Duchenne Muscular Dystrophy Children Research Articles

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.

Gait Characterization in Duchenne Muscular Dystrophy (DMD) Using a Single-Sensor Accelerometer: Classical Machine Learning and Deep Learning Approaches.

Differences in gait patterns of children with Duchenne muscular dystrophy (DMD) and typically developing (TD) peers are visible to the eye, but quantifications of those differences outside of the gait laboratory have been elusive. In this work, we measured vertical, mediolateral, and anteroposterior acceleration using a waist-worn iPhone accelerometer during ambulation across a typical range of velocities. Fifteen TD and fifteen DMD children from 3 to 16 years of age underwent eight walking/running activities, including five 25 m walk/run speed-calibration tests at a slow walk to running speeds (SC-L1 to SC-L5), a 6-min walk test (6MWT), a 100 m fast walk/jog/run (100MRW), and a free walk (FW). For clinical anchoring purposes, participants completed a Northstar Ambulatory Assessment (NSAA). We extracted temporospatial gait clinical features (CFs) and applied multiple machine learning (ML) approaches to differentiate between DMD and TD children using extracted temporospatial gait CFs and raw data. Extracted temporospatial gait CFs showed reduced step length and a greater mediolateral component of total power (TP) consistent with shorter strides and Trendelenberg-like gait commonly observed in DMD. ML approaches using temporospatial gait CFs and raw data varied in effectiveness at differentiating between DMD and TD controls at different speeds, with an accuracy of up to 100%. We demonstrate that by using ML with accelerometer data from a consumer-grade smartphone, we can capture DMD-associated gait characteristics in toddlers to teens.

Dual task impact on functional mobility and interaction of functional level and balance in patients with Duchenne muscular dystrophy

BackgroundDystrophin, a protein crucial for various brain regions governing higher-order functions like learning and memory is notably absent in individuals with Duchenne muscular dystrophy (DMD). This absence of dystrophin in the brain is believed to underlie cognitive challenges in DMD. Cognitive and motor challenges observed in DMD could potentially hinder the execution of dual tasks. Research questionIs there a significant correlation between dual-task performance, functional mobility, and balance in children with DMD? MethodThe study included 28 participants (14 DMD, 14 typical development). Timed Up and Go (TUG) test results were recorded for single and dual-task conditions (motor-motor, cognitive-motor). Functional level was assessed using Motor Function Measurement-32 (MFM-32), Brooke Upper Extremity Scale, and Vignos Scale. Balance was evaluated using Balance Master System and Pediatric Functional Reach Test (PFRT). ResultsSignificant differences in TUG test scores across conditions were observed in both DMD and typical development groups (p < 0.05). Children with DMD exhibited longer completion times compared to typical development children (p < 0.05). Among children with DMD, there was a significant correlation between TUG scores in different task conditions and balance assessment (p < 0.05, r = 0.571 to −0.819). Lower MFM-32 scores in DMD children were correlated with worse TUG performance across conditions (p < 0.05, r = 0.586 to −0.868). SignifianceThis study sheds light on the multifaceted nature of dual-tasking challenges in individuals with DMD, thereby contributing to a deeper understanding of the implications for rehabilitation strategies.

