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Neurology Primary Headaches More than 90'l, of headaches are primary headaches, including migraine, tension type headaches, and trigeminal autonomic cephalalgias. Migraine Headache Migraine is the most common headache in clinical practice Diagnosis Approximately 30% of patients with migraine experience aura during orwithin the hourbefore the headache. An aura may mani fest as visual loss, hallucinations, flashing lights, numbness, tingling, aphasia, or confusion, with a typical duration of 5 to 60 minutes. Migraine with brainstem aura is defined by the presence of vertigo, ataxia, dysarthria, diplopia, tinnitus, hyperacusis, or alteration in consciousness. Any aura complex that involves some degree of motor weakness is categorDed as hemiplegic migraine. Sf UDY TABIE: Migraine Headache Duration 4-72 hours and at least 2 of the following: Unilateral Pulsatile Moderate-severe intensity that inhibits/prohibits routine activity Aggravated by routine activity (walking down stairs) Plus at least 1 of the following: Nausea/vomiting Photophobia/phonophobia DOl{'? BE TRICKED . Ninety percent of patients with "sinus headache" have migraine headache that will respond to migraine treatment. o Neuroimaging is indicated only for atypical headache features or for headaches that do not meet the strict definition of migraine. STUDY TABLE: Differential Diagnosis of Migraine Disease Considerations Tension-type headache 30 minutes to 7 days and >2 of the following: Bilateral location Pressure or tight nonpulsating quality Mild-moderate intensity Not aggravated by activity And both of the following: No nausea No photophobia or phonophobia Treat with simple analgesics, such as NSAIDs; a tricyclic antidepressant may be needed for prophylaxis (Continued on the next page) 287

Neurology STUDY TABLE: Differential Diagnosis of Migraine (Continued) Disease Considerations Trigeminal neuralgia Brief paroxysms of unilateral lancinating pain, most often in the V2 or V3 distribution of the trigeminal nerve, often triggered by Iight touch of the affected area Obtain an MRI to exclude intracranial lesions and MS Select carbamazepine for treatment Med ication-induced Use of triptans, ergot alkaloids, opioids, or combination analgesics for >1 0 days/mo or simple analgesics for headache >15 days/mo; must withdraw all pain medications and begin preventive medications for primary headache disorder Chronic migraine Headache occurring >1 5 days/mo for >3 months headache Headache possessing the features of migraine and relieved by a triptan or ergot alkaloid derivative DO]I'T BE TRICKED o Avoid butalbital and opioid analgesics in headache management. o Muscle relaxants, benzodiazepines, and botulinum toxin A have no role in the acute or prophylactic treatment of tension-type headache. Treatment Migraine treatment is categorized as acute, prophylactic, and rescue. First line treatment for acute mild to moderate migraine is aspirin or NSAlDs. A triptan or dihydroergotamine may be used for severe acute migraine or tbr poor response to first-line treatment. Migraine that is present on awakening, is associated with vomiting, or is found to escalate rapidly may be best treated by nasal triptans or subcutaneous sumatriptan. Metoclopramide and prochlorperazine are also effective for migraine-associated nausea and enhance the efficacy ofthe abortive medication. Choose migraine prophylaxis when: . migraines do not respond to therapy o headache occurs >10 days per month . disabling headache occurs >4 days per month Evidence based acute migraine prophylaxis (in nonpregnant patients) includes metoprolol, propranolol, timolol, divalproex, and topiramate.

Treatment Migraine treatment is categorized as acute, prophylactic, and rescue. First line treatment for acute mild to moderate migraine is aspirin or NSAlDs. A triptan or dihydroergotamine may be used for severe acute migraine or tbr poor response to first-line treatment. Migraine that is present on awakening, is associated with vomiting, or is found to escalate rapidly may be best treated by nasal triptans or subcutaneous sumatriptan. Metoclopramide and prochlorperazine are also effective for migraine-associated nausea and enhance the efficacy ofthe abortive medication. Choose migraine prophylaxis when: . migraines do not respond to therapy o headache occurs >10 days per month . disabling headache occurs >4 days per month Evidence based acute migraine prophylaxis (in nonpregnant patients) includes metoprolol, propranolol, timolol, divalproex, and topiramate. DON'T BE TRICKED . Do not choose oral medications for patients with severe nausea and vomiting. . Triptans are contraindicated in the presence ofCAD and cerebrovascular disease, brainstem aura, and hemiplegic migraine. . Do not use acute therapies more than 2 to 3 days per week to avoid medication overuse headaches. o Estrogen containing contraceptives must be avoided in women experiencing aura with migraine because of the increased risk for stroke. TEST YOURSELF A 39 year old woman has chronic headaches that occur daily and do not respond to analgesics. Medications are zolmitriptan, naproxen, acetaminophen with codeine, and amitriptyline. ANSWER: For diagnosis, choose chronic daily headache lrom medication overuse. For management, select taper of all acute head ache medications. 284

Neurology Thunderclap Headaches An important category of secondary headaches is "thunderclap" headaches, defined as reaching maximum intensity within 1 to 60 minutes. Thunderclap headache is a medical emergency that warrants immediate diagnostic evaluation. STUDY TABLE: lmportant Thunderclap Headaches HeadacheType CIues Treatment Subarachnoid Most common cause of thunderclap headache. Sudden Neurosurgery in selected cases (85% of nontraumatic hemorrhage onset of "worst headache of my life." cases caused by ruptured aneurysm) (SAH) Many patients have warning "sentinel" headaches before SAH. Reversible Second most common cause of thunderclap headache. Normalization o{ BP and elimination of any triggering cerebral Recurrent thunderclap headache syndrome, more drug or substance; glucocorticoids may worsen vasoconstricti o n frequent in women. Associated with pregnancy, outcomes syndrome neurosurgical procedures, exposure to adrenergic or serotonergic drugs, cannabis. lmaging shows strokes, hemorrhages, or cerebral edema. Carotid or Neck pain and ipsilateral headache; neurologic findings Aspirin vertebral in territory of involved vessel. A common cause of stroke dissection when age <50 years. Thrombosis of Exacerbation with the Valsalva maneuver, pulsatile LMWH followed by warfarin or dabigatran cerebral vein or tinnitus, and diplopia dural sinus Consider in hypercoagulable states, pregnancy, use o{ oral contraceptives. ld iopathic I ntracranial Hypertension ldiopathic intracranial hypertension (pseudotumor cerebri) is characterized by increased intracranial pressure without identifia ble structural pathologr. Patients are typically female, have obesity, and are of childbearing age. Papilledema is nearly always present. Diagnosis is confirmed by a CSF pressure >250 mm HrO with normal fluid composition. MRI may be normal or show small ventricles, widened optic nerve sheaths, or a partially emp[z sella.

ld iopathic I ntracranial Hypertension ldiopathic intracranial hypertension (pseudotumor cerebri) is characterized by increased intracranial pressure without identifia ble structural pathologr. Patients are typically female, have obesity, and are of childbearing age. Papilledema is nearly always present. Diagnosis is confirmed by a CSF pressure >250 mm HrO with normal fluid composition. MRI may be normal or show small ventricles, widened optic nerve sheaths, or a partially emp[z sella. First line treatment is weight loss if BMI is elevated. First line medication is acetazolamide. Traumatic Brain lnjury Papilledema: Fully developed papilledema is often present in patients with idio- pathic intracranial hypertension.0n Iunduscopic examination, loss of disc margins, cotton-wool spots, and flame shaped hemorrhages may be seen. Funduscopic findings are usually bilateral. Diagnosis Mild TBI typically causes temporary neurologic impairment without evidence of structural damage on conventional neuro imaging. In most patients, the physical examination is normal and diagnostic investigation is unnecessary' Severe TBI may present with altered consciousness, seizures, repeated vomiting, or focal neurologic deficits' Postconcussion syndrome describes the persistence of symptoms of mild TBI beyond a typical recovery period of several weeks' Head injury may result in epidural or subdural hematomas presenting with headache and mental status abnormalities' Rapid neurologic decline with ipsilateral pupillary dilatation and brain herniation may occur. Some patients with epidural hematoma exhibit loss of consciousness followed by a brief "lucid interval" before subsequent precipitous decline. The tempo of clinical deterioration of subdural hematoma is slower, over days to weeks. It is often impossible to clinically distinguish between epi- dural and subdural hematoma. 290

