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The Cochrane Database of Systematic... Feb 2013Scoliosis in people with Duchenne muscular dystrophy is usually progressive and treated with surgery. However, it is unclear whether the existing evidence is... (Review)
Review
BACKGROUND
Scoliosis in people with Duchenne muscular dystrophy is usually progressive and treated with surgery. However, it is unclear whether the existing evidence is sufficiently scientifically rigorous to support a recommendation for spinal surgery for most people with Duchenne muscular dystrophy and scoliosis. This is an updated review and an updated search was undertaken in which no new studies were found.
OBJECTIVES
To determine the effectiveness and safety of spinal surgery in people with Duchenne muscular dystrophy with scoliosis. We intended to test whether spinal surgery is effective in increasing survival, improving respiratory function, improving quality of life and overall functioning; and whether spinal surgery is associated with severe adverse effects.
SEARCH METHODS
We searched the specialized registers of the Cochrane Neuromuscular Disease Group (31 July 2012), MEDLINE (January 1966 to July 2012), EMBASE (January 1947 to July 2012), CENTRAL (2012, Issue 7 in the Cochrane Library), CINAHL Plus(January 1937 to July 2012), Proquest Dissertation and Thesis Database (January 1980 to July 2012), and the National Institute of Health Clinical Trials Database (July 2012). No language restrictions were imposed.
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 people with Duchenne muscular dystrophy 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
Two authors independently examined the search results and evaluated the study characteristics against inclusion criteria to decide which ones would be included in the review.
MAIN RESULTS
On searching, 47 studies were relevant but 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 there were no randomized controlled clinical trials available to evaluate the effectiveness of scoliosis surgery in people with Duchenne muscular dystrophy, no evidence-based recommendation can be made for clinical practice. People with scoliosis should be informed about 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: 23450561
DOI: 10.1002/14651858.CD005375.pub3 -
JAMA Neurology Nov 2016Muscle weakness, the most common symptom of neuromuscular disease, may result from muscle dysfunction or may be caused indirectly by neuronal and neuromuscular junction... (Review)
Review
IMPORTANCE
Muscle weakness, the most common symptom of neuromuscular disease, may result from muscle dysfunction or may be caused indirectly by neuronal and neuromuscular junction abnormalities. To date, more than 780 monogenic neuromuscular diseases, linked to 417 different genes, have been identified in humans. Genome-editing methods, especially the CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 (CRISPR-associated protein 9) system, hold clinical potential for curing many monogenic disorders, including neuromuscular diseases such as Duchenne muscular dystrophy, spinal muscular atrophy, amyotrophic lateral sclerosis, and myotonic dystrophy type 1.
OBJECTIVES
To provide an overview of genome-editing approaches; to summarize published reports on the feasibility, efficacy, and safety of current genome-editing methods as they relate to the potential correction of monogenic neuromuscular diseases; and to highlight scientific and clinical opportunities and obstacles toward permanent correction of disease-causing mutations responsible for monogenic neuromuscular diseases by genome editing.
EVIDENCE REVIEW
PubMed and Google Scholar were searched for articles published from June 30, 1989, through June 9, 2016, using the following keywords: genome editing, CRISPR-Cas9, neuromuscular disease, Duchenne muscular dystrophy, spinal muscular atrophy, amyotrophic lateral sclerosis, and myotonic dystrophy type 1. The following sources were reviewed: 341 articles describing different approaches to edit mammalian genomes; 330 articles describing CRISPR-Cas9-mediated genome editing in cell culture lines (in vitro) and animal models (in vivo); 16 websites used to generate single-guide RNA; 4 websites for off-target effects; and 382 articles describing viral and nonviral delivery systems. Articles describing neuromuscular diseases, including Duchenne muscular dystrophy, spinal muscular atrophy, amyotrophic lateral sclerosis, and myotonic dystrophy type 1, were also reviewed.
FINDINGS
Multiple proof-of-concept studies reveal the feasibility and efficacy of genome-editing-meditated correction of monogenic neuromuscular diseases in cultured cells and animal models.
CONCLUSIONS AND RELEVANCE
Genome editing is a rapidly evolving technology with enormous translational potential once efficacy, delivery, and safety issues are addressed. The clinical impact of this technology is that genome editing can permanently correct disease-causing mutations and circumvent the hurdles of traditional gene- and cell-based therapies.
