Treatment of Edema Associated With Intracerebral Hemorrhage

  • Audrey Leasure
  • W. Taylor Kimberly
  • Lauren H. Sansing
  • Kristopher T. Kahle
  • Golo Kronenberg
  • Hagen Kunte
  • J. Marc Simard
  • Kevin N. Sheth
Critical Care Neurology (K Sheth, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Critical Care Neurology

Opinion statement

Cerebral edema (i.e., “brain swelling”) is a common complication following intracerebral hemorrhage (ICH) and is associated with worse clinical outcomes. Perihematomal edema (PHE) accumulates during the first 72 h after hemorrhage, and during this period, patients are at risk of clinical deterioration due to the resulting tissue shifts and brain herniation. First-line medical therapies for patients symptomatic of PHE include osmotic agents, such as mannitol in low- or high-dose bolus form, or boluses of hypertonic saline (HTS) at varied concentrations with or without subsequent continuous infusion. Decompressive craniectomy may be required for symptomatic edema refractory to osmotherapy. Other strategies that reduce PHE such as hypothermia and minimally invasive surgery have shown promise in pilot studies and are currently being evaluated in larger clinical trials. Ongoing basic, translational, and clinical research seek to better elucidate the pathophysiology of PHE to identify novel strategies to prevent edema formation as a next major advance in the treatment of ICH.


Intracerebral hemorrhage Perihematomal edema Secondary brain injury Hyperosmolar therapy ICP 

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    van Asch CJ. Incidence, case fatality, and functional outcome of intracerebral haemorrhage over time, according to age, sex, and ethnic origin: a systematic review and meta-analysis. Lancet Neurol. 2010;9:167–76.CrossRefPubMedGoogle Scholar
  2. 2.
    Mendelow AD, Gregson BA, Fernandes HM, Murray GD, Teasdale GM, Hope DT, et al. Early surgery versus initial conservative treatment in patients with spontaneous supratentorial intracerebral haematomas in the International Surgical Trial in Intracerebral Haemorrhage (STICH): a randomised trial. Lancet. 2005;365(9457):387–97. doi:10.1016/s0140-6736(05)17826-x.CrossRefPubMedGoogle Scholar
  3. 3.
    Mendelow AD, Gregson BA, Rowan EN, Murray GD, Gholkar A, Mitchell PM. Early surgery versus initial conservative treatment in patients with spontaneous supratentorial lobar intracerebral haematomas (STICH II): a randomised trial. Lancet. 2013;382(9890):397–408. doi:10.1016/s0140-6736(13)60986-1.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Anderson CS, Huang Y, Arima H, Heeley E, Skulina C, Parsons MW, et al. Effects of early intensive blood pressure-lowering treatment on the growth of hematoma and perihematomal edema in acute intracerebral hemorrhage: the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT). Stroke. 2010;41(2):307–12. doi:10.1161/strokeaha.109.561795.CrossRefPubMedGoogle Scholar
  5. 5.
    Anderson CS, Heeley E, Huang Y, Wang J, Stapf C, Delcourt C, et al. Rapid blood-pressure lowering in patients with acute intracerebral hemorrhage. N Engl J Med. 2013;368(25):2355–65. doi:10.1056/NEJMoa1214609.CrossRefPubMedGoogle Scholar
  6. 6.
    Fiorella D, Zuckerman SL, Khan IS, Ganesh NK, Mocco J. Intracerebral hemorrhage: a common and devastating disease in need of better treatment. World Neurosurg. 2015;84(4):1136–41. doi:10.1016/j.wneu.2015.05.063.CrossRefPubMedGoogle Scholar
  7. 7.
    Qureshi AI, Palesch YY. Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH) II: design, methods, and rationale. Neurocrit Care. 2011;15(3):559–76. doi:10.1007/s12028-011-9538-3.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Keep RF, Hua Y, Xi G. Intracerebral haemorrhage: mechanisms of injury and therapeutic targets. Lancet Neurol. 2012;11(8):720–31. doi:10.1016/s1474-4422(12)70104-7.CrossRefPubMedGoogle Scholar
  9. 9.
