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Duchenne muscular dystrophy (DMD) is a progressive, fatal muscle wasting disease caused by X-linked mutations in the dystrophin gene. Alongside the characteristic muscle weakness, patients face a myriad of skeletal complications, including osteoporosis/osteopenia, high susceptibility to vertebral and long bone fractures, fat embolism post-fracture, scoliosis, and growth retardation. Those skeletal abnormalities significantly compromise quality of life and are sometimes life-threatening. These issues were traditionally attributed to loss of ambulation and chronic corticosteroid use, but recent investigations have unveiled a more intricate etiology. Factors such as vitamin D deficiency, hormonal imbalances, systemic inflammation, myokine release from dystrophic muscle, and vascular dysfunction are emerging as significant contributors as well. This expanded understanding illuminates the multifaceted pathogenesis underlying skeletal issues in DMD. Present therapeutic options are limited and lack specificity. Advancements in understanding the pathophysiology of bone complications in DMD will offer promising avenues for novel treatment modalities. In this review, we summarize the current understanding of factors contributing to bone problems in DMD and delineate contemporary and prospective multidisciplinary therapeutic approaches. [ABSTRACT FROM AUTHOR]

Purpose: Patellofemoral pain (PFP) is characterized by pain around the patella during functional actıvıty. The purpose of this study was to determine the effects of the new method of applying the patellar Kinesio taping (KT). Materials and methods: Participants with PFP were randomly assigned to a Kinesio star taping (n = 14), placebo taping (n = 12), or control group (n = 13). Knee pain intensity during activity, resting, at night-time and during buckling were measured using the visual analogue scale under both KT, placebo taping, and home exercising before and after six weeks. Oedema, performance, knee function, and muscle strength were assessed with circumferential measurement, the Kujala questionnaire, vertical jumps, a 10-step down test, squat test, triple jump test, respectively, in all groups before and after taping. Results: Decreases were detected in pain in each group (p < 0.05) but there were no differences in pain during activity, and buckling in the three groups before and after taping (p > 0.05). Performances and knee functions showed similar results in all groups before and after taping (p > 0.05). The outcomes of all tapings showed that there were no differences between the groups in terms of oedema (p > 0.05), the knee functions (p > 0.05), and muscles strength on the affected and unaffected sides, there were no significant differences between inter and intra groups (p > 0.05). Conclusions: A 6-week new technique star taping together with home-based exercises have similar effects with placebo taping and home exercise groups on oedema, pain, performance, function in PFP. The effects of star taping technique may be determined in future studies as long- and short-term in different types of injuries. [ABSTRACT FROM AUTHOR]

Background and Objectives: Muscle loss is a known complication of ICU admission. The aim of the study was to investigate the effect of neuromuscular functional magnetic stimulation (FMS) on quadriceps muscle thickness in critically ill patients. Materials and Methods: Among ICU patients one quadriceps was randomized to FMS (Tesla Stym, Iskra Medical, Ljubljana, Slovenia) stimulation and the other to control care. Quadriceps thickness was measured by ultrasound (US) in transversal and longitudinal planes at enrolment, Days 3–5, and Days 9–12. The trial stopped early following an interim analysis comparing muscle thickness differences between groups using repeated measures ANOVA. Results: Of 18 patients randomized, 2 died before completing the trial. The final analysis reported included 16 patients (female 38%, age 68 ± 10 years, SOFA 10.8 ± 2.7). Three mild skin thermal injuries were noted initially, which were later avoided with proper positioning of FMS probe. Primary outcome comparison showed that quadriceps thickness in transversal and longitudinal planes decreased in the non-stimulated legs and, but it did not change in FMS legs (−4.1 mm (95%CI: −9.4 to −0.6) vs. −0.7 mm (95%CI: −4.1 to −0.7) (p = 0.03) and −4.4 mm (95%CI: −8.9 to −1.1) vs. −1.5 mm (95%CI: −2.6 to −2.2) (p = 0.02), respectively) (ANOVA difference between groups p = 0.036 and 0.01, respectively). Conclusions: In the critically ill, neuromuscular FMS is feasible and safe with precautions applied to avoid possible skin thermal injury. FMS decreases the loss of quadriceps muscle thickness. [ABSTRACT FROM AUTHOR]

Early rehabilitation has beneficial impacts on functional outcomes for patients with acute stroke. However, whether the addition of virtual reality (VR) training could further improve these patients' muscle strength, functional recovery, and psychological health is unknown. A randomized controlled trial was conducted on 33 patients with first-time acute ischemic stroke. The patients were randomly assigned using a 1:1 randomization ratio to either the experimental group (EG) or the comparison group (CG). Both groups received early rehabilitation, and the EG received extra VR training during their stay in the hospital. Muscle strength, functional status, and psychological health were assessed before the intervention and at discharge. Generalized estimating equations were used to examine the intervention effects via the interaction of time and group. After adjusting for potential covariates, the EG showed a more significant decrease in depression at discharge than the CG (ß = 3.77, p = 0.011). There were no differences in muscle strength and functional recovery between groups after intervention. Adding VR training into early rehabilitation facilitates substantial positive effects on psychological health, specifically depression, but not muscle strength and functional recovery, compared to receiving early rehabilitation alone in patients with first-time acute stroke during their hospitalized period. [ABSTRACT FROM AUTHOR]

