Browse the corpus

Stroke Nonconvulsive Status Epilepticus retina, or spinal cord due to occlusion or rupture of a cerebral NCSE refers to episodes of electrical seizure activity without or spinal artery. Ischemic stroke, which results from occlusion clinically evident seizure activity. It should be suspected of an artery, is the most common type of stroke and can be when a patient has altered mental status of unknown cause. further subclassified on the basis of its underlying cause. NCSE is common in medical, surgical, and neurologic inten- Transient ischemic attack (TIA) was formerly defined as focal sive care units and should be considered even whena patient neurologic impairment with symptoms lasting less than has no known neurologic history. NCSE typically occurs in 24 hours, but the distinction between stroke and TIA now rests 15% to 25% of critically ill patients with encephalopathy. on evidence of infarction on neuroimaging. Hemorrhagic Certain situations should prompt immediate continuous EEG stroke has two subtypes, is less common than ischemic stroke, monitoring (see Table 18), which is required for diagnosis. and has higher short-term mortality. Intracerebral hemorrhage Shorter duration EEG is typically inadequate because many (ICH) presents with focal neurologic deficits and, frequently, patients experience intermittent rather than continuous sei- headache and impairment in consciousness. Subarachnoid zures. At least 24 hours of monitoring is recommended in hemorrhage (SAH) presents with sudden onset severe head- noncomatose patients, and at least 48 hours is recommended ache and impairment in consciousness with variable focal in comatose patients. neurologic deficits. Although their clinical manifestations often NCSE that does not occur directly after GTCS or CSE may overlap with stroke, subdural and epidural hematomas are not not carry as high a risk to the patient, and thus treatment is considered to be strokes and are discussed in Head Injury.

in comatose patients. neurologic deficits. Although their clinical manifestations often NCSE that does not occur directly after GTCS or CSE may overlap with stroke, subdural and epidural hematomas are not not carry as high a risk to the patient, and thus treatment is considered to be strokes and are discussed in Head Injury. not necessarily as aggressive as that for CSE. Treatment is Determining the exact subtype of stroke a patient experiences based on clinical examination and not on EEG alone. If the has important implications for acute therapeutics, prevention patient is not comatose, initiating aggressive therapy with strategies, and prognosis. intubation and an IV anesthetic-induced coma is usually avoided because risks may outweigh benefits. Outcomes are ¢ Determining the exact subtype of stroke (ischemic or typically related to seizure cause rather than severity of sei- hemorrhagic) has important implications for acute zures or altered mentation. therapeutics, prevention strategies, and prognosis.

intubation and an IV anesthetic-induced coma is usually avoided because risks may outweigh benefits. Outcomes are ¢ Determining the exact subtype of stroke (ischemic or typically related to seizure cause rather than severity of sei- hemorrhagic) has important implications for acute zures or altered mentation. therapeutics, prevention strategies, and prognosis. e Nonconvulsive status epilepticus should be suspected and continuous electroencephalographic monitoring Diagnosis of Stroke initiated when a patient has altered mental status with Stroke is a clinical diagnosis supported by neuroimaging. an unclear cause, including patients in medical or surgi- Most strokes present with rapid onset of focal (denoting spe- cal ICUs, even those without known neurologic history. cific brain region dysfunction) neurologic symptoms, such as hemiparesis, aphasia, ataxia, loss of balance, visual loss, and unilateral sensory loss. Stroke also may present with more atypical and nonspecific symptoms, such as confusion, diz- Stroke ziness, or loss of consciousness. Posterior circulation strokes presenting with dizziness also typically display focal neuro- Definition of Stroke logic findings, such as multidirectional nystagmus, skew Stroke is the leading cause of serious disability among adults deviation or cranial nerve palsies, abnormal motor findings, and the fifth leading cause of death in the United States. Its and inability to walk. In the acute setting, validated scales incidence increases with each decade of life. The World Health that can be rapidly and reliably performed, such as the Organization defines stroke as a disease of sudden-onset focal National Institutes of Health Stroke Scale (NIHSS), are com- neurologic deficits associated with dysfunction in the brain, monly used (Table 23). Because the neurologic examination

e Nonconvulsive status epilepticus should be suspected and continuous electroencephalographic monitoring Diagnosis of Stroke initiated when a patient has altered mental status with Stroke is a clinical diagnosis supported by neuroimaging. an unclear cause, including patients in medical or surgi- Most strokes present with rapid onset of focal (denoting spe- cal ICUs, even those without known neurologic history. cific brain region dysfunction) neurologic symptoms, such as hemiparesis, aphasia, ataxia, loss of balance, visual loss, and unilateral sensory loss. Stroke also may present with more atypical and nonspecific symptoms, such as confusion, diz- Stroke ziness, or loss of consciousness. Posterior circulation strokes presenting with dizziness also typically display focal neuro- Definition of Stroke logic findings, such as multidirectional nystagmus, skew Stroke is the leading cause of serious disability among adults deviation or cranial nerve palsies, abnormal motor findings, and the fifth leading cause of death in the United States. Its and inability to walk. In the acute setting, validated scales incidence increases with each decade of life. The World Health that can be rapidly and reliably performed, such as the Organization defines stroke as a disease of sudden-onset focal National Institutes of Health Stroke Scale (NIHSS), are com- neurologic deficits associated with dysfunction in the brain, monly used (Table 23). Because the neurologic examination TABLE 23. National Institutes of Health Stroke Scale Parameter (Testing Method) Scores? 1a. Level of consciousness 0=normal 1 =notalert but arousable by minor stimulation 2 =not alert and requires constant verbal or painful stimuli to remain interactive

e Nonconvulsive status epilepticus should be suspected and continuous electroencephalographic monitoring Diagnosis of Stroke initiated when a patient has altered mental status with Stroke is a clinical diagnosis supported by neuroimaging. an unclear cause, including patients in medical or surgi- Most strokes present with rapid onset of focal (denoting spe- cal ICUs, even those without known neurologic history. cific brain region dysfunction) neurologic symptoms, such as hemiparesis, aphasia, ataxia, loss of balance, visual loss, and unilateral sensory loss. Stroke also may present with more atypical and nonspecific symptoms, such as confusion, diz- Stroke ziness, or loss of consciousness. Posterior circulation strokes presenting with dizziness also typically display focal neuro- Definition of Stroke logic findings, such as multidirectional nystagmus, skew Stroke is the leading cause of serious disability among adults deviation or cranial nerve palsies, abnormal motor findings, and the fifth leading cause of death in the United States. Its and inability to walk. In the acute setting, validated scales incidence increases with each decade of life. The World Health that can be rapidly and reliably performed, such as the Organization defines stroke as a disease of sudden-onset focal National Institutes of Health Stroke Scale (NIHSS), are com- neurologic deficits associated with dysfunction in the brain, monly used (Table 23). Because the neurologic examination TABLE 23. National Institutes of Health Stroke Scale Parameter (Testing Method) Scores? 1a. Level of consciousness 0=normal 1 =notalert but arousable by minor stimulation 2 =not alert and requires constant verbal or painful stimuli to remain interactive 3 = unresponsive or responds with only reflexive movements

TABLE 23. National Institutes of Health Stroke Scale Parameter (Testing Method) Scores? 1a. Level of consciousness 0=normal 1 =notalert but arousable by minor stimulation 2 =not alert and requires constant verbal or painful stimuli to remain interactive 3 = unresponsive or responds with only reflexive movements :1b. Level of consciousness questions (state month 0 =answers both correctly and age) 1 =answers one correctly | 2 = answers neither correctly i L (Continued on thennext page) | 26

TABLE 23. National Institutes of Health Stroke Scale (Continued) Parameter (Testing Method) Scores? 1c. Level of consciousness commands (close and 0 =performs both tasks correctly open eyes; make fist or close one hand) 1 =performs one task correctly 2 = performs neither task correctly 2. Best gaze (track a finger in a horizontal plane) 0=normal 1 = partial gaze palsy or isolated cranial nerve paresis 2 = forced gaze deviation or total gaze paresis 3. Visual fields (each eye tested individually) 0=no visual loss 1 =partial hemianopia 2=complete hemianopia 3 = bilateral hemianopia | 4. Facial palsy (show teeth, raise eyebrows, close 0=normal eyes) 1 =minor paralysis (flattening of the nasolabial fold or asymmetry on smiling) 2 = partial paralysis (paralysis of the lower face only) 3 =complete paralysis (upper and lower face) 5. Arm strength (hold arm with palms down or lift O0=no drift arm for 10 s; each arm scored separately) 1 =some drift but does not hit bed 2 = drifts down to bed 3=no effort against gravity 4=no movement 6. Leg strength (hold leg at 30 degrees for 5 s; 0=no drift each leg scored separately) 1 =some drift but does not hit bed | 2 = drifts down to bed 3=no effort against gravity 4=no movement 7. Limb ataxia (finger-nose-finger test, heel-knee- 0=absent | shin slide) 1 =present in one limb 2 = present in two limbs

4=no movement 7. Limb ataxia (finger-nose-finger test, heel-knee- 0=absent | shin slide) 1 =present in one limb 2 = present in two limbs 8. Sensation (pinch/pinprick tested in face, arm, 0=normal and leg) 1 =mild to moderate sensory loss or loss of sensation in only one limb 2 =complete sensory loss 9. Best language (describe a picture, name six 0 =no aphasia objects, and read five sentences) 1 =mild to moderate aphasia (difficulty with fluency and comprehension; meaning can be identified) 2 =severe aphasia (fragmentary language, meaning cannot be clearly identified) 3 = global aphasia or mute 10. Dysarthria (repeat or read words) 0=normal 1 =mild to moderate 2 =severe (speech not understandable) 11. Extinction/inattention (visual and tactile stimuli 0=normal applied on right and left sides) 1 =visual ortactile extinction or mild hemispatial neglect 2 = profound hemi-inattention or extinction to more than one modality *Score interpretation (based on total score): 0 = no stroke; 1-4 = minor stroke; 5-15 = moderate stroke; 16-20 = moderate to severe stroke; 21-42 = severe stroke (maximum score, 42). Adapted from the NIH Stroke Scale. www.ninds.nih.gov/sites/default/files/NIH_Stroke_Scale_Booklet.pdf. Accessed February 3, 2021. 27

Stroke FIGURE 11. Noncontrast CT scans of the head. Top panel, an acute left thalamic intracerebral hemorrhage (arrows) without hydrocephalus or intraventricular extension is shown. Bottom panel, an acute subarachnoid hemorrhage is shown that involves the basal cisterns (thinner arrows) with associated enlargement of the lateral horn of the lateral ventricles, consistent with obstructive hydrocephalus and elevated intracranial pressure (thicker arrows).

FIGURE 11. Noncontrast CT scans of the head. Top panel, an acute left thalamic intracerebral hemorrhage (arrows) without hydrocephalus or intraventricular extension is shown. Bottom panel, an acute subarachnoid hemorrhage is shown that involves the basal cisterns (thinner arrows) with associated enlargement of the lateral horn of the lateral ventricles, consistent with obstructive hydrocephalus and elevated intracranial pressure (thicker arrows). cannot reliably distinguish ischemic from hemorrhagic MRI include the ability to visualize small strokes, multifocal or stroke, neuroimaging is required before initiation of bilateral infarcts that may suggest an embolic cause, and the treatment. Noncontrast head CT is the most widely used presence of microbleeds. Because of its longer acquisition test, given its rapid acquisition, low cost, wide availability, time, brain MRI is never the initial test of choice in acute sus- and high sensitivity for diagnosing hemorrhagic stroke pected stroke; when indicated, it is obtained after the initial (Figure 11). In ischemic stroke, the initial noncontrast head noncontrast head CT. MRI and magnetic resonance perfusion CT scan is often normal, especially in patients seen within may be used in the acute setting instead of CT perfusion for 3 hours of symptom onset (although some patients with specific patients to determine eligibility for endovascular larger deficits can exhibit early findings) (Figure 12). Even therapy. 24 hours after onset, a noncontrast head CT scan may not Among patients with ICH seen on a noncontrast head show evidence of infarction, given the poor resolution of CT scan, MRI, magnetic resonance angiography (MRA), or small infarcts and those located in the brainstem. CT of the CTA is considered if clinical factors are present that raise the head with contrast rarely is indicated in the initial evaluation suspicion of a cause of hemorrhage other than hypertension of a patient with stroke. CT angiography (CTA) of the head or amyloid angiopathy, such as arteriovenous malformation. and neck and CT perfusion may be performed acutely if Likewise, if a patient has symptoms suggestive of SAH and endovascular therapy is considered. noncontrast head CT findings are normal, lumbar puncture MRI is more sensitive than CT for acute infarction, with is required to evaluate for the presence of blood or xan- changes on the diffusion-weighted imaging sequence appar- thochromia (yellow color stemming from erythrocyte break- ent within minutes from onset (Figure 13). The advantages of down). If SAH is confirmed, catheter-based angiography is

cannot reliably distinguish ischemic from hemorrhagic MRI include the ability to visualize small strokes, multifocal or stroke, neuroimaging is required before initiation of bilateral infarcts that may suggest an embolic cause, and the treatment. Noncontrast head CT is the most widely used presence of microbleeds. Because of its longer acquisition test, given its rapid acquisition, low cost, wide availability, time, brain MRI is never the initial test of choice in acute sus- and high sensitivity for diagnosing hemorrhagic stroke pected stroke; when indicated, it is obtained after the initial (Figure 11). In ischemic stroke, the initial noncontrast head noncontrast head CT. MRI and magnetic resonance perfusion CT scan is often normal, especially in patients seen within may be used in the acute setting instead of CT perfusion for 3 hours of symptom onset (although some patients with specific patients to determine eligibility for endovascular larger deficits can exhibit early findings) (Figure 12). Even therapy. 24 hours after onset, a noncontrast head CT scan may not Among patients with ICH seen on a noncontrast head show evidence of infarction, given the poor resolution of CT scan, MRI, magnetic resonance angiography (MRA), or small infarcts and those located in the brainstem. CT of the CTA is considered if clinical factors are present that raise the head with contrast rarely is indicated in the initial evaluation suspicion of a cause of hemorrhage other than hypertension of a patient with stroke. CT angiography (CTA) of the head or amyloid angiopathy, such as arteriovenous malformation. and neck and CT perfusion may be performed acutely if Likewise, if a patient has symptoms suggestive of SAH and endovascular therapy is considered. noncontrast head CT findings are normal, lumbar puncture MRI is more sensitive than CT for acute infarction, with is required to evaluate for the presence of blood or xan- changes on the diffusion-weighted imaging sequence appar- thochromia (yellow color stemming from erythrocyte break- ent within minutes from onset (Figure 13). The advantages of down). If SAH is confirmed, catheter-based angiography is 28

