Cerebrovascular Pathology
Pathology · CNS · lean revision notes
Cerebrovascular Pathology
Cerebrovascular disease is the third commonest cause of death and the leading cause of acquired neurological disability. For NEET PG, this is a first-year pathology gold-mine: the temporal sequence of ischaemic injury (red neurons → ghost cells → liquefactive necrosis → gliosis), the biconvex vs crescentic haematoma shapes, and the artery-of-rupture pairings are asked almost every cycle.
High-yield: The brain is the only organ where infarction produces liquefactive (colliquative) necrosis rather than coagulative necrosis — because of high lipid (myelin) content and scant supportive stroma. This single fact is the most repeated cerebrovascular pathology MCQ.
Classification of cerebrovascular disease
Cerebrovascular accidents (CVA / stroke) are broadly divided by mechanism:
| Type | Frequency | Core mechanism | Classic substrate |
|---|---|---|---|
| Ischaemic stroke | ~80–85% | Reduced perfusion / occlusion | Thrombosis, embolism, hypoperfusion |
| Haemorrhagic stroke | ~15–20% | Vessel rupture, blood into parenchyma/spaces | Hypertension, aneurysm, AVM |
Ischaemia is further split into:
- Global cerebral ischaemia (diffuse hypoperfusion) — cardiac arrest, shock, severe hypotension → watershed infarcts, selective neuronal vulnerability.
- Focal cerebral ischaemia — occlusion of a single vessel → regional infarct (territorial).
Intracranial haemorrhage is classified by the anatomic compartment the blood enters: epidural, subdural, subarachnoid, and intraparenchymal (intracerebral). Knowing which vessel and which space defines each is the examiner's favourite trick.
Ischaemic stroke — etiology & pathophysiology
Three mechanisms drive focal ischaemic infarction:
- Thrombosis — atherosclerosis at branch points; commonest at the carotid bifurcation, MCA origin, and basilar artery. Produces a pale (anaemic) infarct.
- Embolism — the single commonest cause of focal infarct overall; cardiac mural thrombus (post-MI, AF), valvular vegetations, paradoxical emboli. The MCA territory is most often affected (direct continuation of the internal carotid). Embolic infarcts often become haemorrhagic (red) infarcts after reperfusion.
- Hypoperfusion / vasculitis / hyperviscosity — global drops cause watershed (border-zone) infarcts between ACA–MCA and MCA–PCA territories; classic is the "man in a barrel" syndrome.
The neurovascular cascade
Energy failure → loss of ATP → failure of Na⁺/K⁺-ATPase → cytotoxic oedema → glutamate excitotoxicity (NMDA-mediated Ca²⁺ influx) → free-radical and protease activation → neuronal death. The ischaemic penumbra is the hypoperfused-but-salvageable rim around the dead core — the target of reperfusion therapy.
High-yield: Neurons are the most vulnerable CNS cells to hypoxia, followed by oligodendrocytes/astrocytes then microglia; endothelial cells are most resistant. Within neurons, the most vulnerable populations are Sommer sector (CA1) of hippocampus, Purkinje cells of cerebellum, and cortical pyramidal layers 3, 5, 6 ("selective vulnerability").
Morphology of ischaemic infarct — the timeline (MOST TESTED)
The evolving histology of an infarct is a near-guaranteed image/timeline question. Learn the sequence as a flow:
Red neurons (12–24 h) → neutrophils (24–48 h) → macrophages/gitter cells (2–3 weeks) → liquefactive necrosis & cavitation → gliosis with cyst (months)
| Time after infarct | Gross | Microscopic hallmark |
|---|---|---|
| 12–24 hours | Little/none, subtle pallor | Red (eosinophilic) neurons — shrunken, pyknotic nuclei, intensely eosinophilic cytoplasm; loss of Nissl substance ("ghost cells" appearing) |
| 24–48 hours | Pale, soft, swollen | Neutrophilic infiltration |
| 2–3 days to ~2 weeks | Gelatinous, friable | Macrophages (gitter / foamy lipid-laden cells) phagocytose myelin → liquefactive necrosis |
| 2–3 weeks | Liquefied, cavitating | Reactive gliosis at margins (gemistocytic astrocytes) |
| >1 month | Fluid-filled cyst lined by gliotic wall | Dense glial scar; cavity traversed by vessels |
High-yield: Red neurons are the earliest histological marker of irreversible neuronal injury and appear at ~12 hours (acute neuronal injury / hypoxic-ischaemic change). "Ghost cells" / pale eosinophilic neuronal outlines reflect this same process.
