Narcolepsy

Rapport de recherche rendu à la Fondation des maladies rares, 2019, issu d'une recherche en partenariat avec
• Le laboratoire d'ethnologie et de sociologie comparative (LESC), CNRS UMR 7186. La recherche de terrain ainsi que l’analyse du matériau ont été réalisés par Mickaële LANTIN MALLET avec le soutien et l’encadrement d’Aurore BECQUELIN MONOD et de Jacques GALINIER, coordinateurs de l’axe de recherche « Anthropologie de la nuit » et de Anne-Gaël BILHAUT, anthropologue.
• Le centre du sommeil et de la vigilance, centre national de référence des hypersomnies rares / Hôpital Hôtel-Dieu AP-HP, Université Paris Descartes. L’équipe était composée des Dr Brice FARAUT, Dr Caroline GAURIAU, Pr Damien LEGER avec le soutien et l’expertise de la Consultation de Pathologie Professionnelle “Sommeil et Travail” de l’Hôtel-Dieu de Paris, AP-HP.
• L’équipe italienne du Pr Vincenzo NATALE du Département de Psychologie, Université de Bologne est intervenue dans le traitement des données cliniques issues de l’actimétrie. En effet, ils disposent d’une base de données conséquente d’enregistrements actimétriques de longue durée chez des sujets sains contrôles ou insomniaques (avec une insomnie primaire). La comparaison de nos données respectives nous paraît plus pertinente et instructive. L’objectif est de trouver des paramètres d’analyse de l’actimétrie discriminants et caractéristiques des patients narcoleptiques.
• L’association nationale de narcolepsie-cataplexie et d’hypersomnies rares (ANC) qui est notamment associée au volet – en cours – de restitution de la recherche aux patients et familles de patients sous la forme d’un fascicule d’information et de sensibilisation sur la narcolepsie et l’insertion socioprofessionnelle.

Convention de recherche SOMNOPRO

Background: Autoimmunity has been proposed as a cause of narcolepsy. A few studies have assessed comorbid autoimmune diseases in patients with narcolepsy, with conflicting
results; however, no study has assessed autoimmune diseases in Arab narcolepsy patients. This study aimed to assess the coexistence of immune-mediated conditions such as allergies,
autoimmune diseases, and autoinflammatory diseases in patients with narcolepsy type 1 (with cataplexy) (NT1) and narcolepsy type 2 (without cataplexy) (NT2).
Methods: Personal and family history of autoimmune/autoinflammatory and allergic disorders was collected using a questionnaire in 80 consecutive Saudi patients with narcolepsy
(46 NT1 and 24 NT2), who were diagnosed according to the International Classification of Sleep Disorders, Third Edition. The control group comprised 222 adults from the general population.
Results: Comorbid autoimmune/autoinflammatory diseases were reported by 21.4% of the NT1 patients, and 12.2% of the controls, with no significant difference between cases and controls in a model adjusted for confounding covariates. However, allergic disorders were significantly more prevalent among NT1 patients. Both comorbid autoimmune/autoinflammatory and allergic disorders were significantly more prevalent among NT2 patients
compared to controls. No differences in demographic and clinical characteristics were detected between narcolepsy patients with and without autoimmune/autoinflammatory diseases.
Conclusion: NT1 is not associated with increased comorbid autoimmune diseases in the studied sample of Saudi patients. However, autoimmune diseases are associated with NT2, and allergic disorders are associated with both NT1 and NT2. These findings suggest the existence of dysregulation in the immune system of narcolepsy patients that requires further research.

