-
Journal of Neuromuscular Diseases 2022Clinical medical management guidelines of Duchenne muscular dystrophy (DMD) emphasize prevention and early identification and treatment.
BACKGROUND
Clinical medical management guidelines of Duchenne muscular dystrophy (DMD) emphasize prevention and early identification and treatment.
OBJECTIVE
The objective of our study was to review, synthesize, and grade published evidence of the impact of the timing of clinical interventions in DMD.
METHODS
We searched PubMed, Embase, and the Cochrane Library for records published from inception up until November 19, 2021, reporting evidence of the impact of the timing of clinical interventions in DMD. We assessed the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework.
RESULTS
We included 12 publications encompassing 1,623 patients with DMD from seven countries (Australia, France, Germany, Italy, Japan, the United Kingdom, and the United States of America). Six (50%) studies reported evidence of an impact of the timing of initiation of glucocorticoids on loss of ambulation, cardiomyopathy, fractures, forced vital capacity, and height and BMI; four (33%) of cardiac medication (i.e., angiotensin-converting enzyme inhibitors, β-blockers, and eplerenone) on left ventricular size and function and survival; one (8%) of lower limb surgery on motor quotient and loss of ambulation; and one (8%) of ataluren on lower extremity and motor function. The overall quality of the body of evidence was low.
CONCLUSION
While there is a clinical rationale for anticipatory diagnostic and therapeutic strategies, evidence of the impact of the timing of initiation of treatments in patients with DMD is still emerging. Further research of this topic is warranted to inform treatment guidelines in this indication.
Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiomyopathies; Glucocorticoids; Humans; Muscular Dystrophy, Duchenne; Vital Capacity
PubMed: 35431260
DOI: 10.3233/JND-220804 -
Frontiers in Bioengineering and... 2022As one of the most severe forms of muscle dystrophy, Duchenne muscular dystrophy (DMD) results in progressive muscle wasting, ultimately resulting in premature death due...
As one of the most severe forms of muscle dystrophy, Duchenne muscular dystrophy (DMD) results in progressive muscle wasting, ultimately resulting in premature death due to cardiomyopathy. In the many years of research, the solution to DMD remains palliative. Although numerous studies including clinical trials have provided promising results, approved drugs, even, the therapeutic window is still minimal with many shortcomings to be addressed. Logically, to combat DMD that arose from a single genetic mutation with gene therapy made sense. However, gene-based strategies as a treatment option are no stranger to drawbacks and limitations such as the size of the dystrophin gene and possibilities of vectors to elicit immune responses. In this systematic review, we aim to provide a comprehensive compilation on gene-based therapeutic strategies and critically evaluate the approaches relative to its efficacy and feasibility while addressing their current limitations. With the keywords "DMD AND Gene OR Genetic AND Therapy OR Treatment," we reviewed papers published in Science Direct, PubMed, and ProQuest over the past decade (2012-2021).
PubMed: 35402409
DOI: 10.3389/fbioe.2022.833833 -
Neuroscience and Biobehavioral Reviews Jun 2022Brain co-morbidities in DMD are well-documented, less is known about the cognitive, behavioral and psychosocial functioning of patients with BMD. (Review)
Review
BACKGROUND
Brain co-morbidities in DMD are well-documented, less is known about the cognitive, behavioral and psychosocial functioning of patients with BMD.
METHODS
The systematic review was carried out on two databases (Pubmed and Scopus) according to the PRISMA guidelines. We included all research articles specific to BMD written after 1995.
RESULTS
Studies examining neuropsychological and neurobehavioral functioning in BMD are few and have several methods limitations. BMD population is characterized by high rates of cognitive impairment, with specific involvement of different cognitive areas. Unlike DMD, verbal skills are better preserved. Neurodevelopmental and emotional/behavioral disorders have great importance in BMD, due to their high prevalence. Lack of Dp140 or Dp71 can cause intellectual disability, these isoforms are probably responsible for the other brain-related comorbidities as well.
DISCUSSION
The results suggest that cognitive and neuropsychiatric comorbid symptoms may affect a significant proportion of BMD patients therefore it is important to mental health and neuropsychological screening. Finding tools for an adequate assessment is a priority in order to include brain outcome measures in clinical trials.
