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Impact of Recent Studies for the Treatment of Intracerebral Hemorrhage

  • Stroke (H Diener, Section Editor)
  • Published:
Current Neurology and Neuroscience Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

The present review will cover most recent and important studies on acute treatment of intracerebral hemorrhage (ICH).

Recent Findings

Overly pessimistic prognostication in ICH may deny meaningful recovery achieved by specialized neurocritical care. Hematoma enlargement represents the most important target of acute ICH care, which is reduced by aggressive blood pressure management (targeting a systolic blood pressure of 140 mmHg) and appropriate hemostatic treatment especially in anticoagulation-associated ICH (INR reversal using prothrombin complex concentrates, eventually idarucizumab, andexanet, or tranexamic acid). Surgical treatment strategies involving fibrinolytics either used for direct hematoma lysis or used for intraventricular clot removal with/without additional lumbar drainage show great promise. Further novel treatment strategies are underway and need validation or evaluation strongly warranting well-designed future ICH research.

Summary

Several randomized and large-sized observational studies have considerably expanded the field and the evidence on how to treat acute ICH patients. Yet, the one breakthrough intervention to improve functional outcome is still missing, though various treatment concepts possibly interacting with one another have been evaluated and such treatment bundle may improve patients’ outcome.

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Abbreviations

BP:

Blood pressure

CI:

Confidence interval

DNR:

Do not resuscitate

EVD:

External ventricular drain

FFP:

Fresh frozen plasma

HE:

Hematoma enlargement

ICH:

Intracerebral hemorrhage

ICP:

Intracranial pressure

INR:

International normalized ratio

IQR:

Interquartile range

IVH:

Intraventricular hemorrhage

mRS:

Modified Rankin Scale

NOAC:

Non-vitamin k antagonist oral anticoagulant

OR:

Odds ratio

PCC:

Prothrombin complex concentrate

RR:

Risk ratio

rtPA:

Recombinant tissue-type plasminogen activator

TXA:

Tranexamic acid

VKA:

Vitamin K antagonist

References

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

  1. Qureshi AI, Mendelow AD, Hanley DF. Intracerebral haemorrhage. Lancet. 2009;373(9675):1632–44. https://doi.org/10.1016/s0140-6736(09)60371-8.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Qureshi AI, Tuhrim S, Broderick JP, Batjer HH, Hondo H, Hanley DF. Spontaneous intracerebral hemorrhage. N Engl J Med. 2001;344(19):1450–60. https://doi.org/10.1056/nejm200105103441907.

    Article  CAS  PubMed  Google Scholar 

  3. Feigin VL, Roth GA, Naghavi M, Parmar P, Krishnamurthi R, Chugh S, et al. Global burden of stroke and risk factors in 188 countries, during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet Neurol. 2016;15(9):913–24. https://doi.org/10.1016/S1474-4422(16)30073-4.

    Article  PubMed  Google Scholar 

  4. Sacco S, Marini C, Toni D, Olivieri L, Carolei A. Incidence and 10-year survival of intracerebral hemorrhage in a population-based registry. Stroke. 2009;40(2):394–9. https://doi.org/10.1161/STROKEAHA.108.523209.

    Article  PubMed  Google Scholar 

  5. van Asch CJ, Luitse MJ, Rinkel GJ, van der Tweel I, Algra A, Klijn 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(2):167–76. https://doi.org/10.1016/s1474-4422(09)70340-0.

    Article  PubMed  Google Scholar 

  6. Hemphill JC 3rd, Greenberg SM, Anderson CS, Becker K, Bendok BR, Cushman M, 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):2032–60. https://doi.org/10.1161/str.0000000000000069.

    Article  PubMed  Google Scholar 

  7. • Sembill JA, Gerner ST, Volbers B, Bobinger T, Lucking H, Kloska SP, et al. Severity assessment in maximally treated ICH patients: the max-ICH score. Neurology. 2017;89(5):423–31. https://doi.org/10.1212/WNL.0000000000004174. Authors report that overly pessimisitc prognostication may deny a meanignfull recovery and provide a novel prognostic tool.

    Article  PubMed  Google Scholar 

  8. Zahuranec DB, Brown DL, Lisabeth LD, Gonzales NR, Longwell PJ, Smith MA, et al. Early care limitations independently predict mortality after intracerebral hemorrhage. Neurology. 2007;68(20):1651–7. https://doi.org/10.1212/01.wnl.0000261906.93238.72.

