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The Cochrane Database of Systematic... Jan 2017Motor neuron disease (MND), which is also known as amyotrophic lateral sclerosis (ALS), causes a wide range of symptoms but the evidence base for the effectiveness of... (Review)
Review
BACKGROUND
Motor neuron disease (MND), which is also known as amyotrophic lateral sclerosis (ALS), causes a wide range of symptoms but the evidence base for the effectiveness of the symptomatic treatment therapies is limited.
OBJECTIVES
To summarise the evidence from Cochrane Systematic Reviews of all symptomatic treatments for MND.
METHODS
We searched the Cochrane Database of Systematic Reviews (CDSR) on 15 November 2016 for systematic reviews of symptomatic treatments for MND. We assessed the methodological quality of the included reviews using the Assessment of Multiple Systematic Reviews (AMSTAR) tool and the GRADE approach. We followed standard Cochrane study (review) selection and data extraction procedures. We reported findings narratively and in tables.
MAIN RESULTS
We included nine Cochrane Systematic Reviews of interventions to treat symptoms in people with MND. Three were empty reviews with no included randomised controlled trials (RCTs); however, all three reported on non-RCT evidence and the remaining six included mostly one or two studies. We deemed all of the included reviews of high methodological quality. Drug therapy for painThere is no RCT evidence in a Cochrane Systematic Review exploring the efficacy of drug therapy for pain in MND. Treatment for crampsThere is evidence (13 RCTs, N = 4012) that for the treatment of cramps in MND, compared to placebo:- memantine and tetrahydrocannabinol (THC) are probably ineffective (moderate-quality evidence);- vitamin E may have little or no effect (low-quality evidence); and- the effects of L-threonine, gabapentin, xaliproden, riluzole, and baclofen are uncertain as the evidence is either very low quality or the trial specified the outcome but did not report numerical data.The review reported adverse effects of riluzole, but it is not clear whether other interventions had adverse effects. Treatment for spasticityIt is uncertain whether an endurance-based exercise programme improved spasticity or quality of life, measured at three months after the programme, as the quality of evidence is very low (1 RCT, comparison "usual activities", N = 25). The review did not evaluate other approaches, such as use of baclofen as no RCTs were available. Mechanical ventilation for supporting respiratory functionNon-invasive ventilation (NIV) probably improves median survival and quality of life in people with respiratory insufficiency and normal to moderately impaired bulbar function compared to standard care, and improves quality of life but not survival for people with poor bulbar function (1 RCT, N = 41, moderate-quality evidence; a second RCT did not provide data). The review did not evaluate other approaches such as tracheostomy-assisted ('invasive') ventilation, or assess timing of NIV initiation. Treatment for sialorrhoeaA single session of botulinum toxin type B injections to parotid and submandibular glands probably improves sialorrhoea and quality of life at up to 4 weeks compared to placebo injections, but not at 8 or 12 weeks after the injections (moderate-quality evidence from 1 placebo-controlled RCT, N = 20). The review authors found no trials of other approaches. Enteral tube feeding for supporting nutritionThere is no RCT evidence in a Cochrane Systematic Review to support benefit or harms of enteral tube feeding in supporting nutrition in MND. Repetitive transcranial magnetic stimulationIt is uncertain whether repetitive transcranial magnetic stimulation (rTMS) improves disability or limitation in activity in MND in comparison with sham rTMS (3 RCTs, very low quality evidence, N = 50). Therapeutic exerciseThere is evidence that exercise may improve disability in MND at three months after the exercise programme, but not quality of life, in comparison with "usual activities" or "usual care" including stretching (2 RCTs, low-quality evidence, N = 43). Multidisciplinary careThere is no RCT evidence in a Cochrane Systematic Review to demonstrate any benefit or harm for multidisciplinary care in MND.None of the reviews, other than the review of treatment for cramps, reported that adverse events occurred. However, the trials were too small for reliable adverse event reporting.
