Abstract Details

Title Upper Motor Neuron-Predominant Motor Neuron Disease: A Novel Immunotherapy-Responsive Association of GAD65 Autoimmunity

Topic Autoimmune Neurology

Presentation(s) P2 - Poster Session 2 (8:00 AM-9:00 AM)

Poster/Presentation
Number 8-011

Objective We aimed to characterize the clinical phenotypes of patients with motor neuron disease (MND) in the context of high titer serum/CSF GAD65 antibodies (radioimmunoassay).

Background

Autoimmune disorders can present as motor neuronopathies and need to be excluded prior to the diagnosis of Amyotrophic Lateral Sclerosis (ALS).

Design/Methods

A retrospective review of all Mayo patients (between 1/1/2003 and 12/31/2023) with motor neuronopathy and co-existing high titer GAD65 antibodies (≥20nmol/L in serum [equivalent to >10,000 IU, ELISA] or detection in CSF) was performed. Clinical phenotypes and outcomes were compared with ALS patients diagnosed in the last 5 years (1/1/2019-12/31/2023) who tested negative for GAD65 IgG.

Results We identified 12 patients with high-titer serum GAD65 IgG (median 221.5 nmol/L, range: 38.7-3077 nmol/L) and motor neuronopathy confirmed by neurogenic changes in electromyography, who often had lower back spasms, history of an exaggerated startle response with immunotherapy responsiveness compared to ALS patients. A subgroup of these patients had an upper motor neuron (UMN) predominant syndrome (58%), with history of exaggerated startle (57%), lower back spasms (43%), tandem gait impairment (86%) and UMN bladder symptoms (71%) that were significantly different from ALS controls. The UMN predominant GAD65 MN responded favorably to immunotherapy with stable electromyography, significantly lesser worsening in mRS and mortality on long term follow-up.

Conclusions UMN predominant motor neuronopathy is a distinct manifestation of GAD65 autoimmunity. Co-existing symptoms like exaggerated startle response, lower back spasms, impaired tandem gait, and UMN bladder signs might warrant consideration of an immunotherapy trial, with potentially favorable results.

Authors/Disclosures
Naveen K. Paramasivan, MD (Flat B2, AKB SPRINGS) PRESENTER	Dr. Paramasivan has nothing to disclose.
Pallab Sarker (Mayo Clinic)	Pallab Sarker has nothing to disclose.
Anastasia Zekeridou, MD, PhD, FAAN (Neuroimmunology Laboratory, Mayo Clinic)	The institution of Dr. Zekeridou has received research support from Roche/Genentech. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care.
Nathan P. Staff, MD, PhD, FAAN (Mayo Clinic)	Dr. Staff has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Stem Cell Research & Therapy. Dr. Staff has received research support from National Institutes of Health.
Christopher J. Klein, MD, FAAN (Mayo Clinic)	Dr. Klein has received personal compensation in the range of $500-$4,999 for serving as a Consultant for NMD Pharma.
Andrew McKeon, MD (Mayo Clinic)	The institution of Dr. McKeon has received research support from National Institutes of Health. Dr. McKeon has received intellectual property interests from a discovery or technology relating to health care. Dr. McKeon has received intellectual property interests from a discovery or technology relating to health care. Dr. McKeon has received publishing royalties from a publication relating to health care.
Sean J. Pittock, MD, FAAN (Mayo Clinic Dept of Neurology)	Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arialys. The institution of Dr. Pittock has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. The institution of Dr. Pittock has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche/Genentech. The institution of Dr. Pittock has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Alexion/AstraZeneka. The institution of Dr. Pittock has received research support from NIH. Dr. Pittock has received intellectual property interests from a discovery or technology relating to health care. Dr. Pittock has received intellectual property interests from a discovery or technology relating to health care. Dr. Pittock has received publishing royalties from a publication relating to health care.
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.

��ɫ��

��ɫ��