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Pain Physician Nov 2022Complex Regional Pain Syndrome (CRPS) is a chronic debilitating neuropathic pain condition characterized by autonomic and inflammatory features that typically occurs... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Complex Regional Pain Syndrome (CRPS) is a chronic debilitating neuropathic pain condition characterized by autonomic and inflammatory features that typically occurs after a traumatic event. Spinal cord stimulation (SCS) has been shown to be effective in the treatment of chronic CRPS refractory to conventional treatment modalities. The collective evidence of novel parameters of SCS for treating CRPS has not been characterized extensively.
OBJECTIVE
To provide evidence for the use of SCS to treat CRPS and characterize the additional benefits of various SCS waveforms.
STUDY DESIGN
Systematic Review and Meta-analysis.
METHODS
PubMed, Embase and CINHLA were screened for all randomized controlled trials (RCT) comparing SCS parameters for the treatment of CRPS.
RESULTS
Four RCTs were identified that included SCS as a treatment arm for CRPS. Of these, one study compared low frequency tonic SCS (LF-SCS) versus conventional physical therapy, 2 studies compared placebo/sham SCS with LF-SCS and a multitude of waveforms, and one study compared LF-SCS with high-frequency SCS (HF-SCS). Two of the studies were rated as having a low risk of bias, one study was rated as having some concerns for bias, while the final study was rated as having a high risk of bias. A meta-analysis of 4 studies comparing conventional therapy/placebo SCS stimulation against LF-SCS revealed increased benefit of LF-SCS in pain reduction up to a month (mean difference [MD] = -1.17 points; 95% CI = -1.61 to -0.73; P < 0.001, I2 = 42%). Another meta-analysis of 2 studies showed that LF-SCS results in higher global perceived effect scores relative to conventional therapy/placebo SCS stimulation (MD = 1.58; 95% CI = 1.00 to 2.15; P < 0.001, I2 = 0%).
LIMITATIONS
A pooled analysis using different designs for RCTs was conducted. Some studies folded in multiple neuropathic pain pathologies in addition to CRPS. One study was at a high risk for bias in at least one domain.
CONCLUSION
LF-SCS is superior to conventional therapy/placebo SCS stimulation. However, more evidence is required to demonstrate that novel SCS parameters are superior to LF-SCS in improving pain scores and functional outcomes.
Topics: Humans; Spinal Cord Stimulation; Randomized Controlled Trials as Topic; Complex Regional Pain Syndromes; Pain Measurement; Neuralgia; Spinal Cord; Treatment Outcome
PubMed: 36375180
DOI: No ID Found -
European Journal of Psychotraumatology 2022Neurophysiological models link dissociation (e.g. feeling detached during or after a traumatic event) to hypoarousal. It is currently assumed that the initial passive... (Review)
Review
Trauma-related dissociation and the autonomic nervous system: a systematic literature review of psychophysiological correlates of dissociative experiencing in PTSD patients.
Neurophysiological models link dissociation (e.g. feeling detached during or after a traumatic event) to hypoarousal. It is currently assumed that the initial passive reaction to a threat may coincide with a blunted autonomic response, which constitutes the dissociative subtype of post-traumatic stress disorder (PTSD). Within this systematic review we summarize research which evaluates autonomic nervous system activation (e.g. heart rate, blood pressure) and dissociation in PTSD patients to discern the validity of current neurophysiological models of trauma-related hypoarousal. Of 553 screened articles, 28 studies ( = 1300 subjects) investigating the physiological response to stress provocation or trauma-related interventions were included in the final analysis. No clear trend exists across all measured physiological markers in trauma-related dissociation. Extracted results are inconsistent, in part due to high heterogeneity in experimental methodology. The current review is unable to provide robust evidence that peri- and post-traumatic dissociation are associated with hypoarousal, questioning the validity of distinct psychophysiological profiles in PTSD.