AUTHORS' CONCLUSIONS
This overview has highlighted the lack of robust evidence in Cochrane Systematic Reviews on interventions to manage symptoms resulting from MND. It is important to recognise that clinical trials may fail to demonstrate efficacy of an intervention for reasons other than a true lack of efficacy, for example because of insufficient statistical power, the wrong choice of dose, insensitive outcome measures or inappropriate participant eligibility. The trials were mostly too small to reliably assess adverse effects of the treatments. The nature of MND makes it difficult to research clinically accepted or recommended practice, regardless of the level of evidence supporting the practice. It would not be ethical, for example, to design a placebo-controlled trial for treatment of pain in MND or to withhold multidisciplinary care where such care is available. It is therefore highly unlikely that there will ever be classically designed placebo-controlled RCTs in these areas.We need more research with appropriate study designs, robust methodology, and of sufficient duration to address the changing needs-of people with MND and their caregivers-associated with MND disease progression and mortality. There is a significant gap in studies assessing the effectiveness of interventions for symptoms relating to MND, such as pseudobulbar emotional lability and cognitive and behavioural difficulties. Future studies should use appropriate outcome measures that are reliable, have internal and external validity, and are sensitive to change in what is being measured (such as quality of life).
Topics: Amyotrophic Lateral Sclerosis; Enteral Nutrition; Exercise Therapy; Humans; Motor Neuron Disease; Muscle Cramp; Muscle Spasticity; Noninvasive Ventilation; Pain; Respiratory Insufficiency; Review Literature as Topic; Sialorrhea; Transcranial Magnetic Stimulation
PubMed: 28072907
DOI: 10.1002/14651858.CD011776.pub2 -
Nutritional Neuroscience Jul 2023Parkinson's disease (PD) in elderly patients is the second most prevalent neurodegenerative disease. The pathogenesis of PD is associated with dopaminergic neuron...
BACKGROUND
Parkinson's disease (PD) in elderly patients is the second most prevalent neurodegenerative disease. The pathogenesis of PD is associated with dopaminergic neuron degeneration of the substantia nigra in the basal ganglia, causing classic motor symptoms. Oxidative stress, mitochondrial dysfunction, and neuroinflammation have been identified as possible pathways in laboratory investigations. Nutrition, a potentially versatile factor from all environmental factors affecting PD, has received intense research scrutiny.
METHODS
A systematic search was conducted in the MEDLINE, EMBASE, and WEB OF SCIENCE databases from 2000 until the present. Only randomized clinical trials (RCTs), observational case-control studies, and follow-up studies were included.
RESULTS
We retrieved fifty-two studies that met the inclusion criteria. Most selected studies investigated the effects of malnutrition and the Mediterranean diet (MeDiet) on PD incidence and progression. Other investigations contributed evidence on the critical role of microbiota, vitamins, polyphenols, dairy products, coffee, and alcohol intake.
CONCLUSIONS
There are still many concerns regarding the association between PD and nutrition, possibly due to underlying genetic and environmental factors. However, there is a body of evidence revealing that correcting malnutrition, gut microbiota, and following the MeDiet reduced the onset of PD and reduced clinical progression. Other factors, such as polyphenols, polyunsaturated fatty acids, and coffee intake, can have a potential protective effect. Conversely, milk and its accessory products can increase PD risk. Nutritional intervention is essential for neurologists to improve clinical outcomes and reduce the disease progression of PD.
