Intracerebral Hemorrhage

ABSTRACT

Intracerebral hemorrhage (ICH) accounts for 10 to 15% of all strokes, but results in a disproportionately high morbidity and mortality. Although chronic hypertension accounts for the majority of ICH, other common causes include cerebral amyloid angiopathy, sympathomimetic drugs of abuse, and underlying cerebral vascular anomalies. Validated baseline predictors of clinical outcome after ICH include the Glasgow Coma Scale score, hematoma volume, presence and amount of intraventricular hemorrhage, infratentorial ICH location, and advanced age. Although no treatment of proven benefit currently exists for ICH, several recent large clinical trials have demonstrated the feasibility of surgical and medical treatments for ICH. Clinical research into ICH mechanisms of injury has demonstrated that hematoma expansion is common, even in patients without coagulopathy. Basic research has suggested that perihematoma injury is more likely related to toxicity of blood and iron in the brain (“neurohemoinflammation”) rather than primary ischemic injury. Current guidelines for ICH treatment emphasize blood pressure management, urgent and rapid correction of coagulopathy, and surgery for cerebellar ICH. Ongoing clinical trials are investigating surgical evacuation of lobar hemorrhage, minimally invasive surgical hematoma evacuation, and aggressive blood pressure lowering.

Intracerebral hemorrhage - hypertension - hematoma expansion - neurocritical care

REFERENCES

• 1 Qureshi A I, Tuhrim S, Broderick J P, Batjer H H, Hondo H, Hanley D F. Spontaneous intracerebral hemorrhage.  N Engl J Med. 2001;  344 1450-1460
• 2 Gebel J M, Broderick J P. Intracerebral hemorrhage.  Neurol Clin. 2000;  18 419-438
• 3 McCormick W F, Rosenfield D B. Massive brain hemorrhage: a review of 144 cases and an examination of their causes.  Stroke. 1973;  4 946-954
• 4 O'Donnell H C, Rosand J, Knudsen K A et al.. Apolipoprotein E genotype and the risk of recurrent lobar intracerebral hemorrhage.  N Engl J Med. 2000;  342 240-245
• 5 Ariesen M J, Claus S P, Rinkel G J, Algra A. Risk factors for intracerebral hemorrhage in the general population: a systematic review.  Stroke. 2003;  34 2060-2065
• 6 Sturgeon J D, Folsom A R, Longstreth Jr W T, Shahar E, Rosamond W D, Cushman M. Risk factors for intracerebral hemorrhage in a pooled prospective study.  Stroke. 2007;  38 2718-2725
• 7 Suh I, Jee S H, Kim H C, Nam C M, Kim I S, Appel L J. Low serum cholesterol and haemorrhagic stroke in men: Korea Medical Insurance Corporation Study.  Lancet. 2001;  357 922-925
• 8 Juvela S, Hillbom M, Palomaki H. Risk factors for spontaneous intracerebral hemorrhage.  Stroke. 1995;  26 1558-1564
• 9 Thrift A G, Donnan G A, McNeil J J. Heavy drinking, but not moderate or intermediate drinking, increases the risk of intracerebral hemorrhage.  Epidemiology. 1999;  10 307-312
• 10 Iso H, Jacobs Jr D R, Wentworth D, Neaton J D, Cohen J D. Serum cholesterol levels and six-year mortality from stroke in 350,977 men screened for the multiple risk factor intervention trial.  N Engl J Med. 1989;  320 904-910
• 11 Yano K, Reed D M, MacLean C J. Serum cholesterol and hemorrhagic stroke in the Honolulu Heart Program.  Stroke. 1989;  20 1460-1465
• 12 Amarenco P, Bogousslavsky J, Callahan III A et al.. High-dose atorvastatin after stroke or transient ischemic attack.  N Engl J Med. 2006;  355 549-559