    Urday S, Kimberly WT, Beslow LA, Vortmeyer AO, Selim MH, Rosand J, et al. Targeting secondary injury in intracerebral haemorrhage—perihaematomal oedema. Nat Rev Neurol. 2015;11(2):111–22. doi:10.1038/nrneurol.2014.264.CrossRefPubMedGoogle Scholar
  10. 10.•
    Lord AS, Gilmore E, Choi HA, Mayer SA. Time course and predictors of neurological deterioration after intracerebral hemorrhage. Stroke. 2015;46(3):647–52. doi:10.1161/strokeaha.114.007704. This study implicates edema as a driver of neurologic deterioration after ICH in the 24–72 h window.Google Scholar
  11. 11.
    Kamel H, Hemphill 3rd JC. Characteristics and sequelae of intracranial hypertension after intracerebral hemorrhage. Neurocrit Care. 2012;17(2):172–6. doi:10.1007/s12028-012-9744-7.CrossRefPubMedGoogle Scholar
  12. 12.•
    Murthy SB, Moradiya Y, Dawson J, Lees KR, Hanley DF, Ziai WC. Perihematomal edema and functional outcomes in intracerebral hemorrhage: influence of hematoma volume and location. Stroke. 2015;46(11):3088–92. doi:10.1161/strokeaha.115.010054.This study uses a large sample size to demonstrate that PHE expansion in the first 72 hours after ICH is associated with worse outcomes in basal ganglia ICH after adjusting for hematoma volume. This study corroborates previous findings and strengthens the argument that PHE has a clinically significant impact on outcome and is a potential target for therapeutic intervention.
  13. 13.•
    Volbers B, Willfarth W, Kuramatsu JB, Struffert T, Dorfler A, Huttner HB et al. Impact of perihemorrhagic edema on short-term outcome after intracerebral hemorrhage. Neurocritical Care. 2015. doi:10.1007/s12028-015-0185-y.This study demonstrates, in a large sample size and over a longer period of follow-up, that peak PHE volume, rather than PHE growth, may be a predictor of short-term functional outcome at discharge. These findings corroborate data supporting the role of PHE in determining outcomes after ICH and argues that PHE may be a clinically relevant treatment target.
  14. 14.••
    Yang J, Arima H, Wu G, Heeley E, Delcourt C, Zhou J, et al. Prognostic significance of perihematomal edema in acute intracerebral hemorrhage: pooled analysis from the intensive blood pressure reduction in acute cerebral hemorrhage trial studies. Stroke. 2015;46(4):1009–13. doi:10.1161/strokeaha.114.007154. This large study provides evidence of an independent association between the growth of edema after ICH and a poor outcome. Together with 12 and 13, this paper helps to clarify the impact of edema on the outcome and strengthens the argument for the investigation of strategies for attenuating PHE growth.CrossRefPubMedGoogle Scholar
  15. 15.
    Urday S, Beslow LA, Goldstein DW, Vashkevich A, Ayres AM, Battey TW, et al. Measurement of perihematomal edema in intracerebral hemorrhage. Stroke. 2015;46(4):1116–9. doi:10.1161/strokeaha.114.007565.CrossRefPubMedGoogle Scholar
  16. 16.
    Ziai WC. Hematology and inflammatory signaling of intracerebral hemorrhage. Stroke. 2013;44(6 Suppl 1):S74–8. doi:10.1161/strokeaha.111.000662.CrossRefPubMedGoogle Scholar
  17. 17.•
    Urday S BL, Dai F, Zheng F, Battey TWK, Vashkevich A, Ayres A, Selim MH, Simard JM, Rosand J, Kimberly WT, Sheth KN. Rate of peri-hematomal edema expansion predicts outcome after intracerebral hemorrhage. In Press. 2015. This paper provides a new index of edema, PHE expansion rate, and shows that PHE expansion rate predicts the outcome after ICH. Along with 12, 13, and 14, the data from this paper support PHE as an independent predictor of the outcome in the controversial debate on the role of edema in ICH.Google Scholar
  18. 18.
    Parry-Jones AR, Wang X, Sato S, Mould WA, Vail A, Anderson CS, et al. Edema extension distance: outcome measure for phase II clinical trials targeting edema after intracerebral hemorrhage. Stroke. 2015;46(6):e137–40. doi:10.1161/strokeaha.115.008818.CrossRefPubMedGoogle Scholar
  19. 19.
    Appelboom G. Volume-dependent effect of perihaematomal oedema on outcome for spontaneous intracerebral haemorrhages. J Neurol Neurosurg Psychiatry. 2013;84:488–93.CrossRefPubMedGoogle Scholar
  20. 20.
