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

Yujie Wang; Chen Hu; Salman Aljarallah; Maria Reyes Mantilla; Loulwah Mukharesh; Alexandra Simpson; Shuvro Roy; Kimystian Harrison; Thomas Shoemaker; Michael Comisac; Alexandra Balshi; Danielle Obando; Daniela A Pimentel Maldonado; Jacqueline Koshorek; Sarah Snoops; Kathryn C Fitzgerald; Scott D Newsome

doi:10.1007/s00415-023-12123-0

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

J Neurol. 2024 Apr;271(4):1861-1872. doi: 10.1007/s00415-023-12123-0. Epub 2023 Dec 11.

Authors

Yujie Wang^{1

2}, Chen Hu¹, Salman Aljarallah¹, Maria Reyes Mantilla¹, Loulwah Mukharesh¹, Alexandra Simpson¹, Shuvro Roy¹, Kimystian Harrison¹, Thomas Shoemaker¹, Michael Comisac¹, Alexandra Balshi¹, Danielle Obando¹, Daniela A Pimentel Maldonado¹, Jacqueline Koshorek¹, Sarah Snoops¹, Kathryn C Fitzgerald^{1

3}, Scott D Newsome⁴

Affiliations

¹ Division of Neuroimmunology and Neurological Infections, Department of Neurology, Johns Hopkins Hospital, Johns Hopkins University School of Medicine, 600 N Wolfe St, Pathology 627, Baltimore, MD, 21287, USA.
² Department of Neurology, University of Washington School of Medicine, Seattle, WA, USA.
³ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
⁴ Division of Neuroimmunology and Neurological Infections, Department of Neurology, Johns Hopkins Hospital, Johns Hopkins University School of Medicine, 600 N Wolfe St, Pathology 627, Baltimore, MD, 21287, USA. snewsom2@jhmi.edu.

Abstract

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.

Keywords: Anti-GAD65; Progressive encephalomyelitis with rigidity and myoclonus; Stiff limb syndrome; Stiff person syndrome.

Publication types

Observational Study

MeSH terms

Comorbidity
Female
Humans
Myoclonus*
Outcome Assessment, Health Care
Prognosis
Stiff-Person Syndrome*