Sadettin Ciftci, Armagan C Ulusaloglu, M Wade Shrader, Mena T Scavina, William G Mackenzie, Robert Heinle, Kevin M Neal, Alec Stall, Jason J Howard
{"title":"脊髓肌肉萎缩症脊柱侧弯的发展:遗传严重程度、功能水平和疾病改变治疗的影响。","authors":"Sadettin Ciftci, Armagan C Ulusaloglu, M Wade Shrader, Mena T Scavina, William G Mackenzie, Robert Heinle, Kevin M Neal, Alec Stall, Jason J Howard","doi":"10.1097/BPO.0000000000002759","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Spinal muscular atrophy (SMA) is caused by abnormalities of the survival motor neuron (SMN) 1 gene, leading to deficiency in SMN protein and loss of spinal cord alpha motor neurons. Newer disease-modifying agents (DMA) targeting the involved genes, including nusinersen and gene replacement therapies, have improved gross motor and respiratory function, but their impact on scoliosis development has not been established. This study aimed to determine risk factors for scoliosis development in SMA, specifically genetic severity and DMA use.</p><p><strong>Methods: </strong>In this retrospective cohort study, children with SMA and minimum 2-year follow-up were included. The primary outcome was the prevalence of clinically relevant scoliosis. Secondary outcomes included SMA type, SMN2 copy number, Hammersmith Functional Motor Scale (HFMS), ambulatory status [functional mobility scale at 50m (FMS 50 )], DMA use, and hip displacement as risk factors. Univariate/multivariate logistic regression analyses were performed to identify dependent/independent risk factors.</p><p><strong>Results: </strong>One hundred sixty-five patients (51% female) with SMA types I-III met the inclusion criteria, with total follow-up of 9.8 years. The prevalence of scoliosis was 79%; age of onset 7.9 years. The major curve angle for the entire cohort at first assessment and final follow-up was 37 degrees (SD: 27 degrees) and 62 degrees (SD: 31 degrees) ( P <0.0001), respectively. Significant risk factors for scoliosis by univariate analysis were SMA type (I/II, P =0.02), HFMS (>23, P <0.001), nonambulatory status (FMS 50 =1, P <0.0001), DMA treatment ( P =0.02), and hip displacement ( P <0.0001). Multivariate analysis revealed that HFMS >23 ( P =0.02) and DMA ( P =0.05) treatment were independent (protective) risk factors.</p><p><strong>Conclusions: </strong>The development of scoliosis in SMA is high, with risk factors associated with proxy measures of disease severity, including SMA type, nonambulatory status, hip displacement, and most notably, gross motor function (by HFMS). DMA use and HFMS >23 were associated with a decreased risk of scoliosis development. Identified risk factors can be used in the development of surveillance programs for early detection of scoliosis in SMA.</p><p><strong>Level of evidence: </strong>Level III.</p>","PeriodicalId":16945,"journal":{"name":"Journal of Pediatric Orthopaedics","volume":null,"pages":null},"PeriodicalIF":1.4000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Scoliosis Development in Spinal Muscular Atrophy: The Influences of Genetic Severity, Functional Level, and Disease-Modifying Treatments.\",\"authors\":\"Sadettin Ciftci, Armagan C Ulusaloglu, M Wade Shrader, Mena T Scavina, William G Mackenzie, Robert Heinle, Kevin M Neal, Alec Stall, Jason J Howard\",\"doi\":\"10.1097/BPO.0000000000002759\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Spinal muscular atrophy (SMA) is caused by abnormalities of the survival motor neuron (SMN) 1 gene, leading to deficiency in SMN protein and loss of spinal cord alpha motor neurons. Newer disease-modifying agents (DMA) targeting the involved genes, including nusinersen and gene replacement therapies, have improved gross motor and respiratory function, but their impact on scoliosis development has not been established. This study aimed to determine risk factors for scoliosis development in SMA, specifically genetic severity and DMA use.</p><p><strong>Methods: </strong>In this retrospective cohort study, children with SMA and minimum 2-year follow-up were included. The primary outcome was the prevalence of clinically relevant scoliosis. Secondary outcomes included SMA type, SMN2 copy number, Hammersmith Functional Motor Scale (HFMS), ambulatory status [functional mobility scale at 50m (FMS 50 )], DMA use, and hip displacement as risk factors. Univariate/multivariate logistic regression analyses were performed to identify dependent/independent risk factors.