Early Predictors of Future Disability in Stiff Person Syndrome Spectrum Disorders (S40.001)

Abstract

<h3>Objective:</h3> Assess for early predictors of future disability in a large cohort of individuals with stiff person syndrome spectrum disorders (SPSD). <h3>Background:</h3> SPSD are rare disorders with an increasing spectrum of phenotypes. There is a paucity of data identifying whether early predictors for future disability exist. <h3>Design/Methods:</h3> Retrospective review of medical records from 1997–2022 at Johns Hopkins yielded 235 individuals with SPSD. Clinical phenotypes were assigned: classic SPS (torso/back and limb), partial-SPS (limb, trunk), SPS-plus (classic features with cerebellar/brainstem findings), pure cerebellar ataxia (CA, without classic features), and progressive encephalomyelitis with rigidity and myoclonus (PERM). Outcomes were modified Rankin scale (mRS) and use of assistive device for ambulation at last follow-up. Multivariate logistic regression was used to assess for significant predictors of outcomes. <h3>Results:</h3> Mean age at symptom onset was 44 years (SD 14 years), and the majority were white (69%) and female (75%). Mean follow up was 9.8 years and mean disease duration was 9.7 years. Phenotype breakdown: 154 classic SPS, 45 SPS-plus, 16 PERM, 11 pure CA, and 9 partial-SPS. The mean mRS was 2.5. Over 70% required assistive devices for ambulation. Female sex (OR 2.08, CI 1.06–4.11, p=0.03), initial symptom of brainstem/cerebellar (OR 4.41, CI 1.63–14.33, p=0.006), and no immunotherapy in the first three years from symptom onset (OR 2.22, CI 1.09–4.55, p=0.03) predicted poorer outcome by mRS. Female sex (OR 1.99, CI 1.01–3.01, p=0.05), Black race (OR 4.14, CI 1.79–10.63, p=0.002), initial symptom of brainstem/cerebellar (OR 2.44, CI 1.04–7.19, p=0.04), and no immunotherapy in the first three years from symptom onset (OR 1.27, CI 1.06–1.52, p=0.007) predicted poorer outcome by use of assistive device for ambulation. <h3>Conclusions:</h3> Our study identified specific clinical and demographic features associated with future disability in SPSD. Further studies are needed to assess if treating subgroups of SPSD more aggressively will help long-term outcomes. <b>Disclosure:</b> The institution of Dr. Wang has received research support from Genentech. Miss Hu has nothing to disclose. Dr. Mukharesh has nothing to disclose. Dr. Aljarallah has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Aljarallah has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Aljarallah has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Sanofi Genzyme. Dr. Reyes-Mantilla has nothing to disclose. Mr. Comisac has nothing to disclose. Alexandra Balshi has nothing to disclose. Danielle Obando has nothing to disclose. Sarah Snoops has nothing to disclose. The institution of Dr. Fitzgerald has received research support from NIH. The institution of Dr. Fitzgerald has received research support from National MS Society. Dr. Newsome has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Autobahn. Dr. Newsome has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Newsome has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Newsome has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Newsome has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. Dr. Newsome has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Greenwich Biosciences. Dr. Newsome has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bristol Myers Squibb. Dr. Newsome has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon Therapeutics. The institution of Dr. Newsome has received research support from Biogen. The institution of Dr. Newsome has received research support from Genentech/Roche. The institution of Dr. Newsome has received research support from Department of Defense. The institution of Dr. Newsome has received research support from Patient Centered Outcomes Research Institute. The institution of Dr. Newsome has received research support from National MS Society. The institution of Dr. Newsome has received research support from The Stiff Person Syndrome Research Foundation. Dr. Newsome has received personal compensation in the range of $5,000-$9,999 for serving as a Clinical adjudication committee member for clinical trial with medDay Pharmaceuticals. Dr. Newsome has received personal compensation in the range of $10,000-$49,999 for serving as a Lead PI for Clinical Trial with Roche.