Monitoring Nusinersen Treatment Effects in Children with Spinal Muscular Atrophy with Quantitative Muscle MRI

IF 3.2 4区 医学 Q2 CLINICAL NEUROLOGY
L. Otto, M. Froeling, R. V. van Eijk, R. Wadman, I. Cuppen, Danny R van der Woude, B. Bartels, F. Asselman, Jeroen Hendrikse, W. L. van der Pol
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Abstract

Background: Spinal muscular atrophy (SMA) is caused by deficiency of survival motor neuron (SMN) protein. Intrathecal nusinersen treatment increases SMN protein in motor neurons and has been shown to improve motor function in symptomatic children with SMA. Objective: We used quantitative MRI to gain insight in microstructure and fat content of muscle during treatment and to explore its use as biomarker for treatment effect. Methods: We used a quantitative MRI protocol before start of treatment and following the 4th and 6th injection of nusinersen in 8 children with SMA type 2 and 3 during the first year of treatment. The MR protocol allowed DIXON, T2 mapping and diffusion tensor imaging acquisitions. We also assessed muscle strength and motor function scores. Results: Fat fraction of all thigh muscles with the exception of the m. adductor longus increased in all patients during treatment (+3.2%, p = 0.02). WaterT2 showed no significant changes over time (–0.7 ms, p = 0.3). DTI parameters MD and AD demonstrate a significant decrease in the hamstrings towards values observed in healthy muscle. Conclusions: Thigh muscles of children with SMA treated with nusinersen showed ongoing fatty infiltration and possible normalization of thigh muscle microstructure during the first year of nusinersen treatment. Quantitative muscle MRI shows potential as biomarker for the effects of SMA treatment strategies.
用定量肌肉磁共振成像监测脊髓肌肉萎缩症儿童的纽西奈森治疗效果
背景:脊髓性肌萎缩症(SMA)是由存活运动神经元(SMN)蛋白缺乏引起的。鞘内nusinersen治疗增加运动神经元中的SMN蛋白,并已被证明可改善有症状的SMA儿童的运动功能。目的:利用定量MRI技术了解治疗过程中肌肉的微观结构和脂肪含量,并探讨其作为治疗效果的生物标志物。方法:我们对8例2型和3型SMA患儿在治疗开始前和治疗第一年第4次和第6次注射nusinersen后进行定量MRI检查。MR协议允许DIXON, T2映射和扩散张量成像获取。我们还评估了肌肉力量和运动功能评分。结果:除长内收肌外,所有患者在治疗期间所有大腿肌肉的脂肪含量均增加(+3.2%,p = 0.02)。WaterT2随时间变化不显著(-0.7 ms, p = 0.3)。DTI参数MD和AD显示腘绳肌与健康肌肉相比显著降低。结论:nusinersen治疗的SMA儿童大腿肌肉在nusinersen治疗的第一年表现出持续的脂肪浸润和可能的大腿肌肉微结构正常化。定量肌肉MRI显示了作为SMA治疗策略效果的生物标志物的潜力。
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来源期刊
Journal of neuromuscular diseases
Journal of neuromuscular diseases Medicine-Neurology (clinical)
CiteScore
5.10
自引率
6.10%
发文量
102
期刊介绍: The Journal of Neuromuscular Diseases aims to facilitate progress in understanding the molecular genetics/correlates, pathogenesis, pharmacology, diagnosis and treatment of acquired and genetic neuromuscular diseases (including muscular dystrophy, myasthenia gravis, spinal muscular atrophy, neuropathies, myopathies, myotonias and myositis). The journal publishes research reports, reviews, short communications, letters-to-the-editor, and will consider research that has negative findings. The journal is dedicated to providing an open forum for original research in basic science, translational and clinical research that will improve our fundamental understanding and lead to effective treatments of neuromuscular diseases.
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