</p><p><strong>Results: </strong>One hundred sixty-five patients (51% female) with SMA types I-III met the inclusion criteria, with total follow-up of 9.8 years. The prevalence of scoliosis was 79%; age of onset 7.9 years. The major curve angle for the entire cohort at first assessment and final follow-up was 37 degrees (SD: 27 degrees) and 62 degrees (SD: 31 degrees) ( P <0.0001), respectively. Significant risk factors for scoliosis by univariate analysis were SMA type (I/II, P =0.02), HFMS (>23, P <0.001), nonambulatory status (FMS 50 =1, P <0.0001), DMA treatment ( P =0.02), and hip displacement ( P <0.0001). 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引用次数: 0
摘要
背景:脊髓性肌萎缩症(SMA)由存活运动神经元(SMN)1基因异常引起,导致SMN蛋白缺乏和脊髓α运动神经元缺失。针对相关基因的新型疾病修饰药物(DMA),包括奴西那生和基因替代疗法,已经改善了大运动和呼吸功能,但它们对脊柱侧弯发展的影响尚未确定。本研究旨在确定SMA脊柱侧弯发生的风险因素,特别是遗传严重程度和DMA的使用:在这项回顾性队列研究中,纳入了至少随访 2 年的 SMA 患儿。主要结果是临床相关脊柱侧凸的患病率。次要结果包括作为风险因素的SMA类型、SMN2拷贝数、哈默史密斯功能运动量表(HFMS)、活动状态[50米处功能移动量表(FMS50)]、DMA使用情况和髋关节移位。进行了单变量/多变量逻辑回归分析,以确定依赖/独立风险因素:165名I-III型SMA患者(51%为女性)符合纳入标准,总随访时间为9.8年。脊柱侧弯发病率为79%,发病年龄为7.9岁。首次评估和最终随访时,整个群体的主要曲线角度分别为37度(标清:27度)和62度(标清:31度)(P23、P23(P=0.02)和DMA(P=0.05)治疗是独立的(保护性)风险因素:结论:SMA脊柱侧弯的发病率很高,其风险因素与疾病严重程度的代用指标相关,包括SMA类型、不行动状态、髋关节移位,以及最显著的粗大运动功能(通过HFMS)。使用 DMA 和 HFMS >23 与脊柱侧弯发生风险降低有关。确定的风险因素可用于制定监测计划,以早期发现SMA脊柱侧弯:证据等级:III级。
Scoliosis Development in Spinal Muscular Atrophy: The Influences of Genetic Severity, Functional Level, and Disease-Modifying Treatments.
Background: Spinal muscular atrophy (SMA) is caused by abnormalities of the survival motor neuron (SMN) 1 gene, leading to deficiency in SMN protein and loss of spinal cord alpha motor neurons. Newer disease-modifying agents (DMA) targeting the involved genes, including nusinersen and gene replacement therapies, have improved gross motor and respiratory function, but their impact on scoliosis development has not been established. This study aimed to determine risk factors for scoliosis development in SMA, specifically genetic severity and DMA use.
Methods: In this retrospective cohort study, children with SMA and minimum 2-year follow-up were included. The primary outcome was the prevalence of clinically relevant scoliosis. Secondary outcomes included SMA type, SMN2 copy number, Hammersmith Functional Motor Scale (HFMS), ambulatory status [functional mobility scale at 50m (FMS 50 )], DMA use, and hip displacement as risk factors. Univariate/multivariate logistic regression analyses were performed to identify dependent/independent risk factors.
Results: One hundred sixty-five patients (51% female) with SMA types I-III met the inclusion criteria, with total follow-up of 9.8 years. The prevalence of scoliosis was 79%; age of onset 7.9 years. The major curve angle for the entire cohort at first assessment and final follow-up was 37 degrees (SD: 27 degrees) and 62 degrees (SD: 31 degrees) ( P <0.0001), respectively. Significant risk factors for scoliosis by univariate analysis were SMA type (I/II, P =0.02), HFMS (>23, P <0.001), nonambulatory status (FMS 50 =1, P <0.0001), DMA treatment ( P =0.02), and hip displacement ( P <0.0001). Multivariate analysis revealed that HFMS >23 ( P =0.02) and DMA ( P =0.05) treatment were independent (protective) risk factors.
Conclusions: The development of scoliosis in SMA is high, with risk factors associated with proxy measures of disease severity, including SMA type, nonambulatory status, hip displacement, and most notably, gross motor function (by HFMS). DMA use and HFMS >23 were associated with a decreased risk of scoliosis development. Identified risk factors can be used in the development of surveillance programs for early detection of scoliosis in SMA.
期刊介绍:
Journal of Pediatric Orthopaedics is a leading journal that focuses specifically on traumatic injuries to give you hands-on on coverage of a fast-growing field. You''ll get articles that cover everything from the nature of injury to the effects of new drug therapies; everything from recommendations for more effective surgical approaches to the latest laboratory findings.