诺西那生钠治疗脊柱侧凸脊髓性肌萎缩症患者的疗效及安全性研究

doi:10.12372/jcp.2025.24e1128

Abstract

Abstract:

Objective To investigate the efficacy and safety of nusinersen in patients with spinal muscular atrophy (SMA) complicated by scoliosis. Methods A retrospective analysis was performed on the clinical data of SMA patients with scoliosis who regularly received nusinersen treatment at the Spinal Center of our hospital from January 2022 to June 2024. The data encompassed basic information, surgical history, imaging examinations, etc., collected from the electronic medical record system. During the follow-up period, three scales, namely the Revised Upper Limb Module (RULM) score, the Hammersmith Functional Motor Scale-Expanded (HFMSE), and the Spinal Muscular Atrophy Independence Measure-Upper Limb Module (SMAIS-ULM), were employed to assess the patients. The results of these assessments were compared with pre-treatment baseline data. Results A total of 22 SMA patients were included in the analysis. The median age was 13.2 (9.8-21.8) years, and nearly half of the patients (41%) were unable to sit independently. The median pre-treatment Cobb angle was 101.0 (42.3-121.3) degrees, and 17 of these patients (77.3%) underwent scoliosis correction surgery during follow-up period. The median follow-up duration was 22 (13-26) months. After treatment with nusinersen, the RULM scores of the patients were significantly improved (P<0.001). The motor function of 18 patients (81.8%) showed clinically meaningful improvement. Moreover, the SMAIS-ULM scores of both the patients and their caregivers also increased. During the treatment process, 13 patients (59.1%) reported adverse reactions such as dizziness, nausea, and pain at the site of intrathecal injection. Additionally, 2 patients presented with diarrhea and alopecia. Conclusions Nusinersen has been shown to improve upper limb motor function in SMA patients complicated by scoliosis and enhance their independence in daily activities. This effect appears to be independent of surgical intervention and is associated with a favorable safety profile.

Key words: spinal muscular atrophy, nusinersen, scoliosis

CLC Number:

LIU Xinzhu, XING Xiaodong, LIU Yu, LIU Yan, JIANG Wengao, ZHANG Jian, YANG Junlin. Efficacy and safety of nusinersen in spinal muscular atrophy patients with scoliosis[J].Journal of Clinical Pediatrics, 2025, 43(10): 727-733.

