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Neuromodulation : Journal of the... Oct 2023Falls in extrapyramidal disorders, particularly Parkinson's disease (PD), multisystem atrophy (MSA), and progressive supranuclear palsy (PSP), are key milestones... (Review)
Review
BACKGROUND
Falls in extrapyramidal disorders, particularly Parkinson's disease (PD), multisystem atrophy (MSA), and progressive supranuclear palsy (PSP), are key milestones affecting patients' quality of life, incurring increased morbidity/mortality and high healthcare costs. Unfortunately, gait and balance in parkinsonisms respond poorly to currently available treatments. A serendipitous observation of improved gait and balance in patients with PD receiving spinal cord stimulation (SCS) for back pain kindled an interest in using SCS to treat gait disorders in parkinsonisms.
OBJECTIVES
We reviewed preclinical and clinical studies of SCS to treat gait dysfunction in parkinsonisms, covering its putative mechanisms and efficacies.
MATERIALS AND METHODS
Preclinical studies in animal models of PD and clinical studies in patients with PD, PSP, and MSA who received SCS for gait disorders were included. The main outcome assessed was clinical improvement in gait, together with outcome measures used and possible mechanism of actions.
RESULTS
We identified 500 references, and 45 met the selection criteria and have been included in this study for analysis. Despite positive results in animal models, the outcomes in human studies are inconsistent.
CONCLUSIONS
The lack of blind and statistically powered studies, the heterogeneity in patient selection and study outcomes, and the poor understanding of the underlying mechanisms of action of SCS are some of the limiting factors in the field. Addressing these limitations will allow us to draw more reliable conclusions on the effects of SCS on gait and balance in extrapyramidal disorders.
Topics: Humans; Parkinson Disease; Spinal Cord Stimulation; Quality of Life; Parkinsonian Disorders; Multiple System Atrophy; Gait
PubMed: 37452800
DOI: 10.1016/j.neurom.2023.06.003 -
European Journal of Neurology Dec 2023Alpha-synuclein seed amplification assays (α-syn SAAs) are promising diagnostic methods for Parkinson's disease (PD) and other synucleinopathies. However, there is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND PURPOSE
Alpha-synuclein seed amplification assays (α-syn SAAs) are promising diagnostic methods for Parkinson's disease (PD) and other synucleinopathies. However, there is limited consensus regarding the diagnostic and differential diagnostic performance of α-syn SAAs on biofluids and peripheral tissues.
METHODS
A comprehensive research was performed in PubMed, Web of Science, Embase and Cochrane Library. Meta-analysis was performed using a random-effects model. A network meta-analysis based on an ANOVA model was conducted to compare the relative accuracy of α-syn SAAs with different specimens.
RESULTS
The pooled sensitivity and specificity of α-syn SAAs in distinguishing PD from healthy controls or non-neurodegenerative neurological controls were 0.91 (95% confidence interval [CI] 0.89-0.92) and 0.95 (95% CI 0.94-0.96) for cerebrospinal fluid (CSF); 0.91 (95% CI 0.86-0.94) and 0.92 (95% CI 0.87-0.95) for skin; 0.80 (95% CI 0.66-0.89) and 0.87 (95% CI 0.69-0.96) for submandibular gland; 0.44 (95% CI 0.30-0.59) and 0.92 (95% CI 0.79-0.98) for gastrointestinal tract; 0.79 (95% CI 0.70-0.86) and 0.88 (95% CI 0.77-0.95) for saliva; and 0.51 (95% CI 0.39-0.62) and 0.91 (95% CI 0.84-0.96) for olfactory mucosa (OM). The pooled sensitivity and specificity were 0.91 (95% CI 0.89-0.93) and 0.50 (95% CI 0.44-0.55) for CSF, 0.92 (95% CI 0.83-0.97) and 0.22 (95% CI 0.06-0.48) for skin, and 0.55 (95% CI 0.42-0.68) and 0.50 (95% CI 0.35-0.65) for OM in distinguishing PD from multiple system atrophy. The pooled sensitivity and specificity were 0.92 (95% CI 0.89-0.94) and 0.84 (95% CI 0.73-0.91) for CSF, 0.92 (95% CI 0.83-0.97) and 0.88 (95% CI 0.64-0.99) for skin and 0.63 (95% CI 0.52-0.73) and 0.86 (95% CI 0.64-0.97) for OM in distinguishing PD from progressive supranuclear palsy. The pooled sensitivity and specificity were 0.94 (95% CI 0.90-0.97) and 0.95 (95% CI 0.77-1.00) for CSF and 0.94 (95% CI 0.84-0.99) and 0.86 (95% CI 0.42-1.00) for skin in distinguishing PD from corticobasal degeneration.
