Department of Clinical and Health Psychology and Research Methodology, Psychology Faculty, University of the Basque Country (UPV/EHU), San Sebastián, Spain.
Neuroscience Area, Biodonostia Health Research Institute, Donostia-San Sebastián, Gipuzkoa, Spain.
Eur J Neurol. 2023 Jan;30(1):215-223. doi: 10.1111/ene.15604. Epub 2022 Oct 31.
Myotonic dystrophy type 1 (DM1) is a hereditary and multisystemic disease that is characterized by heterogeneous manifestations. Although muscular impairment is central to DM1, a premanifest DM1 form has been proposed for those characterized by the absence of muscle signs in precursory phases. Nevertheless, subtle signs and/or symptoms related to other systems, such as the central nervous system (CNS), may emerge and progress gradually. This study aimed to validate the premanifest DM1 concept and to characterize and track affected individuals from a CNS centred perspective.
Retrospective data of 120 participants (23 premanifest DM1, 25 manifest DM1 and 72 healthy controls) were analysed transversally and longitudinally (over 11.17 years). Compiled data included clinical, neuropsychological and neuroradiological (brain volume and white matter lesion, WML) measures taken at two time points.
Manifest DM1 showed significantly more molecular affectation, worse performance on neuropsychological domains, lower grey and white matter volumes and a different pattern of WMLs than premanifest DM1. The latter was slightly different from healthy controls regarding brain volume and WMLs. Additionally, daytime sleepiness and molecular expansion size explained 50% of the variance of the muscular deterioration at follow-up in premanifest individuals.
Premanifest DM1 individuals showed subtle neuroradiological alterations, which suggests CNS involvement early in the disease. Based on follow-up data, a debate emerges around the existence of a 'non-muscular DM1' subtype and/or a premanifest phase, as a precursory stage to other DM1 manifestations.
1 型肌强直性营养不良（DM1）是一种遗传性多系统疾病，其特征表现具有异质性。虽然肌肉损伤是 DM1 的核心，但已提出对于无前驱期肌肉表现的 DM1 患者存在预表现形式。然而，与中枢神经系统（CNS）等其他系统相关的细微体征和/或症状可能会逐渐出现和进展。本研究旨在验证预表现 DM1 概念，并从以中枢神经系统为中心的角度来描述和追踪受影响的个体。
回顾性分析了 120 名参与者（23 名预表现 DM1、25 名表现 DM1 和 72 名健康对照者）的横断和纵向数据（超过 11.17 年）。汇总的数据包括在两个时间点采集的临床、神经心理学和神经影像学（脑容量和白质病变，WML）测量值。
与预表现 DM1 相比，表现 DM1 表现出明显更多的分子受累、神经心理学领域表现更差、灰质和白质体积更低以及不同的 WML 模式。后者在脑容量和 WML 方面与健康对照组略有不同。此外，日间嗜睡和分子扩展大小解释了预表现个体随访时肌肉恶化的 50%的方差。
预表现 DM1 个体表现出细微的神经影像学改变，这表明疾病早期中枢神经系统受累。基于随访数据，围绕是否存在“非肌肉型 DM1”亚型和/或预表现期，即其他 DM1 表现的前驱阶段，出现了争议。
