Background: Myotonic dystrophy type 2 (DM2) is a pleiotropic multisystemic disease. Although muscle weakness is the main symptom, almost 70% of DM2 patients report cognitive deficits as one of the most disabling symptoms, which markedly affects their quality of life. Previous studies suggest that cerebral white matter (WM) is primarily affected in DM2. However, brain imaging studies incorporate with cognitive and motor endpoints are very limited.
Objective: To evaluate magnetic resonance imaging (MRI) measures of brain structure with a focus on WM integrity and their relationships with cognitive and motor endpoints in DM2.
Methods: 3-Tesla brain MRIs were acquired in 10 adults with DM2 and 10 age and sex-matched controls. Brain morphometry and WM integrity were assessed using T1-MPRAGE and diffusion tensor imaging (DTI) sequences. DTI scalars, including fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD), were compared between groups. A comprehensive battery of cognitive and motor measures was performed and correlated with MRI measures using Spearman’s Correlation (ρ).
Results: Of 20 participants (60% female), mean age (62.2 vs. 62.6 years) and education (16.4 vs. 17.5 years) were not different between groups. Compared to controls, the DM2 group showed a significant reduction in global measures of cerebral gray matter (GM) volume (mean difference=-0.03; P-value<0.01), but not the WM volume. Widespread abnormalities in DTI measures (lower FA, higher RD) were among the most robust findings in the DM2 group (mean differences of FA=0.04; P-value<0.01 and RD=0.00004; P-value<0.01), indicating that the pathology is within WM microstructures. Although not significant, the DM2 group scored lower in all cognitive domains than controls, particularly in executive function (mean difference=-12.5; P-value=0.07). All motor endpoints were significantly different between groups. We found a significant correlation between RD and grip strength (ρ=-0.81, P-value=0.005), while FA was strongly correlated with an executive function test (ρ=0.71, P-value=0.02).
Conclusion: Our data demonstrate robust differences in brain structure, explicitly cerebral WM integrity and GM volume between the DM2 group vs. controls. The strong correlations between DTI measures and clinical endpoints support the notion that WM integrity plays an important role in executive function and mediating motor performance already compromised from dystrophic pathology in DM2.