Cranial Autonomic Symptoms and Migraine: What Relationship and What Meaning? A Review.

Cranial autonomic symptoms (CAS) have been usually associated with trigeminal autonomic cephalalgias (TAC's), however in the last few years several reports in adult and pediatric population have reported important presence of the CAS in migraine. Also several evidences experimentally show that the increased parasympathetic outflow can enhance the sensitization of nociceptive receptors involved in migraine. The presence of CAS suggests an activation of the trigeminal-autonomic reflex, probably related to an over-activation of the trigeminal afferent arm. For these reasons identifing and understanding of these symptoms in migraine may be important to help in the diagnosis and effective management. The purpose of this review is, analyzing the literature data, to discuss the prevalence of these CAS in migraine, the pathophysiological meaning in the pathogenesis of migraine and whether their presence influences the prognosis and therapy of migraine in adult and pediatric age.

Effector mechanisms in the baroreceptor control of blood pressure.

While the effects of changing heart rate and systemic vascular resistance have been generally understood and appreciated, the effects of changes in left ventricular contractility on end-systolic volume may have been less understood and appreciated and the effects of changes in venous capacitance on end-diastolic volume may have been unknown to many readers. Herein, we have provided a brief review for the medical student and beginning graduate student highlighting these sometimes-complex relationships.

The Interplay between Autonomic Nervous System and Inflammation across Systemic Autoimmune Diseases.

The autonomic nervous system (ANS) and the immune system are deeply interrelated. The ANS regulates both innate and adaptive immunity through the sympathetic and parasympathetic branches, and an imbalance in this system can determine an altered inflammatory response as typically observed in chronic conditions such as systemic autoimmune diseases. Rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis all show a dysfunction of the ANS that is mutually related to the increase in inflammation and cardiovascular risk. Moreover, an interaction between ANS and the gut microbiota has direct effects on inflammation homeostasis. Recently vagal stimulation techniques have emerged as an unprecedented possibility to reduce ANS dysfunction, especially in chronic diseases characterized by pain and a decreased quality of life as well as in chronic inflammation.

Changes in vascular function and autonomic balance during the first trimester of pregnancy and its relationship with the new-born weight.

This study aimed to evaluate vascular function changes and autonomic balance during the first trimester of pregnancy and its relationship with the new-born weight. This prospective study performed in pregnant (PG) women and after delivery (not pregnant: NPG) evaluated the endothelial function (EF) and arterial stiffness (AS) by a non-invasive method. We evaluated the heart rate variability (HRV), parasympathetic nervous system (PNS), sympathetic nervous system (SNS) indexes by electrocardiogram (5 min) and the urinary nitrite excretion (NOx). PG increased EF and NOx and decreased AS and HRV. PG decreased the PNS index and augmented the SNS index. The new-born weight positively correlated with the PNS index (Pearson's r: 0.4291; p<.05), NOx, HRV and negatively correlated with AS. In summary, in pregnancy, although haemodynamically, the SNS activation plays a compensatory role, the low rates of PNS inhibition are essential to ensure normal foetal growth.Impact StatementWhat is already known on this subject? In pregnancy, there are adaptive physiological changes in the cardiovascular system that include increases of EF and decreases AS with an SNS activation. The study of HRV lets to predict the SNS and PNS balance and how they affect blood pressure and vascular function.What the results of this study add? Although it is known that SNS activation plays a compensatory role in healthy pregnancy, this study adds the critical role of PNS. Early in pregnancy, the low rates of PNS inhibition are essential to ensure normal foetal growth.What the implications are of these findings for clinical practice and/or further research? The present results show a potential predictive value of SNS and PNS activity early in pregnancy. It will provide valuable information not only on the pregnant woman's vascular function but also on the new-born weight.

Improving the prognosis of renal patients: The effects of blood flow-restricted resistance training on redox balance and cardiac autonomic function.

