Ambulant Duchenne Muscular Dystrophy Research Articles

Meaningful changes in motor function in Duchenne muscular dystrophy (DMD): A multi-center study.

Evaluations of treatment efficacy in Duchenne muscular dystrophy (DMD), a rare genetic disease that results in progressive muscle wasting, require an understanding of the 'meaningfulness' of changes in functional measures. We estimated the minimal detectable change (MDC) for selected motor function measures in ambulatory DMD, i.e., the minimal degree of measured change needed to be confident that true underlying change has occurred rather than transient variation or measurement error. MDC estimates were compared across multiple data sources, representing >1000 DMD patients in clinical trials and real-world clinical practice settings. Included patients were ambulatory, aged ≥4 to <18 years and receiving steroids. Minimal clinically important differences (MCIDs) for worsening were also estimated. Estimated MDC thresholds for >80% confidence in true change were 2.8 units for the North Star Ambulatory Assessment (NSAA) total score, 1.3 seconds for the 4-stair climb (4SC) completion time, 0.36 stairs/second for 4SC velocity and 36.3 meters for the 6-minute walk distance (6MWD). MDC estimates were similar across clinical trial and real-world data sources, and tended to be slightly larger than MCIDs for these measures. The identified thresholds can be used to inform endpoint definitions, or as benchmarks for monitoring individual changes in motor function in ambulatory DMD.

Muscle Ultrasonography in Relation to Motor Function in Children with Duchenne Muscular Dystrophy

Abstract Background and Aim Duchenne muscular dystrophy (DMD) is the most common muscular dystrophy of childhood and affects 1 per 3600 male births. Electromyography and muscle biopsy were a commonly ordered invasive diagnostic procedure, used to evaluate children with weakness suspected to be caused by muscle disease. Recently, neuromuscular imaging is used as non-invasive diagnostic tool for various muscle diseases. Muscle ultrasonography is increasingly used for the diagnosis and follow up of children with DMD. Aim of the Work The aim of this study was to describe the pattern of ultrasonographic thigh muscles involvement, and to correlate the US findings with motor functional status. Patients and Methods Functional motor assessment was the functional performance protocol (GSGC score) Gait (G), Climbing stairs (S), Gower's maneuver (G), and Arising from a chair (C). Sonographic assessment of quadriceps rectus femoris muscles. Results Twenty-four genetically confirmed ambulatory DMD children were enrolled in this cross- sectional study. Their mean age of 7.46 ± 1.82 (4.5–11 years). The Rt and Lt Quadriceps muscles positively correlated with the age. The Rt. and Lt. Quadriceps muscle assessment significantly related to the scores for gait, stairs, chair arising, GSGC total score, time to walk 10 m, Time to rise from the floor. Conclusion Ultrasonography could be used as a non-invasive method to assess progressive muscle hypertrophy in boys with Duchenne muscular dystrophy. Furthermore, Quadriceps muscle US correlates with the motor functions in ambulant DMD boys below the age of 12 years.

Computer-Aided Diagnosis of Duchenne Muscular Dystrophy Based on Texture Pattern Recognition on Ultrasound Images Using Unsupervised Clustering Algorithms and Deep Learning

ObjectiveThe feasibility of using deep learning in ultrasound imaging to predict the ambulatory status of patients with Duchenne muscular dystrophy (DMD) was previously explored for the first time. The present study further used clustering algorithms for the texture reconstruction of ultrasound images of DMD data sets and analyzed the difference in echo intensity between disease stages. Methodsk-means (Kms) and fuzzy c-means (FCM) clustering algorithms were used to reconstruct the DMD data-set textures. Each image was reconstructed using seven texture-feature categories, six of which were used as the primary analysis items. The task of automatically identifying the ambulatory function and DMD severity was performed by establishing a machine-learning model. ResultsThe experimental results indicated that the Gaussian Naïve Bayes and k-nearest neighbors classification models achieved an accuracy of 86.78% in ambulatory function classification. The decision-tree model achieved an identification accuracy of 83.80% in severity classification. A deep convolutional neural network model was established as the main structure of the deep-learning model while automatic auxiliary interpretation tasks of ambulatory function and severity were performed, and data augmentation was used to improve the recognition performance of the trained model. Both the visual geometry group (VGG)-16 and VGG-19 models achieved 98.53% accuracy in ambulatory-function classification. The VGG-19 model achieved 92.64% accuracy in severity classification. ConclusionRegarding the overall results, the Kms and FCM clustering algorithms were used in this study to reconstruct the characteristic texture of the gastrocnemius muscle group in DMD, which was indeed helpful in quantitatively analyzing the deterioration of the gastrocnemius muscle group in patients with DMD at different stages. Subsequent combination of machine-learning and deep-learning technologies can automatically and accurately assist in identifying DMD symptoms and tracking DMD deterioration for long-term observation.

