CEREBROVASCULAR DISEASE Dr. Lilian Bosire — MKU Lecturer, Pathologist — OVERVIEW & DEFINITIONS Cerebrovascular disease = brain injury due to altered blood
CEREBROVASCULAR DISEASE Dr. Lilian Bosire — MKU Lecturer, Pathologist --- OVERVIEW & DEFINITIONS Cerebrovascular disease = brain injury due to altered blood flow; grouped into ischemic and hemorrhagic etiologies — tissue infarction is the ultimate consequence of both. Stroke = neurologic signs/symptoms explained by a vascular mechanism, with acute onset, persisting beyond 24 hours If symptoms resolve within 24 hours → Transient Ischaemic Attack (TIA) Epidemiology: 3rd leading cause of death in the US (after heart disease and cancer); most prevalent cause of neurologic morbidity and mortality. Two Major Mechanisms of Stroke: Mechanism Details --- --- Ischaemia/Hypoxia Impaired blood supply/oxygenation; global or focal; embolism thrombosis Haemorrhage Rupture of CNS vessels; causes include hypertension, aneurysms, vascular malformations --- A. HYPOXIA AND ISCHAEMIA Why the Brain is So Vulnerable: Brain = only 1–2% of body weight but receives ~15% of resting cardiac output and accounts for ~20% of body's oxygen consumption Strictly dependent on aerobic metabolism — no significant anaerobic reserve Cerebral blood flow maintained constant over a wide BP range via autoregulation of vascular resistance Deprivation occurs via: Hypoxaemia — low blood oxygen content Ischaemia — inadequate blood flow (from ↓ perfusion pressure, small/large vessel obstruction, or both) Tissue Survival in Ischaemia Depends On: Presence of collateral circulation Duration of ischaemia Magnitude and rapidity of flow reduction These factors determine the anatomic site, size of lesion, and resulting clinical deficit Special CNS Mechanism — Excitotoxicity: Ischaemia → inappropriate release of excitatory amino acids (especially glutamate ) Glutamate acts on NMDA receptors → excessive Ca²⁺ influx → neuronal death This is termed excitotoxicity — unique to CNS ischaemia The Penumbra — Clinically Important: Zone of "at-risk" brain between necrotic core and normal tissue Cells here can die by apoptosis (not just necrosis) Can potentially be rescued by anti-apoptotic interventions → basis of thrombolytic therapy (tPA within 4.5 hours) --- B. FOCAL CEREBRAL ISCHAEMIA Definition: Reduction or cessation of blood flow to a localized brain area due to partial or complete arterial obstruction → sustained ischaemia → infarction in the territory of the compromised vessel. Collateral Circulation — ⚠️ Know This: Primary collateral: Circle of Willis (supplemented by external carotid-ophthalmic collaterals) Secondary collateral: Leptomeningeal vessels → supply distal branches of ACA, MCA, PCA via cortical-leptomeningeal anastomoses ⚠️ Little to NO collateral flow for deep penetrating vessels of thalamus, basal ganglia, and deep white matter → these areas are most vulnerable to small vessel disease Causes of Focal Ischaemia/Infarction: 1. Embolism (more common than thrombosis in the brain) Source Details --- --- Cardiac mural thrombi Most common; from MI, valvular disease, atrial fibrillation Arterial thromboemboli From atheromatous plaques — most often at carotid bifurcation Paradoxical thromboemboli In children with cardiac anomalies (R→L shunts) Cardiac surgery-related Other Tumour emboli, fat emboli (fractures), air emboli Emboli lodge at vessel branch points or areas of pre-existing luminal stenosis MCA territory most commonly affected (direct extension of ICA) — equal incidence in both hemispheres "Shower embolization" (e.g., fat embolism after fractures) → generalised cerebral dysfunction, disturbances of consciousness, often without localising signs Widespread haemorrhagic white matter lesions = characteristic of bone marrow embolization after trauma 2. Thrombosis Most commonly from acute change in vulnerable atherosclerotic plaques (same mechanism as coronary artery disease) Most common sites: carotid bifurcation , origin of MCA, either end of basilar artery Thrombi → progressive luminal narrowing → anterograde extension → fragmentation → distal embolization Associated with systemic diseases: hypertension and diabetes 3. Vasculitis Inflammatory vessel involvement → luminal narrowing → occlusion → infarcts Infectious vasculitis: syphilis, TB; now more common with immunosuppression/opportunistic infections (e.g., aspergillosis) Non-infectious vasculitis: Polyarteritis nodosa → single or multiple infarcts Primary angiitis of the CNS — develops without systemic vasculitis Other causes of thrombosis: hypercoagulable states, dissecting aneurysm of neck vessels, drug abuse (amphetamines, heroin, cocaine) Types of Brain Infarcts — ⚠️ Key Distinction: Type Mechanism Features --- --- --- Non-haemorrhagic (pale/anaemic) End-organ circulation; limited collateral supply Starts pale; most occlusive infarcts begin this way Haemorrhagic (red) Ischaemia-reperfusion injury after dissolution/fragmentation of occlusive material Secondary haemorrhagic transformation; punctate haemorrhages; can occur with anticoagulation ⚠️ Non-haemorrhagic infarcts are called "ischaemic" cl