Cerebral involvement and related aspects in myotonic dystrophy type 2.

Abstract Myotonic dystrophy type 2 (DM2) is an autosomal dominant multisystemic disorder caused by CCTG repeats expansion in the first intron of the CNBP gene. In this review we focus on the brain involvement in DM2, including its pathogenic mechanisms, microstructural, macrostructural and functional brain changes, as well as the effects of all these impairments on patients’ everyday life. We also try to understand how brain abnormalities in DM2 should be adequately measured and potentially treated. The most important pathogenetic mechanisms in DM2 are RNA gain-of-function and repeat-associated non-ATG (RAN) translation. One of the main neuroimaging findings in DM2 is the presence of diffuse periventricular white matter hyperintensity lesions (WMHLs). Brain atrophy has been described in DM2 patients, but it is not clear if it is mostly caused by a decrease of the white or gray matter volume. The most commonly reported specific cognitive symptoms in DM2 are dysexecutive syndrome, visuospatial and memory impairments. Fatigue, sleep-related disorders and pain are also frequent in DM2. The majority of key symptoms and signs in DM2 has a great influence on patients’ daily lives, their psychological status, economic situation and quality of life.