Authors :
Presenting Author: Hyesun Lee, MD – Asan Medical Center
Sang-Beom Jeon, MD, PhD – Asan Medical Center
Yong Seo Koo, PhD, MD – Asan Medical Center
Hyo Jae Kim, MD, PhD – Asan Medical Center
Rationale:
Autoimmune encephalitis (AE) is an autoimmune disorder of the central nervous system characterized by various manifestations including seizures, psychosis, and cognitive impairment. Although numerous autoantibodies have been identified, many patients remain seronegative; the precise immunopathomechanisms are still poorly understood, and various immunosuppressive therapies have been attempted. We report a case presenting with seronegative AE and super-refractory status epilepticus in a young male patient who had a Janus Kinase (JAK) 1 mutation and a favorable response to tofacitinib, a JAK 1 and 3 inhibitor.
Methods: N/A
Results:
A previously healthy 25-year-old man presented with refractory seizures following a three-day prodrome of fever and headache. At the referring hospital, he was received ten days of intravenous (IV) antiviral therapy and continuous sedation (midazolam and propofol), with a clinical assessment scale for autoimmune encephalitis (CASE) score of 24. Brain MRI demonstrated the Claustrum sign, and serological testing for neuronal autoantibodies was negative. Despite immunotherapies—including high-dose IV corticosteroids, IV immunoglobulin (IVIG), and rituximab—followed by cyclophosphamide, tocilizumab, and a ketogenic diet, nonconvulsive status epilepticus (NCSE)—manifested by electrographic seizures and burst–suppression with highly epileptiform bursts—persisted for six months. Whole-exome sequencing then identified a heterozygous JAK1 variant of uncertain significance (c.1332C >G, p.I444M). Although its clinical relevance remained unclear, continuous daily tofacitinib (a JAK1/3 inhibitor) was initiated in the seventh month of hospitalization. EEG monitoring revealed gradual improvement beginning in month eight, and approximately ten days later the patient regained alertness and was able to follow simple verbal commands. At one year, his CASE score had improved to 7. He continued to require multiple antiseizure medications for drug-refractory autoimmune-associated epilepsy, but his cognitive function improved and follow-up MRI showed resolution of prior cerebral atrophy.
Conclusions:
A heterozygous JAK1 variant of uncertain significance was identified in a patient with seronegative autoimmune encephalitis presenting as new-onset refractory status epilepticus. Although this mutation may be benign and its clinical relevance remains unclear, targeted JAK1 inhibition with tofacitinib produced a marked clinical improvement in an otherwise treatment-refractory case. This report underscores the value of genetic or transcriptomic testing to inform personalized immunotherapy in severe autoimmune encephalitis and suggests that JAK1 inhibitors may represent a viable therapeutic alternative for refractory presentations.
Funding: None