Stroke: An Overview

台北榮民總醫院神經醫學中心 神經血管科

許立奇 醫師

What Is Stroke ?

A stroke occurs when blood flow to the brain is interrupted by

a blocked or burst blood vessel.

Definition of Stroke Stroke (Cerebrovascular accident, CVA): rapidly

developing clinical signs of focal or global disturbance of cerebral function, with symptoms lasting 24 hours or longer, or leading to death, with no apparent cause other than a vascular origin

WHO, 1976 Stroke definition by time course:

Transient ischemia attack (TIA): ischemic events < 24 hours without apparent permanent neurological deficits

Stoke in evolution: progressive neurological deficits over time suggesting a widening of the area of ischemia

Completed stroke: ischemic event with persisted deficit

Two Major Types of Stroke

Stroke SubtypesIschemic Stroke (83%)Hemorrhagic Stroke (17%)AtherothromboticCerebrovascularDisease (20%)

Embolism (20%)Lacunar (25%)Small vessel disease

Cryptogenic and Other KnownCause (30%)

IntracerebralHemorrhage (59%)

Subarachnoid Hemorrhage (41%)

Albers GW, et al. Chest. 1998;114:683S-698S.Rosamond WD, et al. Stroke. 1999;30:736-743.

Epidemiology ( I ): Global Burden

15 million nonfatal stroke each year in the world Second leading cause of death: 5 million each year Major cause of permanent disability: another 5

million each year Risk of stroke: age- and sex-dependent Incidence: varies with geography

388/100,000 in Russia, 247/100,000 in China to 61/100,000 in Fruili, Italy

Epidemiology ( II ): Taiwan

The second leading cause of death Incidence: average annual incidence of

first-ever stroke in Taiwan aged 36 years old or over is 300/100,000 (CI: 71%, ICH: 22%, SAH: 1%,others: 6%)

Prevalence: 1,642/100,000 (>36 years old)

Pathophysiology of Ischemic Brain Injury

Brain: 2% of human body’s mass 20% of cardiac output

Inadequate perfusion: tissue death and functional deficit

Ischemic brain injury: A series of interlocking thresholds – the “ ischemic

thresholds ” Decrement in regional CBF key pathologic events

Effects of Reduced CBF

Normal ml/100g/min

50 – 55 25 20 15 8

Ischemia

Edema Loss of Na/K+

electrical pump

↑lactate activity failure; ↓ ATP

Penumbra

Infarction

Cell Death

Pathophysiology of Ischemic Brain Injury

Topography of focal ischemia Flow gradient: heterogeneous regional CBF reduction

after focal ischemia Densely ischemia region surrounded by areas of less

severe CBF reduction Ischemic penumbra: an area of reduced perfusion

sufficient to cause potentially reversible clinical deficits but insufficient to cause disrupted ionic homeostasis

Pathogenesis of Ischaemic Stroke

Penumbra

Infarction

Ischemic Penumbra: Current Concept

Risk Factors

Importance: Identifying those at greatest risk for stroke Providing targets for preventative therapies

Types: Modifiable Non-modifiable

Stroke: Non-modifiable Risk factors

Age Sex Ethnicity Prior stroke Heredity

Stroke: Well-Documented and Modifiable Risk Factors

Hypertension

Diabetes

Dyslipidemia

Atrial fibrillation

Other cardiac conditions Cigarette smoke

Asymptomatic carotid stenosis

Sickle cell disease Postmenopausal

hormone therapy Diet and nutrition Physical Inactivity Obesity and body fat

distribution

Modifiable Risk Factors: Others

Classification of Ischemic Stroke

By vascular territory Ant. Circulation: carotid

arteries Post. Circulation: VB system

By stroke etiology

Blood Supply to the Brain:Anterior Circulation

Int. Carotid A. arises from

common carotid a. Branches: anterior

cerebral, anterior communicating, middle cerebral, posterior communicating

Blood Supply to the Brain:Anterior Circulation

Blood Supply to the Brain:Posterior Circulation

Brain Structures and Functions

What Is the Cause of Ischemic Stroke?

Atherothrombosis Embolus:

Material: Red (fibrin rich) or White (platelet rich)

Source: Cardiac? Aortic? Carotid Artery? Small artery disease Hypoperfusion: Hemodynamic Others: arterial dissection, arteritis, etc.

Ischemic Stroke: Atherothrombosis Thrombotic

Acute occluding clot Superimposed on chronic

narrowing

Ischemic Stroke: Cerebral Embolism Embolic

Intravascular material, most often a clot, separates proximally

Flows through arterial system until it occludes distally

Atrial fibrillation

Lacunar Syndromes

Ischemic Stroke Subtypes: Data from Taiwan Stroke Registry (2010)

Subtypes Total

Large artery atherosclerosis

Small vessel disease

Cardioembolism

Other specific etiologies

Undetermined etiologies

27.7%

37.7%

10.9%

1.5%

22.3%

Total 100%

Stroke Warning Signs Sudden weakness or numbness of the face, arm or

leg, especially on one side of the body Sudden confusion, trouble speaking

or understanding Sudden trouble seeing in one or both eyes Sudden trouble walking, dizziness/vertigo, loss of

balance or coordination Sudden, severe headaches with no known cause (for

hemorrhagic stroke)

