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Journal of Neuromuscular Diseases 2024Despite advances in the medical management of the disease, respiratory involvement remains a significant source of morbidity and mortality in children and adults with...
BACKGROUND
Despite advances in the medical management of the disease, respiratory involvement remains a significant source of morbidity and mortality in children and adults with Duchenne muscular dystrophy (DMD).
OBJECTIVE
The objective of this systematic literature review was to synthesize and grade published evidence of factors associated with respiratory health and function in DMD.
METHODS
We searched MEDLINE, Embase, and the Cochrane Library for records of studies published from January 1, 2000 (to ensure relevance to current care practices), up until and including December 31, 2022, reporting evidence of prognostic indicators and predictors of disease progression in DMD. The quality of evidence (i.e., very low to high) was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework.
RESULTS
The bibliographic search strategy resulted in the inclusion of 29 articles. In total, evidence of 10 factors associated with respiratory health and function in patients with DMD was identified: glucocorticoid exposure (high- to very low-quality evidence), DMD mutations (low-quality evidence), DMD genetic modifiers (low-quality evidence), other pharmacological interventions (i.e., ataluren, eteplirsen, idebenone, and tamoxifen) (moderate- to very low-quality evidence), body mass index and weight (low-quality evidence), and functional ability (low-quality evidence).
CONCLUSIONS
In conclusion, we identified a total of 10 factors associated with respiratory health in function in DMD, encompassing both pharmacological therapies, genetic mutations and modifiers, and patient clinical characteristics. Yet, more research is needed to further delineate sources of respiratory heterogeneity, in particular the genotype-phenotype association and the impact of novel DMD therapies in a real-world setting. Our synthesis and grading should be helpful to inform clinical practice and future research of this heavily burdened patient population.
Topics: Adult; Child; Humans; Muscular Dystrophy, Duchenne; Glucocorticoids; Activities of Daily Living; Disease Progression
PubMed: 37980679
DOI: 10.3233/JND-230094 -
Journal of Clinical Neuromuscular... Dec 2023As the clinical course of autosomal recessive limb-girdle muscular dystrophy (LGMDR) is highly variable, this study characterized the frequency of loss of ambulation...
OBJECTIVES
As the clinical course of autosomal recessive limb-girdle muscular dystrophy (LGMDR) is highly variable, this study characterized the frequency of loss of ambulation (LOA) among patients by subtype (LGMDR1, LGMDR2, LGMDR3-6, LGMDR9, LGMDR12) and progression to cardiac and respiratory involvement among those with and without LOA.
METHODS
Systematic literature review.
RESULTS
From 2929 abstracts screened, 418 patients were identified with ambulatory status data (LOA: 265 [63.4%]). Cardiac and/or respiratory function was reported for 142 patients (34.0%; all with LOA). Among these, respiratory involvement was most frequent in LGMDR3-6 (74.1%; mean [SD] age 23.9 [11.0] years) and cardiac in LGMDR9 (73.3%; mean [SD] age 23.7 [17.7] years). Involvement was less common in patients without LOA except in LGMDR9 (71.4% respiratory and 52.4% cardiac).
CONCLUSIONS
This study described the co-occurrence of LOA, cardiac, and respiratory involvement in LGMDR and provides greater understanding of the clinical progression of LGMDR.
Topics: Humans; Young Adult; Adult; Muscle, Skeletal; Muscular Dystrophies, Limb-Girdle; Disease Progression
PubMed: 37962193
DOI: 10.1097/CND.0000000000000461 -
Stem Cell Reviews and Reports Jan 2024Duchenne Muscular Dystrophy (DMD) is an inherited genetic disorder characterized by progressive degeneration of muscle tissue, leading to functional disability and... (Review)
Review
Duchenne Muscular Dystrophy (DMD) is an inherited genetic disorder characterized by progressive degeneration of muscle tissue, leading to functional disability and premature death. Despite extensive research efforts, the discovery of a cure for DMD continues to be elusive, emphasizing the need to investigate novel treatment approaches. Cellular therapies have emerged as prospective approaches to address the underlying pathophysiology of DMD. This review provides an examination of the present situation regarding cell-based therapies, including CD133 + cells, muscle precursor cells, mesoangioblasts, bone marrow-derived mononuclear cells, mesenchymal stem cells, cardiosphere-derived cells, and dystrophin-expressing chimeric cells. A total of 12 studies were found eligible to be included as they were completed cell therapy clinical trials, clinical applications, or case reports with quantitative results. The evaluation encompassed an examination of limitations and potential advancements in this particular area of research, along with an assessment of the safety and effectiveness of cell-based therapies in the context of DMD. In general, the available data indicates that diverse cell therapy approaches may present a new, safe, and efficacious treatment modality for patients diagnosed with DMD. However, further studies are required to comprehensively understand the most advantageous treatment approach and therapeutic capacity.