Stroke FIGURE 12. Imaging findings in acute ischemic stroke. Top left panel, CT scan of the head without contrast obtained 4 hours after acute onset of left-sided weakness and hemiparesis. The arrow points to a dense middle cerebral artery sign suggestive of a thrombus. Top middle panel, CT scan of the head showing hypodensity in the right insula (oval). Top right panel, CT scan of the head from the same patient showing early loss of the gray-white matter differentiation in the right middle cerebral artery territory distribution (oval). Bottom left panel, CT angiogram of the head showing abrupt cessation of filling in the right middle cerebral artery (arrow). Bottom middle and right panels, CT scans of the head from the same patient as above 36 hours after symptom onset showing more prominent hypodensity (middle panel, oval) and cerebral edema (right panel, oval). required to diagnose, and potentially treat, a cerebral Stroke Subtypes aneurysm. Transient Ischemic Attack Results of the physical and neurologic examination often TIA is characterized by a temporary focal neurologic deficit will suggest the cause of ischemic stroke, such as the presence with an absence of infarction on neuroimaging. Symptoms of of atrial fibrillation or a carotid bruit. Further evaluation with TIA are similar to those of stroke and include hemiparesis, cardiac testing or vessel imaging is required to confirm these monocular or visual field loss, dysarthria, aphasia, and sen- causes. sory loss. The presence of paresthesia, isolated dizziness or KEY POINTS vertigo, or memory loss is more consistent with migraine or

required to diagnose, and potentially treat, a cerebral Stroke Subtypes aneurysm. Transient Ischemic Attack Results of the physical and neurologic examination often TIA is characterized by a temporary focal neurologic deficit will suggest the cause of ischemic stroke, such as the presence with an absence of infarction on neuroimaging. Symptoms of of atrial fibrillation or a carotid bruit. Further evaluation with TIA are similar to those of stroke and include hemiparesis, cardiac testing or vessel imaging is required to confirm these monocular or visual field loss, dysarthria, aphasia, and sen- causes. sory loss. The presence of paresthesia, isolated dizziness or KEY POINTS vertigo, or memory loss is more consistent with migraine or e Neuroimaging, preferably noncontrast head CT, is seizure. Patients with TIA are at high risk of stroke within the

required to diagnose, and potentially treat, a cerebral Stroke Subtypes aneurysm. Transient Ischemic Attack Results of the physical and neurologic examination often TIA is characterized by a temporary focal neurologic deficit will suggest the cause of ischemic stroke, such as the presence with an absence of infarction on neuroimaging. Symptoms of of atrial fibrillation or a carotid bruit. Further evaluation with TIA are similar to those of stroke and include hemiparesis, cardiac testing or vessel imaging is required to confirm these monocular or visual field loss, dysarthria, aphasia, and sen- causes. sory loss. The presence of paresthesia, isolated dizziness or KEY POINTS vertigo, or memory loss is more consistent with migraine or e Neuroimaging, preferably noncontrast head CT, is seizure. Patients with TIA are at high risk of stroke within the required before initiating treatment for stroke. first 48 hours after symptom onset and should be evaluated promptly. e Although MRI is more sensitive than CT for diagnosing Several post-TIA stroke prediction scoring systems have acute infarction, it is not the initial test of choice to been developed, with the most widely used being the ABCD? exclude hemorrhagic stroke or to make treatment deci- score, which is based on Age, Blood pressure, Clinical presenta- sions about thrombolysis for ischemic stroke because of tion, Duration of symptoms, and the presence of Diabetes melli- its longer acquisition time. tus (Table 24). TIA scoring systems, however, do not identify with

required before initiating treatment for stroke. first 48 hours after symptom onset and should be evaluated promptly. e Although MRI is more sensitive than CT for diagnosing Several post-TIA stroke prediction scoring systems have acute infarction, it is not the initial test of choice to been developed, with the most widely used being the ABCD? exclude hemorrhagic stroke or to make treatment deci- score, which is based on Age, Blood pressure, Clinical presenta- sions about thrombolysis for ischemic stroke because of tion, Duration of symptoms, and the presence of Diabetes melli- its longer acquisition time. tus (Table 24). TIA scoring systems, however, do not identify with 29

Stroke those with greater than 70% stenosis, although 50% to 70% steno- sis also carries significant associated risk. In the long term, the risk of stroke is high among patients with atrial fibrillation or other cardioembolic sources requiring anticoagulation. Expedited vascular imaging of the ICA and cardiac evalu- ation for atrial fibrillation are required for all patients with TIA. The initial test of choice for evaluating ICA stenosis is duplex ultrasonography because of its wide availability, low cost, and low risk; if high-grade ICA stenosis is detected and the patient is a candidate for surgery or stenting, confirmatory testing is required before intervention. Cardiac evaluation should include ECG for atrial fibrillation, which may be fol- lowed by longer-term monitoring. Echocardiography is per- formed if there is a clinical suspicion of a cardioembolic source or structural heart disease.

those with greater than 70% stenosis, although 50% to 70% steno- sis also carries significant associated risk. In the long term, the risk of stroke is high among patients with atrial fibrillation or other cardioembolic sources requiring anticoagulation. Expedited vascular imaging of the ICA and cardiac evalu- ation for atrial fibrillation are required for all patients with TIA. The initial test of choice for evaluating ICA stenosis is duplex ultrasonography because of its wide availability, low cost, and low risk; if high-grade ICA stenosis is detected and the patient is a candidate for surgery or stenting, confirmatory testing is required before intervention. Cardiac evaluation should include ECG for atrial fibrillation, which may be fol- lowed by longer-term monitoring. Echocardiography is per- formed if there is a clinical suspicion of a cardioembolic source or structural heart disease. e Patients with a greater than 70% extracranial stenosis of the internal carotid artery who have a transient ischemic attack in a downstream neurologic territory have the highest risk of stroke within 2 weeks.

e Patients with a greater than 70% extracranial stenosis of the internal carotid artery who have a transient ischemic attack in a downstream neurologic territory have the highest risk of stroke within 2 weeks. e Expedited vascular imaging of the internal carotid artery and cardiac evaluation for atrial fibrillation are required for all patients with transient ischemic attack. FIGURE 13. Diffusion-weighted MRIs from a patient with symptomatic atherosclerosis of the left middle cerebral artery reveal an acute infarction in deep (thinner arrows) and superficial (thicker arrows) structures in the left cerebral Ischemic Stroke hemisphere. Large Artery Atherosclerosis The main mechanism of stroke due to large-artery atheroscle- sufficient sensitivity the highest-risk patients for whom treat- rosis is plaque rupture with artery-to-artery embolism. The ment can ameliorate the risk of stroke. Patients with high-grade extracranial carotid artery and vertebral artery are frequently extracranial internal carotid artery (ICA) stenosis who have a TIA involved. Intracranial arteries most commonly affected are in a downstream neurologic territory have the greatest short- the intracranial carotid, middle cerebral, vertebral-basilar term risk of stroke. This risk is highest within 2 weeks of TIA for junction, and midbasilar arteries. Patients with stenoses of the extracranial ICA and the intracranial arteries are at high TABLE 24. ABCD? Score? short-term risk of recurrent stroke and require prompt evalu- | Patient Characteristics Score? ation. As with TIAs, the extracranial carotid arteries are best

e Expedited vascular imaging of the internal carotid artery and cardiac evaluation for atrial fibrillation are required for all patients with transient ischemic attack. FIGURE 13. Diffusion-weighted MRIs from a patient with symptomatic atherosclerosis of the left middle cerebral artery reveal an acute infarction in deep (thinner arrows) and superficial (thicker arrows) structures in the left cerebral Ischemic Stroke hemisphere. Large Artery Atherosclerosis The main mechanism of stroke due to large-artery atheroscle- sufficient sensitivity the highest-risk patients for whom treat- rosis is plaque rupture with artery-to-artery embolism. The ment can ameliorate the risk of stroke. Patients with high-grade extracranial carotid artery and vertebral artery are frequently extracranial internal carotid artery (ICA) stenosis who have a TIA involved. Intracranial arteries most commonly affected are in a downstream neurologic territory have the greatest short- the intracranial carotid, middle cerebral, vertebral-basilar term risk of stroke. This risk is highest within 2 weeks of TIA for junction, and midbasilar arteries. Patients with stenoses of the extracranial ICA and the intracranial arteries are at high TABLE 24. ABCD? Score? short-term risk of recurrent stroke and require prompt evalu- | Patient Characteristics Score? ation. As with TIAs, the extracranial carotid arteries are best | Age 260y 1 | evaluated with duplex ultrasonography. MRA and CTA are both appropriate confirmatory tests after ultrasonography to | Blood pressure =>140/90 mm Hg 1 | inform intervention or if duplex examination is not available | Clinical symptoms | (Figure 14). Transcranial Doppler ultrasonography may help | Focal weakness with the TIA 2 | diagnose large-vessel intracranial atherosclerosis, although | Speech impairment without weakness 1 MRA and CTA are more sensitive tests. Catheter-based angi- | Duration of TIA | ography is rarely used to diagnose either extracranial or

| Age 260y 1 | evaluated with duplex ultrasonography. MRA and CTA are both appropriate confirmatory tests after ultrasonography to | Blood pressure =>140/90 mm Hg 1 | inform intervention or if duplex examination is not available | Clinical symptoms | (Figure 14). Transcranial Doppler ultrasonography may help | Focal weakness with the TIA 2 | diagnose large-vessel intracranial atherosclerosis, although | Speech impairment without weakness 1 MRA and CTA are more sensitive tests. Catheter-based angi- | Duration of TIA | ography is rarely used to diagnose either extracranial or | 260 min 2 | intracranial vessel disease, in part because of the procedural risk of stroke. 10-59 min 1 | Diabetes mellitus present 1 | Cardioembolic Stroke TIA = transient ischemic attack. | A cardioembolic cause is suggested by clinical and radiologic *Based on age, blood pressure, clinical presentation, duration of symptoms, and factors (such as infarcts that occur in multiple arterial territo- the presence of diabetes mellitus. | ries or locations near the cortical surface of the brain) when ’The 48-hour stroke risk based on total score: 0-1 = 0%; 2-3 = 1.3%; 4-5 = 4.1%; 6-7 =8.1%. arterial imaging is unrevealing. Atrial fibrillation is the most common cardioembolic cause of stroke. Other potential cardi- Data from Johnston SC, Rothwell PM, Nguyen-Huynh MN, Giles MF, Elkins JS, Bernstein AL, et al. Validation and refinement of scores to predict very early stroke | oembolic sources include a new ventricular thrombus (after risk after transient ischaemic attack. Lancet. 2007;369:283-92. [PMID: 17258668] myocardial infarction or due to diminished ejection fraction),

| 260 min 2 | intracranial vessel disease, in part because of the procedural risk of stroke. 10-59 min 1 | Diabetes mellitus present 1 | Cardioembolic Stroke TIA = transient ischemic attack. | A cardioembolic cause is suggested by clinical and radiologic *Based on age, blood pressure, clinical presentation, duration of symptoms, and factors (such as infarcts that occur in multiple arterial territo- the presence of diabetes mellitus. | ries or locations near the cortical surface of the brain) when ’The 48-hour stroke risk based on total score: 0-1 = 0%; 2-3 = 1.3%; 4-5 = 4.1%; 6-7 =8.1%. arterial imaging is unrevealing. Atrial fibrillation is the most common cardioembolic cause of stroke. Other potential cardi- Data from Johnston SC, Rothwell PM, Nguyen-Huynh MN, Giles MF, Elkins JS, Bernstein AL, et al. Validation and refinement of scores to predict very early stroke | oembolic sources include a new ventricular thrombus (after risk after transient ischaemic attack. Lancet. 2007;369:283-92. [PMID: 17258668] myocardial infarction or due to diminished ejection fraction), 30

Stroke matter, basal ganglia, or brainstem. Pathologically, these infarcts are due to occlusion of small penetrating arteries aris- ing from a large cerebral artery (most commonly the middle cerebral and basilar arteries). The main risk factor is hyperten- sion, which leads to local damage at the level of the penetrat- ing artery with subsequent occlusion. Other stroke sources include artery-to-artery embolic thrombi from more proximal sources. Patients with lacunar infarcts still require vessel imaging of the extracranial ICAs to inform secondary prevention.

matter, basal ganglia, or brainstem. Pathologically, these infarcts are due to occlusion of small penetrating arteries aris- ing from a large cerebral artery (most commonly the middle cerebral and basilar arteries). The main risk factor is hyperten- sion, which leads to local damage at the level of the penetrat- ing artery with subsequent occlusion. Other stroke sources include artery-to-artery embolic thrombi from more proximal sources. Patients with lacunar infarcts still require vessel imaging of the extracranial ICAs to inform secondary prevention. Embolic Stroke of Undetermined Source In many patients with ischemic stroke, a clear cause is not apparent: there is no lacunar infarct, arterial imaging is nor- mal, and no cardioembolic source (such as atrial fibrillation) is FIGURE 14. Diagnostic imaging modalities in a patient with a symptomatic found. When this occurs, the patient’s clinical syndrome, extracranial internal carotid artery atherosclerotic plaque and associated 90% underlying medical comorbidities, and neuroimaging charac- stenosis. The CT angiogram (/eft panel) and magnetic resonance angiogram teristics can inform which additional diagnostic testing should (middle panel) show high-grade stenosis at the origin of the internal carotid artery (arrows). Carotid ultrasounds (right panel) of the extracranial proximal internal be considered, with special attention to hypercoagulable states carotid artery show a large plaque at the origin (arrow) of the artery, with associated including underlying malignancy. elevated systolic (3.33 m/s) and diastolic (1.23 m/s) velocities consistent with 80% Patients with an embolic stroke of unknown source to 99% stenosis. (ESUS; formerly termed cryptogenic stroke) may have undiag- nosed paroxysmal atrial fibrillation. Prolonged cardiac moni- a patent foramen ovale (PFO), and severe valvular disease (for toring with either surface electrodes or an implantable example, rheumatic disease, infective endocarditis, and bio- monitor is indicated and may be positive for atrial fibrillation prosthetic and mechanical heart valves). in approximately one third of these patients. In patients with Radiographic findings suggestive of a cardioembolic an implantable pacemaker, interrogation of the device may source are insufficient grounds for initiating anticoagulation. also reveal episodes consistent with atrial fibrillation. In the Patients admitted to the hospital with ischemic stroke should absence of atrial fibrillation, the routine use of anticoagulation undergo ECG and telemetry monitoring to assess for atrial in patients with ESUS is not indicated. fibrillation. If there is a clinical suspicion of structural heart disease or an embolic source, transthoracic echocardiography Other is indicated to determine if there are indications for anticoagu- In a younger patient without risk factors for cardiovascular lation. The use of transesophageal echocardiography to evalu- disease, an evaluation for autoimmune and hypercoagulable ate for an intracardiac source of stroke is not routinely disorders should be considered. Hypercoagulable disorders indicated, given the low yield for findings that require anti- and other rare cardioembolic causes may present with an coagulation or surgery. In younger patients without stroke infarct pattern similar to that of atrial fibrillation. Cerebral risk factors or in whom suspicion of endocarditis or an vasculitis is an extremely rare cause of stroke and presents with intracardiac tumor (such as myxoma or fibroelastoma) numerous infarcts affecting multiple arterial distributions. exists, transesophageal echocardiography may be consid- ered on a case-by-case basis. Injection of agitated saline ¢ Carotid ultrasonography is indicated in the evaluation (bubble study) is indicated when there is suspicion of a PFO of transient ischemic attack and stroke; magnetic reso- or other right-to -left shunt source of cerebral emboli. A PFO nance angiography and CT angiography are more sensi- is more likely to be a cause of stroke in younger patients tive tests for intracranial large vessel atherosclerosis. (usually, <50 years), and percutaneous closure is associated with a low but significant reduction in risk of second stroke. e Atrial fibrillation is the most common cardioembolic cause For further information, including recent recommendations of stroke, and anticoagulation is indicated; radiographic