Topics: Humans; Stress Disorders, Post-Traumatic; Dissociative Disorders; Autonomic Nervous System; Heart Rate; Psychophysiology
PubMed: 36340007
DOI: 10.1080/20008066.2022.2132599 -
Neuroscience and Biobehavioral Reviews Dec 2022Childhood adversity (CA) is associated with increased risk for physical and mental health problems, with alterations in vagal regulation (an aspect of autonomic... (Meta-Analysis)
Meta-Analysis Review
Childhood adversity (CA) is associated with increased risk for physical and mental health problems, with alterations in vagal regulation (an aspect of autonomic functioning indexed by vagally-mediated heart rate variability [vmHRV]) implicated as a mechanism. Three-level meta-analyses were conducted to synthesize research on the relationship between CA and 1) baseline vagal activity, and 2) vagal reactivity to challenges including stress tests, emotion-eliciting tasks and cognitive tasks. No significant overall association was found between CA and vagal activity (r = -.015; p = .11) or vagal reactivity (r = -.017; p = .13). However, analyses controlling for moderator interrelatedness revealed an association between CA and lower baseline vagal activity in samples including participants diagnosed with a psychiatric disorder, and for direct adversities such as maltreatment. For vagal reactivity, CA was associated with lower reactivity if the adversity was experienced less recently, and for studies operationalizing reactivity using task mean levels of vmHRV. These findings indicate that small alterations in vagal functioning occur for specific CA subtypes and subgroups of individuals.
Topics: Humans; Adverse Childhood Experiences; Vagus Nerve; Heart Rate; Mental Disorders
PubMed: 36272580
DOI: 10.1016/j.neubiorev.2022.104920 -
International Journal of Environmental... Sep 2022At present, ambient air pollution poses a significant threat to patients with cardiovascular disease (CVD). The heart rate variability (HRV) is a marker of the cardiac... (Meta-Analysis)
Meta-Analysis
At present, ambient air pollution poses a significant threat to patients with cardiovascular disease (CVD). The heart rate variability (HRV) is a marker of the cardiac autonomic nervous system, and it is related to air pollution and cardiovascular disease. There is, however, considerable disagreement in the literature regarding the association between ozone (O) and HRV. To further investigate the effects of short-term exposure to O on HRV, we conducted the first meta-analysis of relevant studies. The percentage change of HRV indicator(s) is the effect estimate extracted for the quantitative analysis in this study. In our meta-analysis, per 10 ppb increase in O was significantly associated with decreases in the time-domain measurements, for standard deviation of the normal-to-normal (NN) interval (SDNN) -1.11% (95%CI: -1.35%, -0.87%) and for root mean square of successive differences (RMSSD) -3.26% (95%CI: -5.42%, -1.09%); in the frequency-domain measurements, for high frequency (HF) -3.01% (95%CI: -4.66%, -1.35%) and for low frequency (LF) -2.14% (95%CI: -3.83%, -0.45%). This study showed short-term exposure to O was associated with reduced HRV indicators in adults, which suggested that the cardiac autonomic nervous system might be affected after O exposure, contributing to the association between O exposure and CVD risk.
Topics: Adult; Air Pollutants; Air Pollution; Cardiovascular Diseases; Heart Rate; Humans; Ozone
PubMed: 36141453
DOI: 10.3390/ijerph191811186 -
European Journal of Pain (London,... Nov 2022To conduct a systematic review to identify which tools are being used to assess body perception disturbances in Complex Regional Pain Syndrome (CRPS) and to provide an... (Review)
Review
OBJECTIVE
To conduct a systematic review to identify which tools are being used to assess body perception disturbances in Complex Regional Pain Syndrome (CRPS) and to provide an evidence-based recommendation in the selection of an assessment tool, based on measurement properties.
