Relationship of white and gray matter abnormalities to clinical and genetic features in myotonic dystrophy type 1

Zanigni, Stefano; Evangelisti, Stefania; Giannoccaro, Maria Pia; Oppi, Federico; Poda, Roberto; Giorgio, Antonio; Testa, Claudia; Manners, David Neil; Avoni, Patrizia; Gramegna, Laura Ludovica; Stefano, Nicola De; Lodi, Raffaele; Tonon, Caterina; Liguori, Rocco

doi:10.1016/j.nicl.2016.04.012

Cited by 56 publications

(75 citation statements)

References 60 publications

(75 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Subcortical involvement in DM1 has repeatedly been ª 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association reported 26,28,29,[40][41][42] and this is confirmed in our study. Moreover only in the adult/late subgroup was the opposite result found, primarily located in the temporal lobe.…”

Section: Discussionsupporting

confidence: 90%

Neurodegeneration trajectory in pediatric and adult/late DM1: A follow‐up MRI study across a decade

Labayru

Jiménez-Marín

Fernández

et al. 2020

Ann Clin Transl Neurol

View full text Add to dashboard Cite

Objective: To characterize the progression of brain structural abnormalities in adults with pediatric and adult/late onset DM1, as well as to examine the potential predictive markers of such progression. Methods: 21 DM1 patients (pediatric onset: N = 9; adult/late onset: N = 12) and 18 healthy controls (HC) were assessed longitudinally over 9.17 years through brain MRI. Additionally, patients underwent neuropsychological, genetic, and muscular impairment assessment. Inter-group comparisons of total and voxel-level regional brain volume were conducted through Voxel Based Morphometry (VBM); cross-sectionally and longitudinally, analyzing the associations between brain changes and demographic, clinical, and cognitive outcomes. Results: The percentage of GM loss did not significantly differ in any of the groups compared with HC and when assessed independently, adult/late DM1 patients and their HC group suffered a significant loss in WM volume. Regional VBM analyses revealed subcortical GM damage in both DM1 groups, evolving to frontal regions in the pediatric onset patients. Muscular impairment and the outcomes of certain neuropsychological tests were significantly associated with follow-up GM damage, while visuoconstruction, attention, and executive function tests showed sensitivity to WM degeneration over time. Interpretation: Distinct patterns of brain atrophy and its progression over time in pediatric and adult/late onset DM1 patients are suggested. Results indicate a possible neurodevelopmental origin of the brain abnormalities in DM1, along with the possible existence of an additional neurodegenerative process. Fronto-subcortical networks appear to be involved in the disease progression at young adulthood in pediatric onset DM1 patients. The involvement of a multimodal integration network in DM1 is discussed.

show abstract

Section: Discussionsupporting

confidence: 90%

Neurodegeneration trajectory in pediatric and adult/late DM1: A follow‐up MRI study across a decade

Labayru

Jiménez-Marín

Fernández

et al. 2020

Ann Clin Transl Neurol

View full text Add to dashboard Cite

show abstract

“…In contrast, Parkinson’s is characterized by the loss of dopaminergic neurons in the substantia nigra (Shulman et al, 2011) and Huntington disease for loss of medium spiny neurons in the striatum (Vonsattel et al, 2011). Although CNS features in DM, including executive function deficits, are highly problematic for patients and white matter abnormalities are detected by MRI and pathological examination (Minnerop et al, 2011; Ogata et al, 1998), routine pathological findings are diffuse and previous reports suggest findings are non-specific (Conforti et al, 2016; Wozniak et al, 2013; Wozniak et al, 2014; Wozniak et al, 2011; Zanigni et al, 2016). The discovery that LPAC and QAGR tetrapeptide proteins accumulate in DM2 provides a new opportunity to understand the impact of the DM2 expansion mutation on the brain and to look for pathological findings at sites of RAN protein accumulation.…”

