To Look Beyond Vasospasm in Aneurysmal Subarachnoid Haemorrhage

Abstract

Delayed cerebral vasospasm has classically been considered the most important and treatable cause of mortality and morbidity in patients with aneurysmal subarachnoid hemorrhage (aSAH). Secondary ischemia (or delayed ischemic neurological deficit, DIND) has been shown to be the leading determinant of poor clinical outcome in patients with aSAH surviving the early phase and cerebral vasospasm has been attributed to being primarily responsible. Recently, various clinical trials aimed at treating vasospasm have produced disappointing results. DIND seems to have a multifactorial etiology and vasospasm may simply represent one contributing factor and not the major determinant. Increasing evidence shows that a series of early secondary cerebral insults may occur following aneurysm rupture (the so-called early brain injury). This further aggravates the initial insult and actually determines the functional outcome. A better understanding of these mechanisms and their prevention in the very early phase is needed to improve the prognosis. The aim of this review is to summarize the existing literature on this topic and so to illustrate how the presence of cerebral vasospasm may not necessarily be a prerequisite for DIND development. The various factors determining DIND that worsen functional outcome and prognosis are then discussed.

A Phase I proof-of-concept and safety trial of sildenafil to treat cerebral vasospasm following subarachnoid hemorrhage

“…4,82 A significant predictor of developing DCI is angiographic CVS of intracranial vessels. 6,7,47 Approximately abbreviatioNs cGMP = cyclic guanosine monophosphate; CVS = cerebrovascular vasospasm; DCI = delayed cerebral ischemia; DSA = digital subtraction angiography; DSMB = Data Safety Monitoring Board; eNOS = endothelial nitric oxide synthase; ICA = internal carotid artery; ICP = intracranial pressure; MAP = mean arterial pressure; MCA = middle cerebral artery; NNICU = Neurology/Neurosurgery ICU; NO = nitric oxide; PDE-V = phosphodiesterase-V; SAH = subarachnoid hemorrhage. obJective Studies show that phosphodiesterase-V (PDE-V) inhibition reduces cerebral vasospasm (CVS) and improves outcomes after experimental subarachnoid hemorrhage (SAH).…”

“…4,6,74 Occurring in 30%-40% of patients, DCI is the most common and potentially treatable contributor to outcome. 6,57,78 Though the mechanisms underlying DCI are multifactorial, the processes considered most responsible are delayed cerebrovascular vasospasm (CVS), cerebrovascular autoregulatory dysfunction, and cortical spreading ischemia. 6,47 Unfortunately, to date few therapies have proven effective for the prevention and treatment of DCI.…”

“…6,57,78 Though the mechanisms underlying DCI are multifactorial, the processes considered most responsible are delayed cerebrovascular vasospasm (CVS), cerebrovascular autoregulatory dysfunction, and cortical spreading ischemia. 6,47 Unfortunately, to date few therapies have proven effective for the prevention and treatment of DCI. 4,82 A significant predictor of developing DCI is angiographic CVS of intracranial vessels.…”

“…4,6,7,11 In those patients, 50% will develop DCI. 7,8,17,61 With this strong correlation, it is recommended that CVS be used as an initial outcome measure when assessing potential treatments for DCI.…”

Vertebrobasilar Vasospasm after Aneurysmal Subarachnoid Hemorrhage: Review

“…Aneurysmal subarachnoid hemorrhage (SAH) affects 5-10 per 100,000 individuals per year 1 and is associated with high rates of morbidity and mortality [1][2][3][4]. Main contributor to poor outcomes after SAH are the early cerebral injury (ECI) caused by the immediate increase in intracranial pressure, decreased cerebral perfusion pressure and global ischemia [1,[5][6][7][8][9] and delayed cerebral ischemia (DCI) which affects 30% of the SAH survivors leading to neurological deficit, cognitive decline [4,6,[9][10][11][12][13], and death [14].…”