    Sun W, Pan W, Kranz PG, Hailey CE, Williamson RA, Sun W, et al. Predictors of late neurological deterioration after spontaneous intracerebral hemorrhage. Neurocrit Care. 2013;19(3):299–305. doi:10.1007/s12028-013-9894-2.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Staykov D. Natural course of perihemorrhagic edema after intracerebral hemorrhage. Stroke. 2011;42:2625–9.CrossRefPubMedGoogle Scholar
  22. 22.
    Sansing LH, Messe SR, Cucchiara BL, Lyden PD, Kasner SE. Anti-adrenergic medications and edema development after intracerebral hemorrhage. Neurocrit Care. 2011;14:395–400.CrossRefPubMedGoogle Scholar
  23. 23.
    Li YH, Wang JB, Li MH, Li WB, Wang D. Quantification of brain edema and hemorrhage by MRI after experimental traumatic brain injury in rabbits predicts subsequent functional outcome. Neurol Sci. 2012;33(4):731–40. doi:10.1007/s10072-011-0768-0.CrossRefPubMedGoogle Scholar
  24. 24.
    Arima H. Significance of perihematomal edema in acute intracerebral hemorrhage: the INTERACT trial. Neurology. 2009;73:1963–8.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Ziai W, Moullaali T, Nekoovaght-Tak S, Ullman N, Brooks JS, Morgan TC, et al. No exacerbation of perihematomal edema with intraventricular tissue plasminogen activator in patients with spontaneous intraventricular hemorrhage. Neurocrit Care. 2013;18(3):354–61. doi:10.1007/s12028-013-9826-1.CrossRefPubMedGoogle Scholar
  26. 26.
    Zhao X, Zhang Y, Strong R, Zhang J, Grotta JC, Aronowski J. Distinct patterns of intracerebral hemorrhage-induced alterations in NF-kappaB subunit, iNOS, and COX-2 expression. J Neurochem. 2007;101(3):652–63. doi:10.1111/j.1471-4159.2006.04414.x.CrossRefPubMedGoogle Scholar
  27. 27.
    Zhang ZL, Liu YG, Huang QB, Wang HW, Song Y, Xu ZK, et al. Nuclear factor-kappaB activation in perihematomal brain tissue correlates with outcome in patients with intracerebral hemorrhage. J Neuroinflammation. 2015;12:53. doi:10.1186/s12974-015-0277-9.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Gebel Jr JM. Relative edema volume is a predictor of outcome in patients with hyperacute spontaneous intracerebral hemorrhage. Stroke. 2002;33:2636–41.CrossRefPubMedGoogle Scholar
  29. 29.
    Babu R, Bagley JH, Di C, Friedman AH, Adamson C. Thrombin and hemin as central factors in the mechanisms of intracerebral hemorrhage-induced secondary brain injury and as potential targets for intervention. Neurosurg Focus. 2012;32(4):E8. doi:10.3171/2012.1.focus11366.CrossRefPubMedGoogle Scholar
  30. 30.
    Zheng GQ. Long-time course of protease-activated receptor-1 expression after intracerebral hemorrhage in rats. Neurosci Lett. 2009;459:62–5.CrossRefPubMedGoogle Scholar
  31. 31.
    Gebel JM. Decreased perihematomal edema in thrombolysis-related intracerebral hemorrhage compared with spontaneous intracerebral hemorrhage. Stroke. 2000;31:596–600.CrossRefPubMedGoogle Scholar
  32. 32.
    Xi G, Hua Y, Keep RF, Younger JG, Hoff JT. Systemic complement depletion diminishes perihematomal brain edema in rats. Stroke. 2001;32(1):162–7.CrossRefPubMedGoogle Scholar
  33. 33.
    Zhou Y, Wang Y, Wang J, Anne Stetler R, Yang QW. Inflammation in intracerebral hemorrhage: from mechanisms to clinical translation. Prog Neurobiol. 2014;115:25–44. doi:10.1016/j.pneurobio.2013.11.003.CrossRefPubMedGoogle Scholar
  34. 34.
    Ropper AH. Management of raised intracranial pressure and hyperosmolar therapy. Pract Neurol. 2014;14(3):152–8. doi:10.1136/practneurol-2014-000811.CrossRefPubMedGoogle Scholar
  35. 35.
