Psychogenic Pseudosyncope: Real or Imaginary? Results from a Case-Control Study in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Patients

Background and objectives: Orthostatic intolerance (OI) is a clinical condition in which symptoms worsen upon assuming and maintaining upright posture and are ameliorated by recumbency. OI has a high prevalence in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Exact numbers on syncopal spells especially if they are on a weekly or even daily basis are not described. Although not a frequent phenomenon, this symptomatology is of very high burden to the patient if present. To explore whether patients with very frequent (pre)syncope spells diagnosed elsewhere with conversion or psychogenic pseudosyncope (PPS) might have another explanation of their fainting spells than behavioral psychiatric disorders, we performed a case–control study comparing ME/CFS patients with and without PPS spells. Methods and results: We performed a case–control study in 30 ME/CFS patients diagnosed elsewhere with PPS and compared them with 30 control ME/CFS patients without syncopal spells. Cases were gender, age and ME/CFS disease duration matched. Each underwent a tilt test with extracranial Doppler measurements for cerebral blood flow (CBF). ME/CFS cases with PPS had a significant larger CBF reduction at end tilt than controls: 39 (6)% vs. 25 (4)%; (p < 0.0001). Cases had more severe disease compared with controls (chi-square p < 0.01 and had a p = 0.01) for more postural orthostatic tachycardia syndrome in cases compared with controls. PETCO2 end-tilt differed also, but the magnitude of difference was smaller than compared with the CBF reduction: there were no differences in heart rate and blood pressure at either end-tilt testing period. Compared with the test with the stockings off, the mean percentage reduction in cardiac output during the test with compression stockings on was lower, 25 (5) mmHg versus 29 (4) mmHg (p < 0.005). Conclusions: This study demonstrates that in ME/CFS patients suspected of having PPS, or conversion, CBF measurements end-tilt show a large decline compared with a control group of ME/CFS patients. Therefore, hypoperfusion offers an explanation of the orthostatic intolerance and syncopal spells in these patients, where it is clear that origin might not be behavioral or psychogenic, but have a clear somatic pathophysiologic background.

A case report of severe cardioinhibitory reflex syncope associated with COVID-19

Background Coronavirus disease 2019 (COVID-19) has been recognised as a disease with a broad spectrum of clinical manifestations. In this report we illustrate an extraordinary case of severe cardioinhibitory reflex syncope with prolonged asystole associated with COVID-19. Case summary A 35-year-old male patient presented to the emergency department with a ten-day history of postural syncope and fever. ECG monitoring during positional change revealed reflex syncope with cardioinhibitory response, exhibiting sinus bradycardia, subsequent asystole and transient loss of consciousness (TLOC). The patient tested positive for severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and was admitted to the ICU where temporary transvenous pacing was necessary because of prolonged episodes of asystole. Work-up included extensive cardiac and neurological diagnostic testing, but did not yield any structural abnormalities. Although temporary pacing was able to abort syncope, a decision was made to hold off on permanent pacing as the most likely aetiology was felt to be temporary cardioinhibitory reflex syncope associated with COVID-19. The patient was discharged with mild symptoms of orthostatic intolerance and responded well to education and lifestyle modification. Outpatient follow-up with repeat tilt testing after three and six months initially showed residual inducible syncope but was eventually normal and the patient remained asymptomatic. Discussion We believe that autonomic imbalance with a strong vagal activation due to acute SARS-CoV-2 infection played a pivotal role in the occurrence of transient syncope in this patient’s condition. Although pacemaker implantation would have been a reasonable alternative, a watch-and-wait approach should be considered in similar instances.

