Brain positron emission tomography in patients with myotonic dystrophy type 1 and type 2

Perić, Stojan; Brajkovic, L.; Belanovic, Bozidar; Ilic, Vera; Salak-Djokic, Biljana; Basta, Ivana; Stojanović, Vidosava Rakočević

doi:10.1016/j.jns.2017.05.013

Cited by 21 publications

(25 citation statements)

References 29 publications

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“…In contrast to this, a recent FDG-PET study by Peric et al on 13 DM2 (and 16 DM1) patients observed numerous correlations with neuropsychological test results ( 68 ). They detected hypometabolism in pericentral, prefrontal, temporal regions, but also in insula, thalamus, and striatum.…”

Section: Introductionmentioning

confidence: 87%

“…However, no correlations with NPT were found. The most recent FDG-PET by Peric et al analyzed glucose metabolism and its relation to neuropsychological testing, excluding congenital and late-onset DM1 cases ( 68 ). The most prominent hypometabolism was present in prefrontal, frontotemporal, temporal, and precentral regions, subcortical GM regions were less affected than cortical areas.…”

Section: Introductionmentioning

confidence: 99%

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Current Progress in CNS Imaging of Myotonic Dystrophy

2018

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Neuroimaging in myotonic dystrophies provided a major contribution to the insight into brain involvement which is highly prevalent in these multisystemic disorders. Particular in Myotonic Dystrophy Type 1, conventional MRI first revealed hyperintense white matter lesions, predominantly localized in the anterior temporal lobe. Brain atrophy and ventricle enlargement were additional early findings already described almost 30 years ago. Since then, more advanced and sophisticated imaging methods have been applied in Myotonic Dystrophy Types 1 and 2. Involvement of actually normal appearing white matter and widespread cortical affection in PET studies were key results toward the recognition of diffuse and not only focally localized brain pathology in vivo. Later, structural abnormalities of both, gray and white matter, have been found in both forms of the disorder, albeit more prominent in myotonic dystrophy type 1. In Type 1, a consistent widespread cortical and subcortical involvement of gray and white matter affecting all lobes, brainstem and cerebellum was observed. Spectroscopy studies gave additional evidence of neuronal and glial damage in both types. Central questions regarding the origin and spatiotemporal evolution of the CNS involvement and its relevance for clinical symptoms had already been raised 30 years ago, however are still not answered. Results of correlation analyses between neuroimaging and clinical parameters are diverse and with few exceptions not well reproducible across studies. It may be related to the fact that most of the reported studies included only small numbers of subjects, sometimes even not separating Myotonic Dystrophy Type 1 from Type 2. But this heterogeneity may also support the current point of view that the clinical impairments are not simply linked to specific and regionally circumscribed structural or functional brain alterations. It seems more convincing that disturbed networks build the functional and structural substrate of clinical symptoms in these disorders as it is proposed in other neuropsychiatric diseases. Consecutively, structural and functional network analyses may provide additional information regarding the link between brain pathology and clinical symptoms. Up to now, only cross-sectional neuroimaging studies have been published. To analyze the temporal evolution of brain affection, longitudinal studies are urgently needed, and systematic natural history data would be useful to identify potential biomarkers for therapeutic studies.

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Section: Introductionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Current Progress in CNS Imaging of Myotonic Dystrophy

2018

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“…Importantly, white matter abnormalities correlate with disease duration and cognitive deficits ( 2 , 126 ). Functional imaging revealed low glucose uptake and cerebral hypoperfusion, as well as abnormal connectivity patterns that correlate with atypical personality traits and executive dysfunction ( 142 , 143 ). The correlation between imaging data and neuropsychological profiles hints to the involvement of complex neuronal networks, through defective neurodevelopment, neurodegeneration or neurodysfuntion.…”

Section: The Role Of Gaba Glutamate and Glia In Dm1 Neuronal Hyperexmentioning

confidence: 99%

Of Mice and Men: Advances in the Understanding of Neuromuscular Aspects of Myotonic Dystrophy

et al. 2018

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Intensive effort has been directed toward the modeling of myotonic dystrophy (DM) in mice, in order to reproduce human disease and to provide useful tools to investigate molecular and cellular pathogenesis and test efficient therapies. Mouse models have contributed to dissect the multifaceted impact of the DM mutation in various tissues, cell types and in a pleiotropy of pathways, through the expression of toxic RNA transcripts. Changes in alternative splicing, transcription, translation, intracellular RNA localization, polyadenylation, miRNA metabolism and phosphorylation of disease intermediates have been described in different tissues. Some of these events have been directly associated with specific disease symptoms in the skeletal muscle and heart of mice, offering the molecular explanation for individual disease phenotypes. In the central nervous system (CNS), however, the situation is more complex. We still do not know how the molecular abnormalities described translate into CNS dysfunction, nor do we know if the correction of individual molecular events will provide significant therapeutic benefits. The variability in model design and phenotypes described so far requires a thorough and critical analysis. In this review we discuss the recent contributions of mouse models to the understanding of neuromuscular aspects of disease, therapy development, and we provide a reflective assessment of our current limitations and pressing questions that remain unanswered.

