Autoimmune Autonomic Ganglionopathy Associated with Voltage-Gated Potassium Channel Antibodies (P05.209)

Abstract

Objective: To report a case of autoimmune autonomic ganglionopathy (AAG) associated with neuronal voltage-gated potassium channel (VGKC) antibodies. Background Ganglionic acetylcholine receptor (AChR) autoantibodies have been described in patients with idiopathic autonomic neuropathies, and with further characterization of the pathophysiologic role of these antibodies, the terminology of this condition has changed to AAG. The majority of patients fulfilling clinical and laboratory criteria for AAG are, however, seronegative and additional pathogenetic antibodies have been postulated. Recently, an association between N-type calcium channel antibodies and AAG has been described. Design/Methods: A 65 year-old woman with a one year history of orthostatic intolerance, heat intolerance, diarrhea, and sicca complex underwent comprehensive autonomic and laboratory evaluations and was diagnosed with AAG associated with VGKC antibodies. She underwent serial standardized autonomic, clinical, and laboratory evaluations for 2 years, before and during treatment with intravenous immunoglobulin (IVIG). Results: During her initial evaluation, the patient was found to have widespread anhidrosis with otherwise essentially normal autonomic function. A paraneoplastic antibody panel was positive for VGKC antibodies, which did not react to recently recognized specific VGKC-associated antigens (Lgi1, Caspr2). A search for an occult malignancy remained negative. During subsequent evaluations, progressive cardiovascular adrenergic impairment was documented with evidence of orthostatic hypotension, associated with a rise in the antibody titer. At that time, treatment with IVIG was initiated. Six months after initiation of IVIG, autonomic testing had essentially normalized, associated with a notable decrease in antibody titer. Conclusions: AAG may be associated with autoimmune antibodies other than the classic ganglionic ACHR and the recently reported calcium-channel antibodies. Whether the VGKC antibodies in our patient have a pathophysiologic role or are nonspecific indicators of an underlying immune process remains subject for further study. This association is, however, important to recognize regardless of the underlying mechanism, considering this patient9s remarkable response to immunomodulatory therapy. Supported by: R.F. Kinney Executive Dean for Research Career Development Award and NIH (BIRCWH 5K12HD065987-02 and NS44233). Disclosure: Dr. Singer has nothing to disclose. Dr. Klein has received personal compensation for activities with Pfizer Inc as a consultant. Dr. McKeon has nothing to disclose. Dr. Low has received personal compensation for activities with Chelsea, Pfizer, and WR Medical Inc. as a consultant.Dr. Low has received personal compensation in an editorial capacity for Autonomic Neuroscience.