CEREBROVASCULAR DISEASE Dr. Lilian Bosire — MKU Lecturer, Pathologist --- OVERVIEW & DEFINITIONS Cerebrovascular disease = brain injury due to altered blood flo
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" clinically — confusing because ALL infarcts are caused by ischaemia; the term refers specifically to pale/non-haemorrhagic ones. --- C. MORPHOLOGY OF CEREBRAL INFARCTION — ⚠️ High Yield Timeline Gross Changes: Time Gross Appearance --- --- 0–6 hours Little to no visible change By 48 hours Pale, soft, swollen; grey-white junction becomes indistinct 2–10 days Gelatinous and friable; boundary between normal and infarcted tissue becomes more distinct as oedema resolves 10 days–3 weeks Tissue liquefies → fluid-filled cavity that expands as dead tissue is removed Microscopic Changes (Sequential): Time Microscopic Finding --- --- 6–12 hours Eosinophilic neuronal necrosis ("dead red neurons") — ↑ eosinophilia of cytoplasm → nuclear pyknosis → karyorrhexis; both cytotoxic and vasogenic oedema present; astrocytes and endothelial cells swell; myelinated fibres disintegrate Up to 48 hours Progressive neutrophilic emigration then falls off — never as prominent as in myocardial infarction 48–72 hours Phagocytic cells (monocyte-derived macrophages + activated microglia) appear; become predominant cell type over next 2–3 weeks; macrophages stuffed with myelin breakdown products and blood → persist months to years 1 week Reactive astrocytes and newly formed vessels appear at periphery of lesion Months Astrocytic response recedes → dense meshwork of glial fibres + new capillaries + perivascular connective tissue = gliosis Remote/healed Fluid-filled cavity surrounded by residual gliosis; pia and arachnoid not affected ⚠️ Infarcts heal from the edges inward → different areas of same lesion may appear at different stages simultaneously. Haemorrhagic Infarction: - Temporal evolution parallels ischaemic infarction + blood extravasation and resorption - In patients on anticoagulants → may be associated with extensive intracerebral haematomas Venous Infarcts: - Often haemorrhagic - Occur after thrombotic occlusion of superior sagittal sinus , other sinuses, or deep cerebral veins - Risk factors: neoplasms, localised infections, hypercoagulable states --- D. INTRACRANIAL HAEMORRHAGE Overview: Haemorrhage may occur at any intracranial site: - Epidural/subdural → typically traumatic - Intraparenchymal/subarachnoid → more often manifestation of underlying cerebrovascular disease --- 1. INTRAPARENCHYMAL (PRIMARY) HAEMORRHAGE Definition: Rupture of a small intraparenchymal vessel → primary haemorrhage within the brain → sudden onset neurologic symptoms (stroke). ⚠️ Must not be confused with secondary haemorrhagic transformation of an occlusive infarct. Epidemiology: Peak incidence ~60 years of age; middle to late adult life. Patterns of Haemorrhage: Pattern Location Main Cause --- --- --- Ganglionic haemorrhage Basal ganglia, thalamus Hypertension (most common) Lobar haemorrhage Cerebral hemispheric lobes Cerebral Amyloid Angiopathy (CAA) A. Hypertensive Haemorrhage: - Hypertension = risk factor most commonly asso