Background: Autoimmunity has been proposed as a cause of narcolepsy. A few studies have assessed comorbid autoimmune diseases in patients with narcolepsy, with conflicting results; however, no study has assessed autoimmune diseases in Arab narcolepsy patients. This study aimed to assess the coexistence of immune-mediated conditions such as allergies, autoimmune diseases, and autoinflammatory diseases in patients with narcolepsy type 1 (with cataplexy) (NT1) and narcolepsy type 2 (without cataplexy) (NT2). Methods: Personal and family history of autoimmune/autoinflammatory and allergic disorders was collected using a questionnaire in 80 consecutive Saudi patients with narcolepsy (46 NT1 and 24 NT2), who were diagnosed according to the International Classification of Sleep Disorders, Third Edition. The control group comprised 222 adults from the general population. Results: Comorbid autoimmune/autoinflammatory diseases were reported by 21.4% of the NT1 patients, and 12.2% of the controls, with no significant difference between cases and controls in a model adjusted for confounding covariates. However, allergic disorders were significantly more prevalent among NT1 patients. Both comorbid autoimmune/autoinflam-matory and allergic disorders were significantly more prevalent among NT2 patients compared to controls. No differences in demographic and clinical characteristics were detected between narcolepsy patients with and without autoimmune/autoinflammatory diseases. Conclusion: NT1 is not associated with increased comorbid autoimmune diseases in the studied sample of Saudi patients. However, autoimmune diseases are associated with NT2, and allergic disorders are associated with both NT1 and NT2. These findings suggest the existence of dysregulation in the immune system of narcolepsy patients that requires further research.

Sleep disorders are prevalent in the Saudi population, and the demand for sleep
medicine services is expected to increase significantly. The prevalence of various
sleep disorders in the Kingdom of Saudi Arabia (KSA) is comparable to that in
Western countries. The practice of sleep medicine in the KSA began in the mid to
late 1990s and continued to expand since. Clear guidelines for accrediting sleep
medicine specialists and technologists were developed recently. Nevertheless, there remain numerous challenges to the progress of this specialty, including the
lack of trained technicians, specialists, and funding. To meet these challenges,
two training programs that provide structured training and certification in sleep
medicine have been established. Additionally, special training programs and
courses are organized for sleep technologists. In this chapter, we address the
current structure of sleep medicine practice in the KSA and the Arab world, the
prevalence of sleep disorders, and the strategies needed to overcome the current
challenges that hamper the progress of sleep medicine as a specialty in the
country.

Narcolepsy is a very rare disease among Israeli Jews with a frequency of 7/3 X 10(6). An investigation of the association of narcolepsy with the human leukocyte antigen system was conducted in Israeli Jews at the serologic and genomic levels. The human leukocyte antigen class I and class II antigen typing of 7 clinically diagnosed narcoleptics, 3 individuals suffering from sleep disorders other than narcolepsy, and 11 healthy matched controls revealed that all narcoleptic patients (100%) investigated in the present study carried the HLA-DR2 haplotype, whereas patients with other sleep disorders did not. The HLA-B7 and DR2 occurred jointly in 57% (4/7) of the narcoleptic patients, as compared to 2% in randomly selected Israeli healthy controls. Restriction fragment length polymorphism analysis was performed with several restriction enzymes and three cDNA probes for DQ alpha, DQ beta, and DR beta genes on genomic DNAs obtained from narcoleptics and patients with other sleep disorders, matched controls, and 3 homozygous typing cells representing the DR2 subtypes Dw2, Dw12, and DwAZH. The restriction fragment length polymorphism analysis showed that all narcoleptics (7 of 7) shared virtually identical restriction fragment length polymorphisms with one of the homozygous typing cells (GSO), which defines DR2,Dw2. The frequency of the DR2,Dw2 haplotype in the healthy Israeli population is 3.2%. Other non-narcoleptic patients did not share these restriction fragment length polymorphisms. These findings indicate that narcolepsy is associated worldwide with the HLA-DR2,Dw2 haplotype.

