Distinct Behavior of Traumatic versus Nontraumatic Intracerebral Hematomas: Different Biology or Impact of Age?

Abstract

Background and Study Aims Patients with large intracerebral hematomas (ICH) may demonstrate different demographics and underlying brain and systemic diseases, as well as different radiologic courses and distinct outcomes. It remains unclear whether their different behavior attributes to a different biology of the ICH or to the asymmetric characteristics of the two populations. To analyze and adjust for potential sources of selection and treatment bias, our study compared age-matched patients with traumatic and nontraumatic ICH in a single cohort diagnosed and treated in the same surgical department.

Material and Methods We analyzed 135 consecutive patients with traumatic (n = 90) or spontaneous ICH (n = 45) undergoing treatment at a surgical intensive care unit of an urban university hospital. We documented their differences before and after adjustment for age in terms of demographics, the therapies applied, their radiologic (i.e., volume and rate of ICH expansion [HE]) and clinical (patients' outcome at 30 days) course, the length of hospital and ICU stay, as well as the hospital costs.

Results Patients with traumatic ICH demonstrated more favorable clinical and radiologic characteristics at admission, that is, higher Glasgow Coma Scale score (p < 0.001), less frequently dilated pupil (p = 0.028), lower Charlson Comorbidity Index (p < 0.001), smaller ICH volume (p < 0.001), noneloquent (p < 0.001) or nonintraventricular (p = 0.003) ICH locations, as well as underwent fewer neurosurgical interventions (p < 0.001) and showed a better outcome (p = 0.041), defined as Glasgow Outcome Scale 4 and 5. After adjustment for age, no different outcomes were observed. Of note, elderly patients on novel oral anticoagulants (NOACs) were more likely to develop an HE compared with those on vitamin K antagonists (VKAs, p = 0.05) after traumatic brain injury (TBI) but not after spontaneous ICH.

Conclusion Our data reveal a significant heterogeneity within the traumatic series. Whereas younger patients show an excellent outcome, the elderly population of the traumatic cases demonstrates a poor outcome similar to that of the nontraumatic cohort. HE under NOACs rather than under VKAs is more likely in the elderly after TBI. Larger prospective trials are warranted to elucidate the potential individual underlying molecular mechanisms for the development of an ICH and HE in these diseases.

Keywords

intracerebral hematoma - elderly - novel oral anticoagulants - hematoma expansion - traumatic brain injury

Author Contribution

K.G., U.H., and M.M. were responsible for the conception and design of the paper. Acquisition of data was done by M.M., B.P., M.G., S.S., U.H., and K.G.. M.M. and K.G. took care of the analysis and interpretation of data. Treatment of patients was done by B.P., U.H., T.A.S., R.M., and K.G. All the authors participated in drafting and critically revising the article. K.G. approved the final version of the manuscript on behalf of all authors. Statistical analysis was done by U.H., M.M., and K.G. K.G. supervised the study.

