Grey and white matter loss along cerebral midline structures in myotonic dystrophy type 2

Abstract

Myotonic dystrophy type 2 (DM2) is an autosomal dominantly inherited multisystemic disorder and a common cause of muscular dystrophy in adults. Although neuromuscular symptoms predominate, there is clinical and imaging evidence of cerebral involvement. We used voxel-based morphometry (VBM) based on T1-weighted magnetic resonance images to investigate brain morphology in 13 DM2 patients in comparison to 13 sex-and age-matched controls. Further, we employed novel computational surface-based methods that specifically assess callosal thickness. We found grey and white matter loss along cerebral midline structures in our patient group. Grey matter reductions were present in brainstem and adjacent hypothalamic and thalamic regions, while white matter was mainly reduced in corpus callosum. The reduced callosal size was highly significant and independently confirmed by different methods. Our data provide first evidence for grey and white matter loss along brain midline structures in DM2 patients. The reduced size of the corpus callosum further extends the spectrum of white matter changes in DM2 and may represent the morphological substrate of neuropsychological abnormalities previously described in this disorder.

mTOR-dependent proliferation defect in human ES-derived neural stem cells affected by Myotonic Dystrophy Type1

“…Central nervous system involvement in DM1 implicates cognitive impairment, hypersomnolence, and personality and behavioral disturbances (Abe et al, 1994;Delaporte, 1998;Meola et al, 2003;Modoni et al, 2008;Turnpenny et al, 1994). Grey matter reduction has also been described in various cortical regions, the hippocampus and the thalamus of DM1 patients (Minnerop et al, 2008;Minnerop et al, 2011;Weber et al, 2010). At the molecular level, nuclear aggregation of mutant mRNAs in combination with MBNL1 has been described in cortical and subcortical neuronal cells of DM1 patients post-mortem (Jiang et al, 2004).…”

Diffusion tensor imaging reveals widespread white matter abnormalities in children and adolescents with myotonic dystrophy type 1

“…Previous magnetic resonance imaging (MRI) studies of adult-onset DM1 have revealed evidence of atrophy (cortical, brainstem, and callosal) and white matter lesions (Censori, Provinciali et al 1994; Hashimoto, Tayama et al 1995; Bachmann, Damian et al 1996; Martinello, Piazza et al 1999; Antonini, Mainero et al 2004; Minnerop, Luders et al 2008; Romeo, Pegoraro et al 2010). Volumetric changes, including ventriculomegaly and callosal hypoplasia, have also been observed in the childhood-onset form (Glantz, Wright et al 1988; Hashimoto, Tayama et al 1995; Martinello, Piazza et al 1999).…”

White matter abnormalities and neurocognitive correlates in children and adolescents with myotonic dystrophy type 1: A diffusion tensor imaging study

“…The most common brain changes seen in magnetic resonance imaging (MRI) studies of both early-onset and adult-onset DM1 have been ventricular enlargement, cortical atrophy, and white matter hyperintensities [8, 14, 20–24]. Previous studies have illustrated a very wide range in severity of brain involvement in this disease and some studies, but not all, have shown associations between imaging abnormalities and cognitive function [14, 21, 25].…”