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Neuromuscular Disorders : NMD Nov 2023We conducted a systematic literature review and meta-analysis on the effectiveness of vitamin D supplementation in maintaining or restoring vitamin D levels in Duchenne... (Meta-Analysis)
Meta-Analysis Review
We conducted a systematic literature review and meta-analysis on the effectiveness of vitamin D supplementation in maintaining or restoring vitamin D levels in Duchenne muscular dystrophy. Due to a lack of randomised controlled trials, cross-sectional and retrospective and prospective cohort studies were taken as the best available evidence. Inclusion criteria included reporting mean serum vitamin D levels in a supplement-taking group. After screening 102 records; 13 were included in a narrative synthesis and eight of these in a meta-analysis. We show that current dosing regimens are preventing severe deficiency but are not effective at maintaining sufficient vitamin D levels within the Duchenne population. Despite high levels of daily vitamin D supplementation (>1000 International Units), at least 20 % of people with Duchenne remain vitamin D deficient. No significant association between dose and serum vitamin D levels was found (r = 0.3, p = 0.237). A meta-analysis of mean serum vitamin D levels across eight studies also revealed substantial variability in response to vitamin D supplementation and high heterogeneity (I = 99.59 %). These data could impact on an individual's risk and severity of osteoporosis and vertebral fractures.
Topics: Humans; Muscular Dystrophy, Duchenne; Retrospective Studies; Prospective Studies; Cross-Sectional Studies; Vitamin D; Vitamins; Dietary Supplements
PubMed: 37932186
DOI: 10.1016/j.nmd.2023.10.008 -
Neurology Jan 2024Bisphosphonates are routinely used to treat osteoporosis in patients with Duchenne muscular dystrophy (DMD), a rare, severely debilitating neuromuscular disease. We...
BACKGROUND AND OBJECTIVES
Bisphosphonates are routinely used to treat osteoporosis in patients with Duchenne muscular dystrophy (DMD), a rare, severely debilitating neuromuscular disease. We sought to synthesize and grade benefits and harms evidence of bisphosphonates in glucocorticoid-treated patients with DMD.
METHODS
In this systematic review (PROSPERO identifier: CRD42020157606), we searched MEDLINE, CINAHL, Embase, PsycINFO, Web of Science, and CENTRAL for articles published from inception up to and including March 31, 2023, reporting results in any language from any study type. Quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations framework.
RESULTS
We identified 19 publications involving 1,010 children and adults from 12 countries across all inhabited continents except South America. We found high-quality evidence that bisphosphonates significantly increase the areal lumbar spine bone mineral density (BMD) Z score in glucocorticoid-treated patients with DMD. The greatest improvements were recorded in controlled settings among patients treated with intravenous zoledronate. Evidence of benefits to fracture risks was inconclusive and/or of low quality, primarily due to lack of controlled data and small samples. Bisphosphonates were generally well-tolerated, although adverse events related to the first infusion (i.e., "acute phase reaction") were frequently reported.
DISCUSSION
There is high-quality evidence supporting the use of bisphosphonates to increase the areal lumbar spine BMD Z score in patients with DMD and glucocorticoid-induced osteoporosis. Our synthesis and grading affirm current recommendations put forward in the 2018 DMD Clinical Care Considerations and should be helpful in raising awareness about anticipated benefits of bisphosphonates, prevailing unmet needs, and potential safety issues in their use.