• 13 Goldstein L B, Amarenco P, Szarek M et al.. Hemorrhagic stroke in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels study.  Neurology. 2008;  70(24 Pt 2) 2364-2370 , Epub 2007 Dec 12
• 14 Qureshi A I, Suri M A, Safdar K, Ottenlips J R, Janssen R S, Frankel M R. Intracerebral hemorrhage in blacks. Risk factors, subtypes, and outcome.  Stroke. 1997;  28 961-964
• 15 Gunel M, Awad I A, Finberg K et al.. A founder mutation as a cause of cerebral cavernous malformation in Hispanic Americans.  N Engl J Med. 1996;  334 946-951
• 16 Kuriyama S, Kusaka Y, Fujimura M et al.. Prevalence and clinicoepidemiological features of moyamoya disease in Japan: findings from a nationwide epidemiological survey.  Stroke. 2008;  39 42-47
• 17 Labovitz D L, Halim A, Boden-Albala B, Hauser W A, Sacco R L. The incidence of deep and lobar intracerebral hemorrhage in whites, blacks, and Hispanics.  Neurology. 2005;  65 518-522
• 18 Rosand J, Eckman M H, Knudsen K A, Singer D E, Greenberg S M. The effect of warfarin and intensity of anticoagulation on outcome of intracerebral hemorrhage.  Arch Intern Med. 2004;  164 880-884
• 19 Becker K J, Baxter A B, Cohen W A et al.. Withdrawal of support in intracerebral hemorrhage may lead to self-fulfilling prophecies.  Neurology. 2001;  56 766-772
• 20 Flaherty M L, Haverbusch M, Sekar P et al.. Long-term mortality after intracerebral hemorrhage.  Neurology. 2006;  66 1182-1186
• 21 Hemphill III J C, Newman J, Zhao S, Johnston S C. Hospital usage of early do-not-resuscitate orders and outcome after intracerebral hemorrhage.  Stroke. 2004;  35 1130-1134
• 22 Zahuranec D B, Brown D L, Lisabeth L D et al.. Early care limitations independently predict mortality after intracerebral hemorrhage.  Neurology. 2007;  68 1651-1657
• 23 Holloway R G, Witter Jr D M, Lawton K B, Lipscomb J, Samsa G. Inpatient costs of specific cerebrovascular events at five academic medical centers.  Neurology. 1996;  46 854-860
• 24 Reed S D, Blough D K, Meyer K, Jarvik J G. Inpatient costs, length of stay, and mortality for cerebrovascular events in community hospitals.  Neurology. 2001;  57 305-314
• 25 Taylor T N, Davis P H, Torner J C, Holmes J, Meyer J W, Jacobson M F. Lifetime cost of stroke in the United States.  Stroke. 1996;  27 1459-1466
• 26 Fisher C M. Pathological observations in hypertensive cerebral hemorrhage.  J Neuropathol Exp Neurol. 1971;  30 536-550
• 27 Gebel Jr J M, Jauch E C, Brott T G et al.. Relative edema volume is a predictor of outcome in patients with hyperacute spontaneous intracerebral hemorrhage.  Stroke. 2002;  33 2636-2641
• 28 Gingrich M B, Junge C E, Lyuboslavsky P, Traynelis S F. Potentiation of NMDA receptor function by the serine protease thrombin.  J Neurosci. 2000;  20 4582-4595
• 29 Butcher K S, Baird T, MacGregor L, Desmond P, Tress B, Davis S. Perihematomal edema in primary intracerebral hemorrhage is plasma derived.  Stroke. 2004;  35 1879-1885
• 30 Tejima E, Zhao B Q, Tsuji K et al.. Astrocytic induction of matrix metalloproteinase-9 and edema in brain hemorrhage.  J Cereb Blood Flow Metab. 2007;  27 460-468
• 31 Aronowski J, Hall C E. New horizons for primary intracerebral hemorrhage treatment: experience from preclinical studies.  Neurol Res. 2005;  27 268-279
• 32 Wagner K R. Modeling intracerebral hemorrhage: glutamate, nuclear factor-kappa B signaling and cytokines.  Stroke. 2007;  38 753-758
