Outcomes of Surgical Resection and VNS in Patients with Medically Refractory Epilepsy and GAD65 Antibody Positivity (S40.004)

Abstract

<h3>Objective:</h3> To determine effectiveness of vagus nerve stimulator (VNS) and surgical resection in patients with drug-resistant epilepsy associated with glutamic acid decarboxylase 65 (GAD65) antibodies. <h3>Background:</h3> Epilepsy associated with high-titer GAD65 antibodies is often refractory to immunotherapies and antiseizure medications (ASMs), underscoring the need for alternate treatment strategies. <h3>Design/Methods:</h3> We retrospectively identified Mayo Clinic Rochester patients (January 2003 – April 2022) with drug-resistant epilepsy and high serum GAD65-antibody titers (&gt;20 nnmol/L) who underwent surgical resection and/or VNS implantation. A “favorable” surgical outcome was defined as Engel I-II, and a responder to VNS was defined as a &gt;50% reduction in seizure frequency from baseline. <h3>Results:</h3> We identified 15 patients (13 females, 86.7%) who underwent surgical resection (n=7), VNS implantation (n=6), and both (n=2). Patients had failed a median of 5.5 anti-seizure medications. Twelve patients had GAD65 tested in the CSF, all were positive (median titer 3.8). Of the nine patients who underwent surgical intervention (all involving the temporal region), three (33.3%) had a favorable outcome, which was sustained for at least 3.5 years in one, 10 years in another, and the third was lost to follow-up after 1 year. Pathology was available in four patients, only one had evidence of inflammation. Of the 8 patients who underwent VNS implantation, 3 (37.5%) were initially considered a responder, but this was not sustained in two of the three. No clinical factors were statistically associated with favorable surgical or VNS outcomes. <h3>Conclusions:</h3> Temporal surgical resection and VNS are not highly effective in drug-resistant autoimmune-associated epilepsy related to high-titer GAD65 antibodies. Additional therapies are greatly needed for this challenging clinical scenario. <b>Disclosure:</b> Dr. Zhao-Fleming has nothing to disclose. Dr. Britton has received personal compensation in the range of $0-$499 for serving as a Online course with American Clinical Neurophysiology Society. The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. The institution of Dr. Dubey has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Astellas. The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Argenx. Dr. Dubey has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for AGRIMS. Dr. Dubey has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Advances in Neurology . Dr. Dubey has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Moffit Cancer Center . Dr. Dubey has received research support from Department of Defense . Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. The institution of Dr. Smith has received research support from CURE Epilepsy.