Do manual therapies have a specific autonomic effect? An overview of systematic reviews

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

An investigation into central nervous system involvement in distal symmetrical diabetic neuropathy in type 1 diabetes mellitus.

Diabetes is a leading cause of peripheral neuropathy. It is the main initiating factor for foot ulceration and amputation resulting in considerable morbidity and remarkable consumption of scarce medical resources. Relatively little is known about the pathophysiology underlying DPN. Research into DPN has focused mainly on the peripheral nervous system (PNS) with central nervous system (CNS) involvement relatively overlooked. The studies undertaken have been designed to investigate CNS involvement in DPN. 1. Before embarking on spinal cord studies, I reviewed and modified the techniques employed in the pilot study to improve the precision and accuracy of cord cross sectional area measurements. These modifications were patiented to quality control studies, which are reported in Chapter 2. 2. I performed in-vivo cross-sectional magnetic resonance imaging of the cervical spine and reported evidence of spinal cord shrinkage (atrophy) in Painless DPN (Chapter 3). This study showed spinal cord atrophy to be an early phenomenon, present even in subclinical DPN. As the spinal cord is the caudal portion of the CNS, its involvement made us question whether the brain too may be involved. 3. Using MR spectroscopy I examined thalamic involvement in Painless DPN (Chapter 4). This deep brain nucleus is considered the gateway to all somatosensory information entering the brain, and responsible for modulation of sensory information prior to presentation to the cerebral cortex. I demonstrated thalamic biochemical abnormalities consistent with possible neuronal dysfunction in patients with Painless DPN. 4. The demonstration of thalamic neuronal dysfunction in DPN suggests that CNS involvement is not limited to the spinal cord but other important areas, responsible for somatosensory perception, may also be involved. Although the pathogenesis of thalamic involvement is unknown, it is likely that both vascular and metabolic factors that have been implicated in the pathogenesis of DPN are involved. In Chapter 4, I examined the possible role of metabolic factors in the pathogenesis of thalamic neuronal dysfunction in DPN. Using MR spectroscopy, I demonstrated a significant elevation in thalamic glutamine/glutamate in patients with diabetes. Glutamate is the most abundant excitatory neurotransmitter and implicated in various models of neuronal cell death. Astrocytes, which play an important role in glutamate/glutamine metabolism, were impaired in the thalamus of diabetic patients in this study. The combination of elevated glutamate and impaired thalamic astrocytes may provide a pathophysiological explanation for thalamic dysfunction in DPN. 5. In Chapter 5, an alternative hypothesis for thalamic neuronal dysfunction in DPN was tested. Using dynamic contrast enhanced MR perfusion imaging, I demonstrated that Painful DPN is associated with unique thalamic perfusion abnormalities. Intriguingly, these abnormalities were present in patients with Painful but not Painless DPN. 6. Finally, in Chapter 6, I conducted a randomised, double blind and placebo-control trial (RCT) comparing the efficacy and tolerability of sativex, a cannabis based medicinal extract (CBME), with placebo in the symptomatic treatment of painful DPN. This is the first ever RCT using a CBME in painful DPN. We report no significant difference in the primary outcome measure due to a massive placebo effect and that depression is a potential major confounder in such clinical trials

Indicators of stress in equitation

Stress is a generic concept describing the body’s reaction to external stimuli, including both physiological and psychological factors. Therefore, by definition, the assessment of psychological stress in the exercising horse encompasses the problem of teasing apart the psychological and physiological factors both of which result in stress responses. The present study reviews the existing literature on various measures of stress taken specifically in the context of equitation science. Particular attention has been paid to short-term effects, and commonly used measurements of short-term stress include heart rate, a number of heart rate variability parameters, blood or saliva cortisol levels, eye temperature, and various behaviour parameters including in particular behaviour patterns presumably indicative of conflict with the rider’s/trainer’s aids. Inspection of the individual studies’ results revealed that disagreement between these different measures of stress is commonplace. For physiological parameters, the largest proportion of agreement (i.e. both parameters simultaneously indicated either higher, insignificant or lower stress compared to a control treatment) was found for heart rate and heart rate variability parameters, while generally limited agreement was found for cortisol. It appears that cortisol levels may not be particularly useful for assessing/assessment of the valence of a situation in the exercising horse as cortisol levels are predominantly linked to activation and exercise levels. Although heart rate variability parameters reflect in theory more closely sympathovagal balance compared to cortisol levels, great care has to be taken regarding the use of appropriate time-frames, appropriate raw data correction methods as well as the use of appropriate equipment. In spite of its wide-spread and apparently successful use, popular equipment may in fact not be accurate enough under field conditions. Eye temperature is another promising parameter for assessment of psychological stress, but the technique is likewise susceptible to application errors. Given the high susceptibility of physiological parameters to errors at various experimental stages, behavioural rather than physiological parameters may in fact provide more accurate measures of valence when conducting experiments in the exercising horse. Behavioural parameters that appear to be particularly practical in assessing stress in ridden horses’ behaviour are associated with frequencies of behaviour indicative of conflict. However, while increased frequencies of are a good indicator of stress, the absence of conflict behaviour does not provide proof of the absence of stress due to the possible occurrence of conditions such as Learned Helplessness. In future studies, the above issues should be taken into consideration when designing experiments to assess psychological stress in ridden horses

