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Movement Disorders : Official Journal... Mar 2022α-synucleinopathies, encompassing Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy, are devastating neurodegenerative diseases for which... (Review)
Review
α-synucleinopathies, encompassing Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy, are devastating neurodegenerative diseases for which available therapeutic options are scarce, mostly because of our limited understanding of their pathophysiology. Although these pathologies are attributed to an intracellular accumulation of the α-synuclein protein in the nervous system with subsequent neuronal loss, the trigger(s) of this accumulation is/are not clearly identified. Among the existing hypotheses, interest in the hypothesis advocating the involvement of infectious agents in the onset of these diseases is renewed. In this article, we aimed to review the ongoing relevant factors favoring and opposing this hypothesis, focusing on (1) the potential antimicrobial role of α-synuclein, (2) potential entry points of pathogens in regard to early symptoms of diverse α-synucleinopathies, (3) pre-existing literature reviews assessing potential associations between infectious agents and Parkinson's disease, (4) original studies assessing these associations for dementia with Lewy bodies and multiple system atrophy (identified through a systematic literature review), and finally (5) potential susceptibility factors modulating the effects of infectious agents on the nervous system. © 2022 International Parkinson and Movement Disorder Society.
Topics: Humans; Lewy Body Disease; Multiple System Atrophy; Parkinson Disease; Synucleinopathies; alpha-Synuclein
PubMed: 35040520
DOI: 10.1002/mds.28925 -
Europace : European Pacing,... Jul 2022Vasovagal syncope (VVS) is a common clinical condition that lacks effective medical therapies despite being associated with significant morbidity. Current guidelines... (Meta-Analysis)
Meta-Analysis
AIMS
Vasovagal syncope (VVS) is a common clinical condition that lacks effective medical therapies despite being associated with significant morbidity. Current guidelines suggest that midodrine, a prodrug for an α1-adrenergic receptor agonist, might suppress VVS but supporting studies have utilized heterogeneous methods and yielded inconsistent results. To evaluate the efficacy of midodrine to prevent syncope in patients with recurrent VVS by conducting a systematic review and meta-analysis of published studies.
METHODS AND RESULTS
Relevant randomized controlled trials were identified from the MEDLINE, Embase, CENTRAL, and CINAHL databases without language restriction from inception to June 2021. All studies were conducted in clinical syncope populations and compared the benefit of midodrine vs. placebo or non-pharmacological standard care. Weighted relative risks (RRs) were estimated using random effects meta-analysis techniques. Seven studies (n = 315) met inclusion criteria. Patients were 33 ± 17 years of age and 31% male. Midodrine was found to substantially reduce the likelihood of positive head-up-tilt (HUT) test outcomes [RR = 0.37 (0.23-0.59), P < 0.001]. In contrast, the pooled results of single- and double-blind clinical trials (I2 = 54%) suggested a more modest benefit from midodrine for the prevention of clinical syncope [RR = 0.51 (0.33-0.79), P = 0.003]. The two rigorous double-blind, randomized, placebo-controlled clinical trials included 179 VVS patients with minimal between-study heterogeneity (I2 = 0%) and reported a risk reduction with midodrine [RR = 0.71 (0.53-0.95), P = 0.02].
CONCLUSIONS
Midodrine is effective in preventing syncope induced by HUT testing and less, but still significant, RR reduction in randomized, double-blinded clinical trials.
Topics: Double-Blind Method; Female; Humans; Male; Midodrine; Randomized Controlled Trials as Topic; Syncope; Syncope, Vasovagal; Tilt-Table Test
PubMed: 35025999
DOI: 10.1093/europace/euab323 -
Nutrients Dec 2021Dysbiosis secondary to environmental factors, including dietary patterns, antibiotics use, pollution exposure, and other lifestyle factors, has been associated to many...
Autonomic Nervous System Neuroanatomical Alterations Could Provoke and Maintain Gastrointestinal Dysbiosis in Autism Spectrum Disorder (ASD): A Novel Microbiome-Host Interaction Mechanistic Hypothesis.
