Hemorrhage Expansion Rates Before and After Minimally Invasive Surgery for Intracerebral Hemorrhage: Post Hoc Analysis of MISTIE II/III

Background: Stereotactic thrombolysis for evacuation of large spontaneous intracerebral (ICH) and intraventricular hemorrhage (IVH) typically requires stabilizing the hemorrhage preoperatively. We investigated intracranial hemorrhage expansion (HE) in the pre- and postrandomization phase of 2 clinical trials of surgical candidates with protocolized computed tomography (CT) imaging up to 10 days after presentation. Methods: Prospective assessment of sequential pre- and post-randomization CT scans of 141 patients enrolled in MISTIE (Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation) II/ICES (Intraoperative CT-guided Endoscopic Surgery for ICH) and 499 patients enrolled in MISTIE III. Primary outcomes were prerandomization HE of ICH >6 mL and IVH >5 mL. Secondary outcome was postrandomization HE. Stability was defined as CT time after which no further HE was observed. We evaluated risk factors for ICH/IVH expansion using multivariable logistic regression analyses after adjustment for demographics, ICH characteristics and treatment. Results: Median (interquartile range) diagnostic ICH volume was 40.4 (29.5-54.1) mL. Prerandomization HE >6 mL was detected in 216 (33.8%) subjects. Median time to hematoma stability from diagnostic CT was 7 (4.7-13.6) hours. Median diagnostic IVH volume was 0 (0-1.9) mL. IVH expansion >5 mL occurred in 40 (6.3%) with stability at 6.9 (4.7-11.2) hours. Of subjects with HE, final expansion events were not yet detected at 12 hours from diagnostic CT in 36% (ICH expansion) and 33% (IVH expansion), respectively, with 91% detected by 24 hours. Independent associations with ICH expansion included age, male sex, White race, anticoagulation, ICH volume, deep ICH location, IVH, and time from symptom onset to diagnostic CT. Postsurgical ICH expansion occurred in 24 patients (6.9%) and was associated with delay in achieving stability, number of alteplase doses, and fewer CT hypodensities on diagnostic CT but not with functional outcome. Conclusion: In patients with a large ICH eligible for surgical evacuation, about two thirds of HE events stabilize within 12 hours and most within 24 hours. An earlier time window for stereotactic thrombolysis may be feasible.