Neurology DOil'T BE TRICKED . Subdural hematomas may occur in the absence of significant trauma, particularly among older persons and those taking anticoagulant drugs. Testing STUDY TABLE: lndications for Head CT in Mild TBI Age >60 years with loss of consciousness or age >65 years with no loss of consciousness Vomiting Severe headache Posttraumatic seizure Drug or alcohol intoxication Persistent drowsiness or short-term memory deficit "Dangerous" mechanisms of injury (fall from height >3 feet or 5 steps, ejection from a vehicle, being struck by a vehicle as a pedestrian) Coagulopathy Treatment Athletes suspected of having a mild TBI should be immediately removed lrom play and should undergo sideline assessment. Return to play may be considered after 1 or 2 days of physical and Epidunl Hematoma: CT scan of an epidural hematoma shows biconvex lens cognitive rest, resolution of symptoms both at rest and with exer- appearance between the skull and outer margin of the dura (arow). tion, and normalization of cognition. Subdural Hematoma: CI scan of a subdural hematoma shows the crescent shape of blood separating the dura from the arachnoid membrane (arows). 291

Neurology Management of postconcussion syndrome is supportive and rehabilitative. NSAIDs and triptans may be useful in treating post- traumatic headache. Tricyclic antidepressants, SSRIs, and SNRIs can also manage posttraumatic headache as well as mood and anxiety disorders. The treatment for epidural hematoma is emergent e\acuation of blood to prevent death. The treatment of subdural hematoma depends on clinical circumstancesi observation is appropriate in stable, asymptomatic patients. Epilepsy Diagnosis Epilepsy is characterized by two or more unprovoked seizures occurring more than 24 hours apart or one unprovoked seizure with a significant ongoing risk for further unprovoked seizures. Focal seizures result from an electrical discharge that originates in a focal region ofthe brain. Focal seizures may be classified as "aware" or "with impaired awareness." Focal seizures may present as "staring episodes." Focal seizures may transform into secondary generalized seizures. Primary generalized seizures are caused by an electrical discharge that involves all areas of the brain simultaneously. The electri cal discharge in secondary generalized seizures is focal in onset but rapidly spreads to involve the entire cerebral cortex. Common epilepsy comorbidities include mood disorders, sleep disorders, metabolic bone disease, and hyperlipidemia. STUDY TABLE: Seizure Classifications Seizure Type Characteristics Focal seizure with Normal consciousness and awareness awareness Single neurologic modality (sensory, motor, ol{actory, visual, gustatory) involving a single region of the body, such as the hand or arm Focal seizure Conscious but unresponsive or staring with impaired awareness Automatism (lip smacking, swallowing, or manipulating objects) Postictal confusion Primary generalized Loss of consciousness or awareness at onset setzure No prodromal or localizing symptoms

STUDY TABLE: Seizure Classifications Seizure Type Characteristics Focal seizure with Normal consciousness and awareness awareness Single neurologic modality (sensory, motor, ol{actory, visual, gustatory) involving a single region of the body, such as the hand or arm Focal seizure Conscious but unresponsive or staring with impaired awareness Automatism (lip smacking, swallowing, or manipulating objects) Postictal confusion Primary generalized Loss of consciousness or awareness at onset setzure No prodromal or localizing symptoms STUDY TABLE: Common Epilepsy Syndromes Temporal lobe Most common adult focal seizure characterized by impaired awareness preceded by an aura. Automatisms may be epilepsy seen. Mesialtemporal sclerosis is a characteristic finding on MRl. Frontal lobe Nocturnal complex seizures that awaken patients from sleep. Often associated with underlying structural pathology epilepsy (e.9., tumor, vascular malformations). ldiopathic (genetic) Any combination of tonic-clonic seizures, absence seizures, and myoclonic seizures. MRI typically normal. EEG may generalized show generalized spike-wave abnormality. epilepsy Myoclonic Most common adult generalized epilepsy characterized by brief, lightning-like jerks of the arms, not associated seizure with loss of consciousness. Age of onset is during teenage years or shortly thereafter and associated with sleep deprivation, alcohol use, visual stimuli, and stress ("college seizures"). Convulsive status Characterized by continuous seizure for >5 minutes. Most common cause is low AED level; associated with a epilepticus mortality rate of up to 20%. Several medical conditions may provoke seizures, including metabolic disturbances, drug intoxication or withdrawal, or infec tion. Single seizures that are provoked should be addressed by correcting the underlying condition or removing the offending agent; single seizures usually do not require treatment with an antiepileptic drug.

Several medical conditions may provoke seizures, including metabolic disturbances, drug intoxication or withdrawal, or infec tion. Single seizures that are provoked should be addressed by correcting the underlying condition or removing the offending agent; single seizures usually do not require treatment with an antiepileptic drug. DON'T BE IRICKED . Diagnostic evaluation may not be needed for a provoked seizure if the patient has normal flndings on neurologic examination. 292

Neurology Psychogenic nonepileptic spells (PNES) are a type of conversion disorder. Some of the characteristic features include: . forced eye closure o long duration . hypermotor activity that starts and stops . asynchronous, asymmetric flailing of extremities Testing Initial evaluation for a first unprovoked seizure: . EEG (although a normal EEG does not rule out a seizure) . CBC, electrolyte and glucose levels, and toxicologr screen . brain MRI (or head CT in an emergency) o CSF examination if the patient has fever, has prolonged altered mental status after the seizure, is immunosuppressed, or has a severe headache Inpatient video EEG monitoring is required to make the diagnosis of PNES because of the difficulSr in distinguishing between PNES and epileptic seizures. PNES is strongly associated with PTSD in military veterans. If the patient is not returning toward baseline mental status by 15 minutes after a seizure, obtain continuous EEG monitoring to rule out nonconvulsive status epilepticus. DOil'T BE TRICKED . Syncope may be associated with brief loss of consciousness and occasional tonic clonic jerking, but recovery is quick and complete, unlike a seizure. . Do not choose absence seizure in an adult. Treatment Most adults do not require antiepileptic drug therapy (AED) after a Iirst unprovoked seizure. Start anticonvulsant therapy after >2 unprovoked seizures. Start AEDs after a single high risk unprovoked seizure characterized by focal findings on neuroimag ing, focal findings on EEG, or significant risk factors for epilepsy, such as severe head trauma. Although serum drug level monitoring may be helpful, targeting a clinical response is more important than achieving a specific serum level. Adding new medications that alter the metabolism of anticonvulsants may result in a loss of seDure control.