Topics: Humans; Muscular Dystrophy, Duchenne; Muscle, Skeletal; Mesenchymal Stem Cells; Treatment Outcome; Cell- and Tissue-Based Therapy
PubMed: 37955832
DOI: 10.1007/s12015-023-10653-8 -
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 Nov 2023Spinal muscular atrophy (SMA) is a progressive neuromuscular disorder associated with continuous motor function loss and complications, such as scoliosis and...
BACKGROUND AND OBJECTIVES
Spinal muscular atrophy (SMA) is a progressive neuromuscular disorder associated with continuous motor function loss and complications, such as scoliosis and contractures. Understanding the natural history of SMA is key to demonstrating the long-term outcomes of SMA treatments. This study reviews the natural history of motor function, scoliosis, and contractures in patients with SMA.
METHODS
Electronic databases were searched from inception to June 27, 2022 (Embase, MEDLINE, and Evidence-Based Medicine Reviews). Observational studies, case-control studies, cross-sectional studies, and case series reporting on motor function (i.e., sitting, standing, and walking ability), scoliosis, and contracture outcomes in patients with types 1-3 SMA were included. Data on study design, baseline characteristics, and treatment outcomes were extracted. Data sets were generated from studies that reported Kaplan-Meier (KM) curves and pooled to generate overall KM curves.
RESULTS
Ninety-three publications were included, of which 68 reported on motor function. Of these, 10 reported KM curves (3 on the probability of sitting in patients with types 2 and 3 SMA and 8 on the probability of walking/ambulation in patients with type 3 SMA). The median time to loss of sitting (95% CI) was 14.5 years (14.1-31.5) for the type 2 SMA sitter population (their maximum ability was independent sitting). The median time to loss of ambulation (95% CI) was 13.4 years (12.5-14.5) for type 3a SMA (disease onset at age younger than 3 years) and 44.2 years (43.0-49.4) for type 3b SMA (disease onset at age 3 years or older). Studies including scoliosis and contracture outcomes mostly reported non-time-to-event data.
DISCUSSION
The results demonstrate that a high degree of motor function loss is inevitable, affecting patients of all ages. In addition, data suggest that untreated patients with types 2 and 3 SMA remain at risk of losing motor milestones during late adulthood, and patients with types 3a and 3b SMA are at risk of loss of ambulation over time. These findings support the importance of stabilization of motor function development even at older ages. Natural history data are key for the evaluation of SMA treatments as they contextualize the assessment of long-term outcomes.
Topics: Humans; Adult; Child, Preschool; Scoliosis; Cross-Sectional Studies; Muscular Atrophy, Spinal; Spinal Muscular Atrophies of Childhood; Contracture
PubMed: 37813581
DOI: 10.1212/WNL.0000000000207878 -
Orphanet Journal of Rare Diseases Sep 2023To obtain updated estimates of the incidence and prevalence of neurofibromatosis type 1 (NF1) and type 2 (NF2). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To obtain updated estimates of the incidence and prevalence of neurofibromatosis type 1 (NF1) and type 2 (NF2).
STUDY DESIGN
We conducted a systematic search of NF1 and NF2 incidence or prevalence studies, in OVID Medline, OVID Embase, Web of Science, and Cinahl. Studies were appraised with the Joanna Briggs Institute Prevalence Critical Appraisal tool. Pooled incidence and prevalence rates were estimated through random-effects meta-analysis.
