Yonsei Med J.  2017 Jul;58(4):807-815. 10.3349/ymj.2017.58.4.807.

Cortical Thickness and White Matter Integrity are Associated with CTG Expansion Size in Myotonic Dystrophy Type I

• Yoo WK
• Park YG
• Choi YC
• Kim SM

• KMID: 2419088
• DOI: http://doi.org/10.3349/ymj.2017.58.4.807

Abstract

PURPOSE
Myotonic dystrophy type 1 (DM1) is characterized by progressive muscular weakness with symptoms caused by involvement of the brain. The aim of this study was to delineate global changes in cortical thickness and white matter integrity in patients with DM1, compared to age-matched healthy controls, and in brain areas highly correlated with CTG repeat size.
MATERIALS AND METHODS
Cortical thickness and white matter integrity were compared in nine adult DM1 patients and age matched healthy controls using T1-weighted and diffusion tensor imaging. The patients' intelligence quotient (IQ) and CTG repeat size were measured in each individual.
RESULTS
Cortical thickness was significantly reduced in the frontal, temporal, and occipital cortices, while tract-based spatial statistics showed decreased diffusion metrics in widespread areas, including the bilateral orbitofrontal, anterior frontal, insular, external capsule, and occipital cortices in DM1 patients, compared to controls. Additionally, thickness was negatively correlated with the number of CTG repeats in those areas. White matter integrity was negatively correlated with CTG repeats in the left entorhinal, anterior corona radiata, orbitofrontal, and lateral occipital areas. No statistically significant correlation was found between IQ scores and the size of CTG repeats.
CONCLUSION
Our results suggest that DM1 is associated with wide distributions of network changes in both gray and white matter. Some of areas related to cognition showed significant correlations with CTG repeats.

Keyword

Myotonia; cognitive function; myelinopathy; resting network; orbitofrontal network; CTG expansion size

MeSH Terms

Adult
Case-Control Studies
Cerebral Cortex/*pathology
Demography
Diffusion Tensor Imaging
Female
Humans
Intelligence Tests
Male
Middle Aged
Myotonic Dystrophy/*genetics/*pathology
Trinucleotide Repeat Expansion/*genetics
White Matter/*pathology
Young Adult

Figure

• 

  Fig. 1 MRI images of cortical thickness (A) and white matter integrity (B) maps based on age-adjusted means of patients compared to those of healthy control subjects (n=9). (A) The map shows the distribution of p-values for pairwise comparisons between patients and healthy controls (p=0.01 to p=0.00001). Blue color represents decreased cortical thickness in patients with myotonia compared to controls (p<0.01 corrected for multiple comparisons; Monte Carlo simulation: 10000 iterations). The color-coding for p-values is on a logarithmic scale of 1–5. Cooler colors (negative values) represent cortical thinning. (B) TBSS shows decreased areas of white matter integrity in patients compared to controls (p<0.002; cluster-wise corrected). Blue color represents areas of decreased FA in patients compared to controls (right 1st row), whereas pink colored areas represent areas of increased AD (right 2nd row), and green colored area showed areas of increased RD (right 3rd row). TBSS, tract-based spatial statistics; FA, fractional anisotropy; AD, axial diffusivity; RD, radial diffusivity.

• 

  Fig. 2 Areas of correlation of cortical thickness (A) and FA value with number of CTG repeats (B). (A) Blue color represents areas where cortical thickness negatively correlated with the number of CTG repeats (p<0.01, uncorrected). (B) Red-orange color represents areas where FA value negatively correlated with the number of CTG repeats (p<0.003, uncorrected). FA, fractional anisotropy.

• 

  Fig. 3 Correlation of cortical thickness (A) and FA value (B), with number of CTG repeats (p<0.05). CT, cortical thickness; FA, fractional anisotropy.

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