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Home , Abulia, Aphasia, Homonymous hemianopsia, Lacunar stroke

Definition of / Attack Stroke II: • A caused by disruption in the flow of Diagnosis, Evaluation, and Prevention blood to part of the brain due to either: – occlusion of a blood vessel • ischemic stroke Lenore N. Joseph, MD – rupture of a blood vessel Service Chief, McGuire VAMC • hemorrhagic stroke Assistant Professor of Neurology • The interruption in blood flow deprives the brain VCU Health System of nutrients and oxygen resulting in injury to cells Medical College of Virginia in the affected vascular territory of the brain

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Stroke: The Problem Stroke: The Problem

• Third leading cause of death in US • Among 6 month or longer survivors: – after heart disease and cancer – 48% have a • 740,000 new each year – 22% cannot walk • 4.5 million stroke survivors – 24-53% report complete or partial • Leading cause of disability in adults in US dependence for activities • $45.5 billion per year in the USA – 12-18% are aphasic • 1 of 6 Americans will be affected – 32% are clinically depressed – only 10% fully recover

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Symptoms of Brain Attack: Symptoms of Brain Attack: Teach your patients! Teach your patients!

• Sudden weakness, , or numbness of: • Sudden unexplained dizziness –face – especially when associated with other – arm and the leg on one or both sides of the neurologic symptoms body – unsteadiness • Sudden loss of , or difficulty speaking or – sudden falls understanding speech • Sudden severe and/or loss of • Sudden dimness or loss of vision consciousness – particularly in only one eye

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1 Ischemic Stroke Risk Factors: Ischemic Stroke Nonmodifiable

• Most common stroke type • Older age – 85% of all strokes • Male sex • 65% of 1st time strokes •Race • Genetic factors

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Ischemic Stroke Risk Factors: Ischemic Stroke Risk Factors: Modifiable Modifiable

• • Cigarette smoking – increases risk 6-8 times above baseline – RR =1.5 population • Asymptomatic carotid – even “borderline” HTN is associated with • Physical inactivity increased risk of stroke • mellitus • Controlling HTN is the single most important – RR+1.5 - 3 measure to be taken in decreasing the risk of stroke • Elevated cholesterol • Prior TIA • Cardiac risk factors – Afib, etc. 9 10

Ischemic Stroke Risk Factors: Modifiable/Putative • Elevated • Is it a stroke? homocysteine – chlamydia • – pneumonia • Oral contraceptives • Hypercoagulable states • Obesity • Systemic inflammation/ • Alcohol abuse connective tissue •Stress disorders • Sleep apnea • Sympathomimetic • Illegal drug use medications

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2 Stroke by Location: NINDS Classification: Ischemic Strokes Middle Cerebral Artery (MCA)

• Clinical • Arterial territory – atherothrombotic – internal carotid – cardioembolic – middle cerebral – lacunar – anterior cerebral – vertebral • Mechanism – basilar – thrombotic – posterior cerebral – embolic – hemodynamic

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Stroke Syndromes by Vascular Territory: MCA Stroke Syndromes by Location: MCA

• Complete • Contralateral face=arm>leg paralysis • Superior division • Contralateral cortical and primary sensory • Inferior division impairment • Gerstman Syndrome –face – - inability to write – arm – acalculia - inability to calculate –leg – right-left confusion – finger - inability to recognize fingers • ideomotor may be associated • Ataxic hemiparesis 15 16

Stroke Syndromes by Location: MCA Stroke Syndromes by Location: MCA

• Language disorders: • Anosognosia - ignorance of deficit – – unilateral neglect – alexia – constructional apraxia – agraphia – abnormal spatial localization • cortical signs c/w dominant hemisphere • cortical signs c/w nondominant hemisphere involvement involvement

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3 Stroke Syndromes by Vascular Territory: Large Vessel Ischemic Stroke Anterior Cerebral Artery (ACA)

• MCA territory distribution stroke due to critical stenosis of the right internal carotid artery

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Stroke Syndromes by Location: Stroke Syndromes by Location: ACA Posterior Circulation

• Contralateral foot and leg paralysis • Contralateral “cortical sensory” impairment of the lower extremity • Extreme () especially in bilateral lesions • Gait apraxia or “cerebral paraplegia” in bilateral lesions with injury to the

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Stroke Syndromes by Location: Stroke Syndromes by Vascular Territory: Posterior Cerebral Artery (PCA) PCA

