Aneurysmal Subarachnoid Hemorrhage—Status Quo and Perspective

Abstract

Aneurysmal subarachnoid hemorrhage (SAH) accounts for about 5 % of all strokes and continues to be a major cause of morbidity and mortality, especially in younger patients (mean age of 52). The global incidence of SAH is 9 per 100, 000 per year with some regional variations [1]. Data from population-based studies suggests a distinct decrease in case fatality (0.9 % per year) over the past four decades to about 30 %, which is likely originated in earlier and more advanced aneurysm repair as well as improved neurocritical care of SAH patients following aneurysm repair [2]. Nevertheless, the incidence of poor functional outcome in SAH patients remains high (about one third of patients). The main determinants for poor outcome after SAH are the degree of early brain injury (EBI) and the incidence of delayed cerebral ischemia (DCI) (see below) [3, 4]. The clinical course of SAH is complex and can be divided into an acute stage (the initial 72 h after SAH ictus) and a subacute stage, which lasts up until 20 days after SAH ictus. The potential main complications in the acute phase are EBI, rebleeding from the ruptured aneurysms, with a frequency of up to 23 % within the first 72 h, and acute hydrocephalus, occurring in about 20 % of the patients, whereas the main complications occurring in the subacute phase are DCI (formerly referred to as Bvasospasm,^ see below), cardiopulmonary or other medical complications, as well as permanent hydrocephalus [5–7]. The term EBI refers not only to direct mechanical damage to the brain tissue due to the hemorrhage but also to a cascade of different pathomechanisms, incl. a temporary increase of intracranial pressure, consecutive reduction of cerebral blood flow and/or microcirculatory spasm, transient global ischemia, neuronal injury or apoptosis, and edema formation [8]. The degree of EBI is a strong and independent predictor for clinical outcome after SAH [9, 3, 4]. The term DCI describes a complex phenomenon as a consequence of several pathomechanisms, incl. (1) macrovascular or angiographic vasospasm, i.e., narrowing of proximal cerebral arteries, (2) microvascular spasm, (3) microthromboembolism, (4) cortical spreading depolarization/ischemia, (5) autoregulatory dysfunction, and (6) inflammation [10–13, 7, 14–17]. The radiological term vasospasm has been widely replaced with the clinical term DCI, which describes a secondary neurological deterioration in the course SAH, excluding other causes of neurological deterioration; an explicit definition for DCI has been proposed by a multidisciplinary research group [16]. This Bparadigm shift^ came along with the insight that angiographic vasospasm occurs in up to 70 % of SAH patients, whereas only 30 % of SAH patients develop clinical features of DCI and, moreover, because pharmaceutical treatments exclusively targeting of angiographic vasospasm failed to improve neurological outcome after SAH [18–20]. However, in those clinical studies where cerebral infarction due to DCI was effectively reduced by experimental pharmaceutical treatments, a significant improvement of clinical outcome was also seen. These data further underlined the concept that DCI comprises several, pro-ischemic pathomechanisms, which ultimately result in cerebral infarction, but the individual importance of each of these pro-ischemic pathomechanisms remains to elucidated [21, 22]. The general shift in scientific focus, i.e., away from ‘vasospasm’ towards DCI and EBI, can also be * Nima Etminan etminan@uni-duesseldorf.de