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Life (Basel, Switzerland) Jan 2023The main objectives of this review were, firstly, to study the effect of different physiotherapy interventions on BDNF levels, and, secondly, to analyze the influence of... (Review)
Review
OBJECTIVE
The main objectives of this review were, firstly, to study the effect of different physiotherapy interventions on BDNF levels, and, secondly, to analyze the influence of physiotherapy on pain levels to subsequently draw conclusions about its possible relationship with BDNF.
BACKGROUND
Based on the theory that neurotrophic factors such as BDNF play a fundamental role in the initiation and/or maintenance of hyperexcitability of central neurons in pain, it was hypothesized that the levels of this neurotrophic factor may be modified by the application of therapeutic interventions, favoring a reduction in pain intensity.
METHODS
A literature search of multiple electronic databases (Pubmed, PsycINFO, Medline (Ebsco), Scopus, WOS, Embase) was conducted to identify randomized control trials (RCTs) published without language restrictions up to and including March 2022. The search strategy was based on the combination of medical terms (Mesh) and keywords relating to the following concepts: "pain", "chronic pain", "brain derived neurotrophic factor", "BDNF", "physiotherapy", and "physical therapy". A total of seven papers were included.
RESULTS
There were two studies that showed statistically significant differences in pain intensity reduction and an increase in the BDNF levels that used therapies such as rTMS and EIMS in patients with chronic myofascial pain. However, the same conclusions cannot be drawn for the other physical therapies applied.
CONCLUSIONS
rTMS and EIMS interventions achieved greater short-term reductions in pain intensity and increased BDNF over other types of interventions in chronic myofascial pain patients, as demonstrated by a moderate amount of evidence. In contrast, other types of physical therapy (PT) interventions did not appear to be more effective in decreasing pain intensity and increasing BDNF levels than placebo PT or minimal intervention, as a low amount of evidence was found.
PubMed: 36676112
DOI: 10.3390/life13010163 -
Frontiers in Immunology 2022Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive motor neuron damage. Due to the complexity of the ALS, so far the...
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive motor neuron damage. Due to the complexity of the ALS, so far the etiology and underlying pathogenesis of sporadic ALS are not completely understood. Recently, many studies have emphasized the role of inflammatory networks, which are comprised of various inflammatory molecules and proteins in the pathogenesis of ALS. Inflammatory molecules and proteins may be used as independent predictors of patient survival and might be used in patient stratification and in evaluating the therapeutic response in clinical trials. This review article describes the latest advances in various inflammatory markers in ALS and its animal models. In particular, this review discusses the role of inflammatory molecule markers in the pathogenesis of the disease and their relationship with clinical parameters. We also highlight the advantages and disadvantages of applying inflammatory markers in clinical manifestations, animal studies, and drug clinical trials. Further, we summarize the potential application of some inflammatory biomarkers as new therapeutic targets and therapeutic strategies, which would perhaps expand the therapeutic interventions for ALS.
Topics: Animals; Amyotrophic Lateral Sclerosis; Neurodegenerative Diseases; Biomarkers; Motor Neurons; Proteins
PubMed: 36618399
DOI: 10.3389/fimmu.2022.1059994 -
JAMA Network Open Dec 2022Peripheral neuropathies are common conditions and can result in numbness, paresthesia, motor deficits, and pain. There is increasing evidence for the use of biomarkers... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Peripheral neuropathies are common conditions and can result in numbness, paresthesia, motor deficits, and pain. There is increasing evidence for the use of biomarkers as clinical indicators of the presence, severity, and prognosis of nerve lesions; however, biomarker identification has largely been focused on disorders of the central nervous system, and less is known about their role in the peripheral nervous system.
OBJECTIVE
To assess blood-based biomarker concentrations associated with nerve involvement in patients with peripheral neuropathy compared with control participants.
DATA SOURCES
Ovid, MEDLINE, Embase, and CINAHL were searched from inception to September 23, 2021.
