Abstract
BACKGROUND AND OBJECTIVES: IVIg has been the preferred immunotherapy in stiff-person syndrome (SPS) based on a 3-month controlled trial, but whether it is also effective in inducing long-term benefits or arresting disease progression is unknown. The information is needed because SPS is a progressively disabling disease and IVIg is liberally used as chronic therapy without efficacy data. The present study explores the long-term effects of IVIg in the largest cohort of well-characterized patients with SPS followed by the same clinicians over 10 years. METHODS: Data of 36 patients (32 glutamic acid decarboxylase [GAD] positive), diagnosed and treated with monthly maintenance IVIg by the same neurologists, were analyzed. Response was assessed by physician-observed changes, patients' reports of symptom improvement, modified Rankin Scale (mRS) scores, and dependency trials evaluating symptom recurrence after stopping IVIg, prolonging infusion frequency, decreasing monthly dose, or wearing-off effects in between doses. Clinically meaningful long-term response was defined by improved mRS scores, improvement in physician-assessed stiffness, balance and gait, and functional decline with dependency trials. RESULTS: Twenty-four of 36 (67%) patients had clinically meaningful response over a median 40-month period. Patients with improved mRS scores by 1-2 points manifested improved gait, posture, balance and decreased stiffness, spasms, and startle response; some patients using a wheelchair and those ambulating with devices walked unassisted. In 25% of responders, treatment benefit was sustained for a 40-month median period, but in 29.1%, it declined over a 39-month period; 12.5% exhibited a conditioning effect. Three of 5 patients with cerebellar GAD-SPS variant also improved over time. The 12 patients who did not respond the first 3 months remained unresponsive even if IVIg continued for several months. DISCUSSION: This is a large study in 36 patients with SPS demonstrating that monthly maintenance IVIg therapy offers long-term benefits in 67% of patients for a median 3.3-year period. Because 29.1% experienced diminishing benefit over time due to disease progression, the study highlights the need for more effective therapies.