Laurent Gergelé

Neuromuscular Consequences of an Extreme Mountain Ultra-Marathon

We investigated the physiological consequences of one of the most extreme exercises realized by humans in race conditions: a 166-km mountain ultra-marathon (MUM) with 9500 m of positive and negative elevation change. For this purpose, (i) the fatigue induced by the MUM and (ii) the recovery processes over two weeks were assessed. Evaluation of neuromuscular function (NMF) and blood markers of muscle damage and inflammation were performed before and immediately following (n = 22), and 2, 5, 9 and 16 days after the MUM (n = 11) in experienced ultra-marathon runners. Large maximal voluntary contraction decreases occurred after MUM (−35% [95% CI: −28 to −42%] and −39% [95% CI: −32 to −46%] for KE and PF, respectively), with alteration of maximal voluntary activation, mainly for KE (−19% [95% CI: −7 to −32%]). Significant modifications in markers of muscle damage and inflammation were observed after the MUM as suggested by the large changes in creatine kinase (from 144±94 to 13,633±12,626 UI L−1), myoglobin (from 32±22 to 1,432±1,209 µg L−1), and C-Reactive Protein (from <2.0 to 37.7±26.5 mg L−1). Moderate to large reductions in maximal compound muscle action potential amplitude, high-frequency doublet force, and low frequency fatigue (index of excitation-contraction coupling alteration) were also observed for both muscle groups. Sixteen days after MUM, NMF had returned to initial values, with most of the recovery process occurring within 9 days of the race. These findings suggest that the large alterations in NMF after an ultra-marathon race are multi-factorial, including failure of excitation-contraction coupling, which has never been described after prolonged running. It is also concluded that as early as two weeks after such an extreme running exercise, maximal force capacities have returned to baseline.

Are Females More Resistant to Extreme Neuromuscular Fatigue

PURPOSE Despite interest in the possibility of females outperforming males in ultraendurance sporting events, little is known about the sex differences in fatigue during prolonged locomotor exercise. This study investigated possible sex differences in central and peripheral fatigue in the knee extensors and plantar flexors resulting from a 110-km ultra-trail-running race. METHODS Neuromuscular function of the knee extensors and plantar flexors was evaluated via transcranial magnetic stimulation (TMS) and electrical nerve stimulation before and after an ultra-trail-running race in 20 experienced ultraendurance trail runners (10 females and 10 males matched by percent of the winning time by sex) during maximal and submaximal voluntary contractions and in relaxed muscle. RESULTS Maximal voluntary knee extensor torque decreased more in males than in females (-38% vs -29%, P = 0.006) although the reduction in plantar flexor torque was similar between sexes (-26% vs -31%). Evoked mechanical plantar flexor responses decreased more in males than in females (-23% vs -8% for potentiated twitch amplitude, P = 0.010), indicating greater plantar flexor peripheral fatigue in males. Maximal voluntary activation assessed by TMS and electrical nerve stimulation decreased similarly in both sexes for both muscle groups. Indices of knee extensor peripheral fatigue and corticospinal excitability and inhibition changes were also similar for both sexes. CONCLUSIONS Females exhibited less peripheral fatigue in the plantar flexors than males did after a 110-km ultra-trail-running race and males demonstrated a greater decrease in maximal force loss in the knee extensors. There were no differences in the magnitude of central fatigue for either muscle group or TMS-induced outcomes. The lower level of fatigue in the knee extensors and peripheral fatigue in the plantar flexors could partly explain the reports of better performance in females in extreme duration running races as race distance increases.

Shear-Wave Elastography Assessments of Quadriceps Stiffness Changes prior to, during and after Prolonged Exercise: A Longitudinal Study during an Extreme Mountain Ultra-Marathon

