scholarly journals Drumming motor sequence training induces apparent myelin remodelling in Huntington’s disease: a longitudinal diffusion MRI and quantitative magnetization transfer study

2019 ◽  
Author(s):  
Chiara Casella ◽  
Jose Bourbon-Teles ◽  
Sonya Bells ◽  
Elizabeth Coulthard ◽  
Greg D. Parker ◽  
...  
Keyword(s):  
Executive Function ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Diffusion Tensor ◽  
Magnetization Transfer ◽  
Motor Sequence ◽  
Longitudinal Diffusion ◽  
Microstructural Changes ◽  
Before And After ◽  
The Right

1.AbstractBackgroundImpaired myelination may contribute to Huntington’s disease (HD) pathogenesis. This study assessed differences in white matter (WM) microstructure between HD patients and controls, and tested whether drumming training stimulates WM remodelling in HD. Furthermore, it examined whether training-induced microstructural changes are related to improvements in motor and cognitive function.MethodsParticipants undertook two months of drumming exercises. Working memory and executive function were assessed before and after training. Changes in WM microstructure were investigated with diffusion tensor magnetic resonance imaging (DT-MRI)-based metrics, the restricted diffusion signal fraction (Fr) from the composite hindered and restricted model of diffusion (CHARMED) and the macromolecular proton fraction (MPF) from quantitative magnetization transfer (qMT) imaging. WM pathways linking the putamen and the supplementary motor area (SMA-Putamen), and three segments of the corpus callosum (CCI, CCII, CCIII) were studied using deterministic tractography. Baseline MPF differences between patients and controls were assessed with tract-based spatial statistics (TBSS).ResultsMPF was reduced in HD patients compared to controls in the mid-section of the CC in HD subjects at baseline, while a significantly greater change in MPF was detected in HD patients relative to controls in the CCII, CCIII, and the right SMA-putamen post-training. Further, although patients improved their drumming and executive function performance, such improvements did not correlate with microstructural changes.ConclusionsIncreased MPF suggests training-induced myelin changes in HD. Tailored behavioural stimulation may lead to neural benefits in early HD that could be exploited for delaying disease progression.

scholarly journals Drumming Motor Sequence Training Induces Apparent Myelin Remodelling in Huntington’s Disease: A Longitudinal Diffusion MRI and Quantitative Magnetization Transfer Study

2020 ◽  
Vol 9 (3) ◽  
pp. 303-320
Author(s):  
Chiara Casella ◽  
Jose Bourbon-Teles ◽  
Sonya Bells ◽  
Elizabeth Coulthard ◽  
Greg D. Parker ◽  
...  
Keyword(s):  
Executive Function ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Diffusion Tensor ◽  
Small Sample Size ◽  
Magnetization Transfer ◽  
Small Sample ◽  
Motor Sequence ◽  
Longitudinal Diffusion ◽  
Microstructural Changes

Background: Impaired myelination may contribute to Huntington’s disease (HD) pathogenesis. Objective: This study assessed differences in white matter (WM) microstructure between HD patients and controls, and tested whether drumming training stimulates WM remodelling in HD. Furthermore, it examined whether training-induced microstructural changes are related to improvements in motor and cognitive function. Methods: Participants undertook two months of drumming exercises. Working memory and executive function were assessed before and post-training. Changes in WM microstructure were investigated with diffusion tensor magnetic resonance imaging (DT-MRI)-based metrics, the restricted diffusion signal fraction (Fr) from the composite hindered and restricted model of diffusion (CHARMED) and the macromolecular proton fraction (MPF) from quantitative magnetization transfer (qMT) imaging. WM pathways linking putamen and supplementary motor areas (SMA-Putamen), and three segments of the corpus callosum (CCI, CCII, CCIII) were studied using deterministic tractography. Baseline MPF differences between patients and controls were assessed with tract-based spatial statistics. Results: MPF was reduced in the mid-section of the CC in HD subjects at baseline, while a significantly greater change in MPF was detected in HD patients relative to controls in the CCII, CCIII, and the right SMA-putamen post-training. Further, although patients improved their drumming and executive function performance, such improvements did not correlate with microstructural changes. Increased MPF suggests training-induced myelin changes in HD. Conclusion: Though only preliminary and based on a small sample size, these results suggest that tailored behavioural stimulation may lead to neural benefits in early HD, that could be exploited for delaying disease progression.

scholarly journals Longitudinal Diffusion Tensor Imaging Shows Progressive Changes in White Matter in Huntington’s Disease

2015 ◽  
Vol 4 (4) ◽  
pp. 333-346 ◽  
Author(s):  
Sarah Gregory ◽  
James H. Cole ◽  
Ruth E. Farmer ◽  
Elin M. Rees ◽  
Raymund A.C. Roos ◽  
...  
Keyword(s):  
Diffusion Tensor Imaging ◽  
White Matter ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Diffusion Tensor ◽  
Longitudinal Diffusion