Publikationsverlauf

Eingereicht: 12. April 2020

Angenommen: 26. November 2020

Artikel online veröffentlicht:
14. Juni 2021

• References

• 1 Taylor CA, Bell JM, Breiding MJ, Xu L. Traumatic brain injury-related emergency department visits, hospitalizations, and deaths: United States, 2007 and 2013. MMWR Surveill Summ 2017; 66 (09) 1-16
• 2 Dewan MC, Rattani A, Gupta S. et al. Estimating the global incidence of traumatic brain injury. J Neurosurg 2018; 1-18
• 3 Gardner AJ, Zafonte R. Neuroepidemiology of traumatic brain injury. Handb Clin Neurol 2016; 138: 207-223
• 4 Fu TS, Jing R, McFaull SR, Cusimano MD. Recent trends in hospitalization and in-hospital mortality associated with traumatic brain injury in Canada: a nationwide, population-based study. J Trauma Acute Care Surg 2015; 79 (03) 449-454
• 5 Maegele M, Lefering R, Sakowitz O. et al. The incidence and management of moderate to severe head injury. Dtsch Arztebl Int 2019; 116 (10) 167-173
• 6 Qureshi AI, Mendelow AD, Hanley DF. Intracerebral haemorrhage. Lancet 2009; 373 (9675): 1632-1644
• 7 Feigin VL, Lawes CM, Bennett DA, Barker-Collo SL, Parag V. Worldwide stroke incidence and early case fatality reported in 56 population-based studies: a systematic review. Lancet Neurol 2009; 8 (04) 355-369
• 8 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 (02) 167-176
• 9 Krishnamurthi RV, Feigin VL, Forouzanfar MH. et al; Global Burden of Diseases, Injuries, Risk Factors Study 2010 (GBD 2010), GBD Stroke Experts Group. Global and regional burden of first-ever ischaemic and haemorrhagic stroke during 1990-2010: findings from the Global Burden of Disease Study 2010. Lancet Glob Health 2013; 1 (05) e259-e281
• 10 Krishnamurthi RV, Moran AE, Forouzanfar MH. et al; Global Burden of Diseases, Injuries, and Risk Factors 2010 Study Stroke Expert Group. The global burden of hemorrhagic stroke: a summary of findings from the GBD 2010 study. Glob Heart 2014; 9 (01) 101-106
• 11 Kim JY, Bae HJ. Spontaneous intracerebral hemorrhage: management. J Stroke 2017; 19 (01) 28-39
• 12 Steiner T, Al-Shahi Salman R, Beer R. et al; European Stroke Organisation. European Stroke Organisation (ESO) guidelines for the management of spontaneous intracerebral hemorrhage. Int J Stroke 2014; 9 (07) 840-855
• 13 Hemphill III JC, Greenberg SM, Anderson CS. et al; American Heart Association Stroke Council, Council on Cardiovascular and Stroke Nursing, Council on Clinical Cardiology. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2015; 46 (07) 2032-2060
• 14 Carney N, Totten AM, O'Reilly C. et al. Guidelines for the management of severe traumatic brain injury, fourth edition. Neurosurgery 2017; 80 (01) 6-15
• 15 Fu C, Wang N, Chen B. et al. Surgical management of moderate basal ganglia intracerebral hemorrhage: comparison of safety and efficacy of endoscopic surgery, minimally invasive puncture and drainage, and craniotomy. World Neurosurg 2019; 122: e995-e1001
• 16 Bhatia K, Hepburn M, Ziu E, Siddiq F, Qureshi AI. Modern approaches to evacuating intracerebral hemorrhage. Curr Cardiol Rep 2018; 20 (12) 132
• 17 Choo YS, Chung J, Joo JY, Kim YB, Hong CK. Borderline basal ganglia hemorrhage volume: patient selection for good clinical outcome after stereotactic catheter drainage. J Neurosurg 2016; 125 (05) 1242-1248
• 18 Hanley DF, Thompson RE, Muschelli J. et al; MISTIE Investigators. 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) 1228-1237
• 19 Kolias AG, Guilfoyle MR, Helmy A, Allanson J, Hutchinson PJ. Traumatic brain injury in adults. Pract Neurol 2013; 13 (04) 228-235
• 20 Hill MD, Muir KW. INTERACT-2: should blood pressure be aggressively lowered acutely after intracerebral hemorrhage?. Stroke 2013; 44 (10) 2951-2952
• 21 Qureshi AI, Palesch YY, Barsan WG. et al; ATACH-2 Trial Investigators and the Neurological Emergency Treatment Trials Network. Intensive blood-pressure lowering in patients with acute cerebral hemorrhage. N Engl J Med 2016; 375 (11) 1033-1043
• 22 Mendelow AD, Gregson BA, Rowan EN. et al; STITCH(Trauma) Investigators. Early Surgery versus Initial Conservative Treatment in Patients with Traumatic Intracerebral Hemorrhage (STITCH[Trauma]): The First Randomized Trial. J Neurotrauma 2015; 32 (17) 1312-1323
• 23 Mendelow AD, Gregson BA, Rowan EN, Murray GD, Gholkar A, Mitchell PM. STICH II Investigators. 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
• 24 Francis R, Gregson BA, Mendelow AD, Rowan E. STITCH(Trauma) investigators (Appendix). Characteristics of traumatic intracerebral haemorrhage: an assessment of screening logs from the STITCH(Trauma) Trial. Br J Neurosurg 2015; 29 (05) 655-660
