Stroke 101 Elisheva Coleman, MD Assistant Professor of Neurology UC Stroke Team February 9, 2018

A. Intracerebral hemorrhage B. Ischemic stroke C. Meningitis Case 1 An 88-year-old woman is evaluated in the emergency department 1 hour after the acute onset of language disturbance and right-sided weakness. The family members who witnessed the onset say that the symptoms progressed over a few minutes and they describe the patient holding her head as if in pain. She has a 20-year history of hypertension but no other medical problems; her only medication is lisinopril. During the examination, the patient becomes increasingly difficult to arouse and vomits repeatedly. She is afebrile, blood pressure is 220/110 mm Hg, pulse rate is 110/min, and respiration rate is 20/min. There is no nuchal rigidity. Carotid upstrokes are normal; there are no bruits and no jugular venous distention. Other than tachycardia, the cardiopulmonary examination is unremarkable. Global aphasia and right hemiplegia are noted. On the basis of her preliminary clinical evaluation, which of the following is the most likely diagnosis? A. Intracerebral hemorrhage B. Ischemic stroke C. Meningitis D. Transient ischemic attack

Stroke Definition: Focal neurologic deficit caused by cerebrovascular event lasting at least 24 hours, usually of sudden onset Ischemic (85%) Hemorrhagic ICH (10%) SAH (5%) TIA: same as above, except resolving completely within 24 hours

Epidemiology Annual incidence in US: 795,000 610,000 are first-ever strokes 185,000 are recurrent strokes Fifth leading cause of death Leading cause of long-term disability Higher incidence and mortality in southeastern United States ("stroke belt") c0mpared to rest of the country Blacks and Hispanics have an increased risk of stroke compared with whites The risk of first-ever stroke for blacks is almost twice that of whites

Risk Factors Nonmodifiable: Modifiable: Age Hypertension Race Smoking Gender TIAs/previous strokes Family history Atrial fibrillation Collagen vascular disease Diabetes Obesity Alcohol/drugs (cocaine) Hypercholesterolemia Structural heart disease Hypercoagulable states Migraine

Order outpatient diagnostic studies Case 2 An 82-year-old man is evaluated in the office for an episode of hesitancy in speech, word-finding difficulty, right facial droop, and weakness and awkwardness of the right hand and arm. The episode occurred early yesterday, lasted 20 minutes, and was witnessed by his wife. The patient has a history of coronary artery disease, hypertension, and hyperlipidemia. Current medications are metoprolol, aspirin, hydrochlorothiazide, and lovastatin. On physical examination, temperature is normal, blood pressure is 148/88 mm Hg, pulse rate is 70/min, and respiration rate is 12/min. Neurologic examination reveals no abnormalities. Which of the following is the most appropriate next step in management? Add clopidogrel Admit to the hospital Order outpatient diagnostic studies Schedule a follow-up visit in 1 week Answer and Critique (Correct Answer: B) Educational Objective:Manage a transient ischemic attack. Key Point Patients with a diagnosis of a recent transient ischemic attack are at an appreciably high short-term risk of stroke and should be evaluated in a hospital in an expedited and emergent fashion. This patient should be admitted to the hospital. Given his clinical history, he most likely has had a recent transient ischemic attack (TIA). His ABCD2 score (based on Age, Blood pressure, Clinical features, the Duration of symptoms, and the presence of Diabetes) is 5: one point is for his age (>60 years), one point for his hypertension, one point for a symptom duration of greater than 10 minutes, and two points for the focal weakness he described. This score is moderately high and carries an estimated stroke risk of 5% over the next 2 days, 7% over the next week, 10% over the next 30 days, and 12% over the next 3 months. Therefore, the most appropriate response is for this patient to undergo urgent evaluation within the next 24 hours at an emergency department, at a hospital during a brief admission, or at an organized urgent TIA clinic. It is reasonable to review the stroke prevention regimen of a patient with risk factors and make adjustments to any antiplatelet medications in the context of a new stroke or TIA. However, the priority is an expedited evaluation to determine the cause and mechanism of the stroke or TIA, such as symptomatic extracranial carotid artery stenosis amenable to endarterectomy, intracranial stenosis amenable to angioplasty and stenting, or cardioembolism with requirements for long-term anticoagulation. Therefore, adding clopidogrel to this patient’s drug regimen is not the most appropriate next step in management. Outpatient diagnostic studies may play a role in the assessment of this patient, but only if they occur and results are back within 24 hours. Because this scenario is unlikely, such studies are clearly not the most appropriate next step in management. Given the high probability of an acute ischemic stroke event and the high short-term risk of stroke in this patient, scheduling a follow-up appointment in 1 week in the absence of diagnostic testing or evaluation could be life threatening. Transient ischemic attack should be approached with urgency because up to 20% of affected patients will have an acute stroke within 90 days and approximately 50% of these strokes will occur within the first 2 days. The ABCD2 score, which is based on Age, Blood pressure, the Clinical presence of unilateral weakness or speech impairment, the Duration of symptoms, and the presence of Diabetes, predicts the risk of stroke at 2, 7, and 90 days after a transient ischemic attack. Emergency department assessment and hospitalization are recommended for patients who have had a first or frequently recurring transient ischemic attack within the past 48 hours. Bibliography Johnston SC, Nguyen-Huynh MN, Schwartz ME, et al. National Stroke Association guidelines for the management of transient ischemic attacks. Ann Neurol. 2006;60(3):301-313. [PMID: 16912978]