Topics: Amyotrophic Lateral Sclerosis; Animals; Clustered Regularly Interspaced Short Palindromic Repeats; Gene Editing; Genetic Therapy; Humans; Muscular Atrophy, Spinal; Muscular Dystrophy, Duchenne; Myotonic Dystrophy
PubMed: 27668807
DOI: 10.1001/jamaneurol.2016.3388 -
Quality of Life Research : An... Mar 2020Preferences for health states for Duchenne muscular dystrophy (DMD) are necessary to assess costs and benefits of novel therapies. Because DMD progression begins in...
BACKGROUND
Preferences for health states for Duchenne muscular dystrophy (DMD) are necessary to assess costs and benefits of novel therapies. Because DMD progression begins in childhood, the impact of DMD on health-related quality-of-life (HRQoL) affects preferences of both DMD patients and their families. The objective of this review was to synthesize published evidence for health state utility from the DMD patient and caregiver perspectives.
METHODS
A systematic review was performed using MEDLINE and Embase, according to best practices. Data were extracted from studies reporting DMD patient or caregiver utilities; these included study and patient characteristics, health states considered, and utility estimates. Quality appraisal of studies was performed.
RESULTS
From 888 abstracts, eight publications describing five studies were identified. DMD utility estimates were from preference-based measures presented stratified by ambulatory status, ventilation, and age. Patient (or patient-proxy) utility estimates ranged from 0.75 (early ambulatory DMD) to 0.05 (day-and-night ventilation). Caregiver utilities ranged from 0.87 (for caregivers of adults with DMD) to 0.71 (for caregivers of predominantly childhood patients). Both patient and caregiver utilities trended lower with higher disease severity. Variability in utilities was observed based on instrument, respondent type, and country. Utility estimates for health states within non-ambulatory DMD are under reported; nor were utilities for DMD-related health states such as scoliosis or preserved upper limb function identified.
CONCLUSION
Published health state utilities document the substantial HRQoL impacts of DMD, particularly with disease progression. Additional research in patient utilities for additional health states, particularly in non-ambulatory DMD patients, is warranted.
Topics: Adolescent; Adult; Child; Female; Health Services; Humans; Male; Muscular Dystrophy, Duchenne; Quality of Life
PubMed: 31811595
DOI: 10.1007/s11136-019-02355-x -
The Cochrane Database of Systematic... Jan 2006Abnormal delayed relaxation of skeletal muscles, known as myotonia, can cause disability in myotonic disorders. Sodium channel blockers, tricyclic antidepressive drugs,... (Review)
Review
BACKGROUND
Abnormal delayed relaxation of skeletal muscles, known as myotonia, can cause disability in myotonic disorders. Sodium channel blockers, tricyclic antidepressive drugs, benzodiazepines, calcium-antagonists, taurine and prednisone may be of use in reducing myotonia.
OBJECTIVES
To consider the evidence from randomised controlled trials on the efficacy and tolerability of drug treatment in patients with clinical myotonia due to a myotonic disorder.
SEARCH STRATEGY
We searched the Cochrane Neuromuscular Disease Group trials register (April 2004), MEDLINE (January 1966 to December 2003) and EMBASE (January 1980 to December 2003). Grey literature was handsearched and reference lists of identified studies and reviews were examined. Authors, disease experts and manufacturers of anti-myotonic drugs were contacted.
SELECTION CRITERIA
We considered all (quasi) randomised trials of participants with myotonia treated with any drug treatment versus no therapy, placebo or any other active drug treatment. The primary outcome measure was:reduced clinical myotonia using two categories: (1) no residual myotonia or improvement of myotonia or (2) No change or worsening of myotonia. Secondary outcome measures were:(1) clinical relaxation time; (2) electromyographic relaxation time; (3) stair test; (4) presence of percussion myotonia; and (5) proportion of adverse events.
DATA COLLECTION AND ANALYSIS
Two authors extracted the data independently onto standardised extraction forms and disagreements were resolved by discussion.
MAIN RESULTS
Nine randomised controlled trials were found comparing active drug treatment versus placebo or another active drug treatment in patients with myotonia due to a myotonic disorder. Included trials were double-blind or single-blind crossover studies involving a total of 137 patients of which 109 had myotonic dystrophy type 1 and 28 had myotonia congenita. The studies were of poor quality. Therefore, we were not able to analyse the results of all identified studies. Two small crossover studies without a washout period demonstrated a significant effect of imipramine and taurine in myotonic dystrophy. One small crossover study with a washout period demonstrated a significant effect of clomipramine in myotonic dystrophy. Meta-analysis was not possible.
