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Neuroepidemiology 2014Determining the prevalence of neuromuscular disorders for the general population is important to identify the scope of burden on society and enable comparisons with... (Review)
Review
BACKGROUND
Determining the prevalence of neuromuscular disorders for the general population is important to identify the scope of burden on society and enable comparisons with other health conditions. This systematic review aims to identify and collate the findings of studies published between 1960 and 2013 on the prevalence of all types of muscular dystrophies.
SUMMARY
Relevant articles were identified through electronic database searches and manual searches of reference lists. There were 38 articles from across 19 countries that met the inclusion criteria. The total combined prevalence for all muscular dystrophies for studies classified as having a low risk of bias ranged between 19.8 and 25.1 per 100,000 person-years. Myotonic dystrophy (0.5-18.1 per 100,000), Duchenne muscular dystrophy (1.7-4.2) and facioscapulohumeral muscular dystrophy (3.2-4.6 per 100,000) were found to be the most common types of disorder. There was wide variation in study methodology, case ascertainment, and verification procedures and populations studied, all of which may contribute to the wide prevalence range, in addition to the likely variation in prevalence by country. Key Messages: Greater consistency in the conduct and reporting of neuroepidemiological studies is urgently needed to enable comparisons to be made between studies, countries, and over time.
Topics: Bias; Cross-Sectional Studies; Female; Humans; Male; Muscular Dystrophies; Prevalence
PubMed: 25532075
DOI: 10.1159/000369343 -
Pharmacological Reports : PR Oct 2020Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular childhood disorder that causes progressive muscle weakness and degeneration and results in...
BACKGROUND
Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular childhood disorder that causes progressive muscle weakness and degeneration and results in functional decline, loss of ambulation and early death of young men due to cardiac or respiratory failure. Although the major cause of the disease has been known for many years-namely mutation in the DMD gene encoding dystrophin, one of the largest human genes-DMD is still incurable, and its treatment is challenging.
METHODS
A comprehensive and systematic review of literature on the gene, cell, and pharmacological experimental therapies aimed at restoring functional dystrophin or to counteract the associated processes contributing to disease progression like inflammation, fibrosis, calcium signaling or angiogenesis was carried out.
RESULTS
Although some therapies lead to satisfying effects in skeletal muscle, they are highly ineffective in the heart; therefore, targeting defective cardiac and respiratory systems is vital in DMD patients. Unfortunately, most of the pharmacological compounds treat only the symptoms of the disease. Some drugs addressing the underlying cause, like eteplirsen, golodirsen, and ataluren, have recently been conditionally approved; however, they can correct only specific mutations in the DMD gene and are therefore suitable for small sub-populations of affected individuals.
CONCLUSION
In this review, we summarize the possible therapeutic options and describe the current status of various, still imperfect, strategies used for attenuating the disease progression.
Topics: Animals; Dystrophin; Heart; Humans; Muscle, Skeletal; Muscular Dystrophy, Duchenne; Mutation
PubMed: 32691346
DOI: 10.1007/s43440-020-00134-x -
The Cochrane Database of Systematic... Feb 2023'Neurodisability' refers to a group of conditions that result primarily from a neurological problem (e.g. cerebral palsy), neuromuscular problem (e.g. a muscular... (Review)
Review
BACKGROUND
'Neurodisability' refers to a group of conditions that result primarily from a neurological problem (e.g. cerebral palsy), neuromuscular problem (e.g. a muscular dystrophy) or developmental problems (e.g. developmental impairment, Down syndrome). Children and young people with these conditions may have similar problems with mobility, feeding and airway clearance. Chest and breathing problems (including pulmonary infections) are commonly experienced by children and young people with neurodisabilities and are often a cause for them requiring hospital care. For those who are unable to completely clear their airway of secretions, or have frequent infections, pulmonary infections may not be able to be completely eradicated and therefore become chronic. It is unclear what treatment is best for children and young people in this position.