TIA Risk Stratification ABCD2 Score A: age > 60 = 1 B: Blood pressure > 140/90 = 1 C: Clinical syndrome Speech difficulty = 1 Unilateral weakness = 2 D1: Duration 10-60 minutes = 1 >60 minutes = 2 D2: Diabetes = 1 48-hour Stroke Risk: Score 1-3 (low) = 1.0% Score 4-5 (mod) = 4.1% Score 6–7 (high) = 8.1%

Continuous intravenous heparin Case 3 A 74-year-old man is brought to the emergency department by ambulance 1 hour after acute witnessed onset of aphasia and right hemiparesis. He has a history of hypertension and atrial fibrillation. His current medications are hydrochlorothiazide, metoprolol, and warfarin. On physical examination, blood pressure is 178/94 mm Hg and pulse rate is 80/min and irregular. Neurologic examination confirms nonfluent aphasia, a right pronator drift, a right leg drift, and an extensor plantar response on the right. Results of laboratory studies performed within 1 hour of his arrival at the emergency department show an INR of 1.5. An electrocardiogram obtained on the patient’s arrival at the emergency department confirms atrial fibrillation. A CT scan of head obtained within 1 hour of his arrival reveals no early ischemic changes. Which of the following is the best treatment? Answer and Critique (Correct Answer: E) Educational Objective:Treat an acute hemispheric stroke. Key Point A patient with acute ischemic stroke who is taking warfarin but who has a subtherapeutic INR (≤1.7) is still eligible to receive thrombolysis with intravenous recombinant tissue plasminogen activator within the recommended window of 3 hours from stroke onset. This patient should receive intravenous recombinant tissue plasminogen activator (rtPA). He has clinical symptoms and signs and radiologic evidence of an acute left hemispheric stroke. The probable mechanism of stroke is a cardioembolism, given his history of atrial fibrillation and his subtherapeutic INR. He was brought to the emergency department within 1 hour of the witnessed onset of stroke symptoms, and his evaluation is completed 1 hour later. He does not appear to have any clinical, radiologic, or laboratory contraindication to receiving the preferred treatment of intravenous rtPA, and he can receive it within the recommended window of 3 hours from stroke onset. The standard dose is 0.9 mg/kg. Although he is on warfarin, rtPA is not contraindicated because his INR is 1.5; an INR less than or equal to 1.7 is required for rtPA administration in a patient on anticoagulation. Aspirin is indicated for acute ischemic stroke in patients who are not eligible for rtPA, as this patient is. For patients with acute stroke who are eligible for thrombolysis, aspirin should be withheld in the emergency department and for 24 hours after rtPA administration. Although long-term anticoagulation is an effective treatment for prevention of cardioembolic stroke in patients with atrial fibrillation, acute anticoagulation with heparin has not been shown to be beneficial in patients with acute ischemic stroke. Intra-arterial administration of rtPA is indicated for selected patients with acute stroke who have major intracranial artery occlusion within 6 hours of symptom onset and who are not otherwise candidates for intravenous administration of rtPA. This patient was eligible for intravenous administration of rtPA within 3 hours of stroke onset. The latter treatment takes precedence. Elevated blood pressure is common at the time of initial stroke presentation, even among patients without chronic hypertension. Rapid lowering of blood pressure may further impair cerebral blood flow and worsen the ischemic injury. Elevated blood pressure often will resolve spontaneously or improve gradually during the first few days after a stroke. The threshold for acute blood pressure lowering in patients with acute stroke who are eligible for thrombolysis is 185/110 mm Hg. In such a setting, preferred agents include intravenous infusions of labetalol or nicardipine. Because this patient’s blood pressure is already below that threshold, there is no indication for intravenous use of labetalol at this time. Bibliography Adams HP Jr, del Zoppo G, Alberts MJ, et al. Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: the American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists [errata in Stroke. 2007;38(6):e38 and Stroke. 2007;38(9):e96]. Stroke. 2007;38(5):1655-1711. [PMID: 17431204] - Aspirin Continuous intravenous heparin Intra-arterial recombinant tissue plasminogen activator (rtPA) Intravenous labetalol Intravenous rtPA

