To describe the presentation and management of a biopsy-confirmed severe case of refractory ANLE post-SARS-CoV-2 infection 

Severe neuroimmune complications of SARS-CoV-2 infection have been described, including acute disseminated encephalomyelitis (ADEM), acute necrotizing leukoencephalitis, and acute necrotizing hemorrhagic encephalopathy. Here we describe a case of biopsy-confirmed fulminant, refractory acute necrotizing leukoencephalitis following mild SARS-CoV-2 infection.

A 54-year-old woman developed mild SARS-CoV-2 infection in June 2022. One month later, she presented with acute confusion, apraxia, aphasia, and right-sided weakness. On initial assessment, CSF studies were unremarkable. MRI showed several enhancing FLAIR hyperintensities. She received five days IV methylprednisolone (IVMP) and three days of IV immunoglobulin (IVIG). Rather than improving, she became obtunded with decorticate posturing and pseudobulbar affect. She did not improve with PLEX, five more days of IVIG, two more courses of IVMP, or acyclovir. Repeated CSF studies showed leukocytosis of 14. Brain biopsy showed demyelination, numerous macrophages, and necrosis. She was later found to have a high titer of anti-GAD 65 IgG in the serum but not CSF. Cyclophosphamide IV was started.

Patient improved radiographically with increased alertness after a third dose of cyclophosphamide. She continued a stable clinical course without further significant improvement, representing monophasic illness. She was discharged without further maintenance immunotherapy. Stable but severely debilitated, she was transitioned to hospice and passed away seven months after onset of illness.

This case demonstrates a pathologically confirmed case of fulminant post-viral ANLE one month after mild SARS-CoV-2 infection. It also highlights the importance of aggressive and repeated immunotherapy for refractory cases.