NEW FINDINGS: What is the central question of this study? Can resistance training with and without blood flow restriction improve redox balance and positively impact the autonomic cardiac modulation in chronic kidney disease patients? What is the main finding and its importance? Resistance training with and without blood flow restriction improved antioxidant defence (paraoxonase 1), decreased the pro-oxidative myeloperoxidase, improved cardiac autonomic function and slowed the decrease in renal function. We draw attention to the important clinical implications for the management of redox balance and autonomic cardiac function in chronic kidney disease patients. ABSTRACT: Patients with chronic kidney disease (CKD) are prone to cardiovascular diseases secondary to abnormalities in both autonomic cardiac function and redox balance [myeloperoxidase (MPO) to paraoxonase 1 (PON1) ratio]. Although aerobic training improves both autonomic balance and redox balance in patients with CKD, the cardioprotective effects of resistance training (RT), with and without blood flow restriction (BFR), remain unknown. We aimed to compare the effects of RT and RT+BFR on antioxidant defence (PON1), pro-oxidative status (MPO), cardiac autonomic function (quantified by heart rate variability analysis) and renal function. Conservative CKD (stages 1 to 5 who do not need hemodialysis) patients (n = 105, 33 female) of both sexes were randomized into three groups: control (CTL; 57.6 ± 5.2 years; body mass index, 33.23 ± 1.62 kg/m2 ), RT (58.09 ± 6.26 years; body mass index 33.63 ± 2.05 kg/m2 ) and RT+BFR (58.06 ± 6.47 years; body mass index, 33.32 ± 1.87 kg/m2 ). Patients completed 6 months of RT or RT+BFR on three non-consecutive days per week under the supervision of strength and conditioning professionals. Training loads were adjusted every 2 months. Heart rate variability was recorded with a Polar-RS800 and data were analysed for time and frequency domains using Kubios software. The redox balance markers were PON1 and MPO, which were analysed in plasma samples. Renal function was estimated as estimated glomerular filtration rate. The RT and RT+BFR decreased pro-oxidative MPO (RT, ∼34 ng/ml and RT+BFR, ∼27 ng/ml), improved both antioxidant defence (PON1: RT, ∼23 U/L and RT+BFR, ∼31 U/L) and cardiac autonomic function (R-R interval: RT, ∼120.4 ms and RT+BFR, ∼117.7 ms), and slowed the deterioration of renal function (P < 0.0001). Redox balance markers were inversely correlated with heart rate variability time-domain indices. Our data indicated that both training models were effective as non-pharmacological tools to increase the antioxidant defences, decrease oxidative stress and improve the cardiac autonomic function of CKD patients.

Diabetes and subclinical hypothyroidism on heart rate variability.

BACKGROUND: We aimed to analyse if the effects of coexistent diabetes and subclinical hypothyroidism extend to the cardio autonomic nervous system, using heart rate variability baseline data from the Brazilian Longitudinal Study of Adult Health. MATERIALS AND METHODS: Heart rate variability analyses were performed by linear time and frequency domains in 5-minute time series collected in the supine position. The associations of diabetes and subclinical hypothyroidism with the lowest quartile group for heart rate and the highest quartile group for each heart rate variability parameter were analysed using additive and multiplicative terms in logistic models. For the first approach, the subsample was categorized into four groups: subjects without diabetes and normal thyroid function (controls); subjects without diabetes and subclinical hypothyroidism; patients with diabetes and normal thyroid function; and patients with diabetes and subclinical hypothyroidism. For the interaction alnalysis, diabetes and subclinical hypothyroidism diagnoses were included in separate, along with a multiplicative interaction term between them. RESULTS: Point odds ratio estimates for the 4th quartiles of heart rate, and 1st quartiles of all heart rate variability measurements were higher for subjects with combined diabetes and subclinical hypothyroidism than for diabetes only, independently of main sociodemographic and clinical variables (HR: 8.33 vs 2.63; SDNN: 2.59 vs 1.61; RMSSD: 2.37 vs 1.42; LF: 2.83 vs 1.71; HF: 3.06 vs 1.39), but not independently of HbA1c and TSH. Only the interaction term for the association with heart rate, adjusted for sociodemographic and clinical variables, had borderline statistical significance. CONCLUSION: Diabetes and subclinical hypothyroidism exert a potential joint impact on cardiac autonomic control, showed by additive effects between diabetes and subclinical hypothyroidism, as well as a significant interaction term for the association with heart rate.

