2 型和 3 型脊髓性肌萎缩症患者的呼吸轨迹：iSMAC 队列研究。
Respiratory Trajectories in Type 2 and 3 Spinal Muscular Atrophy in the iSMAC Cohort Study.
机构信息
From the Dubowitz Neuromuscular Centre (F.T., M.S., M.L.M., F.M.) and Population, Policy and Practice Programme (D.R.), UCL GOS Institute of Child Health, London, UK; DINOGMI, University of Genoa (F.T.), IRCCS Istituto G. Gaslini, Italy; NIHR Great Ormond Street Hospital Biomedical Research Centre (D.R., F.M.), Great Ormond Street Institute of Child Health, University College London, and Great Ormond Street Hospital Trust, UK; Paediatric Neurology (G.C., M.P., E.M.), Catholic University; Centro Clinico Nemo (G.C., M.P., E.M.), Fondazione Policlinico Universitario Agostino Gemelli IRCSS, Rome, Italy; John Walton Muscular Dystrophy Research Centre (R.M.L., C.M.-B.), Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK; Departments of Neurology and Pediatrics (J.M., D.C.D.V.) and Departments of Rehabilitation and Regenerative Medicine (J.M.), Columbia University Irving Medical Center, New York, NY; Paediatric Neurology and Centro Clinico Nemo (V.S., E.A.), Milan; Unit of Neuromuscular and Neurodegenerative Disorders (A.D., E.B.), Post-Graduate Bambino Gesù Children's Research Hospital, IRCCS, Rome; Department of Clinical and Experimental Medicine (S.M.), University of Messina Paediatric Neurology and Nemo Sud Clinical Centre; Center of Translational and Experimental Myology (C.B.), IRCCS Istituto Giannina Gaslini, Genova, Italy; University Hospitals Birmingham NHSFT (D.P.); Leeds Children Hospital (A.-M.C.); Evelina Children's Hospital (V.G.), London; The Robert Jones and Agnes Hunt Orthopaedic Hospital (T.W.), Oswestry; Sheffield Children's Hospital (M.O.), UK; Department of Neurology (B.T.D.), Boston Children's Hospital and Harvard Medical School, MA; Stanford University (J.D.), Medical Centre, Palo Alto, CA; Divisions of Pediatric Neurology (E.A.K.), Pulmonology (O.H.M.) and Physical Therapy (A.M.G.), The Children's Hospital of Philadelphia, and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia; and Divisions of Neurology (R.S.F.) and Pulmonary Medicine (A.A.N.N.), Department of Pediatrics, Nemours Children's Hospital, Orlando, FL.
出版信息
Neurology. 2021 Jan 26;96(4):e587-e599. doi: 10.1212/WNL.0000000000011051. Epub 2020 Oct 16.
OBJECTIVE
To describe the respiratory trajectories and their correlation with motor function in an international pediatric cohort of patients with type 2 and nonambulant type 3 spinal muscular atrophy (SMA).
METHODS
This was an 8-year retrospective observational study of patients in the International SMA Consortium (iSMAc) natural history study. We retrieved anthropometrics, forced vital capacity (FVC) absolute, FVC percent predicted (FVC%P), and noninvasive ventilation (NIV) requirement. Hammersmith Functional Motor Scale (HFMS) and revised Performance of Upper Limb (RULM) scores were correlated with respiratory function. We excluded patients in interventional clinical trials and on nusinersen commercial therapy.
RESULTS
There were 437 patients with SMA: 348 with type 2 and 89 with nonambulant type 3. Mean age at first visit was 6.9 (±4.4) and 11.1 (±4) years. In SMA type 2, FVC%P declined by 4.2%/y from 5 to 13 years, followed by a slower decline (1.0%/y). In type 3, FVC%P declined by 6.3%/y between 8 and 13 years, followed by a slower decline (0.9%/y). Thirty-nine percent with SMA type 2% and 9% with type 3 required NIV at a median age 5.0 (1.8-16.6) and 15.1 (13.8-16.3) years. Eighty-four percent with SMA type 2% and 80% with type 3 had scoliosis; 54% and 46% required surgery, which did not significantly affect respiratory decline. FVC%P positively correlated with HFMS and RULM scores in both subtypes.
CONCLUSIONS
In SMA type 2 and nonambulant type 3, lung function declines differently, with a common leveling after age 13 years. Lung and motor function correlated in both subtypes. Our data further define the milder SMA phenotypes and provide information to benchmark the long-term efficacy of new treatments for SMA.
目的
描述 2 型和非运动型 3 型脊髓性肌萎缩症（SMA）国际儿科队列患者的呼吸轨迹及其与运动功能的相关性。
方法
这是一项对国际 SMA 联合会（iSMAc）自然史研究中患者进行的 8 年回顾性观察研究。我们检索了人体测量学、用力肺活量（FVC）绝对值、FVC%预测值（FVC%P）和无创通气（NIV）需求。哈默史密斯运动功能量表（HFMS）和修订后的上肢功能量表（RULM）评分与呼吸功能相关。我们排除了接受干预性临床试验和接受 nusinersen 商业治疗的患者。
结果
共有 437 名 SMA 患者：348 名 2 型，89 名非运动型 3 型。首次就诊时的平均年龄为 6.9（±4.4）岁和 11.1（±4）岁。在 2 型 SMA 中，FVC%P 从 5 岁到 13 岁每年下降 4.2%，然后下降速度较慢（1.0%/年）。在 3 型 SMA 中，FVC%P 在 8 至 13 岁之间每年下降 6.3%，然后下降速度较慢（0.9%/年）。39%的 2 型 SMA 患者和 9%的 3 型 SMA 患者需要在中位年龄 5.0（1.8-16.6）和 15.1（13.8-16.3）岁时接受 NIV。84%的 2 型 SMA 患者和 80%的 3 型 SMA 患者有脊柱侧凸；54%和 46%需要手术，但这并没有显著影响呼吸功能的下降。FVC%P 在两种亚型中均与 HFMS 和 RULM 评分呈正相关。
结论
在 2 型 SMA 和非运动型 3 型 SMA 中，肺功能下降方式不同，13 岁后趋于稳定。两种亚型的肺功能和运动功能均相关。我们的数据进一步定义了更轻微的 SMA 表型，并为新 SMA 治疗方法的长期疗效提供了基准。
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