scholarly journals MRI vastus lateralis fat fraction predicts loss of ambulation in Duchenne muscular dystrophy

Neurology ◽  
2020 ◽  
Vol 94 (13) ◽  
pp. e1386-e1394 ◽  
Author(s):  
Karin J. Naarding ◽  
Harmen Reyngoudt ◽  
Erik W. van Zwet ◽  
Melissa T. Hooijmans ◽  
Cuixia Tian ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Predictive Value ◽  
Mixed Model ◽  
Cox Model ◽  
Medical Center ◽  
Vastus Lateralis ◽  
Hazard Ratio ◽  
Quantitative Mri ◽  
Fat Fraction

ObjectiveWe studied the potential of quantitative MRI (qMRI) as a surrogate endpoint in Duchenne muscular dystrophy by assessing the additive predictive value of vastus lateralis (VL) fat fraction (FF) to age on loss of ambulation (LoA).MethodsVL FFs were determined on longitudinal Dixon MRI scans from 2 natural history studies in Leiden University Medical Center (LUMC) and Cincinnati Children's Hospital Medical Center (CCHMC). CCHMC included ambulant patients, while LUMC included a mixed ambulant and nonambulant population. We fitted longitudinal VL FF values to a sigmoidal curve using a mixed model with random slope to predict individual trajectories. The additive value of VL FF over age to predict LoA was calculated from a Cox model, yielding a hazard ratio.ResultsEighty-nine MRIs of 19 LUMC and 15 CCHMC patients were included. At similar age, 6-minute walking test distances were smaller and VL FFs were correspondingly higher in LUMC compared to CCHMC patients. Hazard ratio of a percent-point increase in VL FF for the time to LoA was 1.15 for LUMC (95% confidence interval [CI] 1.05–1.26; p = 0.003) and 0.96 for CCHMC (95% CI 0.84–1.10; p = 0.569).ConclusionsThe hazard ratio of 1.15 corresponds to a 4.11-fold increase of the instantaneous risk of LoA in patients with a 10% higher VL FF at any age. Although results should be confirmed in a larger cohort with prospective determination of the clinical endpoint, this added predictive value of VL FF to age on LoA supports the use of qMRI FF as an endpoint or stratification tool in clinical trials.

scholarly journals Association of Elbow Flexor MRI Fat Fraction With Loss of Hand-to-Mouth Movement in Patients With Duchenne Muscular Dystrophy

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012724
Author(s):  
Karin J. Naarding ◽  
Menno van der Holst ◽  
Erik W. van Zwet ◽  
Nienke M. van de Velde ◽  
Imelda J.M. de Groot ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Predictive Value ◽  
Cox Model ◽  
Hazard Ratio ◽  
Elbow Flexor ◽  
Quantitative Mri ◽  
Phone Calls ◽  
Fat Fraction ◽  
Mouth Movement

Objective:To study the potential of quantitative MRI (qMRI) fat fraction (FF) as biomarker in non-ambulant Duchenne muscular dystrophy (DMD) patients, we assessed the additive predictive value of elbow flexor FF to age on loss of hand-to-mouth movement.Methods:Non-ambulant DMD patients (≥8 years) were included. 4-point Dixon MRI scans of the right upper arm were performed at baseline and at 12, 18 or 24 months follow-up. Elbow flexor FFs were determined from five central slices. Loss of hand-to-mouth movement was determined at study visits and by phone-calls every four months. FFs were fitted to a sigmoidal curve using a mixed model with random slope to predict individual trajectories. The added predictive value of elbow flexor FF to age on loss of hand-to-mouth movement was calculated from a Cox model with the predicted FF as a time varying covariate, yielding a hazard ratio.Results:Forty-eight MRIs of 20 DMD patients were included. The hazard ratio of a percent-point increase in elbow flexor FF for the time to loss of hand-to-mouth movement was 1.12 (95%-confidence interval 1.04-1.21; p=0.002). This corresponded to a 3.13-fold increase of the instantaneous risk of loss of hand-to-mouth movement in patients with a 10 percent-points higher elbow flexor FF at any age.Conclusion:In this prospective study, elbow flexor FF predicted loss of hand-to-mouth movement independent of age. qMRI measured elbow flexor FF can be used as surrogate endpoint or stratification tool for clinical trials in non-ambulant DMD patients.Classification of Evidence:This study provides Class II evidence that qMRI FF of elbow flexor muscles in patients with DMD predicts loss of hand-to-mouth movement independent of age.

scholarly journals Quantitative muscle MRI biomarkers in Duchenne muscular dystrophy: cross-sectional correlations with age and functional tests

