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Clinical Aspects of Stroke

Pierre Fayad, MDReynolds Centennial Professor & Chairman,

Department of Neurological Sciences

University of Nebraska Medical Center, Omaha, NE

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“Stroke”

• APOPLEXY from Greek “Apo Plexe” meaning “a stroke”.

• Anyone seized by sudden disability was thought to be “struck down” by the Gods.

Haubrich WS. Medical Meanings: A Glossary of Word Origins. Publisher: American College of Physicians 2003

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Steps in Neurologic Evaluation

Gather information– Chief complaint– Symptoms, evolution– Physical examination

Analysis– Localization– Pattern of disease– Comparison to clinical database

Gather information– Diagnostic tests

Diagnosis & Treatment

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Steps in Stroke EvaluationGather information

– Chief complaint– Symptoms and history: risk factors, chronologic

evolution– Physical examination: vascular and neurologic

Analysis– Localization: CNS level, large vessel, branch, …– Pattern of disease: tempo, risk factors– Comparison to clinical datatbase

Gather information– Diagnostic tests: location, size, type, mechanism

Diagnosis & Treatment

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What Is A “STROKE”?

CLINICAL DEFINITION of focal neurologic deficit, of vascular etiology, lasting > 24 HOURS.

Diagnosis is dependent on neurologic deficit and NOT imaging.

“Generic term for a clinical syndrome that includes infarction, hemorrhage, and SAH.”

NINDS Classification of CVD III. Stroke 1990, 20:627-680

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Types of Stroke

• Ischemic Stroke– Brain damage from lack of blood flow– Occlusion of blood vessel– Thrombosis, embolism

• Hemorrhagic stroke– Rupture of blood vessel– Brain damage from blood invasion

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Stroke Subtypes: Stroke Data Bank

Lacunar19%

SAH13%

ICH13%

Other3%

Cardioembolic14%

Atherosclerotic6%

Undetermined32%

Stroke Data Bank, Foulkes et al, Stroke 1988;19:547

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Definition of Transient Ischemic Attack• Classic definition

– A sudden, focal neurologic deficit lasting less than 24 hours, presumed to be of vascular origin, and confined to an area of the brain or eye perfused by a specific artery

• Proposed definition– A brief episode of neurologic dysfunction caused by

focal brain or retinal ischemia, with clinical symptoms typically lasting less than 1 hour, and without evidence of acute infarction

Albers GW et al. N Engl J Med. 2002;347:1713-1716.

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Short-term Prognosis after Emergency Department Diagnosis of TIA

Johnston SC, et al. JAMA 2000;284:2901-2906.

Inclusion criteria:

Objective:

Outcome measures:

Total events:

TIA by ED physicians

Short-term risk of strokeafter ED diagnosis

Risk of stroke and otherevents during the 90 daysafter index TIA

25.1%

Outcome events

10.5%

12.7%

2.6% 2.6%

Stroke RecurrentTIA

CV event Death

0 %

5 %

10 %

15 %

Within90 days

Within48 hr

5.3%

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US Stroke Facts 2003• Incidence

– 700,000 new or recurrent stroke yearly– One stroke every 45 seconds

• Mortality– 168,000 Stroke-related death yearly (1 of 14 deaths)– Third leading cause of death after heart and cancer– One stroke-related death every 3 minutes– Of every 5 stroke deaths: 2 men, 3 women

• Costs– $51 billion in 2003 for stroke related medical costs and

disability

American Stroke Association

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Stroke Risk Factors

Medical Conditions Hypertension Cardiac disease Atrial fibrillation Hyperlipidemia Diabetes mellitus Carotid stenosis Prior TIA or stroke

Non-Modifiable

Age, Gender, Race, Heredity

Behaviors Cigarette smoking Heavy alcohol use Physical inactivity

Modifiable

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Goals For Acute Stroke Care• Rapid triage and identification of stroke

• Stroke type: Ischemic vs Hemorrhagic• Eligibility for “acute stroke therapy”• Determine size, location, & vascular territory• Establish plans for efficient Management &

discharge• Stabilization & prevention of complications• Determine etiology & mechanism• Initiate secondary stroke prevention strategies• Initiate rehabilitation assessment and therapy

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Intracerebral Hemorrhage

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Hypertensive ICH: Post-Mortem

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Clinical Features Suggestive Of ICH

• Severe headache

• Depressed consciousness

• Nausea and vomiting

• Horizontal diplopia

• Papilledema and pre-retinal hemorrhages.