Treatment Most adults do not require antiepileptic drug therapy (AED) after a Iirst unprovoked seizure. Start anticonvulsant therapy after >2 unprovoked seizures. Start AEDs after a single high risk unprovoked seizure characterized by focal findings on neuroimag ing, focal findings on EEG, or significant risk factors for epilepsy, such as severe head trauma. Although serum drug level monitoring may be helpful, targeting a clinical response is more important than achieving a specific serum level. Adding new medications that alter the metabolism of anticonvulsants may result in a loss of seDure control. STUDY TABLE: Treatment of Epilepsy Population First-Line Agent Considerations Patients with focal seizures Lamotrigine lncludes treatment of secondary generalized tonic-clonic seizures Levetiracetam Oxcarbazepine Patients with generalized seizures Lamotrigine (may worsen myoclonic Seizure type may be worsened by seizures) gabapentin, pregabalin, carbamazepine, and oxcarbazepine Levetiracetam Valproate Women of childbearing age Lamotrigine Avoid carbamazepine, phenobarbital, phenytoin, topiramate, and valproate Levetiracetam Older patients Gabapentin Higher risk for hyponatremia with carbamazepine, especially with concomitant Lamotrigine diuretics Levetiracetam 293

Neurology AED important adverse effects: . carbamazepine: interactions with other hepatically metabolized drugs and increased risk for osteoporosis and hypercholesterolemia . carbamazepine and oxcarbazepine: hyponatremia, pancytopenia . valproic acid: weight gain, hypercholesterolemia, PCOS, teratogeniciry hepatotoxicity . topiramate and zonisamide: increased risk of kidney stones . all AEDs: drug hypersensitivity syndrome, SJS, and suicidal ideation Patients not responding to either their first or second AED (in sequence or combination) are candidates for epilepsy surgery. The most common surgical procedure is resection of mesial temporal lobe sclerotic lesions associated with focal seizures. AEDs may be effectively withdrawn in many patients who have been seizure-free for 2 to 5 years. Convulsive status epilepticus is defined as a generalized tonic-clonic seizure lasting more than 5 minutes or two seizures within 5 minutes without return to baseline between seizures. Thiamine and glucose are administered if alcohol abuse is suspected or the cause of the status epilepticus is unknown. Emergent head imaging should be obtained in the absence of a known underly- ing cause but should not delay treatment. The most common cause of convulsive status epilepticus is a low AED blood level. First line treatment is IV lorazepam, IV diaz epam, or IM midazolam. Benzodiazepines should be followed by an IV AED to avoid seizure recurrence. Fosphenytoin is pre ferred over phenytoin in patients not already taking an AED. All patients with convulsive status epilepticus who stop seizing but do not return to baseline within 30 minutes should have continuous EEG monitoring for nonconvulsive seizures. For patients with PNES, referral to appropriate psychological resources provides the best chance of a good outcome. DO['T BE TRICKED . Primary prophylaxis with AEDs is not indicated for a new stroke or tumor. . Patients with juvenile myoclonic epilepsy require lifelong medication. . Carbamazepine, oxcarbazepine, phenytoin, and topiramate inactivate many forms of hormonal contraception.

For patients with PNES, referral to appropriate psychological resources provides the best chance of a good outcome. DO['T BE TRICKED . Primary prophylaxis with AEDs is not indicated for a new stroke or tumor. . Patients with juvenile myoclonic epilepsy require lifelong medication. . Carbamazepine, oxcarbazepine, phenytoin, and topiramate inactivate many forms of hormonal contraception. TEST YOURSELF A 33-year old woman has "spells" during which she is conscious but unresponsive and unaware of her environment. She has repetitive hand movements that last approximately 1 minute followed by several minutes of mild confusion. ANSWER: For diagnosis, choose temporal lobe seizure. For management, select lamotrigine, levetiracetam, or oxcarbazepine. lschemic Stroke and Transient lschemic Attack Prevention Risk factor modification is mandatory for all patients (diabetes, hypertension, hyperlipidemia, tobacco use) Begin warfarin or a DOAC in most patients with nonvalvular AF. DOil'T BE TRICKED . Warfarin is the only approved drug for valvular AF 294

Neurology t Diagnosis : Stroke is a sudden focal neurologic deficit caused by ischemia (g5%) or hemorrhage (t5,2,). Ischemic stroke may be further char I acterized by the causative mechanism (large artery atherosclerosis, cardioembolic stroke, small vessel disease. embolic stroke of undetermined source). Hemorrhagic stroke is classified as either subarachnoid or intracerebral. t I TIA is a transient focal neurologic deficit resulting from ischemia rather than infarction. TIA is defined by the absence of infarc_ i tion on neuroimaging, independent of symptom duration. t All patients with stroke or TIA require: i L- I o emergent head CT without contrast (to rule out intracranial hemorrhage) t r ECG and telemetry (to rule out AF) , L o duplex ultrasonography of internal carotid artery; MRA and CTA are appropriate confirmatory tests I I . echocardiography (to rule out LV or valvular thrombus) L I I L Patients with TIA have an elevated risk for subsequent stroke, particularly in the next 48 hours. The decision to hospitalize I patients is based on risk stratification. I I L L DON'T BE TRIGKED I r Routine evaluation for thrombophilia is not indicated for patients with TIA or stroke. I o Patients with suspected cardioembolic stroke should undergo prolonged cardiac rhythm monitoring to rule out AF L . Consider vertebrobasilar stroke in older adults with persistent, acute onset vertigo. t . The routine use ofTEE to evaluate the source ofstroke is not indicated. L Treatment ; I Select intubation and mechanical ventilation for patients with a decreased level of consciousness. Administer rtPA to all patients with ischemic stroke within 3 hours of stroke onset (if unknown onset, then within 3 hours of the last time the patient was seen to be well). rtPA may rarely be administered up to 4.5 hours after onset in selected patients who do not possess any of the following exclusionary criteria:

Administer rtPA to all patients with ischemic stroke within 3 hours of stroke onset (if unknown onset, then within 3 hours of the last time the patient was seen to be well). rtPA may rarely be administered up to 4.5 hours after onset in selected patients who do not possess any of the following exclusionary criteria: . age >80 years o severe stroke . diabetes mellitus with a previous infarct r anticoagulant use Exclusionary criteria for thrombolysis in general include any increased risk for bleeding, diagnosis of ICH, recent head trauma, stroke (before current stroke), cranial surgery or SBP >185 mm Hg and DBP >110 mm Hg despite treatment. In patients with suspicion of a thrombolysis-induced intracranial hemorrhage manifesting as neurologic deterioration, stop ongoing infusion of rtPA and evaluate with another CT. Additional therapy in patients with stroke o acetaminophen for temperature >38.0 "C (100.4 "F) . normal saline to maintain euvolemia . aspirin (unless thrombo$sis is planned) . DVT prophylaxis initiation within 48 hours 295

Neurology Do not begin antihypertensive treatment within the first 48 hours unless: . SBP is >220 mm Hg, DBP is >120 mm Hg o ACS, aortic dissection, or end-organ damage is present If the patient is eligible for thrombolysis, BP must be lowered to <180 mm Hg systolic and <105 mm Hg diastolic and maintained below these levels for at least 24 hours after therapy. Preferred antihypertensive agents include IV labetalol and IV nicardipine. A swallowing assessment is recommended for patients with stroke before they start to eat, drink, or take oral medications. Early stroke rehabilitation improves clinical outcomes. ETUDY TABLE: Secondary Prevention of Stroke lntervention lndication Antiplatelet ln the acute setting, begin aspirin immediately or within 24 hours after giving thrombolytic agents. therapy ln the chronic setting (>90 days after stroke), aspirin is reasonable monotherapy; aspirin plus dipyridamole is slightly superior to aspirin alone. Clopidogrel is equivalent to aspirin and dipyridamole. Anticoagulation After 48 hours, treat cardioembolic causes of stroke and TIA with warfarin (valvular atrialfibrillation)or a DOAC therapy (nonvalvular atrial fibrillation). Revascularization Early endarterectomy or stenting is recommended after a nondisabling stroke or TIA if ipsilateral carotid stenosis is>70/o, provided the patient is likely to live 5 years. Statins High-intensity statin therapy is started for all patients regardless of cholesterol level. Hypertension Maintain BP <1 30/80 mm Hg after recovery from the acute event. Glucose lntensive glucose control (80-130 mg/dL) does not improve stroke outcome compared with standard therapy (80-179 mg/dL). Depression Prevalent in the acute and chronic setting; identification and treatment improve recovery Device closure of To prevent second stroke in patients with PFO and no other cause of stroke PFO plus aspirin

