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Frontiers in Neuroscience 2022Spinal cord injury (SCI) is a devastating condition with few treatment options. Metformin, a classical antidiabetic and antioxidant, has extended its application to...
The effect of metformin on ameliorating neurological function deficits and tissue damage in rats following spinal cord injury: A systematic review and network meta-analysis.
Spinal cord injury (SCI) is a devastating condition with few treatment options. Metformin, a classical antidiabetic and antioxidant, has extended its application to experimental SCI treatment. Here, we performed a systematic review to evaluate the neurobiological roles of metformin for treating SCI in rats, and to assess the potential for clinical translation. PubMed, Embase, China National Knowledge Infrastructure, WanFang data, SinoMed, and Vip Journal Integration Platform databases were searched from their inception dates to October 2021. Two reviewers independently selected controlled studies evaluating the neurobiological roles of metformin in rats following SCI, extracted data, and assessed the quality of methodology and evidence. Pairwise meta-analyses, subgroup analyses and network analysis were performed to assess the roles of metformin in neurological function and tissue damage in SCI rats. Twelve articles were included in this systematic review. Most of them were of moderate-to-high methodological quality, while the quality of evidence from those studies was not high. Generally, Basso, Beattie, and Bresnahan scores were increased in rats treated with metformin compared with controls, and the weighted mean differences (WMDs) between metformin and control groups exhibited a gradual upward trend from the 3rd (nine studies, = 164, WMD = 0.42, 95% CI = -0.01 to 0.85, = 0.06) to the 28th day after treatment (nine studies, = 136, WMD = 3.48, 95% CI = 2.04 to 4.92, < 0.00001). Metformin intervention was associated with improved inclined plane scores, tissue preservation ratio and number of anterior horn motor neurons. Subgroup analyses indicated an association between neuroprotection and metformin dose. Network meta-analysis showed that 50 mg/kg metformin exhibited greater protection than 10 and 100 mg/kg metformin. The action mechanisms behind metformin were associated with activating adenosine monophosphate-activated protein kinase signaling, regulating mitochondrial function and relieving endoplasmic reticulum stress. Collectively, this review indicates that metformin has a protective effect on SCI with satisfactory safety and we demonstrate a rational mechanism of action; therefore, metformin is a promising candidate for future clinical trials. However, given the limitations of animal experimental methodological and evidence quality, the findings of this pre-clinical review should be interpreted with caution.
PubMed: 36117612
DOI: 10.3389/fnins.2022.946879 -
Frontiers in Neurology 2022The lack of systematic evidence on neuroimaging findings in motor neuron diseases (MND) hampers the diagnostic utility of magnetic resonance imaging (MRI). Thus, we...
OBJECTIVES
The lack of systematic evidence on neuroimaging findings in motor neuron diseases (MND) hampers the diagnostic utility of magnetic resonance imaging (MRI). Thus, we aimed at performing a systematic review and meta-analysis of MRI features in MND including their histopathological correlation.
METHODS
In a comprehensive literature search, out of 5941 unique publications, 223 records assessing brain and spinal cord MRI findings in MND were eligible for a qualitative synthesis. 21 records were included in a random effect model meta-analysis.
RESULTS
Our meta-analysis shows that both T2-hyperintensities along the corticospinal tracts (CST) and motor cortex T2-hypointensitites, also called "motor band sign", are more prevalent in ALS patients compared to controls [OR 2.21 (95%-CI: 1.40-3.49) and 10.85 (95%-CI: 3.74-31.44), respectively]. These two imaging findings correlate to focal axonal degeneration/myelin pallor or glial iron deposition on histopathology, respectively. Additionally, certain clinical MND phenotypes such as amyotrophic lateral sclerosis (ALS) seem to present with distinct CNS atrophy patterns.
CONCLUSIONS
Although CST T2-hyperintensities and the "motor band sign" are non-specific imaging features, they can be leveraged for diagnostic workup of suspected MND cases, together with certain brain atrophy patterns. Collectively, this study provides high-grade evidence for the usefulness of MRI in the diagnostic workup of suspected MND cases.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42020182682.