In sports medicine, there is increasing interest in quantifying the elastic properties of skeletal muscle, especially during extreme muscular stimulation, to improve our understanding of the impact of alterations in skeletal muscle stiffness on resulting pain or injuries, as well as the mechanisms underlying the relationships between these parameters. Our main objective was to determine whether real-time shear-wave elastography (SWE) can monitor changes in quadriceps muscle elasticity during an extreme mountain ultra-marathon, a powerful mechanical stress model. Our study involved 50 volunteers participating in an extreme mountain marathon (distance: 330 km, elevation: +24,000 m). Quantitative SWE velocity and shear modulus measurements were performed in most superficial quadriceps muscle heads at the following 4 time points: before the race, halfway through the race, upon finishing the race and after recovery (+48 h). Blood biomarker levels were also measured. A significant decrease in the quadriceps shear modulus was observed upon finishing the race (3.31±0.61 kPa) (p<0.001) compared to baseline (3.56±0.63 kPa), followed by a partial recovery +48 h after the race (3.45±0.6 kPa) (p = 0.002) across all muscle heads, as well as for each of the following three muscle heads: the rectus femoris (p = 0.003), the vastus medialis (p = 0.033) and the vastus lateralis (p = 0.001). Our study is the first to assess changes in muscle stiffness during prolonged extreme physical endurance exercises based on shear modulus measurements using non-invasive SWE. We concluded that decreases in stiffness, which may have resulted from quadriceps overuse in the setting of supra-physiological stress caused by the extreme distance and unique elevation of the race, may have been responsible for the development of inflammation and muscle swelling. SWE may hence represent a promising tool for monitoring physiologic or pathological variations in muscle stiffness and may be useful for diagnosing and monitoring muscle changes.

Transcranial Color Duplex Ultrasound: A Reliable Tool for Cerebral Hemodynamic Assessment in Brain Injuries.

Background: Transcranial color duplex ultrasound (TCCD) is becoming an important tool for cerebral monitoring of brain-injured patients. To date, TCCD reproducibility has been studied in healthy volunteers or patients with subarachnoid hemorrhage and its efficiency in many brain injuries has not been proved. Our aim was to evaluate TCCD interobserver agreement in different brain injuries. Patients and Methods: We performed a prospective monocentric trial conducted from January 2014 to September 2014 in intensive care unit (ICU) of Saint-Etienne university teaching hospital, France. Brain-damaged patients admitted in ICU were included, excluding those with decompressive craniectomy. Two randomized operators among the ICU medical staff consecutively performed measurements of cerebral blood flow velocities with TCCD. Results: One hundred measurements were obtained from 42 patients. Hemodynamic and end-tidal CO2 pressure were similar between both measurement set. The results obtained with the Bland-Altman method showed bias at 0.52 (95% confidence interval [CI], −4.19 to 3.16), 0.53 (95% CI, −1.86 to 2.92), and 0.002 (95% CI, −0.06 to 0.06) for mean velocity, diastolic velocity, and pulsatility index, respectively. The limits of agreement were (−32.4; 31.4), (−20.4; 21.4), (−0.5; 0.5) for mean velocity, diastolic velocity, and pulsatility index, respectively. The Passing and Bablok regression have shown a quasilinear relationship between measurements. Conclusions: We reported the reliability of TCCD interobserver agreement in brain-damaged patients.

Strategies to reduce external ventricular drain–related infections: a multicenter retrospective study

OBJECTIVEVarious strategies have been proposed to reduce the incidence of external ventricular drain (EVD)-related infections. The authors retrospectively studied the impact of EVD care management on EVD-related infections at 3 French university hospital intensive care units.METHODSBetween 2010 and 2014, 462 consecutive adult patients with no evidence of a preexisting CSF infection received EVDs as part of their care at one of the following sites: Grenoble (221 patients), Saint-Etienne (130 patients), and Marseille (111 patients). Written protocols describing the EVD placement procedure, management, and removal were implemented at the 3 sites. Daily CSF sampling and intraventricular administration of antibiotics prior to EVD removal were performed at the Grenoble site only. EVD-related infection was considered for any confirmed ventriculostomy-related infection (VRI) and ventriculitis. VRI was defined as one or more positive CSF cultures or Gram stain with CSF pleocytosis and biochemical abnormalities. Ventriculitis was defined as CSF pleocytosis and biochemical abnormalities with degradation of neurological status and fever.RESULTSA total of 6945 EVD days were observed in the entire population. In the Grenoble cohort, the mean cumulative incidence of EVD-related infections was significantly lower than that in the 2 other cohorts: 1.4% (95% CI 0.0%-2.9%) versus 9.2% (95% CI 4.2%-14.2%) and 7.2% (95% CI 2.4%-12.0%) at Saint-Etienne and Marseille, respectively (p < 0.01). Accounting for the duration of external ventricular drainage at each site, the risk for EVD-related CSF infections was significantly higher at Saint-Etienne and Marseille than at Grenoble, with ORs of 15.9 (95% CI 3.6-71.4, p < 0.001) and 10.0 (95% CI 2.2-45.5, p = 0.003), respectively.CONCLUSIONSThese findings indicate that it is possible to attain a low incidence of EVD-related infections, provided that an EVD care bundle, which can include routine daily CSF sampling, is implemented and strongly adhered to.

