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Cerebral vasospasm after subarachnoid hemorrhage: the emerging revolution

Nature Clinical Practice Neurology volume 3, pages 256–263 (2007)Cite this article

Abstract

Cerebral vasospasm is the classic cause of delayed neurological deterioration after aneurysmal subarachnoid hemorrhage, leading to cerebral ischemia and infarction, and thus to poor outcome and occasionally death. Advances in diagnosis and treatment—principally the use of nimodipine, intensive care management, hemodynamic manipulations and endovascular neuroradiology procedures—have improved the prospects for these patients, but outcomes remain disappointing. Recent clinical trials have demonstrated marked prevention of vasospasm with the endothelin receptor antagonist clazosentan, yet patient outcome was not improved. This Review considers possible explanations for this result and proposes alternative causes of neurological deterioration and poor outcome after subarachnoid hemorrhage, including delayed effects of global cerebral ischemia, thromboembolism, microcirculatory dysfunction and cortical spreading depression.

Key Points

  • Delayed vasospasm of the large cerebral arteries is an important cause of cerebral ischemia and infarction after aneurysmal subarachnoid hemorrhage

  • Vasospasm causes delayed neurological deterioration as a consequence of ischemia

  • Recent clinical trials demonstrated marked prevention of vasospasm with the endothelin receptor antagonist clazosentan, yet patient outcome was not improved

  • There might be other causes for delayed neurological deterioration, including thromboembolism, microcirculatory changes, cortical spreading depression, and delayed neuronal apoptosis

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Figure 1: Complications of subarachnoid hemorrhage, their time of occurrence and their possible contribution to delayed neurological deterioration
Figure 2: Extracellular processes leading to large-artery vasospasm by elevation of intracellular calcium level in smooth muscle cells

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Acknowledgements

This research was supported in part by the Intramural Research Program of the NIH, National Institute of Neurological Disorders and Stroke.

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Authors and Affiliations

  1. RL Macdonald is Head of the Division of Neurosurgery at St Michael's Hospital and the Keenan Endowed Chair in Surgery and Professor of Surgery at the University of Toronto, Toronto, Canada.,

    R Loch Macdonald

  2. RM Pluta works as a Clinical Staff Scientist at the Surgical Neurology Branch of the National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD.,

    Ryszard M Pluta

  3. JH Zhang is the Director of Neurosurgery Research, Director of Anesthesiology Basic Science Research, and Director of Physiology Graduate Program at the Loma Linda University, CA, USA.,

    John H Zhang

Authors
  1. R Loch Macdonald
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  2. Ryszard M Pluta
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  3. John H Zhang
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Corresponding author

Correspondence to R Loch Macdonald.

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Competing interests

RH Macdonald is supported by grants from the National Institutes of Health, American Heart Association and Brain Research Foundation. He is a consultant for Actelion Pharmaceuticals. JH Zhang is supported by grants from the National Institutes of Health and American Heart Association. R Pluta declared he has no competing interests.

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Macdonald, R., Pluta, R. & Zhang, J. Cerebral vasospasm after subarachnoid hemorrhage: the emerging revolution. Nat Rev Neurol 3, 256–263 (2007). https://doi.org/10.1038/ncpneuro0490

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