The dystrophinopathies encompass the phenotypically variable forms of muscular dystrophy caused by pathogenic variants in the DMD gene. The dystrophinopathies include the most common inherited muscular dystrophy among 46,XY individuals, Duchenne muscular dystrophy, as well as Becker muscular dystrophy and other less common phenotypic variants. With increased access to and utilization of genetic testing in the diagnostic and carrier setting, genetic counselors and clinicians in diverse specialty areas may care for individuals with and carriers of dystrophinopathy. This practice resource was developed as a tool for genetic counselors and other health care professionals to support counseling regarding dystrophinopathies, including diagnosis, health risks and management, psychosocial needs, reproductive options, clinical trials, and treatment. Genetic testing efforts have enabled genotype/phenotype correlation in the dystrophinopathies, but have also revealed unexpected findings, further complicating genetic counseling for this group of conditions. Additionally, the therapeutic landscape for dystrophinopathies has dramatically changed with several FDA-approved therapeutics, an expansive research pathway, and numerous clinical trials. Genotype-phenotype correlations are especially complex and genetic counselors' unique skill sets are useful in exploring and explaining this to families. Given the recent advances in diagnostic testing and therapeutics related to dystrophinopathies, this practice resource is a timely update for genetic counselors and other healthcare professionals involved in the diagnosis and care of individuals with dystrophinopathies., (© 2024 National Society of Genetic Counselors.)

This study explored the effects of a modular overground exoskeleton on plantar pressure distribution in healthy individuals and individuals with Acquired Brain Injury (ABI). The research involved 21 participants, including ABI patients and healthy controls, who used a unique exoskeleton with adaptable modular configurations. The primary objective was to assess how these configurations, along with factors such as muscle strength and spasticity, influenced plantar pressure distribution. The results revealed significant differences in plantar pressures among participants, strongly influenced by the exoskeleton's modularity. Notably, significant distinctions were found between ABI patients and healthy individuals. Configurations with two modules led to increased pressure in the heel and central metatarsus regions, whereas configurations with four modules exhibited higher pressures in the metatarsus and hallux regions. Future research should focus on refining and customizing rehabilitation technologies to meet the diverse needs of ABI patients, enhancing their potential for functional recovery. [ABSTRACT FROM AUTHOR]

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Brain function and its effect on motor performance in Duchenne muscular dystrophy (DMD) is an emerging concept. The present study explored how cumulative dystrophin isoform loss, age, and a corticosteroid treatment affect DMD motor outcomes. A total of 133 genetically confirmed DMD patients from Sri Lanka were divided into two groups based on whether their shorter dystrophin isoforms (Dp140, Dp116, and Dp71) were affected: Group 1, containing patients with Dp140, Dp116, and Dp71 affected (n = 98), and Group 2, containing unaffected patients (n = 35). A subset of 52 patients (Group 1, n = 38; Group 2, n = 14) was followed for up to three follow-ups performed in an average of 28-month intervals. The effect of the cumulative loss of shorter dystrophin isoforms on the natural history of DMD was analyzed. A total of 74/133 (56%) patients encountered developmental delays, with 66/74 (89%) being in Group 1 and 8/74 (11%) being in Group 2 (p < 0.001). Motor developmental delays were predominant. The hip and knee muscular strength, according to the Medical Research Council (MRC) scale and the North Star Ambulatory Assessment (NSAA) activities, "standing on one leg R", "standing on one leg L", and "walk", declined rapidly in Group 1 (p < 0.001 In the follow-up analysis, Group 1 patients became wheelchair-bound at a younger age than those of Group 2 (p = 0.004). DMD motor dysfunction is linked to DMD mutations that affect shorter dystrophin isoforms. When stratifying individuals for clinical trials, considering the DMD mutation site and its impact on a shorter dystrophin isoform is crucial. [ABSTRACT FROM AUTHOR]