    Article  CAS  PubMed  Google Scholar 

  9. Morgenstern LB, Zahuranec DB, Sanchez BN, Becker KJ, Geraghty M, Hughes R, et al. Full medical support for intracerebral hemorrhage. Neurology. 2015;84(17):1739–44. https://doi.org/10.1212/WNL.0000000000001525.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Becker KJ, Baxter AB, Cohen WA, Bybee HM, Tirschwell DL, Newell DW, et al. Withdrawal of support in intracerebral hemorrhage may lead to self-fulfilling prophecies. Neurology. 2001;56(6):766–72.

    Article  CAS  PubMed  Google Scholar 

  11. Yogendrakumar V, Smith EE, Demchuk AM, Aviv RI, Rodriguez-Luna D, Molina CA, et al. Lack of early improvement predicts poor outcome following acute intracerebral hemorrhage. Crit Care Med. 2018;46(4):e310–e7. https://doi.org/10.1097/CCM.0000000000002962.

    Article  PubMed  Google Scholar 

  12. Maas MB, Francis BA, Sangha RS, Lizza BD, Liotta EM, Naidech AM. Refining prognosis for intracerebral hemorrhage by early reassessment. Cerebrovasc Dis. 2017;43(3–4):110–6. https://doi.org/10.1159/000452679000452679.

    Article  PubMed  Google Scholar 

  13. Suo Y, Chen WQ, Pan YS, Peng YJ, Yan HY, Zhao XQ, Liu LP, Wang YL, Liu GF, Wang YJ The max-intracerebral hemorrhage score predicts long-term outcome of intracerebral hemorrhage. CNS Neurosci Ther. 2018. https://doi.org/10.1111/cns.12846.

  14. Jacobs BS, Poggesi A, Terry JB. Max-ICH score: can it prevent self-fulfilling prophecy in ICH? Neurology. 2017;89(5):417–8. https://doi.org/10.1212/WNL.0000000000004195.

    Article  PubMed  Google Scholar 

  15. Langhorne P, Fearon P, Ronning OM, Kaste M, Palomaki H, Vemmos K, Kalra L, Indredavik B, Blomstrand C, Rodgers H, Dennis MS, Salman RAS, on behalf of the Stroke Unit Trialists’ Collaboration, The following collaborators provided new data, advice and comment, and assisted with the redrafting of the report:, Blomstrand C, Indredavik B, Kalra L, Kaste M, Palomaki H, Rodgers H, Ronning MO, Vemmos K, The Stroke Unit Trialists’ Collaboration supported and provided for the main stroke unit review:, Asplund K, Berman P, Blomstrand C, Britton M, Cabral NL, Cavallini A, Dey P, Hamrin E, Hankey G, Indredavik B, Kalra L, Kaste M, Laursen SO, Ma RH, Patel N, Rodgers H, Ronning MO, Sivenius J, Stevens R, Sulter G, Svensson A, Vemmos K, Wood-Dauphinee S, Yagura H Stroke unit care benefits patients with intracerebral hemorrhage: systematic review and meta-analysis. Stroke 2013;44(11):3044–3049. https://doi.org/10.1161/STROKEAHA.113.001564

    Article  PubMed  Google Scholar 

  16. Damian MS, Ben-Shlomo Y, Howard R, Bellotti T, Harrison D, Griggs K, et al. The effect of secular trends and specialist neurocritical care on mortality for patients with intracerebral haemorrhage, myasthenia gravis and Guillain-Barre syndrome admitted to critical care : an analysis of the Intensive Care National Audit & Research Centre (ICNARC) national United Kingdom database. Intensive Care Med. 2013;39(8):1405–12. https://doi.org/10.1007/s00134-013-2960-6.

    Article  PubMed  Google Scholar 

  17. Middleton S, McElduff P, Ward J, Grimshaw JM, Dale S, D’Este C, et al. Implementation of evidence-based treatment protocols to manage fever, hyperglycaemia, and swallowing dysfunction in acute stroke (QASC): a cluster randomised controlled trial. Lancet. 2011;378(9804):1699–706. https://doi.org/10.1016/S0140-6736(11)61485-2.

