64 - Stiff-Person Syndrome

Abstract

Stiff-person syndrome (SPS) is a rare autoimmune disorder characterized by progressive muscle stiffness and rigidity, with superimposed painful spasms. In classic SPS, axial muscles are preferentially affected, resulting in lumbar hyperlordosis and impaired gait. SPS variants of stiff-limb syndrome, paraneoplastic SPS, and progressive encephalomyelitis with rigidity and myoclonus (PERM) are also reviewed here. SPS is often associated with type 1 diabetes mellitus as well as other autoimmune disorders such as thyroiditis, pernicious anemia, or vitiligo. The most common antibody associated with SPS is directed against glutamic acid decarboxylase (GAD), leading to impairment of gamma-amino-butyric acid (GABA) inhibitory pathways in brainstem and spinal cord. Glycine receptor and amphiphysin antibodies have been linked to PERM and paraneoplastic SPS, respectively. While SPS remains a clinical diagnosis, detection of antibodies and electrodiagnostic testing showing continuous motor unit activity is often supportive. Treatment with GABA receptor agonists such as benzodiazepines and baclofen usually results in symptomatic improvement and may suffice in mild cases. More severe cases may require immune therapies with intravenous immunoglobulin, corticosteroids, rituximab, or long-term immunosuppressive agents.