We need to know in order to understand the sleep disorder narcolepsy, sleep and wakefulness , sleep, sleeping ,''said Claperede on the body is a function of the strength of will automatically be delayed for a while , but when a higher level of fatigue would be defeated and the people succumb to sleep.'' Protection of biological instinct as a condition of sleep and the body representing the De Sanctic A.Forel , O , and P Wogt Janet has a different interpretation , and finally a study of brain cells during sleep, shrinking cracks between neurons and thus the expansion of fluids through here allows the brain to cleanse , Research also is likely to lead to diseases of the brain in the direction of these toxic proteins opinions of arındırılamamasının say... The main question that researchers are looking for answers , especially the vulnerable despite the drop were caused by animals slept. The largest effect on the brain's ability to repair, and memory, sleep learning is already known. But experts to sleep lightly "cleaning" function that thinks. Due to the limited amount of energy that the brain can spend the researchers have to choose one of two functions : awake and aware , or in sleep and cleaning. Narcolepsy Description Physiological mechanisms of sleep and wakefulness to sleep in 1948-50 Dr.Magoun that the animal experiments, the brain stem centers (along the spinal cord) to the brain and central

We investigate how characteristics of sleep-wake dynamics in humans are modified by narcolepsy, a clinical condition that is supposed to destabilize sleep-wake regulation. Subjects with and without cataplexy are considered separately. Differences in sleep scoring habits as a possible confounder have been examined. Four groups of subjects are considered: narcolepsy patients from China with (n=88) and without (n=15) cataplexy, healthy controls from China (n=110) and from Europe (n=187, two nights each). After sleep stage scoring and calculation of sleep characteristic parameters, the distributions of wake-episode durations and sleep-episode durations are determined for each group and fitted by power-laws (exponent α) and by exponentials (decay time τ). We find that wake duration distributions are consistent with power laws for healthy subjects (China: α=0.88, Europe: α=1.02). Wake durations in all groups of narcolepsy patients, however, follow the exponential law (τ=6.2-8.1 min). All ...

Normal sleep consists of 4-5 sleep cycles including light-, deep- and rapid eye-movement sleep. Restoration of physical and psychological function are the main effects of sleep. In most cases, disturbances of normal sleep become clinically evident as problems of initiating and maintaining sleep and/or as increased daytime sleepiness. Approximately 10% of adults suffer from pronounced insomnia, a similar percentage from markedly increased daytime sleepiness. Sleep disorders cause high socio-economic costs due to increased accident risk, cardiovascular sequelae and sick leave. Most of the 88 distinct diagnoses summarized in the international classification of sleep disorders can be differentiated and managed according to patients history. In patients with severe daytime sleepiness - sleep disordered breathing being the most frequent cause - the diagnostic evaluation and treatment in the sleep laboratory is required. Effective therapeutic strategies are available for many sleep disorders. According to the underlying disorder, treatment includes a variety of measures like life style changes, differentiated medical treatment and the use of nasally applied positive pressure in patients suffering from sleep disordered breathing.

This study assessed the efficacy and safety of armodafinil, the longer half-life enantiomer of modafinil, for the treatment of excessive sleepiness in patients with narcolepsy. This was a multicenter double-blind study with 196 patients (aged 18-65 years) randomized to receive armodafinil 150 mg (n = 65), armodafinil 250 mg (n = 67), or placebo (n = 64) once daily for 12 weeks. Efficacy was assessed using the Maintenance of Wakefulness Test (MWT) (six 20-min subtests across the day), the Clinical Global Impression of Change (CGI-C), subjective measures of sleepiness (Epworth Sleepiness Scale), patient diaries, and evaluations of cognitive performance (Cognitive Drug Research) and fatigue (Brief Fatigue Inventory). Armodafinil significantly increased MWT mean sleep latency (at 0900-1500) compared with placebo. The mean change from baseline at final visit for armodafinil was an increase of 1.3, 2.6, and 1.9 min in the 150-mg, 250-mg, and combined groups, respectively, compared with a decrease of 1.9 min for placebo (p < 0.01 for all three comparisons). Mean late-day MWT latency (1500-1900) was also significantly improved (difference of armodafinil combined group relative to placebo at final visit: 2.8 min, p = 0.0358). The proportions of patients who showed at least minimal improvement in the CGIC rating from baseline to final visit in the armodafinil 150-mg, 250-mg, and combined groups were 69%, 73%, and 71%, respectively, compared with 33% for placebo (p < 0.0001). Both doses were associated with statistically significant improvements in memory, attention, and fatigue (p < 0.05). The most common adverse events in patients receiving armodafinil were headache, nausea, and dizziness. Armodafinil significantly improved ability to sustain wakefulness throughout the day in patients with narcolepsy. Armodafinil also significantly improved overall clinical condition, memory, attention, and fatigue when compared with placebo.