High-yield: Unlike myocardial or renal infarcts (coagulative necrosis with eventual fibrous scar), the brain liquefies and ends as a fluid-filled cyst — there are no fibroblasts/collagen scar in the CNS parenchyma; the "scar" is glial (astrocytic), not fibrous.
Mnemonic for infarct timeline — "Red, Neat, Macro, Glia": Red neurons (12 h) → Neutrophils (1–2 d) → Macrophages (week+) → Glial cyst (month).
Global ischaemia / hypoxic-ischaemic encephalopathy
After cardiac arrest or profound hypotension:
- Laminar necrosis of the cortex (preferential loss of mid-cortical layers → "pseudolaminar necrosis").
- Watershed infarcts in the ACA–MCA / MCA–PCA border zones, sickle-shaped band of necrosis over the convexity.
- Severe global anoxia → respirator brain (autolysed, softened, non-viable brain in a ventilated brain-dead patient).
Haemorrhagic stroke — intraparenchymal (intracerebral) haemorrhage
Hypertensive intracerebral haemorrhage
The commonest cause of spontaneous (non-traumatic) intraparenchymal bleed. Chronic hypertension produces hyaline arteriolosclerosis and Charcot–Bouchard microaneurysms (tiny <1 mm aneurysms on penetrating vessels, 100–300 µm), which rupture.
High-yield: The single most common site of hypertensive (Charcot–Bouchard) haemorrhage is the basal ganglia / putamen (via the lenticulostriate branches of the MCA), followed by thalamus, pons, and cerebellum. Putamen = commonest; cerebellum = surgically most important to evacuate.
Cerebral amyloid angiopathy (CAA)
Deposition of β-amyloid (Aβ) in the walls of small/medium cortical and leptomeningeal vessels (Congo red positive, apple-green birefringence) → lobar haemorrhages in the elderly, often recurrent. Distinguished from hypertensive bleeds by their lobar/cortical (not deep ganglionic) location and association with Alzheimer disease.
Subarachnoid haemorrhage (SAH) & berry (saccular) aneurysm
Saccular ("berry") aneurysm
The commonest cause of spontaneous (non-traumatic) SAH. Thin-walled outpouchings at arterial bifurcations of the circle of Willis, lacking media and internal elastic lamina at the neck.
- Commonest site: anterior circulation (~90%) — junction of anterior communicating artery with ACA is the single most frequent; then posterior communicating–ICA junction; then MCA bifurcation.
- ~20–30% are multiple.
- Associations: autosomal dominant polycystic kidney disease (ADPKD), Ehlers–Danlos type IV, Marfan, fibromuscular dysplasia, coarctation of aorta, NF1.
Clinical: "Thunderclap headache" — "worst headache of my life," ± loss of consciousness, neck stiffness. Rupture risk rises sharply with size >10 mm.
High-yield: A berry aneurysm is NOT an atherosclerotic aneurysm and is congenital tendency, acquired rupture — it results from a developmental medial defect at bifurcations, not from a "congenital aneurysm present at birth."
Other vascular malformations
- Arteriovenous malformation (AVM): commonest symptomatic vascular malformation; tangle of abnormal vessels (arteries shunting to veins, no capillary bed) most often in the MCA territory; presents in young adults (10–30 yrs) with haemorrhage or seizures. Male predominance.
- Cavernous malformation (cavernoma): dilated thin-walled channels with no intervening neural tissue; "popcorn" on MRI.
