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Disease-modifying agent (DMA) treatments have improved longevity and motor milestones for children with spinal muscular atrophy (SMA). But do they have a protective role in preventing scoliosis, which can develop with truncal muscle weakness? 

Most prior work exploring scoliosis in SMA was conducted before the advent of DMA treatments, most of which target survival motor neuron (SMN) 2 gene splicing or SMN1 gene replacement. A new retrospective cohort study in the Journal of Pediatric Orthopedics uses data from a tertiary children鈥檚 hospital to characterize the prevalence and risk factors for scoliosis development in SMA.

Sadettin Diftci, MD, from the Department of Orthopedics at Nemours Children鈥檚 Health in Delaware, and colleagues followed 165 patients with SMA types I-III, just over half of them female. A lengthy follow-up of almost 10 years marks one of the study鈥檚 key strengths. In addition, the researchers assessed risk factors using validated functional outcomes, including the functional mobility scale (FMS) and the Hammersmith functional motor scale (HFMS), which have the benefit of clearly illustrating progress from DMA use.

Scoliosis risk depends on SMA type

The development of scoliosis in SMA was high in this study, with a prevalence of 79%. The authors point out that this finding is much higher than what was previously reported in an all-surgical cohort; however, the current study is more comprehensive, including all patients with SMA regardless of orthopedic status.

The risk of scoliosis was largely related to what type of SMA a patient had. Children with non-ambulatory type I SMA developed scoliosis at a similar but slightly higher rate than those with type II (90% and 88%, respectively) (I/II, P=.02). 鈥淏ecause patients classified as type II are sitters with improved trunk strength, we expected the prevalence for type I to be higher than type II,鈥� the authors commented in their discussion. However, while the prevalence of scoliosis was similar between non-ambulatory types, children with type I SMA developed scoliosis earlier (6.9 y) than those with type II (8.2 y), suggesting a functional advantage in the latter group. In addition, for patients with ambulatory type III SMA, the relative risk of developing scoliosis was much lower at 51%.

The authors highlighted several additional risk factors for scoliosis. Children with SMA who were non-ambulatory faced a greater risk of developing the secondary neuromotor disorder (FMS50=1, P<.0001), as did those with hip displacement (P<.0001). Notably, the most significant risk factor was gross motor function (P<.001), with an HFMS score >23 considered an independent protective factor against scoliosis development. Contrary to the authors鈥� hypothesis, the number of SMN2 copies did not confer scoliosis risk, though past studies have used this feature as a predictor of functional impairment. 

DMA treatment makes an impact

Unsurprisingly, DMA treatment was linked with a lesser risk of scoliosis development in general, bearing a protective effect. 鈥淕iven the observed relationship to functional impairment, it would seem logical that DMA treatment would reduce scoliosis risk in SMA,鈥� the authors wrote in their discussion. They also theorized that DMA treatment might delay the onset of scoliosis, which in this cohort was 7.9 years and considerably higher among patients with type II than type I. 

In the literature, it remains an open question whether scoliosis can precipitate a decline in pulmonary function. Encouragingly, while pulmonary function decreased in children with scoliosis across all SMA types in the present study, DMA treatment was shown to be protective against %FVC deterioration.

Despite the study鈥檚 novelty, the authors note that their sample size is relatively small, and the study is not population-based. Many patients were assessed before the current era of DMA treatments; only 27% received treatment before scoliosis onset. Still, the risk factors considered in this study can be channeled towards early detection of scoliosis in SMA. 鈥淧rospective studies are needed to determine the most appropriate timing of radiographic surveillance, with validated quality-of-life measures to assess the impact of scoliosis on patients with SMA,鈥� the authors concluded.

Published: September 26, 2024