Heart rate variability and cold-induced vascular dilation after stimulation of two different areas of the ear: a prospective, single-blinded, randomized crossover study.

BACKGROUND: Both noninvasive transauricular vagus nerve stimulation (taVNS) and traditional medical practice (TMP), such as auriculotherapy, use the auricle as a starting point for stimulation, but with two different conceptual frameworks: taVNS depends on vagal afferences to account for its effects, whereas TMP requires stimulation of the ear with high topographical accuracy regardless of the afferent nerves. The aim of this study was to measure heart rate variability (HRV) and cold water-induced vasodilation (CIVD) after puncturing two different ear points with the same afference but that should have opposite effects according to TMP. METHODS: Ten healthy subjects were investigated in this single-blinded crossover study over three sessions. In the first session, sympathetic activation was performed via cold water immersion of the right hand, with recordings taken from multiple fingers. HRV was assessed in the time domain (square root of the mean squared differences of NN intervals (RMSSD)) and frequency domain (low (LF) and high frequencies (HF)). In the second and third sessions, the same skin immersion test was performed, and mechanical stimulation was applied to the ear at two different points on the internal surface of the antitragus, one with alleged parasympathetic activity and the other with alleged sympathetic activity. The stimulation was done with semipermanent needles. RESULTS: Stimulation of the point with alleged parasympathetic activity immediately resulted in a significant decrease in RMSSD in 75% of the subjects and in LF in 50% of the subjects, while stimulation of the point with alleged sympathetic activity resulted in an increase in HF and RMSSD in 50% of the subjects. Stimulation of these points did not affect the CIVD reflex. The 20 min cold water immersion induced an immediate decrease in LF and the LF/HF ratio and an increase in HF. The skin temperature of the nonimmersed medius significantly decreased when the contralateral hand was immersed, from 34.4 °C to 31.8 °C. CONCLUSIONS: Stimulation of two different ear points innervated by the same afferent nerves elicited different HRV responses, suggesting somatotopy and a vagal effect beyond vagal afferences. These results are not in accordance with the claims of TMP. TRIAL REGISTRATION: NCT04130893 (18/10/2019) clinicaltrials.com.

Aurimatrix: Software-as-a-Service Solution for Clinical Work and Research in Auriculotherapy.

Objective: Auriculotherapy practitioners need a digital record-keeping method to track their cases that provides different ear maps and methodologies from different schools of auriculotherapy in one place. Materials and Methods: Main requirement were as followed: to be run whatever the platform; to manage different representations of the ear and to allow data analysis from multiple users. Results: Aurimatrix® is a software-as-a-service solution developed to help the practitioner enter all data pertaining to an auriculotherapy session. Although the software was originally designed for the two schools of French auriculotherapy, this software is highly configurable and can support the use of any ear chart in any language. Moreover, the ear charts are divided in several layers, allowing use of a representation of the ear of one school with the set of auricular points in use in another school. Because the list of medical conditions is limited and the modalities of variables used to evaluate the effectiveness of auriculotherapy are unchangeable, Aurimatrix enables comparison between different sessions, different patients, and different practitioners. Conclusions: Doing so, the software helps pave the way to improve auriculotherapy protocols.

How to detect and track chronic neurologic sequelae of COVID-19? Use of auditory brainstem responses and neuroimaging for long-term patient follow-up.