Two-hour infusion of vasoactive intestinal polypeptide induces delayed headache and extracranial vasodilation in healthy volunteers.

BACKGROUND: In recent years, vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptides (PACAPs) have gained special interest in headache science. VIP and PACAPs (two isoforms, PACAP27 and PACAP38) are related in structure and function, as are their receptors, but they show differences in vasodilating- and headache-inducing properties. Intravenous infusion of PACAP27 or PACAP38, but not VIP, induces a long-lasting dilation of cranial arteries and delayed headache. The relationship between the long-lasting cranial vasodilation and headache development is not fully clarified. METHODS: In a double-blinded, placebo-controlled, crossover study in 12 healthy volunteers, diameter changes of cranial arteries, occurrence of headache and the parasympathetic system were examined before, during and after a 2-hour continuous intravenous infusion of VIP and placebo. Primary endpoints were the differences in area under the curve for the superficial temporal artery diameter and headache intensity scores, as well as in headache incidence, between VIP and placebo. RESULTS: The superficial temporal artery diameter was significantly larger on the VIP day compared to placebo (p < 0.001) and the dilation lasted for more than 2 h. The incidence of headache was higher (p = 0.003) on the VIP day compared to the placebo day. The difference in headache intensity scores was more evident in the post-infusion period (120-200 min, p = 0.034) and in the post-hospital phase (4-12 h, p = 0.025). Cranial parasympathetic activity, measured through the production of tears, was higher during VIP compared to placebo (p = 0.033). CONCLUSION: Continuous intravenous infusion of VIP over 2 h induced a long-lasting cranial vasodilation, activation of the cranial parasympathetic system, and delayed mild headaches in healthy volunteers.Trial Registration: The study is registered at ClinicalTrials.gov (NCT03989817).

Orthostatic change in systolic blood pressure associated with cold pressor reflection and heart rate variability in the elderly.

Background: Impaired orthostatic blood pressure (BP) response is a frequent finding in the elderly. The goal of the study was to investigate the association of variability of supine-to-orthostatic BP with cold pressor reflection and heart rate variability in the elderly.Methods: From June 2010 to September 2013, 287 elderly aged ≥ 60 years were enrolled in Jinan area, China. The elderly were classified into lower (n = 96), intermediate (n = 95), and higher (n = 96) tertile groups according to the tertile of the percentage change of supine-to-orthostatic systolic BP.Results: There were significant increasing trends in systolic BP response to the CPT at 0 and 60 sec; the plasma levels of epinephrine, norepinephrine, and angiotensin II; and decreasing trends in DNN, SDNN index, and SDANN from the lower to the higher tertile group, and differences between any two groups were significant (P < .05). The percentage change of supine-to-orthostatic systolic BP was positively correlated with systolic BP response to CPT at 0 and 60 sec, VLF, epinephrine, norepinephrine, and angiotensin II (P < .001) and negatively correlated with SDNN, SDNN index, SDANN, rMSSD, pNN50, LF, and ratio of LF/HF (P < .001). The BP response to CPT, parameters of HRV, and the plasma levels of norepinephrine and angiotensin II were independently associated with the percentage change of supine-to-orthostatic systolic BP after adjustment for confounders.Conclusion: Aggressive variability of supine-to-orthostatic systolic BP might be significantly associated with the imbalance of sympathetic and parasympathetic activity, especially high sensitivity sympathetic response in the elderly.Abbreviations: BP: blood pressure; BMI: body mass index; CPT: cold pressor test; HRV: heart rate variability; SDNN: standard deviation of all normal-to-normal R-R intervals; SDNN index: mean of the standard deviations of all 5-min normal-to-normal R-R intervals of the entire recording; SDANN: standard deviation of the averages of normal-to-normal R-R intervals during all 5-min periods of the entire recording; rMSSD: square root of the mean squared differences between successive normal R-R intervals; pNN50: number of adjacent normal R-R intervals differing by more than 50 ms; VLF: very low frequency; LF: low frequency; HF: high frequency; TCHO: total cholesterol; HDL-c: high-density lipoprotein cholesterol; LDL-c: low-density lipoprotein cholesterol; FPG: fasting plasma glucose; SD: standard deviation.