AUTHORS' CONCLUSIONS
Due to insufficient good quality data and lack of randomised studies, it is impossible to determine whether drug treatment is safe and effective in the treatment of myotonia. Small single studies give an indication that clomipramine and imipramine have a short-term beneficial effect and that taurine has a long-term beneficial effect on myotonia. Larger, well-designed randomised controlled trials are needed to assess the efficacy and tolerability of drug treatment for myotonia.
Topics: Humans; Myotonia; Myotonic Dystrophy; Randomized Controlled Trials as Topic
PubMed: 16437496
DOI: 10.1002/14651858.CD004762.pub2 -
PloS One 2013Although muscular dystrophy causes muscle weakness and muscle loss, the role of exercise in the management of this disease remains controversial. (Review)
Review
BACKGROUND
Although muscular dystrophy causes muscle weakness and muscle loss, the role of exercise in the management of this disease remains controversial.
OBJECTIVE
The purpose of this systematic review is to evaluate the role of exercise interventions on muscle strength in patients with muscular dystrophy.
METHODS
We performed systematic electronic searches in Medline, Embase, Web of Science, Scopus and Pedro as well as a list of reference literature. We included trials assessing muscle exercise in patients with muscular dystrophy. Two reviewers independently abstracted data and appraised risk of bias.
RESULTS
We identified five small (two controlled and three randomized clinical) trials comprising 242 patients and two ongoing randomized controlled trials. We were able to perform two meta-analyses. We found an absence of evidence for a difference in muscle strength (MD 4.18, 95% CIs - 2.03 to 10.39; p = 0.91) and in endurance (MD -0.53, 95% CIs -1.11 to 0.05; p = 0.26). In both, the direction of effects favored muscle exercise.
CONCLUSIONS
The first included trial about the efficacy of muscular exercise was published in 1978. Even though some benefits of muscle exercise were consistently reported across studies, the benefits might be due to the small size of studies and other biases. Detrimental effects are still possible. After several decades of research, doctors cannot give advice and patients are, thus, denied basic information. A multi-center randomized trial investigating the strength of muscles, fatigue, and functional limitations is needed.
Topics: Exercise; Humans; Muscle Strength; Muscular Dystrophies; Quality of Life
PubMed: 23894268
DOI: 10.1371/journal.pone.0065414 -
Diagnostics (Basel, Switzerland) Jul 2021Biomarkers play a vital role in clinical care. They enable early diagnosis and treatment by identifying a patient's condition and disease course and act as an outcome... (Review)
Review
Biomarkers play a vital role in clinical care. They enable early diagnosis and treatment by identifying a patient's condition and disease course and act as an outcome measure that accurately evaluates the efficacy of a new treatment or drug. Due to the rapid development of digital technologies, digital biomarkers are expected to grow tremendously. In the era of change, this scoping review was conducted to see which digital biomarkers are progressing in neuromuscular disorders, a diverse and broad-range disease group among the neurological diseases, to discover available evidence for their feasibility and reliability. Thus, a total of 10 studies were examined: 9 observational studies and 1 animal study. Of the observational studies, studies were conducted with amyotrophic lateral sclerosis (ALS), Duchenne muscular dystrophy (DMD), and spinal muscular atrophy (SMA) patients. Non-peer reviewed poster presentations were not considered, as the articles may lead to erroneous results. The only animal study included in the present review investigated the mice model of ALS for detecting rest disturbances using a non-invasive digital biomarker.
PubMed: 34359358
DOI: 10.3390/diagnostics11071275 -
Journal of Neuromuscular Diseases 2024Facial weakness is a key feature of facioscapulohumeral muscular dystrophy (FSHD) and may lead to altered facial expression and subsequent psychosocial impairment. There...
BACKGROUND
Facial weakness is a key feature of facioscapulohumeral muscular dystrophy (FSHD) and may lead to altered facial expression and subsequent psychosocial impairment. There is no cure and supportive treatments focus on optimizing physical fitness and compensation of functional disabilities.