Topics: Adult; Child; Humans; Diphosphonates; Muscular Dystrophy, Duchenne; Glucocorticoids; Zoledronic Acid; Osteoporosis
PubMed: 38165327
DOI: 10.1212/WNL.0000000000207948 -
Seizure Oct 2021Epilepsy is a common, often severe, feature of LAMA2-related muscular dystrophy (LAMA2-RD) and could represent its onset and main manifestation, even in the absence of... (Review)
Review
Epilepsy is a common, often severe, feature of LAMA2-related muscular dystrophy (LAMA2-RD) and could represent its onset and main manifestation, even in the absence of overt muscle involvement. To date, there is no systematic characterization of epilepsy in LAMA2-RD, and its impact on neurodevelopment and on the clinical course remains poorly established. In view of this knowledge gap, we conducted a systematic review of the literature and, as an illustrative example, reported the clinical case of a boy with late-onset LAMA2-related limb-girdle muscular dystrophy presenting with severe epilepsy. Our analyses of the literature data revealed a mean age at first seizure of 8 years, with significant differences between early- versus late-onset disease (5.78 ± 4.11 and 9.00 ± 2.65 years, respectively; p = 0.0007), and complete versus partial merosin deficiency (5.33 ± 3.70 and 10.36 ± 5.49 years, respectively; p = 0.0176). A generalized onset was the most common seizure presentation, regardless of merosin expression levels or the timing of muscular distrophy onset. Cortical malformations were not significantly associated with an earlier epilepsy onset, and were found to be quasi-significantly associated with a greater incidence of focal, or focal and generalized, onset seizures. No clear conclusions could be reached on the electrophysiological and neurodevelopmental features of the disorder, or on the relative efficacy of anti-epileptic treatments; further research on these aspects is needed. This systematic review helps to show that epilepsy in LAMA2-RD may be more than an ancillary manifestation of the disease, but rather one of its core features. A targeted and prompt electroencephalographic and epilepsy assessment, in addition to the specific neuromuscular workup, is therefore mandatory in early clinical management to pursue the best possible outcome for affected children.
Topics: Child; Electroencephalography; Epilepsy; Humans; Laminin; Male; Muscular Dystrophies; Muscular Dystrophies, Limb-Girdle
PubMed: 34325301
DOI: 10.1016/j.seizure.2021.07.020 -
Journal of Neuromuscular Diseases 2024The objective of this study was to describe predictors of loss of ambulation in Duchenne muscular dystrophy (DMD). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The objective of this study was to describe predictors of loss of ambulation in Duchenne muscular dystrophy (DMD).
METHODS
This systematic review and meta-analysis included searches of MEDLINE ALL, Embase, and the Cochrane Database of Systematic Reviews from January 1, 2000, to December 31, 2022, for predictors of loss of ambulation in DMD. Search terms included "Duchenne muscular dystrophy" as a Medical Subject Heading or free text term, in combination with variations of the term "predictor". Risk of bias was assessed using the Newcastle-Ottawa Scale. We performed meta-analysis pooling of hazard ratios of the effects of glucocorticoids (vs. no glucocorticoid therapy) by fitting a common-effect inverse-variance model.
RESULTS
The bibliographic searches resulted in the inclusion of 45 studies of children and adults with DMD from 17 countries across Europe, Asia, and North America. Glucocorticoid therapy was associated with delayed loss of ambulation (overall meta-analysis HR deflazacort/prednisone/prednisolone: 0.44 [95% CI: 0.40-0.48]) (n = 25 studies). Earlier onset of first signs or symptoms, earlier loss of developmental milestones, lower baseline 6MWT (i.e.,<350 vs. ≥350 metres and <330 vs. ≥330 metres), and lower baseline NSAA were associated with earlier loss of ambulation (n = 5 studies). Deletion of exons 3-7, proximal mutations (upstream intron 44), single exon 45 deletions, and mutations amenable of skipping exon 8, exon 44, and exon 53, were associated with prolonged ambulation; distal mutations (intron 44 and downstream), deletion of exons 49-50, and mutations amenable of skipping exon 45, and exon 51 were associated with earlier loss of ambulation (n = 13 studies). Specific single-nucleotide polymorphisms in CD40 gene rs1883832, LTBP4 gene rs10880, SPP1 gene rs2835709 and rs11730582, and TCTEX1D1 gene rs1060575 (n = 7 studies), as well as race/ethnicity and level of family/patient deprivation (n = 3 studies), were associated with loss of ambulation. Treatment with ataluren (n = 2 studies) and eteplirsen (n = 3 studies) were associated with prolonged ambulation. Magnetic resonance biomarkers (MRI and MRS) were identified as significant predictors of loss of ambulation (n = 6 studies). In total, 33% of studies exhibited some risk of bias.
CONCLUSION
Our synthesis of predictors of loss of ambulation in DMD contributes to the understanding the natural history of disease and informs the design of new trials of novel therapies targeting this heavily burdened patient population.
