[Show abstract][Hide abstract] ABSTRACT: IntroductionSleep in intensive care unit (ICU) patients is severely altered. In a large proportion of critically ill patients, conventional sleep electroencephalogram (EEG) patterns are replaced by atypical sleep. On the other hand, some non-sedated patients can display usual sleep EEG patterns. In the latter, sleep is highly fragmented and disrupted and conventional rules may not be optimal. We sought to determine whether sleep continuity could be a useful metric to quantify the amount of sleep with recuperative function in critically ill patients with usual sleep EEG features.Methods
We retrospectively reanalyzed polysomnographies recorded in non-sedated critically ill patients requiring non-invasive ventilation (NIV) for acute hypercapnic respiratory failure. Using conventional rules, we built two-state hypnograms (sleep and wake) and identified all sleep episodes. The percentage of time spent in sleep bouts (<10 min), short naps (>10 and <30 min) and long naps (>30 min) was used to describe sleep continuity. In a first study, we compared these measures regarding good (NIV success) or poor outcome (NIV failure). In a second study performed on a different patient group, we compared these measurements during NIV and during spontaneous breathing.ResultsWhile fragmentation indices were similar in the two groups, the percentage of total sleep time spent in short naps was higher and the percentage of sleep time spent in sleep bouts was lower in patients with successful NIV. The percentage of total sleep time spent in long naps was higher and the percentage of sleep time spent in sleep bouts was lower during NIV than during spontaneous breathing; the level of reproducibility of sleep continuity measures between scorers was high.Conclusion
Sleep continuity measurements could constitute a clinically relevant and reproducible assessment of sleep disruption in non-sedated ICU patients with usual sleep EEG.
Critical care (London, England) 11/2014; 18(6):628. · 5.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Patients with Parkinson's disease (PD) display significant sleep disturbances and daytime sleepiness. Dopaminergic treatment dramatically improves PD motor symptoms, but its action on sleep remains controversial, suggesting a causal role of nondopaminergic lesions in these symptoms. Because the pedunculopontine nucleus (PPN) regulates sleep and arousal, and in view of the loss of its cholinergic neurons in PD, the PPN could be involved in these sleep disorders. The aims of this study were as follows: (1) to characterize sleep disorders in a monkey model of PD; (2) to investigate whether l-dopa treatment alleviates sleep disorders; and (3) to determine whether a cholinergic PPN lesion would add specific sleep alterations. To this end, long-term continuous electroencephalographic monitoring of vigilance states was performed in macaques, using an implanted miniaturized telemetry device. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment induced sleep disorders that comprised sleep episodes during daytime and sleep fragmentation and a reduction of sleep efficiency at nighttime. It also induced a reduction in time spent in rapid eye movement (REM) sleep and slow-wave sleep and an increase in muscle tone during REM and non-REM sleep episodes and in the number of awakenings and movements. l-Dopa treatment resulted in a partial but significant improvement of almost all sleep parameters. PPN lesion induced a transient decrease in REM sleep and in slow-wave sleep followed by a slight improvement of sleep quality. Our data demonstrate the efficacy of l-dopa treatment in improving sleep disorders in parkinsonian monkeys, and that adding a cholinergic PPN lesion improves sleep quality after transient sleep impairment.
Journal of Neuroscience 07/2014; 34(27):9124-33. · 6.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Parkinson's disease is typically treated with oral dopamine replacement therapies; however, long-term treatment leads to motor complications and, occasionally, impulse control disorders caused by intermittent stimulation of dopamine receptors and off-target effects, respectively. We aimed to assess the safety, tolerability, and efficacy of bilateral, intrastriatal delivery of ProSavin, a lentiviral vector-based gene therapy aimed at restoring local and continuous dopamine production in patients with advanced Parkinson's disease.
We undertook a phase 1/2 open-label trial with 12-month follow-up at two study sites (France and UK) to assess the safety and efficacy of ProSavin after bilateral injection into the putamen of patients with Parkinson's disease. All patients were then enrolled in a separate open-label follow-up study of long-term safety. Three doses were assessed in separate cohorts: low dose (1·9×10(7) transducing units [TU]); mid dose (4·0×10(7) TU); and high dose (1×10(8) TU). Inclusion criteria were age 48-65 years, disease duration 5 years or longer, motor fluctuations, and 50% or higher motor response to oral dopaminergic therapy. The primary endpoints of the phase 1/2 study were the number and severity of adverse events associated with ProSavin and motor responses as assessed with Unified Parkinson's Disease Rating Scale (UPDRS) part III (off medication) scores, at 6 months after vector administration. Both trials are registered at ClinicalTrials.gov, NCT00627588 and NCT01856439.
