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 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 Albers GW, et al. Chest. 1998;114:683S-698S. Rosamond WD, et al. Stroke. 1999;30:736-743. Embolism (20%) 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 Ischemia 50 – 55 Normal ml/100g/mi n 25 Edema ↑lactate ATP Infarction Penumbra 20 15 8 Loss of Na/K+ electrical pump 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 Asymptomatic carotid stenosis Sickle cell disease Dyslipidemia Atrial fibrillation Other cardiac conditions Diet and nutrition Cigarette smoke Physical Inactivity Postmenopausal hormone therapy 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 Intracranial atherosclerosis Carotid plaque with arteriogenic emboli Aortic arch plaque Cardiogeni c emboli Penetrating artery disease Flow-reducing carotid stenosis 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, ofConventional 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 Tissue Status Perfusion Status CTA 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) : Perfusion-weighted imaging (PWI): Detects areas of restricted diffusion of water Bright-up in acute ischemic stroke Differentiation between new and old lesions Detects abnormal tissue perfusion Diffusion-perfusion mismatch: Area of penumbra? Target of thrombolysis Multimodal MRI Imaging DWI Tissue Status PWI Perfusion Status MRA 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 Secondary prevention recurrent stroke high risk strategy 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 Pharmacological intervention: DM, HTN, hyperlipidemia, cardiac diseases, Management: Improved CBF Cerebral arterial stenosis/occlusion LAA/CE/SVD/others Decreased CBF Cerebral autoregulation (endothelial function etc) 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