Search

The aim of the study was to present a woman affected of a narcolepsy with cataplexy (narcolepsy type 1) comorbid with an asymptomatic Primary Biliary Cholangitis (PBC). The HLA haplotype was DRB1*15:01, DQA1*01:02, DQB1*06:02. The allele DQB1*06:02 has been considered until now protective for PBC and dual pathology has not been published. We think the important clinical message of the Case would be of continuing to monitor adults with narcolepsy type 1 for late complications that may be associated with other autoimmune conditions. Clinicians should be aware of the relationship between Narcolepsy and PBC. This highlights the need for screening and management in these individuals., Competing Interests: Declaration of competing interest No declared., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: To assess the evolution of narcolepsy symptoms in first-, second, and third-degree relatives and to compare multiplex and simplex families., Methods: A total of 4045 family members and 362 narcoleptic individuals were entered in the study; with 3255 family members interviewed twice, five to seven years apart. A control group (n = 178) composed of spouses or housemates was also interviewed twice. Family members were divided according to their blood relationship with the probands and further divided into multiplex (ie, more than one narcolepsy cases) and simplex (only one narcolepsy case) families. Telephone interviews were conducted with the help of the Sleep-EVAL system; narcolepsy probands were evaluated and diagnosed by a Sleep Specialist in a Sleep Clinic Center., Results: A total of 1123 family members from 72 families were identified as members of multiplex families while the rest of the sample were a part of simplex families (n = 2132). Multiplex families had higher incidence and chronicity of hypersomnolence than the simplex family members and the control group. For cataplexy-like symptoms, only prevalence at the time of the first assessment distinguished multiplex (5.5%) and simplex (2.9%) families. Prevalence of sleep paralysis was higher among the first- and second-degree relatives coming from multiplex families, while incidence was the highest among second- and third-degree relatives. Hypnagogic hallucinations had similar prevalence between multiplex and simplex families but the incidence and chronicity were significantly higher among multiplex families. For each symptom, predictive factors were also determined in simplex and multiplex families., Conclusions: Our results show that individuals coming from multiplex families are at greater risks of a broad range of narcolepsy symptoms compared to simplex families., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Study Objectives: we performed a meta-analysis to assess the usefulness of HLA testing for Narcolepsy diagnosis in four major ethnical groups: Asians, Afro-Americans, Amerindians and Caucasians., Methods: PubMed, EMBASE, Web of Science, Scopus and Cochrane databases were searched for articles in English and French published before October 2017 on HLA class II alleles in Narcolepsy. We included case-control studies, cross-sectional and retrospective cohort studies with patients diagnosed following the International classifications of sleep disorders (1990-2012) and ethnically matched controls. Following PRISMA guidelines, two investigators independently extracted data according to the inclusion criteria listed in PROSPERO CRD42017058677. A third researcher was consulted for discrepancies. We extracted and pooled adjusted OR using random-effect models. We verified the strength of the association between HLA-DQB1*06:02 and the worldwide distribution of Narcolepsy type 1 (NT1) and type 2 (NT2); furthermore, we pooled the OR measuring the association between HLA-DQB1*06:02 and NT1, NT2 and hypersomniacs., Results: We identified 511 titles. Of these, 12 case-control studies were included, for a total of 2077 NT1 patients, 235 NT2 patients, 161 hypersomniacs and 7802 controls. In the population-stratified analysis, HLA-DQB1*06:02 conferred an increased risk for NT1 (OR: 24.1, IC: 14.6-39.5, p < 0.001) and NT2 (OR: 3.9; IC: 2.2-6.8, p < 0.001). For NT1 the pooled estimated positive Likelihood Ratio (LR+) was 5.94 (IC: 3.71-9.51) and the negative Likelihood Ratio (LR-) was 0.23 (IC: 0.16-0.33); for NT2 LR+ was 3.35 (IC: 2.08-5.38) and LR- 0.72 (IC: 0.63-0.81). Moreover, for hypersomniacs LR+ was 1.436 (IC 0.668-3.089) and LR- 0.903 (IC 0.714-1.142)., Conclusions: Our data support the preponderant role of HLA-DQB1*06:02 in susceptibility to NT1/NT2 across all ethnicities. HLA-DQB1*06:02 negativity should make clinicians cautious in excluding other diagnoses., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Narcolepsy is a rare, chronic, disabling neuropsychiatric disorder characterized by excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, sleep paralysis, and abnormal rapid eye movement sleep. It is strongly associated with the HLA-DQB1(∗)06:02 allele in various ethnic groups. Our study aimed to investigate the allelic spectrum of HLA-DQB1 in a sample of Han Chinese patients with narcolepsy and control subjects from Taiwan., Methods: We determined the genotype of the major histocompatibility complex, class II, DQ β1 gene, HLA-DQB1, in 72 narcolepsy subjects (44 men, 28 women), including 52 narcolepsy subjects with cataplexy (narcolepsy+cataplexy), 20 narcolepsy subjects without cataplexy (narcolepsy-cataplexy), and 194 control subjects (94 men, 100 women) using a sequence-specific oligonucleotide-probe hybridization technique., Results: We found a strong HLA-DQB1(∗)06:02 association in narcolepsy+cataplexy subjects (odds ratio [OR], 321.4 [95% confidence interval {CI}, 70.7-1461.4]). The association was less prominent in narcolepsy-cataplexy subjects (OR, 6.9 [95% CI, 2.4-20.1]). In addition to the DQB1(∗)06:02, we found that (∗)03:01 also was a predisposing allele (OR, 2.0 [95% CI, 1.1-3.7]) in narcolepsy+cataplexy subjects, though the (∗)06:01 was a predisposing allele (OR, 2.8 [95% CI, 1.2-6.7]) in narcolepsy-cataplexy subjects. Furthermore, we found a significant overrepresentation of DQB1(∗)06:02 homozygotes in narcolepsy+cataplexy subjects., Conclusions: Our data add further support to the strong association of the HLA-DQB1(∗)06:02 allele with narcolepsy, especially in narcolepsy+cataplexy patients. Our study also indicates additional HLA-DQB1 alleles may modify the presentation of narcolepsy+cataplexy patients, such as DQB1(∗)03:01 and DQB1(∗)06:01 in our study. Our results are limited by the small sample size and can only be considered as preliminary findings., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: Narcolepsy is a neuropsychiatric disorder characterized by excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, and abnormal rapid eye movement (REM) sleep. Tumor necrosis factor α (TNF α) and its cognate receptors have been reported to be involved in the pathophysiology of narcolepsy in addition to the HLA antigen system. Our study aimed to determine if the TNF-α system was associated with narcolepsy in our patients., Methods: We first measured the plasma level of TNF α in 56 narcoleptic patients and 53 control subjects using a highly sensitive enzyme-linked immunosorbent assay. We next determined the genotype of three single nucleotide polymorphisms (SNPs) (T-1031C, C-863A, and C-857T) at the promoter region of the TNF-α gene and one missense SNP (T587G, M196R) at the exon 6 of the tumor necrosis factor receptor 2 gene, TNFR2, in a sample of 75 narcoleptic patients and 201 control subjects by direct sequencing analysis., Results: We found a significant elevation of plasma level of TNF α in patients with narcolepsy compared with the control subjects (4.64pg/mL vs 1.06pg/mL; P=.0013). However, we did not find significant differences between these two groups in the allelic and genotypic distributions of the investigated polymorphisms., Conclusions: Our study suggests that an increased TNF-α level was associated with narcolepsy in our patients, and that chronic inflammation due to various factors might have led to the increased TNF-α levels found in our patients., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Sleep disorders commonly involve genetic susceptibility, environmental effects, and interactions between these factors. The heritability of sleep patterns has been shown in studies of monozygotic twins, and sleep electroencephalogram patterns offer a unique genetic fingerprint which may assist in the identification of genes involved in the regulation of sleep. Genetic factors are also thought to play a role in sleep disorders; narcolepsy is a disabling sleep condition and research has revealed the complexity of underlying genetic and environmental influences in the development of this disorder. An understanding of sleep regulation at the molecular level is essential in the identification of new targets for the treatment of sleep disorders, and genome-wide association studies for both normal sleep and sleep disorders may shed new light on the molecular architecture of mechanisms regulating these behaviours.

