Transcutaneous auricular branch vagal nerve stimulation as a non-invasive add-on therapeutic approach for pain in systemic sclerosis.

OBJECTIVE: Systemic sclerosis (SSc) is an autoimmune disease with health-related quality of life (HRQoL) high impairment. Pain is of paramount importance to be targeted by therapeutical approaches. Our study aim was to perform an add-on device-based non-invasive neuromodulatory treatment through transcutaneous auricular vagal nerve stimulation (tVNS) in patients with SSc, assessing its effects on pain as primary endpoint and on inflammation, cardiovascular autonomic control and HRQoL. METHODS: Thirty-two patients with SSc were enrolled based on reported pain assessed through Numeric Rating Scale (NRS). Twenty-one (90% with limited cutaneous SSc) completed a randomised, cross-over, patient-blind trial, in which interventional and active control were used in random order for 4 weeks, interspersed with 4 weeks washout. NRS, Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29) Item4 for pain interference, heart rate variability (HRV), serum cytokines and HRQoL questionnaires (Health Assessment Questionnaire, Patient Health Questionnaire-9, University of California, Los Angeles Gastrointestinal Tract, Pittsburgh Sleep Quality Index) were assessed at baseline, at T1 (after 1 month of tVNS or active control), at T2 (after washout) and at T3 (after 1 month of active control or tVNS). T-test for paired data and Wilcoxon signed-rank test for non-normally distributed parameters were performed to compare the effect of tVNS and active control. RESULTS: NRS pain was significantly reduced by tVNS and not by active control (Mean±SD: -27.7%±21.3% vs -7.7%±26.3%, p=0.002). Interleukin-6 was downregulated in tVNS versus active control (p=0.029). No significant differences were observed in tVNS versus active control for PROMIS-29 Item4, QoL scales and HRV with both spectral and symbolic analyses. CONCLUSION: tVNS demonstrated to be a safe and non-invasive add-on tool to reduce pain in SSc.

Cardiovascular autonomic modulation during passive heating protocols: a systematic review.

Objective.To conduct a systematic review of the possible effects of passive heating protocols on cardiovascular autonomic control in healthy individuals.Approach.The studies were obtained from MEDLINE (PubMed), LILACS (BVS), EUROPE PMC (PMC), and SCOPUS databases, simultaneously. Studies were considered eligible if they employed passive heating protocols and investigated cardiovascular autonomic control by spontaneous methods, such as heart rate variability (HRV), systolic blood pressure variability (SBPV), and baroreflex sensitivity (BRS), in healthy adults. The revised Cochrane risk-of-bias tool (RoB-2) was used to assess the risk of bias in each study.Main results.Twenty-seven studies were included in the qualitative synthesis. Whole-body heating protocols caused a reduction in cardiac vagal modulation in 14 studies, and two studies reported both increased sympathetic modulation and vagal withdrawal. Contrariwise, local-heating protocols and sauna bathing seem to increase cardiac vagal modulation. A reduction of BRS was reported in most of the studies that used whole-body heating protocols. However, heating effects on BRS remain controversial due to methodological differences among baroreflex analysis and heating protocols.Significance.Whole-body heat stress may increase sympathetic and reduce vagal modulation to the heart in healthy adults. On the other hand, local-heating therapy and sauna bathing seem to increase cardiac vagal modulation, opposing sympathetic modulation. Nonetheless, further studies should investigate acute and chronic effects of thermal therapy on cardiovascular autonomic control.

Effects of transcutaneous auricular vagus nerve stimulation on cardiovascular autonomic control in health and disease.