86 Memory Performance in Children with Duchenne and Becker Muscular Dystrophy

Objective:There is limited and mixed research describing the memory performance of boys with Duchenne muscular dystrophy (DMD), a progressive disorder that affects the muscle and the brain, presumably due to the absence of dystrophin; however, the literature indicates either the existence of a selective deficit in verbal working memory, or more generalized impairment in both verbal and visual memory. Far less is documented about the neurocognitive profile of boys with Becker muscular dystrophy (BMD), a closely related neuromuscular disorder which allows for at least some functional dystrophin protein to circulate. The Child and Adolescent Memory Profile (ChAMP) is a valid and widely used memory battery that has not been studied in either DMD or BMD. This study aimed to assess the verbal and visual memory performance in boys having either a DMD or a BMD diagnosis using the ChAMP. A working memory measure, the Digit Span subtest from the Wechsler Intelligence Scale for Children-Fifth Edition, was also included for comparison.Participants and Methods:Twenty-one patients (Age M = 12.19 ± 3.60; 100% male; 76% DMD, 24% Becker) were selected from retrospective data collection of neuropsychological performance in children with neuromuscular disorders. Patients were recruited and assessed as part of a larger scale IRB-approved research study designed to better understand the neurocognitive and behavioral trajectories of boys with DMD or BMD with a complete neuropsychological battery.Results:Independent samples f-tests revealed no significant differences between groups across verbal (DMD M = 88.71; BMD M = 100.80; p = .08), visual (DMD M =90.36; BMD M 93.60; p = .33), and working memory (DMD M = 84.69; BMD: M 82.60; p = .40) domains. In additional analyses, a one sample f-test comparing verbal and visual memory within DMD children revealed significantly worse verbal than visual memory scores (verbal memory M = 88.71; visual memory M = 90.36; p = &lt;.001).Conclusions:There were no significant differences between groups in verbal, visual, and working memory performance, though sample size was a significant limitation. However, based on a comparison of means, children with BMD appear to have stronger verbal memory skills than children with DMD. Furthermore, significant differences between verbal and visual memory within DMD children were observed, such that verbal memory skills were weaker. These findings add to the absence of literature on verbal and visual memory outcomes in children with DMD and BMD.

Duchenne Muscular Dystrophy Fatigue Trajectories.

Children with Duchenne muscular dystrophy (DMD) are at risk of experiencing fatigue that negatively impacts their health-related quality of life (HRQoL). This study aimed to assess the association between fatigue and HRQoL, by examining fatigue trajectories over 48 weeks, and assessing factors associated with these fatigue trajectories. The study sample consisted of 173 DMD subjects enrolled in a 48-week-long phase 2 clinical trial (NCT00592553) for a novel therapeutic who were between the ages of 5 and 16 years. The results of regression modeling show baseline fatigue and baseline HRQoL (R 2 = 0. 54 for child self-report and 0.51 for parent proxy report) and change in fatigue and HRQoL over 48 weeks (R 2 = 0.47 for child self-report and 0.36 for parent proxy report) were significantly associated with one another. Three unique fatigue trajectories using Latent Class Growth Models were identified for child and parent proxy reported fatigue. The risk of being in the high fatigue group as compared to the low fatigue group increased by 24% with each year increase in age and also with decreasing walking distance, as reported by children and parent proxy, respectively. This study identified fatigue trajectories and risk factors associated with greater fatigue, helping clinicians and researchers identify the profile of fatigue in DMD children.

Neuro-Cardio-Autonomic Modulations in Children with Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD) is a degenerative X-linked muscle disease. Death frequently results from complications in cardiopulmonary systems. Preclinical/early diagnosis of cardiac autonomic abnormalities may aid initiate cardioprotective therapy and enhance prognosis. A cross sectional, prospective study of 38 DMD boys compared with 37 age-matched healthy controls was conducted. Lead II electrocardiography and beat-to-beat blood pressure were recorded to assess heart rate variability (HRV), blood pressure variability (BPV), and baroreceptor sensitivity (BRS) in a standardized environment. Data were analysed and correlated with disease severity and genotype. In the DMD group, the median age at assessment was 8 years [IQR 7-9 years], the median age at disease onset was 3 years [IQR, 2-6 years], and the mean duration of illness was 4 years [IQR, 2.5-5]. DNA sequencing showed deletions in 34/38 (89.5 %) and duplications in 4/38 (10.5%) patients. The median heart rate in DMD children was significantly higher [101.19 (Range, 94.71-108.49)] /min compared to controls [81 (Range, 76.2-92.76)] /min (p < 0.05). All the assessed HRV and BPV parameters were significantly impaired in DMD cases except for the coefficient of variance of systolic blood pressure. Further, BRS parameters were also significantly reduced in DMD, excluding alpha-LF. A positive correlation was found between alpha HF with age at onset and duration of illness. This study demonstrates a distinct early impairment of neuro-cardio-autonomic regulation in DMD. Simple yet effective non-invasive techniques such as HRV, BPV, and BRS may help identify cardiac dysfunction in a pre-clinical state, paving the way for early cardio-protective therapies and limiting disease progression in DMD patients.

