Stiff-Person Syndrome Spectrum Disorders

Stiff-person syndrome was first described in 1956, and its further characterization as an autoimmune neurological disorder occurred more than 30 years later with the discovery of glutamic acid decarboxylase-65 (GAD65) antibodies (Abs), frequently coexisting in these patients. In the following years, clinical variants of SPS have been characterized and a paraneoplastic presentation was also recognized, the latter mainly associated with amphiphysin antibodies. Although the presence of GAD-Abs has led to theorize that these antibodies cause disinhibition of the central nervous system through decreased production of the inhibitory neurotransmitter γ-aminobutyric acid (GABA), the pathogenic role of GAD65-Abs is still a matter of debate. However, the evidence suggests that antibodies directed against other targets such as amphiphysin or the glycine receptor α1 are likely pathogenic. The treatment aims to attenuate the immunological response through immunotherapy; control the symptoms, mainly with GABAergic drugs; and remove an underlying tumor, if present. Course is usually chronic and the prognosis is frequently poor. Treatment should be initiated as soon as possible to improve the quality of life of patients.