Autonomic nervous system (ANS) dysfunction is a well-known feature of cardiovascular diseases (CVDs). Studies on heart rate variability (HRV), a non-invasive method useful in investigating the status of cardiovascular autonomic control, have shown that a predominance of sympathetic modulation not only contributes to the progression of CVDs but has a pivotal role in their onset. Current therapies focus more on inhibition of sympathetic activity, but the presence of drug-resistant conditions and the invasiveness of some surgical procedures are an obstacle to complete therapeutic success. On the other hand, targeting the parasympathetic branch of the autonomic nervous system through invasive vagus nerve stimulation (VNS) has shown interesting results as alternative therapeutic approach for CVDs. However, the invasiveness and cost of the surgical procedure limit the clinical applicability of VNS and hinder the research on the physiological pathway involved. Transcutaneous stimulation of the auricular branch of the vagus nerve (tVNS) seems to represent an important non-invasive alternative with effects comparable to those of VNS with surgical implant. Thus, in the present narrative review, we illustrate the main studies on tVNS performed in healthy subjects and in three key examples of CVDs, namely heart failure, hypertension and atrial fibrillation, highlighting the neuromodulatory effects of this technique.

Comparison between deep brain stimulation and magnetic resonance-guided focused ultrasound in the treatment of essential tremor: a systematic review and pooled analysis of functional outcomes.

The current gold standard surgical treatment for medication-resistant essential tremor (ET) is deep brain stimulation (DBS). However, recent advances in technologies have led to the development of incisionless techniques, such as magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy. The authors perform a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement to compare unilateral MRgFUS thalamotomy to unilateral and bilateral DBS in the treatment of ET in terms of tremor severity and quality of life improvement. PubMed, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials and SCOPUS databases were searched. 45 eligible articles, published between 1990 and 2019, were retrieved. 1202 patients were treated with DBS and 477 were treated with MRgFUS thalamotomy. Postoperative tremor improvement was greater following DBS than MRgFUS thalamotomy (p<0.001). A subgroup analysis was carried out stratifying by treatment laterality: bilateral DBS was significantly superior to both MRgFUS and unilateral DBS (p<0.001), but no significant difference was recorded between MRgFUS and unilateral DBS (p<0.198). Postoperative quality of life improvement was significantly greater following MRgFUS thalamotomy than DBS (p<0.001). Complications were differently distributed among the two groups (p<0.001). Persistent complications were significantly more common in the MRgFUS group (p=0.042). While bilateral DBS proves superior to unilateral MRgFUS thalamotomy in the treatment of ET, a subgroup analysis suggests that treatment laterality is the most significant determinant of tremor improvement, thus highlighting the importance of future investigations on bilateral staged MRgFUS thalamotomy.

Depression and cardiovascular autonomic control: a matter of vagus and sex paradox.

Depression is a well-established stress-related risk factor for several diseases, mainly for those with cardiovascular outcomes. The mechanisms that link depression disorders with cardiovascular diseases (CVD) include dysfunctions of the autonomic nervous system. Heart rate variability analysis is a widely-used non-invasive method that can simultaneously quantify the activity of the two branches of cardiac autonomic neural control and provide insights about their pathophysiological alterations. Recent scientific literature suggests that sex influences the relationship between depressive symptoms and cardiac autonomic dysfunction. Moreover, a few studies highlight a possible sex paradox: depressed women, despite a greater vagal tone, experience a higher risk of adverse cardiovascular events than depressed men. Although there are striking sex differences in the incidence of depression, scanty data on this topic are available. Lastly, studies on the heart-brain axis bidirectionality and the role of sex are fundamental not only to clarify the biological bases of depression-CVD comorbidity, but also to develop alternative therapies, where vagus nerve appears to be a promising target of non-invasive neuromodulation techniques.

Sudarshan Kriya Yoga improves cardiac autonomic control in patients with anxiety-depression disorders.