This review intends to provide an overview of the current knowledge on neurologic sequelae of COVID-19 and their possible etiology, and, based on available data, proposes possible improvements in current medical care procedures. We conducted a thorough review of the scientific literature on neurologic manifestations of COVID-19, the neuroinvasive propensity of known coronaviruses (CoV) and their possible effects on brain structural and functional integrity. It appears that around one third of COVID-19 patients admitted to intensive care units (ICU) for respiratory difficulties exhibit neurologic symptoms. This may be due to progressive brain damage and dysfunction triggered by severe hypoxia and hypoxemia, heightened inflammation and SARS-CoV-2 dissemination into brain parenchyma, as suggested by current reports and analyses of previous CoV outbreaks. Viral invasion of the brain may particularly target and alter brainstem and thalamic functions and, consequently, result in sensorimotor dysfunctions and psychiatric disorders. Moreover, data collected from other structurally homologous CoV suggest that SARS-CoV-2 infection may lead to brain cell degeneration and demyelination similar to multiple sclerosis (MS). Hence, current evidence warrants further evaluation and long-term follow-up of possible neurologic sequelae in COVID-19 patients. It may be particularly relevant to evaluate brainstem integrity in recovered patients, as it is suspected that this cerebral area may particularly be dysfunctional following SARS-CoV-2 infection. Because CoV infection can potentially lead to chronic neuroinflammation and progressive demyelination, neuroimaging features and signs of MS may also be evaluated in the long term in recovered COVID-19 patients.

Variations in the TRPV1 gene are associated to exertional heat stroke.

OBJECTIVES: Exertional Heat Stroke (EHS) is one of the top three causes of sudden death in athletes. Extrinsic and intrinsic risk factors have been identified but the genetic causes still remain unclear. Our aim was to identify genes responsible for EHS, which is a necessary step to identify patients at risk and prevent crises. DESIGN: Genetic and functional laboratory studies METHODS: Whole Exome Sequencing (WES) was performed to search for candidate genes in a cohort of 15 soldiers who had a documented EHS episode. In silico and in vitro functional studies were performed to evaluate the effect of mutations identified in the candidate gene TRPV1. RESULTS: WES led to the identification of two missense variations in the TRPV1 gene. These variations were very rare or unreported in control databases and located in critical domains of the protein. In vitro functional studies revealed that both variations induce a strong modification of the channel response to one of its natural agonist, the capsaicin. CONCLUSIONS: We evidenced mutations altering channel properties of the TRPV1 gene and demonstrated that TRPV1, which is involved in thermoregulation and nociception, is a new candidate gene for EHS. Our data provide the bases to explore genetic causes and molecular mechanisms governing the pathophysiology of EHS.

Anxiety and Psycho-Physiological Stress Response to Competitive Sport Exercise.

Introduction: Sport is recognized as beneficial for health. In certain situation of practice, it nevertheless appears likely to induce a stress response. Anxiety is a stress response-modulating factor. Our objective is to characterize the role of anxiety in the stress response induced by a selective physical exercise. Method: Sixty-three young male military conducted a selective sporting running event (a 8-km commando-walk) and were recorded the day before, the day of the race, and the day after. The variables were psychometric [personality questionnaires, coping and anxious/stress state, and physiological (nocturnal heart rate variability and actigraphy)]. The subjects were classified, using scores on anxiety questionnaires at baseline, into two groups according to their anxious (G ANX) or non-anxious (G N-ANX). Results: Before the race, the G ANX was characterized by a lower level of self-esteem, higher scores in dysfunctional coping and a greater perceived stress compared to the G N-ANX. Compared to G N-ANX, the stress response to the exercise was higher in G ANX: G ANX exhibited (Selye, 1950) in immediate post-exercise, greater level in activation markers, and mental fatigue associated with a same level of physical fatigue and (Kim et al., 2018) in nocturnal post-exercise, an increase in sympathetic activation associated with a higher sleep fragmentation. Conclusion: A competition selection sport exercise causes a stress response, particularly for anxious subjects. Anxious status could be involved in the risk of emergence of overtraining in sport practice. These results must be taken into account when sport practice is used for anxiety management.

Thermoregulatory Response to Exercise After Exertional Heat Stroke.

