Advances in the pathogenesis and treatment of patients with stiff person syndrome.
Advances in the clinical diagnosis, prognosis, pathogenesis, and therapies for stiff person syndrome (SPS), based on observations in more than 50 consecutive patients, are presented. The syndrome varies from mild to severe, but if untreated it can be progressive and disabling. SPS remains a largely underdiagnosed condition. Anti-glutamic acid decarboxylase (GAD) antibodies provide an excellent diagnostic marker, but their role in disease pathogenesis is uncertain. Research focused on identifying new autoantigens has provided evidence that gamma-aminobutyric acid (GABA)(A) receptor-associated protein (GABARAP), a 14-kD protein localized at the postsynaptic regions of GABAergic synapses, is a new antigenic target. In up to 65% of SPS patients, there are circulating anti-GABARAP antibodies that inhibit the GABA(A) receptor expression on GABAergic neurons. This review examines the diagnostic criteria for SPS, SPS variants, common errors in diagnosis, and a step-by-step therapeutic approach, including new advances in therapy.
Dalakas
Marinos C
MC
Neuromuscular Diseases Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA. marinos.dalakas@jefferson.edu
D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology; D051017:Apoptosis Regulatory Proteins; D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D002490:Central Nervous System / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D005968:Glutamate Decarboxylase / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods / Q000639:trends; D008869:Microtubule-Associated Proteins / Q000276:immunology; D010276:Parasympatholytics / Q000627:therapeutic use; D013035:Spasm / Q000175:diagnosis* / Q000276:immunology / Q000628:therapy*; D016750:Stiff-Person Syndrome / Q000175:diagnosis* / Q000276:immunology / Q000628:therapy*; D005680:gamma-Aminobutyric Acid / Q000096:biosynthesis
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D001323:Autoantibodies; D001324:Autoantigens; C116741:GABARAP protein, human; D008869:Microtubule-Associated Proteins; D010276:Parasympatholytics; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase