CEREBROVASCULAR DISEASE MKU Pathology Dr. Lilian Bosire --- OVERVIEW Cerebrovascular disease = brain injury from altered blood flow. Stroke = acute-onset neurol
CEREBROVASCULAR DISEASE MKU Pathology Dr. Lilian Bosire --- OVERVIEW Cerebrovascular disease = brain injury from altered blood flow. Stroke = acute-onset neurologic deficits from a vascular mechanism, persisting 24 hours. - Symptoms resolve In the brain, embolism thrombosis as cause of vascular occlusion. --- CAUSES OF OCCLUSION 1. Embolism (most common) Source Examples --- --- Cardiac Mural thrombi (MI, AF, valvular disease) Arterial Atheromatous plaques from carotids Other Fat (post-fracture), paradoxical, air, tumor - Most common territory affected: MCA — equal in both hemispheres - Emboli lodge at branch points or areas of preexisting stenosis - Fat embolism → "shower embolization" → diffuse dysfunction + hemorrhagic white matter lesions --- 2. Thrombosis - Mechanism: acute change in vulnerable atherosclerotic plaque - Common sites: carotid bifurcation, origin of MCA, either end of basilar artery - Thrombi → progressive narrowing → anterograde extension → may fragment and embolize distally - Strongly associated with hypertension and diabetes --- 3. Vasculitis Type Examples --- --- Infectious Syphilis, TB; aspergillosis (immunosuppressed) Non-infectious Polyarteritis nodosa; primary CNS angiitis Other prothrombotic Hypercoagulable states, dissecting aneurysm, drug abuse (cocaine, amphetamines, heroin) --- TYPES OF INFARCTS Type Mechanism Key Feature --- --- --- Non-hemorrhagic (pale) Sustained occlusion, end-organ circulation Most common initial pattern Hemorrhagic (red) Reperfusion after occlusion dissolves Petechiae or confluent bleed into necrotic tissue Venous infarct Dural sinus / deep vein thrombosis Often hemorrhagic --- MORPHOLOGY OF NON-HEMORRHAGIC INFARCT Gross Timeline Time Gross Appearance --- --- 0–6 hours No visible change 48 hours Pale, soft, swollen; gray-white junction blurred 2–10 days Gelatinous, friable; border becomes distinct as edema resolves 10 days–3 weeks Liquefaction → fluid-filled cavity Months Expanding cystic cavity = healed infarct Microscopic Timeline Stage Time Key Features --- --- --- Acute 6–12 hrs "Dead red neurons" — eosinophilic necrosis, nuclear pyknosis/karyorrhexis; cytotoxic + vasogenic edema; neutrophils peak at 48 hrs (less prominent than in MI) Subacute 2 days–3 weeks Foamy macrophages (monocyte-derived + microglia) dominate; reactive astrocytes + new vessels at periphery from 1 week Healed Months Dense glial fiber meshwork + new capillaries; cystic cavity lined by gliotic tissue; pia and arachnoid unaffected Different zones of the same lesion may be at different stages simultaneously — edges heal inward. --- PART 3: INTRAPARENCHYMAL HEMORRHAGE Rupture of small intraparenchymal vessel → primary hemorrhage → acute stroke. - Distinct from secondary hemorrhagic transformation of occlusive infarct - Peak incidence: ~60 years of age - Other contributing causes: coagulation disorders, neoplasms, vasculitis, aneurysms, vascular malformations Patterns & Causes Pattern Location Main Cause --- --- --- Ganglionic hemorrhage Putamen, thalamus, pons, cerebellum Hypertension Lobar hemorrhage Cerebral hemispheres Cerebral Amyloid Angiopathy (CAA) --- HYPERTENSIVE HEMORRHAGE - Accounts for 50% of clinically significant hemorrhages - Responsible for ~15% of deaths in chronic hypertension - Most common site: putamen (50–60%) , then thalamus, pons, cerebellar hemispheres Pathogenesis: Hypertension → vessel wall changes: Vessel Size Change --- --- Large arteries Accelerated atherosclerosis Small arteries Hyaline arteriolosclerosis Arterioles (severe) Proliferative changes + frank necrosis - Hyalinized walls are thickened but fragile → rupture → ganglionic hemorrhage - If same vessels occlude instead of rupture → lacunar infarct - Changes most prominent in basal ganglia and subcortical white matter --- CEREBRAL AMYLOID ANGIOPATHY (CAA) - Most common cause of lobar hemorrhage - Aβ peptides (same as