GNB5 Mutations Cause an Autosomal-Recessive Multisystem Syndrome with Sinus Bradycardia and Cognitive Disability.

GNB5 encodes the G protein ß subunit 5 and is involved in inhibitory G protein signaling. Here, we report mutations in GNB5 that are associated with heart-rate disturbance, eye disease, intellectual disability, gastric problems, hypotonia, and seizures in nine individuals from six families. We observed an association between the nature of the variants and clinical severity; individuals with loss-of-function alleles had more severe symptoms, including substantial developmental delay, speech defects, severe hypotonia, pathological gastro-esophageal reflux, retinal disease, and sinus-node dysfunction, whereas related heterozygotes harboring missense variants presented with a clinically milder phenotype. Zebrafish gnb5 knockouts recapitulated the phenotypic spectrum of affected individuals, including cardiac, neurological, and ophthalmological abnormalities, supporting a direct role of GNB5 in the control of heart rate, hypotonia, and vision.

Sex Differences in Autonomic Response to Exercise Testing in Patients with Brugada Syndrome.

INTRODUCTION: Cardiac events in patients with Brugada syndrome (BS) typically occur at rest and mainly during sleep, suggesting that changes in autonomic modulation play an important role in the arrhythmogenesis of the disease. Moreover, sex differences in clinical manifestations of BS have been reported, identifying male patients with worse prognosis. The aim of our work was to assess and compare, according to sex, autonomic response to exercise in a clinical series including 105 BS patients. METHOD: Standard 12-lead electrocardiogram recordings were collected during a physical stress test divided into four phases: warm-up, incremental exercise, active recovery, and passive recovery. Spectral non-stationary heart rate variability indicators were extracted by means of a smoothed pseudo Wigner-Ville distribution approach that adapts frequency bands to respiratory information. These indicators were then averaged in non-overlapped windows of 1 min for each patient to compare groups at each minute of the physical stress test. RESULTS: From the last minute of warm-up and until the third minute of incremental exercise, asymptomatic male patients presented significantly greater low-frequency (LF) values ([Formula: see text]: p = 0.015;[Formula: see text]: p = 0.024; [Formula: see text]: p = 0.011; [Formula: see text]: p = 0.002) than asymptomatic females. Conversely, asymptomatic women showed increased vagal modulation during the first minutes of incremental exercise ([Formula: see text]: p = 0.031; [Formula: see text]: p = 0.001). However, no significant differences were observed between symptomatic male and female patients. CONCLUSION: As previously reported in healthy subjects, enhanced parasympathetic and decreased sympathetic tones appear to be not only greater in women but also defensive during cardiac stress. Based on the results, asymptomatic patients presented same-sex tendencies. However, we observed that symptomatic males developed a more female-like autonomic modulation, probably related to a more protective autonomic response to exercise. These results could be a step forward toward the understanding of the autonomic function in BS along with a potential impact on risk stratification.

Higher locus coeruleus MRI contrast is associated with lower parasympathetic influence over heart rate variability.

The locus coeruleus (LC) is a key node of the sympathetic nervous system and suppresses parasympathetic activity that would otherwise increase heart rate variability. In the current study, we examined whether LC-MRI contrast reflecting neuromelanin accumulation in the LC was associated with high-frequency heart rate variability (HF-HRV), a measure reflecting parasympathetic influences on the heart. Recent evidence indicates that neuromelanin, a byproduct of catecholamine metabolism, accumulates in the LC through young and mid adulthood, suggesting that LC-MRI contrast may be a useful biomarker of individual differences in habitual LC activation. We found that, across younger and older adults, greater LC-MRI contrast was negatively associated with HF-HRV during fear conditioning and spatial detection tasks. This correlation was not accounted for by individual differences in age or anxiety. These findings indicate that individual differences in LC structure relate to key cardiovascular parameters.

Integrity of the Ganglionated Plexi Is Essential to Parasympathetic Innervation of the Atrioventricular Node by the Right Vagus Nerve.

