Changes In Autonomic Function Research Articles

Potential autonomic nervous system dysfunction in COVID-19 patients detected by heart rate variability is a sign of SARS-CoV-2 neurotropic features.

Increasing evidence strongly support that the newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to the development of COVID-19-associated central nervous system (CNS) manifestations. The presence of SARS-CoV-2 viral protein in the brainstem, which includes cardiovascular control centers, has been documented previously. Given the changes in autonomic nervous system function evaluated by heart rate variability (HRV) metrics, which are observed even prior to clinical signs, the potential effect of SARS-CoV-2 on the autonomic nervous system (ANS) center is likely. The integral parts of the brain renin-angiotensin system, as ACE2 enzyme, are highly expressed in the brainstem, which may also be involved in baroreflex sensitivity, playing an important role in HRV. SARS-CoV-2 may bind to ACE2 in order to enter the host brainstem cell and change baroreflex sensitivity due to the altered ratio of the concentration of angiotensin II (Ag II) to angiotensin (1-7). In this article, we discussed the information on the possibility that the SARS-CoV-2 viral particle by disrupting the homeostasis of the brain renin-angiotensin system even without brainstem neuropathological changes, may affect the function of the ANS center in the brainstem. SARS-CoV-2 could influence ANS function before affecting the immune system. It is possible that the altered HRV parameters imply the potential neurotropic characteristics of SARS-CoV-2. Therefore, this potential feature should be taken into account in diagnostic and therapeutic approaches for COVID-19 patients.

Severe tauopathy and axonopathy in the medulla oblongata in Alzheimer’s disease implicate the changes in autonomic nervous function

The autonomic dysfunctions in Alzheimer’s disease (AD) have been identified from many clinical studies, however, there is still a lack of evidence directly verifying the structural abnormalities of the autonomic nervous system in AD. Human medulla oblongatas from four AD patients or five non-AD subjects were obtained and observed by using immunohistochemical staining of hyperphosphorylated tau and Aβ amyloid, and post-mortem tracing techniques. We found distinct axonal and somatic immunoreactivities for the tau markers AT8 and Tau-5 in the different areas of the medulla oblongata in AD patients, which was particularly obvious in the dorsal nucleus of the vagus nerve, the nucleus of the solitary tract and the reticular nucleus. The swollen axons, which are a typical feature of axonopathy, were not only identified in the axons with immunohistochemical labeling of AT8 and Tau-5 in the different nuclei of the medulla oblongata, but also in the tracer-labeled afferent and efferent fibres of the vagus nerve in AD patients. Such changes in tauopathy and axonopathy were only occasionally found in the non-AD aged subjects. Interestingly, we did not observe any intra- or extracellular Aβ deposits in the medulla oblongatas of the AD patients or of the non-AD subjects. These results in small samples suggest that occurrence of tauopathy and axonopathy in the parasympathetic nuclei of the medulla oblongata in AD patients may implicate the change of autonomic nervous function.

PO-703-01 POLAR RESPIRATORY SINUS ARRHYTHMIA MAP FEATURES ARE POTENTIAL BIOMARKERS OF ACUTE CARDIAC AUTONOMIC DYSREGULATION DUE TO PSYCHOLOGICAL STRESSORS

Exposure to psychological stressors could trigger acute autonomic dysregulation, increasing the risk of catecholaminergic polymorphic ventricular tachycardia (CPVT) in vulnerable patients. Changes in respiratory sinus arrhythmia (RSA) could indicate autonomic dysregulation due to acute external stressors. In addition, respiration habituation with respect to average RR interval from polar RSA maps could demonstrate changes in autonomic function.

Roles of sleep-related cardiovascular autonomic functions in voluntary-exercise-induced alleviation of hypertension in spontaneously hypertensive rats.