• Homonymous • Balint Syndrome – due to ischemia of the calcarine cortex – loss of voluntary but not reflex eye movements – usually with macular or the optic radiation – optic ataxia • – asimultagnosia – bilateral homonymous hemianopsia • unable to understand visual objects as a whole – may see Anton’s syndrome: visual confabulation • Alexia without agraphia • Thalamic syndromes • Weber Syndrome () – sensory loss or spontaneous pain/dysaesthesias – weakness contralateral upper and lower extremity or movement disorders – ipsilateral gaze palsy (CN3) • /tremor

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4 Stroke Syndromes by Vascular Territory: Stroke Syndromes by Location: PCA Posterior Circulation

Patient with alexia w/o agraphia 25 26

Stroke Syndromes by Vascular Territory: Stroke Syndromes by Vascular Territory: Posterior Circulation Basilar Branch

• Hallmarks of / involvement: • Anterior Inferior Cerebellar Artery – • Lateral pontine syndrome - Marie-Foix Syndrome – Ipsilateral due to involvement of – vertigo cerebellar tracts (middle cerebellar peduncle) – ataxia – Contralateral hemiparesis due to corticospinal tract – involvement – Variable contralateral hemihypesthesia for pain and temperature due to spinothalamic tract involvement • Posterior inferior cerebellar artery • Lateral medullary syndrome - of Wallenberg – ipsi pain and numbness, esp on the face – ipsilateral limb ataxia, vertigo, nausea, nystagmus, 27 , Horner syndrome 28

Stroke Syndromes by Vascular Territory: Stroke Syndromes by Vascular Territory: Basilar Branch/Penetrators Vertebral Artery

• Locked-in Syndrome • Lateral Medullary syndrome - of Wallenburg • Lateral pontine syndrome - Marie-Foix Syndrome • Medial medullary syndrome - Dejerine Syndrome • Ventral pontine syndrome - Raymond Syndrome • May also be seen with involvement • Ventral pontine syndrome - Millard-Gubler – rare stroke syndrome (<1% of vertebrobasilar strokes, Syndrome Bassetti et al., 1994) – medial medullary infarct is associated with clinical • Inferior medial pontine syndrome - Foville Syndrome triad of ipsilateral hypoglossal palsy, contralateral • Ataxic Hemiparesis hemiparesis, and contralateral lemniscal sensory loss • Cortical blindness - Anton Syndrome – variable manifestations may include isolated • Medial medullary syndrome hemiparesis, tetraparesis, ipsilateral hemiparesis, I or C facial palsy, ataxia, vertigo, nystagmus, dysphagia • See www.strokecenter.org for details – palatal and pharyngeal weakness rare in pure MMI,

29 common in lateral medullary infarct 30

5 NINDS Classification: Ischemic Strokes Large Vessel Ischemic Stroke

• Clinical • Arterial territory • The large extracranial and intracranial – atherothrombotic/ – internal carotid are predisposed to atherosclerotic large vessel ischemia – middle cerebral narrowing/occlusion – cardioembolic – anterior cerebral • Bifurcations are common sites: – lacunar – vertebral – internal carotid artery at the bulb – basilar – vertebral and basilar arteries • Mechanism – posterior cerebral – middle cerebral arteries – thrombotic – embolic – hemodynamic 31 32

Large Vessel Ischemic Stroke: Large Vessel Ischemic Stroke: Mechanisms Mechanisms

• Artery to artery • Normal carotid – plaque/thrombus from a proximal artery becomes bifurcation dislodged, travels distally, and obstructs a • Stenosis of the ICA smaller segment or branch of the artery will usually produce • Thrombosis stroke syndromes – propagation of thrombus along arterial wall until referable to the the vessel is occluded or critically stenosed middle cerebral • Hypoperfusion artery territory – through a critical arteriosclerotic stenosis affecting the territory of that artery

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Large Vessel Ischemic Stroke Large Vessel Ischemic Stroke

• MCA territory distribution stroke due to critical stenosis of the right internal carotid artery

Doppler study of the right internal carotid artery showing 80% stenosis near the origin (in the bulb)

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6 Cardiac Embolism Cardiogenic Embolism

• Among the most devastating of the stroke types • • Least likely to present with prior transient • Acute Myocardial ischemic attacks Infarction • Most likely to recur if patient is not adequately • Valvular disease prophylaxed for subsequent events – mitral and aortic valves • Cortical, rather than deep white matter, strokes • Dilated cardiomyopathy predominate • Intracardiac tumors – atrial myxoma • Intracardiac defects