CONCLUSIONS
α-Synuclein SAAs of CSF, skin, saliva, submandibular gland, gastrointestinal tract and OM are promising diagnostic assays for PD, with CSF and skin α-syn SAAs demonstrating higher diagnostic performance.
Topics: Humans; Parkinson Disease; alpha-Synuclein; Network Meta-Analysis; Biomarkers; Multiple System Atrophy
PubMed: 37573472
DOI: 10.1111/ene.16041 -
Ageing Research Reviews Jun 2023Autonomic dysfunction and frailty are two common and complex geriatric syndromes. Their prevalence increases with age and they have similar negative health outcomes. In... (Meta-Analysis)
Meta-Analysis Review
Autonomic dysfunction and frailty are two common and complex geriatric syndromes. Their prevalence increases with age and they have similar negative health outcomes. In PubMed and Web of Science we screened studies identifying a relationship between autonomic function (AF) and frailty in adults aged ≥ 65 years. Twenty-two studies of which two prospective and 20 cross-sectional were included (n = 8375). We performed a meta-analysis for the articles addressing orthostatic hypotension (OH). Frailty was associated with 1.6 higher odds of suffering from consensus OH (COH) {OR= 1.607 95%CI [1.15-2.24]; 7 studies; n = 3488}. When measured for each type of OH the largest trend was seen between initial OH (IOH) and frailty {OR= 3.08; 95%CI [1.50-6.36]; 2 studies; n = 497}. Fourteen studies reported other autonomic function alterations in frail older adults with 4-22% reduction in orthostatic heart rate increase, 6% reduction in systolic blood pressure recovery, 9-75% reduction in most common used heart rate variability (HRV) parameters. Frail older adults were more likely to have impaired AF. Diagnosis of frailty should promptly lead to orthostatic testing as OH implicates specific treatment modalities, which differ from frailty management. As IOH is most strongly correlated with frailty, continuous beat to beat blood pressure measurements should be performed when present at least until cut-off values for heart rate variability testing are defined.
Topics: Aged; Humans; Frail Elderly; Frailty; Prospective Studies; Cross-Sectional Studies; Hypotension, Orthostatic
PubMed: 37028604
DOI: 10.1016/j.arr.2023.101925 -
Seminars in Arthritis and Rheumatism Dec 2014Rheumatoid arthritis (RA) is a chronic inflammatory condition with increased all-cause and cardiovascular mortality. Accumulating evidence indicates that the immune and... (Review)
Review
OBJECTIVES
Rheumatoid arthritis (RA) is a chronic inflammatory condition with increased all-cause and cardiovascular mortality. Accumulating evidence indicates that the immune and autonomic nervous systems (ANS) are major contributors to the pathogenesis of cardiovascular disease. We performed the first systematic literature review to determine the prevalence and nature of ANS dysfunction in RA and whether there is a causal relationship between inflammation and ANS function.
METHODS
Electronic databases (MEDLINE, Central and Cochrane Library) were searched for studies of RA patients where autonomic function was assessed.
RESULTS
A total of 40 studies were included. ANS function was assessed by clinical cardiovascular reflex tests (CCTs) (n = 18), heart rate variability (HRV) (n = 15), catecholamines (n = 5), biomarkers of sympathetic activity (n = 5), sympathetic skin responses (n = 5), cardiac baroreflex sensitivity (cBRS) (n = 2) and pupillary light reflexes (n = 2). A prevalence of ~60% (median, range: 20-86%) of ANS dysfunction (defined by abnormal CCTs) in RA was reported in 9 small studies. Overall, 73% of studies (n = 27/37) reported at least one of the following abnormalities in ANS function: parasympathetic dysfunction (n = 20/26, 77%), sympathetic dysfunction (n = 16/30, 53%) or reduced cBRS (n = 1/2, 50%). An association between increased inflammation and ANS dysfunction was found (n = 7/19, 37%), although causal relationships could not be elucidated from the studies available to date.
CONCLUSIONS
ANS dysfunction is prevalent in ~60% of RA patients. The main pattern of dysfunction is impairment of cardiovascular reflexes and altered HRV, indicative of reduced cardiac parasympathetic (strong evidence) activity and elevated cardiac sympathetic activity (limited evidence). The literature to date is underpowered to determine causal relationships between inflammation and ANS dysfunction in RA.