• 25 Ting HW, Chien TY, Lai KR. et al. Differences in spontaneous intracerebral hemorrhage cases between urban and rural regions of Taiwan: big data analytics of government open data. Int J Environ Res Public Health 2017; 14 (12) E1548
• 26 Krishnan K, Beishon L, Berge E. et al; VISTA-ICH collaboration and ENOS Investigators. Relationship between race and outcome in Asian, Black, and Caucasian patients with spontaneous intracerebral hemorrhage: Data from the Virtual International Stroke Trials Archive and Efficacy of Nitric Oxide in Stroke trial. Int J Stroke 2018; 13 (04) 362-373
• 27 Markou M, Pleger B, Grözinger M. et al. Intake of NOAC is associated with hematoma expansion of intracerebral hematomas after traumatic brain injury. Eur J Trauma Emerg Surg 2021; 47 (02) 565-571
• 28 Hanley DF, Thompson RE, Rosenblum M. et al; MISTIE III Investigators. Efficacy and safety of minimally invasive surgery with thrombolysis in intracerebral haemorrhage evacuation (MISTIE III): a randomised, controlled, open-label, blinded endpoint phase 3 trial. Lancet 2019; 393 (10175): 1021-1032
• 29 Morgan TC, Dawson J, Spengler D. et al; CLEAR and VISTA Investigators. The Modified Graeb Score: an enhanced tool for intraventricular hemorrhage measurement and prediction of functional outcome. Stroke 2013; 44 (03) 635-641
• 30 Purrucker JC, Haas K, Rizos T. et al. Early clinical and radiological course, management, and outcome of intracerebral hemorrhage related to new oral anticoagulants. JAMA Neurol 2016; 73 (02) 169-177
• 31 Fiebach JB, Steiner T, Neumann-Haefelin T. Neuroimaging evaluation of intracerebral hemorrhage. Nervenarzt 2009; 80 (02) 205-213 , quiz 214
• 32 Mendelow AD, Gregson BA, Fernandes HM. et al; STICH investigators. 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): 387-397
• 33 Ruff CT, Giugliano RP, Braunwald E. et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet 2014; 383 (9921): 955-962
• 34 Coleman CI, Peacock WF, Bunz TJ, Alberts MJ. Effectiveness and safety of apixaban, dabigatran, and rivaroxaban versus warfarin in patients with nonvalvular atrial fibrillation and previous stroke or transient ischemic attack. Stroke 2017; 48 (08) 2142-2149
• 35 Zeeshan M, Jehan F, O'Keeffe T. et al. The novel oral anticoagulants (NOACs) have worse outcomes compared with warfarin in patients with intracranial hemorrhage after TBI. J Trauma Acute Care Surg 2018; 85 (05) 915-920
• 36 Marshall LF, Marshall SB, Klauber MR. et al. The diagnosis of head injury requires a classification based on computed axial tomography. J Neurotrauma 1992; 9 (Suppl. 01) S287-S292
• 37 Tsivgoulis G, Lioutas VA, Varelas P. et al. Direct oral anticoagulant- vs vitamin K antagonist-related nontraumatic intracerebral hemorrhage. Neurology 2017; 89 (11) 1142-1151
• 38 Wilson D, Seiffge DJ, Traenka C. et al; And the CROMIS-2 collaborators. Outcome of intracerebral hemorrhage associated with different oral anticoagulants. Neurology 2017; 88 (18) 1693-1700
• 39 Adachi T, Hoshino H, Takagi M, Fujioka S. Saiseikai Stroke Research Group. Volume and characteristics of intracerebral hemorrhage with direct oral anticoagulants in comparison with warfarin. Cerebrovasc Dis Extra 2017; 7 (01) 62-71
• 40 Maegele M, Schöchl H, Cohen MJ. An update on the coagulopathy of trauma. Shock 2014; 41 (Suppl. 01) 21-25
• 41 Frith D, Goslings JC, Gaarder C. et al. Definition and drivers of acute traumatic coagulopathy: clinical and experimental investigations. J Thromb Haemost 2010; 8 (09) 1919-1925
• 42 Maegele M, Lefering R, Yucel N. et al; AG Polytrauma of the German Trauma Society (DGU). Early coagulopathy in multiple injury: an analysis from the German Trauma Registry on 8724 patients. Injury 2007; 38 (03) 298-304
• 43 Rossaint R, Bouillon B, Cerny V. et al. The European guideline on management of major bleeding and coagulopathy following trauma: fourth edition. Crit Care 2016; 20: 100
• 44 Kobayashi L, Barmparas G, Bosarge P. et al; AAST Multicenter Prospective Observational Study of Trauma Patients on Novel Oral Anticoagulants Study Group. Novel oral anticoagulants and trauma: The results of a prospective American Association for the Surgery of Trauma Multi-Institutional Trial. J Trauma Acute Care Surg 2017; 82 (05) 827-835
• 45 von der Brelie C, Doukas A, Naumann R. et al. Clinical and radiological course of intracerebral haemorrhage associated with the new non-vitamin K anticoagulants. Acta Neurochir (Wien) 2017; 159 (01) 101-109
• 46 Raj R, Bendel S, Reinikainen M. et al. Costs, outcome and cost-effectiveness of neurocritical care: a multi-center observational study. Crit Care 2018; 22 (01) 225