Figures/Tables 3

Table 1

Figure 1

Figure 2

References 26

[1]	Mercuri E, Sumner CJ, Muntoni F, et al. Spinal muscular atrophy[J]. Nat Rev Dis Primers, 2022, 8(1): 52. doi: 10.1038/s41572-022-00380-8 pmid: 35927425
[2]	Xing X, Liu X, Li X, et al. Insights into spinal muscular atrophy from molecular biomarkers[J]. Neural Regen Res, 2025, 20(7): 1849-1863.
[3]	杨军林, 隋文渊, 张天元. 脊髓性肌萎缩症合并脊柱侧凸的临床诊治[J]. 临床儿科杂志, 2022, 40(3): 161-164.
	Yang JL, Sui WY, Zhang TY. Clinical diagnosis and treatment of spinal muscular atrophy with scoliosis[J]. Linchuang Erke Zazhi, 2022, 40(3): 161-164.
[4]	Mercuri E, Finkel RS, Muntoni F, et al. Diagnosis and management of spinal muscular atrophy: Part 1: Recommendations for diagnosis, rehabilitation, orthopedic and nutritional care[J]. Neuromuscul Disord, 2018, 28(2): 103-115.
[5]	Finkel RS, Chiriboga CA, Vajsar J, et al. Treatment of infantile-onset spinal muscular atrophy with nusinersen: a phase 2, open-label, dose-escalation study[J]. Lancet, 2016, 388(10063): 3017-3026. doi: S0140-6736(16)31408-8 pmid: 27939059
[6]	李海冰, 夏雨, 叶文松, 等. 脊髓性肌萎缩症髋关节和脊柱畸形的初步研究[J]. 中华小儿外科杂志, 2020, 41(10): 926-932.
	Li MB, Xia Y, Ye WS, et al. Preliminary research of hipor spinal deformity in children with spinal muscular atrophy[J]. Zhonghua Xiaoer Waike Zazhi, 2020, 41(10): 926-932.
[7]	Glanzman AM, O'Hagen JM, McDermott MP, et al. Validation of the expanded Hammersmith functional notor scale in spinal muscular atrophy type II and III[J]. J Child Neurol, 2011, 26(12): 1499-1507. doi: 10.1177/0883073811420294 pmid: 21940700
[8]	Mazzone ES, Mayhew A, Montes J, et al. Revised upper limb module for spinal muscular atrophy: development of a new module[J]. Muscle Nerve, 2017, 55(6): 869-874. doi: 10.1002/mus.25430 pmid: 27701745
[9]	Trundell D, Skalicky A, Staunton H, et al. Development of the SMA independence scale-upper limb module (SMAIS-ULM): a novel scale for individuals with Type 2 and non-ambulant Type 3 SMA[J]. J Neurol Sci, 2022, 432: 120059.
[10]	Glanzman AM, McDermott MP, Montes J, et al. Validation of the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND)[J]. Pediatr Phys Ther, 2011, 23(4): 322-326. doi: 10.1097/PEP.0b013e3182351f04 pmid: 22090068
[11]	Łusakowska A, Wójcik A, Frączek A, et al. Long-term nusinersen treatment across a wide spectrum of spinal muscular atrophy severity: a real-world experience[J]. Orphanet J Rare Dis, 2023, 18(1): 230. doi: 10.1186/s13023-023-02769-4 pmid: 37542300
[12]	Vázquez-Costa JF, Povedano M, Nascimiento-Osorio AE, et al. Validation of motor and functional scales for the evaluation of adult patients with 5q spinal muscular atrophy[J]. Eur J Neurol, 2022, 29(12): 3666-3675. doi: 10.1111/ene.15542 pmid: 36047967
[13]	Vázquez-Costa JF, Branas-Pampillón M, Medina-Cantillo J, et al. Validation of a set of instruments to assess patient- and caregiver-oriented measurements in spinal muscular atrophy: results of the SMA-TOOL study[J]. Neurol Ther, 2023, 12(1): 89-105.
[14]	Mercuri E, Deconinck N, Mazzone ES, et al. Safety and efficacy of once-daily risdiplam in type 2 and non-ambulant type 3 spinal muscular atrophy (SUNFISH part 2): a phase 3, double-blind, randomised, placebo-controlled trial[J]. Lancet Neurol, 2022, 21(1): 42-52. doi: 10.1016/S1474-4422(21)00367-7 pmid: 34942136
[15]	Chiriboga CA, Bruno C, Duong T, et al. JEWELFISH: 24-month results from an open-label study in non-treatment-naïve patients with SMA receiving treatment with risdiplam[J]. J Neurol, 2024, 271(8): 4871-4884. doi: 10.1007/s00415-024-12318-z pmid: 38733387
[16]	Alves CRR, Petrillo M, Spellman R, et al. Implications of circulating neurofilaments for spinal muscular atrophy treatment early in life: a case series[J]. Mol Ther Methods Clin Dev, 2021, 23: 524-538.
[17]	Parnetti L, Gaetani L, Di Filippo M. Serum neurofilament light chain as a preclinical marker of neurodegeneration[J]. Lancet Neurol, 2019, 18(12): 1070-1071. doi: S1474-4422(19)30405-3 pmid: 31701888
[18]	Finkel RS, Ryan MM, Pascual Pascual SI, et al. Scientific rationale for a higher dose of nusinersen[J]. Ann Clin Transl Neurol, 2022, 9(6): 819-829.
[19]	Reilly A, Chehade L, Kothary R. Curing SMA: Are we there yet?[J]. Gene Ther, 2023, 30(1-2): 8-17.
[20]	Groen EJN, Talbot K, Gillingwater TH. Advances in therapy for spinal muscular atrophy: promises and challenges[J]. Nat Rev Neurol, 2018, 14(4): 214-224. doi: 10.1038/nrneurol.2018.4 pmid: 29422644
[21]	Lapp HS, Freigang M, Hagenacker T, et al. Biomarkers in 5q-associated spinal muscular atrophy-a narrative review[J]. J Neurol, 2023, 270(9): 4157-4178. doi: 10.1007/s00415-023-11787-y pmid: 37289324
[22]	Messina S, Pane M, Sansone V, et al. Expanded access program with nusinersen in SMA type I in Italy: strengths and pitfalls of a successful experience[J]. Neuromuscul Disord, 2017, 27(12): 1084-1086.
[23]	Labianca L, Weinstein SL. Scoliosis and spinal muscular atrophy in the new world of medical therapy: providing lumbar access for intrathecal treatment in patients previously treated or undergoing spinal instrumentation and fusion[J]. J Pediatr Orthop B, 2019, 28(4): 393-396. doi: 10.1097/BPB.0000000000000632 pmid: 30932967
[24]	Machida S, Miyagi M, Saito W, et al. Posterior spinal correction and fusion durgery in patients with spinal muscular atrophy-associated scoliosis for whom treatment with nusinersen was planned[J]. Spine Surg Relat Res, 2021, 5(2): 109-113. doi: 10.22603/ssrr.2020-0091 pmid: 33842719
[25]	Wang Z, Feng E, Jiao Y, et al. Unilateral interlaminar fenestration on the convex side provides a reliable access for intrathecal administration of nusinersen in spinal muscular atrophy: a retrospective study[J]. Orphanet J Rare Dis, 2023, 18(1): 369. doi: 10.1186/s13023-023-02972-3 pmid: 38031122
[26]	Carson VJ, Young M, Brigatti KW, et al. Nusinersen by subcutaneous intrathecal catheter for symptomatic spinal muscular atrophy patients with complex spine anatomy[J]. Muscle Nerve, 2022, 65(1): 51-59.