5q-associated spinal muscular atrophy (SMA) is a rare genetic disease caused by mutations in the SMN1 gene, resulting in a loss of functional SMN protein and consecutive degeneration of motor neurons in the ventral horn. The disease is clinically characterized by proximal paralysis and secondary skeletal muscle atrophy. New disease-modifying drugs driving SMN gene expression have been developed in the past decade and have revolutionized SMA treatment. The rise of treatment options led to a concomitant need of biomarkers for therapeutic guidance and an improved disease monitoring. Intensive efforts have been undertaken to develop suitable markers, and numerous candidate biomarkers for diagnostic, prognostic, and predictive values have been identified. The most promising markers include appliance-based measures such as electrophysiological and imaging-based indices as well as molecular markers including SMN-related proteins and markers of neurodegeneration and skeletal muscle integrity. However, none of the proposed biomarkers have been validated for the clinical routine yet. In this narrative review, we discuss the most promising candidate biomarkers for SMA and expand the discussion by addressing the largely unfolded potential of muscle integrity markers, especially in the context of upcoming muscle-targeting therapies. While the discussed candidate biomarkers hold potential as either diagnostic (e.g., SMN-related biomarkers), prognostic (e.g., markers of neurodegeneration, imaging-based markers), predictive (e.g., electrophysiological markers) or response markers (e.g., muscle integrity markers), no single measure seems to be suitable to cover all biomarker categories. Hence, a combination of different biomarkers and clinical assessments appears to be the most expedient solution at the time. [ABSTRACT FROM AUTHOR]

Pathogenetic mechanism recognition and proof-of-concept clinical trials were performed in our patients affected by collagen VI-related myopathies. This study, which included 69 patients, aimed to identify innovative clinical data to better design future trials. Among the patients, 33 had Bethlem myopathy (BM), 24 had Ullrich congenital muscular dystrophy (UCMD), 7 had an intermediate phenotype (INTM), and five had myosclerosis myopathy (MM). We obtained data on muscle strength, the degree of contracture, immunofluorescence, and genetics. In our BM group, only one third had a knee extension strength greater than 50% of the predicted value, while only one in ten showed similar retention of elbow flexion. These findings should be considered when recruiting BM patients for future trials. All the MM patients had axial and limb contractures that limited both the flexion and extension ranges of motion, and a limitation in mouth opening. The immunofluorescence analysis of collagen VI in 55 biopsies from 37 patients confirmed the correlation between collagen VI defects and the severity of the clinical phenotype. However, biopsies from the same patient or from patients with the same mutation taken at different times showed a progressive increase in protein expression with age. The new finding of the time-dependent modulation of collagen VI expression should be considered in genetic correction trials. [ABSTRACT FROM AUTHOR]

Duchenne muscular dystrophy (DMD) is a severe, progressive, and ultimately fatal disease of skeletal muscle wasting, respiratory insufficiency, and cardiomyopathy. The identification of the dystrophin gene as central to DMD pathogenesis has led to the understanding of the muscle membrane and the proteins involved in membrane stability as the focal point of the disease. The lessons learned from decades of research in human genetics, biochemistry, and physiology have culminated in establishing the myriad functionalities of dystrophin in striated muscle biology. Here, we review the pathophysiological basis of DMD and discuss recent progress toward the development of therapeutic strategies for DMD that are currently close to or are in human clinical trials. The first section of the review focuses on DMD and the mechanisms contributing to membrane instability, inflammation, and fibrosis. The second section discusses therapeutic strategies currently used to treat DMD. This includes a focus on outlining the strengths and limitations of approaches directed at correcting the genetic defect through dystrophin gene replacement, modification, repair, and/or a range of dystrophin-independent approaches. The final section highlights the different therapeutic strategies for DMD currently in clinical trials. [ABSTRACT FROM AUTHOR]

This paper presents a mechatronics design of a gait-assistance exoskeleton for therapy in children with Duchenne muscular dystrophy (DMD). This type of muscular dystrophy is a severe condition that causes muscle wasting, which results in a progressive loss of mobility. Clinical studies have shown the benefits of physical therapy in prolonging the mobility of patients with DMD. However, the therapy sessions are exhaustive activities executed by highly qualified rehabilitation personnel, which makes providing appropriate treatment for every patient difficult. This paper develops a mechatronics design of a gait-assistance exoskeleton to automate therapy sessions. The exoskeleton design uses adaptable mechanisms to adjust the device to the patient's needs and includes the design of a series-elastic actuator to reduce the effects of nonalignment of the rotation axis between the exoskeleton and the patient. A mathematical dynamic hybrid model of the exoskeleton and a child's body is developed using anthropometry of a population of six-year-old children. The hybrid model is used to design a nonlinear control strategy, which uses differential geometry to perform feedback linearization and to guarantee stable reference tracking. The proposed control law is numerically validated in a simulation to evaluate the control system's performance and robustness under parameter variation during therapy with trajectory-tracking routines. [ABSTRACT FROM AUTHOR]

