Expanding clinical profiles and prognostic markers in stiff person syndrome spectrum disorders

Objective To describe the clinical features of a cohort of individuals with stiff person syndrome spectrum disorders (SPSD) and identify potential early predictors of future disability. Background There is a need to better understand the full spectrum of clinical and paraclinical features and long-term impact of SPSD. Design/Methods Observational study from 1997 to 2022 at Johns Hopkins. Clinical phenotypes included classic SPS, partial SPS (limb or trunk limited), SPS-plus (classic features plus cerebellar/brainstem involvement), and progressive encephalomyelitis with rigidity and myoclonus (PERM). Outcome measures were modified Rankin scale (mRS) and use of assistive device for ambulation. Multivariate logistic regression was used to assess significant predictors of outcomes. Results Cohort included 227 individuals with SPSD with mean follow-up of 10 years; 154 classic, 48 SPS-plus, 16 PERM, and 9 partial. Mean age at symptom onset was 42.9 ± 14.1 years, majority were white (69.2%) and female (75.8%). Median time to diagnosis was 36.2 months (longest for SPS-plus and PERM) and 61.2% were initially misdiagnosed. Most had systemic co-morbidities and required assistive devices for ambulation. Female sex (OR 2.08; CI 1.06–4.11) and initial brainstem/cerebellar involvement (OR 4.41; CI 1.63–14.33) predicted worse outcome by mRS. Older age at symptom onset (OR 1.04; CI 1.01–1.06), female sex (OR 1.99; CI 1.01–4.01), Black race (OR 4.14; CI 1.79–10.63), and initial brainstem/cerebellar involvement (OR 2.44; CI 1.04–7.19) predicted worse outcome by use of assistive device. Early implementation of immunotherapy was associated with better outcomes by either mRS (OR 0.45; CI 0.22–0.92) or use of assistive device (OR 0.79; CI 0.66–0.94). Conclusions We present the expanding phenotypic variability of this rare spectrum of disorders and highlight potential predictors of future disability.