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Novel Treatments in Neuroprotection for Aneurysmal Subarachnoid Hemorrhage

  • Critical Care Neurology (K Sheth, Section Editor)
  • Published:
Current Treatment Options in Neurology Aims and scope Submit manuscript

Opinion statement

New neuroprotective treatments aimed at preventing or minimizing “delayed brain injury” are attractive areas of investigation and hold the potential to have substantial beneficial effects on aneurysmal subarachnoid hemorrhage (aSAH) survivors. The underlying mechanisms for this “delayed brain injury” are multi-factorial and not fully understood. The most ideal treatment strategies would have the potential for a pleotropic effect positively modulating multiple implicated pathophysiological mechanisms at once. My personal management (RFJ) of patients with aneurysmal subarachnoid hemorrhage closely follows those treatment recommendations contained in modern published guidelines. However, over the last 5 years, I have also utilized a novel treatment strategy, originally developed at the University of Maryland, which consists of a 14-day continuous low-dose intravenous heparin infusion (LDIVH) beginning 12 h after securing the ruptured aneurysm. In addition to its well-known anti-coagulant properties, unfractionated heparin has potent anti-inflammatory effects and through multiple mechanisms may favorably modulate the neurotoxic and neuroinflammatory processes prominent in aneurysmal subarachnoid hemorrhage. In my personal series of patients treated with LDIVH, I have found significant preservation of neurocognitive function as measured by the Montreal Cognitive Assessment (MoCA) compared to a control cohort of my patients treated without LDIVH (RFJ unpublished data presented at the 2015 AHA/ASA International Stroke Conference symposium on neuroinflammation in aSAH and in abstract format at the 2015 AANS/CNS Joint Cerebrovascular Section Annual Meeting). It is important for academic physicians involved in the management of these complex patients to continue to explore new treatment options that may be protective against the potentially devastating “delayed brain injury” following cerebral aneurysm rupture. Several of the treatment options included in this review show promise and could be carefully adopted as the level of evidence for each improves. Other proposed neuroprotective treatments like statins and magnesium sulfate were previously thought to be very promising and to varying degrees were adopted at numerous institutions based on somewhat limited human evidence. Recent clinical trials and meta-analysis have shown no benefit for these treatments, and I currently no longer utilize either treatment as prophylaxis in my practice.

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Authors and Affiliations

  1. Department of Neurosurgery, University of Louisville, Louisville, KY, USA

    Robert F. James MD, Zaid S. Aljuboori MD, Shawn W. Adams MD, Jessica C. Eaton BA & Hussam Abou Al-Shaar

  2. Department of Neurosurgery, University of Southern California Keck School of Medicine, Los Angeles, CA, USA

    Daniel R. Kramer MD & William J. Mack MD

  3. Program in Trauma, Department of Neurology, University of Maryland School of Medicine, Baltimore, MD, USA

    Gunjan Parikh MD & Neeraj Badjatia MD

  4. Departments of Neurosurgery, Physiology and Pathology, University of Maryland School of Medicine, Baltimore, MD, USA

    J. Marc Simard MD, PhD

  5. Frazier Neuroscience and Rehab Center, 220 Abraham Flexner Way, 15th Floor, Louisville, KY, 40202, USA

    Robert F. James MD

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Conflict of Interest

Robert F. James, MD and J. Marc Simard, MD, PhD, are national co-principal investigators for the ASTROH study (A phase II, multi-center randomized trial evaluating a continuous low-dose IV heparin infusion for aneurysmal SAH). Neither has any personal financial gain at stake for this therapeutic option. NCT02501434 Robert F. James, MD and J. Marc Simard, MD, PhD, own private stock in Remedy Pharmaceuticals, which manufactures and develops therapeutic indications for intravenous glyburide (Cirara/RP1127). Dr. Simard is a company board member for Remedy Pharmaceuticals, Inc. and has received royalty payments.

Neeraj Badjatia, MD is the national study chair for the NASH trial (Normothermia after Aneurysmal Subarachnoid Hemorrhage) which is a double-blinded, placebo-controlled study evaluating continuous intravenous ibuprofen in aSAH. Dr. Badjatia has no personal financial gain at stake for this therapeutic option.

Daniel R. Kramer, Zaid S. Aljuboori, Gunjan Parikh, Shawn W. Adams, Jessica C. Eaton, Hussam Abou Al-Shaar, and William J. Mack declare that they have no conflict of interest.

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James, R.F., Kramer, D.R., Aljuboori, Z.S. et al. Novel Treatments in Neuroprotection for Aneurysmal Subarachnoid Hemorrhage. Curr Treat Options Neurol 18, 38 (2016). https://doi.org/10.1007/s11940-016-0421-6

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