    Article  PubMed  Google Scholar 

  18. Sreekrishnan A, Leasure AC, Shi FD, Hwang DY, Schindler JL, Petersen NH, et al. Functional improvement among intracerebral hemorrhage (ICH) survivors up to 12 months post-injury. Neurocrit Care. 2017;27(3):326–33. https://doi.org/10.1007/s12028-017-0425-4.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Delcourt C, Huang Y, Arima H, Chalmers J, Davis SM, Heeley EL, et al. Hematoma growth and outcomes in intracerebral hemorrhage: the INTERACT1 study. Neurology. 2012;79(4):314–9. https://doi.org/10.1212/WNL.0b013e318260cbba.

    Article  PubMed  Google Scholar 

  20. •• Kuramatsu JB, Gerner ST, Schellinger PD, Glahn J, Endres M, Sobesky J, et al. Anticoagulant reversal, blood pressure levels, and anticoagulant resumption in patients with anticoagulation-related intracerebral hemorrhage. JAMA. 2015;313(8):824–36. https://doi.org/10.1001/jama.2015.0846. Large cohort study reporting on both acute and long-term management in anticoaugulation-associated ICH. For the first time provides INR targets to minimize hematoma expansion.

    Article  CAS  PubMed  Google Scholar 

  21. Demchuk AM, Dowlatshahi D, Rodriguez-Luna D, Molina CA, Blas YS, Dzialowski I, et al. Prediction of haematoma growth and outcome in patients with intracerebral haemorrhage using the CT-angiography spot sign (PREDICT): a prospective observational study. Lancet Neurol. 2012;11(4):307–14. https://doi.org/10.1016/S1474-4422(12)70038-8.

    Article  PubMed  Google Scholar 

  22. Morotti A, Boulouis G, Romero JM, Brouwers HB, Jessel MJ, Vashkevich A, et al. Blood pressure reduction and noncontrast CT markers of intracerebral hemorrhage expansion. Neurology. 2017;89(6):548–54. https://doi.org/10.1212/WNL.0000000000004210.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Morotti A, Dowlatshahi D, Boulouis G, Al-Ajlan F, Demchuk AM, Aviv RI, et al. Predicting intracerebral hemorrhage expansion with noncontrast computed tomography: the BAT score. Stroke. 2018;49(5):1163–9. https://doi.org/10.1161/STROKEAHA.117.020138.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Wang X, Arima H, Al-Shahi Salman R, Woodward M, Heeley E, Stapf C, et al. Clinical prediction algorithm (BRAIN) to determine risk of hematoma growth in acute intracerebral hemorrhage. Stroke. 2015;46(2):376–81. https://doi.org/10.1161/STROKEAHA.114.006910.

    Article  CAS  PubMed  Google Scholar 

  25. Flibotte JJ, Hagan N, O’Donnell J, Greenberg SM, Rosand J. Warfarin, hematoma expansion, and outcome of intracerebral hemorrhage. Neurology. 2004;63(6):1059–64.

    Article  CAS  PubMed  Google Scholar 

  26. Biffi A, Battey TW, Ayres AM, Cortellini L, Schwab K, Gilson AJ, et al. Warfarin-related intraventricular hemorrhage: imaging and outcome. Neurology. 2011;77(20):1840–6. https://doi.org/10.1212/WNL.0b013e3182377e12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Kobayashi J, Koga M, Tanaka E, Okada Y, Kimura K, Yamagami H, et al. Continuous antihypertensive therapy throughout the initial 24 hours of intracerebral hemorrhage: the stroke acute management with urgent risk-factor assessment and improvement-intracerebral hemorrhage study. Stroke. 2014;45(3):868–70. https://doi.org/10.1161/STROKEAHA.113.004319.

    Article  CAS  PubMed  Google Scholar 

  28. Tsivgoulis G, Katsanos AH, Butcher KS, Boviatsis E, Triantafyllou N, Rizos I, et al. Intensive blood pressure reduction in acute intracerebral hemorrhage: a meta-analysis. Neurology. 2014;83(17):1523–9. https://doi.org/10.1212/WNL.0000000000000917.

    Article  PubMed  Google Scholar 

  29. Butcher KS, Jeerakathil T, Hill M, Demchuk AM, Dowlatshahi D, Coutts SB, et al. The Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial. Stroke. 2013;44(3):620–6. https://doi.org/10.1161/strokeaha.111.000188.