Duchenne muscular dystrophy (DMD) is a striated muscle degenerative disease due to loss of functional dystrophin protein. Loss of dystrophin results in susceptibility of muscle membranes to damage, leading to muscle degeneration and continuous inflammation and fibrosis that further exacerbate pathology. Long-term glucocorticoid receptor (GR) agonist treatment, the current standard-of-care for DMD, modestly improves prognosis but has serious side effects. The mineralocorticoid receptor (MR), a ligand-activated transcription factor present in many cell types, has been implicated as a therapeutic target for DMD. MR antagonists (MRAs) have fewer side effects than GR agonists and are used clinically for heart failure. MRA efficacy has recently been demonstrated for DMD cardiomyopathy and in preclinical studies, MRAs also alleviate dystrophic skeletal muscle pathology. MRAs lead to improvements in muscle force and membrane stability and reductions in degeneration, inflammation, and fibrosis in dystrophic muscles. Myofiber-specific MR knockout leads to most of these improvements, supporting an MR-dependent mechanism of action, but MRAs additionally stabilize myofiber membranes in an MR-independent manner. Immune cell MR signaling in dystrophic and acutely injured normal muscle contributes to wound healing, and myeloid-specific MR knockout is detrimental. More research is needed to fully elucidate MR signaling in striated muscle microenvironments. Direct comparisons of genomic and non-genomic effects of glucocorticoids and MRAs on skeletal muscles and heart will contribute to optimal temporal use of these drugs, since they compete for binding conserved receptors. Despite the advent of genetic medicines, therapies targeting inflammation and fibrosis will be necessary to achieve optimal patient outcomes. [ABSTRACT FROM AUTHOR]

Importance: Corticosteroids improve strength and function in boys with Duchenne muscular dystrophy. However, there is uncertainty regarding the optimum regimen and dosage.Objective: To compare efficacy and adverse effects of the 3 most frequently prescribed corticosteroid regimens in boys with Duchenne muscular dystrophy.Design, Setting, and Participants: Double-blind, parallel-group randomized clinical trial including 196 boys aged 4 to 7 years with Duchenne muscular dystrophy who had not previously been treated with corticosteroids; enrollment occurred between January 30, 2013, and September 17, 2016, at 32 clinic sites in 5 countries. The boys were assessed for 3 years (last participant visit on October 16, 2019).Interventions: Participants were randomized to daily prednisone (0.75 mg/kg) (n = 65), daily deflazacort (0.90 mg/kg) (n = 65), or intermittent prednisone (0.75 mg/kg for 10 days on and then 10 days off) (n = 66).Main Outcomes and Measures: The global primary outcome comprised 3 end points: rise from the floor velocity (in rise/seconds), forced vital capacity (in liters), and participant or parent global satisfaction with treatment measured by the Treatment Satisfaction Questionnaire for Medication (TSQM; score range, 0 to 100), each averaged across all study visits after baseline. Pairwise group comparisons used a Bonferroni-adjusted significance level of .017.Results: Among the 196 boys randomized (mean age, 5.8 years [SD, 1.0 years]), 164 (84%) completed the trial. Both daily prednisone and daily deflazacort were more effective than intermittent prednisone for the primary outcome (P < .001 for daily prednisone vs intermittent prednisone using a global test; P = .017 for daily deflazacort vs intermittent prednisone using a global test) and the daily regimens did not differ significantly (P = .38 for daily prednisone vs daily deflazacort using a global test). The between-group differences were principally attributable to rise from the floor velocity (0.06 rise/s [98.3% CI, 0.03 to 0.08 rise/s] for daily prednisone vs intermittent prednisone [P = .003]; 0.06 rise/s [98.3% CI, 0.03 to 0.09 rise/s] for daily deflazacort vs intermittent prednisone [P = .017]; and -0.004 rise/s [98.3% CI, -0.03 to 0.02 rise/s] for daily prednisone vs daily deflazacort [P = .75]). The pairwise comparisons for forced vital capacity and TSQM global satisfaction subscale score were not statistically significant. The most common adverse events were abnormal behavior (22 [34%] in the daily prednisone group, 25 [38%] in the daily deflazacort group, and 24 [36%] in the intermittent prednisone group), upper respiratory tract infection (24 [37%], 19 [29%], and 24 [36%], respectively), and vomiting (19 [29%], 17 [26%], and 15 [23%]).Conclusions and Relevance: Among patients with Duchenne muscular dystrophy, treatment with daily prednisone or daily deflazacort, compared with intermittent prednisone alternating 10 days on and 10 days off, resulted in significant improvement over 3 years in a composite outcome comprising measures of motor function, pulmonary function, and satisfaction with treatment; there was no significant difference between the 2 daily corticosteroid regimens. The findings support the use of a daily corticosteroid regimen over the intermittent prednisone regimen tested in this study as initial treatment for boys with Duchenne muscular dystrophy.Trial Registration: ClinicalTrials.gov Identifier: NCT01603407. [ABSTRACT FROM AUTHOR]

