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Stiff-person syndrome

INTRODUCTION

Stiff-person syndrome (SPS, formerly called stiff-man syndrome) is an uncommon disorder characterized by progressive muscle stiffness, rigidity, and spasm involving the axial muscles, resulting in severely impaired ambulation [1,2]. SPS is often associated with type 1 diabetes mellitus, which is a reflection of shared pathogenetic features.

PATHOGENESIS

An autoimmune process was originally postulated to underlie stiff-person syndrome (SPS, formerly called stiff-man syndrome) since the disorder often occurred in conjunction with a variety of autoimmune diseases. These include thyroiditis, vitiligo, pernicious anemia, and, particularly, type 1 diabetes mellitus [1,3-6].

Additional insight into an autoimmune mechanism was provided by the observation of polyclonal and oligoclonal IgG antibody elevations in the cerebrospinal fluid of the majority of patients with SPS [6,7]. These antibodies were found to target GABAergic (gamma amino butyric acid) neurons and their nerve terminals. The dominant antigen recognized by these antibodies is the GABA-synthesizing enzyme, glutamic acid decarboxylase (GAD) [8].

Outside the central nervous system (CNS), a high concentration of anti-GAD antibodies also recognizes pancreatic beta cells; this may explain the link between SPS and type 1 diabetes [9]. (See 'Type 1 diabetes mellitus' below and "Pathogenesis of type 1 diabetes mellitus".)

Anti-GAD antibodies — Circulating anti-GAD antibodies are present in approximately 60 percent of patients with SPS [6,10]. These antibodies can be reliably detected using a commercially available radioimmunoassay [11,12]. The relevance of these antibodies to the pathogenesis of SPS is supported by the following observations:

                       

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Literature review current through: Nov 2014. | This topic last updated: Sep 16, 2014.
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