High-Dose Intravenous Immune Globulin for Stiff-Person Syndrome

Abstract

Background Stiff-person syndrome is a disabling central nervous system disorder with no satisfactory treatment that is characterized by muscle rigidity, ep- isodic muscle spasms, high titers of antibodies against glutamic acid decarboxylase (GAD65), and a frequent association with autoimmune disorders. Because stiff- person syndrome is most likely immune-mediated, we evaluated the efficacy of intravenous immune globulin. Methods We assigned 16 patients who had stiff- person syndrome and anti-GAD65 antibodies, in ran- dom order, to receive intravenous immune globulin or placebo for three months, followed by a one-month washout period and then by three months of therapy with the alternative agent. Efficacy was judged by improvements in scores on the distribution-of-stiff- ness index and heightened-sensitivity scale from base line (month 1) to the second and third month of each treatment phase. Direct and carryover effects of treat- ment were compared in the two groups. Results Among patients who received immune globulin first, stiffness scores decreased significantly (P=0.02) and heightened-sensitivity scores decreased substantially during immune globulin therapy but re- bounded during placebo administration. In contrast, the scores in the group that received placebo first re- mained constant during placebo administration but dropped significantly during immune globulin thera- py (P=0.01). When the data were analyzed for a direct and a first-order carryover effect, there was a signif- icant difference in stiffness scores (P=0.01 and P< 0.001, respectively) between the immune globulin and placebo groups, and immune globulin therapy had a significant direct treatment effect on sensitivity scores (P=0.03). Eleven patients who received immune globulin became able to walk more easily or without as- sistance, their frequency of falls decreased, and they were able to perform work-related or household tasks. The duration of the beneficial effects of immune glob- ulin varied from six weeks to one year. Anti-GAD65 an- tibody titers declined after immune globulin therapy but not after placebo administration. Conclusions Intravenous immune globulin is a well-tolerated and effective, albeit costly, therapy for patients with stiff-person syndrome and anti-GAD65 antibodies. (N