Classic stiff person syndrome

Classic stiff person syndrome (SPS), also known as stiff-man syndrome, is a rare autoimmune neurological disorder characterized by progressive, fluctuating muscular rigidity and painful spasms primarily affecting the axial muscles (trunk and abdomen) and proximal limb muscles. The condition results from autoimmune-mediated impairment of gamma-aminobutyric acid (GABA)-ergic inhibitory pathways in the central nervous system. Approximately 60-80% of patients have autoantibodies against glutamic acid decarboxylase (GAD65), the enzyme responsible for synthesizing GABA. Some patients may have antibodies against amphiphysin or other synaptic proteins. The hallmark features include continuous stiffness of the paraspinal and abdominal muscles, leading to a characteristic hyperlordotic posture, along with superimposed episodic spasms that can be triggered by unexpected stimuli such as noise, touch, or emotional distress. These spasms can be severely disabling and may cause falls and injuries. Patients often develop task-specific phobias and heightened anxiety related to the fear of triggering spasms. Classic SPS is frequently associated with other autoimmune conditions, particularly type 1 diabetes mellitus, autoimmune thyroiditis, pernicious anemia, and vitiligo. Treatment involves both symptomatic and immunomodulatory approaches. GABAergic medications such as diazepam and baclofen are first-line symptomatic therapies to reduce stiffness and spasm frequency. Immunotherapy options include intravenous immunoglobulin (IVIg), which has demonstrated efficacy in randomized controlled trials, as well as plasmapheresis, rituximab, and corticosteroids. While there is no cure, many patients achieve meaningful symptom improvement with a combination of symptomatic and immune-directed treatments. The disease typically follows a chronic progressive course if untreated.

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