    Article  PubMed  Google Scholar 

  30. Anderson CS, Huang Y, Wang JG, Arima H, Neal B, Peng B, et al. Intensive blood pressure reduction in acute cerebral haemorrhage trial (INTERACT): a randomised pilot trial. Lancet Neurol. 2008;7(5):391–9. https://doi.org/10.1016/S1474-4422(08)70069-3.

    Article  PubMed  Google Scholar 

  31. Qureshi AI, Palesch YY, Martin R, Novitzke J, Cruz-Flores S, Ehtisham A, et al. Effect of systolic blood pressure reduction on hematoma expansion, perihematomal edema, and 3-month outcome among patients with intracerebral hemorrhage: results from the antihypertensive treatment of acute cerebral hemorrhage study. Arch Neurol. 2010;67(5):570–6. https://doi.org/10.1001/archneurol.2010.61.

    Article  PubMed  PubMed Central  Google Scholar 

  32. 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. https://doi.org/10.1161/strokeaha.109.561795.

    Article  PubMed  Google Scholar 

  33. •• 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. https://doi.org/10.1056/NEJMoa1214609. Randomized controlled trial showing improved functional outcomes with intensive lowering of blood pressure among ordinal analysis of the modified Rankin scale.

    Article  CAS  PubMed  Google Scholar 

  34. •• Qureshi AI, Palesch YY, Barsan WG, Hanley DF, Hsu CY, Martin RL, et al. Intensive blood-pressure lowering in patients with acute cerebral hemorrhage. N Engl J Med. 2016;375(11):1033–43. https://doi.org/10.1056/NEJMoa1603460. Most recent randomized controlled trial documenting no significant benefit of intensive blood pressure lowering.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Burgess LG, Goyal N, Jones GM, Khorchid Y, Kerro A, Chapple K et al. Evaluation of acute kidney injury and mortality after intensive blood pressure control in patients with intracerebral hemorrhage. J Am Heart Assoc. 2018;7(8). https://doi.org/10.1161/JAHA.117.008439.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Morotti A, Brouwers HB, Romero JM, Jessel MJ, Vashkevich A, Schwab K, et al. Intensive blood pressure reduction and spot sign in intracerebral hemorrhage: a secondary analysis of a randomized clinical trial. JAMA Neurol. 2017;74(8):950–60. https://doi.org/10.1001/jamaneurol.2017.1014.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Shoamanesh A, Morotti A, Romero JM, Oliveira-Filho J, Schlunk F, Jessel MJ, et al. Cerebral microbleeds and the effect of intensive blood pressure reduction on hematoma expansion and functional outcomes: a secondary analysis of the ATACH-2 randomized clinical trial. JAMA Neurol. 2018;75:850–9. https://doi.org/10.1001/jamaneurol.2018.0454.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Qureshi AI, Palesch YY, Foster LD, Barsan WG, Goldstein JN, Hanley DF, et al. Blood pressure-attained analysis of ATACH 2 trial. Stroke. 2018;49(6):1412–8. https://doi.org/10.1161/STROKEAHA.117.019845.

    Article  PubMed  PubMed Central  Google Scholar 

  39. •• Boulouis G, Morotti A, Goldstein JN, Charidimou A. Intensive blood pressure lowering in patients with acute intracerebral haemorrhage: clinical outcomes and haemorrhage expansion. Systematic review and meta-analysis of randomised trials. J Neurol Neurosurg Psychiatry. 2017;88(4):339–45. https://doi.org/10.1136/jnnp-2016-315346. Meta-analysis of randomized data ( n = 4360) investigating the effect of intensive blood pressure reductions on outcomes.

