ABSTRACT
BACKGROUND: 5q spinal muscular atrophy (SMA) is a progressive autosomal recessive motor neuron disease. OBJECTIVE: We aimed to assess the effects of nusinersen on motor function and electrophysiological parameters in adolescent and adult patients with 5q SMA. METHODS: Patients with genetically confirmed 5q SMA were eligible for inclusion, and clinical data were collected at baseline (V1), 63 days (V4), 180 days (V5), and 300 days (V6). The efficacy of nusinersen was monitored by encompassing clinical assessments, including the Revised Upper Limb Module (RULM), Hammersmith Functional Motor Scale Expanded (HFMSE), 6-Minute Walk Test (6MWT), and percent-predicted Forced Vital Capacity in sitting position (FVC%) and Compound Muscle Action Potential (CMAP) amplitude. The patients were divided into "sitter" and "walker" subgroups according to motor function status. RESULTS: 54 patients were screened, divided into "sitter" (N = 22) and "walker" (N = 32), with the mean age at baseline of 27.03 years (range 13-53 years). The HFMSE in the walker subgroup increased significantly from baseline to V4 (mean change +2.32-point, P = 0.004), V5 (+3.09, P = 0.004) and V6 (+4.21, P = 0.005). The patients in both the sitter and walker subgroup had no significant changes in mean RULM between V1 and the following time points. Significant increases in CMAP amplitudes were observed in both upper and lower limbs after treatment. Also, patients with RULM ≥ 36 points showed significant CMAP improvements. Our analysis predicted that patients with CMAP amplitudes of trapezius ≥ 1.76 mV were more likely to achieve significant motor function improvements. CONCLUSIONS: Nusinersen effectively improves motor function and electrophysiological data in adolescent and adult patients with SMA. This is the first report on the CMAP amplitude changes in the trapezius after treatment in patients with SMA. The CMAP values effectively compensate for the ceiling effect observed in the RULM, suggesting that CMAP could serve as an additional biomarker for evaluating treatment efficacy.
