Relationship between neuropsychological impairment and grey and white matter changes in adult-onset myotonic dystrophy type 1

Abstract

Myotonic dystrophy type 1 (DM1) has a wide phenotypic spectrum and potentially may affect central nervous system with mild to severe involvement. Our aim was to investigate grey matter (GM) and white matter (WM) structural alterations in a sample of adult-onset DM1 patients and to evaluate relationship with clinical and cognitive variables. Thirty DM1 patients underwent neuropsychological investigation and 3T-MRI protocol. GM and WM changes were evaluated calculating brain parenchymal fraction (BPF), voxel-based morphometry (VBM), white matter lesion load (LL% and Fazekas scale) and tract based spatial statistical (TBSS). Patients showed main impairment in tests exploring executive and mnesic domains with visuo-spatial involvement, significantly related to BPF. VBM revealed clusters of widespread GM reduction and TBSS revealed areas of decreased fractional anisotropy (FA) and increased radial diffusivity (RD), mean diffusivity (MD) and axial diffusivity (AD) in patients compared to a group of matched healthy controls. Multiple regression analyses showed areas of significant negative relationship between left temporal atrophy and verbal memory, between RD and mnesic and visuo-spatial cognitive domains, and between AD and verbal memory. TBSS results indicate that the involvement of normal appearance WM, beyond the signal changes detected with conventional MR imaging (Fazekas scale and LL%), was associated with neuropsychological deficit. These data suggest that disrupted complex neuronal networks can underlie cognitive-behavioural dysfunctions in DM1.

Keywords: DM1; MR imaging; Neuropsychology; TBSS; VBM.

Fig. 1

VBM analysis reveals clusters of grey matter atrophy (in green) in DM1 patients compared to healthy controls superimposed on axial slices (a) or volumes (b) of MNI standard brain (TFCE p < 0.001 corrected for multiple comparisons). Clusters are diffuse in both hemispheres, particularly in perirolandic, orbitofrontal, dorsolateral frontal, insular, temporo occipital, parietomesial, anterior and posterior cingulated areas. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 2

Negative relationship between RAVLT-DR scores and grade of atrophy (in green) in DM1 patients superimposed on volume (a) and coronal and axial slices (b) of MNI standard brain (TFCE p < 0.05 corrected for multiple comparisons). Clusters are located in left postcentral*, left middle and inferior temporal⁺ gyri and left supramarginal° gyrus. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 3

TBSS maps show the tracts of significantly decreased FA (a, in blue) and the tracts of significantly increased RD (b, in red), MD (c, in yellow) and AD (d, in purple) in DM1 patients compared to healthy controls superimposed on axial and sagittal slices of MNI standard brain (TFCE p < 0.05 corrected for multiple comparisons). Green indicates the skeleton template. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 4

Multiple regression analyses reveal negative relationship (in red) between RD and ROCF-copy (a), RAVLT-DR (b) and CBT (c) scores in DM1 patients. AD had a significant negative relationship (in purple) with RAVLT-DR (d) and digit span (e) scores in DM1 patients. Results are superimposed on axial and sagittal slices of MNI standard brain (TFCE p < 0.05 corrected for multiple comparisons). Green indicates the skeleton template. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)