Lefeuvre C, Brisset M, Sarlon M, Petit N, Orlikowski D, Clair B, Thiry T, Carlier R-Y, Prigent H, Nicolas G, Annane D, Laforet P, Pouplin S
Neurology department, Raymond-Poincaré university hospital, AP-HP, Garches, France; Nord-Est-Île-de-France neuromuscular reference center, FHU PHENIX, France; Université Paris-Saclay, UVSQ, ERPHAN, 78000 Versailles, France.
Neurology department, Raymond-Poincaré university hospital, AP-HP, Garches, France; Nord-Est-Île-de-France neuromuscular reference center, FHU PHENIX, France; Université Paris-Saclay, UVSQ, ERPHAN, 78000 Versailles, France.
Rev Neurol (Paris). 2022 Mar;178(3):234-240. doi: 10.1016/j.neurol.2021.10.010. Epub 2022 Jan 6.
Spinal muscular atrophy (SMA) is a progressive neurodegenerative disease due to homozygous loss-of-function of the survival motor neuron gene SMN1 with absence of the functional SMN protein. Nusinersen, a costly intrathecally administered drug approved in 2017 in Europe, induces alternative splicing of the SMN2 gene, which then produces functional SMN protein, whose amount generally increases with the number of SMN2 gene copies.
We retrospectively collected data from consecutive wheelchair-bound adults with SMA managed at a single center in 2018-2020. The following were collected at each injection, on days 1, 14, 28, 63, 183, and 303: 32-item Motor Function Measurement (MFM) total score and D2 and D3 subscores; the Canadian Occupational Performance Measure (COPM) performance and satisfaction scores; and lung function tests. The patients were divided into two groups based on whether their MFM total score was<or≥the mean (15.6%). Adverse events were recorded.
We identified 18 patients who received 4 to 8 Nusinersen injections. No significant improvements occurred over time in any of the MFM scores or lung function test results, which did not differ between groups. The COPM performance score improved significantly from day 0 to day 303 in the high-MFM group and the COPM satisfaction score in the overall population from D0 to D183. Half the patients achieved the minimal clinically important difference for both COPM scores.
The overall stability of conventional motor assessment in this population with advanced disabilities is encouraging to use more sensitive tools based on self-perception and autonomy in daily life activities, such as COPM. Our finding of a significant COPM performance score improvement from days 0 to 303 only in the patients with initial MFM-32 scores above the mean in the population suggests that the severity of the baseline disabilities may affect treatment efficacy.
IV, retrospective observational cohort study.
脊髓性肌萎缩症（SMA）是一种进行性神经退行性疾病，由生存运动神经元基因SMN1的纯合功能丧失导致功能性SMN蛋白缺失所致。诺西那生是一种昂贵的鞘内注射药物，于2017年在欧洲获批，可诱导SMN2基因的可变剪接，进而产生功能性SMN蛋白，其数量通常随SMN2基因拷贝数增加而增多。
我们回顾性收集了2018年至2020年在单一中心接受治疗的连续成年轮椅型SMA患者的数据。在每次注射时，即第1、14、28、63、183和303天，收集以下数据：32项运动功能测量（MFM）总分及D2和D3子分数；加拿大职业表现测量（COPM）表现和满意度分数；以及肺功能测试。根据患者的MFM总分是<还是≥平均值（15.6%）将患者分为两组。记录不良事件。
我们确定了18例接受4至8次诺西那生注射的患者。任何MFM分数或肺功能测试结果均未随时间出现显著改善，两组之间也无差异。高MFM组的COPM表现分数从第零天到第303天有显著改善，总体人群的COPM满意度分数从D0到D183有显著改善。一半的患者在两项COPM分数上均达到了最小临床重要差异。
在这群重度残疾人群中，传统运动评估的总体稳定性令人鼓舞，促使我们使用基于自我认知和日常生活活动自主性的更敏感工具，如COPM。我们发现，仅在初始MFM-32分数高于人群平均值的患者中，COPM表现分数从第零天到第303天有显著改善，这表明基线残疾的严重程度可能会影响治疗效果。
IV，回顾性观察队列研究。