Longitudinal diffusion tensor imaging in Huntington's Disease

2009 ◽  
Vol 216 (2) ◽  
pp. 525-529 ◽  
Author(s):  
Kurt E. Weaver ◽  
Todd L. Richards ◽  
Olivia Liang ◽  
Mercy Y. Laurino ◽  
Ali Samii ◽  
...  
Keyword(s):  
Diffusion Tensor Imaging ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Diffusion Tensor ◽  
Longitudinal Diffusion

scholarly journals Neuroimaging, Urinary, and Plasma Biomarkers of Treatment Response in Huntington’s Disease: Preclinical Evidence with the p75NTR Ligand LM11A-31

2021 ◽  
Author(s):  
Danielle A. Simmons ◽  
Brian D. Mills ◽  
Robert R. Butler III ◽  
Jason Kuan ◽  
Tyne L. M. McHugh ◽  
...  
Keyword(s):  
Mouse Model ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Treatment Response ◽  
Diffusion Tensor ◽  
Disease Onset ◽  
Therapeutic Effects ◽  
Plasma Cytokine ◽  
Cytokine Levels ◽  
Pharmacodynamic Biomarkers

AbstractHuntington’s disease (HD) is caused by an expansion of the CAG repeat in the huntingtin gene leading to preferential neurodegeneration of the striatum. Disease-modifying treatments are not yet available to HD patients and their development would be facilitated by translatable pharmacodynamic biomarkers. Multi-modal magnetic resonance imaging (MRI) and plasma cytokines have been suggested as disease onset/progression biomarkers, but their ability to detect treatment efficacy is understudied. This study used the R6/2 mouse model of HD to assess if structural neuroimaging and biofluid assays can detect treatment response using as a prototype the small molecule p75NTR ligand LM11A-31, shown previously to reduce HD phenotypes in these mice. LM11A-31 alleviated volume reductions in multiple brain regions, including striatum, of vehicle-treated R6/2 mice relative to wild-types (WTs), as assessed with in vivo MRI. LM11A-31 also normalized changes in diffusion tensor imaging (DTI) metrics and diminished increases in certain plasma cytokine levels, including tumor necrosis factor-alpha and interleukin-6, in R6/2 mice. Finally, R6/2-vehicle mice had increased urinary levels of the p75NTR extracellular domain (ecd), a cleavage product released with pro-apoptotic ligand binding that detects the progression of other neurodegenerative diseases; LM11A-31 reduced this increase. These results are the first to show that urinary p75NTR-ecd levels are elevated in an HD mouse model and can be used to detect therapeutic effects. These data also indicate that multi-modal MRI and plasma cytokine levels may be effective pharmacodynamic biomarkers and that using combinations of these markers would be a viable and powerful option for clinical trials.

scholarly journals Antidopaminergic treatment is associated with reduced chorea and irritability but impaired cognition in Huntington’s disease (Enroll-HD)

2020 ◽  
Vol 91 (6) ◽  
pp. 622-630
Author(s):  
Kate L Harris ◽  
Wei-Li Kuan ◽  
Sarah L Mason ◽  
Roger A Barker
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Case Reports ◽  
Controlled Trial ◽  
Rate Of Change ◽  
Control Group ◽  
Open Label ◽  
Double Blind ◽  
Before And After ◽  
Rate Of Decline

ObjectivesAlterations in dopamine neurotransmission underlie some of the clinical features of Huntington’s disease (HD) and as such are a target for therapeutic intervention, especially for the treatment of chorea and some behavioural problems. However, justification for such an intervention is mainly based on case reports and small open label studies and the effects these drugs have on cognition in HD remain unclear.MethodsIn this study, we used the Enroll-HD observational database to assess the effects of antidopaminergic medication on motor, psychiatric and cognitive decline, over a 3-year period. We first looked at the annual rate of decline of a group of HD patients taking antidopaminergic medication (n=466) compared with an untreated matched group (n=466). The groups were matched on specified clinical variables using propensity score matching. Next, we studied a separate group of HD patients who were prescribed such medications part way through the study (n=90) and compared their rate of change before and after the drugs were introduced and compared this to a matched control group.ResultsWe found that HD patients taking antidopaminergic medication had a slower progression in chorea and irritability compared with those not taking such medications. However, this same group of patients also displayed significantly greater rate of decline in a range of cognitive tasks.ConclusionIn conclusion we found that antidopaminergic treatment is associated with improvements in the choreic movements and irritability of HD but worsens cognition. However, further research is required to prospectively investigate this and whether these are causally linked, ideally in a double-blind placebo-controlled trial.

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