Mathias Poussel

Organ dysfunction and muscular disability in myotonic dystrophy type 1.

Myotonic dystrophy type 1 (DM1) is a multisystemic disorder characterized by muscle weakness and multiple organ impairment, especially the eyes, lung, and heart. We conducted the current study to analyze the prevalence and intercorrelation among these disorders and their respective relationships with muscular disability. We assessed medical history, anthropometric data, lung volumes, arterial and venous blood samples, surface 12-lead electrocardiogram, echocardiography, ophthalmologic examination, and muscular impairment rating scale (MIRS) in 106 patients (48 male and 58 female) with DM1, aged 43.7 ± 12.8 years. Obesity, hypertriglyceridemia, and diabetes were found in respectively 25.6%, 47.6%, and 17.1% of patients. Disabling cataract was found in 43.4%, and was independently predicted by age and MIRS. Restrictive lung disease was noted in 34%, and was predicted by MIRS, CTG repeat expansion, and body mass index. Conduction disorders were found in 30.2% of patients and were predicted by left ventricular ejection fraction, MIRS, and CTG repeat expansion. We found significant relationships between cataract, restrictive lung disease, and conduction disorders: patients with cataract and those with conduction disorders exhibited more severe restrictive lung disease than the other patients. Conversely, the relative risk of restrictive lung disease was 2.42 (1% confidence interval [CI], 1.06-5.51) in patients with cataract and 2.54 (1% CI, 1.26-5.07) in patients with conduction disorders. Multivariate analysis revealed that MIRS was the only independent predictor for conduction disorders and restrictive lung disease. MIRS ≥3 and MIRS ≥4 were the best simple cutoff values to predict, respectively, lung and cardiac involvements. To conclude, muscular disability, ophthalmologic, and cardiac and pulmonary involvement are strongly correlated. Particular attention should be given to these entities in patients with distal or proximal muscular weakness. Abbreviations: BMI = body mass index, CI = confidence interval, DM1 = myotonic dystrophy type 1, ECG = surface 12-lead electrocardiogram, FEV1 = forced expiratory volume in 1 second, FSH = follicle-stimulating hormone, IgG = immunoglobulin G, LVEF = left ventricular ejection fraction, MIRS = muscular impairment rating scale, PaCO2 = arterial CO2 partial pressure, PaO2 = arterial O2 partial pressure, RNA = ribonucleic acid, RR = relative risk, RV = residual volume, TLC = total lung capacity, VC = vital capacity.

Combined effects of sleep deprivation and strenuous exercise on cognitive performances during The North Face® Ultra Trail du Mont Blanc® (UTMB®)

Abstract This study investigated the effects of combined sleep deprivation and strenuous exercise on cognitive and neurobehavioral performance among long-distance runners completing one of the most difficult ultramarathons in the world. Seventeen runners participated. Each had a wrist-worn actigraph throughout the race to record their sleep time. In addition, each individual’s performance in 10-min response-time tests before and after the race was recorded and a questionnaire enabled participants to report any difficulties they experienced during the competition. During race completion times of 27 to 44 h, combined acute lack of sleep (12 ± 17 min of rest during the race) and strenuous exercise (168.0 km) had marked adverse effects on cognitive performances ranging from mere lengthening of response time to serious symptoms such as visual hallucinations. This study suggests that regardless of rest duration and time in race, cognitive performances of ultramarathoners are adversely affected.

Fatal cardiac arrhythmia following voluntary caffeine overdose in an amateur body-builder athlete☆

Caffeine (1,3,7-trimethylxanthine, CAS 58-08-2) is one of the most commonly consumed substances in the world and is well known to have extensive effects on physiological functions, especially on the cardiovascular system. We report a fatal cardiac arrhythmia following voluntary caffeine overdose in an amateur body-builder athlete.