Topics: Adult; Arthritis, Rheumatoid; Autonomic Nervous System; Autonomic Nervous System Diseases; Cardiovascular Diseases; Female; Humans; Immune System; Male; Middle Aged; Prevalence
PubMed: 25151910
DOI: 10.1016/j.semarthrit.2014.06.003 -
Journal of the Neurological Sciences Sep 2016Tetanus is a continued public health neuroinfectious burden in Africa; it accounts for significant proportion of lengthy intensive care unit (ICU) and hospital... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Tetanus is a continued public health neuroinfectious burden in Africa; it accounts for significant proportion of lengthy intensive care unit (ICU) and hospital admissions.
OBJECTIVES
This study aimed to describe the pooled case-fatality rates of adult tetanus at African hospitals along with relevant discussions and recommendations.
METHODS
A systematic review using advanced search strategies employing PubMed/MEDLINE and Web of Science inclusive of gray literature handsearch was conducted for facility-based studies on adult tetanus by combining the terms "tetanus", "Africa" spanning all previous years until January 15, 2016. PRISMA and MOOSE guidelines were followed. Studies from non-African countries and studies on neonatal and childhood tetanus were excluded. A meta-analysis with fixed- and random-effects model was performed to identify pooled migraine prevalence. Inter-study heterogeneity was analyzed employing I Oshinaike et al. (2012) (inconsistency).
RESULTS
Twenty-seven studies involving 3043 patients were included. Median age was 33.7years (IQR 30-36). Median female to male ratio was 0.5. The geographic distribution of the studies was as follows: 15 (55.5%) studies were from Nigeria, 7 (26%) from Ethiopia, and the remaining single-centered studies were from Ghana (1; 3.7%), Uganda (1; 3.7%), Senegal (1; 3.7%), Democratic Republic of Congo (1; 3.7%), and Tanzania (1; 3.7%). The majority (88%) of the studies were from tertiary specialized or teaching university hospital settings.Median duration of the study period was 6.5years (IQR 4-9.25). Pooled crude tetanus case-fatality rate was found to be 43.2% (95% CI 36.9%-49.5%) on random-effects meta-analysis and 45.5% (95% CI 43.7%-47.2%) on fixed-effects meta-analysis. There was considerable inter-study heterogeneity. A time-series observation did not reveal a trend of decreasing case-fatality rates. Leading causes of death were complications from dysautonomia, aspiration pneumonia, hypoxemia, and sepsis (in descending order). Longer incubation period and longer onset time were associated with lower fatality; the further the wound site from the head, the longer the incubation period. Mechanical ventilation was not available in 26% of the studies; where available, mechanical ventilation and ICU admission was not utilized among most of the cases as the patients could not afford ICU care costs.
CONCLUSION
Despite declining tetanus incidence rates, case-fatality is still high in African care facilities. High rates of tetanus case fatality indicate lower quality of medical care at hospital settings.Most common causes of death are complication arising from dysautonomia and respiratory arrest secondary to laryngospasm. These can be prevented by potent medications and mechanical ventilation; where resources are lacking, nursing in darker and quieter rooms have been proven to be efficacious in reducing the frequency of spasms.
Topics: Africa; Databases, Factual; Humans; Mortality; Risk Factors; Tetanus
PubMed: 27538652
DOI: 10.1016/j.jns.2016.07.025 -
Heart Rhythm Mar 2023Vasovagal syncope (VVS) is a transient loss of consciousness that currently imposes a high burden on health care systems with limited evidence of the comparative... (Meta-Analysis)
Meta-Analysis Review
Vasovagal syncope (VVS) is a transient loss of consciousness that currently imposes a high burden on health care systems with limited evidence of the comparative efficacy of available pharmacologic interventions. This study aims to compare all pharmacologic therapies suggested in randomized controlled trials (RCTs) through systematic review and network meta-analysis. A systematic search in PubMed, Embase, Web of Science, and Cochrane Library was conducted to identify RCTs evaluating pharmacologic therapies for patients with VVS. The primary outcome was spontaneous VVS recurrence. The secondary outcome was a positive head-up tilt test (HUTT) after receiving intervention, regarded as a lower level of evidence. Pooled risk ratio (RR) with 95% confidence interval (CI) was calculated using random-effect network meta-analysis. Pairwise meta-analysis for comparison with placebo was also performed when applicable. The surface under the cumulative ranking curve analysis was conducted to rank the treatments for each outcome. Twenty-eight studies with 1744 patients allocated to different medications or placebo were included. Network meta-analysis of the reduction in the primary outcome showed efficacy for midodrine (RR 0.55; 95% CI 0.35-0.85) and fluoxetine (especially in patients with concomitant anxiety) (RR 0.36; 95% CI 0.16-0.84). In addition, midodrine and atomoxetine were superior to other treatment options, considering positive HUTT (RR 0.37; 95% CI 0.23-0.59; and RR 0.49; 95% CI 0.28-0.86, respectively). Overall, midodrine was the only agent shown to reduce spontaneous syncopal events. Fluoxetine also seems to be beneficial but should be studied further in RCTs. Our network meta-analysis did not find evidence of the efficacy of any other medication.