• 33 Xi G, Keep R F, Hoff J T. Mechanisms of brain injury after intracerebral haemorrhage.  Lancet Neurol. 2006;  5 53-63
• 34 Kidwell C S, Saver J L, Mattiello J et al.. Diffusion-perfusion MR evaluation of perihematomal injury in hyperacute intracerebral hemorrhage.  Neurology. 2001;  57 1611-1617
• 35 Mayer S A, Lignelli A, Fink M E et al.. Perilesional blood flow and edema formation in acute intracerebral hemorrhage: a SPECT study.  Stroke. 1998;  29 1791-1798
• 36 Siddique M S, Fernandes H M, Arene N U, Wooldridge T D, Fenwick J D, Mendelow A D. Changes in cerebral blood flow as measured by HMPAO SPECT in patients following spontaneous intracerebral haemorrhage.  Acta Neurochir Suppl. 2000;  76 517-520
• 37 Herweh C, Juttler E, Schellinger P D et al.. Evidence against a perihemorrhagic penumbra provided by perfusion computed tomography.  Stroke. 2007;  38 2941-2947
• 38 Qureshi A I, Wilson D A, Hanley D F, Traystman R J. No evidence for an ischemic penumbra in massive experimental intracerebral hemorrhage.  Neurology. 1999;  52 266-272
• 39 Zazulia A R, Diringer M N, Videen T O et al.. Hypoperfusion without ischemia surrounding acute intracerebral hemorrhage.  J Cereb Blood Flow Metab. 2001;  21 804-810
• 40 Brott T, Broderick J, Kothari R et al.. Early hemorrhage growth in patients with intracerebral hemorrhage.  Stroke. 1997;  28 1-5
• 41 Fujii Y, Takeuchi S, Sasaki O, Minakawa T, Tanaka R. Multivariate analysis of predictors of hematoma enlargement in spontaneous intracerebral hemorrhage.  Stroke. 1998;  29 1160-1166
• 42 Fujitsu K, Muramoto M, Ikeda Y, Inada Y, Kim I, Kuwabara T. Indications for surgical treatment of putaminal hemorrhage. Comparative study based on serial CT and time-course analysis.  J Neurosurg. 1990;  73 518-525
• 43 Kazui S, Naritomi H, Yamamoto H, Sawada T, Yamaguchi T. Enlargement of spontaneous intracerebral hemorrhage. Incidence and time course.  Stroke. 1996;  27 1783-1787
• 44 Davis S M, Broderick J, Hennerici M et al.. Hematoma growth is a determinant of mortality and poor outcome after intracerebral hemorrhage.  Neurology. 2006;  66 1175-1181
• 45 Ezzeddine M A, Suri M F, Hussein H M, Qureshi A I. Blood pressure management in patients with acute stroke: pathophysiology and treatment strategies.  Neurosurg Clin N Am. 2006;  17(Suppl 1) 41-56
• 46 Mayer S A, Brun N C, Begtrup K et al.. Recombinant activated factor VII for acute intracerebral hemorrhage.  N Engl J Med. 2005;  352 777-785
• 47 Tentschert S, Wimmer R, Greisenegger S, Lang W, Lalouschek W. Headache at stroke onset in 2196 patients with ischemic stroke or transient ischemic attack.  Stroke. 2005;  36 e1-e3
• 48 Broderick J P, Brott T G, Duldner J E, Tomsick T, Huster G. Volume of intracerebral hemorrhage. A powerful and easy-to-use predictor of 30-day mortality.  Stroke. 1993;  24 987-993
• 49 Cheung R T, Zou L Y. Use of the original, modified, or new intracerebral hemorrhage score to predict mortality and morbidity after intracerebral hemorrhage.  Stroke. 2003;  34 1717-1722
• 50 Hemphill III J C, Bonovich D C, Besmertis L, Manley G T, Johnston S C. The ICH score: a simple, reliable grading scale for intracerebral hemorrhage.  Stroke. 2001;  32 891-897
• 51 Tuhrim S, Horowitz D R, Sacher M, Godbold J H. Validation and comparison of models predicting survival following intracerebral hemorrhage.  Crit Care Med. 1995;  23 950-954