Alzheimer disease) deposited in walls of meningeal, cortical, and cerebellar vessels - Vessels become rigid — fail to collapse during tissue processing - On H&E: resembles hyaline arteriolosclerosis, but material is β-amyloid not collagen - Affects leptomeningeal and cortical vessels — NOT basal ganglia/white matter (contrast with hypertension) CADASIL - Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy - Caused by NOTCH3 gene mutations → misfolding of NOTCH3 extracellular domain - Recurrent small vessel strokes (infarcts hemorrhages) + dementia - First changes in white matter , appearing around age 35 , progressive - Related disorder: COL4A1 mutations (vascular basement membrane component) MORPHOLOGY OF INTRAPARENCHYMAL HEMORRHAGE Acute: - Central core of clotted blood compressing adjacent parenchyma - Compression → secondary infarction of adjacent tissue - Anoxic neuronal/glial changes + edema Resolving: - Edema resolves - Hemosiderin- and lipid-laden macrophages appear - Reactive astrocytes proliferate at periphery - Follows same cellular timeline as cerebral infarction Old hemorrhage: - Cavitary parenchymal destruction with rim of brownish discoloration (hemosiderin) --- PART 4: SUBARACHNOID HEMORRHAGE & SACCULAR ANEURYSM Causes of Subarachnoid Hemorrhage (SAH) Cause Note --- --- Ruptured saccular (berry) aneurysm Most common cause of spontaneous SAH Trauma Most common cause of SAH overall Rupture of intracerebral hemorrhage into ventricles — Vascular malformation — Hematologic disturbances, tumors — --- SACCULAR (BERRY) ANEURYSM - Most common type of intracranial aneurysm - Found in ~2% of the population - 90% occur near major arterial branch points in the anterior circulation - 20–30% of cases have multiple aneurysms Other aneurysm types: - Atherosclerotic (fusiform) — mostly basilar artery - Mycotic, traumatic, dissecting — more often cause infarction than SAH Common Sites (Circle of Willis) Location Frequency --- --- Anterior communicating artery 40% Middle cerebral artery bifurcation 34% Internal carotid / posterior communicating junction 20% Basilar artery / posterior circulation 4% --- PATHOGENESIS OF SACCULAR ANEURYSMS - Structural defect: absence of smooth muscle and intimal elastic lamina - Suggests developmental anomaly — though not present at birth; develops over time - Majority are sporadic , but genetic factors contribute Associated conditions: Condition Type --- --- Autosomal dominant polycystic kidney disease Mendelian Ehlers-Danlos syndrome type IV Mendelian Neurofibromatosis type 1 (NF1) Mendelian Marfan syndrome Mendelian Fibromuscular dysplasia Vascular Coarctation of the aorta Structural Other risk factors: cigarette smoking, hypertension (present in ~50% of affected individuals) --- MORPHOLOGY OF SACCULAR ANEURYSM Unruptured: - Thin-walled outpouching at arterial branch point - Size: few mm to 2–3 cm - Bright red, shiny surface; thin translucent wall - May contain: atheromatous plaques, calcification, or thrombus - Wall: thickened hyalinized intima + adventitia covering — no smooth muscle or elastic lamina in the sac Ruptured: - Rupture occurs at the apex of the sac - Blood extravasates into subarachnoid space , brain parenchyma, or both - Adjacent brain/meninges may show brownish discoloration from prior hemorrhage --- KEY CONCEPTS SUMMARY Concept Key Point --- --- Stroke definition Acute neurologic deficit 24 hrs from vascular cause TIA Same but resolves <24 hrs Most common cause of brain infarction Embolism Most vulnerable deep structures Thalamus, basal ganglia — no collateral flow Excitotoxicity mediator Glutamate → NMDA → Ca²⁺ influx Penumbra At-risk zone; salvageable; dies by apoptosis Ganglionic hemorrhage cause Hypertension → hyaline arteriolosclerosis Lobar hemorrhage cause Cerebral amyloid angiopathy (CAA) Lacunar infarct cause Same hyalinized vessels that occlude instead of rupture Most common cause of spontaneous SAH Ruptured saccular (berry) aneurysm CADASIL gene NOTCH3 mutation --- Note from lecture: Self-read Lacunar infarcts and Global cerebral h