BACKGROUND: After one episode of exertional heat stroke (EHS), risk factors must be identified to determine the potential for subsequent episodes. One of these risk factors, core body temperature (Tco) kinetics during strenuous exercise, may be a surrogate marker suggestive of impaired thermoregulation. This study aimed to determine the kinetics of increases in Tco among military subjects who had a history of EHS. METHODS: Forty subjects (38 males, mean age 28.4 ± 4.9 years, mean body mass index 24.9 ± 2.4) who had a history of EHS ran 8 km in full combat gear with continuous monitoring of Tco and heart rate. The run was a qualifying event for military service. Tco was assessed using an ingestible sensor (Cortemp HQ Inc., Palmetto, Florida). Maximum oxygen uptake (VO2max) was measured on the day before the run. FINDINGS: The mean performance time for the run was 44.6 ± 6.6 minutes achieved under mild climatic conditions. No neurological impairment was observed. The mean maximum Tco was 39.9 ± 0.5°C. On the basis of Tco during the last 10 minutes of running, two Tco profiles were identified: increased Tco (Tco increase > 0.5°C) and plateaued Tco. Neither profile depended on initial, mid-run, or maximal Tco, VO2max, speed running, body surface area or body fat mass. DISCUSSION: Subjects who had a history of EHS exhibited different Tco profiles at the end of an 8-km run. Laboratory studies will be necessary to identify the mechanisms underlying these profiles; future longitudinal studies can determine whether a Tco increase >0.5°C during the last 10 minutes is a risk factor for EHS recurrence.

Occupational Exposures to Ebola Virus in Ebola Treatment Center, Conakry, Guinea.

We report 77 cases of occupational exposures for 57 healthcare workers at the Ebola Treatment Center in Conakry, Guinea, during the Ebola virus disease outbreak in 2014-2015. Despite the high incidence of 3.5 occupational exposures/healthcare worker/year, only 18% of workers were at high risk for transmission, and no infections occurred.

Predictive factors of efficacy of rituximab in patients with anti-MAG neuropathy.

OBJECTIVE: To identify factors associated with efficacy of rituximab (RTX) infusions in patients with anti-myelin associated glycoprotein (MAG) neuropathy. METHODS: 33 patients with anti-MAG neuropathy treated with RTX were retrospectively evaluated. All patients underwent neurological, biological, and electrophysiological examinations. Good response was defined as an improvement of at least one point of the Overall Neuropathy Limitation Scale (ONLS) at 6months or at the last follow-up. Disease evolution was defined as sub-acute if the ONLS increased by at least 2 points the year before therapy. RESULTS: Ten patients (30%) were improved 6months after RTX and 6/20 (30%) at the last follow-up (mean 42months). Response to RTX was significantly associated with subacute evolution and proximal weakness of the lower limbs at the onset of disease. Improvement was not correlated with electrophysiological data and anti-MAG antibodies titers. DISCUSSION: This study suggests that RTX may be efficacious in a sub-population of patients with anti-MAG neuropathy, particularly in those with proximal weakness of the lower limbs or sub-acute evolution.

Round Table on Malignant Hyperthermia in Physically Active Populations: Meeting Proceedings.

CONTEXT: Recent case reports on malignant hyperthermia (MH)-like syndrome in physically active populations indicate potential associations among MH, exertional heat stroke (EHS), and exertional rhabdomyolysis (ER). However, an expert consensus for clinicians working with these populations is lacking. OBJECTIVE: To provide current expert consensus on the (1) definition of MH; (2) history, etiology, and pathophysiology of MH; (3) epidemiology of MH; (4) association of MH with EHS and ER; (5) identification of an MH-like syndrome; (6) recommendations for acute management of an MH-like syndrome; (7) special considerations for physically active populations; and (8) future directions for research. SETTING: An interassociation task force was formed by experts in athletic training, exercise science, anesthesiology, and emergency medicine. The "Round Table on Malignant Hyperthermia in Physically Active Populations" was convened at the University of Connecticut, Storrs, September 17-18, 2015. CONCLUSIONS: Clinicians should consider an MH-like syndrome when a diagnosis of EHS or ER cannot be fully explained by clinical signs and symptoms presented by a patient or when recurrent episodes of EHS or ER (or both) are unexplained. Further research is required to elucidate the genetic and pathophysiological links among MH, EHS, and ER.

