Etiology, risk factors and basic pathophysiology of CVAs.

1. Approach to a patient with stroke AshwinHaridas Asem Ali Ashraf Adam EAH Adam

2. Definitions Stroke Clinical syndrome of rapid onset of focal deficits of brain function lasting more than 24 hours or leading to death Transient Ischemic attack (TIA) Clinical syndrome of rapid onset of focal deficits of brain function which resolves within 24 hours

3. Definitions Progressive Stroke A stroke in which the focal neurological deficits worsen with time Also called stroke in evolution Completed Stroke A stroke in which the focal neurological deficits persist and do not worsen with time

4. Epidemiology Third most common cause of death after cancer and ischeamic heart disease Most common cause of severe physical disability Prevalence of stroke in India is about 1.54 per 1000 Death rate is about 0.6 per 1000 Incidence and prevalence of stroke is on the rise due to increasing adoption of unhealthy lifestyle & an increasing life expectancy

5. Stroke Risk Factors Fixed Age Gender (Male>Female) Race (Afro-Caribbean>Asian>European) Heredity Previous vascular event eg. MI, peripheral embolism High fibinogen Modifiable Hypertension Heart disease (Atrial fibrillation, endocarditis) Diabetes mellitus Hyperlipidaemia Smoking Excess alcohol consumption Oral contraceptives

6. Types of Stroke Ischemic Hemorrhagic

7. Anterior Circulation Posterior Circulation

8. Middle Cerebral Artery

9. Anterior Cerebral Artery

10. Posterior Cerebral Artery

11. Ischemic Stroke 80% of strokes Arterial occlusion of an intracranial vessel leads to hypoperfusion of the brain region it supplies

12. Etiology of ischemic stroke Thrombotic Lacunar stroke Large vessel thrombosis Hypercoagulable disorders Embolic Artery to artery Carotid bifurcation Aortic arch Cardioembolic Atrial fibrillation Myocardial infarction Mural thrombus Bacterial endocarditis Mitral stenosis Paradoxical embolus

13. Thrombotic Stroke Atherosclerosis is the most common pathology leading to thrombotic occlusion of blood vessels Hypercoagulable disorders – uncommon cause Antiphospholipid syndrome Sickle cell anemia Polycythemiavera Homocysteinemia Vasculitis: PAN, Wegener’s granulomatosis, giant cell arteritis

14. Thrombotic Stroke Lacunar stroke Accounts for 20% of all strokes Results from occlusion of small deep penetrating arteries of the brain Pathology: lipohyalinosis & microatheroma Thrombosis leads to small infarcts known as lacunes Clinically manifested as lacunar syndromes

15. Embolic Stroke Cardioembolic stroke Embolus from the heart gets lodged in intracranial vessels MCA most commonly affected Atrial fibrillation is the most common cause Others: MI, prosthetic valves, rheumatic heart disease Artery to artery embolism Thrombus formed on atherosclerotic plaques gets embolized to intracranial vessels Carotid bifurcation atherosclerosis is the most comon source Others: aortic arch, vertebral arteries etc.

16. Etiology of ischemic stroke

17. Blood supply to the brain is autoregulated Blood flow If zero leads to death of brain tissue within 4-10min <16-18ml/100g tissue/min infarction within an hour Ischemia leads to development of an ischemic core and an ischemic penumbra Pathophysiology of Ischemic Stroke

19. Ischemic Penumbra Tissue surrounding the core region of infarction which is ischemic but reversibly dysfunctional Maintained by collaterals Can be salvaged if reperfused in time Primary goal of revascuralization therapies

20. Thrombus/embolus Hypoperfusion ATP depletion Failure of Na+/K+ATPase membrane ionic pump Activation of pro-coagulant pathways Membrane depolarization & cytotoxic cellular edema Free fatty acid release Calcium entry Glutamate release Activation of lipid peroxidases, proteases & NO synthase Destruction of intracellular organelles, cell membrane & release of free radicals Liquefactive necrosis

21. Hemorrhagic Stroke Two types Intracerebral hemorrhage(ICH) Subarachnoid hemorrhage(SAH) Higher mortality rates when compared to ischemic stroke

23. Small arteries are damaged due to hypertension

24. In advanced stages vessel wall is disrupted and leads to leakage

26. Pathophysiology Of Hemorhagic Stroke Explosive entry of blood into the brain parenchyma structurally disrupts neurons White matter fibre tracts are split Immediate cessation of neuronal function Expanding hemorrhage can act as a mass lesion and cause further progression of neurological deficits Large hemorrhages can cause transtentorial coning and rapid death