STUDY SELECTION
Observational studies reporting on blood biomarkers in patients diagnosed with peripheral neuropathy were included. This review was preregistered on PROSPERO and followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Data were abstracted by 1 investigator and independently reviewed by a second.
DATA EXTRACTION AND SYNTHESIS
Data were meta-analyzed when at least 2 studies reported the same biomarker with comparable methodology. Fixed-effects models were used when only 2 studies were included; random-effects models were used when more than 2 studies were included.
MAIN OUTCOMES AND MEASURES
The outcome of interest was concentration of biomarkers.
RESULTS
This review included 36 studies reporting on 4414 participants, including 2113 control participants and 2301 patients with peripheral neuropathy with 13 distinct peripheral neuropathy diagnoses. Diabetic neuropathy was the most common neuropathy diagnosis (13 studies), followed by Charcot-Marie-Tooth disease (6 studies) and Guillain-Barre syndrome (6 studies). Overall, 16 different blood-based biomarkers associated with nerve involvement were evaluated. The most used were neurofilament light chain, S100B, brain-derived neurotrophic factor, and neuron-specific enolase. Patients with peripheral neuropathy demonstrated significantly higher levels of neurofilament light chain compared with controls (standardized mean difference [SMD], 0.93 [95% CI, 0.82 to 1.05]; P < .001). There were no significant differences in levels of S100B (SMD, 1.10 [95% CI, -3.08 to 5.28]; P = .38), brain-derived neurotrophic factor (SMD, -0.52 [95% CI, -2.23 to 1.19]; P = .40), or neuron-specific enolase (SMD, -0.00 [95% CI, -1.99 to 1.98]; P = .10) in patients with peripheral neuropathy compared with control participants.
CONCLUSIONS AND RELEVANCE
The findings of this systematic review and meta-analysis support the use of neurofilament light chain as a blood-based measure associated with the presence of neuronal injury in patients with peripheral neuropathy.
Topics: Humans; Adult; Brain-Derived Neurotrophic Factor; Biomarkers; Diabetic Neuropathies; Prognosis; Pain
PubMed: 36574244
DOI: 10.1001/jamanetworkopen.2022.48593 -
Frontiers in Neural Circuits 2022Vocal communication is used across extant vertebrates, is evolutionarily ancient, and been maintained, in many lineages. Here I review the neural circuit architectures...
Vocal communication is used across extant vertebrates, is evolutionarily ancient, and been maintained, in many lineages. Here I review the neural circuit architectures that support intraspecific acoustic signaling in representative anuran, mammalian and avian species as well as two invertebrates, fruit flies and Hawaiian crickets. I focus on hindbrain motor control motifs and their ties to respiratory circuits, expression of receptors for gonadal steroids in motor, sensory, and limbic neurons as well as divergent modalities that evoke vocal responses. Hindbrain and limbic participants in acoustic communication are highly conserved, while forebrain participants have diverged between anurans and mammals, as well as songbirds and rodents. I discuss the roles of natural and sexual selection in driving speciation, as well as exaptation of circuit elements with ancestral roles in respiration, for producing sounds and driving rhythmic vocal features. Recent technical advances in whole brain fMRI across species will enable real time imaging of acoustic signaling partners, tying auditory perception to vocal production.