Embolic Stroke of Undetermined Source In many patients with ischemic stroke, a clear cause is not apparent: there is no lacunar infarct, arterial imaging is nor- mal, and no cardioembolic source (such as atrial fibrillation) is FIGURE 14. Diagnostic imaging modalities in a patient with a symptomatic found. When this occurs, the patient’s clinical syndrome, extracranial internal carotid artery atherosclerotic plaque and associated 90% underlying medical comorbidities, and neuroimaging charac- stenosis. The CT angiogram (/eft panel) and magnetic resonance angiogram teristics can inform which additional diagnostic testing should (middle panel) show high-grade stenosis at the origin of the internal carotid artery (arrows). Carotid ultrasounds (right panel) of the extracranial proximal internal be considered, with special attention to hypercoagulable states carotid artery show a large plaque at the origin (arrow) of the artery, with associated including underlying malignancy. elevated systolic (3.33 m/s) and diastolic (1.23 m/s) velocities consistent with 80% Patients with an embolic stroke of unknown source to 99% stenosis. (ESUS; formerly termed cryptogenic stroke) may have undiag- nosed paroxysmal atrial fibrillation. Prolonged cardiac moni- a patent foramen ovale (PFO), and severe valvular disease (for toring with either surface electrodes or an implantable example, rheumatic disease, infective endocarditis, and bio- monitor is indicated and may be positive for atrial fibrillation prosthetic and mechanical heart valves). in approximately one third of these patients. In patients with Radiographic findings suggestive of a cardioembolic an implantable pacemaker, interrogation of the device may source are insufficient grounds for initiating anticoagulation. also reveal episodes consistent with atrial fibrillation. In the Patients admitted to the hospital with ischemic stroke should absence of atrial fibrillation, the routine use of anticoagulation undergo ECG and telemetry monitoring to assess for atrial in patients with ESUS is not indicated. fibrillation. If there is a clinical suspicion of structural heart disease or an embolic source, transthoracic echocardiography Other is indicated to determine if there are indications for anticoagu- In a younger patient without risk factors for cardiovascular lation. The use of transesophageal echocardiography to evalu- disease, an evaluation for autoimmune and hypercoagulable ate for an intracardiac source of stroke is not routinely disorders should be considered. Hypercoagulable disorders indicated, given the low yield for findings that require anti- and other rare cardioembolic causes may present with an coagulation or surgery. In younger patients without stroke infarct pattern similar to that of atrial fibrillation. Cerebral risk factors or in whom suspicion of endocarditis or an vasculitis is an extremely rare cause of stroke and presents with intracardiac tumor (such as myxoma or fibroelastoma) numerous infarcts affecting multiple arterial distributions. exists, transesophageal echocardiography may be consid- ered on a case-by-case basis. Injection of agitated saline ¢ Carotid ultrasonography is indicated in the evaluation (bubble study) is indicated when there is suspicion of a PFO of transient ischemic attack and stroke; magnetic reso- or other right-to -left shunt source of cerebral emboli. A PFO nance angiography and CT angiography are more sensi- is more likely to be a cause of stroke in younger patients tive tests for intracranial large vessel atherosclerosis. (usually, <50 years), and percutaneous closure is associated with a low but significant reduction in risk of second stroke. e Atrial fibrillation is the most common cardioembolic cause For further information, including recent recommendations of stroke, and anticoagulation is indicated; radiographic regarding percutaneous PFO closure to prevent a secondary findings suggestive of a cardioembolic source, however, are stroke and additional details on anticoagulation criteria, see insufficient grounds for initiating anticoagulation. MKSAP 19 Cardiovascular Medicine. e The use of transesophageal echocardiography to evalu- HVC ate for an intracardiac source of stroke is not routinely Small Subcortical Infarcts (Lacunar Infarcts) indicated, given the low yield for findings that require Lacunar infarcts commonly lead to isolated motor or sensory anticoagulation or surgery. syndromes; they rarely affect cognition or mental status. These (Continued) infarcts (which are <1.5 cm in diameter) involve the deep white

regarding percutaneous PFO closure to prevent a secondary findings suggestive of a cardioembolic source, however, are stroke and additional details on anticoagulation criteria, see insufficient grounds for initiating anticoagulation. MKSAP 19 Cardiovascular Medicine. e The use of transesophageal echocardiography to evalu- HVC ate for an intracardiac source of stroke is not routinely Small Subcortical Infarcts (Lacunar Infarcts) indicated, given the low yield for findings that require Lacunar infarcts commonly lead to isolated motor or sensory anticoagulation or surgery. syndromes; they rarely affect cognition or mental status. These (Continued) infarcts (which are <1.5 cm in diameter) involve the deep white 31

Stroke TABLE 25. Determination of the ICH Score e Lacunar (or small subcortical) infarcts resulting in iso- | Component ICH Score Points lated motor or sensory syndromes are caused by occlu- | GCS score | sion of the small penetrating arteries arising from 3-4 D | intracranial arteries; the main risk factor for lacunar 5-12 1 | infarcts is hypertension. 13-15 0 | ¢ Many patients with embolic stroke of unknown source ICH volume, cm? | (formerly known as cryptogenic stroke) may have undi- agnosed paroxysmal atrial fibrillation, and prolonged 330 1 | cardiac monitoring should be considered. <30 0 |

e Lacunar (or small subcortical) infarcts resulting in iso- | Component ICH Score Points lated motor or sensory syndromes are caused by occlu- | GCS score | sion of the small penetrating arteries arising from 3-4 D | intracranial arteries; the main risk factor for lacunar 5-12 1 | infarcts is hypertension. 13-15 0 | ¢ Many patients with embolic stroke of unknown source ICH volume, cm? | (formerly known as cryptogenic stroke) may have undi- agnosed paroxysmal atrial fibrillation, and prolonged 330 1 | cardiac monitoring should be considered. <30 0 | IVH Hemorrhagic Stroke | Yes Subarachnoid Hemorrhage | No 0 | Examination findings suggestive of SAH include confusion | Infratentorial origin of ICH | and somnolence, nuchal rigidity, pupillary dilation from compression of the oculomotor nerve (cranial nerve III) by Yes | a posterior communicating artery aneurysm, or subhyaloid No 0 | hemorrhages on funduscopy. The most common cause of Age,y | SAH is saccular (berry) aneurysm rupture, with intracranial | 280 1 arterial dissection and mycotic aneurysm rupture being less <80 common. Other rare causes of SAH are the reversible cere- | Total ICH score 0-6 | bral vasoconstriction syndromes, dural sinus thrombosis, vascular malformations, and cerebral amyloid angiopathy. GSC = Glasgow Coma Scale; ICH = intracerebral hemorrhage; IVH = intraventricular hemorrhage. Saccular aneurysms often can be visualized with CTA or GCS score indicates GCS score on initial presentation (or after resuscitation); ICH MRA, although the resolution is insufficient to detect volume, volume on initial CT calculated using ABC/2 method; and IVH, presence of any IVH on initial CT. smaller aneurysms; catheter-based angiography is neces- sary for the definitive diagnosis of aneurysms and other Reprinted with permission from Hemphill JC 3rd, Bonovich DC, Besmertis L, | Manley GT, Johnston SC. The ICH score: a simple, reliable grading scale for causes of SAH. | intracerebral hemorrhage. Stroke. 2001;32:891-7. [PMID: 11283388]

IVH Hemorrhagic Stroke | Yes Subarachnoid Hemorrhage | No 0 | Examination findings suggestive of SAH include confusion | Infratentorial origin of ICH | and somnolence, nuchal rigidity, pupillary dilation from compression of the oculomotor nerve (cranial nerve III) by Yes | a posterior communicating artery aneurysm, or subhyaloid No 0 | hemorrhages on funduscopy. The most common cause of Age,y | SAH is saccular (berry) aneurysm rupture, with intracranial | 280 1 arterial dissection and mycotic aneurysm rupture being less <80 common. Other rare causes of SAH are the reversible cere- | Total ICH score 0-6 | bral vasoconstriction syndromes, dural sinus thrombosis, vascular malformations, and cerebral amyloid angiopathy. GSC = Glasgow Coma Scale; ICH = intracerebral hemorrhage; IVH = intraventricular hemorrhage. Saccular aneurysms often can be visualized with CTA or GCS score indicates GCS score on initial presentation (or after resuscitation); ICH MRA, although the resolution is insufficient to detect volume, volume on initial CT calculated using ABC/2 method; and IVH, presence of any IVH on initial CT. smaller aneurysms; catheter-based angiography is neces- sary for the definitive diagnosis of aneurysms and other Reprinted with permission from Hemphill JC 3rd, Bonovich DC, Besmertis L, | Manley GT, Johnston SC. The ICH score: a simple, reliable grading scale for causes of SAH. | intracerebral hemorrhage. Stroke. 2001;32:891-7. [PMID: 11283388] Elevated intracranial pressure from obstructive hydro- cephalus and/or global cerebral edema is a common thereby weakening the arterial wall and making it prone to consequence of SAH and has a high mortality without rupture. intervention. Examination findings that raise concern for The mainstay of acute treatment and prevention is control elevated intracranial pressure include impairment in con- of blood pressure. Clinical and radiologic features can be used sciousness, loss of brainstem reflexes, and stereotyped pos- to calculate a patient’s ICH score, which informs 30-day mor- turing movements to painful stimuli. The presence of tality and is recommended in the assessment of patients with hydrocephalus on neuroimaging should prompt neurosur- ICH (Table 25). The main cause of early neurologic deteriora- gical placement of an external ventricular drain to measure tion is hematoma expansion. Another leading cause of death and relieve elevated intracranial pressure. Impaired con- is early withdrawal of care. Guidelines caution against termi- sciousness due to nonconvulsive status epilepticus also may nation of care within the first 48 hours. occur and requires electroencephalographic monitoring for diagnosis.

Elevated intracranial pressure from obstructive hydro- cephalus and/or global cerebral edema is a common thereby weakening the arterial wall and making it prone to consequence of SAH and has a high mortality without rupture. intervention. Examination findings that raise concern for The mainstay of acute treatment and prevention is control elevated intracranial pressure include impairment in con- of blood pressure. Clinical and radiologic features can be used sciousness, loss of brainstem reflexes, and stereotyped pos- to calculate a patient’s ICH score, which informs 30-day mor- turing movements to painful stimuli. The presence of tality and is recommended in the assessment of patients with hydrocephalus on neuroimaging should prompt neurosur- ICH (Table 25). The main cause of early neurologic deteriora- gical placement of an external ventricular drain to measure tion is hematoma expansion. Another leading cause of death and relieve elevated intracranial pressure. Impaired con- is early withdrawal of care. Guidelines caution against termi- sciousness due to nonconvulsive status epilepticus also may nation of care within the first 48 hours. occur and requires electroencephalographic monitoring for diagnosis. ¢ Catheter-based angiography is necessary for the defini- Intracerebral Hemorrhage tive diagnosis of aneurysms and other causes of suba- ICH can present similarly to ischemic stroke, with headache rachnoid hemorrhage. and impaired consciousness as distinguishing characteristics. ¢ In subarachnoid hemorrhage, the presence of hydro- The most common cause of ICH that affects deep structures of cephalus on neuroimaging is associated with high mor- the brain (basal ganglia, thalamus, pons, cerebellum) is hyper- tality and should prompt neurosurgical placement of an tension. Lobar hemorrhages near the cortical surface may have external ventricular drain to relieve elevated intracranial various causes, including hypertension, hemorrhagic tumors, pressure. and cortical vein thrombosis. In patients older than 55 years, ¢ The most common cause of intracerebral hemorrhage especially in those without hypertension, lobar ICH may be that affects deep structures of the brain (basal ganglia, due to cerebral amyloid angiopathy. In this syndrome, amyloid thalamus, pons, cerebellum) is hypertension; the main- protein similar to that seen pathologically in Alzheimer dis- stay of prevention is control of blood pressure. ease deposits in cerebral arterioles near the cortical surface,

¢ Catheter-based angiography is necessary for the defini- Intracerebral Hemorrhage tive diagnosis of aneurysms and other causes of suba- ICH can present similarly to ischemic stroke, with headache rachnoid hemorrhage. and impaired consciousness as distinguishing characteristics. ¢ In subarachnoid hemorrhage, the presence of hydro- The most common cause of ICH that affects deep structures of cephalus on neuroimaging is associated with high mor- the brain (basal ganglia, thalamus, pons, cerebellum) is hyper- tality and should prompt neurosurgical placement of an tension. Lobar hemorrhages near the cortical surface may have external ventricular drain to relieve elevated intracranial various causes, including hypertension, hemorrhagic tumors, pressure. and cortical vein thrombosis. In patients older than 55 years, ¢ The most common cause of intracerebral hemorrhage especially in those without hypertension, lobar ICH may be that affects deep structures of the brain (basal ganglia, due to cerebral amyloid angiopathy. In this syndrome, amyloid thalamus, pons, cerebellum) is hypertension; the main- protein similar to that seen pathologically in Alzheimer dis- stay of prevention is control of blood pressure. ease deposits in cerebral arterioles near the cortical surface, 32

