Clinical Autonomic Research Research Articles

EFAS/EAN survey on the influence of the COVID-19 pandemic on European clinical autonomic education and research

PurposeTo understand the influence of the coronavirus disease 2019 (COVID-19) pandemic on clinical autonomic education and research in Europe.MethodsWe invited 84 European autonomic centers to complete an online survey, recorded the pre-pandemic-to-pandemic percentage of junior participants in the annual congresses of the European Federation of Autonomic Societies (EFAS) and European Academy of Neurology (EAN) and the pre-pandemic-to-pandemic number of PubMed publications on neurological disorders.ResultsForty-six centers answered the survey (55%). Twenty-nine centers were involved in clinical autonomic education and experienced pandemic-related didactic interruptions for 9 (5; 9) months. Ninety percent (n = 26/29) of autonomic educational centers reported a negative impact of the COVID-19 pandemic on education quality, and 93% (n = 27/29) established e-learning models. Both the 2020 joint EAN–EFAS virtual congress and the 2021 (virtual) and 2022 (hybrid) EFAS and EAN congresses marked higher percentages of junior participants than in 2019. Forty-one respondents (89%) were autonomic researchers, and 29 of them reported pandemic-related trial interruptions for 5 (2; 9) months. Since the pandemic begin, almost half of the respondents had less time for scientific writing. Likewise, the number of PubMed publications on autonomic topics showed the smallest increase compared with other neurological fields in 2020–2021 and the highest drop in 2022. Autonomic research centers that amended their trial protocols for telemedicine (38%, n = 16/41) maintained higher clinical caseloads during the first pandemic year.ConclusionsThe COVID-19 pandemic had a substantial negative impact on European clinical autonomic education and research. At the same time, it promoted digitalization, favoring more equitable access to autonomic education and improved trial design.

Toward a Biomarker Panel measured in CNS-originating Extracellular Vesicles for Differential Diagnosis of Parkinson’s Disease and Multiple System Atrophy (S37.005)

Toward a Biomarker Panel measured in CNS-originating Extracellular Vesicles for Differential Diagnosis of Parkinson’s Disease and Multiple System Atrophy (S37.005)

Brain-heart interaction in perseverative cognition.

The move from the concept of homeostasis to that of allostasis has led reactivity stress research to widen the object of its investigation: from the brief physiological response that occurs when one is facing a stressor to what happens when one is anticipating or recovering from a stressor. A paradigmatic example is represented by perseverative cognition, during which human beings react "as if" they were constantly facing a concrete stressor. The core idea behind this review is that the cognitive inflexibility that characterizes perseverative cognition is reflected in both our body (by increased autonomic nervous system rigidity assessed by heart rate variability; HRV) and our brain (by reduced prefrontal-amygdala functional connectivity). This is a review of studies conducted in different settings (laboratory, daily life), populations (healthy, major depression, generalized anxiety), location (United States, Europe), and age groups (children, adults) that consistently replicated the association between autonomic, subjective, and behavioral measures of cognitive inflexibility during perseverative cognition. Moreover, compelling neuroimaging data suggest that HRV reduction from pre- to post-induction of perseverative cognition is associated with both structural and functional brain abnormalities reflecting impaired prefrontal inhibitory control over subcortical structures (e.g., diminished prefrontal-amygdala functional connectivity). The integration of neuroscience techniques with clinical autonomic research has advanced our understanding of the neurobiology of brain-heart interaction during perseverative cognition, potentially yielding to more effective treatment packages. This is clinically relevant if one considers that perseverative cognition is a pervasive transdiagnostic factor that carries prognostic risk for both psychological and somatic health.

Clinical autonomic research: carrying on the torch

Clinical autonomic research: carrying on the torch

Cardiac Dysautonomia in Huntington's Disease.

