Treatment of Symptomatic Spinal Muscular Atrophy with Nusinersen: A Prospective Longitudinal Study on Scoliosis Progression

Abstract

Background: Nusinersen treatment has demonstrated efficacy in improving clinical outcomes for spinal muscular atrophy (SMA), yet its impact on scoliosis progression remains unclear. Objective: This study aimed to assess the progression of scoliosis in pediatric patients with SMA undergoing nusinersen treatment. Methods: In this prospective study, data were systematically collected from Hong Kong pediatric SMA patients receiving nusinersen between 2018 and 2023. All patients had longitudinal radiographic studies pre-nusinersen, and at half-yearly or yearly intervals during treatment based on the scoliosis severity. Motor function evaluations were conducted pre-nusinersen, and after starting treatment at 6- and 12-month intervals. Results: Twenty-three patients ((SMA type 1 (SMA1) = 8, SMA type 2 (SMA2) = 7, SMA type 3 (SMA3) = 8)) with a median age of 5.8 years (range: 0.4–17.5 years) at nusinersen initiation, and median follow-up duration of 3.4 years (range: 1.1–5.2 years) were included. During the study period, motor scores remained stable or improved in 83% of patients. However, scoliosis progressed across all subtypes, with mean annual progression rates of 5.2, 11.9, and 3.6 degrees in SMA1, SMA2, and SMA3 respectively. Patients initiating nusinersen between ages 5 and 11 years exhibited the most rapid progression, with rates of 11.8, 16.5, and 7.3 degrees per year in SMA1, SMA2, and SMA3 respectively. Positive correlations were observed between the difference in CHOP-INTEND score post-nusinersen and scoliosis progression in SMA1 (rs = 0.741, p = 0.041). Conversely, negative correlations were found between the difference in HFMSE score post-nusinersen and scoliosis progression in SMA2 (rs =−0.890, p = 0.012) and SMA3 (rs =−0.777, p = 0.028). Conclusions: This study reveals that nusinersen treatment in symptomatic pediatric SMA patients with motor improvement is linked to increased scoliosis progression in SMA1, whereas it is associated with decreased progression in SMA2 and SMA3. Age, baseline Cobb angle, and motor milestone improvement are influential factors in scoliosis progression.

Spinal Muscular Atrophy Scoliosis in the Era of Background Therapies—A Review of the Literature

“…We have observed a significant shift in clinical phenotypes among symptomatically treated SMA type I patients who historically would not have survived. These patients now exhibit motor functions akin to those of SMA type II patients but still face a high risk of developing spinal deformities [ 32 , 35 , 40 , 50 , 51 ]. For SMA types II and III patients receiving symptomatic treatment, the progression of scoliosis appears to be slower compared to those in control groups [ 50 ].…”

“…These patients now exhibit motor functions akin to those of SMA type II patients but still face a high risk of developing spinal deformities [ 32 , 35 , 40 , 50 , 51 ]. For SMA types II and III patients receiving symptomatic treatment, the progression of scoliosis appears to be slower compared to those in control groups [ 50 ]. In cases where treatment is administered in a presymptomatic stage, it could potentially prevent the development of scoliosis entirely or at least delay its onset, though longer follow-up is needed to confirm these possibilities.…”

“…SMA type I patients, who ordinarily would not live long enough to develop scoliosis, now face a high risk of developing spinal deformities which may require surgical intervention as a result [ 47 , 48 , 49 ]. A study by Ip et al observed that treating symptomatic pediatric SMA patients with nusinersen leads to increased scoliosis progression in SMA type I patients—individuals who would not have survived without treatment—while it decreases scoliosis progression in patients with SMA types II and III [ 50 ]. Phase III trials of symptomatically treated SMA type I patients have demonstrated an extended time to death or need for permanent ventilation compared to the sham control group.…”