Topics: Humans; Aged; Parkinson Disease; Coffee; Nutritional Status; Malnutrition; Polyphenols
PubMed: 35730414
DOI: 10.1080/1028415X.2022.2073107 -
Pharmacotherapy Jan 2024This systematic review and meta-analysis aimed to assess the efficacy and safety of risdiplam on motor and respiratory function in spinal muscular atrophy (SMA). We... (Meta-Analysis)
Meta-Analysis Review
This systematic review and meta-analysis aimed to assess the efficacy and safety of risdiplam on motor and respiratory function in spinal muscular atrophy (SMA). We systematically searched Medline, Scopus, Web of Science, and the Cochrane Library from inception to March 2023. We included pre-post studies that determined the effect of risdiplam on the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND), the 32-item Motor Function Measure (MFM32), the Revised Upper Limb Module (RULM), the Hammersmith Functional Motor Scale - Expanded (HFMSE), respiratory function, and the proportion of risdiplam-related adverse events in a population with SMA (phenotypes 1 and 2/3). Meta-analyses were also performed where possible. Eleven studies were included. After 12 months of treatment, 57% of participants with SMA1 achieved a CHOP-INTEND score ≥ 40 points, and more than half were able to feed orally and had head control. In SMA2/3, MFM32, RULM, and HFMSE increased by 2.09 (1.17, 3.01), 1.73 (1.25, 2.20), and 1.00 (0.40, 1.59) points, respectively. Efficacy on respiratory function in SMA2/3 was inconsistent. Finally, 16% of participants experienced adverse events, but serious adverse events could not be quantified due to a lack of cases. The limited available evidence suggests that risdiplam is an effective and safe drug for the treatment of SMA. In addition, long-term clinical benefit may be partly determined by the stage of disease at which treatment is initiated.
Topics: Child; Infant; Humans; Spinal Muscular Atrophies of Childhood; Muscular Atrophy, Spinal; Azo Compounds; Pyrimidines
PubMed: 37574770
DOI: 10.1002/phar.2866 -
JAMA Neurology Feb 2021Accurate and up-to-date estimates on incidence, prevalence, mortality, and disability-adjusted life-years (burden) of neurological disorders are the backbone of...
IMPORTANCE
Accurate and up-to-date estimates on incidence, prevalence, mortality, and disability-adjusted life-years (burden) of neurological disorders are the backbone of evidence-based health care planning and resource allocation for these disorders. It appears that no such estimates have been reported at the state level for the US.
OBJECTIVE
To present burden estimates of major neurological disorders in the US states by age and sex from 1990 to 2017.
DESIGN, SETTING, AND PARTICIPANTS
This is a systematic analysis of the Global Burden of Disease (GBD) 2017 study. Data on incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) of major neurological disorders were derived from the GBD 2017 study of the 48 contiguous US states, Alaska, and Hawaii. Fourteen major neurological disorders were analyzed: stroke, Alzheimer disease and other dementias, Parkinson disease, epilepsy, multiple sclerosis, motor neuron disease, migraine, tension-type headache, traumatic brain injury, spinal cord injuries, brain and other nervous system cancers, meningitis, encephalitis, and tetanus.
EXPOSURES
Any of the 14 listed neurological diseases.
MAIN OUTCOME AND MEASURE
Absolute numbers in detail by age and sex and age-standardized rates (with 95% uncertainty intervals) were calculated.
RESULTS
The 3 most burdensome neurological disorders in the US in terms of absolute number of DALYs were stroke (3.58 [95% uncertainty interval [UI], 3.25-3.92] million DALYs), Alzheimer disease and other dementias (2.55 [95% UI, 2.43-2.68] million DALYs), and migraine (2.40 [95% UI, 1.53-3.44] million DALYs). The burden of almost all neurological disorders (in terms of absolute number of incident, prevalent, and fatal cases, as well as DALYs) increased from 1990 to 2017, largely because of the aging of the population. Exceptions for this trend included traumatic brain injury incidence (-29.1% [95% UI, -32.4% to -25.8%]); spinal cord injury prevalence (-38.5% [95% UI, -43.1% to -34.0%]); meningitis prevalence (-44.8% [95% UI, -47.3% to -42.3%]), deaths (-64.4% [95% UI, -67.7% to -50.3%]), and DALYs (-66.9% [95% UI, -70.1% to -55.9%]); and encephalitis DALYs (-25.8% [95% UI, -30.7% to -5.8%]). The different metrics of age-standardized rates varied between the US states from a 1.2-fold difference for tension-type headache to 7.5-fold for tetanus; southeastern states and Arkansas had a relatively higher burden for stroke, while northern states had a relatively higher burden of multiple sclerosis and eastern states had higher rates of Parkinson disease, idiopathic epilepsy, migraine and tension-type headache, and meningitis, encephalitis, and tetanus.