Decreased quality of life in Duchenne muscular disease patients related to functional neurological and cardiac impairment.

In this prospective study involving 37 Duchenne muscular dystrophy (DMD) patients aged 8-18 years and older, we examined the impact of neurological and cardiac factors on quality of life (QoL). Our findings revealed a negative correlation between upper limb movement and overall mobility, self-service, and usual activities. Ambulatory and non-ambulatory DMD patients showed significant differences in mobility-related parameters. Cardiac evaluations demonstrated associations between mitral annular plane systolic excursion (MAPSE) and mobility-related aspects. The PEDSQL 3.0 neuromuscular model questionnaire further highlighted age-related and movement-related correlations with QoL. The loss of ambulatory status and reduced upper limb movement were negatively associated with QoL, while upper limb movement positively correlated with septal MAPSE. However, no significant associations were found between MAPSE and anxiety/depression. These findings underscore the multifaceted impact of DMD on QoL and emphasize the importance of considering both neurological and cardiac factors in comprehensive patient care.

Patient reported outcome measure for upper limb in Duchenne muscular dystrophy: correlation with PUL2.0.

The increasing pressure to include non ambulant Duchenne muscular dystrophy (DMD) boys in clinical trials has highlighted the need for outcome measures that could address the impact of upper limb function on activities of daily living. The aim of the present study was to establish the correlation between the recently developed Patient Reported Outcome Measure for the upper limb (PROM UL) and the observer rated functional scale Performance of Upper Limb (PUL 2.0) in a large cohort of DMD boys and young adults. As part of a larger natural history study, non ambulant DMD patients were assessed using PUL2.0 and PROM UL. One hundred and twenty-five concurrent PUL 2.0 and PROM UL evaluations from 60 non ambulant DMD boys were taken into consideration. The total PROM UL scores showed a strong correlation with both PUL 2.0 total scores and with PUL 2.0 entry item score. The strong correlation between the two tools confirms the clinical meaningfulness of the PUL2.0 and that the PROM UL can help to detect the gradient of progression of upper limb involvement.

High-Speed T2 -Corrected Multiecho Magnetic Resonance Spectroscopy for Quantitatively Detecting Skeletal Muscle Fatty Infiltration and Predicting the Loss of Ambulation in Patients With Duchenne Muscular Dystrophy.

High-speed T2 -corrected multiecho MRS (HISTO-MRS) is emerging as a quantitative modality for detecting muscle fat infiltration (MFF). However, the predictive value of HISTO-MRS for the loss of ambulation (LoA) in Duchenne muscular dystrophy (DMD) is unknown. To determine the feasibility of HISTO-MRS for assessing MFF in DMD and further identify the predictive value of HISTO-MRS for the LoA. Prospective. A total of 134 DMD boys (9.20 ± 2.43 years old) and 21 healthy boys (9.25 ± 2.10 years old). A 3 T, fast spin echo T1 -weighted imaging (T1 WI), two-point-Dixon gradient echo sequence (2-pt-Dixon) and HISTO-MRS. Subjective T1 WI fat grades by three radiologists, ROI analysis for MFF on 2pt-Dixon (Dixon MFF) and MFF on HISTO-MRS (HISTO MFF) by two radiologists. Clinical motor function: North Star Ambulatory Assessment, 10-m run/walk time, Gowers maneuver, and time to four-stairs climb and descend. Spearman rank correlation was used to assess the relation of fat filtration assessments and motor ability. Bland-Altman plots was performed to determine the agreement of HISTO MFF and Dixon MFF. Receiver operating characteristic (ROC) curves were analyzed to determine the discriminating ability of above MRI modalities for ambulatory and nonambulatory DMD. Logistic regression was used to identify the predictor of LoA. Variables with P < 0.05 in univariate logistic regression analysis were entered into the multivariate logistic regression model. HISTO MFF was significantly correlated with Dixon MFF. Bland-Altman plots show good agreement of HISTO MFF and Dixon MFF. ROC curves indicated that HISTO MFF show similar discrimination of LoA for DMD with Dixon MFF but better value than T1WI fat grades. Logistic regression showed that HISTO MFF was an independent predictor for LoA. HISTO-MRS is a potential quantitative method for assessing fat infiltration and shows predictive value for LoA in DMD patients. Stage 5.

