Epidemiology and pathophysiology of cerebral vasospasm following subarachnoid hemorrhage.

Cerebral vasospasm still accounts for a significant percent of morbidity and mortality after subarachnoid hemorrhage (SAH). There is a clear-cut temporal course for this phenomenon, with a peak of incidence at the end of the first week after SAH. The occurrence of vasospasm is significantly related to the amount of blood deposited in the subarachnoid cisterns. Non-invasive diagnosis and monitoring of vasospasm is now possible with transcranial Doppler, recording the flow velocity on the middle cerebral artery. Under the current knowledge, the pathophysiology of vasospasm is quite complex: the main biological mechanisms are constituted by the direct contraction of the cerebral arteries, and the impairment of the vasodilatory activity elicited by the endothelium, although other mechanisms cannot be excluded. Some of the observed biological changes are induced by the cisternal clot, with formation of oxyhemoglobin, activation of lipid peroxidation and consequent endothelial injury, impaired nourishment of the arterial wall (encased by the clot). Other biological changes occur in the cerebral arteries, with decreased synthesis of prostacyclin, reduced availability of high energy phosphates, impairment of EDRF-induced vasodilatation and production of the powerful vasoconstrictor endothelin. The final result is arterial contraction, due to phosphorylation of the contractile proteins of the smooth muscle cell. Two mechanisms concur to contraction: a) activation of calcium-calmodulin-dependent protein kinases, and b) elevation of protein kinase C (PKC). While the first mechanism leads to a transient contraction, PKC-induced contraction is lasting for longer time. An additional influence on arterial contraction is played by the protease calpain.