Blue-Enriched White Light Therapy Reduces Fatigue in Survivors of Severe Traumatic Brain Injury: A Randomized Controlled Trial.

OBJECTIVE: Fatigue is one of the disabling sequelae of traumatic brain injury (TBI), with repercussions on quality of life, rehabilitation, and professional reintegration. Research is needed on effective interventions. We evaluated efficacy of blue-enriched white light (BWL) therapy on fatigue of patients with severe TBI. SETTING: Physical Medicine and Rehabilitation and Physiology departments of University hospitals. PARTICIPANTS: Adult patients with fatigue symptoms following severe TBI, Fatigue Severity Scale (FSS) score 4 or more, Epworth Sleepiness Scale (ESS) score 10 or more, and/or Pittsburgh Sleep Quality Index (PSQI]) more than 5 were randomly assigned to one of 2 parallel groups: a BWL therapy group, with 30-minute exposure to waking white light enriched with blue for 4 weeks, and a group without light therapy (N-BWL), no light. DESIGN: Randomized controlled trial. ClinicalTrials.gov number: NCT02420275. MAIN MEASURES: The primary outcome measure was the response of the FSS to 4 weeks of treatment. In addition, we assessed latency change of the P300 component of event-related potentials before and after therapy. RESULTS: Significant improvement in the FSS score (P = .026) was found in the BWL group compared with the N-BWL group. CONCLUSION: BWL phototherapy reduces fatigue in patients with severe TBI.

Effect of Smoked Cannabis on Vigilance and Accident Risk Using Simulated Driving in Occasional and Chronic Users and the Pharmacokinetic-Pharmacodynamic Relationship.

BACKGROUND: The pharmacokinetic-pharmacodynamic relationship between whole blood δ-9-tetrahydrocannabinol (THC) and driving risk is poorly understood. METHODS: Fifteen chronic cannabis consumers (1-2 joints/day; CC) and 15 occasional cannabis consumers (1-2 joints/week; OC) of 18 to 34 years of age were included. A pharmacokinetic study was conducted with 12 blood samplings over a 24-h period before and after controlled random inhalation of placebo or 10 mg or 30 mg of THC. THC and metabolites were quantified using LC-MS/MS. Effects on reaction time by psychomotor vigilance tests and driving performance through a York driving simulator were evaluated 7 times. A pharmacokinetic-pharmacodynamic analysis was performed using R software. RESULTS: Whole blood peak THC was 2 times higher in CC than in OC for a same dose and occurred 5 min after the end of consumption. THC remained detectable only in CC after 24 h. Despite standardized consumption, CC consumed more available THC from each cigarette regardless of dose. Maximal effect for reaction time was dose- and group-dependent and only group-dependent for driving performance, both being decreased and more marked in OC than in CC. These effects were maximal around 5 h after administration, and the duration was longer in OC than in CC. A significant pharmacokinetic-pharmacodynamic relationship was observed only between T max for blood THC and the duration effect on mean reciprocal reaction time. CONCLUSIONS: Inhalation from cannabis joints leads to a rapid increase in blood THC with a delayed decrease in vigilance and driving performance, more pronounced and lasting longer in OC than in CC. ClinicalTrials.gov Identifier: NCT02061020.

Circadian Rhythm Disturbances in the Blind.