Effect of respiratory muscle training using Ultrabreathe device on pulmonary function in Duchenne Muscular Dystrophy through telephysiotherapy

Background. Duchenne Muscular Dystrophy (DMD), an X linked disorder resulting in respiratory insufficiency, caused by progressive respiratory muscle weakness particularly in diaphragm. During this pandemic, Telerehabilitation played a major role among patients, especially disabled children. OBJECTIVE: To find out the effect on the pulmonary function in DMD children by training the respiratory muscles by telephysiotherapy. Methodology. Non Experimental design, Case series- pre and post test type. Convenient sampling, sample size was 5. Boys and girls between 9 and 16 years of age were included in the study. Procedure. 5 subjects were selected based on the inclusion and exclusion criteria and were trained for one minute with minimum resistance using ultrabreathe through Telephysiotherapy which is repeated for 3 times in a session with a rest period of 20–30 seconds for six weeks. Outcome measure. Pulmonary Function test. Results. The results of this study shows increased mean value of post test Tidal volume, Forced Vital Capacity, Inspiratory time/Respiration time and Tidal Volume / Inspiration time compared with pre test, whereas other parameters like Duration of Inspiration, Total Lung Volume, Inspiratory Capacity, Forced Expiratory Volume1 does not increased. Conclusion This study concluded that the Duchenne Muscular Dystrophy children improved in Tidal Volume, Forced Vital Capacity, Tidal Volume/Inspiration Time, and Inspiration Time/Respiration Time whereas all other parameters such as Duration of Inspiration, Total lung volume, Inspiratory capacity and Forced Expiratory volume1 maintained after 6 weeks of respiratory muscles training with ultrabreathe device.

Cross-Sectional Study of Nutritional Status and Dietary Nutrient Intake in Children with Duchenne Muscular Dystrophy (DMD) in China

To investigate the dietary nutrient intake and the nutritional status of children with Duchenne muscular dystrophy (DMD), and to explore the correlation between them, so as to provide theoretical basis for the formulation of proper nutritional treatment for children with DMD. A total of 223 children aged 2 to 14 years who came to West China Second University Hospital, Sichuan University from July 2017 to April 2021, and who were diagnosed with DMD by genetic testing were enrolled as the subjects of the study. Dietary assessment was conducted with a 3-day 24-hour dietary recall, and serum vitamin D level was measured by chemiluminescence method. Only 33.2% of the children with DMD were found to be of normal nutritional status. The incidences of stunted growth, underweight, overweight and obesity were 13.5%, 14.4%, 14.3% and 8.1%, respectively. Among the children with DMD, those with serum vitamin D deficiency and insufficiency accounted for 9.0% and 89.7%, respectively. According to the dietary recall of the children with MDM, the daily energy ratio of carbohydrate, protein and fat were (47.40±6.64)%, (14.46±2.22)%, and (38.17±5.30)%, respectively. The daily intake of dietary calcium and vitamin D were (433.32±164.39) mg per day and (155.73±89.30) IU per day, respectively. The ratio of daily protein intake to the estimated average requirement for protein ( P=0.003) and ratio of daily energy intake to the estimated energy requirement ( P=0.007) were lower in children with stunted growth than those of DMD children of normal nutritional status. The dietary structure of children with DMD is obviously not suited to their condition and nutritional deficiency coexists with overnutrition among them. Further research needs to be done for developing appropriate nutritional guidance programs and standardized nutritional management measures for children with DMD.

Validation of Pedsql™ Duchenne Muscular Dystrophy Module (Acute Version 3.0), in Young Children (Age 5-7)

Objective: The goal of this project was to accurately translate the “PedsQLTM 3.0 DMD” Module into Urdu and to assess its validity in health-related quality of life in the Duchenne muscular dystrophy (DMD)” children age 5 to 7 years reported by their parents. Method: The study was conducted with the parents/caregivers of DMD children in Rising Sun Institute, PSRD, Hope,Gosha e Shifa, Special gems, Ghazali Foundation Rawalpindi and DHQ hospital Jhang. Study was cross cultural validation including 56 primary care givers. First of all questionnaire of primary care giver was translated in Urdu by using forward translation, the second step was reconciliation of items; in this the best Urdu translation was selected. Backward translation was completed in the third phase, and a review was conducted to evaluate the full forward-backward procedure in order to produce a final forward translation. Validity &amp; Reliabity were measured. To determine in the internal consistency Cronbach’s Alpha was used Test-Retest reliability was checked. Content Validity Index and Content Validity Ratio were measured through 5 experts. To analyze the collected data SPSS 26 was used. Results: The results showed that in both genders from age 5 to 7 years DMD affects the quality of life of child as reported by parents. The value of Cronbach's alpha was 0.913.After factor analysis KMO was 0.793 and because the p value was less than 0.05, the test was significant. Conclusion: Urdu version of “PedsQLTM Duchenne Muscular Dystrophy Acute Version 3.0(age 5-7) Parent report for young children” is a stable and consistent instrument for assessing quality of life measures of the DMD children and can be applied in Urdu speaking population throughout the world. Keywords: Duchenne Muscular Dystrophy, “PedsQL™ 3.0 DMD Module”, Urdu translation, validity, quality of life.

