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Current Management of Delayed Cerebral Ischemia: Update from Results of Recent Clinical Trials

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Abstract

Subarachnoid hemorrhage (SAH) accounts for 5–7 % of all strokes worldwide and is associated with high mortality and morbidity. Even after surgical intervention, approximately 30 % of patients develop long-term cognitive and neurological deficits that significantly affect their capacity to return to work or daily life unassisted. Much of this stems from a secondary ischemic phenomenon referred to as delayed cerebral ischemia (DCI). While DCI has been historically attributed to the narrowing of the large basal cerebral arteries, it is now recognized that numerous pathways contribute to its pathogenesis, including microcirculatory dysfunction, microthrombosis, cortical spreading depression, and early brain injury. This paper seeks to summarize some of the key pathophysiological events that are associated with poor outcome after SAH, provide a general overview of current methods of treating SAH patients, and review the results of recent clinical trials directed at improving outcome after SAH. The scientific basis of these studies will be discussed, in addition to the available results and recommendations for effective patient management. Therapeutic methods under current clinical investigation will also be addressed. In particular, the mechanisms by which they are expected to elicit improved outcome will be investigated, as well as the specific study designs and anticipated time lines for completion.

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Conflict of Interest

Dr. Macdonald receives grant support from the Physicians Services Incorporated Foundation, Brain Aneurysm Foundation, Canadian Institutes for Health Research, and the Heart and Stroke Foundation of Canada; and is Chief Scientific Officer of Edge Therapeutics, Inc.

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Authors and Affiliations

  1. Division of Neurosurgery, Department of Surgery, St. Michael’s Hospital, 30 Bond Street, Toronto, Ontario, Canada, M5B 1W8

    Shakira Brathwaite & R. Loch Macdonald

  2. Labatt Family Centre of Excellence in Brain Injury and Trauma Research, Keenan Research Centre of the Li Ka Shing Knowledge Institute of St. Michael’s Hospital, 30 Bond Street, Toronto, Ontario, Canada, M5B 1W8

    Shakira Brathwaite & R. Loch Macdonald

  3. Department of Surgery, University of Toronto, Toronto, Ontario, Canada

    Shakira Brathwaite & R. Loch Macdonald

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  1. Shakira Brathwaite
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  2. R. Loch Macdonald
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Correspondence to R. Loch Macdonald.

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Review Criteria

The term “subarachnoid hemorrhage” was used to search Clinicaltrials.gov for ongoing randomized controlled trials, as well as those that had been completed within the last 5 years. All included trials were phase 2 and beyond, with a focus on preventive and therapeutic applications. Additionally, PubMed was searched for articles published after 1 January 2009, including electronic early release publications. The search term utilized was as follows: (delayed cerebral ischemia or delayed ischemic neurological deficits) and subarachnoid hemorrhage. The abstracts of the papers obtained were reviewed, and full articles were acquired when content was considered appropriate for inclusion.

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Brathwaite, S., Macdonald, R.L. Current Management of Delayed Cerebral Ischemia: Update from Results of Recent Clinical Trials. Transl. Stroke Res. 5, 207–226 (2014). https://doi.org/10.1007/s12975-013-0316-8

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  • DOI: https://doi.org/10.1007/s12975-013-0316-8

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