Mice lacking orexin/hypocretin signaling have sudden episodes of atonia and paralysis during active wakefulness. These events strongly resemble cataplexy, episodes of sudden muscle weakness triggered by strong positive emotions in people with narcolepsy, but it remains unknown whether murine cataplexy is triggered by positive emotions. To determine whether positive emotions elicit murine cataplexy, we placed orexin knockout (KO) mice on a scheduled feeding protocol with regular or highly palatable food. Baseline sleep/wake behavior was recorded with ad libitum regular chow. Mice were then placed on a scheduled feeding protocol in which they received 60% of their normal amount of chow 3 h after dark onset for the next 10 days. Wild-type and KO mice rapidly entrained to scheduled feeding with regular chow, with more wake and locomotor activity prior to the feeding time. On day 10 of scheduled feeding, orexin KO mice had slightly more cataplexy during the food-anticipation period and more cataplexy in the second half of the dark period, when they may have been foraging for residual food. To test whether more palatable food increases cataplexy, mice were then switched to scheduled feeding with an isocaloric amount of Froot Loops, a food often used as a reward in behavioral studies. With this highly palatable food, orexin KO mice had much more cataplexy during the food-anticipation period and throughout the dark period. The increase in cataplexy with scheduled feeding, especially with highly palatable food, suggests that positive emotions may trigger cataplexy in mice, just as in people with narcolepsy. Establishing this connection helps validate orexin KO mice as an excellent model of human narcolepsy and provides an opportunity to better understand the mechanisms that trigger cataplexy.

Canine narcolepsy is an animal model of the human rapid eye movement sleep disorder. Dogs exhibit bouts of sleep attacks and muscle atonia (cataplexy) that are induced by emotions and thought to be abnormal rapid eye movement sleep episodes. We have previously demonstrated that cataplexy is strongly inhibited by increases in noradrenergic activity. This effect is mediated through central alpha 1-adrenoceptors, presumably of the alpha 1B subtype. In this study, we demonstrate with the canine model that SDZ NVI-085, a new compound with alerting effects, is a potent anticataplectic agent that may act through stimulation of an alpha 1-adrenoceptor subtype.