Autonomic dysfunction and sleep problems are closely associated with hypertension and predict cardiovascular morbidity and mortality. Animal studies and clinical observations have identified exercise as an important factor in preventing and treating hypertension. However, the roles of autonomic function and sleep in the antihypertensive mechanisms of exercise are still not fully understood. This study aimed to clarify the physiological mechanisms associated with autonomic function and sleep through wheel exercise. Male spontaneously hypertensive rats (SHRs) were grouped into a wheel-exercised group and a sedentary group (controls). Electroencephalogram, electromyogram, electrocardiogram, and mean arterial pressure (MAP) were recorded simultaneously for 24 h once a week over 11 weeks. Wheel exercise was initiated in the SHRs at 12 weeks old and continued for another eight weeks. A significant suppression in the age-related elevation of MAP was noted in the SHRs undergoing wheel exercise. The reduction in MAP was correlated with increased parasympathetic activity and baroreflex sensitivity and decreased sympathetic activity, mainly during quiet sleep. Exercise increased the paradoxical sleep time and theta power (associated with cognitive function) but not the delta power (an indicator of sleep depth) or the attenuation of circadian rhythm flattening (characterized by increased wakefulness and less sleep during the light period and the opposite during the dark period). Furthermore, the exercise-induced changes in autonomic function occurred before those in sleep patterns, which were dependent on each other. In conclusion, wheel exercise can modulate sleep-related cardiovascular dysfunction and the flattening of circadian rhythm, preventing the progression of hypertension, which reduces the incidence of cardiovascular diseases.

IDF21-0409 Hypoglycemia and heart rate variability: synchronous detection by Holter and continuous glucose monitors

Background: Hypoglycemia is a notorious diabetic side effect leading to unwanted major vascular events and sudden cardiac death due to change in autonomic cardiac function. Previous studies have reported electrocardiographic (ECG) abnormalities such as QT interval prolongation in patients with hypoglycemia, so did heart rate variability (HRV). Aim: To document ECG and HRV changes during hypoglycemia and expect to establish a portable device to early detect hypoglycemia in the future. Method: Seventeen participants including ten poor controlled type 2 diabetes, six type 1 diabetes and one Latent autoimmune diabetes in adults (LADA) were enrolled in this study. There were six males and eleven females, aged from 37 to 77 (mean 50.3 ± 12.0) years old, with self-reported duration of diabetes from 6 to 33 (mean 20.8 ± 8.7) years. The mean HbA1c was 8.3 ± 1.4 % on the time of the examination. We used Holter- electrocardiogram (VitalSigns) and continuous glucose monitor (Medtronic) to record ECG waveform, heart rate variability and glucose level with synchronization of time for a duration of seven days. Results: Two of the seventeen participants did not experience hypoglycemia (≦70 mg/dL). The other participants who experienced hypoglycemia revealed, as a whole, a trend of correlation between blood glucose, corrected QT Interval (QTc), and HRV. When the participants experienced hypoglycemia were sub-divided into response and non-response groups according to the appearance of QTc prolongation, significant difference of age was found between two groups, most of them were type 1 diabetic patients. Among 90 events of hypoglycemia, 56 events (62%) presented with increased heart rate and/or Low Frequency/ High Frequency (LF/HF) ratio and /or decreased Root Mean Square of the Successive Differences (RMSSD). Besides, there were a trend of difference of glucose nadir, HRV include heart rate, RMSSD and LF/HF ratio between two groups. Discussion: In this study, Type 1 DM patient and younger age were easier to have QT interval prolongation during hypoglycemia. Besides, increased LF/HF ratio may represent that these group of patients have better regulation of autonomic nervous system. Heart rate variability can be seen during hypoglycemic events in both type 1 and type 2 diabetic patients especially in the response group.

Autonomic aging \u2013 A dataset to quantify changes of cardiovascular autonomic function during healthy aging

Autonomic regulation of blood pressure and cardiac rhythm progressively declines with increasing age. Impaired cardiovascular control promotes a variety of age-related cardio-vascular conditions. This study aims to provide a database of high-resolution biological signals to describe the effect of healthy aging on cardiovascular regulation. Electrocardiogram and continuous non-invasive blood pressure signals were recorded simultaneously at rest in 1,121 healthy volunteers. With this database, we provide raw signals as well as basic demographic information such as gender and body mass index. To demonstrate validity of the acquired data, we present the well-known decline of heart rate variability with increasing age in this database.

