Genetic or Autoimmune: POLG-Related Epilepsy Initially Treated as an Autoimmune Encephalitis,a Case Report

Hospital neurologists participate at the forefront of managing fulminant acute and subacute onset epilepsy, frequently attributed to autoimmune encephalitis (AE). As the recognition of antibody-mediated AE grows, there is a growing number of patients who are treated as antibody-negative AE. While antibody-negative autoimmune processes should be considered in the setting of acute and subacute onset of fulminant epilepsy, other causes must be considered before subjecting patients to long-term immunomodulatory treatments and other potential therapeutic toxicities. We present the case of a previously healthy young man who presented with new-onset refractory seizures treated with escalating doses of anti-epileptic drugs as well as immunosuppression for presumed autoimmune epilepsy. He developed valproic acid induced hepatotoxicity requiring liver transplantation and was later found to have a POLG mutation. We discuss the presentation of POLG mutations as well as the diagnosis of seronegative autoimmune encephalitis. We highlight the need for a broad differential when evaluating new onset refractory seizures in an otherwise healthy person.