Abstract Introduction Super-refractory status epilepticus (SRSE) represents a severe neurological emergencyoften requiring prolonged anesthetic coma and mechanical ventilation. Autoimmuneencephalitis is an increasingly recognized cause of SRSE, and cases without detectableantibodies—termed seronegative autoimmune encephalitis—pose major diagnostic andtherapeutic challenges. We describe a critically ill patient with seronegative autoimmuneencephalitis causing SRSE requiring extensive critical care and immunotherapy. Case Presentation A 47-year-old right-handed woman with epilepsy, chronic respiratory failure,hyperlipidemia, urinary incontinence, chronic pain, and anxiety/depression was admittedfrom a skilled nursing facility with recurrent seizures characterized by eye and legtwitching consistent with status epilepticus. She had recently undergone antiepilepticregimen adjustment, discontinuing oxcarbazepine due to dizziness while continuinglevetiracetam 1500 mg BID and lacosamide 200 mg BID. Despite therapy, she developed refractory seizures necessitating escalation to multiple anesthetic agents and a pharmacologically induced coma. Brain MRI revealed no structural or enhancing lesion. CT chest/abdomen/pelvis showed no malignancy. Cerebrospinal fluid (CSF) demonstrated WBC 1/µL, protein 55 mg/dL, negative culture, and negative PCR for meningoencephalitis pathogens. Serum and CSF autoimmune encephalitis panels were negative. Despite absent serologic markers, she exhibited partial improvement following pulse-dose methylprednisolone and intravenous immunoglobulin (IVIG), raising suspicion for seronegative autoimmune encephalitis.During hospitalization, she required prolonged mechanical ventilation for respiratory failure and developed multiple complications including stress-induced cardiomyopathy, ventilator-associated pneumonia, and adrenal insufficiency. Continuous EEG monitoring confirmed recurrent electrographic seizures, prompting re-induction of pentobarbital coma with adjunctive infusions of midazolam and ketamine. She remained on a multidrug antiepileptic regimen including levetiracetam, lacosamide, valproic acid, oxcarbazepine, and phenobarbital. Inflammatory and infectious markers improved with antibiotics, and ammonia levels normalized. The overall CSF profile (elevated protein, minimal pleocytosis) favored inflammatory etiology over infection. Discussion This case exemplifies the complexity of diagnosing and managing seronegative autoimmune encephalitis presenting as SRSE. Absence of antibody confirmation should not delay empiric immunotherapy when clinical and CSF findings suggest autoimmune inflammation. In the ICU, management requires coordination of aggressive seizure suppression, immunotherapy, and treatment of systemic complications such as sepsis and stress cardiomyopathy. Conclusion Seronegative autoimmune encephalitis should be considered in patients with unexplained SRSE, even when antibody panels are negative. Early initiation of steroids and IVIG, combined with multidisciplinary critical-care management, may offer functional recoverydespite prolonged coma and mechanical ventilation. This abstract is funded by: N/A
Khan et al. (Fri,) studied this question.