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

IF 3.2 4区医学 Q2 CLINICAL NEUROLOGY

Journal of neuromuscular diseases Pub Date : 2024-01-01 DOI:10.3233/JND-230077

Hoi Ning Hayley Ip, Michael Kwan Leung Yu, Wilfred Hing Sang Wong, Amanda Liu, Kenny Yat Hong Kwan, Sophelia Hoi Shan Chan

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引用次数: 0

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.

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用 Nusinersen 治疗症状性脊髓肌肉萎缩症：脊柱侧凸进展的前瞻性纵向研究

背景：纽西那生治疗在改善脊髓性肌萎缩症（SMA）的临床预后方面具有疗效，但其对脊柱侧弯进展的影响仍不明确：本研究旨在评估接受奴西那生治疗的 SMA 儿童患者脊柱侧弯的进展情况：在这项前瞻性研究中，系统收集了2018年至2023年期间接受纽西奈森治疗的香港儿科SMA患者的数据。所有患者在接受纽西奈森治疗前均接受了纵向影像学检查，并在治疗期间根据脊柱侧弯的严重程度每半年或一年进行一次检查。在使用纽西奈森前以及开始治疗后，每隔 6 个月和 12 个月进行一次运动功能评估：共纳入 23 例患者（SMA 1 型 (SMA1) = 8 例，SMA 2 型 (SMA2) = 7 例，SMA 3 型 (SMA3) = 8 例），开始使用纽西奈森时的中位年龄为 5.8 岁（范围：0.4-17.5 岁），中位随访时间为 3.4 年（范围：1.1-5.2 年）。在研究期间，83%的患者运动评分保持稳定或有所改善。然而，脊柱侧弯在所有亚型中均有所进展，SMA1、SMA2 和 SMA3 的年平均进展率分别为 5.2 度、11.9 度和 3.6 度。5-11 岁开始服用纽西奈森的患者病情进展最快，在 SMA1、SMA2 和 SMA3 中的年均进展率分别为 11.8 度、16.5 度和 7.3 度。在 SMA1 中，纽西奈森治疗后的 CHOP-INTEND 评分差异与脊柱侧弯进展之间呈正相关（rs = 0.741，p = 0.041）。相反，在 SMA2（rs =-0.890，p = 0.012）和 SMA3（rs =-0.777，p = 0.028）中，nusinersen 后的 HFMSE 评分差异与脊柱侧弯进展之间呈负相关：本研究揭示，对有症状的小儿 SMA 患者进行奴西那生治疗并改善运动功能后，SMA1 患者的脊柱侧凸发展速度会加快，而 SMA2 和 SMA3 患者的脊柱侧凸发展速度会减慢。年龄、基线Cobb角和运动里程碑改善是脊柱侧弯进展的影响因素。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of neuromuscular diseases Medicine-Neurology (clinical)

CiteScore

5.10

自引率

6.10%

发文量

102

期刊介绍： The Journal of Neuromuscular Diseases aims to facilitate progress in understanding the molecular genetics/correlates, pathogenesis, pharmacology, diagnosis and treatment of acquired and genetic neuromuscular diseases (including muscular dystrophy, myasthenia gravis, spinal muscular atrophy, neuropathies, myopathies, myotonias and myositis). The journal publishes research reports, reviews, short communications, letters-to-the-editor, and will consider research that has negative findings. The journal is dedicated to providing an open forum for original research in basic science, translational and clinical research that will improve our fundamental understanding and lead to effective treatments of neuromuscular diseases.