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“…PET and SPECT studies showed merely diffuse and widespread metabolic changes in white matter (WM) and widespread cortical gray matter (GM) affection including reduced energy metabolism in the left frontal lobe in DM1 and in frontal and temporal regions of both sides in DM1 and DM2 (6)(7)(8). In addition, PET showed reduced energy metabolism in the striatum in both DM1 and DM2, as well as in the thalamus in DM2 patients (9). Voxel-based morphometric MRI studies revealed predominant white matter involvement in all cerebral lobes, brainstem and corpus callosum in myotonic dystrophy types 1 and 2, while partly divergent findings of gray matter decrease (cortical areas, thalamus, putamen) were reported for DM1 and DM2 (3,10).…”

Section: Introductionmentioning

confidence: 99%

“…The deep gray matter nuclei (DGM) are suggested to be involved in the control and regulation of different functional brain networks which are not only related to motor control, but also to emotional, executive and associative functional circuits (33,34). Correlation studies between neuropsychological test results and morphometric or functional brain imaging in DM1 and DM2 exhibited interrelations between alterations of the DGM and cognitive deficits, depression and daytime sleepiness in both disorders (3,9,35,36).…”

Section: Introductionmentioning

confidence: 99%

Characterization of Iron Accumulation in Deep Gray Matter in Myotonic Dystrophy Type 1 and 2 Using Quantitative Susceptibility Mapping and R2* Relaxometry: A Magnetic Resonance Imaging Study at 3 Tesla

et al. 2019

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Quantitative mapping of the magnetic susceptibility and the effective transverse relaxation rate (R2 * ) are suitable to assess the iron content in distinct brain regions. In this prospective, explorative study the iron accumulation in deep gray matter nuclei (DGM) in myotonic dystrophy type 1 (DM1) and 2 (DM2) and its clinical and neuro-cognitive relevance using susceptibility and R2 * mapping was examined. Twelve classical DM1, four childhood-onset DM1 (DM1 c.o. ), twelve DM2 patients and twenty-nine matched healthy controls underwent MRI at 3 Tesla, neurological and neuro-cognitive tests. Susceptibility, R2 * and volumes were determined for eleven DGM structures and compared between patients and controls. Twelve classical DM1, four childhood-onset DM1, and 12 DM2 patients as well as 29 matched healthy controls underwent MRI at 3 Tesla, and neurological and neuro-cognitive tests. Susceptibility, R2 * and volumes were determined for 11 DGM structures and compared between patients and controls. Iron accumulation in DGM reflected by R2 * or susceptibility was found in the putamen and accumbens of DM1 and in DM2, but was more widespread in DM1 (caudate, pallidum, hippocampus, subthalamic nucleus, thalamus, and substantia nigra). Opposed changes of R2 * or susceptibility were detected in caudate, putamen and accumbens in the childhood-onset DM1 patients compared to classical DM1. R2 * or susceptibility alterations in DGM were significantly associated with clinical symptoms including muscular weakness (DM1), daytime sleepiness (DM1), depression (DM2), and with specific cognitive deficits in DM1 and DM2.Keywords: myotonic dystrophy type 1, DM1, myotonic dystrophy type 2, DM2, R2 * relaxometry, quantitative susceptibility mapping, iron, deep gray matter Ates et al. QSM/R2 * in Myotonic Dystrophy

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Brain positron emission tomography in patients with myotonic dystrophy type 1 and type 2

Cited by 21 publications

References 29 publications

Current Progress in CNS Imaging of Myotonic Dystrophy

Current Progress in CNS Imaging of Myotonic Dystrophy

Of Mice and Men: Advances in the Understanding of Neuromuscular Aspects of Myotonic Dystrophy

Characterization of Iron Accumulation in Deep Gray Matter in Myotonic Dystrophy Type 1 and 2 Using Quantitative Susceptibility Mapping and R2* Relaxometry: A Magnetic Resonance Imaging Study at 3 Tesla

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