PURPOSE OF REVIEW: Sleep timing, quantity, and quality are controlled by homeostatic and circadian systems. Circadian clock systems are present in all cells and organs and their timing is determined by a transcriptional-translational feedback loop of circadian genes. Individual cellular clocks are synchronized by the central body clock, situated in the suprachiasmatic nucleus, which communicates with them through humoral and neural signals including melatonin. The circadian system controls both the circadian period: (i.e., the length of the intrinsic clock), but also the circadian phase (i.e., the clock timing). An important determinant of the circadian system is light exposure. In most humans, the circadian period is slightly longer than 24 h and without regular resetting it tends to drift, leading to progressively later bedtimes and wake times and a tendency to cycle though periods of normal and abnormal sleep. Blind patients are thus at an increased risk of abnormal circadian function. The purpose of this article is to review recent research and clinical management of circadian rhythm disorders in blind patients. RECENT FINDINGS: Blind patients can present delayed and advanced sleep phase disorders but the most common abnormality in totally blind patients without light perception is non-24-hour sleep-wake disorder (N24SWD). This is rare in the general population but may affect up to 50% of blind patients without light perception. The diagnosis of a circadian rhythm disorder in the blind is complex. New screening tools have been developed but actigraphy and repeated melatonin profiles over 24 h remain essential. Circadian disorders in the blind are frequent, especially in the patients without light perception. They require accurate diagnosis in order to target treatment. Determining the precise nature of a sleep disorder in blind patients with a suspected circadian rhythm abnormality is complex and requires a detailed clinical history with sleep diaries and the use of actigraphy and melatonin profiles.

Nocturnal hypoventilation in neuromuscular disease: prevalence according to different definitions issued from the literature.

PURPOSE: Restrictive respiratory failure is a major cause of morbidity and mortality in neuromuscular diseases (NMD). Home mechanical ventilation (HMV) is used to treat hypoventilation, identified by daytime hypercapnia or nocturnal desaturation. Recently, transcutaneous measure of CO2 (TcCO2) has been increasingly used to detect hypoventilation, using different cut-offs. We aimed to compare the prevalence of hypoventilation in an unselected adult NMD population according to different definitions issued from the literature. METHODS: All consecutive nocturnal capno-oximetries performed between 2010 and 2014 in unventilated adult NMD patients were analysed retrospectively. Concomitant blood gas analysis and lung function data were collected. Patients on oxygen therapy were excluded. Hypoventilation was defined according to eight criteria, based on daytime PaCO2, daytime base excess, nocturnal SpO2 or TcCO2. RESULTS: Data from 232 patients were analysed (mean age 43.1 ± 15.4 years; 50.0 % women; vital capacity 59.2 ± 24.2 % of predicted). The hypoventilation prevalence was 10.3 to 61.2 %, depending on the used definition. The different definitions showed 49.1 to 94.8 % concordance (Cohen's kappa for agreement 0.115 to 0.763). Overall agreement between the eight definitions was poor (Light's kappa 0.267), and agreement between definitions based on nocturnal SpO2 and those based on TcCO2 was even lower (Light's kappa 0.204). CONCLUSIONS: We found large differences in hypoventilation prevalence according to the used definition. This has practical consequences, as HMV indication relies upon hypoventilation detection. We believe that capno-oximetry should be included in the diagnostic tools used to detect hypoventilation but this requires an update of consensus guidelines to agree upon the best definition.

Utility of the bispectral index for assessing natural physiological sleep stages in children and young adults.

Polysomnography (PSG) is the gold standard for the analysis of sleep architecture but is not always available in routine practice, as it is time consuming and cumbersome for patients. Bispectral index (BIS), developed to quantify the deepness of general anesthesia, may be used as a simplified tool to evaluate natural sleep depth. We objectively recorded sleep architecture in young patients using the latest BIS Vista monitor and correlated BIS values with PSG sleep stages in order to determine BIS thresholds. Patients, referred for the screening of sleep apnea/hypopnea syndrome or differential diagnosis of hypersomnia were recruited. Overnight PSG and BIS were performed simultaneously. BIS values were averaged for each sleep stage. Pre-sleep wakefulness (W) and wake after sleep onset (WASO) were also differentiated. BIS values were discarded for a signal quality index <90 %. ROC curves were plotted to discriminate sleep stages from each other. Twelve patients (5.7-29.3 years old) were included. Mean BIS values were 83 ± 8, 76 ± 12, 77 ± 11, 70 ± 10, 43 ± 10, and 75 ± 10 for W, WASO, N1, N2, N3 and R (REM) stages, respectively. BIS failed to distinguish W, WASO, N1 and R stages. BIS threshold that identified stage N2 was <73 (AUC = 0.784, p < 0.001) with low sensitivity (75 %) and poor specificity (64 %). BIS threshold that identified stage N3 was <55 (AUC = 0.964, p < 0.001) with an 87 %-sensitivity and a 93 %-specificity. BIS identified stage N3 with satisfactory sensitivity and specificity but is limited by its inability to distinguish REM sleep from wake. Further studies combining BIS with chin electromyogram and/or electrooculogram could be of interest.