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.

Effectiveness of Inspiratory muscle training using Ultrabreathe on Pulmonary function in Duchenne Muscular Dystrophy

Background: Individual with Duchenne Muscular Dystrophy are more prone for respiratory dysfunction. And thus the leading cause for death DMD. Objective: To find the effectiveness of inspiratory muscle training using ULTRABREATHE on pulmonary function in Duchenne Muscular Dystrophy. Methodology: The quasi experimental study was done in 5 Duchenne Muscular Dystrophy children as one group of age ranging from 9 to 16 years in wheelchair bound stage and they have been given for an ULTRABREATHE as an inspiratory muscle trainer for duration of six weeks. Outcome Measures: Pulmonary Function Test was analyzed using spirometry. Results: Statistical analysis shows, the mean and standard deviation value is 1.5380 and .84736 in pretest and the mean and standard deviation is 1.71 and .88752 with respect to tidal volume which shows significant improvement at p value&gt; 0.038, whereas the other components like Duration of Inspiration, Total Lung Volume/Inspiration Time, Total Lung Volume, Inspiratory Capacity, Inspiration Time/Respiration Time, Forced Vital Capacity and Forced Expiratory Volume in One second (FEV1) not showed an significant improvement. Conclusion: The study concluded that the Effectiveness of inspiratory muscle training using ULTRABREATHE on pulmonary function in Duchenne Muscular Dystrophy children showed improvement only in Tidal Volume whereas all other components not showed a significant improvement.

Assessment of left ventricular dyssynchrony by speckle tracking echocardiography in children with Duchenne muscular dystrophy

Prognosis of Duchenne muscular dystrophy (DMD) is related to cardiac dysfunction. Two dimensional-speckle tracking echocardiography (2D-STE) has recently emerged as a non-invasive functional biomarker for early detection of DMD-related cardiomyopathy. This study aimed to determine, in DMD children, the existence of a left ventricle (LV) dyssynchrony using 2D-STE analysis. This prospective controlled study enrolled 25 boys with DMD (mean age 11.0 ± 3.5 years) with normal LV ejection fraction and 50 age-matched controls. Three measures were performed to assess LV mechanical dyssynchrony: the opposing-wall delays (longitudinal and radial analyses), the modified Yu index, and the time-to-peak delays of each segment. Feasibility and reproducibility of 2D-STE dyssynchrony were evaluated. All three mechanical dyssynchrony criteria were significantly higher in the DMD group than in healthy subjects: – opposing-wall delays in basal inferoseptal to basal anterolateral segments (61.4 ± 45.3 msec vs. 18.3 ± 50.4 msec, P < 0.001, respectively) and in mid inferoseptal to mid anterolateral segments (58.6 ± 35.3 msec vs. 42.4 ± 36.4 msec, P < 0.05, respectively); – modified Yu index (33.3 ± 10.1 msec vs. 28.5 ± 8.1 msec, P < 0.05, respectively); – most of time-to-peak values, especially in basal and mid anterolateral segments. Feasibility was excellent and reliability was moderate to excellent, with ICC values ranging from 0.49 to 0.97 ( Fig. 1 ). Detection of LV mechanical dyssynchrony using 2D-STE analysis is an easily and reproducible method in pediatrics. The existence of an early LV mechanical dyssynchrony visualized using 2D-STE analysis in children with DMD before the onset of cardiomyopathy represents a perspective for future pediatric drug trials in the DMD-related cardiomyopathy prevention.