Rhabdomyolysis in Ebola Virus Disease. Results of an Observational Study in a Treatment Center in Guinea.

BACKGROUND: The pathogenesis of Ebola virus disease (EVD) remains unclear. The sporadic nature of Ebola outbreaks and their occurrence in resource-limited settings have precluded the acquisition of extensive clinical and laboratory data. Rhabdomyolysis during EVD has been suggested to occur in previous studies showing increased aspartate aminotransferase-alanine aminotransferase ratios, but, to date, has not been confirmed with creatine kinase (CK) assays. METHODS: We performed an observational study of 38 patients admitted to an Ebola treatment center from January to April 2015. CK values from patients with confirmed EVD were compared with those in patients without confirmed EVD. A panel of other analyses were also performed. In patients with EVD, characteristics were compared between survivors and nonsurvivors. RESULTS: High levels of CK were more frequent in patients with EVD than in those without (P = .002), and rhabdomyolysis was more frequent (59% vs 19%, respectively; P = .03). CK levels >5000 U/L were observed in 36% of patients with EVD. Also in patients with EVD, fatal outcome was significantly associated with higher creatinine and bilirubin levels, international normalized ratio, and viral load. CONCLUSIONS: Rhabdomyolysis is a frequent disorder in EVD and seems to be more common than in other viral infections. It may contribute to the renal failure observed in nonsurviving patients. More studies are needed to determine the impact of rhabdomyolysis on EVD outcome.

Moderate Thermal Strain in Healthcare Workers Wearing Personal Protective Equipment During Treatment and Care Activities in the Context of the 2014 Ebola Virus Disease Outbreak.

The extent of thermal strain while wearing personal protective equipment (PPE) during care activities for Ebola virus disease patients has not yet been characterized. From January to March 2015, 25 French healthcare workers (HCWs) in Conakry, Guinea, volunteered to be monitored while wearing PPE using an ingestible thermal sensor. The mean (standard deviation) working ambient temperature and relative humidity were 29.6 °C (2.0 °C) and 65.4% (10.3%), respectively; the mean time wearing PPE was 65.7 (13.5) minutes; and the mean core body temperature increased by 0.46 °C (0.20 °C). Four HCWs reached or exceeded a mean core body temperature of ≥ 38.5 °C. HCWs wearing PPE for approximately 1 hour exhibited moderate but safe thermal strain.

Is there a link between exertional heat stroke and susceptibility to malignant hyperthermia?

OBJECTIVE: The identification of a predisposition toward malignant hyperthermia (MH) as a risk factor for exertional heat stroke (EHS) remains a matter of debate. Such a predisposition indicates a causal role for MH susceptibility (MHS) after EHS in certain national recommendations and has led to the use of an in vitro contracture test (IVCT) to identify the MHS trait in selected or unselected EHS patients. The aim of this study was to determine whether the MHS trait is associated with EHS. METHODS: EHS subjects in the French Armed Forces were routinely examined for MHS after experiencing an EHS episode. This retrospective study compared the features of IVCT-diagnosed MHS (iMHS) EHS subjects with those of MH-normal EHS patients and MH patients during the 2004-2010 period. MHS status was assessed using the European protocol. RESULTS: During the study period, 466 subjects (median age 25 years; 31 women) underwent MHS status investigation following an EHS episode. None of the subjects reported previous MH events. An IVCT was performed in 454 cases and was diagnostic of MHS in 45.6% of the study population, of MH susceptibility to halothane in 18.5%, of MH susceptibility to caffeine in 9.9%, and of MH susceptibility to halothane and caffeine in 17.2%. There were no differences in the clinical features, biological features or outcomes of iMHS EHS subjects compared with those of MH-normal or caffeine or halothane MHS subjects without known prior EHS episode. The recurrence rate was 12.7% and was not associated with MH status or any clinical or biological features. iMHS EHS patients exhibited a significantly less informative IVCT response than MH patients. CONCLUSIONS: The unexpected high prevalence of the MHS trait after EHS suggested a latent disturbance of calcium homeostasis that accounted for the positive IVCT results. This study did not determine whether EHS patients have an increased risk of MH, and it could not determine whether MH susceptibility is a risk factor for EHS.