Disease progression rates in ambulatory Duchenne muscular dystrophy by steroid type, patient age and functional status.

Aim: To examinebenefits of corticosteroids for Duchenne muscular dystrophy (DMD) by age and disease progression. Methods: Data from daily steroid users (placebo-treated) were pooled from four phase 2b/3 trials in DMD. Outcomes assessed overall and among subgroups included changes from baseline to 48weeks in six-minute walk distance (6MWD), timed function testsand North Star Ambulatory Assessment total score. Results: Among 231 patients receiving deflazacort (n=127) or prednisone (n=104), observed differences in 6MWD favoring deflazacort over prednisone were significant for patients with relatively older age (≥8-years-old), greater disease progression (baseline timed stand from supine ≥5 s), or longer corticosteroid use (>3years). Conclusion: Daily deflazacort had greater benefits than daily prednisone particularly among older/more progressed patients.

P.65 Consistency of changes in percent-predicted forced vital capacity between real-world data and trial placebo arms in ambulatory Duchenne muscular dystrophy

Use of real-world and natural history data (RWD/NHD) as external controls for pulmonary outcomes is of interest for drug development in ambulatory Duchenne muscular dystrophy (DMD). However, differences across patient populations and RWD/NHD settings raise appropriate concerns about risk of bias. To assess this risk, we compared change in pulmonary function, as measured by percent-predicted forced vital capacity (FVC%p) between RWD/NHD sources and trial placebo arms in ambulatory boys with DMD. RWD/NHD data came from PRO-DMD-01, UZ Leuven, the North Star UK Clinical Network and Cincinnati Children's Hospital Medical Center. Placebo arm data came from phase 3 trials of tadalafil and drisapersen, and one phase 2 trial of drisapersen. PRO-DMD-01 and drisapersen trial data were provided by CureDuchenne. Change in FVC%p over 48-week intervals was studied in ambulatory, steroid-treated boys aged ≥5 years with baseline FVC%p > 50%. Primary analyses included 409 48-week intervals (263 patients) from RWD/NHD, and 161 intervals (161 patients) from placebo arms. At baseline, average ages in these groups were 9.5 and 8.8 years, respectively, and averages for FVC%p were 97.2% and 103.6%. Mean 48-week change in FVC%p was 2.9% greater in in RWD/NHD vs. placebo arms (95% confidence interval [CI]: -1.0%, 6.7%; p=0.14) in unadjusted analyses. After adjusting for baseline status (age, FVC%p, steroid type, height, weight, body mass index, North Star Ambulatory Assessment total score, and 10-meter walk run and rise from supine velocities) the difference in FVC%p between RWD/NHD and placebo arms decreased to -0.1% (95% CI: -3.6, 3.5; p=0.97). Similarly high consistency was observed in sensitivity analyses adjusting for fewer baseline characteristics. These findings are encouraging for use of external controls for FVC%p outcomes in this population. Additional research is needed to assess consistency of FVC%p over longer-time frames, and among older and non-ambulatory boys.

P.67 Development and evaluation of a time to event endpoint for clinical trials in Duchenne muscular dystrophy (DMD)

Event-driven clinical trials, commonly used in oncology, offer several benefits over continuous outcome measures: i) each patient is assessed individually, ii) after the event has occurred, patients can receive therapy without breaking the blind. This study aimed to develop a time-to-event outcome measure for the North Star Ambulatory Assessment (NSAA) corresponding to clinically meaningful disease progression in DMD. Three candidate definitions based on changes in NSAA were investigated: A) Loss of 3 NSAA total score points; B) Loss of 2 distinct NSAA items; C) Loss of 3 NSAA points or loss of 2 NSAA items. To evaluate these definitions, 619 DMD patients with expected decline in motor function (baseline rise from supine ≥5 seconds) were studied from 3 clinical trial placebo arms and 4 natural history studies. At baseline, mean age was 9.3 years (range: 6-18yrs), mean NSAA total score was 22 (range:12-34); 63% were receiving prednisone, 37% deflazacort, and 0.4% no steroids. For each definition, median time to progression was 11.0, 14.0 and 8.3 months, respectively, based on Kaplan-Meier analyses. As a measure of prognostic validity, a progression event during the first year of follow-up was associated with significantly shorter time to loss of ambulation, with hazard ratios of 2.5, 6.5 and 3.2, respectively (all p<0.05), based on landmark analyses. Stability of the progression definitions varied, with approximately 10%, 19% and 12%, respectively, regaining their baseline level of function within a year. Definition A exhibited a favorable combination of event rate, prognostic validity, and stability. A hypothetical, well-powered, randomized, event-driven trial based on endpoint A and enrolling 160 DMD patients over a period of 9 months would require an expected duration of 10, 14, or 25 months to detect treatment effects delaying progression by 13.0, 8.4 or 5.4 months, respectively. Thus, event-driven trials may be viable for drug development in ambulatory DMD.

