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Cortical and Subcortical Grey and White Matter Atrophy in Myotonic Dystrophies Type 1 and 2 Is Associated with Cognitive Impairment, Depression and Daytime Sleepiness.

Schneider-Gold C, Bellenberg B, Prehn C, Krogias C, Schneider R, Klein J, Gold R, Lukas C - PLoS ONE (2015)

Bottom Line: Volumes of brain, ventricles, cerebellum, brainstem, cervical cord, lesion load and VBM results of the patient groups were compared to 33 matched healthy subjects.In DM2, depression was associated with brainstem atrophy, Daytime sleepiness correlated with volume decrease in the middle cerebellar peduncles, pons/midbrain and the right medio-frontal cortex.GM and WM atrophy was significant in DM1 and DM2.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany.

ABSTRACT

Objectives: Central nervous system involvement is one important clinical aspect of myotonic dystrophy type 1 and 2 (DM1 and DM2). We assessed CNS involvement DM1 and DM2 by 3T MRI and correlated clinical and neuocognitive symptoms with brain volumetry and voxel-based morphometry (VBM).

Methods: 12 patients with juvenile or classical DM1 and 16 adult DM2 patients underwent 3T MRI, a thorough neurological and neuropsychological examination and scoring of depression and daytime sleepiness. Volumes of brain, ventricles, cerebellum, brainstem, cervical cord, lesion load and VBM results of the patient groups were compared to 33 matched healthy subjects.

Results: Clinical symptoms were depression (more pronounced in DM2), excessive daytime sleepiness (more pronounced in DM1), reduced attention and flexibility of thinking, and deficits of short-term memory and visuo-spatial abilities in both patient groups. Both groups showed ventricular enlargement and supratentorial GM and WM atrophy, with prevalence for more GM atrophy and involvement of the motor system in DM1 and more WM reduction and affection of limbic structures in DM2. White matter was reduced in DM1 in the splenium of the corpus callosum and in left-hemispheric WM adjacent to the pre- and post-central gyrus. In DM2, the bilateral cingulate gyrus and subgyral medio-frontal and primary somato-sensory WM was affected. Significant structural-functional correlations of morphological MRI findings (global volumetry and VBM) with clinical findings were found for reduced flexibility of thinking and atrophy of the left secondary visual cortex in DM1 and of distinct subcortical brain structures in DM2. In DM2, depression was associated with brainstem atrophy, Daytime sleepiness correlated with volume decrease in the middle cerebellar peduncles, pons/midbrain and the right medio-frontal cortex.

Conclusion: GM and WM atrophy was significant in DM1 and DM2. Specific functional-structural associations related morphological changes to cognitive impairment, depression and daytime sleepiness, partly indicating involvement of complex neuronal networks.

No MeSH data available.


Related in: MedlinePlus

Flexibility of thinking and brain GM.Areas of significant negative correlations between GM volume and flexibility of thinking (RWT semantic verbal fluency with change of categories) in 12 DM1 patients (green) and 15 DM2 patients (red). Voxelwise multiple regression analysis with the test outcome (pathologic / normal) and age as covariates. Age was used as a covariate of no interest. Areas with adjusted p at cluster level < 0.05 after FWE correction are shown; X,Y,Z: MNI-coordinates: negative X-values reflect left side and positive X-values right sided location.
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pone.0130352.g005: Flexibility of thinking and brain GM.Areas of significant negative correlations between GM volume and flexibility of thinking (RWT semantic verbal fluency with change of categories) in 12 DM1 patients (green) and 15 DM2 patients (red). Voxelwise multiple regression analysis with the test outcome (pathologic / normal) and age as covariates. Age was used as a covariate of no interest. Areas with adjusted p at cluster level < 0.05 after FWE correction are shown; X,Y,Z: MNI-coordinates: negative X-values reflect left side and positive X-values right sided location.

Mentions: We examined voxelwise regression analyses for GM and WM using the results of the most relevant neuropsychological tests as covariates (Table 3). These were: Attention (reflected by tonic and phasic alertness), flexibility of thinking (RWT test with change of categories), non-verbal short-term memory (WMS-R: block-tapping-forward and-backwards), and verbal short term memory (WMS-R, repetition of numbers backward). The only statistically significant association was an inverse correlation between GM volume and flexibility of thinking, when using the group classification according to pathological or normal neuropsychological test outcome and age as covariates. In DM1, significant clusters were detected in the left hemispheric secondary visual cortex (medio-parietal cortex: BA18, BA19). In DM2 significant clusters were located in the periaqueductal grey matter, in parts of the midbrain, the bilateral thalamus (pulvinar), in the bilateral parahippocampal gyrus (BA34) and in the anterior cingulate (BA25), (Fig 5 and S5 Table). All other associations between voxelwise brain volumes and neuropsychological parameters were non-significant.