Report of 182 cases of exertional heatstroke in the French Armed Forces.

OBJECTIVES: Exertional heatstroke (EHS) remains a major problem for the military. The aim of our study was to describe medical history and clinical and biological features of EHS in a large military cohort. METHODS: We conducted a retrospective study among military subjects admitted to the Military Teaching Hospital Laveran for EHS from 2004 to 2006. RESULTS: Of the 182 subjects, EHS occurred most often at the end (80%) of a timed race of 8 km in battle clothes (84%) between the months of May and October (87%). The subjects were physically fit. Motivation was the primary intrinsic factor reported. A previous episode of EHS was reported by 15.4% of the subjects. Comas or seizures occurred more frequently in subjects whose temperatures exceeded 41°C (p = 0.03). Alanine aminotransferase was consistently increased in subjects who experienced EHS. We observed acute renal failure in 31.3% of the subjects, liver insufficiency in 12%, and disseminated intravascular coagulation in 1%. High creatine kinase levels alone did not correlate with renal failure. CONCLUSIONS: Detection of severe EHS in the field before the onset of multiple organ failure is challenging. The determination of the factors contributing to recurrence is urgently needed as EHS remains a life-threatening condition.

Is muscle energy production disturbed in exertional heat stroke?

BACKGROUND: Exertional heat stroke (EHS) is a life-threatening disease that shares some clinical similarities with malignant hyperthermia (MH). By use of (31)Phosphorus magnetic resonance spectroscopy (MRS), EHS patients with MH susceptibility and MH patients shared common metabolic abnormalities. The aim of this study was to determine whether subjects who suffered from an EHS episode had disturbed muscle energetics. METHOD: This retrospective study was performed within the French database of military subjects that were explored from 2004 to 2010 after they suffered an EHS. All subjects had both in vitro contracture test to determine their MH susceptibility and (31)Phosphorus MRS at 4.7 Tesla to assess muscle energetics by means of MRS score, a composite score corresponding to the sum of metabolic abnormalities recorded during a standardized rest-exercise-recovery protocol. RESULTS: 437 subjects were investigated and 32.5% of them exhibited abnormal MRS score. MRS score did not segregate subjects on demographic, clinical, or biological grounds. No clear correlation could be done between MH status and MRS score. DISCUSSION: These results did not confirm the potential relationship between calcium homeostasis and muscle energetics previously reported. However, muscle energy production was disturbed in a significant number of EHS subjects.

Adult-brain-derived neural stem cells grafting into a vein bridge increases postlesional recovery and regeneration in a peripheral nerve of adult pig.

We attempted transplantation of adult neural stem cells (ANSCs) inside an autologous venous graft following surgical transsection of nervis cruralis with 30 mm long gap in adult pig. The transplanted cell suspension was a primary culture of neurospheres from adult pig subventricular zone (SVZ) which had been labeled in vitro with BrdU or lentivirally transferred fluorescent protein. Lesion-induced loss of leg extension on the thigh became definitive in controls but was reversed by 45-90 days after neurosphere-filled vein grafting. Electromyography showed stimulodetection recovery in neurosphere-transplanted pigs but not in controls. Postmortem immunohistochemistry revealed neurosphere-derived cells that survived inside the venous graft from 10 to 240 post-lesion days and all displayed a neuronal phenotype. Newly formed neurons were distributed inside the venous graft along the severed nerve longitudinal axis. Moreover, ANSC transplantation increased CNPase expression, indicating activation of intrinsic Schwann cells. Thus ANSC transplantation inside an autologous venous graft provides an efficient repair strategy.