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Curr Treat Options Neurol. 2016 Aug;18(8):38. doi: 10.1007/s11940-016-0421-6.

Novel Treatments in Neuroprotection for Aneurysmal Subarachnoid Hemorrhage.

Current treatment options in neurology

Robert F James, Daniel R Kramer, Zaid S Aljuboori, Gunjan Parikh, Shawn W Adams, Jessica C Eaton, Hussam Abou Al-Shaar, Neeraj Badjatia, William J Mack, J Marc Simard

Affiliations

  1. Department of Neurosurgery, University of Louisville, Louisville, KY, USA. [email protected].
  2. Frazier Neuroscience and Rehab Center, 220 Abraham Flexner Way, 15th Floor, Louisville, KY, 40202, USA. [email protected].
  3. Department of Neurosurgery, University of Southern California Keck School of Medicine, Los Angeles, CA, USA.
  4. Department of Neurosurgery, University of Louisville, Louisville, KY, USA.
  5. Program in Trauma, Department of Neurology, University of Maryland School of Medicine, Baltimore, MD, USA.
  6. Departments of Neurosurgery, Physiology and Pathology, University of Maryland School of Medicine, Baltimore, MD, USA.

PMID: 27325362 DOI: 10.1007/s11940-016-0421-6

Abstract

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.

Keywords: Aneurysmal subarachnoid hemorrhage; Cilostazol; Cortical spreading depolarization; Glyburide; Ibuprofen; Ischemic preconditioning; Molsidomine; Omega 3 fatty acid; Partial aortic occlusion; SAH; Unfractionated heparin

References

  1. Neuroreport. 1993 Jun;4(6):709-11 - PubMed
  2. Stroke. 2012 Jun;43(6):1711-37 - PubMed
  3. J Physiol. 2011 Sep 1;589(17):4147-55 - PubMed
  4. Neurosurgery. 2002 Dec;51(6):1457-65; discussion 1465-7 - PubMed
  5. Exp Biol Med (Maywood). 2007 Feb;232(2):204-13 - PubMed
  6. Lancet Neurol. 2009 Jul;8(7):635-42 - PubMed
  7. Brain. 2002 Jan;125(Pt 1):102-12 - PubMed
  8. Trends Neurosci. 2003 May;26(5):248-54 - PubMed
  9. Chem Biol Drug Des. 2008 Dec;72(6):455-82 - PubMed
  10. Acta Neurochir Suppl. 2011;110(Pt 1):111-7 - PubMed
  11. J Cereb Blood Flow Metab. 1996 Nov;16(6):1090-9 - PubMed
  12. J Cereb Blood Flow Metab. 1992 Mar;12 (2):223-9 - PubMed
  13. J Cereb Blood Flow Metab. 1996 Mar;16(2):202-13 - PubMed
  14. Neurocrit Care. 2010 Dec;13(3):439-49 - PubMed
  15. Brain Res. 2005 Sep 21;1056(2):200-8 - PubMed
  16. Am J Physiol Heart Circ Physiol. 2004 Apr;286(4):H1339-46 - PubMed
  17. J Cereb Blood Flow Metab. 2012 Feb;32(2):203-12 - PubMed
  18. J Cereb Blood Flow Metab. 1992 May;12(3):371-9 - PubMed

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