COVID-19 Related Acute Hemorrhagic Necrotizing Encephalitis: A Report of Two Cases and Literature Review

Abstract

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus, has proven neurotropism and causes a multitude of neurologic manifestations. Acute hemorrhagic necrotizing encephalitis (AHNE), though rare, can be seen in patients with severe infection and is associated with devastating neurologic outcomes. The true prevalence of this syndrome is unknown due to underrecognition, difficulty in timely acquisition of neuroimaging, and high mortality in this subset of patients escaping detection. It is a distinct clinicoradiological syndrome, with patients suffering from rapidly worsening encephalopathy and coma within the first two weeks of severe illness and hemorrhagic necrotizing parenchymal changes on neuroimaging. The pathophysiology of this syndrome is unclear but hypothesized to occur due to cytokine storm, blood-brain-barrier dysfunction, and direct viral-mediated endotheliopathy. Diagnosis requires a high index of suspicion in patients who have unexplained persistent severe encephalopathy associated with COVID-19 infection. Most patients have elevated systemic inflammatory markers and severe lung disease with hypoxic respiratory failure requiring mechanical ventilation. MRI is the imaging modality of choice, with a distinct neuroimaging pattern. CSF (cerebrospinal fluid) studies have a low yield for viral particle detection with currently available testing. While long-term outcomes are unclear, early immunomodulatory treatment with intravenous immunoglobulin, plasma exchange, and steroids may portend a favorable outcome. We discuss two cases of COVID-19 related AHNE and also include a pertinent literature search of similar cases in PubMed to consolidate the AHNE clinical syndrome, neuroimaging characteristics, management strategies, and reported short-term prognosis.

Keywords: acute hemorrhagic necrotizing encephalitis; cerebral microhemorrhage; covid-19; cytokine release storm; dexamethasone convalescent plasma; disorder of consciousness; remdesivir; sars-cov-2 (severe acute respiratory syndrome coronavirus -2).

Figure 1. Imaging findings of patient 1

(A) CT (axial section) of the chest with contrast showing diffuse bilateral subpleural and perihilar ground-glass opacities (orange arrowheads). (B, C) CT head (axial sections) of the brain showing punctate hemorrhages in the right frontal and left frontal and parietal areas (yellow arrows). (D) MRI of the brain (axial section, diffusion-weighted imaging) showing hyperintensities in bilateral centrum semiovale areas (orange arrows). (E-H) MRI of the brain (susceptibility-weighted imaging) showing innumerable punctate microhemorrhages in the cerebellar peduncles and subcortical regions of bilateral hemispheres including bilateral basal ganglia and internal capsules (red arrows). CT, computed tomography; MRI, magnetic resonance imaging

Figure 2. Imaging findings of patient 2

(A) CT (axial section) of the chest with contrast showing diffuse bilateral subpleural and perihilar ground-glass opacities (orange arrowheads). (B-D) MRI of the brain (diffusion-weighted imaging, axial sections) showing hyperintensities in bilateral centrum semiovale, basal ganglia, and bilateral cerebellar hemispheres (yellow arrows). (E, F) T2/FLAIR sagittal images showing confluent hyperintensities in periventricular regions, centrum semiovale in frontoparietal areas, and cerebellum (blue arrows). (G, H) Susceptibility-weighted imaging showing multiple foci of microhemorrhages in cortical and subcortical regions, and bilateral basal ganglia (red arrows). CT, computed tomography; MRI, magnetic resonance imaging; T2/FLAIR, T2-weighted/fluid-attenuated inversion recovery