RESULTS
From 1,939 abstracts, 20 studies were fully appraised and 12 were included in the final review. Pooled NF1 prevalence was 1 in 3,164 (95%CI: 1 in 2,132-1 in 4,712). This was higher in studies that screened for NF1, compared to identification of NF1 through medical records (1 in 2,020 and 1 in 4,329, respectively). NF1 pooled birth incidence was 1 in 2,662 (95%CI: 1 in 1,968-1 in 3,601). There were only 2 studies on NF2 prevalence, so data were not pooled. Pooled NF2 birth incidence was 1.08 per 50,000 births (95%CI: 1 in 32,829-1 in 65,019).
CONCLUSION
We present updated estimates of the incidence and prevalence of NF1 and NF2, to help plan for healthcare access and allocation. The prevalence of NF1 from screening studies is higher than from medical record studies, suggesting that the disease may be under recognized. More studies are needed regarding the prevalence of NF2.
Topics: Humans; Incidence; Neurofibromatosis 1; Prevalence; Health Services Accessibility; Medical Records
PubMed: 37710322
DOI: 10.1186/s13023-023-02911-2 -
Muscle & Nerve Jan 2024In this review we sought to characterize the lived experience of people living with FSHD (pwFSHD) to help clinicians to orient their services to the needs of these... (Review)
Review
INTRODUCTION
In this review we sought to characterize the lived experience of people living with FSHD (pwFSHD) to help clinicians to orient their services to the needs of these individuals.
METHODS
Five electronic databases were systematically searched for qualitative research studies containing quotations from pwFSHD. ENhancing Transparency in REporting the Synthesis of Qualitative research and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines informed the methodology. Study quality was assessed using the Critical Appraisal Skills Programme Checklist tool, which measures the methodological quality of qualitative research. Data extracted from included studies were analyzed using thematic synthesis.
RESULTS
Ninety-nine pwFSHD took part in the six studies included in this review - from research teams based in two countries. Five descriptive themes emerged: "Engaging with life as symptoms progress"; "The emotional journey"; "A family burden to bear"; "Social connection and disconnection"; and "Tension between visibility and invisibility." From these, two analytical themes were derived: "The emotional challenge of continuing and intensifying adaptation" and "The relational burden of rare disease."
DISCUSSION
The lived experience of pwFSHD is characterized by physical, emotional, and social challenges that impact on engagement with life, particularly as symptoms progress. Further research is needed to provide a fuller understanding of the experience of pain in FSHD and of the lived experience of FSHD across cultures.
Topics: Humans; Muscular Dystrophy, Facioscapulohumeral; Qualitative Research; Emotions; Pain; Physical Examination
PubMed: 37691606
DOI: 10.1002/mus.27964 -
International Journal of Molecular... Aug 2023Muscular dystrophy is a heterogenous group of hereditary muscle disorders caused by mutations in the genes responsible for muscle development, and is generally defined... (Review)
Review
Muscular dystrophy is a heterogenous group of hereditary muscle disorders caused by mutations in the genes responsible for muscle development, and is generally defined by a disastrous progression of muscle wasting and massive loss in muscle regeneration. is closely associated with myogenesis, which is governed by various signaling pathways throughout a lifetime and is frequently used as an indicator in muscle research. In this review, an extensive literature search adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was performed to identify research that examined signaling pathways in living models, while quantifying expression in myogenesis. A total of 247 articles were retrieved from the Web of Science (WoS), PubMed and Scopus databases and were thoroughly examined and evaluated, resulting in 19 articles which met the inclusion criteria. Admittedly, we were only able to discuss the quantification of carried out in research affecting various type of genes and signaling pathways, rather than the expression of itself, due to the massive differences in approach, factor molecules and signaling pathways analyzed across the research. However, we highlighted the thorough evidence for the alteration of the muscle stem cell precursor in multiple signaling pathways described in different living models, with an emphasis on the novel approach that could be taken in manipulating expression itself in dystrophic muscle, towards the discovery of an effective treatment for muscular dystrophy. Therefore, we believe that this could be applied to the potential gap in muscle research that could be filled by tuning the well-established marker expression to improve dystrophic muscle.
