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Neuropathology : Official Journal of... Feb 2021Brain involvement in myotonic dystrophy type 1 (DM1) is characterized by heterogeneous cognitive, behavioral, and affective symptoms and imaging alterations indicative...
Brain involvement in myotonic dystrophy type 1 (DM1) is characterized by heterogeneous cognitive, behavioral, and affective symptoms and imaging alterations indicative of widespread grey and white matter involvement. The aim of the present study was to systematically review the literature on brain pathology in DM1. We conducted a structured search in EMBASE (index period 1974-2017) and MEDLINE (index period 1887-2017) on December 11, 2017, using free text and index search terms related to myotonic dystrophy type 1 and brain structures or regions. Eligible studies were full-text studies reporting on microscopic brain pathology of DM1 patients without potentially interfering comorbidity. We discussed the findings based on the anatomical region and the nature of the anomaly. Neuropathological findings in DM1 can be classified as follows: (1) protein and nucleotide deposits; (2) changes in neurons and glial cells; and (3) white matter alterations. Most findings are unspecific to DM1 and may occur with physiological aging, albeit to a lesser degree. There are similarities and contrasts with Alzheimer's disease; both show the appearance of neurofibrillary tangles in the limbic system without plaque occurrence. Likewise, there is myelin loss and gliosis, and there are dilated perivascular spaces in the white matter resemblant of cerebral small vessel disease. However, we did not find evidence of lacunar infarction or microbleeding. The various neuropathological findings in DM1 are reflective of the heterogeneous clinical and neuroimaging features of the disease. The strength of conclusions from this study's findings is bounded by limited numbers of participants in studies, methodological constraints, and lack of assessed associations between histopathology and clinical or neuroimaging findings.
Topics: Brain; Gray Matter; Humans; Inclusion Bodies; Myotonic Dystrophy; Neurofibrillary Tangles; Neuroimaging; White Matter
PubMed: 33599033
DOI: 10.1111/neup.12721 -
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 -
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 -
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 -
Respiration; International Review of... 2021Chronic hypercapnic respiratory failure induces considerable morbidity and mortality in patients with myotonic dystrophy type 1 (DM1). This study systematically reviews...
INTRODUCTION
Chronic hypercapnic respiratory failure induces considerable morbidity and mortality in patients with myotonic dystrophy type 1 (DM1). This study systematically reviews the effects of noninvasive home mechanical ventilation (HMV) on gas exchange, quality of life, survival, and compliance in DM1 patients.
METHODS
A systematic Medline and Embase search was performed (January 1995 to January 2020). Records were screened for eligibility criteria, data were extracted from included studies, and risk of bias was assessed. We present findings mainly using a narrative synthesis.
RESULTS
Twenty-eight relevant full-text articles were screened for eligibility criteria. Nine studies were included. Randomized controlled trials were not found. Studies had either an observational (n = 8) or interventional (n = 1) design. In the pooled data analysis, HMV showed to improve mean oxygen saturation with 4.8% and decreased mean carbon dioxide values with 3 mm Hg. Compliance varied widely between studies, from no use to more than 12 h per day. Quality of life was not studied extensively, but some studies reported positive effects of HMV on symptoms of chronic respiratory failure. HMV may improve survival in DM1 patients with chronic hypercapnic respiratory failure.
CONCLUSION
This review shows that HMV can improve gas exchange and relieve symptoms with a possible survival benefit in DM1 patients with chronic hypercapnic respiratory failure. Future studies should focus on developing strategies to optimize the timing of HMV initiation and to promote compliance.
Topics: Adult; Humans; Myotonic Dystrophy; Noninvasive Ventilation; Patient Compliance; Pulmonary Gas Exchange; Quality of Life; Respiratory Insufficiency
PubMed: 33965950
DOI: 10.1159/000515453 -
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 -
Journal of Neurology, Neurosurgery, and... Apr 2024Management of muscular dystrophies (MD) relies on conservative non-pharmacological treatments, but evidence of their effectiveness is limited and inconclusive. (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Management of muscular dystrophies (MD) relies on conservative non-pharmacological treatments, but evidence of their effectiveness is limited and inconclusive.
OBJECTIVE
To investigate the effectiveness of conservative non-pharmacological interventions for MD physical management.
METHODS
This systematic review and meta-analysis followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and searched Medline, CINHAL, Embase, AMED and Cochrane Central Register of Controlled Trial (inception to August 2022). Effect size (ES) and 95% Confidence Interval (CI) quantified treatment effect.
