and lack of need for or if CSE was clinically diagnosed. monitoring. Reinitiation of intravenous propofol (Option D) may Oxygen supplementation (Option C) is not recom stop the twitching but is not the best next step in manage mended in patients with acute medical or neurologic injury ment. Propofol is an appropriate treatment for either NCSE unless there is a decline in the oxygen saturation. Supple- or CSE. However, in this case, empiric treatment would not mental oxygen in patients with normal oxygen saturation help ascertain the cause of the otherwise unexplained coma. increases mortality in patients with stroke and other acute In general, expert opinion recommends that an effort should illnesses. be made to diagnose NCSE as quickly as possible but with

e Patients with a stroke should receive a formal swallow ed Bibliography = evaluation before any oral intake. wn Homayoun H. Parkinson disease. Ann Intern Med. 2018;169:ITC33-ITC48. = [PMID: 30178019] doi:10.7326/AITC201809040 @o =e Bibliography A) Powers WJ, Rabinstein AA, Ackerson T, et al; American Heart Association m& = Stroke Council. 2018 Guidelines for the Early Management of Qa. Patients With Acute Ischemic Stroke: A Guideline for Healthcare (2) Item 60 Answer: E Professionals From the American Heart Association/American Stroke me Association. Stroke. 2018;49:e46-e110. [PMID: 29367334] doi:10.1161/ =. Educational Objective: Manage acute ischemic stroke STR.0000000000000158 2 fe treated with thrombolysis. oO vn The most appropriate next step is to perform a swallow eval Item 61 Answer: 8B uation (Option E) for dysphagia. She had an acute ischemic Educational Objective: Diagnose nonconvulsive status stroke treated appropriately with intravenous alteplase. She epilepticus. was not eligible for thrombectomy, given the absence of a large vessel occlusion. The patient’s neurologic status has The most appropriate next step in management is to initi not changed since she received treatment, but she should ate immediate continuous electroencephalography (EEG) continue to have neurologic checks and blood pressure mon- (Option B). This patient has coma of unexplained etiol- itoring once every hour for the first 24 hours. Any change in ogy, and left-sided extremity twitching. In this patient with neurologic status should prompt repeat imaging to ensure altered mental status and continuous focal motor seizures that there is not symptomatic intracerebral hemorrhage. in the setting of critical illness, the diagnosis is most likely which would also require reversal. Oral medications can be nonconvulsive status epilepticus (NCSE). NCSE should be considered after a formal dysphagia evaluation to minimize suspected whena patient, particularly a critically ill patient, the risk of aspiration pneumonia. has altered mental status with an unclear cause. NCSE is Atorvastatin (Option A) and other statins have not characterized as electrical seizure activity without clinically been shown to reduce the risk of recurrent stroke when evident seizure activity. Patients with NCSE may manifest administered within 30 days but can be considered after rhythmic twitching of one or more muscle groups but these a dysphagia evaluation has been completed, especially in findings are often subtle and can be missed. NCSE requires those patients with an atherosclerotic stroke subtype. This continuous (24-hour) EEG confirmation for diagnosis. patient most likely had a cardioembolic stroke, and the Additional brain imaging (Option A) will not estab- need for statin therapy will be determined by measurement lish the diagnosis of NCSE. Because the patient's CT of the of lipid levels. head has excluded new structural intracranial pathologies, Intravenous heparin (Option B) is not effective in acute additional imaging is unlikely to be helpful. MRI may reveal ischemic stroke of cardioembolic etiology; in this patient indirect signs of potentially harmful, neuronal hyperactivity it is contraindicated because she received thrombolysis. but has no role in management. Oral anticoagulation in patients with atrial fibrillation can Unlike evidence for convulsive status epilepticus (CSE), be restarted closer to hospital discharge if there are no evidence does not clearly favor empiric treatment for NCSE. hemorrhagic complications. A direct acting anticoagulant Initiation of intravenous fosphenytoin (Option C) would be will be a better choice than restarting warfarin because of considered only after EEG confirmed the diagnosis of NCSE, superior effectiveness, standard dosing, and lack of need for or if CSE was clinically diagnosed. monitoring. Reinitiation of intravenous propofol (Option D) may Oxygen supplementation (Option C) is not recom stop the twitching but is not the best next step in manage mended in patients with acute medical or neurologic injury ment. Propofol is an appropriate treatment for either NCSE unless there is a decline in the oxygen saturation. Supple- or CSE. However, in this case, empiric treatment would not mental oxygen in patients with normal oxygen saturation help ascertain the cause of the otherwise unexplained coma. increases mortality in patients with stroke and other acute In general, expert opinion recommends that an effort should illnesses. be made to diagnose NCSE as quickly as possible but with 146

_Answers and Critiques minimal sedation, so as to avoid inducing or prolonging coma and intubation. CON T. e Neuromyelitis optica is an inflammatory disorder of the central nervous system characterized by immune- mediated demyelination and axonal damage primarily e Nonconvulsive status epilepticus should be suspected affecting the spinal cord and optic nerves. in patients with critical illness who develop altered mental status of unclear cause. e The aquaporin-4 antibody is a specific biomarker for NMO and has a direct role in the pathogenesis. ¢ The diagnosis of nonconvulsive status epilepticus is confirmed with continuous (24-hour) electroenceph- Bibliography alography. Wingerchuk DM, Banwell B, Bennett JL, et al; International Panel for NMO Diagnosis. International consensus diagnostic criteria for neuromyelitis Bibliography optica spectrum disorders. Neurology. 2015;85:177-89. [PMID: 26092914] wn Herman ST, Abend NS, Bleck TP, et al; Critical Care Continuous EEG Task a = Force of the American Clinical Neurophysiology Society. Consensus statement on continuous EEG in critically ill adults and children, part I: = Item 63 Answer: B ‘ded

minimal sedation, so as to avoid inducing or prolonging coma and intubation. CON T. e Neuromyelitis optica is an inflammatory disorder of the central nervous system characterized by immune- mediated demyelination and axonal damage primarily e Nonconvulsive status epilepticus should be suspected affecting the spinal cord and optic nerves. in patients with critical illness who develop altered mental status of unclear cause. e The aquaporin-4 antibody is a specific biomarker for NMO and has a direct role in the pathogenesis. ¢ The diagnosis of nonconvulsive status epilepticus is confirmed with continuous (24-hour) electroenceph- Bibliography alography. Wingerchuk DM, Banwell B, Bennett JL, et al; International Panel for NMO Diagnosis. International consensus diagnostic criteria for neuromyelitis Bibliography optica spectrum disorders. Neurology. 2015;85:177-89. [PMID: 26092914] wn Herman ST, Abend NS, Bleck TP, et al; Critical Care Continuous EEG Task a = Force of the American Clinical Neurophysiology Society. Consensus statement on continuous EEG in critically ill adults and children, part I: = Item 63 Answer: B ‘ded indications. J Clin Neurophysiol. 2015;32:87-95. [PMID: 25626778] o— =) Educational Objective: Treat headache associated with s intracranial hypotension. = & Item 62 Answer: C wn This patient’s presentation is most compatible with intra- em

indications. J Clin Neurophysiol. 2015;32:87-95. [PMID: 25626778] o— =) Educational Objective: Treat headache associated with s intracranial hypotension. = & Item 62 Answer: C wn This patient’s presentation is most compatible with intra- em Educational Objective: Diagnose neuromyelitis optica. ag cranial hypotension, and the most appropriate treatment is = a] The most appropriate management is serum aquaporin-4 an epidural blood patch (Option B). Headache is the most i C4 antibody testing (Option C). This patient presents with common symptom of intracranial hypotension. Although bilateral optic neuritis. T2-weighted MRI of the thoracic this condition occurs most frequently after lumbar puncture, spine shows a longitudinally extensive (23 spinal segments) it can develop spontaneously. Headache presentation may myelitis. These findings are most suggestive of neuromyelitis be orthostatic, thunderclap, or subacute in nature. As with optica (NMO), a demyelinating disorder caused by antibod- post-lumbar puncture headache, associated symptoms may ies against aquaporin-4 channels that results in inflam- include tinnitus, diplopia, neck pain, nausea, photophobia, matory demyelination in the optic nerves and spinal cord. and phonophobia. Diagnosis can be confirmed by a cere- Although NMO may present with symptoms that are similar brospinal fluid (CSF) opening pressure of less than 60 mm to multiple sclerosis, distinguishing features include bilateral H,O, but lumbar puncture may introduce another site of (rather than unilateral) optic neuritis and longitudinally potential CSF leakage. Most clinicians rely on the contrast- extensive (rather than segmental) myelitis. If there is brain enhanced brain MRI finding of diffuse nonnodular pachy- involvement, brainstem or hypothalamic syndromes may meningeal enhancement, which is seen in nearly 80% of be seen. However, the brain may not be involved, as in this affected patients. Cerebellar tonsillar descent, subdural fluid patient whose brain MRI was normal. The marked spinal collections, decreased ventricular size, and engorgement of fluid pleocytosis with mostly neutrophils also is consistent the pituitary gland are other common findings. Leaks typi- with NMO and would be highly unusual for multiple scle- cally are spinal, with precise site detection made in only 50% rosis (MS) (in which cerebrospinal fluid [CSF] leukocytes are of patients by MRI or CT myelography. Those without identifi- often normal or slightly elevated). Aquaporin-4 antibody is able sites are empirically treated with “blind” lumbar epidural a specific biomarker for NMO and has a direct role in the blood patch (EBP) procedures, and those with definable loca- pathogenesis; diagnostic sensitivity and specificity has been tions receive “targeted” EBP procedures at the appropriate site. reported to be as high as 91% and 100%, respectively. Acetazolamide (Option A) is the treatment of choice for This patient is unlikely to have MS, and treatment with idiopathic intracranial hypertension. Papilledema is usually interferon beta (Option A) is unnecessary. Further, there present on examination. Enhanced brain MRI with magnetic is evidence to suggest that interferon beta can worsen the resonance venography may reveal widening of the optic condition of patients with NMO. nerve sheaths or flattening of the posterior optic globes, but Oligoclonal band testing (Option B) cannot adequately is otherwise unremarkable. discriminate between those with NMO and MS. Although There is no evidence of any generalized inflammatory 90% to 95% of patients with MS will have CSF-unique oligo- condition or one localized to the central nervous system and, clonal bands, up to 25% of patients with NMO can also have therefore, no role for systemic glucocorticoids, such as meth- this finding. Aquaporin-4 antibody testing would be a much ylprednisolone (Option C). Nodular or patchy enhancement, more specific test to discriminate between these conditions. not diffuse smooth enhancement, of dura would be antici- Copper (Option D) deficiency can cause optic neuropa pated with malignant or inflammatory disorders. thy and myelopathy. However, the presence of MRI contrast Chiari malformations describe a group of disorders enhancement and CSF pleocytosis in this patient are indica- that have in common anatomic anomalies of the cere- tions of a marked inflammatory response, which would not bellum, brainstem, and craniocervical junction, with be seen in copper deficiency. downward displacement of the cerebellum. Symptoms are

Educational Objective: Diagnose neuromyelitis optica. ag cranial hypotension, and the most appropriate treatment is = a] The most appropriate management is serum aquaporin-4 an epidural blood patch (Option B). Headache is the most i C4 antibody testing (Option C). This patient presents with common symptom of intracranial hypotension. Although bilateral optic neuritis. T2-weighted MRI of the thoracic this condition occurs most frequently after lumbar puncture, spine shows a longitudinally extensive (23 spinal segments) it can develop spontaneously. Headache presentation may myelitis. These findings are most suggestive of neuromyelitis be orthostatic, thunderclap, or subacute in nature. As with optica (NMO), a demyelinating disorder caused by antibod- post-lumbar puncture headache, associated symptoms may ies against aquaporin-4 channels that results in inflam- include tinnitus, diplopia, neck pain, nausea, photophobia, matory demyelination in the optic nerves and spinal cord. and phonophobia. Diagnosis can be confirmed by a cere- Although NMO may present with symptoms that are similar brospinal fluid (CSF) opening pressure of less than 60 mm to multiple sclerosis, distinguishing features include bilateral H,O, but lumbar puncture may introduce another site of (rather than unilateral) optic neuritis and longitudinally potential CSF leakage. Most clinicians rely on the contrast- extensive (rather than segmental) myelitis. If there is brain enhanced brain MRI finding of diffuse nonnodular pachy- involvement, brainstem or hypothalamic syndromes may meningeal enhancement, which is seen in nearly 80% of be seen. However, the brain may not be involved, as in this affected patients. Cerebellar tonsillar descent, subdural fluid patient whose brain MRI was normal. The marked spinal collections, decreased ventricular size, and engorgement of fluid pleocytosis with mostly neutrophils also is consistent the pituitary gland are other common findings. Leaks typi- with NMO and would be highly unusual for multiple scle- cally are spinal, with precise site detection made in only 50% rosis (MS) (in which cerebrospinal fluid [CSF] leukocytes are of patients by MRI or CT myelography. Those without identifi- often normal or slightly elevated). Aquaporin-4 antibody is able sites are empirically treated with “blind” lumbar epidural a specific biomarker for NMO and has a direct role in the blood patch (EBP) procedures, and those with definable loca- pathogenesis; diagnostic sensitivity and specificity has been tions receive “targeted” EBP procedures at the appropriate site. reported to be as high as 91% and 100%, respectively. Acetazolamide (Option A) is the treatment of choice for This patient is unlikely to have MS, and treatment with idiopathic intracranial hypertension. Papilledema is usually interferon beta (Option A) is unnecessary. Further, there present on examination. Enhanced brain MRI with magnetic is evidence to suggest that interferon beta can worsen the resonance venography may reveal widening of the optic condition of patients with NMO. nerve sheaths or flattening of the posterior optic globes, but Oligoclonal band testing (Option B) cannot adequately is otherwise unremarkable. discriminate between those with NMO and MS. Although There is no evidence of any generalized inflammatory 90% to 95% of patients with MS will have CSF-unique oligo- condition or one localized to the central nervous system and, clonal bands, up to 25% of patients with NMO can also have therefore, no role for systemic glucocorticoids, such as meth- this finding. Aquaporin-4 antibody testing would be a much ylprednisolone (Option C). Nodular or patchy enhancement, more specific test to discriminate between these conditions. not diffuse smooth enhancement, of dura would be antici- Copper (Option D) deficiency can cause optic neuropa pated with malignant or inflammatory disorders. thy and myelopathy. However, the presence of MRI contrast Chiari malformations describe a group of disorders enhancement and CSF pleocytosis in this patient are indica- that have in common anatomic anomalies of the cere- tions of a marked inflammatory response, which would not bellum, brainstem, and craniocervical junction, with be seen in copper deficiency. downward displacement of the cerebellum. Symptoms are 147

Answers andCritiques related to obstructive hydrocephalus, presence of abnor- Clonazepam (Option E) is sometimes used for treat- mal eye movements, and cerebellar deficits. The cerebellar ment of tardive dyskinesia. There is no indication to discon- tonsillar descent in the presence of dural thickening and tinue this medication. enhancement suggests that the finding is secondary to intracranial hypotension and not a Chiari malformation. Surgical suboccipital decompression (Option D) is thus not ¢ Tardive dyskinesia is characterized by choreiform and indicated. dystonic craniofacial movements, which often involve other body parts, such as the neck and trunk. e Tardive dyskinesia is an extrapyramidal complication e Postural headache is a common manifestation of of dopamine receptor-blocking medications. intracranial hypotension. ¢ Intracranial hypotension is most appropriately treated Bibliography > with an epidural blood patch procedure. Niemann N, Jankovic J. Treatment of tardive dyskinesia: a general overview => with focus on the vesicular monoamine transporter 2 inhibitors. Drugs. wn

¢ Intracranial hypotension is most appropriately treated Bibliography > with an epidural blood patch procedure. Niemann N, Jankovic J. Treatment of tardive dyskinesia: a general overview => with focus on the vesicular monoamine transporter 2 inhibitors. Drugs. wn = 2018;78:525-41. [PMID: 29484607] doi:10.1007/s40265-018-0874-x i) Bibliography = wn Kranz P, Gray L, Amrhein T. Spontaneous intracranial hypotension: 10 gy myths and misperceptions. Headache 2018 Jul;58(7):948-59. Epub 2018 = May 14. [PMID: 29797515] doi: 10.1111/head.13328. Item 65 Answer: B Qa. oO Educational Objective: Treat a multiple sclerosis relapse. = = a Item 64 Answer: C The most appropriate treatment is intravenous high-dose = glucocorticoids (Option B). This patient with relapsing- @ Educational Objective: Treat tardive dyskinesia. w remitting multiple sclerosis (MS) presents with a new MS The most appropriate treatment is to add valbenazine relapse, triggered by the development of a new, active cer (Option C). This patient has tardive dyskinesia, which con- ebellar lesion. The first-line treatment for an MS relapse is sists of persistent involuntary movements that are often a high-dose glucocorticoids, typically administered as intra combination of chorea (lip and face twitching) and dystonia venous methylprednisolone (1 g/d for 3 to 5 days). Patients (jaw closure, tongue protrusion). They can emerge after long- treated with methylprednisolone have a significant reduc- term exposure to dopamine D, receptor antagonists used as tion in the risk of either worsening or not improving within antipsychotic or antiemetic and prokinetic agents, such as 5 weeks of treatment when compared with placebo. Oral metoclopramide. All patients receiving these agents must equivalency studies have shown that oral methylprednis be warned about the risk for this complication. First step in olone (1 g/d) or prednisone (1250 mg/d) may act as viable management should be removal of the offending drug, as alternatives to this regimen. Frequent or prolonged glucocor- was done in this patient. If dyskinesia persists and causes ticoid treatment should be avoided to minimize the risks of functional or social impairment, treatment with a vesicular osteopenia and early cataracts. Any patient with a suspected monoamine transporter 2 inhibitor, such as valbenazine, relapse should be screened for causes of Uhthoff phenome- deutetrabenazine, or tetrabenazine, can be helpful. Potential non masquerading as a relapse (or “pseudorelapse”) to avoid adverse effects include sedation, depression, and suicidality; unnecessary treatment. The Uhthoff phenomenon describes patients should be monitored closely for psychiatric side a transient worsening of baseline neurologic symptoms in effects. In trials, valbenazine and deutetrabenazine have the setting of hot weather, physical exertion, or fever. shown a lower rate of psychiatric adverse effects compared Intramuscular adrenocorticotropin hormone (ACTH) with tetrabenazine. Other options include amantadine, gel (Option A) and plasmapheresis (Option E) have demon clonazepam, and, in the case of tardive dystonia, botulinum strated benefits for treatment of multiple sclerosis exacer- toxin injection. In refractory cases, deep-brain stimulation bations, but neither is the most appropriate intervention for can be beneficial. this patient. Given the extremely high cost of ACTH gel and Addition of aripiprazole (Option A), an atypical anti- the inconvenience and cost of hospitalization and the possi- psychotic agent, should, as with other dopamine-blocking ble adverse effects with plasmapheresis, these interventions agents, be avoided in patients with tardive dyskinesia. are typically reserved as second-line treatments for relapses Addition of ropinirole (Option B) is inappropriate as refractory to glucocorticoid treatment. treatment. This dopamine agonist is likely to exacerbate Intravenous immunoglobulin (Option C) may have a rather than benefit choreiform dyskinesia. similar benefit as plasmapheresis, but this intervention has Beginning cognitive behavioral therapy (Option D) is not been adequately studied as an alternative to glucocorti- recommended in patients with tic disorders (an unlikely coid treatment for MS relapses. diagnosis in this patient, given the history of exposure to Ocrelizumab (Option D) is an anti-CD20 monoclonal metoclopramide and lack of suppressibility). This patient has antibody. This medication has demonstrated benefit as a difficulty with eating because of dyskinesia, and pharmaco- disease-modifying therapy for long-term management of logic treatment is warranted instead of cognitive behavioral MS but has not been studied as a treatment for acute exac therapy. erbations.

= 2018;78:525-41. [PMID: 29484607] doi:10.1007/s40265-018-0874-x i) Bibliography = wn Kranz P, Gray L, Amrhein T. Spontaneous intracranial hypotension: 10 gy myths and misperceptions. Headache 2018 Jul;58(7):948-59. Epub 2018 = May 14. [PMID: 29797515] doi: 10.1111/head.13328. Item 65 Answer: B Qa. oO Educational Objective: Treat a multiple sclerosis relapse. = = a Item 64 Answer: C The most appropriate treatment is intravenous high-dose = glucocorticoids (Option B). This patient with relapsing- @ Educational Objective: Treat tardive dyskinesia. w remitting multiple sclerosis (MS) presents with a new MS The most appropriate treatment is to add valbenazine relapse, triggered by the development of a new, active cer (Option C). This patient has tardive dyskinesia, which con- ebellar lesion. The first-line treatment for an MS relapse is sists of persistent involuntary movements that are often a high-dose glucocorticoids, typically administered as intra combination of chorea (lip and face twitching) and dystonia venous methylprednisolone (1 g/d for 3 to 5 days). Patients (jaw closure, tongue protrusion). They can emerge after long- treated with methylprednisolone have a significant reduc- term exposure to dopamine D, receptor antagonists used as tion in the risk of either worsening or not improving within antipsychotic or antiemetic and prokinetic agents, such as 5 weeks of treatment when compared with placebo. Oral metoclopramide. All patients receiving these agents must equivalency studies have shown that oral methylprednis be warned about the risk for this complication. First step in olone (1 g/d) or prednisone (1250 mg/d) may act as viable management should be removal of the offending drug, as alternatives to this regimen. Frequent or prolonged glucocor- was done in this patient. If dyskinesia persists and causes ticoid treatment should be avoided to minimize the risks of functional or social impairment, treatment with a vesicular osteopenia and early cataracts. Any patient with a suspected monoamine transporter 2 inhibitor, such as valbenazine, relapse should be screened for causes of Uhthoff phenome- deutetrabenazine, or tetrabenazine, can be helpful. Potential non masquerading as a relapse (or “pseudorelapse”) to avoid adverse effects include sedation, depression, and suicidality; unnecessary treatment. The Uhthoff phenomenon describes patients should be monitored closely for psychiatric side a transient worsening of baseline neurologic symptoms in effects. In trials, valbenazine and deutetrabenazine have the setting of hot weather, physical exertion, or fever. shown a lower rate of psychiatric adverse effects compared Intramuscular adrenocorticotropin hormone (ACTH) with tetrabenazine. Other options include amantadine, gel (Option A) and plasmapheresis (Option E) have demon clonazepam, and, in the case of tardive dystonia, botulinum strated benefits for treatment of multiple sclerosis exacer- toxin injection. In refractory cases, deep-brain stimulation bations, but neither is the most appropriate intervention for can be beneficial. this patient. Given the extremely high cost of ACTH gel and Addition of aripiprazole (Option A), an atypical anti- the inconvenience and cost of hospitalization and the possi- psychotic agent, should, as with other dopamine-blocking ble adverse effects with plasmapheresis, these interventions agents, be avoided in patients with tardive dyskinesia. are typically reserved as second-line treatments for relapses Addition of ropinirole (Option B) is inappropriate as refractory to glucocorticoid treatment. treatment. This dopamine agonist is likely to exacerbate Intravenous immunoglobulin (Option C) may have a rather than benefit choreiform dyskinesia. similar benefit as plasmapheresis, but this intervention has Beginning cognitive behavioral therapy (Option D) is not been adequately studied as an alternative to glucocorti- recommended in patients with tic disorders (an unlikely coid treatment for MS relapses. diagnosis in this patient, given the history of exposure to Ocrelizumab (Option D) is an anti-CD20 monoclonal metoclopramide and lack of suppressibility). This patient has antibody. This medication has demonstrated benefit as a difficulty with eating because of dyskinesia, and pharmaco- disease-modifying therapy for long-term management of logic treatment is warranted instead of cognitive behavioral MS but has not been studied as a treatment for acute exac therapy. erbations. 148