Background: Duchenne muscular dystrophy (DMD) is a rare, severely debilitating, and fatal neuromuscular disease characterized by progressive muscle degeneration. Like in many orphan diseases, randomized controlled trials are uncommon in DMD, resulting in the need to indirectly compare treatment effects, for example by pooling individual patient-level data from multiple sources. However, to derive reliable estimates, it is necessary to ensure that the samples considered are comparable with respect to factors significantly affecting the clinical progression of the disease. To help inform such analyses, the objective of this study was to review and synthesise published evidence of prognostic indicators of disease progression in DMD. We searched MEDLINE (via Ovid), Embase (via Ovid) and the Cochrane Library (via Wiley) for records published from inception up until April 23 2021, reporting evidence of prognostic indicators of disease progression in DMD. Risk of bias was established with the grading system of the Centre for Evidence-Based Medicine (CEBM). Results: Our search included 135 studies involving 25,610 patients from 18 countries across six continents (Africa, Asia, Australia, Europe, North America and South America). We identified a total of 23 prognostic indicators of disease progression in DMD, namely age at diagnosis, age at onset of symptoms, ataluren treatment, ATL1102, BMI, cardiac medication, DMD genetic modifiers, DMD mutation type, drisapersen, edasalonexent, eteplirsen, glucocorticoid exposure, height, idebenone, lower limb surgery, orthoses, oxandrolone, spinal surgery, TAS-205, vamorolone, vitlolarsen, ventilation support, and weight. Of these, cardiac medication, DMD genetic modifiers, DMD mutation type, and glucocorticoid exposure were designated core prognostic indicators, each supported by a high level of evidence and significantly affecting a wide range of clinical outcomes. Conclusion: This study provides a current summary of prognostic indicators of disease progression in DMD, which will help inform the design of comparative analyses and future data collection initiatives in this patient population. [ABSTRACT FROM AUTHOR]

Suppressing mineralocorticoid receptor (MR) activity with MR antagonists is therapeutic for chronic skeletal muscle pathology in Duchenne muscular dystrophy (DMD) mouse models. Although mechanisms underlying clinical MR antagonist efficacy for DMD cardiomyopathy and other cardiac diseases are defined, mechanisms in skeletal muscles are not fully elucidated. Myofiber MR knockout improves skeletal muscle force and a subset of dystrophic pathology. However, MR signaling in myeloid cells is known to be a major contributor to cardiac efficacy. To define contributions of myeloid MR in skeletal muscle function and disease, we performed parallel assessments of muscle pathology, cytokine levels, and myeloid cell populations resulting from myeloid MR genetic knockout in muscular dystrophy and acute muscle injury. Myeloid MR knockout led to lower levels of C-C motif chemokine receptor 2 (CCR2)-expressing macrophages, resulting in sustained myofiber damage after acute injury of normal muscle. In acute injury, myeloid MR knockout also led to increased local muscle levels of the enzyme that produces the endogenous MR agonist aldosterone, further supporting important contributions of MR signaling in normal muscle repair. In muscular dystrophy, myeloid MR knockout altered cytokine levels differentially between quadriceps and diaphragm muscles, which contain different myeloid populations. Myeloid MR knockout led to higher levels of fibrosis in dystrophic diaphragm. These results support important contributions of myeloid MR signaling to skeletal muscle repair in acute and chronic injuries and highlight the useful information gained from cell-specific genetic knockouts to delineate mechanisms of pharmacological efficacy. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to investigate whether trunk control is associated with the upper limb function of children with Duchenne Muscular Dystrophy (DMD). Methods: The children included in the study were divided into two groups according to the Trunk Control Measurement Scale total scores. Twenty-five children whose trunk control levels were lower than 30.5 points were included in Group 1 while 31 children who had good levels of trunk control between 30.5 and 58 points were included in Group 2. General functional levels, muscular strength, and function of the upper limb were assessed and compared between the groups. Results: According to the results of the assessments, children in Group 2 were found to have better upper limb function and muscular strength than Group 1 (p <.001). Conclusions: The current study demonstrated better upper limb functional performance of children with DMD that had good-level trunk control thus suggesting the possible association between trunk stability and upper limb function. The results reveal the need to improve and protect trunk muscle strength and stability as well as upper limb strength, and to optimize trunk stability during upper limb movement in rehabilitation programs. [ABSTRACT FROM AUTHOR]

Objective: To determine the inter-rater reliability of the 13-point manual muscle test (MMT) in two upper limb muscle groups of people with tetraplegia Setting: The study was conducted at three spinal cord injury (SCI) units. Participants: Sixty people with complete or incomplete tetraplegia. Methods: The inter-rater reliability of the 13-point MMT was investigated. Strength of the elbow flexors and/or wrist extensors in people with tetraplegia was measured by two physiotherapists on the same day. Results: The weighted kappa coefficient (95% confidence interval) reflecting the agreement between the two strength assessments by two different assessors for the wrist extensors and elbow flexors were 0.96 (0.93 to 0.99) and 0.94 (0.89 to 0.99), respectively. Repeat measurements by different physiotherapists were within 1 of 13 points of each other 82% of the time for wrist extensors and 87% of the time for the elbow flexors. Conclusion: The 13-point MMT is a reliable measure of strength in the wrist extensors and elbow flexors of people with tetraplegia. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The purpose of this longitudinal study was to identify and verify the compensatory motor strategies for upper limb functioning of individuals with Duchenne Muscular Dystrophy (DMD). We evaluated 32 patients diagnosed with DMD (aged 6-19 years) for cognitive and motor functioning using the Mini Mental State Examination (MMSE), Vignos Scale Jebsen Taylor Test (JTT) and Functional Skill Scale (FSS) at baseline testing and over retest intervals of six and 12 months. We used the MMSE to screen participants for capacity to engage in the research, and we analyzed absolute and percentile changes in the frequency distribution of motor strategies participants used on each JTT subtest. We also used analysis of variance with repeated measures and Bonferroni post-hoc testing of multiple comparisons to identify disease progression through FSS scores. We observed an increased frequency of compensatory motor strategies over six months. We recommend the associated use of the JTT and FSS to assess patients with DMD, since we observed worsened movement quality over a time interval of six months even while essential motor competence was maintained. [ABSTRACT FROM AUTHOR]