Natural history of circulating miRNAs in Duchenne disease: Association with muscle injury and metabolic parameters

This study aimed to evaluate whether the expression of circulating dystromiRs and a group of oxidative stress-related (OS-R) miRNAs is associated with muscle injury and circulating metabolic parameters in Duchenne muscular dystrophy (DMD) patients. Twenty-four DMD patients were included in this cross-sectional study. Clinical scales to evaluate muscle injury (Vignos, GMFCS, Brooke, and Medical Research Council), enzymatic muscle injury parameters (CPK, ALT, and AST), anthropometry, metabolic indicators, physical activity, serum dystromiRs (miR-1-3p, miR-133a-3p, and miR-206), and OS-R miRNAs (miR-21-5p, miR-31-5p, miR-128-3p, and miR-144-3p) levels were measured in ambulatory and non-ambulatory DMD patients. DystromiRs (except miR-1-3p) and miRNAs OS-R levels were lower (p-value <.05) in the non-ambulatory group than the ambulatory group. The expression of those miRNAs correlated with Vignos scale score (For instance, rho=-0.567, p-value <0.05 for miR-21-5p) and with other scales scores of muscle function and strength. CPK, AST, and ALT concentration correlated with expression of all miRNAs (For instance, rho=0.741, p-value <.05 between miR-206 level and AST concentration). MiR-21-5p level correlated with glucose concentration (rho=-0.369, p-value=.038), and the miR-1-3p level correlated with insulin concentration (rho=0.343, p-value=.05). Non-ambulatory DMD patients have lower circulating dystromiRs and OS-R miRNAs levels than ambulatory DMD patients. The progressive muscle injury is associated with a decrease in the expression of those miRNAs, evidencing DMD progress. These findings add new information about the natural history of DMD.

Comparison of telerehabilitation versus home-based video exercise in patients with Duchenne muscular dystrophy: a single-blind randomized study

IntroductionPatients with Duchenne muscular dystrophy (DMD) have lost their access to on-site rehabilitation due to the COVID-19 pandemic. Telerehabilitation can be a viable approach for these patients to protect their muscle strength and functional status. The aim of this study is to compare telerehabilitation with home-based video exercises.Patients and methodsMale, ambulatory DMD patients were randomized into telerehabilitation and video-exercise groups. Nineteen patients were included in the final analyses. Telerehabilitation consisted of live online exercises, while video exercise implemented a pre-recorded video as a home-based program. Both programs spanned 8 weeks, three times a week. Patients’ muscle strength with a hand-held dynamometer, Quick Motor Function Test, North-Star Ambulatory Assessment (NSAA), 6-Minute Walk Test (6MWT) and Caregiver Burden were recorded before and after treatment.ResultsThe 6MWT of the telerehabilitation group was391.26 ± 95.08 m before and387.75 ± 210.93 after treatment (p = 0.94) and 327.46 ± 103.88 m before treatment and313.77 ± 114.55 after treatment in video group (p = 0.63). The mean NSAA score of the telerehabilitation group were26.70 ± 8.04 before treatment and 25.20 ± 11.33 after treatment (p = 0.24). In the video group scores were 21.66 ± 6.65 before to 22.00 ± 8.61 after treatment (p = 0.87). There were no significant changes between groups at the end of the treatments. The telerehabilitation group's neck extension, bilateral shoulder abduction, and left shoulder flexion, bilateral knee flexion and extension, bilateral ankle dorsiflexion, and left ankle plantar flexion strength improved significantly and were better than the video group (p < 0.05 for all measurements).ConclusionA telerehabilitation approach is superior in improving muscle strength than a video-based home exercise, but none of the programs improved functional outcomes in ambulatory patients with DMD.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13760-022-01975-4.