Acute Interventions: tPA Inclusions Known last well within 4.5 hours (FDA approved up to 3 hours but AHA guidelines approve up to 4.5) Focal neurologic deficits attributable to ischemic stroke Exclusions Hypodensity on CT involving more than 1/3 of middle cerebral artery territory SBP > 185 mm Hg, DBP > 110 mm Hg Coumadin with INR > 1.7; NoAC use Heparin within 48 hours AND an elevated PTT Platelet count below 100 X 109/L History of spontaneous intracranial hemorrhage Relative contraindications: Potential sites of bleeding Stroke or head trauma within 3 months Major surgery within 14 days Gastrointestinal hemorrhage within 21 days Urinary tract hemorrhage within 21 days Arterial puncture at noncompressable site w/in 7 days LP within 7 days Blood glucose < 50 mg/dl or > 400 mg/dl Rapidly improving or minor symptoms Seizures at the onset of stroke

Acute Interventions: Thrombectomy Stent-retriever Aspiration AHA 2015 Guideline Indications: Large vessel occlusion (ICA, proximal MCA, basilar) Able to puncture groin < 6 hours from last well (longer times may be pursued in basilar occlusions) Baseline independent functional status NIHSS >5 ASPECTS score >5

Extended-window thrombectomy Two new trials established benefit of thrombectomy in selected patients beyond 6 hours Must have large vessel occlusion (ICA or M1) Selection based upon perfusion imaging (CT or MRI) Mismatch between ischemic core and clinical symptoms/NIHSS (DAWN) or perfusion defect (DEFUSE3)

Endovascular treatment effect HERMES Meta-analysis (standard window) ARR = 19.5% NNT = 5.1 NNT to reduce mRS by ≥1 point: 2.6 DAWN ARR = 36% NNT = 2.8

Diagnosis Based on history and physical exam Symptoms/signs localizing to a vascular distribution Lab tests may exclude mimics (e.g. hypoglycemia) Non-contrast head CT: hemorrhage vs. ischemia CT can be normal acutely Other imaging modalities: CT angiography, MRI with diffusion weighted imaging, perfusion CT/MR