Topics: Humans; Fluoxetine; Midodrine; Syncope, Vasovagal; Network Meta-Analysis; Randomized Controlled Trials as Topic
PubMed: 36509319
DOI: 10.1016/j.hrthm.2022.12.010 -
Clinical Autonomic Research : Official... Aug 2019Diabetic neuropathy is a common and disabling disorder, and there are currently no proven effective disease-modifying treatments. Physical activity and dietary... (Review)
Review
PURPOSE
Diabetic neuropathy is a common and disabling disorder, and there are currently no proven effective disease-modifying treatments. Physical activity and dietary interventions in patients with diabetes and diabetic neuropathy have multiple beneficial effects and are generally low risk, which makes lifestyle interventions an attractive treatment option. We reviewed the literature on the effects of physical activity and dietary interventions on length-dependent peripheral neuropathy and cardiac autonomic neuropathy in diabetes.
METHODS
The electronic database PubMed was systematically searched for original human and mouse model studies examining the effect of either dietary or physical activity interventions in subjects with diabetes, prediabetes, or metabolic syndrome.
RESULTS
Twenty studies are included in this review. Fourteen studies were human studies and six were in mice. Studies were generally small with few controlled trials, and there are no widely agreed upon outcome measures.
CONCLUSIONS
Recent research indicates that dietary interventions are effective in modifying diabetic neuropathy in animal models, and there are promising data that they may also ameliorate diabetic neuropathy in humans. It has been known for some time that lifestyle interventions can prevent the development of diabetic neuropathy in type 2 diabetes mellitus subjects. However, there is emerging evidence that lifestyle interventions are effective in individuals with established diabetic neuropathy. In addition to the observed clinical value of lifestyle interventions, there is emerging evidence of effects on biochemical pathways that improve muscle function and affect other organ systems, including the peripheral nerve. However, data from randomized controlled trials are needed.
Topics: Animals; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Diet, Healthy; Exercise; Humans; Overweight; Risk Reduction Behavior
PubMed: 31076938
DOI: 10.1007/s10286-019-00607-x -
Biomedical Engineering Online Mar 2022Mental illness represents a major global burden of disease worldwide. It has been hypothesised that individuals with mental illness have greater blood pressure... (Review)
Review
BACKGROUND
Mental illness represents a major global burden of disease worldwide. It has been hypothesised that individuals with mental illness have greater blood pressure fluctuations that lead to increased cardiovascular risk and target organ damage. This systematic review aims to (i) investigate the association between mental illness and blood pressure variability (BPV) and (ii) describe methods of BPV measurements and analysis which may affect pattern and degree of variability.
METHODS
Four electronic databases were searched from inception until 2020. The quality assessment was performed using STROBE criteria. Studies were included if they investigated BPV (including either frequency or time domain analysis) in individuals with mental illness (particularly anxiety/generalised anxiety disorder, depression/major depressive disorder, panic disorder and hostility) and without hypertension. Two authors independently screened titles, abstracts and full texts. A third author resolved any disagreements.
RESULTS
Twelve studies met the inclusion criteria. Three studies measured short-term BPV, two measured long-term BPV and seven measured ultra-short-term BPV. All studies related to short-term BPV using ambulatory and home blood pressure monitoring found a higher BPV in individuals with depression or panic disorder. The two studies measuring long-term BPV were limited to the older population and found mixed results. Mental illness is significantly associated with an increased BPV in younger and middle-aged adults. All studies of ultra-short-term BPV using standard cardiac autonomic assessment; non-invasive continuous finger blood pressure and heart rate signals found significant association between BPV and mental illness. A mixed result related to degree of tilt during tilt assessment and between controlled and spontaneous breathing were observed in patients with psychological state.