First manifestation and evolution of early left ventricular dysfunction in children with Duchenne muscular dystrophy

Background: Standard pediatric cardiology examinations and echocardiography fail to discover when the cardiomyopathy will occur in patient with Duchenne muscular dystrophy (DMD). Noninvasive markers are needed to fill this gap. Material and methods: This cohort study included a total number of 30 children (21 children (70%) with DMD and 9 (30%) healthy children. Blood samples were used for biochemical (level of creatine kinase, creatine kinase-MB, lactate dehydrogenase) and miRNA (presence of miR133a 3p, miR133b 3p, miR206 3p, miR208a 3p, miR208b 3p) analysis. All patients underwent partial conventional echocardiography ECOCG and Speckle Tracking. Results: The children in the working group presented compared to healthy children: FCC values increased by 15 (71%) vs 2 (22%), high levels of CK, CK-MB, LDH, which is characteristic for the disease and reflects its stage. Also, there is a decrease in systolic function indicators in the working group: mean FE 59 ± 3.8 %, and GLS: -16.2 ± 3.1%. MiRNA analyses confirmed the presence of miR133a 3p, miR133b 3p, miR206 3p, miR208a 3p, miR208b 3p in both working and control group. Conclusions: For the first time in the Republic of Moldova, we developed and adapted protocols for RNA extraction from human blood, performing screening of specific miRNA in the serum of patients with DMD and healthy children. Also, altered LV strain notwithstanding a normal or mildly modified LVEF represents an essential viewpoint for prospective pediatric drug trials in DMD-related cardiomyopathy prevention.

Characterizing the quality-of-life impact of Duchenne muscular dystrophy on caregivers: a case-control investigation

BackgroundThis study examined the impact of Duchenne muscular dystrophy (DMD) on family-member caregivers in terms of quality of life, life stress, and indirect costs, as compared to a stratified comparison group of parents of similar-age children without DMD.MethodsA web-based survey included DMD caregivers and a nationally representative comparison group of parents of children without DMD stratified by Child Age Group. Outcomes included quality of life, resilience, caregiver impact, stressful life events, financial strain, out-of-pocket expenditures, work productivity and unrealized ambitions. General linear models assessed the main effect of Caregiver Group and the interaction of Caregiver Group with Child-Age-Group, after adjusting for demographic covariates.ResultsCompared to parents without a DMD child, DMD Caregivers reported better physical health but worse mental health, positive affect/well-being, environmental mastery, difficulty paying bills, and more hours missed from work. Providing caregiving support for DMD teenagers was the most challenging. DMD caregivers curtailed their educational and professional ambitions, and modified their homes to accommodate the disability associated with DMD. Their non-DMD children had to make sacrifices as well. Nonetheless, in resilience and life stress, DMD caregivers were comparable to the comparison group, and showed consistent levels of positive emotions across the age of their DMD child.ConclusionDMD caregivers fared worse on most outcomes and faced more hurdles in work life. They face constraints and hidden costs that impact their health and financial well-being. Caregivers of teenagers with DMD reported higher impact. Nonetheless, parents of DMD children of all ages maintained notable resilience and positivity.

Genotype-related respiratory progression in Duchenne muscular dystrophy-A multicenter international study.

Mutations amenable to skipping of specific exons have been associated with different motor progression in Duchenne muscular dystrophy (DMD). Less is known about their association with long-term respiratory function. In this study we investigated the features of respiratory progression in four DMD genotypes relevant in ongoing exon-skipping therapeutic strategies. This was a retrospective longitudinal study including DMD children followed by the UK NorthStar Network and international AFM Network centers (May 2003 to October 2020). We included boys amenable to skip exons 44, 45, 51, or 53, who were older than 5 years of age and ambulant at first recorded visit. Subjects who were corticosteroid-naive or enrolled in interventional clinical trials were excluded. The progression of respiratory function (absolute forced vital capacity [FVC] and calculated as percent predicted [FVC%]) was compared across the four subgroups (skip44, skip45, skip51, skip53). We included 142 boys in the study. Mean (standard deviation) age at first visit was 8.6 (2.5) years. Median follow-up was 3 (range, 0.3-8.3) years. In skip45 and skip51, FVC% declined linearly from the first recorded visit. From the age of 9 years, FVC% declined linearly in all genotypes. Skip44 had the slowest (2.7%/year) and skip51 the fastest (5.9%/year) annual FVC% decline. The absolute FVC increased progressively in skip44, skip45, and skip51. In skip53, FVC started declining from 14 years of age. The progression of respiratory dysfunction follows different patterns for specific genotype categories. This information is valuable for prognosis and for the evaluation of exon-skipping therapies.