    Article  PubMed  Google Scholar 

  40. • Morotti A, Charidimou A, Phuah CL, Jessel MJ, Schwab K, Ayres AM, et al. Association between serum calcium level and extent of bleeding in patients with intracerebral hemorrhage. JAMA Neurol. 2016;73(11):1285–90. https://doi.org/10.1001/jamaneurol.2016.22522546924. Authors report on a novel parameter associated with ICH volumes.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Liotta EM, Prabhakaran S, Sangha RS, Bush RA, Long AE, Trevick SA, et al. Magnesium, hemostasis, and outcomes in patients with intracerebral hemorrhage. Neurology. 2017;89(8):813–9. https://doi.org/10.1212/WNL.0000000000004249.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Goyal N, Tsivgoulis G, Malhotra K, Houck AL, Khorchid YM, Pandhi A et al. Serum magnesium levels and outcomes in patients with acute spontaneous intracerebral hemorrhage. J Am Heart Assoc. 2018;7(8). https://doi.org/10.1161/JAHA.118.008698

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Hoffman M, Monroe DM 3rd, Roberts HR. Activated factor VII activates factors IX and X on the surface of activated platelets: thoughts on the mechanism of action of high-dose activated factor VII. Blood Coagul Fibrinolysis. 1998;9(Suppl 1):S61–5.

    CAS  PubMed  Google Scholar 

  44. Mayer SA, Brun NC, Begtrup K, Broderick J, Davis S, Diringer MN, et al. Recombinant activated factor VII for acute intracerebral hemorrhage. N Engl J Med. 2005;352(8):777–85. https://doi.org/10.1056/NEJMoa042991.

    Article  CAS  PubMed  Google Scholar 

  45. Mayer SA, Brun NC, Begtrup K, Broderick J, Davis S, Diringer MN, et al. Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage. N Engl J Med. 2008;358(20):2127–37. https://doi.org/10.1056/NEJMoa0707534.

    Article  CAS  PubMed  Google Scholar 

  46. Roberts I, Shakur H, Coats T, Hunt B, Balogun E, Barnetson L, et al. The CRASH-2 trial: a randomised controlled trial and economic evaluation of the effects of tranexamic acid on death, vascular occlusive events and transfusion requirement in bleeding trauma patients. Health Technol Assess. 2013;17(10):1–79. https://doi.org/10.3310/hta17100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. •• Sprigg N, Flaherty K, Appleton JP, Salman RA, Bereczki D, Beridze M, et al. Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage (TICH-2): an international randomised, placebo-controlled, phase 3 superiority trial. Lancet. 2018;391:2107–15. https://doi.org/10.1016/S0140-6736(18)31033-X. Randomized controlled trial on effects of tranexamic acid in ICH patients showing a decreased early (7 days) mortality, reduced hematoma enlargement, and a favorable safety profile for tranexamic acid. Sub-group analyses favored treatment in patients with systolic blood pressures below 170 mmHg, lobar ICH location, and ICH volumes between 30 and 60 mL.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Meretoja A, Churilov L, Campbell BC, Aviv RI, Yassi N, Barras C, et al. The spot sign and tranexamic acid on preventing ICH growth--AUStralasia Trial (STOP-AUST): protocol of a phase II randomized, placebo-controlled, double-blind, multicenter trial. Int J Stroke. 2014;9(4):519–24. https://doi.org/10.1111/ijs.12132.

    Article  PubMed  Google Scholar 

  49. Liu L, Wang Y, Meng X, Li N, Tan Y, Nie X, et al. Tranexamic acid for acute intracerebral hemorrhage growth predicted by spot sign trial: rationale and design. Int J Stroke. 2017;12(3):326–31. https://doi.org/10.1177/1747493017694394.

    Article  PubMed  Google Scholar 

  50. Brouwers HB, Chang Y, Falcone GJ, Cai X, Ayres AM, Battey TW, et al. Predicting hematoma expansion after primary intracerebral hemorrhage. JAMA Neurol. 2014;71(2):158–64. https://doi.org/10.1001/jamaneurol.2013.5433.

    Article  PubMed  PubMed Central  Google Scholar 

  51. • Steiner T, Poli S, Griebe M, Husing J, Hajda J, Freiberger A, et al. Fresh frozen plasma versus prothrombin complex concentrate in patients with intracranial haemorrhage related to vitamin K antagonists (INCH): a randomised trial. Lancet Neurol. 2016;15(6):566–73. https://doi.org/10.1016/S1474-4422(16)00110-1. Randomized controlled trial comparing PCC versus FFP in VKA ICH patients providing evidence in favor of PCC for reversal of anticoagulation.