Answers and Critiques had a stroke without other risk factors in whom the TTE has been uninformative; older patients who have other indica ¢ The first-line treatment for multiple sclerosis relapses tions, including a high suspicion for valvular pathology or is high-dose glucocorticoids, typically administered as an intracardiac tumor; and patients with recurrent embolic intravenous methylprednisolone (1 g/d for 3 to 5 days). strokes despite anticoagulation. e Intramuscular adrenocorticotropin hormone gel and plasmapheresis are typically reserved as second-line treatments for multiple sclerosis relapses refractory to e Leading causes of stroke in young patients with no glucocorticoid treatment. risk factors include cervicocephalic artery dissection, hypercoagulable state, vasculitis, and embolism via a Bibliography patent foramen ovale.

glucocorticoid treatment. risk factors include cervicocephalic artery dissection, hypercoagulable state, vasculitis, and embolism via a Bibliography patent foramen ovale. Galea I, Ward-Abel N, Heesen C. Relapse in multiple sclerosis. BMJ. e Transthoracic echocardiography with agitated saline 2015;350:h1765. Published 2015 Apr 14. [PMID: 25872511] doi:10.1136/ wn bmj.h1765 injection is indicated in younger patients with stroke a = without other risk factors. = = Item 66 Answer: D Bibliography rs) <s Messé SR, Gronseth GS, Kent DM, et al. Practice advisory update summary: Educational Objective: Evaluate an embolic stroke in a = Patent foramen ovale and secondary stroke prevention: Report of the © patient younger than 50 years. Guideline Subcommittee of the American Academy of Neurology. wn a] Neurology. 2020;94:876-885. [PMID: 32350058] doi:10.1212/WNL. o The most appropriate diagnostic test to perform next is 0000000000009443 > n transthoracic echocardiography (TTE) with agitated saline = <= (Option D). The patient had an embolic stroke, given the location in the occipital lobe and normal findings on vascu- Item 67 Answer: A lar imaging. Leading causes of stroke in young patients with Educational Objective: Diagnose primary central no risk factors include cervicocephalic artery dissection, nervous system lymphoma. a hypercoagulable state, vasculitis, and embolism from a patent foramen ovale. This patient does not have a headache, The most appropriate next step in management is brain and the magnetic resonance angiogram was normal, making biopsy (Option A). This patient most likely has primary a dissection very unlikely. Her lack of other systemic symp- central nervous system lymphoma (PCNSL). PCNSL is typ toms, including fevers, rash, and joint pain, makes vasculitis ically a B-cell non-Hodgkin lymphoma. Immunodeficiency, less likely. A primary hypercoagulable state remains possible including HIV infection, is the most consistent risk factor, and should be investigated, although it is less likely given but PCNSL incidence is increasing in older, immunocom- her normal laboratory values and prior pregnancies without petent patients. On MRI, PCNSL appears as a single, well- complications. TTE with agitated saline injection can reveal demarcated, deep white matter (periventricular) lesion with a right-to-left shunt, is less invasive than other cardiac imag- minimal to no mass effect or edema. The finding of lym ing, and is indicated in younger patients with stroke without phomatous cells in vitreous or cerebrospinal fluid samples other risk factors. Agitated saline with a TTE is not indicated (identified by cytology and flow cytometry) may obviate in patients older than 45 to 50 years because a patent fora- the need for biopsy. When these less invasive diagnostic men ovale is less likely to be causally related to symptoms in measures are negative, brain biopsy should be obtained to that age group. confirm the diagnosis. Catheter angiography (Option A) is not indicated Dexamethasone (Option B) is not indicated for this because there are no signs or imaging findings consistent patient, because there is no evidence of severe edema on her with vasculitis or dissection. This test can be indicated in brain MRI, and the examination is normal. Furthermore, young patients with stroke to evaluate for a vasculopathy, unless there is impending risk of death from herniation, glu- although noninvasive imaging, such as magnetic resonance cocorticoids should be avoided prior to biopsy in cases of angiography and CT angiography, will usually provide suffi- suspected PCNSL; glucocorticoids are known to temporarily cient resolution. suppress lymphoma, leading to false-negative biopsy results, Lumbar puncture (Option B) is not indicated because delays in diagnosis, and possibly a negative effect on outcomes. the patient does not have evidence of vasculitis. An inflam High-dose methotrexate (Option C) is often used as matory condition is unlikely, given the lack of fever and first-line treatment for PCNSL. However, tissue diagnosis is normal complete blood count and C-reactive protein level. If required before initiating. Methotrexate is frequently com- vasculitis is suspected, a lumbar puncture can demonstrate bined with rituximab in these cases. inflammation with elevated leukocyte count and protein PCNSL is typically not treated with surgical resection level in the spinal fluid. (Option D), because this has not been shown to improve Transesophageal echocardiography (TEE) (Option C) patient outcomes. Although these tumors are chemo- and is not appropriate as an initial cardiac imaging test. TEE is radiosensitive, recurrence is common and the prognosis is indicated in the following patients: young patients who have generally poor.

Galea I, Ward-Abel N, Heesen C. Relapse in multiple sclerosis. BMJ. e Transthoracic echocardiography with agitated saline 2015;350:h1765. Published 2015 Apr 14. [PMID: 25872511] doi:10.1136/ wn bmj.h1765 injection is indicated in younger patients with stroke a = without other risk factors. = = Item 66 Answer: D Bibliography rs) <s Messé SR, Gronseth GS, Kent DM, et al. Practice advisory update summary: Educational Objective: Evaluate an embolic stroke in a = Patent foramen ovale and secondary stroke prevention: Report of the © patient younger than 50 years. Guideline Subcommittee of the American Academy of Neurology. wn a] Neurology. 2020;94:876-885. [PMID: 32350058] doi:10.1212/WNL. o The most appropriate diagnostic test to perform next is 0000000000009443 > n transthoracic echocardiography (TTE) with agitated saline = <= (Option D). The patient had an embolic stroke, given the location in the occipital lobe and normal findings on vascu- Item 67 Answer: A lar imaging. Leading causes of stroke in young patients with Educational Objective: Diagnose primary central no risk factors include cervicocephalic artery dissection, nervous system lymphoma. a hypercoagulable state, vasculitis, and embolism from a patent foramen ovale. This patient does not have a headache, The most appropriate next step in management is brain and the magnetic resonance angiogram was normal, making biopsy (Option A). This patient most likely has primary a dissection very unlikely. Her lack of other systemic symp- central nervous system lymphoma (PCNSL). PCNSL is typ toms, including fevers, rash, and joint pain, makes vasculitis ically a B-cell non-Hodgkin lymphoma. Immunodeficiency, less likely. A primary hypercoagulable state remains possible including HIV infection, is the most consistent risk factor, and should be investigated, although it is less likely given but PCNSL incidence is increasing in older, immunocom- her normal laboratory values and prior pregnancies without petent patients. On MRI, PCNSL appears as a single, well- complications. TTE with agitated saline injection can reveal demarcated, deep white matter (periventricular) lesion with a right-to-left shunt, is less invasive than other cardiac imag- minimal to no mass effect or edema. The finding of lym ing, and is indicated in younger patients with stroke without phomatous cells in vitreous or cerebrospinal fluid samples other risk factors. Agitated saline with a TTE is not indicated (identified by cytology and flow cytometry) may obviate in patients older than 45 to 50 years because a patent fora- the need for biopsy. When these less invasive diagnostic men ovale is less likely to be causally related to symptoms in measures are negative, brain biopsy should be obtained to that age group. confirm the diagnosis. Catheter angiography (Option A) is not indicated Dexamethasone (Option B) is not indicated for this because there are no signs or imaging findings consistent patient, because there is no evidence of severe edema on her with vasculitis or dissection. This test can be indicated in brain MRI, and the examination is normal. Furthermore, young patients with stroke to evaluate for a vasculopathy, unless there is impending risk of death from herniation, glu- although noninvasive imaging, such as magnetic resonance cocorticoids should be avoided prior to biopsy in cases of angiography and CT angiography, will usually provide suffi- suspected PCNSL; glucocorticoids are known to temporarily cient resolution. suppress lymphoma, leading to false-negative biopsy results, Lumbar puncture (Option B) is not indicated because delays in diagnosis, and possibly a negative effect on outcomes. the patient does not have evidence of vasculitis. An inflam High-dose methotrexate (Option C) is often used as matory condition is unlikely, given the lack of fever and first-line treatment for PCNSL. However, tissue diagnosis is normal complete blood count and C-reactive protein level. If required before initiating. Methotrexate is frequently com- vasculitis is suspected, a lumbar puncture can demonstrate bined with rituximab in these cases. inflammation with elevated leukocyte count and protein PCNSL is typically not treated with surgical resection level in the spinal fluid. (Option D), because this has not been shown to improve Transesophageal echocardiography (TEE) (Option C) patient outcomes. Although these tumors are chemo- and is not appropriate as an initial cardiac imaging test. TEE is radiosensitive, recurrence is common and the prognosis is indicated in the following patients: young patients who have generally poor. 149

Answers and Critiques Although whole-brain radiation (Option E) is often Zolpidem (Option D) is a nonbenzodiazepine y-amino- considered in the management of PCNSL, there is significant butyric acid receptor agonist that is second-line therapy to CONT. neurocognitive morbidity associated with this treatment. CBT-I for patients with chronic insomnia. Treatment with However, whole-brain radiation would not be initiated in zolpidem will not improve this patient’s symptoms and will this patient without a biopsy-confirmed diagnosis of PCNSL. subject the patient to many potential side effects, including daytime sleepiness and impaired driving skills.

Although whole-brain radiation (Option E) is often Zolpidem (Option D) is a nonbenzodiazepine y-amino- considered in the management of PCNSL, there is significant butyric acid receptor agonist that is second-line therapy to CONT. neurocognitive morbidity associated with this treatment. CBT-I for patients with chronic insomnia. Treatment with However, whole-brain radiation would not be initiated in zolpidem will not improve this patient’s symptoms and will this patient without a biopsy-confirmed diagnosis of PCNSL. subject the patient to many potential side effects, including daytime sleepiness and impaired driving skills. e In patients with suspected central nervous system lymphoma, the finding of lymphomatous cells in ¢ Restless legs syndrome is characterized by an uncom- vitreous or cerebrospinal fluid samples (identified by fortable urge to move the legs that is worse at rest and cytology and flow cytometry) may obviate the need at night and is transiently relieved by movement. for biopsy. e Patients with restless legs syndrome should be = e In the evaluation of suspected central nervous system screened for iron deficiency because iron supplemen- = nn lymphoma, glucocorticoids should be avoided prior to tation in the presence of low-normal ferritin levels = @o diagnostic tissue sampling because glucocorticoids may resolve the symptoms. = wn can result in false-negative results. rot) = Bibliography [=m (=) Bibliography O’Regan D, Anderson KN. Restless legs syndrome and periodic limb move- =e ments of sleep. Br J Hosp Med (Lond). 2020;81(1):1-8. [PMID: 32003620] Han CH, Batchelor TT. Primary central nervous system lymphoma. =. doi:10.12968/hmed.2019.0319 2 Continuum (Minneap Minn). 2017;23:1601-1618. [PMID: 29200113] = @o wn Item 69 Answer: D Item 68 Answer: B Educational Objective: Evaluate the clinical course of Educational Objective: Diagnose restless legs syndrome. multiple sclerosis.

e In patients with suspected central nervous system lymphoma, the finding of lymphomatous cells in ¢ Restless legs syndrome is characterized by an uncom- vitreous or cerebrospinal fluid samples (identified by fortable urge to move the legs that is worse at rest and cytology and flow cytometry) may obviate the need at night and is transiently relieved by movement. for biopsy. e Patients with restless legs syndrome should be = e In the evaluation of suspected central nervous system screened for iron deficiency because iron supplemen- = nn lymphoma, glucocorticoids should be avoided prior to tation in the presence of low-normal ferritin levels = @o diagnostic tissue sampling because glucocorticoids may resolve the symptoms. = wn can result in false-negative results. rot) = Bibliography [=m (=) Bibliography O’Regan D, Anderson KN. Restless legs syndrome and periodic limb move- =e ments of sleep. Br J Hosp Med (Lond). 2020;81(1):1-8. [PMID: 32003620] Han CH, Batchelor TT. Primary central nervous system lymphoma. =. doi:10.12968/hmed.2019.0319 2 Continuum (Minneap Minn). 2017;23:1601-1618. [PMID: 29200113] = @o wn Item 69 Answer: D Item 68 Answer: B Educational Objective: Evaluate the clinical course of Educational Objective: Diagnose restless legs syndrome. multiple sclerosis. The most appropriate management is ferritin measurement This patient’s clinical course at this time can best be (Option B). Although most patients with insomnia do not described as secondary progressive multiple sclerosis (MS) benefit from diagnostic testing, signs or symptoms suggest- with progression and activity (Option D). The three main ing an associated medical condition, such as depression, phenotypes of MS are primary progressive, relapsing- anxiety, or sleep apnea, should be evaluated. This patient remitting, and secondary progressive. Relapsing-remitting has symptoms of restless leg syndrome (RLS). RLS is a MS can be further classified by activity status, and progres- common movement disorder characterized by an urge to sive forms of multiple sclerosis can be further classified by move the legs. Patients report an uncomfortable sensation activity and progression status. Clinical relapses or MRI evi- that is worse at rest and at night and is transiently relieved dence of new or enlarging lesions define “activity,” whereas by movement. RLS can interfere with falling or staying the gradual accumulation of neurologic deficits indepen- asleep and may be associated with periodic limb move- dent of relapses defines “progression.” Relapsing MS is typ- ments of sleep. Periodic limb movements of sleep (PLMS) ified by relapses or exacerbations, whereas progressive MS are brief triple flexion movements of the legs that repeat is typified by slow, progressive accumulation of disability. in 20-second cycles during sleep. This disorder is very If relapses occur initially and are followed by progression, common and can occur independently of or be associated as seen in this patient, the status can be described as sec- with RLS, sleep-disordered breathing, or narcolepsy. The ondary progressive. If relapses are not initially seen but diagnosis of PLMS is made by using polysomnography. progression occurs from onset, the status can be described Treatment of PLMS is required only if it causes marked as primary progressive. sleep fragmentation. Patients with RLS should be screened This patient does not have primary progressive (Option for iron deficiency because iron supplementation in the A) or relapsing-remitting (Options B and C) MS. She experi- presence of low-normal serum ferritin levels may resolve enced an initial relapse (optic neuritis 8 years ago), followed the symptoms. later by progression (3-year history of slowly worsening Cognitive behavioral therapy for insomnia (CBT-I) bilateral lower extremity weakness, fatigue, and numbness (Option A) is the first-line treatment for chronic insomnia in the hands); thus, her status is secondary progressive MS. but would not address the patient’s RLS. This patient does not have secondary progressive MS Polysomnography (Option C) is not indicated in the with progression but without activity (Option E). Current routine assessment of insomnia and is not required to status of MS is evaluated by the presence or absence of diagnose RLS unless there is concern for additional sleep current relapsing activity (such as new relapses or new disorders, such as obstructive sleep apnea or PLMS, that lesions or contrast enhancement seen on T2-weighted MRI) are thought to be contributing to arousal from sleep. This and the presence or absence of progression (such as recent patient’s symptoms seem directly related to RLS, and mea- progressive disability accumulation). This patient presents surement of serum ferritin is the best initial management. with recent disability accumulation, and her MRI shows

The most appropriate management is ferritin measurement This patient’s clinical course at this time can best be (Option B). Although most patients with insomnia do not described as secondary progressive multiple sclerosis (MS) benefit from diagnostic testing, signs or symptoms suggest- with progression and activity (Option D). The three main ing an associated medical condition, such as depression, phenotypes of MS are primary progressive, relapsing- anxiety, or sleep apnea, should be evaluated. This patient remitting, and secondary progressive. Relapsing-remitting has symptoms of restless leg syndrome (RLS). RLS is a MS can be further classified by activity status, and progres- common movement disorder characterized by an urge to sive forms of multiple sclerosis can be further classified by move the legs. Patients report an uncomfortable sensation activity and progression status. Clinical relapses or MRI evi- that is worse at rest and at night and is transiently relieved dence of new or enlarging lesions define “activity,” whereas by movement. RLS can interfere with falling or staying the gradual accumulation of neurologic deficits indepen- asleep and may be associated with periodic limb move- dent of relapses defines “progression.” Relapsing MS is typ- ments of sleep. Periodic limb movements of sleep (PLMS) ified by relapses or exacerbations, whereas progressive MS are brief triple flexion movements of the legs that repeat is typified by slow, progressive accumulation of disability. in 20-second cycles during sleep. This disorder is very If relapses occur initially and are followed by progression, common and can occur independently of or be associated as seen in this patient, the status can be described as sec- with RLS, sleep-disordered breathing, or narcolepsy. The ondary progressive. If relapses are not initially seen but diagnosis of PLMS is made by using polysomnography. progression occurs from onset, the status can be described Treatment of PLMS is required only if it causes marked as primary progressive. sleep fragmentation. Patients with RLS should be screened This patient does not have primary progressive (Option for iron deficiency because iron supplementation in the A) or relapsing-remitting (Options B and C) MS. She experi- presence of low-normal serum ferritin levels may resolve enced an initial relapse (optic neuritis 8 years ago), followed the symptoms. later by progression (3-year history of slowly worsening Cognitive behavioral therapy for insomnia (CBT-I) bilateral lower extremity weakness, fatigue, and numbness (Option A) is the first-line treatment for chronic insomnia in the hands); thus, her status is secondary progressive MS. but would not address the patient’s RLS. This patient does not have secondary progressive MS Polysomnography (Option C) is not indicated in the with progression but without activity (Option E). Current routine assessment of insomnia and is not required to status of MS is evaluated by the presence or absence of diagnose RLS unless there is concern for additional sleep current relapsing activity (such as new relapses or new disorders, such as obstructive sleep apnea or PLMS, that lesions or contrast enhancement seen on T2-weighted MRI) are thought to be contributing to arousal from sleep. This and the presence or absence of progression (such as recent patient’s symptoms seem directly related to RLS, and mea- progressive disability accumulation). This patient presents surement of serum ferritin is the best initial management. with recent disability accumulation, and her MRI shows 150

Answers and Critiques two contrast-enhancing lesions. Thus, her classification is There is no evidence of efficacy of any selective sero- secondary progressive MS with progression and activity. tonin reuptake inhibitor, such as sertraline (Option D), in the preventive treatment of migraine. Although evidence supports the use of verapamil e The three main phenotypes of multiple sclerosis are pri- (Option E) for prevention of episodic cluster headache, no mary progressive, relapsing-remitting, and secondary evidence exists to support its use in episodic migraine with progressive. or without aura.

two contrast-enhancing lesions. Thus, her classification is There is no evidence of efficacy of any selective sero- secondary progressive MS with progression and activity. tonin reuptake inhibitor, such as sertraline (Option D), in the preventive treatment of migraine. Although evidence supports the use of verapamil e The three main phenotypes of multiple sclerosis are pri- (Option E) for prevention of episodic cluster headache, no mary progressive, relapsing-remitting, and secondary evidence exists to support its use in episodic migraine with progressive. or without aura. e Relapsing-remitting multiple sclerosis can be further classified by activity status, and progressive forms of e Pharmacologic prophylaxis for migraine should be multiple sclerosis can be further classified by activity considered when the headache frequency reaches 4 to and progression status. 5 days per month and almost always is initiated when the frequency reaches 10 days per month. wn Bibliography <7) = Lublin FD, Reingold SC, Cohen JA, et al. Defining the clinical course of mul- ¢ Three B-blockers [propranolol, timolol, metoprolol] = tiple sclerosis: the 2013 revisions. Neurology. 2014;83:278-86. [PMID: and two antiepileptic drugs [divalproex sodium and a= 24871874] doi:10.1212/WNL.0000000000000560 Bre

e Relapsing-remitting multiple sclerosis can be further classified by activity status, and progressive forms of e Pharmacologic prophylaxis for migraine should be multiple sclerosis can be further classified by activity considered when the headache frequency reaches 4 to and progression status. 5 days per month and almost always is initiated when the frequency reaches 10 days per month. wn Bibliography <7) = Lublin FD, Reingold SC, Cohen JA, et al. Defining the clinical course of mul- ¢ Three B-blockers [propranolol, timolol, metoprolol] = tiple sclerosis: the 2013 revisions. Neurology. 2014;83:278-86. [PMID: and two antiepileptic drugs [divalproex sodium and a= 24871874] doi:10.1212/WNL.0000000000000560 Bre topiramate] and four monoclonal antibodies [ere- 1S) cs numab, fremanezumab, eptinezumab, galcanezumab] t c Item 70 Answer: A have Level A evidence supporting their use for the w”n

topiramate] and four monoclonal antibodies [ere- 1S) cs numab, fremanezumab, eptinezumab, galcanezumab] t c Item 70 Answer: A have Level A evidence supporting their use for the w”n pharmacologic prevention of episodic migraine; level Bae c<F) Educational Objective: Prevent migraine with biologic B evidence supports the use of amitriptyline and ven- = therapy. wn <= lafaxine. & The most appropriate treatment is erenumab (Option A). The patient has migraine meeting criteria for migraine with aura. Bibliography They remain episodic (<15 days monthly) but have become Parikh SK, Silberstein SD. Preventive treatment for episodic migraine. increasingly frequent. Pharmacologic prophylaxis should be Neurol Clin. 2019 Nov;37(4):753-70. [PMID: 31563231] doi: 10.1016/j-ncl. 2019.07.004. considered when the headache frequency reaches 4 to 5 days per month and almost always is initiated when the frequency reaches 10 days per month. Data suggest preventive medication Item 71 Answer: B can reduce migraine attack frequency and intensity, patient Educational Objective: Treat juvenile myoclonic epilepsy disability, and medical costs. According to evidence-based in a woman with childbearing potential. guidelines, five medications (three B-blockers [propranolol, timolol, metoprolol] and two antiepileptic drugs [divalproex The most appropriate management is to start levetiracetam sodium and topiramate]) have Level A evidence support- (Option B). This patient most likely has juvenile myoclonic ing their use for the pharmacologic prevention of episodic epilepsy (JME). In adults, JME is the most common form migraine; level B evidence supports the use of amitriptyline of idiopathic generalized epilepsy. JME seizures often are and venlafaxine. Migraine-specific biologic therapies have called “college seizures” because of the age of onset (teens or been developed and proven extremely effective in the pre- twenties) and associated triggers (sleep deprivation, alcohol vention of both episodic and chronic migraine. The mono- use, and stress). Epilepsy may not be diagnosed until the clonal antibodies erenumab, fremanezumab, eptinezumab, first generalized tonic-clonic seizure (GTCS) occurs because and galcanezumab target the calcitonin gene-related peptide myoclonic seizures often remain unrecognized. The pres- or its receptor and are delivered by monthly subcutaneous ence of myoclonic seizures is required for the diagnosis of injection. Guidelines recommend integrating these agents JME; patients may report dropping items from their hands, into prevention of episodic or chronic migraine after two commonly a coffee cup or hairbrush, because myoclonic sei- or three adequate but unsuccessful trials of oral preventive zures in JME generally occur in the morning. Most affected medication. patients have GTCSs, and approximately 30% of patients Menstrually associated migraine may occasionally have absence seizures. Seizures are often controlled with respond to the introduction of exogenous estrogen deliv- one or two antiepileptic drugs (AEDs). Lifelong AED therapy ered at the time of menses. Because of an increased risk is typically required. Because she is planning a pregnancy, of stroke, oral contraceptives containing estrogen, such as lamotrigine and levetiracetam are the preferred treatment ethinyl estradiol (Option B), are contraindicated in migraine options and are considered among the safest seizure medica- with aura. tions from a teratogenicity standpoint and for general, long- Level A evidence exists for the efficacy of onabotuli- term safety. However, since lamotrigine has been reported to num toxin A (Option C) for the prevention of chronic but worsen myoclonic seizures in some patients, levetiracetam not episodic migraine. Chronic migraine is a consideration may be preferred. in patients experiencing headaches occurring on at least Gabapentin (Option A) is used to treat focal seizures, 15 days per month or more whose attacks meet full criteria not generalized seizures. Both tonic-clonic and myoclonic for migraine on at least 8 days per month. seizures are considered generalized seizures.