OBJECTIVE
We hypothesize that symptomatic treatment options and psychosocial interventions for other neurological diseases with altered facial expression could be applicable to FSHD. Therefore, the aim of this review is to collect symptomatic treatment approaches that target facial muscle function and psychosocial interventions in various neurological diseases with altered facial expression in order to discuss the applicability to FSHD.
METHODS
A systematic search was performed. Selected studies had to include FSHD, Bell's palsy, Moebius syndrome, myotonic dystrophy type 1, or Parkinson's disease and treatment options which target altered facial expression. Data was extracted for study and patients' characteristics, outcome assessment tools, treatment, outcome of facial expression and or psychosocial functioning.
RESULTS
Forty studies met the inclusion criteria, of which only three studies included FSHD patients exclusively. Most, twenty-one, studies were performed in patients with Bell's palsy. Studies included twelve different therapy categories and results were assessed with different outcomes measures.
CONCLUSIONS
Five therapy categories were considered applicable to FSHD: training of (non-verbal) communication compensation strategies, speech training, physical therapy, conference attendance, and smile restoration surgery. Further research is needed to establish the effect of these therapies in FSHD. We recommend to include outcome measures in these studies that cover at least cosmetic, functional, communication, and quality of life domains.
Topics: Muscular Dystrophy, Facioscapulohumeral; Humans; Facial Expression; Facial Muscles; Bell Palsy
PubMed: 38517799
DOI: 10.3233/JND-230213 -
Journal of Neuromuscular Diseases 2022BackgroundThe impact of age at autosomal recessive limb girdle muscular dystrophy (LGMDR) onset on progression to loss of ambulation (LOA) has not been well established,...
UNLABELLED
BackgroundThe impact of age at autosomal recessive limb girdle muscular dystrophy (LGMDR) onset on progression to loss of ambulation (LOA) has not been well established, particularly by subtype.
OBJECTIVES
To describe the characteristics of patients with adult-, late childhood-, and early childhood-onset LGMDR by subtype and characterize the frequency and timing of LOA.
METHODS
A systematic review was conducted in MEDLINE, Embase and the Cochrane library. Frequency and timing of LOA in patients with LGMDR1, LGMDR2/Miyoshi myopathy (MM), LGMDR3-6, LGMDR9, and LGMDR12 were synthesized from published data.
RESULTS
In 195 studies, 695 (43.4%) patients had adult-, 532 (33.2%) had late childhood-, and 376 (23.5%) had early childhood-onset of disease across subtypes among those with a reported age at onset (n = 1,603); distribution of age at onset varied between subtypes. Among patients with LOA (n = 228), adult-onset disease was uncommon in LGMDR3-6 (14%) and frequent in LGMDR2/MM (42%); LGMDR3-6 cases with LOA primarily had early childhood-onset (74%). Mean (standard deviation [SD]) time to LOA varied between subtypes and was shortest for patients with early childhood-onset LGMDR9 (12.0 [4.9] years, n = 19) and LGMDR3-6 (12.3 [10.7], n = 56) and longest for those with late childhood-onset LGMDR2/MM (21.4 [11.5], n = 36).
CONCLUSIONS
This review illustrated that patients with early childhood-onset disease tend to have faster progression to LOA than those with late childhood- or adult-onset disease, particularly in LGMDR9. These findings provide a greater understanding of progression to LOA by LGMDR subtype, which may help inform clinical trial design and provide a basis for natural history studies.
Topics: Adult; Child; Child, Preschool; Distal Myopathies; Humans; Muscular Atrophy; Muscular Dystrophies, Limb-Girdle; Walking
PubMed: 35527561
DOI: 10.3233/JND-210771 -
Therapeutic Advances in Chronic Disease 2019The purpose of this systematic review was to summarize the different dysphagia screening and evaluation tools, and to identify their measurement properties in adults... (Review)
Review
BACKGROUND
The purpose of this systematic review was to summarize the different dysphagia screening and evaluation tools, and to identify their measurement properties in adults with neuromuscular diseases (NMDs).
METHODS
A systematic review was performed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search strategy was conducted across three databases ( and ). Measurement properties of each tools and the Quality Index, developed by Downs and Black, were considered for the different investigated studies.