    Article  CAS  PubMed  Google Scholar 

  52. Kuramatsu JB, Sembill JA, Gerner ST, Sprugel MI, Hagen M, Roeder SS, et al. Management of therapeutic anticoagulation in patients with intracerebral haemorrhage and mechanical heart valves. Eur Heart J. 2018;39:1709–23. https://doi.org/10.1093/eurheartj/ehy056.

    Article  PubMed  PubMed Central  Google Scholar 

  53. • Gerner ST, Kuramatsu JB, Sembill JA, Sprugel MI, Endres M, Haeusler KG, et al. Association of prothrombin complex concentrate administration and hematoma enlargement in non-vitamin K antagonist oral anticoagulant-related intracerebral hemorrhage. Ann Neurol. 2018;83(1):186–96. https://doi.org/10.1002/ana.25134. Large cohort study reporting on reversal strategies in non-vitamin K anticoaugulation-associated ICH.

    Article  CAS  PubMed  Google Scholar 

  54. Purrucker JC, Haas K, Rizos T, Khan S, Wolf M, Hennerici MG, et al. Early clinical and radiological course, management, and outcome of intracerebral hemorrhage related to new oral anticoagulants. JAMA Neurol. 2016;73(2):169–77. https://doi.org/10.1001/jamaneurol.2015.3682.

    Article  PubMed  Google Scholar 

  55. Boulouis G, Morotti A, Pasi M, Goldstein JN, Gurol ME, Charidimou A. Outcome of intracerebral haemorrhage related to non-vitamin K antagonists oral anticoagulants versus vitamin K antagonists: a comprehensive systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2018;89(3):263–70. https://doi.org/10.1136/jnnp-2017-316631.

    Article  PubMed  Google Scholar 

  56. Wilson D, Seiffge DJ, Traenka C, Basir G, Purrucker JC, Rizos T, et al. Outcome of intracerebral hemorrhage associated with different oral anticoagulants. Neurology. 2017;88(18):1693–700. https://doi.org/10.1212/WNL.0000000000003886.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Kurogi R, Nishimura K, Nakai M, Kada A, Kamitani S, Nakagawara J, et al. Comparing intracerebral hemorrhages associated with direct oral anticoagulants or warfarin. Neurology. 2018;90(13):e1143–e9. https://doi.org/10.1212/WNL.0000000000005207.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Tsivgoulis G, Lioutas VA, Varelas P, Katsanos AH, Goyal N, Mikulik R, et al. Direct oral anticoagulant- vs vitamin K antagonist-related nontraumatic intracerebral hemorrhage. Neurology. 2017;89(11):1142–51. https://doi.org/10.1212/WNL.0000000000004362.

    Article  CAS  PubMed  Google Scholar 

  59. Inohara T, Xian Y, Liang L, Matsouaka RA, Saver JL, Smith EE, et al. Association of intracerebral hemorrhage among patients taking non-vitamin K antagonist vs vitamin K antagonist oral anticoagulants with in-hospital mortality. JAMA. 2018;319(5):463–73. https://doi.org/10.1001/jama.2017.21917.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Ebner M, Birschmann I, Peter A, Spencer C, Hartig F, Kuhn J, et al. Point-of-care testing for emergency assessment of coagulation in patients treated with direct oral anticoagulants. Crit Care. 2017;21(1):32. https://doi.org/10.1186/s13054-017-1619-z.

    Article  PubMed  PubMed Central  Google Scholar 

  61. •• Pollack CV Jr, Reilly PA, van Ryn J, Eikelboom JW, Glund S, Bernstein RA, et al. Idarucizumab for dabigatran reversal - full cohort analysis. N Engl J Med. 2017;377(5):431–41. https://doi.org/10.1056/NEJMoa1707278. Full cohort analysis of idarucizumab for dabigatran reversal.

    Article  CAS  PubMed  Google Scholar 

  62. Connolly SJ, Milling TJ Jr, Eikelboom JW, Gibson CM, Curnutte JT, Gold A, et al. Andexanet alfa for acute major bleeding associated with factor Xa inhibitors. N Engl J Med. 2016;375:1131–41. https://doi.org/10.1056/NEJMoa1607887.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Siegal DM, Curnutte JT, Connolly SJ, Lu G, Conley PB, Wiens BL, et al. Andexanet alfa for the reversal of factor Xa inhibitor activity. N Engl J Med. 2015;373(25):2413–24. https://doi.org/10.1056/NEJMoa1510991.