• 52 Tuhrim S, Horowitz D R, Sacher M, Godbold J H. Volume of ventricular blood is an important determinant of outcome in supratentorial intracerebral hemorrhage.  Crit Care Med. 1999;  27 617-621
• 53 Kidwell C S, Chalela J A, Saver J L et al.. Comparison of MRI and CT for detection of acute intracerebral hemorrhage.  JAMA. 2004;  292 1823-1830
• 54 Zhu X L, Chan M S, Poon W S. Spontaneous intracranial hemorrhage: which patients need diagnostic cerebral angiography? A prospective study of 206 cases and review of the literature.  Stroke. 1997;  28 1406-1409
• 55 Flint A C, Roebken A, Singh V. Primary intraventricular hemorrhage: yield of diagnostic angiography and clinical outcome.  Neurocrit Care. 2008;  8(3) 330-336
• 56 Hoh B L, Cheung A C, Rabinov J D, Pryor J C, Carter B S, Ogilvy C S. Results of a prospective protocol of computed tomographic angiography in place of catheter angiography as the only diagnostic and pretreatment planning study for cerebral aneurysms by a combined neurovascular team.  Neurosurgery. 2004;  54 1329-1340 discussion 1340-1322
• 57 Becker K J, Baxter A B, Bybee H M, Tirschwell D L, Abouelsaad T, Cohen W A. Extravasation of radiographic contrast is an independent predictor of death in primary intracerebral hemorrhage.  Stroke. 1999;  30 2025-2032
• 58 Goldstein J N, Fazen L E, Snider R et al.. Contrast extravasation on CT angiography predicts hematoma expansion in intracerebral hemorrhage.  Neurology. 2007;  68 889-894
• 59 Kim J, Smith A, Hemphill III J C et al.. Contrast extravasation on CT predicts mortality in primary intracerebral hemorrhage.  AJNR Am J Neuroradiol. 2008;  29 520-525
• 60 Wada R, Aviv R I, Fox A J et al.. CT angiography “spot sign” predicts hematoma expansion in acute intracerebral hemorrhage.  Stroke. 2007;  38 1257-1262
• 61 Jauch E C, Lindsell C J, Adeoye O et al.. Lack of evidence for an association between hemodynamic variables and hematoma growth in spontaneous intracerebral hemorrhage.  Stroke. 2006;  37 2061-2065
• 62 Kazui S, Minematsu K, Yamamoto H, Sawada T, Yamaguchi T. Predisposing factors to enlargement of spontaneous intracerebral hematoma.  Stroke. 1997;  28 2370-2375
• 63 Ohwaki K, Yano E, Nagashima H, Hirata M, Nakagomi T, Tamura A. Blood pressure management in acute intracerebral hemorrhage: relationship between elevated blood pressure and hematoma enlargement.  Stroke. 2004;  35 1364-1367
• 64 Powers W J, Zazulia A R, Videen T O et al.. Autoregulation of cerebral blood flow surrounding acute (6 to 22 hours) intracerebral hemorrhage.  Neurology. 2001;  57 18-24
• 65 Broderick J, Connolly S, Feldmann E et al.. Guidelines for the management of spontaneous intracerebral hemorrhage in adults: 2007 update: a guideline from the American Heart Association/American Stroke Association Stroke Council, High Blood Pressure Research Council, and the Quality of Care and Outcomes in Research Interdisciplinary Working Group.  Stroke. 2007;  38 2001-2023
• 66 Koch S, Romano J G, Forteza A M, Otero C M, Rabinstein A A. Rapid blood pressure reduction in acute intracerebral hemorrhage: feasibility and safety.  Neurocrit Care. 2008;  8 316-321
• 67 Qureshi A I. Antihypertensive treatment of acute cerebral hemorrhage (ATACH): rationale and design.  Neurocrit Care. 2007;  6 56-66
