How to manage a patient with epilepsy and psychogenic non-epileptic seizures (PNES) with a long history of abnormal electroencephalograms (EEGs) and normal magnetic resonance imaging (MRI) results, considering autoimmune epilepsy?

Management of Suspected Autoimmune Epilepsy in a Patient with Persistent EEG Abnormalities and Possible PNES

Your clinical suspicion of autoimmune epilepsy deserves serious investigation given the 30+ year history of persistently abnormal EEGs with consistently normal MRIs, especially since the current clinical picture doesn't fit typical PNES patterns.

Why This Case Raises Red Flags for Autoimmune Epilepsy

The clinical presentation you describe is atypical for pure PNES and warrants autoimmune workup:

• PNES events lasting only seconds are extremely unusual – typical PNES episodes last minutes to hours, with most lasting 2-10 minutes 1, 2. Brief events of a few seconds are far more consistent with epileptic seizures 3.

• PNES occurring predominantly during sleep transitions (falling asleep, waking up, during sleep) is highly atypical – PNES rarely occur from sleep and almost never during sleep itself, as they require conscious psychological mechanisms 1, 4. This pattern strongly suggests genuine epileptic activity.

• Persistently abnormal EEGs for 30+ years with normal MRIs is a recognized pattern in antibody-negative autoimmune encephalitis 5. In one documented case, EEG abnormalities were the only objective finding that led to successful diagnosis and treatment of autoimmune encephalitis when MRI and CSF were normal 5.

Immediate Diagnostic Steps

Pursue autoimmune epilepsy evaluation with the following specific tests:

• Autoimmune encephalitis antibody panel including anti-NMDA receptor, anti-LGI1, anti-CASPR2, anti-AMPA receptor, anti-GABA-B receptor, and anti-GAD65 antibodies in both serum and CSF 5. Remember that antibody-negative autoimmune encephalitis exists and absence of antibodies does not exclude the diagnosis 5.

• Video-EEG monitoring is essential to capture both the brief events and the sleep-related events to definitively characterize them 3, 6. This should be inpatient monitoring for 3-5 days to capture multiple event types 6, 7.

• Consider emergent EEG if there is any concern for non-convulsive status epilepticus, particularly given the frequent brief events 8. Non-convulsive status can present with subtle symptoms and requires EEG for definitive diagnosis 8.

• CSF analysis including cell count, protein, glucose, oligoclonal bands, and IgG index even if prior CSF studies were normal, as autoimmune markers can evolve over time 5.

Critical Distinction: This is NOT Typical PNES

The semiology you describe contradicts established PNES patterns:

• PNES diagnosis requires video-EEG documentation showing typical events without EEG correlate 1, 2, 4. Your patient has persistently abnormal EEGs, which argues against pure PNES.

• PNES events from sleep are extraordinarily rare – the European Heart Journal guidelines specifically note that events during sleep favor epilepsy over PNES 8.

• Brief duration (seconds) strongly favors epileptic seizures over PNES 8, 3. The syncope guidelines note that loss of consciousness >1 minute favors seizure, but conversely, very brief events of seconds are classic for epileptic seizures 8.

Addressing the Dual Diagnosis Possibility

If both epilepsy and PNES coexist (occurs in 10-40% of epilepsy monitoring unit admissions), video-EEG is mandatory to distinguish event types 2, 9:

• Approximately 20-25% of patients with PNES also have true epilepsy, creating a "dual diagnosis" that is a serious management challenge 9.

• The brief, sleep-related events are almost certainly epileptic, while any longer daytime events may represent PNES 1, 9.

• Misdiagnosis of PNES in a patient with true epilepsy leads to dangerous undertreatment 9. Conversely, treating PNES as epilepsy leads to unnecessary medication escalation and pseudo-refractory epilepsy 9.

Treatment Implications if Autoimmune Epilepsy is Confirmed

Autoimmune epilepsy requires immunotherapy, not just anti-seizure medications:

• The case report of antibody-negative autoimmune encephalitis showed complete resolution of seizures, movement disorders, and psychiatric symptoms with immunotherapy when anti-epileptic medications had failed 5.

• Early therapeutic intervention is critical for autoimmune encephalitis – delays in treatment are associated with worse outcomes 5.

• Standard immunotherapy includes corticosteroids, IVIG, or plasma exchange as first-line, with rituximab or cyclophosphamide for refractory cases 5.

Common Pitfalls to Avoid

• Do not accept a PNES diagnosis based solely on clinical impression without video-EEG documentation 1, 2, 4. The gold standard for PNES diagnosis is capturing typical events on video-EEG without EEG correlate 1.

• Do not dismiss persistently abnormal EEGs as "non-specific" – in the context of clinical seizures and normal MRI, this pattern warrants autoimmune investigation 5.

• Do not assume all brief events are PNES – this contradicts established semiology where brief events favor epilepsy 8, 3.

• Do not delay autoimmune workup waiting for "classic" presentations – antibody-negative autoimmune encephalitis exists and can present with isolated seizures 5.

Recommended Algorithm

1. Obtain comprehensive autoimmune panel (serum and CSF) immediately 5
2. Schedule inpatient video-EEG monitoring for 3-5 days to capture multiple event types 6, 7
3. If video-EEG confirms epileptic events during the brief/sleep-related episodes, strongly consider empiric immunotherapy trial even if antibodies are negative 5
4. If video-EEG shows some events are non-epileptic, refer to psychiatry for cognitive-behavioral therapy for those specific events 4
5. Maintain close neurologic follow-up regardless of findings, as dual diagnosis requires coordinated multidisciplinary care 2, 9