Prevalence of Diamine Oxidase Enzyme (DAO) Deficiency in Subjects with Insomnia-Related Symptoms.

Background: To assess the prevalence of diamine oxidase (DAO) enzyme deficiency caused by single nucleotide polymorphisms (SNPs) of the AOC1 gene in a sample of patients with symptoms of insomnia. Methods: A total of 167 adult patients (>18 years of age) with symptoms of insomnia attended a specialized institute for healthy sleep, in Barcelona (Spain), between May and November 2023, and underwent genotyping analysis of the four most relevant SNP variants, including c.691G>7 (rs2052129), c.47C>T (rs10156191), c.995C>T (rs1049742), and c.1990C>G (rs1049793). Results: Genetic DAO deficiency was present in 138 patients, with a prevalence rate of 82.6% (95% CI 76-88.1%). Difficulties in staying asleep were the most common complaints in 88% of patients followed by trouble falling asleep in 60.5%. More than half of patients suffered from insomnia symptoms every day. Also, 99.4% reported daytime consequences of insomnia, with fatigue (79.6%), mood changes (72.5%), and impaired concentration in 70.1%. When patients were grouped by DAO-score, which reflected the number of heterozygous and homozygous SNPs variants, the group with a DAO-score ≥ 4 vs. 1 showed higher percentages of insomnia-related symptoms, in particular, trouble staying asleep and early morning awakening. These two symptoms were also more common in the presence of the c.1990C>G (rs1049793) variant. Conclusions: This preliminary real-world study presents novel evidence of a potential link between a DAO enzyme deficiency of a genetic origin and clinical symptoms of insomnia, which may suggest the potential benefit of DAO supplementation to improve the quality of sleep in these subjects. The study was registered at ClinicalTrials.gov (NCT06488027).

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.

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.

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.

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.

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.

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.