Huntington's disease is a fatal, hereditary, neurodegenerative disorder best known for its clinical triad of progressive motor impairment, cognitive deficits and psychiatric disturbances. Although a disease of the central nervous system, mortality surveys indicate that heart disease is a leading cause of death. The nature of such cardiac abnormalities remains unknown. Clinical findings indicate a high prevalence of autonomic nervous system dysfunction - dysautonomia - which may be a result of pathology of the central autonomic network. Dysautonomia can have profound effects on cardiac health, and pronounced autonomic dysfunction can be associated with neurogenic arrhythmias and sudden cardiac death. Significant advances in the knowledge of neural mechanisms in cardiac disease have recently been made which further aid our understanding of cardiac mortality in Huntington's disease. Even so, despite the evidence of aberrant autonomic activity the potential cardiac consequences of autonomic dysfunction have been somewhat ignored. In fact, underlying cardiac abnormalities such as arrhythmias have been part of the exclusion criteria in clinical autonomic Huntington's disease research. A comprehensive analysis of cardiac function in Huntington's disease patients is warranted. Further experimental and clinical studies are needed to clarify how the autonomic nervous system is controlled and regulated in higher, central areas of the brain - and how these regions may be altered in neurological pathology, such as Huntington's disease. Ultimately, research will hopefully result in an improvement of management with the aim of preventing early death in Huntington's disease from cardiac causes.

Afferent baroreflex failure and tako-tsubo cardiomyopathy

Tako-tsubo is a Japanese fisherman’s octopus trapping pot. The word has become popular to describe a type of cardiomyopathy in which the left ventricle of the heart transiently balloons at the apex and mid portions and, with a little imagination, looks like a tako-tsubo [1]. Variant forms of transient left ventricular dysfunction in which the apex is not affected have also been described [2]. Additional names for this clinical syndrome are transient left ventricular dysfunction syndrome, stress cardiomyopathy or apical ballooning cardiomyopathy. Patients present similarly to those with myocardial infarction, typically with chest pain and dyspnea and with findings on electrocardiography which are characteristic of myocardial infarction such as ST segment elevation and T wave inversion [3–5]. However, elevation of cardiac biomarkers such as troponin is modest and, in addition, the coronary arteries show no flow-limiting stenosis on conventional angiography [3]. Tako-tsubo cardiomyopathy resolves spontaneously and nearly all patients completely recover within a few weeks [6]. Thus, tako-tsubo cardiomyopathy may be considered to represent myocardial ‘‘stunning’’ rather than a permanent injury. What is so special about this peculiar ballooning of the heart? First, it affects women much more often than men, and perhaps most intriguingly, it occurs frequently after a catastrophic emotional stress, such as an earthquake [7] or the unexpected death of a close friend or relative [3, 4]. Of course, events that occur after emotionally charged situations are always suspected to be caused by high levels of catecholamines, both norepinephrine, the neurotransmitter of the sympathetic nervous system, and epinephrine, the hormone that classically increases with stress. Indeed, patients with tako-tsubo cardiomyopathy have a 30-fold increase in their plasma levels of norepinephrine and epinephrine, which is substantially higher than the increase seen in patients with acute myocardial infarction [4]. Moreover, cases of tako-tsubo cardiomyopathy have been reported following intravenous infusion of epinephrine [8] or norephinephrine [9] as well as in patients with pheochromocytoma who have endogenous catecholamine surges [10–12]. Furthermore, microscopic analysis of myocardium in patients with tako-tsubo syndrome may show contraction band necrosis and focal inflammatory infiltrates, as seen in syndromes of catecholamine excess [13]. Recently, analysis of endomyocardial biopsies taken from patients who have tako-tsubo cardiomyopathy has shown alteration in expression of the sarcoplasmic reticulum calcium ATPase and dephosphorylation of phospholamban, changes which suggest overstimulation of myocardial beta adrenoceptors in this syndrome [14]. In this issue of clinical autonomic research Berganzo et al. suggest a possible link between afferent baroreflex dysfunction and tako-tsubo cardiomyopathy. This is not surprising. Normally, increases in sympathetic activity are restrained by the baroreflexes, which are classic negative feedback loops. Afferent baroreflex dysfunction (also called baroreflex failure to distinguish it from autonomic efferent failure) is a neuro-visceral disorder that selectively affects the relay of afferent baroreceptor information from the carotid sinus and aortic arch to the nucleus tractus solitarius (NTS) in the brainstem [15–17]. In patients with L. J. Norcliffe-Kaufmann (&) Department of Physiology and Neuroscience, New York University School of Medicine, New York, NY, USA e-mail: lucynorcliffe@gmail.com

