Shedding light on motor premanifest myotonic dystrophy type 1: A molecular, muscular and central nervous system follow‐up study

BACKGROUND AND PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.