Abstract Details

Title Outcomes of Surgical Resection and VNS in Patients with Medically Refractory Epilepsy and GAD65 Antibody Positivity

Topic Autoimmune Neurology

Presentation(s) S40 - Autoimmune Neurology: Stiff Person Syndrome/GAD65 Neurological Autoimmunity, CIDP, and MOGAD (4:06 PM-4:18 PM)

Poster/Presentation
Number 004

Background Epilepsy associated with high-titer GAD65 antibodies is often refractory to immunotherapies and antiseizure medications (ASMs), underscoring the need for alternate treatment strategies.

Objective 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.

Design/Methods

We retrospectively identified Mayo Clinic Rochester patients (January 2003 – April 2022) with drug-resistant epilepsy and high serum GAD65-antibody titers (>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 >50% reduction in seizure frequency from baseline.

Results 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.

Conclusions 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.

Authors/Disclosures
Hannah Zhao-Fleming, MD, PhD (Mayo Clinic At Rochester) PRESENTER	Dr. Zhao-Fleming has nothing to disclose.
Jeffrey W. Britton, MD, FAAN (Mayo Graduate School of Medicine)	Dr. Britton has received personal compensation in the range of $0-$499 for serving as a Online course with American Clinical Neurophysiology Society.
Divyanshu Dubey, MD, FAAN (Mayo Clinic)	The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Argenx. The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arialys. The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB . Dr. Dubey has received research support from Department of Defense . Dr. Dubey has received research support from Department of Defense . Dr. Dubey has received research support from UCB. Dr. Dubey has received research support from David J. Tomassoni ALS Research Grant Program . 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. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care.
Kelsey M. Smith, MD (Mayo Clinic)	The institution of Dr. Smith has received research support from CURE Epilepsy. The institution of Dr. Smith has received research support from UCB Pharmaceuticals.