Stiff Person Syndrome: Bridging Neuroimmunology and Rehabilitation for Improved Patient Outcomes

Stiff person syndrome (SPS) is a rare autoimmune neurologic disorder characterized by progressive muscle rigidity, painful stimulus-triggered spasms, and impaired inhibitory neurotransmission. Once considered a singular entity, SPS is now recognized as part of a broader spectrum of autoimmune neurologic disorders with diverse clinical phenotypes, antibody profiles, and functional outcomes. Although advances in neuroimmunology have improved understanding of disease mechanisms and expanded therapeutic options, the functional consequences of SPS and the role of rehabilitation remain comparatively underrepresented in the literature. This comprehensive review provides the current evidence regarding the epidemiology, immunopathogenesis, clinical spectrum, diagnosis, treatment, functional outcomes, and rehabilitation considerations of stiff person syndrome and stiff person spectrum disorders. A review of the literature was conducted using peer-reviewed publications identified through PubMed and Google Scholars. Priority was given to original research, clinical trials, systematic reviews, and landmark studies, with an emphasis on contemporary literature published within the past five years. Additional studies were included to provide historical context and highlight the evolution of current concepts. SPS is increasingly recognized as a heterogeneous autoimmune disorder associated with anti-glutamic acid decarboxylase, glycine receptor, and amphiphysin antibodies, including rituximab, hematopoietic stem cell transplantation, and chimeric antigen receptor T-cell therapy, offer promise for refractory disease. Despite advances in medical management, SPS continues to impose substantial functional limitations affecting mobility, activities of daily living, and quality of life. Rehabilitation interventions, including physical and occupational therapy, spasticity management, neuromodulation, and multidisciplinary care, demonstrate potential to improve functional outcomes, although evidence remains limited. SPS is a complex autoimmune disorder requiring multidisciplinary management that extends beyond immunotherapy alone. Continued advances in biomarker discovery, targeted immunotherapies, standardized functional outcome measures, and evidence-based rehabilitation strategies are essential to improve diagnosis, optimize functional recovery, and enhance long-term quality of life.