Blood Pressure Variability

A series of articles1–4⇓⇓⇓ published recently in The Lancet and Lancet Neurology raise an interesting issue that has implications for both the clinical management of hypertension and future research in hypertension, particularly in the development and use of different classes of blood pressure (BP)–lowering drugs. These studies, which were led by Peter Rothwell at the John Radcliffe Hospital in Oxford, United Kingdom, suggest that, whereas there is undoubted and well-proven benefit in the current practice of reducing mean BP to prevent cardiovascular events, there may be additional benefit in also reducing BP variability (BPV), especially to prevent stroke. The studies suggest, moreover, that different classes of drugs are superior to others in reducing BPV (calcium channel blockers being best and the β-blocker atenolol being worst). However, these articles, by virtue of their sheer volume (≈50 pages of printed text and many pages of supplementary web appendix data), could overwhelm all but the most stoic readers, and misinterpretation of the data could lead to confusion and have an adverse effect on clinical practice. It is important, therefore, to assess the scientific reality and determine how attention to BPV might benefit patients with hypertension. In the first analysis, systolic BPV between visits and maximum BP reached in 4 cohorts of patients with previous transient ischemic attacks were strong predictors for subsequent stroke.1 In treated hypertensive patients in the Anglo-Scandinavian Cardiac Outcome Trial-Blood Pressure Lowering Arm systolic BPV between visits was also a strong predictor of stroke and coronary events independent of mean clinic or ambulatory BP measurement (ABPM). BPV on ABPM was a weaker predictor overall but was related to visit-to-visit variability. Traditional measures of variability, such as SD and coefficient of variation (CV), were used in these analyses, but one of the problems encountered in the …

CIH: from sleep apnea to breath-hold diving

Recurrent apneas associated with sleep-disordered breathing increase sympathetic nerve activity and arterial blood pressure, and enhance sympathetic and ventilatory responses to acute hypoxia [14, 19]. Chronic intermittent hypoxia (CIH) and activation of arterial carotid body chemoreceptors are primarily responsible for driving the increase in sympathetic activity [4, 17]. The excessive sympathetic activity and hypertension are sustained and contribute to high morbidity and mortality in afflicted patients [15, 19]. Certain recreational and vocational activities involve episodes of volitional apnea. One example is underwater breath-hold diving. In this issue of Clinical Autonomic Research, Breskovic and colleagues [1] address the question: Do elite breath-hold divers exhibit exaggerated increases in muscle sympathetic nerve activity (MSNA) and ventilation during exposure to acute hypoxia? Such a finding would raise concern that the CIH imposed by these types of activities may increase cardiovascular risk in otherwise healthy individuals. The investigators measured arterial oxygen saturation, ventilation, MSNA, blood pressure, heart rate and stroke volume in elite divers and healthy control subjects at baseline (while breathing room air) and during progressive isocapnic hypoxia [1]. Resting blood pressure and MSNA were not significantly different in divers versus control subjects. Furthermore, hypoxia-induced increases in ventilation and MSNA were also not different between the groups. While good news for the divers, these negative results raise several important questions.

Postural Tachycardia Syndrome

When a person stands up, he or she assumes that the body will automatically make any changes necessary to compensate for the increased gravitational stress this change of position brings. Indeed, standing causes gravity to try to pull nearly one quarter of the body’s blood downward toward the lower arms, legs, and abdomen, reducing the amount of blood available to keep the brain supplied with oxygen. To maintain a constant oxygen supply to the brain and upper body, standing is normally accompanied by an automatic increase in heart rate and the force with which the heart contracts and, most important, a tightening of the blood vessels in the lower part of the body. The combination of these 3 actions pushes blood upward against the force of gravity, thereby maintaining an uninterrupted flow of blood to the brain. The aspect of the nervous system that governs these …

Mechanisms of vasoconstriction with direct skin cooling in humans

direct skin cooling causes a vasoconstriction partly dependent on α2-adrenergic function. In in vitro studies, this is a manifestation of reactive oxygen species stimulating Rho and Rho kinase to cause translocation of α2C-receptors from the Golgi to the plasma membrane. In this issue of American

COUNTERPOINT: ACTIVE VENOCONSTRICTION IS NOT IMPORTANT IN MAINTAINING OR RAISING END-DIASTOLIC VOLUME AND STROKE VOLUME DURING EXERCISE AND ORTHOSTASIS

Veins were considered merely as passive conduits of blood until Mellander ([13][1]) reported that stimulation of sympathetic nerves supplying the cat's hindquarters resulted in a decrease in regional blood volume. This and other work led Folkow and Mellander ([4][2]) to assert that veins were “at