    Tan G, Zhou J, Yuan D, Sun S. Formula for use of mannitol in patients with intracerebral haemorrhage and high intracranial pressure. Clin Drug Investig. 2008;28(2):81–7.CrossRefPubMedGoogle Scholar
  36. 36.
    Koenig MA, Bryan M, Lewin 3rd JL, Mirski MA, Geocadin RG, Stevens RD. Reversal of transtentorial herniation with hypertonic saline. Neurology. 2008;70(13):1023–9. doi:10.1212/01.wnl.0000304042.05557.60.CrossRefPubMedGoogle Scholar
  37. 37.
    Diringer MN. New trends in hyperosmolar therapy? Curr Opin Crit Care. 2013;19(2):77–82. doi:10.1097/MCC.0b013e32835eba30.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Wagner I. Effects of continuous hypertonic saline infusion on perihemorrhagic edema evolution. Stroke. 2011;42:1540–5.CrossRefPubMedGoogle Scholar
  39. 39.•
    Wang X, Arima H, Yang J, Zhang S, Wu G, Woodward M et al. Mannitol and outcome in intracerebral hemorrhage: propensity score and multivariable Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial 2 results. Stroke. 2015. doi:10.1161/strokeaha.115.009357. This study found no significant difference in poor outcome between ICH patients who received mannitol and those who did not. This study shows that the most commonly used treatment strategy for edema is not associated with better outcomes and highlights the lack of evidence-based strategies for treatment of edema and ICP.Google Scholar
  40. 40.
    Kamel H, Navi BB, Nakagawa K, Hemphill 3rd JC, Ko NU. Hypertonic saline versus mannitol for the treatment of elevated intracranial pressure: a meta-analysis of randomized clinical trials. Crit Care Med. 2011;39(3):554–9. doi:10.1097/CCM.0b013e318206b9be.CrossRefPubMedGoogle Scholar
  41. 41.••
    Mould WA. Minimally invasive surgery plus recombinant tissue-type plasminogen activator for intracerebral hemorrhage evacuation decreases perihematomal edema. Stroke. 2013;44:627–34. This study shows that minimally invasive surgery for hematomal evacuation significantly reduces PHE.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Barnes B, Hanley DF, Carhuapoma JR. Minimally invasive surgery for intracerebral haemorrhage. Curr Opin Crit Care. 2014;20(2):148–52. doi:10.1097/mcc.0000000000000077.CrossRefPubMedGoogle Scholar
  43. 43.
    Wijdicks EF, Sheth KN, Carter BS, Greer DM, Kasner SE, Kimberly WT, et al. Recommendations for the management of cerebral and cerebellar infarction with swelling: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45(4):1222–38. doi:10.1161/01.str.0000441965.15164.d6.CrossRefPubMedGoogle Scholar
  44. 44.
    Ramnarayan R, Anto D, Anilkumar TV, Nayar R. Decompressive hemicraniectomy in large putaminal hematomas: An Indian experience. J Stroke Cerebrovasc Dis. 2009;18(1):1–10. doi:10.1016/j.jstrokecerebrovasdis.2008.09.001.CrossRefPubMedGoogle Scholar
  45. 45.
    Fung C, Murek M, Z’Graggen WJ, Krahenbuhl AK, Gautschi OP, Schucht P, et al. Decompressive hemicraniectomy in patients with supratentorial intracerebral hemorrhage. Stroke. 2012;43(12):3207–11. doi:10.1161/strokeaha.112.666537.CrossRefPubMedGoogle Scholar
  46. 46.
    Heuts SG, Bruce SS, Zacharia BE, Hickman ZL, Kellner CP, Sussman ES, et al. Decompressive hemicraniectomy without clot evacuation in dominant-sided intracerebral hemorrhage with ICP crisis. Neurosurg Focus. 2013;34(5), E4. doi:10.3171/2013.2.focus1326.CrossRefPubMedGoogle Scholar
  47. 47.
    Esquenazi Y, Savitz SI, El Khoury R, McIntosh MA, Grotta JC, Tandon N. Decompressive hemicraniectomy with or without clot evacuation for large spontaneous supratentorial intracerebral hemorrhages. Clin Neurol Neurosurg. 2015;128:117–22. doi:10.1016/j.clineuro.2014.11.015.CrossRefPubMedGoogle Scholar
  48. 48.
    Beck J. Decompressive Hemicraniectomy in Intracerebral Hemorrhage (SWITCH). 2014.
  49. 49.
