-
The Cochrane Database of Systematic... Jan 2020Spinal muscular atrophy (SMA) is caused by a homozygous deletion of the survival motor neuron 1 (SMN1) gene on chromosome 5, or a heterozygous deletion in combination... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Spinal muscular atrophy (SMA) is caused by a homozygous deletion of the survival motor neuron 1 (SMN1) gene on chromosome 5, or a heterozygous deletion in combination with a (point) mutation in the second SMN1 allele. This results in degeneration of anterior horn cells, which leads to progressive muscle weakness. Children with SMA type II do not develop the ability to walk without support and have a shortened life expectancy, whereas children with SMA type III develop the ability to walk and have a normal life expectancy. This is an update of a review first published in 2009 and previously updated in 2011.
OBJECTIVES
To evaluate if drug treatment is able to slow or arrest the disease progression of SMA types II and III, and to assess if such therapy can be given safely.
SEARCH METHODS
We searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, and ISI Web of Science conference proceedings in October 2018. In October 2018, we also searched two trials registries to identify unpublished trials.
SELECTION CRITERIA
We sought all randomised or quasi-randomised trials that examined the efficacy of drug treatment for SMA types II and III. Participants had to fulfil the clinical criteria and have a homozygous deletion or hemizygous deletion in combination with a point mutation in the second allele of the SMN1 gene (5q11.2-13.2) confirmed by genetic analysis. The primary outcome measure was change in disability score within one year after the onset of treatment. Secondary outcome measures within one year after the onset of treatment were change in muscle strength, ability to stand or walk, change in quality of life, time from the start of treatment until death or full-time ventilation and adverse events attributable to treatment during the trial period. Treatment strategies involving SMN1-replacement with viral vectors are out of the scope of this review, but a summary is given in Appendix 1. Drug treatment for SMA type I is the topic of a separate Cochrane Review.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methodology.
MAIN RESULTS
The review authors found 10 randomised, placebo-controlled trials of treatments for SMA types II and III for inclusion in this review, with 717 participants. We added four of the trials at this update. The trials investigated creatine (55 participants), gabapentin (84 participants), hydroxyurea (57 participants), nusinersen (126 participants), olesoxime (165 participants), phenylbutyrate (107 participants), somatotropin (20 participants), thyrotropin-releasing hormone (TRH) (nine participants), valproic acid (33 participants), and combination therapy with valproic acid and acetyl-L-carnitine (ALC) (61 participants). Treatment duration was from three to 24 months. None of the studies investigated the same treatment and none was completely free of bias. All studies had adequate blinding, sequence generation and reporting of primary outcomes. Based on moderate-certainty evidence, intrathecal nusinersen improved motor function (disability) in children with SMA type II, with a 3.7-point improvement in the nusinersen group on the Hammersmith Functional Motor Scale Expanded (HFMSE; range of possible scores 0 to 66), compared to a 1.9-point decline on the HFMSE in the sham procedure group (P < 0.01; n = 126). On all motor function scales used, higher scores indicate better function. Based on moderate-certainty evidence from two studies, the following interventions had no clinically important effect on motor function scores in SMA types II or III (or both) in comparison to placebo: creatine (median change 1 higher, 95% confidence interval (CI) -1 to 2; on the Gross Motor Function Measure (GMFM), scale 0 to 264; n = 40); and combination therapy with valproic acid and carnitine (mean difference (MD) 0.64, 95% CI -1.1 to 2.38; on the Modified Hammersmith Functional Motor Scale (MHFMS), scale 0 to 40; n = 61). Based on low-certainty evidence from other single studies, the following interventions had no clinically important effect on motor function scores in SMA types II or III (or both) in comparison to placebo: gabapentin (median change 0 in the gabapentin group and -2 in the placebo group on the SMA Functional Rating Scale (SMAFRS), scale 0 to 50; n = 66); hydroxyurea (MD -1.88, 95% CI -3.89 to 0.13 on the GMFM, scale 0 to 264; n = 57), phenylbutyrate (MD -0.13, 95% CI -0.84 to 0.58 on the Hammersmith Functional Motor Scale (HFMS) scale 0 to 40; n = 90) and monotherapy of valproic acid (MD 0.06, 95% CI -1.32 to 1.44 on SMAFRS, scale 0 to 50; n = 31). Very low-certainty evidence suggested that the following interventions had little or no effect on motor function: olesoxime (MD 2, 95% -0.25 to 4.25 on the Motor Function Measure (MFM) D1 + D2, scale 0 to 75; n = 160) and somatotropin (median change at 3 months 0.25 higher, 95% CI -1 to 2.5 on the HFMSE, scale 0 to 66; n = 19). One small TRH trial did not report effects on motor function and the certainty of evidence for other outcomes from this trial were low or very low. Results of nine completed trials investigating 4-aminopyridine, acetyl-L-carnitine, CK-2127107, hydroxyurea, pyridostigmine, riluzole, RO6885247/RG7800, salbutamol and valproic acid were awaited and not available for analysis at the time of writing. Various trials and studies investigating treatment strategies other than nusinersen (e.g. SMN2-augmentation by small molecules), are currently ongoing.
