Infratentorial Brain Injury Among Patients Suspected of Death by Neurologic Criteria A Systematic Review and Meta-analysis

Background and Objectives There is a paucity of data on the frequency and prognosis of infratentorial brain injury among patients suspected of death by neurologic criteria (DNC), which likely contributes to scientific uncertainty regarding the role of isolated brainstem death in DNC determination. Our aim was to synthesize the prevalence, characteristics, and evolution of infratentorial brain injury, including isolated brainstem death, among patients suspected of DNC. Methods We conducted a systematic review by searching Medline, Embase, EBM Reviews, CINAHL Complete, and the gray literature from inception to March 26, 2021. We selected cohort and cross-sectional studies, case reports, and case series that included patients suspected of DNC. Two study investigators independently performed study selection, data collection, and risk of bias assessment. Our primary outcomes were the respective prevalence of infratentorial brain injury and isolated brainstem death, which we meta-analyzed using mixed-effects Bayesian hierarchical models with diffuse priors. Our secondary outcomes were the characteristics and evolution of patients with infratentorial brain injury and isolated brainstem death. Results Twenty-one studies met the selection criteria, most of which were of moderate to high risk of bias. Among patients suspected of DNC, the prevalence of infratentorial brain injury ranged from 2% to 16% (n = 3,602, mean prevalence: 6.3%, 95% highest density interval [2.4%-14.2%]), whereas the prevalence of isolated brainstem death ranged from 1% to 4% (n = 3,692, mean prevalence: 1.5%, 95% highest density interval [0.5%-3.9%]). A total of 38 isolated brainstem death cases with data on clinical characteristics and/or evolution were included. All had infratentorial strokes. Twenty patients had EEG background activity in the alpha or theta frequencies, 19 had preserved cerebral blood flow, 2 had preserved supratentorial cerebral perfusion, 2 had cortical responses to visual evoked potentials, and 1 had cortical responses to somatosensory evoked potentials. At the latest follow-up, 28 had progressed to whole-brain death. Discussion Studies with moderate to high risk of bias suggest that infratentorial brain injury is relatively uncommon among patients suspected of DNC. Isolated brainstem death is rarer and seems to carry a high risk of progression to whole-brain death. These findings require further high-quality investigation.