Disrupted structural connectome and neurocognitive functions in Duchenne muscular dystrophy: classifying and subtyping based on Dp140 dystrophin isoform.

Neurocognitive disabilities in Duchenne muscular dystrophy (DMD) children beginning in early childhood and distal DMD gene deletions involving disruption of Dp140 isoform are more likely to manifest significant neurocognitive impairments. MRI data analysis techniques like brain-network metrics can provide information on microstructural integrity and underlying pathophysiology. A prospective study on 95 participants [DMD = 57, and healthy controls (HC) = 38]. The muscular dystrophy functional rating scale (MDFRS) scores, neuropsychology batteries, and multiplex ligand-dependent probe amplification (MLPA) testing were used for clinical assessment, IQ estimation, and genotypic classification. Diffusion MRI and network-based statistics were used to analyze structural connectomes at various levels and correlate with clinical markers. Motor and executive sub-networks were extracted and analyzed. Out of 57 DMD children, 23 belong to Dp140 + and 34 to Dp140- subgroup. Motor disabilities are pronounced in Dp140- subgroup as reflected by lower MDFRS scores. IQ parameters are significantly low in all-DMD cases; however, the Dp140- has specifically lowest scores. Significant differences were observed in global efficiency, transitivity, and characteristic path length between HC and DMD. Subgroup analysis demonstrates that the significance is mainly driven by participants with Dp140- than Dp140 + isoform. Finally, a random forest classifier model illustrated an accuracy of 79% between HC and DMD and 90% between DMD- subgroups. Current findings demonstrate structural network-based characterization of abnormalities in DMD, especially prominent in Dp140-. Our observations suggest that participants with Dp140 + have relatively intact connectivity while Dp140- show widespread connectivity alterations at global, nodal, and edge levels. This study provides valuable insights supporting the genotype-phenotype correlation of brain-behavior involvement in DMD children.

Neuromuscular Diseases Affect Number Representation and Processing: An Exploratory Study.

Spinal muscular atrophy (SMA) and Duchenne muscular dystrophy (DMD) both are rare genetic neuromuscular diseases with progressive loss of motor ability. The neuromotor developmental course of those diseases is well documented. In contrast, there is only little evidence about characteristics of general and specific cognitive development. In both conditions the final motor outcome is characterized by an inability to move autonomously: children with SMA never accomplish independent motoric exploration of their environment, while children with DMD do but later lose this ability again. These profound differences in developmental pathways might affect cognitive development of SMA vs. DMD children, as cognition is shaped by individual motor experiences. DMD patients show impaired executive functions, working memory, and verbal IQ, whereas only motor ability seems to be impaired in SMA. Advanced cognitive capacity in SMA may serve as a compensatory mechanism for achieving in education, career progression, and social satisfaction. This study aimed to relate differences in basic numerical concepts and arithmetic achievement in SMA and DMD patients to differences in their motor development and resulting sensorimotor and environmental experiences. Horizontal and vertical spatial-numerical associations were explored in SMA/DMD children ranging between 6 and 12 years through the random number generation task. Furthermore, arithmetic skills as well as general cognitive ability were assessed. Groups differed in spatial number processing as well as in arithmetic and domain-general cognitive functions. Children with SMA showed no horizontal and even reversed vertical spatial-numerical associations. Children with DMD on the other hand revealed patterns in spatial numerical associations comparable to healthy developing children. From the embodied Cognition perspective, early sensorimotor experience does play a role in development of mental number representations. However, it remains open whether and how this becomes relevant for the acquisition of higher order cognitive and arithmetic skills.