2021 ◽  
Author(s):  
Sarah P Sherlock ◽  
Yao Zhang ◽  
Michael Binks ◽  
Shannon Marraffino
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
T2 Mapping ◽  
Quantitative Mri ◽  
Thigh Muscle ◽  
Ambulatory Assessment ◽  
Functional Tests ◽  
Muscle Mri ◽  
Cross Sectional ◽  
Fat Fraction

Aim: Using baseline data from a clinical trial of domagrozumab in Duchenne muscular dystrophy, we evaluated the correlation between functional measures and quantitative MRI assessments of thigh muscle. Patients & methods: Analysis included timed functional tests, knee extension/strength and North Star Ambulatory Assessment. Patients (n = 120) underwent examinations of one thigh, with MRI sequences to enable measurements of muscle volume (MV), MV index, mean T2 relaxation time via T2-mapping and fat fraction. Results: MV was moderately correlated with strength assessments. MV index, fat fraction and T2-mapping measures had moderate correlations ( r ∼ 0.5) to all functional tests, North Star Ambulatory Assessment and age. Conclusion: The moderate correlation between functional tests, age and baseline MRI measures supports MRI as a biomarker in Duchenne muscular dystrophy clinical trials. Trial registration: ClinicalTrials.gov , NCT02310763 ; registered 4 November 2014.

scholarly journals Genotype characterization and delayed loss of ambulation by glucocorticoids in a large cohort of patients with Duchenne muscular dystrophy

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Shu Zhang ◽  
◽  
Dongdong Qin ◽  
Liwen Wu ◽  
Man Li ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Hazard Ratio ◽  
Large Cohort ◽  
Muscle Disease ◽  
Clinical Progression ◽  
Large Deletions ◽  
The Mean ◽  
Lower Hazard

Abstract Background Duchenne muscular dystrophy (DMD) is the most common genetic muscle disease in human. We aimed to describe the genotype distribution in a large cohort of Chinese DMD patients and their delayed loss of ambulation by glucocorticoid (GC) treatments. This is to facilitate protocol designs and outcome measures for the emerging DMD clinical trials. Results A total of 1163 patients with DMD were recruited and genotyped. Genotype variations were categorized as large deletions, large duplications, and small mutations. Large deletions were further analyzed for those amenable to exon-skipping therapies. Participants aged 5 years or older were grouped into GC-treated and GC-naïve groups. Clinical progression among different genotypes and their responses to GC treatments were measured by age at loss of ambulation (LOA). Among the mutation genotypes, large deletions, large duplications, and small mutations accounted for 68.79%, 7.14%, and 24.07%, respectively. The mean age at diagnosis was 4.59 years; the median ages at LOA for the GC-naïve, prednisone/prednisolone-treated, and deflazacort-treated groups were 10.23, 12.02, and 13.95 years, respectively. The “deletion amenable to skipping exon 44” subgroup and the nonsense-mutation subgroup had older ages at LOA than the “other deletions” subgroup. Subgroups were further analyzed by both genotypes and GC status. All genotypes showed significant beneficial responses to GC treatment. Deletions amenable to skipping exon 44 showed a lower hazard ratio (0.155). The mean age at death was 18.57 years in this DMD group. Conclusion Genotype variation influences clinical progression in certain DMD groups. Beneficial responses to GC treatment were observed among all DMD genotypes. Compared with other genotypes, deletions amenable to skipping exon 44 had a lower hazard ratio, which may indicate a stronger protective effect of GC treatments on this subgroup. These data are valuable for designing future clinical trials, as clinical outcomes may be influenced by the genotypes.

scholarly journals MR biomarkers predict clinical function in Duchenne muscular dystrophy

Neurology ◽  
2020 ◽  
Vol 94 (9) ◽  
pp. e897-e909 ◽  
Author(s):  
Alison M. Barnard ◽  
Rebecca J. Willcocks ◽  
William T. Triplett ◽  
Sean C. Forbes ◽  
Michael J. Daniels ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Lower Extremity ◽  
Vastus Lateralis ◽  
Strong Relationship ◽  
Biceps Femoris ◽  
Loss Of Function ◽  
Long Head ◽  
Biceps Femoris Long Head ◽  
Over Time

