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Brain Structural Features of Myotonic Dystrophy Type 1 and their Relationship with CTG Repeats
BACKGROUND: Few adequately-powered studies have systematically evaluated brain morphology in adult-onset myotonic dystrophy type 1 (DM1). OBJECTIVE: The goal of the present study was to determine structural brain differences between individuals with and without adult-onset DM1 in a multi-site, case-...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480174/ https://www.ncbi.nlm.nih.gov/pubmed/31306140 http://dx.doi.org/10.3233/JND-190397 |
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author | van der Plas, Ellen Hamilton, Mark J. Miller, Jacob N. Koscik, Timothy R. Long, Jeffrey D. Cumming, Sarah Povilaikaite, Julija Farrugia, Maria Elena McLean, John Jampana, Ravi Magnotta, Vincent A. Gutmann, Laurie Monckton, Darren G. Nopoulos, Peggy C. |
author_facet | van der Plas, Ellen Hamilton, Mark J. Miller, Jacob N. Koscik, Timothy R. Long, Jeffrey D. Cumming, Sarah Povilaikaite, Julija Farrugia, Maria Elena McLean, John Jampana, Ravi Magnotta, Vincent A. Gutmann, Laurie Monckton, Darren G. Nopoulos, Peggy C. |
author_sort | van der Plas, Ellen |
collection | PubMed |
description | BACKGROUND: Few adequately-powered studies have systematically evaluated brain morphology in adult-onset myotonic dystrophy type 1 (DM1). OBJECTIVE: The goal of the present study was to determine structural brain differences between individuals with and without adult-onset DM1 in a multi-site, case-controlled cohort. We also explored correlations between brain structure and CTG repeat length. METHODS: Neuroimaging data was acquired in 58 unaffected individuals (29 women) and 79 individuals with DM1 (50 women). CTG repeat length, expressed as estimated progenitor allele length (ePAL), was determined by small pool PCR. Statistical models were adjusted for age, sex, site, and intracranial volume (ICV). RESULTS: ICV was reduced in DM1 subjects compared with controls. Accounting for the difference in ICV, the DM1 group exhibited smaller volume in frontal grey and white matter, parietal grey matter as well as smaller volume of the corpus callosum, thalamus, putamen, and accumbens. In contrast, volumes of the hippocampus and amygdala were significantly larger in DM1. Greater ePAL was associated with lower volumes of the putamen, occipital grey matter, and thalamus. A positive ePAL association was observed for amygdala volume and cerebellar white matter. CONCLUSIONS: Smaller ICV may be a marker of aberrant neurodevelopment in adult-onset DM1. Volumetric analysis revealed morphological differences, some associated with CTG repeat length, in structures with plausible links to key DM1 symptoms including cognitive deficits and excessive daytime somnolence. These data offer further insights into the basis of CNS disease in DM1, and highlight avenues for further work to identify therapeutic targets and imaging biomarkers. |
format | Online Article Text |
id | pubmed-7480174 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
record_format | MEDLINE/PubMed |
spelling | pubmed-74801742020-09-09 Brain Structural Features of Myotonic Dystrophy Type 1 and their Relationship with CTG Repeats van der Plas, Ellen Hamilton, Mark J. Miller, Jacob N. Koscik, Timothy R. Long, Jeffrey D. Cumming, Sarah Povilaikaite, Julija Farrugia, Maria Elena McLean, John Jampana, Ravi Magnotta, Vincent A. Gutmann, Laurie Monckton, Darren G. Nopoulos, Peggy C. J Neuromuscul Dis Article BACKGROUND: Few adequately-powered studies have systematically evaluated brain morphology in adult-onset myotonic dystrophy type 1 (DM1). OBJECTIVE: The goal of the present study was to determine structural brain differences between individuals with and without adult-onset DM1 in a multi-site, case-controlled cohort. We also explored correlations between brain structure and CTG repeat length. METHODS: Neuroimaging data was acquired in 58 unaffected individuals (29 women) and 79 individuals with DM1 (50 women). CTG repeat length, expressed as estimated progenitor allele length (ePAL), was determined by small pool PCR. Statistical models were adjusted for age, sex, site, and intracranial volume (ICV). RESULTS: ICV was reduced in DM1 subjects compared with controls. Accounting for the difference in ICV, the DM1 group exhibited smaller volume in frontal grey and white matter, parietal grey matter as well as smaller volume of the corpus callosum, thalamus, putamen, and accumbens. In contrast, volumes of the hippocampus and amygdala were significantly larger in DM1. Greater ePAL was associated with lower volumes of the putamen, occipital grey matter, and thalamus. A positive ePAL association was observed for amygdala volume and cerebellar white matter. CONCLUSIONS: Smaller ICV may be a marker of aberrant neurodevelopment in adult-onset DM1. Volumetric analysis revealed morphological differences, some associated with CTG repeat length, in structures with plausible links to key DM1 symptoms including cognitive deficits and excessive daytime somnolence. These data offer further insights into the basis of CNS disease in DM1, and highlight avenues for further work to identify therapeutic targets and imaging biomarkers. 2019 /pmc/articles/PMC7480174/ /pubmed/31306140 http://dx.doi.org/10.3233/JND-190397 Text en http://creativecommons.org/licenses/by/4.0/ This article is published online with Open Access and distributed under the terms of the Creative Commons Attribution Non-Commercial License (CC BY-NC 4.0). |
spellingShingle | Article van der Plas, Ellen Hamilton, Mark J. Miller, Jacob N. Koscik, Timothy R. Long, Jeffrey D. Cumming, Sarah Povilaikaite, Julija Farrugia, Maria Elena McLean, John Jampana, Ravi Magnotta, Vincent A. Gutmann, Laurie Monckton, Darren G. Nopoulos, Peggy C. Brain Structural Features of Myotonic Dystrophy Type 1 and their Relationship with CTG Repeats |
title | Brain Structural Features of Myotonic Dystrophy Type 1 and their Relationship with CTG Repeats |
title_full | Brain Structural Features of Myotonic Dystrophy Type 1 and their Relationship with CTG Repeats |
title_fullStr | Brain Structural Features of Myotonic Dystrophy Type 1 and their Relationship with CTG Repeats |
title_full_unstemmed | Brain Structural Features of Myotonic Dystrophy Type 1 and their Relationship with CTG Repeats |
title_short | Brain Structural Features of Myotonic Dystrophy Type 1 and their Relationship with CTG Repeats |
title_sort | brain structural features of myotonic dystrophy type 1 and their relationship with ctg repeats |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480174/ https://www.ncbi.nlm.nih.gov/pubmed/31306140 http://dx.doi.org/10.3233/JND-190397 |
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