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  • Review Article
  • Published:

Delayed neurological deterioration after subarachnoid haemorrhage

Nature Reviews Neurology volume 10, pages 44–58 (2014)Cite this article

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Key Points

  • The two main effects of subarachnoid haemorrhage (SAH) are early brain injury and delayed cerebral ischaemia (DCI)

  • The pathogenesis of DCI is hypothesized to be multifactorial and includes angiographic vasospasm, cortical spreading ischaemia, microthrombosis and microcirculation constriction

  • Early brain injury, which refers to the acute effects of subarachnoid blood and the transient global ischaemia that may accompany aneurysm rupture, has also been suggested to contribute to DCI

  • Risk of DCI is increased by volume, density and persistence of the subarachnoid thrombus, early brain injury, factors that reduce brain oxygen and glucose supply and, probably, pre-existing hypertension

  • Treatments that reduce the risk of DCI include nimodipine, rescue therapy consisting of balloon or pharmacological angioplasty, and induced hypertension

  • Drugs under investigation for DCI include intrathecal dihydropyridines, magnesium, albumin, sodium nitrite, statins, dantrolene and cilostazol

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.

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Figure 1: Early pathophysiology of subarachnoid haemorrhage.
Figure 2: Pathophysiological processes in delayed cortical ischaemia.
Figure 3: Pathophysiological causes of ischaemia.
Figure 4: CT scan and cerebral angiography of SAH.
Figure 5: A management scheme—our approach to SAH and DCI.

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Change history

  • 17 December 2013

    In the version of this article initially published online, the figure legend for part e of Figure 4 was omitted. The error has been corrected for the print, HTML and PDF versions of the article.

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Acknowledgements

The author receives grant support from the Physicians Services Incorporated Foundation, the Brain Aneurysm Foundation, the Canadian Stroke Network, and the Heart and Stroke Foundation of Ontario.

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  1. Division of Neurosurgery, St Michael's Hospital, 30 Bond Street, Toronto, M5B 1W8, ON, Canada

    R. Loch Macdonald

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R. L. Macdonald is Chief Scientific Officer of Edge Therapeutics, Inc.

Supplementary information

Supplementary Table 1

Randomized, blinded clinical trials for treatment of subarachnoid haemorrhage (not directed at aneurysm repair or preventing rebleeding) (DOC 43 kb)

Supplementary Table 2

Meta-analyses of subarachnoid haemorrhage trials (DOC 18 kb)

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Macdonald, R. Delayed neurological deterioration after subarachnoid haemorrhage. Nat Rev Neurol 10, 44–58 (2014). https://doi.org/10.1038/nrneurol.2013.246

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