15 patients received ProSavin and were followed up (three at low dose, six mid dose, six high dose). During the first 12 months of follow-up, 54 drug-related adverse events were reported (51 mild, three moderate). Most common were increased on-medication dyskinesias (20 events, 11 patients) and on-off phenomena (12 events, nine patients). No serious adverse events related to the study drug or surgical procedure were reported. A significant improvement in mean UPDRS part III motor scores off medication was recorded in all patients at 6 months (mean score 38 [SD 9] vs 26 , n=15, p=0·0001) and 12 months (38 vs 27 ; n=15, p=0·0001) compared with baseline.
ProSavin was safe and well tolerated in patients with advanced Parkinson's disease. Improvement in motor behaviour was observed in all patients.
[Show abstract][Hide abstract] ABSTRACT: An increased incidence of narcolepsy in children was detected in Scandinavian countries where pandemic H1N1 influenza ASO3-adjuvanted vaccine was used. A campaign of vaccination against pandemic H1N1 influenza was implemented in France using both ASO3-adjuvanted and non-adjuvanted vaccines. As part of a study considering all-type narcolepsy, we investigated the association between H1N1 vaccination and narcolepsy with cataplexy in children and adults compared with matched controls; and compared the phenotype of narcolepsy with cataplexy according to exposure to the H1N1 vaccination. Patients with narcolepsy-cataplexy were included from 14 expert centres in France. Date of diagnosis constituted the index date. Validation of cases was performed by independent experts using the Brighton collaboration criteria. Up to four controls were individually matched to cases according to age, gender and geographic location. A structured telephone interview was performed to collect information on medical history, past infections and vaccinations. Eighty-five cases with narcolepsy-cataplexy were included; 23 being further excluded regarding eligibility criteria. Of the 62 eligible cases, 59 (64% males, 57.6% children) could be matched with 135 control subjects. H1N1 vaccination was associated with narcolepsy-cataplexy with an odds ratio of 6.5 (2.1-19.9) in subjects aged <18 years, and 4.7 (1.6-13.9) in those aged 18 and over. Sensitivity analyses considering date of referral for diagnosis or the date of onset of symptoms as the index date gave similar results, as did analyses focusing only on exposure to ASO3-adjuvanted vaccine. Slight differences were found when comparing cases with narcolepsy-cataplexy exposed to H1N1 vaccination (n = 32; mostly AS03-adjuvanted vaccine, n = 28) to non-exposed cases (n = 30), including shorter delay of diagnosis and a higher number of sleep onset rapid eye movement periods for exposed cases. No difference was found regarding history of infections. In this sub-analysis, H1N1 vaccination was strongly associated with an increased risk of narcolepsy-cataplexy in both children and adults in France. Even if, as in every observational study, the possibility that some biases participated in the association cannot be completely ruled out, the associations appeared robust to sensitivity analyses, and a specific analysis focusing on ASO3-adjuvanted vaccine found similar increase.
[Show abstract][Hide abstract] ABSTRACT: Patients with Parkinson's disease frequently complain of sleep disturbances and loss of muscle atonia during rapid-eye-movement (REM) sleep is not rare. The orexin-A (hypocretin-1) hypothalamic system plays a central role in controlling REM sleep. Loss of orexin neurons results in narcolepsy-cataplexy, a condition characterized by diurnal sleepiness and REM sleep without atonia. Alterations in the orexin-A system have been also documented in Parkinson's disease, but whether these alterations have clinical consequences remains unknown.
Here, we measured orexin-A levels in ventricular cerebrospinal fluid from eight patients with Parkinson's disease (four males and four females) who underwent ventriculography during deep brain-stimulation surgery and performed full-night polysomnography before surgery.
Our results showed a positive correlation between orexin-A levels and REM sleep without muscle atonia.