Topics: Brain; Cognition; Dystrophin; Humans; Muscular Dystrophy, Duchenne; Protein Isoforms
PubMed: 35367224
DOI: 10.1016/j.neubiorev.2022.104648 -
Health and Quality of Life Outcomes Apr 2022Duchenne muscular dystrophy is a rare, progressive, life-limiting genetic neuromuscular condition that significantly impacts the quality of life of informal caregivers.... (Review)
Review
INTRODUCTION
Duchenne muscular dystrophy is a rare, progressive, life-limiting genetic neuromuscular condition that significantly impacts the quality of life of informal caregivers. Carer quality of life is measured using heterogeneous self-report scales, yet their suitability for Duchenne remains unclear. This review aimed to identify and evaluate the reliability and validity of quality of life instruments in Duchenne carers.
MATERIALS AND METHODS
Systematic searches were conducted in Embase, MEDLINE, CINAHL, PsycINFO, Cochrane Library and Google Scholar. Full research articles reporting data on multiple-item self-report quality of life instruments in informal Duchenne carers were included. Extracted evidence was qualitatively synthesised and evaluated, including risk of bias, against the Consensus-based Standards for the selection of health Measurement Instruments. Duchenne carer collaborators (N = 17) helped rate the instruments' content validity.
RESULTS
Thirty-one articles featuring thirty-two quality of life instruments were included. Content validity was rated as "inconsistent" based on very low quality evidence. For Duchenne carer collaborators, the best instrument was PedsQL Family Impact Module. Only one instrument had evidence for structural validity (rated "unsatisfactory") and measurement invariance (rated "satisfactory"). Instruments received "satisfactory" ratings for internal consistency and mixed ratings for construct validity and responsiveness. There was no evidence for reliability, measurement error, or criterion validity.
DISCUSSION
Instruments used to measure Duchenne carer quality of life have limited and often inconsistent supportive psychometric evidence. Further work must investigate instruments' measurement properties in Duchenne carers and/or the development of new tools. In the interim, we recommend considering the PedsQL Family Impact Module based on Duchenne carer ratings.
Topics: Caregivers; Humans; Muscular Dystrophy, Duchenne; Quality of Life; Reproducibility of Results; Self Report; Surveys and Questionnaires
PubMed: 35366897
DOI: 10.1186/s12955-022-01964-4 -
Neuromuscular Disorders : NMD May 2022Myotonic dystrophy type 1 (DM1) is a progressive neuromuscular disease affecting both smooth and striated muscles. It has been suggested that this multisystemic disease... (Review)
Review
Myotonic dystrophy type 1 (DM1) is a progressive neuromuscular disease affecting both smooth and striated muscles. It has been suggested that this multisystemic disease also impairs the genitourinary and lower gastrointestinal systems, but information is scattered and no systematic review has been conducted. The objectives of this systematic review were to document (1) symptoms and signs associated with genitourinary and lower gastrointestinal systems in the DM1 population; (2) impacts on quality of life and participation; and (3) efficacy of treatments available to treat those conditions. Among the 75 studies included, 30 articles presented genitourinary outcomes and 67, lower gastrointestinal outcomes. A wide range of symptoms was reported for both systems but most studies were of poor quality, using medical chart reviews without the use of standardized questionnaires. Urinary incontinence, erectile dysfunction, anal incontinence, constipation, diarrhea and abdominal pain were the most described symptoms. Smooth and striated muscle impairment has been documented in small sample size studies. No experimental study evaluated the efficacy of treatments for these conditions. Few descriptive studies described altered quality of life or participation related to these conditions. Further studies should use standardized questionnaires, provide a clear definition of symptoms and investigate treatment options.