ETUDY TABLE: Secondary Prevention of Stroke lntervention lndication Antiplatelet ln the acute setting, begin aspirin immediately or within 24 hours after giving thrombolytic agents. therapy ln the chronic setting (>90 days after stroke), aspirin is reasonable monotherapy; aspirin plus dipyridamole is slightly superior to aspirin alone. Clopidogrel is equivalent to aspirin and dipyridamole. Anticoagulation After 48 hours, treat cardioembolic causes of stroke and TIA with warfarin (valvular atrialfibrillation)or a DOAC therapy (nonvalvular atrial fibrillation). Revascularization Early endarterectomy or stenting is recommended after a nondisabling stroke or TIA if ipsilateral carotid stenosis is>70/o, provided the patient is likely to live 5 years. Statins High-intensity statin therapy is started for all patients regardless of cholesterol level. Hypertension Maintain BP <1 30/80 mm Hg after recovery from the acute event. Glucose lntensive glucose control (80-130 mg/dL) does not improve stroke outcome compared with standard therapy (80-179 mg/dL). Depression Prevalent in the acute and chronic setting; identification and treatment improve recovery Device closure of To prevent second stroke in patients with PFO and no other cause of stroke PFO plus aspirin DON'T BE TRICKED o If the patient is unable to report the time of onset, and no other person witnessed the onset, rtPA treatment is contraindicated. . Do not select heparin for most patients with ischemic stroke. . Do not select anticonvulsant medications after stroke unless the patient has had a seizure. . Do not select carotid endarterectomy for 100% carotid artery stenosis

DON'T BE TRICKED o If the patient is unable to report the time of onset, and no other person witnessed the onset, rtPA treatment is contraindicated. . Do not select heparin for most patients with ischemic stroke. . Do not select anticonvulsant medications after stroke unless the patient has had a seizure. . Do not select carotid endarterectomy for 100% carotid artery stenosis Subarachnoid Hemorrhage Prevention Patients with small (<7 mm posterior or <12 mm anterior circulation) unruptured aneu rysms may be monitored with MRI; those with larger aneurysms are candidates for surgery. lsrhemic Stroke: CT scan of the brain without c0ntrast shows a large wedge-shaped hypodensity with mass effect 24 hours after symptom onset. Diagnosis Most patients present to the emergency department with sudden onset of the ,,worst headache of my life,, or ,,thunderclap headache." However, up to,l0,/, of patients with SAH experience a,,sentinel hemorrhage.'characterized as severe headache during the previous 2 to 3 weeks. Focal neurologic deficits may occur from aneurysms that compress a cranial nerve (third nerve palsy and dilated pupil), bleed into brain parenchyma, or cause focal ischemia because of vasospasm. 296

Neurology the oral direct Xa inhibitor and treat with either 4f-PCC or andexanet alfa. Idarucizumab should be given for dabigatran reversal. Mannitol, barbiturate coma, and hyperventilation may be used to reduce intracranial pressure. If SBP is >150 mm Hg, use IV medications to achieve target (140 mm Hg). Elevated intracranial pressure can temporarily be reduced with mannitol or hyper- tonic saline. DOil'T BETRICKED . Do not select nitroglycerin or nitroprusside to lower BP because they can increase intracerebral pressure. o Platelet transfusions or glucocorticoids are not recommended for intracranial hemorrhage' Dementia Prevention Control of vascular risk factors (diabetes, high blood pressure, lipids), dietary modifications, and exercise are the most impor- tant interventions to prevent cognitive impairment. Diagnosis Cognitive impairment is the loss of cognitive function in at least one major domain: memory language, executive function, visuospatial function, or behavior. When the cognitive impairment is progressive, involves more than one cognitive domain, and results in a loss of independent function, it is considered a dementia syndrome. Mild cognitive impairment is a decline in cognitive abilities with relative preservation of day-to day function and evidence of cognitive impairment on cognitive testing. DOil'T BETRICKED . No medications or supplements prevent progression of mild cognitive impairment to dementia. Alzheimer disease is the most prevalent neurodegenerative dementia, accounting for 60'7, to 80% of cases. Characteristic findings of Alzheimer disease are memory loss; getting lost; difficulty finding words; and difficulty with dressing, grooming, and doing housework. Bedside cognitive tests are adequately sensitive and specific for detecting cognitive impairment; these include the Mini-Cog, Memory Impairment Screen, General Practitioner Assessment of Cognition, and Montreal Cognitive Assessment. Testing For a slowly progressive dementia syndrome in an older patient, the minimal evaluation includes the following elements

Bedside cognitive tests are adequately sensitive and specific for detecting cognitive impairment; these include the Mini-Cog, Memory Impairment Screen, General Practitioner Assessment of Cognition, and Montreal Cognitive Assessment. Testing For a slowly progressive dementia syndrome in an older patient, the minimal evaluation includes the following elements . general neurologic examination, including a cognitive screening evaluation r evaluation for depression, sleep disorders, alcohol use, and family history of dementia . a detailed medication review . serum chemistries, including plasma glucose level and hepatic function o complete blood count o determination of vitamin B,, and thyroid-stimulating hormone levels . basic neuroimaging (MRI or CT without contrast) 298

Neurology RPR testing is recommended to evaluate for syphilis in high risk populations. gTUDY ?ABtEl Dementia Syndromes Dementia Type Clinical Features Alzheimer lmpaired memory or forgetfulness as prominent early symptom disease Minimal motor symptoms until disease reaches moderate severity (i.e., at the point of significant impairment of activities of daily living) Rare late-onset visual hallucinations Delusions uncommon at early stages of disease (e.g., at the point of relatively preserved activities of daily living) MRI shows decreased volume of the hippocampi Dementia with Severe autonomic symptoms (such as orthostatic hypotension, constipation, and erectile dysfunction) Lewy bodies Sleep disorders (such as REM sleep behavior disorder and daytime hypersomnia) Severe fluctuations in mental status or seizure-like activity Early visual hallucinations Syncopal events or unexplained episodes of severe alteration in mentation Repeated falls Severe sensitivity to medications that act on the CNS Frontotemporal Poor insight into impairment or denial of impairment, especially when cognitive impairment is mild dementia New-onset obsessive-compulsive behaviors Gluttonous eating behaviors or adoption of bizarre food restrictions or fads Motor neuron disease (such as muscle wasting) Vascu la Pronounced gait disorder and repeated falls, especially early in the disease course (at mild dementia stage) cognitive Emotional incontinence (explosive crying, laughter) mpa rm nt Pronounced apathy Severe cognitive slowing Normal pressure Pronounced gait disorder and repeated falls, especially early in the disease course (at mild dementia stage) hydrocephalus Minimal cognitive impairment, compared with much greater gait disorder and non-memory-predominant pattern Pronounced bladder incontinence proximate to onset of gait changes Ventriculomegaly on MRI must be present to diagnose normal pressure hydrocephalus

Syncopal events or unexplained episodes of severe alteration in mentation Repeated falls Severe sensitivity to medications that act on the CNS Frontotemporal Poor insight into impairment or denial of impairment, especially when cognitive impairment is mild dementia New-onset obsessive-compulsive behaviors Gluttonous eating behaviors or adoption of bizarre food restrictions or fads Motor neuron disease (such as muscle wasting) Vascu la Pronounced gait disorder and repeated falls, especially early in the disease course (at mild dementia stage) cognitive Emotional incontinence (explosive crying, laughter) mpa rm nt Pronounced apathy Severe cognitive slowing Normal pressure Pronounced gait disorder and repeated falls, especially early in the disease course (at mild dementia stage) hydrocephalus Minimal cognitive impairment, compared with much greater gait disorder and non-memory-predominant pattern Pronounced bladder incontinence proximate to onset of gait changes Ventriculomegaly on MRI must be present to diagnose normal pressure hydrocephalus DO]II,T BE TRICKED . Do not order apolipoprotein E genotyping in patients with suspected Alzheimer disease. . Do not order CSF tests or dopamine transporter single photon emission CT and PET scans. o When dementia occurs well after the motor symptoms of Parkinson disease, it is considered Parkinson disease dementia; when dementia and motor symptoms develop within I to 2 years of each other, it is classified as dementia with Lewy bodies. Treatment Select acetylcholinesterase inhibitors (donepezil, rivastigmine, and galantamine) to slow intellectual decline in patients with mild to moderate Alzheimer disease. Donepezil and rivastigmine are approved for moderate to severe Alzheimer disease. Acetylcholinesterase inhibitors may have prominent cholinergic adverse effects, including bradycardia, diarrhea, heart block, nausea and vomiting, and s,.ncope. Memantine delays cognitive decline in patients with moderate to advanced Alzheimer disease. Also choose:

