Muscle impairment and nusinersen affect variability in patients with spinal muscular atrophy type 2 and 3: a retrospective cohort study

Abstract BACKGROUNDReal-world data have shown variability in treatment responses to nusinersen in patients with 5q spinal muscular atrophy (SMA). It could be hypothesized that the degree of muscle impairment may confer to the drug response variability. Magnetic resonance imaging (MRI) is a useful tool to identify muscle involvement patterns in SMA; therefore, we investigated whether the magnitude of muscle involvement assessed by MRI at baseline can predict the change in gross motor function after the initiation of nusinersen treatment.RESULTSWe retrospectively assessed the clinical outcome of our treated cohort, in relevance to the thigh and pelvic MRI taken before the nusinersen treatment. A total of 16 patients with SMA types 2 and 3 (age = mean (SD); 9.2 (4.6) year) receiving nusinersen treatment were enrolled in the study. Hammersmith Functional Motor Scale-Expanded (HFMSE) was assessed to observe the change in motor function. The T1-weighted MR images of the pelvis and thigh were scored for muscle fatty infiltration and atrophy, and the interrater reliabilities of MR image evaluation were verified in all 16 images. The minimally clinically important difference (MCID) was considered as gaining at least 3 points of HFMSE from baseline. Of these 16 individuals, 14 had been treated for at least 15 months and had baseline data. At 15 months, seven individuals obtained MCID in HFMSE, and seven did not. Baseline muscle MRI score could not differentiate the two groups; however, individuals who obtained MCID had significantly less severe scoliosis. In addition, there was a significant and negative relationship between baseline MRI score and the change of score in HFMSE after 15 months of treatment. Further, baseline Cobb angle along with MRI score also correlated to the degree of change in motor function.CONCLUSIONIt was indicated that the degree of muscle damage may confer the variability in response to nusinersen for individuals with SMA types 2 and 3. Muscle MRI score in addition to the severity of scoliosis assessed at baseline may help to predict the gross motor function change after the drug initiation.