Sudden unexpected death in epilepsy.

Sudden unexpected death in epilepsy (SUDEP) is a major contributor to premature mortality in people with epilepsy. This review provides an update on recent findings on the epidemiology of SUDEP, clinical risk factors and potential mechanisms. The overall risk rate of SUDEP is approximately 1 per 1000 patients per year in the general epilepsy population and that children and older adults have a similar incidence. Generalized convulsive seizures (GCS), perhaps through their effects on brainstem cardiopulmonary networks, can cause significant postictal respiratory and autonomic dysfunction though other mechanisms likely exist as well. Work in animal models of SUDEP has identified multiple neurotransmitter systems, which may be future targets for pharmacological intervention. There are also chronic functional and structural changes in autonomic function in patients who subsequently die from SUDEP suggesting that some SUDEP risk is dynamic. Modifiable risks for SUDEP include GCS seizure frequency, medication adherence and nighttime supervision. Current knowledge of SUDEP risk factors has identified multiple targets for SUDEP prevention today as we await more specific therapeutic targets that are emerging from translational research studies.

A Feasibility Study Exploring Measures of Autonomic Function in Patients With Failed Back Surgery Syndrome Undergoing Spinal Cord Stimulation

ObjectivesFailed back surgery syndrome (FBSS) is associated with impaired autonomic tone, characterized by sympathetic prevalence and vagal withdrawal. Although spinal cord stimulation (SCS) alleviates pain in FBSS, there is limited research investigating how SCS affects measures of autonomic function. This was a prospective, open-label, feasibility study exploring measures of autonomic function in patients with FBSS receiving SCS therapy. Materials and MethodsA total of 14 patients with FBSS were recruited for baseline measurements and underwent a trial of 10-kHz SCS. There were three failed trials, resulting in the remaining 11 participants receiving a fully implanted 10-kHz SCS system. One participant requested an explant, resulting in ten participants completing both baseline and follow-up (three to six months after SCS implant) measurements. Autonomic function was assessed using time- and frequency-domain heart rate variability (HRV), baroreceptor reflex sensitivity (BRS), and muscle sympathetic nerve activity (MSNA) using microneurography. Because this was a feasibility study, most of the analysis was descriptive. However, paired t-tests and Wilcoxon signed-rank tests tested for differences between baseline and follow-up. ResultsIn the whole (N = 14) and final (N = 10) samples, there was between-participant variation in baseline and follow-up measures. This, combined with a small sample, likely contributed to finding no statistically significant differences in any of the measures between baseline and follow-up. However, plotting baseline and follow-up scores for individual participants revealed that those who showed increases in MSNA frequency, square root of the mean of the squared differences between adjacent RR intervals (RMSSD), percentage of the number of RR intervals >50 ms (pRR50), total power, and up BRS between baseline and follow-up had distinct clustering of baseline values compared with those who showed decreases in these measures. ConclusionsFindings from this feasibility study will aid with informing hypotheses for future research. A key aspect that should be considered in future research concerns exploring the role of baseline measures of autonomic function in influencing change in autonomic function with SCS therapy.

Two days of simulated CrossFit competition affect autonomic nervous system but not anaerobic power or fatigue.

We examined changes in autonomic nervous system function, anaerobic power, and fatigue over two days of simulated CrossFit competition in CrossFit athletes. In addition, we determined the relationship between these internal training load variables and variables characterizing two weeks of tapering preceding the competition. In total, 21 participants (intervention group, N.=10, INT; control group, N.=11, CON) completed the assessments. INT performed the assessments at baseline (pre-day 1), during the competition (post-day 1 and pre-day 2), and after the competition (post-day 2), while CON performed only the baseline assessments. Autonomic nervous system function, anaerobic power, and fatigue did not differ between the beginning of day 1 and day 2. Autonomic nervous system function was impaired at the end of each day. Anaerobic power and fatigue did not change during either day. Finally, the two training weeks preceding the two days of simulated competition were related to anaerobic power but not autonomic nervous system function or fatigue. CrossFit coaches and athletes should be aware of the limited effects of step taper on heart rate variability and fatigue.

