Journal article
Brain Structural Features of Myotonic Dystrophy Type 1 and their Relationship with CTG Repeats
Journal of neuromuscular diseases, Vol.6(3), pp.321-332
2019
DOI: 10.3233/JND-190397
PMCID: PMC7480174
PMID: 31306140
Abstract
Few adequately-powered studies have systematically evaluated brain morphology in adult-onset myotonic dystrophy type 1 (DM1).
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.
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).
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.
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.
Details
- Title: Subtitle
- Brain Structural Features of Myotonic Dystrophy Type 1 and their Relationship with CTG Repeats
- Creators
- Ellen van der Plas - Department of Psychiatry, University of Iowa Hospital and Clinics, Iowa City, IA, USAMark J Hamilton - Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UKJacob N Miller - Department of Psychiatry, University of Iowa Hospital and Clinics, Iowa City, IA, USATimothy R Koscik - Department of Psychiatry, University of Iowa Hospital and Clinics, Iowa City, IA, USAJeffrey D Long - Department of Biostatistics, University of Iowa, College of Public Health, Iowa City, IA, USASarah Cumming - Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UKJulija Povilaikaite - Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UKMaria Elena Farrugia - Department of Neurology, Institute of Neurological Sciences, Queen Elizabeth University Hospital, Glasgow, UKJohn McLean - Department of Neuroradiology, Institute of Neurological Sciences, Queen Elizabeth University Hospital, Glasgow, UKRavi Jampana - Department of Neuroradiology, Institute of Neurological Sciences, Queen Elizabeth University Hospital, Glasgow, UKVincent A Magnotta - Department of Radiology, University of Iowa Hospital and Clinics, Iowa City, IA, USALaurie Gutmann - Department of Neurology, University of Iowa Hospital and Clinics, Iowa City, IA, USADarren G Monckton - Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UKPeggy C Nopoulos - Department of Psychiatry, University of Iowa Hospital and Clinics, Iowa City, IA, USA
- Resource Type
- Journal article
- Publication Details
- Journal of neuromuscular diseases, Vol.6(3), pp.321-332
- Publisher
- Netherlands
- DOI
- 10.3233/JND-190397
- PMID
- 31306140
- PMCID
- PMC7480174
- ISSN
- 2214-3599
- eISSN
- 2214-3602
- Grant note
- CAF/MD/15/01 / Chief Scientist Office R01 NS094387 / NINDS NIH HHS
- Language
- English
- Date published
- 2019
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Neurology; Radiology; Psychiatry; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Biostatistics
- Record Identifier
- 9984066381402771
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