A pooled analysis of six month comparative efficacy and tolerability in four randomized clinical trials: agomelatine versus escitalopram, fluoxetine, and sertraline.

OBJECTIVE: A pooled-analysis on the long-term outcome in four head-to-head studies: agomelatine versus fluoxetine, sertraline, and (twice) escitalopram. Method A meta-analytic approach was used. Hamilton Depression Rating Scale (HAM-D) scores, response and remission rates, Clinical Global Impression of Improvement (CGI-I) scores, response and remission rates, and completion rates/discontinuation rates due to adverse events were analyzed. RESULTS: At the last post-baseline assessment on the 24-week treatment period, the final HAM-D-17 score was significantly lower in patients treated with agomelatine than in patients treated with selective serotonin reuptake inhibitors (SSRIs), as well in the total group of patients with severe depression (P = 0.014 and 0.040, respectively). HAM-D response rates at the end of 24 weeks were significantly higher in patients treated with agomelatine than in patients treated with SSRIs, as well in the total group of patients with severe depression (P = 0.031 and 0.048, respectively). HAM-D remission rates at the end of 24 weeks were numerically but not significantly higher in patients treated with agomelatine than in patients treated with SSRIs. Final CGI-I scores were significantly lower for agomelatine. CGI-I response as well as remission rates were numerically higher in patients treated with agomelatine, without statistical significance. The percentage of patients with at least one emergent adverse event leading to treatment discontinuation was 9.4% in patients treated with SSRIs and 6.6% in patients treated with agomelatine (P = 0.065). CONCLUSION: The present pooled analysis shows that, from a clinical point of view, agomelatine is at least as efficacious as the investigated SSRIs with a trend to fewer discontinuations due to adverse events.

The melatonergic system in mood and anxiety disorders and the role of agomelatine: implications for clinical practice.

Melatonin exerts its actions through membrane MT1/MT2 melatonin receptors, which belong to the super family of G-protein-coupled receptors consisting of the typical seven transmembrane domains. MT1 and MT2 receptors are expressed in various tissues of the body either as single ones or together. A growing literature suggests that the melatonergic system may be involved in the pathophysiology of mood and anxiety disorders. In fact, some core symptoms of depression show disturbance of the circadian rhythm in their clinical expression, such as diurnal mood and other symptomatic variation, or are closely linked to circadian system functioning, such as sleep-wake cycle alterations. In addition, alterations have been described in the circadian rhythms of several biological markers in depressed patients. Therefore, there is interest in developing antidepressants that have a chronobiotic effect (i.e., treatment of circadian rhythm disorders). As melatonin produces chronobiotic effects, efforts have been aimed at developing agomelatine, an antidepressant with melatonin agonist activity. The present paper reviews the role of the melatonergic system in the pathophysiology of mood and anxiety disorders and the clinical characteristics of agomelatine. Implications of agomelatine in "real world" clinical practice will be also discussed.

Pilot study assessing the impact of intrathecal baclofen administration mode on sleep-related respiratory parameters.

OBJECTIVE: To assess the impact of intrathecal baclofen (ITB) mode of administration on sleep and sleep-related breathing events in severely disabled patients with severe spasticity. DESIGN: Open prospective trial. SETTING: Physical medicine and rehabilitation department. PARTICIPANTS: Patients (N=11) treated with ITB pump for severe spasticity. INTERVENTION: Assessment of patients' sleep before and after ITB pump implantation, and comparison of polysomnography results after continuous or bolus mode of administration of ITB. MAIN OUTCOME MEASURES: Polysomnography and sleep-related breathing events. RESULTS: ITB reduced periodic limb movements and increased the respiratory disturbance index (RDI) and central apneas in our population of patients. This study showed that ITB mode of administration may affect sleep-disordered breathing. Indeed, we observed a significant increase of respiratory events in the bolus condition (RDI and central apneas). In contrast, continuous infusion did not induce a significant modification of sleep-disordered breathing. When a sleep apnea syndrome was preexisting, it was generally severely worsened by the bolus mode of administration. CONCLUSIONS: These results indicate that sleep function and sleep-related respiratory events should be assessed before ITB pump implantation. It is probably better to use a continuous mode of infusion if patients have preexisting sleep-disordered breathing.