Treatment Select acetylcholinesterase inhibitors (donepezil, rivastigmine, and galantamine) to slow intellectual decline in patients with mild to moderate Alzheimer disease. Donepezil and rivastigmine are approved for moderate to severe Alzheimer disease. Acetylcholinesterase inhibitors may have prominent cholinergic adverse effects, including bradycardia, diarrhea, heart block, nausea and vomiting, and s,.ncope. Memantine delays cognitive decline in patients with moderate to advanced Alzheimer disease. Also choose: . acetylcholinesterase inhibitors for dementia with Lewy bodies . risk factor modification and acetylcholinesterase inhibitors for vascular cognitive impairment o large-volume LP with symptom assessment before and after to evaluate response to shunting for normal pressure hydrocephalus 299

Neurology Nonpharmacologic interventions are first-line treatment fbr behavioral symptoms. Atypical antipsychotics can treat agitation, aggression, delusions, and hallucinations but have a black box warning for increased mortality; they are used when patient safety is jeopardized. Treat depression with SSRIs. DON'T BE TRICKED . First-generation antipsychotic agents are strongly contraindicated in patients with dementia with Lewy bodies, because they may worsen symptoms and may result in neuroleptic malignant syndrome. . No drug is beneficial for frontotemporal dementia; SSRIs may help compulsive behaviors. o Benzodiazepines are not recommended to treat behavioral symptoms in patients with dementia. . Do not select tricyclic antidepressants in patients with dementia, because they may exacerbate confusion. Delirium Diagnosis Diagnosis of delirium is based on the Confusion Assessment Method diagnostic algorithm, which provides greater accuracy than laboratory tests or imaging studies. Diagnose delirium if the first two points and either point 3 or point 4 are present: 1. Acute onset and fluctuating course 2. Inattention 3. Disorganized thinking 4. Altered level ofconsciousness Look fbr triggers of delirium, particularly alcohol, medications known to cause delirium, and polypharmacy. Pay particular attention to anticholinergics, anticonvulsants, antidepressants, antihistamines, antipsychotics, barbiturates, opioid analgesics, sedative-hypnotics, fluoroquinolones, and antiparkinsonian agents. Also consider fluid and electrolyte abnormalities, uncon trolled pain, hypoxemia, anemia, infections, immobility, visual and hearing impairment, sleep cycle disruption, and catheters and other "tethers" (ECG leads, IV lines, and restraints). DON'T BE TRICKED . Brain imaging is usually not helpful in diagnosing delirium unless a history of falls or evidence of focal neurologic impairment is present. Treatment Treat or eliminate precipitating factors. Achieve behavior control with environmental or social measures rather than pharma cologic or physical restraints. In severe cases and especially when safety is a concern, newer generation antipsychotic agents may help control behavior.

DON'T BE TRICKED . Brain imaging is usually not helpful in diagnosing delirium unless a history of falls or evidence of focal neurologic impairment is present. Treatment Treat or eliminate precipitating factors. Achieve behavior control with environmental or social measures rather than pharma cologic or physical restraints. In severe cases and especially when safety is a concern, newer generation antipsychotic agents may help control behavior. Al1 atypical antipsychotics (aripiprazole, clozapine, olanzapine, quetiapine, risperidone, and ziprasidone) and older antipsy chotics (haloperidol) are associated with an increased risk for mortality in patients with dementia and psychosis or behavioral disturbances. DOil'T BE TRICKED . Always select behavioral interventions flrst instead of using restraints or drugs. . Benzodiazepines may worsen delirium and are not recommended, except in the management of alcohol withdrawal. 300

Neurology Adverse eflects of dopamine agonists include sedation and an increase in compulsive behaviors such as gambling, shopping, and hypersexuality. Increasing the dose or frequency of levodopa or using a sustained release formulation is indicated to treat the symptoms of wearing off. Deep brain stimulation is indicated for patients who have sustained motor benefit from levodopa but are limited by disabling medication related adverse eff'ects refractory to medical management. DON'T BE TRICKED . Begin drug therapy for Parkinson disease when symptoms begin to interfere with function. . Failure to respond to dopamine therapy is the most important red flag indicating atypical parkinsonism. TESTYOURSELF A 68 year old woman has a 2 year history of falls and imbalance. She has a staring facial expression and impaired upward gaze. ANSWER: For diagnosis, choose supranuclear palsy. Hyperkinetic Movement Disorders Diagnosis Hyperkinetic movement disorders include

DON'T BE TRICKED . Begin drug therapy for Parkinson disease when symptoms begin to interfere with function. . Failure to respond to dopamine therapy is the most important red flag indicating atypical parkinsonism. TESTYOURSELF A 68 year old woman has a 2 year history of falls and imbalance. She has a staring facial expression and impaired upward gaze. ANSWER: For diagnosis, choose supranuclear palsy. Hyperkinetic Movement Disorders Diagnosis Hyperkinetic movement disorders include . tremors (rhythmic oscillation) . dystonia (sustained contraction of opposing muscles, resulting in repetitive movements or abnormal posture) . myoclonus (nonrhythmic jerking movements of the extremities) o tics (stereotyped, brief, rapid movements) r chorea (random, nonrepetitive, flowing dance like movements) STUDY TABLE: Hyperkinetic Movement Disorders ] Condition Key Manifestations Treatment Essentialtremor Typically slowly progressive or stable over time Propranolol, primidone, or topiramate Bilateral postural or kinetic tremor; improves with alcohol Family history positive in 50% H u ntington Most common neurodegenerative cause of generalized Symptomatic treatment with valbenazine, i d isease chorea tetrabenazine, a nd deutetrabenazine Also progressive dementia and psychiatric manifestations Autosomal dominant Drug-induced Tardive dyskinesia associated with choreiform and dystonic Stop the offending drug dystonia craniofacial movements Valbenazine, deutetrabenazine, tetrabenazine, May be caused by neuroleptic, antiemetic, and antidepressant amantadine, and clonazepam medications Cervical dystonia Cervical muscle contractions resulting in abnormal posture of Anticholinergic agents, benzod iazepines, (torticollis) the head and neck baclofen, levodopa, injection with botulinum toxi n To U rette Childhood onset, multiple complex motortics, and presence Reassurance or cognitive behavioral therapy syndrome of vocaltics (e.g., echolalia) Myoclonu Rapid, shock-like, jerky movements of isolated body parts Treat the underlying metabolic disorder Underlying metabolic disorder, serotonin syndrome, postanoxic, Creutzfeldt-Jakob disease, corticobasal degeneration

. tremors (rhythmic oscillation) . dystonia (sustained contraction of opposing muscles, resulting in repetitive movements or abnormal posture) . myoclonus (nonrhythmic jerking movements of the extremities) o tics (stereotyped, brief, rapid movements) r chorea (random, nonrepetitive, flowing dance like movements) STUDY TABLE: Hyperkinetic Movement Disorders ] Condition Key Manifestations Treatment Essentialtremor Typically slowly progressive or stable over time Propranolol, primidone, or topiramate Bilateral postural or kinetic tremor; improves with alcohol Family history positive in 50% H u ntington Most common neurodegenerative cause of generalized Symptomatic treatment with valbenazine, i d isease chorea tetrabenazine, a nd deutetrabenazine Also progressive dementia and psychiatric manifestations Autosomal dominant Drug-induced Tardive dyskinesia associated with choreiform and dystonic Stop the offending drug dystonia craniofacial movements Valbenazine, deutetrabenazine, tetrabenazine, May be caused by neuroleptic, antiemetic, and antidepressant amantadine, and clonazepam medications Cervical dystonia Cervical muscle contractions resulting in abnormal posture of Anticholinergic agents, benzod iazepines, (torticollis) the head and neck baclofen, levodopa, injection with botulinum toxi n To U rette Childhood onset, multiple complex motortics, and presence Reassurance or cognitive behavioral therapy syndrome of vocaltics (e.g., echolalia) Myoclonu Rapid, shock-like, jerky movements of isolated body parts Treat the underlying metabolic disorder Underlying metabolic disorder, serotonin syndrome, postanoxic, Creutzfeldt-Jakob disease, corticobasal degeneration 302