pharmacologic prevention of episodic migraine; level Bae c<F) Educational Objective: Prevent migraine with biologic B evidence supports the use of amitriptyline and ven- = therapy. wn <= lafaxine. & The most appropriate treatment is erenumab (Option A). The patient has migraine meeting criteria for migraine with aura. Bibliography They remain episodic (<15 days monthly) but have become Parikh SK, Silberstein SD. Preventive treatment for episodic migraine. increasingly frequent. Pharmacologic prophylaxis should be Neurol Clin. 2019 Nov;37(4):753-70. [PMID: 31563231] doi: 10.1016/j-ncl. 2019.07.004. considered when the headache frequency reaches 4 to 5 days per month and almost always is initiated when the frequency reaches 10 days per month. Data suggest preventive medication Item 71 Answer: B can reduce migraine attack frequency and intensity, patient Educational Objective: Treat juvenile myoclonic epilepsy disability, and medical costs. According to evidence-based in a woman with childbearing potential. guidelines, five medications (three B-blockers [propranolol, timolol, metoprolol] and two antiepileptic drugs [divalproex The most appropriate management is to start levetiracetam sodium and topiramate]) have Level A evidence support- (Option B). This patient most likely has juvenile myoclonic ing their use for the pharmacologic prevention of episodic epilepsy (JME). In adults, JME is the most common form migraine; level B evidence supports the use of amitriptyline of idiopathic generalized epilepsy. JME seizures often are and venlafaxine. Migraine-specific biologic therapies have called “college seizures” because of the age of onset (teens or been developed and proven extremely effective in the pre- twenties) and associated triggers (sleep deprivation, alcohol vention of both episodic and chronic migraine. The mono- use, and stress). Epilepsy may not be diagnosed until the clonal antibodies erenumab, fremanezumab, eptinezumab, first generalized tonic-clonic seizure (GTCS) occurs because and galcanezumab target the calcitonin gene-related peptide myoclonic seizures often remain unrecognized. The pres- or its receptor and are delivered by monthly subcutaneous ence of myoclonic seizures is required for the diagnosis of injection. Guidelines recommend integrating these agents JME; patients may report dropping items from their hands, into prevention of episodic or chronic migraine after two commonly a coffee cup or hairbrush, because myoclonic sei- or three adequate but unsuccessful trials of oral preventive zures in JME generally occur in the morning. Most affected medication. patients have GTCSs, and approximately 30% of patients Menstrually associated migraine may occasionally have absence seizures. Seizures are often controlled with respond to the introduction of exogenous estrogen deliv- one or two antiepileptic drugs (AEDs). Lifelong AED therapy ered at the time of menses. Because of an increased risk is typically required. Because she is planning a pregnancy, of stroke, oral contraceptives containing estrogen, such as lamotrigine and levetiracetam are the preferred treatment ethinyl estradiol (Option B), are contraindicated in migraine options and are considered among the safest seizure medica- with aura. tions from a teratogenicity standpoint and for general, long- Level A evidence exists for the efficacy of onabotuli- term safety. However, since lamotrigine has been reported to num toxin A (Option C) for the prevention of chronic but worsen myoclonic seizures in some patients, levetiracetam not episodic migraine. Chronic migraine is a consideration may be preferred. in patients experiencing headaches occurring on at least Gabapentin (Option A) is used to treat focal seizures, 15 days per month or more whose attacks meet full criteria not generalized seizures. Both tonic-clonic and myoclonic for migraine on at least 8 days per month. seizures are considered generalized seizures. 151

Answers and Critiques Topiramate (Option C) is a reasonable treatment option The main complication of alteplase treatment (Option for patients with generalized epilepsy, and it is often used B) is symptomatic intracerebral hemorrhage (ICH), which in patients with comorbid migraine. However, topiramate occurs in up to 6% of treated patients, and mortality can should not be considered first-line treatment for patients be as high as 50% when present. Hypertension is a primary with childbearing potential because it is known for its tera- risk factor for hemorrhage, and therefore, blood pressure togenicity and is associated with cleft lip/palate in offspring. should be less than 185/110 mm Hg before treatment; this Valproic acid (Option D) can also be considered first- patient’s blood pressure exceeds this goal. Treatment with line treatment for JME, but given the negative adverse effects alteplase without achieving the blood pressure target with for women (weight gain, polycystic ovary syndrome, terato- pharmacologic intervention is associated with a higher risk genicity), it is a less appropriate management choice for this of hemorrhagic complications. patient, unless she is resistant to other treatments. Intravenous nitroprusside (Option D) is a vasodilator that can rapidly reduce blood pressure. The vasodilating > effects of nitroprusside can increase intracranial pressure = e In adults, juvenile myoclonic epilepsy is the most wn and should therefore be avoided in patients with preexisting = common form of idiopathic generalized epilepsy; increased intracranial pressure or with ischemic or hemor- oO ~~ wn associated myoclonic seizures are often called “college rhagic stroke. oo seizures” because of the age of onset (teens or twenties) s a. and associated triggers (sleep deprivation, alcohol use, (a) and stress). ¢ For patients with mild but disabling stroke symptoms, =e =. intravenous alteplase is indicated within 3 hours from 2 ¢ Ina woman with childbearing potential, lamotrigine < symptom onset of symptoms and up to 4.5 hours in © and levetiracetam are the safest antiepileptic drug wn select patients who meet treatment criteria. options. e Intravenous alteplase is recommended in patients

Topiramate (Option C) is a reasonable treatment option The main complication of alteplase treatment (Option for patients with generalized epilepsy, and it is often used B) is symptomatic intracerebral hemorrhage (ICH), which in patients with comorbid migraine. However, topiramate occurs in up to 6% of treated patients, and mortality can should not be considered first-line treatment for patients be as high as 50% when present. Hypertension is a primary with childbearing potential because it is known for its tera- risk factor for hemorrhage, and therefore, blood pressure togenicity and is associated with cleft lip/palate in offspring. should be less than 185/110 mm Hg before treatment; this Valproic acid (Option D) can also be considered first- patient’s blood pressure exceeds this goal. Treatment with line treatment for JME, but given the negative adverse effects alteplase without achieving the blood pressure target with for women (weight gain, polycystic ovary syndrome, terato- pharmacologic intervention is associated with a higher risk genicity), it is a less appropriate management choice for this of hemorrhagic complications. patient, unless she is resistant to other treatments. Intravenous nitroprusside (Option D) is a vasodilator that can rapidly reduce blood pressure. The vasodilating > effects of nitroprusside can increase intracranial pressure = e In adults, juvenile myoclonic epilepsy is the most wn and should therefore be avoided in patients with preexisting = common form of idiopathic generalized epilepsy; increased intracranial pressure or with ischemic or hemor- oO ~~ wn associated myoclonic seizures are often called “college rhagic stroke. oo seizures” because of the age of onset (teens or twenties) s a. and associated triggers (sleep deprivation, alcohol use, (a) and stress). ¢ For patients with mild but disabling stroke symptoms, =e =. intravenous alteplase is indicated within 3 hours from 2 ¢ Ina woman with childbearing potential, lamotrigine < symptom onset of symptoms and up to 4.5 hours in © and levetiracetam are the safest antiepileptic drug wn select patients who meet treatment criteria. options. e Intravenous alteplase is recommended in patients Bibliography with ischemic stroke whose blood pressure can be Sazgar M. Treatment of women with epilepsy. Continuum (Minneap Minn). lowered safely to less than 185/110 mm Hg with anti- 2019;25:408-30. [PMID: 30921016] hypertensive agents.

Bibliography with ischemic stroke whose blood pressure can be Sazgar M. Treatment of women with epilepsy. Continuum (Minneap Minn). lowered safely to less than 185/110 mm Hg with anti- 2019;25:408-30. [PMID: 30921016] hypertensive agents. Bibliography Item 72 Answer: C Powers WJ, Rabinstein AA, Ackerson T, et al; American Heart Association Stroke Council. 2018 Guidelines for the Early Management of Educational Objective: Treat blood pressure in a patient Patients With Acute Ischemic Stroke: A Guideline for Healthcare with ischemic stroke prior to thrombolytic therapy. Professionals From the American Heart Association/American Stroke Association. Stroke. 2018;49:e46-e110. [PMID: 29367334] doi:10.1161/ The most appropriate treatment for this patient is intrave- STR.0000000000000158

Bibliography Item 72 Answer: C Powers WJ, Rabinstein AA, Ackerson T, et al; American Heart Association Stroke Council. 2018 Guidelines for the Early Management of Educational Objective: Treat blood pressure in a patient Patients With Acute Ischemic Stroke: A Guideline for Healthcare with ischemic stroke prior to thrombolytic therapy. Professionals From the American Heart Association/American Stroke Association. Stroke. 2018;49:e46-e110. [PMID: 29367334] doi:10.1161/ The most appropriate treatment for this patient is intrave- STR.0000000000000158 nous labetalol (Option C). The patient has sudden-onset disabling focal neurologic symptoms without evidence of hemorrhage on imaging, with the most likely diagnosis being Item 73 Answer: C ischemic stroke. For patients with mild but disabling stroke Educational Objective: Treat Guillain-Barré syndrome. symptoms, intravenous alteplase is indicated within 3 hours from symptom onset and up to 4.5 hours in select patients The most appropriate treatment is plasma exchange who meet treatment criteria. Because her blood pressure is (Option C). This patient with rapidly progressive dysesthe- above the recommended target of less than 185/110 mm Hg, sia, weakness, and areflexia after recent vaccination likely she is ineligible for intravenous thrombolysis. Intravenous has Guillain-Barré syndrome. Onset is often preceded by a medications such as labetalol or nicardipine are therefore respiratory or gastrointestinal infection, triggering a T-cell- indicated to achieve that blood pressure target. Once this mediated autoimmune attack against peripheral nerve and target blood pressure is achieved, intravenous alteplase can root myelin. A very few patients develop Guillain-Barré syn- be administered. Blood pressure should be maintained at drome after immunization, surgery, or trauma. The weak- less than 180/105 mm Hg following alteplase administration. ness may occur first in the proximal muscles. Paresthesia Abciximab (Option A) is an intravenous glycoprotein and early low back pain are common. Dysautonomia can be IIb/IIIa receptor inhibitor that interferes with binding of severe and predispose patients to labile blood pressure and fibrinogen on the platelet surface and subsequent plate- arrhythmias. Progressive respiratory and bulbar weakness let aggregation. A systematic review of glycoprotein ITb/ may lead to rapid respiratory failure. Both plasma exchange Ila receptor antagonists in the treatment of acute ischemic and intravenous immunoglobulin are equally effective stroke found that these agents are associated with a signifi- and appropriate options in this setting. The combination cant risk for intracranial hemorrhage without a measurable of plasma exchange and immunoglobulin therapy is no improvement in death or disability. Most of the data were more effective than treatment with either modality alone. related to the use of abciximab. These agents are not recom- Although albuminocytologic dissociation (elevated protein mended in the treatment of acute ischemic stroke. level with a normal or mildly elevated leukocyte count) on

nous labetalol (Option C). The patient has sudden-onset disabling focal neurologic symptoms without evidence of hemorrhage on imaging, with the most likely diagnosis being Item 73 Answer: C ischemic stroke. For patients with mild but disabling stroke Educational Objective: Treat Guillain-Barré syndrome. symptoms, intravenous alteplase is indicated within 3 hours from symptom onset and up to 4.5 hours in select patients The most appropriate treatment is plasma exchange who meet treatment criteria. Because her blood pressure is (Option C). This patient with rapidly progressive dysesthe- above the recommended target of less than 185/110 mm Hg, sia, weakness, and areflexia after recent vaccination likely she is ineligible for intravenous thrombolysis. Intravenous has Guillain-Barré syndrome. Onset is often preceded by a medications such as labetalol or nicardipine are therefore respiratory or gastrointestinal infection, triggering a T-cell- indicated to achieve that blood pressure target. Once this mediated autoimmune attack against peripheral nerve and target blood pressure is achieved, intravenous alteplase can root myelin. A very few patients develop Guillain-Barré syn- be administered. Blood pressure should be maintained at drome after immunization, surgery, or trauma. The weak- less than 180/105 mm Hg following alteplase administration. ness may occur first in the proximal muscles. Paresthesia Abciximab (Option A) is an intravenous glycoprotein and early low back pain are common. Dysautonomia can be IIb/IIIa receptor inhibitor that interferes with binding of severe and predispose patients to labile blood pressure and fibrinogen on the platelet surface and subsequent plate- arrhythmias. Progressive respiratory and bulbar weakness let aggregation. A systematic review of glycoprotein ITb/ may lead to rapid respiratory failure. Both plasma exchange Ila receptor antagonists in the treatment of acute ischemic and intravenous immunoglobulin are equally effective stroke found that these agents are associated with a signifi- and appropriate options in this setting. The combination cant risk for intracranial hemorrhage without a measurable of plasma exchange and immunoglobulin therapy is no improvement in death or disability. Most of the data were more effective than treatment with either modality alone. related to the use of abciximab. These agents are not recom- Although albuminocytologic dissociation (elevated protein mended in the treatment of acute ischemic stroke. level with a normal or mildly elevated leukocyte count) on 152

Answers and Critiques cerebrospinal fluid (CSF) analysis and demyelinating poly- medication withdrawal). The dosing strategy can be sum- : radiculoneuropathy on electromyography are characteristic marized as “start low and go slow” because older adults CON ’ of Guillain-Barré syndrome, these findings may be absent usually require lower antiepileptic drug doses and are at early in the course of disease; the tests may need to be increased risk of interactions and decreased drug clearance. repeated later if diagnostic uncertainty persists. However, Multiple studies suggest lamotrigine, gabapentin, and leve- treatment should not be delayed for confirmatory testing. In tiracetam are better-tolerated and equally effective seizure this patient with characteristic symptoms and normal find medications when compared with older antiepileptic drugs ings on spinal imaging and CSF cell count, the most likely in treatment of older adults. diagnosis is Guillain-Barré syndrome and treatment should Oxcarbazepine (Option B) is not an appropriate treat- be initiated. ment measure because it is known to cause hyponatremia, Doxycycline (Option A) can be administered for treat- as does carbamazepine and eslicarbazepine. The risk for ment of Lyme disease, a condition that should be considered hyponatremia is particularly high in elderly patients, includ- in the differential diagnosis of Guillain-Barré syndrome in ing this patient, who is taking other medications that can wn @ endemic areas. In this patient, normal electromyographic lower sodium levels, such as thiazide diuretics. 3

: radiculoneuropathy on electromyography are characteristic marized as “start low and go slow” because older adults CON ’ of Guillain-Barré syndrome, these findings may be absent usually require lower antiepileptic drug doses and are at early in the course of disease; the tests may need to be increased risk of interactions and decreased drug clearance. repeated later if diagnostic uncertainty persists. However, Multiple studies suggest lamotrigine, gabapentin, and leve- treatment should not be delayed for confirmatory testing. In tiracetam are better-tolerated and equally effective seizure this patient with characteristic symptoms and normal find medications when compared with older antiepileptic drugs ings on spinal imaging and CSF cell count, the most likely in treatment of older adults. diagnosis is Guillain-Barré syndrome and treatment should Oxcarbazepine (Option B) is not an appropriate treat- be initiated. ment measure because it is known to cause hyponatremia, Doxycycline (Option A) can be administered for treat- as does carbamazepine and eslicarbazepine. The risk for ment of Lyme disease, a condition that should be considered hyponatremia is particularly high in elderly patients, includ- in the differential diagnosis of Guillain-Barré syndrome in ing this patient, who is taking other medications that can wn @ endemic areas. In this patient, normal electromyographic lower sodium levels, such as thiazide diuretics. 3 studies and CSF analysis do not support a diagnosis of Lyme Treatment with valproic acid (Option C) should be = disease; therefore, there is no indication for empiric therapy avoided in the elderly because it has an overall high risk i rs) with doxycycline. for multiple adverse effects, including tremor and cognitive s <= Glucocorticoids (Option B) are contraindicated in impairment (for example, parkinsonism with dementia that © Guillain-Barré syndrome and may worsen outcome. is often reversible). rn tere o No additional treatment (Option D) would be required Not initiating seizure medication (Option D) in this = wn in patients with pure sensory neuropathy and without defin patient is inappropriate despite the normal findings on his S itive diagnosis. However, this patient's progressive weakness brain MRI and electroencephalogram. These tests are inad- 9

studies and CSF analysis do not support a diagnosis of Lyme Treatment with valproic acid (Option C) should be = disease; therefore, there is no indication for empiric therapy avoided in the elderly because it has an overall high risk i rs) with doxycycline. for multiple adverse effects, including tremor and cognitive s <= Glucocorticoids (Option B) are contraindicated in impairment (for example, parkinsonism with dementia that © Guillain-Barré syndrome and may worsen outcome. is often reversible). rn tere o No additional treatment (Option D) would be required Not initiating seizure medication (Option D) in this = wn in patients with pure sensory neuropathy and without defin patient is inappropriate despite the normal findings on his S itive diagnosis. However, this patient's progressive weakness brain MRI and electroencephalogram. These tests are inad- 9 and areflexia should prompt initiation of therapy, with the equately sensitive for the diagnosis of epilepsy. Clinically, goal of preventing respiratory failure and reducing time to this patient meets the criteria for the diagnosis of epilepsy functional recovery. based on having two generalized tonic-clonic seizures that occurred more than 24 hours apart and without clear pro- voking factors. ¢ Guillain-Barré syndrome is an acute autoimmune demyelinating polyradiculoneuropathy that presents with rapidly progressive flaccid weakness. e Lamotrigine, gabapentin, and levetiracetam are better-

and areflexia should prompt initiation of therapy, with the equately sensitive for the diagnosis of epilepsy. Clinically, goal of preventing respiratory failure and reducing time to this patient meets the criteria for the diagnosis of epilepsy functional recovery. based on having two generalized tonic-clonic seizures that occurred more than 24 hours apart and without clear pro- voking factors. ¢ Guillain-Barré syndrome is an acute autoimmune demyelinating polyradiculoneuropathy that presents with rapidly progressive flaccid weakness. e Lamotrigine, gabapentin, and levetiracetam are better- e Plasma exchange and intravenous immunoglobulin tolerated and equally effective seizure medications when compared with older antiepileptic drugs in are equally effective treatment options for Guillain- Barré syndrome. treatment of older adults. Bibliography Bibliography Lezaic N, Gore G, Josephson CB, et al. The medical treatment of epilepsy in Willison HJ, Jacobs BC, van Doorn PA. Guillain-Barré syndrome. Lancet. the elderly: a systematic review and meta-analysis. Epilepsia. 2019;60: 2016;388:717-27. [PMID: 26948435] doi:10.1016/S0140-6736(16)00339-1 1325-40. [PMID: 31185130] Item 74 Answer: A Item 75 Answer: C Educational Objective: Treat epilepsy in older adults. Educational Objective: Diagnose diabetic amyotrophy.

Bibliography Bibliography Lezaic N, Gore G, Josephson CB, et al. The medical treatment of epilepsy in Willison HJ, Jacobs BC, van Doorn PA. Guillain-Barré syndrome. Lancet. the elderly: a systematic review and meta-analysis. Epilepsia. 2019;60: 2016;388:717-27. [PMID: 26948435] doi:10.1016/S0140-6736(16)00339-1 1325-40. [PMID: 31185130] Item 74 Answer: A Item 75 Answer: C Educational Objective: Treat epilepsy in older adults. Educational Objective: Diagnose diabetic amyotrophy. The most appropriate treatment for this patient is lamo- The most likely diagnosis is diabetic amyotrophy (Option trigine (Option A), which is a recommended treatment C), a subacute lumbosacral plexopathy that can present for older adults with new-onset epilepsy. Incidence of in patients with well-controlled type 2 diabetes mellitus. new- onset epilepsy is highest in adults older than 60 years. Diabetes often causes a distal symmetric sensorimotor Major risk factors for seizure recurrence include stroke and polyneuropathy, but other neuromuscular manifestations, dementia, but about one-third to one-half of cases are of including mononeuropathy, radiculopathy, small-fiber and unknown cause. The diagnosis of seizures in older adults autonomic neuropathies, and plexopathies are also possi- may be difficult because of atypical presentations that may ble. Onset of diabetic amyotrophy is often acute or subacute, mimic delirium, transient ischemic attack, or syncope. Pos- with asymmetric prominent pain followed by proximal sible seizures should always be included in the differential weakness and muscle loss. Sensory loss may occur to a vari- diagnosis of older patients with intermittent or fluctuating able degree. Electromyography often reveals diffuse dener- confusional states of unclear etiology. Antiepileptic drug vation and axon loss. MRI of the lumbar spine and CT of therapy should be started in older adults following two the abdomen and pelvis are indicated to rule out alternative clearly documented unprovoked seizures (e.g., seizures not causes, such as cauda equina syndrome and retroperitoneal related to alcohol metabolic derangements, medication, or hematoma. Management consists of supportive measures,

The most appropriate treatment for this patient is lamo- The most likely diagnosis is diabetic amyotrophy (Option trigine (Option A), which is a recommended treatment C), a subacute lumbosacral plexopathy that can present for older adults with new-onset epilepsy. Incidence of in patients with well-controlled type 2 diabetes mellitus. new- onset epilepsy is highest in adults older than 60 years. Diabetes often causes a distal symmetric sensorimotor Major risk factors for seizure recurrence include stroke and polyneuropathy, but other neuromuscular manifestations, dementia, but about one-third to one-half of cases are of including mononeuropathy, radiculopathy, small-fiber and unknown cause. The diagnosis of seizures in older adults autonomic neuropathies, and plexopathies are also possi- may be difficult because of atypical presentations that may ble. Onset of diabetic amyotrophy is often acute or subacute, mimic delirium, transient ischemic attack, or syncope. Pos- with asymmetric prominent pain followed by proximal sible seizures should always be included in the differential weakness and muscle loss. Sensory loss may occur to a vari- diagnosis of older patients with intermittent or fluctuating able degree. Electromyography often reveals diffuse dener- confusional states of unclear etiology. Antiepileptic drug vation and axon loss. MRI of the lumbar spine and CT of therapy should be started in older adults following two the abdomen and pelvis are indicated to rule out alternative clearly documented unprovoked seizures (e.g., seizures not causes, such as cauda equina syndrome and retroperitoneal related to alcohol metabolic derangements, medication, or hematoma. Management consists of supportive measures, 153