Section: Discussionmentioning

confidence: 99%

RAN Translation Regulated by Muscleblind Proteins in Myotonic Dystrophy Type 2

Cleary

Liu

et al. 2017

Neuron

125

159

View full text Add to dashboard Cite

SUMMARY Several microsatellite-expansion diseases are characterized by the accumulation of RNA foci and RAN proteins raising the possibility of a mechanistic connection. We explored this question using myotonic dystrophy type 2, a multisystemic disease thought to be primarily caused by RNA gain-of-function effects. We demonstrate the DM2 CCTG•CAGG expansion expresses sense and antisense tetrapeptide poly-(LPAC) and poly-(QAGR) RAN proteins, respectively. In DM2 autopsy brains, LPAC is found in neurons, astrocytes and glia in grey matter and antisense QAGR proteins accumulate within white matter. LPAC and QAGR proteins are toxic to cells independent of RNA gain of function. RNA foci and nuclear sequestration of CCUG transcripts by MBNL1 is inversely correlated with LPAC expression. These data suggest a model, that involves nuclear retention of expansion RNAs by RNA-binding proteins (RBPs) and an acute phase in which expansion RNAs exceed RBP sequestration capacity, are exported to the cytoplasm and undergo RAN translation.

show abstract

“…Consistent evidence has been produced proving that structural and functional changes in DM1 brains account for some specific higher-level dysfunctions. So far, structural magnetic resonance imaging (MRI) studies have mainly focused on the assessment of regional gray matter volumetric and microstructural changes of the white matter tissue (4)(5)(6)(7)(8)(9)(10)(11)(12). Importantly, a strict relationship has been reported not only between structural brain abnormalities and DM1 patients' cognitive profile (e.g., executive functions, reasoning and visuospatial abilities) (7,9) but also with patients' CTG triplet expansion (6,8,13).…”

Section: Introductionmentioning

confidence: 99%

Abnormal Cortical Thickness Is Associated With Deficits in Social Cognition in Patients With Myotonic Dystrophy Type 1

et al. 2020

View full text Add to dashboard Cite

Aim: To investigate the cortical thickness in myotonic dystrophy type 1 (DM1) and its potential association with patients' genetic triplet expansion and social cognition deficits.Methods: Thirty patients with DM1 underwent the Social Cognition Battery Test and magnetic resonance imaging (MRI) scanning at 3 T. Twenty-five healthy subjects (HSs) were enrolled in the study to serve as a control group for structural MRI data. To assess changes in cortical thickness in DM1 patients, they were compared to HSs using a t-test model. Correlations were used to assess potential associations between genetic and clinical characteristics and social cognition performances in the patient group. Additionally, multiple regression models were used to explore associations between cortical thickness, CTG triplet expansion size, and scores obtained by DM1 patients on the Social Cognition Battery.Results: DM1 patients showed low performances in several subtests of the Social Cognition Battery. Specifically, they obtained pathological scores at Emotion Attribution Test (i.e., Sadness, Embarrassment, Happiness, and Anger) and at the Social Situations Test (i.e., recognition of normal situation, recognition of aberrant behavior). Significant negative correlations were found between CTG triplet expansion size and Embarrassment, and Severity of Aberrant Behavior. Similarly, a negative correlation was found between patients' MIRS scores and Sadness. DM1 patients compared to HSs showed reduced thickness in the right premotor cortex, angular gyrus, precuneus, and inferior parietal lobule. Significant associations were found between patients' CTG triplet expansion size and thickness in left postcentral gyrus and in the left primary somatosensory cortex, in the posterior cingulate cortex bilaterally, and in the right lingual gyrus. Finally, significant associations were found between cortical thickness and sadness in the superior temporal gyrus, the right precentral gyrus, the right angular gyrus, and the left medial frontal gyrus bilaterally. DM1 patients showed a negative correlation between cortical thickness in the bilateral precuneus and in the left lateral occipital cortex Serra et al. Social Cognition Deficits in DM1 Brains and performance at the Social Situations Test. Finally, DM1 patients showed a negative correlation between cortical thickness in the left precuneus and in the superior frontal gyrus and scores at the Moral Distinction Test.Discussion: The present study shows both cortical thickness changes in DM1 patients compared to controls and significant associations between cortical thickness and patients' social cognition performances. These data confirm the presence of widespread brain damages associated with cognitive impairment in DM1 patients.

show abstract

Relationship of white and gray matter abnormalities to clinical and genetic features in myotonic dystrophy type 1

Cited by 56 publications

References 60 publications

Neurodegeneration trajectory in pediatric and adult/late DM1: A follow‐up MRI study across a decade

Neurodegeneration trajectory in pediatric and adult/late DM1: A follow‐up MRI study across a decade

RAN Translation Regulated by Muscleblind Proteins in Myotonic Dystrophy Type 2

Abnormal Cortical Thickness Is Associated With Deficits in Social Cognition in Patients With Myotonic Dystrophy Type 1

Contact Info

Product

Resources

About