Topics: Humans; Muscular Dystrophies; Muscles; Databases, Factual; Muscle Development; Signal Transduction; PAX7 Transcription Factor
PubMed: 37685856
DOI: 10.3390/ijms241713051 -
Journal of Neuromuscular Diseases 2023Eating an adequate diet and maintaining a healthy body weight can be challenging for patients with muscular disorders (MD). Starting tube feeding can have a positive...
BACKGROUND
Eating an adequate diet and maintaining a healthy body weight can be challenging for patients with muscular disorders (MD). Starting tube feeding can have a positive impact on nutritional status, functioning and quality of life. Guidelines on when to start tube feeding in adults with MD are lacking.
OBJECTIVE
We aim to review the scientific literature on indications to start tube feeding in adults with facioscapulohumeral dystrophy (FSHD), inclusion body myositis (IBM), muscular dystrophy type 1 (DM1), oculopharyngeal muscular dystrophy (OPMD) and congenital myopathies.
METHODS
This scoping review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews (PRISMA-ScR) guidelines. Relevant studies were identified in Pubmed, Embase and Cinahl (April 2022). The medical subject headings (MeSH) and text words used were related to FSHD, IBM, DM1, OPMD or congenital myopathies and dysphagia, enteral nutrition or malnutrition.
RESULTS
Of 1046 unique articles, 9 case reports and 2 retrospective case series were included. Indications to start tube feeding were dysphagia, malnutrition/weight loss and respiratory infections (due to aspiration). Percutaneous endoscopic gastrostomy (PEG) tubes were used most often and complications were respiratory failure, problems with the tube itself, accidental tube removal, cutaneous symptoms, digestive symptoms, and peritonitis.
CONCLUSION
Data on tube feeding in MD is scarce. Indications to start tube feeding were similar across the various MD. We call for more research in this field and suggest to include screening for dysphagia, aspiration and malnutrition in for the treatment of various MD.
Topics: Humans; Adult; Enteral Nutrition; Deglutition Disorders; Quality of Life; Muscular Dystrophy, Facioscapulohumeral; Retrospective Studies; Malnutrition; Muscular Diseases
PubMed: 37483025
DOI: 10.3233/JND-230014 -
Clinical Neurology and Neurosurgery Sep 2023Mutations in the valosin-containing protein (VCP) gene cause autosomal dominant multisystem proteinopathy 1 (MSP1), characterized by a variable combination of inclusion...
OBJECTIVE
Mutations in the valosin-containing protein (VCP) gene cause autosomal dominant multisystem proteinopathy 1 (MSP1), characterized by a variable combination of inclusion body myopathy (IBM), Paget's disease of bone (PDB), and frontotemporal dementia (FTD). Here we report a novel VCP missense mutations in an Italian family with FTD as the prevalent manifestation and compare our results with those described in the literature.
METHODS
We described the clinical, molecular, and imaging data of the studied family. We also conducted a systematic literature search with the aim of comparing our findings with previously reported VCP-related phenotypes.
RESULTS
A novel heterozygous VCP missense mutation (c 0.473 T > C/p.Met158Thr) was found in all the affected family members. The proband is a 69-year-old man affected by progressive muscle weakness since the age of 49. Muscle MRI showed patchy fatty infiltration in most muscles, and STIR sequences revealed an unusual signal increase in distal leg muscles. At age 65, he presented a cognitive disorder suggestive of behavioral variant FTD. A bone scintigraphy also revealed PDB. The patient's mother, his maternal aunt and her daughter had died following a history of cognitive deterioration consistent with FTD; the mother also had PDB. No relatives had any muscular impairments. Reviewing the literature data, we observed a different sex distribution of VCP-related phenotypes, being FTD prevalence higher among women as compared to men (51.2 % vs 31.2 %) and IBM prevalence higher among men as compared to women (92.1 % vs 72.8 %).
DISCUSSION
This study broadened our clinical, genetic, and imaging knowledge of VCP-related disorders.
Topics: Male; Humans; Female; Aged; Valosin Containing Protein; Frontotemporal Dementia; Mutation; Phenotype; Muscular Dystrophies, Limb-Girdle
PubMed: 37441929
DOI: 10.1016/j.clineuro.2023.107875