Efficacy and safety of selective brain cooling in the treatment of acute cerebrovascular accidents: A systematic review and meta-analysis

Background: Despite advances in treatment, stroke remains a major public health burden and a leading cause of death. While therapeutic hypothermia (TH) has demonstrated neuroprotective potential, whole-body cooling is not without risk. Selective brain cooling (SBC) offers a targeted alternative by lowering brain temperature while maintaining core normothermia. This approach could preserve the benefits of TH while simultaneously reducing systemic complications, rendering SBC a promising strategy for neuroprotection in stroke management. The objective of this systematic review (SR) was to identify, critically assess and synthesize all available evidence regarding the efficacy and safety of SBC in humans, and its potential role in the treatment of acute stroke in particular. Methods: We searched Medline/PubMed, Cochrane and Scopus for published research without applying a date restriction. The last search was conducted on March 20th for PubMed and October 10th for the other databases. We also searched grey literature, conference proceedings and registries for ongoing trials. Inclusion criteria were adult patients with acute ischemic stroke (AIS) or intracerebral hemorrhage (ICH) who received any form of SBC. Exclusion criteria were non-English language records, studies on animals, editorials, case reports, case series and studies involving whole body hypothermia. We evaluated the risk of bias of the included studies using the RoB2 tool for RCTs and the ROBINS-I tool for non-randomized studies. We employed a random effects model to pool effect sizes with 95% Confidence Intervals (CIs). We calculated pooled Odds ratios (ORs) for dichotomous outcomes. Results: We identified 23 relevant studies, ten of which were still ongoing at the time the study selection process was carried, while another five were preliminary safety and feasibility studies. We identified two RCTs on ICH, and another six studies on AIS, including three RCTs. Four AIS studies were included in the meta-analysis, involving 459 patients (52.7% male), 202 of which received SBC in addition to intravenous thrombolysis (IVT) or endovascular thrombectomy (EVT). We found no statistically significant benefit in overall mortality, (OR 0.84, 95% CI 0.59-1.2), but SBC was associated with improved functional outcome (defined as modified Rankin Scale 0-2 at 90 days) (OR 2.07, 95% CI 1.03–4.16), while rates of adverse effects were comparable between groups. Discussion: This SR and meta-analysis has several limitations, stemming from the small number of studies included in the quantitative syntheses, the potential publication bias (e.g due to the exclusion of non-English language records) and the unavailability of the results of a large number of studies that were still ongoing at the time the review was conducted. However, it has demonstrated that the existing SBC techniques are not only safe and feasible, but also potentially beneficial for the functional outcome of stroke patients. Future updated meta-analyses could help draw firmer conclusions on the benefit of incorporating SBC in the management of stroke.