Dysbiosis secondary to environmental factors, including dietary patterns, antibiotics use, pollution exposure, and other lifestyle factors, has been associated to many non-infective chronic inflammatory diseases. Autism spectrum disorder (ASD) is related to maternal inflammation, although there is no conclusive evidence that affected individuals suffer from systemic low-grade inflammation as in many psychological and psychiatric diseases. However, neuro-inflammation and neuro-immune abnormalities are observed within ASD-affected individuals. Rebalancing human gut microbiota to treat disease has been widely investigated with inconclusive and contradictory findings. These observations strongly suggest that the forms of dysbiosis encountered in ASD-affected individuals could also originate from autonomic nervous system (ANS) functioning abnormalities, a common neuro-anatomical alteration underlying ASD. According to this hypothesis, overactivation of the sympathetic branch of the ANS, due to the fact of an ASD-specific parasympathetic activity deficit, induces deregulation of the gut-brain axis, attenuating intestinal immune and osmotic homeostasis. This sets-up a dysbiotic state, that gives rise to immune and osmotic dysregulation, maintaining dysbiosis in a vicious cycle. Here, we explore the mechanisms whereby ANS imbalances could lead to alterations in intestinal microbiome-host interactions that may contribute to the severity of ASD by maintaining the brain-gut axis pathways in a dysregulated state.
Topics: Autism Spectrum Disorder; Autonomic Nervous System; Brain-Gut Axis; Dysbiosis; Gastrointestinal Microbiome; Humans
PubMed: 35010940
DOI: 10.3390/nu14010065 -
Journal of Integrative Neuroscience Dec 2021Parkinson's disease-related pain has increasingly been investigated in research studies. Still, only a few studies have addressed the prevalence and clinical...
Parkinson's disease-related pain has increasingly been investigated in research studies. Still, only a few studies have addressed the prevalence and clinical characteristics of pain in neurodegenerative disorders with atypical parkinsonism. The existing evidence, although scarce, suggests that, similarly as in Parkinson's disease, individuals with neurodegenerative diseases with atypical parkinsonism might be predisposed to the development of persistent pain. Today, as the global population is aging and we face an epidemic of neurodegenerative disorders, under-treated pain is taking a great toll on an ever-rising number of people. Here, we provide an up-to-date review of the current knowledge on the prevalence of pain, its clinical features, and findings from experimental studies that might signpost altered pain processing in the most prevalent neurodegenerative disorders with atypical parkinsonism: multiple system atrophy, progressive supranuclear palsy, corticobasal syndrome, frontotemporal dementia, and dementia with Lewy bodies. Finally, we point out the current gaps and unmet needs that future research studies should focus on. Large-scale, high-quality clinical trials, coupled with pre-clinical research, are urgently needed to reveal the exact pathophysiological mechanisms underpinning heightened pain and pave the path for mechanistically-driven analgesic interventions to be developed, ultimately leading to an improvement in the quality of life of individuals with neurodegenerative disorders.
Topics: Corticobasal Degeneration; Frontotemporal Dementia; Humans; Lewy Body Disease; Multiple System Atrophy; Musculoskeletal Pain; Neuralgia; Prevalence; Supranuclear Palsy, Progressive
PubMed: 34997730
DOI: 10.31083/j.jin2004108 -
Neurological Sciences : Official... Feb 2022Nocebo effect is prevalent among neurological diseases, resulting in low adherence and treatment outcome. We sought to examine the nocebo effect in randomized controlled... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Nocebo effect is prevalent among neurological diseases, resulting in low adherence and treatment outcome. We sought to examine the nocebo effect in randomized controlled trials (RCTs) in multiple system atrophy (MSA).
METHODS
We searched RCTs in MSA from Medline since September, 2021. RCTs for drug treatment conducted in adult MSA patients with more than 5 cases in each treatment arm were included. We assessed the number of dropout due to placebo intolerance. We also did a symptomatic/disease-modifying subgroup analysis based on two different treatment purposes. The STATA software was used for statistical analysis. Overall heterogeneity was assessed using the Cochran Q and I.
RESULTS
Data were extracted from 11 RCTs fulfilling our search criteria. Of 540 placebo-treated patients, 64.2% reported at least one adverse event (AE) and 7.5% reported dropout because of AEs. The chance of dropping out because of an AE and experiencing at least one AE did not differ between placebo and active drug treatment arms. Besides, the pooled nocebo dropout rate in the symptomatic subgroup was similar to that of the disease-modifying subgroup.
CONCLUSION
In MSA RCTs, nocebo dropout rate was not at a low level among neurological disorders. Nocebo effect was an important reason of dropout because of AE in placebo and active drug treatment arms. Different treatment purposes may not influence nocebo effect.