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ICHSx

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CAUSES OF INTRACRANIAL HEMORRHAGE

HTNHTN50%50%Amyloid angiopathyAmyloid angiopathy12%12%AnticoagulantsAnticoagulants10%10%TumorsTumors 8%8%Prescription and street drugsPrescription and street drugs 6%6%AVMs and aneurysmsAVMs and aneurysms 5%5%MiscellaneousMiscellaneous 9%9%

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Charcot-Bouchard Microaneurysms

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Intracranial Vascular Malformations

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ICH - General Management

• Nutrition• DVT prophylaxis• Hydration and electrolytes• Acute arterial hypertension• Intracranial hypertension• Hydrocephalus• Seizure prophylaxis and treatment• Surgery and decompression

AHA Special Writing Group, Stroke 1999;30:905-915AHA Special Writing Group, Stroke 1999;30:905-915

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Dose-Ranging Study: rFVIIa in Preventing Early Hematoma Growth in Acute ICH

• Multicenter, international, Phase II study, 400 patients, CT < 3 hrs from Sx, Rx < 60 min CT.

• Arms: Placebo, 40, 80, 160 mcg/kg• Significantly reduces

– 45-62% RR Dose-dependent hematoma growth– 38% RR Mortality

• Significantly improves– Global functional outcome (mRS and BI) at 90 days

• Small increase in the risk of acute thromboembolic events

Mayer SA et al. N Engl J Med. 2005;352:777-785.

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Subarachnoid Hemorrhage

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Subarachnoid Hemorrhage: Schematic

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Berry Aneurysm Rupture

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Location of Berry Aneurysms

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SAH Symptoms

& Diagnosis

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IntracranialAneurysms Sx

31Johnston SC, et al. Ann Neurol. 2000;48:11-19.

Aneurysm Coiling or Clipping

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SAH - Delayed Vasospasm• Facts

– A leading cause of death and disability

– Starts 3-5 d after SAH, and maximal at 3-14 d.

– 20-30% delayed neurologic ischemic deficits.

• Diagnosis – TCD, angiography.

• Treatment– Nimodipine

– Hypertensive, hypervolemic, hyperosmolar Rx (HHH)

– Local IA papaverine -> transluminal angioplasty

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Ischemic Stroke

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Stroke Mimics• Metabolic

–Hyper/hypoglycemia, Hyponatremia, Hypo/hyperthyroidism, Hepatic encephalopathy

• Seizures• Subdural hematoma• Infections

–Brain abscess, encephalitis, meningitis

• Neoplasm• Drug overdose (also a cause of stroke).• Hypertensive encephalopathy• Psychogenic• Migraine

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Vascular Localization

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!!!Learn Neurology Stroke-By-Stroke!!!

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Brain Picture

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What The Brain Does

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Cortical Functional Localization

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Homunculus

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Localizing Stroke

• Stroke affects three main areas of the brain

–Left hemisphere

–Right hemisphere

–Brainstem/cerebellum

• Neurologic deficits patterned in syndromes according to brain part affected and location

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Cerebral Circulation

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Cerebral Vascular Territories

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Left (Dominant) Cerebral Hemisphere Syndrome

• Aphasia.

• Left gaze preference.

• Right visual field cut.

• Right hemiparesis.

• RIght hemisensory loss.

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Right (Non-dominant) Cerebral Hemispheric Syndrome

• Neglect (left hemi-inattention)

• Right gaze preference.

• Left visual field deficit.

• Left hemiparesis.

• Left hemisensory loss.

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Syndromes of Carotid Branch Occlusions

Location

Frontal Lobe

Parietal lobe

Temporal lobe

Occipital lobe

Artery

ACA

MCA: ant division

MCA: post division

MCA: post division

PCA

Dominant Non-dominant

Contralat LE weaknessAbulia

Contralat LE weaknessAbulia

Expressive aphasiaContralat hemiparesisIpsilat gaze deviation

AprosodiaContralat hemiparesisIpsilat gaze deviation

Conduction aphasiaGerstman’s synd, HH Contral hypoesthesia

Anosognosia, Apraxia, Contralateral neglect, Hypoesthesia, HH

Receptive aphasia, Contralateral HH

Contralateral Hemianopia

Alexia without agraphiaContralateral HH

Contralateral Hemianopia

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Brainstem Syndrome

• Crossed signs.