ObjectiveTo investigate the potential of lower extremity magnetic resonance (MR) biomarkers to serve as endpoints in clinical trials of therapeutics for Duchenne muscular dystrophy (DMD) by characterizing the longitudinal progression of MR biomarkers over 48 months and assessing their relationship to changes in ambulatory clinical function.MethodsOne hundred sixty participants with DMD were enrolled in this longitudinal, natural history study and underwent MR data acquisition of the lower extremity muscles to determine muscle fat fraction (FF) and MRI T2 biomarkers of disease progression. In addition, 4 tests of ambulatory function were performed. Participants returned for follow-up data collection at 12, 24, 36, and 48 months.ResultsLongitudinal analysis of the MR biomarkers revealed that vastus lateralis FF, vastus lateralis MRI T2, and biceps femoris long head MRI T2 biomarkers were the fastest progressing biomarkers over time in this primarily ambulatory cohort. Biomarker values tended to demonstrate a nonlinear, sigmoidal trajectory over time. The lower extremity biomarkers predicted functional performance 12 and 24 months later, and the magnitude of change in an MR biomarker over time was related to the magnitude of change in function. Vastus lateralis FF, soleus FF, vastus lateralis MRI T2, and biceps femoris long head MRI T2 were the strongest predictors of future loss of function, including loss of ambulation.ConclusionsThis study supports the strong relationship between lower extremity MR biomarkers and measures of clinical function, as well as the ability of MR biomarkers, particularly those from proximal muscles, to predict future ambulatory function and important clinical milestones.ClinicalTrials.gov identifierNCT01484678.

Quantitative MRI and strength measurements in the assessment of muscle quality in Duchenne muscular dystrophy

2014 ◽  
Vol 24 (5) ◽  
pp. 409-416 ◽  
Author(s):  
B.H. Wokke ◽  
J.C. van den Bergen ◽  
M.J. Versluis ◽  
E.H. Niks ◽  
J. Milles ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Quantitative Mri ◽  
Muscle Quality

scholarly journals The natural history of the patients with Duchenne muscular dystrophy in Taiwan: A medical center experience

2018 ◽  
Vol 59 (2) ◽  
pp. 176-183 ◽  
Author(s):  
Wen-Chen Liang ◽  
Chen-Hua Wang ◽  
Po-Ching Chou ◽  
Wan-Zi Chen ◽  
Yuh-Jyh Jong
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Natural History ◽  
Medical Center ◽  
History Of

Predictive Value of Myocardial Delayed Enhancement in Duchenne Muscular Dystrophy

2014 ◽  
Vol 35 (7) ◽  
pp. 1279-1285 ◽  
Author(s):  
Shaji C. Menon ◽  
Susan P. Etheridge ◽  
Kirk N. Liesemer ◽  
Richard V. Williams ◽  
Tyler Bardsley ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Predictive Value ◽  
Delayed Enhancement ◽  
Myocardial Delayed Enhancement

Towards objective and reproducible measures of thigh muscle fat fraction in patients with Duchenne Muscular Dystrophy

2017 ◽  
Vol 27 ◽  
pp. S7
Author(s):  
A. Fischmann ◽  
C. Trentin ◽  
M. Gloor ◽  
R. Andriantsimiavona ◽  
D. Fischer ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Thigh Muscle ◽  
Fat Fraction

scholarly journals Large-scale serum protein biomarker discovery in Duchenne muscular dystrophy

2015 ◽  
Vol 112 (23) ◽  
pp. 7153-7158 ◽  
Author(s):  
Yetrib Hathout ◽  
Edward Brody ◽  
Paula R. Clemens ◽  
Linda Cripe ◽  
Robert Kirk DeLisle ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Healthy Volunteers ◽  
Large Scale ◽  
Biomarker Discovery ◽  
Medical Center ◽  
Drug Effects ◽  
Serum Samples ◽  
Normal Volunteers ◽  
Surrogate Outcome

Serum biomarkers in Duchenne muscular dystrophy (DMD) may provide deeper insights into disease pathogenesis, suggest new therapeutic approaches, serve as acute read-outs of drug effects, and be useful as surrogate outcome measures to predict later clinical benefit. In this study a large-scale biomarker discovery was performed on serum samples from patients with DMD and age-matched healthy volunteers using a modified aptamer-based proteomics technology. Levels of 1,125 proteins were quantified in serum samples from two independent DMD cohorts: cohort 1 (The Parent Project Muscular Dystrophy–Cincinnati Children’s Hospital Medical Center), 42 patients with DMD and 28 age-matched normal volunteers; and cohort 2 (The Cooperative International Neuromuscular Research Group, Duchenne Natural History Study), 51 patients with DMD and 17 age-matched normal volunteers. Forty-four proteins showed significant differences that were consistent in both cohorts when comparing DMD patients and healthy volunteers at a 1% false-discovery rate, a large number of significant protein changes for such a small study. These biomarkers can be classified by known cellular processes and by age-dependent changes in protein concentration. Our findings demonstrate both the utility of this unbiased biomarker discovery approach and suggest potential new diagnostic and therapeutic avenues for ameliorating the burden of DMD and, we hope, other rare and devastating diseases.

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