INTRODUCTION: Radiofrequency isolation of pulmonary vein can be accompanied by transient sinus bradycardia or atrioventricular nodal (AVN) block, suggesting an influence on vagal cardiac innervation. However, the importance of the atrial fat pads in relation with the vagal innervation of AVN in humans remains largely unknown. The aim of this study was to evaluate the role of ganglionated plexi (GP) in the innervation of the AVN by the right vagus nerve. METHODS AND RESULTS: Direct epicardial high-frequency stimulation (HFS) of the GP (20 patients) and the right vagus nerve (10 patients) was performed before and after fat pad exclusion or destruction in 20 patients undergoing thoracoscopic epicardial ablation for the treatment of persistent AF. Asystole longer than 3 seconds or acute R-R prolongation over 25% was considered as a positive response to HFS. Prior to the ablation, positive responses to HFS were detected in 3 GPs in 7 patients (35%), 2 GPs in 5 patients (25%), and one GP in 8 patients (40%). After exclusion of the fat pads, all patients had a negative response to HFS. All the patients who exhibited a positive response to right vagus nerve stimulation (n = 10) demonstrated negative responses after the ablation. CONCLUSION: The integrity of the GP is essential for the right vagus nerve to exert physiological effects of on AVN in humans.

Red Ear Syndrome.

The Red Ear syndrome (RES) is an intriguing syndrome originally described for the first time nearly 20 years ago. RES is characterized by unilateral/bilateral episodes of pain and burning sensation of the ear, associated with ipsilateral erythema. RES episodes are indeed isolated in some patients, but they can occur in association with primary headaches, including in particular migraine in the developmental age. Although the underlying pathophysiological mechanisms are still uncertain, in the recent years the described comorbidities have aroused increasing interest because of possible clinical implications. Moreover, RES seems to be more often associated with clinical features of migraine partially provoked by the involvement of the parasympathetic system. This clinical association has shed new light on the pathophysiology of RES, supporting the hypothesis of a shared pathophysiological background, for example, through the activation of the trigeminal autonomic reflex. Current therapies of RES will be also discussed. Finally, we will resume the more controversial aspects of this relatively new and probably underestimated neurological syndrome.

Comparison of pupillary dynamics to light in the mild traumatic brain injury (mTBI) and normal populations.

PURPOSE: To determine if mTBI adversely affects the pupillary light reflex (PLR). METHODS: The PLR was evaluated in mTBI and compared to normal individuals under a range of test conditions. Nine pupil parameters (maximum, minimum and final pupil diameter, latency, amplitude and peak and average constriction and dilation velocities) and six stimulus conditions (dim pulse, dim step, bright pulse, bright step, bright red step and bright blue step) were assessed in 32 adults with mTBI (21-60 years of age) and compared to 40 normal (22-56 years of age). The Neuroptics, infrared, DP-2000 binocular pupillometer was used (30 Hz sampling rate; 0.05 mm resolution) with binocular stimulation and recording. RESULTS: Different test conditions allowed for discrimination of different parameters. For any of the given six test conditions, five-to-eight of the nine pupillary parameters were statistically different (p < 0.05) between the two diagnostic groups. The most promising parameters for diagnostic differentiation were constriction latency, all pupillary diameters, average constriction velocity and peak dilation velocity. CONCLUSIONS: MTBI adversely affects the PLR. This suggests an impairment of the autonomic nervous system. The findings suggest the potential for quantitative pupillary dynamics to serve as an objective mTBI biomarker.

Pupillary responses to light in chronic non-blast-induced mTBI.

PURPOSE: To evaluate objectively and quantitatively human pupillary responses to a light stimulus under photopic conditions in individuals with non-blast-induced, chronic, mild traumatic brain injury (mTBI). METHODS: Seventeen individuals with chronic, non-blast-induced mTBI and 15 visually-normal (VN) controls were tested (aged 21-45 years). Pupillary responsivity to a brief step-input light stimulus was assessed objectively in each eye for 5 seconds using the Neuroptics PLR-200 monocular, hand-held pupillometer with its pre-set and automated eight parameter analysis. RESULTS: Five of the eight parameters assessed were significantly reduced (p ≤ 0.05) in the mTBI group as compared to the VN control group: maximum (or peak) constriction velocity, average constriction velocity, average dilation velocity, maximum diameter and amplitude of constriction. The remaining three parameters were similar in each group (p > 0.05): constriction latency, 75% dilation recovery time and minimum diameter. CONCLUSIONS: The slowed dilation dynamics and reduced maximum pupillary diameter in mTBI suggest deficiency primarily of the sympathetic control system. The reduced peak velocities and related amplitudes suggest subtle parasympathetic involvement.