CONCLUSIONS
Current review found that people with mental illness is significantly associated with an increased BPV regardless of age. Since mental illness can contribute to the deterioration of autonomic function (HRV, BPV), early therapeutic intervention in mental illness may prevent diseases associated with autonomic dysregulation and reduce the likelihood of negative cardiac outcomes. Therefore, these findings may have important implications for patients' future physical health and well-being, highlighting the need for comprehensive cardiovascular risk reduction.
Topics: Adult; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Depressive Disorder, Major; Humans; Hypertension; Mental Disorders; Middle Aged
PubMed: 35313918
DOI: 10.1186/s12938-022-00985-w -
Frontiers in Neuroscience 2019Autonomic dysfunctions may precede the development of cognitive impairment, but the connection between these dimensions is unclear. This systematic review aims to... (Review)
Review
Autonomic dysfunctions may precede the development of cognitive impairment, but the connection between these dimensions is unclear. This systematic review aims to analyze the relationship between heart rate variability (HRV) and cognitive functions. The review process was conducted according to the PRISMA-Statement. Restrictions were made, selecting the studies in English and published in peer-review journals, including at least one cognitive measure and presenting the measurement of HRV. Studies that included participants with medical conditions, dementia, psychiatric disorders, strokes, and traumatic brain injury were excluded. Twenty studies were selected, with a total of 19,431 participants. The results were divided into different cognitive domains determined : global cognitive functioning, attention, processing speed, executive functions, memory, language and visuospatial skills. Both increased sympathetic activity and decreased parasympathetic activity seem to be associated with a worse performance in the cognitive domains considered, in the absence of dementia and severe cardiovascular diseases or other medical and psychiatric diseases. The results highlight the influence of the autonomic nervous system (ANS) in cognitive functioning. However, the marked interest facing toward a specific domain, i.e., the executive functions, and the relatively small number of the studies on this topic do not allow understanding better this relationship. Despite these limits, HRV could be considered a promising early biomarker of cognitive impairment in populations without dementia or stroke. This index should be evaluated within a preventative perspective to minimize the risk of developing cognitive impairment.
PubMed: 31354419
DOI: 10.3389/fnins.2019.00710 -
Frontiers in Immunology 2024Recent evidence supports the contribution of gut microbiota dysbiosis to the pathophysiology of rheumatic diseases, neuropathic pain, and neurodegenerative disorders.... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Recent evidence supports the contribution of gut microbiota dysbiosis to the pathophysiology of rheumatic diseases, neuropathic pain, and neurodegenerative disorders. The bidirectional gut-brain communication network and the occurrence of chronic pain both involve contributions of the autonomic nervous system and the hypothalamic pituitary adrenal axis. Nevertheless, the current understanding of the association between gut microbiota and chronic pain is still not clear. Therefore, the aim of this study is to systematically evaluate the existing knowledge about gut microbiota alterations in chronic pain conditions.
METHODS
Four databases were consulted for this systematic literature review: PubMed, Web of Science, Scopus, and Embase. The Newcastle-Ottawa Scale was used to assess the risk of bias. The study protocol was prospectively registered at the International prospective register of systematic reviews (PROSPERO, CRD42023430115). Alpha-diversity, β-diversity, and relative abundance at different taxonomic levels were summarized qualitatively, and quantitatively if possible.
RESULTS
The initial database search identified a total of 3544 unique studies, of which 21 studies were eventually included in the systematic review and 11 in the meta-analysis. Decreases in alpha-diversity were revealed in chronic pain patients compared to controls for several metrics: observed species (SMD= -0.201, 95% CI from -0.04 to -0.36, p=0.01), Shannon index (SMD= -0.27, 95% CI from -0.11 to -0.43, p<0.001), and faith phylogenetic diversity (SMD -0.35, 95% CI from -0.08 to -0.61, p=0.01). Inconsistent results were revealed for beta-diversity. A decrease in the relative abundance of the Lachnospiraceae family, genus and , and species of and , as well as an increase in spp., was revealed in chronic pain patients compared to controls.
DISCUSSION
Indications for gut microbiota dysbiosis were revealed in chronic pain patients, with non-specific disease alterations of microbes.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42023430115.
Topics: Humans; Chronic Pain; Dysbiosis; Hypothalamo-Hypophyseal System; Phylogeny; Pituitary-Adrenal System; Clostridiales
PubMed: 38352865
DOI: 10.3389/fimmu.2024.1342833