SynthesisJournal of neurology2026
Comorbid autoimmune disease in stiff-person syndrome spectrum disorder: a systematic review and meta-analysis.
Synthesis in Journal of neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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7 authors.
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Abstract
backgroundStiff-person syndrome spectrum disorder (SPSD) is a rare autoimmune disorder characterized by progressive muscle stiffness and painful spasms. Autoimmune comorbidities are frequently reported in SPSD, contributing to disease burden; however, their pooled frequency has not been systematically quantified. This meta-analysis aimed to estimate the pooled frequency of autoimmune comorbidities in SPSD and to examine differences across clinical subtypes and between GAD65 antibody-positive and -negative patients.
methodsWe searched PubMed, Embase, the Cochrane Library, Web of Science, and Scopus from inception to August 23, 2025. Two reviewers independently screened studies and extracted data. Studies reporting autoimmune comorbidity frequency in confirmed SPSD were included; reviews, case reports, overlapping cohorts, and studies with fewer than five patients were excluded. Pooled overall and disease-specific frequencies of autoimmune comorbidity were estimated using random- or fixed-effects models, with separate estimates for SPSD subtype and GAD65 antibody-positive and -negative patients.
resultsA total of 38 studies were included, encompassing 1166 patients with SPSD. The pooled frequency of autoimmune comorbidities in this population was 51.2%. The most common were diabetes (including T1D and LADA; 29.0%), autoimmune thyroid disease (25.1%), and hypothyroidism (12.0%), followed by pernicious anemia (10.3%), myasthenia gravis (9.3%), Graves' disease (7.3%), vitiligo (5.8%), and celiac disease (5.0%). Sjögren's syndrome (2.4%), systemic lupus erythematosus (2.1%), and rheumatoid arthritis (1.9%) were relatively uncommon. These frequencies were substantially higher than those in the general population. Frequencies varied across SPSD subtypes: PERM (79.5%), classic SPS (61.9%), and focal or segmental SPS (38.2%). Autoimmune comorbidities were approximately twice as frequent among GAD65-positive patients (63.9%) compared with GAD65-negative patients (34.3%).
conclusionsAutoimmune comorbidities are highly prevalent in SPSD, particularly in PERM, classic SPS, and GAD65-positive patients. These findings guide screening and management to improve clinical outcomes and provide insights for future research into SPSD pathophysiology.
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