Goran Rakocevic1, Raghavanpillai Raju, Marinos C Dalakas. 1. Neuromuscular Diseases Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Abstract
BACKGROUND: Stiff-person syndrome (SPS) is an immune-mediated central nervous system disorder characterized by fluctuating muscle stiffness, disabling spasms, and heightened sensitivity to external stimuli. Up to 80% of patients with SPS have anti-glutamic acid decarboxylase (GAD) antibodies in the serum or cerebral spinal fluid (CSF). Whether these antibodies are clinically relevant and correlate with disease severity is unknown. OBJECTIVE: To correlate anti-GAD antibody titers in the serum and CSF of patients with SPS with the degree of clinical severity. DESIGN: Patients studied the last 6 years. SETTING: The Clinical Center of the National Institutes of Health, Bethesda, MD. PATIENTS: Sixteen patients with typical SPS and elevated serum anti-GAD antibody titers. INTERVENTIONS: Antibody titers in serum and CSF were measured by radioimmunoassay, and the intrathecal anti-GAD-specific IgG production was calculated. MAIN OUTCOME MEASURES: Comparison of antibody titers with stiffness index and heightened sensitivity scores based on scales that reliably measure disease severity. RESULTS: The mean disease duration was 11 years (range, 5-30 years). The mean anti-GAD antibody titer in the serum was 51 500 U/mL (range, 24 000-200 000 U/mL); and in the CSF, 181 U/mL (range, 30-400 U/mL). A 10-fold increased intrathecal production of GAD-specific IgG antibodies was noted. No correlation was found between antibody titers in serum or CSF with disease severity. In 4 patients, the anti-GAD antibody titers measured serially during a 2-year period did not correlate with clinical fluctuations. CONCLUSIONS: In patients with SPS, the anti-GAD antibody titers in serum and CSF do not correlate with disease severity or duration. Anti-GAD antibodies are an excellent marker for SPS, but monitoring their titers during the course of the disease may not be of practical value.
BACKGROUND:Stiff-person syndrome (SPS) is an immune-mediated central nervous system disorder characterized by fluctuating muscle stiffness, disabling spasms, and heightened sensitivity to external stimuli. Up to 80% of patients with SPS have anti-glutamic acid decarboxylase (GAD) antibodies in the serum or cerebral spinal fluid (CSF). Whether these antibodies are clinically relevant and correlate with disease severity is unknown. OBJECTIVE: To correlate anti-GAD antibody titers in the serum and CSF of patients with SPS with the degree of clinical severity. DESIGN:Patients studied the last 6 years. SETTING: The Clinical Center of the National Institutes of Health, Bethesda, MD. PATIENTS: Sixteen patients with typical SPS and elevated serum anti-GAD antibody titers. INTERVENTIONS: Antibody titers in serum and CSF were measured by radioimmunoassay, and the intrathecal anti-GAD-specific IgG production was calculated. MAIN OUTCOME MEASURES: Comparison of antibody titers with stiffness index and heightened sensitivity scores based on scales that reliably measure disease severity. RESULTS: The mean disease duration was 11 years (range, 5-30 years). The mean anti-GAD antibody titer in the serum was 51 500 U/mL (range, 24 000-200 000 U/mL); and in the CSF, 181 U/mL (range, 30-400 U/mL). A 10-fold increased intrathecal production of GAD-specific IgG antibodies was noted. No correlation was found between antibody titers in serum or CSF with disease severity. In 4 patients, the anti-GAD antibody titers measured serially during a 2-year period did not correlate with clinical fluctuations. CONCLUSIONS: In patients with SPS, the anti-GAD antibody titers in serum and CSF do not correlate with disease severity or duration. Anti-GAD antibodies are an excellent marker for SPS, but monitoring their titers during the course of the disease may not be of practical value.