AUTHORS' CONCLUSIONS
Nusinersen improves motor function in SMA type II, based on moderate-certainty evidence. Creatine, gabapentin, hydroxyurea, phenylbutyrate, valproic acid and the combination of valproic acid and ALC probably have no clinically important effect on motor function in SMA types II or III (or both) based on low-certainty evidence, and olesoxime and somatropin may also have little to no clinically important effect but evidence was of very low-certainty. One trial of TRH did not measure motor function.
Topics: Adolescent; Amines; Child; Child, Preschool; Creatine; Cyclohexanecarboxylic Acids; Humans; Hydroxyurea; Neuroprotective Agents; Randomized Controlled Trials as Topic; Spinal Muscular Atrophies of Childhood; Thyrotropin-Releasing Hormone; gamma-Aminobutyric Acid
PubMed: 32006461
DOI: 10.1002/14651858.CD006282.pub5 -
Journal of Neuromuscular Diseases 2017Free-living or habitual physical activity (HPA) refers to someone's performance in his or her free-living environment. Neuromuscular disorders (NMD) manifest through... (Review)
Review
BACKGROUND
Free-living or habitual physical activity (HPA) refers to someone's performance in his or her free-living environment. Neuromuscular disorders (NMD) manifest through HPA, and the observation of HPA can be used to identify clinical risks and to quantify outcomes in research. This review summarizes and analyses previous studies reporting the assessment of HPA in NMD, and may serve as the basis for evidence-based decision-making when considering assessing HPA in this population.
METHODS
A systematic review was performed to identify all studies related to HPA in NMD, followed by a critical appraisal of the assessment methodology and a final review of the identified HPA tools.
RESULTS
A total of 22 studies were selected, reporting on eight different direct tools (or activity monitors) and ten structured patient-reported outcomes. Overall, HPA patterns in NMD differ from healthy control populations. There was a noticeable lack of validation studies for these tools and outcome measures in NMD. Very little information regarding feasibility and barriers for the application of these tools in this population have been published.
CONCLUSIONS
The variety and heterogeneity of tools and methods in the published literature makes the comparison across different studies difficult, and methodological guidelines are warranted. We propose a checklist of considerations for the assessment and reporting of HPA in NMD.
Topics: Case-Control Studies; Exercise; Fitness Trackers; Habits; Humans; Neuromuscular Diseases; Patient Reported Outcome Measures; Surveys and Questionnaires
PubMed: 28269791
DOI: 10.3233/JND-160195 -
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 -
Developmental Medicine and Child... Jun 2017Dysphagia is frequent in paediatric patients with neuromuscular diseases (pNMD). Its detection is important for initiating early diagnosis and treatment as well as for... (Review)
Review
AIM
Dysphagia is frequent in paediatric patients with neuromuscular diseases (pNMD). Its detection is important for initiating early diagnosis and treatment as well as for minimizing related complications. The aim of this study was to review the literature on dysphagia screening and evaluation tools in pNMD.
METHOD
A systematic review was performed on the basis of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Three databases (PubMed, CINAHL, and ScienceDirect) were searched. Measurement properties of tools and the quality index developed by Downs and Black were considered.