PubMed: 36110394
DOI: 10.3389/fneur.2022.947347 -
Neurological Sciences : Official... Dec 2022The aim of this systematic review (SR) was to gather all available epidemiological evidence on former participation in any type of sport, at a professional and varsity...
OBJECTIVE
The aim of this systematic review (SR) was to gather all available epidemiological evidence on former participation in any type of sport, at a professional and varsity level, as a potential risk factor for neurodegenerative diseases (NDs) and neurocognitive disorders (NCDs).
DESIGN
Systematic searches were performed on PubMed, the Cochrane databases, and the ISI Web of Knowledge databases. Included studies were assessed using the NOS checklist.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
All epidemiological studies reporting data on the possible association between a clinical diagnosis of amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND), dementia or mild cognitive impairment (MCI), Parkinson's disease (PD), chronic traumatic encephalopathy (CTE) at any stage and with any clinical pattern and the former participation in any types of sport at a varsity and professional level were included.
RESULTS
Data from the 17 included studies showed a higher frequency of NDs and NCDs in former soccer and American football players. Updating the previous SR confirmed a higher frequency of ALS/MND in former soccer players. Data reported a significantly higher risk of dementia/AD in former soccer players, and of MCI in former American football players. Results also showed a significantly higher risk of PD in former soccer and American football players, and a significantly higher risk of CTE in former boxers and American football players. This SR confirmed a higher risk of NDs and NCDs in former professional/varsity athletes. However, the pathological mechanisms underlying this association remain unclear, and further high-quality studies should be performed to clarify whether the association could be sport specific.
Topics: Humans; Amyotrophic Lateral Sclerosis; Athletes; Chronic Traumatic Encephalopathy; Cognitive Dysfunction; Dementia; Football; Neurodegenerative Diseases; Parkinson Disease; Soccer
PubMed: 35976476
DOI: 10.1007/s10072-022-06319-x -
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 -
Neuropathology and Applied Neurobiology Dec 2022Over the past decade, considerable efforts have been made to accelerate pathophysiological understanding of fatal neurodegenerative diseases such as amyotrophic lateral... (Review)
Review
Over the past decade, considerable efforts have been made to accelerate pathophysiological understanding of fatal neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) with brain banks at the forefront. In addition to exploratory disease mechanisms, brain banks have aided our understanding with regard to clinical diagnosis, genetics and cell biology. Across neurodegenerative disorders, the impact of brain tissue in ALS research has yet to be quantified. This review aims to outline (i) how postmortem tissues from brain banks have influenced our understanding of ALS over the last 15 years, (ii) correlate the location of dedicated brain banks with the geographical prevalence of ALS, (iii) identify the frequency of features reported from postmortem studies and (iv) propose common reporting standards for materials obtained from dedicated brain banks. A systematic review was conducted using PubMed and Web of Science databases using key words. From a total of 1439 articles, 73 articles were included in the final review, following PRISMA guidelines. Following a thematic analysis, articles were categorised into five themes; clinico-pathological (13), genetic (20), transactive response DNA binding protein 43 (TDP-43) pathology (12), non-TDP-43 neuronal pathology (nine) and extraneuronal pathology (19). Research primarily focused on the genetics of ALS, followed by protein pathology. About 63% of the brain banks were in the United States of America and United Kingdom. The location of brain banks overall aligned with the incidence of ALS worldwide with 88% of brain banks situated in Europe and North America. An overwhelming lack of consistency in reporting and replicability was observed, strengthening the need for a standardised reporting system. Overall, postmortem material from brain banks generated substantial new knowledge in areas of genetics and proteomics and supports their ongoing role as an important research tool.