Topics: Humans; MEDLINE; Multiple System Atrophy; Nocebo Effect; Treatment Outcome
PubMed: 34973075
DOI: 10.1007/s10072-021-05758-2 -
Journal of Geriatric Psychiatry and... Sep 2022Orthostatic hypotension (OH) is multifactorial in Parkinson's disease (PD). Antiparkinsonian medication can contribute to OH, leading to increased risk of falls,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Orthostatic hypotension (OH) is multifactorial in Parkinson's disease (PD). Antiparkinsonian medication can contribute to OH, leading to increased risk of falls, weakness and fatigue.
METHODS
We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) of antiparkinsonian drugs associated with OH as an adverse effect, compared to placebo. We searched EMBASE, MEDLINE and Web of Science databases until November 2020. Analysis used fixed-effects models and the GRADE tool to rate quality of evidence. Meta-analysis was performed if 3 or more studies of a drug group were available.
RESULTS
Twenty-one RCTs including 3783 patients were included comparing 6 PD drug groups to placebo (MAO-B inhibitors, dopamine agonists, levodopa, COMT inhibitors, levodopa and adenosine receptor antagonists). OH was recorded as an adverse event or measurement of vital signs, without further specification on how this was defined or operationalised. Meta-analysis was performed for MAO-B inhibitors and dopamine agonists, as there were 3 or more studies for these drug groups. In this analysis, compared with placebo, neither MAO-B inhibitors or dopamine agonists were associated with increased risk of OH, (OR 2.28 [95% CI:0.81-6.46]), (OR 1.39 [95% CI:0.97-1.98]).
CONCLUSIONS
Most studies did not specifically report OH, or reporting of OH was limited, including how and when it was measured. Furthermore, studies specifically reporting OH included participants that were younger than typical PD populations without multimorbidity. Future trials should address this, for example,, by including individuals over the age of 75, to improve estimations of how antiparkinsonian medications affect risk of OH.
Topics: Antiparkinson Agents; Dopamine Agonists; Humans; Hypotension, Orthostatic; Levodopa; Monoamine Oxidase; Parkinson Disease
PubMed: 34964392
DOI: 10.1177/08919887211060017 -
Diagnostics (Basel, Switzerland) Nov 2021Psychological stress is a well-established risk factor for cardiovascular disease (CVD). Heart rate variability (HRV)-biofeedback could significantly reduce stress... (Review)
Review
Psychological stress is a well-established risk factor for cardiovascular disease (CVD). Heart rate variability (HRV)-biofeedback could significantly reduce stress levels and improve autonomic nervous system function and cardiovascular endpoints. We aimed to systematically review the literature to investigate the impact of HRV modulation through HRV-biofeedback on clinical outcomes in patients with CVD. A literature search was performed in the following databases: MEDLINE (PubMed), Embase, and Cochrane from the inception until 1 October 2021. Patients in the HRV-biofeedback group had significantly lower rates of all-cause readmissions than patients who received psychological education (respectively, = 0.028 and = 0.001). Heart failure following HRV-biofeedback displayed an inverse association with stress and depression (respectively, = 0.022 and = 0.033). When stratified according to left ventricular ejection fraction (LVEF), patients with LVEF ≥ 31% showed improved values of the 6 min walk test after HRV-biofeedback interventions ( = 0.05). A reduction in systolic and diastolic blood pressure associated with HRV-biofeedback was observed ( < 0.01) in pre-hypertensive patients. HRV-biofeedback had beneficial effects on different cardiovascular diseases documented in clinical trials, such as arterial hypertension, heart failure, and coronary artery disease. A standard breathing protocol should be applied in future studies to obtain equivalent results and outcomes. However, data regarding mortality in patients with coronary artery disease are scarce and need further research.
PubMed: 34943435
DOI: 10.3390/diagnostics11122198 -
Scientific Reports Dec 2021Surgical removal is the treatment of choice for many neoplasms of the parotid gland. This meta-analysis aimed to evaluate the differences between parotidectomy using a... (Meta-Analysis)
Meta-Analysis
Surgical removal is the treatment of choice for many neoplasms of the parotid gland. This meta-analysis aimed to evaluate the differences between parotidectomy using a modified facelift incision (MFI) and parotidectomy using a modified Blair incision (MBI). A systematic search of the available literature in PubMed, Embase and the Cochrane Library was performed. Studies of adult patients who underwent open parotidectomy with presumed benign parotid neoplasms based on preoperative examinations were reviewed. The surgical outcomes of the MFI and MBI groups were collected. Intraoperative and postoperative parameters, including operative time, tumor size, cosmetic satisfaction, and incidences of facial palsy, Frey's syndrome and salivary complications, were compared. Dichotomous data and continuous data were analyzed by calculating the risk difference (RD) and the mean difference (MD) with the 95% confidence interval (CI), respectively. Seven studies were included in the final analysis. The pooled analysis demonstrated that the cosmetic satisfaction score was significantly higher in the MFI group (MD = 1.66; 95% CI 0.87-2.46). The operative duration in the MFI group was significantly longer than that in the MBI group (MD = 0.07; 95% CI 0.00-0.14). The MFI group exhibited a smaller tumor size (MD = - 2.27; 95% CI - 4.25 to - 0.30) and a lower incidence of Frey's syndrome (RD = - 0.18; 95% CI - 0.27 to - 0.10). The incidence of postoperative temporary facial palsy (RD = - 0.05; 95% CI - 0.12 to 0.03), permanent facial palsy (RD = - 0.01; 95% CI - 0.06 to 0.03) and salivary complications (RD = - 0.00; 95% CI - 0.05 to 0.05) was comparable between the two groups. Based on these results, MFI may be a feasible technique for improving the cosmetic results of patients who need parotidectomy when oncological safety can be ensured.