Evaluating the Feasibility and Reliability of Remotely Delivering and Scoring the North Star Ambulatory Assessment in Ambulant Patients with Duchenne Muscular Dystrophy.

Objective: The North Star Ambulatory Assessment (NSAA) is a validated 17-item functional rating scale and widely used to assess motor function in boys with Duchenne muscular dystrophy (DMD). The SARS-CoV-2 pandemic and subsequent Government ‘lockdown’ resulted in no face-to-face clinic visits hence the motor abilities were not monitored. The aim was to investigate whether the NSAA was feasible and reliable by video assessment. Method: Ten ambulant DMD boys were selected from the electronic hospital records. Two physiotherapists scored the boys’ NSAA independently and the intraclass correlation coefficient was used to assess agreement. The video scores were compared to two previous NSAA in-clinic scores. Results: Mean scores (SD) for clinic visit one were 22.6 (4.19) and clinic visit two 21.8 (5.3). The two physiotherapists video mean scores were 20.6 (5.66) for physiotherapist 1 and 20.6 (6.53) for physiotherapist 2. The intraclass correlation coefficient was 0.98 (95% CI 0.93–1.00) for the total NSAA and 1.00 (95% CI 1.00 to 1.00) for the rise time. The mean decline in score from clinic visit one (−12 months) to video assessment was 2.0 (2.8SD). Conclusion: The results from the study suggest that video NSAA is partially feasible and reliable.

Muscle-MRI and Functional Levels for the Evaluation of Upper Limbs in Duchenne Muscular Dystrophy: A Critical Review of the Literature.

Many qualitative and quantitative Magnetic Resonance Imaging (MRI) techniques have been applied to evaluate muscle fat degeneration in Duchenne muscular dystrophy (DMD) subjects, but only few studies have focused on the upper limbs. We reviewed the literature in order to evaluate the association between muscle MRI findings and motor function levels in the upper limbs of DMD patients. Ten studies with upper limb muscle MRI data were available. Four explored all upper limb segments, while six explored only the forearm. Functional assessments were performed in nine of the ten studies. All of the studies showed a significant correlation between muscle MRI changes and motor function levels in both ambulant and non-ambulant DMD patients.

Ambulatory Duchenne muscular dystrophy children: cross-sectional correlation between function, quantitative muscle ultrasound and MRI.

Duchenne muscular dystrophy (DMD) is a progressive genetic muscle disease. Quantitative muscle ultrasound (US), muscle MRI, and functional tools are important to delineate characteristics of muscle involvement. We aimed to establish correlations between clinical/functional and above-named imaging tools respecting their diagnostic and prognostic role in DMD children. A cross-sectional retrospective study of 27 steroid-naive, ambulant male children/adolescents with genetically-confirmed DMD (mean age, 8.8 ± 3.3 years). Functional performance was assessed using motor function measure (MFM) which assess standing/transfer (D1), proximal (D2) and distal (D3) motor function, and six-minute walk test (6MWT). Imaging evaluation included quantitative muscle MRI which measured muscle fat content in a specific location of right rectus femoris by mDixon sequence. Quantitative muscle US measured right rectus femoris muscle brightness in standardized US image as an indicator of muscle fat content. We found a highly significant positive correlation between the mean MFM total score and 6MWT (R = 0.537, p = 0.007), and a highly significant negative correlation between fat content by muscle US and MFM total score (R = -0.603, p = 0.006) and its D1 subscore (R =-0.712, p = 0.001), and a significant negative correlation between fat content by US and 6MWT (R = -0.529, p = 0.02), and a significant positive correlation between muscle fat content by mDixon MRI and patient's age (R = 0.617, p = 0.01). Quantitative muscle US correlates significantly with clinical/functional assessment tools as MFM and 6MWT, and augments their role in disease-tracking of DMD. Quantitative muscle US has the potential to act as a substitute to functional assessment tools.