    Zheng D, Arima H, Heeley E, Karpin A, Yang J, Chalmers J, et al. Ambient temperature and volume of perihematomal edema in acute intracerebral haemorrhage: the INTERACT1 study. Int J Stroke. 2015;10(1):25–7. doi:10.1111/ijs.12389.CrossRefPubMedGoogle Scholar
  50. 50.
    Kawanishi M, Kawai N, Nakamura T, Luo C, Tamiya T, Nagao S. Effect of delayed mild brain hypothermia on edema formation after intracerebral hemorrhage in rats. J Stroke Cerebrovasc Dis. 2008;17(4):187–95. doi:10.1016/j.jstrokecerebrovasdis.2008.01.003.CrossRefPubMedGoogle Scholar
  51. 51.
    Wei S, Sun J, Li J, Wang L, Hall CL, Dix TA, et al. Acute and delayed protective effects of pharmacologically induced hypothermia in an intracerebral hemorrhage stroke model of mice. Neuroscience. 2013;252:489–500. doi:10.1016/j.neuroscience.2013.07.052.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Kollmar R, Staykov D, Dorfler A, Schellinger PD, Schwab S, Bardutzky J. Hypothermia reduces perihemorrhagic edema after intracerebral hemorrhage. Stroke. 2010;41(8):1684–9. doi:10.1161/strokeaha.110.587758.CrossRefPubMedGoogle Scholar
  53. 53.
    Staykov D, Schwab S, Dorfler A, Kollmar R. Hypothermia reduces perihemorrhagic edema after intracerebral hemorrhage: but does it influence functional outcome and mortality? Ther Hypothermia Temp Manag. 2011;1(2):105–6. doi:10.1089/ther.2011.0004.CrossRefPubMedGoogle Scholar
  54. 54.
    Staykov D. Mild prolonged hypothermia for large intracerebral hemorrhage. Neurocrit Care. 2013;18:178–83.CrossRefPubMedGoogle Scholar
  55. 55.
    Kollmar R. Cooling in Intracerebral Hemorrhage (CINCH) trial: protocol of a Randomized German-Austrian clinical trial. Int J Stroke. 2012;7:168–72.CrossRefPubMedGoogle Scholar
  56. 56.
    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):646–51. doi:10.1111/ijs.12220.CrossRefPubMedGoogle Scholar
  57. 57.
    Cui HJ, He HY, Yang AL, Zhou HJ, Wang C, Luo JK, et al. Efficacy of deferoxamine in animal models of intracerebral hemorrhage: a systematic review and stratified meta-analysis. PLoS One. 2015;10(5):e0127256. doi:10.1371/journal.pone.0127256.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Lou M, Lieb K, Selim M. The relationship between hematoma iron content and perihematoma edema: an MRI study. Cerebrovasc Dis. 2009;27:266–71.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Yeatts SD, Palesch YY, Moy CS, Selim M. High Dose Deferoxamine in Intracerebral Hemorrhage (HI-DEF) trial: rationale, design, and methods. Neurocrit Care. 2013;19(2):257–66. doi:10.1007/s12028-013-9861-y.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Fu Y, Hao J, Zhang N, Ren L, Sun N, Li YJ, et al. Fingolimod for the treatment of intracerebral hemorrhage: a 2-arm proof-of-concept study. JAMA Neurol. 2014;71(9):1092–101. doi:10.1001/jamaneurol.2014.1065.
  61. 61.
    Colombo E, Di Dario M, Capitolo E, Chaabane L, Newcombe J, Martino G, et al. Fingolimod may support neuroprotection via blockade of astrocyte nitric oxide. Ann Neurol. 2014;76(3):325–37. doi:10.1002/ana.24217.CrossRefPubMedGoogle Scholar
  62. 62.
    Choi JW, Gardell SE, Herr DR, Rivera R, Lee CW, Noguchi K, et al. FTY720 (fingolimod) efficacy in an animal model of multiple sclerosis requires astrocyte sphingosine 1-phosphate receptor 1 (S1P1) modulation. Proc Natl Acad Sci U S A. 2011;108(2):751–6. doi:10.1073/pnas.1014154108.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Sheth KN, Rosand J. Targeting the immune system in intracerebral hemorrhage. JAMA Neurology. 2014;71(9):1083–4. doi:10.1001/jamaneurol.2014.1653.CrossRefPubMedGoogle Scholar
  64. 64.
