The pathophysiology and treatment of delayed cerebral ischaemia following subarachnoid haemorrhage

Abstract

Cerebral vasospasm has traditionally been regarded as an important cause of delayed cerebral ischaemia (DCI) which occurs after aneurysmal subarachnoid haemorrhage, and often leads to cerebral infarction and poor neurological outcome. However, data from recent studies argue against a pure focus on vasospasm as the cause of delayed ischaemic complications. Findings that marked reduction in the incidence of vasospasm does not translate to a reduction in DCI, or better outcomes has intensified research into other possible mechanisms which may promote ischaemic complications. Early brain injury and cell death, blood-brain barrier disruption and initiation of an inflammatory cascade, microvascular spasm, microthrombosis, cortical spreading depolarisations and failure of cerebral autoregulation, have all been implicated in the pathophysiology of DCI. This review summarises the current knowledge about the mechanisms underlying the development of DCI. Furthermore, it aims to describe and categorise the known pharmacological treatment options with respect to the presumed mechanism of action and its role in DCI.

Longitudinal profile of iron accumulation in good‐grade subarachnoid hemorrhage

“…However, it should be noted that the FAB performance of our patient group was within the range of standardized norms and that no association between R2* signal alterations and cognitive functions were found at 1‐year follow‐up. Although it is tempting to link iron overload in those structures with MRI parameters of axonal and neuronal damage as well as measures of cognitive function, other causes such as neuroinflammation, microthrombosis, mitochondrial and endothelial dysfunction, and cortical spreading depolarizations may have also contributed to microstructural brain tissue damage 48. Interestingly, none of our patients had clinical or radiographic evidence of cerebral infarctions suggesting a minor role of marked delayed cerebral ischemia in this process.…”

Haptoglobin phenotype predicts the development of focal and global cerebral vasospasm and may influence outcomes after aneurysmal subarachnoid hemorrhage

“…CV has long been regarded as a key contributor to poor outcomes after aSAH, mainly due to the resulting DCI and cerebral infarction that may occur (15). The purpose of this study was to determine whether individuals with the Hp2-2 phenotype had increased risk for CV, DCI, mortality, and poor outcomes following aSAH.…”

Are We Barking Up the Wrong Vessels?

“…Однако на сегодняшний день при использовании стратегий по лечению отсроченного вазоспазма не удалось улуч-шить исход после САК, о чем свидетельствуют резуль-таты недавно опубликованного испытания Clazosentan to Overcome Neurological Ischemia and Infarct Occurring After Subarachnoid Hemorrhage (CONCIOUS-2) [16]. В этом исследовании показали, что в основе разви-тия постгеморрагической ишемии лежат механизмы, отличные от спазма крупных артерий, и в течение последних десятилетий это феномен был в центре вни-мания большинства научно-исследовательских работ по изучению патогенеза САК [17,18]. Из-за этого сдвига парадигмы в области САК цель настоящей работы заключалась в анализе и обсуждении данных, свидетельствующих о том, что основным компонентом патогенеза САК является не спазм крупных артерий, а механизмы развития дисфункции церебральной мик-роциркуляции.…”

“…16 These results suggest that posthemorrhagic ischemia is caused by mechanisms different from large artery spasms, a phenomenon which was the focus of most research efforts trying to understand the pathogenesis of SAH in the past decades. 17,18 Because of this paradigm shift in the SAH field, the current article aims to review and discuss data suggesting that mechanisms independent of delayed large artery spasms and located on the level of the cerebral microcirculation may be major components of the pathogenesis of SAH.…”