Objective: Delineate demographic and clinical differences between GAD-65-antibody positive (seropositive) and negative (seronegative) SPS.

Background: Elevated Glutamic Acid Decarboxylase 65 antibody (GAD-65 Ab) titers are seen in up to 80% of individuals with stiff person syndrome (SPS), a rare progressive autoimmune or paraneoplastic disorder comprised of multifocal painful spasms predominantly affecting the lower back and extremities. Few individuals are antibody negative.

Method: Retrospective medical record review of patients fulfilling ICD-10 codes for “stiff man syndrome”, “stiff person syndrome”, and “progressive encephalopathy with rigidity and myoclonus”(PERM) (G25.82) at New York Presbyterian Hospital.

Results: Twenty-two individuals, 18 (81.8%) female, 13 (59.1%) antibody positive, 6 (27.3%) antibody-negative, and 3 (13.6%) antibody status unknown (diagnosed with electrophysiologic data only), were included. Average onset age was 46.88 +/- 18.81 years (18-81 years), with a mean disease duration of 9.27 +/- 4.56 years (4-18 years) on the latest evaluation (2011 to 2024). None in our cohort exhibited antibodies to amphiphysin or presented with PERM). All individuals exhibited axial (59.1%) and appendicular (68.2%) rigidity. Over 90% of individuals in both antibody-positive and -negative subgroups reported spasms and gait impairment. Depression, anxiety, and phobias were present in 35-40% of all individuals. While a third of individuals with seronegative SPS exhibited parkinsonian features (bradykinesia and rigidity), none of the seropositive individuals exhibited these features. Dystonia was more common in seronegative individuals (33% versus 15%) while cerebellar and pyramidal signs were more common in seropositive individuals. Up to 61.5% of individuals with GAD-65 antibodies showed some response to IVIg compared to only 16.7% in GAD-65 antibody-negative individuals. Symptomatic improvement to PLEX (55.5%) was observed in seropositive patients with less consistent responses among seronegative individuals. About 30% of all individuals treated with corticosteroids responded well. Five GAD-65 antibody individuals were tried on rituximab with one individual demonstrating moderate symptomatic relief.

Conclusion: Compared to seronegative SPS, seropositive SPS presents with more cerebellar and less extrapyramidal signs, similar rates of spasms and neuropsychiatric disease burden, and more symptom response to immunotherapy.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/gad-positive-versus-gad-negative-stiff-person-syndrome-a-retrospective-study/