NIHSS 1) LOC: 0 =keenly responsive 1=arousable by minor stim 5&6) Motor: 0=no drift 1=drift but doesn’t hit bed 2=some effort against gravity but falls to bed 3=no effort against gravity, limb falls 4=no movement left arm ____ right arm_____ left leg____ right leg____ 7) Ataxia: 0=absent, 1=one limb, 2=two limbs 8) Sensory: 0=nl, 1=mild to mod 2=severe or total sensory loss 9) Language: 1=mild-mod aphasia loss of fluency or comprehension 2=severe aphasia, all communication fragmentary, 3=mute 10) Dysarthria 1=mild to mod some words understandable, 2= severe aphasia, not understandable, 3=intubated or physical barrier 11) Neglect: 1= neglect in one modality 2=profound hemi-inattention in more than one modality 1) LOC: 0 =keenly responsive 1=arousable by minor stim 2=not alert, requires strong stim to respond 3=unresponsive or posturing 1a) LOC ? (month/age): 0=both correct 1=1 correct 2=neither correct 1b) LOC commands (close eyes/fist): 2=neither 2) Gaze: 0=nl, 1=partial gaze palsy, 2=forced deviation 3)Visual: 1=partial hemianopia, 2=complete hemianopia, 3=blind 4) Facial: 1=minor paralysis, 2=partial paralysis (lower face), 3=complete

Stroke Mimics Seizure with Todd’s paralysis or non-convulsive status Hypo- or hyper-glycemia Complicated migraine Mass lesion Recrudesence: worsening or emergence of previous deficit due to infection, toxic/metabolic process Conversion disorder

Diagnosis: Stroke Mechanism Large vessel Extracranial vs intracranial 17-27% of all first strokes in US Small vessel Penetrating vessels 18-25% of all first strokes Cardioembolic 20-40% of all first strokes Other 3-5 of all first strokes Unknown 25-50% of all first strokes Large vessel = more than 50% stenosis in the appropriate vessel Small vessel = lacunar

C. Spontaneous left internal carotid artery dissection Case 4 A previously healthy 50-year-old woman is admitted to the hospital after three recent, transient episodes of nonfluent aphasia and right-hand numbness and weakness. One week before onset of these focal neurologic symptoms, she developed aching left jaw pain, which has persisted. She has no other medical problems and takes no medications. On physical examination, vital signs are normal. A left carotid bruit is heard on auscultation. Left miosis and left ptosis are noted. Results of laboratory studies and a CT scan of the head are normal. Which of the following is the most likely diagnosis? A. Cluster headache B. Giant cell arteritis C. Spontaneous left internal carotid artery dissection D. Spontaneous left vertebral artery occlusion Answer and Critique (Correct Answer: C) Educational Objective:Diagnose carotid artery dissection. Key Point Dissection of the cervical arteries, although an infrequent occurrence, is a leading cause of stroke in young and otherwise healthy persons. The most likely clinical diagnosis to explain this patient’s focal neurologic symptoms is a left internal carotid artery dissection with resultant transient ischemic attacks (TIAs). Carotid dissection characteristically develops after head or neck trauma but may occur spontaneously. Manifestations of this condition include ipsilateral throbbing neck, head, or orbital pain with possible Horner syndrome. The pain from carotid dissection may occur suddenly or develop gradually. Such a dissection can cause a TIA or ischemic stroke by one of two mechanisms: either the mural hematoma expands to the point of occluding the lumen, or a thrombus forms and embolizes to cause distal arterial branch occlusion. Dissection of the cervical arteries, although an infrequent occurrence, is a leading cause of stroke in young and otherwise healthy persons. Magnetic resonance angiography of the carotid arteries and carotid duplex ultrasonography are indicated in the clinical evaluation of possible carotid dissection. A cluster headache is an excruciating unilateral headache of extreme intensity, with a typical duration of 15 minutes to 3 hours. Its pain is lancinating or boring in quality and is located behind the eye (periorbital) or in the temple, sometimes radiating to the neck or shoulder. The cardinal symptoms of a cluster headache attack are ptosis (drooping eyelid), conjunctival injection (redness of the conjunctiva), lacrimation (tearing), rhinorrhea (a runny nose), and, less commonly, facial blushing, swelling, or sweating. These features are known as the autonomic symptoms. The neck is often stiff or tender in the aftermath of a headache, with jaw or tooth pain sometimes present. Although this patient had ptosis and jaw pain, there were no other features to support a diagnosis of cluster headache. Additionally, one would not expect a patient with a cluster headache to have focal cortical dysfunction (such as aphasia). Giant cell arteritis (or temporal arteritis) is a granulomatous vasculitis that predominantly affects the extracranial branches of the carotid artery. This condition occurs almost exclusively in patients older than 50 years of age and has a female predominance. Clinical manifestations of giant cell arteritis include headache, jaw or tongue claudication, scalp tenderness, systemic symptoms, and fever. Involvement of the primary branches of the aorta also may cause limb claudication. Giant cell arteritis is not associated with pain along the carotid artery or cerebral hemispheric symptoms and would be an unusual diagnosis in this relatively young patient. The patient’s clinical symptoms are aphasia, right hemiparesis, and right hemisensory loss; all are referable to the middle cerebral artery territory of the dominant left hemisphere and thus are consistent with an anterior circulation stroke event. There are no posterior circulation symptoms (in the vertebrobasilar artery territory) to suggest that a vertebral artery occlusion has occurred. Although an ipsilateral Horner syndrome can accompany a lateral medullary infarction secondary to a vertebral artery occlusion, a patient with this condition would also be expected to have dysphagia, hoarseness, a reduced gag reflex, vertigo, nystagmus, vomiting, ipsilateral cerebellar findings, ipsilateral loss of pain and temperature sensations in the face, and contralateral loss of pain and temperature sensations in the body, none of which this patient has. Bibliography Jensen MB, Chacon MR, Aleu A. Cervicocerebral arterial dissection. Neurologist. 2008;14(1):5-6. [PMID: 18195650]

