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.

Prolonged Encephalopathy in COVID 19

“…The host immune response can be characterized as parainfectious i.e., the bystander host damage occurring due to innate immune response to acute COVID 19 infection vs postinfectious i.e., abnormal adaptive autoimmune response occurring weeks following acute infection [9]. Parainfectious neurological manifestations contributing to prolonged encephalopathy include acute necrotizing encephalopathy reported in multiple studies, which otherwise is a rare disease process [10]. Post-infectious included more specifically acute disseminated encephalomyelitis (ADEM) leading to prolonged encephalopathy [9,11].…”

Encephalopathy as a prognostic factor in adults with acute disseminated encephalomyelitis following COVID-19

“…Six patients (26.1%) received no speci c treatment 9,27,29,34,37,38 . Three patients (13%) received low-dose steroid treatment 9,29,30 . Six patients (26.1%) were treated with IVMP pulse therapy 9,31,32,35,36,39 and six others (26.1%) with IVMP followed by IVIG 9,23,25,26,33 .…”

“…91.3% of the patients presented with encephalopathy. An altered consciousness state after the end of sedation arose the suspicion of a CNS neurological disorder in 30.4% of the cases 9,23,27,29,38 . In one case ANHLE was associated with AIDP 9 .…”

“…The treatment strategy was reported in all cases. Six patients (26.1%) received no speci c treatment 9,27,29,34,37,38 . Three patients (13%) received low-dose steroid treatment 9,29,30 .…”

“…Good clinical recovery was observed in one patient (4.5%) 38 , while partial/poor recovery was reported in 13 cases (59.1%) 9,[23][24][25]27,[32][33][34]37,39 . Eight patients died (36.4%) 9,26,[29][30][31]35,36 .…”