• 68 Fang M C, Chang Y, Hylek E M et al.. Advanced age, anticoagulation intensity, and risk for intracranial hemorrhage among patients taking warfarin for atrial fibrillation.  Ann Intern Med. 2004;  141 745-752
• 69 The Stroke Prevention in Reversible Ischemia Trial (SPIRIT) Study Group . A randomized trial of anticoagulants versus aspirin after cerebral ischemia of presumed arterial origin.  Ann Neurol. 1997;  42 857-865
• 70 Flibotte J J, Hagan N, O'Donnell J, Greenberg S M, Rosand J. Warfarin, hematoma expansion, and outcome of intracerebral hemorrhage.  Neurology. 2004;  63 1059-1064
• 71 Goldstein J N, Thomas S H, Frontiero V et al.. Timing of fresh frozen plasma administration and rapid correction of coagulopathy in warfarin-related intracerebral hemorrhage.  Stroke. 2006;  37 151-155
• 72 Ansell J, Hirsh J, Poller L, Bussey H, Jacobson A, Hylek E. The pharmacology and management of the vitamin K antagonists: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.  Chest. 2004;  126 204S-233S
• 73 British Committee for Standards in Haematology . Guidelines on oral anticoagulation: third edition.  Br J Haematol. 1998;  101 374-387
• 74 Lankiewicz M W, Hays J, Friedman K D, Tinkoff G, Blatt P M. Urgent reversal of warfarin with prothrombin complex concentrate.  J Thromb Haemost. 2006;  4 967-970
• 75 Makris M, Greaves M, Phillips W S, Kitchen S, Rosendaal F R, Preston E F. Emergency oral anticoagulant reversal: the relative efficacy of infusions of fresh frozen plasma and clotting factor concentrate on correction of the coagulopathy.  Thromb Haemost. 1997;  77 477-480
• 76 Yasaka M, Sakata T, Minematsu K, Naritomi H. Correction of INR by prothrombin complex concentrate and vitamin K in patients with warfarin related hemorrhagic complication.  Thromb Res. 2002;  108 25-30
• 77 Huttner H B, Schellinger P D, Hartmann M et al.. Hematoma growth and outcome in treated neurocritical care patients with intracerebral hemorrhage related to oral anticoagulant therapy: comparison of acute treatment strategies using vitamin K, fresh frozen plasma, and prothrombin complex concentrates.  Stroke. 2006;  37 1465-1470
• 78 Baker R I, Coughlin P B, Gallus A S, Harper P L, Salem H H, Wood E M. Warfarin reversal: consensus guidelines, on behalf of the Australasian Society of Thrombosis and Haemostasis.  Med J Aust. 2004;  181 492-497
• 79 Hanley J P. Warfarin reversal.  J Clin Pathol. 2004;  57 1132-1139
• 80 Mayer S A, Brun N C, Broderick J et al.. Safety and feasibility of recombinant factor VIIa for acute intracerebral hemorrhage.  Stroke. 2005;  36 74-79
• 81 Mayer S A, Brun N C, Begtrup K et al.. Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage.  N Engl J Med. 2008;  358 2127-2137
• 82 Foerch C, Sitzer M, Steinmetz H, Neumann-Haefelin T. Pretreatment with antiplatelet agents is not independently associated with unfavorable outcome in intracerebral hemorrhage.  Stroke. 2006;  37 2165-2167
• 83 Toyoda K, Okada Y, Minematsu K et al.. Antiplatelet therapy contributes to acute deterioration of intracerebral hemorrhage.  Neurology. 2005;  65 1000-1004
• 84 Broderick J P, Diringer M N, Hill M D et al.. Determinants of intracerebral hemorrhage growth: an exploratory analysis.  Stroke. 2007;  38 1072-1075
• 85 Schwarz S, Hafner K, Aschoff A, Schwab S. Incidence and prognostic significance of fever following intracerebral hemorrhage.  Neurology. 2000;  54 354-361