Is snoring intensity responsible for the sleep partner's poor quality of sleep?

PURPOSE: This study aimed to determine if the intensity of breathing noise (including snoring) and/or the presence of abnormal breathing events (ABE) are factors that trigger arousal/awakening of a snorer's bed partner. METHODS: We conducted a prospective multicenter study investigating couples where the male had a chronic disturbing snoring. We simultaneously recorded the male's respiration and snoring and the female' sleep. We counted the number of arousals and awakenings during N2 sleep and randomly took nine of each. Then, for periods before, during, and after each arousal and awakening, we observed on the respiratory tracings what was happening in terms of breathing noise intensity and presence/absence of snoring and/or ABE. RESULTS: Thirteen couples were analyzed. The intensity of breathing noise and the presence/absence of snoring and/or ABE were comparable before and at initiation of arousal/awakening and between arousal and awakening. However, breathing volume intensity was lower and the presence of snoring and/or ABE was less frequent when the bed partner returned back to sleep from awakening compared to the other periods (p always <0.001). CONCLUSIONS: The intensity of breathing noise or the presence of ABE does not seem to be essential to trigger an arousal or an awakening. However, the persistence of noise or events may prolong the duration of wakefulness during the sleep period and could be one factor that explains the bothersome snoring.

Nocturnal oximetry and transcutaneous carbon dioxide in home-ventilated neuromuscular patients.

BACKGROUND: Pulse oximetry alone has been suggested to determine which patients on home mechanical ventilation (MV) require further investigation of nocturnal gas exchange. In patients with neuromuscular diseases, alveolar hypoventilation (AH) is rarely accompanied with ventilation-perfusion ratio heterogeneity, and, therefore, oximetry may be less sensitive for detecting AH than in patients with lung disease. OBJECTIVE: To determine whether pulse oximetry (S(pO(2))) and transcutaneous carbon dioxide (P(tcCO(2))) during the same night were interchangeable or complementary for assessing home MV efficiency in patients with neuromuscular diseases. METHODS: Data were collected retrospectively from the charts of 58 patients with chronic neuromuscular respiratory failure receiving follow-up at a home MV unit. S(pO(2)) and P(tcCO(2)) were recorded during a 1-night hospital stay as part of standard patient care. We compared AH detection rates by P(tcCO(2)), S(pO(2)), and both. RESULTS: AH was detected based on P(tcCO(2)) alone in 24 (41%) patients, and based on S(pO(2)) alone with 3 different cutoffs in 3 (5%), 8 (14%), and 13 (22%) patients, respectively. Using both P(tcCO(2)) and S(pO(2)) showed AH in 25 (43%) patients. CONCLUSIONS: Pulse oximetry alone is not sufficient to exclude AH when assessing home MV efficiency in patients with neuromuscular diseases. Both P(tcCO(2)) and S(pO(2)) should be recorded overnight as the first-line investigation in this population.

Smoking and obesity among long-haul truck drivers in France.