Duchenne muscular dystrophy (DMD) is an X-linked muscle-wasting disease caused by the loss of dystrophin. DMD is associated with muscle degeneration, necrosis, inflammation, fatty replacement, and fibrosis, resulting in muscle weakness, respiratory and cardiac failure, and premature death. There is no curative treatment. Investigations on disease-causing mechanisms offer an opportunity to identify new therapeutic targets to treat DMD. An abnormal elevation of the intracellular calcium (Ca i 2 + ) concentration in the dystrophin-deficient muscle is a major secondary event, which contributes to disease progression in DMD. Emerging studies have suggested that targeting Ca2+-handling proteins and/or mechanisms could be a promising therapeutic strategy for DMD. Here, we provide an updated overview of the mechanistic roles the sarcolemma, sarcoplasmic/endoplasmic reticulum, and mitochondria play in the abnormal and sustained elevation of Ca i 2 + levels and their involvement in DMD pathogenesis. We also discuss current approaches aimed at restoring Ca2+ homeostasis as potential therapies for DMD. [ABSTRACT FROM AUTHOR]

Childhood onset chronic inflammatory demyelinating polyneuropathy (CIDP) often requires long‐term immunomodulatory therapy. We report a comprehensive review of our treatment of pediatric CIDP with a focus on high‐dose weekly corticosteroids ("pulse oral corticosteroids"), a treatment method that is not commonly reported. We retrospectively reviewed medical records of pediatric patients with CIDP treated at our center between 2000 and 2018 for whom we had at least 12 mo follow‐up. Here, we describe the demographics, disease course, treatment regimens, and long‐term outcomes of these patients. Twenty‐five patients were identified for analysis. Pulse oral corticosteroid monotherapy was the predominant maintenance treatment in 56% of patients. Patients were followed for a median of 4 y. Side effects were seen in a minority of patients. The probability of a normal exam or being off treatment at last follow‐up was similar regardless of predominant maintenance therapy. Pulse oral corticosteroid therapy is a safe and effective long‐term treatment option in children with CIDP. [ABSTRACT FROM AUTHOR]

In the past decade, the number of genes linked to neuromuscular diseases of childhood has expanded dramatically, and this genetic information is forming the basis for gene-specific and even mutation-specific therapies. At the forefront of these advances are the two recently approved treatments for spinal muscular atrophy: one, an antisense oligonucleotide that modifies splicing of the SMN2 gene, and, the other, a gene therapy vector that delivers the SMN1 gene to motor neurons, both of which are allowing patients to acquire developmental milestones previously unseen in this fatal disease. This review highlights these advances and emerging targeted therapies for Duchenne muscular dystrophy and centronuclear myopathy, while also covering enzyme replacement therapy and small molecule-based targeted therapies for conditions such as Pompe's disease and congenital myasthenic syndromes. With these and other newer techniques for targeted correction of genetic defects, such as CRISPR/Cas9, there is now hope that treatments for many more genetic diseases of the nervous system will follow in the near future. [ABSTRACT FROM AUTHOR]

Duchenne and Becker muscular dystrophy (DBMD) are X‐linked conditions causing progressive muscle weakness, muscle wasting, and cardiomyopathy in affected males. Two‐thirds of cases of DBMD are inherited from a carrier female while one‐third of cases occur sporadically. Women who are DBMD carriers typically do not manifest noticeable muscular symptoms. However, about 10% may develop cardiomyopathy while up to 60% are at risk for cardiac abnormalities including myocardial damage, fibrosis, and abnormalities detectable by echocardiogram and electrocardiogram (EKG). The American Academy of Pediatrics (AAP) recommends that carriers of DBMD receive a complete cardiac evaluation beginning at age 25–30 which includes an echocardiogram and EKG, with re‐evaluation at least every 5 years. As many as 54.5% carriers may not be adhering to the AAP recommendations (Bogue et al., 2016). This study was conducted to define the perceived challenges carriers of DBMD face in obtaining cardiac care. A questionnaire was completed by 60 carriers of DBMD recruited through The Duchenne Registry to determine their current cardiac care practices. The majority of carriers surveyed (71.7%, 43/60) self‐reported obtaining appropriate cardiac care while 28.3% (17/60) of carriers surveyed did not. Eleven semi‐structured telephone interviews were conducted with a subset of those who completed the questionnaire. Individuals were eligible for telephone interview if they had not: (a) seen a cardiologist in the last 5 years, (b) had an echocardiogram in the last 5 years, or (c) had an EKG in the last 5 years. The primary theme identified from this cohort was a perceived lack of awareness among healthcare providers regarding cardiac risks in carriers (11/11). Increased awareness, health education regarding risks for carriers, and advocacy efforts are needed for healthcare providers and DBMD carriers in order to ensure that this entire population receives the cardiac care they need. [ABSTRACT FROM AUTHOR]

