To evaluate the clinical characteristics, timing, and outcomes of early immunotherapy in adults with autoimmune-associated seizures, and to compare findings with previously described NORSE and autoimmune encephalitis cohorts.

Autoimmune seizures and new-onset refractory status epilepticus (NORSE) are severe immune-mediated neurological conditions that may occur without detectable antibodies. Early immunotherapy is believed to improve seizure control and outcomes, though evidence remains limited. Optimal timing and treatment sequencing are not well established.

We retrospectively reviewed six adults (mean age 67 years; all male) admitted with new-onset focal or focal-to-bilateral tonic–clonic seizures refractory to ≥3 antiseizure drugs. Two patients were excluded due to seizure improvement prior to immunotherapy. All underwent MRI, EEG, CSF, and autoimmune/paraneoplastic antibody testing. Autoimmune probability was assessed using APE2 and STAM3P scores. Timing, type, and response to immunotherapy were analyzed.

All four patients met criteria for possible or probable autoimmune encephalitis with median APE2 of 5 (range 3–8) and STAM3P of 3 (range 2–5). Three patients received early immunotherapy—high-dose IV methylprednisolone with or without IVIg—within 2–5 days of presentation, resulting in rapid seizure control in two patient and gradual improvement in one. One patient received delayed therapy required escalation to plasmapheresis but ultimately improved. MRI showed nonspecific or limbic findings; CSF revealed mild protein elevation without pleocytosis. All antibody panels were negative, and no infectious etiologies or immunotherapy complications were identified. Early treatment was associated with faster seizure resolution and better recovery.

Autoimmune-associated seizures respond favorably to early immunotherapy, even in antibody-negative cases. Prompt initiation of corticosteroids and IVIg, with escalation to plasmapheresis when needed, may shorten seizure duration and enhance neurological outcomes, supporting early empiric immune modulation in this population.