NMR voxel-based morphometry and functional analysis as neural correlates of neuropsychological dysfunction in DM1

The variable phenotypic spectrum of myotonic dystrophy type 1 (DM1) includes central nervous system with mild to severe involvement. Our aim was to investigate grey matter (GM) and white matter (WM) structural alterations, as well as brain functional activation, by nuclear magnetic resonance (NMR) in a sample of adult-onset DM1 patients and to evaluate relationship with clinical and cognitive variables. Thirty DM1 patients underwent neuropsychological investigation and brain 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 executive and mnesic domains with visuospatial 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 analysis showed areas of significant negative relationship between atrophy in the left temporal lobe and verbal memory, and between RD and mnesic and visuo-spatial cognitive domains. Our data show extensive atrophy in DM1 over both cerebral hemispheres. Global atrophy, expressed with BPF, correlated with impaired executive and visuo-spatial abilities. 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 to neuropsychological deficit. Finally, brain functional NMR activation showed fronto-temporal correlates of anosognosia. These data suggest that disrupted complex neuronal networks can underlie cognitive-behavioural dysfunctions in DM1.