Topics: Muscular Dystrophy, Duchenne; Humans; Glucocorticoids; Walking; Pregnenediones; Latent TGF-beta Binding Proteins
PubMed: 38669554
DOI: 10.3233/JND-230220 -
Frontiers in Neurology 2023Recent studies evaluated the role of vamorolone in treating Duchenne muscular dystrophy (DMD), so we aimed in our Meta-analysis to assess the efficacy of vamorolone in...
BACKGROUND AND AIM
Recent studies evaluated the role of vamorolone in treating Duchenne muscular dystrophy (DMD), so we aimed in our Meta-analysis to assess the efficacy of vamorolone in comparison with placebo and corticosteroids for treating DMD patients.
METHODS
We searched PubMed, Web of Science, Scopus, and Cochrane library databases. We included any randomized control trials and controlled observational studies that investigated the role of vamorolone in treating DMD patients. We used RevMan software, version 5.4. to perform our meta-analysis.
RESULTS
After a search of the literature, 4 studies were included in the meta-analysis; the total number of patients included in the study is 277 patients, 125 patients in the vamorolone group, 106 in the glucocorticoids group, and 46 in placebo (steroid naïve) group. The pooled analysis showed a statistically significant association between the vamorolone group and increased TTSTAND velocity, TTRW velocity and TTCLIMB velocity compared with the placebo group (MD = 0.04, 95% CI = 0.02-0.07, = 0.002), (MD = 0.24, 95% CI = 0.11-0.37, = 0.0003), and (MD = 0.06, 95% CI = 0.05-0.06, < 0.00001), respectively. Also, the analysis showed a statistically significant association between vamorolone and increased TTRW velocity and increased Height percentile for age compared with the glucocorticoid group (MD = -0.14, 95% CI = -0.26 to -0.01, = 0.03) and (MD = 17.82, 95% CI = 3.89-31.75, = 0.01), respectively.
CONCLUSION
Our study revealed a significant association between vamorolone and increased TTSTAND velocity, TTRW velocity, and TTCLIMB velocity compared with the placebo (steroid naïve), also showed a statistically significant association between increased TTRW velocity and increased Height percentile for age compared with the glucocorticoid that enhances the privilege of vamorolone over glucocorticoid in treating DMD patients. More multicenter randomized studies are needed to support our results.
PubMed: 36816559
DOI: 10.3389/fneur.2023.1107474 -
Pediatric Cardiology Jun 2018Duchenne muscular dystrophy (DMD) is a genetic recessive disorder with progressive muscle weakness. Despite the general muscle wasting, degeneration and necrosis of... (Review)
Review
Duchenne muscular dystrophy (DMD) is a genetic recessive disorder with progressive muscle weakness. Despite the general muscle wasting, degeneration and necrosis of cardiomyocytes have been the main causes of morbidity and death in individuals with DMD. Cardiac failure is generally preceded by disturbances in heart rate variability (HRV), and non-invasive measurement of the autonomic nervous system has been an important tool to predict adverse cardiovascular events. Hence, the application of HRV to study autonomic modulation in DMD individuals, and the establishment of correlations between HRV and heart/lung diseases, age, and mortality will have the potential to improve quality of life and life expectancy of individuals with DMD. In order to evaluate the state of the art in this field, we conducted a systematic search in Medline/PubMed and BVS (virtual library in health) databases. We selected 8 studies using pre-defined criteria and meta-analysis revealed decreased parasympathetic activity and increased sympathetic predominance in individuals with DMD as major observations. Moreover, there is a strong association between diminished HRV and myocardial fibrosis with DMD. These patterns are evident in patients at early-stage DMD and become more prominent as disease severity and age increase. Thus, data minning clearly indicates that HRV assessment can be used as a predictor for sudden death in individuals with DMD. The use of the HRV, which is inexpensive, ubiquitously available in clinics and hospitals, and a non-invasive analysis tool, can save lives and decrease the morbity in DMD by alerting care givers to consider autonomic nervous system intervention.
