Pathology of Cerebrovascular Disease

ByProf. J.T. Anim

Department of Pathology

Cerebrovascular DiseaseAffected blood vessels

Intracranial vesselsMiddle cerebral arteryAnterior cerebral arteryBasilar artery (posterior cerebral arteries)

Extracranial vesselsCarotid artery

Common carotid arteryInternal carotid artery(external carotid artery)

Vertebral arteryothers

Brain: Blood supply

Brain: Blood supply

Arterial blood supply to the brain

Brain: Blood supply

Cerebrovascular DiseaseTransient ischaemic attack (TIA)

A fully reversible neurological deficit often lasting for no more than a few minutes, but occasionally up to 24 hours.

No structural brain damage has occurred

Cerebrovascular DiseaseFactors predisposing to TIA

AtherosclerosisSuperimposed hypotensionSpasm of diseased vessel

Disorders in the neck (spondylosis)Other extracranial vascular diseases eg. embolism

Cerebrovascular DiseaseStroke

Rapid onset of a focal disturbance of cerebral function of presumed vascular origin and of more than 24 hours duration.

Permanent brain damage has occured

STROKE

Ischaemic/Occlusive Haemorrhagic/Disruptive

Intraparenchymal

Subarachnoid

Mixed

Thrombosis Embolism Hypotension

Atherosclerosis

Fibromuscular dysplasia

Arteritis

Dissection

Cardiac

Extracranial vessels

Paradoxical

Other emboli

Pump failure

Hypovolaemia

Stroke: Causes

Ischaemic StrokeAtherosclerosis

Carotid arteryCommon carotidInternal carotid(external carotid)

Vertebro-basilar systemPosterior cerebral

With normal BP, >90% cross sectional area reduction is necessary to impair blood flow

Ischaemic StrokeFactors affecting tissue survival

Adequacy of collateral circulationState of systemic circulation

Reduced blood flow, cardiac pump failure, hypovolaemia, hyperviscosity

Serological factorsLow blood sugar, high blood sugar, hypoxia, elevated serum calcium, high blood alcohol

Ischaemic StrokeFactors affecting tissue survival contd.

Changes within obstructing vascular lesion

Fragmentation and advancing of embolusReactive vasoconstriction (spasm)Reperfusion – stunned cells may recoverPropagation of thrombus – collateral occlusionEmbolisation from previous thrombus

Ischaemic StrokeFactors affecting tissue survival contd.

Resistance within microcirculatory bedHypertensionDiabetes mellitus – thickened vessel wallsHyperviscosityDiffuse thromboses (low microcirculatory flow)

Oedema and raised ICPIncreased resistance to blood flow

Ischaemic StrokeIntracranial vascular occlusion

Effects usually confined to area of supply of affected vessel

Extracranial vascular occlusionEffects may be modified by collateral circulationWatershed infarction may be seen

Brain: Distribution of cerebral infarction

CNS IschaemiaSelective vulnerability of CNS cells

Neurons – most sensitiveOligodendrogliaAstrocytesMicrogliaBlood vessels

In descending order of sensitivity

Brain: Effect of global ischaemia

Consequences of global ischaemia

Effects of global ischaemia

CNS IschaemiaMild hypoxia

Selective neuronal necrosis eg. respirator lung

Moderate hypoxiaNeuronal necrosisNeuroglial necrosisBlood vessels and microglia are spared

Partial cerebral infarction

Ischaemic StrokeInfarction (stroke)

Thrombotic – usually anaemic (may be haemorrhagic)Embolic – usually haemorrhagic, often multiple. Haemorrhagic nature due to:

Necrosis of vessel wallLysis of embolus with restoration of some blood flow.

CNS InfarctionVascular occlusion causes:

Necrosis of neurons, neuroglia and blood vessels4-6 hrs. – coagulative necrosis12-15 hrs. – sharp demarcation (swelling of neuropil)24 hrs. – reactive changes

Proliferation of microglia, astrocytes, capillariesInflammatory reaction

CNS InfarctionInfarction contd.