Cardioneuroablation for Cardioinhibitory Vasovagal Syncope: Rationale, Approaches, and Its Role in Long-Term Management.

Purpose of Review: Cardioneuroablation (CNA) has emerged as a potential alternative to pacemaker therapy in well-selected cases with vasovagal syncope (VVS). In recent years, the number of CNA procedures performed by electrophysiologists has considerably risen. However, some important questions, including proper patient selection and long-term results, remain unanswered. The present article aims to critically review and interpret latest scientific evidence for clinical indications and how to approach long-term management. Recent Findings: CNA is a new approach that has been supported mainly by retrospective or observational data for its use in syncope. Overall, in mixed population studies treated with CNA, 83.3 to 100% have been reported to be free of syncope over follow-up periods of 6 to 52.1 months. For studies including patients who underwent CNA with pure VVS, 73.2 to 100% have been reported to be syncope-free over follow-up periods of 4 to 45.1 months. One large meta-analysis showed 91.9% freedom from syncope after CAN. To date, only one randomized controlled trial with small case number has been performed of CNA compared to non-pharmacological treatment in VVS. In this study of 48 patients with an average of 10 ± 9 spontaneous syncopal episodes prior to study enrollment and 3 ± 2 episodes in the year prior to CNA. After CNA, 92% were free of syncope compared with 46% treated with optimal non-pharmacological treatment to prevent new syncope episodes (P = 0.0004). To date, most studies have included younger patients (< 60 years of age). There are only limited data in patients older than 60, and some studies suggest less of an effect in relatively older patients. Summary: Cardioneuroablation can be performed to decrease syncope recurrence in adult patients aged < 60 years, with severe or recurrent cardioinhibitory syncope without prodromal symptoms, after proven failure of conventional therapies. Due to a paucity of data supporting efficacy in older individuals or for vasodepressor components, CNA in adult patients aged > 60 years or in the presence of a dominant vasodepressor should be considered investigational in severely symptomatic patients after proven failure of pharmacological and non-pharmacological therapies.

Psychological, cognitive, and physiological impact of hazards casualties' trainings on first responders: the example of a chemical and radiological training. An exploratory study.

Background: First responders are among the first to respond to hazards casualties. They might operate in volatile, uncertain, complex, and ambiguous (VUCA) environments. While they have underlined the need to improve their knowledge and training to face these environments, there are few data regarding the stress induced by these trainings. Chemical, biological, radiological, and nuclear (CBRN) hazards casualties' trainings seem to be a good model of "in vivo" stress. First responders must operate in a hostile and encountered environment with a CBRN protective equipment that places demand on their psychological, cognitive, and physiological capacities. Current research recognizes that the activity of the parasympathetic system (PSS) can be used as an objective marker of stress adaptation, measured as heart rate variability (HRV). Objectives: To compare between baseline and simulation the evolution of the parasympathetic activity (primary outcome), anxiety, emotions, cognitive load, and body posture awareness (secondary outcomes). Methods: A total of 28 first responders attended to three simulated scenarios requiring CBRN management of casualties. One day before simulation, we collected HRV data (baseline). The simulations' day (pre-, post-simulation) we collected anxiety score (STAI-Y B), emotions (SPANE), cognitive load (NASA TLX), body posture awareness (PAS) and HRV. The morning after we collected the PAS score (recovery). We compare data' evolution between different times of the simulation. Results: (i) A high level of anxiety at baseline [Median 51 (46; 56)] which decreased between pre- and post-simulation (p = 0.04; F = 2.93); (ii) a post-simulation decrease in negative feelings (p = 0.03); (iii) a decrease in body awareness after simulation which returned to the initial level at recovery (p = 0.03; F = 3.48); (iv) a decrease in mean RR between baseline, pre- and post-simulation (p = 0.009; F = 5.11). There were no significant difference between times on others analysis of HRV. Conclusion: Prior to simulation, participants experienced anticipatory anxiety. Simulations training practiced regularly could be one way to combat anticipatory anxiety.