Topics: Animals; Acoustics; Sound; Neurons; Auditory Perception; Rhombencephalon; Drosophila; Mammals
PubMed: 36466364
DOI: 10.3389/fncir.2022.976789 -
Neural Regeneration Research Jun 2023Trehalose, a unique nonreducing crystalline disaccharide, is a potential disease-modifying treatment for neurodegenerative diseases associated with protein misfolding... (Review)
Review
Trehalose, a unique nonreducing crystalline disaccharide, is a potential disease-modifying treatment for neurodegenerative diseases associated with protein misfolding and aggregation due to aging, intrinsic mutations, or autophagy dysregulation. This systematic review summarizes the effects of trehalose on its underlying mechanisms in animal models of selected neurodegenerative disorders (tau pathology, synucleinopathy, polyglutamine tract, and motor neuron diseases). All animal studies on neurodegenerative diseases treated with trehalose published in Medline (accessed via EBSCOhost) and Scopus were considered. Of the 2259 studies screened, 29 met the eligibility criteria. According to the SYstematic Review Center for Laboratory Animal Experiment (SYRCLE) risk of bias tool, we reported 22 out of 29 studies with a high risk of bias. The present findings support the purported role of trehalose in autophagic flux and protein refolding. This review identified several other lesser-known pathways, including modifying amyloid precursor protein processing, inhibition of reactive gliosis, the integrity of the blood-brain barrier, activation of growth factors, upregulation of the downstream antioxidant signaling pathway, and protection against mitochondrial defects. The absence of adverse events and improvements in the outcome parameters were observed in some studies, which supports the transition to human clinical trials. It is possible to conclude that trehalose exerts its neuroprotective effects through both direct and indirect pathways. However, heterogeneous methodologies and outcome measures across the studies rendered it impossible to derive a definitive conclusion. Translational studies on trehalose would need to clarify three important questions: 1) bioavailability with oral administration, 2) optimal time window to confer neuroprotective benefits, and 3) optimal dosage to confer neuroprotection.
PubMed: 36453391
DOI: 10.4103/1673-5374.360164 -
Frontiers in Neural Circuits 2022To systematically evaluate the effectiveness and safety of repetitive transcranial magnetic stimulation (rTMS) on spasticity after upper motor neuron (UMN) injury. Eight... (Meta-Analysis)
Meta-Analysis
To systematically evaluate the effectiveness and safety of repetitive transcranial magnetic stimulation (rTMS) on spasticity after upper motor neuron (UMN) injury. Eight electronic databases were searched from inception to August 6, 2022. Randomized controlled trials (RCTs) investigating the effectiveness and safety of rTMS on spasticity after UMN injury were retrieved. Two reviewers independently screened studies, extracted data, and assessed the risk of bias. Review Manager 5.3 and Stata 14.0 software were used to synthesize data. The certainty of the evidence was appraised with the Grade of Recommendation, Assessment, Development and Evaluation tool. Forty-two studies with a total of 2,108 patients were included. The results of meta-analysis revealed that, compared with control group, rTMS could significantly decrease scores of the Modified Ashworth Scale (MAS) in patients with UMN injury. The subgroup analysis discovered that rTMS effectively decreased the MAS scores in patients with stroke. Meanwhile, rTMS treatment > 10 sessions has better effect and rTMS could decrease the MAS scores of upper limb. Thirty-three patients complained of twitching facial muscles, headache and dizziness, etc. In summary, rTMS could be recommended as an effective and safe therapy to relieve spasticity in patients with UMN injury. However, due to high heterogeneity and limited RCTs, this conclusion should be treated with caution.
Topics: Humans; Transcranial Magnetic Stimulation; Stroke Rehabilitation; Upper Extremity; Stroke; Motor Neurons
PubMed: 36426136
DOI: 10.3389/fncir.2022.973561 -
Frontiers in Neurology 2022Spasticity is a common motor disorder resulting from upper motor neuron lesions. It has a serious influence on an individual's motor function and daily activity....
Effects of repetitive peripheral magnetic stimulation on spasticity evaluated with modified Ashworth scale/Ashworth scale in patients with spastic paralysis: A systematic review and meta-analysis.
BACKGROUND
Spasticity is a common motor disorder resulting from upper motor neuron lesions. It has a serious influence on an individual's motor function and daily activity. Repetitive peripheral magnetic stimulation (rPMS) is a non-invasive and painless approach developed for therapeutic intervention in clinical rehabilitation. However, the effectiveness of this intervention on spasticity in patients with spastic paralysis remains uncertain.