1-2 weeks – Swelling resolvesSofteningShrunken granular grey matterAccumulation of lipid-laden phagocytes (gitter cells) in infarcted area

Several months – shrunken cystic lesion traversed by glial fibrils and small blood vessels

Brain: Recent anaemic infarct

Brain: Older infarct showing cavity formation

Brain: Older infarct

Bilateral posterior cerebral infarcts

Brain: Recent haemorrhagic infarct

Brain: Haemorrhagic infarct

Brain: Haemorrhagic infarct

Brain: Multiple haemorrhagic infarcts

Brain: Relatively recent infarct - Histology

Brain: Older infarct showing ‘gitter’ cells

Brain: Older infarct - Histology

Brain: Old infarct with cavity formation - Histology

Brain: Laminar infarct

Brain: Watershed infarct

Brain: Very old infarct showing atrophy of hemisphere

CNS InfarctionVertebro-basilar occlusion

Infarction of brainstemInfarction of cerebellumInfarction of posterior cerebral arterial territory

Clinical effects of basilar artery occlusion

Brain: Haemorrhagic cerebellar infarcts

Chronic CNS IschaemiaLacunae

Small cavities located deep within cerebral hemispheres (basal ganglia) and ponsElderly subjects - >90% with hypertension? Small infarcts? Expanded perivascular spaces? Resolving haemorrhagesAssociated with vascular dementia

Multi-infarct dementiaBinswanger’s disease

Brain: Lacuna in pons

Brain: Lacunar lesions

CNS InfarctionVenous thrombosis

Primary – non-infectiousPregnancy, puerperium and oral contraceptivesHaematological disordersExtreme dehydration

Haemorrhagic infarction

Secondary – pyogenic infectionsInfections from sinuses, middle earCompound fracture

Septic infarction

Brain: Bilateral haemorrhagic infarct – Sup. Saggital sinus thrombosis

Haemorrhagic StrokeBrain and spinal cord substance (intraparenchymal)SubarachnoidMixed

Haemorrhagic StrokeMajor predisposing factors

HypertensionCongenital anomaliesVascular malformations

Minor predisposing factorsVasculitisBleeding diatheses

Haemorrhagic StrokePrimary intraparenchmal haemorrhage

Predisposing vascular changes include:Fibrinoid necrosisHyaline arteriolosclerosis (lipohyalinosis)Microaneurysms (Charcôt-Bouchard)

Sizes of haemorrhageMassive - >3cm diam. Cerebral hemisphere

> 1.5cm diam. brainstem

Brain: Charcot-Bouchard microaneurysm

Brain:

Common sites of spontaneous haemorrhage

Brain: Haemorrhage into basal ganglia

Brain: Massive hemispheric haemorrhage

Brain: Haemorrhage into basal ganglia

Brain: Pontine haemorrhage

Brain: Pontine haemorrhage

Haemorrhagic StrokeSubarachnoid haemorrhage

Saccular aneurysm 65%Females = malesDevelopmental medial defectSuperimposed degenerative changes eg. atheroma15-20% multiple

A-V malformations 5%Others (blood dyscrasias) 5%No cause found 20%

Haemorrhagic StrokeSubarachnoid haemorrhage

Secondary effects include:RebleedingVasoconstriction (spasm)hydrocephalus

Brain: Distribution of saccular (berry) aneurysms

Brain: Multiple berry aneurysms

Brain: Berry aneurysm - arrow

Brain: A large berry aneurysm

Brain: Subarachnoid haemorrhage – ruptured berry aneurysm

Brain: Giant atherosclerotic aneurysm

Haemorrhagic StrokeMixed (intraparenchymal and subarachnoid) haemorrhage

A-V malformationsCapillary angiomas

Focal irritation may predispose to convulsions (epileptiform attacks)

Brain:

Causes of mixed subarachnoid and intracerebral haemorrhages

Brain:

Vascular malformations

Brain: Vascular malformation – cerebral hemisphere

Brain: Arterio-venous malformation

Brain: Vascular malformation