Topics: Fecal Incontinence; Humans; Male; Muscle, Skeletal; Myotonic Dystrophy; Quality of Life; Surveys and Questionnaires
PubMed: 35305881
DOI: 10.1016/j.nmd.2022.01.008 -
Journal of Neurology Jul 2022Dystrophin alterations in the brain have been associated with an increased risk of epilepsy in Becker and Duchenne muscular dystrophies (BMD and DMD). Moreover, an... (Meta-Analysis)
Meta-Analysis Review
Dystrophin alterations in the brain have been associated with an increased risk of epilepsy in Becker and Duchenne muscular dystrophies (BMD and DMD). Moreover, an association between the mutation site and the risk of epilepsy is not ruled out. The aim of this systematic review and meta-analysis was to estimate the prevalence of epilepsy in BMD and DMD populations and to establish a possible association between the site of mutation in the dystrophin gene and the risk of epilepsy. Systematic searches of Medline, Scopus, Web of Science, and Cochrane Library were conducted to identify relevant studies published from inception to January 2022. Observational studies of participants with BMD/DMD estimating the prevalence of epilepsy were included. The main outcome was the prevalence of epilepsy, and the secondary outcome was the prevalence ratio considering genotype. A random effects meta-analysis was performed for the prevalence of epilepsy. Eight studies were included in the systematic review and meta-analysis. The prevalence of epilepsy was 7% (95% CI 3-11%) in BMD, 5% (95% CI 2-8%) in DMD, and 5% (95% CI 3-7%) in the overall estimate. No association was observed between mutation site and the prevalence of epilepsy. BMD/DMD is strongly associated with the prevalence of epilepsy, with a higher prevalence in BMD/DMD populations than in the general population, probably owing to alterations in Dp427. The current evidence does not support the hypothesis that Dp140 or Dp71 affect epilepsy risk.
Topics: Dystrophin; Epilepsy; Exons; Humans; Muscular Dystrophy, Duchenne; Mutation
PubMed: 35229191
DOI: 10.1007/s00415-022-11040-y -
Journal of Orthopaedic Surgery and... Feb 2022A variety of mutations in the largest human gene, dystrophin, cause a spectrum from mild to severe dystrophin-associated muscular dystrophies. Duchenne (DMD) and Becker... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A variety of mutations in the largest human gene, dystrophin, cause a spectrum from mild to severe dystrophin-associated muscular dystrophies. Duchenne (DMD) and Becker (BMD) muscular dystrophies are located at the severe end of the spectrum that primarily affects skeletal muscle. Progressive muscle weakness in these purely genetic disorders encourages families with a positive history for genetic counseling to prevent a recurrence, which requires an accurate prevalence of the disorder. Here, we provide a systematic review and meta-analysis to determine the prevalence of DMD and BMD worldwide.
METHOD
The current systematic review and meta-analysis was carried out using Cochrane seven-step procedure. After determining the research question and inclusion and exclusion criteria, the MagIran, SID, ScienceDirect, WoS, ProQuest, Medline (PubMed), Embase, Cochrane, Scopus, and Google Scholar databases were searched to find relevant studies using defined keywords and all possible keyword combinations using the AND and OR, with no time limit until 2021. The heterogeneity of studies was calculated using the I test, and the publication bias was investigated using the Begg and Mazumdar rank correlation test. Statistical analysis of data was performed using Comprehensive Meta-Analysis software (version 2).
RESULTS
A total of 25 articles involving 901,598,055 people were included. The global prevalence of muscular dystrophy was estimated at 3.6 per 100,000 people (95 CI 2.8-4.5 per 100,000 people), the largest prevalence in the Americans at 5.1 per 100,000 people (95 CI 3.4-7.8 per 100,000 people). According to the subgroup analysis, the prevalence of DMD and BMD was estimated at 4.8 per 100,000 people (95 CI 3.6-6.3 per 100,000 people) and 1.6 per 100,000 people (95 CI 1.1-2.4 per 100,000 people), respectively.
CONCLUSION
Knowing the precise prevalence of a genetic disorder helps to more accurately predict the likelihood of preventing its occurrence in families. The global prevalence of DMD and BMD was very high, indicating the urgent need for more attention to prenatal screening and genetic counseling for families with a positive history.
Topics: Dystrophin; Humans; Muscle Weakness; Muscular Dystrophies; Muscular Dystrophy, Duchenne; Mutation; Prevalence
PubMed: 35168641
DOI: 10.1186/s13018-022-02996-8 -
Irish Journal of Medical Science Dec 2022Mutations in the alpha-sarcoglycan gene cause limb-girdle muscular dystrophy 2D, an autosomal recessive muscle wasting disorder primarily affecting the muscles of the...
BACKGROUND
Mutations in the alpha-sarcoglycan gene cause limb-girdle muscular dystrophy 2D, an autosomal recessive muscle wasting disorder primarily affecting the muscles of the shoulder and pelvic girdles. To date, no previous study has collated all known mutations in alpha-sarcoglycan and mapped these to the associated phenotypes.
