Subarachnoid hemorrhage (SAH) is characterized by bleeding into the subarachnoid space, often caused by ruptured aneurysm. Aneurysmal rupture occurs in 700,000 individuals per year worldwide, with 40,000 cases taking place in the United States. Beyond the high mortality associated with SAH alone, morbidity and mortality are further increased with the occurrence of cerebral vasospasm, a pathologic constriction of blood vessels that can lead to delayed ischemic neurologic deficits (DIND). Treatment of cerebral vasospasm is a source of contention. One extensively studied therapy is Magnesium (Mg) as both a competitive antagonist of calcium at the N-methyl D-aspartate (NMDA) receptor, and a noncompetitive antagonist of both IP3 and voltage-gated calcium channels, leading to smooth muscle relaxation. In our literature review, several animal and human studies are summarized in addition to two Phase III trials assessing the use of intravenous Mg in the treatment of SAH (IMASH and MASH-2). Though many studies have shown promise for the use of Mg in SAH, there has been inconsistency in study design and outcomes. Furthermore, the results of the recently completed clinical trials have shown no significant benefit from using intravenous Mg as adjuvant therapy in the treatment of cerebral vasospasm. 1. Introduction Subarachnoid hemorrhage (SAH) due to ruptured aneurysm occurs in 700,000 individuals a year [1], with nearly 40,000 of those cases occurring in the United States [2]. The mortality rate associated with the occurrence of SAH appears to have improved over the last 50 years [3], though it still remains that nearly half of all patients with a SAH will die within one month of the initial bleed [1]. Treatment of SAH is challenged by a number of complications. Cerebral vasospasm can occur in a majority of patients [4, 5] and is associated with poor outcome [5–8]. Despite having been recorded in patients treated for aneurysmal subarachnoid hemorrhage in 1951 [9], cerebral vasospasm (CVS) still remains a prevalent and morbid complication of SAH [10]. The occurrence of secondary ischemia and delayed ischemic neurologic deficits (DIND) is common sequelae in vasospasm and often leads to poor long-term outcomes. The diagnosis and treatment of CVS are made complicated by the heterogeneity of presentation and ambiguous etiology. Cerebral vasospasm is defined both clinically and angiographically, though these definitions are not mutually inclusive [11]. The occurrence of vasospasm is biphasic [1] with an acute phase that has been reported to begin 10 minutes [12] to 3-4
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