Profile and Prognosis of Spontaneous Lobar Intracerebral Hemorrhage: Comparison of 6-month Survival with STICH II and the MISTIE III Lobar Hemorrhage Subset

Abstract

Background Randomized trials on spontaneous lobar intracerebral hemorrhage (ICH) provided no convincing evidence of the superiority of surgical treatment. Since recruitment in the trials was under the premise of equipoise, a selection bias toward patients who did not need surgery or were in hopeless condition must be suspected. The aim of the actual analysis was to compare outcome and patient profile of an unselected hospital series with recent randomized trials and to develop a prognostic model.

Methods Of 821 patients with spontaneous ICH managed at the neurosurgical department of the University Hospital Düsseldorf between 2013 and 2018, 159 had lobar bleedings. Patient characteristics, hematoma volume, treatment modality, and 6-month survival were compared with STICH II and the subset of lobar hemorrhage in the MISTIE III trial. In addition, a prognostic model for 6-month survival in our patients was developed using a random forest classifier.

Results One hundred and seven patients were managed by surgical evacuation of the hematoma and 52 without surgical evacuation. Median hemorrhage volume in our surgical cohort was 66 and 42 mL in the conservative cohort, compared with 38 and 36 mL in the STICH II trial, and 46 and 47 mL in the surgical and conservative MISTIE III lobar hemorrhage subset. Median initial Glasgow Coma Scale (GCS) score was 12 in our surgical group and 11 in the conservative group, compared with 13 in the STICH II cohorts and 12 in the MISTIE III lobar hemorrhage subset. Median age in our surgical and conservative cohorts was 73 and 74 years, respectively, compared with 65 years in both STICH II cohorts and 68 years in the MISTIE II subsets. Twenty-nine percent of our surgical cohort and 55% of our conservatively managed patients deceased within the first 6 months, compared with 18 and 24%, respectively, in STICH II and 17 and 24% in the MISTIE III subset. Our prognostic model identified large hemorrhage volumes and low admission GCS score as main unfavorable prognostic factors for 6-month survival. The random forest classifier achieved a predictive accuracy of 78% and an area under curve (AUC)- value of 88% regarding survival at 6 months, on a test set independent of the training set.

Conclusions In comparison with our surgical group, the STICH II and MISTIE III cohorts, recruited under the premise of physician equipoise, underrepresented patients with large ICHs. The cohorts in the randomized trials were therefore biased toward patients with a favorable perspective under conservative management. Initial hematoma volume and admission GCS were the main prognostic factors in our patients.

Keywords

lobar brain hemorrhage - intracerebral hemorrhage - STICH II trial - surgery - craniotomy - outcome