INTRODUCTION: This study examines the health status of long-haul truck drivers (LHTDs) and more specifically smoking and obesity, in France. METHODS: A total of 373 French and other LHTDs were randomly interviewed at six highway rest stops. Variables recorded were self-reported sociodemographic characteristics (age, gender, marital status, and nationality), behavioral variables (consumption of sodas, daily exercise, smoking status), weight and height. Body mass index (BMI) was also calculated. Statistical analysis was conducted using chi-squared analysis and multiple logistic ordinal regression models (MLR) were developed. RESULTS: The mean age was 43.4 and the largest proportion (41.2%) of respondents were aged 40-50 years. Most respondents were French (70.3%), married (73.8%) and did not report having an active exercise routine (66.0%). Almost two-thirds of the drivers consumed daily 1-2 sodas (34.2%) or 3-4 sodas (33.2%). Based on the BMI, respondents were divided into normal (34.3%), overweight (39.8%), obese (19.5%) or morbidly obese (9.4%) categories. The mean BMI was 27.9 kg/m2 and 51.1% of LHTDs were current or active smokers. MLR analysis revealed that French LHTDs were more likely (OR=3.04; 95% CI: 1.62-5.69) to have a normal BMI compared to other drivers. Smokers were significantly more likely than non-smokers (OR=2.12; 95% CI: 1.26-3.58) to have an above normal BMI. CONCLUSIONS: These results confirm that French and other LHTDs are at high risk of non-communicable diseases. They also highlight the need to address the health risks associated with smoking and obesity among LHTDs using multifaceted strategies.

Impact of the novel antidepressant agomelatine on disturbed sleep-wake cycles in depressed patients.

BACKGROUND: Disturbance of sleep-wake cycles is common in major depressive disorder (MDD), usually as insomnia, but also as hypersomnia or reduced daytime alertness. Agomelatine, an MT(1) and MT(2) receptor agonist and 5-HT(2C) receptor antagonist, represents a novel approach in MDD, with proven antidepressant efficacy and a positive impact on the sleep-wake cycle. We review the effects of agomelatine 25/50 mg/day on objective and subjective measures of the sleep-wake cycle in MDD. SUBJECTIVE MEASURES: Agomelatine improved all aspects of the sleep-wake cycle from as early as 1 week in randomized trials versus selective serotonin reuptake inhibitors and venlafaxine, particularly getting off to sleep and quality of sleep, with an improvement in daytime alertness. OBJECTIVE MEASURES: Agomelatine's effect on sleep architecture in MDD has been measured by polysomnography (PSG). There were significant improvements in sleep efficiency, slow-wave sleep (SWS), and the distribution of delta activity throughout the night, but no change in amount or latency of rapid eye movement (REM) sleep. Furthermore, the slow-wave sleep was resynchronized to the first sleep cycle of the night. CONCLUSION: Agomelatine, a novel antidepressant, improves disturbed sleep-wake cycles in MDD. The improvement of both nighttime sleep and daytime functioning with agomelatine are promising features of this antidepressant regarding the management of MDD.

Sleep disorders in aging polio survivors: A systematic review.

BACKGROUND: Sleep disturbances, especially sleep disordered breathing and sleep movement disorders, seem to be highly prevalent among aging polio survivors. They could contribute to late functional deterioration, fatigue, poor quality of life and negative health outcomes, thereby increasing cardiovascular risk. OBJECTIVES: This review focused on current knowledge of the prevalence of sleep disorders in polio survivors, their features, predictive factors and management. DATA SOURCES: Articles were searched in PubMed and the Cochrane Library up to March 2018. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS AND INTERVENTIONS: Articles needed to 1) be written in English; 2) include only participants with previous poliomyelitis or post-polio syndrome diagnosis; and 3) involve any form of sleep disorders. Articles about isolated fatigue or non-specific sleep complaints as well as non-polio specific articles (neuromuscular disorders) were not included in the qualitative analysis. RESULTS: Among 166 studies identified, 41 were included in this review. The prevalence of sleep apnea syndrome, nocturnal alveolar hypoventilation and restless legs syndrome seemed higher than in the general population (from 7.3% to 65%, 15% to 20% and 28% to 63%, respectively). This review highlights the lack of randomised studies assessing sleep disorder management in this specific population. LIMITATIONS: Because of the small number of eligible publications, none was excluded for methodological limitations, and only a qualitative analysis was provided. CONCLUSIONS AND IMPLICATIONS: Follow-up of polio survivors should include systematic screening for sleep disorders because they are associated with adverse consequences. Sleep disorder evaluation and management should improve the long-term survival and quality of life of polio survivors. Methodologically robust clinical trials are needed, but the decreasing prevalence and large clinical spectrum of the disease may complicate the creation of comparable groups.

