无力发作后开始使用 nusinersen 并不能预防髋关节不稳定的进展。

Nusinersen Initiation After Onset of Weakness Does Not Prevent Progression of Hip Instability.

机构信息

Department of Orthopaedics & Traumatology, Hong Kong Children's Hospital.

Department of Orthopaedics & Traumatology, Duchess of Kent Children's Hospital.

出版信息

J Pediatr Orthop. 2024 Aug 1;44(7):e657-e661. doi: 10.1097/BPO.0000000000002709. Epub 2024 May 1.

DOI:10.1097/BPO.0000000000002709

PMID:38689487

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11232935/

Abstract

BACKGROUND

We report changes in the natural history of hip instability with nusinersen treatment among patients with spinal muscular atrophy (SMA) type II after onset of weakness, historically wheelchair-bound but now potentially ambulatory in the era of disease-modifying therapy.

METHODS

Patients with genetically confirmed diagnoses of SMA type II who received intrathecal nusinersen from January 1, 2018, to June 30, 2022, were screened for inclusion. Patients with less than 6 months of follow-up, or prior hip surgeries were excluded. Primary clinical outcome measures included scores from Hammersmith motor functional scale expanded (HMFSE), revised upper limb module (RULM), 6-minute walk test (6MWT), and ambulatory status. Radiographic outcomes, including Reimer migration index, the presence of scoliosis, and pelvic obliquity, were also assessed. Secondary outcomes involved comparisons with a historical cohort of SMA type II patients treated at our institution who never received nusinersen.

RESULTS

Twenty hips from 5 boys and 5 girls were included in the analysis, with a mean follow-up of 3 years and 8 months. The median age at time of nusinersen initiation was 6.8 years old, ranging between 2.5 and 10.3 years. All patients developed lower limb motor weakness before nusinersen initiation. After treatment with nusinersen, 1 previously stable hip (5%) developed subluxation, 15 hips (75%) remain subluxated, 3 hips (15%) remain dislocated, and 1 hip (5%) remained stable, with a statistically significant difference between the pretreatment and posttreatment groups ( P <0.01). Six patients (60%) were ambulatory at latest follow-up. Six patients (60%) had improved ambulatory ability; 2 had static ambulatory ability (20%); and 2 had deterioration in their walking ability. The median HFMSE score improved from 18.5 (range 0 to 46) to 22 (range 0 to 49) ( P =0.813), whereas the median RULM score improved from 17 (range 2 to 28) to 21.5 (range 5 to 37), which was statistically significant ( P =0.007).

CONCLUSIONS

Hip instability persists despite treatment with nusinersen among patients with SMA type II who received nusinersen after onset of lower limb weakness.

LEVEL OF EVIDENCE

Therapeutic Level IV.

摘要

背景

我们报告了在接受脊髓性肌萎缩症（SMA）Ⅱ型治疗后，那些曾因下肢无力而历史上一直依赖轮椅、但现在在疾病修正治疗时代有潜在行走能力的患者，其髋关节不稳定的自然病史发生了变化。

方法

筛选了自 2018 年 1 月 1 日至 2022 年 6 月 30 日期间接受鞘内注射 nusinersen 的确诊为 SMA Ⅱ型的患者，以纳入研究。排除了随访时间不足 6 个月或之前有髋关节手术的患者。主要临床结局评估指标包括改良 Hammersmith 运动功能量表（HMFSE）、修订后的上肢模块（RULM）、6 分钟步行测试（6MWT）和活动状态评分。还评估了影像学结果，包括 Reimer 迁移指数、脊柱侧凸的存在和骨盆倾斜。次要结局涉及与我们机构治疗的从未接受过 nusinersen 治疗的 SMA Ⅱ型历史队列患者的比较。

结果

5 名男孩和 5 名女孩的 20 个髋关节纳入了分析，平均随访时间为 3 年 8 个月。开始使用 nusinersen 时的中位年龄为 6.8 岁，范围在 2.5 至 10.3 岁之间。所有患者在开始 nusinersen 治疗前均出现下肢运动无力。治疗后，1 个先前稳定的髋关节（5%）出现半脱位，15 个髋关节（75%）仍处于半脱位状态，3 个髋关节（15%）仍处于脱位状态，1 个髋关节（5%）保持稳定，治疗前后组间有统计学显著差异（P <0.01）。6 名患者（60%）在随访时能够行走。6 名患者（60%）的行走能力得到改善；2 名患者（20%）的静态行走能力得到改善；2 名患者（20%）的行走能力恶化。中位 HFMSE 评分从 18.5（范围 0 至 46）提高到 22（范围 0 至 49）（P =0.813），而中位 RULM 评分从 17（范围 2 至 28）提高到 21.5（范围 5 至 37），具有统计学意义（P =0.007）。