Real-world and natural history data for drug evaluation in Duchenne muscular dystrophy: suitability of the North Star Ambulatory Assessment for comparisons with external controls

Using external controls based on real-world or natural history data (RWD/NHD) for drug evaluations in Duchenne muscular dystrophy (DMD) is appealing given the challenges of enrolling placebo-controlled trials, especially for multi-year trials. Comparisons to external controls, however, face risks of bias due to differences in outcomes between trial and RWD/NHD settings. To assess this bias empirically, we conducted a multi-institution study comparing mean 48-week changes in North Star Ambulatory Assessment (NSAA) total score between trial placebo arms and RWD/NHD sources, with and without adjustment for baseline prognostic factors. Analyses used data from three placebo arms (235 48-week intervals, N = 235 patients) and three RWD/NHD sources (348 intervals, N = 202 patients). Differences in mean ΔNSAA between placebo arms and RWD/NHD sources were small before adjustment (-1.2 units, 95% CI: [-2.0 -0.5]) and were attenuated and no longer statistically significant after adjustment (0.1 units (95% CI: [-0.6, 0.8]). Results were similar whether adjusting using multivariable regression or propensity score matching. This consistency in ΔNSAA between trial placebo arms and RWD/NHD sources accords with prior findings for the six-minute walk distance, provides a well-validated framework for baseline adjustment of prognostic factors, and supports the suitability of RWD/NHD external controls for drug evaluations in ambulatory DMD.

Differentiation of Pediatric-Onset Duchenne and Becker Muscular Dystrophy Subphenotypes Using Data from the Muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet).

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) phenotypes are used to describe disease progression in affected individuals. However, considerable heterogeneity has been observed across and within these two phenotypes, suggesting a spectrum of severity rather than distinct conditions. Characterizing the phenotypes and subphenotypes aids researchers in the design of clinical studies and clinicians in providing anticipatory guidance to affected individuals and their families. Using data from the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet), we used K-means cluster analysis to group phenotypically similar males with pediatric-onset dystrophinopathy. We identified four dystrophinopathy clusters: Classical BMD, Classical DMD, late ambulatory DMD, and severe DMD. The clusters that we identified align with both 'classical' and 'non-classical' dystrophinopathy described in the literature. Individuals with dystrophinopathies have heterogenous clinical presentations that cluster into phenotypically similar groups. Use of clinically-derived phenotyping may provide a clearer understanding of disease trajectories, reduce variability in study results, and prevent exclusion of certain cohorts from analysis. Findings from studying subphenotypes may ultimately improve our ability to predict disease progression.

BODY-MASS INDEX AND BLOOD PRESSURE AS DISEASE MODIFIERS IN DYSTROPHINIC CARDIOMYOPATHY

Objective: Introduction: Duchenne muscular dystrophy (DMD) is one of many neuromuscular diseases, that commonly creates severe disability and early death. Cardiomyopathy associated with DMD is an increasingly acknowledged presentation of this neuromuscular disorder, significantly increasing morbidity and mortality, as well as the requirement for cardiological treatment. Design and method: Purpose: is to review literature data relatively the presence of elevated blood pressure values and body mass index in children with DMD and their impact on the development of heart disease. Results: Several studies have published cross-sectional data about the prevalence of hypertension and increased BMI in children with DMD. Wong et al., 2017 reported that 25.5% of patients on daily steroids aged 10–13 years had systolic hypertension. In patients aged 13–16 years, they reported systolic hypertension in 10.3% of patients. Corticosteroid treatment is thus an essential part of the standards of care in DMD and is recommended from the age of 4 to 5 years onward. Ricotti et al., 2013 observed hypertension in 5% of the patients aged 3–15 years on intermittent steroids while in a study by Braat et al., 2015, 45% of the patients had hypertension. In N.M. van de Velde et al., 2019, study increased BMI, but not systolic blood pressure, was related to early myocardial deformation defined by peak systolic GLS in young DMD patients &lt; 11 years of age. Prevalence of obesity has been described up to 73% in steroid-native DMD patients &lt; 13 years and higher BMI was associated with longer duration and higher cumulative dose in ambulant DMD patients using prednisone (Lamb et al., 2016). In Barber et al. study, 2013 use of corticosteroids has managed to prolongation of the ambulant stage in DMD by almost 3 years. It has also been correlated with a delayed onset of dystrophinic cardiomyopathy in Markham et al., 2008 and Davidson et al., 2014 studies. Conclusions: The results of this review suggest that factors influencing afterload, such as increased blood pressure and BMI, may play a role in the deterioration of cardiac function in DMD.