Answers and Critiques physical therapy, and pain control; despite sporadic reports Botulinum toxin injection (Option A) can be consid- of benefit from immunomodulatory therapies, the benefit ered for management of essential tremor of the head and of these therapies remains unproven. vocal cord, but its benefit for limb tremor is limited by the Alcohol misuse often causes a toxic neuropathy (Option common adverse effect of local weakness. In addition, this A) characterized by symmetric distal sensory or sensorim- treatment is not FDA-approved for treatment of tremor. otor involvement. Plexopathy is not a typical presentation Levodopa (Option C) can be beneficial for resting tremor of alcohol-related neuropathy. Plexopathies originate at the associated with parkinsonism. Tremor in Parkinson disease level of the brachial or lumbosacral plexus and involve mul- is asymmetric and associated with increased tone and bra- tiple sensory and motor nerves simultaneously. dykinesia. A large-amplitude bilateral action tremor, as seen Autoimmune ganglionopathy (Option B) is character- in this patient, is inconsistent with Parkinson disease. ized by severe loss of vibration and joint position sense in a Occupational therapy (Option D) can help patients with single limb without motor deficits. This phenotype should mild essential tremor through adaptive strategies, such as Pa prompt a search for possible underlying malignancy. This weighted utensils and wrist weights. However, these strat- = n diagnosis is not consistent with this patient’s symptoms. egies are often ineffective against severe high-amplitude = Hypothyroidism often presents with proximal myop- tremor. o = i) athy or distal sensorimotor axonal neuropathy but not a & = lumbosacral plexopathy. Compressive brachial plexopathy a (Option D) caused by encroachment from an enlarged thy- e First-line pharmacologic treatments for essential tremor a roid gland or mass has been reported rarely. include propranolol, primidone, and topiramate. = =. 2 e Surgical therapies, including deep-brain stimulation < Oo and focused ultrasound thalamotomy, can control A) e Diabetic amyotrophy can occur in patients with well- tremor in refractory essential tremor associated with controlled diabetes. functional disability. ¢ Onset of diabetic amyotrophy is often acute or subacute, with asymmetric prominent pain followed by proximal Bibliography weakness and muscle loss. Haubenberger D, Hallett M. Essential tremor. N Engl J Med. 2018;378:1802- 10. [PMID: 29742376] doi:10.1056/NEJMcp1707928

physical therapy, and pain control; despite sporadic reports Botulinum toxin injection (Option A) can be consid- of benefit from immunomodulatory therapies, the benefit ered for management of essential tremor of the head and of these therapies remains unproven. vocal cord, but its benefit for limb tremor is limited by the Alcohol misuse often causes a toxic neuropathy (Option common adverse effect of local weakness. In addition, this A) characterized by symmetric distal sensory or sensorim- treatment is not FDA-approved for treatment of tremor. otor involvement. Plexopathy is not a typical presentation Levodopa (Option C) can be beneficial for resting tremor of alcohol-related neuropathy. Plexopathies originate at the associated with parkinsonism. Tremor in Parkinson disease level of the brachial or lumbosacral plexus and involve mul- is asymmetric and associated with increased tone and bra- tiple sensory and motor nerves simultaneously. dykinesia. A large-amplitude bilateral action tremor, as seen Autoimmune ganglionopathy (Option B) is character- in this patient, is inconsistent with Parkinson disease. ized by severe loss of vibration and joint position sense in a Occupational therapy (Option D) can help patients with single limb without motor deficits. This phenotype should mild essential tremor through adaptive strategies, such as Pa prompt a search for possible underlying malignancy. This weighted utensils and wrist weights. However, these strat- = n diagnosis is not consistent with this patient’s symptoms. egies are often ineffective against severe high-amplitude = Hypothyroidism often presents with proximal myop- tremor. o = i) athy or distal sensorimotor axonal neuropathy but not a & = lumbosacral plexopathy. Compressive brachial plexopathy a (Option D) caused by encroachment from an enlarged thy- e First-line pharmacologic treatments for essential tremor a roid gland or mass has been reported rarely. include propranolol, primidone, and topiramate. = =. 2 e Surgical therapies, including deep-brain stimulation < Oo and focused ultrasound thalamotomy, can control A) e Diabetic amyotrophy can occur in patients with well- tremor in refractory essential tremor associated with controlled diabetes. functional disability. ¢ Onset of diabetic amyotrophy is often acute or subacute, with asymmetric prominent pain followed by proximal Bibliography weakness and muscle loss. Haubenberger D, Hallett M. Essential tremor. N Engl J Med. 2018;378:1802- 10. [PMID: 29742376] doi:10.1056/NEJMcp1707928 Bibliography Li Y. Axonal sensorimotor polyneuropathies. Continuum (Minneap Minn). 2017;23:1378-93. [PMID: 28968367] doi:10.1212/CON.0000000000000514 Item 77 Answer: A

physical therapy, and pain control; despite sporadic reports Botulinum toxin injection (Option A) can be consid- of benefit from immunomodulatory therapies, the benefit ered for management of essential tremor of the head and of these therapies remains unproven. vocal cord, but its benefit for limb tremor is limited by the Alcohol misuse often causes a toxic neuropathy (Option common adverse effect of local weakness. In addition, this A) characterized by symmetric distal sensory or sensorim- treatment is not FDA-approved for treatment of tremor. otor involvement. Plexopathy is not a typical presentation Levodopa (Option C) can be beneficial for resting tremor of alcohol-related neuropathy. Plexopathies originate at the associated with parkinsonism. Tremor in Parkinson disease level of the brachial or lumbosacral plexus and involve mul- is asymmetric and associated with increased tone and bra- tiple sensory and motor nerves simultaneously. dykinesia. A large-amplitude bilateral action tremor, as seen Autoimmune ganglionopathy (Option B) is character- in this patient, is inconsistent with Parkinson disease. ized by severe loss of vibration and joint position sense in a Occupational therapy (Option D) can help patients with single limb without motor deficits. This phenotype should mild essential tremor through adaptive strategies, such as Pa prompt a search for possible underlying malignancy. This weighted utensils and wrist weights. However, these strat- = n diagnosis is not consistent with this patient’s symptoms. egies are often ineffective against severe high-amplitude = Hypothyroidism often presents with proximal myop- tremor. o = i) athy or distal sensorimotor axonal neuropathy but not a & = lumbosacral plexopathy. Compressive brachial plexopathy a (Option D) caused by encroachment from an enlarged thy- e First-line pharmacologic treatments for essential tremor a roid gland or mass has been reported rarely. include propranolol, primidone, and topiramate. = =. 2 e Surgical therapies, including deep-brain stimulation < Oo and focused ultrasound thalamotomy, can control A) e Diabetic amyotrophy can occur in patients with well- tremor in refractory essential tremor associated with controlled diabetes. functional disability. ¢ Onset of diabetic amyotrophy is often acute or subacute, with asymmetric prominent pain followed by proximal Bibliography weakness and muscle loss. Haubenberger D, Hallett M. Essential tremor. N Engl J Med. 2018;378:1802- 10. [PMID: 29742376] doi:10.1056/NEJMcp1707928 Bibliography Li Y. Axonal sensorimotor polyneuropathies. Continuum (Minneap Minn). 2017;23:1378-93. [PMID: 28968367] doi:10.1212/CON.0000000000000514 Item 77 Answer: A Educational Objective: Treat acute ischemic stroke with thrombolysis. Item 76 Answer: B This patient should receive intravenous alteplase (Option Educational Objective: Treat refractory essential tremor. A). She has an acute ischemic stroke and is seen within The most appropriate treatment is deep-brain stimulation 3 hours of onset of symptoms, which include the disabling (Option B). This patient has severe medication-refractory neurologic feature of hemiparesis involving the left face, left essential tremor. Essential tremor is the most common arm and leg, and left-sided sensation. Her National Institutes movement disorder, affecting 1% to 2% of the population. of Health Stroke Scale score is 6. The patient does not have It is defined as an isolated tremor syndrome of at least any absolute or relative exclusion criteria for thromboly- 3 years’ duration characterized by action tremor in the upper sis, including recent surgery, prior or current intracranial extremities, with or without involvement of other body hemorrhage, extensive hypodensity on imaging, or blood parts, such as the head, larynx, or lower limbs. A family his- pressure above the target of 185/110 mm Hg. The benefits tory of tremor is present in 50% of patients. First-line treat- of intravenous alteplase in acute ischemic stroke, including ment for essential tremor includes propranolol, primidone, the lower likelihood of neurologic disability at 3 months and topiramate. Clonazepam is a second-line treatment. poststroke, are generally thought to outweigh the small risk In this patient, propranolol, primidone, and clonazepam of hemorrhage. have already proved ineffective, and topiramate (Option E) Acute administration of anticoagulation in ischemic is contraindicated because of his history of kidney stones. strokes (whether related to atrial fibrillation or not) does not Surgical therapies, including deep-brain stimulation (uni- reduce the short-term risk of recurrent stroke and increases lateral or bilateral) and focused ultrasound thalamotomy the risk of hemorrhage into the territory of cerebral infarc- (only unilateral), can control tremor in refractory essential tion (hemorrhagic conversion). Low-molecular-weight hep- tremor associated with functional disability. Results of a arin (Option B) is not indicated. randomized trial suggest that deep-brain stimulation results Treatment of blood pressure with antihypertensive in greater functional improvements than thalamotomy and agents (such as nicardipine [Option C]) is not indicated in fewer adverse events, such as dysarthria, sensory distur- acute ischemic stroke unless the blood pressure of a patient bances, and gait disturbances. eligible for alteplase is greater than 185/110 mm Hg (or is

Educational Objective: Treat acute ischemic stroke with thrombolysis. Item 76 Answer: B This patient should receive intravenous alteplase (Option Educational Objective: Treat refractory essential tremor. A). She has an acute ischemic stroke and is seen within The most appropriate treatment is deep-brain stimulation 3 hours of onset of symptoms, which include the disabling (Option B). This patient has severe medication-refractory neurologic feature of hemiparesis involving the left face, left essential tremor. Essential tremor is the most common arm and leg, and left-sided sensation. Her National Institutes movement disorder, affecting 1% to 2% of the population. of Health Stroke Scale score is 6. The patient does not have It is defined as an isolated tremor syndrome of at least any absolute or relative exclusion criteria for thromboly- 3 years’ duration characterized by action tremor in the upper sis, including recent surgery, prior or current intracranial extremities, with or without involvement of other body hemorrhage, extensive hypodensity on imaging, or blood parts, such as the head, larynx, or lower limbs. A family his- pressure above the target of 185/110 mm Hg. The benefits tory of tremor is present in 50% of patients. First-line treat- of intravenous alteplase in acute ischemic stroke, including ment for essential tremor includes propranolol, primidone, the lower likelihood of neurologic disability at 3 months and topiramate. Clonazepam is a second-line treatment. poststroke, are generally thought to outweigh the small risk In this patient, propranolol, primidone, and clonazepam of hemorrhage. have already proved ineffective, and topiramate (Option E) Acute administration of anticoagulation in ischemic is contraindicated because of his history of kidney stones. strokes (whether related to atrial fibrillation or not) does not Surgical therapies, including deep-brain stimulation (uni- reduce the short-term risk of recurrent stroke and increases lateral or bilateral) and focused ultrasound thalamotomy the risk of hemorrhage into the territory of cerebral infarc- (only unilateral), can control tremor in refractory essential tion (hemorrhagic conversion). Low-molecular-weight hep- tremor associated with functional disability. Results of a arin (Option B) is not indicated. randomized trial suggest that deep-brain stimulation results Treatment of blood pressure with antihypertensive in greater functional improvements than thalamotomy and agents (such as nicardipine [Option C]) is not indicated in fewer adverse events, such as dysarthria, sensory distur- acute ischemic stroke unless the blood pressure of a patient bances, and gait disturbances. eligible for alteplase is greater than 185/110 mm Hg (or is 154

_Answers and Critiques greater than 220/120 mm Hg for patients who are not can- features include rapid progression or presence of hemody- didates for thrombolysis). If intravenous alteplase is admin- namic failure seen on transcranial Doppler ultrasonography ONT. istered, target blood pressure is less than 180/105 mm Hg. or cerebral blood flow measures. Aspirin (Option D) should be held for 24 hours after CT angiography of the neck (Option C) is not appro- thrombolysis to reduce the risk of intracerebral hemorrhage. priate because it is not likely to change management and is If this patient were not a candidate for thrombolysis, aspirin associated with potential risks from radiation and contrast administered within 48 hours is indicated in order to reduce material. CT angiography can be considered in patients with the risk of subsequent stroke but should not be administered greater than 80% stenosis, particularly if surgical interven- now given the positive dysphagia screen and the need for tion is being considered, to confirm the degree of stenosis thrombolytic therapy. seen on ultrasound and to outline anatomic features that may help in choosing between stenting and endarterectomy. ¢ Alteplase administration within 3 hours of ischemic rn o stroke onset with disabling symptoms is associated e Patients with asymptomatic carotid artery stenosis s

¢ Alteplase administration within 3 hours of ischemic rn o stroke onset with disabling symptoms is associated e Patients with asymptomatic carotid artery stenosis s with a significant reduction in disability at 3 months. less than 80% have a low annual risk for stroke, likely = less than 1%. = ¢ Acute administration of anticoagulation in ischemic oO strokes does not reduce the short-term risk of recur- e The U.S. Preventive Services Task Force does not rec- sc < rent stroke and increases the risk of intracerebral ommend screening for carotid artery stenosis in the ec wn hemorrhage. general adult population. id o = rn

with a significant reduction in disability at 3 months. less than 80% have a low annual risk for stroke, likely = less than 1%. = ¢ Acute administration of anticoagulation in ischemic oO strokes does not reduce the short-term risk of recur- e The U.S. Preventive Services Task Force does not rec- sc < rent stroke and increases the risk of intracerebral ommend screening for carotid artery stenosis in the ec wn hemorrhage. general adult population. id o = rn Bibliography Bibliography © of Powers WJ, Rabinstein AA, Ackerson T, et al; American Heart Association Naylor AR, Ricco JB, de Borst GJ, et al. Editor’s choice - management of Stroke Council. 2018 Guidelines for the Early Management of atherosclerotic carotid and vertebral artery disease: 2017 clinical practice Patients With Acute Ischemic Stroke: A Guideline for Healthcare guidelines of the European Society for Vascular Surgery (ESVS). Eur J Professionals From the American Heart Association/American Stroke Vasc Endovasc Surg. 2018;55:3-81. [PMID: 28851594] doi:10.1016/j-ejvs. Association. Stroke. 2018;49:e46-e110. [PMID: 29367334] doi:10.1161/ 2017.06.021 STR.0000000000000158

Bibliography Bibliography © of Powers WJ, Rabinstein AA, Ackerson T, et al; American Heart Association Naylor AR, Ricco JB, de Borst GJ, et al. Editor’s choice - management of Stroke Council. 2018 Guidelines for the Early Management of atherosclerotic carotid and vertebral artery disease: 2017 clinical practice Patients With Acute Ischemic Stroke: A Guideline for Healthcare guidelines of the European Society for Vascular Surgery (ESVS). Eur J Professionals From the American Heart Association/American Stroke Vasc Endovasc Surg. 2018;55:3-81. [PMID: 28851594] doi:10.1016/j-ejvs. Association. Stroke. 2018;49:e46-e110. [PMID: 29367334] doi:10.1161/ 2017.06.021 STR.0000000000000158 Item 78 Answer: D Item 79 Answer: E Educational Objective: Treat asymptomatic internal Educational Objective: Prevent episodic migraine. carotid artery stenosis. The most appropriate preventive measure is venlafaxine The most appropriate management is no further testing (Option E). The patient has migraine without aura. Migraine or intervention (Option D). The patient has asymptomatic is a chronic neurobiologic disorder characterized by attacks stenosis of the internal carotid artery (ICA) of less than 80%, of head pain and various associated features. Attacks are and neither surgical intervention nor further imaging is often separated by periods of normal brain function. Even at indicated. Patients with ICA stenosis less than 80% have a times of symptom freedom, patients possess an underlying low annual risk for stroke (likely <1%), and the risk associ- predisposition for migraine episodes possibly because of a

Educational Objective: Treat asymptomatic internal Educational Objective: Prevent episodic migraine. carotid artery stenosis. The most appropriate preventive measure is venlafaxine The most appropriate management is no further testing (Option E). The patient has migraine without aura. Migraine or intervention (Option D). The patient has asymptomatic is a chronic neurobiologic disorder characterized by attacks stenosis of the internal carotid artery (ICA) of less than 80%, of head pain and various associated features. Attacks are and neither surgical intervention nor further imaging is often separated by periods of normal brain function. Even at indicated. Patients with ICA stenosis less than 80% have a times of symptom freedom, patients possess an underlying low annual risk for stroke (likely <1%), and the risk associ- predisposition for migraine episodes possibly because of a ated with surgical intervention is higher. The patient should biologically based inherent hypersensitivity of the central be treated with the best medical therapy to prevent further nervous system. Exposure to certain internal and external progression; the use of a high-intensity statin in patients factors may trigger a migraine attack in migraine-prone with dyslipidemia is especially indicated. The U.S. Preven- individuals while leaving those without such a predispo- tive Services Task Force (USPSTF) does not recommend sition unaffected. Patient surveys indicate stress or a post- screening for carotid artery stenosis in the general adult stress period (let-down effect) as the most common trig- population. The USPSTF concludes with moderate certainty gering factor. Changes in female hormones, sleep or meal that the harms of screening (mainly related to subsequent pattern disruptions, weather factors, and strong sensory interventions, such as carotid artery endarterectomy) for light, sound, or odor stimuli are also frequently reported as

ated with surgical intervention is higher. The patient should biologically based inherent hypersensitivity of the central be treated with the best medical therapy to prevent further nervous system. Exposure to certain internal and external progression; the use of a high-intensity statin in patients factors may trigger a migraine attack in migraine-prone with dyslipidemia is especially indicated. The U.S. Preven- individuals while leaving those without such a predispo- tive Services Task Force (USPSTF) does not recommend sition unaffected. Patient surveys indicate stress or a post- screening for carotid artery stenosis in the general adult stress period (let-down effect) as the most common trig- population. The USPSTF concludes with moderate certainty gering factor. Changes in female hormones, sleep or meal that the harms of screening (mainly related to subsequent pattern disruptions, weather factors, and strong sensory interventions, such as carotid artery endarterectomy) for light, sound, or odor stimuli are also frequently reported as asymptomatic carotid artery stenosis outweigh the benefits. triggers. The goal of migraine prevention is the reduction Carotid endarterectomy (Option A) and carotid stent- of migraine frequency, intensity, and duration. The best ing (Option B) are not appropriate because the patient did agents may reduce migraine frequency by half in approxi- not experience a stroke or transient ischemic attack stem- mately half of the patients treated. Pharmacologic prophy- ming from ICA stenosis. Carotid revascularization can be laxis should be considered when the headache frequency considered on a case-by-case basis in patients with greater reaches 5 days per month and almost always is initiated than 80% asymptomatic ICA stenosis when surgical risk when the frequency exceeds 10 days per month. Venlafaxine, for stroke is less than 3%, although these patients are rec- a serotonin-norepinephrine reuptake inhibitor, is among the ommended for enrollment in an NIH-funded clinical trial. agents with Level A or Level B evidence of effectiveness in Patients with stenosis greater than 80% and other high-risk episodic migraine prevention. Propranolol, timolol, metopro- features can be considered for surgical intervention; such lol, amitriptyline, topiramate, sodium valproate, erenumab,

asymptomatic carotid artery stenosis outweigh the benefits. triggers. The goal of migraine prevention is the reduction Carotid endarterectomy (Option A) and carotid stent- of migraine frequency, intensity, and duration. The best ing (Option B) are not appropriate because the patient did agents may reduce migraine frequency by half in approxi- not experience a stroke or transient ischemic attack stem- mately half of the patients treated. Pharmacologic prophy- ming from ICA stenosis. Carotid revascularization can be laxis should be considered when the headache frequency considered on a case-by-case basis in patients with greater reaches 5 days per month and almost always is initiated than 80% asymptomatic ICA stenosis when surgical risk when the frequency exceeds 10 days per month. Venlafaxine, for stroke is less than 3%, although these patients are rec- a serotonin-norepinephrine reuptake inhibitor, is among the ommended for enrollment in an NIH-funded clinical trial. agents with Level A or Level B evidence of effectiveness in Patients with stenosis greater than 80% and other high-risk episodic migraine prevention. Propranolol, timolol, metopro- features can be considered for surgical intervention; such lol, amitriptyline, topiramate, sodium valproate, erenumab, 155

Answers and Critiques fremanezumab, eptinezumab, and galcanezumab are also Furthermore, phenytoin is an older medication with more considered beneficial in this setting. adverse effects, and other less morbid options should be No evidence supports the use of selective serotonin considered first. reuptake inhibitor antidepressants, such as citalopram Temporal lobectomy (Option B) leads to seizure free- (Option A), in migraine prevention. dom in 60% to 70% of appropriately chosen patients, but Although commonly prescribed for migraine preven- candidacy must be determined by video EEG and MRI tion, gabapentin (Option B) has not been shown to be useful or other advanced imaging. Surgical resection candidacy in migraine prophylaxis. should not be determined by history alone. Although indomethacin (Option C) may be useful in Use of a vagus nerve stimulator (Option C) is a palliative the management of hemicrania continua, paroxysmal hemi- measure and should be offered only if resection is not an crania, and (usually) primary stabbing and primary cough option. In addition, use of a vagus nerve stimulator does not headache, none of these conditions is present in this patient. result in complete freedom from seizures. > Lamotrigine (Option D) has shown some benefit in = wn reducing the likelihood of cortical spreading depression, = felt to be a surrogate for migraine aura, in animal models of ¢ Drug-resistant epilepsy is defined as having ongoing @o seizures despite treatment with two tolerated, appro- = wn migraine. Clinical studies have shown no benefit in patients <3) with migraine. priately chosen, and adequately dosed antiepileptic = 2. medications. (@) oe e Video electroencephalography is the first step in = e Venlafaxine, propranolol, timolol, metoprolol, ami- 2 determining candidacy for epilepsy surgery in = triptyline, topiramate, sodium valproate, erenumab, oO patients with drug-resistant epilepsy followed by wn fremanezumab, eptinezumab and galcanezumab are advanced brain imaging. all beneficial in episodic migraine prevention.

fremanezumab, eptinezumab, and galcanezumab are also Furthermore, phenytoin is an older medication with more considered beneficial in this setting. adverse effects, and other less morbid options should be No evidence supports the use of selective serotonin considered first. reuptake inhibitor antidepressants, such as citalopram Temporal lobectomy (Option B) leads to seizure free- (Option A), in migraine prevention. dom in 60% to 70% of appropriately chosen patients, but Although commonly prescribed for migraine preven- candidacy must be determined by video EEG and MRI tion, gabapentin (Option B) has not been shown to be useful or other advanced imaging. Surgical resection candidacy in migraine prophylaxis. should not be determined by history alone. Although indomethacin (Option C) may be useful in Use of a vagus nerve stimulator (Option C) is a palliative the management of hemicrania continua, paroxysmal hemi- measure and should be offered only if resection is not an crania, and (usually) primary stabbing and primary cough option. In addition, use of a vagus nerve stimulator does not headache, none of these conditions is present in this patient. result in complete freedom from seizures. > Lamotrigine (Option D) has shown some benefit in = wn reducing the likelihood of cortical spreading depression, = felt to be a surrogate for migraine aura, in animal models of ¢ Drug-resistant epilepsy is defined as having ongoing @o seizures despite treatment with two tolerated, appro- = wn migraine. Clinical studies have shown no benefit in patients <3) with migraine. priately chosen, and adequately dosed antiepileptic = 2. medications. (@) oe e Video electroencephalography is the first step in = e Venlafaxine, propranolol, timolol, metoprolol, ami- 2 determining candidacy for epilepsy surgery in = triptyline, topiramate, sodium valproate, erenumab, oO patients with drug-resistant epilepsy followed by wn fremanezumab, eptinezumab and galcanezumab are advanced brain imaging. all beneficial in episodic migraine prevention. Bibliography Bibliography Yoo JY, Panov F. Identification and treatment of drug-resistant epilepsy. Parikh SK, Silberstein SD. Preventive treatment for episodic migraine. Continuum (Minneap Minn). 2019;25:362-80. [PMID: 30921014] doi:10. Neurol Clin. 2019 Nov:37(4):753-70. [PMID: 31563231] doi: 10.1016 /j.ncl. 1212/CON.0000000000000710 2019.07.004