OBJECTIVE
This study aimed to investigate the effectiveness of rPMS on spasticity, motor function, and activities of daily living in individuals with spastic paralysis.
METHODS
PubMed, PEDro, Embase, Cochrane Library, and Web of Science were searched for eligible papers with date up to March 31, 2022. Two independent researchers conducted study screening, data extraction, and methodological quality assessment. RCTs that explored the effects of rPMS on spasticity, motor function, and activities of daily living in patients with spastic paralysis were included for review. The Cochrane collaboration tool was used to assess methodological quality. The cumulative effects of available data were processed for a meta-analysis using Reedman software.
RESULTS
Eight studies with 297 participants were included. Most of the studies presented low to moderate risk of bias. Compared with the control group, the results showed that rPMS had a significant effect on spasticity (all spasticity outcomes: standardized mean difference [SMD] = -0.55, 95% confidence interval [CI]: -0.94 to -0.16, = 40%, and = 0.006, Modified Ashworth Scale: mean difference [MD] = -0.48, 95% CI: -0.82 to -0.14, = 0%, and = 0.006), motor function (Fugl-Meyer Assessment: MD = 4.17, 95% CI: 0.89 to 7.46, = 28%, and = 0.01), and activities of daily living (Barthel Index: MD = 5.12, 95% CI: 2.58 to 7.67, = 0%, and < 0.0001). No side effect was reported.
CONCLUSION
The meta-analysis demonstrated that the evidence supported rPMS in improving spasticity especially for passive muscle properties evaluated with Modified Ashworth Scale/Ashworth Scale, as well as motor function and daily activity of living in individuals with spastic paralysis.
STUDY REGISTRATION
The reviewed protocol of this study is registered in the international prospective register of systematic reviews (PROSPERO) (CRD42022322395).
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier CRD42022322395.
PubMed: 36425797
DOI: 10.3389/fneur.2022.997913 -
Toxins Oct 2022Disabling limb spasticity can result from stroke, traumatic brain injury or other disorders causing upper motor neuron lesions such as multiple sclerosis. Clinical... (Review)
Review
Disabling limb spasticity can result from stroke, traumatic brain injury or other disorders causing upper motor neuron lesions such as multiple sclerosis. Clinical studies have shown that abobotulinumtoxinA (AboBoNT-A) therapy reduces upper and lower limb spasticity in adults. However, physicians may administer potentially inadequate doses, given the lack of consensus on adjusting dose according to muscle volume, the wide dose ranges in the summary of product characteristics or cited in the published literature, and/or the high quantity of toxin available for injection. Against this background, a systematic literature review based on searches of MEDLINE and Embase (via Ovid SP) and three relevant conferences (2018 to 2020) was conducted in November 2020 to examine AboBoNT-A doses given to adults for upper or lower limb muscles affected by spasticity of any etiology in clinical and real-world evidence studies. From the 1781 unique records identified from the electronic databases and conference proceedings screened, 49 unique studies represented across 56 publications (53 full-text articles, 3 conference abstracts) were eligible for inclusion. Evidence from these studies suggested that AboBoNT-A dose given per muscle in clinical practice varies considerably, with only a slight trend toward a relationship between dose and muscle volume. Expert-based consensus is needed to inform recommendations for standardizing AboBoNT-A treatment initiation doses based on muscle volume.
Topics: Adult; Humans; Injections, Intramuscular; Treatment Outcome; Botulinum Toxins, Type A; Muscle Spasticity; Stroke; Lower Extremity; Neuromuscular Agents; Upper Extremity
PubMed: 36355984
DOI: 10.3390/toxins14110734 -
Frontiers in Psychiatry 2022Mirror neuron system (MNS) consists of visuomotor neurons that are responsible for the mirror neuron activity (MNA), meaning that each time an individual observes...