RESULTS
Our search yielded four studies and four different tools for paediatric patients with Duchenne muscular dystrophy (DMD). The Sydney Swallow Questionnaire, surface electromyography, Neuromuscular Disease Swallowing Status Scale, and videofluoroscopic swallow study showed interesting properties for DMD. No data were available for other NMD and children under 9 years. The mean total score for the quality index was 17.5.
INTERPRETATION
We did not identify any superior validated tools, either for screening or for evaluation of dysphagia, and no widely accepted protocol. Further studies are needed to identify the simplest assessment with the best psychometric properties for pNMD. We recommend establishing a specific tool for pNMD.
Topics: Child; Deglutition Disorders; Humans; Neuromuscular Diseases
PubMed: 27935021
DOI: 10.1111/dmcn.13354 -
Frontiers in Neurology 2020Muscular dystrophy causes weakness and muscle loss. The effect of muscular exercise in these patients remains controversial. To assess the effects of muscular exercise...
Muscular dystrophy causes weakness and muscle loss. The effect of muscular exercise in these patients remains controversial. To assess the effects of muscular exercise vs. no exercise in patients with muscular dystrophy. We performed a comprehensive systematic literature search in the Medline, Embase, Web of Science, Scopus, and Pedro electronic databases, as well as in the reference literature. We included randomized clinical trials (RCTs) that reported the effect of muscular exercise on muscle strength, endurance during walking, motor abilities, and fatigue. Data were extracted independently by two reviewers. Mean difference (MD) and 95% confidence intervals (CI) were used to quantify the effect associated with each outcome. We performed pairwise meta-analyses and trial sequential analyses (TSA) and used GRADE to rate the overall certainty of evidence. We identified 13 RCTs involving 617 patients. The median duration of exercise interventions was 16 weeks [interquartile range [IQR] 12-24]. In the patients with facio-scapulo-humeral dystrophy and myotonic dystrophy, no significant difference in extensor muscle strength was noted between the exercise and the control groups [four studies, 115 patients, MD 4.34, 95% CI -4.20 to 12.88, = 69%; = 0.32; minimal important difference [MID] 5.39 m]. Exercise was associated with improved endurance during walking [five studies, 380 patients, MD 17.36 m, 95% CI 10.91-23.81, = 0; < 0.00001; MID 34 m]. TSA excluded random error as a cause of the findings for endurance during walking. Differences in fatigue and motor abilities were small. Not enough information was found for other types of dystrophy. Muscular exercise did not improve muscle strength and was associated with modest improvements in endurance during walking in patients with facio-scapulo-humeral and myotonic dystrophy. Future trials should explore which type of muscle exercise could lead to better improvements in muscle strength. CRD42019127456.
PubMed: 33281695
DOI: 10.3389/fneur.2020.00958 -
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 -
Journal of Neuromuscular Diseases Aug 2016Quality of life and well-being are frequently restricted in adults with neuromuscular disorders. As such, identification of appropriate interventions is imperative. The... (Review)
Review
Quality of life and well-being are frequently restricted in adults with neuromuscular disorders. As such, identification of appropriate interventions is imperative. The objective of this paper was to systematically review and critically appraise quantitative studies (RCTs, controlled trials and cohort studies) of psychosocial interventions designed to improve quality of life and well-being in adults with neuromuscular disorders. A systematic review of the published and unpublished literature was conducted. Studies meeting inclusion criteria were appraised using a validated quality assessment tool and results presented in a narrative synthesis. Out of 3,136 studies identified, ten studies met criteria for inclusion within the review. Included studies comprised a range of interventions including: cognitive behavioural therapy, dignity therapy, hypnosis, expressive disclosure, gratitude lists, group psychoeducation and psychologically informed rehabilitation. Five of the interventions were for patients with Amyotrophic Lateral Sclerosis (ALS). The remainder were for patients with post-polio syndrome, muscular dystrophies and mixed disorders, such as Charcot-Marie-Tooth disease, myasthenia gravis and myotonic dystrophy. Across varied interventions and neuromuscular disorders, seven studies reported a short-term beneficial effect of intervention on quality of life and well-being. Whilst such findings are encouraging, widespread issues with the methodological quality of these studies significantly compromised the results. There is no strong evidence that psychosocial interventions improve quality of life and well-being in adults with neuromuscular disorders, due to a paucity of high quality research in this field. Multi-site, randomised controlled trials with active controls, standardised outcome measurement and longer term follow-ups are urgently required.
