Relationship of white and gray matter abnormalities to clinical and genetic features in myotonic dystrophy type 1

Abstract

Background: Myotonic dystrophy type 1 (DM1) represents a multisystemic disorder in which diffuse brain white and gray matter alterations related to clinical and genetic features have been described. We aimed to evaluate in the brain of adult patients with DM1 (i) white and gray matter differences, including cortical-subcortical gray matter volume and cortical thickness and (ii) their correlation with clinical disability, global neuropsychological performance and triplet expansion.

Methods: We included 24 adult genetically-confirmed DM1 patients (14 males; age: 38.5 ± 11.8 years) and 25 age- and sex-matched healthy controls (14 males; age: 38.5 ± 11.3 years) who underwent an identical brain MR protocol including high-resolution 3D T1-weighted, axial T2 FLAIR and DTI sequences. All patients underwent an extensive clinical and neuropsychological evaluation. Voxel-wise analyses of white matter, performed by using Tract Based Spatial Statistics, and of gray matter, with Voxel-based Morphometry and Cortical Thickness, were carried out in order to test for differences between patients with DM1 and healthy controls (p < 0.05, corrected). The correlation between MRI measures and clinical-genetic features was also assessed.

Results: Patients with DM1 showed widespread abnormalities of all DTI parameters in the white matter, which were associated with reduced gray matter volume in all brain lobes and thinning in parieto-temporo-occipital cortices, albeit with less extensive cortical alterations when congenital cases were removed from the analyses. White matter alterations correlated with clinical disability, global cognitive performance and triplet expansions.

Conclusion: In patients with DM1, the combined smaller overall gray matter volume and white matter alterations seem to be the main morpho-structural substrates of CNS involvement in this condition. The correlation of white matter differences with both clinical and genetic findings lends support to this notion.

Keywords: DTI; TBSS; VBM; cortical thickness; myotonic dystrophy type 1.

Fig. 1

Tract-based spatial statistics (TBSS) group comparison results, displayed at p < 0.05 corrected for multiple comparisons. Voxel-wise differences between myotonic dystrophy type 1 (DM1) patients and healthy controls (HC) are shown for fractional anisotropy (FA; in red, decreased in patients), mean diffusivity (MD; in blue, higher in patients), axial diffusivity (AD; in yellow, higher in patients) and radial diffusivity (RD; in violet, higher in patients) values. All statistical maps are overlaid on the group mean FA image and on the white matter skeleton mask (green). Images are shown in radiological convention. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 2

Tract-based spatial statistics (TBSS) correlations results, displayed at p < 0.05 corrected for multiple comparisons. Voxel-wise correlations between fractional anisotropy (FA) values and clinical variables in myotonic dystrophy type 1 (DM1) patients are shown in red. The correlations are all inverse, except for FA - MMSE which showed a direct correlation. All statistical maps (with tracts thickened for visualization purposes) are overlaid on the group mean FA image and on the white matter skeleton mask (green). Images are shown in radiological convention. Legend. MMSE: Mini-Mental State Examination; NP: neuropsychological. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 3

Voxel-based morphometry (VBM) group comparison results displayed at p < 0.05 corrected for multiple comparisons. Voxel-wise differences between myotonic dystrophy type 1 (DM1) patients and healthy controls are displayed with (1-p) values in red-to-white. Areas of gray matter atrophy are overlaid on the group gray matter template and shown in radiological convention. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 4

Group comparison results of cortical thickness (CT) analysis displayed at p < 0.05, corrected for multiple comparisons. Whole brain vertex-wise differences of cortical thickness between myotonic dystrophy type 1 (DM1) patients and healthy controls are displayed with − log10(p) values. Areas of gray matter thinning are overlaid on a reference gray matter surface; left hemisphere is shown on right and right hemisphere on left; lateral view on top and medial view at bottom.