The pathophysiology of SAH is complex and involves both early brain injury (EBI) and later
delayed cerebral ischemia (DCI).

Hemorrhage into the subarachnoid space occurs under arterial pressure, resulting in massive, transient
elevation of the ICP. The compressing effects of the raised ICP and concomitant, transient acute
vasospasm of the ruptured and surrounding vessel(s) usually causes hemorrhage to cease, but may
precipitate early ischemic damage. Studies using diffusion-weighted MRI have documented that
many patients have infarction even within the first 48 to 72 hours. CBF autoregulation is often
impaired, further increasing the vulnerability of the brain to ischemia.

The presence of blood in the subarachnoid space triggers a cascade of biochemical processes. A relative
lack of cerebral nitric oxide (NO) is a factor in promoting transient vasoconstriction, platelet
aggregation, and inflammation. An excess of the potent vasoconstrictor endothelin-1 is another
important contributor to vascular narrowing. Vascular pathology may occur in both large and small
vessels, accompanied by damage to the basement membrane, disruption of the blood–brain barrier, and
endothelial dysfunction. Cortical spreading depression, where clusters of neuronal depolarization
produce an influx of calcium and sodium, results in fluctuations in regional CBF (both hyperemia and
ischemia) and brain oxygenation, with possible uncoupling of flow and metabolism. Persistent or
recurrent spreading depression may be a major factor associated with both early and delayed
cerebral ischemia.

Delayed arterial narrowing, or “vasospasm,” occurs in two-thirds of patients, beginning about 72
hours after SAH, and may last for as long as 2 to 3 weeks. The most important risk factors for the
development of vasospasm are the amount of blood in the basal cisterns and the initial level of con-
sciousness. The presence of vasospasm is a clear predictor of neurological deterioration, delayed
cerebral infarction, and worse outcomes. Some patients with radiographic evidence of severe vaso-
spasm do not become symptomatic. Conversely, some patients deteriorate neurologically despite no
more than mild radiographic vasospasm. Thus, the degree to which vasospasm is a direct cause of neu-
rological decline, rather than a co-existing process, has been questioned. The pathophysiology of DCI is
undoubtedly more complex than being attributable solely to vasospasm, and includes factors such as
cortical spreading depression, inflammation, and increased coagulation