PDF(Pubmed)
Abstract：
OBJECTIVE: Spinal muscular atrophy (SMA) is a progressive neuromuscular disorder associated with continuous motor function loss and complications, such as scoliosis and contractures. Understanding the natural history of SMA is key to demonstrating the long-term outcomes of SMA treatments. This study reviews the natural history of motor function, scoliosis, and contractures in patients with SMA.
METHODS: Electronic databases were searched from inception to June 27, 2022 (Embase, MEDLINE, and Evidence-Based Medicine Reviews). Observational studies, case-control studies, cross-sectional studies, and case series reporting on motor function (i.e., sitting, standing, and walking ability), scoliosis, and contracture outcomes in patients with types 1-3 SMA were included. Data on study design, baseline characteristics, and treatment outcomes were extracted. Data sets were generated from studies that reported Kaplan-Meier (KM) curves and pooled to generate overall KM curves.
RESULTS: Ninety-three publications were included, of which 68 reported on motor function. Of these, 10 reported KM curves (3 on the probability of sitting in patients with types 2 and 3 SMA and 8 on the probability of walking/ambulation in patients with type 3 SMA). The median time to loss of sitting (95% CI) was 14.5 years (14.1-31.5) for the type 2 SMA sitter population (their maximum ability was independent sitting). The median time to loss of ambulation (95% CI) was 13.4 years (12.5-14.5) for type 3a SMA (disease onset at age younger than 3 years) and 44.2 years (43.0-49.4) for type 3b SMA (disease onset at age 3 years or older). Studies including scoliosis and contracture outcomes mostly reported non-time-to-event data.
CONCLUSIONS: The results demonstrate that a high degree of motor function loss is inevitable, affecting patients of all ages. In addition, data suggest that untreated patients with types 2 and 3 SMA remain at risk of losing motor milestones during late adulthood, and patients with types 3a and 3b SMA are at risk of loss of ambulation over time. These findings support the importance of stabilization of motor function development even at older ages. Natural history data are key for the evaluation of SMA treatments as they contextualize the assessment of long-term outcomes.
METHODS: Electronic databases were searched from inception to June 27, 2022 (Embase, MEDLINE, and Evidence-Based Medicine Reviews). Observational studies, case-control studies, cross-sectional studies, and case series reporting on motor function (i.e., sitting, standing, and walking ability), scoliosis, and contracture outcomes in patients with types 1-3 SMA were included. Data on study design, baseline characteristics, and treatment outcomes were extracted. Data sets were generated from studies that reported Kaplan-Meier (KM) curves and pooled to generate overall KM curves.
RESULTS: Ninety-three publications were included, of which 68 reported on motor function. Of these, 10 reported KM curves (3 on the probability of sitting in patients with types 2 and 3 SMA and 8 on the probability of walking/ambulation in patients with type 3 SMA). The median time to loss of sitting (95% CI) was 14.5 years (14.1-31.5) for the type 2 SMA sitter population (their maximum ability was independent sitting). The median time to loss of ambulation (95% CI) was 13.4 years (12.5-14.5) for type 3a SMA (disease onset at age younger than 3 years) and 44.2 years (43.0-49.4) for type 3b SMA (disease onset at age 3 years or older). Studies including scoliosis and contracture outcomes mostly reported non-time-to-event data.
CONCLUSIONS: The results demonstrate that a high degree of motor function loss is inevitable, affecting patients of all ages. In addition, data suggest that untreated patients with types 2 and 3 SMA remain at risk of losing motor milestones during late adulthood, and patients with types 3a and 3b SMA are at risk of loss of ambulation over time. These findings support the importance of stabilization of motor function development even at older ages. Natural history data are key for the evaluation of SMA treatments as they contextualize the assessment of long-term outcomes.
摘要：
目的：脊髓性肌萎缩症（SMA）是一种进行性神经肌肉疾病，与持续的运动功能丧失和并发症如脊柱侧凸和挛缩有关。了解SMA的自然史是证明SMA治疗长期结果的关键。本研究回顾了运动功能的自然史，脊柱侧弯,SMA患者的挛缩。
方法：从开始到2022年6月27日搜索电子数据库(Embase，MEDLINE,和循证医学评论)。观察性研究,病例对照研究，横断面研究，和关于运动功能的案例系列报告(即，坐着,站立,和行走能力)，脊柱侧弯,包括1-3型SMA患者的挛缩结局。研究设计数据，基线特征，并提取治疗结果。从报告Kaplan-Meier(KM)曲线的研究产生数据集,并汇集以产生整体KM曲线。
结果：包括93种出版物，其中68人报告了运动功能。其中,10条报告的KM曲线(关于2型和3型SMA患者坐位概率的三条，3型SMA患者行走/下床的概率为8）。2型SMA坐位人群的中位坐位时间（95％置信区间[CI]）为14.5年（14.1-31.5）（他们的最大能力是独立坐位）。3a型SMA（发病年龄<3岁）的步行时间中位数（95％CI）为13.4年（12.5-14.5），3b型SMA（发病年龄≥3岁）为44.2年（43.0-49.4）。包括脊柱侧凸和挛缩结局在内的研究大多报告了非事件发生时间数据。
结论：结果表明，运动功能的高度丧失是不可避免的，影响所有年龄段的患者。此外,数据表明，未经治疗的2型和3型SMA患者在成年后期仍有失去运动里程碑的风险，随着时间的推移，3a型和3b型SMA患者有失去下床活动的风险。这些发现支持了即使在老年人中稳定运动功能发育的重要性。自然历史数据是SMA治疗评估的关键，因为它们将长期结果的评估作为背景。
方法：从开始到2022年6月27日搜索电子数据库(Embase，MEDLINE,和循证医学评论)。观察性研究,病例对照研究，横断面研究，和关于运动功能的案例系列报告(即，坐着,站立,和行走能力)，脊柱侧弯,包括1-3型SMA患者的挛缩结局。研究设计数据，基线特征，并提取治疗结果。从报告Kaplan-Meier(KM)曲线的研究产生数据集,并汇集以产生整体KM曲线。
结果：包括93种出版物，其中68人报告了运动功能。其中,10条报告的KM曲线(关于2型和3型SMA患者坐位概率的三条，3型SMA患者行走/下床的概率为8）。2型SMA坐位人群的中位坐位时间（95％置信区间[CI]）为14.5年（14.1-31.5）（他们的最大能力是独立坐位）。3a型SMA（发病年龄<3岁）的步行时间中位数（95％CI）为13.4年（12.5-14.5），3b型SMA（发病年龄≥3岁）为44.2年（43.0-49.4）。包括脊柱侧凸和挛缩结局在内的研究大多报告了非事件发生时间数据。
结论：结果表明，运动功能的高度丧失是不可避免的，影响所有年龄段的患者。此外,数据表明，未经治疗的2型和3型SMA患者在成年后期仍有失去运动里程碑的风险，随着时间的推移，3a型和3b型SMA患者有失去下床活动的风险。这些发现支持了即使在老年人中稳定运动功能发育的重要性。自然历史数据是SMA治疗评估的关键，因为它们将长期结果的评估作为背景。