Stroke Mechanism--Other Dissection Hypoperfusion/watershed Hypercoagulable state Hematologic disorders (sickle cell, polycythemia) Drug use (cocaine) Inflammatory (vasculitis) Autoregulatory disorders (PRES)

Large-artery disease Carotid Stenosis MCA Stenosis

Small Vessel/Lacunar Lipohyalinosis Obstruction of a single small penetrating arteriole supplying deep structures (e.g. basal ganglia, internal capsule, thalamus, pons) Infarcts < 15 mm Microatheroma (lipohyalinosis), or microembolism Small cortical infarcts are not lacunes! Lipohyalinosis Wall thickening due to accumulations of fibrinoid material Endothelial dysfunction Mostly due to hypertension (age, diabetes, smoking also contribute)

Lacunar syndromes Pure motor stroke/hemiparesis Pure sensory stroke Mixed sensorimotor stroke Ataxic hemiparesis Dysarthria/clumsy hand

Lacunar Infarct

Cardioembolic High Risk Potential Risk Atrial fibrillation/flutter Rheumatic mitral or aortic valve disease Bioprosthetic and mechanical heart valves Atrial or ventricular thrombus Endocarditis (Infective, Marantic) Symptomatic congestive heart failure with ejection fraction <30 percent Recent myocardial infarction (within one month) Potential Risk Patent foramen ovale (paradoxical embolism) Mitral annular calcification Atrial septal aneurysm Left ventricular aneurysm without thrombus Isolated left atrial “smoke” on echocardiography Complex atheroma in the ascending aorta or proximal arch

Cardioembolic infarcts

Management Limiting cellular injury Neurologic Complications Reperfusion – salvage penumbra (oligemic but potentially salvageable tissue Prevent secondary injury Neurologic Complications Systemic Complications Rehabilitation

Secondary injury Maintain cerebral perfusion Impaired cerebral autoregulation Large vessel occlusion/stenosis relying on collateral flow Permissive hypertension, don’t lower precipitously Maintain cerebral oxygenation Hypoxia is bad for injured brain, but there is no evidence for supplemental O2 in patients without hypoxia Maintain normothermia Fever  increased oxygen metabolism/demand Maintain euglycemia Hyperglycemia exacerbates ischemic damage