Decreased cardiac autonomic activity and increased sympathetic vascular control in advanced stages of amyotrophic lateral sclerosis

To explore the changes in cardiovascular autonomic function in patients with amyotrophic lateral sclerosis (ALS) during disease progression.

The effects of slow deep breathing on microvascular and autonomic function and symptoms in adults with irritable bowel syndrome: A pilot study.

Irritable bowel syndrome (IBS) is linked to disruptions in sympathovagal balance, which could impair vascular homeostasis and cause IBS symptoms. Studies have shown reductions in sympathetic activity following a single slow, deep breathing (SDB) bout in healthy adults; however, no studies have investigated its chronic effects in IBS.The purpose of this study was to evaluate the feasibility and impact of a SDB intervention on microvascular and autonomic function and symptoms in adults with IBS. Fourteen participants (ages 18-65years) with IBS were randomly assigned to 4-week SDB or control conditions. The SDB group completed a 20-min video 5 times weekly while the control group maintained their normal activities. Microvascular endothelial function was measured using laser Doppler in response to thermal provocation and expressed as cutaneous vascular conductance at 39°C relative to a maximum response at 43.5°C (%CVCmax ). Heart rate variability (HRV) and post-exercise heart rate recovery (HRR) were employed as surrogate measures of autonomic function. IBS symptoms were assessed using the IBS-Severity Scale (IBS-SS). Thirteenparticipants (6 controls and 7 SDB) completed the study. Age (p = 0.541) and body mass index (p = 0.157) were similar between groups. In the SDB group, %CVCmax increased from 45% to 59% (p < 0.00001) after the 4-week intervention. HRV, HRR, and IBS-SS scores were unaltered. and Inferences. These results demonstrate the feasibility of a SDB intervention in adults with IBS and suggest improvements in microvascular function in the absence of changes in symptoms or autonomic function in this population.

ПОКАЗАТЕЛИ ТУРБУЛЕНТНОСТИ СЕРДЕЧНОГО РИТМА В КЛИНИЧЕСКОЙ ПРАКТИКЕ

Background. Heart disease is the leading cause of death in developed countries. Approximately half of these fatalities are due to sudden cardiac death. Electrocardiogram recording from the body surface allows stratification of patients according to the risk of cardiac arrest without the use of invasive methods. Arrhythmias, particularly ventricular extrasystole, can affect the sinus rhythm pattern. The change in sinus rhythm that occurs after an extrasystole is defined as heart rate turbulence. This phenomenon is not pathological, but some variants are associated with a risk of fatal arrhythmias. Aim. To analyze the indices and clinical significance of cardiac rhythm turbulence according to Holter monitoring in patients with various cardiological abnormalities at the hospital profile department. Material and methods. The study included 54 patients who were routinely treated in a cardiac hospital. Cardiac rhythm turbulence indices were obtained by Holter monitoring. Patients in severe and moderately severe clinical condition were not included in the study. Concomitant and past somatic diseases affecting the state of heart and cardiovascular system were considered. Results and discussion. Deviations in heart rhythm turbulence indices can be detected both in life- threatening arrhythmias and in benign extrasystoles. They are associated with the influence of the autonomic nervous system, but probably have different mechanisms. Deviations of heart rhythm turbulence indices were associated with left ventricular myocardial hypertrophy of concentric remodeling type and with an increased number of low-risk ventricular extrasystoles. To identify patients with arrhythmias of different risk, various threshold values of cardiac rhythm turbulence indices can be used. Conclusion. Factors likely to affect the indices of cardiac rhythm turbulence such as left ventricular myocardial remodeling and hypertrophy were revealed, as well as changes in autonomic nervous system regulatory function, including those associated with the constitutional features of the patient.