Stroke In-Hospital Stroke Considerations latest guidelines clarifying relative exclusion criteria and defin- In-hospital stroke is most often ischemic and frequently ing nondisabling symptoms (Table 26). Other thrombolytic observed perioperatively. Patients undergoing cardiac surgery agents have not yet been approved for use in acute ischemic involving cardiopulmonary bypass, particularly multivalve stroke. procedures, are at highest risk for stroke in the postoperative The main complication of alteplase treatment is sympto setting. The most common cause is atrial fibrillation. matic ICH, which can present with headache or worsening of The modifiable preoperative risk factors for in-hospital NIHSS score or level of consciousness. Symptomatic hemor- stroke are similar to those causing stroke in the short term rhage occurs in up to 6% of treated patients, and mortality can without surgery, including symptomatic extracranial ICA ste- be as high as 50% when present. The main risk factors for nosis of greater than 70%. Patients with a recent stroke sec- symptomatic hemorrhage are treatment after 4.5 hours and ondary to ICA stenosis who are undergoing nonemergent hypertension before and after treatment. Accordingly, before surgery are likely to benefit from revascularization before- treatment with alteplase, the patient’s blood pressure should hand. The presence of asymptomatic ICA stenosis, however, is be less than 185/110 mm Hg. Higher readings should prompt not clearly associated with perioperative stroke, and routine administration of IV labetalol or nicardipine before alteplase. prophylactic ICA revascularization is not indicated. Nitrates should be avoided because of their potential to Stroke within 30 days of surgery, regardless of cause, increase intracranial pressure. increases the risk of perioperative stroke; elective surgeries After treatment with alteplase, frequent monitoring of within this time should be avoided. Patients with stroke neurologic status and vital signs is required in the first involving a large brain volume or with a recent hemorrhagic 24 hours. Neurologic worsening should prompt urgent neuro-

increases the risk of perioperative stroke; elective surgeries After treatment with alteplase, frequent monitoring of within this time should be avoided. Patients with stroke neurologic status and vital signs is required in the first involving a large brain volume or with a recent hemorrhagic 24 hours. Neurologic worsening should prompt urgent neuro- stroke also are at risk of cerebral hemorrhage if placed on car- imaging. Blood pressure should be maintained below diopulmonary bypass and/or anticoagulation. If possible, 180/105 mm Hg, and both antiplatelet and anticoagulant agents nonemergency major cardiac procedures should be avoided. should be held for the first 24 hours after alteplase administra- tion. After 24 hours, antiplatelet agents for stroke prevention and anticoagulant agents for deep venous thrombosis preven- e Patients undergoing cardiac surgery involving cardio- tion can be started if hemorrhage is absent on imaging. pulmonary bypass, particularly multivalve procedures, Endovascular therapy (primarily with intra-arterial are at highest risk for stroke in the postoperative setting, mechanical thrombectomy) within 24 hours of stroke onset most commonly from atrial fibrillation. can be considered for select patients with a clinically sus- e Stroke within 30 days of surgery, regardless of cause, pected large-vessel occlusion and specific examination and

nonemergency major cardiac procedures should be avoided. should be held for the first 24 hours after alteplase administra- tion. After 24 hours, antiplatelet agents for stroke prevention and anticoagulant agents for deep venous thrombosis preven- e Patients undergoing cardiac surgery involving cardio- tion can be started if hemorrhage is absent on imaging. pulmonary bypass, particularly multivalve procedures, Endovascular therapy (primarily with intra-arterial are at highest risk for stroke in the postoperative setting, mechanical thrombectomy) within 24 hours of stroke onset most commonly from atrial fibrillation. can be considered for select patients with a clinically sus- e Stroke within 30 days of surgery, regardless of cause, pected large-vessel occlusion and specific examination and increases the risk of perioperative stroke, and elective radiologic findings, such as a measurable neurologic deficit surgeries within this time should be avoided. and small but radiographically evident ischemic changes. In patients for whom endovascular therapy is considered, prompt noninvasive vessel imaging with CTA or MRA is recommended. The evaluation for endovascular stroke therapy with vessel Acute Stroke Therapy imaging, however, should not replace or delay the administra- Ischemic Stroke Treatment tion of alteplase in otherwise eligible patients. A treatment Thrombolysis and Endovascular Therapy algorithm for stroke within 6 hours of onset is provided in Intravenous (IV) recombinant tissue plasminogen activator Figure 15. (e.g., alteplase) is the only thrombolytic agent approved for use in acute ischemic stroke. Alteplase is most effective when Antiplatelet Therapy, Anticoagulation, administered early, and treatment within 3 hours of ischemic and Medical Management stroke onset with disabling symptoms is associated with a sig- For patients with acute ischemic stroke who are not eligible for nificant reduction in disability at 3 months. In patients with either thrombolysis or endovascular stroke therapy, antiplate- acute ischemic stroke who awake with stroke symptoms or have let therapy is the mainstay of acute treatment. When adminis- unclear time of onset >4.5 hours from baseline state, MRI to tered either orally or rectally within 48 hours of stoke, aspirin identify diffusion-positive FLAIR-negative lesions can be useful reduces the short-term risk of recurrent stroke, and its use in for selecting those who can benefit from IV alteplase adminis- the acute setting is a stroke-specific quality-of-care core meas- tration within 4.5 hours of stroke symptom recognition. Because ure. Monotherapy with clopidogrel, however, has no estab- of the associated delays, obtaining advanced imaging or labora- lished benefit in the acute stroke setting. tory values should be avoided before treatment unless coagu- The patient with TIA or minor stroke, usually defined as lopathy or thrombocytopenia is suspected. Treatment should an NIHSS score of 5 or less, has been the focus of recent trials start within 60 minutes of arrival at the emergency department of antiplatelet therapy because of the high short-term risk of or detection of in-hospital stroke, with best practices recom- recurrent events. In one recent trial, aspirin was compared to mending treatment within 30 minutes. Contraindications for ticagrelor within 24 hours of stroke onset, and no difference treatment with alteplase have evolved over the years, with the between the two medications in the risk of recurrent stroke

increases the risk of perioperative stroke, and elective radiologic findings, such as a measurable neurologic deficit surgeries within this time should be avoided. and small but radiographically evident ischemic changes. In patients for whom endovascular therapy is considered, prompt noninvasive vessel imaging with CTA or MRA is recommended. The evaluation for endovascular stroke therapy with vessel Acute Stroke Therapy imaging, however, should not replace or delay the administra- Ischemic Stroke Treatment tion of alteplase in otherwise eligible patients. A treatment Thrombolysis and Endovascular Therapy algorithm for stroke within 6 hours of onset is provided in Intravenous (IV) recombinant tissue plasminogen activator Figure 15. (e.g., alteplase) is the only thrombolytic agent approved for use in acute ischemic stroke. Alteplase is most effective when Antiplatelet Therapy, Anticoagulation, administered early, and treatment within 3 hours of ischemic and Medical Management stroke onset with disabling symptoms is associated with a sig- For patients with acute ischemic stroke who are not eligible for nificant reduction in disability at 3 months. In patients with either thrombolysis or endovascular stroke therapy, antiplate- acute ischemic stroke who awake with stroke symptoms or have let therapy is the mainstay of acute treatment. When adminis- unclear time of onset >4.5 hours from baseline state, MRI to tered either orally or rectally within 48 hours of stoke, aspirin identify diffusion-positive FLAIR-negative lesions can be useful reduces the short-term risk of recurrent stroke, and its use in for selecting those who can benefit from IV alteplase adminis- the acute setting is a stroke-specific quality-of-care core meas- tration within 4.5 hours of stroke symptom recognition. Because ure. Monotherapy with clopidogrel, however, has no estab- of the associated delays, obtaining advanced imaging or labora- lished benefit in the acute stroke setting. tory values should be avoided before treatment unless coagu- The patient with TIA or minor stroke, usually defined as lopathy or thrombocytopenia is suspected. Treatment should an NIHSS score of 5 or less, has been the focus of recent trials start within 60 minutes of arrival at the emergency department of antiplatelet therapy because of the high short-term risk of or detection of in-hospital stroke, with best practices recom- recurrent events. In one recent trial, aspirin was compared to mending treatment within 30 minutes. Contraindications for ticagrelor within 24 hours of stroke onset, and no difference treatment with alteplase have evolved over the years, with the between the two medications in the risk of recurrent stroke 33

Stroke TABLE 26. Contraindications to Intravenous Alteplase in Adults with Acute Ischemic Stroke Absolute Exclusion Criteria Relative Exclusion Criteria | Significant head trauma or prior stroke in the previous 3 months Minor or rapidly improving nondisabling symptoms? | Suspicion of subarachnoid hemorrhage Pregnancy | | Noncompressible site arterial puncture within 7 days Seizure at onset | Intracranial neoplasm, arteriovenous malformation, aneurysm Major surgery or serious trauma within 14 days | Recent intracranial or spinal surgery Recent gastrointestinal or genitourinary bleeding within 21 days | Blood pressure 185/110 mm Hg despite treatment Recent acute myocardial infarction Active internal bleeding Active bleeding diathesis | Platelet count 100,000/uL (100 x 109/L) Heparin within 48 hours with an activated partial thromboplastin time above normal range Current use of anticoagulant with INR >1.7 Current use of non-vitamin K antagonist anticoagulants (within | | 48 hours) with associated elevated relevant laboratory tests Blood glucose less 50 mg/dL (2.8 mmol/L) Noncontrast head CT demonstrated multi-lobar infarction with | >1/3 of the hemisphere involved @Disabling symptoms are defined as complete hemianopia (score of 2-3 on National Institutes of Health Stroke Scale [NIHSS] question 3), visual or sensory extinction (score of 1-2 on NIHSS question 11), any weakness against gravity (score of 2-4 on NIHSS question 6 or 7), and total NIHSS score >5.

Noncontrast head CT demonstrated multi-lobar infarction with | >1/3 of the hemisphere involved @Disabling symptoms are defined as complete hemianopia (score of 2-3 on National Institutes of Health Stroke Scale [NIHSS] question 3), visual or sensory extinction (score of 1-2 on NIHSS question 11), any weakness against gravity (score of 2-4 on NIHSS question 6 or 7), and total NIHSS score >5. Adapted from Demaerschalk BM, Kleindorfer DO, Adeoye OM, Demchuk AM, Fugate JE, Grotta JC, et al; American Heart Association Stroke Council and Council on Epidemiology —_ | and Prevention. Scientific Rationale for the Inclusion and Exclusion Criteria for Intravenous Alteplase in Acute Ischemic Stroke: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2016;47:581-641. [PMID: 26696642] doi:10.1161/STR.0000000000000086 New onset neurologic deficit within 24 hours of onset with no hemorrhage noted on head CT Less than 4.5 4.5-24 hours from hours from onset onset v Eligible for intravenous thrombolysis? Yes i | Ne Administer intravenous a. Suspected large vessel occlusion Vv. tissue plasminogen activator b. Measurable neurologic deficit c. Lack of large area of hypodensity on head CT (1/3 of middle cerebral artery territory)

Yes i | Ne Administer intravenous a. Suspected large vessel occlusion Vv. tissue plasminogen activator b. Measurable neurologic deficit c. Lack of large area of hypodensity on head CT (1/3 of middle cerebral artery territory) No | Yes No if given intravenousitissue Refer for immediate intracranial vessel ffnet given plasminogen activator imaging with CT or MR angiography. intravenous tissue a plasminogen a. Admit to step down unit or ICU for neurologic checks and ae vance! ‘ pi a, activator blood pressure monitoring (goal, < 180/105 mm Hg): SaaibaIayy Pie seu oeclusioniabsent ¢ Every 15 minutes for 2 hours from the initial infusion v. ¢ Every 30 minutes for the following 6 hours Admit to stroke unit: ¢ Every hour for the following 16 hours a. Start aspirin (rectally if b. Hold all antiplatelet or anticoagulant agents. dysphagia screen is positive). c. Avoid placement of indwelling bladder catheters, b. Allow blood pressures up to nasogastric tubes, and intra-arterial blood pressure catheters v 220/120 mm Hg unless evidence unless needed for safe management of the patient. Referforendovasculsr of end-organ damage exists. c. Repeat neuroimaging with either CT or MRI at least 24 < strokethera c. Start deep venous thrombosis hours before starting antiplatelet or anticoagulant agents. = prophylaxis.

No | Yes No if given intravenousitissue Refer for immediate intracranial vessel ffnet given plasminogen activator imaging with CT or MR angiography. intravenous tissue a plasminogen a. Admit to step down unit or ICU for neurologic checks and ae vance! ‘ pi a, activator blood pressure monitoring (goal, < 180/105 mm Hg): SaaibaIayy Pie seu oeclusioniabsent ¢ Every 15 minutes for 2 hours from the initial infusion v. ¢ Every 30 minutes for the following 6 hours Admit to stroke unit: ¢ Every hour for the following 16 hours a. Start aspirin (rectally if b. Hold all antiplatelet or anticoagulant agents. dysphagia screen is positive). c. Avoid placement of indwelling bladder catheters, b. Allow blood pressures up to nasogastric tubes, and intra-arterial blood pressure catheters v 220/120 mm Hg unless evidence unless needed for safe management of the patient. Referforendovasculsr of end-organ damage exists. c. Repeat neuroimaging with either CT or MRI at least 24 < strokethera c. Start deep venous thrombosis hours before starting antiplatelet or anticoagulant agents. = prophylaxis. FIGURE 15. Proposed pathway for the evaluation and treatment of an acute stroke within 24 hours of onset. ASPECTS: Alberta Stroke Program Early CT Score

No | Yes No if given intravenousitissue Refer for immediate intracranial vessel ffnet given plasminogen activator imaging with CT or MR angiography. intravenous tissue a plasminogen a. Admit to step down unit or ICU for neurologic checks and ae vance! ‘ pi a, activator blood pressure monitoring (goal, < 180/105 mm Hg): SaaibaIayy Pie seu oeclusioniabsent ¢ Every 15 minutes for 2 hours from the initial infusion v. ¢ Every 30 minutes for the following 6 hours Admit to stroke unit: ¢ Every hour for the following 16 hours a. Start aspirin (rectally if b. Hold all antiplatelet or anticoagulant agents. dysphagia screen is positive). c. Avoid placement of indwelling bladder catheters, b. Allow blood pressures up to nasogastric tubes, and intra-arterial blood pressure catheters v 220/120 mm Hg unless evidence unless needed for safe management of the patient. Referforendovasculsr of end-organ damage exists. c. Repeat neuroimaging with either CT or MRI at least 24 < strokethera c. Start deep venous thrombosis hours before starting antiplatelet or anticoagulant agents. = prophylaxis. FIGURE 15. Proposed pathway for the evaluation and treatment of an acute stroke within 24 hours of onset. ASPECTS: Alberta Stroke Program Early CT Score See Table 26 for exclusion criteria for alteplase (tissue plasminogen activator).