Neurologic complications Progressive infarction or recurrent cerebral ischemia Increased intracranial pressure hemorrhagic transformation cytotoxic edema (+/- vasogenic edema) Edema maximal at 36-72 hours, usually manifests as decline in level of consciousness Hemicraniectomy is only treatment proven to improve outcomes Reduces disability-free survival in patients <60 years old Reduces morbidity in >60 Seizures Early seizures occur in about 5% of patients Recurrence rate for early seizures is 30% Prophylactic anticonvulsants are not recommended

Bedside screening for dysphagia Case 5 A 79-year-old woman is to be transferred from the emergency department to a hospital ward for ongoing care. She awoke at home 5 hours ago with slurred speech, difficulty swallowing food and drink, and left hemiparesis. A right hemispheric ischemic stroke was diagnosed in the emergency department after a CT scan of the head confirmed a right hemispheric infarction. Because the time of stroke onset could not be determined, no recombinant tissue plasminogen activator was administered. The patient has no other medical problems and takes no medications. On physical examination, blood pressure is 168/86 mm Hg, pulse rate is 80/min, and respiration rate is 18/min. Neurologic assessment reveals dysarthria, dysphagia, left facial droop, and left hemiparesis. Laboratory studies show a plasma LDL cholesterol level of 158 mg/dL (4.09 mmol/L) but no other abnormalities. Which of the following is the most appropriate first step in management after transfer is completed? Answer and Critique (Correct Answer: A) Educational Objective:Manage in-hospital stroke care. Key Point In a patient with stroke, dysphagia screening should be performed before food, oral medication, or liquids are administered. On admission to a hospital ward, a patient with stroke should be given nothing by mouth (kept NPO) until a swallowing assessment is conducted. Dysphagia screening is especially appropriate for this patient, who had difficulty swallowing when she first awoke with stroke symptoms. Dysphagia occurs in 45% of all hospitalized patients with stroke and can lead to poor outcomes, including aspiration pneumonia and death. Bedside screening of swallowing ability should thus be completed before oral intake of any medication or food; if the screening results are abnormal, a complete examination of swallowing ability is recommended. The American Heart Association/American Stroke Association recommends a water swallow test performed at the bedside by a trained observer as the best bedside predictor of aspiration. A prospective study of the water swallow test demonstrated a significantly decreased risk of aspiration pneumonia of 2.4% versus 5.4% in patients who were not screened. Angiotensin-converting enzyme inhibitors, statins, and aspirin are appropriate treatments for secondary stroke prevention in some patients, but they should not be orally administered before ruling out the risk of aspiration. Like most patients with stroke, this patient will undoubtedly require physical therapy and rehabilitation during her recovery. However, consulting with the department(s) responsible for such care is not an immediate concern and should not be the first step taken when the patient arrives in the hospital ward. Bibliography Hinchey JA, Shephard T, Furie K, Smith D, Wang D, Tonn S; Stroke Practice Improvement Network Investigators. Formal dysphagia screening protocols prevent pneumonia. Stroke. 2005;36(9):1972-1976. [PMID: 16109909] Bedside screening for dysphagia Oral administration of an angiotensin-converting enzyme inhibitor Oral administration of a statin Physical therapy and rehabilitation consultation

Systemic complications Aspiration  NPO, early dysphagia screen, feeding tubes if needed DVT subQ Heparin, SCDs Early mobilization Infection (leading cause of late death) Remove foleys ASAP Incentive spirometry Skin Breakdown  Early mobilization

Secondary Prevention Risk factor modification Anti-hypertensive Lipid management DM management Smoking cessation Diet and exercise Appropriate medical or surgical therapy Guided by mechanism of stroke Echo to look for cardiac source  Anticoagulation Imaging to look for carotid source  Endarterectomy or stenting Anti-platelet

Questions?

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