CONCLUSIONS AND RELEVANCE
There is a large and increasing burden of noncommunicable neurological disorders in the US, with up to a 5-fold variation in the burden of and trends in particular neurological disorders across the US states. The information reported in this article can be used by health care professionals and policy makers at the national and state levels to advance their health care planning and resource allocation to prevent and reduce the burden of neurological disorders.
Topics: Cost of Illness; Disability-Adjusted Life Years; Global Burden of Disease; Global Health; Humans; Nervous System Diseases; United States
PubMed: 33136137
DOI: 10.1001/jamaneurol.2020.4152 -
Journal of Clinical Nursing Jul 2021To systematically review previous studies on the variables associated with coping strategies in people with amyotrophic lateral sclerosis and motor neuron disease... (Review)
Review
AIMS AND OBJECTIVES
To systematically review previous studies on the variables associated with coping strategies in people with amyotrophic lateral sclerosis and motor neuron disease (ALS/MND), such as demographics, clinical features and patient-reported outcomes.
BACKGROUND
Coping strategies are important factors for adjustment and quality of life (QOL) in patients with long-term conditions, and this topic in people with ALS/MND has not yet been the subject of a systematic review.
DESIGN
A systematic review was performed based on the PRISMA checklist.
METHODS
Electronic databases, including CINAHL, MEDLINE and EMBASE, were systemically searched from their inception to December 2019 for articles meeting the following inclusion criteria: (1) written in English, (2) published in peer-reviewed journals, (3) included subjects with ALS/MND and (4) used quantitative measurements of coping strategies in people with ALS/MND.
RESULTS
Twenty-one articles were included. Significant relationships between participants' demographics (age and sex) and any coping strategy aspect were shown in six studies. Eight studies found significant relationships between clinical characteristics (disease duration and physical functional status) and coping strategies, and ten studies reported coping strategies that were associated with patients' QOL and mental health outcomes.
CONCLUSION
Younger people used relatively more problem-focused, emotion-focused and social support coping strategies, and women used relatively more social support coping strategies. Problem-focused coping was generally related to better QOL and mental health, and emotion-focused coping was generally related to less depression.
RELEVANCE TO CLINICAL PRACTICE
As the pattern of coping strategies is related to demographic and clinical characteristics, this study could be used to inform the provision of patient-centred nursing in clinical care. Coping patterns are related to mental health and QOL; thus, in clinical care, it is recommended that people with ALS be encouraged to develop skills that enable them to cope more effectively and that their coping strategies be assessed.
Topics: Adaptation, Psychological; Amyotrophic Lateral Sclerosis; Female; Humans; Motor Neuron Disease; Quality of Life; Social Support
PubMed: 33555628
DOI: 10.1111/jocn.15692 -
International Journal of Environmental... May 2022Background: Hand trauma requires specific rehabilitation protocol depending on the different structures involved. According to type of surgical intervention, and for... (Meta-Analysis)
Meta-Analysis
Background: Hand trauma requires specific rehabilitation protocol depending on the different structures involved. According to type of surgical intervention, and for monitoring pain and edema, post-operative rehabilitation of a hand that has experienced trauma involves different timings for immobilization. Several protocols have been used to reduce immobilization time, and various techniques and methods are adopted, depending on the structures involved. Objective: To measure the effects of mirror neurons-based rehabilitation techniques in hand injuries throughout a systematic review and meta-analysis. Methods: The protocol was accepted in PROSPERO database. A literature search was conducted in Cinahl, Scopus, Medline, PEDro, OTseeker. Two authors independently identified eligible studies, based on predefined inclusion criteria, and extracted the data. RCT quality was assessed using the JADAD scale. Results: Seventy-nine suitable studies were screened, and only eleven were included for qualitative synthesis, while four studies were selected for quantitative analysis. Four studies were case reports/series, and seven were RCTs. Nine investigate the effect of Mirror Therapy and two the effect of Motor Imagery. Quantitative analyses revealed Mirror Therapy as effective for hand function recovery (mean difference = −14.80 95% Confidence Interval (CI) = −17.22, −12.38) (p < 0.00001) in the short term, as well as in long follow-up groups (mean difference = −13.11 95% Confidence Interval (CI) = −17.53, −8.69) (p < 0.00001). Clinical, but not statistical, efficacy was found for manual dexterity (p = 0.15), while no benefit was reported for range of motion. Conclusions: Mirror neurons-based rehabilitation techniques, combined with conventional occupational and physical therapy, can be a useful approach in hand trauma. Mirror therapy seems to be effective for hand function recovery, but, for motor imagery and action observation, there is not sufficient evidence to recommend its use. Further research on the efficacy of the mirror neurons-based technique in hand injury is recommended.