Localization

Carotid territory Amaurosis fugax Dysphasia Hemiparesis Hemi-sensory loss

Vertebrobasilar Hemianopia Quadraparesis Cranial N dysfunction Cerebellar syndrome Crossed deficit Loss of consciousness

Laboratory Examinations

Hb, Hcr, thromb, leuc glu, CRP, SR, CK, CK-MB, creat APTT, TT-SPA/INR Electrolytes, osmolarity Urine analysis CSF (if needed for differential diagnosis and only

after CT scan, if available) Others, e.g., coagulation survey, homocysteine for

young stroke, rheumotology/immunology screening

Cardiac evaluation: ECG, echocardiography

Evaluation of the Vascular System

Reprinted with permission from Albers GW, et al. Chest. 2001;119:300S-320S.

Penetrating arterydisease

Flow-reducingcarotid stenosis

Atrial fibrillation

Valve disease

Left ventricularthrombi

Cardiogenic

emboli

Aortic archplaque

Carotid plaque witharteriogenic emboli

Intracranialatherosclerosis

Stroke Diagnostic Tests Brain imaging: CT, MR Cardiac Imaging: TTE, TEE, heart monitoring Lipid, coagulation testing Vascular Imaging: Noninvasive

MR angiography (MRA) Intracranial, extracranial

CT angiography (CTA) Intracranial, extracranial

Ultrasound: Carotid, TCD

Invasive Conventional cerebral angiographyImage courtesy of Regional Neurosciences Unit,

Newcastle General Hospital, Newcastle, UK.

Distinguishes reliably between haemorrhagic and ischemic stroke

Detects signs of ischemia as early as 2 h after stroke onset

Identifies haemorrhage immediately Detects acute SAH in 95% of cases Helps to identify other neurological diseases

(e.g. neoplasms)

Diagnosis: CT Scan

CT: Cerebral infarction

Brain swelling

Ventricular compression

Focal cortical effacement

Multimodal CT Imaging

Perfusion Status

CT PCTCTA

CT, computed tomography; PCT, positron computed tomography; CTA, computed tomography angiography.Images courtesy of UCLA Stroke Center.

Tissue Status

Vessel Status

Ischemic stroke Hemorrhage stroke

Craniocerebral / cervical trauma

Meningitis/encephalitis

Intracranial mass

•Tumor

•Subdural hematoma

 Seizure with persistent neurological signs

Migraine with persistent neurological signs

Metabolic

•Hyperglycemia (nonketotic hyperosmolar coma)

•Hypoglycemia

•Post-cardiac arrest ischemia

•Drug/narcotic overdose

Differential Diagnosis of Stroke

Diagnosis: MRI (DWI and PWI)

Acute Ischemic Stroke Diffusion-weighted imaging (DWI) :

Detects areas of restricted diffusion of water Bright-up in acute ischemic stroke Differentiation between new and old lesions

Perfusion-weighted imaging (PWI): Detects abnormal tissue perfusion

Diffusion-perfusion mismatch: Area of penumbra? Target of thrombolysis

Multimodal MRI Imaging

Tissue Status

Perfusion Status

Vessel Status

DWI PWI MRA

DWI, diffusion-weighted imaging; PWI, perfusion-weighted imaging; MRA, magnetic resonance angiography.Images courtesy of UCLA Stroke Center.

Diagnosis: Vascular Imaging Carotid Ultrasound Cerebral Angiography

Management of Cerebrovascular Disease: Current Strategies

Treatment of risk factors in large populations Treatment of highest risk persons Management of acute stroke Prevention and treatment of medical and neurological

complications Rehabilitation Prevention of recurrent stroke

Strategies for Preventing Stroke and Reducing Stroke Disability

First stroke

blood pressureglucosesmokinglipids

mass popl.strategy

hypertensionTIAAtrial fibrillationother vascular disease

high risk strategy

stroke mortality

acute treatment

Secondary prevention

recurrentstroke

Stroke related disability

Rehabilitation

Stroke Therapy: Overview

Risk Factors: Lifestyle modification Risk factor management

Acute stroke therapy Prevention of stroke:

Primary prevention Secondary prevention

Management of Risk Factors

Non-pharmacological intervention: Life style modification: cessation of smoking,

drinking Exercise, weight reduction

Pharmacological intervention: DM, HTN, hyperlipidemia, cardiac diseases,

Management: Improved CBF

Prevention: endarterectomy, stenting Acute management: thrombolytics – medical and mechanical Targeting endothelial cell functions (ACEI, calcium blocker,

statins, etc.)

Cerebral arterial stenosis/occlusi

onLAA/CE/SVD/others

Decreased CBFCerebral autoregulation

(endothelial function etc)

Brain tissue

ischemia

Antithrombotic Therapies to Prevent Ischemic Stroke

Oral anticoagulants Antiplatelet agents

Aspirin 50-325 mg/day Ticlopidine 250 mg twice daily Clopidogrel 75 mg/day Aspirin (25 mg) plus extended-release

dipyridamole (200 mg) twice a day