• References

• 1 Mayer SA, Rincon F. Treatment of intracerebral haemorrhage. Lancet Neurol 2005; 4 (10) 662-672
• 2 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
• 3 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
• 4 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
• 5 Vespa P, Hanley D, Betz J. et al; ICES Investigators. ICES (intraoperative stereotactic computed tomography-guided endoscopic surgery) for brain hemorrhage: a multicenter randomized controlled trial. Stroke 2016; 47 (11) 2749-2755
• 6 Ziai WC, McBee N, Lane K. et al; MISTIE III Investigators. A randomized 500-subject open-label phase 3 clinical trial of minimally invasive surgery plus alteplase in intracerebral hemorrhage evacuation (MISTIE III). Int J Stroke 2019; 14 (05) 548-554
• 7 Fahlström A, Nittby Redebrandt H, Zeberg H. et al. A grading scale for surgically treated patients with spontaneous supratentorial intracerebral hemorrhage: the Surgical Swedish ICH Score. J Neurosurg 2020; 133 (03) 800-807
• 8 Mattishent K, Kwok CS, Ashkir L, Pelpola K, Myint PK, Loke YK. Prognostic tools for early mortality in hemorrhagic stroke: systematic review and meta-analysis. J Clin Neurol 2015; 11 (04) 339-348
• 9 Kirkman MA, Greenwood N, Singh N, Tyrrell PJ, King AT, Patel HC. Difficulties with recruiting into neurosurgical clinical trials: the Surgical Trial in IntraCerebral Haemorrhage II as an example. Br J Neurosurg 2011; 25 (02) 231-234
• 10 Prasad KS, Gregson BA, Bhattathiri PS, Mitchell P, Mendelow AD. STICH Investigators. The significance of crossovers after randomization in the STICH trial. Acta Neurochir Suppl (Wien) 2006; 96: 61-64
• 11 Kirkman MA, Mahattanakul W, Gregson BA, Mendelow AD. The effect of the results of the STICH trial on the management of spontaneous supratentorial intracerebral haemorrhage in Newcastle. Br J Neurosurg 2008; 22 (06) 739-746 , discussion 747
• 12 Adeoye O, Woo D, Haverbusch M. et al. Surgical management and case-fatality rates of intracerebral hemorrhage in 1988 and 2005. Neurosurgery 2008; 63 (06) 1113-1117 , discussion 1117–1118
• 13 Adeoye O, Woo D, Haverbusch M. et al. Eligibility for the surgical trial in intracerebral hemorrhage II study in a population-based cohort. Neurocrit Care 2008; 9 (02) 237-241
• 14 Morgenstern LB, Hemphill III JC, Anderson C. et al; American Heart Association Stroke Council and Council on Cardiovascular Nursing. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2010; 41 (09) 2108-2129
• 15 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
• 16 Broderick JP, Brott TG, Duldner JE, Tomsick T, Huster G. Volume of intracerebral hemorrhage. A powerful and easy-to-use predictor of 30-day mortality. Stroke 1993; 24 (07) 987-993
• 17 Webb AJ, Ullman NL, Morgan TC. et al; MISTIE and CLEAR Investigators. Accuracy of the ABC/2 score for intracerebral hemorrhage: systematic review and analysis of MISTIE, CLEAR-IVH, and CLEAR III. Stroke 2015; 46 (09) 2470-2476
• 18 Roberts SJ. Parametric and non-parametric unsupervised cluster analysis. Pattern Recognit 1997; 30 (02) 261-272
• 19 Chawla NV, Bowyer KW, Hall LO, Kegelmeyer WP. SMOTE: synthetic minority over-sampling technique. J Artif Intell Res 2002; 16: 321-357
• 20 Lovelock CE, Rinkel GJ, Rothwell PM. Time trends in outcome of subarachnoid hemorrhage: population-based study and systematic review. Neurology 2010; 74 (19) 1494-1501
• 21 La Pira B, Singh TD, Rabinstein AA, Lanzino G. Time trends in outcomes after aneurysmal subarachnoid hemorrhage over the past 30 years. Mayo Clin Proc 2018; 93 (12) 1786-1793
• 22 Kadar R, Rochford D, Omi E, Thomas Y, Patel K, Kulstad E. Trends in demographics and outcome of patients presenting with traumatic brain injury. Clin Exp Emerg Med 2019; 6 (02) 113-118
• 23 Maslehaty H, Petridis AK, Barth H, Doukas A, Mehdorn HM. Treatment of 817 patients with spontaneous supratentorial intracerebral hemorrhage: characteristics, predictive factors and outcome. Clin Pract 2012; 2 (03) e56
• 24 Hessington A, Tsitsopoulos PP, Fahlström A, Marklund N. Favorable clinical outcome following surgical evacuation of deep-seated and lobar supratentorial intracerebral hemorrhage: a retrospective single-center analysis of 123 cases. Acta Neurochir (Wien) 2018; 160 (09) 1737-1747
• 25 Fahlström A, Tobieson L, Redebrandt HN. et al. Differences in neurosurgical treatment of intracerebral haemorrhage: a nation-wide observational study of 578 consecutive patients. Acta Neurochir (Wien) 2019; 161 (05) 955-965