    Chu K. Celecoxib induces functional recovery after intracerebral hemorrhage with reduction of brain edema and perihematomal cell death. J Cereb Blood Flow Metab. 2004;24:926–33.CrossRefPubMedGoogle Scholar
  65. 65.
    Park HK, Lee SH, Chu K, Roh JK. Effects of celecoxib on volumes of hematoma and edema in patients with primary intracerebral hemorrhage. J Neurol Sci. 2009;279(1–2):43–6. doi:10.1016/j.jns.2008.12.020.CrossRefPubMedGoogle Scholar
  66. 66.
    Lee S, Brait VH, Arumugam TV, Evans MA, Kim HA, Widdop RE, et al. Neuroprotective effect of an angiotensin receptor type 2 agonist following cerebral ischemia in vitro and in vivo. Exp Translat Stroke Med. 2012;4(1):16. doi:10.1186/2040-7378-4-16.CrossRefGoogle Scholar
  67. 67.
    Zhao X, Sun G, Zhang J, Strong R, Song W, Gonzales N, et al. Hematoma resolution as a target for intracerebral hemorrhage treatment: role for peroxisome proliferator-activated receptor gamma in microglia/macrophages. Ann Neurol. 2007;61(4):352–62. doi:10.1002/ana.21097.CrossRefPubMedGoogle Scholar
  68. 68.
    Gonzales NR. Design of a prospective, dose-escalation study evaluating the Safety of Pioglitazone for Hematoma Resolution in Intracerebral Hemorrhage (SHRINC). Int J Stroke. 2013;8:388–96.CrossRefPubMedGoogle Scholar
  69. 69.
    Naval NS, Abdelhak TA, Urrunaga N, Zeballos P, Mirski MA, Carhuapoma JR. An association of prior statin use with decreased perihematomal edema. Neurocrit Care. 2008;8(1):13–8. doi:10.1007/s12028-007-0081-1.CrossRefPubMedGoogle Scholar
  70. 70.
    Tapia-Perez H, Sanchez-Aguilar M, Torres-Corzo JG, Rodriguez-Leyva I, Gonzalez-Aguirre D, Gordillo-Moscoso A, et al. Use of statins for the treatment of spontaneous intracerebral hemorrhage: results of a pilot study. Cent Eur Neurosurg. 2009;70(1):15–20. doi:10.1055/s-0028-1082064.CrossRefPubMedGoogle Scholar
  71. 71.
    Tapia Perez JH, 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):2521–6. doi:10.1016/j.jstrokecerebrovasdis.2015.06.036.CrossRefPubMedGoogle Scholar
  72. 72.
    Tymianski M. Novel approaches to neuroprotection trials in acute ischemic stroke. Stroke. 2013;44(10):2942–50. doi:10.1161/strokeaha.113.000731.CrossRefPubMedGoogle Scholar
  73. 73.
    Olivot JM, Mlynash M, Kleinman JT, Straka M, Venkatasubramanian C, Bammer R, et al. MRI profile of the perihematomal region in acute intracerebral hemorrhage. Stroke. 2010;41(11):2681–3. doi:10.1161/strokeaha.110.590638.CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Javier J Provencio M. Systemic Normothermia in Intracerebral Hemorrhage (ICH) (SNICH). 2014.
  75. 75.
    Rong Hu MP. Decompressive Craniectomy After Removing Hematoma to Treat Intracerebral Hemorrhage (CARICH). 2014. Scholar
  76. 76.
    Switzer J. A Pilot Study of Minocycline in Intracerebral Hemorrhage Patients (MACH). 2013. Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Audrey Leasure
    • 1
  • W. Taylor Kimberly
    • 2
  • Lauren H. Sansing
    • 1
  • Kristopher T. Kahle
    • 3
  • Golo Kronenberg
    • 4
  • Hagen Kunte
    • 4
  • J. Marc Simard
    • 5
  • Kevin N. Sheth
    • 1
  1. 1.Department of NeurologyYale University School of MedicineNew HavenUSA
  2. 2.Department of NeurologyMassachusetts General HospitalBostonUSA
  3. 3.Yale Program on Neurogenetics, Department of Neurosurgery and PediatricsNew HavenUSA
  4. 4.Department of NeurologyCharité-Universitätsmedizin BerlinBerlinGermany
  5. 5.Department of NeurosurgeryUniversity of Maryland School of MedicineBaltimoreUSA

Personalised recommendations