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

Timothy R Koscik; Ellen van der Plas; Laurie Gutmann; Sarah A Cumming; Darren G Monckton; Vincent Magnotta; Richard K Shields; Peggy C Nopoulos

doi:10.1038/s41598-021-84520-2

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

Journal article

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Peer reviewed

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

Timothy R Koscik, Ellen van der Plas, Laurie Gutmann, Sarah A Cumming, Darren G Monckton, Vincent Magnotta, Richard K Shields and Peggy C Nopoulos

Scientific reports, Vol.11(1), pp.4886-4886

03/01/2021

DOI: 10.1038/s41598-021-84520-2

PMCID: PMC7921687

PMID: 33649422

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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.

Biomarkers

Neurology

Neuroscience

Motor control

Diseases of the nervous system

Diseases

Details

Title: Subtitle: White matter microstructure relates to motor outcomes in myotonic dystrophy type 1 independently of disease duration and genetic burden
Creators: Timothy R Koscik - 200 Hawkins Drive, Iowa City, IA 52242 USA
Ellen van der Plas - 200 Hawkins Drive, Iowa City, IA 52242 USA
Laurie Gutmann - Iowa City, USA
Sarah A Cumming - Glasgow, Scotland
Darren G Monckton - Glasgow, Scotland
Vincent Magnotta - Iowa City, USA
Richard K Shields - Iowa City, USA
Peggy C Nopoulos - 200 Hawkins Drive, Iowa City, IA 52242 USA
Resource Type: Journal article
Publication Details: Scientific reports, Vol.11(1), pp.4886-4886
DOI: 10.1038/s41598-021-84520-2
PMID: 33649422
PMCID: PMC7921687
NLM abbreviation: Sci Rep
ISSN: 2045-2322
eISSN: 2045-2322
Publisher: Nature Publishing Group UK; London
Grant note: NS094387 / ;
Language: English
Date published: 03/01/2021
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Neurology; Radiology; Psychiatry; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Orthopedics and Rehabilitation; Physical Therapy and Rehabilitation Science
Record Identifier: 9984070769602771

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