Department of Psychiatry, Carver College of Medicine, University of Iowa, 200 Hawkins Drive, Iowa City, IA, 52242, USA.
Department of Neurology, Carver College of Medicine, University of Iowa, Iowa City, USA.
Sci Rep. 2021 Mar 1;11(1):4886. doi: 10.1038/s41598-021-84520-2.
Deficits in white matter (WM) integrity and motor symptoms are among the most robust and reproducible features of myotonic dystrophy type 1 (DM1). In the present study, we investigate whether WM integrity, obtained from diffusion-weighted MRI, corresponds to quantifiable motor outcomes (e.g., fine motor skills and grip strength) and patient-reported, subjective motor deficits. Critically, we explore these relationships in the context of other potentially causative variables, including: disease duration, elapsed time since motor symptom onset; and genetic burden, the number of excessive CTG repeats causing DM1. We found that fractional anisotropy (a measure of WM integrity) throughout the cerebrum was the strongest predictor of grip strength independently of disease duration and genetic burden, while radial diffusivity predicted fine motor skill (peg board performance). Axial diffusivity did not predict motor outcomes. Our results are consistent with the notion that systemic degradation of WM in DM1 mediates the relationship between DM1 progression and genetic burden with motor outcomes of the disease. Our results suggest that tracking changes in WM integrity over time may be a valuable biomarker for tracking therapeutic interventions, such as future gene therapies, for DM1.
在 1 型肌强直性营养不良（DM1）患者中，脑白质（WM）完整性缺陷和运动症状是最显著且可重现的特征之一。在本研究中，我们探究了弥散加权 MRI 得到的 WM 完整性是否与可量化的运动结果（如精细运动技能和握力）以及患者报告的主观运动缺陷相关。重要的是，我们在其他潜在致病因素的背景下探讨了这些关系，包括：疾病持续时间、运动症状出现后的时间间隔；以及引起 DM1 的异常 CTG 重复数量（即遗传负担）。我们发现，大脑各处的各向异性分数（衡量 WM 完整性的指标）是独立于疾病持续时间和遗传负担预测握力的最强指标，而径向弥散度则预测精细运动技能（钉板测试表现）。轴向弥散度不能预测运动结果。我们的研究结果与以下观点一致，即在 DM1 中，WM 的系统性退化介导了疾病进展和遗传负担与运动结果之间的关系。我们的研究结果表明，随着时间的推移跟踪 WM 完整性的变化可能是跟踪治疗干预（如未来的基因治疗）的有价值的生物标志物，适用于 DM1。