项目	合计(n=22)	Ⅰ型(n=4)	Ⅱ型(n=12)	Ⅲ型(n=6)
性别[n(%)]
男	8(36.4)	2(50.0)	3(25.0)	3(50.0)
女	14(63.6)	2(50.0)	9(75.0)	3(50.0)
发病年龄[M(P₂₅~P₇₅)]/岁	0.9(0.5~1.5)	0.4(0.3~0.5)	0.8(0.6~1.2)	1.5(1.4~6.3)
入组年龄[M(P₂₅~P₇₅)]/岁	13.2(9.8~21.8)	4.8(0.6~18.0)	12.6(9.8~18.3)	19.1(13.6~26.1)
体质指数[M(P₂₅~P₇₅)/ kg·m^-2]	16.8(12.9~22.5)	13.3(9.4~16.1)	16.8(13.1~22.7)	18.9(15.9~24.1)
独走[n(%)]	2(9.0)	1(50.0)	1(50.0)	0(0)
独坐[n(%)]	11(50.0)	1(9.1)	6(54.5)	4(36.4)
SMN2的拷贝数[n(%)]
2拷贝	3(13.6)	1(33.3)	0(0)	2(66.7)
3拷贝	18(81.8)	3(16.7)	12(66.7)	3(16.7)
4拷贝	1(4.5)	0(0)	0(0)	1(100)
Cobb角[M(P₂₅~P₇₅)]/°	101.0(42.3~121.3)	59.0(12.3~120.0)	100.0(48.5~117.5)	105.5(75.0~142.8)
脊柱侧凸矫正术[n(%)]	17(77.3)	2(11.8)	10(58.8)	5(29.4)
肺通气功能限制性障碍[n(%)]	8(36.4)	2(25.0)	4(50.0)	2(25.0)
吞咽困难、饮水呛咳[n(%)]	6(27.3)	2(33.3)	3(50.0)	1(16.7)

Efficacy and safety of nusinersen in spinal muscular atrophy patients with scoliosis

RichHTML

PDF (PC)