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Atrial Fibrillation (AF) Incidence of Stroke

• Most common cardiac arrhythmia and affecting • Incidence of stroke associated with AF 1% of the population increases with age • Prevalence increases with increasing age Stroke Rate Age Group • Relatively infrequent in those under 40 years old (percent per year) (years) • occurs in upwards of 5% of those over 80 years 1.3 50-59 of age 2.2 60-69 4.2 70-79 5.1 80-89

Circulation 2002;106:14; Arch Intern Med 1987;147:1561 39 Wolf et.al, Stroke 1991;22:983 40

Risk of Stroke in AF: Other Studies Cardiogenic Embolism

• Once you have had a cardioembolic stroke, the • “Hyperdense MCA sign” risk of recurrence in the first 2-3 years may be – due to embolic as high as 12% per year if untreated occlusion of the right • International Stroke Trial middle cerebral artery – Lancet 1997;349:1569 with distal clot • Oxfordshire community stroke project propagation – BMJ1992;305:1460

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7 Small Vessel Ischemic Stroke Small Vessel Ischemic Stroke Lacunar Infarctions Lacunar Infarctions

• Occlusion of one of the lenticulostriate vessels with resultant lacunar stroke • Typically <1.5 cm in diameter • Stuttering clinical course

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Small Vessel Ischemic Stroke Lacunar Infarctions Lacunar Syndromes

• Due to occlusion of the lumen of small Anatomical Site Stroke Syndrome penetrating blood vessels through the process of Genu of the -Clumsy Hand media hypertrophy and fibrinoid deposition Syndrome – lipohyalinization Ventral posterior Pure sensory loss without • Common in hypertensive and diabetic patients weakness • Account for about 18% of strokes Posterior of the internal Pure motor weakness capsule without sensory loss • Almost always affect the deep white matter 3rd nerve and cerebral Weber’s syndrome: – rare cortical syndromes peduncle 3rd n. palsy + contralateral weakness

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Transient Ischemic Attack (TIA) TIA

• Occur in over half of patients who subsequently • Transient monocular visual loss develop a stroke – • Not a stroke – suggests lesion of the ipsilateral carotid artery – “warning” event that eventual stroke is likely • Episodic/Transient aphasia • Deficits may be as profound as that of major • Episodic/Transient hemiparesis stroke--but transient • Episodic/Transient vertigo • Symptoms last less than 24 hours with full return – brain stem TIA to baseline by definition • Episodic/Transient diplopia – typically, less than 30 minutes – double vision – brain stem TIA 47 48

8 TIA: Implications The “Stroke Work-up”

• 10.5% of patients with a TIA will go on to have a • Avoid the “Million-Dollar-Shot-Gun” work-up stroke in the next 90 days – tailor testing to the relevant clinical picture • Half (5.2%) of these strokes will occur within 2 and feasible treatment options days of TIA presentation • 20% of patients with a TIA will have a stroke within the 2 years following the event • Patients should be evaluated just as fully as if they have had a completed stroke

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The “Stroke Work-up”: The “Stroke Work-up” Other Studies

• Basics (for everybody): • Cardiac monitoring – chest X-ray – glucose, urinalysis – ICU, floor monitoring, Holter monitoring in – EKG – stool hemoccult selected patients –CBC – liver panel • Hypercoagulable state work-up – electrolytes • Initial CT scan • Immune mediated/vasculitic serological studies – renal function – in just about every • Modifiable risk factor screens – basis coagulation acute presentation • Cerebrospinal fluid evaluation studies of stroke • Toxin, pregnancy, myocardial infarction screens

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The “Stroke Work-up”: Imaging Studies

•Consider: • 15-20% of all strokes – Carotid Duplex Ultrasound • Poorer prognosis than ischemic stroke • dopplers • 40-50% mortality in 30 days – MRI of the brain with diffusion/ perfusion – rate is higher if 2nd bleed in 2 weeks sequences • Large decline in this stroke type primarily due to – MR-angiography control of HTN over the past 30+ years •MRA – Conventional angiography – Cardiac imaging in suspected cardiac embolism • echocardiography

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9 Intracerebral Hemorrhage: Mechanisms/Subtypes ICH: Hypertensive Hemorrhage • Hypertensive intracerebral hemorrhage – usually involves deep structures such as • the –, globus pallidus, caudate • thalamus, , and deep layers of the cerebellum. – on presentation, BP is usually extremely elevated, but not always. – occurs as a result of chronic uncontrolled (severe) hypertension

