What is the best course of action for managing brief seizures not detected as epileptic on EEG in a patient with controlled epilepsy awaiting autoimmune panel results?

Management of Brief Seizures Not Detected on EEG in Controlled Epilepsy with Pending Autoimmune Workup

While awaiting autoimmune panel results, maintain current antiseizure medications and prepare for immediate immunotherapy initiation if autoimmune encephalitis is confirmed, as early treatment within 4 weeks of symptom onset provides the best recovery outcomes. 1

Understanding the Clinical Picture

The brief stereotyped events you describe—arms going up, turning to one side, grunting during sleep-wake transitions—are highly suspicious for epileptic seizures despite negative EEG correlation. This discordance is not uncommon and does not exclude epilepsy or autoimmune etiology:

• Brief seizures (<10 seconds) frequently escape scalp EEG detection, particularly if they originate from deep structures like the insula or mesial temporal regions 2, 3
• Autoimmune-associated epilepsy commonly presents with multifocal seizures and normal or minimally abnormal scalp EEG, even when intracranial recordings show extensive epileptiform activity 3
• The presence of "activity kept at bay with medications" on EEG suggests ongoing epileptiform discharges that are being partially controlled 4

Immediate Management Steps

Continue Current Antiseizure Medications

• Do not reduce or withdraw ASMs while awaiting autoimmune results, as premature withdrawal increases risk of breakthrough seizures and potential status epilepticus 4
• The number of ASMs required correlates with higher risk of developing chronic epilepsy in autoimmune encephalitis (28.4% develop epilepsy long-term) 4

Expedite Autoimmune Evaluation

Your provider appropriately ordered the autoimmune panel. Ensure it includes 1, 5:

• Serum neuronal autoantibody panel (NMDAR, LGI1, GABABR, CASPR2, AMPAR)
• Paraneoplastic antibodies (Hu, Yo, Ma2, CRMP5, amphiphysin)
• Thyroid antibodies (TPO, thyroglobulin) for Hashimoto's encephalopathy
• Morning cortisol and ACTH to exclude adrenal insufficiency mimicking encephalopathy

Consider Additional Diagnostic Testing

If not already performed 1, 6:

• MRI brain with and without contrast looking for T2/FLAIR hyperintensities in limbic or perisylvian regions (though normal imaging does not exclude autoimmune encephalitis) 3
• Repeat EEG or prolonged video-EEG monitoring to capture interictal abnormalities, as EEG patterns can change over time in autoimmune cases 7
• Lumbar puncture with comprehensive CSF analysis including cell count, protein, glucose, oligoclonal bands, autoimmune encephalopathy panel, and viral PCRs if clinical suspicion remains high 6, 1

If Autoimmune Encephalitis is Confirmed

Initiate First-Line Immunotherapy Immediately

The single most critical factor affecting outcomes is early immunotherapy—do not delay waiting for complete antibody results 1:

• High-dose corticosteroids: Methylprednisolone 1-2 mg/kg/day IV (typically 1000 mg daily for 3-5 days) 6, 1, 5
• IVIG: 0.4 g/kg/day for 5 days (total 2 g/kg), preferred if patient is agitated or has difficulty with central line placement 1, 5
• Plasma exchange (PLEX): 5-10 sessions every other day, preferred for severe hyponatremia or high thromboembolic risk 1, 5

Seizure Management in Autoimmune Context

• Continue or optimize antiseizure medications during immunotherapy 1
• Prioritize immunotherapy over escalating ASMs, as controlling the underlying autoimmune process is more effective than adding multiple antiepileptic drugs 4
• Delayed immunotherapy independently predicts development of chronic epilepsy 4

Second-Line Therapy if No Response

If no meaningful improvement after 2-4 weeks of first-line therapy 1:

• Rituximab for antibody-mediated autoimmune encephalitis
• Cyclophosphamide for cell-mediated autoimmunity

Critical Pitfalls to Avoid

• Do not assume normal EEG excludes epileptic seizures or autoimmune etiology—seronegative autoimmune epilepsy with normal scalp EEG is well-documented 7, 3
• Do not delay immunotherapy waiting for antibody confirmation—early treatment (within 4 weeks) is the most important prognostic factor 1
• Do not rapidly taper ASMs if autoimmune encephalitis is confirmed—abnormal EEG findings and multiple ASMs predict epilepsy development, warranting continued treatment 4
• Do not collect blood samples after IVIG/PLEX administration, as this causes false-negative antibody results 1

Monitoring and Follow-Up

• Assess treatment response at 2-4 weeks with clinical evaluation, repeat EEG, and consideration of repeat MRI 1
• Serial monitoring of inflammatory markers (CRP, ferritin), CBC, and comprehensive metabolic panel 1
• Tumor screening if paraneoplastic antibodies are positive or patient has cancer risk factors 1
• Long-term surveillance: Annual tumor screening for several years, particularly if treatment response is poor 1