To describe a representative case of anti–leucine-rich glioma-inactivated 1 (LGI1) autoimmune encephalitis presenting with refractory seizures and to highlight the importance of early recognition and immunotherapy in improving neurological outcomes.

Anti-LGI1 encephalitis is a rare autoimmune neurological disorder with an estimated annual incidence of less than one case per million individuals. It typically manifests with subacute cognitive decline, psychiatric and behavioral symptoms, focal or generalized seizures—often including faciobrachial dystonic seizures—and autonomic dysfunction. Neuroimaging frequently demonstrates involvement of the medial temporal lobes, hippocampi, or amygdala. Laboratory abnormalities such as hyponatremia, commonly due to syndrome of inappropriate antidiuretic hormone secretion (SIADH), and cerebrospinal fluid (CSF) inflammatory changes may support the diagnosis, though findings are variable. Prompt identification is critical, as immunotherapy is associated with favorable prognosis and potential return to baseline function.

A 74-year-old man with no prior seizure history presented after a witnessed generalized tonic–clonic seizure following six months of nonspecific symptoms, including malaise and pruritus. Initial evaluation revealed significant hyponatremia, treated with hypertonic saline, and antiseizure therapy was initiated. Despite escalation to multiple antiseizure medications, continuous EEG monitoring demonstrated persistent focal right temporal seizures. Brain MRI revealed active inflammation of the right mesial temporal lobe, and CSF analysis showed elevated protein without pleocytosis. An APE2 score of seven raised concern for autoimmune encephalitis. High-dose intravenous methylprednisolone and intravenous immunoglobulin were initiated, resulting in marked EEG improvement within 36 hours. Subsequent serum testing confirmed anti-LGI1 antibodies, allowing de-escalation to monotherapy antiseizure treatment.

This case emphasizes the need to consider autoimmune encephalitis in older adults with new-onset, drug-refractory seizures and hyponatremia. Early recognition and immunotherapy can rapidly control seizures, limit neuropsychiatric sequelae, and significantly improve clinical outcomes.