An introduction to the pathophysiology of aneurysmal subarachnoid hemorrhage

Abstract

Pathophysiological processes following subarachnoid hemorrhage (SAH) present survivors of the initial bleeding with a high risk of morbidity and mortality during the course of the disease. As angiographic vasospasm is strongly associated with delayed cerebral ischemia (DCI) and clinical outcome, clinical trials in the last few decades focused on prevention of these angiographic spasms. Despite all efforts, no new pharmacological agents have shown to improve patient outcome. As such, it has become clear that our understanding of the pathophysiology of SAH is incomplete and we need to reevaluate our concepts on the complex pathophysiological process following SAH. Angiographic vasospasm is probably important. However, a unifying theory for the pathophysiological changes following SAH has yet not been described. Some of these changes may be causally connected or present themselves as an epiphenomenon of an associated process. A causal connection between DCI and early brain injury (EBI) would mean that future therapies should address EBI more specifically. If the mechanisms following SAH display no causal pathophysiological connection but are rather evoked by the subarachnoid blood and its degradation production, multiple treatment strategies addressing the different pathophysiological mechanisms are required. The discrepancy between experimental and clinical SAH could be one reason for unsuccessful translational results.

Selected aspects of retinal signaling and energy metabolism and its perspective as a cerebral surrogate model

“…Up to 70% of all arterioles are affected during microvascular spasms. They are thought to originate from exposure to blood components, particularly oxygenated hemoglobin and partially by blood degradation products such as bilirubin and its oxidation endproducts (BOXes) [35]. Aside from that, a set of typical pathophysiological mechanisms contributes to DCI including microvascular dysfunction, microthrombosis, cortical spreading depolarization and inflammation reactions.…”

“…Recent reviews have summarized the present understanding of the pathophysiology of aneurysmal subarachnoid hemorrhage (SAH) quite in detail [34,35]. In most patients, the reason for spontaneous SAH arises from cerebral aneurysm rupture [36].…”

Automated Grading of Cerebral Vasospasm to Standardize Computed Tomography Angiography Examinations After Subarachnoid Hemorrhage

“…The resulting decline in cerebral perfusion pressure then induces transient global cerebral ischemia. Early brain injury can occur as an immediate effect of the bleeding and the transient global cerebral ischemia (4,5). The intracranial pressure eventually decreases and cerebral perfusion returns (5).…”

“…Early brain injury can occur as an immediate effect of the bleeding and the transient global cerebral ischemia (4,5). The intracranial pressure eventually decreases and cerebral perfusion returns (5). Of the patients who survive the initial bleeding event, up to 30% then suffer delayed cerebral ischemia (DCI) during the first weeks after SAH (4,5).…”

“…The intracranial pressure eventually decreases and cerebral perfusion returns (5). Of the patients who survive the initial bleeding event, up to 30% then suffer delayed cerebral ischemia (DCI) during the first weeks after SAH (4,5). DCI is defined as a new global or focal neurological impairment that lasts for at least 1 h or a new cerebral infarction that was not immediately apparent after aneurysm occlusion and which is attributable to ischemia and not to other causes (6).…”