Neurology DOil'T BE TRICKED . Rigidity and resting tremor are not features of essential tremor. . Screen patients <40 years with "essential tremor" or dystonia for Wilson disease with serum ceruloplasmin and 24 hour urine copper measurements. Multiple Sclerosis Diagnosis MS is characterized by episodes of dysfunction resulting from demyelinating lesions (plaques) in different areas of the CNS (brain; brainstem, including optic nerve; or spinal cord) at different times. Clinical course follows one of three basic patterns: . Relapsing-remitting: Clinical episodes of neurologic dysfunction, typically lasting weeks before improving, that may lead to the accumulation of disabiliSr. . Secondary progressive disease: Disappearance of evidence of clinical relapses in the relapsing remitting form and by progressive disability. r Primary progressive disease: Progressive disability accumulation fiom the time of disease onset. Patients who do not meet the full diagnostic criteria for MS after a first event have a clinically isolated syndrome. The 10 year risk for MS associated with a clinically isolated syndrome and lesions on brain MRI is 90%. STUDY TABLE: Common Symptoms/Findings Associated With MS Finding orAnatomical Description lnvolvement Optic neuritis Subacute visual deficit in one eye along with pain with eye movement Afferent pupillary defect Paradoxical dilation of the pupil when light is rapidly shifted from the unaffected to the affected eye Papillitis lnflammatory changes in the retina causing a flared appearance of the optic disc Myelitis Focal inflammation within the spinal cord manifesting as sensory, autonomic, or motor symptoms below the affected spinal level Lhermitte sign A shock-like sensation radiating down the spine or limbs induced by neck flexion Bladder Urinary frequency, urgency, or retention Cerebellum Ataxia and vertigo Brainstem (internuclear lnability to adduct one eye and nystagmus in the abducting eye ophthalmoplegia) Uhthoff phenomenon Transient worsening of baseline neurologic symptoms with elevations of body temperature

Bladder Urinary frequency, urgency, or retention Cerebellum Ataxia and vertigo Brainstem (internuclear lnability to adduct one eye and nystagmus in the abducting eye ophthalmoplegia) Uhthoff phenomenon Transient worsening of baseline neurologic symptoms with elevations of body temperature Diagnosis requires evidence of CNS demyelination disseminated in both space and time as demonstrated through a combination of documented clinical relapses, signs on physical examination, and the distribution of lesions on an M RI. CSF may contain oligoclonal IgG bands or an elevated IgG index. CSF analysis is not necessary but may be helpful if the diagnosis remains questionable. DO]II,T BE TRICKED . MS generally is not associated with cortical syndromes, such as aphasia and neglect. . Migraine, microvascular ischemic disease, and head trauma may also cause white matter lesions on MRI. 303

Neurology Treatment Treat spinal cord compression caused by metastatic disease emergently with high-dose glucocorticoids and subsequent surgical decompression followed by radiation for most tumor types. Spinal cord infarction has no treatment. For treatment of demyelinating diseases, see Multiple Sclerosis. Treat vitamin B, and copper deficiencies with supplementation. Direct inflammatory and infectious myelopathy treatment at the underlying disorder. Treat transverse myelitis with IV methylprednisolone. DON'T BE TRICKED . Spinal cord compression caused by leukemia, lymphoma, myeloma, and germ cell tumors may be treated urgently with radiation therapy rather than surgery. . Do not use glucocorticoids to treat spinal cord compression caused by infection or hematoma. Amyotrophic Latera I Sclerosis Diagnosis and Testing The defining characteristic is the combination of upper motoneuron signs (e.g., hyperreflexia, spasticity, and extensor plantar response) coexistent with lower motoneuron findings (e.g., atrophy and fasciculation). Sensory deficits are characteristically absent. Muscle weakness in patients with ALS usually begins distally and asymmetrically, although 20% of patients have bulbar-onset ALS with difficulty speaking and swallowing. Alternative diagnoses also must be excluded by brain and cervical spinal imaging and Iaboratory testing; cervical cord compression, vitamin B,, and copper deflciencies, Lyme disease, hyperparathyroidism, and thyrotoxicosis must be excluded. Spirometry and ovemight pulse oximetry studies can establish the presence of respiratory insufficiency. Patients with bulbar signs or symptoms require evaluation of swallowing function. DOil'T BETRICKED . Findings not typical for ALS include predominant sensory symptoms or pain, early cognitive impairment, and ocular muscle weakness. . Fasciculations in the absence of associated muscle atrophy or weakness are not caused by ALS. . Weakness in the absence of fasciculations is not a result of ALS. Treatment Riluzole and edaravone may modestly increase survival. Begin noninvasive ventilatory support for patients with respiratory insufficiency. Placement of a percutaneous endoscopic gastrostomy tube is indicated when weight loss or swallowing difficulty occurs. 306

Neurology Myasthenia Gravis Diagnosis MG is an autoimmune disease caused by antibodies directed against the acetylcholine receptor, which results in impaired neuromuscular transmission. Characteristic findings of MG include: r ptosis or diplopia (first manifestation in most patients) . muscle weakness, including dysphagia and dyspnea o positive anti acetylcholine receptor antibody titer (found in 90%, of patients; negative titer does not rule out MG) . normal deep tendon reflexes and sensation r decremental response to repetitive stimulation on EMG Myasthenic crisis, which may include rapidly progressive respiratory failure, may occur as part of the natural history of myas thenia or be triggered by infection, surgery or medications. Look for aminoglycosides, quinolones, magnesium, B blockers, or calcium channel blockers as precipitants of myasthenic crisis. Include botulism and Lambert Eaton myasthenic syndrome in the differential diagnosis. Botulism starts with cranial nerve involvement, including diplopia, dysphagia, and sluggish or nonreactive pupils, whereas the pupils are normal in MG. Lambert-Eaton myasthenic syndrome involves progressive proximal weakness and diminished tendon reflexes that transiently improve with repetitive movement of affected muscles. Diagnosis is confirmed by detection of serum anti voltage gated cal cium channel antibodies and the EMG finding of facilitation of motor response to rapid repetitive stimulation. Most patients with this syndrome have an undetected malignancy, typically SCLC. Testing Single-fiber EMG can establish the diagnosis. Look for elevated serum TSH levels because of the association of MG with autoim mune thyroid disorders. Perform CT of the chest to detect thymoma. Treatment Pyridostigmine is the initial therapy. Thymectomy is indicated if a thymoma is found on imaging; in other patients with active disease who are <65 years and within 3 years of diagnosis, it can be offered as an option to (potentially) avoid or minimize immunotherapy. Myasthenic crisis and refractory disease should be treated with plasmapheresis or IV immune globulin. DON'T BE TRICKED . Pyridostigmine monotherapy should be avoided in patients with myasthenic crisis because the drug increases respiratory secretions. I

Treatment Pyridostigmine is the initial therapy. Thymectomy is indicated if a thymoma is found on imaging; in other patients with active disease who are <65 years and within 3 years of diagnosis, it can be offered as an option to (potentially) avoid or minimize immunotherapy. Myasthenic crisis and refractory disease should be treated with plasmapheresis or IV immune globulin. DON'T BE TRICKED . Pyridostigmine monotherapy should be avoided in patients with myasthenic crisis because the drug increases respiratory secretions. I Peripheral Neuropathy Diagnosis Patients with neuropathy may present with pain, paresthesias, r.neakness, or autonomic dysfunction. Neuropathies may be clas sified by: o distribution of sensorimotor deficits (symmetric vs asymmetric, distal vs proximal, focal vs generalized) o patholory (demyelinating vs axonal) 307

Neurology . size of nerve fibers involved (large vs small fibers) . family history o autonomic involvement Mononeuropathies, isolated disorders affecting a single peripheral nerve, are most frequently caused by nerve entrapment or compression (carpal tunnel syndrome). Mononeuropathy multiplex involves several noncontiguous peripheral nerves, either simultaneously or sequentially. It is often the result of vasculitis or a systemic disease. Polyneuropathy refers to a diffuse, generalized, and usually symmetric peripheral neuropathy. Polyneuropathy is often a man- ifestation of systemic disease (e.g., diabetes, vitamin B,2 deflciency) or exposure to a toxin (e.g., alcohol) or medication (e.g., chemotherapy). EMG and nerve conduction velocity may be helpful in characterizing the type (axonal or demyelinating), severity, and distribu- tion of the disease. Other routine tests include vitamin B,, level, SPEB UPEP, ESR, hemoglobin A,., and fasting blood glucose level.