Bibliography Bibliography Yoo JY, Panov F. Identification and treatment of drug-resistant epilepsy. Parikh SK, Silberstein SD. Preventive treatment for episodic migraine. Continuum (Minneap Minn). 2019;25:362-80. [PMID: 30921014] doi:10. Neurol Clin. 2019 Nov:37(4):753-70. [PMID: 31563231] doi: 10.1016 /j.ncl. 1212/CON.0000000000000710 2019.07.004 Item 80 Answer: D Item 81 Answer: A Educational Objective: Evaluate drug-resistant epilepsy. Educational Objective: Treat acute hypertension in intracerebral hemorrhage. The most appropriate management is video electroenceph- alography (EEG) monitoring (Option D). Continuous video The patient should receive intravenous nicardipine (Option EEG monitoring is performed in an epilepsy monitoring unit. A). She has an acute intracerebral hemorrhage (ICH) in the Based on the symptoms described, this patient most likely basal ganglia that is most likely due to hypertension, given its has focal impaired awareness seizures (formerly known as location and her history. For patients with ICH and a systolic focal dyscognitive seizures or complex partial seizures) of blood pressure (SBP) of 150 mm Hg or greater, acute lower: temporal lobe origin. She has drug-resistant epilepsy, hav- ing of SBP to 140 mm Hg is safe and effective in improving ing ongoing seizures despite treatment with two tolerated, functional outcome. A recently completed trial that com appropriately chosen, and adequately dosed antiepileptic pared a blood pressure target of 120 mm Hg with a target of medications (whether as monotherapy or in combination). 140 mm Hg in patients with ICH reported increased renal The patient should be referred to an epilepsy center for video adverse events in the lower blood pressure arm, although no EEG monitoring to confirm the diagnosis of temporal lobe neurologic worsening was noted. Intravenous nicardipine epilepsy and evaluate her for epilepsy surgery. Mesial tempo- can be rapidly titrated and thus achieve the target systolic ral sclerosis with hippocampal atrophy is the most common blood pressure without causing hypotension. cause of drug-resistant adult-onset focal epilepsy. Therefore, Intravenous nitroprusside (Option B) is not appropri brain MRI is also an appropriate next step because surgical ate in a patient with ICH who already is at risk for elevated candidacy requires confirmation that seizure manifestations intracranial pressure (ICP) because nitroprusside can further on video EEG match the location of pathology on MRI or increase ICP by causing intracerebral vasodilation. other advanced functional imaging (single-photon emission Platelet transfusion (Option C) is not appropriate CT or PET). These steps are required to determine if the because the patient does not have thrombocytopenia, and patient can be considered for temporal lobectomy. there is no evidence that platelet transfusions reverse the Phenytoin (Option A) is a treatment option, but surgi- coagulopathy associated with antiplatelet agents or pre- cal candidacy should be evaluated first; only 5% to 10% of vent hematoma expansion. Additionally, such transfusions patients with drug-resistant epilepsy achieve seizure free- increase the risk of coronary stent thrombosis, volume over- dom from an additional drug after failing two medications. load, transfusion-related reactions, and acute lung injury.

Item 80 Answer: D Item 81 Answer: A Educational Objective: Evaluate drug-resistant epilepsy. Educational Objective: Treat acute hypertension in intracerebral hemorrhage. The most appropriate management is video electroenceph- alography (EEG) monitoring (Option D). Continuous video The patient should receive intravenous nicardipine (Option EEG monitoring is performed in an epilepsy monitoring unit. A). She has an acute intracerebral hemorrhage (ICH) in the Based on the symptoms described, this patient most likely basal ganglia that is most likely due to hypertension, given its has focal impaired awareness seizures (formerly known as location and her history. For patients with ICH and a systolic focal dyscognitive seizures or complex partial seizures) of blood pressure (SBP) of 150 mm Hg or greater, acute lower: temporal lobe origin. She has drug-resistant epilepsy, hav- ing of SBP to 140 mm Hg is safe and effective in improving ing ongoing seizures despite treatment with two tolerated, functional outcome. A recently completed trial that com appropriately chosen, and adequately dosed antiepileptic pared a blood pressure target of 120 mm Hg with a target of medications (whether as monotherapy or in combination). 140 mm Hg in patients with ICH reported increased renal The patient should be referred to an epilepsy center for video adverse events in the lower blood pressure arm, although no EEG monitoring to confirm the diagnosis of temporal lobe neurologic worsening was noted. Intravenous nicardipine epilepsy and evaluate her for epilepsy surgery. Mesial tempo- can be rapidly titrated and thus achieve the target systolic ral sclerosis with hippocampal atrophy is the most common blood pressure without causing hypotension. cause of drug-resistant adult-onset focal epilepsy. Therefore, Intravenous nitroprusside (Option B) is not appropri brain MRI is also an appropriate next step because surgical ate in a patient with ICH who already is at risk for elevated candidacy requires confirmation that seizure manifestations intracranial pressure (ICP) because nitroprusside can further on video EEG match the location of pathology on MRI or increase ICP by causing intracerebral vasodilation. other advanced functional imaging (single-photon emission Platelet transfusion (Option C) is not appropriate CT or PET). These steps are required to determine if the because the patient does not have thrombocytopenia, and patient can be considered for temporal lobectomy. there is no evidence that platelet transfusions reverse the Phenytoin (Option A) is a treatment option, but surgi- coagulopathy associated with antiplatelet agents or pre- cal candidacy should be evaluated first; only 5% to 10% of vent hematoma expansion. Additionally, such transfusions patients with drug-resistant epilepsy achieve seizure free- increase the risk of coronary stent thrombosis, volume over- dom from an additional drug after failing two medications. load, transfusion-related reactions, and acute lung injury. 156

Answers and Critiques C) Prothrombin complex concentrate (Option D) is used The benefit of oral acyclovir (Option C) for classic Bell in patients with coagulopathy with prolonged prothrom- palsy remains controversial, and guidelines differ in their CONT. bin time and activated partial thromboplastin time. usually recommendations. Nevertheless, in this patient with atypi- associated with warfarin toxicity and life-threatening hem cal findings, initiation of acyclovir before further evaluation orrhage. Prothrombin complex concentrates are inappropri is not indicated. ate because the patient has no evidence of a coagulopathy. In classic Bell palsy, a 10-day course of oral prednisone and infusing them could increase the risk of thrombotic (Option D), started within 72 hours of onset, is recom- complications, such as a pulmonary embolism, for which mended to expedite the rate and speed of full recovery. patients with ICH are already at risk. However, given this patient’s 10-day course and atypical findings, MRI and, if needed, cerebrospinal fluid analysis should be prioritized. ¢ For patients with intracranial hemorrhage anda systolic No further testing or intervention (Option E) would be blood pressure (SBP) of 150 mm Hg or greater, acute inappropriate, given the progressive course and involvement wn sf) lowering of SBP to 140 mm Hg is safe and effective in of other cranial nerves. If this patient had presented more =

C) Prothrombin complex concentrate (Option D) is used The benefit of oral acyclovir (Option C) for classic Bell in patients with coagulopathy with prolonged prothrom- palsy remains controversial, and guidelines differ in their CONT. bin time and activated partial thromboplastin time. usually recommendations. Nevertheless, in this patient with atypi- associated with warfarin toxicity and life-threatening hem cal findings, initiation of acyclovir before further evaluation orrhage. Prothrombin complex concentrates are inappropri is not indicated. ate because the patient has no evidence of a coagulopathy. In classic Bell palsy, a 10-day course of oral prednisone and infusing them could increase the risk of thrombotic (Option D), started within 72 hours of onset, is recom- complications, such as a pulmonary embolism, for which mended to expedite the rate and speed of full recovery. patients with ICH are already at risk. However, given this patient’s 10-day course and atypical findings, MRI and, if needed, cerebrospinal fluid analysis should be prioritized. ¢ For patients with intracranial hemorrhage anda systolic No further testing or intervention (Option E) would be blood pressure (SBP) of 150 mm Hg or greater, acute inappropriate, given the progressive course and involvement wn sf) lowering of SBP to 140 mm Hg is safe and effective in of other cranial nerves. If this patient had presented more = improving functional outcome. than 72 hours after the onset of classic Bell palsy, observation Ao - e Intravenous nitroprusside is not appropriate in patients would have been appropriate. =) Ss with elevated intracranial pressure (ICP) because it can i= cs further increase ICP. e Atypical Bell palsy, including subacute onset or involve- wn os om ment of multiple facial nerves, requires additional eval- Bibliography > uation with imaging and other laboratory testing. ia Hemphill J 3rd, Greenberg S, Anderson C, et al; American Heart Association <= P Stroke Council; Council on Cardiovascular and Stroke Nursing; Council ¢ Classic Bell palsy, characterized by the acute onset of a on Clinical Cardiology. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from peripheral facial nerve neuropathy, is a clinical diag- the American Heart Association/American Stroke Association. Stroke. nosis requiring no additional evaluation. 2015 Jul;46(7):2032-60. Epub 2015 May 28. [PMID 26022637] doi: 10.1161/ STR.0000000000000069. Bibliography Fuller G, Morgan C. Bell’s palsy syndrome: mimics and chameleons. Pract Neurol. 2016;16:439-444. [PMID: 27034243] doi:10.1136/practneurol- Item 82 Answer: 8B 2016-001383

improving functional outcome. than 72 hours after the onset of classic Bell palsy, observation Ao - e Intravenous nitroprusside is not appropriate in patients would have been appropriate. =) Ss with elevated intracranial pressure (ICP) because it can i= cs further increase ICP. e Atypical Bell palsy, including subacute onset or involve- wn os om ment of multiple facial nerves, requires additional eval- Bibliography > uation with imaging and other laboratory testing. ia Hemphill J 3rd, Greenberg S, Anderson C, et al; American Heart Association <= P Stroke Council; Council on Cardiovascular and Stroke Nursing; Council ¢ Classic Bell palsy, characterized by the acute onset of a on Clinical Cardiology. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from peripheral facial nerve neuropathy, is a clinical diag- the American Heart Association/American Stroke Association. Stroke. nosis requiring no additional evaluation. 2015 Jul;46(7):2032-60. Epub 2015 May 28. [PMID 26022637] doi: 10.1161/ STR.0000000000000069. Bibliography Fuller G, Morgan C. Bell’s palsy syndrome: mimics and chameleons. Pract Neurol. 2016;16:439-444. [PMID: 27034243] doi:10.1136/practneurol- Item 82 Answer: 8B 2016-001383 Educational Objective: Evaluate atypical facial nerve palsy. Item 83 Answer: D The most appropriate next step in management is MRI of Educational Objective: Diagnose vascular cognitive the brain (Option B). Patients with atypical features of impairment. Bell palsy, including multiple cranial nerve palsies, require additional evaluation. This patient should undergo MRI of The most likely diagnosis is vascular cognitive impairment the brain with and without gadolinium and with attention (Option D). Vascular cognitive impairment is associated to the brainstem and internal auditory canal. Bell palsy is with systemic vascular risk factors and a history of stroke an acute-onset (usually over a period of hours) peripheral (either clinically diagnosed or based on neuroimaging evi- mononeuropathy involving the facial nerve (cranial nerve dence). Two major signs of vascular cognitive impairment VII) that leads to weakness in the muscles of facial expres- are early gait impairment and personality or mood changes. sion in both the upper and lower face, hyperacusis, and The cognitive profile of vascular cognitive impairment most impaired taste. In classic Bell palsy, initial brain imaging characteristically shows slowed processing speed out of and laboratory testing are not required. However, muscles of proportion to deficits in other domains of cognition. The mastication are innervated by the motor branch of the tri- diagnosis of vascular dementia is based on the lack of hip- geminal nerve (cranial nerve V) and ocular abduction (ability pocampal atrophy and presence of confluent white matter to bury the sclera on lateral gaze) is innervated by the abdu- hyperintensities on MRI of the brain. cens nerve (cranial nerve VI). Presence of these findings and The typical presentation of Alzheimer disease (Option a subacute progressive course over 10 days are red flags that A) is that of an insidious worsening of memory, language, should prompt further workup, including brain imaging. and visuospatial abilities. Manifestations include forgetful- In addition, serologic testing for causes of multiple cranial ness, word-finding difficulties, hesitation in speech, and neuropathies and, if needed, cerebrospinal fluid analysis visuospatial dysfunction (navigation problems). The inability with cytology should also be considered. to copy line drawings also suggests visuospatial dysfunction. Facial electromyography (Option A) would not be an MRI will show evidence of decreased volume of the hippo- appropriate next step. Electromyography can be nondiag- campi out of proportion to rest of the brain. nostic at an early phase (<3-4 weeks from onset) of most The clinical diagnosis of dementia with Lewy bodies neuropathies and, even if abnormal, would not explain the (Option B) rests on the key features of dementia, parkin- presence of trigeminal and abducens nerve involvement. sonian motor features, visual hallucinations, rapid eye

Educational Objective: Evaluate atypical facial nerve palsy. Item 83 Answer: D The most appropriate next step in management is MRI of Educational Objective: Diagnose vascular cognitive the brain (Option B). Patients with atypical features of impairment. Bell palsy, including multiple cranial nerve palsies, require additional evaluation. This patient should undergo MRI of The most likely diagnosis is vascular cognitive impairment the brain with and without gadolinium and with attention (Option D). Vascular cognitive impairment is associated to the brainstem and internal auditory canal. Bell palsy is with systemic vascular risk factors and a history of stroke an acute-onset (usually over a period of hours) peripheral (either clinically diagnosed or based on neuroimaging evi- mononeuropathy involving the facial nerve (cranial nerve dence). Two major signs of vascular cognitive impairment VII) that leads to weakness in the muscles of facial expres- are early gait impairment and personality or mood changes. sion in both the upper and lower face, hyperacusis, and The cognitive profile of vascular cognitive impairment most impaired taste. In classic Bell palsy, initial brain imaging characteristically shows slowed processing speed out of and laboratory testing are not required. However, muscles of proportion to deficits in other domains of cognition. The mastication are innervated by the motor branch of the tri- diagnosis of vascular dementia is based on the lack of hip- geminal nerve (cranial nerve V) and ocular abduction (ability pocampal atrophy and presence of confluent white matter to bury the sclera on lateral gaze) is innervated by the abdu- hyperintensities on MRI of the brain. cens nerve (cranial nerve VI). Presence of these findings and The typical presentation of Alzheimer disease (Option a subacute progressive course over 10 days are red flags that A) is that of an insidious worsening of memory, language, should prompt further workup, including brain imaging. and visuospatial abilities. Manifestations include forgetful- In addition, serologic testing for causes of multiple cranial ness, word-finding difficulties, hesitation in speech, and neuropathies and, if needed, cerebrospinal fluid analysis visuospatial dysfunction (navigation problems). The inability with cytology should also be considered. to copy line drawings also suggests visuospatial dysfunction. Facial electromyography (Option A) would not be an MRI will show evidence of decreased volume of the hippo- appropriate next step. Electromyography can be nondiag- campi out of proportion to rest of the brain. nostic at an early phase (<3-4 weeks from onset) of most The clinical diagnosis of dementia with Lewy bodies neuropathies and, even if abnormal, would not explain the (Option B) rests on the key features of dementia, parkin- presence of trigeminal and abducens nerve involvement. sonian motor features, visual hallucinations, rapid eye 157

Answers and Critiques movement sleep behavior disorder, and frequent fluctu- The use of stimulants such as methylphenidate (Option ations in attention, which may manifest as acute confu- C) has not been shown to be effective at promoting stroke sional episodes. Reduced dopamine transporter uptake in recovery and could pose harm by increasing blood pressure. the basal ganglia on a single photon emission CT or PET In patients for whom reversible causes of fatigue have been scan is supportive of the diagnosis. ruled out and who may have an anatomic basis for fatigue The most prominent feature of behavioral-variant and slowness, such as a bilateral thalamic or medial frontal frontotemporal dementia (FTD) (Option C) is an alteration infarct, stimulants could be considered on a case-by-case in personality and behavior that typically develops years basis. In this patient, however, reversible causes such as before the onset of cognitive impairment. A clue to the diag- sleep-disordered breathing have not yet been investigated. nosis early in the disease is discordance between normal MRI (Option D) is not necessary because the patient or near-normal performance on objective cognitive testing has not had any new acute focal neurologic symptoms, and a significant degree of functional impairment. Many such as sensory loss or aphasia. Reversible causes of QS patients with behavioral-variant FTD have frontotemporal poststroke fatigue should be considered before pursuing = wn lobe atrophy. additional imaging, which has low yield for identifying = reversible causes. oO = Lo) 2 ¢ Two major signs of vascular cognitive impairment are = Qa early gait impairment and personality or mood changes. e In patients with poststroke fatigue, polysomnography (=) to evaluate for sleep-disordered breathing should be = e The diagnosis of vascular dementia is based on the S considered. 2 lack of hippocampal atrophy and presence of confluent } e Depression is highly prevalent in stroke survivors and is © white matter hyperintensities on MRI of the brain. 17) one of the leading modifiable risk factors for long-term Bibliography disability. van der Flier WM, Skoog I, Schneider JA, et al. Vascular cognitive impair- ment. Nat Rev Dis Primers. 2018;4:18003. Published 2018 Feb 15. [PMID: Bibliography 29446769] doi:10.1038) nrdp.2018.3 Hinkle JL, Becker KJ, Kim JS, et al; American Heart Association Council on Cardiovascular and Stroke Nursing and Stroke Council. Poststroke Fatigue: Emerging Evidence and Approaches to Management: A Scientific Item 84 Answer: E Statement for Healthcare Professionals From the American Heart Association. Stroke. 2017;48:e159-e170. [PMID: 28546322] doi:10.1161/STR. Educational Objective: Evaluate a patient with post- 0000000000000132

movement sleep behavior disorder, and frequent fluctu- The use of stimulants such as methylphenidate (Option ations in attention, which may manifest as acute confu- C) has not been shown to be effective at promoting stroke sional episodes. Reduced dopamine transporter uptake in recovery and could pose harm by increasing blood pressure. the basal ganglia on a single photon emission CT or PET In patients for whom reversible causes of fatigue have been scan is supportive of the diagnosis. ruled out and who may have an anatomic basis for fatigue The most prominent feature of behavioral-variant and slowness, such as a bilateral thalamic or medial frontal frontotemporal dementia (FTD) (Option C) is an alteration infarct, stimulants could be considered on a case-by-case in personality and behavior that typically develops years basis. In this patient, however, reversible causes such as before the onset of cognitive impairment. A clue to the diag- sleep-disordered breathing have not yet been investigated. nosis early in the disease is discordance between normal MRI (Option D) is not necessary because the patient or near-normal performance on objective cognitive testing has not had any new acute focal neurologic symptoms, and a significant degree of functional impairment. Many such as sensory loss or aphasia. Reversible causes of QS patients with behavioral-variant FTD have frontotemporal poststroke fatigue should be considered before pursuing = wn lobe atrophy. additional imaging, which has low yield for identifying = reversible causes. oO = Lo) 2 ¢ Two major signs of vascular cognitive impairment are = Qa early gait impairment and personality or mood changes. e In patients with poststroke fatigue, polysomnography (=) to evaluate for sleep-disordered breathing should be = e The diagnosis of vascular dementia is based on the S considered. 2 lack of hippocampal atrophy and presence of confluent } e Depression is highly prevalent in stroke survivors and is © white matter hyperintensities on MRI of the brain. 17) one of the leading modifiable risk factors for long-term Bibliography disability. van der Flier WM, Skoog I, Schneider JA, et al. Vascular cognitive impair- ment. Nat Rev Dis Primers. 2018;4:18003. Published 2018 Feb 15. [PMID: Bibliography 29446769] doi:10.1038) nrdp.2018.3 Hinkle JL, Becker KJ, Kim JS, et al; American Heart Association Council on Cardiovascular and Stroke Nursing and Stroke Council. Poststroke Fatigue: Emerging Evidence and Approaches to Management: A Scientific Item 84 Answer: E Statement for Healthcare Professionals From the American Heart Association. Stroke. 2017;48:e159-e170. [PMID: 28546322] doi:10.1161/STR. Educational Objective: Evaluate a patient with post- 0000000000000132 stroke fatigue.

movement sleep behavior disorder, and frequent fluctu- The use of stimulants such as methylphenidate (Option ations in attention, which may manifest as acute confu- C) has not been shown to be effective at promoting stroke sional episodes. Reduced dopamine transporter uptake in recovery and could pose harm by increasing blood pressure. the basal ganglia on a single photon emission CT or PET In patients for whom reversible causes of fatigue have been scan is supportive of the diagnosis. ruled out and who may have an anatomic basis for fatigue The most prominent feature of behavioral-variant and slowness, such as a bilateral thalamic or medial frontal frontotemporal dementia (FTD) (Option C) is an alteration infarct, stimulants could be considered on a case-by-case in personality and behavior that typically develops years basis. In this patient, however, reversible causes such as before the onset of cognitive impairment. A clue to the diag- sleep-disordered breathing have not yet been investigated. nosis early in the disease is discordance between normal MRI (Option D) is not necessary because the patient or near-normal performance on objective cognitive testing has not had any new acute focal neurologic symptoms, and a significant degree of functional impairment. Many such as sensory loss or aphasia. Reversible causes of QS patients with behavioral-variant FTD have frontotemporal poststroke fatigue should be considered before pursuing = wn lobe atrophy. additional imaging, which has low yield for identifying = reversible causes. oO = Lo) 2 ¢ Two major signs of vascular cognitive impairment are = Qa early gait impairment and personality or mood changes. e In patients with poststroke fatigue, polysomnography (=) to evaluate for sleep-disordered breathing should be = e The diagnosis of vascular dementia is based on the S considered. 2 lack of hippocampal atrophy and presence of confluent } e Depression is highly prevalent in stroke survivors and is © white matter hyperintensities on MRI of the brain. 17) one of the leading modifiable risk factors for long-term Bibliography disability. van der Flier WM, Skoog I, Schneider JA, et al. Vascular cognitive impair- ment. Nat Rev Dis Primers. 2018;4:18003. Published 2018 Feb 15. [PMID: Bibliography 29446769] doi:10.1038) nrdp.2018.3 Hinkle JL, Becker KJ, Kim JS, et al; American Heart Association Council on Cardiovascular and Stroke Nursing and Stroke Council. Poststroke Fatigue: Emerging Evidence and Approaches to Management: A Scientific Item 84 Answer: E Statement for Healthcare Professionals From the American Heart Association. Stroke. 2017;48:e159-e170. [PMID: 28546322] doi:10.1161/STR. Educational Objective: Evaluate a patient with post- 0000000000000132 stroke fatigue. This patient should have polysomnography to evaluate for Item 85 Answer: C sleep-disordered breathing (Option E). He has poststroke Educational Objective: Evaluate cardiac rhythm in a fatigue, which is highly prevalent (23% to 77%) in survivors patient with embolic stroke of undetermined source. of stroke and can significantly affect recovery, rehabilitation, and quality of life. There is likely a neuroanatomic and physi- The most appropriate management is prolonged ambula- ologic basis for poststroke fatigue; however, reversible causes tory ECG (Option C). The patient had an embolic stroke of need to be identified and treated first. Sleep-disordered undetermined source (ESUS), based on the infarction on breathing after stroke is highly prevalent (50% to 70%) and the cortical surface without an alternative source of emboli may not necessarily present with symptoms of snoring or be identified (e.g., large artery atherosclerosis or atrial fibrilla- purely obstructive. Treatment of sleep-disordered breathing tion). Prolonged cardiac rhythm evaluation with ambulatory in stroke patients can reduce poststroke fatigue and cognitive cardiac ECG or an implantable loop recorder may be positive impairment. Certain strokes may be more likely to lead to for atrial fibrillation in approximately one third of patients sleep-disordered breathing, including those involving the with ESUS and dictate a change in therapy. The patient has brainstem (such as in this patient); a normal BMI does not several predictors of finding atrial fibrillation, including left rule out sleep-disordered breathing. atrial enlargement and hypertension. Depression after stroke is common and may present Dual antiplatelet therapy (DAPT) with aspirin and with lack of energy and fatigue. It is one of the leading mod- clopidogrel (Option A) started 12 to 24 hours after stroke ifiable risk factors for long-term disability in stroke. In this onset and continued for 21 to 90 days in patients with TIA patient, depression is unlikely given the negative screening and minor ischemic stroke results in a small but significant for depression. As such, bupropion (Option A) is not an reduction in risk of recurrent stroke at 90 days. This patient appropriate option. has missed the window for DAPT and more than likely has Fluoxetine (Option B) is commonly used to promote an embolic rather than large vessel ischemic stroke; there- stroke recovery based on a small clinical trial showing fore, DAPT is not indicated. improvement in arm function. A more recently completed Changing aspirin to rivaroxaban (Option B) is not trial, however, showed that fluoxetine in the acute setting appropriate because direct-acting anticoagulants have not did not change the long-term degree of disability after stroke. been established as effective and safe therapy in patients

