Evaluating the Effects of Nusinersen Treatment in Adults With Spinal Muscular Atrophy Using Axonal Excitability and MscanFit MUNE.

IF 3.1 3区 医学 Q2 CLINICAL NEUROLOGY
Muscle & Nerve Pub Date : 2025-09-01 Epub Date: 2025-07-24 DOI:10.1002/mus.28476
Abir Alaamel, Nazan Şimşek Erdem, Gökçe Yağmur Güneş Gencer, Hüseyin Can Kaya, Hilmi Uysal
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引用次数: 0

Abstract

Introduction/aims: The biological changes in motor neurons and motor axons that correlate with the clinical benefits of nusinersen, an antisense oligonucleotide, in spinal muscular atrophy (SMA) remain poorly understood. This study aimed to investigate changes in axonal excitability and motor unit number estimation (MUNE) parameters following a four-dose loading regimen of nusinersen in adult SMA patients.

Methods: Adult patients with SMA were assessed using the Hammersmith Functional Motor Scale Expanded (HFMSE) and the Medical Research Council (MRC) scale at baseline and after nusinersen treatment. Axonal excitability studies and MScanFit MUNE were conducted in SMA patients before and after treatment. Baseline axonal excitability and MScanFit MUNE parameters in SMA patients were compared with those of a healthy control (HC) group.

Results: Compared to the HC group (n = 10), SMA patients (n = 12) exhibited a significantly prolonged strength-duration time constant (SDTC), a higher resting current/voltage (I/V) slope, and prolonged refractoriness at 2.5 ms. However, no significant changes in axonal excitability parameters were observed following nusinersen treatment. Similarly, there were no significant changes in MUNE or in other parameters, including D50, compound muscle action potentials, and steps%. In contrast, a significant increase in HFMSE and MRC scores was observed after treatment (p < 0.01 and p = 0.01, respectively).

Discussion: A prolongation of SDTC, likely due to its effect on sodium channel function, was observed in this study, consistent with existing literature. Despite improvements in motor function, no significant electrophysiological changes were detected in adult SMA patients.

Abstract Image

利用轴突兴奋性和MscanFit MUNE评价Nusinersen治疗成人脊髓性肌萎缩的效果。
简介/目的:在脊髓性肌萎缩症(SMA)中,运动神经元和运动轴突的生物学变化与nusinersen(一种反义寡核苷酸)的临床益处相关,但人们对其了解甚少。本研究旨在探讨成人SMA患者轴突兴奋性和运动单位数估计(MUNE)参数在四剂量nusinsen负荷方案后的变化。方法:采用Hammersmith功能运动量表扩展版(HFMSE)和医学研究委员会(MRC)量表对成年SMA患者在基线和nusinersen治疗后进行评估。在治疗前后对SMA患者进行轴突兴奋性研究和MScanFit MUNE。将SMA患者的基线轴突兴奋性和MScanFit MUNE参数与健康对照组(HC)进行比较。结果:与HC组(n = 10)相比,SMA患者(n = 12)表现出明显延长的强度-持续时间常数(SDTC),更高的静息电流/电压(I/V)斜率,并且在2.5 ms时延长了耐火时间。然而,在nusinersen处理后,未观察到轴突兴奋性参数的显著变化。同样,MUNE或其他参数(包括D50、复合肌肉动作电位和步长%)也没有显著变化。相比之下,治疗后观察到HFMSE和MRC评分显著增加(p)。讨论:本研究观察到SDTC延长,可能是由于其对钠通道功能的影响,与现有文献一致。尽管运动功能有所改善,但在成年SMA患者中未检测到明显的电生理变化。
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来源期刊
Muscle & Nerve
Muscle & Nerve 医学-临床神经学
CiteScore
6.40
自引率
5.90%
发文量
287
审稿时长
3-6 weeks
期刊介绍: Muscle & Nerve is an international and interdisciplinary publication of original contributions, in both health and disease, concerning studies of the muscle, the neuromuscular junction, the peripheral motor, sensory and autonomic neurons, and the central nervous system where the behavior of the peripheral nervous system is clarified. Appearing monthly, Muscle & Nerve publishes clinical studies and clinically relevant research reports in the fields of anatomy, biochemistry, cell biology, electrophysiology and electrodiagnosis, epidemiology, genetics, immunology, pathology, pharmacology, physiology, toxicology, and virology. The Journal welcomes articles and reports on basic clinical electrophysiology and electrodiagnosis. We expedite some papers dealing with timely topics to keep up with the fast-moving pace of science, based on the referees'' recommendation.
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