Compression Stockings Improve Cardiac Output and Cerebral Blood Flow during Tilt Testing in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Patients: A Randomized Crossover Trial

Background and Objectives: Orthostatic intolerance (OI) is a clinical condition in which symptoms worsen upon assuming and maintaining upright posture and are ameliorated by recumbency. OI has a high prevalence in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Limited data are available to guide the treatment of OI in ME/CFS patients. We and others have previously described patient-reported subjective improvement in symptoms using compression stockings. We hypothesized that these subjective reports would be accompanied by objective hemodynamic improvements. Materials and Methods: We performed a randomized crossover trial in 16 ME/CFS patients. Each underwent two 15-min head-up tilt table tests, one with and one without wearing knee-high compression stockings that provided 20–25 mm Hg compression. The order of the tests was randomized. We measured heart rate and blood pressure as well as cardiac output and cerebral blood flow (CBF) using extracranial Doppler of the internal carotid and vertebral arteries. Results: There were no differences in supine measurements between the 2 baseline measurements. There were no differences in heart rate and blood pressure at either end-tilt testing period. Compared to the test with the stockings off, the mean percentage reduction in cardiac output during the test with compression stockings on was lower, 15 (4)% versus 27 (6)% (p < 0.0001), as was the mean percentage CBF reduction, 14 (4)% versus 25 (5)% (p < 0.0001). Conclusion: In ME/CFS patients with orthostatic intolerance symptoms, cardiac output and CBF are significantly reduced during a tilt test. These abnormalities were present without demonstrable heart rate and blood pressure changes and were ameliorated by the use of compression stockings.

The Cardiovascular System in Space: Focus on In Vivo and In Vitro Studies

On Earth, humans are subjected to a gravitational force that has been an important determinant in human evolution and function. During spaceflight, astronauts are subjected to several hazards including a prolonged state of microgravity that induces a myriad of physiological adaptations leading to orthostatic intolerance. This review summarises all known cardiovascular diseases related to human spaceflight and focusses on the cardiovascular changes related to human spaceflight (in vivo) as well as cellular and molecular changes (in vitro). Upon entering microgravity, cephalad fluid shift occurs and increases the stroke volume (35–46%) and cardiac output (18–41%). Despite this increase, astronauts enter a state of hypovolemia (10–15% decrease in blood volume). The absence of orthostatic pressure and a decrease in arterial pressures reduces the workload of the heart and is believed to be the underlying mechanism for the development of cardiac atrophy in space. Cellular and molecular changes include altered cell shape and endothelial dysfunction through suppressed cellular proliferation as well as increased cell apoptosis and oxidative stress. Human spaceflight is associated with several cardiovascular risk factors. Through the use of microgravity platforms, multiple physiological changes can be studied and stimulate the development of appropriate tools and countermeasures for future human spaceflight missions in low Earth orbit and beyond.

Development of a Telehealth Examination for Sport-Related Concussion in the Outpatient Setting

ObjectiveTo develop a brief, focused telehealth physical examination for use in the outpatient setting by sports medicine physicians, pediatricians, neurologists, and primary care physicians.BackgroundTelemedicine has become a key resource for addressing healthcare access limitations for individuals living in rural communities. The COVID-19 pandemic has forced physicians and other healthcare providers to adopt telemedicine practices. Published literature guiding the evaluation of patients with concussion via telemedicine is sparse.Design/MethodsThe Buffalo Concussion Physical Examination (BCPE) is a practical and pertinent clinical assessment that helps to diagnose concussion and that has prognostic value when repeated over the first weeks after injury. An interdisciplinary team with experience in telemedicine services utilized a modified-Glaser approach to consensus to translate elements of the BCPE into virtual methods enabling clinicians to provide care to patients over the internet.ResultsThe Telehealth version of the BCPE (Tele-BCPE) includes an orthostatic intolerance screen, examination of the cranial nerves, and tests of the oculomotor, vestibular and cervical systems. History and examination templates as well as detailed instructions for performance are included. The Tele-BCPE is meant to be used at initial and follow-up visits for patients acutely after concussion as well as in those with prolonged symptoms.ConclusionsWe developed a telehealth physical examination to help direct treatment to patients at any stage after concussion and reduce barriers to healthcare access posed by the COVID-19 pandemic and for patients living in rural or underserved areas. Prospective evaluation of the validity and reliability of the Tele-BCPE for the diagnosis and management of patients with concussion is warranted.

