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

Abstract

ObjectivesCentral 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).Methods12 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.ResultsClinical 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.ConclusionGM 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.

Association of peripheral neuropathy with sleep-related breathing disorders in myotonic dystrophies

“…Similarly to previous reports, daytime sleepiness was more pronounced in patients with DM1 38. This difference was not associated with respective differences in the severity of SRBDs, BMI, or muscle weakness, the factors that may limit the restorative function of sleep and thus indirectly provoke excessive sleepiness.…”

Transcranial Sonography Findings in Depression in Association With Psychiatric and Neurologic Diseases: A Review

“…Myotonic dystrophies (DM type 1 and DM type 2) are similar but distinct multisystemic diseases related to different repeat expansion mutations which results to manifold cerebral involvement . MRI studies revealed a broad spectrum of abnormalitiers including white and grey matter abnormalities . So far, two studies evaluated TCS findings in patients with DM .…”

“…61 MRI studies revealed a broad spectrum of abnormalitiers including white and grey matter abnormalities. 62 So far, two studies evaluated TCS findings in patients with DM. 63,64 Peric et al studied 66 patients with DM type 1 and detected reduced BR echogenicity in 25 (37.7%) of them.…”

Clinical neuropsychology in the management of myotonic dystrophy

“…Other studies found an association between unstable cytosine–thymine–guanine (CTG) repeat expansion size and cognitive test performance and behavior changes in myotonic dystrophy . This is unsurprising given that, in myotonic dystrophy type 1, a positive association exists between brain pathology and CTG repeat expansion, whereas the extent of white‐matter lesions is positively correlated with cognitive impairment and behavioral symptoms . In addition, other contextual factors—which may be less dependent on underlying brain pathology—may also affect cognitive functioning.…”

“…5,6,8 This is unsurprising given that, in myotonic dystrophy type 1, a positive association exists between brain pathology and CTG repeat expansion, 9 whereas the extent of white-matter lesions is positively correlated with cognitive impairment and behavioral symptoms. 10,11 In addition, other contextual factors-which may be less dependent on underlying brain pathologymay also affect cognitive functioning. Reactive depression, perhaps resulting from difficulties adjusting to physical symptoms, may worsen performance on cognitive testing; fatigue, sleepiness, or pain may also lead to problems with effort.…”