• 86 Fogelholm R, Murros K, Rissanen A, Avikainen S. Admission blood glucose and short term survival in primary intracerebral haemorrhage: a population based study.  J Neurol Neurosurg Psychiatry. 2005;  76 349-353
• 87 Kimura K, Iguchi Y, Inoue T et al.. Hyperglycemia independently increases the risk of early death in acute spontaneous intracerebral hemorrhage.  J Neurol Sci. 2007;  255 90-94
• 88 Van den Berghe G, Schoonheydt K, Becx P, Bruyninckx F, Wouters P J. Insulin therapy protects the central and peripheral nervous system of intensive care patients.  Neurology. 2005;  64 1348-1353
• 89 Van den Berghe G, Wouters P, Weekers F et al.. Intensive insulin therapy in the critically ill patients.  N Engl J Med. 2001;  345 1359-1367
• 90 Vespa P, Boonyaputthikul R, McArthur D L et al.. Intensive insulin therapy reduces microdialysis glucose values without altering glucose utilization or improving the lactate/pyruvate ratio after traumatic brain injury.  Crit Care Med. 2006;  34 850-856
• 91 Gregory P C, Kuhlemeier K V. Prevalence of venous thromboembolism in acute hemorrhagic and thromboembolic stroke.  Am J Phys Med Rehabil. 2003;  82 364-369
• 92 Lacut K, Bressollette L, Le Gal G et al.. Prevention of venous thrombosis in patients with acute intracerebral hemorrhage.  Neurology. 2005;  65 865-869
• 93 Boeer A, Voth E, Henze T, Prange H W. Early heparin therapy in patients with spontaneous intracerebral haemorrhage.  J Neurol Neurosurg Psychiatry. 1991;  54 466-467
• 94 Gregson B A, Mendelow A D. International variations in surgical practice for spontaneous intracerebral hemorrhage.  Stroke. 2003;  34 2593-2597
• 95 Mendelow A D, Gregson B A, Fernandes H M 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;  365 387-397
• 96 Mendelow A D, Teasdale G M, Barer D, Fernandes H M, Murray G D, Gregson B A. Outcome assignment in the International Surgical Trial of Intracerebral Haemorrhage.  Acta Neurochir (Wien). 2003;  145 679-681 discussion 681
• 97 Prasad K S, Gregson B A, Bhattathiri P S, Mitchell P, Mendelow A D. The significance of crossovers after randomization in the STICH trial.  Acta Neurochir Suppl. 2006;  96 61-64
• 98 Firsching R, Huber M, Frowein R A. Cerebellar haemorrhage: management and prognosis.  Neurosurg Rev. 1991;  14 191-194
• 99 Kirollos R W, Tyagi A K, Ross S A, van Hille P T, Marks P V. Management of spontaneous cerebellar hematomas: a prospective treatment protocol.  Neurosurgery. 2001;  49 1378-1386 discussion 1386-1377
• 100 Tanikawa T, Amano K, Kawamura H et al.. CT-guided stereotactic surgery for evacuation of hypertensive intracerebral hematoma.  Appl Neurophysiol. 1985;  48 431-439
• 101 Backlund E O, von Holst H. Controlled subtotal evacuation of intracerebral haematomas by stereotactic technique.  Surg Neurol. 1978;  9 99-101
• 102 Niizuma H, Shimizu Y, Yonemitsu T, Nakasato N, Suzuki J. Results of stereotactic aspiration in 175 cases of putaminal hemorrhage.  Neurosurgery. 1989;  24 814-819
• 103 Vespa P, McArthur D, Miller C et al.. Frameless stereotactic aspiration and thrombolysis of deep intracerebral hemorrhage is associated with reduction of hemorrhage volume and neurological improvement.  Neurocrit Care. 2005;  2 274-281
• 104 Auer L M, Deinsberger W, Niederkorn K et al.. Endoscopic surgery versus medical treatment for spontaneous intracerebral hematoma: a randomized study.  J Neurosurg. 1989;  70 530-535