Vasovagal fainting as an evolutionary remnant of the fight against hemorrhage

Major bleeding is one of the most frequently occurring medical conditions that require the attention of physicians and surgeons. The most frequent causes of major bleeding in most hospitals are trauma, peri-operative bleeding (which can in fact be viewed as a variant of trauma), gastro-intestinal disease, and bleeding due to the use of anticoagulant agents [6]. Severe hemorrhage leads to an insufficient circulation and an inadequate supply of oxygen to tissue. Patients with serious bleeding often present with circulatory shock and collapse. Impaired brain perfusion and subsequent syncope seems an understandable sequence of events following a severe drop in systemic blood pressure as a consequence of acute blood loss. However, it is intriguing to speculate whether syncope may not only be a logical consequence of major hemorrhage but can rather be viewed as a response with distinct protective effects for the organism and as such has been carefully preserved as a beneficial mechanism throughout the evolution. In this issue of Clinical Autonomic Research, Dr. Diehl proposes an interesting explanation for the occurrence of vasovagal syncope, as a mechanism that was originally developed as a protective strategy against exsanguination upon major bleeding in mammals [3]. Dr. Diehl hypothesizes that low blood pressure and bradycardia that is associated with vasovagal syncope is beneficial for the organism that is threatened by ongoing major blood loss,when the initial physiological and compensatory responses, such as vasoconstriction and tachycardia, have failed. Indeed, a low blood pressure is likely to result in reduced blood loss during major hemorrhage and clinical studies indeed suggest that to strive for normalization of blood pressure in patients with trauma and serious bleeding by large volume intravenous infusion may do more harm than good [7]. Based on this notion, strategies that employ permissive hypotension awaiting further medical intervention are currently being investigated [8]. Dr. Diehl’s hypothesis is interesting and thought-provoking and is indeed supported by various physiological and clinical observations. As the author himself indicates, the hypothesis can be challenged by experimental studies in bleeding animals. In addition to this, we must also identify a mechanism by which fainting would not only be beneficial to slow the rate of bleeding but may be helpful in arresting the blood loss. The answer to this question may be found in the response of the coagulation system to circulatory collapse. Fainting leads to an immediate and marked increase in von Willebrand factor (and associated factor VIII), presumably due to release from Weibel Palade bodies in endothelial cells of the vessel wall [2]. Interestingly, post-fainting blood not only has a four-fold higher concentration of von Willebrand factor, but also the released von Willebrand factor occurs in unusually large multimers, which are known to be hemostatically much more potent than normal von Willebrand factor multimers. Under normal circumstances the constitutive release of large von Willebrand factor multimers is followed by enzymatic degradation by the von Willebrand factor cleaving protease (ADAMTS-13) [9]. It may be hypothesized that the immediate release of large amounts of von Willebrand factor as induced by fainting does not allow this cleaving protease to act properly, leaving the large multimers for C A R 52 M. Levi, MD ( ) Dept. Internal Medicine (F-4) Academic Medical Centre University of Amsterdam Meibergdreef 9 1105 AZ Amsterdam, The Netherlands Tel.: +31-20/5662171 Fax: +31-20/6919658 E-Mail: m.m.levi@amc.uva.nl

Annual Meeting of the Clinical Autonomic Research Society

Annual Meeting of the Clinical Autonomic Research Society

Annual Meeting of the Clinical Autonomic Research Society

Annual Meeting of the Clinical Autonomic Research Society

The neuranatomical basis of central control of cardiorespiratory interactions in vertebrates.

The neuranatomical basis of central control of cardiorespiratory interactions in vertebrates.

Clinical Autonomic Research Society and European Federation of Autonomic Societies Joint Meeting

Clinical Autonomic Research Society and European Federation of Autonomic Societies Joint Meeting

Clinical autonomic research in the new millennium

Clinical autonomic research in the new millennium

Clinical Autonomic Research Society—18th Annual Meeting

Clinical Autonomic Research Society—18th Annual Meeting

16th Annual Scientific Meeting of the Clinical Autonomic Research Society and the Inaugural Meeting of the European Federation of Autonomic Societies

16th Annual Scientific Meeting of the Clinical Autonomic Research Society and the Inaugural Meeting of the European Federation of Autonomic Societies

15th Annual Scientific Meeting of the Clinical Autonomic Research Society

15th Annual Scientific Meeting of the Clinical Autonomic Research Society