No | Yes No if given intravenousitissue Refer for immediate intracranial vessel ffnet given plasminogen activator imaging with CT or MR angiography. intravenous tissue a plasminogen a. Admit to step down unit or ICU for neurologic checks and ae vance! ‘ pi a, activator blood pressure monitoring (goal, < 180/105 mm Hg): SaaibaIayy Pie seu oeclusioniabsent ¢ Every 15 minutes for 2 hours from the initial infusion v. ¢ Every 30 minutes for the following 6 hours Admit to stroke unit: ¢ Every hour for the following 16 hours a. Start aspirin (rectally if b. Hold all antiplatelet or anticoagulant agents. dysphagia screen is positive). c. Avoid placement of indwelling bladder catheters, b. Allow blood pressures up to nasogastric tubes, and intra-arterial blood pressure catheters v 220/120 mm Hg unless evidence unless needed for safe management of the patient. Referforendovasculsr of end-organ damage exists. c. Repeat neuroimaging with either CT or MRI at least 24 < strokethera c. Start deep venous thrombosis hours before starting antiplatelet or anticoagulant agents. = prophylaxis. FIGURE 15. Proposed pathway for the evaluation and treatment of an acute stroke within 24 hours of onset. ASPECTS: Alberta Stroke Program Early CT Score See Table 26 for exclusion criteria for alteplase (tissue plasminogen activator). 34

Stroke during 90 days of treatment was noted. In patients presenting with minor noncardioembolic ischemic stroke (NIHSS score e Treatment with intravenous (IV) recombinant tissue <3) who did not receive IV alteplase, treatment with dual plasminogen activator (e.g., alteplase) within 3 hours of antiplatelet therapy (aspirin and clopidogrel) started within ischemic stroke onset is associated with a significant 24 hours after symptom onset and continued for 21 days is reduction in disability at 3 months after stroke; in effective in reducing recurrent ischemic stroke for a period of patients with acute ischemic stroke who awake with up to 90 days from symptom onset. stroke symptoms or have unclear time of onset more Acute administration of anticoagulation in ischemic than 4.5 hours from baseline state, MRI to identify dif- stroke (whether related to atrial fibrillation or not) does not fusion-positive FLAIR-negative lesions can be useful for reduce the short-term risk of recurrent stroke and increases selecting those who can benefit from IV alteplase the risk of hemorrhage into the territory of cerebral infarction administration within 4.5 hours of stroke symptom (hemorrhagic conversion). recognition. Management of acute hypertension in ischemic stroke e Endovascular therapy within 24 hours of stroke onset differs when thrombolysis is not involved. Early treatment of can be considered for select patients with a clinically hypertension is indicated when required by comorbid con- suspected large-vessel occlusion and specific examina- ditions (such as concomitant acute coronary event, acute tion and radiologic findings, such as a measurable neu- heart failure, aortic dissection, postfibrinolysis intracranial rologic deficit and small but radiographically evident hemorrhage, or preeclampsia/eclampsia). In patients with ischemic changes. blood pressure 220/120 mm Hg or greater who did not e When administered within 48 hours of ischemic stroke receive IV alteplase or mechanical thrombectomy and have that is not eligible for thrombolysis, aspirin reduces the no comorbid conditions requiring urgent antihypertensive short-term risk of recurrent stroke. treatment, the benefit of initiating or reinitiating treatment of hypertension within the first 48 to 72 hours is uncertain. e Acute administration of anticoagulation for ischemic

during 90 days of treatment was noted. In patients presenting with minor noncardioembolic ischemic stroke (NIHSS score e Treatment with intravenous (IV) recombinant tissue <3) who did not receive IV alteplase, treatment with dual plasminogen activator (e.g., alteplase) within 3 hours of antiplatelet therapy (aspirin and clopidogrel) started within ischemic stroke onset is associated with a significant 24 hours after symptom onset and continued for 21 days is reduction in disability at 3 months after stroke; in effective in reducing recurrent ischemic stroke for a period of patients with acute ischemic stroke who awake with up to 90 days from symptom onset. stroke symptoms or have unclear time of onset more Acute administration of anticoagulation in ischemic than 4.5 hours from baseline state, MRI to identify dif- stroke (whether related to atrial fibrillation or not) does not fusion-positive FLAIR-negative lesions can be useful for reduce the short-term risk of recurrent stroke and increases selecting those who can benefit from IV alteplase the risk of hemorrhage into the territory of cerebral infarction administration within 4.5 hours of stroke symptom (hemorrhagic conversion). recognition. Management of acute hypertension in ischemic stroke e Endovascular therapy within 24 hours of stroke onset differs when thrombolysis is not involved. Early treatment of can be considered for select patients with a clinically hypertension is indicated when required by comorbid con- suspected large-vessel occlusion and specific examina- ditions (such as concomitant acute coronary event, acute tion and radiologic findings, such as a measurable neu- heart failure, aortic dissection, postfibrinolysis intracranial rologic deficit and small but radiographically evident hemorrhage, or preeclampsia/eclampsia). In patients with ischemic changes. blood pressure 220/120 mm Hg or greater who did not e When administered within 48 hours of ischemic stroke receive IV alteplase or mechanical thrombectomy and have that is not eligible for thrombolysis, aspirin reduces the no comorbid conditions requiring urgent antihypertensive short-term risk of recurrent stroke. treatment, the benefit of initiating or reinitiating treatment of hypertension within the first 48 to 72 hours is uncertain. e Acute administration of anticoagulation for ischemic It might be reasonable to lower blood pressure by 15% dur- stroke (whether related to atrial fibrillation or not) does

during 90 days of treatment was noted. In patients presenting with minor noncardioembolic ischemic stroke (NIHSS score e Treatment with intravenous (IV) recombinant tissue <3) who did not receive IV alteplase, treatment with dual plasminogen activator (e.g., alteplase) within 3 hours of antiplatelet therapy (aspirin and clopidogrel) started within ischemic stroke onset is associated with a significant 24 hours after symptom onset and continued for 21 days is reduction in disability at 3 months after stroke; in effective in reducing recurrent ischemic stroke for a period of patients with acute ischemic stroke who awake with up to 90 days from symptom onset. stroke symptoms or have unclear time of onset more Acute administration of anticoagulation in ischemic than 4.5 hours from baseline state, MRI to identify dif- stroke (whether related to atrial fibrillation or not) does not fusion-positive FLAIR-negative lesions can be useful for reduce the short-term risk of recurrent stroke and increases selecting those who can benefit from IV alteplase the risk of hemorrhage into the territory of cerebral infarction administration within 4.5 hours of stroke symptom (hemorrhagic conversion). recognition. Management of acute hypertension in ischemic stroke e Endovascular therapy within 24 hours of stroke onset differs when thrombolysis is not involved. Early treatment of can be considered for select patients with a clinically hypertension is indicated when required by comorbid con- suspected large-vessel occlusion and specific examina- ditions (such as concomitant acute coronary event, acute tion and radiologic findings, such as a measurable neu- heart failure, aortic dissection, postfibrinolysis intracranial rologic deficit and small but radiographically evident hemorrhage, or preeclampsia/eclampsia). In patients with ischemic changes. blood pressure 220/120 mm Hg or greater who did not e When administered within 48 hours of ischemic stroke receive IV alteplase or mechanical thrombectomy and have that is not eligible for thrombolysis, aspirin reduces the no comorbid conditions requiring urgent antihypertensive short-term risk of recurrent stroke. treatment, the benefit of initiating or reinitiating treatment of hypertension within the first 48 to 72 hours is uncertain. e Acute administration of anticoagulation for ischemic It might be reasonable to lower blood pressure by 15% dur- stroke (whether related to atrial fibrillation or not) does ing the first 24 hours after onset of stroke. Statins have not not reduce the short-term risk of recurrent stroke and increases the risk of hemorrhagic conversion. been shown to reduce the risk of recurrent stroke when administered within 30 days but can be considered after a dysphagia evaluation has been completed, especially in Hemorrhagic Stroke Treatment those patients with an atherosclerotic stroke subtype. See Intracerebral Hemorrhage Treatment MKSAP 19 General Internal Medicine 1. Treatment of acute ICH is centered on preventing hematoma Hyperglycemia in the setting of an acute ischemic stroke expansion. The primary predictor of early hematoma expan- is a common clinical problem. A recent randomized clinical sion is elevated blood pressure. Treatment of blood pressure is trial notes the lack of benefit and increased harm associated recommended for patients with ICH who have a systolic blood with intensive treatment of hyperglycemia in acute ischemic pressure greater than 180 mm Hg. The most appropriate agent stroke (see MKSAP 19 Endocrinology and Metabolism). for blood pressure control in this circumstance is not well A 2018 systematic review found that supplemental oxy- established. Parenteral medications delivered by IV infusion gen in patients with normal oxygen saturation as measured with frequent blood pressure monitoring have the benefit of by pulse oximetry (SpO,) increases mortality in patients close titration to the intended target. IV nitrates (such as nitro- with stroke and other acute illnesses (see MKSAP 19 glycerin) and nitroprusside may raise intracranial pressure Pulmonary and Critical Care Medicine). An international and reduce blood flow to the ischemic region and should be guideline makes a strong recommendation that oxygen ther- avoided in patients with ICH. Guidelines for the treatment of apy not be initiated in patients with stroke and an SpO, of ICH indicate that acutely treating the systolic blood pressure in 93% or greater and a weak recommendation that oxygen a specialized intensive care unit until it is 140 mm Hg is rea- therapy be withheld in patients with stroke and an SpO, of sonable if the presenting systolic pressure is 180 to 220 mm Hg. 90% or greater; in patients receiving oxygen therapy, the A recently completed trial compared a goal systolic blood SpO, should be maintained at less than 96% (with a pressure of 110 to 140 mm Hg with one of 140 to 180 mm Hg in suggested therapeutic range for SpO, of 93% to less than patients with a systolic blood pressure of greater than 180 mm 96%). The American Heart Association/American Stroke Hg seen within 4.5 hours of ICH onset. The more intensive Association (2018 guideline) recommends oxygen to main- control arm achieved a mean systolic blood pressure of tain an oxygen saturation of 94% or greater, with no upper 128 mm Hg versus 141 mm Hg in the usual care arm. No differ- limit provided, and the European Academy of Neurology ence in mortality or neurologic outcomes was seen, but a sig- recommends oxygen to maintain normoxia in patients with nificantly higher rate of adverse renal events occurred with an arterial oxygen saturation less than 95%, with no upper intensive control. Treating systolic blood pressure if greater limit provided. than 180 mm Hgis still advised but should be performed

ing the first 24 hours after onset of stroke. Statins have not not reduce the short-term risk of recurrent stroke and increases the risk of hemorrhagic conversion. been shown to reduce the risk of recurrent stroke when administered within 30 days but can be considered after a dysphagia evaluation has been completed, especially in Hemorrhagic Stroke Treatment those patients with an atherosclerotic stroke subtype. See Intracerebral Hemorrhage Treatment MKSAP 19 General Internal Medicine 1. Treatment of acute ICH is centered on preventing hematoma Hyperglycemia in the setting of an acute ischemic stroke expansion. The primary predictor of early hematoma expan- is a common clinical problem. A recent randomized clinical sion is elevated blood pressure. Treatment of blood pressure is trial notes the lack of benefit and increased harm associated recommended for patients with ICH who have a systolic blood with intensive treatment of hyperglycemia in acute ischemic pressure greater than 180 mm Hg. The most appropriate agent stroke (see MKSAP 19 Endocrinology and Metabolism). for blood pressure control in this circumstance is not well A 2018 systematic review found that supplemental oxy- established. Parenteral medications delivered by IV infusion gen in patients with normal oxygen saturation as measured with frequent blood pressure monitoring have the benefit of by pulse oximetry (SpO,) increases mortality in patients close titration to the intended target. IV nitrates (such as nitro- with stroke and other acute illnesses (see MKSAP 19 glycerin) and nitroprusside may raise intracranial pressure Pulmonary and Critical Care Medicine). An international and reduce blood flow to the ischemic region and should be guideline makes a strong recommendation that oxygen ther- avoided in patients with ICH. Guidelines for the treatment of apy not be initiated in patients with stroke and an SpO, of ICH indicate that acutely treating the systolic blood pressure in 93% or greater and a weak recommendation that oxygen a specialized intensive care unit until it is 140 mm Hg is rea- therapy be withheld in patients with stroke and an SpO, of sonable if the presenting systolic pressure is 180 to 220 mm Hg. 90% or greater; in patients receiving oxygen therapy, the A recently completed trial compared a goal systolic blood SpO, should be maintained at less than 96% (with a pressure of 110 to 140 mm Hg with one of 140 to 180 mm Hg in suggested therapeutic range for SpO, of 93% to less than patients with a systolic blood pressure of greater than 180 mm 96%). The American Heart Association/American Stroke Hg seen within 4.5 hours of ICH onset. The more intensive Association (2018 guideline) recommends oxygen to main- control arm achieved a mean systolic blood pressure of tain an oxygen saturation of 94% or greater, with no upper 128 mm Hg versus 141 mm Hg in the usual care arm. No differ- limit provided, and the European Academy of Neurology ence in mortality or neurologic outcomes was seen, but a sig- recommends oxygen to maintain normoxia in patients with nificantly higher rate of adverse renal events occurred with an arterial oxygen saturation less than 95%, with no upper intensive control. Treating systolic blood pressure if greater limit provided. than 180 mm Hgis still advised but should be performed 35