This patient should have polysomnography to evaluate for Item 85 Answer: C sleep-disordered breathing (Option E). He has poststroke Educational Objective: Evaluate cardiac rhythm in a fatigue, which is highly prevalent (23% to 77%) in survivors patient with embolic stroke of undetermined source. of stroke and can significantly affect recovery, rehabilitation, and quality of life. There is likely a neuroanatomic and physi- The most appropriate management is prolonged ambula- ologic basis for poststroke fatigue; however, reversible causes tory ECG (Option C). The patient had an embolic stroke of need to be identified and treated first. Sleep-disordered undetermined source (ESUS), based on the infarction on breathing after stroke is highly prevalent (50% to 70%) and the cortical surface without an alternative source of emboli may not necessarily present with symptoms of snoring or be identified (e.g., large artery atherosclerosis or atrial fibrilla- purely obstructive. Treatment of sleep-disordered breathing tion). Prolonged cardiac rhythm evaluation with ambulatory in stroke patients can reduce poststroke fatigue and cognitive cardiac ECG or an implantable loop recorder may be positive impairment. Certain strokes may be more likely to lead to for atrial fibrillation in approximately one third of patients sleep-disordered breathing, including those involving the with ESUS and dictate a change in therapy. The patient has brainstem (such as in this patient); a normal BMI does not several predictors of finding atrial fibrillation, including left rule out sleep-disordered breathing. atrial enlargement and hypertension. Depression after stroke is common and may present Dual antiplatelet therapy (DAPT) with aspirin and with lack of energy and fatigue. It is one of the leading mod- clopidogrel (Option A) started 12 to 24 hours after stroke ifiable risk factors for long-term disability in stroke. In this onset and continued for 21 to 90 days in patients with TIA patient, depression is unlikely given the negative screening and minor ischemic stroke results in a small but significant for depression. As such, bupropion (Option A) is not an reduction in risk of recurrent stroke at 90 days. This patient appropriate option. has missed the window for DAPT and more than likely has Fluoxetine (Option B) is commonly used to promote an embolic rather than large vessel ischemic stroke; there- stroke recovery based on a small clinical trial showing fore, DAPT is not indicated. improvement in arm function. A more recently completed Changing aspirin to rivaroxaban (Option B) is not trial, however, showed that fluoxetine in the acute setting appropriate because direct-acting anticoagulants have not did not change the long-term degree of disability after stroke. been established as effective and safe therapy in patients 158

ie ae with ESUS. In two clinical trials examining rivaroxaban or pain at the site of infection that later radiates down the dabigatran versus aspirin in ESUS, aspirin was equivalent spine or into the legs. Blood cultures should be obtained for stroke prevention and was associated with fewer hemor- before starting empiric antibiotics, but antibiotics should rhagic complications. Further trials are ongoing in patients not be delayed by other diagnostic testing. MRI is the imag- with a higher suspicion for atrial fibrillation. ing modality of choice to identify location and extent of Transesophageal echocardiography (TEE) (Option D) the abscess and is the preferred imaging modality for other can be considered in younger patients without risk factors causes of spine injury. The entire spine should be visual- in whom a transthoracic echocardiogram was negative for ized because infection, bleeding, or metastatic cancer may a source of emboli or in patients with a high suspicion be multifocal. Decompressive surgery followed by culture- for high-risk embolic sources, such as bacterial endocarditis directed long-term antibiotics is the treatment of choice for or an atrial myxoma. TEE is a low-yield diagnostic test in an epidural abscess. older patient in sinus rhythm with multiple risk factors for Cerebrospinal fluid analysis and culture (Option A) stroke. rarely provides a bacteriologic diagnosis, and lumbar punc- wn @ ture is contraindicated because of the risk of entering the =! x infected space and contaminating the spinal fluid. = e In approximately one third of patients with embolic When MRI is not feasible, CT myelography (Option B) = oO stroke of undetermined source, prolonged cardiac can show compressive myelopathy but often does not reveal | < rhythm evaluation may be positive for atrial fibrilla- the cause of compression and thus is not most appropriate. c tion. Lumbar spine radiography (Option C) may show evi- wn al cn) e Aspirin is preferred to rivaroxaban or dabigatran in dence of vertebral body infection, such as osteomyelitis, but > wn the secondary prevention of stroke in patients with these findings can take weeks to manifest and are inferior to = MRI or CT myelography in the diagnosis of spinal epidural = embolic stroke of undetermined origin. abscess.

with ESUS. In two clinical trials examining rivaroxaban or pain at the site of infection that later radiates down the dabigatran versus aspirin in ESUS, aspirin was equivalent spine or into the legs. Blood cultures should be obtained for stroke prevention and was associated with fewer hemor- before starting empiric antibiotics, but antibiotics should rhagic complications. Further trials are ongoing in patients not be delayed by other diagnostic testing. MRI is the imag- with a higher suspicion for atrial fibrillation. ing modality of choice to identify location and extent of Transesophageal echocardiography (TEE) (Option D) the abscess and is the preferred imaging modality for other can be considered in younger patients without risk factors causes of spine injury. The entire spine should be visual- in whom a transthoracic echocardiogram was negative for ized because infection, bleeding, or metastatic cancer may a source of emboli or in patients with a high suspicion be multifocal. Decompressive surgery followed by culture- for high-risk embolic sources, such as bacterial endocarditis directed long-term antibiotics is the treatment of choice for or an atrial myxoma. TEE is a low-yield diagnostic test in an epidural abscess. older patient in sinus rhythm with multiple risk factors for Cerebrospinal fluid analysis and culture (Option A) stroke. rarely provides a bacteriologic diagnosis, and lumbar punc- wn @ ture is contraindicated because of the risk of entering the =! x infected space and contaminating the spinal fluid. = e In approximately one third of patients with embolic When MRI is not feasible, CT myelography (Option B) = oO stroke of undetermined source, prolonged cardiac can show compressive myelopathy but often does not reveal | < rhythm evaluation may be positive for atrial fibrilla- the cause of compression and thus is not most appropriate. c tion. Lumbar spine radiography (Option C) may show evi- wn al cn) e Aspirin is preferred to rivaroxaban or dabigatran in dence of vertebral body infection, such as osteomyelitis, but > wn the secondary prevention of stroke in patients with these findings can take weeks to manifest and are inferior to = MRI or CT myelography in the diagnosis of spinal epidural = embolic stroke of undetermined origin. abscess. Bibliography Kamel H, Merkler AE, Iadecola C, et al. Tailoring the approach to embolic stroke of undetermined source: a review. JAMA Neurol. 2019;76:855-861. e The three most common atraumatic spinal emergencies [PMID: 30958521] doi:10.1001/jamaneurol.2019.0591 are spinal epidural abscess, cauda equina syndrome, and spontaneous spinal epidural hematoma.

Bibliography Kamel H, Merkler AE, Iadecola C, et al. Tailoring the approach to embolic stroke of undetermined source: a review. JAMA Neurol. 2019;76:855-861. e The three most common atraumatic spinal emergencies [PMID: 30958521] doi:10.1001/jamaneurol.2019.0591 are spinal epidural abscess, cauda equina syndrome, and spontaneous spinal epidural hematoma. Item 86 Answer: D ¢ MRI is the imaging modality of choice to identify the cause, location, and extent of spinal injury. Educational Objective: Diagnose epidural abscess. The most appropriate initial step in management is MRI of Bibliography the entire spine (Option D). Atraumatic spinal emergencies Babu JM, Patel SA, Palumbo MA, et al. Spinal emergencies in primary care are most commonly seen first by emergency department cli- practice. Am J Med. 2019;132:300-6. [PMID: 30291829]

The most appropriate initial step in management is MRI of Bibliography the entire spine (Option D). Atraumatic spinal emergencies Babu JM, Patel SA, Palumbo MA, et al. Spinal emergencies in primary care are most commonly seen first by emergency department cli- practice. Am J Med. 2019;132:300-6. [PMID: 30291829] nicians or primary care specialists. The three most common atraumatic spinal emergencies are spinal epidural abscess, cauda equina syndrome, and spontaneous spinal epidural Item 87 Answer: A hematoma. Specific signs and symptoms can provide clues Educational Objective: Prevent infection in a patient as to the cause of compression. The presence of fever and with multiple sclerosis. focal back pain and tenderness, especially in patients who have had recent back instrumentation or have a history of The most appropriate immunization is annual influenza intravenous drug use, may indicate an epidural abscess. vaccination (Option A). The American Academy of Neur- A history of cancer and focal back pain should raise con- ology recommends annual influenza vaccination for all cern for metastatic disease or pathologic vertebral fracture. patients with multiple sclerosis (MS) based on the increased Anticoagulant use raises the risk of compression from an risk for infection in patients receiving immunosuppressive/ epidural hematoma, particularly in the setting of recent back immunomodulating therapy and data that suggest worse MS instrumentation or excessive anticoagulation. Spinal epi- outcomes in patients who experience frequent infections. dural abscess most commonly results from hematogenous Inactivated influenza vaccination and other indicated non- dissemination, with S. aureus accounting for approximately live immunizations are not contraindicated with the use 50% of infections; streptococcus and gram-negative bacilli of disease-modifying therapies. The American Academy of (such as Escherichia coli) are also implicated. Predisposing Neurology recommends that patients ideally receive other factors for bacteremia include endocarditis, injection drug needed immunizations 4 to 6 weeks prior to the initiation of use, long-term intravenous catheters (hemodialysis cath- immunosuppressive/immunomodulating therapy and that eters, central lines), diabetes, and urinary tract infection. immunization be delayed in patients during a MS relapse. Spinal epidural abscess can also occur after neurosurgi- Pneumococcal vaccination is also recommended in all adults cal procedures (spinal fusion, epidural catheter placement) aged 65 years and older and adults aged 19 to 64 years or paraspinal injection. Patients usually develop localized with immunosuppression. Two pneumococcal vaccines are

nicians or primary care specialists. The three most common atraumatic spinal emergencies are spinal epidural abscess, cauda equina syndrome, and spontaneous spinal epidural Item 87 Answer: A hematoma. Specific signs and symptoms can provide clues Educational Objective: Prevent infection in a patient as to the cause of compression. The presence of fever and with multiple sclerosis. focal back pain and tenderness, especially in patients who have had recent back instrumentation or have a history of The most appropriate immunization is annual influenza intravenous drug use, may indicate an epidural abscess. vaccination (Option A). The American Academy of Neur- A history of cancer and focal back pain should raise con- ology recommends annual influenza vaccination for all cern for metastatic disease or pathologic vertebral fracture. patients with multiple sclerosis (MS) based on the increased Anticoagulant use raises the risk of compression from an risk for infection in patients receiving immunosuppressive/ epidural hematoma, particularly in the setting of recent back immunomodulating therapy and data that suggest worse MS instrumentation or excessive anticoagulation. Spinal epi- outcomes in patients who experience frequent infections. dural abscess most commonly results from hematogenous Inactivated influenza vaccination and other indicated non- dissemination, with S. aureus accounting for approximately live immunizations are not contraindicated with the use 50% of infections; streptococcus and gram-negative bacilli of disease-modifying therapies. The American Academy of (such as Escherichia coli) are also implicated. Predisposing Neurology recommends that patients ideally receive other factors for bacteremia include endocarditis, injection drug needed immunizations 4 to 6 weeks prior to the initiation of use, long-term intravenous catheters (hemodialysis cath- immunosuppressive/immunomodulating therapy and that eters, central lines), diabetes, and urinary tract infection. immunization be delayed in patients during a MS relapse. Spinal epidural abscess can also occur after neurosurgi- Pneumococcal vaccination is also recommended in all adults cal procedures (spinal fusion, epidural catheter placement) aged 65 years and older and adults aged 19 to 64 years or paraspinal injection. Patients usually develop localized with immunosuppression. Two pneumococcal vaccines are 159

Answers and Critiques available: the 13-valent conjugate vaccine (PCV13) and the parkinsonism, hallucinations, and attention fluctuations. 23-valent polysaccharide vaccine (PPSV23). Both vaccines The latter may manifest as acute confusional episodes in are recommended by the Advisory Committee on Immuni- which the patient is less responsive than usual or as inter- zation Practices for patients with diseases requiring treat- mittent days with excessive daytime sleepiness. Addi- ment with immunosuppressive drugs, including long-term tionally, this patient may also have REM sleep behavior systemic glucocorticoids and radiation therapy. disorder (acting out his dreams), but polysomnography Measles, mumps, and rubella vaccine (Option B) is a live is required to confirm this diagnosis. Clinical history vaccine and is contraindicated in patients who are immuno- and neurologic examination findings are critical for the compromised. Ideally the patient should have received this diagnosis of dementia with Lewy bodies to avoid inappro- immunization during childhood. priate treatment, particularly with antipsychotic drugs Meningococcal vaccines (Option C) used in the adult to which these patients are uniquely sensitive. Indicative population include the quadrivalent meningococcal conju- biomarkers also have been developed to support the diag- > gate vaccine (MenACWY), which protects against serogroups nosis when sufficient clinical history is lacking. =] wn A, C, W135, and Y infection, and the MenB vaccine, which Alzheimer disease dementia (Option A) is associ- = protects against serogroup B disease. The quadrivalent con- ated with hippocampal atrophy on MRI of the brain, and © a jugate vaccine is used in most patients, whereas the MenB patients do not typically have associated parkinsonism po =} vaccine is reserved for specific high-risk situations. Men- (although this can happen in the later stages of disease). 2. ACWY is indicated in patients with functional or anatomic Distinguishing Alzheimer disease from dementia with ra) = asplenia, HIV infection, persistent complement component Lewy bodies on the basis of cognition alone can be diffi- a. deficiency, treatment with a complement inhibitor (e.g., 2 cult, but other symptoms can help differentiate the two. = eculizumab), or travel to countries hyperendemic for menin- REM sleep behavior disorder is much more common in ° ~” gococcal disease, and in first-year college students living in dementia with Lewy bodies than Alzheimer disease. Delu- residential dormitories. This patient has no indication for sions and hallucinations are common in dementia with meningococcal vaccination. Lewy bodies and frequently occur at the mild stages of The recombinant herpes zoster vaccine (RZV) is indi- disease. Additionally, significant sleep problems, espe- cated for patients age 50 years and older and, therefore, is cially daytime sleepiness, can be a debilitating feature of not indicated in this patient. The role of RZV in immuno- dementia with Lewy bodies. The fluctuations in Alzheimer compromised patients is currently under review. disease can be described as days when memory is better or worse, whereas in dementia with Lewy bodies, the bad days involve decreased alertness. e The American Academy of Neurology recommends The patient does not have the behavioral or language annual inactivated influenza vaccination for all symptoms typically associated with frontotemporal demen- patients with multiple sclerosis. tia (Option C). In some familial forms of the disease, there e With the exception of annual influenza immuniza- can be parkinsonism, but this is rare. Visual hallucinations

available: the 13-valent conjugate vaccine (PCV13) and the parkinsonism, hallucinations, and attention fluctuations. 23-valent polysaccharide vaccine (PPSV23). Both vaccines The latter may manifest as acute confusional episodes in are recommended by the Advisory Committee on Immuni- which the patient is less responsive than usual or as inter- zation Practices for patients with diseases requiring treat- mittent days with excessive daytime sleepiness. Addi- ment with immunosuppressive drugs, including long-term tionally, this patient may also have REM sleep behavior systemic glucocorticoids and radiation therapy. disorder (acting out his dreams), but polysomnography Measles, mumps, and rubella vaccine (Option B) is a live is required to confirm this diagnosis. Clinical history vaccine and is contraindicated in patients who are immuno- and neurologic examination findings are critical for the compromised. Ideally the patient should have received this diagnosis of dementia with Lewy bodies to avoid inappro- immunization during childhood. priate treatment, particularly with antipsychotic drugs Meningococcal vaccines (Option C) used in the adult to which these patients are uniquely sensitive. Indicative population include the quadrivalent meningococcal conju- biomarkers also have been developed to support the diag- > gate vaccine (MenACWY), which protects against serogroups nosis when sufficient clinical history is lacking. =] wn A, C, W135, and Y infection, and the MenB vaccine, which Alzheimer disease dementia (Option A) is associ- = protects against serogroup B disease. The quadrivalent con- ated with hippocampal atrophy on MRI of the brain, and © a jugate vaccine is used in most patients, whereas the MenB patients do not typically have associated parkinsonism po =} vaccine is reserved for specific high-risk situations. Men- (although this can happen in the later stages of disease). 2. ACWY is indicated in patients with functional or anatomic Distinguishing Alzheimer disease from dementia with ra) = asplenia, HIV infection, persistent complement component Lewy bodies on the basis of cognition alone can be diffi- a. deficiency, treatment with a complement inhibitor (e.g., 2 cult, but other symptoms can help differentiate the two. = eculizumab), or travel to countries hyperendemic for menin- REM sleep behavior disorder is much more common in ° ~” gococcal disease, and in first-year college students living in dementia with Lewy bodies than Alzheimer disease. Delu- residential dormitories. This patient has no indication for sions and hallucinations are common in dementia with meningococcal vaccination. Lewy bodies and frequently occur at the mild stages of The recombinant herpes zoster vaccine (RZV) is indi- disease. Additionally, significant sleep problems, espe- cated for patients age 50 years and older and, therefore, is cially daytime sleepiness, can be a debilitating feature of not indicated in this patient. The role of RZV in immuno- dementia with Lewy bodies. The fluctuations in Alzheimer compromised patients is currently under review. disease can be described as days when memory is better or worse, whereas in dementia with Lewy bodies, the bad days involve decreased alertness. e The American Academy of Neurology recommends The patient does not have the behavioral or language annual inactivated influenza vaccination for all symptoms typically associated with frontotemporal demen- patients with multiple sclerosis. tia (Option C). In some familial forms of the disease, there e With the exception of annual influenza immuniza- can be parkinsonism, but this is rare. Visual hallucinations tion, patients ideally should receive other needed are not typical of frontotemporal dementia.