Topics: Humans; Hand Injuries; Mirror Neurons; Neurological Rehabilitation; Physical Therapy Modalities; Recovery of Function
PubMed: 35564920
DOI: 10.3390/ijerph19095526 -
Amyotrophic Lateral Sclerosis &... May 2022To summarize applications of muscle magnetic resonance imaging (MRI) in cross-sectional assessment and longitudinal monitoring of motor neuron diseases and evaluate... (Review)
Review
To summarize applications of muscle magnetic resonance imaging (MRI) in cross-sectional assessment and longitudinal monitoring of motor neuron diseases and evaluate associations with clinical assessment techniques. PubMed and Scopus were searched for research published up to May 2021 relating to muscle MRI in motor neuron diseases, according to predefined inclusion and exclusion criteria. Studies were systematically appraised for bias and data were extracted for discussion. Twenty-eight papers met inclusion criteria. The studies assessed muscle T1- and T2-weighted signal, diffusion, muscle volume, and fat infiltration, employing quantitative, qualitative, and semi-quantitative approaches. Various regions of interest were considered; changes in thigh and calf muscles were most frequently reported. Preliminary evidence of concordance between clinical and radiological findings and utility as an objective longitudinal biomarker is emerging. Muscle MRI appears a promising objective, versatile, and practical biomarker to assess motor neuron diseases.
Topics: Amyotrophic Lateral Sclerosis; Biomarkers; Cross-Sectional Studies; Humans; Magnetic Resonance Imaging; Motor Neuron Disease; Muscle, Skeletal
PubMed: 34151652
DOI: 10.1080/21678421.2021.1936062 -
NPJ Digital Medicine Dec 2023Motor Neuron Disease (MND) is a progressive and largely fatal neurodegeneritve disorder with a lifetime risk of approximately 1 in 300. At diagnosis, up to 25% of people... (Review)
Review
Motor Neuron Disease (MND) is a progressive and largely fatal neurodegeneritve disorder with a lifetime risk of approximately 1 in 300. At diagnosis, up to 25% of people with MND (pwMND) exhibit bulbar dysfunction. Currently, pwMND are assessed using clinical examination and diagnostic tools including the ALS Functional Rating Scale Revised (ALS-FRS(R)), a clinician-administered questionnaire with a single item on speech intelligibility. Here we report on the use of digital technologies to assess speech features as a marker of disease diagnosis and progression in pwMND. Google Scholar, PubMed, Medline and EMBASE were systematically searched. 40 studies were evaluated including 3670 participants; 1878 with a diagnosis of MND. 24 studies used microphones, 5 used smartphones, 6 used apps, 2 used tape recorders and 1 used the Multi-Dimensional Voice Programme (MDVP) to record speech samples. Data extraction and analysis methods varied but included traditional statistical analysis, CSpeech, MATLAB and machine learning (ML) algorithms. Speech features assessed also varied and included jitter, shimmer, fundamental frequency, intelligible speaking rate, pause duration and syllable repetition. Findings from this systematic review indicate that digital speech biomarkers can distinguish pwMND from healthy controls and can help identify bulbar involvement in pwMND. Preliminary evidence suggests digitally assessed acoustic features can identify more nuanced changes in those affected by voice dysfunction. No one digital speech biomarker alone is consistently able to diagnose or prognosticate MND. Further longitudinal studies involving larger samples are required to validate the use of these technologies as diagnostic tools or prognostic biomarkers.