- Capillary telangiectasia and venous angioma — usually incidental.
High-yield: Investigation of choice for the bleed is non-contrast CT head; for the aneurysm/AVM source, CT angiography / digital subtraction angiography (DSA, gold standard). If CT is negative but SAH still suspected → lumbar puncture showing xanthochromia (yellow CSF from bilirubin, the most reliable LP sign, appears ~12 h) and uniformly blood-stained CSF that does not clear across successive tubes.
Traumatic extra-axial haematomas — epidural vs subdural (CLASSIC PAIR)
This comparison is among the most repeated tables in all of pathology.
| Feature | Epidural (extradural) haematoma | Subdural haematoma |
|---|---|---|
| Bleeding source | Middle meningeal artery (artery) | Bridging cortical veins (vein) |
| Typical cause | Skull fracture at pterion (thin temporal bone) | Acceleration–deceleration, shaken-baby, elderly fall |
| Speed | Rapid, arterial | Slow, venous |
| CT shape | Biconvex / lentiform (lens) | Crescentic (concavo-convex / sickle) |
| Crosses suture lines? | No (bound by sutures) | Yes (limited by dura folds, not sutures) |
| Crosses dural reflections (falx/tentorium)? | Yes | No |
| Classic course | Lucid interval then rapid deterioration | Fluctuating; chronic in elderly/alcoholics |
| Predisposed groups | Young (dura adherent loosens) | Elderly, alcoholics, infants (stretched veins, brain atrophy) |
Memory hook — shapes:
- Epidural = Egg / lEns, biconvEx; bound by sutures, crosses falx.
- SuBdural = Banana / crescent; crosses sutures, bound by falx.
High-yield: Epidural bleed = middle meningeal artery + biconvex lens + lucid interval + does not cross sutures. Subdural bleed = bridging veins + crescent + crosses suture lines but limited by midline falx.
Chronic subdural in the elderly: a slowly enlarging collection with a neomembrane of granulation tissue and recurrent micro-bleeds; can present weeks later with confusion/headache and mimic dementia. Infants with bilateral subdurals + retinal haemorrhages → suspect non-accidental injury (shaken baby).
Clinical features by territory (correlate with pathology)
A quick stepwise localisation aids vignette MCQs:
Identify deficit → map to artery → predict infarct location:
- MCA (commonest stroke) → contralateral face & arm > leg weakness/sensory loss; aphasia (dominant), neglect (non-dominant); gaze toward lesion.
- ACA → contralateral leg > arm weakness, abulia, urinary incontinence.
- PCA → contralateral homonymous hemianopia with macular sparing.
- Lacunar (lenticulostriate) → pure motor / pure sensory stroke; internal capsule, basal ganglia, pons — caused by lipohyalinosis of small penetrators in hypertension/diabetes.
- Posterior circulation (basilar/vertebral) → crossed signs, vertigo, diplopia, dysphagia (e.g., lateral medullary / Wallenberg from PICA).
Diagnosis & investigation of choice
- First test in any acute stroke: non-contrast CT head — to exclude haemorrhage before thrombolysis. Early ischaemic signs: loss of grey-white differentiation, insular ribbon sign, hyperdense MCA sign (acute thrombus).
- MRI with DWI is the most sensitive for early ischaemia (restricted diffusion within minutes) — investigation of choice to confirm infarct.
- CT/MR/DSA angiography for vascular source (aneurysm, AVM, large-vessel occlusion).
- SAH workup: CT first → if negative, LP for xanthochromia.
- Look for the embolic source: ECG/Holter (AF), echocardiography, carotid Doppler.
Management / drug of choice (pathology-relevant essentials)
- Acute ischaemic stroke: IV thrombolysis with alteplase (rt-PA) within 4.5 hours (after CT excludes bleed); mechanical thrombectomy for large-vessel occlusion up to 24 h in selected cases. Aspirin for secondary prevention; anticoagulation if cardioembolic (AF).
- Hypertensive ICH: BP control, reverse coagulopathy, neurosurgical evacuation for cerebellar bleeds.