available: the 13-valent conjugate vaccine (PCV13) and the parkinsonism, hallucinations, and attention fluctuations. 23-valent polysaccharide vaccine (PPSV23). Both vaccines The latter may manifest as acute confusional episodes in are recommended by the Advisory Committee on Immuni- which the patient is less responsive than usual or as inter- zation Practices for patients with diseases requiring treat- mittent days with excessive daytime sleepiness. Addi- ment with immunosuppressive drugs, including long-term tionally, this patient may also have REM sleep behavior systemic glucocorticoids and radiation therapy. disorder (acting out his dreams), but polysomnography Measles, mumps, and rubella vaccine (Option B) is a live is required to confirm this diagnosis. Clinical history vaccine and is contraindicated in patients who are immuno- and neurologic examination findings are critical for the compromised. Ideally the patient should have received this diagnosis of dementia with Lewy bodies to avoid inappro- immunization during childhood. priate treatment, particularly with antipsychotic drugs Meningococcal vaccines (Option C) used in the adult to which these patients are uniquely sensitive. Indicative population include the quadrivalent meningococcal conju- biomarkers also have been developed to support the diag- > gate vaccine (MenACWY), which protects against serogroups nosis when sufficient clinical history is lacking. =] wn A, C, W135, and Y infection, and the MenB vaccine, which Alzheimer disease dementia (Option A) is associ- = protects against serogroup B disease. The quadrivalent con- ated with hippocampal atrophy on MRI of the brain, and © a jugate vaccine is used in most patients, whereas the MenB patients do not typically have associated parkinsonism po =} vaccine is reserved for specific high-risk situations. Men- (although this can happen in the later stages of disease). 2. ACWY is indicated in patients with functional or anatomic Distinguishing Alzheimer disease from dementia with ra) = asplenia, HIV infection, persistent complement component Lewy bodies on the basis of cognition alone can be diffi- a. deficiency, treatment with a complement inhibitor (e.g., 2 cult, but other symptoms can help differentiate the two. = eculizumab), or travel to countries hyperendemic for menin- REM sleep behavior disorder is much more common in ° ~” gococcal disease, and in first-year college students living in dementia with Lewy bodies than Alzheimer disease. Delu- residential dormitories. This patient has no indication for sions and hallucinations are common in dementia with meningococcal vaccination. Lewy bodies and frequently occur at the mild stages of The recombinant herpes zoster vaccine (RZV) is indi- disease. Additionally, significant sleep problems, espe- cated for patients age 50 years and older and, therefore, is cially daytime sleepiness, can be a debilitating feature of not indicated in this patient. The role of RZV in immuno- dementia with Lewy bodies. The fluctuations in Alzheimer compromised patients is currently under review. disease can be described as days when memory is better or worse, whereas in dementia with Lewy bodies, the bad days involve decreased alertness. e The American Academy of Neurology recommends The patient does not have the behavioral or language annual inactivated influenza vaccination for all symptoms typically associated with frontotemporal demen- patients with multiple sclerosis. tia (Option C). In some familial forms of the disease, there e With the exception of annual influenza immuniza- can be parkinsonism, but this is rare. Visual hallucinations tion, patients ideally should receive other needed are not typical of frontotemporal dementia. immunizations 4 to 6 weeks prior to the initiation of Parkinson disease dementia (Option D) can have symp-

available: the 13-valent conjugate vaccine (PCV13) and the parkinsonism, hallucinations, and attention fluctuations. 23-valent polysaccharide vaccine (PPSV23). Both vaccines The latter may manifest as acute confusional episodes in are recommended by the Advisory Committee on Immuni- which the patient is less responsive than usual or as inter- zation Practices for patients with diseases requiring treat- mittent days with excessive daytime sleepiness. Addi- ment with immunosuppressive drugs, including long-term tionally, this patient may also have REM sleep behavior systemic glucocorticoids and radiation therapy. disorder (acting out his dreams), but polysomnography Measles, mumps, and rubella vaccine (Option B) is a live is required to confirm this diagnosis. Clinical history vaccine and is contraindicated in patients who are immuno- and neurologic examination findings are critical for the compromised. Ideally the patient should have received this diagnosis of dementia with Lewy bodies to avoid inappro- immunization during childhood. priate treatment, particularly with antipsychotic drugs Meningococcal vaccines (Option C) used in the adult to which these patients are uniquely sensitive. Indicative population include the quadrivalent meningococcal conju- biomarkers also have been developed to support the diag- > gate vaccine (MenACWY), which protects against serogroups nosis when sufficient clinical history is lacking. =] wn A, C, W135, and Y infection, and the MenB vaccine, which Alzheimer disease dementia (Option A) is associ- = protects against serogroup B disease. The quadrivalent con- ated with hippocampal atrophy on MRI of the brain, and © a jugate vaccine is used in most patients, whereas the MenB patients do not typically have associated parkinsonism po =} vaccine is reserved for specific high-risk situations. Men- (although this can happen in the later stages of disease). 2. ACWY is indicated in patients with functional or anatomic Distinguishing Alzheimer disease from dementia with ra) = asplenia, HIV infection, persistent complement component Lewy bodies on the basis of cognition alone can be diffi- a. deficiency, treatment with a complement inhibitor (e.g., 2 cult, but other symptoms can help differentiate the two. = eculizumab), or travel to countries hyperendemic for menin- REM sleep behavior disorder is much more common in ° ~” gococcal disease, and in first-year college students living in dementia with Lewy bodies than Alzheimer disease. Delu- residential dormitories. This patient has no indication for sions and hallucinations are common in dementia with meningococcal vaccination. Lewy bodies and frequently occur at the mild stages of The recombinant herpes zoster vaccine (RZV) is indi- disease. Additionally, significant sleep problems, espe- cated for patients age 50 years and older and, therefore, is cially daytime sleepiness, can be a debilitating feature of not indicated in this patient. The role of RZV in immuno- dementia with Lewy bodies. The fluctuations in Alzheimer compromised patients is currently under review. disease can be described as days when memory is better or worse, whereas in dementia with Lewy bodies, the bad days involve decreased alertness. e The American Academy of Neurology recommends The patient does not have the behavioral or language annual inactivated influenza vaccination for all symptoms typically associated with frontotemporal demen- patients with multiple sclerosis. tia (Option C). In some familial forms of the disease, there e With the exception of annual influenza immuniza- can be parkinsonism, but this is rare. Visual hallucinations tion, patients ideally should receive other needed are not typical of frontotemporal dementia. immunizations 4 to 6 weeks prior to the initiation of Parkinson disease dementia (Option D) can have symp- immunosuppressive/immunomodulating therapy; toms similar to those of dementia with Lewy bodies. How-

tion, patients ideally should receive other needed are not typical of frontotemporal dementia. immunizations 4 to 6 weeks prior to the initiation of Parkinson disease dementia (Option D) can have symp- immunosuppressive/immunomodulating therapy; toms similar to those of dementia with Lewy bodies. How- immunizations should be delayed in patients during a ever, diagnosis of Parkinson disease dementia requires that the motor symptoms precede the cognitive impairment by MS relapse. at least 2 years. Bibliography Farez MF, Correale J, Armstrong MJ. et al. Practice guideline update summary: vaccine-preventable infections and immunization in ¢ The clinical diagnosis of dementia with Lewy bodies multiple sclerosis: report of the Guideline Development, Dissemination, rests on the key features of dementia, parkinsonian and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2019;93:584-94. [PMID: 31462584] doi: 10.1212/ motor features, visual hallucinations, rapid eye move- WNL.0000000000008157. ment sleep behavior disorder, and frequent fluctuations in attention. item 88 Answer: 8B ¢ Unlike Alzheimer disease, delusions and hallucinations

Bibliography Farez MF, Correale J, Armstrong MJ. et al. Practice guideline update summary: vaccine-preventable infections and immunization in ¢ The clinical diagnosis of dementia with Lewy bodies multiple sclerosis: report of the Guideline Development, Dissemination, rests on the key features of dementia, parkinsonian and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2019;93:584-94. [PMID: 31462584] doi: 10.1212/ motor features, visual hallucinations, rapid eye move- WNL.0000000000008157. ment sleep behavior disorder, and frequent fluctuations in attention. item 88 Answer: 8B ¢ Unlike Alzheimer disease, delusions and hallucinations Educational Objective: Diagnose dementia with Lewy are common in dementia with Lewy bodies, as are bodies. daytime sleepiness and rapid eye movement sleep behavior disorder. The most likely diagnosis is dementia with Lewy bodies (Option B). Of the four core features of this condition— parkinsonian motor features (particularly gait problems Bibliography and slowness of movements), visual hallucinations, rapid MckKeith IG, Boeve BF, Dickson DW, et al. Diagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB eye movement (REM) sleep behavior disorder, and fre- Consortium. Neurology. 2017;89:88-100. [PMID: 28592453] doi:10.1212/ quent fluctuations in attention—this patient has three: WNL.0000000000004058 160

Answers and Critiques Item 89 Answer: D Item 90 Answer: B Educational Objective: Diagnose acetylcholinesterase Educational Objective: Evaluate traumatic brain injury inhibitor-related bradycardia. with a head CT scan.

Answers and Critiques Item 89 Answer: D Item 90 Answer: B Educational Objective: Diagnose acetylcholinesterase Educational Objective: Evaluate traumatic brain injury inhibitor-related bradycardia. with a head CT scan. The most appropriate next step in management for this patient The patient should undergo head CT (Option B). The pre- with symptomatic bradycardia is to stop the donepezil (Option sentation is compatible with a minor traumatic brain injury D). Sinus bradycardia is the presence of sinus rhythm with a (TBI) or concussion. The patient sustained a direct blow to heart rate of less than 60/min. Pathologic sinus bradycardia the head followed by brief loss of consciousness. Indications is most commonly caused by sinus node dysfunction due to for neuroimaging in this scenario include the history of a age-related myocardial fibrosis. The most common extrinsic posttraumatic seizure and the presence of amnesia and gait cause is medication use. The acetylcholinesterase inhibitors unsteadiness on physical examination. Other commonly donepezil, rivastigmine, and galantamine modestly improve cited indications for head CT in patients with TBI or concus- cognitive performance in patients with mild or moderate Alz- sion include progressive headache, recurrent vomiting, age 4) a heimer disease. However, these drugs can be associated with older than 60 years, drug or alcohol intoxication, presence =] bradycardia, heart block, and syncope due to drug-related of coagulopathy, suspected skull fracture, and dangerous = enhanced vagal tone. Acetylcholinesterase inhibitors should mechanism of injury. Noncontrast head CT is the imaging = rs) be avoided in patients with pre-existing bradycardia or docu- modality of choice for minor TBI. cs = mented conduction disease and should be stopped in patients Head CT is recommended over brain MRI (Option A) in cs who develop symptomatic bradycardia or hypotension. The patients with acute traumatic brain injury. It is more widely wn hh

The most appropriate next step in management for this patient The patient should undergo head CT (Option B). The pre- with symptomatic bradycardia is to stop the donepezil (Option sentation is compatible with a minor traumatic brain injury D). Sinus bradycardia is the presence of sinus rhythm with a (TBI) or concussion. The patient sustained a direct blow to heart rate of less than 60/min. Pathologic sinus bradycardia the head followed by brief loss of consciousness. Indications is most commonly caused by sinus node dysfunction due to for neuroimaging in this scenario include the history of a age-related myocardial fibrosis. The most common extrinsic posttraumatic seizure and the presence of amnesia and gait cause is medication use. The acetylcholinesterase inhibitors unsteadiness on physical examination. Other commonly donepezil, rivastigmine, and galantamine modestly improve cited indications for head CT in patients with TBI or concus- cognitive performance in patients with mild or moderate Alz- sion include progressive headache, recurrent vomiting, age 4) a heimer disease. However, these drugs can be associated with older than 60 years, drug or alcohol intoxication, presence =] bradycardia, heart block, and syncope due to drug-related of coagulopathy, suspected skull fracture, and dangerous = enhanced vagal tone. Acetylcholinesterase inhibitors should mechanism of injury. Noncontrast head CT is the imaging = rs) be avoided in patients with pre-existing bradycardia or docu- modality of choice for minor TBI. cs = mented conduction disease and should be stopped in patients Head CT is recommended over brain MRI (Option A) in cs who develop symptomatic bradycardia or hypotension. The patients with acute traumatic brain injury. It is more widely wn hh N-methyl-p-aspartate receptor antagonist memantine is o available, faster to complete and allows for better visualiza- 2 approved for moderate to severe Alzheimer disease associated tion of acute hemorrhage and skull fracture wn < with significant functional impairment and might be consid- Levetiracetam (Option C) would be indicated in the <= ered as a substitute for donepezil in this case. Memantine is not presence of recurrent seizures or following the adminis- associated with adverse cardiovascular effects. tration of benzodiazepines for status epilepticus in order to In patients with syncope or near syncope, echocardi- maintain seizure control. Neither is present in this patient. A ography (Option A) is indicated to detect suspected valvular seizure occurring within the first week of a traumatic brain heart disease, hypertrophic cardiomyopathy, and reduced event is thought to be symptomatic and does not warrant left ventricular function. This patient has documented bra- antiepileptic therapy. dycardia related to the initiation of donepezil, and echocar- TBI is commonly classified using injury severity scores, diography will provide no additional diagnostic information. such as the Glasgow Coma Scale (GCS). A GCS score of 13 The intermittent and fleeting nature of arrhythmias can to 15 is considered mild injury, 9 to 12 is considered moder make diagnosis difficult. If symptoms occur daily, a 24-hour ate injury, and 8 or less is considered severe TBI. Mannitol ambulatory ECG monitor (Option B) may be used. However, (Option D) is indicated in the management of severe TBI this patient’s arrhythmia is evident on physical examination with signs of increased intracranial pressure. This patient and ECG, and a medication cause is evident. 24-Hour ambu- has not had a severe TBI, and there is no evidence of intra- latory ECG monitoring is not necessary. cranial hypertension. In hemodynamically stable patients, reversible and Blood pressure support with intravenous crystalloid extrinsic causes of bradycardia should always be addressed fluids and norepinephrine (Option E) or phenylephrine is before more invasive measures, such as permanent pacing, indicated in the intensive care unit in the setting of severe are considered. This patient has a reversible cause of brady- TBI with severe hypotension. This patient sustained a minor cardia and pacemaker insertion (Option C) is not the first TBI and is alert, oriented, and hemodynamically stable and management option. does not require blood pressure support. Thiazide diuretics are associated with many metabolic side effects, sleep disturbance, and sexual dysfunction but not presyncope, syncope, or falls (Option D). e Noncontrast head CT is the imaging modality of choice in selected patients with traumatic brain injury.

N-methyl-p-aspartate receptor antagonist memantine is o available, faster to complete and allows for better visualiza- 2 approved for moderate to severe Alzheimer disease associated tion of acute hemorrhage and skull fracture wn < with significant functional impairment and might be consid- Levetiracetam (Option C) would be indicated in the <= ered as a substitute for donepezil in this case. Memantine is not presence of recurrent seizures or following the adminis- associated with adverse cardiovascular effects. tration of benzodiazepines for status epilepticus in order to In patients with syncope or near syncope, echocardi- maintain seizure control. Neither is present in this patient. A ography (Option A) is indicated to detect suspected valvular seizure occurring within the first week of a traumatic brain heart disease, hypertrophic cardiomyopathy, and reduced event is thought to be symptomatic and does not warrant left ventricular function. This patient has documented bra- antiepileptic therapy. dycardia related to the initiation of donepezil, and echocar- TBI is commonly classified using injury severity scores, diography will provide no additional diagnostic information. such as the Glasgow Coma Scale (GCS). A GCS score of 13 The intermittent and fleeting nature of arrhythmias can to 15 is considered mild injury, 9 to 12 is considered moder make diagnosis difficult. If symptoms occur daily, a 24-hour ate injury, and 8 or less is considered severe TBI. Mannitol ambulatory ECG monitor (Option B) may be used. However, (Option D) is indicated in the management of severe TBI this patient’s arrhythmia is evident on physical examination with signs of increased intracranial pressure. This patient and ECG, and a medication cause is evident. 24-Hour ambu- has not had a severe TBI, and there is no evidence of intra- latory ECG monitoring is not necessary. cranial hypertension. In hemodynamically stable patients, reversible and Blood pressure support with intravenous crystalloid extrinsic causes of bradycardia should always be addressed fluids and norepinephrine (Option E) or phenylephrine is before more invasive measures, such as permanent pacing, indicated in the intensive care unit in the setting of severe are considered. This patient has a reversible cause of brady- TBI with severe hypotension. This patient sustained a minor cardia and pacemaker insertion (Option C) is not the first TBI and is alert, oriented, and hemodynamically stable and management option. does not require blood pressure support. Thiazide diuretics are associated with many metabolic side effects, sleep disturbance, and sexual dysfunction but not presyncope, syncope, or falls (Option D). e Noncontrast head CT is the imaging modality of choice in selected patients with traumatic brain injury. e¢ Commonly cited indications for head CT following e The acetylcholinesterase inhibitors donepezil, riv- traumatic brain injury include: abnormal neurologic astigmine, and galantamine can be associated with exam, including testing of gait; progressive headache; bradycardia, heart block, and syncope. recurrent vomiting; loss of consciousness; prolonged e Acetylcholinesterase inhibitors should be avoided in anterograde amnesia; seizure; skull fracture; age patients with pre-existing bradycardia or documented greater than 60 years; alcohol or drug intoxication; conduction disease. coagulopathy; and dangerous mechanism of injury.

e¢ Commonly cited indications for head CT following e The acetylcholinesterase inhibitors donepezil, riv- traumatic brain injury include: abnormal neurologic astigmine, and galantamine can be associated with exam, including testing of gait; progressive headache; bradycardia, heart block, and syncope. recurrent vomiting; loss of consciousness; prolonged e Acetylcholinesterase inhibitors should be avoided in anterograde amnesia; seizure; skull fracture; age patients with pre-existing bradycardia or documented greater than 60 years; alcohol or drug intoxication; conduction disease. coagulopathy; and dangerous mechanism of injury. Bibliography Bibliography Oh ES, Rabins PV. Dementia. Ann Intern Med. 2019;171:ITC33-ITC48. Mullally WJ. Concussion. Am J Med. 2017;130:885-92. [PMID: 28502817]. [PMID: 31476229] doi: 10.7326/AITC201909030 doi: 10.1016/j.amjmed.2017.04.016 161

Item 91 Answer: B Item 92 Answer: 8B Educational Objective: Evaluate a patient with a thun- Educational Objective: Diagnose migraine. derclap headache. The most likely diagnosis is migraine (Option B). Migraine The most appropriate first step in management is head CT is the most common severe headache in both population- (Option B). The patient has an acute-onset severe headache based and clinic-based studies. Annual prevalence for that differs from her migraine episodes. Red flags for second- migraine approximates 13% of adults, and greater than 90% ary headache include abrupt onset, new headache in a patient of headache visits to primary care and specialty settings older than 50 years, and a fundamental change in headache involve migraine. According to criteria published in the pattern. The abrupt nature in this patient’s headache is char- International Classification of Headache Disorders, 3rd edi- acteristic of a “thunderclap” headache, which is defined as a tion, migraine involves recurrent attacks (at least 5 lifetime) severe attack of headache pain developing abruptly and reach- of head pain lasting, without treatment, from 4 to 72 hours.

Item 91 Answer: B Item 92 Answer: 8B Educational Objective: Evaluate a patient with a thun- Educational Objective: Diagnose migraine. derclap headache. The most likely diagnosis is migraine (Option B). Migraine The most appropriate first step in management is head CT is the most common severe headache in both population- (Option B). The patient has an acute-onset severe headache based and clinic-based studies. Annual prevalence for that differs from her migraine episodes. Red flags for second- migraine approximates 13% of adults, and greater than 90% ary headache include abrupt onset, new headache in a patient of headache visits to primary care and specialty settings older than 50 years, and a fundamental change in headache involve migraine. According to criteria published in the pattern. The abrupt nature in this patient’s headache is char- International Classification of Headache Disorders, 3rd edi- acteristic of a “thunderclap” headache, which is defined as a tion, migraine involves recurrent attacks (at least 5 lifetime) severe attack of headache pain developing abruptly and reach- of head pain lasting, without treatment, from 4 to 72 hours. > ing maximum intensity within 1 minute. Thunderclap head- The pain of migraine involves at least two of four features = wn” ache is a medical emergency that warrants immediate diagnos- (unilateral location, throbbing nature, moderate to severe = tic evaluation. Subarachnoid hemorrhage, the most common intensity, worsening with routine physical activity) and is @ = wa cause of thunderclap headache, is discovered in nearly 25% of associated with at least one of two features: (1) nausea and/or <3) affected patients. Noncontrast head CT should be performed vomiting and (2) photophobia and phonophobia. Neurologic = Qa without delay. The differential diagnosis of thunderclap head- examination is typically normal. Migraine may be subclassi- (=) ache also includes intracranial venous or sinus thrombosis, fied qualitatively (with or without aura) and quantitatively = = cervical artery dissection, reversible cerebral vasoconstriction (episodic or chronic). Migraine in patients reporting visual wf tj syndrome, posterior reversible encephalopathy syndrome, and or neurologic symptoms meeting appropriate criteria will oO wn ischemic stroke or transient ischemic attack. be subclassified as migraine with aura, but very few patients Brain MRI (Option A) is preferred to head CT in the eval- with migraine will ever experience aura. The number of total uation of subacute or chronic headaches, given its greater headache days per month differentiates episodic (<15 days) sensitivity and safety. In the acute setting, however, head from chronic (15 or more days) migraine. Because of the CT is performed more rapidly and may be more accurate in extensive phenotypic variation, nearly half of migraine pre- identifying acute intracranial hemorrhage. sentations are misdiagnosed. Neck pain (75%) and “sinus” Lumbar puncture (Option C) with measurement of symptoms, such as tearing or nasal drainage (50%), are opening pressure, cell counts, and xanthochromia should be both more common than features felt to be characteristic of performed if the head CT is nondiagnostic. Lumbar puncture migraine, such as vomiting or aura. is considered only after a screening neuroimaging study Cluster headache (Option A) may be severe or throb- because acute hydrocephalus or space-occupying lesions bing and may result in nausea and nasal congestion or drain- could present with thunderclap onset and an elevated risk age. However, cluster headache pain is strictly unilateral, and for herniation during a lumbar puncture procedure. attacks by definition do not extend beyond 3 hours without Sumatriptan (Option D) is an effective treatment for treatment. acute migraine, but this presentation is atypical for migraine. Primary stabbing (Option C) headache involves epi- The use of sumatriptan would also be contraindicated within sodes of stabbing head pain lasting seconds and occurring 24 hours of the administration of rizatriptan. Additionally, a in isolation or in series. There are no associated autonomic response to triptans should not be a diagnostic indicator for features. The attacks described by this patient are much lon- migraine because some secondary headaches may respond ger in duration. The location of pain is fixed in one third of to subcutaneous sumatriptan. patients and extratrigeminal in most patients. Indomethacin can be helpful during cycles of more frequent attacks. Nausea, severe intensity, throbbing quality, and resul- ¢ Head CT is the preferred imaging modality in patients tant disability from headache pain are not features seen with with thunderclap headache, a medical emergency that tension-type headache (Option D). warrants immediate diagnostic evaluation.

> ing maximum intensity within 1 minute. Thunderclap head- The pain of migraine involves at least two of four features = wn” ache is a medical emergency that warrants immediate diagnos- (unilateral location, throbbing nature, moderate to severe = tic evaluation. Subarachnoid hemorrhage, the most common intensity, worsening with routine physical activity) and is @ = wa cause of thunderclap headache, is discovered in nearly 25% of associated with at least one of two features: (1) nausea and/or <3) affected patients. Noncontrast head CT should be performed vomiting and (2) photophobia and phonophobia. Neurologic = Qa without delay. The differential diagnosis of thunderclap head- examination is typically normal. Migraine may be subclassi- (=) ache also includes intracranial venous or sinus thrombosis, fied qualitatively (with or without aura) and quantitatively = = cervical artery dissection, reversible cerebral vasoconstriction (episodic or chronic). Migraine in patients reporting visual wf tj syndrome, posterior reversible encephalopathy syndrome, and or neurologic symptoms meeting appropriate criteria will oO wn ischemic stroke or transient ischemic attack. be subclassified as migraine with aura, but very few patients Brain MRI (Option A) is preferred to head CT in the eval- with migraine will ever experience aura. The number of total uation of subacute or chronic headaches, given its greater headache days per month differentiates episodic (<15 days) sensitivity and safety. In the acute setting, however, head from chronic (15 or more days) migraine. Because of the CT is performed more rapidly and may be more accurate in extensive phenotypic variation, nearly half of migraine pre- identifying acute intracranial hemorrhage. sentations are misdiagnosed. Neck pain (75%) and “sinus” Lumbar puncture (Option C) with measurement of symptoms, such as tearing or nasal drainage (50%), are opening pressure, cell counts, and xanthochromia should be both more common than features felt to be characteristic of performed if the head CT is nondiagnostic. Lumbar puncture migraine, such as vomiting or aura. is considered only after a screening neuroimaging study Cluster headache (Option A) may be severe or throb- because acute hydrocephalus or space-occupying lesions bing and may result in nausea and nasal congestion or drain- could present with thunderclap onset and an elevated risk age. However, cluster headache pain is strictly unilateral, and for herniation during a lumbar puncture procedure. attacks by definition do not extend beyond 3 hours without Sumatriptan (Option D) is an effective treatment for treatment. acute migraine, but this presentation is atypical for migraine. Primary stabbing (Option C) headache involves epi- The use of sumatriptan would also be contraindicated within sodes of stabbing head pain lasting seconds and occurring 24 hours of the administration of rizatriptan. Additionally, a in isolation or in series. There are no associated autonomic response to triptans should not be a diagnostic indicator for features. The attacks described by this patient are much lon- migraine because some secondary headaches may respond ger in duration. The location of pain is fixed in one third of to subcutaneous sumatriptan. patients and extratrigeminal in most patients. Indomethacin can be helpful during cycles of more frequent attacks. Nausea, severe intensity, throbbing quality, and resul- ¢ Head CT is the preferred imaging modality in patients tant disability from headache pain are not features seen with with thunderclap headache, a medical emergency that tension-type headache (Option D). warrants immediate diagnostic evaluation. e If head CT is nondiagnostic in the evaluation of a thunderclap headache, lumbar puncture with meas- e Migraine is the most common severe headache. urement of opening pressure, cell counts, and xan- e Established criteria for migraine include recurrent thochromia should be performed. attacks of head pain lasting from 4 to 72 hours with- out treatment, involving at least two of four features

e If head CT is nondiagnostic in the evaluation of a thunderclap headache, lumbar puncture with meas- e Migraine is the most common severe headache. urement of opening pressure, cell counts, and xan- e Established criteria for migraine include recurrent thochromia should be performed. attacks of head pain lasting from 4 to 72 hours with- out treatment, involving at least two of four features Bibliography (unilateral location, throbbing nature, moderate- Godwin SA, Cherkas DS, Panagos PD, et al; American College of Emergency severe intensity, worsening with routine physical Physicians Clinical Policies Subcommittee (Writing Committee) on Acute activity), and possessing at least one of the following Headache: Clinical Policy: Critical Issues in the Evaluation and Management of Adult Patients Presenting to the Emergency Department With Acute two associations: (1) nausea and/or vomiting and Headache. Ann Emerg Med. 2019:74:e41-e74. [PMID: 31543134] (2) photophobia and phonophobia. doi:10.1016/j.annemergmed.2019.07.009 162