Topics: Humans; Amyotrophic Lateral Sclerosis; Knowledge Discovery; Brain; Neurons; United Kingdom
PubMed: 35921237
DOI: 10.1111/nan.12845 -
Physical Therapy Oct 2022The purpose of this study was to critically appraise and summarize the evidence for reliability of muscle strength and muscle power assessment in patients with...
OBJECTIVE
The purpose of this study was to critically appraise and summarize the evidence for reliability of muscle strength and muscle power assessment in patients with neuromuscular diseases (NMDs) using isokinetic dynamometry.
METHODS
PubMed, CINAHL, and Embase electronic databases were searched from inception to March 8, 2022. Studies designed to evaluate reliability of muscle strength and power measurements using isokinetic dynamometry were included in this review. First, the methodological quality of the studies was assessed according to the Consensus-Based Standards for the Selection of Health Measurement Instruments guidelines. Next, the quality of measurement properties was determined. Finally, the methodological quality and quality of measurement properties of the studies were combined to obtain a best-evidence synthesis.
RESULTS
A best-evidence synthesis of reliability was performed in 11 studies including postpoliomyelitis syndrome (n = 5), hereditary motor and sensory neuropathy (n = 2), motor neuron diseases (n = 1), myotonic dystrophy (n = 1), and groups of pooled NMDs (n = 2). A best-evidence synthesis on measurement error could not be performed. Quality of evidence on reliability ranged from high in postpoliomyelitis syndrome to very low in hereditary motor and sensory neuropathy, motor neuron diseases, and groups of pooled NMDs. The most frequently used outcome measure was peak torque, which was reliable in all populations (intraclass correlation coefficient >0.7).
CONCLUSION
The quality of evidence for reliability of isokinetic dynamometry was found to vary substantially among different NMDs. High quality of evidence has been obtained only in patients with postpoliomyelitis syndrome. Further research is needed in the majority of known NMDs to determine reliability and validity of isokinetic dynamometry.
IMPACT
The ability of isokinetic dynamometers to capture clinically relevant changes in muscle strength and muscle power in NMDs remains unclear. Isokinetic dynamometry results in NMDs should be interpreted with caution.
Topics: Humans; Muscle Strength Dynamometer; Reproducibility of Results; Postpoliomyelitis Syndrome; Muscle Strength; Neuromuscular Diseases; Hereditary Sensory and Motor Neuropathy; Muscles; Muscle, Skeletal
PubMed: 35899532
DOI: 10.1093/ptj/pzac099 -
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 Neurophysiology Sep 2022Spinal cord injury (SCI) results in sensory, motor, and autonomic dysfunction. Obesity, cardiovascular disease, and metabolic disease are highly prevalent after SCI.... (Review)
Review
Spinal cord injury (SCI) results in sensory, motor, and autonomic dysfunction. Obesity, cardiovascular disease, and metabolic disease are highly prevalent after SCI. Although inadequate voluntary activation of skeletal muscle contributes, it is absent or inadequate activation of thoracic spinal sympathetic neural circuitry and suboptimal activation of homeostatic (cardiovascular and temperature) and metabolic support systems that truly limits exercise capacity, particularly for those with cervical SCI. Thus, when electrical spinal cord stimulation (SCS) studies aimed at improving motor functions began mentioning effects on exercise-related autonomic functions, a potential new area of clinical application appeared. To survey this new area of potential benefit, we performed a systematic scoping review of clinical SCS studies involving these spinally mediated autonomic functions. Nineteen studies were included, 8 used transcutaneous and 11 used epidural SCS. Improvements in blood pressure regulation at rest or in response to orthostatic challenge were investigated most systematically, whereas reports of improved temperature regulation, whole body metabolism, and peak exercise performance were mainly anecdotal. Effective stimulation locations and parameters varied between studies, suggesting multiple stimulation parameters and rostrocaudal spinal locations may influence the same sympathetic function. Brainstem and spinal neural mechanisms providing excitatory drive to sympathetic neurons that activate homeostatic and metabolic tissues that provide support for movement and exercise and their integration with locomotor neural circuitry are discussed. A unifying conceptual framework for the integrated neural control of locomotor and sympathetic function is presented which may inform future research needed to take full advantage of SCS for improving these spinally mediated autonomic functions.