OBJECTIVES
To assess the effectiveness and adverse effects of antibiotic treatment for chronic pulmonary infection in children and young people living with a neurodisability, including quality-of-life measures, effects on hospitalisation and healthcare contacts.
SEARCH METHODS
We searched the Cochrane Airways Trials Register, Cochrane Acute Respiratory Infections Group Register of Trials (CARIGRT), Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid), Embase (Ovid), Cumulative Index to Nursing and Allied Health Literature (CINAHL), OpenGrey (www.opengrey.eu) and three trials registries up to 8 February 2022. Additionally, we identified related systematic reviews through Epistemonikos.org (8 February 2022) and searched reference lists of these.
SELECTION CRITERIA
All randomised controlled trials of antibiotic therapy for chronic pulmonary infection in children and young people up to the age of 18 living with a neurodisability were eligible.
DATA COLLECTION AND ANALYSIS
Two independent review authors screened results of the searches against predetermined inclusion criteria, resolving any discrepancies by discussion.
MAIN RESULTS
We identified a total of 1968 independent records through our searches, of which we assessed six full-text articles for eligibility. We identified one ongoing study as well as one related substudy but did not identify any completed studies eligible for inclusion in this systematic review.
AUTHORS' CONCLUSIONS
The findings of this systematic review highlight a lack of evidence in the antibiotic treatment of chronic pulmonary infection in children and young people up to the age of 18 living with a neurodisability. Further research examining this topic is therefore required.
Topics: Child; Humans; Adolescent; Anti-Bacterial Agents; Respiration Disorders; Hospitalization; Pneumonia; Neurodevelopmental Disorders
PubMed: 36757320
DOI: 10.1002/14651858.CD013813.pub2 -
Diagnostics (Basel, Switzerland) Jan 2023Methodological advancements, such as relative haplotype and relative mutation dosage analyses, have enabled non-invasive prenatal diagnosis of autosomal recessive and... (Review)
Review
BACKGROUND
Methodological advancements, such as relative haplotype and relative mutation dosage analyses, have enabled non-invasive prenatal diagnosis of autosomal recessive and X-linked diseases. Duchenne muscular dystrophy (DMD) is an X-linked recessive disease characterized by progressive proximal muscular dystrophy and a high mortality rate before the age of twenty. We aimed to systematically present obtainable data regarding a non-invasive prenatal diagnosis of DMD and provide a comprehensive resume on the topic. The emphasis was given to the comparison of different available protocols and molecular methods used for fetal inheritance deduction, as well as their correlation with prognostic accuracy.
METHODS
We searched the Scopus and PubMed databases on 11 November 2022 and included articles reporting a non-invasive prenatal diagnosis of DMD in families at risk using relative dosage analysis methods.
RESULTS
Of the 342 articles identified, 7 met the criteria. The reported accuracy of NIPT for DMD was 100% in all of the studies except one, which demonstrated an accuracy of 86.67%. The combined accuracy for studies applying indirect RHDO, direct RHDO, and RMD approaches were 94.74%, 100%, and 100%, respectively. Confirmatory results by invasive testing were available in all the cases. Regardless of the technological complexity and low prevalence of the disease that reduces the opportunity for systematic research, the presented work demonstrates substantial accuracy of NIPT for DMD.
CONCLUSIONS
Attempts for its implementation into everyday clinical practice raise many ethical and social concerns. It is essential to provide detailed guidelines and arrange genetic counseling in order to ensure the proper indications for testing and obtain informed parental consent.
PubMed: 36672993
DOI: 10.3390/diagnostics13020183 -
The Cochrane Database of Systematic... Oct 2015Scoliosis in patients with Duchenne muscular dystrophy (DMD) is usually progressive and is treated with surgery. However, it is unclear whether the existing evidence is... (Review)
Review
BACKGROUND
Scoliosis in patients with Duchenne muscular dystrophy (DMD) is usually progressive and is treated with surgery. However, it is unclear whether the existing evidence is sufficiently scientifically rigorous to support a recommendation for spinal surgery for most patients with DMD and scoliosis. This is an updated review, and an updated search was undertaken in which no new studies were found for inclusion.