PubMed: 38062079
DOI: 10.1038/s41746-023-00959-9 -
Frontiers in Aging Neuroscience 2022Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular disease whose primary hallmark is the progressive degeneration of motor neurons in the brainstem,...
Mixed Comparison of Different Exercise Interventions for Function, Respiratory, Fatigue, and Quality of Life in Adults With Amyotrophic Lateral Sclerosis: Systematic Review and Network Meta-Analysis.
BACKGROUND
Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular disease whose primary hallmark is the progressive degeneration of motor neurons in the brainstem, spinal cord, and cerebral cortex that leads to weakness, spasticity, fatigue, skeletal muscle atrophy, paralysis, and even death. Exercise, as a non-pharmacological tool, may generally improve muscle strength, cardiovascular function, and quality of life. However, there are conflicting reports about the effect of exercise training in adults with ALS.
AIMS
This systematic review and network meta-analysis aim to conduct a mixed comparison of different exercise interventions for function, respiratory, fatigue, and quality of life in adults with ALS.
METHODS
Randomized controlled trials with ALS participants were screened and included from the databases of PubMed, Medline, and Web of Science. Physical exercise interventions were reclassified into aerobic exercise, resistance training, passive exercise, expiratory muscle exercise, and standard rehabilitation. Patient-reported outcome measures would be reclassified from perspectives of function, respiratory, fatigue, and quality of life. The effect size would be transferred into the percentage change of the total score.
RESULT
There were 10 studies included, with the agreement between authors reaching a kappa-value of 0.73. The network meta-analysis, which was conducted under the consistency model, identified that a combined program of aerobic exercise, resistance exercise, and standard rehabilitation showed the highest potential to improve quality of life (0.64 to be the best) and reduce the fatigue (0.39 to be the best) for ALS patients, while exercise program of aerobic and resistance training showed the highest potential (0.51 to be the best) to improve ALS patients' physical function. The effect of exercise on the respiratory was still unclear.
CONCLUSION
A multi-modal exercise and rehabilitation program would be more beneficial to ALS patients. However, the safety and guide for practice remain unclear, and further high-quality randomized controlled trials (RCTs) with a larger sample are still needed.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021253442, CRD42021253442.
PubMed: 35898325
DOI: 10.3389/fnagi.2022.919059 -
Journal of Neurology Dec 2022Amyotrophic lateral sclerosis (ALS) is the most common subtype of motor neuron disease (MND). The current gold-standard measure of progression is the ALS Functional... (Review)
Review
Amyotrophic lateral sclerosis (ALS) is the most common subtype of motor neuron disease (MND). The current gold-standard measure of progression is the ALS Functional Rating Scale-Revised (ALS-FRS(R)), a clinician-administered questionnaire providing a composite score on physical functioning. Technology offers a potential alternative for assessing motor progression in both a clinical and research capacity that is more sensitive to detecting smaller changes in function. We reviewed studies evaluating the utility and suitability of these devices to evaluate motor function and disease progression in people with MND (pwMND). We systematically searched Google Scholar, PubMed and EMBASE applying no language or date restrictions. We extracted information on devices used and additional assessments undertaken. Twenty studies, involving 1275 (median 28 and ranging 6-584) pwMND, were included. Sensor type included accelerometers (n = 9), activity monitors (n = 4), smartphone apps (n = 4), gait (n = 3), kinetic sensors (n = 3), electrical impedance myography (n = 1) and dynamometers (n = 2). Seventeen (85%) of studies used the ALS-FRS(R) to evaluate concurrent validity. Participant feedback on device utility was generally positive, where evaluated in 25% of studies. All studies showed initial feasibility, warranting larger longitudinal studies to compare device sensitivity and validity beyond ALS-FRS(R). Risk of bias in the included studies was high, with a large amount of information to determine study quality unclear. Measurement of motor pathology and progression using technology is an emerging, and promising, area of MND research. Further well-powered longitudinal validation studies are needed.
Topics: Humans; Amyotrophic Lateral Sclerosis; Digital Technology; Motor Neuron Disease; Disease Progression
PubMed: 35945397
DOI: 10.1007/s00415-022-11312-7