Focus on Subarachnoid Hemorrhage and Delayed Cerebral Ischemia
Subarachnoid hemorrhage (SAH) is bleeding into the space around the brain that is filled with cerebrospinal fluid (the subarachnoid space). A spontaneous SAH is often due to a ruptured brain aneurysm. 90% of patients survive to reach the hospital, but over half will be disabled or dead. This occurs despite the patient being in hospital and with optimal medical treatment. This risk of poor outcome or death shows the obvious need for better treatment for SAH.
Delayed cerebral ischemia (DCI) is a serious complication arising from SAH that results from a number of mechanisms including cerebral vasospasm, cortical spreading ischemia, and microthrombembolism. Currently an effective and safe therapy does not exist to prevent DCI. Since oral nimodipine was FDA approved in 1989, it has become standard of care and has been given universally to aneurysmal SAH patients in oral or intravenous form (only available outside the U.S.) to improve outcome, but it is only marginally effective because it does not achieve therapeutic drug concentrations at the site of brain injury to more effectively block the pathways leading to DCI. Higher dosages of nimodipine that might be more effective in the brain cause dangerous side effects in other parts of the body such as low blood pressure (hypotension) and lung complications.
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