OBJECTIVES
To determine the effectiveness and safety of spinal surgery in patients with DMD with scoliosis. We intended to test whether spinal surgery is effective in increasing survival and improving respiratory function, quality of life, and overall functioning, and whether spinal surgery is associated with severe adverse effects.
SEARCH METHODS
On 16 June 2015 we searched the Cochrane Neuromuscular Disease Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and CINAHL Plus. We also searched ProQuest Dissertation and Thesis database (January 1980 to June 2015), the National Institutes of Health Clinical Trials Database (6 January 2015), and the WHO International Clinical Trials Registry Platform (17 June 2015), and checked references. We imposed no language restrictions.
SELECTION CRITERIA
We planned to include controlled clinical trials using random or quasi-random allocation of treatment evaluating all forms of spinal surgery for scoliosis in patients with DMD in the review. The control interventions would have been no treatment, non-operative treatment, or a different form of spinal surgery.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by The Cochrane Collaboration. Two review authors independently examined the search results and evaluated the study characteristics against inclusion criteria in order to decide which studies to include in the review.
MAIN RESULTS
Of the 49 relevant studies we found, none met the inclusion criteria for the review because they were not clinical trials, but prospective or retrospective reviews of case series.
AUTHORS' CONCLUSIONS
Since no randomized controlled clinical trials were available to evaluate the effectiveness of scoliosis surgery in patients with DMD, we can make no good evidence-based conclusion to guide clinical practice. Patients with scoliosis should be informed as to the uncertainty of benefits and potential risks of surgery for scoliosis. Randomized controlled trials are needed to investigate the effectiveness of scoliosis surgery, in terms of quality of life, functional status, respiratory function, and life expectancy.
Topics: Humans; Muscular Dystrophy, Duchenne; Scoliosis; Spine
PubMed: 26423318
DOI: 10.1002/14651858.CD005375.pub4 -
Developmental Medicine and Child... Jun 2023To estimate the global prevalence of intellectual developmental disorder (IDD) and the IDD prevalence-genotype association in Becker muscular dystrophy (BMD) or Duchenne... (Meta-Analysis)
Meta-Analysis Review
AIM
To estimate the global prevalence of intellectual developmental disorder (IDD) and the IDD prevalence-genotype association in Becker muscular dystrophy (BMD) or Duchenne muscular dystrophy (DMD) according to the affected isoforms of the DMD gene: Dp427, Dp140, Dp71.
METHOD
Systematic searches in MEDLINE, Scopus, Web of Science, and the Cochrane Library were conducted from inception of each database to March 2022. Observational studies that determined the prevalence of IDD in the population with BMD or DMD were included. Meta-analyses of IDD prevalence and prevalence ratios of the IDD-genotype association were conducted.
RESULTS
Forty-nine studies were included. The prevalence of IDD in BMD was 8.0% (95% confidence interval 5.0-11.0), and in DMD it was 22.0% (18.0-27.0). Meta-analyses of IDD-genotype association showed a deleterious association between IDD and the number of isoforms affected in DMD, with a prevalence ratio = 0.43 (0.28-0.64) and 0.17 (0.09-0.34) for Dp140 /Dp71 versus Dp140 /Dp71 and Dp140 /Dp71 versus Dp140 /Dp71 comparisons respectively. However, in BMD, there was no association for Dp140 /Dp71 versus Dp140 /Dp71 .
INTERPRETATION
There is a high prevalence of IDD in BMD and DMD. Moreover, the number of isoforms affected is strongly and negatively associated with the prevalence of IDD in DMD.
WHAT THIS PAPER ADDS
The global prevalence of intellectual developmental disorder (IDD) was 8% in Becker muscular dystrophy and 22% in Duchenne muscular dystrophy (DMD). The global prevalence of IDD in DMD was 12%, 29%, and 84% in participants with Dp427 /Dp140 /Dp71 , Dp427 /Dp140 /Dp71 , and Dp427 /Dp140 /Dp71 genotypes respectively. In DMD, 12% and 22% of participants had abnormal performance IQ and verbal IQ values respectively.