- SAH from aneurysm: endovascular coiling or surgical clipping; nimodipine to prevent delayed cerebral vasospasm (the classic drug-of-choice MCQ).
- Extradural / large subdural: emergency surgical evacuation (burr-hole/craniotomy).
High-yield: Nimodipine (a calcium-channel blocker) is the drug of choice to prevent vasospasm-related delayed ischaemia after aneurysmal SAH — it improves outcome chiefly by neuroprotection rather than by reversing angiographic spasm.
Complications
- Cytotoxic/vasogenic oedema → raised ICP → transtentorial (uncal) or tonsillar herniation → Duret haemorrhages (secondary brainstem bleeds from herniation).
- Haemorrhagic transformation of an embolic infarct after reperfusion.
- Vasospasm (days 4–14) and communicating hydrocephalus after SAH (blood blocks arachnoid granulations).
- Rebleeding (highest risk in unsecured aneurysm), seizures, post-stroke dementia (vascular/multi-infarct).
- Chronic infarct → cystic encephalomalacia.
Key differentials
- Stroke mimics: hypoglycaemia, Todd's paralysis (post-ictal), migraine with aura, hemiplegic conversion disorder, space-occupying tumour, abscess.
- Ring-enhancing lesion DDx (vs old infarct/abscess): MAGIC DR — Metastasis, Abscess, Glioblastoma, Infarct (subacute), Contusion, Demyelination, Radiation necrosis.
- Haemorrhage location DDx: deep/ganglionic = hypertensive; lobar in elderly = amyloid angiopathy; young + AVM/aneurysm = structural.
Recently asked / exam angle
- Earliest histological change in cerebral infarct? → Red neurons at ~12 hours.
- Type of necrosis in brain infarct? → Liquefactive.
- Commonest site of hypertensive haemorrhage? → Putamen / basal ganglia (lenticulostriate arteries).
- Biconvex/lentiform clot on CT, lucid interval, ruptured artery? → Epidural — middle meningeal artery, pterion fracture.
- Crescentic clot crossing suture lines in an elderly alcoholic? → Subdural — bridging veins.
- Commonest site of berry aneurysm? → Anterior communicating artery. Association → ADPKD.
- Microaneurysm in hypertensives? → Charcot–Bouchard.
- Apple-green birefringence in cortical vessels with lobar bleed? → Cerebral amyloid angiopathy.
- Drug to prevent vasospasm after SAH? → Nimodipine.
- Most reliable LP finding in SAH? → Xanthochromia.
- Glial scar cell at infarct margin? → Gemistocytic astrocyte.
Rapid revision
- Brain infarct = liquefactive necrosis; ends as a fluid-filled cyst with glial (not fibrous) scar.
- Red neurons at 12 h = earliest irreversible injury; macrophages (gitter cells) clear debris over weeks.
- Neurons most vulnerable to hypoxia; CA1 (Sommer sector), Purkinje cells, cortical layers 3/5/6 = selectively vulnerable.
- Embolism = commonest focal infarct; MCA territory most often hit; reperfusion → red (haemorrhagic) infarct.
- Watershed infarcts = global hypoperfusion → "man-in-a-barrel."
- Hypertensive ICH → Charcot–Bouchard microaneurysms → putamen/basal ganglia via lenticulostriate arteries.
- Epidural = middle meningeal artery, biconvex, lucid interval, doesn't cross sutures.
- Subdural = bridging veins, crescent, crosses sutures, common in elderly/alcoholics/infants.
- Berry aneurysm at circle of Willis bifurcations, commonest at AComm; linked to ADPKD; rupture → SAH with thunderclap headache.
- AVM = young adult, MCA territory, seizures/bleed; cavernoma has no intervening neural tissue.
- SAH workup: non-contrast CT → LP for xanthochromia; treat with clipping/coiling + nimodipine for vasospasm.
- Ischaemic stroke first test = NCCT (rule out bleed) before alteplase ≤4.5 h; DWI-MRI is most sensitive for early ischaemia.