DATABASES AND DATA TREATMENT
Five electronic databases (EMBASE, Pubmed, PsycInfo, Science Direct and Web of Science) were searched for English or French written articles, with no time restrictions. All original articles using a body perception assessment tool with adult patients with CRPS were selected, regardless of their design (controlled trials, single case, qualitative study). Two investigators screened abstracts, selected full articles and extracted data independently.
RESULTS
Thirty-eight full-text papers were obtained and three main methods to evaluate body perception disturbances were identified: The Bath Body Perception Disturbance Scale, the Neglect-like Symptoms questionnaire adapted from Galer and the patient's body perception description. No full psychometric assessments were found. The Limb Laterality Recognition Task was also used in conjunction with another method.
CONCLUSIONS
Three main assessment methods for CRPS body perception disturbances are currently used. Full psychometric evaluation has not been completed for any of the assessment methods. As a consequence, we could not fully apply the COSMIN guideline. To date, there is no agreement concerning the use of a specific questionnaire or scale. The results indicate a need for further research such as psychometric properties of these questionnaires.
SIGNIFICANCE
This systematic review identified body perception disturbances assessment methods and their the psychometric properties in order to provide help and guidance to researchers and clinicians to investigate those clinical features.
Topics: Adult; Complex Regional Pain Syndromes; Humans; Illusions; Psychometrics; Qualitative Research; Surveys and Questionnaires
PubMed: 36065635
DOI: 10.1002/ejp.2032 -
European Journal of Pain (London,... Nov 2022The pathophysiology of complex regional pain syndrome (CRPS) is multifactorial, with an exaggerated inflammatory response being the most prominent. Treatment for CRPS is... (Review)
Review
BACKGROUND AND OBJECTIVE
The pathophysiology of complex regional pain syndrome (CRPS) is multifactorial, with an exaggerated inflammatory response being the most prominent. Treatment for CRPS is carried out according to the presenting pathophysiological mechanism. Anti-inflammatory treatment with glucocorticoids is therefore an option. The aim of this study was to systematically review the efficacy of glucocorticoids in CRPS.
DATABASES AND DATA TREATMENT
Embase, Medline, Web of Science and Google Scholar were systematically searched for articles focusing on glucocorticoid treatment and CRPS. Screening based on title and abstract was followed by full-text reading (including reference lists) to determine the final set of relevant articles. Bias was assessed using the revised Cochrane risk-of-bias-tool for randomized trials (Rob2).
RESULTS
Forty-one studies were included, which reported on 1208 CRPS patients. A wide variety of glucocorticoid administration strategies were applied, with oral being the most frequently chosen. Additionally, researchers found great heterogeneity in outcome parameters, including clinical symptoms, pain relief and range of motion. The use of glucocorticoids caused an improvement of parameters in all but two studies. In particular, improvement in pain relief and range of motion were reported. Using glucocorticoids in CRPS of longer duration (i.e. more than 3 months) appears to be less effective.
CONCLUSION
Based on the present review, there is evidence to support glucocorticoid treatment in CRPS. However, the ideal administration route and dose remain unclear. We therefore recommend future research via an intervention study, as well as studies on the aetiological mechanisms and corresponding optimal treatment because CRPS pathogenesis is only partially understood.
SIGNIFICANCE
Several studies point towards CRPS being an inflammatory response after tissue or nerve damage, with higher levels of pro-inflammatory cytokines in serum, plasma, cerebrospinal fluid and artificial skin blisters. Inflammation provides a possible role for glucocorticoids in treating CRPS. This systematic review provides a structured overview of glucocorticoid treatment in patients with CRPS. Improvement in pain and range of motion is shown. Systematic review registration number: PROSPERO-CRD42020144671.
Topics: Anti-Inflammatory Agents; Complex Regional Pain Syndromes; Cytokines; Glucocorticoids; Humans; Pain
PubMed: 35983980
DOI: 10.1002/ejp.2025 -
Frontiers in Aging Neuroscience 2022Aging is the biggest risk factor for developing Parkinson's disease (PD), the second most common neurodegenerative disorder. Several animal models have been developed to...