Our results suggest that high levels of orexin-A in Parkinson's disease may be associated with loss of REM muscle atonia.
Nature and Science of Sleep 06/2013; 5:87-91.
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[Show abstract][Hide abstract] ABSTRACT: BACKGROUND:: In mechanically ventilated patients under mechanical ventilation in the ICU, ventilatory mode or settings may influence sleep quality. The aim of this study was to evaluate the direct impact of mechanical ventilation per se on sleep quantity and quality in patients who were able to tolerate separation from mechanical ventilation over prolonged periods. DESIGN AND SETTING:: Randomized crossover clinical trial in a medical ICU. PATIENTS:: Sixteen conscious patients, free of sedation and tracheostomized because of prolonged weaning from mechanical ventilation, were included in the study when able to tolerate at least 5 hours of spontaneous ventilation. INTERVENTIONS:: Patients were randomized to receive either spontaneous ventilation or mechanical ventilation at low levels of pressure support for two crossover periods of 5-hour duration each, from 22:00 to 08:00. Polysomnography was performed throughout the study. MEASUREMENTS AND RESULTS:: Total sleep time was higher during mechanical ventilation than during spontaneous ventilation (183 min vs. 132 min, p = 0.04). No significant differences between mechanical ventilation and spontaneous ventilation were observed in slow wave sleep time (45 min vs. 28 min), rapid eye movement sleep time (11 min vs. 3 min), or the fragmentation index (25 vs. 23 arousals and awakenings per hour). In four patients, however, our analysis of patient-ventilator interaction suggested that the ventilatory settings were suboptimal and could have been improved to potentially improve sleep. CONCLUSIONS:: In difficult-to-wean tracheostomized patients, sleep quality was similar with or without the ventilator. Sleep quantity was higher during mechanical ventilation. Reconnection to the ventilator during the night period may favor sleep efficiency in tracheostomized patients in prolonged weaning.
Critical care medicine 03/2013; · 6.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE:: To compare sleep quality between two types of ventilators commonly used for noninvasive ventilation: conventional ICU ventilators and dedicated noninvasive ventilators; and to evaluate sleep during and between noninvasive ventilation sessions in critically ill patients. DESIGN:: Physiological sleep study with a randomized assessment of the ventilator type. SETTING:: Medical ICU in a university hospital. PATIENTS:: Twenty-four patients admitted for acute hypercapnic respiratory failure requiring noninvasive ventilation. INTERVENTIONS:: Patients were randomly assigned to receive noninvasive ventilation with either an ICU ventilators (n = 12) or a dedicated noninvasive ventilators (n = 12), and their sleep and respiratory parameters were recorded by polysomnography from 4 PM to 9 AM on the second, third, or fourth day after noninvasive ventilation initiation. MEASUREMENTS AND MAIN RESULTS:: Sleep architecture was similar between ventilator groups, including sleep fragmentation (number of arousals and awakenings/hr), but the dedicated noninvasive ventilators group showed a higher patient-ventilator asynchrony-related fragmentation (28% [17-44] vs. 14% [7.0-22]; p = 0.02), whereas the ICU ventilators group exhibited a higher noise-related fragmentation. Ineffective efforts were more frequent in the dedicated noninvasive ventilators group than in the ICU ventilators group (34 ineffective efforts/hr of sleep [15-125] vs. two [0-13]; p < 0.01), possibly as a result of a higher tidal volume (7.2 mL/kg [6.7-8.8] vs. 5.8 [5.1-6.8]; p = 0.04). More sleep time occurred and sleep quality was better during noninvasive ventilation sessions than during spontaneous breathing periods (p < 0.05) as a result of greater slow wave and rapid eye movement sleep and lower fragmentation. CONCLUSIONS:: There were no observed differences in sleep quality corresponding to the type of ventilator used despite slight differences in patient-ventilator asynchrony. Noninvasive ventilation sessions did not prevent patients from sleeping; on the contrary, they seem to aid sleep when compared with unassisted breathing.
