Brain imaging in myotonic dystrophy type 1

Abstract

Objective:To systematically review brain imaging studies in myotonic dystrophy type 1 (DM1).Methods:We searched Embase (index period 1974–2016) and MEDLINE (index period 1946–2016) for studies in patients with DM1 using MRI, magnetic resonance spectroscopy (MRS), functional MRI (fMRI), CT, ultrasound, PET, or SPECT. From 81 studies, we extracted clinical characteristics, primary outcomes, clinical-genetic correlations, and information on potential risk of bias. Results were summarized and pooled prevalence of imaging abnormalities was calculated, where possible.Results:In DM1, various imaging changes are widely dispersed throughout the brain, with apparently little anatomical specificity. We found general atrophy and widespread gray matter volume reductions in all 4 cortical lobes, the basal ganglia, and cerebellum. The pooled prevalence of white matter hyperintensities is 70% (95% CI 64–77), compared with 6% (95% CI 3–12) in unaffected controls. DTI shows increased mean diffusivity in all 4 lobes and reduced fractional anisotropy in virtually all major association, projection, and commissural white matter tracts. Functional studies demonstrate reduced glucose uptake and cerebral perfusion in frontal, parietal, and temporal lobes, and abnormal fMRI connectivity patterns that correlate with personality traits. There is significant between-study heterogeneity in terms of imaging methods, which together with the established clinical variability of DM1 may explain divergent results. Longitudinal studies are remarkably scarce.Conclusions:DM1 brains show widespread white and gray matter involvement throughout the brain, which is supported by abnormal resting-state network, PET/SPECT, and MRS parameters. Longitudinal studies evaluating spatiotemporal imaging changes are essential.

Brain Structural Features of Myotonic Dystrophy Type 1 and their Relationship with CTG Repeats

“…In contrast to some previous data [11], we found that volumetric changes were generally less marked in white matter structures compared with associated grey matter. Nonetheless, white matter pathology clearly represents an important component of the CNS structural landscape in DM1, as evidenced by the frequent occurrence of T2 hyperintense lesions [10], and widespread reduced fractional anisotropy on diffusion tensor imaging, even in normal-appearing white matter [64]. It remains uncertain to what extent white matter disease represents a primary manifestation of the DM1 disease process, versus Wallerian degeneration secondary to loss of associated grey matter [16].…”

Brain gray matter structural network in myotonic dystrophy type 1

“…On the contrary, significant negative correlations were found between regional GM volumes and CTG repeat length in other studies [ 16 , 19 ]. These conflicting results may be due to differences in the detailed analysis methods, the clinical variability of the study population, the somatic mosaicism of CTG repeat lengths, or repeat number increases throughout life, even in post-mitotic tissues [ 3 , 31 ]. There are considerable tissue variations in repeat lengths, and repeat size in the blood might not correlate with that in the brain.…”

Outcome Measures for Central Nervous System Evaluation in Myotonic Dystrophy Type 1 May Be Confounded by Deficits in Motor Function or Insight

“…Further, diffusion tensor imaging (DTI) reveals the presence of diffuse, microstructural disruption even in apparently normal-looking white matter ( 27 ). Correlations have been described between impairment in specific cognitive domains or CTG repeat length with measures of gray matter volume ( 28 – 31 ), total volume of white matter lesions (VWML) ( 31 – 34 ) and DTI measures ( 29 , 31 – 36 ), although findings are inconsistent between studies, and no consensus imaging biomarker for CNS involvement has yet been identified ( 37 ).…”