Department of Neurology, Washington University in St. Louis School of Medicine, St. Louis, Missouri, USA.
Department of Pediatrics, Norton Children's Medical Group, University of Louisville, Louisville, Kentucky, USA.
Muscle Nerve. 2024 Dec;70(6):1247-1256. doi: 10.1002/mus.28267. Epub 2024 Oct 6.
INTRODUCTION/AIMS: While prompt identification and treatment of infants with spinal muscular atrophy (SMA) can ameliorate outcomes, variability persists. This study assessed management and outcomes of early-treated infants with SMA.
We analyzed retrospective data at 12 centers on infants with SMA treated at age ≤6 weeks from August 2018 to December 2023.
Sixty-six patients, 35 with two SMN2 copies and 31 with ≥3 SMN2 copies, were included. Twenty-five (38%, 22 with two SMN2 copies), had SMA findings before initial treatment which was onasemnogene abeparvovec in 47 (71%) and nusinersen in 19 (29%). Thirty-two received sequential or combination treatments, including 16 adding nusinersen or risdiplam due to SMA findings following onasemnogene abeparvovec. All sat independently. Compared to children with ≥3 SMN2 copies, those with two SMN2 copies were less likely to walk (23/34 [68%] vs. 31/31 [100%], p < .001) and less likely to walk on time (9/34 [26%] vs. 29/31 [94%], p < .001); one non-ambulatory child was <18 months old and was excluded from this analysis. No patients required permanent ventilation or exclusively enteral nutrition; six required nocturnal non-invasive ventilation and four utilized supplemental enteral nutrition, all with two SMN2 copies.
Early treatment of infants with SMA can improve outcomes as indicated by our cohort, all of whom sat independently and are without permanent ventilation. However, our study demonstrates ongoing disability in most children with two SMN2 copies despite early monotherapy and emphasizes the need for additional research, including earlier monotherapy, initial combination therapy, prenatal treatment, and non-SMN modifying treatments.
介绍/目的：尽管及时识别和治疗脊髓性肌萎缩症（SMA）患儿可以改善预后，但仍存在变异性。本研究评估了早期治疗 SMA 婴儿的管理和结局。
我们分析了 2018 年 8 月至 2023 年 12 月期间 12 个中心的 SMA 婴儿的回顾性数据，这些婴儿在 ≤6 周龄时接受治疗。
66 例患儿中，35 例有 2 个 SMN2 拷贝，31 例有≥3 个 SMN2 拷贝。25 例（38%，其中 22 例有 2 个 SMN2 拷贝）在初始治疗前就有 SMA 表现，初始治疗使用onasemnogene abeparvovec 的有 47 例（71%），使用 nusinersen 的有 19 例（29%）。32 例接受了序贯或联合治疗，包括 16 例因 onasemnogene abeparvovec 后出现 SMA 表现而加用 nusinersen 或 risdiplam。所有患儿均可独立坐。与有≥3 个 SMN2 拷贝的患儿相比，有 2 个 SMN2 拷贝的患儿行走的可能性更小（34 例中有 23 例[68%] vs. 31 例中有 31 例[100%]，p<0.001），按时行走的可能性更小（34 例中有 9 例[26%] vs. 31 例中有 29 例[94%]，p<0.001）；1 名不能行走的患儿年龄<18 个月，因此被排除在本分析之外。无患儿需要永久性通气或完全肠内营养；6 例需要夜间无创通气，4 例需要补充肠内营养，均有 2 个 SMN2 拷贝。
我们的队列研究表明，早期治疗 SMA 婴儿可以改善预后，所有患儿均可独立坐，且无需永久性通气。然而，我们的研究表明，尽管早期接受单药治疗，大多数有 2 个 SMN2 拷贝的患儿仍存在持续性残疾，这强调了需要进一步研究，包括更早的单药治疗、初始联合治疗、产前治疗和非 SMN 修饰治疗。