Topics: Child; Humans; Muscular Dystrophy, Duchenne; Dystrophin; Developmental Disabilities; Prevalence; Intellectual Disability; Protein Isoforms
PubMed: 36440509
DOI: 10.1111/dmcn.15481 -
The Cochrane Database of Systematic... Dec 2021Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder characterised by progressive muscle weakness beginning in early childhood. Respiratory failure and... (Review)
Review
BACKGROUND
Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder characterised by progressive muscle weakness beginning in early childhood. Respiratory failure and weak cough develop in all patients as a consequence of muscle weakness leading to a risk of atelectasis, pneumonia, or the need for ventilatory support. There is no curative treatment for DMD. Corticosteroids are the only pharmacological intervention proven to delay the onset and progression of muscle weakness and thus respiratory decline in DMD. Antioxidant treatment has been proposed to try to reduce muscle weakness in general, and respiratory decline in particular. OBJECTIVES: To assess the effects of antioxidant agents on preventing respiratory decline in people with Duchenne muscular dystrophy during the respiratory decline phase of the condition. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and two trials registers to 23 March 2021, together with reference checking, citation searching, and contact with study authors to identify additional studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and quasi-RCTs that met our inclusion criteria. We included male patients with a diagnosis of DMD who had respiratory decline evidenced by a forced vital capacity (FVC%) less than 80% but greater than 30% of predicted values, receiving any antioxidant agent compared with other therapies for the management of DMD or placebo. DATA COLLECTION AND ANALYSIS: Two review authors screened studies for eligibility, assessed risk of bias of studies, and extracted data. We used standard methods expected by Cochrane. We assessed the certainty of the evidence using the GRADE approach. The primary outcomes were FVC and hospitalisation due to respiratory infections. Secondary outcomes were quality of life, adverse events, change in muscle function, forced expiratory volume in the first second (FEV1), and peak expiratory flow (PEF). MAIN RESULTS: We included one study with 66 participants who were not co-treated with corticosteroids, which was the only study to contribute data to our main analysis. We also included a study that enrolled 255 participants treated with corticosteroids, which was only available as a press release without numerical results. The studies were parallel-group RCTs that assessed the effect of idebenone on respiratory function compared to placebo. The trial that contributed numerical data included patients with a mean (standard deviation) age of 14.3 (2.7) years at the time of inclusion, with a documented diagnosis of DMD or severe dystrophinopathy with clinical features consistent with typical DMD. The overall risk of bias across most outcomes was similar and judged as 'low'. Idebenone may result in a slightly less of a decline in FVC from baseline to one year compared to placebo (mean difference (MD) 3.28%, 95% confidence interval (CI) -0.41 to 6.97; 64 participants; low-certainty evidence), and probably has little or no effect on change in quality of life (MD -3.80, 95% CI -10.09 to 2.49; 63 participants; moderate-certainty evidence) (Pediatric Quality of Life Inventory (PedsQL), range 0 to 100, 0 = worst, 100 = best quality of life). As a related but secondary outcome, idebenone may result in less of a decline from baseline in FEV1 (MD 8.28%, 95% CI 0.89 to 15.67; 53 participants) and PEF (MD 6.27%, 95% CI 0.61 to 11.93; 1 trial, 64 participants) compared to placebo. Idebenone was associated with fewer serious adverse events (RR 0.42, 95% CI 0.09 to 2.04; 66 participants; low-certainty evidence) and little to no difference in non-serious adverse events (RR 1.00, 95% CI 0.88 to 1.13; 66 participants; low-certainty evidence) compared to placebo. Idebenone may result in little to no difference in change in arm muscle function (MD -2.45 N, 95% CI -8.60 to 3.70 for elbow flexors and MD -1.06 N, 95% CI -6.77 to 4.65 for elbow extensors; both 52 participants) compared to placebo. We found no studies evaluating the outcome hospitalisation due to respiratory infection. The second trial, involving 255 participants, for which data were available only as a press release without numerical data, was prematurely discontinued due to futility after an interim efficacy analysis based on FVC. There were no safety concerns. The certainty of the evidence was low for most outcomes due to imprecision and publication bias (the lack of a full report of the larger trial, which was prematurely terminated).