Aging is the biggest risk factor for developing Parkinson's disease (PD), the second most common neurodegenerative disorder. Several animal models have been developed to explore the pathophysiology underlying neurodegeneration and the initiation and spread of alpha-synuclein-related PD pathology, and to investigate biomarkers and therapeutic strategies. However, bench-to-bedside translation of preclinical findings remains suboptimal and successful disease-modifying treatments remain to be discovered. Despite aging being the main risk factor for developing idiopathic PD, most studies employ young animals in their experimental set-up, hereby ignoring age-related cellular and molecular mechanisms at play. Consequently, studies in young animals may not be an accurate reflection of human PD, limiting translational outcomes. Recently, it has been shown that aged animals in PD research demonstrate a higher susceptibility to developing pathology and neurodegeneration, and present with a more disseminated and accelerated disease course, compared to young animals. Here we review recent advances in the investigation of the role of aging in preclinical PD research, including challenges related to aged animal models that are limiting widespread use. Overall, current findings indicate that the use of aged animals may be required to account for age-related interactions in PD pathophysiology. Thus, although the use of older animals has disadvantages, a model that better represents clinical disease within the elderly would be more beneficial in the long run, as it will increase translational value and minimize the risk of therapies failing during clinical studies. Furthermore, we provide recommendations to manage the challenges related to aged animal models.
PubMed: 35966779
DOI: 10.3389/fnagi.2022.909273 -
Journal of Gastroenterology and... Sep 2022Hypermobile Ehlers-Danlos syndrome (hEDS) and the hypermobility spectrum disorders (HSD) can be challenging to diagnose and manage. Gastrointestinal symptoms and... (Review)
Review
BACKGROUND AND AIM
Hypermobile Ehlers-Danlos syndrome (hEDS) and the hypermobility spectrum disorders (HSD) can be challenging to diagnose and manage. Gastrointestinal symptoms and disorders of gut-brain interaction are common in this cohort and multifactorial in origin. The primary aim of this review is to arm the gastroenterologist with a clinically useful understanding of HSD/hEDS, by exploring the association of gastrointestinal disorders with HSD/hEDS, highlighting current pathophysiological understanding and providing a pragmatic approach to managing these patients.
METHODS
Literature relevant to the gastrointestinal system and hypermobile Ehlers-Danlos syndrome was systematically searched, critically appraised, and summarized.
RESULTS
Diagnosis is based upon clinical criteria and a genetic basis is yet to be defined. The prevalence of many gut symptoms, including abdominal pain (69% vs 27%, P < 0.0001), postprandial fullness (34% vs 16%, P = 0.01), constipation (73% vs 16%, P < 0.001), and diarrhea (47% vs 9%, P < 0.001) are significantly higher in HSD/hEDS compared with non-HSD/hEDS individuals. Disorders of gut-brain interaction are also common, particularly functional dyspepsia. The pathophysiology of gut symptoms is poorly understood but may involve effects of connective tissue laxity and its functional consequences, and the influence of autonomic dysfunction, medication and comorbid mental health disorders. Awareness is the key to early diagnosis. Management is limited in evidence-base but ideally should include an integrated multidisciplinary approach.
CONCLUSIONS
HSD/hEDS is a multisystemic disorder in which gastrointestinal symptoms, particularly related to disorders of gut-brain interaction are common. Deficiencies in knowledge regarding the pathophysiological processes limit evidence-based interventions and remain important areas for future research.