AIMS
To examine for correlations between mutation locations, or mutation type, and the phenotype caused in all reported mutations in alpha-sarcoglycan.
METHODS
We present a systematic literature review examining correlations between mutation locations, or mutation type, and the phenotype caused in all reported cases of limb-girdle muscular dystrophy 2D.
RESULTS
From 134 unique genotypes collated, a strong prevalence of missense mutations (64% of all unique mutations) was found in this gene. Mutation hotspots were noted in exon three and the extracellular domain, with mutation densities varying significantly between both exons and protein domains (p ≤ 0.01). All compound heterozygous limb-girdle muscular dystrophy 2D patients with cardiac involvement contained at least one mutation in exon three, a novel finding. All non-sense mutations in alpha-sarcoglycan give a severe phenotype, as do genotypes involving a combination of exons four and five. This study confirms on a large, diverse cohort the extremely high prevalence of the c.229C > T mutation.
CONCLUSIONS
This study demonstrates the vast variation in disease severity seen between patients possessing the same mutation, highlighting the difficulty identifying genotype-phenotype correlations in this condition. Novel findings including the involvement of exon three in all compound heterozygous patients who suffered from cardiomyopathy, and the severity of mutations involving exons four and five may help to guide investigations and therapeutic decisions in an era of personalised medicine.
Topics: Humans; Sarcoglycanopathies; Sarcoglycans; Exons; Phenotype; Mutation; Genetic Association Studies
PubMed: 35040091
DOI: 10.1007/s11845-021-02855-1 -
Neuromuscular Disorders : NMD Feb 2022Measurement of muscle strength is fundamental for the management of patients with myotonic dystrophy type 1 (DM1). Nevertheless, guidance on this topic is somewhat... (Review)
Review
Measurement of muscle strength is fundamental for the management of patients with myotonic dystrophy type 1 (DM1). Nevertheless, guidance on this topic is somewhat limited due to heterogeneous outcome measures used. This systematic literature review aimed to summarize the most frequent outcome measures to assess muscle strength in patients with DM1. We searched on Pubmed, Web of Science and Embase databases. Observational studies using measures of muscle strength assessment in adult patients with DM1 were included. From a total of 80 included studies, 24 measured cardiac, 45 skeletal and 23 respiratory muscle strength. The most common method and outcome measures used to assess cardiac muscle strength were echocardiography and ejection fraction, for skeletal muscle strength were quantitative muscle test, manual muscle test and maximum isometric torque and medical research council and for respiratory muscle strength were manometry and maximal inspiratory and expiratory pressure. We successfully gathered the more consensual methods and measures to evaluate muscle strength in future clinical studies, particularly to test muscle strength response to treatments in patients with DM1. Future consensus on a set of measures to evaluate muscle strength (core outcome set), is important for these patients.
Topics: Adult; Humans; Muscle Strength; Muscle, Skeletal; Myotonic Dystrophy; Outcome Assessment, Health Care; Torque
PubMed: 35031191
DOI: 10.1016/j.nmd.2021.09.014 -
Neuromuscular Disorders : NMD Feb 2022Eosinophilic myositis belong to the idiopathic inflammatory myopathies and are defined by an inflammatory infiltrate composed of eosinophils within the muscle. To date,... (Review)
Review
Eosinophilic myositis belong to the idiopathic inflammatory myopathies and are defined by an inflammatory infiltrate composed of eosinophils within the muscle. To date, no consensus exists for diagnosis and care of such patients. The aim of this review was to describe clinical and histological presentation, treatment, and outcome of eosinophilic myositis based on a systematic review of all published histologically proven cases of eosinophilic myositis. A total of 453 records were identified in MEDLINE until November 2020. A total of 69 published cases were identified. The analysis of these allowed the distinction of the 3 previously described pathological subtypes: focal eosinophilic myositis (n = 17); diffuse eosinophilic myositis (n = 36); and eosinophilic perimyositis (n = 16). We propose a simple algorithm for diagnosis and treatment strategy for the care of patient with muscular symptoms and blood eosinophilia. This work also highlights eosinophilic myositis pathogenesis and the need for careful investigations in order to rule out differential diagnoses.
Topics: Eosinophilia; Eosinophils; Humans; Muscular Dystrophies, Limb-Girdle; Myositis
PubMed: 34980535
DOI: 10.1016/j.nmd.2021.10.003