Delayed neurological deterioration after subarachnoid haemorrhage

Abstract

Subarachnoid haemorrhage (SAH) causes early brain injury (EBI) that is mediated by effects of transient cerebral ischaemia during bleeding plus effects of the subarachnoid blood. Secondary effects of SAH include increased intracranial pressure, destruction of brain tissue by intracerebral haemorrhage, brain shift, and herniation, all of which contribute to pathology. Many patients survive these phenomena, but deteriorate days later from delayed cerebral ischaemia (DCI), which causes poor outcome or death in up to 30% of patients with SAH. DCI is thought to be caused by the combined effects of angiographic vasospasm, arteriolar constriction and thrombosis, cortical spreading ischaemia, and processes triggered by EBI. Treatment for DCI includes prophylactic administration of nimodipine, and current neurointensive care. Prompt recognition of DCI and immediate treatment by means of induced hypertension and balloon or pharmacological angioplasty are considered important by many physicians, although the evidence to support such approaches is limited. This Review summarizes the pathophysiology of DCI after SAH and discusses established treatments for this condition. Novel strategies--including drugs such as statins, sodium nitrite, albumin, dantrolene, cilostazol, and intracranial delivery of nimodipine or magnesium--are also discussed.

Operative complications and differences in outcome after clipping and coiling of ruptured intracranial aneurysms

“…A neurysmAl subarachnoid hemorrhage (aSAH) occurs in 8-9 people per 100,000, 21,23 leading to significant morbidity 1 and mortality. 3,13,14,31 To reduce the risk of rehemorrhage, the ruptured aneurysm is treated either by neurosurgical clipping 29 or endovascular coiling.…”

A Site-Specific, Sustained-Release Drug Delivery System for Aneurysmal Subarachnoid Hemorrhage

“…The limitations of this approach include that animal models that reproduce brain injury and DCI similar to what occurs after human aneurysmal SAH are not well characterized or even nonexistent. The current dog efficacy study assessed angiographic vasospasm, but this is an imperfect surrogate measure of DCI [7]. No dose response may be detected, as was the case in the human nimodipine studies, in which the highest safe dose was approved for use.…”

“…Importantly, this was not observed in beagles. Nimodipine has fibrinolytic activity that may contribute to its efficacy and could theoretically cause hemorrhage [7,23]. However, there is no evidence that nimodipine is associated with hemorrhage in humans with SAH, even after intracisternal or intraventricular administration [9].…”

“…DCI is hypothesized to be due to a combination of angiographic vasospasm, microcirculatory dysfunction, cortical spreading ischemia, microthromboembolism, and delayed effects of early brain injury [7]. Nimodipine was noted to be a somewhat selective cerebral artery vasodilator that was studied in patients with SAH in order to reduce angiographic vasospasm.…”

“…One example is aneurysmal SAH, outcome from which remains poor with 35 % of patients dying and many having permanent neurological and neurocognitive morbidity [5,6]. Furthermore, an important cause of morbidity after SAH is delayed cerebral ischemia (DCI), which does not occur until days after SAH and thus may permit some time to elapse before drug delivery [7]. Despite testing of >50 drugs, no pharmacologic treatment for improving outcome after SAH has been developed since nimodipine was approved for use in the USA in 1988 [8,9].…”