Presence Of Voltage-Gated Potassium Channel (VGKC)-Complex Antibody In A Case Of Genetic Prion Disease (P5.231)

OBJECTIVE: To report the second case in the literature of positive voltage-gated potassium channel (VGKC)-complex antibody in case of definite genetic Creutzfeldt-Jakob disease (CJD). BACKGROUND: VGKC-mediated encephalitis is a recently recognized entity which often mimics the clinical presentation of Creutzfeldt-Jakob disease (CJD). Several recent reports suggested that the presence of VGKC-complex antibody is a true marker of neurological autoimmunity and a predictor of a positive response to immunomodulating therapy. DESIGN/METHODS: Retrospective review of medical records, brain autopsy, and genetic analysis. RESULTS: A 67- year-old woman was admitted with two weeks of worsening speech difficulty and impaired right arm and leg use. There was a personal history of hypertension, lumbar spinal stenosis and peptic ulcer disease. Her father had died of a progressive neurological illness, with a presumptive diagnosis of ALS. Clinical evaluation revealed expressive aphasia, ideomotor apraxia and alien limb phenomenon involving her right arm and leg. CSF analysis revealed a normal cell count, elevated tau levels and minimally elevated protein. Brain MRI showed gyriform hyperintensity on diffusion-weighted imaging (DWI) confined to the cerebral cortex of the left insula, posterior temporal, anterior parietal, lateral frontal and paracentral frontal gyri. No hypermetabolic foci were noted on whole body Positron emission tomography. Serum paraneoplastic antibody evaluation was positive for VGKC-complex antibody by radioimmunoprecipitation assay (RIA) with a titer of 406 picomole (pM) (normal <20pM). No clinical improvement was noted after sequential treatment with pulse steroids (3-day course of 1000 mg/day of methylprednisolone) and Intravenous Immunoglobulin. Hospital course was noted for brief subclinical seizures, progressive encephalopathy and aphasia. She ultimately died 4 months post-symptom onset. Brain autopsy confirmed the diagnosis of CJD. Genetic analysis revealed an E200K-129M mutation in the Prion Protein-encoding gene, the most common genetic CJD mutation in North America. CONCLUSIONS: A positive VGKC-complex antibody should not be regarded as unequivocal evidence of autoimmune- mediated limbic encephalitis, as it can also be present in CJD. Study Supported by: None. Disclosure: Dr. Jammoul has nothing to disclose. Dr. Lederman has nothing to disclose. Dr. Tavee has nothing to disclose. Dr. Li has nothing to disclose.