Successful Autologous Hematopoietic Stem Cell Transplant in a Case of Stiff Person Spectrum Disorder with a positive Glycine Receptor antibody
Sofia Celli1, Richard Nash2, Constance McMenamin1, Madeline Garza1, Gloria Von Geldern3, George Georges4, Amanda Piquet1
1University of Colorado, Anschutz Medical Campus, 2Colorado Blood Cancer Institute at Presbyterian/St. Luke’s Medical Center, HealthOne, 3University of Washington, 4Fred Hutch Cancer Center
Objective:
To present a case of glycine receptor (GlyR) antibody-positive Stiff Person Syndrome Spectrum Disorder (SPSD) treated with autologous hematopoietic stem cell transplant (aHSCT).
Background:
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.
Results:
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.
Conclusions:
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.