Topics: Ehlers-Danlos Syndrome; Gastroenterologists; Gastrointestinal Diseases; Humans; Joint Instability
PubMed: 35750466
DOI: 10.1111/jgh.15927 -
Clinical Autonomic Research : Official... Jun 2022Orthostatic syncope (transient loss of conscious when standing-fainting) is common and negatively impacts quality of life. Many patients with syncope report experiencing... (Review)
Review
BACKGROUND
Orthostatic syncope (transient loss of conscious when standing-fainting) is common and negatively impacts quality of life. Many patients with syncope report experiencing fatigue, sometimes with "brain fog", which may further impact their quality of life, but the incidence and severity of fatigue in patients with syncope remain unclear. In this systematic review, we report evidence on the associations between fatigue and conditions of orthostatic syncope.
METHODS
We performed a comprehensive literature search of four academic databases to identify articles that evaluated the association between orthostatic syncope [postural orthostatic tachycardia syndrome (POTS), vasovagal syncope (VVS), orthostatic hypotension (OH)] and fatigue. Studies were independently screened using a multi-stage approach by two researchers to maintain consistency and limit bias.
RESULTS
Our initial search identified 2797 articles, of which 13 met our inclusion criteria (POTS n = 10; VVS n = 1; OH n = 1; VVS and POTS n = 1). Fatigue scores were significantly higher in patients with orthostatic syncope than healthy controls, and were particularly severe in those with POTS. Fatigue associated with orthostatic syncope disorders spanned multiple domains, with each dimension contributing equally to increased fatigue. "Brain fog" was an important symptom of POTS, negatively affecting productivity and cognition. Finally, fatigue was negatively associated with mental health in patients with POTS.
CONCLUSION
In conditions of orthostatic syncope, fatigue is prevalent and debilitating, especially in patients with POTS. The consideration of fatigue in patients with orthostatic disorders is essential to improve diagnosis and management of symptoms, thus improving quality of life for affected individuals.
Topics: Fatigue; Humans; Hypotension, Orthostatic; Postural Orthostatic Tachycardia Syndrome; Quality of Life; Syncope; Syncope, Vasovagal; Tilt-Table Test
PubMed: 35689118
DOI: 10.1007/s10286-022-00868-z -
PloS One 2022Hypothyroidism may be associated with changes in the autonomic regulation of the cardiovascular system, which may have clinical implications. (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Hypothyroidism may be associated with changes in the autonomic regulation of the cardiovascular system, which may have clinical implications.
OBJECTIVE
To conduct a systematic review and meta-analysis on the impact of hypothyroidism on HRV.
MATERIALS AND METHODS
PubMed, Cochrane, Embase and Google Scholar were searched until 20 August 2021 for articles reporting HRV parameters in untreated hypothyroidism and healthy controls. Random-effects meta-analysis were stratified by degree of hypothyroidism for each HRV parameters: RR intervals (or normal to normal-NN intervals), SDNN (standard deviation of RR intervals), RMSSD (square root of the mean difference of successive RR intervals), pNN50 (percentage of RR intervals with >50ms variation), total power (TP), LFnu (low-frequency normalized unit), HFnu (high-frequency), VLF (very low frequency), and LF/HF ratio.
RESULTS
We included 17 studies with 11438 patients: 1163 hypothyroid patients and 10275 healthy controls. There was a decrease in SDNN (effect size = -1.27, 95% CI -1.72 to -0.83), RMSSD (-1.66, -2.32 to -1.00), pNN50 (-1.41, -1.98 to -0.84), TP (-1.55, -2.1 to -1.00), HFnu (-1.21, -1.78 to -0.63) with an increase in LFnu (1.14, 0.63 to 1.66) and LF/HF ratio (1.26, 0.71 to 1.81) (p <0.001). HRV alteration increased with severity of hypothyroidism.
CONCLUSIONS
Hypothyroidism is associated with a decreased HRV, that may be explained by molecular mechanisms involving catecholamines and by the effect of TSH on HRV. The increased sympathetic and decreased parasympathetic activity may have clinical implications.
Topics: Autonomic Nervous System; Cardiovascular System; Heart Rate; Humans; Hypothyroidism
PubMed: 35657799
DOI: 10.1371/journal.pone.0269277