Stroke cautiously, and systolic blood pressure goals of less 140 mm Hg edema, seizures, and cerebral vasospasm are other leading should be avoided. causes of poor outcomes. Another risk factor for hematoma expansion is coagu- Cerebral vasospasm with resultant cerebral ischemia and lopathy due to either antiplatelet agents or anticoagulation. neurologic worsening may develop beginning near day 5. The There is no benefit, and potential harm, with the use of plate- degree of hemorrhage on a head CT scan may predict the risk let transfusions for patients taking antiplatelet agents at the of vasospasm, but frequent monitoring and daily transcranial time of hemorrhage. Anticoagulation should be reversed, Doppler imaging is recommended in all patients. Nimodipine although this incurs an increased risk of thrombotic events. should be started as early as possible to improve neurologic For patients without coagulopathy, recombinant factor VII has outcomes. The drug is continued for 21 days or until hospital no neurologic benefit and is associated with high rates of discharge. If there is a high clinical suspicion of vasospasm, venous thromboembolic events. CTA or catheter-based angiography may be needed to establish Another source of neurologic decline in patients with ICH vasospasm as the cause of neurologic worsening. The latter has is nonconvulsive status epilepticus, which may present with the added benefit of potential endovascular treatment, includ- impaired consciousness. Use of prophylactic antiepileptic ing use of intra-arterial vasodilators and angioplasty. Another medications in patients with ICH is not reeommended, how- treatment option for vasospasm in patients with a treated ever, unless there are definitive clinical or electroencephalo- aneurysm is induced hypertension, although the exact treat- graphic seizures. ment targets are not well established. Elevated intracranial pressure is a major determinant of Medical complications are a significant source of morbid- morbidity and mortality in ICH. Osmotherapy with mannitol ity and mortality in patients with SAH. Patients with impaired or hypertonic saline may temporarily reduce intracranial pres- consciousness and coma at presentation are at highest risk for sure in ICH; glucocorticoids are ineffective in reducing cere- stunned myocardium (with a decrease in left ventricular ejec- bral edema in ICH and should not be routinely administered. tion fraction) and pulmonary edema due to the large sympa- External ventricular drainage is indicated with hydrocephalus thetic surge in SAH. Other medical complications include and impaired consciousness; other surgical measures are not pulmonary and urinary tract infections, dysphagia, the syn- routinely indicated unless as life-saving measures in rapidly drome of inappropriate antidiuretic hormone secretion, and deteriorating patients. Cerebellar hemorrhages greater than cerebral salt wasting. Because of these possible medical and 3 centimeters in diameter are the exception because early neurologic complications, patients with SAH require care in a surgical evacuation is necessary to prevent hydrocephalus, specialized ICU with experience in treating SAH. brainstem compression, and neurologic deterioration.

cautiously, and systolic blood pressure goals of less 140 mm Hg edema, seizures, and cerebral vasospasm are other leading should be avoided. causes of poor outcomes. Another risk factor for hematoma expansion is coagu- Cerebral vasospasm with resultant cerebral ischemia and lopathy due to either antiplatelet agents or anticoagulation. neurologic worsening may develop beginning near day 5. The There is no benefit, and potential harm, with the use of plate- degree of hemorrhage on a head CT scan may predict the risk let transfusions for patients taking antiplatelet agents at the of vasospasm, but frequent monitoring and daily transcranial time of hemorrhage. Anticoagulation should be reversed, Doppler imaging is recommended in all patients. Nimodipine although this incurs an increased risk of thrombotic events. should be started as early as possible to improve neurologic For patients without coagulopathy, recombinant factor VII has outcomes. The drug is continued for 21 days or until hospital no neurologic benefit and is associated with high rates of discharge. If there is a high clinical suspicion of vasospasm, venous thromboembolic events. CTA or catheter-based angiography may be needed to establish Another source of neurologic decline in patients with ICH vasospasm as the cause of neurologic worsening. The latter has is nonconvulsive status epilepticus, which may present with the added benefit of potential endovascular treatment, includ- impaired consciousness. Use of prophylactic antiepileptic ing use of intra-arterial vasodilators and angioplasty. Another medications in patients with ICH is not reeommended, how- treatment option for vasospasm in patients with a treated ever, unless there are definitive clinical or electroencephalo- aneurysm is induced hypertension, although the exact treat- graphic seizures. ment targets are not well established. Elevated intracranial pressure is a major determinant of Medical complications are a significant source of morbid- morbidity and mortality in ICH. Osmotherapy with mannitol ity and mortality in patients with SAH. Patients with impaired or hypertonic saline may temporarily reduce intracranial pres- consciousness and coma at presentation are at highest risk for sure in ICH; glucocorticoids are ineffective in reducing cere- stunned myocardium (with a decrease in left ventricular ejec- bral edema in ICH and should not be routinely administered. tion fraction) and pulmonary edema due to the large sympa- External ventricular drainage is indicated with hydrocephalus thetic surge in SAH. Other medical complications include and impaired consciousness; other surgical measures are not pulmonary and urinary tract infections, dysphagia, the syn- routinely indicated unless as life-saving measures in rapidly drome of inappropriate antidiuretic hormone secretion, and deteriorating patients. Cerebellar hemorrhages greater than cerebral salt wasting. Because of these possible medical and 3 centimeters in diameter are the exception because early neurologic complications, patients with SAH require care in a surgical evacuation is necessary to prevent hydrocephalus, specialized ICU with experience in treating SAH. brainstem compression, and neurologic deterioration. e Within the first 48 hours of a subarachnoid hemor- e Treatment of blood pressure is recommended for rhage, aneurysmal rebleeding is a major cause of mor- patients with intracerebral hemorrhage whose systolic bidity; early surgical exclusion of the ruptured aneu- blood pressure is greater than 180 mm Hg; intravenous rysm and maintaining a blood pressure of less than nitrates should be avoided. 140/80 mm Hg is required.

e Within the first 48 hours of a subarachnoid hemor- e Treatment of blood pressure is recommended for rhage, aneurysmal rebleeding is a major cause of mor- patients with intracerebral hemorrhage whose systolic bidity; early surgical exclusion of the ruptured aneu- blood pressure is greater than 180 mm Hg; intravenous rysm and maintaining a blood pressure of less than nitrates should be avoided. 140/80 mm Hg is required. HVC e Routine use of platelet transfusion in patients with e In aneurysmal subarachnoid hemorrhage, cerebral vasos- intracerebral hemorrhage who are being treated with pasm with resultant cerebral ischemia and neurologic antiplatelet agents is not indicated. worsening may develop beginning near day 5, and all ¢ Osmotherapy with mannitol or hypertonic saline may patients should be treated with nimodipine to prevent temporarily reduce intracranial pressure in patients poor neurologic outcomes. with intracerebral hemorrhage; glucocorticoids are ineffective and should not be routinely administered.

¢ Osmotherapy with mannitol or hypertonic saline may patients should be treated with nimodipine to prevent temporarily reduce intracranial pressure in patients poor neurologic outcomes. with intracerebral hemorrhage; glucocorticoids are ineffective and should not be routinely administered. e In patients with intracerebral hemorrhage, early surgi- Stroke Prevention cal evacuation of cerebellar hemorrhages greater than Primary Prevention 3 cm in diameter is necessary to prevent hydrocephalus, MKSAP 19 General Internal Medicine 1 provides information brainstem compression, and neurologic deterioration. on the treatment of cardiovascular risk factors related to pri- mary prevention of stroke. Patients with asymptomatic ICA Subarachnoid Hemorrhage Treatment stenosis require primary prevention strategies similar to those Treatment of SAH focuses on prevention of early (<48 hours) used for patients with asymptomatic atherosclerotic disease. and late neurologic complications. Within the first 48 hours, a Contemporary best medical therapy, including high-intensity major cause of morbidity is aneurysmal rebleeding; early surgi- statin therapy, is associated with a low risk of first stroke, likely cal exclusion of the ruptured aneurysm and maintenance of a less than 2% per year. ICA revascularization may reduce the blood pressure of less than 140/80 mm Hg is required. Elevated risk of stroke further, but the risk of the procedure itself must intracranial pressure from obstructive hydrocephalus, cerebral be weighed against the potential benefit. ICA revascularization 36

Stroke for primary prevention is not warranted unless high-risk to be of atherosclerotic origin. See MKSAP 19 General Internal stroke features are present, such as stenosis greater than 80% Medicine 1 for more information. or rapid progression of stenosis. For patients with high-risk The choice of an antiplatelet agent for long-term (+90 days predictors, the decision to refer for revascularization should be from stroke) secondary stroke prevention in the absence of made on an individual basis. Ongoing clinical trials may pro- atrial fibrillation has been the subject of several clinical trials. vide more information on the relative advantages of revascu- Consistent across trials is the finding that long-term use of larization and medical therapy. aspirin and clopidogrel combined, versus a single antiplatelet The main modifiable risk factors for intracranial arterial agent, is associated with no reduction in risk of stroke but an aneurysm growth and rupture are hypertension and active increased risk of hemorrhage and death. Dual antiplatelet tobacco use. Treatment of both is indicated. Surgical treat- therapy with clopidogrel and aspirin given within 24 hours ment of aneurysms with either endovascular therapy or after minor noncardioembolic ischemic stroke in patients who craniotomy is associated with sufficiently high neurologic did not receive IV alteplase and continued for 21 days reduced morbidity that treatment is reserved for patients at high risk recurrent ischemic stroke for a period of up to 90 days from of rupture and low surgical risk. The location and size of the symptom onset. Aspirin should be continued following dual aneurysm are the primary determinants of rupture risk, and antiplatelet therapy for long-term secondary prevention of both MRA and CTA can show these features noninvasively. stroke. Aspirin monotherapy is a reasonable first-line anti- Aneurysms less than 7 millimeters in diameter in the poste- platelet regimen for secondary stroke prevention, although rior circulation and less than 12 millimeters in the anterior clopidogrel or aspirin-dipyridamole is often prescribed circulation have a low risk of rupture and can be managed because of their small absolute risk benefits over aspirin. conservatively. Patients with these aneurysms should Clopidogrel monotherapy, when compared with aspirin mon- undergo annual noninvasive imaging because aneurysmal otherapy in a trial involving ischemic stroke, peripheral arte- growth is a risk factor for rupture and may be an indication rial disease, and myocardial infarction, was associated with a for surgery. Patients with two or more relatives with intracra- 0.9% per year absolute benefit; however, the results of this trial nial aneurysms or SAH also should be offered screening with were driven by peripheral arterial disease outcomes, with no noninvasive neuroimaging. Other predictors of aneurysmal clear difference in recurrent stroke. The combination of aspi- rupture that should prompt surgical consideration include a rin and dipyridamole versus aspirin alone has been associated previous aneurysmal SAH, rapid aneurysm growth, or the with a modestly lower risk of recurrent stroke in the long presence of cranial nerve palsy. term, although the combination is associated with high risk of discontinuation because of headache and other adverse effects.

for primary prevention is not warranted unless high-risk to be of atherosclerotic origin. See MKSAP 19 General Internal stroke features are present, such as stenosis greater than 80% Medicine 1 for more information. or rapid progression of stenosis. For patients with high-risk The choice of an antiplatelet agent for long-term (+90 days predictors, the decision to refer for revascularization should be from stroke) secondary stroke prevention in the absence of made on an individual basis. Ongoing clinical trials may pro- atrial fibrillation has been the subject of several clinical trials. vide more information on the relative advantages of revascu- Consistent across trials is the finding that long-term use of larization and medical therapy. aspirin and clopidogrel combined, versus a single antiplatelet The main modifiable risk factors for intracranial arterial agent, is associated with no reduction in risk of stroke but an aneurysm growth and rupture are hypertension and active increased risk of hemorrhage and death. Dual antiplatelet tobacco use. Treatment of both is indicated. Surgical treat- therapy with clopidogrel and aspirin given within 24 hours ment of aneurysms with either endovascular therapy or after minor noncardioembolic ischemic stroke in patients who craniotomy is associated with sufficiently high neurologic did not receive IV alteplase and continued for 21 days reduced morbidity that treatment is reserved for patients at high risk recurrent ischemic stroke for a period of up to 90 days from of rupture and low surgical risk. The location and size of the symptom onset. Aspirin should be continued following dual aneurysm are the primary determinants of rupture risk, and antiplatelet therapy for long-term secondary prevention of both MRA and CTA can show these features noninvasively. stroke. Aspirin monotherapy is a reasonable first-line anti- Aneurysms less than 7 millimeters in diameter in the poste- platelet regimen for secondary stroke prevention, although rior circulation and less than 12 millimeters in the anterior clopidogrel or aspirin-dipyridamole is often prescribed circulation have a low risk of rupture and can be managed because of their small absolute risk benefits over aspirin. conservatively. Patients with these aneurysms should Clopidogrel monotherapy, when compared with aspirin mon- undergo annual noninvasive imaging because aneurysmal otherapy in a trial involving ischemic stroke, peripheral arte- growth is a risk factor for rupture and may be an indication rial disease, and myocardial infarction, was associated with a for surgery. Patients with two or more relatives with intracra- 0.9% per year absolute benefit; however, the results of this trial nial aneurysms or SAH also should be offered screening with were driven by peripheral arterial disease outcomes, with no noninvasive neuroimaging. Other predictors of aneurysmal clear difference in recurrent stroke. The combination of aspi- rupture that should prompt surgical consideration include a rin and dipyridamole versus aspirin alone has been associated previous aneurysmal SAH, rapid aneurysm growth, or the with a modestly lower risk of recurrent stroke in the long presence of cranial nerve palsy. term, although the combination is associated with high risk of discontinuation because of headache and other adverse effects. HVC e Routine internal carotid artery revascularization for pri- Clopidogrel has been compared with the aspirin-dipyridamole

