Stroke: An Overview

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 Subtypes
Hemorrhagic Stroke (17%)
Intracerebral Hemorrhage (59%)

Ischemic Stroke (83%)

Atherothrombotic Cerebrovascular Disease (20%)
Cryptogenic and Other Known Cause (30%)

Subarachnoid Hemorrhage (41%) Lacunar (25%) Small vessel disease Embolism (20%)

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 bodys 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

Ischemia Penumbra

Infarction
8

50 55

25
Edema

20
Loss of electrical

15
Na/K+ pump

Normal ml/100g/mi n

lactate ATP

activity

failure;

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

Asymptomatic carotid stenosis Sickle cell disease

Postmenopausal hormone therapy

Diet and nutrition

Cigarette smoke

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 Large artery atherosclerosis Small vessel disease Cardioembolism Other specific etiologies Undetermined etiologies Total Total 27.7% 37.7% 10.9% 1.5% 22.3% 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

Vertebrobasilar

Amaurosis fugax Dysphasia Hemiparesis Hemi-sensory loss

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

Intracranial atherosclerosis

Penetrating artery disease Flow-reducing carotid stenosis

Carotid plaque with arteriogenic emboli

Aortic arch plaque Cardiogeni c emboli

Atrial fibrillation Valve disease

Left ventricular thrombi

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

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
Image courtesy Regional Neurosciences Unit, of Conventional cerebral angiography Newcastle General Hospital, Newcastle, UK.

Diagnosis: CT Scan

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)

CT: Cerebral infarction

Brain swelling

Focal cortical effacement

Ventricular compression

Multimodal CT Imaging
CT PCT
CTA

Tissue Status

Perfusion Status

Vessel Status

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

Differential Diagnosis of Stroke

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

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 Detects abnormal tissue perfusion Area of penumbra? Target of thrombolysis

Perfusion-weighted imaging (PWI):

Diffusion-perfusion mismatch:

Multimodal MRI Imaging

DWI PWI MRA

Tissue Status

Perfusion Status

Vessel Status

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

blood pressure glucose smoking lipids

stroke mortality
mass popl. strategy

acute treatment

First stroke
high risk strategy

Secondary prevention

recurrent stroke

hypertension TIA Atrial fibrillation other vascular disease

Rehabilitation

Stroke related disability

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 DM, HTN, hyperlipidemia, cardiac diseases,

Pharmacological intervention:

Management: Improved CBF

Cerebral arterial stenosis/occlusion
LAA/CE/SVD/others Cerebral autoregulation (endothelial function etc)

Decreased CBF

Brain tissue ischemia

Prevention: endarterectomy, stenting Acute management: thrombolytics medical and mechanical Targeting endothelial cell functions (ACEI, calcium blocker, statins, etc.)

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