cerebrovascular disease

Cerebrovascular Disease

FM Brett , MD, FRCPath

~ In USA 0.5 million new strokes diagnosed annually and 3 million survivors of a previous stroke

~ Stroke 3rd most frequent cause of death

~ 2nd most frequent cause of dementia

~ Major reason for severe disability and long term dependency

Epidemiological aspects of stroke

~ In the USA stroke is the third commonest cause of death

~ Incidence increases with age

~ Major risk factors for stroke are hypertension, cardiac disease, smoking, hyperlipidemia, and diabetes

~ Other causes OCP, sickle cell, coagulation disorders

~ In USA - brain infarction 10 times commoner than haemorrhage

Blood supply to the brain

~ Human brain approx 2% of body weight~ Receives 15% of total cardiac output O2 consumption approximately 20% of whole body (i.e high metabolic rate)~ How long would the brain survive if blood flow interrupted

Terminology

~ Ischaemia - arterial stenosis or occlusionInfarction - perfusion territory of the affected vessel

~ Global brain ischaemia - < CPP below the threshold for autoregulation i.e when systemic blood pressure falls very low e.g cardiac tamponade, heroin overdose, or ICP rises to a level that compromises cerebral perfusion

Resultant brain damage or infarction is accentuated in the

WATERSHED REGIONS

CPP= SAP - ICP

CPP > 40 mmHg - necessary for autoregulation

If CPP < 40 mmHg CBF falls dramatically

Principal causes of hypoxia

Hypoxemic hypoxia - low O2 in blood~ Carbon monoxide poisoning~ Near drowning~ Respiratory arrest~ Prolonged status epilepticus

Stagnant hypoxia - (inadequate supply of oxygenated O2~ Cardiac arrest~ Rise ICP~ Respirator brain

Histotoxic hypoxia (inability of tissues to use O2)~ Cyanide and sulphide exposure - inhibition of mitochondrial enzymes involved in oxidative respiration

Selectively vulnerable zones

~ Hippocampus - CA1

~ Laminae 3 and 5 of cortex

~ Purkinje cells cerebellum

HYPOXIA - blood flow to the CNS may be normal or increased

Damage occurs in selectively vulnerable neurones

Hypoxic ischaemic encephalopathy

~ Variable clinical presentation

~ Clinical recovery generally better after hypoxemic hypoxia than after global brain ischaemia

~ Severity and duration of HIE after transient cerebral hypoxia depends on I) duration of insult2) completeness of insult3) blood glucose level (high level poor outcome)4) CNS temperature

~ Long term sequelae - difficult to predict

Persistent vegetative state

Clininical condition of complete unawareness of self andenvironment, accompanied by sleep-wake cycles, with eithercomplete or partial preservation of hypothalamic and brainstemautonomic functions

Occurs with;~ Diffuse cortical injury~ Bilateral thalamic injury~ Diffuse white matter~ Major developmental abnormalitires

Infarct - region of cell death

Infarct may become secondarily haemorrhagic and may mimic aprimary haemorrhage

STROKE - rapid onset of focal disturbance of cerebral function lasting > 24 hours

TIA - less than 24 hours

Infarcts may be caused by:

~ Large vessel or macrovasculature disease~ Small vessel or microvasculature disease~ Emboli~ Venous thrombosis

Types of vascular diseaseAnterior circulation

A. Small vessel disease – e.g microangiopathy

B. Occlusive large vessel disease of pial arteries

C. Occlusive large- vessel disease of brain supplying arteries in the neck

D. Embolising heart disease including aortic plaques and R-L shunts

1 a, b – small vessel disease

2 a,b. Atherosclerotic orembolic occlusion of cerebellar artery

3 – intracranial thrombosis

4 – atheromatosis of vertebro-basilar artery

5 – embolus sticking in mid-basilar artery

6. In situ thrombosis of basilar artery

Thalamic infarction

Sensory or sensiomotor hemi-deficits with disassociatedsensory loss, hemispasticity or even severe impairment of position sense; Segmental and focal dystonia without jerks and abnormal dystonic posture of affected hand

Time after infarction

Histological changes

15-20 hrs

24-30 hrs

24-36 hrs

36-48 hrs

1-2 weeks

Mths

Defined margin between ischaemiac and normal brain

Early app of PML

Activation of microglia and astrocytes

App of macrophages

Liquefaction of tissue; gliosis

Cavitation and completion of glial scar

~ Large vessel disease includes atherosclerosis, fibromuscular dysplasia, arterial dissection, giant cell arteritis

ATHEROSCLEROSIS IS THE COMMONEST OF THESE

ATHEROSCLEROSIS - leading vasculopathy producing brain infarcts. Affects intracranial and extracranial large vessels

RISK FACTORS~ Hyperlipidemia~ Hypertension~ Cigarette smoking~ Obesity~ Age~ Sex

PACNS

~ Isolated granulomatous or primary angiitis of the CNS

(PACNS)

Small vessel disease includes cerebral vasulitides

PACNS

~ Recognised in the mid 1950’s~ Diagnosis:~ Clinical~ Imaging~ Biopsy

Case presentation

EMBOLIC DISEASEEMBOLIC DISEASE

Embolic stroke results when any solid material:• forms within the aterial circulation• is introduced into the arterial circulation• forms within the venous and has a conduit to the arterial circulation ì.e right to left shunt

Resultant infarct is :• clinically abrupt• haemorrhagic

•

Autopsy of a stroke patient

If infarction

1. Examine major cranial arteries i.ecarotid and vertebral arteries in the neck

2. Carefully examine heart for: infective endocarditisvalvular abnormalitiesseptal defects

IF haemorrhage

Look for evidence of:1. Hypertension i.e cardiomegaly, LVH, nephrosclerosis2. Neoplasia3. Drug abuse4. If dementia CAA

Blood in the cranial cavity

• Source?• Spread• Occur?• Cause?• Sufficient to cause death

Intracranial haemorrhage

• Extradural• Subdural• Subarachnoid• Intracerebral

SAH

• Berry aneurysm• Infectious• Fusiform aneurysm• AVM• CAA

CIRCLE OF WILLIS

Berry aneurysms

Congenital

Risk of bleeding inc;• Hypertension• AVM • systemic vascular disease• defects collagen• polcystic renal disease

ICH causesICH causes

• Hypertension• Trauma• CAA• Berry aneurysm• AVM• Bleeding diathesis• Vasculitides• Drugs • Neoplasm• Infective

Hypertension Hypertension - major risk factor for brain brain haemorrhagehaemorrhage

OccursOccurs due to rupture of arteriolesrupture of arterioles that have become weakened

DUE TODUE TO• Replacement of smooth muscle by fibrocartilagenous material• Fragmentation of elastic tissue• Charcot-Bouchard aneurysms

Haemorrhages involving the basal ganglia- putamen in particular tend to be non-traumatic and caused by hypertension

Chronic hypertensionleads to arteriolar sclerosisresulting in small lacunar infarcts

OCCUROCCUR~ BASAL GANGLIA~ PONS~ DEEP WHITE MATTER

AVM

• Commonest 3-4th decade• Rarely familial • Rarely multiple• have a nidus• commonest vascular malformation identified in surgical specimens

End result of herniation is compression and Duret haemorrhages as seen in the pons

Venous Thrombosis

~ Often secondary to infectious causes

~ Pregnancy

~ Puerperium

~ OCP

~ Haematological abnormalities