Polyneuropathy refers to a diffuse, generalized, and usually symmetric peripheral neuropathy. Polyneuropathy is often a man- ifestation of systemic disease (e.g., diabetes, vitamin B,2 deflciency) or exposure to a toxin (e.g., alcohol) or medication (e.g., chemotherapy). EMG and nerve conduction velocity may be helpful in characterizing the type (axonal or demyelinating), severity, and distribu- tion of the disease. Other routine tests include vitamin B,, level, SPEB UPEP, ESR, hemoglobin A,., and fasting blood glucose level. lf you see this... Think this... And choose this.. lsolated anterolateral thigh numbness Meralgia paresthetica (a compressive Locate and relieve pressure (binding without weakness neuropathy of the lateral femoral clothes, excessive weight) cutaneous nerve) Sensory loss over palmar surface of first Carpal tunnel syndrome (median Wrist splints or glucocorticoid injections three digits and weakness with thumb neuropathy) for mild disease; surgical release if severe abduction and opposition Numbness of the fourth and fifth fingers Cubital tunnel syndrome (ulnar Elbow splinting or elbow pads; surgical and weakness of interosseous muscles neuropathy) release if severe Pain, tingling, and numbness in great toe Tarsal tunnel syndrome (posterior tibial Local glucocorticoid injection; and along medialfoot neuropathy) decompression surgery if severe Upper and lower face weakness Bell palsy Prednisone if within 72 hours of onset Assess for diabetes mellitus, vasculitis, Lyme disease, sarcoidosis, HIV infection, and compressive or infiltrative malignancies only if additional suggestive features are present Multi ple nonconti guous nerve deficits Consider vasculitis (especially if painful), Treat underlyi ng disorder (mononeuritis multiplex) lymphoma, amyloidosis, sarcoidosis, Lyme disease, HlV, leprosy, and diabetes Distal and symmetric (stocking-glove) Axonal polyneuropathies; diabetes and Treat underlying disorder; treat pain and sensory or sensorimotor findings alcohol are the most common causes; dysesthesias sym ptomatically small fiber neuropathy will present with pain only Severe unilateral leg pain, numbness, Diabetic lumbosacral radiculoplexus Treat diabetes proximal weakness, atrophy, and weig ht neuropathy (diabetic amyotrophy) loss

lf you see this... Think this... And choose this.. lsolated anterolateral thigh numbness Meralgia paresthetica (a compressive Locate and relieve pressure (binding without weakness neuropathy of the lateral femoral clothes, excessive weight) cutaneous nerve) Sensory loss over palmar surface of first Carpal tunnel syndrome (median Wrist splints or glucocorticoid injections three digits and weakness with thumb neuropathy) for mild disease; surgical release if severe abduction and opposition Numbness of the fourth and fifth fingers Cubital tunnel syndrome (ulnar Elbow splinting or elbow pads; surgical and weakness of interosseous muscles neuropathy) release if severe Pain, tingling, and numbness in great toe Tarsal tunnel syndrome (posterior tibial Local glucocorticoid injection; and along medialfoot neuropathy) decompression surgery if severe Upper and lower face weakness Bell palsy Prednisone if within 72 hours of onset Assess for diabetes mellitus, vasculitis, Lyme disease, sarcoidosis, HIV infection, and compressive or infiltrative malignancies only if additional suggestive features are present Multi ple nonconti guous nerve deficits Consider vasculitis (especially if painful), Treat underlyi ng disorder (mononeuritis multiplex) lymphoma, amyloidosis, sarcoidosis, Lyme disease, HlV, leprosy, and diabetes Distal and symmetric (stocking-glove) Axonal polyneuropathies; diabetes and Treat underlying disorder; treat pain and sensory or sensorimotor findings alcohol are the most common causes; dysesthesias sym ptomatically small fiber neuropathy will present with pain only Severe unilateral leg pain, numbness, Diabetic lumbosacral radiculoplexus Treat diabetes proximal weakness, atrophy, and weig ht neuropathy (diabetic amyotrophy) loss Acute, ascending, areflexic paralysis and Guillain-Ba116 syndrome Plasma exchange or lV immune globulin paresthesias often preceded by Gl illness (usually Campylobacter infection); CSF shows elevated protein and a normal cell count (albuminocytologic dissociation) Progressive proximal motor and sensory Chronic inflammatory demyelinating Prednisone, plasma exchange, or lV neuropathy that evolves over months. polyneuropathy immune globulin lnitial EMG and CSF findings similar to those of Guillain-Ba116 syndrome Symmetric distal sensory neuropathy in Paraproteinemic neuropathy Treat underlying disorder the setting of MGUS, multiple myeloma, amyloidosis, and cryoglobulinemia

Acute, ascending, areflexic paralysis and Guillain-Ba116 syndrome Plasma exchange or lV immune globulin paresthesias often preceded by Gl illness (usually Campylobacter infection); CSF shows elevated protein and a normal cell count (albuminocytologic dissociation) Progressive proximal motor and sensory Chronic inflammatory demyelinating Prednisone, plasma exchange, or lV neuropathy that evolves over months. polyneuropathy immune globulin lnitial EMG and CSF findings similar to those of Guillain-Ba116 syndrome Symmetric distal sensory neuropathy in Paraproteinemic neuropathy Treat underlying disorder the setting of MGUS, multiple myeloma, amyloidosis, and cryoglobulinemia 308

Neurology Primary Central Nervous System Lymphoma Diagnosis PCNSL is a non Hodgkin lymphoma that commonly presents as a focal supratentorial lesion. PCNSL most commonly affects immunocompromised patients but may occur in patients with intact immune systems. A brain biopsy specimen is usually required to make a diagnosis. Ocular involvement in the vitreous confirmed by vitreal biopsy obviates the need for brain biopsy. Treatment In patients with PCNSL and HIV infection, start ART; for those who have undergone organ transplantation, immunosuppressive therapy should be stopped. PCNSL is sensitive to both whole brain radiation and chemotherapy, but relapses are common. DOil'T BE TRICKED . Empiric glucocorticoids should be avoided before biopsy because they can temporarily suppress lymphoma and prevent or delay a tissue diagnosis. o Resection of PCNSL is not indicated and may worsen patient outcomes. Meningioma Diagnosis Meningiomas are usually benign in histologr and behavior. These tumors are usually discovered incidentally during neuroimaging for unrelated symptoms. Symptomatic patients typically have progressive headache and focal neurologic lesions. CT scan of the head will show a homogeneously enhancing extra-axial mass adherent to the dura and an enhancing dural "tail." Treatment Surgical resection is the treatment of choice for symptomatic meningiomas or enlarging meningiomas. Observation is appro priate for small, asymptomatic meningiomas. DOil'T BE TRIGKED . Chemotherapy has no established role in patients with meningioma. Meningioma: Coronal MRI with contrast shows meningioma with the enhancing dural "tail" inferior to the tumor's dural attachment. Metastatic Brain Tumors Diagnosis Parenchymal metastases usually present as multiple, ring-enhancing, centrally necrotic lesions. These lesions have a proclivity for the junction between the gray and white matter and are typically associated with significant surrounding edema and mass effect. If a metastatic brain tumor is the first indication of malignancy, evaluate the patient for lung cancer, breast cancer, and melanoma. 310

