Cerebral white matter affection in myotonic dystrophy type 1 and 2– A Diffusion-Tensor-Imaging Study at3T

Myotonic dystrophy type 1 (DM1) and 2 (DM2) are autosomal dominantly inherited neuromuscular disorders with multisystemic involvement. Although cognitive impairment and white matter changes are more common in DM1 patients, brain volume loss and white matter changes have been described in DM2 patients as well. Using voxel-based morphometry (VBM) we previously found grey and white matter loss along cerebral midline structures in DM2 patients [13 DM2 patients (m/f: 8/5, age 53.4±12.0 years, disease duration/DD 12.0±8.8 years); 13 controls (m/f: 8/5, age 53.5±10.2 years)]. To further investigate white matter changes in DM1 and DM2 patients, we used diffusion-tensor-imaging (DTI) and correlated changes with clinical data.

We compared 22 DM1 patients (m/f: 9/13, age 43.1±12.6 years, DD 13.2±7.0 years) and 22 DM2 patients (m/f: 12/10, age 52.5±10.1 years, DD 11.9±9.9 years) with age- and sex-matched healthy controls (m/f: 11/11, age 50.0±10.2 years). All subjects underwent clinical-neurological examinations and neuropsychological testing. Diffusion weighted images were obtained using a 3T MRI scanner with 60 gradient directions, and a novel registration and analysis approach (TBSS – Tract Based Spatial Statistics) was applied. FMRIB software library (FSL) was used for both preprocessing and statistical analysis of DTI data. Group comparisons were calculated as 2-sample t tests (FWE-corrected threshold, p<0.05).

In DM1 patients, we found significant degradation of fractional anisotropy (FA) throughout the whole brain, affecting association fibres such as the superior and inferior longitudinal fascicles (sLF, iLF), the inferior fronto-occipital fascicles (iFOF), uncinate fascicles and cinguli as well as commissural fibres [corpus callosum (CC)] and projection fibres along the dorsal brainstem and internal capsule (corticospinal tracts). In DM2 patients, degradation of FA primarily involved anterior parts of the CC, both cinguli, iFOFs, left sLF, right iLF, and corticospinal tracts. Brainstem was not affected in DM2 patients.

DTI analyses demonstrated distinct involvement of cerebral white matter in DM1 and DM2 patients. Our study results extent previous findings on CNS affection in myotonic dystrophies. CC affection and association fibre changes were our predominant findings. Regression analyses revealed an identical pattern of fibre decline related to age and disease duration in DM1 patients, but not in DM2 patients. The limbic system (cingulum) was more affected in DM1 patients, the extent of changes correlated with disease duration and age.

Widespread white matter changes could be the morphologic substrate of cognitive impairment in both patient groups. Dorsal brainstem affection in DM1 patients may be associated with hypersomnia and disturbed vigilance. Regression analyses with neuropsychological parameters are currently underway.

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