Bipolar disorder (BPD) is a severe and chronic mental disease with high rates of social and functional disability. To explain the emergence and maintenance of BPD, increasing attention has been focused on dimensions of inflammation and oxidative stress (OTS). Coenzyme Q10 (CoQ10) is known for its anti-oxidant and anti-inflammatory effects; accordingly, the aim of the present study was to investigate, if compared to placebo, adjuvant CoQ10 might favorably impact on serum levels of inflammatory and OTS biomarkers in patients with BPD during their depressive phase. A total of 89 BPD patients, currently in a depressive episode were allocated by block randomization either to the adjuvant CoQ10 (200 mg/day) condition or to the placebo condition. At baseline and 8 weeks later at the end of the study, serum levels of total antioxidant capacity (TAC), total thiol groups (TTG), catalase activity (CAT), nitric oxide (NO), malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), interlukin-6 (IL-6), and IL-10 were assessed. 69 patients completed the 8-week lasting study. Compared to baseline and to the placebo condition, serum levels of TTG and TAC significantly increased, and TNF-α, IL-10, and NO statistically decreased over time in the adjuvant CoQ10 condition. No statistically significant changes were observed for CAT, MDA, and IL-6. The pattern of results suggests that compared to placebo and over a time lapse of 8 weeks, adjuvant CoQ10 favorably impacted on OTS and inflammatory biomarkers in patients with BPD during the depressive episode. Thus, CoQ10 might be considered a safe and effective strategy for treatment of patients with BPD during their depressive phase. [ABSTRACT FROM AUTHOR]

Background: Advances in treatment for Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA) hold promise for children with these disorders. Accurate genetic diagnosis, early in the disease process, will allow these treatments to be most effective. Newborn screening (NBS) for SMA has been recommended in the United States, and a pilot DMD NBS program is underway in Hangzhou, China. Data sources: A PubMed search, limited to the past 5 years, was conducted to identify: (1) therapeutic advancements for DMD/SMA approved by the United States Food and Drug Administration or the European Medicine Agency and (2) The status of NBS for DMD/SMA. Results: We review the current state of approved treatments for DMD/SMA. We present recommendations regarding the future of NBS for these diseases, with a focus on the outcomes and challenges of SMA NBS in New York, USA, and the DMD NBS pilot program in Hangzhou, China. Conclusions: Approved treatments for DMD and SMA may change the natural history of these diseases. Long-term studies of these treatments are underway. To avoid the known diagnostic delay associated with these disorders and provide optimal effectiveness of these treatments, early identification of patients through NBS will be necessary. Establishing comprehensive follow-up plans for positively identified patients will need to be in place for NBS programs to be successful. [ABSTRACT FROM AUTHOR]

Introduction: Glucocorticosteroids (GC) are effective in slowing weakness in boys with Duchenne muscular dystrophy (DMD). Methods: This is a multisite, 1‐year, open‐label trial of twice‐weekly prednisolone (5 mg/kg/dose) in infants/young boys (0.4–2.4 years) with DMD. We compared changes in Bayley III Scales of Infant Development (Bayley‐III) with untreated boys followed for 1 year (historical control cohort [HCC]). Twenty‐three of 25 participants completed the study. Results: Treated boys gained an average of 0.5 points on the Bayley‐III gross motor scaled score (GMSS) compared with the HCC who, on average, declined 1.3 points (P = 0.03). All boys maintained linear growth, and none developed Cushingoid features. Excessive weight gain occurred in 13 of 23 (56%) boys. Discussion: This study provides evidence that twice‐weekly GC is well tolerated in infants and young boys with DMD and improves GMSS. Excessive weight gain is a potential risk. Longer follow‐up is required to determine whether early GC initiation is feasible in most infants/boys with DMD. Muscle Nerve 59:650–657, 2019 See editorial on pages 638–639 in this issue. [ABSTRACT FROM AUTHOR]