Like

Knowledge

Abstract

Cite this article

share this article

Figures/Tables 3

References 26

Related Articles 15

Metrics

Comments

Recommended 0

[1]	. Expert consensus on pre-symptomatic treatment for pediatric spinal muscular atrophy (2025 edition) [J]. Journal of Clinical Pediatrics, 2025, 43(9): 643-651.
[2]	DUAN Haolin, ZHANG Ciliu, XIONG Juan, PANG Nan, YIN Fei, PENG Jing. Clinical efficacy analysis of disease-modifying therapies for spinal muscular atrophy with SMN1 gene compound heterozygous variants [J]. Journal of Clinical Pediatrics, 2025, 43(7): 543-548.
[3]	WANG Fan, MA Fei, DAI Wenjing, XIAO Bing, PAN Chenlin. Progress in multidisciplinary diagnosis and treatment of spinal muscular atrophy [J]. Journal of Clinical Pediatrics, 2025, 43(3): 233-236.
[4]	XING Xiaodong, LIU Yan, LIU Xinzhu, JIANG Wengao, ZHANG Jian. Medication therapy management of patients with spinal muscular atrophy during the perioperative period of scoliosis correction surgery [J]. Journal of Clinical Pediatrics, 2025, 43(1): 70-76.
[5]	WU Xian, LIU Yan, LIU Xinzhu, HUANG Xiaohui, MA Jing, XU A-jing, XIN Xiaodong, JIANG Wengao, ZHANG Jian. Advances in real-world research on disease-modifying treatments for spinal muscular atrophy [J]. Journal of Clinical Pediatrics, 2025, 43(1): 61-69.
[6]	LUO Zhiqiang, CHEN Li, LU Xinguo, LIAO Jianxiang, LUO Xufeng. The treatment of the first case of presymptomatic spinal muscular atropy in the Chinese Mainland: a case report with 43 months follow-up [J]. Journal of Clinical Pediatrics, 2025, 43(1): 40-44.
[7]	HE Guanlan, WEI Qiufen, LI Na, CHEN Shaoping, LIU Yunyuan, LIAO Shasha, TANG Xiuneng. Meta-analysis of clinical efficacy of nusinersen in the treatment of children with spinal muscular atrophy [J]. Journal of Clinical Pediatrics, 2023, 41(12): 946-954.
[8]	WANG Wenqiao, MAO Shanshan, MA Ming. Research progress in nutritional management of children with spinal muscular atrophy [J]. Journal of Clinical Pediatrics, 2022, 40(3): 235-240.
[9]	YAO Mei, FENG Yijie, XIA Yu, ZHOU Dongming, JIN Jianing, WEI Jia, CUI Yiqin, MAO Shanshan. A rare case of children with compound heterozygous variant of spinal muscular atrophy [J]. Journal of Clinical Pediatrics, 2022, 40(3): 212-217.
[10]	LUO Zhiqiang, LU Xinguo, LIU Liqin, LIAO Jianxiang. Clinical efficacy of nusinersen in treating presymptomatic 5q spinal muscular atrophy: a case report and literature review [J]. Journal of Clinical Pediatrics, 2022, 40(3): 208-211.
[11]	MAO Shanshan. Diagnosis and treatment of spinal muscular atrophy in China in the era of precision medicine [J]. Journal of Clinical Pediatrics, 2022, 40(3): 165-169.
[12]	YANG Junlin, SUI Wenyuan, ZHANG Tianyuan. Clinical diagnosis and treatment of spinal muscular atrophy with scoliosis [J]. Journal of Clinical Pediatrics, 2022, 40(3): 161-164.
[13]	ZHOU Lulu, DING Le, ZHENG Guo. TBCD gene variation causing tubulinopathy with atypical spinal muscular atrophy: one case report [J]. Journal of Clinical Pediatrics, 2022, 40(11): 854-857.
[14]	YAO Lingsong, LIN Xinzhu, SHEN Wei. Spinal muscular atrophy with congenital bone fractures-2: two cases in one family and literature review [J]. Journal of Clinical Pediatrics, 2021, 39(10): 750-.
[15]	CHEN Yuyi, HAN Yunli, LI Xing, et al. Clinical and genetic analysis of 31 children with spinal muscular atrophy [J]. Journal of Clinical Pediatrics, 2021, 39(10): 745-.