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Background <p> Stiff-person syndrome (SPS) and stiff-person spectrum disorders (SPSD) are rare, immune-mediated neurological conditions characterized by progressive muscle rigidity, painful spasms, exaggerated startle responses, and substantial functional and psychosocial morbidity. Clinical heterogeneity, frequent diagnostic delay, and evolving immunopathogenic insights continue to complicate diagnosis and management. </p> Methods <p> This narrative review synthesizes current evidence on the epidemiology, clinical phenotypes, immunopathogenesis, diagnostic strategies, therapeutic approaches, monitoring tools, and psychosocial impact of SPS and SPSD. Evidence from randomized controlled trials, cohort studies, systematic reviews, and recent advances in immunotherapy is integrated, with attention to both adult- and pediatric-onset disease.</p> Results <p> Classic SPS is most commonly associated with high-titer antibodies against glutamic acid decarboxylase 65 and presents with axial and proximal limb rigidity, stimulus-sensitive spasms, hyperlordosis, and gait impairment. The SPS spectrum includes stiff limb syndrome, SPS-plus, progressive encephalomyelitis with rigidity and myoclonus, paraneoplastic SPS, and seronegative forms, each with distinct clinical and immunological profiles. Impaired GABAergic inhibition represents a central pathophysiological mechanism, although the direct pathogenic role of anti-glutamic acid decarboxylase antibodies remains debated. Diagnosis relies on characteristic clinical features, targeted autoantibody testing, and neurophysiological evidence of continuous motor unit activity. Management is anchored in symptomatic GABAergic agents and immunomodulatory therapies, with intravenous immunoglobulin supported by randomized trial evidence. Emerging treatments—including B-cell–depleting therapies, plasma exchange, autologous hematopoietic stem cell transplantation, neonatal Fc receptor blockade, and chimeric antigen receptor T-cell therapy—offer potential benefit in refractory disease. Standardized clinical scales are essential for monitoring disease burden and treatment response.</p>

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Stiff person syndrome: an overview

  • 期刊论文

  • 发表日期：

    2026年4月24日

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  • Richard A. Rison

摘要

Background

Stiff-person syndrome (SPS) and stiff-person spectrum disorders (SPSD) are rare, immune-mediated neurological conditions characterized by progressive muscle rigidity, painful spasms, exaggerated startle responses, and substantial functional and psychosocial morbidity. Clinical heterogeneity, frequent diagnostic delay, and evolving immunopathogenic insights continue to complicate diagnosis and management.

Methods

This narrative review synthesizes current evidence on the epidemiology, clinical phenotypes, immunopathogenesis, diagnostic strategies, therapeutic approaches, monitoring tools, and psychosocial impact of SPS and SPSD. Evidence from randomized controlled trials, cohort studies, systematic reviews, and recent advances in immunotherapy is integrated, with attention to both adult- and pediatric-onset disease.

Results

Classic SPS is most commonly associated with high-titer antibodies against glutamic acid decarboxylase 65 and presents with axial and proximal limb rigidity, stimulus-sensitive spasms, hyperlordosis, and gait impairment. The SPS spectrum includes stiff limb syndrome, SPS-plus, progressive encephalomyelitis with rigidity and myoclonus, paraneoplastic SPS, and seronegative forms, each with distinct clinical and immunological profiles. Impaired GABAergic inhibition represents a central pathophysiological mechanism, although the direct pathogenic role of anti-glutamic acid decarboxylase antibodies remains debated. Diagnosis relies on characteristic clinical features, targeted autoantibody testing, and neurophysiological evidence of continuous motor unit activity. Management is anchored in symptomatic GABAergic agents and immunomodulatory therapies, with intravenous immunoglobulin supported by randomized trial evidence. Emerging treatments—including B-cell–depleting therapies, plasma exchange, autologous hematopoietic stem cell transplantation, neonatal Fc receptor blockade, and chimeric antigen receptor T-cell therapy—offer potential benefit in refractory disease. Standardized clinical scales are essential for monitoring disease burden and treatment response.