Spasticity or periodic limb movements?

BACKGROUND: Spasticity and spasms are distressing features of the upper motor neuron syndrome (UMNS) following spinal cord injuries (SCI) or multiple sclerosis (MS), and have common therapeutic implications. Despite an increase of antispastic drugs and strategies, sometimes up to the surgical implant of intrathecal baclofen pump, some patients still complain of disabling spasms, which poses diagnostic and therapeutic challenges. Although clinically similar, flexor spasms due to pyramidal tract disruption must be clearly differentiated from periodic limb movements (PLM), often accompanying restless leg syndrome (RLS) and occurring during sleep. We raised the hypothesis of this differential as a diagnostic confusion in this particular population. AIM: The aim of this study was twofold: 1) to search for RLS with PLM in consecutive patients referred for uncontrolled disabling spasms despite treatment, by nocturnal polysomnography (PSG); 2) to report the efficacy of dopaminergic agonists on PLM in this population. DESIGN: Observational prospective study. SETTING: Spasticity Clinic at the Raymond-Poincaré University Hospital, Garches, France. POPULATION: All consecutive patients with MS or SCI, referred to our spasticity clinic from March 2014 to July 2016 for the management of persistent and disabling spasms despite treatment. Obvious daytime spasticity or flexor spasms were not considered. When spasms prevailed at evening, night, or in supine position, patients underwent a nocturnal PSG. METHODS: Patients were assessed for RLS by clinical interview and for PLM by PSG. Patients with confirmed PLM (≥15 per hour of sleep) were treated with low dosage of pramipexole (after an iron deficiency was ruled out) and reassessed by PSG the following night. RESULTS: Forty-five patients were included. All fulfilled RLS criteria, and PLMs were confirmed in 39 patients. Median PLM index, and related arousals were 45.9 (19.8-76.2) and 5.1 (1.5-15) events per hour respectively. Nine patients treated with pramipexole underwent an early second PSG which showed an improvement of PLM index and arousals (P=0.0007 and P=0.01, respectively). CONCLUSIONS: In this princeps study, we demonstrated that in SCI and MS patients, "persistent spasms" inefficiently treated by antispastic drugs could in fact be PLM. Furthermore, we first reported the efficacy of dopaminergic agonists for PLM in an MS and SCI population. CLINICAL REHABILITATION IMPACT: This study brings new insights on abnormal movements, often misinterpreted as spasticity, and their management. We suggest to include a PSG in the diagnostic approach of uncontrolled spasms prevailing at night or in supine position, to search for PLM, which are easily treatable.

Non-REM sleep instability in patients with major depressive disorder: subjective improvement and improvement of non-REM sleep instability with treatment (Agomelatine).

OBJECTIVE: To assess the importance of non-rapid eye movement (NREM) sleep disturbance in major depressive disorder (MDD) patients using cyclic alternating pattern (CAP) analysis, and to determine the usefulness of CAP analysis in evaluating treatment effect. METHODS: Baseline sleep-staging data and CAP analysis of NREM sleep was compared in 15 MDD patients (Hamilton depression scale score>20) and normal controls. Longitudinal evaluation of sleep changes using similar analysis during a treatment trial was also performed. ANALYSIS: A single-blinded researcher scored and analyzed the sleep of MDD and age-matched normal controls at baseline and during a treatment trial using the international scoring system as well as CAP analysis. RESULTS: MDD patients had evidence of disturbed sleep with both analyses, but CAP analysis revealed more important changes in NREM sleep of MDD patients at baseline than did conventional sleep staging. There was a significant decrease in CAP rate, time, and cycle and disturbances of phase A subtype of CAP. NREM abnormalities, observed by CAP analysis, during the treatment trial paralleled subjective responses. Analysis of subtype A phase of CAP demonstrated better sleep improvement. CONCLUSION: CAP analysis demonstrated the presence of more important NREM sleep disturbances in MDD patients than did conventional sleep staging, suggesting the involvement of slow wave sleep (SWS) in the sleep impairment of MDD patients. Improvement of NREM sleep paralleled subjective mood improvement and preceded REM sleep improvement. CAP analysis allowed objective investigation of the effect of treatment on sleep disturbances.