Mountain ultra-marathon finishers exhibit marked immune alterations similar to those of severe trauma patients

Dear Editor, Runners competing in mountain ultra-marathons (MUMs) are known to display features of marked inflammation due to muscle microtrauma, oxidative stress, gastrointestinal dysfunction, or endotoxin translocation [1]. Furthermore, most immune functions exhibit adverse changes following prolonged, heavy exertion like competitive MUMs. This period of immune alteration may last for a few days and be responsible for increased occurrence of upper respiratory tract infection (URTI) or even more severe bacterial complications [2]. This resonates with the concept of injury-induced immunosuppression, in which the body would develop compensatory mechanisms aimed at blocking deleterious inflammation regardless of its cause [3]. We thus hypothesized that certain similarities exist between MUM runners and intensive care unit (ICU) patients. So far, the best parameters to assess immunosuppression in ICU patients are based on cellular immunology: HLA-DR expression on monocytes (mHLA-DR), CD4 lymphocyte count, and regulatory T cells (Treg) percentage [3]. The goal of the present work was to assess the impact of MUMs on these parameters. We monitored 28 experienced MUM runners (all having participated in at least two MUMs within the preceding 2-year period) competing in a 110km race (Table S1), which included a total positive elevation change of 5800 m. Blood was collected before the race and within 60 min upon arrival. For a subgroup of 10 runners, we were able to obtain additional blood 6 days later. Standard blood results are provided in Table S2. As indicated in Fig. 1, a slight decrease in CD4 count accompanied by a significant rise in Treg% (up to median levels seen in septic shock patients) was observed. The most compelling result, however, was the drop in mHLA-DR across all participants. Upon arrival, the median value was 8.376 ABC (similar to that in trauma patients [4]) and the lower quartile was 7300 ABC (Fig. 1). In other words, at least 25% of runners presented mHLA-DR values indicating severe immunosuppression. Importantly, in current immunostimulation clinical trials in septic shock, mHLA-DR values less than 8000 ABC act as the criterion for patient inclusion [5]. All parameters had returned to the normal range after 6 days of recovery. To our knowledge, this is the first report on mHLADR values during MUM. One striking observation is the homogeneous (i.e., seen in all subjects) fall in mHLADR expression that accompanies inflammatory response (highlighted by increased CRP, neutrophil count, and inflammatory cytokines; Tables S2, S3 and Fig. S1). This confirms that the body develops counter mechanisms to control inflammation that may cause damage. This can be considered a transient homeostatic mechanism, as values were found in the normal range a few days later. However, in the case of persistence in some athletes, this may contribute to the “open window” period associated with URTI following strenuous races [1, 2], similar to observations reported in ICU after injury. Lastly, it is worth noting that immunological parameters obtained in “healthy” *Correspondence: guillaume.monneret@chu‐lyon.fr †2 Laboratoire d’Immunologie, Hospices Civils de Lyon, Hôpital Edouard Herriot, 5 Places d’Arsonval, 69003 Lyon Cedex 03, France Full author information is available at the end of the article

Impact of an ultra-marathon of 330km on plasma levels of cardiac biomarkers

Background While a moderate exercise benefits on the cardiovascular system, consequences of a supraphysiological effort are not yet clear. Objective The aim of our study was to evaluate the consequences of an ultra-marathon on cardiac and muscles markers (CK, myoglobin, hsTnT, NT-proBNP, copeptin, H-FABP) but also markers of inflammation CRP DFO, GB) and of renal function (urinary NGAL and plasma and urinary creatinine). This project also studied the evolution of new cardiac fibrosis biomarkers: ST2 and Gal-3. Design Longitudinal, cohort study. Setting The Tor des Geants (TdG), a 330 km long ultra distance trail running, with +24,000 m elevation changes in the Valley of Aosta (Italy), is considered as one of the most difficult mountain marathon race in the world. The maximum time allowed to complete the race is 150 h. Patients (or Participants) 51 participants attending the TdG have been followed and the study was conducted on 33 subjects having reached at least half of the race (148.7 km). Interventions (or Assessment of Risk Factors) Repeated blood and urine samples collection were carried out at four key time points: before, during (mid-point) and after the race (less than 1 h) and 3 days after the end of the race. Main Outcome Measurements Biological samples were collected at these four different times. Several biomarkers were assayed on different analyzers such COBAS®, KRYPTOR®, VIDAS® and ETIMAX®, meanwhile, the ST2 and Gal-3 were measured manually. Results During the TdG, the plasma levels of cardiac markers, muscle and inflammation have increased significantly to halfway. Meanwhile, the markers of renal function have only slightly varied, excepting plasma creatinine. Conclusions The study suggests that there is no permanent structural damage at the myocardium level. However, the low pace adopted by the tired runners caused an inflammatory response as well as muscle damage less important than a shorter race.

