Both AMPA and GAD-65 receptor antibodies have been associated with intractable epilepsy, but we report co-occurrence of both antibodies in a patient with stiff person syndrome (SPS) and epilepsy who responded remarkably with immunotherapy.

A 29-year-old woman with history of a single seizure presented to an outside hospital with abnormal movements in sleep, progressive muscle stiffness and spasms. Routine EEG, MRI brain, and lumbar puncture were performed and were unremarkable. Patient developed illusions of grandeur during THE hospitalization and was diagnosed with bipolar disorder and adult-onset scoliosis.  Her psychiatric symptoms improved on olanzapine.

Patient received a second opinion at our institution 4 months later. Her examination was notable for marked stiffness of the neck and lower extremities with lumbar hyperlordosis. She had impaired gait due to limitation range of motion at her knees related to her stiffness. She had frequent muscle spasms.   A 96 hour video EEG revealed 30 electrographic seizures arising in the right parietal region. Serum GAD-65 R antibody returned elevated at >3100 nmol/L (reference range normal <0.02) and AMPA R antibody was also reported as positive (reference range negative) on serum Mayo Autoimmune Encephalopathy panel. Lumbar puncture revealed elevated GAD-65 ab at 80.6 nmol/L (reference range ≤ 0.02 nmol/L) on the Mayo serum autoimmune encephalopathy panel and >5 oligoclonal bands, but was otherwise was unremarkable. She underwent malignancy workup including US breast, mammogram, CT of the chest, abdomen and pelvis, and pelvic ultrasound that were negative for malignancy.

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She was treated with 2 gm/kg IVIG, diazepam, and lamotrigine with resolution of muscle spasms, improvement of stiffness, but she suffered from fatigue. She received rituximab 500 mg IV x 2 doses and had near complete resolution of symptoms.

Intractable epilepsy and SPS can co-occur in the context of SPS-plus and be treated with marked improvements with immunotherapies.