To investigate the effect of repetitive transcranial magnetic stimulation (rTMS) in patients with narcolepsy. Using rTMS, three patients with narcolepsy and cataplexy were investigated with and without their anticataplectic medication. rTMS of the motor cortex was performed at an intensity of 110% of resting motor threshold, a frequency of 20 Hz, and a duration of 2s. EMG activity was recorded for both the right and left first dorsal interosseous muscle (FDI). Eight healthy controls were also investigated under the same conditions. The study was carried out in the sleep laboratory of the Neurology Department (University of Aachen). One female and two male patients with narcolepsy/cataplexy. N/A. In three narcoleptic patients, after three days of not taking their usual anticataplectic medication, rTMS of the motorcortex induced an interruption of voluntary EMG activity in the FDI. EMG reduction lasted from 0.6 to 3.5s and was more pronounced in the hand contralateral to the stimulate...

To examine the specificity of low CSF hypocretin-1 levels in narcolepsy and explore the potential role of hypocretins in other neurologic disorders. A method to measure hypocretin-1 in 100 microL of crude CSF sample was established and validated. CSF hypocretin-1 was measured in 42 narcolepsy patients (ages 16-70 years), 48 healthy controls (ages 22-77 years,) and 235 patients with various other neurologic conditions (ages 0-85 years). As previously reported, CSF hypocretin-1 levels were undetectably low (<100 pg/mL) in 37 of 42 narcolepsy subjects. Hypocretin-1 levels were detectable in all controls (224-653 pg/mL) and all neurologic patients (117-720 pg/mL), with the exception of three patients with Guillain-Barré syndrome (GBS). Hypocretin-1 was within the control range in most neurologic patients tested, including patients with AD, PD, and MS. Low but detectable levels (100-194 pg/mL) were found in a subset of patients with acute lymphocytic leukemia, intracranial tumors, craniocerebral trauma, CNS infections, and GBS. Undetectable CSF hypocretin-1 levels are highly specific to narcolepsy and rare cases of GBS. Measuring hypocretin-1 levels in the CSF of patients suspected of narcolepsy is a useful diagnostic procedure. Low hypocretin levels are also observed in a large range of neurologic conditions, most strikingly in subjects with head trauma. These alterations may reflect focal lesions in the hypothalamus, destruction of the blood brain barrier, or transient or chronic hypofunction of the hypothalamus. Future research in this area is needed to establish functional significance.

Narcolepsy is a unique model for dysfunction in mechanisms that regulate sleep and wakefulness. The narcolepsy syndrome is characterized by excessive daytime sleepiness with recurrent episodes of irresistible sleep, cataplexy, hypnagogic and/or hypnopompic hallucinations and sleep paralysis. The current hypothesis for the etiology of narcolepsy is that it is an autoimmune disorder because of its strong association with the human leukocyte antigen (HLA) system. HLA-DQ alleles are not particularly mutated in narcoleptic patients but they directly influence susceptibility to the disease. DQB10602 homozygote carriers have a two to four times higher risk of developing the disease than heterozygote carriers. In the present study we report a rare multiplex familial case of narcolepsy-cataplexy and show the strong effect of the HLA-DQB10602 allele upon the disease phenotype. In the family studied herein, both the proband and his brother are severely affected and homozygous DQB10602, whereas their sister does not carry the allele and is not affected at all. These data corroborate previous findings proposing DQB10602 homozygous subjects to be far more susceptible to narcolepsy. Insights into the DQB10602 positive family that include homozygous subjects may prove to be an important asset in the investigation of genetic vs. environmental factors predisposing to narcolepsy.