Topics: Autonomic Nervous System; Cardiomyopathies; Disease Progression; Female; Heart Failure; Heart Rate; Humans; Male; Muscular Dystrophy, Duchenne; Quality of Life
PubMed: 29696428
DOI: 10.1007/s00246-018-1881-0 -
Hellenic Journal of Cardiology : HJC =... 2023Duchenne muscular dystrophy is a fatal X-linked recessive disease affecting approximately 1 in 3500 births. It is characterized by a genetic lack of dystrophin, which is... (Review)
Review
Duchenne muscular dystrophy is a fatal X-linked recessive disease affecting approximately 1 in 3500 births. It is characterized by a genetic lack of dystrophin, which is an essential protein for maintaining muscle integrity. The lack of dystrophin plays a pathophysiological role in the development of dilated cardiomyopathy in Duchenne muscular dystrophy. Currently, no consensus exists on specific pharmacological therapy guidelines for these patients; however, it centers around the guidelines for heart failure management. This systematic review investigated 12 randomized control trials dating back to 2005 in the pharmacotherapy of patients with dilated cardiomyopathy Duchenne muscular dystrophy. This review specifically included angiotensin-converting enzyme inhibitors, aldosterone receptor blockers, angiotensin receptor/neprilysin inhibitors, beta-blockers, and mineralocorticoid receptor antagonists. Despite their limitations, these studies have shown promising effects in improving the overall heart function and prognosis in patients with this condition. However, to attain higher statistical significance, future studies should investigate larger populations and for longer periods.
Topics: Humans; Cardiomyopathy, Dilated; Muscular Dystrophy, Duchenne; Dystrophin; Angiotensin-Converting Enzyme Inhibitors; Adrenergic beta-Antagonists
PubMed: 37406964
DOI: 10.1016/j.hjc.2023.06.007 -
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 -
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 -
Developmental Medicine and Child... Dec 2022To identify the standardized assessment scales for people with muscular dystrophy and investigate the quality/level of evidence of their measurement properties. (Review)
Review
AIM
To identify the standardized assessment scales for people with muscular dystrophy and investigate the quality/level of evidence of their measurement properties.
METHOD
A systematic review of patient-reported outcome measures was conducted on the MEDLINE, Embase, AMED, DiTA, and PsycINFO databases in August 2020. We included psychometric studies that investigated the validity, reliability, and responsiveness of instruments assessing activity and participation for muscular dystrophy of any type (Duchenne, Becker, limb-girdle, facioscapulohumeral, congenital, and myotonic) or age. Two independent reviewers selected the studies, extracted data, and evaluated the instruments' quality and level of evidence following the COnsensus-based Standards for the selection of health status Measurement INstruments (COSMIN) checklist. The study followed the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) 2020 guidelines.
RESULTS
The searches identified 6675 references; a total of 46 studies with 28 condition-specific or general instruments were included. The measurement properties of most instruments had sufficient (68.8%) or indeterminate (25.7%) results according to COSMIN. The quality of evidence of the measurement properties was moderate (23.8%) or low (22.6%) according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE).
INTERPRETATION
There is a lack of high-quality instruments whose psychometric properties are adequately measured. The highest quality instrument is the Muscular Dystrophy Functional Rating Scale. The Motor Function Measure (general instrument), Duchenne Muscular Dystrophy Upper-limb Patient-reported Outcome Measure, North Star Ambulatory Assessment, and Myotonic Dystrophy Type 1 Activity and Participation Scale for Clinical Use (specific) are also recommended.
WHAT THIS PAPER ADDS
There are 28 available instruments for activity and participation of people with muscular dystrophy. The evidence quality is moderate or low because of imprecision and indirectness. The Muscular Dystrophy Functional Rating Scale is the highest quality instrument. The Motor Function Measure is the second most recommended instrument. The Duchenne Muscular Dystrophy Upper-limb Patient-reported Outcome Measure, North Star Ambulatory Assessment, and Myotonic Dystrophy Type 1 Activity and Participation Scale for Clinical Use are also recommended.
Topics: Humans; Muscular Dystrophy, Duchenne; Reproducibility of Results; Myotonic Dystrophy; Psychometrics; Patient Reported Outcome Measures
PubMed: 35862363
DOI: 10.1111/dmcn.15345