Critical care medicine 12/2012; · 6.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Sleep disorders in humans have become a public health issue in recent years. Sleep can be analysed by studying the electroencephalogram (EEG) recorded during a night's sleep. Alternating between sleep-wake stages gives information related to the sleep quality and quantity since this alternating pattern is highly affected during sleep disorders. Spectral composition of EEG signals varies according to sleep stages, alternating phases of high energy associated to low frequency (deep sleep) with periods of low energy associated to high frequency (wake and light sleep). The analysis of sleep in humans is usually made on periods (epochs) of 30-s length according to the original Rechtschaffen and Kales sleep scoring manual. In this work, we propose a new phase space-based (mainly based on Poincaré plot) algorithm for automatic classification of sleep-wake states in humans using EEG data gathered over relatively short-time periods. The effectiveness of our approach is demonstrated through a series of experiments involving EEG data from seven healthy adult female subjects and was tested on epoch lengths ranging from 3-s to 30-s. The performance of our phase space approach was compared to a 2-dimensional state space approach using the power spectral (PS) in two selected human-specific frequency bands. These powers were calculated by dividing integrated spectral amplitudes at selected human-specific frequency bands. The comparison demonstrated that the phase space approach gives better performance in the case of short as well as standard 30-s epoch lengths.
Computer methods and programs in biomedicine 11/2012; · 1.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The goal of our study was to investigate different aspects of sleep, namely the sleep-wake cycle and sleep stages, in the vegetative state/unresponsive wakefulness syndrome (VS/UWS) and minimally conscious state (MCS). 24h polysomnography was performed in 20 patients in a UWS (n=10) or in a MCS (n=10) due to brain injury. The data were first tested for the presence of a sleep-wake cycle and the observed sleep patterns were compared to standard scoring criteria. Sleep spindles, slow waves sleep and rapid eye movement sleep were quantified and their clinical value was investigated. According to our results, an electrophysiological sleep-wake cycle was identified in 5 MCS and 3 VS/UWS patients. Sleep stages did not always match the standard scoring criteria which therefore needed to be adapted. Sleep spindles were more present in patients who clinically improved within 6 months. Slow wave sleep was present in 8 MCS and 3 VS/UWS patients but never in the ischemic etiology. Rapid eye movement sleep, and therefore dreaming which is a form of consciousness, was present in all MCS and 3 VS/UWS patients. In conclusion, the presence of alternating periods of eyes-open/eyes-closed cycles does not necessarily imply preserved electrophysiological sleep architecture in the UWS and MCS, contrary to previous definition. The investigation of sleep is a little studied yet simple and informative way to evaluate the integrity of residual brain function in patients with disorders of consciousness with possible clinical diagnostic and prognostic implications.
Journal of neurotrauma 11/2012; 30(5). · 4.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine whether severity patterns or nocturnal ventilation to treat sleep-disordered breathing (SDB) during chronic heart failure (CHF) is associated with adverse outcomes. Although SDB is frequent during CHF, the relationships between SDB and CHF outcomes are unknown.
A total of 384 CHF patients (82% men, mean age 59 ± 13 years) with a left ventricular ejection fraction (LVEF) of ≤45% (mean LVEF 29 ± 9%) were assessed by polygraphy in our clinic between 2001 and 2009. Nocturnal ventilation was started according to the severity of SDB. Combined endpoints were death, heart transplant, and implant of a ventricular assist device. The prevalence of obstructive sleep apnoea (OSA), central sleep apnoea (CSA), and Cheyne-Stokes respiration (CSR) was 62, 26, and 29%, respectively. A primary endpoint occurred in 31%. Mean follow-up for survivors was 47 ± 25 months. Those with moderate [apnoea-hypopnoea index (AHI) ≤5-20/h] and severe SDB (AHI ≥20/h), and OSA and CSA, had poor prognoses compared with patients without SDB (P = 0.036, P = 0.003, respectively). A total of 31% of SDB patients were treated with nocturnal ventilation. Treated SDB had a better outcome than untreated severe SDB after adjustment for confounding factors [P = 0.031; hazard ratio (HR) 0.56; 95% confidence interval (CI) 0.33-0.95]. Subgroup analysis that included only OSA showed a similar result after adjustment (P = 0.017; HR 0.40; 95% CI 0.19-0.95).
In CHF, SDB is associated with a poor prognosis whatever the SDB pattern, and nocturnal ventilation is associated with a better outcome.
European Journal of Heart Failure 06/2012; 14(9):1009-19. · 6.58 Impact Factor