Abstract Introduction New-onset seizures in adults present a diagnostic challenge due to a broad differential including structural, metabolic, infectious, autoimmune, and toxicologic causes. Among rarer yet critical etiologies are paraneoplastic neurologic syndromes (PNS), particularly paraneoplastic limbic encephalitis (PLE), an immune-mediated disorder affecting the nervous system, strongly linked to cancer and associated with specific neuronal antibodies. PLE typically presents subacutely with short-term memory loss, seizures, confusion, mood changes, or psychosis. Diagnosis is based on antibodies targeting either intracellular antigens (e.g., anti-Hu/ANNA-1), which induce cytotoxic T-cell responses and respond poorly to immunotherapy, or cell surface/synaptic antigens (e.g., anti-GABA-B receptor), which respond better to immunomodulation. We report a patient with new-onset seizures and CSF neuronal antibodies, leading to the discovery of mediastinal lymphadenopathy and a lung nodule. Case Presentation A 71-year-old female, current 30 pack-year smoker with prior B-cell lymphoma and endometrial cancer, presented after a one-minute episode of unresponsiveness with persistent blinking and open-mouth posture, followed by postictal confusion. Symptoms began a week after being struck on the head without loss of consciousness. Initial workup including EKG, CT head, and MRI brain was unremarkable. EEG showed multiple focal seizures, and she was diagnosed with temporal lobe epilepsy, started on levetiracetam 1 g twice daily, with plans for outpatient lumbar puncture. Despite adherence, seizures recurred, requiring dose escalation to 1.5 g twice daily, providing temporary control. She was later admitted for continuous EEG and lumbar puncture showing mild lymphocytic predominance and positivity for ANNA-1 and GABA-B receptor antibodies. She was discharged on levetiracetam 2 g twice daily. One month later, she returned with recurrent seizures and progressive confusion, gait instability, slurred speech, weakness, nausea, and vomiting. CT was unremarkable, but CTA neck incidentally revealed a 1.7 cm right apical lung nodule with enlarged mediastinal lymph nodes. Pulmonology correlated findings with prior CSF results, diagnosing PLE. Bronchoscopy confirmed small cell lung carcinoma (SCLC). Treatment with IV methylprednisolone, IVIG, and carboplatin/etoposide chemotherapy produced excellent results. Discussion Persistent seizures despite appropriate management warrant reassessment for rare etiologies. Recognition of antibodies such as ANNA-1 and GABA-B receptor is crucial, as PLE frequently precedes SCLC, accounting for over half of reported cases. Anti-Hu indicates a T-cell-mediated, treatment-resistant process, whereas GABA-B receptor antibodies predict better immunotherapy response. Co-expression may reflect aggressive disease, necessitating close follow-up. Conclusion In refractory seizures, paraneoplastic syndromes should prompt malignancy evaluation. Identifying specific neuronal antibodies offers prognostic insight and guides therapy, directly improving patient outcomes. This abstract is funded by: None
Cook et al. (Fri,) studied this question.