[Management of Cerebral Vasospasm in Subarachnoid Hemorrhage]

Cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH) is a major cause of delayed cerebral ischemia (DCI) and remains a critical determinant of neurological outcomes. DCI pathophysiology is multifactorial and involves large artery vasospasm and microcirculatory dysfunction, including endothelial injury, microthrombosis, impaired autoregulation, and cortical spreading depolarization. In Japan, pharmacological management has traditionally included fasudil hydrochloride and other agents targeting the vascular tone or platelet aggregation, often combined with strategies to remove subarachnoid blood. The recent approval of clazosentan, a selective endothelin A receptor antagonist, has introduced a new therapeutic approach to prevent vasospasm after aSAH. Clinical trials conducted in Japan have demonstrated that clazosentan reduces vasospasm-related morbidity and mortality, as well as improves clinical outcomes. However, large international trials have shown reductions in angiographic vasospasms without consistent improvements in functional outcomes, highlighting DCI's complex pathophysiology beyond large vessel narrowing. In clinical practice, clazosentan has been associated with favorable outcomes, but requires careful management because of adverse events such as fluid retention and pulmonary complications. Future strategies should focus on optimizing treatment protocols centered on clazosentan and identifying effective combination therapies that target multiple mechanisms underlying DCI.