Study of autonomic modulation by non-linear analysis of heart rate variability in different age groups and analysis of health status, disease and risk of death in dogs.

The symbolic analysis of heart rate variability (biomarker of cardiac autonomic homeostasis) is a nonlinear and effective tool for pattern extraction and classification in a series analysis, which implies the transformation of an original time series into symbols, represented by numbers. Autonomic heart rate control is influenced by different factors, and better indicators of heart rate variability are found in healthy young individuals than in older and sicker individuals. The aim of this study was to compare the indicators of heart rate variability among healthy dogs in different age groups and in health status using the nonlinear method of symbolic analysis to evaluate the diagnostic accuracy of this method for the risk of death in dogs. An increase in cardiac sympathetic modulation was observed in puppies and dogs at risk of death, which was evidenced by a marked increase of 0 V% (without variation - associated with sympathetic modulation) and a decrease in patterns of 2 V% (two variations - associated with parasympathetic modulation), while the opposite was observed in young adult dogs with increased parasympathetic modulation. Elderly dogs showed a gradual decrease in parasympathetic activity, which tended to worsen with loss of health. It is concluded that the variables of symbolic analysis may be useful to evaluate autonomic modulation in dogs and assist in the differentiation between health states, advanced disease and death throughout the life cycle and have been shown to be indices with high specificity, sensitivity and diagnostic accuracy to help identify dogs at risk of death.

Plasma levels of VIP are not elevated during PACAP- and VIP-induced cluster headache attacks: an exploratory study.

Background: Pituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal peptide (VIP) provoked cluster headache attacks in individuals with episodic cluster headache during their active phase and individuals with chronic cluster headache. In this study, we investigated whether infusions of PACAP and VIP caused alterations in plasma levels of VIP and their potential contribution to induced cluster headache attacks. Methods: Participants received either PACAP or VIP infusion for 20 min on 2 separate days with an interval of at least 7 days in between. Blood collection was performed at T0, T20, T30, and T90. Plasma levels of VIP were measured using a validated radioimmunoassay method. Results: Blood samples were collected from participants with episodic cluster headache in the active phase (eCHA, n = 14), remission (eCHR, n = 15), and from participants with chronic cluster headache (cCH, n = 15). Baseline levels of VIP did not differ among the three groups (p = 0.1161). During PACAP infusion, mixed-effects analysis revealed a significant increase in plasma levels of VIP in eCHA (p = 0.0300) and eCHR (p = 0.0058) but not in cCH (p = 0.2930). We found no difference in the increase of plasma VIP levels between patients who developed PACAP38- or VIP-induced attacks. Conclusion: Cluster headache attacks induced by PACAP38 or VIP infusion are not associated with changes in plasma levels of VIP. Further studies are needed to investigate the role of VIP and the parasympathetic system in cluster headache. Clinical trial registration: The parent study is registered at ClinicalTrials.gov (NCT03814226).

Bradyarrhythmia in a marathonist: Cardiac vagal denervation as alternative treatment.

Although not routinely used, cardioneuroablation or modulation of the cardiac autonomic nervous system has been proposed as an alternative approach to treat young individuals with enhanced vagal tone and significant atrioventricular (AV) disturbances. We report the case of a 42-year-old athlete with prolonged ventricular pauses associated with sinus bradycardia and paroxysmal episodes of AV block (maximum of 6.6 s) due to enhanced vagal tone who was admitted to our hospital for pacemaker implantation. Cardiac magnetic resonance and stress test were normal. Although he was asymptomatic, safety concerns regarding possible neurological damage and sudden cardiac death were raised, and he accordingly underwent electrophysiological study (EPS) and cardiac autonomic denervation. Mapping and ablation were anatomically guided and radiofrequency pulses were delivered at empirical sites of ganglionated plexi. Modulation of the parasympathetic system was confirmed through changes in heart rate and AV nodal conduction properties associated with a negative cardiac response to atropine administration. After a follow-up of nine months, follow-up 24-hour Holter revealed an increase in mean heart rate and no AV disturbances, with rare non-significant ventricular pauses, suggesting that this technique may become a safe and efficient procedure in this group of patients.