A novel methodology for the synchronous collection and multimodal visualisation of continuous neurocardiovascular and neuromuscular physiological data in adults with long COVID

Reports suggest that adults with post-COVID-19 syndrome or long COVID may be affected by orthostatic intolerance syndromes, with autonomic nervous system dysfunction as a possible causal factor of neurocardiovascular instability (NCVI). Long COVID can also manifest as prolonged fatigue, which may be linked to neuromuscular function impairment (NMFI). The current clinical assessment for NCVI monitors neurocardiovascular performance upon the application of orthostatic stressors such as an active (i.e. self-induced) stand or a passive (tilt table) standing test. Lower limb muscle contractions may be important in orthostatic recovery via the skeletal muscle pump. In this study, adults with long COVID were assessed with a protocol that, in addition to the standard NCVI tests, incorporated simultaneous lower limb muscle monitoring for NMFI assessment. To accomplish such an investigation, a wide range of continuous non-invasive biomedical technologies were employed, including digital artery photoplethysmography for the extraction of cardiovascular signals, near-infrared spectroscopy for the extraction of regional tissue oxygenation in brain and muscle, and electromyography for assessment of timed muscle contractions in the lower limbs. With the novel technique described and exemplified in this paper, we were able to integrate signals from all instruments used in the assessment in a precisely synchronized fashion. We demonstrate that it is possible to visualize the interactions between all different physiological signals during the combined NCVI/NMFI assessment. Multiple counts of evidence were collected, which can capture the dynamics between skeletal muscle contractions and neurocardiovascular responses. The proposed multimodal data visualization can offer an overview of the functioning of the muscle pump during both supine rest and orthostatic recovery and can conduct comparison studies with signals from multiple participants at any given time in the assessment. This could help researchers and clinicians generate and test hypotheses based on the multimodal inspection of raw data, in long COVID and other clinical cohorts.

Relationships Between Cardiovascular Autonomic Profile and Work Ability in Patients With Pure Autonomic Failure

Pure autonomic failure (PAF) is a rare disorder belonging to the group of synucleinopathies, characterized by autonomic nervous system degeneration. Severe orthostatic intolerance with recurrent syncope while standing are the two most disabling manifestations. Symptoms may start at middle age, thus affecting people at their working age. The aims of this study were to evaluate the autonomic and work ability impairment of a group of PAF patients and assess the relationships between cardiovascular autonomic control and work ability in these patients. Eleven PAF patients (age 57.3 ± 6.7 years), engaged in work activity, participated in the study. They completed the Composite Autonomic Symptom Score (COMPASS-31, range 0 no symptom-100 maximum symptom intensity) and Work Ability questionnaires (Work Ability Index, WAI, range 7–49; higher values indicate better work ability and lower values indicating unsatisfactory or jeopardized work ability). Electrocardiogram, blood pressure and respiratory activity were continuously recorded for 10 min while supine and during 75° head-up tilt (HUT). Autoregressive spectral analysis of cardiac cycle length approximated as the time distance between two consecutive R-wave peaks (RR) and systolic arterial pressure (SAP) variabilities provided the power in the high frequency (HF, 0.15–0.40 Hz) and low frequency (LF, 0.04–0.15 Hz) bands of RR and SAP variabilities. Cardiac sympatho-vagal interaction was assessed by LF to HF ratio (LF/HF), while the LF power of SAP (LFSAP) quantified the vascular sympathetic modulation. Changes in cardiovascular autonomic indexes induced by HUT were calculated as the delta (Δ) between HUT and supine resting positions. Spearman correlation analysis was applied. PAF patients were characterized by a moderate autonomic dysfunction (COMPASS-31 total score 47.08 ± 20.2) and by a reduction of work ability (WAI 26.88 ± 10.72). Direct significant correlations were found between WAI and ΔLFRR (r = 0.66, p = 0.03) and ΔLF/HFRR (r = 0.70, p = 0.02). Results indicate that patients who were better able to modulate heart rate, as revealed by a greater cardiac sympathetic increase and/or vagal withdrawal during the orthostatic stimulus, were those who reported higher values of WAI. This finding could be relevant to propose new strategies in the occupational environment to prevent early retirement or to extend the working life of these patients.