Short-lived sensitization of cardiovascular outcomes of postpartum endotoxemia in preeclamptic rats: Role of medullary solitary tract neuroinflammation

Preeclampsia (PE) is a pregnancy-related disorder with serious maternal complications. Considering the increased importance of postpartum infection in maternal morbidity and mortality, we investigated whether preeclamptic maternal programming alters cardiovascular consequences of endotoxemia in rats and the role of cardiac and brainstem neuroinflammation in this interaction. Preeclampsia was induced by oral administration of L-NAME (50 mg/kg/day) for 7 days starting from day 14 of conception. Changes in blood pressure, heart rate, and cardiac autonomic function caused by lipopolysaccharide (LPS, 5 mg/kg i.v.) were assessed in mothers at 3 weeks (weaning time) and 9 weeks postnatally. Compared with respective non-PE counterparts, LPS treatment of weaning PE mothers caused significantly greater (i) falls in blood pressure, (ii) rises in heart rate and left ventricular contractility (dP/dtmax), (iii) reductions in time and frequency domain indices of heart rate variability and shifts in cardiac sympathovagal balance (low-frequency/high-frequency ratio, LF/HF) towards parasympathetic dominance, and (iv) attenuation of reflex bradycardic responses measured by the vasoactive method. The intensified LPS effects in weaning PE rats subsided after 9 weeks of delivery. Immunohistochemical studies showed increased protein expression of nuclear factor kappa B (NF-κB) in brainstem neuronal pools of the nucleus of the solitary tract (NTS), but not rostral ventrolateral medulla (RVLM), in endotoxic PE weaning rats compared with non-PE rats. Cardiac NF-κB expression was increased by LPS but this was similarly noted in PE and non-PE rats. Together, preeclamptic maternal programming elicits short-term exacerbation of endotoxic cardiovascular and autonomic derangements due possibly to exaggerated NTS neuroinflammatory insult.

Short-term fasting induced changes in HRV are associated with interoceptive accuracy: Evidence from two independent within-subjects studies

Previous research suggested increased cardiac interoceptive accuracy after 24-h food-deprivation by means of the heartbeat tracking task. The present study investigated if 16-h of voluntary fasting shows similar effects and whether changes in interoceptive accuracy are accompanied by changes in autonomic function. In two independent within-subjects studies two measures of interoceptive accuracy, the heartbeat tracking task and the heartbeat discrimination task were applied. In study 1 (n = 24) and study 2 (n = 72) vagally-mediated HRV increases and heart rate decreases were observed. Stronger effects of fasting on vagally-mediated HRV went along with a higher interoceptive accuracy increase in the heartbeat tracking task. Furthermore, the fasting associated changes in interoceptive accuracy in both tasks were significantly associated, suggesting that these tasks are suitable to track changes in cardiac interoception. Taken together, fasting of 16-h might be suitable to increase participants’ parasympathetic efference, thereby facilitating interoception.

Evidence and Challenges in Left Atrial Appendage Management

This review aimed to discuss the anatomical properties of the left atrial appendage (LAA), its relationship with atrial fibrillation (AF), effectiveness of LAA occlusion (LAAO), techniques, and new devices used to perform this procedure. An electronic search was performed to identify studies, in the English language, on LAA management. Searches were performed on PubMed Central, Scopus, and Medline from the dates of database inception to February 2020. For the assessed papers, data were extracted from the reviewed text, tables, and figures, by two independent authors. Anticoagulant therapy for patients with AF has proven beneficial and is highly recommended, but it is challenging for many patients to maintain optimal treatment. Surgery is the most cost-effective option; surgical methods include simple LAA resection, thoracoscopic surgery, and catheter treatment. Each procedure has its advantages and disadvantages, and many prospective studies have been conducted to evaluate various treatment methods. In managing the LAA, dissection of the LAA, such as changes in its shape and size due to remodeling during AF, changes in autonomic nerve function, and thrombosis, must be understood anatomically and physiologically. We believe that early treatment intervention for the LAA should be considered particularly in cases of recurrent AF.Conclusion: SLET under artificial pneumothorax is feasible and safe in minimally invasive McKeown esophagectomy.