    Article  CAS  PubMed  Google Scholar 

  64. • Baharoglu MI, Cordonnier C, Salman RA, de Gans K, Koopman MM, Brand A, et al. Platelet transfusion versus standard care after acute stroke due to spontaneous cerebral haemorrhage associated with antiplatelet therapy (PATCH): a randomised, open-label, phase 3 trial. Lancet. 2016;387(10038):2605–13. https://doi.org/10.1016/S0140-6736(16)30392-0. Randomized controlled trial investigating platelet transfusions in ICH patients using platelet inhibitors, showing evidence in disfavor of platelet transfusions.

    Article  PubMed  Google Scholar 

  65. 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. https://doi.org/10.1016/s0140-6736(05)17826-x.

    Article  PubMed  Google Scholar 

  66. 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. https://doi.org/10.1016/s0140-6736(13)60986-1.

    Article  PubMed  PubMed Central  Google Scholar 

  67. •• Hanley DF, Thompson RE, Muschelli J, Rosenblum M, McBee N, Lane K, et al. Safety and efficacy of minimally invasive surgery plus alteplase in intracerebral haemorrhage evacuation (MISTIE): a randomised, controlled, open-label, phase 2 trial. Lancet Neurol. 2016;15(12):1228–37. https://doi.org/10.1016/s1474-4422(16)30234-4. Randomized controlled trial investigating intraventricular thrombolysis, showing a reduced mortality at 180 days, a safe profile, and faster clot removal which was associated with favorable functional outcome.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. van Loon J, Van Calenbergh F, Goffin J, Plets C. Controversies in the management of spontaneous cerebellar haemorrhage. A consecutive series of 49 cases and review of the literature. Acta Neurochir. 1993;122(3–4):187–93.

    Article  PubMed  Google Scholar 

  69. Firsching R, Huber M, Frowein RA. Cerebellar haemorrhage: management and prognosis. Neurosurg Rev. 1991;14(3):191–4.

    Article  CAS  PubMed  Google Scholar 

  70. Tamaki T, Kitamura T, Node Y, Teramoto A. Paramedian suboccipital mini-craniectomy for evacuation of spontaneous cerebellar hemorrhage. Neurol Med Chir (Tokyo). 2004;44(11):578–82. discussion 83

    Article  Google Scholar 

  71. Hackenberg KA, Unterberg AW, Jung CS, Bosel J, Schonenberger S, Zweckberger K. Does suboccipital decompression and evacuation of intraparenchymal hematoma improve neurological outcome in patients with spontaneous cerebellar hemorrhage? Clin Neurol Neurosurg. 2017;155:22–9. https://doi.org/10.1016/j.clineuro.2017.01.019.

    Article  PubMed  Google Scholar 

  72. Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, et al. 2018 guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2018;49(3):e46–e110. https://doi.org/10.1161/STR.0000000000000158.

    Article  PubMed  Google Scholar 

  73. Volbers B, Giede-Jeppe A, Gerner ST, Sembill JA, Kuramatsu JB, Lang S, et al. Peak perihemorrhagic edema correlates with functional outcome in intracerebral hemorrhage. Neurology. 2018;90(12):e1005–e12. https://doi.org/10.1212/WNL.0000000000005167.

    Article  PubMed  Google Scholar 

  74. Xi G, Keep RF, Hoff JT. Mechanisms of brain injury after intracerebral haemorrhage. Lancet Neurol. 2006;5(1):53–63. https://doi.org/10.1016/s1474-4422(05)70283-0.

    Article  PubMed  Google Scholar 

  75. 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;46(10):2762–7. https://doi.org/10.1161/STROKEAHA.115.009357.

    Article  CAS  PubMed  Google Scholar 

  76. Shah M, Birnbaum L, Rasmussen J, Sekar P, Moomaw CJ, Osborne J, et al. Effect of hyperosmolar therapy on outcome following spontaneous intracerebral hemorrhage: Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study. J Stroke Cerebrovasc Dis. 2018;27(4):1061–7. https://doi.org/10.1016/j.jstrokecerebrovasdis.2017.11.013.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Volbers B, Herrmann S, Willfarth W, Lucking H, Kloska SP, Doerfler A, et al. Impact of hypothermia initiation and duration on perihemorrhagic edema evolution after intracerebral hemorrhage. Stroke. 2016;47(9):2249–55. https://doi.org/10.1161/STROKEAHA.116.013486.

