Guidelines are also rather silent about addressing secondary mechanisms of brain injury in ICH, but not from lack of trying. Trials targeting inflammatory cascades with statins13 and intra-lesional alteplase14 have shown some promise. Current trials investigating the use of iron chelation,15 therapeutic hypothermia,16 and fingolimod17 are underway with other targets being investigated in animal models.2
Dr Qureshi and colleagues have demonstrated that in contrast to current guidelines, intensive SBP lowering alone in acute ICH is likely not effective. Despite trial evidence to the contrary, it is hard to believe that therapies that reduce hematoma expansion and peri-hematomal edema have zero effect. Perhaps what we are observing is that complex secondary cascades causing damage beyond the initial hemorrhage contribute more to long-term functional outcomes. What may be required to ensure the best outcome for patients suffering acute intracerebral hemorrhage is a multi-faceted medical and surgical approach targeting more than one mediator of injury. In the meantime, we wait for further evidence.
- Qureshi AI, Palesch YY, Barsan WG, et al. Intensive blood-pressure lowering in patients with acute cerebral hemorrhage. N Engl J Med. 2016. doi: 10.1056/NEJMoa1603460.
- Belur PK, Chang JJ, He S, Emanuel BA, Mack WJ. Emerging experimental therapies for intracerebral hemorrhage: Targeting mechanisms of secondary brain injury. Neurosurg Focus. 2013;34(5):E9.
- Qureshi AI, Tuhrim S, Broderick JP, Batjer HH, Hondo H, Hanley DF. Spontaneous intracerebral hemorrhage. N Engl J Med. 2001;344(19):1450-1460.
- Broderick JP, Diringer MN, Hill MD, et al. Determinants of intracerebral hemorrhage growth: An exploratory analysis. Stroke. 2007;38(3):1072-1075.
- Aronowski J, Zhao X. Molecular pathophysiology of cerebral hemorrhage: Secondary brain injury. Stroke. 2011;42(6):1781-1786.
- Wang J, Doré S. Inflammation after intracerebral hemorrhage. Journal of Cerebral Blood Flow & Metabolism. 2007;27(5):894-908.
- Arima H, Wang JG, Huang Y, et al. Significance of perihematomal edema in acute intracerebral hemorrhage: The INTERACT trial. Neurology. 2009;73(23):1963-1968.
- Mayer SA, Brun NC, Begtrup K, et al. Recombinant activated factor VII for acute intracerebral hemorrhage. N Engl J Med. 2005;352(8):777-785.
- Mayer SA, Brun NC, Begtrup K, et al. Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage. N Engl J Med. 2008;358(20):2127-2137.
- Anderson CS, Huang Y, Wang JG, et al. Intensive blood pressure reduction in acute cerebral haemorrhage trial (INTERACT): A randomised pilot trial. The Lancet Neurology. 2008;7(5):391-399.
- Anderson CS, Heeley E, Huang Y, et al. Rapid blood-pressure lowering in patients with acute intracerebral hemorrhage. N Engl J Med. 2013;368(25):2355-2365.
- Hemphill JC, Greenberg SM, Anderson CS, et al. Guidelines for the management of spontaneous intracerebral hemorrhage: A guideline for healthcare professionals from the american heart association/american stroke association. Stroke. 2015;46(7):2032-2060.
- Pérez JHT, Yildiz OC, Schneider T, Nimsky C. Meta-analysis of statin use for the acute therapy of spontaneous intracerebral hemorrhage. J Stroke Cerebrovasc Dis. 2015;24(11):2521-2526.
- Morgan T, Zuccarello M, Narayan R, Keyl P, Lane K, Hanley D. Preliminary findings of the minimally-invasive surgery plus rtPA for intracerebral hemorrhage evacuation (MISTIE) clinical trial. Acta Neurochir Suppl. 2008;105:147-51.
- Selim M, Yeatts S, Goldstein JN, et al. Safety and tolerability of deferoxamine mesylate in patients with acute intracerebral hemorrhage. Stroke. 2011;42(11):3067-3074.
- Rincon F, Friedman DP, Bell R, Mayer SA, Bray PF. Targeted temperature management after intracerebral hemorrhage (TTM‐ICH): Methodology of a prospective randomized clinical trial. Int J Stroke. 2014;9(5):646-651.
- Fu Y, Hao J, Zhang N, et al. Fingolimod for the treatment of intracerebral hemorrhage: A 2-arm proof-of-concept study. JAMA Neurol. 2014;71(9):1092-1101.