Background Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder, due to the loss of function of the survival motor neuron (SMN1) gene. The first treatment for the condition, recently approved, is based on the reduction of exon 7 skipping in mRNAs produced by a highly homologous gene (SMN2). The primary objective of the present study was to evaluate the applicability of the dosage of SMN gene produts in blood, as biomarker for SMA, and the safety of oral salbutamol, a beta2-adrenergic agonist modulating SMN2 levels. Methods We have performed a 1-year multicentre, double-blind, placebo-controlled study with salbutamol in 45 adult patients with SMA. Patients assumed 4 mg of salbutamol or placebo/three times a day. Molecular tests were SMN2 copy number, SMN transcript and protein levels. We have also explored the clinical effect, by the outcome measures available at the time of study design. Results T hirty-six patients completed the study. Salbutamol was safe and well tolerated. We observed a significant and progressive increase in SMN2 full-length levels in peripheral blood of the salbutamol-treated patients (p<0.00001). The exploratory analysis of motor function showed an improvement in most patients. Conclusions Our data demonstrate safety and molecular efficacy of salbutamol. We provide the first longitudinal evaluation of SMN levels (both transcripts and protein) in placebo and in response to a compound modulating the gene expression: SMN transcript dosage in peripheral blood is reliable and may be used as pharmacodynamic marker in clinical trials with systemic compounds modifying SMN2levels. [ABSTRACT FROM AUTHOR]

Introduction: RNS60 is a novel immune-modulatory agent that has shown neuroprotective effects in amytrophic lateral sclerosis (ALS) preclinical models. RNS60 is administered by weekly intravenous infusion and daily nebulization. The objective of this pilot open-label trial was to test the feasibility, safety, and tolerability of long-term RNS60 administration in ALS patients.Methods: The planned treatment duration was 23 weeks and the primary outcomes were safety and tolerability. Secondary outcomes included PBR28 positron emission tomography (PET) imaging and plasma biomarkers of inflammation.Results: Sixteen participants with ALS received RNS60 and 13 (81%) completed 23 weeks of RNS60 treatment. There were no serious adverse events and no participants withdrew from the trial due to drug-related adverse events. There were no significant changes in the biomarkers.Discussion: Long-term RNS60 administration was safe and well-tolerated. A large, multicenter, phase II trial of RNS60 is currently enrolling participants to test the effects of RNS60 on ALS biomarkers and disease progression. Muscle Nerve 59:303-308, 2019. [ABSTRACT FROM AUTHOR]

Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder. It is still an incurable disease and many clinical trials are going on to find the cure for this disease. There is a need for sensitive and reliable measures for detecting the disease progression. This manuscript focuses on reviewing the different outcome measures which can be used in the Indian DMD patients. [ABSTRACT FROM AUTHOR]

Duchenne muscular dystrophy (DMD) is an X-linked disorder that leads to cardiac and skeletal myopathy. The complex immune activation in boys with DMD is incompletely understood. To better understand the contribution of the immune system into the progression of DMD, we performed a systematic characterization of immune cell subpopulations obtained from peripheral blood of DMD subjects and control donors. We found that the number of CD8 cells expressing CD26 (also known as adenosine deaminase complexing protein 2) was increased in DMD subjects compared to control. No differences, however, were found in the levels of circulating factors associated with pro-inflammatory activation of CD8/CD26 cells, such as tumor necrosis factor-a (TNFa), granzyme B, and interferon-g (IFNg). The number of CD8/CD26 cells correlated directly with quantitative muscle testing (QMT) in DMD subjects. Since CD26 mediates binding of adenosine deaminase (ADA) to the T cell surface, we tested ADA-binding capacity of CD8/CD26 cells and the activity of bound ADA. We found that mononuclear cells (MNC) obtained from DMD subjects with an increased number of CD8/CD26 T cells had a greater capacity to bind ADA. In addition, these MNC demonstrated increased hydrolytic deamination of adenosine to inosine. Altogether, our data demonstrated that (1) an increased number of circulating CD8/CD26 T cells is associated with preservation of muscle strength in DMD subjects, and (2) CD8/CD26 T cells from DMD subjects mediated degradation of adenosine by adenosine deaminase. These results support a role for T cells in slowing the decline in skeletal muscle function, and a need for further investigation into contribution of CD8/CD26 T cells in the regulation of chronic inflammation associated with DMD. [ABSTRACT FROM AUTHOR]

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Introduction: Improved outcome measures are essential to efficiently screen the growing number of potential amyotrophic lateral sclerosis (ALS) therapies.Methods: This longitudinal study of 100 (70 male) participants with ALS compared Accurate Test of Limb Isometric Strength (ATLIS), using a fixed, wireless load cell, with ALS Functional Rating Scale-Revised (ALSFRS-R) and vital capacity (VC).Results: Participants enrolled at 5 U.S. sites. Data were analyzed from 66 participants with complete ATLIS, ALSFRS-R, and VC data over at least 3 visits. Change in ATLIS was less variable both within- and among-person than change in ALSFRS-R or VC. Additionally, participants who had normal ALSFRS-R arm and leg function averaged 12 to 32% below expected strength values measured by ATLIS.Conclusions: ATLIS was more sensitive to change than ALSFRS-R or VC and could decrease sample size requirements by approximately one-third. The ability of ATLIS to detect prefunctional change has potential value in early trials. Muscle Nerve 56: 710-715, 2017. [ABSTRACT FROM AUTHOR]