for primary prevention is not warranted unless high-risk to be of atherosclerotic origin. See MKSAP 19 General Internal stroke features are present, such as stenosis greater than 80% Medicine 1 for more information. or rapid progression of stenosis. For patients with high-risk The choice of an antiplatelet agent for long-term (+90 days predictors, the decision to refer for revascularization should be from stroke) secondary stroke prevention in the absence of made on an individual basis. Ongoing clinical trials may pro- atrial fibrillation has been the subject of several clinical trials. vide more information on the relative advantages of revascu- Consistent across trials is the finding that long-term use of larization and medical therapy. aspirin and clopidogrel combined, versus a single antiplatelet The main modifiable risk factors for intracranial arterial agent, is associated with no reduction in risk of stroke but an aneurysm growth and rupture are hypertension and active increased risk of hemorrhage and death. Dual antiplatelet tobacco use. Treatment of both is indicated. Surgical treat- therapy with clopidogrel and aspirin given within 24 hours ment of aneurysms with either endovascular therapy or after minor noncardioembolic ischemic stroke in patients who craniotomy is associated with sufficiently high neurologic did not receive IV alteplase and continued for 21 days reduced morbidity that treatment is reserved for patients at high risk recurrent ischemic stroke for a period of up to 90 days from of rupture and low surgical risk. The location and size of the symptom onset. Aspirin should be continued following dual aneurysm are the primary determinants of rupture risk, and antiplatelet therapy for long-term secondary prevention of both MRA and CTA can show these features noninvasively. stroke. Aspirin monotherapy is a reasonable first-line anti- Aneurysms less than 7 millimeters in diameter in the poste- platelet regimen for secondary stroke prevention, although rior circulation and less than 12 millimeters in the anterior clopidogrel or aspirin-dipyridamole is often prescribed circulation have a low risk of rupture and can be managed because of their small absolute risk benefits over aspirin. conservatively. Patients with these aneurysms should Clopidogrel monotherapy, when compared with aspirin mon- undergo annual noninvasive imaging because aneurysmal otherapy in a trial involving ischemic stroke, peripheral arte- growth is a risk factor for rupture and may be an indication rial disease, and myocardial infarction, was associated with a for surgery. Patients with two or more relatives with intracra- 0.9% per year absolute benefit; however, the results of this trial nial aneurysms or SAH also should be offered screening with were driven by peripheral arterial disease outcomes, with no noninvasive neuroimaging. Other predictors of aneurysmal clear difference in recurrent stroke. The combination of aspi- rupture that should prompt surgical consideration include a rin and dipyridamole versus aspirin alone has been associated previous aneurysmal SAH, rapid aneurysm growth, or the with a modestly lower risk of recurrent stroke in the long presence of cranial nerve palsy. term, although the combination is associated with high risk of discontinuation because of headache and other adverse effects. HVC e Routine internal carotid artery revascularization for pri- Clopidogrel has been compared with the aspirin-dipyridamole mary prevention of stroke is not warranted unless high- combination in one large clinical trial, with both having simi-

for primary prevention is not warranted unless high-risk to be of atherosclerotic origin. See MKSAP 19 General Internal stroke features are present, such as stenosis greater than 80% Medicine 1 for more information. or rapid progression of stenosis. For patients with high-risk The choice of an antiplatelet agent for long-term (+90 days predictors, the decision to refer for revascularization should be from stroke) secondary stroke prevention in the absence of made on an individual basis. Ongoing clinical trials may pro- atrial fibrillation has been the subject of several clinical trials. vide more information on the relative advantages of revascu- Consistent across trials is the finding that long-term use of larization and medical therapy. aspirin and clopidogrel combined, versus a single antiplatelet The main modifiable risk factors for intracranial arterial agent, is associated with no reduction in risk of stroke but an aneurysm growth and rupture are hypertension and active increased risk of hemorrhage and death. Dual antiplatelet tobacco use. Treatment of both is indicated. Surgical treat- therapy with clopidogrel and aspirin given within 24 hours ment of aneurysms with either endovascular therapy or after minor noncardioembolic ischemic stroke in patients who craniotomy is associated with sufficiently high neurologic did not receive IV alteplase and continued for 21 days reduced morbidity that treatment is reserved for patients at high risk recurrent ischemic stroke for a period of up to 90 days from of rupture and low surgical risk. The location and size of the symptom onset. Aspirin should be continued following dual aneurysm are the primary determinants of rupture risk, and antiplatelet therapy for long-term secondary prevention of both MRA and CTA can show these features noninvasively. stroke. Aspirin monotherapy is a reasonable first-line anti- Aneurysms less than 7 millimeters in diameter in the poste- platelet regimen for secondary stroke prevention, although rior circulation and less than 12 millimeters in the anterior clopidogrel or aspirin-dipyridamole is often prescribed circulation have a low risk of rupture and can be managed because of their small absolute risk benefits over aspirin. conservatively. Patients with these aneurysms should Clopidogrel monotherapy, when compared with aspirin mon- undergo annual noninvasive imaging because aneurysmal otherapy in a trial involving ischemic stroke, peripheral arte- growth is a risk factor for rupture and may be an indication rial disease, and myocardial infarction, was associated with a for surgery. Patients with two or more relatives with intracra- 0.9% per year absolute benefit; however, the results of this trial nial aneurysms or SAH also should be offered screening with were driven by peripheral arterial disease outcomes, with no noninvasive neuroimaging. Other predictors of aneurysmal clear difference in recurrent stroke. The combination of aspi- rupture that should prompt surgical consideration include a rin and dipyridamole versus aspirin alone has been associated previous aneurysmal SAH, rapid aneurysm growth, or the with a modestly lower risk of recurrent stroke in the long presence of cranial nerve palsy. term, although the combination is associated with high risk of discontinuation because of headache and other adverse effects. HVC e Routine internal carotid artery revascularization for pri- Clopidogrel has been compared with the aspirin-dipyridamole mary prevention of stroke is not warranted unless high- combination in one large clinical trial, with both having simi- risk stroke features are present, such as stenosis greater lar efficacy in stroke prevention. Cilostazol has been compared

HVC e Routine internal carotid artery revascularization for pri- Clopidogrel has been compared with the aspirin-dipyridamole mary prevention of stroke is not warranted unless high- combination in one large clinical trial, with both having simi- risk stroke features are present, such as stenosis greater lar efficacy in stroke prevention. Cilostazol has been compared than 80% or rapid progression of stenosis. to aspirin in clinical trials in Japan and China; it has had simi- lar efficacy in reducing ischemic stroke and resulted in slightly HVC e Aneurysms less than 7 millimeters in diameter in the lower hemorrhagic complications, although its use is limited posterior circulation and less than 12 millimeters in the by adverse effects. Other antiplatelet agents, such as ticagrelor anterior circulation have a low risk of rupture and can or prasugrel, have not been examined in long-term trials of be managed conservatively with annual noninvasive secondary stroke prevention, although prasugrel is associated neuroimaging. with a high risk of hemorrhage when used in patients with coronary artery disease who have a history of stroke. No data Secondary Prevention are available on blood assays examining a lack of response to Lifestyle Modifications and Medical Management antiplatelet agents in secondary stroke prevention or on the The risk factors for a second stroke are similar to those for choice of antiplatelet agent after an additional clinical event. ischemic heart disease and other atherosclerotic disease. Warfarin has been compared to aspirin for secondary stroke

Lifestyle Modifications and Medical Management antiplatelet agents in secondary stroke prevention or on the The risk factors for a second stroke are similar to those for choice of antiplatelet agent after an additional clinical event. ischemic heart disease and other atherosclerotic disease. Warfarin has been compared to aspirin for secondary stroke Patients with stroke benefit from diet and exercise changes to prevention in the absence of atrial fibrillation, with no difference maintain cardiometabolic health. Patients with ICH are at high in stroke outcomes reported. In a trial of patients with intracra- risk for recurrent stroke due to hypertension; after the acute nial atherosclerosis, warfarin was associated with increased in-hospital setting, a target blood pressure of less than mortality compared with aspirin. Non-vitamin K antagonist 130/80 mm Hg is advised. Similarly, patients with small sub- anticoagulants have not been tested in clinical trials of stroke not cortical infarcts in whom hypertension is the primary risk involving atrial fibrillation and are not routinely indicated in this factor may also benefit from a systolic blood pressure of less setting. In patients with ESUS, the routine use of direct oral anti- than 130 mm Hg. High-intensity statin therapy to achieve an coagulants is not associated with a reduction in the risk of LDL cholesterol reduction of 50% or greater lowers the risk of stroke. For a review of anticoagulation in atrial fibrillation- stroke among patients with ischemic stroke or TIA presumed related stroke, see MKSAP 19 Cardiovascular Medicine. 37

Stroke Whether to start antithrombotic agents after hemorrhagic stroke has not been as well studied. Patients with cerebral amy- ¢ Symptomatic high-grade intracranial arterial stenosis is HVC loid angiopathy are at particularly high risk of recurrent lobar associated with a high risk of recurrent stroke, but ICH, and the use of antiplatelet agents should only be considered stenting of the affected artery is associated with a high in those with clear secondary prevention indications, such as risk of procedural stroke and should be avoided. coronary stents. Anticoagulation should be avoided in patients with lobar ICH because of the high risk of recurrence. Anticoagulation after ICH also should be avoided in most patients with indications of low thromboembolic risk, such as atrial fibril- Standardized Discharge Orders lation with a low CHA,DS,-Vasc score, and used with caution in Adherence to secondary stroke prevention guidelines is incon- higher-risk scenarios (such as pulmonary emboli). Finally, with sistent after hospital discharge. Standardized discharge orders, adequate control of hypertension, anticoagulation and antiplate- aligned with recommended core measures for patients with let treatment can be considered for appropriate indications ischemic stroke, can reduce the risk of both hospital readmis-

higher-risk scenarios (such as pulmonary emboli). Finally, with sistent after hospital discharge. Standardized discharge orders, adequate control of hypertension, anticoagulation and antiplate- aligned with recommended core measures for patients with let treatment can be considered for appropriate indications ischemic stroke, can reduce the risk of both hospital readmis- 4 weeks after a deep ICH secondary to hypertension. sion and recurrent stroke. These standardized orders ensure that appropriate antiplatelet or anticoagulation agents and high-intensity statin therapy are started on hospital discharge. Surgical Management They include the essential component of patient education The use of surgical approaches for secondary stroke prevention about diet, exercise, smoking cessation, and other healthy has been examined in patients with extracranial ICA and ver- lifestyle choices to reduce the risk of recurrent events. Lastly, tebral artery stenosis, ICA occlusion, intracranial atherosclero- these discharge orders allow for stroke-specific education sis, and PFO-related stroke. In extracranial ICA disease, patients regarding typical stroke symptoms and the importance of with nondisabling stroke or TIA due to ICA stenosis of greater rapid return to care if symptoms occur so that acute stroke than 70% are at high risk for recurrent stroke and may benefit therapeutics can be initiated. from early revascularization. The choice of endarterectomy or angioplasty with stenting is dictated by several patient-specific factors and by local surgical experience. A consistent finding in Prognosis and Recovery trials has been a higher risk of perioperative stroke with stent- Neurologic Complications ing and a higher risk of perioperative myocardial infarction Patients with stroke are at high risk for developing in-hospital with endarterectomy. In patients with a complete symptomatic and long-term neurologic complications beyond those previ- occlusion of the ICA, however, direct revascularization is not ously outlined. Patients with ischemic stroke may develop wors- feasible, and external carotid-to-internal carotid bypass is not ening deficits from hemorrhagic conversion of the infarct, usu- effective for stroke prevention. Stenting of the extracranial ver- ally within 48 hours. Antiplatelet agents should be held for at tebral artery is associated with a high risk of stroke recurrence least 1 week in most patients with hemorrhagic conversion (for and is not routinely indicated. example, a hematoma seen on brain imaging that is associated Symptomatic intracranial arterial stenosis of greater than with mass effect or edema). Patients with hemorrhagic conver- 70% is associated with a high risk of recurrent stroke and sion not involving a hematoma and with stable repeat imaging should be treated with a statin. Stenting of the affected artery, can be started on antiplatelet agents within 48 hours. Patients however, is associated with a high risk of procedural stroke with a large hemispheric ischemic stroke are at risk for neuro- and should be avoided. Endovascular closure of a PFO for sec- logic deterioration from cerebral edema starting on day 2 after a ondary stroke prevention may be considered in select patients stroke. Patients with significant symptomatic cerebral edema (see MKSAP 19 Cardiovascular Medicine). and increased intracranial pressure after an ischemic stroke have a survival advantage with decompressive hemicraniectomy,

4 weeks after a deep ICH secondary to hypertension. sion and recurrent stroke. These standardized orders ensure that appropriate antiplatelet or anticoagulation agents and high-intensity statin therapy are started on hospital discharge. Surgical Management They include the essential component of patient education The use of surgical approaches for secondary stroke prevention about diet, exercise, smoking cessation, and other healthy has been examined in patients with extracranial ICA and ver- lifestyle choices to reduce the risk of recurrent events. Lastly, tebral artery stenosis, ICA occlusion, intracranial atherosclero- these discharge orders allow for stroke-specific education sis, and PFO-related stroke. In extracranial ICA disease, patients regarding typical stroke symptoms and the importance of with nondisabling stroke or TIA due to ICA stenosis of greater rapid return to care if symptoms occur so that acute stroke than 70% are at high risk for recurrent stroke and may benefit therapeutics can be initiated. from early revascularization. The choice of endarterectomy or angioplasty with stenting is dictated by several patient-specific factors and by local surgical experience. A consistent finding in Prognosis and Recovery trials has been a higher risk of perioperative stroke with stent- Neurologic Complications ing and a higher risk of perioperative myocardial infarction Patients with stroke are at high risk for developing in-hospital with endarterectomy. In patients with a complete symptomatic and long-term neurologic complications beyond those previ- occlusion of the ICA, however, direct revascularization is not ously outlined. Patients with ischemic stroke may develop wors- feasible, and external carotid-to-internal carotid bypass is not ening deficits from hemorrhagic conversion of the infarct, usu- effective for stroke prevention. Stenting of the extracranial ver- ally within 48 hours. Antiplatelet agents should be held for at tebral artery is associated with a high risk of stroke recurrence least 1 week in most patients with hemorrhagic conversion (for and is not routinely indicated. example, a hematoma seen on brain imaging that is associated Symptomatic intracranial arterial stenosis of greater than with mass effect or edema). Patients with hemorrhagic conver- 70% is associated with a high risk of recurrent stroke and sion not involving a hematoma and with stable repeat imaging should be treated with a statin. Stenting of the affected artery, can be started on antiplatelet agents within 48 hours. Patients however, is associated with a high risk of procedural stroke with a large hemispheric ischemic stroke are at risk for neuro- and should be avoided. Endovascular closure of a PFO for sec- logic deterioration from cerebral edema starting on day 2 after a ondary stroke prevention may be considered in select patients stroke. Patients with significant symptomatic cerebral edema (see MKSAP 19 Cardiovascular Medicine). and increased intracranial pressure after an ischemic stroke have a survival advantage with decompressive hemicraniectomy, HVC ¢ Long-term use of combination aspirin-clopidogrel is although neurologic compromise may be significant. Finally,

