Natural history of SMA IIIb - Muscle strength decreases in a predictable sequence and magnitude

Objective: To assess the natural progression of muscle weakness in spinal muscular atrophy (SMA) IIIb. Methods: Ten patients with SMA IIIb were followed for at least 10 years. Age at disease onset varied between 9 and 18 years. Patients were initially seen 2 to 10 years after disease onset. They were evaluated at approximately 2, 5, 10, 15, and 20 years of disease duration depending on the timing of their initial visit after onset. Medical Research Council (MRC) scale was used with particular attention to proximal muscles. Results: The MRC grade declined with years in all of the muscles. The decline was usually not more than by one MRC grade for each 5-year period. There were 5-10 year periods when some muscles appeared to remain stationary. The succession of weakness was first triceps, then biceps and deltoid for upper extremity muscles and first thigh adductors, then iliopsoas, then quadriceps femoris, then hamstrings, thigh abductors, and gluteus maximus for lower extremity muscles. There was a remarkable uniformity between patients in the MRC grade for each muscle at each stage: in the first 5 years of the disease, triceps, iliopsoas, thigh adductors, and quadriceps femoris were the muscles which had noticeable weakness. Conclusions: These findings show that strength in spinal muscular atrophy IIIb decreases over time, explaining the progressive functional loss. The sequence of weakness in the lower extremities suggests that the disease starts segmentally involving the upper lumbar segments of the medulla spinalis initially. The slowness of the deterioration may have implications for clinical trials.