: Neurology : I Lymphoma and leukemia cause leptomeningeal metastases and may present with headache or spinal pain, cranial nerve or l spinal radicular pain, weakness, and mental status changes. Communicating hydrocephalus may be present. Leptomeningeal L tumors are characterized on MRI by a diffuse or patchy enhancement of the surface of the brain and spinal cord or roots. t, DOil'T BE TRICKED i r MRI is required for all patients with systemic cancer and new neurologic findings. o In patients with active, biopsy-proven systemic malignancy and multiple enhancing brain lesions, brain biopsy is not I indicated. : I Treatment I Glucocorticoids are a first-line treatment for parenchymal and leptomeningeal tumors. L Chemotherapy is the initial therapy for patients with leptomeningeal metastases from ! leukemia and lymphoma. Palliative whole brain radiation therapy is indicated for multi i ple parenchymal metastases from a known primary solid tumor. Resection is an option ! for solitary accessible brain metastases and controlled extracranial disease. L DOil'T BETRICKED . Chemotherapy is not indicated for parenchymal brain metastases from most solid tumors. t TEST YOURSEIF A 60-year old woman with a history of adenocarcinoma of the lung has a 3 week history of diplopia, dysphagia, and foot drop. CT scan of the head shows multiple ring enhancing lesions. ANSWER: The probable diagnosis is metastatic cancer. For management, select glucocor ticoids, and arrange for palliative brain radiation. Parietal lobe Metastatit ilodule: Axial postcon- trast T1-weighted MRI shows an enhancing meta- static nodule in the left parietal lobe with surround- ing edema and mass effect.

TEST YOURSEIF A 60-year old woman with a history of adenocarcinoma of the lung has a 3 week history of diplopia, dysphagia, and foot drop. CT scan of the head shows multiple ring enhancing lesions. ANSWER: The probable diagnosis is metastatic cancer. For management, select glucocor ticoids, and arrange for palliative brain radiation. Parietal lobe Metastatit ilodule: Axial postcon- trast T1-weighted MRI shows an enhancing meta- static nodule in the left parietal lobe with surround- ing edema and mass effect. Coma Diagnosis Coma is a state of unarousable unresponsiveness. It may be caused by diffuse insults to the cerebral hemispheres, damage to the reticular activating system, or a combination of hemispheric and brainstem dysfunction. Unilateral hemispheric lesions do not result in coma unless edema and mass effect cause compression of the contralateral hemisphere or the reticular activating system. Coma may be caused by a variety of structural lesions and toxic, metabolic, and infectious causes. Patients in a vegetative state are unaware of self and the environment and show no purposeful responses to stimuli. They con- tinue to have sleep-wake cycles and brainstem function. The three cardinal findings ofbrain death are coma, absence ofbrainstem reflexes, and apnea.

Coma Diagnosis Coma is a state of unarousable unresponsiveness. It may be caused by diffuse insults to the cerebral hemispheres, damage to the reticular activating system, or a combination of hemispheric and brainstem dysfunction. Unilateral hemispheric lesions do not result in coma unless edema and mass effect cause compression of the contralateral hemisphere or the reticular activating system. Coma may be caused by a variety of structural lesions and toxic, metabolic, and infectious causes. Patients in a vegetative state are unaware of self and the environment and show no purposeful responses to stimuli. They con- tinue to have sleep-wake cycles and brainstem function. The three cardinal findings ofbrain death are coma, absence ofbrainstem reflexes, and apnea. STUDY TABLE: Key Points in the Evaluation of Coma Finding Consider Coma without focal signs, fevel or meningism Hypoxia or a metabolic cause, toxic reaction, drug-induced state, infection, or postictal state Coma without focal signs but with meningismus Meningitis, meningoencephalitis, or SAH Coma with focal signs Stroke, hemorrhage, tumol or abscess Ouadriplegic, mute, but preserved vertical eye movements "Locked-in" state caused by a pontine infarction or hemorrhage 311

Neurology Focal findings or any unexplained coma is an indication for emergent imaging of the brain to exclude hemorrhage or mass lesion. CT is the appropriate test in emergency situations. LP is indicated when meningitis or SAH is zuspected but neuroimaging is normal. Emergent EEG can exclude nonconvulsive status epilepticus. DOil'T EE TRICKED . Respiratory drive and motor posturing signs are incompatible with a diagnosis of brain death. Treatment Attend to airway, breathing, and circulation first. All patients with unexplained coma should be urgently treated with thiamine and glucose (unless rapid finger-stick test rules out hypoglycemia). Give naloxone ifan opioid overdose is suspected. 312

L t t I L I I t I I L Oncology , t I I L I t I Breast Cancer I I t Screening and Diagnosis iI See General Internal Medicine, Breast Cancer Prevention and Screening. \t t The USPSTF recommends biennial screening mammography for asymptomatic average-risk women aged S0 to 74 years, with L I individualized screening decisions for patients aged 40 to 49 years. For women >75 years, evidence is insufficient to recommend t L for or against screening. i L i I Testing I See General Internal Medicine, Breast Mass for evaluation of a breast lump. t ; I I Schedule biopsy for suspicious lesions noted during physical examination or screening mammography. If histopathologic studies confirm invasive breast cancer, determine ER/PR and HER2lneu status. L f The two factors that are most prognostic are tumor size and axillary lymph node status. , I Bone scan, CI, or PET scan is recommended for patients with stage III disease or clinically evident metastatic disease. L i I L I DO]I'T BE TRICKED I L . A normal mammogram or ultrasound does not rule out breast cancer. I I . A breast lump should always be biopsied, even if a mammogram is normal. L I r Bone scan, CT, PET scan, and tumor marker tests are not routine studies for staging DCIS (stage O) or early-stage (I and II) breast cancer. Treatment DCIS is treated with wide excision followed by radiation or with mastectomy if the tumor cannot be completely removed by excision. ER positive tumors are treated with tamoxifen (premenopausal women only) or aromatase inhibitors. Surgery and endocrine therapy decrease the risk for recurrence and contralateral breast cancer but not survival. Follow up includes annual mammography and clinical evaluation for 5 years.

Treatment DCIS is treated with wide excision followed by radiation or with mastectomy if the tumor cannot be completely removed by excision. ER positive tumors are treated with tamoxifen (premenopausal women only) or aromatase inhibitors. Surgery and endocrine therapy decrease the risk for recurrence and contralateral breast cancer but not survival. Follow up includes annual mammography and clinical evaluation for 5 years. Invasive breast cancer is usually treated with excision (lumpectomy), radiation, and adjuvant systemic therapy. Mastectomy is appropriate for patients with inflammatory breast cancer; cancer involving the skin, chest wall, or more than one quadrant of the breast; or contraindications to radiation therapy (previous irradiation). Bilateral mastectomy is an option for women with familial breast cancer syndromes. In patients with clinically negative axillary lymph nodes, a sentinel biopsy is performed. Axillary lymph node dissection is performed if sentinel lymph node biopsy is positive or axillary lymph nodes are clinically involved. Chest wall radiation therapy after mastectomy is recommended in patients with tumors >5 cm, positive surgical margins, skin or chest wall involvement, or inflammatory breast cancer, and for most patients with >4 positive axillary nodes. Postmastectomy radiation increases overall survival. Paget disease of the breast is characterized by a scaly or red rash or ulceration occurring on the nipple and spreading to the areola. It is usually associated with an underlying ductal breast carcinoma and is diagnosed with skin biopsy. 313