Apparent Diffusion coefficient (ADC), T1 and T2 quantitative indexes of the myocardium in athletes before, during and after extreme mountain ultra-marathon: correlation with myocardial damages and inflammation biomarkers

Background: previous MRI and US studies have shown the existence of functional and biochemical alterations in the myocardium after prolonged endurance exercise, demonstrating transient diastolic dysfunction [1]. Simultaneous transient increases of cTnT and NT-proBNP biomarkers have been reported [2, 3] without focal necrosis identified by delayed enhancement imaging, probably due to a cytosolics dropping of biomarkers rather than destruction of myocytes. Inflammation, microstructural & functional modifications caused by extreme loading conditions, have never been explored using quantitative MRI. Methods: We prospectively studied 50 runners enrolled on the 2014 « Tor des Geants » edition (the most extreme mountain ultra-marathon (336 km length, 24000 m cumulative elevation), without clinical evidence of personal history of cardiac or pulmonary disease. Subjects were studied before, at arrival, and after 3 days recovery. Imaging protocol included global and regional LV function analysis and quantitative MRI : T1, T2 and ADC values were obtained using respectively a MOLLI sequence, a radial multi-echo sequence, a Stejskal-Tanner diffusion sequence [4]. T1, T2 and ADC values at 1.5T were compared with plasma levels of inflammation, myocardial stress and/or damage biomarkers including hs-TnT, NT-proBNP, Gal-3 (a carbohydrate binding lectin produced by macrophages, upregulated in hypertrophied heart, emerging as a mediator for fibrosis development and remodeling) and ST2 (a family member of IL-1 receptors known for its role in immunological processes, having a potential role in cardiac pathogenesis). Results: 27 finishers (54%) completed the longitudinal study.T2, T1 and ADC values significantly increased immediately after the race. ADC quickly normalized after recovery while T1, T2 markers remained higher than baseline (Figure 1). Significant correlations were found between myocardial MR biomarkers and blood (Gal3,ST2,NT-proBNP), plasmatic (CRP, CKs, hs-TNT) and cellular (WBC, lymphocytes, neutrophilis) ones (Figure 2). Conclusion: It is the first study investigating the role of quantitative MR diffusion to explore human acute stress in humans together. ADC, T1 and T2 were all able to identify changes in subjects and related to several plasmatic biomarkers and therefore appear as valuable MR biomarkers of myocardial inflammation at least for this specific type of acute stress. Prior to a deeper understanding of the impact of ultra-endurance, this study hightlights an added value of ADC, that differ from T1 and T2 markers, to scrutinize acute stress phenomena in the myocardium. ADC represents a novel information, revealing more about water redistribution leading to ultraexercise-induced reversible myocardial inflammation. Overal it illustrates the usefulness and complementary nature of ADC as an emerging cardiac biomarker, foreseen to be deployed at short-term in the evaluation of innovative therapeutic strategies targeting inflammation.

External hydrocephalus in adults: an insidious cause of delayed intracranial hypertension. Report of 33 relevant cases treated with success by CSF lumbar drainage

The concept of external hydrocephalus refers to situations of CSF flow impairment within subarachnoid spaces (SAS). Classically described in infant and children, literature offers few data on adult.

Delayed management of secondary normal pressure hydrocephalus after cerebrospinal fluid external drainage

External drainage (ED) of cerebrospinal fluid (CSF) is often used during management of brain insult. In absence of robust data and consensual guidelines, weaning ED remains challenging. The objective of the study was to assess the proportion of secondary normal pressure hydrocephalus (NPH), being treated with delay after ED weaning and to evaluate the resulting morbidity.