Orthostatic intolerance in adults with long COVID was not associated with postural orthostatic tachycardia syndrome

In this observational cross-sectional study, we investigated predictors of orthostatic intolerance (OI) in adults with long COVID. Participants underwent a 3-minute active stand (AS) with Finapres NOVA, followed by a 10-minute unmedicated 70-degree head-up tilt test. 85 participants were included (mean age 46 years, range 25-78; 74% women), of which 56 (66%) reported OI during AS (OIAS). OIAS seemed associated with female sex, more fatigue and depressive symptoms, and greater inability to perform activities of daily living (ADL), as well as a higher heart rate (HR) at the lowest systolic blood pressure (SBP) point before the 1st minute post-stand (mean HRnadir: 88 vs 75 bpm, P=0.004). In a regression model also including age, sex, fatigue, depression, ADL inability, and peak HR after the nadir SBP, HRnadir was the only OIAS predictor (OR=1.09, 95% CI: 1.01-1.18, P=0.027). 22 participants had initial (iOH) and 5 classical (cOH) orthostatic hypotension, but neither correlated with OIAS. 71 participants proceeded to tilt, of which 28 had OI during tilt (OItilt). Of the 53 who had a 10-minute tilt, 7 (13%) fulfilled hemodynamic postural orthostatic tachycardia syndrome (POTS) criteria, but 6 did not report OItilt. OIAS was associated with a higher initial HR on AS, which after 1 minute equalized with the non-OIAS group. Despite these initial orthostatic HR differences, POTS was infrequent and largely asymptomatic. ClinicalTrials.gov Identifier: NCT05027724 (retrospectively registered on August 30, 2021).

Central Hypovolemia Detection During Environmental Stress—A Role for Artificial Intelligence?

The first step to exercise is preceded by the required assumption of the upright body position, which itself involves physical activity. The gravitational displacement of blood from the chest to the lower parts of the body elicits a fall in central blood volume (CBV), which corresponds to the fraction of thoracic blood volume directly available to the left ventricle. The reduction in CBV and stroke volume (SV) in response to postural stress, post-exercise, or to blood loss results in reduced left ventricular filling, which may manifest as orthostatic intolerance. When termination of exercise removes the leg muscle pump function, CBV is no longer maintained. The resulting imbalance between a reduced cardiac output (CO) and a still enhanced peripheral vascular conductance may provoke post-exercise hypotension (PEH). Instruments that quantify CBV are not readily available and to express which magnitude of the CBV in a healthy subject should remains difficult. In the physiological laboratory, the CBV can be modified by making use of postural stressors, such as lower body “negative” or sub-atmospheric pressure (LBNP) or passive head-up tilt (HUT), while quantifying relevant biomedical parameters of blood flow and oxygenation. Several approaches, such as wearable sensors and advanced machine-learning techniques, have been followed in an attempt to improve methodologies for better prediction of outcomes and to guide treatment in civil patients and on the battlefield. In the recent decade, efforts have been made to develop algorithms and apply artificial intelligence (AI) in the field of hemodynamic monitoring. Advances in quantifying and monitoring CBV during environmental stress from exercise to hemorrhage and understanding the analogy between postural stress and central hypovolemia during anesthesia offer great relevance for healthy subjects and clinical populations.

Dysautonomia Following Tetanus, Diphtheria, and Pertussis Vaccine (Tdap): The First Case of Extreme Cachexia Caused by Autoimmune/Inflammatory Syndrome Induced by Adjuvants (ASIA Syndrome) in a Human

Autoimmune/inflammatory Syndrome Induced by Adjuvants (ASIA; Shoenfeld’s syndrome) comprehends a group of autoimmune conditions that flourish in genetically predisposed individuals, following an external stimulus by the so-called adjuvants. Many adjuvants were described, such as vaccines, aluminum and other metals, silicone, tattoos, among others. Those conditions entail defined diseases, such as sarcoidosis and Sjogren’s syndrome, and generalized complex symptoms, for example, fatigue, sleep disturbance, orthostatic intolerance, and other dysautonomic manifestations. Those complaints were previously associated with autoantibodies against nervous system autonomic receptors, especially antibeta 1 adrenergic receptor antibodies, suggesting the autoimmune component of the condition. Here we report on a case of an 18-year-old woman who presented with extreme cachexia due to severe dysautonomia caused by the ASIA syndrome induced by the tetanus, diphtheria, and pertussis vaccine (Tdap).