Answers and Critiques Bibliography Bibliography MacGregor EA. Migraine. Ann Intern Med. 2017 Apr 4;166(7):ITC49-ITC64. Sheldon R. How to differentiate syncope from seizure. Cardiol Clin. [PMID: 28384749]. doi:10.7326/AITC201704040. 2015;33(3):377-385. [PMID: 26115824] doi:10.1016 /j.ccl.2015.04.006

Bibliography Bibliography MacGregor EA. Migraine. Ann Intern Med. 2017 Apr 4;166(7):ITC49-ITC64. Sheldon R. How to differentiate syncope from seizure. Cardiol Clin. [PMID: 28384749]. doi:10.7326/AITC201704040. 2015;33(3):377-385. [PMID: 26115824] doi:10.1016 /j.ccl.2015.04.006 Item 93 Answer: B Item 94 Answer: E Educational Objective: Diagnose convulsive syncope. Educational Objective: Manage a suspected pseudorelapse of multiple sclerosis. The patient most likely has convulsive syncope (Option B). Syncope is a transient complete loss of consciousness and The most appropriate next step in management is to obtain postural tone due to global cerebral hypoperfusion and may a urinalysis and urine culture (Option E). This patient has follow stereotyped patterns (as can seizures or migraines). secondary progressive multiple sclerosis (MS) with worsening Its onset is abrupt, with a spontaneous, rapid, and complete neurologic function, which suggests a potential MS relapse 2) recovery. The most common cause of syncope is neurally or disability progression. However, she also has urinary fre rt} 3 mediated syncope, which generally occurs with prolonged quency and an elevated body temperature, which is suggestive — standing or dehydration and has a prodrome of nausea, of a urinary tract infection, possibly an upper tract infection. — oO lightheadedness, warmth, tunnel vision, or palpitations. Many patients with multiple sclerosis experience Uhthoff sc Stereotyped events with warning signs can be mistaken for phenomenon, in which chronic neurologic symptoms become = 6 seizures, but the duration of loss of consciousness is usually more prominent in the setting of elevated body temperature rn —s briefer in syncope (<1 min) than in seizures, and immediate (hot weather, physical exertion, or fever). Because this patient o

Item 93 Answer: B Item 94 Answer: E Educational Objective: Diagnose convulsive syncope. Educational Objective: Manage a suspected pseudorelapse of multiple sclerosis. The patient most likely has convulsive syncope (Option B). Syncope is a transient complete loss of consciousness and The most appropriate next step in management is to obtain postural tone due to global cerebral hypoperfusion and may a urinalysis and urine culture (Option E). This patient has follow stereotyped patterns (as can seizures or migraines). secondary progressive multiple sclerosis (MS) with worsening Its onset is abrupt, with a spontaneous, rapid, and complete neurologic function, which suggests a potential MS relapse 2) recovery. The most common cause of syncope is neurally or disability progression. However, she also has urinary fre rt} 3 mediated syncope, which generally occurs with prolonged quency and an elevated body temperature, which is suggestive — standing or dehydration and has a prodrome of nausea, of a urinary tract infection, possibly an upper tract infection. — oO lightheadedness, warmth, tunnel vision, or palpitations. Many patients with multiple sclerosis experience Uhthoff sc Stereotyped events with warning signs can be mistaken for phenomenon, in which chronic neurologic symptoms become = 6 seizures, but the duration of loss of consciousness is usually more prominent in the setting of elevated body temperature rn —s briefer in syncope (<1 min) than in seizures, and immediate (hot weather, physical exertion, or fever). Because this patient o and complete neurologic recovery is typical. Nonepileptic = has pre-existing lower extremity weakness, she is likely expe- wn < myoclonus (in this patient) and other types of movements riencing Uhthoff phenomenon (or a “pseudorelapse”) caused 4 and shaking are typical of convulsive syncope; in fact, syn- by a urinary tract infection—-associated fever and not a new cope without any movements is the exception rather than inflammatory lesion in her brain or spinal cord. the rule. Increasing this patient's solifenacin dose (Option A) Atonic seizures (Option A) are characterized by abrupt is not the most appropriate management at this time; her falling, a brief loss of consciousness, and decreased tone; urinary frequency is likely being worsened by an underlying there usually are no warning symptoms, such as tun- urinary tract infection. nel vision or palpitations, or precipitating events such as Initiating intravenous high-dose glucocorticoids prolonged standing. The duration of atonic seizures is briefer (Option B) is appropriate therapy for an MS relapse. However, (a few seconds) than that of syncope. there is a higher likelihood that her worsening symptoms Generalized tonic-clonic seizures (GTCS) (Option C) are are caused by Uhthoff phenomenon, which is masquerading characterized by an abrupt loss of consciousness sometimes as a relapse. Diagnosing and treating the underlying cause associated with a scream or choking sound, and increased of her fever is the most appropriate next step. Symptoms tone at onset (tonic phase), followed by rhythmic, synchro- that persist despite treatment of the infection and fever may nous jerking of all limbs (clonic phase) lasting usually more represent a relapse, and intravenous glucocorticoids would than 1 minute. Confusion, lethargy, and occasionally com- be a reasonable consideration. bativeness follow GTCS. Cyanosis, not pallor, is common The stimulant medications modafinil (Option C), with this type of seizure. armodafinil, amantadine, and amphetamines may be helpful Myoclonus (Option D) is a single quick jerk of a limb in managing chronic fatigue. Although this patient's fatigue or the entire body lasting less than a second and is not may be improved by modafinil, it is likely caused by an under- always associated with a seizure. A diagnosis of myoclonic lying infection and may resolve with treatment of the infection. seizures can be confirmed by electroencephalography, with An MRI of the cervical and thoracic spine (Option D) each jerk associated with a generalized spike-and-wave could potentially help determine if her worsened lower discharge. Myoclonic seizures also can occur repetitively extremity weakness is caused by the formation of a new MS and result in falls. Awareness is maintained and duration lesion. However, in the setting of a possible infection, evalu is very short (<1 second), which differentiates it from con- ation and treatment of the infection has a higher utility and vulsive syncope. significantly lower cost than this imaging test.

and complete neurologic recovery is typical. Nonepileptic = has pre-existing lower extremity weakness, she is likely expe- wn < myoclonus (in this patient) and other types of movements riencing Uhthoff phenomenon (or a “pseudorelapse”) caused 4 and shaking are typical of convulsive syncope; in fact, syn- by a urinary tract infection—-associated fever and not a new cope without any movements is the exception rather than inflammatory lesion in her brain or spinal cord. the rule. Increasing this patient's solifenacin dose (Option A) Atonic seizures (Option A) are characterized by abrupt is not the most appropriate management at this time; her falling, a brief loss of consciousness, and decreased tone; urinary frequency is likely being worsened by an underlying there usually are no warning symptoms, such as tun- urinary tract infection. nel vision or palpitations, or precipitating events such as Initiating intravenous high-dose glucocorticoids prolonged standing. The duration of atonic seizures is briefer (Option B) is appropriate therapy for an MS relapse. However, (a few seconds) than that of syncope. there is a higher likelihood that her worsening symptoms Generalized tonic-clonic seizures (GTCS) (Option C) are are caused by Uhthoff phenomenon, which is masquerading characterized by an abrupt loss of consciousness sometimes as a relapse. Diagnosing and treating the underlying cause associated with a scream or choking sound, and increased of her fever is the most appropriate next step. Symptoms tone at onset (tonic phase), followed by rhythmic, synchro- that persist despite treatment of the infection and fever may nous jerking of all limbs (clonic phase) lasting usually more represent a relapse, and intravenous glucocorticoids would than 1 minute. Confusion, lethargy, and occasionally com- be a reasonable consideration. bativeness follow GTCS. Cyanosis, not pallor, is common The stimulant medications modafinil (Option C), with this type of seizure. armodafinil, amantadine, and amphetamines may be helpful Myoclonus (Option D) is a single quick jerk of a limb in managing chronic fatigue. Although this patient's fatigue or the entire body lasting less than a second and is not may be improved by modafinil, it is likely caused by an under- always associated with a seizure. A diagnosis of myoclonic lying infection and may resolve with treatment of the infection. seizures can be confirmed by electroencephalography, with An MRI of the cervical and thoracic spine (Option D) each jerk associated with a generalized spike-and-wave could potentially help determine if her worsened lower discharge. Myoclonic seizures also can occur repetitively extremity weakness is caused by the formation of a new MS and result in falls. Awareness is maintained and duration lesion. However, in the setting of a possible infection, evalu is very short (<1 second), which differentiates it from con- ation and treatment of the infection has a higher utility and vulsive syncope. significantly lower cost than this imaging test. e Syncope is a transient loss of consciousness and pos- e Patients with multiple sclerosis experience Uhthoff tural tone due to global cerebral hypoperfusion that phenomenon, in which chronic neurologic symptoms typically has an abrupt onset and complete, rapid become more prominent in the setting of elevated neurologic recovery. body temperature.

e Syncope is a transient loss of consciousness and pos- e Patients with multiple sclerosis experience Uhthoff tural tone due to global cerebral hypoperfusion that phenomenon, in which chronic neurologic symptoms typically has an abrupt onset and complete, rapid become more prominent in the setting of elevated neurologic recovery. body temperature. ¢ Nonepileptic myoclonus and other types of movements and shaking are typical of convulsive Bibliography syncope. Jain A, Rosso M, Santoro JD. Wilhelm Uhthoff and Uhthoff’s phenomenon. Mult Scler. 2019:1352458519881950. [PMID: 31621479] 163

Answers and Critiques Item 95 Answer: A Bibliography Powers WJ, Rabinstein AA, Ackerson T, et al; American Heart Association Educational Objective: Evaluate a transient ischemic Stroke Council. 2018 Guidelines for the Early Management of attack. Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke This patient should next undergo carotid ultrasonography Association. Stroke. 2018;49:e46-e110. [PMID: 29367334] doi:10.1161/ STR.0000000000000158 (Option A). He had a transient ischemic attack (TIA) charac- terized by the focal neurologic symptom of hemiparesis. The patient has an ABCD? score (Age > 60 years, elevated Blood ltem 96 Answer: C pressure, Clinical presentation of hemiparesis, Duration of Educational Objective: Diagnose facial myoclonus. symptoms, and Diabetes mellitus) of 5, which indicates a high risk of stroke at 48 hours (4.1%) and 90 days (9.8%). The most likely diagnosis is myoclonus (Option C). This The highest risk of stroke after a TIA or minor stroke is patient exhibits focal myoclonus of the left side of the face, > associated with symptomatic large artery atherosclerosis in also known as hemifacial spasm. Myoclonus is character- J w” patients with extracranial internal carotid artery stenosis. ized by brief, shock-like, and jerky contractions that may = These patients benefit from urgent carotid revascularization originate from any part of the nervous system, including the @ =a wv to prevent a subsequent stroke. Carotid ultrasonography is a cortex, subcortical structures, spine, or peripheral nerves. o low-cost, readily available test not associated with radiation Myoclonus can be physiologic (hiccups, hypnic jerks at sleep = Qa. and should be performed emergently in order to identify onset) or pathologic (caused by medications, toxins, or sys- (oe) patients who may require surgery. temic or central disease). Hemifacial spasm is often caused == =. Electroencephalography (Option B) is not appropriate by vascular compression of cranial nerve VII (facial nerve) =3 a because the patient does not have other symptoms of epi- at its exit zone from the brainstem. Irritation of the facial oO 2) lepsy, such as convulsions or loss of awareness. nerve leads to synchronous activation of the muscles of facial Magnetic resonance angiography (Option C) is an expression that are innervated by this nerve. This condition expensive test and may not immediately change manage- can be treated with carbamazepine, botulinum toxin injec- ment. Intracranial atherosclerosis is associated with a high tions, and vascular decompression surgery. risk of stroke after a TIA and minor stroke, and the indicated Chorea (Option A) consists of random, nonrepetitive, treatment for stroke prevention is best medical therapy. Intra- and flowing movements. This patient’s rapid, jerky, synchro- cranial stenting is high risk without a significant reduction in nous, and uniform movements are inconsistent with chorea. stroke. MRI of the brain also will not result in an immediate Dystonia (Option B) can be differentiated from myoclo- change in management and is high cost. The latest American nus on the basis of slow and sustained muscle contractions. Heart Association guidelines do not recommend routine use Focal dystonia can affect periorbital muscles (blepharospasm, of MRI in the inpatient setting; an infarct present on MRI will usually bilateral) or lower facial muscles (oromandibular dys- not change recommendations on initiation of antithrombotic tonia). This patient has rapid, brief facial movements that are treatment or necessarily inform risk of stroke better than the not characteristic of dystonia. less expensive carotid imaging. After the initial diagnostic Stereotypy (Option D) is associated with complex, testing, an MRI may allow for further stroke subtyping and coordinated, and ritualistic movements that are repeated in confirm the diagnosis of minor stroke. prolonged cycles. It is often associated with developmental Transesophageal echocardiography (TEE) (Option D) delay and neurometabolic syndromes. Thus, stereotypy is an has a low yield for identifying source of emboli in patients unlikely diagnosis in this patient. with stroke who have no risk factors and is not routinely Like myoclonus, tics (Option E) can be fast and twitchy. indicated as the initial cardiac diagnostic test. A TEE can be However, tics are often associated with an early age of onset considered in patients who are younger than 45 years who (during childhood), presence of premonitory urges, and have otherwise negative diagnostic testing, including trans- suppressibility, which are absent in this patient. thoracic echocardiography (TTE). TTE also is not routinely indicated in patients with stroke unless there is a clinical suspicion of a cardioembolic stroke based on medical history e Myoclonus is characterized by brief, shock-like, and or examination findings. jerky contractions that may originate from any part of the nervous system.

Item 95 Answer: A Bibliography Powers WJ, Rabinstein AA, Ackerson T, et al; American Heart Association Educational Objective: Evaluate a transient ischemic Stroke Council. 2018 Guidelines for the Early Management of attack. Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke This patient should next undergo carotid ultrasonography Association. Stroke. 2018;49:e46-e110. [PMID: 29367334] doi:10.1161/ STR.0000000000000158 (Option A). He had a transient ischemic attack (TIA) charac- terized by the focal neurologic symptom of hemiparesis. The patient has an ABCD? score (Age > 60 years, elevated Blood ltem 96 Answer: C pressure, Clinical presentation of hemiparesis, Duration of Educational Objective: Diagnose facial myoclonus. symptoms, and Diabetes mellitus) of 5, which indicates a high risk of stroke at 48 hours (4.1%) and 90 days (9.8%). The most likely diagnosis is myoclonus (Option C). This The highest risk of stroke after a TIA or minor stroke is patient exhibits focal myoclonus of the left side of the face, > associated with symptomatic large artery atherosclerosis in also known as hemifacial spasm. Myoclonus is character- J w” patients with extracranial internal carotid artery stenosis. ized by brief, shock-like, and jerky contractions that may = These patients benefit from urgent carotid revascularization originate from any part of the nervous system, including the @ =a wv to prevent a subsequent stroke. Carotid ultrasonography is a cortex, subcortical structures, spine, or peripheral nerves. o low-cost, readily available test not associated with radiation Myoclonus can be physiologic (hiccups, hypnic jerks at sleep = Qa. and should be performed emergently in order to identify onset) or pathologic (caused by medications, toxins, or sys- (oe) patients who may require surgery. temic or central disease). Hemifacial spasm is often caused == =. Electroencephalography (Option B) is not appropriate by vascular compression of cranial nerve VII (facial nerve) =3 a because the patient does not have other symptoms of epi- at its exit zone from the brainstem. Irritation of the facial oO 2) lepsy, such as convulsions or loss of awareness. nerve leads to synchronous activation of the muscles of facial Magnetic resonance angiography (Option C) is an expression that are innervated by this nerve. This condition expensive test and may not immediately change manage- can be treated with carbamazepine, botulinum toxin injec- ment. Intracranial atherosclerosis is associated with a high tions, and vascular decompression surgery. risk of stroke after a TIA and minor stroke, and the indicated Chorea (Option A) consists of random, nonrepetitive, treatment for stroke prevention is best medical therapy. Intra- and flowing movements. This patient’s rapid, jerky, synchro- cranial stenting is high risk without a significant reduction in nous, and uniform movements are inconsistent with chorea. stroke. MRI of the brain also will not result in an immediate Dystonia (Option B) can be differentiated from myoclo- change in management and is high cost. The latest American nus on the basis of slow and sustained muscle contractions. Heart Association guidelines do not recommend routine use Focal dystonia can affect periorbital muscles (blepharospasm, of MRI in the inpatient setting; an infarct present on MRI will usually bilateral) or lower facial muscles (oromandibular dys- not change recommendations on initiation of antithrombotic tonia). This patient has rapid, brief facial movements that are treatment or necessarily inform risk of stroke better than the not characteristic of dystonia. less expensive carotid imaging. After the initial diagnostic Stereotypy (Option D) is associated with complex, testing, an MRI may allow for further stroke subtyping and coordinated, and ritualistic movements that are repeated in confirm the diagnosis of minor stroke. prolonged cycles. It is often associated with developmental Transesophageal echocardiography (TEE) (Option D) delay and neurometabolic syndromes. Thus, stereotypy is an has a low yield for identifying source of emboli in patients unlikely diagnosis in this patient. with stroke who have no risk factors and is not routinely Like myoclonus, tics (Option E) can be fast and twitchy. indicated as the initial cardiac diagnostic test. A TEE can be However, tics are often associated with an early age of onset considered in patients who are younger than 45 years who (during childhood), presence of premonitory urges, and have otherwise negative diagnostic testing, including trans- suppressibility, which are absent in this patient. thoracic echocardiography (TTE). TTE also is not routinely indicated in patients with stroke unless there is a clinical suspicion of a cardioembolic stroke based on medical history e Myoclonus is characterized by brief, shock-like, and or examination findings. jerky contractions that may originate from any part of the nervous system. e Dystonia can be differentiated from myoclonus on the e The risk of stroke after a TIA is highest in patients basis of slow and sustained muscle contractions. with extracranial internal carotid artery stenosis.

Item 95 Answer: A Bibliography Powers WJ, Rabinstein AA, Ackerson T, et al; American Heart Association Educational Objective: Evaluate a transient ischemic Stroke Council. 2018 Guidelines for the Early Management of attack. Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke This patient should next undergo carotid ultrasonography Association. Stroke. 2018;49:e46-e110. [PMID: 29367334] doi:10.1161/ STR.0000000000000158 (Option A). He had a transient ischemic attack (TIA) charac- terized by the focal neurologic symptom of hemiparesis. The patient has an ABCD? score (Age > 60 years, elevated Blood ltem 96 Answer: C pressure, Clinical presentation of hemiparesis, Duration of Educational Objective: Diagnose facial myoclonus. symptoms, and Diabetes mellitus) of 5, which indicates a high risk of stroke at 48 hours (4.1%) and 90 days (9.8%). The most likely diagnosis is myoclonus (Option C). This The highest risk of stroke after a TIA or minor stroke is patient exhibits focal myoclonus of the left side of the face, > associated with symptomatic large artery atherosclerosis in also known as hemifacial spasm. Myoclonus is character- J w” patients with extracranial internal carotid artery stenosis. ized by brief, shock-like, and jerky contractions that may = These patients benefit from urgent carotid revascularization originate from any part of the nervous system, including the @ =a wv to prevent a subsequent stroke. Carotid ultrasonography is a cortex, subcortical structures, spine, or peripheral nerves. o low-cost, readily available test not associated with radiation Myoclonus can be physiologic (hiccups, hypnic jerks at sleep = Qa. and should be performed emergently in order to identify onset) or pathologic (caused by medications, toxins, or sys- (oe) patients who may require surgery. temic or central disease). Hemifacial spasm is often caused == =. Electroencephalography (Option B) is not appropriate by vascular compression of cranial nerve VII (facial nerve) =3 a because the patient does not have other symptoms of epi- at its exit zone from the brainstem. Irritation of the facial oO 2) lepsy, such as convulsions or loss of awareness. nerve leads to synchronous activation of the muscles of facial Magnetic resonance angiography (Option C) is an expression that are innervated by this nerve. This condition expensive test and may not immediately change manage- can be treated with carbamazepine, botulinum toxin injec- ment. Intracranial atherosclerosis is associated with a high tions, and vascular decompression surgery. risk of stroke after a TIA and minor stroke, and the indicated Chorea (Option A) consists of random, nonrepetitive, treatment for stroke prevention is best medical therapy. Intra- and flowing movements. This patient’s rapid, jerky, synchro- cranial stenting is high risk without a significant reduction in nous, and uniform movements are inconsistent with chorea. stroke. MRI of the brain also will not result in an immediate Dystonia (Option B) can be differentiated from myoclo- change in management and is high cost. The latest American nus on the basis of slow and sustained muscle contractions. Heart Association guidelines do not recommend routine use Focal dystonia can affect periorbital muscles (blepharospasm, of MRI in the inpatient setting; an infarct present on MRI will usually bilateral) or lower facial muscles (oromandibular dys- not change recommendations on initiation of antithrombotic tonia). This patient has rapid, brief facial movements that are treatment or necessarily inform risk of stroke better than the not characteristic of dystonia. less expensive carotid imaging. After the initial diagnostic Stereotypy (Option D) is associated with complex, testing, an MRI may allow for further stroke subtyping and coordinated, and ritualistic movements that are repeated in confirm the diagnosis of minor stroke. prolonged cycles. It is often associated with developmental Transesophageal echocardiography (TEE) (Option D) delay and neurometabolic syndromes. Thus, stereotypy is an has a low yield for identifying source of emboli in patients unlikely diagnosis in this patient. with stroke who have no risk factors and is not routinely Like myoclonus, tics (Option E) can be fast and twitchy. indicated as the initial cardiac diagnostic test. A TEE can be However, tics are often associated with an early age of onset considered in patients who are younger than 45 years who (during childhood), presence of premonitory urges, and have otherwise negative diagnostic testing, including trans- suppressibility, which are absent in this patient. thoracic echocardiography (TTE). TTE also is not routinely indicated in patients with stroke unless there is a clinical suspicion of a cardioembolic stroke based on medical history e Myoclonus is characterized by brief, shock-like, and or examination findings. jerky contractions that may originate from any part of the nervous system. e Dystonia can be differentiated from myoclonus on the e The risk of stroke after a TIA is highest in patients basis of slow and sustained muscle contractions. with extracranial internal carotid artery stenosis. ¢ Carotid ultrasonography should be performed emer- Bibliography gently in patients with transient ischemic attack to Chaudhry N, Srivastava A, Joshi L. Hemifacial spasm: The past, present and identify those who may benefit from surgery. future. J Neurol Sci. 2015;356:27-31. [PMID: 26111430] doi:10.1016/j. jns.2015.06.032

¢ Carotid ultrasonography should be performed emer- Bibliography gently in patients with transient ischemic attack to Chaudhry N, Srivastava A, Joshi L. Hemifacial spasm: The past, present and identify those who may benefit from surgery. future. J Neurol Sci. 2015;356:27-31. [PMID: 26111430] doi:10.1016/j. jns.2015.06.032 164