BACKGROUND: Several studies have demonstrated that adjuvant therapies as exercise and breathing training are effective in improving cardiac autonomic control (CAC) in patients with affective spectrum disorders. However, the effects of Sudarshan Kriya Yoga (SKY) on autonomic function in this population is unknown. Our objective was to test the hypothesis that SKY training improves CAC and cardiorespiratory coupling in patients with anxiety and/or depression disorders. METHODS: Forty-six patients with a diagnosis of anxiety and/or depression disorders (DSM-IV) were consecutively enrolled and divided in two groups: 1) conventional therapy (Control) and 2) conventional therapy associated with SKY (Treatment) for 15 days. Anxiety and depression levels were determined using quantitative questionnaires. For the assessment of CAC and cardiorespiratory coupling, cardiorespiratory traces were analyzed using monovariate and bivariate autoregressive spectral analysis, respectively. RESULTS: After 15-days, we observed a reduction of anxiety and depression levels only in Treatment group. Moreover, sympathetic modulation and CAC were significantly lower while parasympathetic modulation and cardiorespiratory coupling were significantly higher in the Treatment compared to Control group. CONCLUSIONS: Intensive breathing training using SKY approach improves anxiety and/or depressive disorders as well as CAC and cardiorespiratory coupling. These finding suggest that the SKY training may be a useful non-pharmacological intervention to improve symptoms and reduce cardiovascular risk in patients with anxiety/depression disorders.

Wrong guidelines: how to detect them and what to do in the case of flawed recommendations.

Any evidence-based recommendation needs careful assessment of its methodological background as well as of its content trustworthiness, especially given that following it will not necessarily produce the intended clinical outcomes. There are no established instruments to evaluate guidelines for their content, while useful tools assessing the quality of methods followed are well recognised and adopted. We suggest a 'safety bundle' considering methodological aspects and content trustworthiness of guidelines, by adopting the GRADE method in a backward fashion. Sharing the critical analysis of the guidelines with patients, including any eventual uncertainty about them, is of key importance in order to avoid the possible adverse effects derived from following the wrong guidelines. Such critical approach is also helpful and beneficial in producing better care pathways, health policy decisions and more relevant and ethical research.

Evaluation of Cardiovascular Risk Factors in the Wistar Audiogenic Rat (WAR) Strain.

INTRODUCTION: Risk factors for life-threatening cardiovascular events were evaluated in an experimental model of epilepsy, the Wistar Audiogenic Rat (WAR) strain. METHODS: We used long-term ECG recordings in conscious, one year old, WAR and Wistar control counterparts to evaluate spontaneous arrhythmias and heart rate variability, a tool to assess autonomic cardiac control. Ventricular function was also evaluated using the pressure-volume conductance system in anesthetized rats. RESULTS: Basal RR interval (RRi) was similar between WAR and Wistar rats (188 ± 5 vs 199 ± 6 ms). RRi variability strongly suggests that WAR present an autonomic imbalance with sympathetic overactivity, which is an isolated risk factor for cardiovascular events. Anesthetized WAR showed lower arterial pressure (92 ± 3 vs 115 ± 5 mmHg) and exhibited indices of systolic dysfunction, such as higher ventricle end-diastolic pressure (9.2 ± 0.6 vs 5.6 ± 1 mmHg) and volume (137 ± 9 vs 68 ± 9 µL) as well as lower rate of increase in ventricular pressure (5266 ± 602 vs 7320 ± 538 mmHg.s-1). Indices of diastolic cardiac function, such as lower rate of decrease in ventricular pressure (-5014 ± 780 vs -7766 ± 998 mmHg.s-1) and a higher slope of the linear relationship between end-diastolic pressure and volume (0.078 ± 0.011 vs 0.036 ± 0.011 mmHg.µL), were also found in WAR as compared to Wistar control rats. Moreover, Wistar rats had 3 to 6 ventricular ectopic beats, whereas WAR showed 15 to 30 ectopic beats out of the 20,000 beats analyzed in each rat. CONCLUSIONS: The autonomic imbalance observed previously at younger age is also present in aged WAR and, additionally, a cardiac dysfunction was also observed in the rats. These findings make this experimental model of epilepsy a valuable tool to study risk factors for cardiovascular events in epilepsy.