Early Predictors of Future Disability in Stiff Person Syndrome Spectrum Disorders
Yujie Wang1, Chen Hu2, Loulwah Mukharesh2, Salman Aljarallah2, Maria Reyes-Mantilla2, Michael Comisac3, Alexandra Balshi2, Danielle Obando3, Sarah Snoops2, Kathryn Fitzgerald3, Scott Newsome3
1Neurology, University of Washington, 2Neurology, Johns Hopkins University, 3Johns Hopkins University
Objective:
Assess for early predictors of future disability in a large cohort of individuals with stiff person syndrome spectrum disorders (SPSD).
Background:
SPSD are rare disorders with an increasing spectrum of phenotypes. There is a paucity of data identifying whether early predictors for future disability exist.
Design/Methods:
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.
Results:
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.
Conclusions:
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.