Pathophysiology

On gross examination, a cerebral infarct may be pale or hemorrhagic. The affected area is soft and swollen and there is loss of demarcation between the grey and white matter. The necrotic cells in the infarcted zone undergo liquefactive necrosis. Pale infarcts are seen in arterial thrombosis. A hemorrhagic infarct looks like a hematoma and usually results from venous thrombosis or breakdown of occlusive arterial emboli. The earliest light microscopic features of ischemic damage are seen a few hours after infarction. If a patient experiences irreversible cerebral necrosis and dies within 1 to 2 hours, there will be no visible neuropathological abnormality (by light microscopy) in affected brain tissue. The first sign is deeply eosinophilic, shrunken neurons (red neurons) with darkly basophilic nucleus with clumped chromatin, followed by swollen astrocytes. Loss of cytoplasmic basophilia is due to loss of Nissl substance or rough endoplasmic reticulum. This is followed by outright necrosis. Vacuolation of cytoplasm, “ghost neurons” with lack of affinity to hematoxylin can be seen. Neutrophils are predominant in the first 48 hours followed by foamy macrophages. Cavitation may be observed by 7-14 days. Macrophages may persist in the infarcted zone for years. Hemorrhagic infarcts may also show hemosiderin laden macrophages. After 3-4 months, an old cystic cavity is formed with peripheral gliosis. Lacunar infarcts will be seen as small cavitations.

Apart from the typical changes seen in infarcted cerebral tissue, HIE characteristically shows a band like laminar or pseudolaminar necrosis is due to differential sensitivity of the neurons to ischemia - cerebral cortex and striatum being more sensitive than the thalamus and brainstem. The loss of pyramidal cell layer is more severe than granular cell layer. Bilateral hippocampal neuronal loss and gliosis (hippocampal sclerosis) is seen in some cases and presents with memory loss, as in Korsakoff’s syndrome. Myelin damage and vacuolization gives a spongy appearance on cut sections and is seen commonly in carbon monoxide poisoning.

Penumbra is the zone of viable cells surrounding the infarcted zone. The cells in the penumbra show metabolic defects but they can be saved with prompt revascularization.

(II) ICH or intracerebral hemorrhage: Spontaneous intracerebral haemorrhage occurs mostly in patients of hypertension. Aneurysms called Charcot-Bouchard aneurysms form in the branches of lenticulostriate branches of the cerebral arteries. Rupture of these aneurysms causes ICH. The common sites of hypertensive intracerebral haemorrhage are the basal ganglia (particularly the putamen and the internal capsule), thalamus, pons and the cerebellar cortex. Clinically the onset is usually sudden with headache and loss of consciousness. Signs and symptoms depend on the location of the lesion.

On gross appearance, a haematoma is seen with sharply demarcated borders. It may push adjoining structures and extend into the ventricles. Slowly, RBCs in the haematoma undergo lysis and hemosiderin laden macrophages can be seen. Resolution of the haematoma takes a few weeks to months with the formation of a cystic lesion surrounded by fibrillary astrocytosis.

(III) SAH or subarachnoid hemorrhage: It is hemorrhage into the subarachnoid space. It is caused by the rupture of congenital or acquired berry aneurysms or bleeding from vascular malformations. Berry aneurysms are typically seen in young adults, but can develop in older age also from chronic diseases. They are saccular aneurysms that develop over time as a result of normal hemodynamic stresses acting on a congenitally defective tunica media. They are frequently associated with polycystic kidney disease and coarctation of aorta. Common sites are bifurcation of arteries in the circle of Willis - most common is at the junction of ACA with the anterior communicating artery, followed by at the junction of ICA with posterior communicating artery; bifurcation of MCA and bifurcation of ICA into the MCA and ACA. Clinically, berry aneurysms are asymptomatic. A prodrome of headache may precede impending rupture. Rupture of berry aneurysm with SAH presents as an acute onset of severe headache, described as “worst headache of my life” or thunderclap headache. Nuchal rigidity, loss of consciousness and neurological deficits are seen. Rebleeding is common.

CSF examination will show presence of blood or xanthochromia (yellow CSF), which can be determined visually or by spectrophotometry. RBCs will be present in CSF, but it has to be differentiated from a traumatic trap. Amount of RBCs in CSF stays constant in SAH while it gradually decreases in traumatic tap (from tube to tube). Bilirubin and oxyhemoglobin in CSF will be high. Siderophages (macrophages with engulfed RBCs) will be seen in later stages. CT scan will show white densities filling up the normally black subarachnoid space, ventricles, cisterns and/or sulci.

Fusiform aneurysms are vascular dilatations due to atherosclerosis. They are seen most commonly in the basilar artery and are associated with thrombosis and brainstem infarction and less frequently with rupture and subarachnoid hemorrhage.