• Hemiparesis or quadraparesis.

• Hemisensory loss or sensory loss in all four limbs.

• Eye movement abnormalities.

• Oropharyngeal weakness.

• Decreased consciousness.

• Hiccups or abnormal respirations.

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Cerebellar Syndrome

• Gait or limb ataxia

• Vertigo, tinnitus

• Nausea, vomiting.

• Decreased Consciousness.

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Acute Stroke Therapy

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Platelets in Acute Vascular Events

AtheroscleroticVessel

PlaqueRupture

PlateletAdhesion,

Recruitment,Activation,

andAggregation

ThrombusFormation

ThromboticOcclusion

MI

Stroke

Acute Peripheral Arterial Occlusion

CollagenPlaquePlatelets Thrombus

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Cerebral Ischemia: Basic Mechanisms

•Perfusion failure•Energy failure•Loss of membrane function•Edema•Cell death

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Ischemic Cascade

QuickTime™ and aPhoto - JPEG decompressor

are needed to see this picture.

Brott T et al, NEJM 2000,343:710-721

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ISCHEMIC PENUMBRA

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Acute Ischemic Stroke: Large MCA, CT

56Time is Brain

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Supportive Acute Stroke Care

• Monitor for potential worsening

• Stabilize vital signs

• Maintain adequate hydration

• Optimize nutrition: early, PO, NG feeds, PEG

• Prevent aspiration: screen for those at risk

• Treat fever aggressively: any elevations

• Mobilize early: within 24 hours

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Therapies for Acute Cerebral Ischemia

• Antithrombotic therapy– Antiplatelet medications

– Aspirin, Clopidogrel, ASA/ER-DP– IV GP IIb IIIa antagonists (Abciximab)

– Anticoagulants – Hypofibrinogenemic (Ancrod)

• Reperfusion and perfusion enhancement– Thrombolytic therapy: Intravenous, intra-Arterial– Mechanical clot dissolution/removal

• Neuroprotective Therapies– Non-specific cellular protection– Specific neuronal protection

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Acute Antiplatelet Therapy for Stroke

• Aspirin 160 mg daily, started within 48 hours, decreases risk of stroke and death at one month.

• Other antiplatelet agents not tested acutely.

• As a rule early AP Rx start recommended.

• Preferable to start same AP agent as OP.

CAST Collaborative Group, Lancet 1997;349:1641-1649

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Acute Anticoagulation For Stroke: Conclusions

• Acute anticoagulation DOES NOT…– Does not improve overall outcome, prevent neurologic deterioration or

prevent recurrence

• Indications– SQ anticoagulation for DVT prophylaxis in immobilized patients or

paralyzed leg

– Sinus venous thrombosis

• Risks– Risk of cerebral hemorrhage and systemic bleed substantially

increased.

• Untested– Acute anticoagulation < 12 hours

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NINDS IV tPA

Primary Outcomes

NEJM 1995;333:1581-1587

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Acute Stroke: Intra-Arterial Lysis

Brott T et al, NEJM 2000,343:710-721

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Merci Clot Retriever Concentric Medical Inc.

Gobain YP. Stroke 2004;35:2848-2854

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MERCI-1: Example of Clots Retrieved

Gobain YP. Stroke 2004;35:2848-2854

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Stroke Prevention Strategies

• Identify stroke subtype and mechanism

• Risk Factors and Lifestyle modification

• Non-Anti-thrombotic Treatments

• Oral Anticoagulation

• Antiplatelet Medications

• Surgery and interventions

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Stroke Mechanism Determination

CT/MRI

Hemorrhagic StrokeHemorrhagic Stroke

Ischemic StrokeIschemic Stroke

Large Artery StrokeLarge Artery Stroke

Cardioembolic Stroke Cardioembolic Stroke

Lacunar syndrome, YesRisk Factors

No Lacunar small vessel Lacunar small vessel

stroke stroke

Other defined etiologies, YesNo

Infarct undetermined Infarct undetermined causecause

other

TIA or Stroke normal or infarct

Specific work-up

Tandem pathology, YesNo

TTE/TEE, ECGcardiac source, Yes

No

Infarction Determined Infarction Determined EtiologyEtiology

Duplex, TCD, MRA, angiogram

blood

Adapted Fayad PB; J. Cardiovascular Diagn & Proc 1994;12 (1):35-42.