Topics: Esthetics; Facial Paralysis; Female; Humans; Incidence; Male; Operative Time; Parotid Gland; Parotid Neoplasms; Patient Satisfaction; Postoperative Complications; Plastic Surgery Procedures; Rhytidoplasty; Sweating, Gustatory
PubMed: 34916561
DOI: 10.1038/s41598-021-03483-6 -
Ageing Research Reviews Jan 2022Neurodegenerative diseases, which frequently present with neuropsychiatric symptoms related to prefrontal cortical dysfunction, can alter the integrity of the neural... (Meta-Analysis)
Meta-Analysis Review
Neurodegenerative diseases, which frequently present with neuropsychiatric symptoms related to prefrontal cortical dysfunction, can alter the integrity of the neural networks involved in central autonomic nervous system regulation, which is proposed to be indexed by heart rate variability (HRV). We systematically reviewed the characteristics, methodology and outcomes of 27 studies of HRV in relation to measures of cognition and behavior in neurodegenerative conditions, and assessed the strength of this relationship, cross-sectionally, across 18 studies. A significant, moderate effect was observed (r = 0.25), such that higher HRV was related to better cognitive and behavioral scores, which was not influenced by mean age or cognitive status. There was no evidence of small-study effects but we could not rule out publication bias, and other factors may have contributed to heterogeneity between studies. Our findings support the proposal that HRV may be a marker of self-regulatory processes in neurodegenerative conditions, and further research on this association is needed in relation to neuropsychiatric symptoms and alongside neuroimaging methods.
Topics: Autonomic Nervous System; Cognition; Heart Rate; Humans; Neurodegenerative Diseases; Neuroimaging
PubMed: 34883203
DOI: 10.1016/j.arr.2021.101539 -
PloS One 2021The impact of manual therapy interventions on the autonomic nervous system have been largely assessed, but with heterogeneous findings regarding the direction of these...
BACKGROUND
The impact of manual therapy interventions on the autonomic nervous system have been largely assessed, but with heterogeneous findings regarding the direction of these effects. We conducted an overview of systematic reviews to describe if there is a specific autonomic effect elicited by manual therapy interventions, its relation with the type of technique used and the body region where the intervention was applied.
METHODS
We conducted an overview according to a publicly registered protocol. We searched the Cochrane Database of Systematic Reviews, MEDLINE, EPISTEMONIKOS and SCOPUS, from their inception to march 2021. We included systematic reviews for which the primary aim of the intervention was to assess the autonomic effect elicited by a manual therapy intervention in either healthy or symptomatic individuals. Two authors independently applied the selection criteria, assessed risk of bias from the included reviews and extracted data. An established model of generalisation guided the data analysis and interpretation.
RESULTS
We included 12 reviews (5 rated as low risk of bias according the ROBIS tool). The findings showed that manual therapies may have an effect on both sympathetic and parasympathetic systems. However, the results from included reviews were inconsistent due to differences in their methodological rigour and how the effects were measured. The reviews with a lower risk of bias could not discriminate the effects depending on the body region to which the technique was applied.
CONCLUSION
The magnitude of the specific autonomic effect elicited by manual therapies and its clinical relevance is uncertain. We point out some specific recommendations in order to improve the quality and relevance of future research in this field.
Topics: Autonomic Agents; Autonomic Nervous System Diseases; Databases, Factual; Humans; Musculoskeletal Manipulations; Parasympathetic Nervous System; Sympathetic Nervous System
PubMed: 34855830
DOI: 10.1371/journal.pone.0260642