Tools for Assessing Neuropathic Pain

Giorgio Cruccu and Andrea Truini discuss a new pain assessment tool published in PLoS Medicine called Standardized Evaluation of Pain and they review other tools to assess neuropathic pain

Vagus nerve stimulation as a novel treatment for systemic lupus erythematous:study protocol for a randomised, parallel-group, sham-controlled investigator-initiated clinical trial, the SLE-VNS study

INTRODUCTION: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. SLE is treated with immunosuppressants with suboptimal efficacy and high risk of serious side effects. Patients with SLE have increased risk of mortality, organ damage and debilitating treatment-resistant fatigue. Autonomic nervous system dysfunction (AD) is present in approximately half of the patients and may promote autoimmunity by weakening the vagally mediated anti-inflammatory reflex. Recent studies suggest that transcutaneous vagus nerve stimulation (tVNS) has few side effects and beneficial effects on fatigue, pain, disease activity and organ function. This study investigates whether adjuvant tVNS improves measures of fatigue (primary end point), AD, clinical disease activity, inflammation, pain, organ function and quality of life. Hence, this study will contribute to the understanding of AD as a potentially important precursor of fatigue, disease activity, progression and complications in SLE, and how tVNS mechanistically may attenuate this. As adjuvant tVNS use may reduce the need for traditional immunosuppressive therapy, this trial may prompt a shift in the treatment of SLE and potentially other autoimmune disorders. METHODS AND ANALYSIS: Eighty-four patients with SLE with fatigue and AD will be randomised 1:1 to active or sham tVNS in this double-blinded parallel-group study. In period 1 (1 week), participants will receive a 4 min tVNS 4 times daily and report on fatigue daily. After a 2-week pause, period 2 (8 weeks) will entail tVNS twice daily and participants will report on fatigue, pain and disease activity weekly. Secondary end points will be assessed before and after each period and after 1 week in period 2. ETHICS AND DISSEMINATION: The study is approved by the Danish Medical Research Ethical Committees (case no: 2120231) and results will be published in international peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05315739

Quantifying training load and its relationship to heart rate recovery

Includes bibliographical references (p. 197-218).Scientific research is playing an increasingly important role in the development of optimal exercise training programmes that meet specific goals within specified times. Improving the accuracy of training prescription first involves quantifying what the athlete is currently doing. Secondly, it needs to be established whether or not the athlete is adapting favourably to the training programme. This thesis investigated current methods of quantifying training load, and proposed the use of heart rate recovery to monitor the physiological response to training. The quantification of exercise training may involve athletes self-reporting their exercise

On the use of contralateral auditory suppression of transient evoked oto-acoustic emissions and heart rate variability to establish baseline measures for concussion and return to play

Concussion injuries have gained the attention of healthcare providers because of the effects that persistent reoccurring symptoms, associated with the injury, can have on normal functioning. As such, there is a recognized need to establish appropriate pre-injury measurements of individuals at risk for concussion so that healthcare providers can establish a more accurate diagnosis, management and treatment post concussion. The purpose of the present study was to assess the stability of heart rate variability (HRV) and contralateral auditory suppression of transient evoked oto-acoustic emissions (CAS TEOAE) as objective measures for the assessment of concussion. The study was conducted in three phases: 1) to assess the stability of the methodologies related to measuring (n=25); 2) to determine the relationship between the clinical measures (HRV & CAS TEOAE) with psychological measures (n=75) (DASS-21 and PASS-20); 3)to assess to response profile following injury on a case study basis (n=1). A test-retest research design was used to establish the stability of the clinical methods. Twenty-five university-aged individuals were assessed on HRV and CAS TEOAE on two separate occasions. The McNemar chi-square of symmetry was used to establish the measure of difference between day 1 and day 14, while the kappa statistic of agreement was used to assess the measure of agreement between the variables. No significant differences were found between test-retest observations for selected measures of CAS TEOAE (Y1414, Diff14141, X2000, SUM2000) and selected measures of HRV (RMSSD and mean HR). In addition, two variables from each of the HRV test and the CAS TEOAE test showed significant agreement between the test-retest days. As part of phase 2 significant relationships, observed independently between HRV and CAS TEOAE were quantified with subscales of the DASS-21 and PASS-20 in a cohort of university varsity athletes. Relationships with the subscale were established using the Spearman Correlation Coefficient both within the entire sample as well as within the sub-cohorts based on concussion history. The relationships in the total population were not present in those who reported a previous history of concussion, indicating a change in psychological measures and their predictability of HRV. In phase three, the case study of one athlete showed notable decreases in HRV (a condition of injury) and a decrease in CAS TEOAE functioning in the immediate post injury state, with a noted increase in both measures during the recovery phases. These results support the need for further study of HRV and CAS TEOAE as objective measures of concussion