    Article  PubMed  Google Scholar 

  78. Staykov D, Wagner I, Volbers B, Doerfler A, Schwab S, Kollmar R. Mild prolonged hypothermia for large intracerebral hemorrhage. Neurocrit Care. 2013;18(2):178–83. https://doi.org/10.1007/s12028-012-9762-5.

    Article  PubMed  Google Scholar 

  79. 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. https://doi.org/10.1111/ijs.12220.

    Article  PubMed  Google Scholar 

  80. Fischer M, Schiefecker A, Lackner P, Frank F, Helbok R, Beer R, et al. Targeted temperature management in spontaneous intracerebral hemorrhage: a systematic review. Curr Drug Targets. 2017;18(12):1430–40. https://doi.org/10.2174/1389450117666160703161511.

    Article  CAS  PubMed  Google Scholar 

  81. Zeng L, Tan L, Li H, Zhang Q, Li Y, Guo J. Deferoxamine therapy for intracerebral hemorrhage: a systematic review. PLoS One. 2018;13(3):e0193615. https://doi.org/10.1371/journal.pone.0193615.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  82. 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. https://doi.org/10.1001/jamaneurol.2014.1065.

    Article  PubMed  Google Scholar 

  83. Morgan T, Awad I, Keyl P, Lane K, Hanley D. Preliminary report of the clot lysis evaluating accelerated resolution of intraventricular hemorrhage (CLEAR-IVH) clinical trial. Acta Neurochir Suppl. 2008;105:217–20.

    Article  CAS  PubMed  Google Scholar 

  84. Hanley DF, Lane K, McBee N, Ziai W, Tuhrim S, Lees KR, et al. Thrombolytic removal of intraventricular haemorrhage in treatment of severe stroke: results of the randomised, multicentre, multiregion, placebo-controlled CLEAR III trial. Lancet. 2017;389(10069):603–11. https://doi.org/10.1016/S0140-6736(16)32410-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Staykov D, Huttner HB, Struffert T, Ganslandt O, Doerfler A, Schwab S, et al. Intraventricular fibrinolysis and lumbar drainage for ventricular hemorrhage. Stroke. 2009;40(10):3275–80. https://doi.org/10.1161/strokeaha.109.551945.

    Article  PubMed  Google Scholar 

  86. Huttner HB, Nagel S, Tognoni E, Kohrmann M, Juttler E, Orakcioglu B, et al. Intracerebral hemorrhage with severe ventricular involvement: lumbar drainage for communicating hydrocephalus. Stroke. 2007;38(1):183–7. https://doi.org/10.1161/01.str.0000251795.02560.62.

    Article  PubMed  Google Scholar 

  87. • Staykov D, Kuramatsu JB, Bardutzky J, Volbers B, Gerner ST, Kloska SP, et al. Efficacy and safety of combined intraventricular fibrinolysis with lumbar drainage for prevention of permanent shunt dependency after intracerebral hemorrhage with severe ventricular involvement: a randomized trial and individual patient data meta-analysis. Ann Neurol. 2017;81(1):93–103. https://doi.org/10.1002/ana.24834. Small randomized controlled trial and meta-analyses investigating the influence of lumbar drains on permanent shunt dependency.

    Article  CAS  PubMed  Google Scholar 

  88. Murthy SB, Awad I, Harnof S, Aldrich F, Harrigan M, Jallo J, et al. Permanent CSF shunting after intraventricular hemorrhage in the CLEAR III trial. Neurology. 2017;89(4):355–62. https://doi.org/10.1212/WNL.0000000000004155.

    Article  PubMed  PubMed Central  Google Scholar 

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  1. Department of Neurology, University Hospital Erlangen-Nürnberg, Schwabachanlage 6, 91054, Erlangen, Germany

    Jochen A. Sembill, Hagen B. Huttner & Joji B. Kuramatsu

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  1. Jochen A. Sembill
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Sembill, J.A., Huttner, H.B. & Kuramatsu, J.B. Impact of Recent Studies for the Treatment of Intracerebral Hemorrhage. Curr Neurol Neurosci Rep 18, 71 (2018). https://doi.org/10.1007/s11910-018-0872-0

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