Lack of correlation between the ventilatory response to CO2 and lung function impairment in myotonic dystrophy patients: Evidence for a dysregulation at central level

Myotonic dystrophy Type 1 (DM1) is the most common muscular dystrophy in adults. Respiratory failure is common but clinical findings support a dysregulation of the control of breathing at central level, furthermore contributing to alveolar hypoventilation independently of the severity of respiratory weakness. We therefore intended to study the relationship between the ventilatory response to CO2 and the impairment of lung function in DM1 patients. Sixty-nine DM1 patients were prospectively investigated (43.5 ± 12.7 years). Systematic pulmonary lung function evaluation including spirometry, plethysmography, measurements of respiratory muscle strength, arterial blood gas analysis and ventilatory response to CO2 were performed. Thirty-one DM1 patients (45%) presented a ventilatory restriction, 38 (55%) were hypoxaemic and 15 (22%) were hypercapnic. Total lung capacity decline was correlated to hypoxaemia (p = 0.0008) and hypercapnia (p = 0.0013), but not to a decrease in ventilatory response to CO2 (p = 0.194). Ventilatory response to CO2 was reduced to 0.85 ± 0.67 L/min/mmHg and not correlated to respiratory muscle weakness. Ventilatory response to CO2 was neither different among restricted/non-restricted patients (p = 0.2395) nor among normoxaemic/hypoxaemic subjects (p = 0.6380). The reduced ventilatory response to CO2 in DM1 patients appeared independent of lung function impairment and respiratory muscle weakness, suggesting a central cause of CO2 insensitivity.

Age, conduction defects and restrictive lung disease independently predict cardiac events and death in myotonic dystrophy.

OBJECTIVE The aim of the study was to identify, in addition to conduction defects, possible predictors of cardiac events and death in patients with myotonic dystrophy (DM1). METHODS AND DESIGN A retrospective observational cohort study was undertaken. Baseline clinical and non-invasive cardiac and respiratory investigations were obtained from 107 DM1 patients, who were regularly re-examined. Primary end-points were occurrence of cardiac events (pacemaker implantation or tachyarrhythmia) or death. Probability of an event was calculated using the Kaplan-Meier method, while contributing factors were assessed using univariate and multivariate (Cox model) analyses. RESULTS Cardiac events occurred in 34 patients (29%). Age, muscular impairment, infantile onset, restrictive lung disease (RLD), ECG conduction defects, left ventricular ejection fraction (LVEF) below 50%, and arrhythmia detected during Holter monitoring were predictors of cardiac events. Multivariate analysis indicated that age, RLD, ECG conduction defects, Holter arrhythmia and LVEF remained independent predictors. Probability of cardiac events was 2.5% (5%CI: 0-7%) at 1 year and 6% (5%CI: 0-14%) at 3 years in patients younger than 42 years with normal ECG, Holter, LVEF and lung volumes. Advancing age, distal or proximal weakness and RLD characterized all non-survivors (n=14). CONCLUSION Cardiac events or death are predicted not only by conduction defects or cardiomyopathy in DM1, but also by RLD, muscular disability and advancing age. Addition of these criteria should modulate time intervals for patient follow-up examinations. In young patients with normal baseline investigations, screening investigations every 2 or 3 years seem to be sufficient.

Within breath ventilatory responses to mechanical tracheal stimulation in anaesthetised rabbits.

Ventilatory responses to airway mechanical stimulation usually consist in mixed cough (CR) and expiration (ER) reflexes. The stimulus characteristics that would favour either reflex may vary with breathing, but the issue cannot be addressed with the usual long lasting stimulus. The aim of the study was to describe respiratory responses evoked by a punctuate tracheal stimulus and their relationship to inspiration and expiration. Experiments were repeated after bronchoconstriction. Eight anesthetized tracheotomized rabbits were stimulated in the trachea by 150 ms probing before and after methacholine inhalation (248 tests). CR and ER were evaluated from tidal volume and expiratory flow. The overall incidence of responses was larger in inspiration than expiration (p < 0.0001). A majority of responses were single CR or ER, also strongly related to breathing: 93% CR occurred with the stimulus in inspiration and 78% ER with the stimulus in expiration (p = 0.001). Bronchoconstriction did not change the incidence of single efforts, increased that of mixed responses and decreased the amplitude of preparatory and expulsive phases of CR. The study demonstrates the strong dependence of CR and ER on the phase of breathing and adds to the current evidence that regulating mechanisms clearly differ for each reflex.