RESULTS
Of 31,285 identified articles, 39 studies (957 participants), mostly at high risk of bias, were included. For children with Duchenne muscular dystrophy (DMD), trunk-oriented strength exercises and usual care were more effective than usual care alone in improving distal upper-limb function, sitting and dynamic reaching balance (ES range: 0.87 to 2.29). For adults with Facioscapulohumeral dystrophy (FSHD), vibratory proprioceptive assistance and neuromuscular electrical stimulation respectively improved maximum voluntary isometric contraction and reduced pain intensity (ES range: 1.58 to 2.33). For adults with FSHD, Limb-girdle muscular dystrophy (LGMD) and Becker muscular dystrophy (BMD), strength-training improved dynamic balance (sit-to-stand ability) and self-perceived physical condition (ES range: 0.83 to 1.00). A multicomponent programme improved perceived exertion rate and gait in adults with Myotonic dystrophy type 1 (DM1) (ES range: 0.92 to 3.83).
CONCLUSIONS
Low-quality evidence suggests that strength training, with or without other exercise interventions, may improve perceived exertion, distal upper limb function, static and dynamic balance, gait and well-being in MD. Although more robust and larger studies are needed, current evidence supports the inclusion of strength training in MD treatment, as it was found to be safe.
Topics: Adult; Child; Humans; Muscular Dystrophy, Facioscapulohumeral; Muscular Dystrophy, Duchenne; Muscular Dystrophies, Limb-Girdle; Myotonic Dystrophy; Exercise
PubMed: 38124127
DOI: 10.1136/jnnp-2023-331988 -
The Cochrane Database of Systematic... Jan 2010Strength training or aerobic exercise programmes might optimise muscle and cardiorespiratory function and prevent additional disuse atrophy and deconditioning in people... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Strength training or aerobic exercise programmes might optimise muscle and cardiorespiratory function and prevent additional disuse atrophy and deconditioning in people with a muscle disease.
OBJECTIVES
To examine the safety and efficacy of strength training and aerobic exercise training in people with a muscle disease.
SEARCH STRATEGY
We searched the Cochrane Neuromuscular Disease Group Trials Specialized Register (July 2009), the Cochrane Rehabilitation and Related Therapies Field Register (October 2002, August 2008 and July 2009), The Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2009) MEDLINE (January 1966 to July 2009), EMBASE (January 1974 to July 2009), EMBASE Classic (1947 to 1973) and CINAHL (January 1982 to July 2009).
SELECTION CRITERIA
Randomised or quasi-randomised controlled trials comparing strength training or aerobic exercise programmes, or both, to no training, and lasting at least 10 weeks.For strength training Primary outcome: static or dynamic muscle strength. Secondary: muscle endurance or muscle fatigue, functional assessments, quality of life, muscle membrane permeability, pain and experienced fatigue.For aerobic exercise training Primary outcome: aerobic capacity expressed as work capacity. Secondary: aerobic capacity (oxygen consumption, parameters of cardiac or respiratory function), functional assessments, quality of life, muscle membrane permeability, pain and experienced fatigue.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed trial quality and extracted the data.
MAIN RESULTS
We included three trials (121 participants). The first compared the effect of strength training versus no training in 36 people with myotonic dystrophy. The second trial compared strength training versus no training, both combined with albuterol or placebo, in 65 people with facioscapulohumeral muscular dystrophy. The third trial compared combined strength training and aerobic exercise versus no training in 18 people with mitochondrial myopathy. In the myotonic dystrophy trial there were no significant differences between training and non-training groups for primary and secondary outcome measures. In the facioscapulohumeral muscular dystrophy trial only a +1.17 kg difference (95% confidence interval 0.18 to 2.16) in dynamic strength of elbow flexors in favour of the training group reached statistical significance. In the mitochondrial myopathy trial there were no significant differences in dynamic strength measures between training and non-training groups. Exercise duration and distance cycled in a submaximal endurance test increased significantly in the training group compared to the control group.
AUTHORS' CONCLUSIONS
In myotonic dystrophy and facioscapulohumeral muscular dystrophy, moderate-intensity strength training appears not to do harm but there is insufficient evidence to conclude that it offers benefit. In mitochondrial myopathy, aerobic exercise combined with strength training appears to be safe and may be effective in increasing submaximal endurance capacity. Limitations in the design of studies in other muscle diseases prevent more general conclusions in these disorders.
Topics: Exercise; Humans; Mitochondrial Myopathies; Muscular Dystrophy, Facioscapulohumeral; Myotonic Dystrophy; Physical Fitness; Randomized Controlled Trials as Topic
PubMed: 20091552
DOI: 10.1002/14651858.CD003907.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 -
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