LGI1 antibody-mediated encephalitis is the second most common neuronal-antibody-associated encephalitis, typically affecting middle-aged to elderly adults with a male predominance. Core features include short-term memory loss, faciobrachial dystonic seizures (FBDS), other seizures, psychiatric symptoms, sleep disturbances, and hyponatremia. First-line treatment is IV methylprednisolone, which appears more effective acutely than IVIG alone for FBDS resolution and functional improvement. IVIG and plasma exchange are added for severe or refractory cases, with rituximab for relapse prevention. Approximately 80–94% achieve favorable outcomes with immunotherapy, with seizures responding early and cognition recovering more slowly. However, despite treatment, around seventy percent of patients retain residual deficits — particularly persistent short-term memory impairment and subtle cognitive, psychiatric, and sleep disturbances. Relapses occur in thirty five to fourth five percent of cases, sometimes years later. Presentation diversity is notable for cases that may mimic schizophrenia, dementia, or stroke, with atypical features that can delay diagnosis. Treatment response also varies by age, HLA status, and disease severity at nadir.

Here we describe three individuals with LGI1 antibody-mediated encephalitis presenting as bilateral faciobrachial dystonic seizures with persistent hyponatremia, intractable epilepsy with sensory auras, and focal epilepsy with mild cognitive impairment. Treatment responses were complicated by delayed rituximab-responsive hyponatremia despite initial steroid efficacy, immunosuppression-related herpes zoster reactivation necessitating rituximab discontinuation, and IVIG hypersensitivity reactions requiring formulation change and bridging corticosteroids.

These cases highlight the heterogeneity of LGI1 encephalitis in both clinical presentation and treatment trajectory, encouraging providers to maintain LGI1 antibody-mediated encephalitis on the differential even in atypical or complex presentations, particularly in older adults with comorbidities where symptoms may be attributed to other etiologies.