Diabetic diarrhoea: A study on gastrointestinal motility, pH levels and autonomic function.

Chronic diarrhoea is a common, but poorly investigated diabetes complication. Autonomic neuropathy is a leading pathophysiological theory founded on old, small studies. Studies of gastrointestinal motility and pH levels are lacking. Using new diagnostic methods, we aimed to find out if diabetic diarrhoea was associated with alterations in gastrointestinal motility, pH levels and autonomic function. Fifty-seven patients (42 women, 46 with type 1 diabetes) were prospectively included. Symptoms were evaluated with the gastrointestinal symptom rating scale, defining ≥4 points as cases with diarrhoea. Patients scoring <4 were used as controls. We used the wireless motility capsule to measure gastrointestinal transit times, pH levels and contractility parameters. Autonomic function was assessed by measuring heart rate variability, baroreflex sensitivity and orthostatic hypotension. Seventeen patients (30%) had diarrhoea. Compared with controls, cases had slower gastric emptying (21:46 vs. 4:14, h:min, p = 0.03) and faster colonic transit (18:37 vs. 54:25, p < 0.001). Cases had increased intraluminal pH in the antrum (2.4 vs. 1.2, p = 0.009), caecum (7.3 vs. 6.4, p = 0.008) and entire colon (7.1 vs. 6.7, p = 0.05). They also had a decreased pH difference across the pylorus (3.3 vs. 4.9, p = 0.004) and ileocaecal junction (0.6 vs 1.0, p = 0.009). The groups did not differ in autonomic function, but diastolic blood pressure drop correlated rs = -0.34 (p = 0.04) with colonic transit time. Patients with diabetic diarrhoea had altered gastrointestinal transit and intraluminal pH levels, but minimal changes in autonomic function. Our results suggest that tests of gastrointestinal function are clinically useful in diabetic diarrhoea.

The novel approach of temporal dependency complexity analysis of heart rate variability in obstructive sleep apnea

Obstructive sleep apnea (OSA) is a serious sleep disorder, which leads to changes in autonomic nerve function and increases the risk of cardiovascular disease. Heart rate variability (HRV) has been widely used as a non-invasive method for assessing the autonomic nervous system (ANS). We proposed the two-dimensional sample entropy of the coarse-grained Gramian angular summation field image (CgSampEn2D) index. It is a new index for HRV analysis based on the temporal dependency complexity. In this study, we used 60 electrocardiogram (ECG) records from the Apnea-ECG database of PhysioNet (20 healthy records and 40 OSA records). These records were divided into 5-min segments. Compared with the classical indices low-to-high frequency power ratio (LF/HF) and sample entropy (SampEn), CgSampEn2D utilizes the correlation information between different time intervals in the RR sequences and preserves the temporal dependency of the RR sequences, which improves the OSA detection performance significantly. The OSA screening accuracy of CgSampEn2D (93.3%) is higher than that of LF/HF (80.0%) and SampEn (73.3%). Additionally, CgSampEn2D has a significant association with the apnea-hypopnea index (AHI) (R = −0.740, p = 0). CgSampEn2D reflects the complexity of the OSA autonomic nerve more comprehensively and provides a novel idea for the screening of OSA disease.

Sleep, Cognition, and Yoga.

