Successful Autologous Hematopoietic Stem Cell Transplant in a Case of Stiff Person Spectrum Disorder with a positive Glycine Receptor antibody (P4-5.019)

To present a case of glycine receptor (GlyR) antibody-positive Stiff Person Syndrome Spectrum Disorder (SPSD) treated with autologous hematopoietic stem cell transplant (aHSCT).

SPSD is an autoimmune disease with progressive neurologic symptoms and in some cases severe disability. The exact pathophysiology of SPSD is unknown and treatment response to immunotherapy is variable. Autoantibodies against glutamic acid decarboxylase epitope 65 (GAD65) and GlyR antibody are commonly associated with SPSD. While large studies using aHSCT are currently lacking and greatly needed, this is a promising treatment approach for refractory SPSD with the potential of significant symptom improvement and perhaps clinical remission from disease. While cases of successful aHSCT in GAD65+ SPSD have been reported, to our knowledge only one other GlyR antibody-positive patient in the setting of progressive encephalomyelitis with rigidity and myoclonus (PERM) has been described.

Case report

A 59-year-old patient with GlyR antibody-positive SPSD was treated with immunotherapy including IVIG, plasma exchange (PLEX), Rituximab, and Mycophenolate Mofetil but continued to have neurological disability. Despite an initial response to PLEX with improved stiffness, muscle spasms, dysautonomia, and mobility, this improvement was not sustained. The patient continued to progress over two years despite immunotherapy, leading to the decision for aHSCT. Nine months after aHSCT, he showed significant clinical amelioration. Comparison of pre- to 21 weeks post-aHSCT findings included a 25-foot walk time reduction from 28.4 seconds to 15 seconds and a stiffness index reduction from 4/6 to 2/6. The patient also had improved gait, phonation, and reduced pain.

We report a case of symptomatic improvement, evidenced by reduced walk time and stiffness index, after aHSCT in an anti-GlyR positive SPSD patient. Nine months after the transplant the patient had further improved symptoms, indicating aHSCT as a beneficial therapy for this patient and potentially others with similar presentations.

Disclosure: Mrs. I Celli has nothing to disclose. Dr. Nash has nothing to disclose. Ms. McMenamin has nothing to disclose. Dr. Garza has nothing to disclose. The institution of Dr. Von Geldern has received research support from Novartis. The institution of Dr. Von Geldern has received research support from National MS Society. Dr. Von Geldern has received personal compensation in the range of $0-$499 for serving as a DSMB member with NIH, NINDS. Dr. Von Geldern has a non-compensated relationship as a editorial board member with MS and Related Disorders Journal that is relevant to AAN interests or activities. George Georges has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Magenta Therapeutics. George Georges has received personal compensation in the range of $0-$499 for serving as a Consultant for Company. George Georges has received personal compensation in the range of $0-$499 for serving as a Consultant for Talaris Therapeutics. George Georges has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Jasper Biotech. The institution of George Georges has received research support from NIH/NIAID. The institution of Dr. Piquet has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech. The institution of Dr. Piquet has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Piquet has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Piquet has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Piquet has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Sands Anderson PC. The institution of Dr. Piquet has received research support from Rocky Mountain MS Center. The institution of Dr. Piquet has received research support from Novartis. The institution of Dr. Piquet has received research support from Abbvie. The institution of Dr. Piquet has received research support from Roche/Genentech. The institution of Dr. Piquet has received research support from NYU. Dr. Piquet has received publishing royalties from a publication relating to health care. Dr. Piquet has received publishing royalties from a publication relating to health care. Dr. Piquet has received personal compensation in the range of $10,000-$49,999 for serving as a Litigative Consultant with US-Dept HHS/DICP.