AUTHORS' CONCLUSIONS
Idebenone is the only antioxidant agent tested in RCTs for preventing respiratory decline in people with DMD for which evidence was available for assessment. Idebenone may result in slightly less of a decline in FVC and less of a decline in FEV1 and PEF, but probably has little to no measurable effect on change in quality of life. Idebenone is associated with fewer serious adverse events than placebo. Idebenone may result in little to no difference in change in muscle function. Discontinuation due to the futility of the SIDEROS trial and its expanded access programmes may indicate that idebenone research in this condition is no longer needed, but we await the trial data. Further research is needed to establish the effect of different antioxidant agents on preventing respiratory decline in people with DMD during the respiratory decline phase of the condition.
Topics: Adolescent; Adrenal Cortex Hormones; Antioxidants; Child; Forced Expiratory Volume; Humans; Male; Muscular Dystrophy, Duchenne; Vital Capacity
PubMed: 34850383
DOI: 10.1002/14651858.CD013720.pub3 -
The Cochrane Database of Systematic... Nov 2021Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder characterised by progressive muscle weakness beginning in early childhood. Respiratory failure and... (Review)
Review
BACKGROUND
Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder characterised by progressive muscle weakness beginning in early childhood. Respiratory failure and weak cough develop in all patients as a consequence of muscle weakness leading to a risk of atelectasis, pneumonia, or the need for ventilatory support. There is no curative treatment for DMD. Corticosteroids are the only pharmacological intervention proven to delay the onset and progression of muscle weakness and thus respiratory decline in DMD. Antioxidant treatment has been proposed to try to reduce muscle weakness in general, and respiratory decline in particular. OBJECTIVES: To assess the effects of antioxidant agents on preventing respiratory decline in people with Duchenne muscular dystrophy during the respiratory decline phase of the condition. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and two trials registers to 23 March 2021, together with reference checking, citation searching, and contact with study authors to identify additional studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and quasi-RCTs that met our inclusion criteria. We included male patients with a diagnosis of DMD who had respiratory decline evidenced by a forced vital capacity (FVC%) less than 80% but greater than 30% of predicted values, receiving any antioxidant agent compared with other therapies for the management of DMD or placebo. DATA COLLECTION AND ANALYSIS: Two review authors screened studies for eligibility, assessed risk of bias of studies, and extracted data. We used standard methods expected by Cochrane. We assessed the certainty of the evidence using the GRADE approach. The primary outcomes were FVC and hospitalisation due to respiratory infections. Secondary outcomes were quality of life, adverse events, change in muscle function, forced expiratory volume in the first second (FEV1), and peak expiratory flow (PEF). MAIN RESULTS: We included one study with 66 participants who were not co-treated with corticosteroids, which was the only study to contribute data to our main analysis. We also included a study that enrolled 255 participants treated with corticosteroids, which was only available as a press release without numerical results. The studies were parallel-group RCTs that assessed the effect of idebenone on respiratory function compared to placebo. The trial that contributed numerical data included patients with a mean (standard deviation) age of 14.3 (2.7) years at the time of inclusion, with a documented diagnosis of DMD or severe dystrophinopathy with clinical features consistent with typical DMD. The overall risk of bias across most outcomes was similar and judged as 'low'. Idebenone may result in a slightly less of a decline in FVC from baseline to one year compared to placebo (mean difference (MD) 3.28%, 95% confidence interval (CI) -0.41 to 6.97; 64 participants; low-certainty evidence), and probably has little or no effect on change in quality of life (MD -3.80, 95% CI -10.09 to 2.49; 63 participants; moderate-certainty evidence) (Pediatric Quality of Life Inventory (PedsQL), range 0 to 100, 0 = worst, 100 = best quality of life). As a related but secondary outcome, idebenone