Topics: Electric Stimulation; Exercise; Humans; Movement; Spinal Cord; Spinal Cord Injuries; Spinal Cord Stimulation
PubMed: 35894427
DOI: 10.1152/jn.00205.2022 -
Journal of Clinical Medicine Jul 2022Parkinson's disease (PD) is a neurodegenerative disease that alters gait patterns from early stages. The visuo-motor training strategies such as action observation (AO)... (Review)
Review
Parkinson's disease (PD) is a neurodegenerative disease that alters gait patterns from early stages. The visuo-motor training strategies such as action observation (AO) and motor imagery (MI) that are based on the activity of the mirror neuron system (MNS) facilitate motor re-learning. The main purpose of this systematic review was to analyze the current scientific evidence about the effectiveness of MNS's treatments (AO and MI) to treat gait in patients with PD. Searches were completed from the databases PubMed, Web of Science, and PEDro between November and December 2021. The following keywords were used: "Parkinson disease", "mirror neurons", "gait", "action observation", and "motor imagery". Randomized control trials of the last 5 years written in English or Spanish were included. Two independent reviewers screened the articles and applied the eligibility criteria, and a third reviewer assisted in this process. A total of six articles were included for final revision. The risk of bias was assessed with the PEDro Scale. The effects of AO and MI using different outcome measures were referenced in terms of disease severity, quality of life, balance, and gait. Training with AO and MI are effective in improving disease severity, quality of life, balance, and gait in patients with PD.
PubMed: 35888000
DOI: 10.3390/jcm11144236 -
Stem Cells and Cloning : Advances and... 2022Brachial plexus injury is an advanced and devastating neurological injury, for which both nerve surgery and tendon transfers sometimes remain insufficient in restoring... (Review)
Review
BACKGROUND
Brachial plexus injury is an advanced and devastating neurological injury, for which both nerve surgery and tendon transfers sometimes remain insufficient in restoring normal movement. Stem cell therapy may be applicable to rescue the injured motor neurons from degeneration which potentially improves muscle strength.
STUDY DESIGN
Systematic Review; Level of evidence V.
DATA SOURCES
A systematic literature search was conducted on PubMed (MEDLINE), EMBASE, the Cochrane Library, and Scopus using the terms ("stem cell") AND ("brachial plexus") as search keywords.
METHODS
The process of study selection was summarized by PRISMA flow diagram. The study included in vivo and in vitro studies with English language, humans or animals with some brachial plexus injuries, interventions, some applications of stem cells to the groups of study, with functional, biomechanical, or safety outcomes.
RESULTS
In total, there were 199 studies identified from the literature sources where 75 articles were qualified for forward evaluation following selecting the titles and abstracts. Ten studies were finally included in this systematic review after full-text assessment. Stem cells can produce neurotrophic factors in vitro and in vivo in rats, and their level was increased after injury. Electrophysiological measurement showed that the intervention group had distinctly higher CMAP amplitude and evidently shorter CMAP latency than the model group. Application of bone marrow stem cells (BMSCs) showed an elevation in the numbers of axons and density of myelinated fibers, the density of nerve fibers, the diameter of regenerating axons, and a decrease in axonal degeneration. A study in humans indicated an improvement of the movements in a patient with traumatic total BPI after injection of Ad-MSC. It is associated with increased muscle mass and sensory recovery and also suggested that mononuclear cell injection enhances muscle regeneration and reinnervation in the partly denervated muscle of brachial plexus injury. Various muscle groups had obtained strength together with restoration, the muscle strength attained after the previous transplantation were preserved. The results of this review support stem cell treatment in brachial plexus injury.
CONCLUSION
This review provides evidence of the positive effects of stem cell treatment in brachial plexus injury.
PubMed: 35770243
DOI: 10.2147/SCCAA.S363415