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Carotid Bifurcation Athero-Thrombo-Embolism

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MCA Embolism

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Common Cardioembolic

Sources

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Intracranial Atherothrombosis

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Lenticulostriate Arteries

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Classic Lacunar SyndromesClinical features Common locationsLacunar Syndrome

Hemiparesis (arm, leg, face equally)

Post limb IC, Ant limb IC, Corona radiata

Sensory loss, dysesthesia (face, arm, leg)

Thalamus, centrum semiovale

Combined hemi motor and sensory deficits

Thalamus, putamen, corona radiata

Homolateral ataxia with crural paresis

Corona radiata, posterior limb IC, thalamus

Combined dysarthria, upper limb ataxia

Anterior limb IC, genu, pons hemorrhage

Pure motor hemiparesis

Pure sensory stroke

Sensory-motor stroke

Ataxic hemiparesis

Dysarthria-clumsy hand syndrome

Fayad et al. Curr. Rev CVD 1996, Current Medicine: 81-92

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CarotidPathologies

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Non Anti-Thrombotic Treatments

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Non-Anti-Thrombotic Medical Therapies For Stroke Prevention-1: Lipid Lowering

• Clear benefit for statins in primary stroke prevention (20-30%) in patients with CAD and even average level of LDL cholesterol.

• No demonstration yet of statin benefit in secondary stroke risk reduction. (Exception HSP, SPARCL pending).

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Non-Anti-Thrombotic Medical Therapies For Stroke Prevention-2: Anti-HTN

• Significant stroke risk reduction (20%-30% RRR ischemic, >50% RRR hemorrhagic) in treating hypertension, systolic or diastolic. (more evidence for systolic)

• Anti-HTN: Significant primary & stroke risk reduction, even in non-hypertensives.

• Superiority of Anti-HTN drug classes in stroke prevention undetermined yet.

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Non-Anti-Thrombotic Medical Therapies For Stroke Prevention-3: Miscellaneous

• No benefit (but clear harm) from hormonal replacement in post-menopausal women.

• No benefit from Vitamin B supplementation in hyperhomocystinemia in patients with stroke or TIA.

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Antiplatelet (AP) Therapy in Stroke Prevention: Summary

• Aspirin (ASA) not indicated for primary stroke prevention.

• Low-dose ASA recommended for secondary stroke prevention.

• No single AP agent more effective than aspirin.• To Date, ASA-ER DP only AP combination

effective and safe (> ASA) in secondary stroke prevention

• In patients at risk for stroke, the combination of Clopidogrel and aspirin significantly increase the risk of ICH, life-threatening and major bleeding.

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AsymptomaticICA/CCA stenosis

Risk factormodification

Warfarin

Asymptomatic and healthywithout risk factors

AntiplateletAnti-HTN?Statins?

Men> 60

Women post-menopausal

Estrogen

Asymptomatic butwith risk factors

NVAFCardioembolic

source/pathology

Endarterectomy

Evaluate CAD

No other pathology

Primary Prevention Of Ischemic Stroke

Adapted From Fayad PB; J. Cardiovascular Diagn & Proc 1994;12 (1):35-42.

AMI

Statins

High riskLow risk

X

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Secondary Prevention of Ischemic Stroke

Adapted From Fayad PB; J. Cardiovascular Diagn & Proc 1994;12 (1):35-42.

Extracranialcarotid stenosis

70-99%

TIA or STROKE

Cardiogenic embolism

Small VesselLacunar

Undeterminedetiology

CEA

50-69% < 50%

Intra/extra-cranialstenosis/occlusion

Large Vessel Athero

Documentedsource/pathology

AF

Antiplatelet, EstrogenAnti-HTN? Statins?

WarfarinXXXX

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Carotid Stenting

Reimers B, et al. Circulation. 2001;104:12-15.

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ACCULINK & ACCUNET Stent System (Guidant): ARCHER & CREST

ACCULINK ACCUNET

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Cerebral Circulation

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72-year-old right-handed African-American woman

admitted with weakness and speech difficulty

Stroke Case

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Stroke Case:

• Sudden onset of right arm and leg weakness• Speech difficulty• Hospital admission ~6 h after symptom onset

72-year-old woman

Presentation

• Hypertension• Dyslipidemia• Diabetes• Nonsmoker• Rarely drinks alcohol

History

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CT scan at 10 days

Stroke Case:72-year-old woman

Should this patient have had a follow-up scan earlier than 10 days post-admission?

Would an MRI have been better?