The clinical spectrum of anti-GAD antibody-positive patients with stiff-person syndrome

Objective: To evaluate the clinical spectrum of anti-GAD-positive patients with stiff-person syndrome (SPS) and provide reproducible means of assessin g stiffness. Background: SPS can be difficult to diagnose. Delineation of t he clinical spectrum in a well defined population will increase diagnostic sensitivity. Methods: In 20 anti-GAD-positive patients with SPS (six men, 1 4 women), screened among 38 referred patients, the authors assessed symptom s and signs, degree of disability, associated conditions, and immunogenetic markers. Degree of bending, distribution of stiff areas, timed activities, and magnitude of heightened sensitivity were examined monthly for 4 months in five patients. Results: Average age at symptom onset was 41.2 years. Ti me to diagnosis was delayed from 1 to 18 years (mean 6.2). Stiffness with s uperimposed episodic spasms and co-contractures of the abdominal and thorac ic paraspinal muscles were characteristic. All had stiff gait and palpable stiffness in the paraspinal muscles. Stiffness was asymmetric or prominent in one leg in 15 patients (stiff-leg syndrome) and involved facial muscles in 13. In one patient spasms lasted for days (status spasticus). Twelve pat ients needed a cane and seven a walker due to truncal stiffness and frequen t falls (average three to four per month). Distribution of stiffness and de gree of heightened sensitivity were two reproducible indices of stiffness a nd spasms. Autoimmune diseases or autoantibodies were noted in 80% and an a ssociation of with DR beta1 0301 allele in 70%. Conclusions: SPS is 1) freq uently misdiagnosed due to multifaceted presentations and asymmetric signs, 2) disabling if untreated, and 3) associated with other autoimmune conditi ons.