Topics: Amyotrophic Lateral Sclerosis; Charcot-Marie-Tooth Disease; Cognitive Behavioral Therapy; Disclosure; Humans; Hypnosis; Mental Health; Muscular Dystrophies; Myasthenia Gravis; Myotonic Dystrophy; Neuromuscular Diseases; Patient Education as Topic; Postpoliomyelitis Syndrome; Quality of Life
PubMed: 27854227
DOI: 10.3233/JND-160155 -
Disability and Rehabilitation Apr 2023Some parents of children with DMD find their role challenging, affecting quality of life. To inform support methods, we aimed to understand the lived experiences of...
PURPOSE
Some parents of children with DMD find their role challenging, affecting quality of life. To inform support methods, we aimed to understand the lived experiences of parents and how these interact with disease progression.
MATERIALS AND METHODS
PRISMA informed protocol development. Qualitative and mixed methods studies were included. Four databases were searched and study quality was assessed using a standardised measure. Extracted data were analysed using thematic synthesis.
RESULTS
26 studies were included, comprising 362 parents. Seven descriptive themes were apparent: "Diagnostic Experiences", "Coping with the Caregiver Role", "Illness Trajectory and Associated Interventions", "Family Communication", "Network of Support", "Navigating Systems" and "Transition Experiences". Four analytical themes were then derived: "The Cyclical Nature of Grief", "Lifelong Expert in the Needs and Experiences of an Individual with DMD", "Navigating Deviation from Typical Life Course" and "Uncertainty as Ever Present".
CONCLUSION
The extant evidence suggests that the experience of parenting a child with DMD is often characterised by: a cycle of grief that begins at diagnosis, which runs parallel to the development of expertise in caregiving; within this parents notice deviations from their child's and their own expected life course and adjust to the emotions and uncertainty that this can bring.IMPLICATIONS FOR REHABILITATIONProfessionals should be cognisant to the complex grief process associated with DMD, which occurs from diagnosis onwards.There should be continued support for parents following bereavement.Peer support groups may also offer parents ways to maintain well-being.The necessity for parents to function effectively within an uncertain context that induces challenging emotions suggests a role for psychological therapies.
Topics: Child; Humans; Quality of Life; Muscular Dystrophy, Duchenne; Parents; Parenting; Adaptation, Psychological
PubMed: 35435109
DOI: 10.1080/09638288.2022.2060336 -
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 -
African Journal of Traditional,... 2017Duchenne muscular dystrophy (DMD) is caused by a defective gene located on the X-chromosome, responsible for the production of the dystrophin protein. Complications in... (Review)
Review
BACKGROUND
Duchenne muscular dystrophy (DMD) is caused by a defective gene located on the X-chromosome, responsible for the production of the dystrophin protein. Complications in the musculoskeletal system have been previously described in DMD patients. Whole body vibration exercise (WBVE) is a treatment that improves musculoskeletal function in movement disorders. The aim of this study was to review the effects of WBVE on functional mobility, bone and muscle in DMD patients.
MATERIALS AND METHODS
Four databases were searched. Three eligible studies were found; all three conclude the management of DMD patients with WBV was clinically well tolerated. The studies used a side-alternating WBV system, frequencies 7 - 24 Hz; and amplitudes 2 - 4 mm.
RESULTS
A work indicates that a temporary increase in creatine kinase in DMD during the first days of WBV was observed, but other authors did not find changes. No significant changes in bone mass, muscle strength or bone markers. Some patients reported subjective functional improvement during training. Interpretation.
CONCLUSION
It is concluded that WBV seems to be a feasible and well tolerated exercise modality in DMD patients.
Topics: Exercise Therapy; Humans; Muscle Strength; Muscle, Skeletal; Muscular Dystrophy, Duchenne; Range of Motion, Articular; Vibration
PubMed: 28740938
DOI: 10.21010/ajtcam.v14i4S.1