BACKGROUND
Mirror neuron system (MNS) consists of visuomotor neurons that are responsible for the mirror neuron activity (MNA), meaning that each time an individual observes another individual performing an action, these neurons encode that action, and are activated in the observer's cortical motor system. Previous studies report its malfunction in autism, opening doors to investigate the underlying pathophysiology of the disorder in a more elaborate way and coming up with new rehabilitation methods. The study of MNA function in schizophrenia patients has not been as frequent and conclusive as in autism. In this research, we aimed to evaluate the functional integrity of MNA and the microstructural integrity of MNS in schizophrenia patients.
METHODS
We included case-control studies that have evaluated MNA in schizophrenia patients compared to healthy controls using a variety of objective assessment tools. In August 2022, we searched Embase, PubMed, and Web of Science for eligible studies. We used an adapted version of the NIH Quality Assessment of Case-Control Studies tool to assess the quality of the included studies. Evidence was analyzed using vote counting methods of the direction of the effect and was tested statistically using the Sign test. Certainty of evidence was assessed using CERQual.
RESULTS
We included 32 studies for the analysis. Statistical tests revealed decreased MNA ( = 0.002) in schizophrenia patients. The certainty of the evidence was judged to be moderate. Investigations of heterogeneity revealed a possible relationship between the age and the positive symptoms of participants in the included studies and the direction of the observed effect.
DISCUSSION
This finding contributes to gaining a better understanding of the underlying pathophysiology of the disorder by revealing its possible relation to some of the symptoms in schizophrenia patients, while also highlighting a new commonality with autism.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO identifier: CRD42021236453.
PubMed: 36213922
DOI: 10.3389/fpsyt.2022.884828 -
Frontiers in Pharmacology 2022The effect of herbal medicine (HM) on amyotrophic lateral sclerosis (ALS) is controversial. Clinical trials investigating HMs continue; however, the use of HM is still...
The effect of herbal medicine (HM) on amyotrophic lateral sclerosis (ALS) is controversial. Clinical trials investigating HMs continue; however, the use of HM is still questioned. We aimed to systematically review the literature pertaining to the effects and safety of HM in ALS. Randomised controlled trials (RCTs) that investigated the efficacy of HMs in ALS patients compared to any types of controls were identified. Nine databases and six registers were searched from their inception dates to 25 March 2022. Per the PRISMA guidelines, trials were identified and extracted. The risk of bias was evaluated using the Cochrane's tool. Certainty of evidence was assessed as per the GRADE criteria. Forest plots were constructed to assess the effect size and corresponding 95% CIs using fixed-effect models, and random-effect models were employed when required. The primary outcome was the activity limitation measured by validated tools, such as the revised ALS Functional Rating Scale. Twenty studies ( = 1,218) were eligible. Of these, only five studies were double-blinded, and two were placebo-controlled. Fourteen HMs (fifty-one single botanicals) were involved; and were commonly used in nine, eight, and six trials, respectively. For delaying activity limitation, injection (MD, 2.84; 95% CI, 1.21 to 4.46; = 0.0006) and injection (SMD, 1.07; 0.69 to 1.45; < 0.00001) were significantly more efficacious than Riluzole, but the evidence was low quality. For ameliorating motor neuron loss, injection [right abductor pollicis brevis (APB): MD, 32.42; 7.91 to 56.93; = 0.01 and left APB: MD, 34.44; 12.85 to 56.03; = 0.002] was favoured, but the evidence was very low quality. Nine studies reported one hundred and twenty-three adverse events, twenty-six of which occurred in the treatment groups and ninety-seven in the control groups. Very low to low quality of evidence suggests that HMs seem to produce superior treatment responses for ALS without increased risk of adverse events. Additional studies with homogeneous participants, reduced methodological issues, and more efficient outcome measures are required to provide confirmatory evidence. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021277443.
PubMed: 36120351
DOI: 10.3389/fphar.2022.946548