Non-24-Hour Sleep-Wake Rhythm Disorder in the Totally Blind: Diagnosis and Management.

Several aspects of human physiology and behavior are dominated by 24-h circadian rhythms with key impacts on health and well-being. These include mainly the sleep-wake cycle, vigilance and performance patterns, and some hormone secretions. The rhythms are generated spontaneously by an internal "pacemaker," the suprachiasmatic nuclei within the anterior hypothalamus. This master clock has, for most humans, an intrinsic rhythm slightly longer than 24 h. Daily retinal light exposure is necessary for the synchronization of the circadian rhythms with the external 24-h solar environment. This daily synchronization process generally poses no problems for sighted individuals except in the context of jetlag or working night shifts being conditions of circadian desynchrony. However, many blind subjects with no light perception had periodical circadian desynchrony, in the absence of light information to the master clock leading to poor circadian rhythm synchronization. Affected patients experience cyclical or periodic episodes of poor sleep and daytime dysfunction, severely interfering with social, academic, and professional life. The diagnosis of Non-24 Sleep-Wake Rhythm Disorder, also named free-running disorder, non-entrained disorder, or hypernycthemeral syndrome, remains challenging from a clinical point of view due to the cyclical symptoms and should be confirmed by measurements of circadian biomarkers such as urinary melatonin to demonstrate a circadian period outside the normal range. Management includes behavioral modification and melatonin. Tasimelteon, a novel melatonin receptor 1 and 2 agonist, has demonstrated its effectiveness and safety with an evening dose of 20 mg and is currently the only treatment approved by the FDA and the European Medicines Agency.

Prognostic value of nocturnal hypoventilation in neuromuscular patients.

In neuromuscular disease (NMD) patients, current guidelines recommend the initiation of home mechanical ventilation (HMV) in case of daytime hypercapnia or nocturnal desaturation as an indirect sign of hypoventilation. Transcutaneous capno-oximetry (TcCO2) enables the direct assessment of nocturnal hypercapnia; however the best cut-off value remains to be defined. We aimed to compare the prognostic value of several published definitions of nocturnal hypercapnia in a cohort of NMD patients. All consecutive TcCO2 recordings performed between 2010 and 2014 in unventilated adult NMD patients in a tertiary reference centre were retrospectively collected. Initiation of HMV and mortality were collected as outcomes of interest. 124 patients with normal daytime blood gazes were analysed (median age 39 [IQR 31-55] years; vital capacity 61% [43-82] of predicted). The prevalence of nocturnal hypercapnia ranged from 3% to 44%, depending on the definition. Over a median follow-up duration of 2.5 years [IQR 1.6-4.1], HMV was initiated for 51 patients, whilst 4 patients died. Nocturnal peak TcCO2 ≥49 mmHg was the best predictor of HMV initiation in the follow-up, being associated with a hazard ratio of 2.6 [95% CI 1.4-4.6] in a multivariate analysis adjusting for lung function parameters. Nocturnal TcCO2 identifies NMD patients at risk for subsequent need for HMV in the following few years, who were not identified by daytime blood gases or nocturnal oximetry. As a consequence, peak nocturnal TcCO2 ≥49 mmHg should be considered as one of the criteria to start HMV in patients with NMDs, along with symptoms of hypoventilation, daytime hypercapnia, abnormal nocturnal oximetry results, and a diminished level of forced vital capacity.

Sleep disorders in childhood-onset myotonic dystrophy type 1.