may result in less of a decline from baseline in FEV1 (MD 8.28%, 95% CI 0.89 to 15.67; 53 participants) and PEF (MD 6.27%, 95% CI 0.61 to 11.93; 1 trial, 64 participants) compared to placebo. Idebenone was associated with fewer serious adverse events (RR 0.42, 95% CI 0.09 to 2.04; 66 participants; low-certainty evidence) and little to no difference in non-serious adverse events (RR 1.00, 95% CI 0.88 to 1.13; 66 participants; low-certainty evidence) compared to placebo. Idebenone may result in little to no difference in change in arm muscle function (MD -2.45 N, 95% CI -8.60 to 3.70 for elbow flexors and MD -1.06 N, 95% CI -6.77 to 4.65 for elbow extensors; both 52 participants) compared to placebo. We found no studies evaluating the outcome hospitalisation due to respiratory infection. The second trial, involving 255 participants, for which data were available only as a press release without numerical data, was prematurely discontinued due to futility after an interim efficacy analysis based on FVC. There were no safety concerns. The certainty of the evidence was low for most outcomes due to imprecision and publication bias (the lack of a full report of the larger trial, which was prematurely terminated).
AUTHORS' CONCLUSIONS
Idebenone is the only antioxidant agent tested in RCTs for preventing respiratory decline in people with DMD for which evidence was available for assessment. Idebenone may result in slightly less of a decline in FVC and less of a decline in FEV1 and PEF, but probably has little to no measurable effect on change in quality of life. Idebenone is associated with fewer serious adverse events than placebo. Idebenone may result in little to no difference in change in muscle function. Discontinuation due to the futility of the SIDEROS trial and its expanded access programmes may indicate that idebenone research in this condition is no longer needed, but we await the trial data. Further research is needed to establish the effect of different antioxidant agents on preventing respiratory decline in people with DMD during the respiratory decline phase of the condition.
Topics: Adolescent; Adrenal Cortex Hormones; Antioxidants; Child; Forced Expiratory Volume; Humans; Male; Muscular Dystrophy, Duchenne; Vital Capacity
PubMed: 34748221
DOI: 10.1002/14651858.CD013720.pub2 -
Restorative treatments of dystrophin expression in Duchenne muscular dystrophy: A systematic review.Annals of Clinical and Translational... Sep 2020To evaluate the effect of pharmacological treatments that increase the synthesis of dystrophin in Duchenne muscular dystrophy (DMD). Systematic searches were carried out... (Meta-Analysis)
Meta-Analysis
To evaluate the effect of pharmacological treatments that increase the synthesis of dystrophin in Duchenne muscular dystrophy (DMD). Systematic searches were carried out in MEDLINE, EMBASE, and Web of Science, and in gray literature from inception to December 2019. Clinical trials addressing the effect of restorative treatments of dystrophin expression in children and adolescents with DMD on functional outcomes {(6-minute walking distance [6MWD], other timed functional tests [TFTs], The North Star Ambulatory Assessment)}, dystrophin expression, cardiorespiratory function, and biochemical tests were included. The DerSimonian-Laird method was used to calculate the pooled estimates for functional outcomes. Eleven studies were included in the systematic review and five in the meta-analysis. Eteplirsen showed a significant effect on 6MWD, Δ6MWD = 67.3 m (95% CI: 27.32, 107.28), and Δ6MWD = 151.0 m (95% CI: 36.15, 265.85) at 48 weeks and 3 years, respectively. In the systematic review, analyzing individually the clinical trials using Ataluren and Drisapersen showed a nonsignificant effect on 6MWD. However, the meta-analysis showed a significant effect on 6MWD for Ataluren and Drisapersen, Δ6MWD = 18.3 m (95% CI: 1.0, 35.5) and Δ6MWD = 21.5 m (95% CI: 4.7, 38.3), respectively. There were no significant differences according to baseline age for Drisapersen. Similarly, the meta-analysis showed effect in TFT with Ataluren. All drugs induced a partial synthesis of dystrophin, and exon skipping was obtained with Eteplirsen and Drisapersen. Eteplirsen also improved forced vital capacity (Δ%pFVC = 1.8%) and maximal inspiratory pressure (Δ%pMIP = 4.4%). Eteplirsen and Ataluren could modestly reduce disease progression. However, more trials are needed to confirm its efficacy, as well as quality of life and cost-utility studies.
