Minimally Invasive Surgery for Patients with Spontaneous Intracerebral Hemorrhage: a Book Reopened

SN Comprehensive Clinical Medicine (2020) 2:640–643 https://doi.org/10.1007/s42399-020-00287-z SURGERY Minimally Invasive Surgery for Patients with Spontaneous Intracerebral Hemorrhage: a Book Reopened Sunit Das 1 & Gustavo Pradilla 2 & Alexander Khalessi 3 Accepted: 16 April 2020 / Published online: 6 May 2020 # Springer Nature Switzerland AG 2020 Abstract In contrast to remarkable recent gains made in the outcomes of patients with ischemic stroke, outcomes for patients with hemorrhagic stroke (spontaneous intracerebral hemorrhage [ICH]) remain poor. The results of past surgical trials for ICH— motivated by the hypothesis that patients would benefit from interventions to reduce intracranial hypertension associated with clot burden and prevent secondary injury induced by blood in the brain parenchyma—have to date been disappointing. Here, we review the results of the recently completed Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation III trial, which suggest that minimally invasive ICH evacuation may be clinically beneficial, but only when significant hematoma evacuation is achieved, and discuss ongoing minimally invasive surgical evacuation trials for ICH. Keywords Stroke . Hemorrhagic stroke . Intracerebral hemorrhage . Minimally invasive surgery In contrast to remarkable recent gains made in the outcomes of patients with ischemic stroke, outcomes for patients with hemorrhagic stroke remain poor [1]. Hemorrhagic stroke makes up about 13% of all stroke cases, accounting for two million strokes worldwide [2], but accounts for a much greater burden of disability: among the 50% who will survive this initial insult, nearly three-quarters will remain dependent on others to meet their activities of daily living [3]. Measures aimed at reducing hematoma expansion have led at best to limited benefit on functional outcomes in this disease [4]. As echoed in guidelines from the American Heart Association and American Stroke Association, class I evidence support the utility of urgent surgical clot evacuation in patients with cerebellar hemorrhage who are deteriorating neurologically or who have brainstem compression or hydrocephalus from ventricular obstruction [4]. The role of surgery in the management of patients with supratentorial This article is part of the Topical Collection on Surgery * Sunit Das 1 Division of Neurosurgery, St. Michael’s Hospital, University of Toronto, Toronto, Canada 2 Department of Neurosurgery, Emory University, Atlanta, USA 3 Department of Neurosurgery, University of California, San Diego, USA hemorrhagic stroke (spontaneous intracerebral hemorrhage [ICH]) is less clear. Surgical trials for supratentorial ICH have been motivated by the hypothesis that patients would benefit from interventions to reduce intracranial hypertension associated with clot burden and prevent secondary injury induced by blood in the brain parenchyma [5]. Toward that end, the STICH (Surgical Trial in Lobar Intracerebral Haemorrhage) I and II trials randomized patients with spontaneous intracerebral hemorrhage (ICH) to early surgery or initial conservative treatment. Both were negative trials: in line with previous trials [6], outcomes for patients randomized to surgical intervention were statistically indistinguishable from outcomes for patients who received best medical care [7, 8]. The null results of the STITCH trials led to the conclusion that the benefits of surgery, if any, are too meager to detect. As noted by Gregson and colleagues, however, analysis and meta-analyses of the STITCH data were innately limited by the assumption that response to a treatment for the population under study is uniform. This assumption is particularly problematic when considering surgical treatments: in addition to the patient-specific variables that affect medical treatments, there are also variations between surgeons. Mechanistic lines of argument also suggest that response to surgery is not uniform from one case of ICH to another but varies with clot volume, hematoma location, and clinical condition. In fact, a recent meta-analysis of the data from 1541 randomized and monitored spontaneous ICH patients accrued from STITCH I, STITCH II, and STITCH (Trauma) found that patients with an SN Compr. Clin. Med. (2020) 2:640–643 intermediate presenting Glascow Coma Scale (GCS) score in the range of 9 to 12 may benefit from surgery whereas those with higher or lower GCS may not [9]. These findings would suggest that the nonsignificant results observed in the STICH trials are attributable mixing patients who benefit from surgery with those who are harmed. Another intuitive hypothesis to explain lack of efficacy of surgical intervention for spontaneous ICH is that the benefits of clot evacuation are negated by delay and by iatrogenic injury associated with surgical clot access. This hypothesis accounted for changes in trial design from STITCH I to STICH II, the latter which imposed a time limit to intervention of 12 h from the time of intervention and was limited to patients with lobar hemorrhage. This hypothesis also served as the foundation for The Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation (MISTIE) trials. MISTIE incorporated an approach to reduce hematoma burden that utilized stereotactic, minimal access surgery (MIS) to initiate hematoma aspiration, followed by thrombolysis of the remaining clot by direct administration of alteplase (rt-PA) every 8 h. MISTIE II included two stages: a dose finding and a safety phase [10]. Patients aged 18– 80 years with nontraumatic (spontaneous) ICH greater than 20 mL in volume were randomized to medical care or imageguided MIS plus rt-PA (0.3 mg or 1.0 mg every 8 h for up to 9 doses) to remove clot using surgical aspiration followed with rt-PA clot irrigation. The aim of the MIS + rt-PA treatment was to achieve near total clot dissolution without procedure-related safety events that would endanger the lives of the patients beyond the risks associated with intensive medical treatment. Primary safety outcomes of mortality, symptomatic bleeding, brain infection, and withdrawal of care did not differ between groups. Overall, event rates were below pre-specified safety thresholds and the primary safety profile of symptomatic events was similar for both groups. Asymptomatic hemorrhages were more common in the surgical group. Those randomized to the treatment arm achieved more rapid ICH volume reduction when compared with the standard medical care group. The authors concluded that MIS and rt-PA appeared safe, with a possible advantage of better functional outcome at 180 days, but noted increased asymptomatic bleeding as a major cautionary finding. The authors also hypothesized that the beneficial effect of the MISTIE treatment on outcome was mediated through clot volume reduction. MISTIE III was designed to test this hypothesis. Once again, the trial randomized patients with spontaneou (...truncated)