Slowness, fatigue, and learning difficulties are common in young patients with myotonic dystrophy type 1. These features may indicate poor sleep quality. The aim of this study was to search for sleep disorders in this population. This prospective study used questionnaires, genetic testing, night-time polysomnography and multiple sleep latency tests to evaluate objective daytime sleepiness. Twenty-one patients were included. Mean age was 15.0+/-3.0. Age of onset of myotonic disorders was after birth and before 10 years old. Age of diagnosis was 12.0+/-2.9. Fatigue was reported by 76% of patients, while somnolence was present in 52%. Sleep was disturbed by numerous microarousals (mean 16.6+/-7.3/h of sleep) caused by abnormal respiratory events (6/21 patients) and/or periodic limb movements (8/21 patients). In young patients with DM1, complaints of fatigue and/or somnolence should lead to a polysomnography to look for sleep apnea syndrome and/or periodic limb movement, which were present in two-thirds of our population.

Insomniac complaints interfere with quality of life but not with absenteeism: respective role of depressive and organic comorbidity.

BACKGROUND AND PURPOSE: Insomnia is common and associated with poor health status and quality of life. We designed a study to evaluate the impact of insomniac complaints with and without comorbidity on health status and absenteeism. PATIENTS AND METHODS: This is a cross-sectional study performed within a 1-year follow up study on a prospective cohort of French employees. Insomniac subjects (n=986) were compared to control subjects (n=584). Insomniacs suffering from self-reported depressive feelings and behavioral and organic sleep complaints were excluded. RESULTS: Subjects with insomniac complaints (whether with mood or behavioral and organic sleep complaints or not) reported poorer quality of life and had a higher absenteeism rate than controls (9.6+/-31 versus 5.8+/-19 days, P<0.01). A logistic regression model adjusting for depressive and behavioral and organic sleep complaints showed that insomniac complaints were no longer predictive of absenteeism. CONCLUSIONS: Insomniac complaints are strongly associated with deterioration in quality of life but not necessarily with higher absenteeism.

Prognostic Value of Initial Assessment of Residual Hypoventilation Using Nocturnal Capnography in Mechanically Ventilated Neuromuscular Patients: A 5-Year Follow-up Study.

BACKGROUND: Restrictive respiratory failure is a major cause of morbidity and mortality in neuromuscular diseases (NMD). Home mechanical ventilation (HMV) is used to treat hypoventilation, and its efficiency is mostly assessed by daytime blood gases or nocturnal oxygen saturation monitoring (SpO2). Non-invasive transcutaneous measure of CO2 (TcCO2) allows to directly assess nocturnal hypercapnia and to detect residual hypoventilation with a higher sensitivity than SpO2. We aimed to compare the prognostic value of nocturnal SpO2 and TcCO2 in ventilated adult NMD patients. METHODS: All consecutive capno-oximetries performed between 2010 and 2011 in ventilated adult NMD patients were analyzed retrospectively. Concomitant blood gas analysis and lung function data were collected. Patients on oxygen therapy were excluded. Nocturnal hypoxemia and hypercapnia (using four different definitions) at baseline were compared in their ability to predict mortality and respiratory events requiring ICU admission during follow-up. RESULTS: Data from 55 patients were analyzed (median age 28 [interquartile range: 25-36.5] years; 71% Duchenne muscular dystrophy; vital capacity 12 [7-27]% of predicted; 51% tracheostomy). Capno-oxymetry showed hypoxemia in 14.5% and hypercapnia in 12.7-41.8%, according to the used definition. Over a follow-up lasting up to 5 years (median 4.0 [3.6-4.5] years), we observed 12 deaths and 20 respiratory events requiring ICU admission. Hypercapnia was significantly associated with the study outcomes, with TcCO2 > 49 mmHg during ≥10% of the time being the best definition, while hypoxemia was not. CONCLUSION: Our data show for the first time that residual hypoventilation, assessed by capnometry, is significantly associated with negative outcomes in adult ventilated NMD patients, while oximetry is not. Accordingly, we suggest capnometry to be included in the systematic assessment of HMV efficiency in NMD patients. CLINICALTRIALSGOV IDENTIFIER: NCT02551406.