Elena Zapata-Arriaza, MD
@ElenaZaps

Wu S, Yuan R, Wang Y, Wei C, Zhang S, Yang X, et al. Early Prediction of Malignant Brain Edema After Ischemic Stroke: A Systematic Review and Meta-Analysis. Stroke. 2018;49:2918-2927

In cases of unsuccessful recanalization or prolonged hypoperfusion, large infarctions may occur, leading to malignant brain edema. In addition to decompressive craniectomy, there are few therapeutic strategies to alleviate this serious complication of ischemic stroke. Given its high mortality and disability in survivors, high-risk patients identification could lead to a more intensive monitoring and maybe an early intervention.

The authors performed a systematic review and meta-analysis based on Medline and Embase search from inception to March 2018, with studies assessing predictors or predictive models for malignant brain edema after ischemic stroke. Malignant edema was defined as a syndrome of clinical worsening (or death or requirement for decompressive hemicraniectomy) with imaging evidence of brain swelling. Studies included were observational with at least 1 potential predictor measured or a developed predictive model for malignant edema, and with published full-text report in a peer-reviewed journal. Studies were excluded if outcomes were defined as imaging-based edema or as clinical worsening or death not attributable to brain edema, or if the study assessed cross-sectional associations. Moreover, the authors performed a post-hoc literature search in May 2018 to identify randomized controlled trials (RCTs) to provide more robust evidence for the effect of reperfusion therapies and successful revascularization on the development of malignant edema. Reperfusion therapies included either intravenous thrombolysis or endovascular interventions.

Among 38 studies with 3278 patients analyzed, 31% (796/2546) of patients included in cohort studies (31) developed malignant edema. The main risk factors related to malignant brain edema (MBE) analyzed in the study are summarized in the following table.

 The main risk factors related to malignant brain edema (MBE) analyzed in the study are summarized.

Data derived from Wu S, Yuan R, Wang Y, Wei C, Zhang S, Yang X, et al. Early Prediction of Malignant Brain Edema After Ischemic Stroke: A Systematic Review and Meta-Analysis. Stroke. 2018;49:2918-2927. *MBE: malignant brain edema.

Within all identified risk factors related to MBE, it would be interesting to highlight some of them. First, two of them work in a complementary way: younger age and brain atrophy. As the authors describe, “age-related brain atrophy is a possible confounder by providing buffering space for brain swelling”. However, although older patients with brain atrophy and lower risk of MBE, the presence of mentioned complication is related to multiple factors, so even in older patients we should stay on alert.

And second, another interesting factor is successful recanalization within 24 hours of stroke onset, which is related to lower MBE risk. This finding should raise a question: Should we use mechanical thrombectomy as a tool to avoid malignant brain edema in those cases with poor functional outcome suspicion despite recanalization? Should we indicate endovascular therapy for younger patients with large vessel occlusion and impaired blood perfusion CT? Of course, the answer is unknown, because mechanical thrombectomy has demonstrated its superiority to intravenous fibrinolysis regarding functional outcome and symptomatic intracranial bleeding, but randomized clinical trials were not designed to display evidence about MBE. However, growing positive results set an interesting starting point to consider revascularization in selected cases with high risk of MBE.

Finally, despite all known risk factors shown in this comprehend study, useful interventions with good clinical outcome aim are still insufficient, so further studies based on identified predictors should assess different MBE prevention measurements.