Histopathological patterns of hypoxic-ischemic encephalopathy after cardiac arrest: A retrospective brain autopsy study of 319 patients

Purpose: Understanding the pathophysiology of hypoxic-ischemic encephalopathy (HIE) provides important knowledge for the interpretation of neuroprognostic investigations after cardiac arrest (CA). One important aspect are the patterns of regional severity of selective neuronal death within the brain. Methods: In a monocentric, retrospective study, we included CA patients with initially successful resuscitation, who had received brain autopsies after death. We quantified selective eosinophilic neuronal death (SEND) in cerebral neocortex, hippocampus, basal ganglia, cerebellum, and brain-stem. Using a previously established classification, we dichotomized HIE severity in SEND 0-1 (<30%, reflecting no or mild HIE) versus SEND 2-4 (>= 30%, reflecting moderate to severe HIE). We analyzed histopathological HIE patterns and analyzed inter-regional and inter-neocortical correlation of SEND. Results: Of 319 patients, the mean SEND was 1.8 in hippocampus, 1.4 in neocortex, and 0.9 in brainstem. Typical histopathological HIE patterns were: (I) No or mild SEND in all brain regions, (II) predominant SEND in hippocampus with no or mild SEND in other brain regions, (III) severe SEND in neocortex, but not in brainstem, and (IV) severe SEND in the brainstem with neocortical HIE. In 7(9.7%) of 72 patients with histopathology from two different neocortical regions, the SEND differed by more than 30%. Among 154 patients with a SEND greater than 30% in at least one brain region, 14(9.1%) had predominant SEND in cerebellum, and 4(2.6%) predominant SEND in basal ganglia. Conclusions: CA causes typical histopathological HIE patterns, with the hippocampus being more susceptible to SEND, than the cerebral neocortex, and the brainstem being the most resistant brain region. The neocortical distribution of SEND is mostly homogeneous; however, a relevant subgroup shows substantial neocortical HIE heterogeneity. Further studies are required to provide a more granular histopathological analysis of infrequent HIE patterns and their implications for neuroprognostication.