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Intracerebral Hemorrhage: Intracerebral Hemorrhage: Mechanisms/Subtypes Mechanisms/Subtypes

• Amyloid Angiopathy – common in the very elderly >75 – usually involves the cerebral lobes • often previously healthy, but may have • temporal/frontal/parietal/occipital Alzheimer’s Disease • with extension to the cortex or subcortex – deposition of amyloid in moderate and small – often will see cortical syndromes vessels rendering them “leaky” • aphasia • neglect

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Intracerebral Hemorrhage: Intracerebral Hemorrhage: Mechanisms/Subtypes Mechanisms/Subtypes

• Due to Ruptured • high mortality Berry • patients present with – sudden “Thunderclap”, worst headache of –severe headache + meningismus one’s life –subhyaloid (retinal) hemorrhages • posterior communicating and anterior –nausea and vomiting communicating arteries are most common sites –+/- deficit/coma

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10 Intracerebral Hemorrhage: Mechanisms/Subtypes ICH: Subarachnoid Hemorrhage

• Subarachnoid Hemorrhage Due to Arterio- venous Malformation (AVM) Bleed – may present like ruptured berry aneurysm • sudden “thunderclap” headache – more often, patients have prior symptoms • frequent episodic, very stereotyped • • seizures

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ICH: Artero-Venous Malformation on ICH: Berry Aneurysm on Contrast CT Contrast CT

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NASCET I: Stroke Rate at 18 Months after Symptomatic First Symptoms (70 to 99% ICA stenosis)

Stenosis Medical Surgical Difference

90-99% 33% 6% 27%

80-89% 28% 8% 20%

Doppler study of the right internal carotid artery showing 70-79% 19% 7% 12% 80% stenosis near the origin (in the bulb) Total 25% 7% 18%

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11 NASCET II: Stroke Rate at 18 Months after Carotid Stenting First Symptoms (50 - 69% ICA stenosis) • Non surgical candidates • Selective benefit for: • Fibromuscular dysplasia –men • Carotid dissection – non/mild hypertensives • Radiation angiitis – non-diabetics • Inaccessible lesions – unilateral lesion only • Carotid Revascularization Endarterectomy vs.Stent – hemispheric symptoms Trial (CREST) now on-going • ACAS (American Carotid Atherosclerosis Study) – As of March, 2004: benefit in asymptomatic men with >60% unilateral • 840 patients enrolled stenosis if surgeon with <3% complication rate • 186 randomized at 55 centers • recruitment of patients and centers is ongoing 67 68 NEJM 1998; 339:1415-1425

Anti-platelet Agents:

• Often first line therapy after first non-cardiac Medications source ischemic stroke • Approximately 20 – 25% stroke recurrence used in the secondary reduction prevention of stroke • Low cost • FDA recommends 50-325 mg Qday • GI side effects most common

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Anti-platelet Agents: Ticlopidine Anti-platelet Agents: Clopidogrel

• More effective in reducing recurrence (21% • More effective than ASA in reducing recurrence RRR) compared to ASA (8%RRR) • Also effectively maintains coronary stent patency • Best maintains coronary stent patency in in combination with ASA combination with ASA • 250 mg BID • Good ASA substitute when there is an allergy to • Risk of Leukopenia, Thrombocytopenia, Hepatic ASA dysfunction • GI symptoms, diarrhea (in 10%) • 75 mg per day • May be more effective, with less side effects in • Less GI side effects than ASA African Americans • Strong benefit in peripheral vascular disease

71 CAPRIE Steering Committee. Lancet. 1996;348:1329-1339 72

12 Anti-platelet Agents: ASA + Extended Release Dipyridamole (ERDP) Antiplatelet Therapy

• More effective in reducing recurrence (23% Relative risk reduction Stroke or Cost per month Stroke/MI/Death RRR) compared to ASA alone (above ASA alone) Clopidogrel (Plavix) • Good safety profile 8% $75 75 mg QD • Can’t use in the ASA allergic Ticlopidine (Ticlid) • May not contain enough ASA for those with 21% $120 or $78 250 mg BID coronary artery disease Aspirin + Extended • 200(ERDP)/25(ASA) BID Release Dipyridamole 23% $81 (Aggrenox) 25/200 BID • Headache in upwards of a third of patients ?16% not SS Clopidogrel and ASA $75 + $3 MATCH

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