Encephalitis in the setting of COVID-19 has been reported, however the mechanism by which SARS-CoV-2 causes encephalitis remains unclear. We aimed to describe a case of fulminant limbic encephalitis associated with acute COVID-19 infection.

A 33-year-old COVID-19 positive female presented after being found unresponsive with seizure-like activity. On arrival, patient was comatose with intermittent left gaze deviation, weak gag and cough reflexes, and no movement to pain. She was intubated for airway protection (without hypoxia). Continuous EEG demonstrated generalized and bilaterally independent epileptiform discharges, with no electrographic or clinical seizures. Patient was prophylactically started on levetiracetam. Brain MRI revealed scattered DWI and T2 hyperintensities involving supratentorial and infratentorial areas more prominent in temporal lobes. CSF analysis showed mild neutrophilic pleocytosis; protein and glucose were normal. Infectious, autoimmune, and paraneoplastic encephalopathy in CSF/serum panels were negative. CSF COVID-19 PCR was negative. ESR, CRP and ferritin were mildly elevated. High-dose steroids and intravenous immunoglobulin were initiated. After 7 days repeated brain MRI demonstrated progression of T2 hyperintensities including midbrain, cerebral peduncles, and right hemispheric cortical ribboning. Patient continued to decline with gradual loss of brainstem reflexes and downward gaze deviation with ocular bobbing movements. Due to clinical deterioration the patient was transitioned to comfort care and deceased after extubating.

There have been increasing reports of severe encephalitis subtypes among younger COVID-19 patients commonly associated with poor outcomes compared to other subtypes of encephalitis. To our knowledge this is the first case of encephalitis associated with COVID-19 infection with no response to immunomodulatory therapies. Other possible etiologies in this case include hypoxic injury, hypoglycemia, or toxic insults, which were considered less likely given clinical scenario. In our case, PCR of CSF was negative for COVID-19 which raises possibility of secondary hyperinflammation or molecular mimicry as potential causes.