Systemic Manifestations and Health-Related Quality of Life in Joint Hypermobility Syndrome/Ehlers-Danlos Syndrome-Hypermobility Type

Joint Hypermobility Syndrome/Ehlers-Danlos Syndrome-Hypermobility Type (JHS/EDS-HT) is a hereditary connective tissue disorder associated with both musculoskeletal and systemic manifestations. There is increasing recognition of the significance of the non-musculoskeletal manifestations of the disorder, such as fatigue, orthostatic intolerance, gastrointestinal symptoms and psychological features, the presence of which have challenged the historical view of the condition as a “benign” disorder characterised only by musculoskeletal and cutaneous features. The experience of adults affected by JHS/EDS-HT is often defined by delays in the diagnosis of the condition, dissatisfaction with the diagnostic process and symptom management, and the occurrence of a complex array of systemic manifestations associated with the disorder. All of these contribute to a disease morbidity similar to that found in other chronic diseases, significant reduction in overall health-related quality of life (HRQoL) and the progression to functional impairment and disability in some of the adult population affected by the disorder. Over the past three decades, understanding of the disorder has progressed significantly to a point where there is now recognition of the multisystem nature of the condition. There is, however, an ongoing need to further investigate the prevalence, mechanisms and determinants of the systemic manifestations of the condition and the HRQoL experienced by those affected by JHS/EDS-HT. The primary aim of this thesis is to describe the disease profile of JHS/EDS-HT in an adult population, in order to provide future direction for the development of targeted management strategies for adults affected by JHS/EDS-HT. Attention will be focused on investigating the prevalence and significance of non-musculoskeletal features of the disorder and their relationship with the overall HRQoL reported by those affected. The prevalence and factors contributing to the severity of fatigue, psychological manifestations of the condition, and overall HRQoL will be a particular focus of this project. Multiple regression analysis will be used to help further define manifestations of the disorder that are predictive of fatigue severity and HRQoL, in order to inform potential future management strategies for the condition. The aims and objectives of this thesis, a review of the current literature relating to JHS/EDS-HT, and the historical background to the development diagnostic criteria over the past century, are presented in Chapters 1 and 2 of the thesis. To achieve the thesis objectives, two studies were undertaken to investigate the manifestations related to JHS/EDS-HT in an adult population, and specifically to investigate the non-musculoskeletal features of fatigue severity, psychological manifestations of the condition, and overall quality of life experienced by those diagnosed with the JHS/EDS-HT. The investigation of the prevalence, severity and identification of possible predictors of fatigue severity was undertaken as Study 1 and is found in Chapter 3 of this thesis. This study established that significant fatigue was present in 79.5% of participants and was identified as the most prevalent systemic manifestation of the disorder, with the strongest correlation with overall HRQoL of all reported manifestations. This study successfully identified five manifestations contributing to fatigue severity, including four that are potentially modifiable, accounting for 52.3% of the variance in the severity of the fatigue. The modifiable predictors of fatigue severity identified were; current levels of physical activity participation, satisfaction with the diagnostic and management process experienced by individuals, the frequency of reported orthostatic dizziness, and levels of participation in community and personal relationships, in addition to the self- perceived extent of joint hypermobility identified as a non-modifiable feature. The results of this study provide an important evidence base for future research investigating the potential impact of various management strategies targeting these factors identified as contributing to the experience of fatigue in this population. The systemic nature of JHS/EDS-HT and the multitude of manifestations that are associated with the condition have previously been found to be associated with reduced HRQoL in this population. Study 2, which constitutes Chapter 4 of this thesis, aimed to identify the features of JHS/EDS-HT associated with overall HRQoL and to determine if there are modifiable predictors of HRQoL in this population. This study identified three determinants of HRQoL, including; the number of joints affected by pain, the current level of physical activity participation and levels of depressive symptoms reported by participants, together accounting for 54.9% of the variance seen in the reported HRQoL of participants. The results of this study provide future direction for interventional studies undertaken with the aim of improving the overall HRQoL experienced by this population by targeting these modifiable determinants. A summary of the thesis and concluding remarks are presented in Chapter 5. This chapter includes suggestions for future research and clinical interventions in the field of JHS/EDS-HT that have arisen as a result of the 2 included studies