Quality Of Life And Coping In Parents Raising Children With Duchenne Muscular Dystrophy (DMD) In Nepal

Introduction: Quality of Life (QoL) and Coping are important components of mental health, especially important to parents raising children with Duchenne Muscular Dystrophy (DMD). Children with DMD face difficulties due to their disability and create special challenges for parents.&#x0D; Material And Method: The study aimed to assess QoL, demographic variables and coping strategies of parents raising children with DMD in Nepal. A descriptive cross-sectional design was adopted to collect data from 32 parents (mothers = 15, 47%; fathers =17, 53%) through purposive sampling. Socio-demographic pro-forma, World Health Organization's Quality of Life Questionnaire-BREF (WHOQOL-BREF) and Brief COPE Inventory were assessed.&#x0D; Results: The results revealed parents scores were below cutoff &lt;60, indicating probable poor quality of life. QOL was moderately positively correlated with coping strategies and highly positively correlated with emotion-focused coping. There were significant differences in psychological health of parents in reference to their occupation, and in reference to their hospital born children. Parents in government job had better psychological health and parents into private business significantly used emotion-focused coping. Mutual caregivers had significantly better psychological health. Parents without health related problems significantly adopted problem focused coping and emotion focused coping.&#x0D; Conclusion: These findings will help stakeholders to understand DMD children and their impact on QOL and coping of parents and will facilitate to develop appropriate psychosocial intervention programs for the parents for the effective management of their children and their psycho-social wellbeing.

Impaired myocardial strain in early stage of Duchenne muscular dystrophy: its relation with age and motor performance.

Duchenne muscular dystrophy (DMD) is complicated by an early and progressive left ventricular (LV) dysfunction. Despite the reduction of ejection fraction (EF) usually manifests in the second decade, subtle alterations in LV mechanics can be detected earlier. Longitudinal and circumferential LV deformation, evaluated by speckle tracking echocardiography (STE), are considered sensitive markers of early dysfunction. We retrospectively examined clinical and echocardiographic data of 32 DMD children with preserved LV function. According to the median age, patients were then divided into younger and older than 9 years, and compared to 24 age-matched healthy subjects. Six-minute-walk test (6MWT), North Star Ambulatory Assessment (NSAA), and a comprehensive cardiac evaluation were performed. Although EF was within the normal range, DMD patients had significantly lower values than healthy controls, and the same occurred for the remaining conventional systolic and diastolic indices. Global longitudinal strain (GLS) was reduced in all patients (older and younger, both p < 0.001). Global circumferential strain (GCS) was reduced only in older patients (< 0.001). Both GLS and GCS worsened with age in DMD patients (GLS p = 0.005; GCS p = 0.024). GLS was significantly worse in the apical segments and in the postero-lateral wall. GCS in the antero-septal, anterior and antero-lateral segments was significantly reduced in older patients, with a prevalent involvement of the sole septal wall in the younger boys. 6MWT appeared to be correlated inversely to GLS and directly to EF. A longitudinal evaluation should be scheduled in DMD boys to assess the global cardiac performance over time and to evaluate the impact of therapies.

Is It Possible for Children in Duchenne Muscular Dystrophy to Preserve Cardiac Function with Medical Assistance?

In patients with Duchenne muscular dystrophy (DMD), death secondary to cardiac or respiratory failure typically occurs in the second or third decade without treatment. Although cardiac dysfunction is treated with standard heart-failure strategies, it remains insufficient in DMD children. The purpose of this study was to evaluate the efficiency of cardiac medication and noninvasive ventilator support in DMD cardiomyopathy children with analyzing echocardiographic data. Forty-eight DMD children patients were included and divided into 2 groups by left ventricular (LV) ejection fraction (EF) at the time of initial treatment. Group 1: LV EF ≥ 45% and Group 2: LV EF < 45%. p-values were calculated using a Linear mixed model to estimate the association between cardiac medications and echocardiographic measurements. Before and after cardiac medications, the change values were significantly different in interventricular septal thickness at end diastole (IVSd), interventricular septal thickness at end systole (IVSs), left ventricular internal diameter end systole (LVIDs), left ventricular posterior wall thickness end diastole (LVPWd), ejection fraction (EF), fractional shortening (FS), deceleration time (DT), DT slope, Lat A’ and Lat E/E’ (p < 0.05). Group 2 patients revealed to take more kinds of cardiac medications than Group 1 (p < 0.05) including ACEIs, beta-blocker, and inotropics, then LV EF was better preserved in Group 2 than Group 1. It is certainly helpful to take individualized medical combination therapy including inotropic agents for cardiomyopathy in DMD children patients with EF < 45%.