title: Autoimmune stiff person syndrome and related myelopathies: understanding of electrophysiological and immunological processes.
abstract: Stiff person syndrome (SPS) is a disabling autoimmune central nervous system disorder characterized by progressive muscle rigidity and gait impairment with superimposed painful spasms that involve axial and limb musculature, triggered by heightened sensitivity to external stimuli. Impaired synaptic GABAergic inhibition resulting from intrathecal B-cell-mediated clonal synthesis of autoantibodies against various presynaptic and synaptic proteins in the inhibitory neurons of the brain and spinal cord is believed to be an underlying pathogenic mechanism. SPS is most often idiopathic, but it can occur as a paraneoplastic condition. Despite evidence that anti-GAD and related autoantibodies impair GABA synthesis, the exact pathogenic mechanism of SPS is not fully elucidated. The strong association with several MHC-II alleles and improvement of symptoms with immune-modulating therapies support an autoimmune etiology of SPS. In this review, we discuss the clinical spectrum, neurophysiological mechanisms, and therapeutic options, including a rationale for agents that modulate B-cell function in SPS.
authors.affiliation: Department of Neurology, Thomas Jefferson University, 900 Walnut Street, Suite 200, Philadelphia, Pennsylvania 19107, USA. goran.rakocevic@jefferson.edu
authors.forename: Goran
authors.initials: G
authors.lastname: Rakocevic
authors.forename: Mary Kay
authors.initials: MK
authors.lastname: Floeter
mesh_terms: D001323:Autoantibodies; D004594:Electrophysiology; D005968:Glutamate Decarboxylase / Q000276:immunology; D006801:Humans; D013118:Spinal Cord Diseases / Q000276:immunology* / Q000503:physiopathology*; D016750:Stiff-Person Syndrome / Q000276:immunology* / Q000503:physiopathology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase