Acute necrotizing encephalopathy associated with COVID-19: case series and systematic review

Acute necrotizing encephalopathy (ANE) is a rare neurological complication related to COVID-19. Here we present a case series of six Chinese cases with ANE associated with COVID-19 and review all reported cases in the literature. A total of six cases with ANE related to COVID-19 were enrolled in this study. Clinical manifestations, neuroimaging data, treatment and outcomes of these patients were analyzed. A literature review was performed in Pubmed and Embase and 25 cases with clinical and neuroimaging data were collected and analyzed. Among our six cases, the age of onset ranged from 15 to 56 years, with a male-to-female ratio of nearly 1:1. All patients presented with reduced consciousness. Elevated interleukin 6 in serum and/or cerebrospinal fluid (CSF) was detected in four patients. Two patients improved clinically after intravenous methylprednisolone and intravenous immunoglobulin (IVIG). Based on the literature review, the majority of cases were from Europe and the United States (60%). Two age peaks at 10-20 years (20%) and 50-60 years (28%) were observed. Two cases were found with a heterozygous Thr585Met mutation. The mortality of ANE caused by COVID-19 was 42%. The use of IVIG in combination with other immunotherapies was related to better outcome (P = 0.041) and both two patients who received Tocilizumab survived. This is the first Chinese case series about ANE associated with COVID-19. Elevated serum and CSF interlukin-6 were found in certain cases. The mortality and morbidity rates remained high although prompt immunotherapy could improve the outcomes.