Enteric synucleinopathy: real entity or only a trendy concept?

An accumulating body of literature has emerged in the past 25 years to show that Parkinson’s disease (PD) is not only a disorder of the brain but also of the gastrointestinal tract and more generally of the gut-brain axis. Gastrointestinal symptoms occur in almost every PD patient at some point and in nearly every case examined pathologically autopsy studies find alpha-synuclein deposits, the pathological hallmarks of PD, in the enteric nervous system. This concept of ‘enteric synucleinopathy’ led to the hypothesis that the enteric nervous system might play a pivotal role in the initiation and spreading of PD. Although this hypothesis opens up interesting perspectives on the pathogenesis of neurodegenerative disorders, some important questions are still pending. The present opinion paper describes and compares the physiological and pathophysiological properties of alpha-synuclein in the brain and the enteric nervous system. We conclude that the existing data supports the existence of pathological alpha-synuclein species in the gut in PD. We also discuss if gut-brain interactions are important in other neurodegenerative disorders

Cumulative association of obstructive sleep apnea severity and short sleep duration with the risk for hypertension.

Obstructive sleep apnea (OSA) and short sleep duration are individually associated with an increased risk for hypertension (HTN). The aim of this multicenter cross-sectional study was to test the hypothesis of a cumulative association of OSA severity and short sleep duration with the risk for prevalent HTN. Among 1,499 patients undergoing polysomnography for suspected OSA, 410 (27.3%) previously diagnosed as hypertensive and taking antihypertensive medication were considered as having HTN. Patients with total sleep time (TST) <6 h were considered to be short sleepers. Logistic regression procedures were performed to determine the independent association of HTN with OSA and sleep duration. Considering normal sleepers (TST ≥6 h) without OSA as the reference group, the odds ratio (OR) (95% confidence intervals) for having HTN was 2.51 (1.35-4.68) in normal sleepers with OSA and 4.37 (2.18-8.78) in short sleepers with OSA after adjustment for age, gender, obesity, diabetes, depression, current smoking, use of thyroid hormones, daytime sleepiness, poor sleep complaint, time in bed, sleep architecture and fragmentation, and study site. The risk for HTN appeared to present a cumulative association with OSA severity and short sleep duration (p<0.0001 for linear trend). The higher risk for HTN was observed in short sleepers with severe OSA (AHI ≥30) (OR, 4.29 [2.03-9.07]). In patients investigated for suspected OSA, sleep-disordered breathing severity and short sleep duration have a cumulative association with the risk for prevalent HTN. Further studies are required to determine whether interventions to optimize sleep may contribute to lower BP in patients with OSA

Positive Airway Pressure Adherence, Mortality and Cardio-Vascular Events in Sleep Apnea Patients

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Cancer risk in adherent users of polyurethane foam-containing CPAP devices for sleep apnoea

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Tolerability of High-Dose Ceftriaxone in CNS Infections: A Prospective Multicentre Cohort Study

International audienceBACKGROUND: Ceftriaxone is widely used to treat community-acquired CNS bacterial infections. French guidelines for meningitis in adults promote 75-100\,mg/kg/day ceftriaxone without an upper limit for dosage, yet little is known about the pharmacology and tolerability of such regimens. PATIENTS AND METHODS: A multicentre prospective cohort study was conducted in adult patients to assess the adverse drug reactions (ADRs) of high-dose ceftriaxone (i.e. daily dosage ≥q4\,g or ≥q75\,mg/kg) in CNS infections and to analyse their related factors. Drug causality was systematically assessed by an expert committee who reviewed the medical charts of all included patients. RESULTS: A total of 196 patients were enrolled over a 31\,month period. Median dosage and duration of ceftriaxone were 96.4\,mg/kg/day (7\,g/day) and 8\,days, respectively. Nineteen ceftriaxone-related ADRs (mainly neurological) occurred in 17 patients (8.7%), with only one case of treatment discontinuation (biliary pseudolithiasis). In univariate analysis, older age, male gender, renal impairment and high trough ceftriaxone plasma concentration were associated with ceftriaxone-related ADRs. CONCLUSIONS: High-dose ceftriaxone for CNS infection administered as recommended by French guidelines in adults was well tolerated overall, suggesting these recommendations could be applied and generalized. In patients with advanced age or renal insufficiency, prescription should be done with caution and therapeutic drug monitoring could be useful

Multivariate adjusted Odds Ratio (OR) (95% confidence interval [CI]) for hypertension associated with sleep duration in the whole obstructive sleep apnea (OSA) group and in the 2 categories of OSA severity.

<p>SDB, sleep-disordered breathing.</p><p>OR were adjusted for age, gender, obesity, diabetes, depression, current smoking, use of thyroid hormones, excessive daytime sleepiness, poor sleep, time spent in slow wave sleep, overall arousal index, time in bed, and study site.</p><p>* p<0.05.</p><p>**p<0.01.</p><p>Multivariate adjusted Odds Ratio (OR) (95% confidence interval [CI]) for hypertension associated with sleep duration in the whole obstructive sleep apnea (OSA) group and in the 2 categories of OSA severity.</p

Multivariate adjusted odds ratio (OR) (95% confidence interval [CI]) for hypertension associated with sleep-disordered breathing or sleep duration.

<p>OSA, obstructive sleep apnea.</p><p>Model 1 included OSA severity or sleep duration adjusted for age, gender, obesity, diabetes, depression, current smoking, use of thyroid hormones, excessive daytime sleepiness, poor sleep, time spent in slow wave sleep, overall arousal index, time in bed, and study site.</p><p>Model 2 included OSA severity or sleep duration adjusted for age, gender, obesity, diabetes, depression, current smoking, use of thyroid hormones, excessive daytime sleepiness, poor sleep, time spent in slow wave sleep, overall arousal index, sleep latency, and study site.</p><p>Model 3 included OSA severity or sleep duration adjusted for age, gender, obesity, diabetes, depression, current smoking, use of thyroid hormones, excessive daytime sleepiness, poor sleep, time spent in slow wave sleep, overall arousal index, wake time after sleep onset, and study site.</p><p>Adjusted OR were all statistically significant with p value <0.01</p>†<p>Tested by the Cochrane-Armitage trend test.</p><p>Multivariate adjusted odds ratio (OR) (95% confidence interval [CI]) for hypertension associated with sleep-disordered breathing or sleep duration.</p

Characteristics of the study population.

<p>Data are expressed as mean (SD) or percentages.</p><p>HTN, hypertension; BMI, body mass index; EDS, excessive daytime sleepiness; WASO, wake time after sleep onset; REM, rapid eye movement; SW, slow wave.</p><p>Characteristics of the study population.</p

Association Between Nocturnal Hypoxemia and Cancer Incidence in Patients Investigated for OSA

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