Sleep Management Strategy and Performance in an Extreme Mountain Ultra-marathon

We intended to assess the relationship between sleep strategies and performance during the North-Face Ultra-Trail du Mont-Blanc 2013, to test the hypothesis that sleep management can influence athletic performance. Almost all runners specifically adopted sleep management strategies before the race. Among the finishers 72% didn’t sleep at all during the race and 28% took a least one break for sleep. Non-sleepers completed the race faster than the sleepers (P = 0.0008). Race time was positively correlated with drowsiness (P < 0.0001) and negatively correlated with the number participations in this race (P = 0.0039). Runners who adopted a sleep management strategy based on increased sleep time before the race completed the race faster (P = 0.0258). Most finishers seemed to be aware of the importance of developing sleep management strategies and increasing sleep time some nights before the race appeared to be the most relevant strategy to improve performance.

Stimulus response latency of cough and expiration reflex depends on breathing in the rabbit.

Expiration reflex and cough may have distinct afferent pathways and/or central integrative mechanisms that may both result in different stimulus response latencies. A newly described method that uses a punctuate mechanical tracheal stimulus to provoke defensive ventilatory reflexes should allow the stimulus response latency to be calculated with reasonable accuracy. The aim of the study was to test whether cough and expiration reflex have different stimulus response latencies. Four hundred and sixty one mechanical tracheal stimulations (50-300 msec) were performed in 21 anesthetized, tracheotomized rabbits. Twenty three percent stimulations (108) provoked a cough reflex and 37% an expiration reflex (171). The individual mean stimulus response latency was computed for each reflex, calculated from stimulus onset to earliest detectable change in ventilatory flow. Cough reflex latency was significantly shorter in inspiration compared to expiration (257±19 msec vs 391±61 msec; p=0.01). In contrast, the expiration reflex latency was significantly shorter in expiration compared to inspiration (210±11 msec vs 329±29 msec, p=0.003). It is concluded that the within breath dependence of the difference in stimulus response latency between cough and expiration reflex is more likely to express different brainstem mechanisms but difference in afferent fibres may not be excluded.

Supine changes in lung function correlate with chronic respiratory failure in myotonic dystrophy patients.

Quality of life and prognosis of patients with myotonic dystrophy type 1 (MD1) often depend on the degree of lung function impairment. This study was designed to assess the respective prevalence of ventilatory restriction, hypoxaemia and hypercapnia in MD1 patients and to determine whether postural changes in lung function could contribute to the early diagnosis of poor respiratory outcome. Fifty-eight patients (42.6±12.9 years) with MD1 were prospectively evaluated from April 2008 to June 2010 to determine their supine and upright lung function and arterial blood gases. The prevalence of ventilatory restriction was 36% and increased with the severity of muscular disability (from 7.7% to 70.6%). The prevalence of hypoxaemia and hypercapnia was 37.9% and 25.9%, respectively. Multiple regression analysis showed that the supine fall in FEV1 was the only variable associated with ventilatory restriction, hypoxaemia and hypercapnia. Our data indicate that supine evaluation of lung function could be helpful to predict poor respiratory outcome, which is closely correlated with hypoxaemia and/or hypercapnia.

Substance use and misuse in a mountain ultramarathon: new insight into ultrarunners population?

ABSTRACT Endurance and ultra-endurance events have become increasingly popular. The aim of our study was to explore the use of medication among endurance runners participating in the 2014 Infernal Trail des Vosges. Among the 389 runners engaged, 297 (76.3%) completed a specific questionnaire dealing with substance use/misuse. Our results show a 27% (before the race) and 18% (during the race) prevalence of substance use. The two major classes of substances used were non-steroidal anti-inflammatory drugs (NSAIDs; 9.8%) and painkillers (6.7%), principally because of osteo-articular pain (29.6%) or to prevent pain (28.2%). A positive correlation was found between substance consumption before (past month) and during the race (overall medication: p < 0.0001; NSAIDs: p = 0.008). Our results could be explained by the specific characteristics of ultrarunners predominantly motivated by personal achievement and general health (recreational approach). However, education interventions should further be delivered regarding the risks of substance use in ultra-endurance events.