RESULTS
The search strategy produced 2221 articles. After removal of duplicates and full-text analysis, 19 studies were included. Most of the publications focused on amyotrophic lateral sclerosis (ALS; = 10) and Duchenne muscular dystrophy (DMD; = 4). A total of 12 tools, listed as instrumental and noninstrumental examinations, were retrieved. A total of five of them used videofluoroscopic swallow study (VFSS). Measurement properties of the tools are not completely described in detail in many studies. The neuromuscular disease swallowing status scale, a noninstrumental tool, is the only one that assessed all measurement properties in ALS patients. The median score reported for the Quality Index was 16.
CONCLUSIONS
This systematic review identified 12 different tools for the screening and evaluation of dysphagia in adults with NMD. Majority of the studies presented VFSS as a valid and reliable examination to assess dysphagia in ALS and DMD. Other tools were mainly evaluated in ALS patients, but further studies are needed to complete their measurement properties. In other NMDs, no firm conclusion can be made because of insufficient data and heterogeneity of NMDs.
PubMed: 30728931
DOI: 10.1177/2040622318821622 -
The Cochrane Database of Systematic... Jan 2017Corticosteroid treatment is considered the 'gold standard' for Duchenne muscular dystrophy (DMD); however, it is also known to induce osteoporosis and thus increase the... (Review)
Review
BACKGROUND
Corticosteroid treatment is considered the 'gold standard' for Duchenne muscular dystrophy (DMD); however, it is also known to induce osteoporosis and thus increase the risk of vertebral fragility fractures. Good practice in the care of those with DMD requires prevention of these adverse effects. Treatments to increase bone mineral density include bisphosphonates and vitamin D and calcium supplements, and in adolescents with pubertal delay, testosterone. Bone health management is an important part of lifelong care for patients with DMD.
OBJECTIVES
To assess the effects of interventions to prevent or treat osteoporosis in children and adults with DMD taking long-term corticosteroids; to assess the effects of these interventions on the frequency of vertebral fragility fractures and long-bone fractures, and on quality of life; and to assess adverse events.
SEARCH METHODS
On 12 September 2016, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL Plus to identify potentially eligible trials. We also searched the Web of Science ISI Proceedings (2001 to September 2016) and three clinical trials registries to identify unpublished studies and ongoing trials. We contacted correspondence authors of the included studies in the review to obtain information on unpublished studies or work in progress.
SELECTION CRITERIA
We considered for inclusion in the review randomised controlled trials (RCTs) and quasi-RCTs involving any bone health intervention for corticosteroid-induced osteoporosis and fragility fractures in children, adolescents, and adults with a confirmed diagnosis of DMD. The interventions might have included oral and intravenous bisphosphonates, vitamin D supplements, calcium supplements, dietary calcium, testosterone, and weight-bearing activity.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed reports and selected potential studies for inclusion, following standard Cochrane methodology. We contacted study authors to obtain further information for clarification on published work, unpublished studies, and work in progress.
MAIN RESULTS
We identified 18 potential studies, of which two, currently reported only as abstracts, met the inclusion criteria for this review. Too little information was available for us to present full results or adequately assess risk of bias. The participants were children aged five to 15 years with DMD, ambulant and non-ambulant. The interventions were risedronate versus no treatment in one trial (13 participants) and whole-body vibration versus a placebo device in the second (21 participants). Both studies reported improved bone mineral density with the active treatments, with no improvement in the control groups, but the abstracts did not compare treatment and control conditions. All children tolerated whole-body vibration treatment. No study provided information on adverse events. Two studies are ongoing: one investigating whole-body vibration, the other investigating zoledronic acid.
AUTHORS' CONCLUSIONS
We know of no high-quality evidence from RCTs to guide use of treatments to prevent or treat corticosteroid-induced osteoporosis and reduce the risk of fragility fractures in children and adults with DMD; only limited results from two trials reported in abstracts were available. We await formal trial reports. Findings from two ongoing relevant studies and two trials, for which only abstracts are available, will be important in future updates of this review.
Topics: Adolescent; Adrenal Cortex Hormones; Bone Density; Bone Density Conservation Agents; Calcium; Child; Child, Preschool; Diphosphonates; Humans; Imidazoles; Male; Muscular Dystrophy, Duchenne; Osteoporosis; Osteoporotic Fractures; Randomized Controlled Trials as Topic; Risedronic Acid; Spinal Fractures; Vibration; Vitamin D; Weight-Bearing; Zoledronic Acid
PubMed: 28117876
DOI: 10.1002/14651858.CD010899.pub2