Jumping Mechanography is a Suitable Complementary Method to Assess Motor Function in Ambulatory Boys with Duchenne Muscular Dystrophy

The number of clinical trials for Duchenne muscular dystrophy (DMD) has increased substantially lately, therefore appropriate clinical instruments are needed to measure disease progression and drug efficacy. Jumping mechanography is a medical diagnostic method for motion analysis, which allows to quantify physical parameters. In this study, we compared mechanography with timed function tests (TFTs). 41 ambulatory DMD patients performed a total of 95 chair rising tests (CRT) and a total of 76 single two-legged jumps (S2LJ) on a mechanography ground reaction force platform. The results were correlated with a 6-minute walk test (6MWT) and the time required to run 10 meters, stand up from a supine position, and climb four stairs, all performed in the same setting. Our measurements show a high correlation between mechanography and the TFTs: S2LJ/10-m run, r = 0.62; CRT/10-m run, r = 0.61; S2LJ/standing up from supine, r = 0.48; CRT/standing up from supine, r = 0.58; S2LJ/climb four stairs, r = 0.55; CRT/climb four stairs, r = 0.51. The correlation between mechanography and the 6MWT was only moderate with r = 0.38 for S2LJ/6MWT and r = 0.39 for CRT/6MWT. Jumping mechanography is a reliable additional method, which can be used for physical endpoint measurements in clinical trials. We confirmed our assumption, that the method provides additional information concerning performance at movement with higher power output. We suggest using the S2LJ as a first-choice tandem tool combined with the 6MWT. In patients with higher disability, the CRT is an alternative measuring method, because with the progression of the disease this is longer feasible.

Novel free-circulating and extracellular vesicle-derived miRNAs dysregulated in Duchenne muscular dystrophy.

Aim: To perform cross-sectional and longitudinal miRNA profilingin plasma from Duchenne muscular dystrophy (DMD) subjects and find non-invasive biomarkers in DMD. Subjects/materials & methods: Plasma was collected from 14 age and sex matched controls and 46 DMD subjects. Free-circulating and extracellular vesicle(EV)-derived miRNAexpression was measured by RT-qPCR. Results: Free-circulating and EVsderived miR-29c-3p and miR-133a-3p are dysregulated in DMD subjects. Free-circulating and EV-derived miR-29c-3p are reduced in DMD subjects undergoing daily corticosteroid treatment. Free-circulating miR-1-3p and miR-122-5p are longitudinally upregulated in ambulant DMD subjects. Conclusion: We detected novel free-circulating and EV-derived dysregulated miRNAs in plasma from DMD subjects and characterized the longitudinal profile of free-circulating miRNA on plasma from DMD subjects.

EP.95Patient perception of outcome measures for non-ambulant Duchenne muscular dystrophy patients

Many therapeutic clinical trials are ongoing in ambulant Duchenne muscular dystrophy (DMD) patients. However, drugs proven effective in ambulant patients will have to be tested separately in non-ambulant patients. Several outcome measures for non-ambulant patients are under development. Natural history data of these measures is needed, while patients struggle to combine this type of extra visits with their daily life. We assessed patient's perception of several different outcome measures for non-ambulant DMD patients. Non-ambulant DMD patients underwent muscle MRI, peak muscle force tests using a Hand-held dynamometer and Myotools, Functional Workspace, Leap Motion and PUL 2.0 assessments of the right arm, and Active-Seated and PROM assessment of both arms. Using visual analogue scale (VAS) scores (range 0-10), all patients were asked directly after the respective assessment how much fun, annoying and tiresome they perceived it. Highest VAS scores on all three domains were correlated to PUL total score using Spearman correlation coefficients. 20 non-ambulant DMD patients (range 8.6-24.1 yrs) were included. Active-Seated scored highest on fun (median 8), followed by muscle force tests and PUL (median 7). MRI was the most annoying (median 5), while all other tests had a median score of 1 or 2. Active-Seated was the most tiresome (median 6), followed by muscle force tests (median 5), and Functional Workspace (median 4). No significant correlation with PUL total score was found for Active-Seated VAS fun and tiresome scores (ρ=-0.04, p=0.871 and ρ=-0.13, p=0.598), and MRI VAS annoying scores (ρ=-0.46, p=0.053). While Active-Seated and muscle force tests score highest on fun, they are also the most tiresome. MRI has the advantage of no motivation component, but scored highest on annoyment. To improve participation in both therapeutic and natural history studies, patient's perception of outcome measures for non-ambulant DMD patients and their respective burden need to be considered.