Background

Most long-term affected spinal muscular atrophy (SMA) type 1 patients have severe impairment of motor function and are dependent on mechanical ventilation with tracheostomy. The efficacy and safety of nusinersen in these patients have not been established.

Methods

We retrospectively evaluated the efficacy of intrathecal nusinersen treatment in patients with SMA type 1 who continued treatment for at least 12 months. There were three patients enrolled in our study (3, 4 and 16 years of age) who had severe impairment of gross motor function without head control or the ability to roll over. All three needed mechanical ventilation with tracheostomy and tube feeding. Motor function was assessed using the Children s Hospital of Philadelphia infant test of neuromuscular disorders (CHOP-INTEND) and the caregivers’ evaluations. Concurrently, we examined nerve conduction longitudinally and compared compound motor action potential (CMAP) amplitudes.

Results

All patients continued nusinersen administration without significant adverse events for more than three years. While CHOP-INTEND scores did not remarkably increase, according to the caregivers, all three patients had improved finger or facial muscle movements that enabled them to make their intentions understood. Some CMAPs before treatment were not identified but became traces after nusinersen administration.

Conclusions

The improvement in motor function that leads to smoother communication could be a basis for continuing nusinersen treatment. Currently available motor function scorings are not efficient for assessing therapeutic interventions in SMA patients with medical care complexity. Longitudinal nerve conduction studies could be an objective indicator.

中文翻译：

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Nusinersen 在运动功能严重受损的 1 型脊髓性肌萎缩症患者中诱导复合运动动作电位反应的可检测变化

 背景

大多数长期受影响的 1 型脊髓性肌萎缩症 (SMA) 患者运动功能严重受损，依赖气管造口机械通气。 nusinersen 在这些患者中的疗效和安全性尚未确定。

 方法

我们回顾性评估了鞘内 nusinersen 治疗对持续治疗至少 12 个月的 1 型 SMA 患者的疗效。我们的研究中登记了三名患者（年龄分别为 3 岁、4 岁和 16 岁），他们的粗大运动功能严重受损，无法控制头部或翻身。所有三人都需要通过气管切开术和管饲进行机械通气。使用费城儿童医院婴儿神经肌肉疾病测试 (CHOP-INTEND) 和护理人员的评估来评估运动功能。同时，我们纵向检查神经传导并比较复合运动动作电位（CMAP）幅度。

 结果

所有患者持续服用nusinersen超过三年，没有出现明显的不良事件。据护理人员称，虽然 CHOP-INTEND 分数没有显着增加，但所有三名患者的手指或面部肌肉运动都有所改善，使他们能够表达自己的意图。一些CMAP在治疗前未被识别，但在nusinersen给药后成为痕迹。

 结论

运动功能的改善导致沟通更加顺畅，这可能是继续努西那森治疗的基础。目前可用的运动功能评分无法有效评估医疗护理复杂的 SMA 患者的治疗干预措施。纵向神经传导研究可能是一个客观指标。