4 weeks after a deep ICH secondary to hypertension. sion and recurrent stroke. These standardized orders ensure that appropriate antiplatelet or anticoagulation agents and high-intensity statin therapy are started on hospital discharge. Surgical Management They include the essential component of patient education The use of surgical approaches for secondary stroke prevention about diet, exercise, smoking cessation, and other healthy has been examined in patients with extracranial ICA and ver- lifestyle choices to reduce the risk of recurrent events. Lastly, tebral artery stenosis, ICA occlusion, intracranial atherosclero- these discharge orders allow for stroke-specific education sis, and PFO-related stroke. In extracranial ICA disease, patients regarding typical stroke symptoms and the importance of with nondisabling stroke or TIA due to ICA stenosis of greater rapid return to care if symptoms occur so that acute stroke than 70% are at high risk for recurrent stroke and may benefit therapeutics can be initiated. from early revascularization. The choice of endarterectomy or angioplasty with stenting is dictated by several patient-specific factors and by local surgical experience. A consistent finding in Prognosis and Recovery trials has been a higher risk of perioperative stroke with stent- Neurologic Complications ing and a higher risk of perioperative myocardial infarction Patients with stroke are at high risk for developing in-hospital with endarterectomy. In patients with a complete symptomatic and long-term neurologic complications beyond those previ- occlusion of the ICA, however, direct revascularization is not ously outlined. Patients with ischemic stroke may develop wors- feasible, and external carotid-to-internal carotid bypass is not ening deficits from hemorrhagic conversion of the infarct, usu- effective for stroke prevention. Stenting of the extracranial ver- ally within 48 hours. Antiplatelet agents should be held for at tebral artery is associated with a high risk of stroke recurrence least 1 week in most patients with hemorrhagic conversion (for and is not routinely indicated. example, a hematoma seen on brain imaging that is associated Symptomatic intracranial arterial stenosis of greater than with mass effect or edema). Patients with hemorrhagic conver- 70% is associated with a high risk of recurrent stroke and sion not involving a hematoma and with stable repeat imaging should be treated with a statin. Stenting of the affected artery, can be started on antiplatelet agents within 48 hours. Patients however, is associated with a high risk of procedural stroke with a large hemispheric ischemic stroke are at risk for neuro- and should be avoided. Endovascular closure of a PFO for sec- logic deterioration from cerebral edema starting on day 2 after a ondary stroke prevention may be considered in select patients stroke. Patients with significant symptomatic cerebral edema (see MKSAP 19 Cardiovascular Medicine). and increased intracranial pressure after an ischemic stroke have a survival advantage with decompressive hemicraniectomy, HVC ¢ Long-term use of combination aspirin-clopidogrel is although neurologic compromise may be significant. Finally, associated with no reduction in risk of stroke but an patients with ischemic and hemorrhagic stroke may show neu-

4 weeks after a deep ICH secondary to hypertension. sion and recurrent stroke. These standardized orders ensure that appropriate antiplatelet or anticoagulation agents and high-intensity statin therapy are started on hospital discharge. Surgical Management They include the essential component of patient education The use of surgical approaches for secondary stroke prevention about diet, exercise, smoking cessation, and other healthy has been examined in patients with extracranial ICA and ver- lifestyle choices to reduce the risk of recurrent events. Lastly, tebral artery stenosis, ICA occlusion, intracranial atherosclero- these discharge orders allow for stroke-specific education sis, and PFO-related stroke. In extracranial ICA disease, patients regarding typical stroke symptoms and the importance of with nondisabling stroke or TIA due to ICA stenosis of greater rapid return to care if symptoms occur so that acute stroke than 70% are at high risk for recurrent stroke and may benefit therapeutics can be initiated. from early revascularization. The choice of endarterectomy or angioplasty with stenting is dictated by several patient-specific factors and by local surgical experience. A consistent finding in Prognosis and Recovery trials has been a higher risk of perioperative stroke with stent- Neurologic Complications ing and a higher risk of perioperative myocardial infarction Patients with stroke are at high risk for developing in-hospital with endarterectomy. In patients with a complete symptomatic and long-term neurologic complications beyond those previ- occlusion of the ICA, however, direct revascularization is not ously outlined. Patients with ischemic stroke may develop wors- feasible, and external carotid-to-internal carotid bypass is not ening deficits from hemorrhagic conversion of the infarct, usu- effective for stroke prevention. Stenting of the extracranial ver- ally within 48 hours. Antiplatelet agents should be held for at tebral artery is associated with a high risk of stroke recurrence least 1 week in most patients with hemorrhagic conversion (for and is not routinely indicated. example, a hematoma seen on brain imaging that is associated Symptomatic intracranial arterial stenosis of greater than with mass effect or edema). Patients with hemorrhagic conver- 70% is associated with a high risk of recurrent stroke and sion not involving a hematoma and with stable repeat imaging should be treated with a statin. Stenting of the affected artery, can be started on antiplatelet agents within 48 hours. Patients however, is associated with a high risk of procedural stroke with a large hemispheric ischemic stroke are at risk for neuro- and should be avoided. Endovascular closure of a PFO for sec- logic deterioration from cerebral edema starting on day 2 after a ondary stroke prevention may be considered in select patients stroke. Patients with significant symptomatic cerebral edema (see MKSAP 19 Cardiovascular Medicine). and increased intracranial pressure after an ischemic stroke have a survival advantage with decompressive hemicraniectomy, HVC ¢ Long-term use of combination aspirin-clopidogrel is although neurologic compromise may be significant. Finally, associated with no reduction in risk of stroke but an patients with ischemic and hemorrhagic stroke may show neu- increased risk of hemorrhage and death when com- rologic worsening from seizures and systemic infections.

HVC ¢ Long-term use of combination aspirin-clopidogrel is although neurologic compromise may be significant. Finally, associated with no reduction in risk of stroke but an patients with ischemic and hemorrhagic stroke may show neu- increased risk of hemorrhage and death when com- rologic worsening from seizures and systemic infections. pared with single-agent antiplatelet use; aspirin mono- therapy is a reasonable first-line antiplatelet regimen ¢ Patients with ischemic stroke may develop worsening for secondary stroke prevention. deficits from hemorrhagic conversion of the infarct, HVC e Patients with nondisabling stroke or TIA due to greater usually within 48 hours; antiplatelet agents should be than 70% stenosis of the internal carotid artery (ICA) held in the setting of hemorrhagic conversion involving may benefit from early revascularization; in those with a hematoma for at least 1 week and for a shorter period a complete symptomatic occlusion of the ICA, however, of time if there is no hematoma seen on imaging and direct revascularization is not feasible. repeat imaging is stable. (Continued) (Continued) 38

Cognitive Impairment Cognitive Impairment e Patients with significant symptomatic cerebral edema and increased intracranial pressure after an ischemic Definition stroke have a survival advantage with decompressive Cognitive impairment is the loss of cognitive function in at hemicraniectomy, although neurologic compromise may least one major domain: memory, language, executive func- be significant. tion, visuospatial function, or behavior. When the cognitive impairment is progressive, involves more than one cognitive Medical Complications and Stroke Units domain, and results in a loss of independent function, it is In-hospital medical complications are a leading cause of considered a neurodegenerative dementia syndrome. Fixed morbidity and mortality in patients with stroke. Admission cognitive disorders occurring after a brain lesion, such as to a specialized stroke unit is associated with a reduced stroke or traumatic brain injury, are excluded from this

In-hospital medical complications are a leading cause of considered a neurodegenerative dementia syndrome. Fixed morbidity and mortality in patients with stroke. Admission cognitive disorders occurring after a brain lesion, such as to a specialized stroke unit is associated with a reduced stroke or traumatic brain injury, are excluded from this long-term risk of all-cause mortality. Specialized stroke discussion. units are effective because they use multidisciplinary care teams that follow structured protocols emphasizing early mobilization, removing indwelling catheters to prevent uri- General Approach to the Patient nary tract infection, preventing aspiration pneumonia by with Cognitive Impairment addressing/preventing dysphagia, and instituting oral Dementia syndromes are chronic disorders that typically hygiene protocols. Care protocols in stroke units also develop over years. Although definitive evidence that earlier emphasize early initiation of pharmacologic prophylaxis of diagnosis improves patient outcomes is lacking, screening for deep venous thrombosis in patients with ischemic stroke dementia has become the subject of increased interest. The and prophylaxis initiation within 48 hours in patients with U.S. Preventive Services Task Force reports insufficient evi- hemorrhagic stroke who have no evidence of active bleeding. dence to endorse screening, but the American Academy of A 2018 systematic review found that supplemental oxygen in Neurology recently recommended annual cognitive health patients with normal SpO, increases mortality in patients assessments for adults 65 years or older who are receiving with stroke and other acute illnesses (see MKSAP 19 neurologic care. Additionally, the Medicare Annual Wellness Pulmonary and Critical Care Medicine). Resultant guidelines Visit requires an assessment of cognition. recommend against starting oxygen therapy in patients at or In the absence of screening, certain signs and behaviors above 93% saturation and discontinuing oxygen if saturation may raise clinical suspicion of a cognitive disorder and pro- is at or above 96%. The American Heart Association/ voke evaluation in a primary care setting. Examples include American Stroke Association (2018 guideline) recommends concerns expressed by family members or caregivers, frequent oxygen to maintain an oxygen saturation of 94% or greater, missed (or late arrival to) appointments, changes in medica- with no upper limit provided, and the European Academy tion adherence, unexplained weight loss, presence of a partner of Neurology recommends oxygen to maintain normoxia in or family member at patient appointments when the patient patients with an arterial oxygen saturation less than 95%, previously was seen alone, and withdrawal from previously with no upper limit provided. enjoyed hobbies. Many bedside cognitive evaluation tools have demon- Long-Term Prognosis and Recovery strated adequate sensitivity and specificity for detecting cogni- Long-term survivors of stroke are at high risk for delayed neu- tive impairment in population-based settings. The most rologic complications. Cognitive impairment, vascular demen- common are the Mini-Cog, the Memory Impairment Screen, tia, and seizures all may occur. Most stroke survivors exhibit the General Practitioner Assessment of Cognition, and the neurologic impairment and disability 1 year after stroke and Montreal Cognitive Assessment. Each of these tests can be beyond. Fatigue can arise from a high prevalence of sleep- performed in approximately 5 to 10 minutes; no compelling disordered breathing. Cardiorespiratory and repetitive task data support the superiority of one test over another. These training and transcranial direct current stimulation may tests are increasingly used to justify billing and medication- improve activities of daily living in adults who have had a authorization decisions by insurers. stroke. Cognitive behavioral therapy, exercise, and selective After cognitive impairment is diagnosed, determining serotonin reuptake inhibitors may reduce symptoms of post- whether it is reversible or nonreversible is imperative in the stroke depression. initial evaluation of the patient. Essential elements in this determination are the time course of symptom onset and pro- gression, the principal cognitive domain or function affected ¢ Most stroke survivors exhibit neurologic impairment and its functional impact, and other associated neurologic and and disability 1 year after stroke and beyond; depression nonneurologic symptoms. Fluctuations in course, inattentive- is highly prevalent in stroke survivors and is one of the ness, disorganized thinking, and altered level of consciousness leading modifiable risk factors for long-term disability. should prompt evaluation for acute or subacute delirium.

long-term risk of all-cause mortality. Specialized stroke discussion. units are effective because they use multidisciplinary care teams that follow structured protocols emphasizing early mobilization, removing indwelling catheters to prevent uri- General Approach to the Patient nary tract infection, preventing aspiration pneumonia by with Cognitive Impairment addressing/preventing dysphagia, and instituting oral Dementia syndromes are chronic disorders that typically hygiene protocols. Care protocols in stroke units also develop over years. Although definitive evidence that earlier emphasize early initiation of pharmacologic prophylaxis of diagnosis improves patient outcomes is lacking, screening for deep venous thrombosis in patients with ischemic stroke dementia has become the subject of increased interest. The and prophylaxis initiation within 48 hours in patients with U.S. Preventive Services Task Force reports insufficient evi- hemorrhagic stroke who have no evidence of active bleeding. dence to endorse screening, but the American Academy of A 2018 systematic review found that supplemental oxygen in Neurology recently recommended annual cognitive health patients with normal SpO, increases mortality in patients assessments for adults 65 years or older who are receiving with stroke and other acute illnesses (see MKSAP 19 neurologic care. Additionally, the Medicare Annual Wellness Pulmonary and Critical Care Medicine). Resultant guidelines Visit requires an assessment of cognition. recommend against starting oxygen therapy in patients at or In the absence of screening, certain signs and behaviors above 93% saturation and discontinuing oxygen if saturation may raise clinical suspicion of a cognitive disorder and pro- is at or above 96%. The American Heart Association/ voke evaluation in a primary care setting. Examples include American Stroke Association (2018 guideline) recommends concerns expressed by family members or caregivers, frequent oxygen to maintain an oxygen saturation of 94% or greater, missed (or late arrival to) appointments, changes in medica- with no upper limit provided, and the European Academy tion adherence, unexplained weight loss, presence of a partner of Neurology recommends oxygen to maintain normoxia in or family member at patient appointments when the patient patients with an arterial oxygen saturation less than 95%, previously was seen alone, and withdrawal from previously with no upper limit provided. enjoyed hobbies. Many bedside cognitive evaluation tools have demon- Long-Term Prognosis and Recovery strated adequate sensitivity and specificity for detecting cogni- Long-term survivors of stroke are at high risk for delayed neu- tive impairment in population-based settings. The most rologic complications. Cognitive impairment, vascular demen- common are the Mini-Cog, the Memory Impairment Screen, tia, and seizures all may occur. Most stroke survivors exhibit the General Practitioner Assessment of Cognition, and the neurologic impairment and disability 1 year after stroke and Montreal Cognitive Assessment. Each of these tests can be beyond. Fatigue can arise from a high prevalence of sleep- performed in approximately 5 to 10 minutes; no compelling disordered breathing. Cardiorespiratory and repetitive task data support the superiority of one test over another. These training and transcranial direct current stimulation may tests are increasingly used to justify billing and medication- improve activities of daily living in adults who have had a authorization decisions by insurers. stroke. Cognitive behavioral therapy, exercise, and selective After cognitive impairment is diagnosed, determining serotonin reuptake inhibitors may reduce symptoms of post- whether it is reversible or nonreversible is imperative in the stroke depression. initial evaluation of the patient. Essential elements in this determination are the time course of symptom onset and pro- gression, the principal cognitive domain or function affected ¢ Most stroke survivors exhibit neurologic impairment and its functional impact, and other associated neurologic and and disability 1 year after stroke and beyond; depression nonneurologic symptoms. Fluctuations in course, inattentive- is highly prevalent in stroke survivors and is one of the ness, disorganized thinking, and altered level of consciousness leading modifiable risk factors for long-term disability. should prompt evaluation for acute or subacute delirium. 39