Stiff person spectrum disorder

Stiff person spectrum disorder (SPSD), formerly known as stiff man syndrome, is a rare autoimmune neurological disorder characterized by progressive rigidity and painful spasms of the axial and limb muscles. The spectrum encompasses classic stiff person syndrome (SPS), stiff limb syndrome (a focal variant), and progressive encephalomyelitis with rigidity and myoclonus (PERM), which represents the most severe form. The condition primarily affects the central nervous system, specifically impairing GABAergic (inhibitory) neurotransmission, leading to continuous motor neuron activity. Approximately 60-80% of patients with classic SPS have autoantibodies against glutamic acid decarboxylase (GAD65), the enzyme responsible for synthesizing the inhibitory neurotransmitter GABA. Some patients instead have antibodies against amphiphysin or glycine receptors, particularly in paraneoplastic cases associated with underlying malignancies such as breast cancer, lung cancer, or thymoma. The hallmark symptoms include fluctuating but progressive muscular rigidity, predominantly affecting the trunk and proximal limbs, along with episodic painful muscle spasms that can be triggered by unexpected stimuli such as noise, touch, or emotional distress. Patients often develop an exaggerated startle response and may adopt a characteristic hyperlordotic posture due to continuous contraction of paraspinal muscles. The spasms can be severe enough to cause falls and fractures. Many patients also experience significant anxiety and agoraphobia related to fear of triggering spasms. Task-specific phobias and depression are common comorbidities. SPSD is frequently associated with other autoimmune conditions, including type 1 diabetes mellitus, thyroiditis, pernicious anemia, and vitiligo. Treatment focuses on symptomatic management and immunomodulation. First-line symptomatic therapy includes benzodiazepines (particularly diazepam) and baclofen to enhance GABAergic inhibition and reduce muscle stiffness and spasms. Immunotherapy options include intravenous immunoglobulin (IVIg), which has demonstrated efficacy in randomized controlled trials, as well as plasmapheresis and rituximab for refractory cases. Corticosteroids and other immunosuppressants such as mycophenolate mofetil may also be used. Physical therapy and rehabilitation play supportive roles. In paraneoplastic cases, treatment of the underlying malignancy is essential. Despite available therapies, many patients experience progressive disability, and the disease can significantly impact quality of life.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Stiff person spectrum disorder