Topics: Dystrophin; Humans; Morpholinos; Muscular Dystrophy, Duchenne; Oligonucleotides; Outcome Assessment, Health Care; Oxadiazoles
PubMed: 33325654
DOI: 10.1002/acn3.51149 -
The Cochrane Database of Systematic... Jun 2013Progressive muscle weakness is a main symptom of most hereditary and acquired muscle diseases. Creatine improves muscle performance in healthy individuals. This is an... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Progressive muscle weakness is a main symptom of most hereditary and acquired muscle diseases. Creatine improves muscle performance in healthy individuals. This is an update of our 2007 Cochrane review that evaluated creatine treatment in muscle disorders. Previous updates were in 2009 and 2011.
OBJECTIVES
To evaluate the efficacy of creatine compared to placebo for the treatment of muscle weakness in muscle diseases.
SEARCH METHODS
On 11 September 2012, we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL (2012, Issue 9 in The Cochrane Library), MEDLINE (January 1966 to September 2012) and EMBASE (January 1980 to September 2012) for randomised controlled trials (RCTs) of creatine used to treat muscle diseases.
SELECTION CRITERIA
RCTs or quasi-RCTs of creatine treatment compared to placebo in hereditary muscle diseases or idiopathic inflammatory myopathies.
DATA COLLECTION AND ANALYSIS
Two authors independently applied the selection criteria, assessed trial quality and extracted data. We obtained missing data from investigators.
MAIN RESULTS
A total of 14 trials, including 364 randomised participants, met the selection criteria. The risk of bias was low in most studies. Only one trial had a high risk of selection, performance and detection bias. No new studies were identified at this update.Meta-analysis of six trials in muscular dystrophies including 192 participants revealed a significant increase in muscle strength in the creatine group compared to placebo, with a mean difference of 8.47%; (95% confidence intervals (CI) 3.55 to 13.38). Pooled data of four trials including 115 participants showed that a significantly higher number of participants felt better during creatine treatment compared to placebo with a risk ratio of 4.51 (95% CI 2.33 to 8.74). One trial in 37 participants with idiopathic inflammatory myopathies also showed a significant improvement in functional performance. No trial reported any clinically relevant adverse event.In metabolic myopathies, meta-analyses of three cross-over trials including 33 participants revealed no significant difference in muscle strength. One trial reported a significant deterioration of activities of daily living (mean difference 0.54 on a 1 to 10 scale; 95% CI 0.14 to 0.93) and an increase in muscle pain during high-dose creatine treatment in McArdle disease.
AUTHORS' CONCLUSIONS
High quality evidence from RCTs shows that short- and medium-term creatine treatment increases muscle strength in muscular dystrophies. There is also evidence that creatine improves functional performance in muscular dystrophy and idiopathic inflammatory myopathy. Creatine is well tolerated in these people. High quality but limited evidence from RCTs does not show significant improvement in muscle strength in metabolic myopathies. High-dose creatine treatment impaired activities of daily living and increased muscle pain in McArdle disease.
Topics: Creatine; Dietary Supplements; Humans; Muscle Contraction; Muscle Strength; Muscular Diseases; Muscular Dystrophies; Myositis; Randomized Controlled Trials as Topic
PubMed: 23740606
DOI: 10.1002/14651858.CD004760.pub4