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

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

Yujie Wang  1   2 , Chen Hu  1 , Salman Aljarallah  1 , Maria Reyes Mantilla  1 , Loulwah Mukharesh  1 , Alexandra Simpson  1 , Shuvro Roy  1 , Kimystian Harrison  1 , Thomas Shoemaker  1 , Michael Comisac  1 , Alexandra Balshi  1 , Danielle Obando  1 , Daniela A Pimentel Maldonado  1 , Jacqueline Koshorek  1 , Sarah Snoops  1 , Kathryn C Fitzgerald  1   3 , Scott D Newsome  4
Affiliations
Observational Study

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

Yujie Wang et al. J Neurol. 2024 Apr.

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.

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Conflict of interest statement

Yujie Wang reports research funding from Genentech. Chen Hu reports no disclosures. Salman Aljarallah reports no disclosures. Maria Reyes Mantilla reports no disclosures. Loulwah Mukharesh reports no disclosures. Alexandra Simpson reports no disclosures. Shuvro Roy reports no disclosures. Kimystian Harrison reports no disclosures. Thomas Shoemaker reports no disclosures. Michael Comisac reports no disclosures. Alexandra Balshi reports no disclosures. Danielle Obando reports no disclosures. Daniela Pimentel Maldonado reports no disclosures. Jacqueline Koshorek reports no disclosures. Sarah Snoops reports no disclosures. Kathryn Fitzgerald reports no disclosures. Scott D. Newsome has received consultant fees for scientific advisory boards from Biogen, Genentech, EMD Serono, Bristol Myers Squibb, Jazz Pharmaceuticals, Novartis, Horizon Therapeutics, TG Therapeutics, is the study lead PI for a Roche clinical trial, and has received research funding (paid directly to institution) from Biogen, Roche, Lundbeck, Genentech, The Stiff Person Syndrome Research Foundation, National MS Society, Department of Defense, and Patient-Centered Outcomes Research Institute.

Figures

Fig. 1
Fig. 1
Anatomical involvement of musculoskeletal symptoms among stiff person syndrome spectrum disorders. Locations where participants experienced stiffness and/or spasms based on phenotype. In classic stiff person syndrome (SPS), SPS-plus, and progressive encephalomyelitis with rigidity and myoclonus (PERM) phenotypes, the most commonly affected regions were the axial musculature (torso, back) and lower limbs. PERM had higher proportion of neck/cervical musculature affected. In partial SPS, lower limb was most commonly affected. Color scheme with red indicating higher and blue indicating lower proportion affected
See this image and copyright information in PMC

References

    1. Budhram A, Sechi E, Flanagan EP, et al. Clinical spectrum of high-titre GAD65 antibodies. J Neurol Neurosurg Psychiatry. 2021;92(6):645–654. doi: 10.1136/jnnp-2020-325275. - DOI - PMC - PubMed
    1. McKeon A, Robinson MT, McEvoy KM, et al. Stiff-man syndrome and variants: clinical course, treatments, and outcomes. Arch Neurol. 2012;69(2):230–238. doi: 10.1001/archneurol.2011.991. - DOI - PubMed
    1. Dalakas MC. Stiff-person syndrome and GAD antibody-spectrum disorders: GABAergic neuronal excitability, immunopathogenesis and update on antibody therapies. Neurother J Am Soc Exp Neurother. 2022 doi: 10.1007/s13311-022-01188-w. - DOI - PMC - PubMed
    1. Dalakas MC. Stiff person syndrome: advances in pathogenesis and therapeutic interventions. Curr Treat Options Neurol. 2009;11(2):102–110. doi: 10.1007/s11940-009-0013-9. - DOI - PubMed
    1. Moersch FP, Woltman HW. Progressive fluctuating muscular rigidity and spasm (“stiff-man” syndrome); report of a case and some observations in 13 other cases. Proc Staff Meet Mayo Clin. 1956;31(15):421–427. - PubMed

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