White matter microstructure relates to motor outcomes in myotonic dystrophy type 1 independently of disease duration and genetic burden

Abstract 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...

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Autores principales:	Timothy R. Koscik, Ellen van der Plas, Laurie Gutmann, Sarah A. Cumming, Darren G. Monckton, Vincent Magnotta, Richard K. Shields, Peggy C. Nopoulos
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0e5a87339ef14fe0b3a871680f6a4da9
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spelling	oai:doaj.org-article:0e5a87339ef14fe0b3a871680f6a4da92021-12-02T15:53:00ZWhite matter microstructure relates to motor outcomes in myotonic dystrophy type 1 independently of disease duration and genetic burden10.1038/s41598-021-84520-22045-2322https://doaj.org/article/0e5a87339ef14fe0b3a871680f6a4da92021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84520-2https://doaj.org/toc/2045-2322Abstract 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.Timothy R. KoscikEllen van der PlasLaurie GutmannSarah A. CummingDarren G. MoncktonVincent MagnottaRichard K. ShieldsPeggy C. NopoulosNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Timothy R. Koscik Ellen van der Plas Laurie Gutmann Sarah A. Cumming Darren G. Monckton Vincent Magnotta Richard K. Shields Peggy C. Nopoulos White matter microstructure relates to motor outcomes in myotonic dystrophy type 1 independently of disease duration and genetic burden
description	Abstract 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.
format	article
author	Timothy R. Koscik Ellen van der Plas Laurie Gutmann Sarah A. Cumming Darren G. Monckton Vincent Magnotta Richard K. Shields Peggy C. Nopoulos
author_facet	Timothy R. Koscik Ellen van der Plas Laurie Gutmann Sarah A. Cumming Darren G. Monckton Vincent Magnotta Richard K. Shields Peggy C. Nopoulos
author_sort	Timothy R. Koscik
title	White matter microstructure relates to motor outcomes in myotonic dystrophy type 1 independently of disease duration and genetic burden
title_short	White matter microstructure relates to motor outcomes in myotonic dystrophy type 1 independently of disease duration and genetic burden
title_full	White matter microstructure relates to motor outcomes in myotonic dystrophy type 1 independently of disease duration and genetic burden
title_fullStr	White matter microstructure relates to motor outcomes in myotonic dystrophy type 1 independently of disease duration and genetic burden
title_full_unstemmed	White matter microstructure relates to motor outcomes in myotonic dystrophy type 1 independently of disease duration and genetic burden
title_sort	white matter microstructure relates to motor outcomes in myotonic dystrophy type 1 independently of disease duration and genetic burden
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/0e5a87339ef14fe0b3a871680f6a4da9
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White matter microstructure relates to motor outcomes in myotonic dystrophy type 1 independently of disease duration and genetic burden

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