Cortical and Subcortical Grey and White Matter Atrophy in Myotonic Dystrophies Type 1 and 2 Is Associated with Cognitive Impairment, Depression and Daytime Sleepiness.

Schneider-Gold C, Bellenberg B, Prehn C, Krogias C, Schneider R, Klein J, Gold R, Lukas C - PLoS ONE (2015)

Flexibility of thinking and brain GM.Areas of significant negative correlations between GM volume and flexibility of thinking (RWT semantic verbal fluency with change of categories) in 12 DM1 patients (green) and 15 DM2 patients (red). Voxelwise multiple regression analysis with the test outcome (pathologic / normal) and age as covariates. Age was used as a covariate of no interest. Areas with adjusted p at cluster level < 0.05 after FWE correction are shown; X,Y,Z: MNI-coordinates: negative X-values reflect left side and positive X-values right sided location.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4482602&req=5

pone.0130352.g005: Flexibility of thinking and brain GM.Areas of significant negative correlations between GM volume and flexibility of thinking (RWT semantic verbal fluency with change of categories) in 12 DM1 patients (green) and 15 DM2 patients (red). Voxelwise multiple regression analysis with the test outcome (pathologic / normal) and age as covariates. Age was used as a covariate of no interest. Areas with adjusted p at cluster level < 0.05 after FWE correction are shown; X,Y,Z: MNI-coordinates: negative X-values reflect left side and positive X-values right sided location.
Mentions: We examined voxelwise regression analyses for GM and WM using the results of the most relevant neuropsychological tests as covariates (Table 3). These were: Attention (reflected by tonic and phasic alertness), flexibility of thinking (RWT test with change of categories), non-verbal short-term memory (WMS-R: block-tapping-forward and-backwards), and verbal short term memory (WMS-R, repetition of numbers backward). The only statistically significant association was an inverse correlation between GM volume and flexibility of thinking, when using the group classification according to pathological or normal neuropsychological test outcome and age as covariates. In DM1, significant clusters were detected in the left hemispheric secondary visual cortex (medio-parietal cortex: BA18, BA19). In DM2 significant clusters were located in the periaqueductal grey matter, in parts of the midbrain, the bilateral thalamus (pulvinar), in the bilateral parahippocampal gyrus (BA34) and in the anterior cingulate (BA25), (Fig 5 and S5 Table). All other associations between voxelwise brain volumes and neuropsychological parameters were non-significant.

Bottom Line: Volumes of brain, ventricles, cerebellum, brainstem, cervical cord, lesion load and VBM results of the patient groups were compared to 33 matched healthy subjects.In DM2, depression was associated with brainstem atrophy, Daytime sleepiness correlated with volume decrease in the middle cerebellar peduncles, pons/midbrain and the right medio-frontal cortex.GM and WM atrophy was significant in DM1 and DM2.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany.

ABSTRACT

Objectives: Central nervous system involvement is one important clinical aspect of myotonic dystrophy type 1 and 2 (DM1 and DM2). We assessed CNS involvement DM1 and DM2 by 3T MRI and correlated clinical and neuocognitive symptoms with brain volumetry and voxel-based morphometry (VBM).

Methods: 12 patients with juvenile or classical DM1 and 16 adult DM2 patients underwent 3T MRI, a thorough neurological and neuropsychological examination and scoring of depression and daytime sleepiness. Volumes of brain, ventricles, cerebellum, brainstem, cervical cord, lesion load and VBM results of the patient groups were compared to 33 matched healthy subjects.

Results: Clinical symptoms were depression (more pronounced in DM2), excessive daytime sleepiness (more pronounced in DM1), reduced attention and flexibility of thinking, and deficits of short-term memory and visuo-spatial abilities in both patient groups. Both groups showed ventricular enlargement and supratentorial GM and WM atrophy, with prevalence for more GM atrophy and involvement of the motor system in DM1 and more WM reduction and affection of limbic structures in DM2. White matter was reduced in DM1 in the splenium of the corpus callosum and in left-hemispheric WM adjacent to the pre- and post-central gyrus. In DM2, the bilateral cingulate gyrus and subgyral medio-frontal and primary somato-sensory WM was affected. Significant structural-functional correlations of morphological MRI findings (global volumetry and VBM) with clinical findings were found for reduced flexibility of thinking and atrophy of the left secondary visual cortex in DM1 and of distinct subcortical brain structures in DM2. In DM2, depression was associated with brainstem atrophy, Daytime sleepiness correlated with volume decrease in the middle cerebellar peduncles, pons/midbrain and the right medio-frontal cortex.

Conclusion: GM and WM atrophy was significant in DM1 and DM2. Specific functional-structural associations related morphological changes to cognitive impairment, depression and daytime sleepiness, partly indicating involvement of complex neuronal networks.

No MeSH data available.


Related in: MedlinePlus