Stress is one of the major problems globally, associated with poor sleep quality and cognitive dysfunction. Modern society is plagued by sleep disturbances, either due to professional demands or lifestyle or both the aspects, often leading to reduced alertness and compromised mental function, besides the well documented ill effects of disturbed sleep on physiological functions. This pertinent issue needs to be addressed. Yoga is an ancient Indian science, philosophy and way of life. Recently, yoga practice has become increasingly popular worldwide. Yoga practice is an adjunct effective for stress, sleep and associated disorders. There are limited well controlled published studies conducted in this area. We reviewed the available literature including the effect of modern lifestyle in children, adolescents, adults and geriatric population. The role of yoga and meditation in optimizing sleep architecture and cognitive functions leading to optimal brain functioning in normal and diseased state is discussed. We included articles published in English with no fixed time duration for literature search. Literature was searched mainly by using PubMed and Science Direct search engines and critically examined. Studies have revealed positive effects of yoga on sleep and cognitive skills among healthy adults as well as patients of some neurological diseases. Further, on evaluating the published studies, it is concluded that sleep and cognitive functions are optimized by yoga practice, which brings about changes in autonomic function, structural changes, changes in metabolism, neurochemistry and improved functional brain network connectivity in key regions of the brain.

Emotional Behavioural and Autonomic Dysregulation (EBAD) in Rett Syndrome – EDA and HRV monitoring using wearable sensor technology

BackgroundRett syndrome (RTT) is a severe genetic neurodevelopmental disorder. Emotional, Behavioural and Autonomic Dysregulation (EBAD), is frequent in RTT and is associated with multiple impairments. There are major challenges in the clinical assessment of emotions, behaviours, and autonomic function in RTT patients that limit the management of symptoms. MethodsWeb-based technology (HealthTracker™) to measure the phenotype, and non-invasive, wearable sensor technology to evaluate autonomic function through Electrodermal Activity (EDA) and Heart Rate Variability (HRV) in 10 RTT patients was used, and treatment response of EBAD symptoms was monitored after different pharmacological treatments. Resultsand discussion: 4 patients received buspirone, 2 sertraline, 1 gabapentin and 3 were not started on medications. Buspirone normalized the EDA in 3 patients with associated improvement in EBAD, whilst another patient only improved marginally. Both patients treated with sertraline (including one with normal EDA) significantly improved symptomatically. The patients on unchanged regimens showed no change in symptoms and autonomic function. Within 24 h of our assessment, one patient required intensive inpatient care due to septicaemia – this patient had been on gabapentin and showed a sharp and sustained EDA increase without obvious worsening of emotional and behavioural symptoms. Unlike the EDA, the analyses of HRV metrics did not reveal patterns that were associated with clinical outcomes. Our findings suggest a reasonable association of EDA normalization and symptomatic improvement in RTT subjects with EBAD treated with buspirone and point out its potential application as a measure of dysautonomia in RTT. Very high and sustained EDA levels may be a biomarker for concurrent serious physical illness in RTT.

Relationship between Cardiopulmonary, Mitochondrial and Autonomic Nervous System Function Improvement after an Individualised Activity Programme upon Chronic Fatigue Syndrome Patients.

Background: The therapeutic effects of exercise from structured activity programmes have recently been questioned; as a result, this study examines the impact of an Individualised Activity Program (IAP) on the relationship with cardiovascular, mitochondrial and fatigue parameters. Methods: Chronic fatigue syndrome (CFS) patients were assessed using Chalder Fatigue Questionnaire (CFQ), Fatigue Severity Score (FSS) and the Fatigue Impact Scale (FIS). VO2peak, VO2submax and heart rate (HR) were assessed using cardiopulmonary exercise testing. Mfn1 and Mfn2 levels in plasma were assessed. A Task Force Monitor was used to assess ANS functioning in supine rest and in response to the Head-Up Tilt Test (HUTT). Results: Thirty-four patients completed 16 weeks of the IAP. The CFQ, FSS and FIS scores decreased significantly along with a significant increase in Mfn1 and Mfn2 levels (p = 0.002 and p = 0.00005, respectively). The relationships between VO2 peak and Mfn1 increase in response to IAP (p = 0.03) and between VO2 at anaerobic threshold and ANS response to the HUTT (p = 0.03) were noted. Conclusions: It is concluded that IAP reduces fatigue and improves functional performance along with changes in autonomic and mitochondrial function. However, caution must be applied as exercise was not well tolerated by 51% of patients.