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Background: The narcolepsy severity scale (NSS) was developed to measure the severity and consequences of symptoms in patients with narcolepsy. The scale has been validated in France, though no other studies have further validated this instrument. The current study aimed to present psychometric properties and describe the score distribution of the Chinese-NSS.Methods: One hundred twenty-two patients with narcolepsy (41 females and 81 males; mean age 26.14 ± 15.40 years) participated in the study. All patients completed the Chinese-NSS. Cronbach's α, item-total score correlations, exploratory factor analysis (EFA), and correlations between NSS total scores and clinical or sleep parameters were then calculated.Results: EFA yielded a three-factor model. Internal consistency was acceptable (Cronbach'sα = 0.799). The NSS total score had significant correlations with the Epworth sleepiness score (0.447), pediatric daytime sleepiness scale (0.318), the insomnia severity index (0.592), Beck depression inventory (0.593), EurQol five dimensions-utility (0.457), EurQol five dimensions -VAS (- 0.323), the sleep disturbance scale for children (0.440), the children depression inventory (0.553), and the pediatric quality of life inventory (0.555) total scores, demonstrating acceptable convergence as predicted.Conclusions: The current study is the first validation study of the narcolepsy severity scale in an Asian population. The findings validated the Chinese-narcolepsy severity scale in a Chinese population with acceptable psychometric properties. There are minor differences between our results and those of the original study due to cultural differences. [ABSTRACT FROM AUTHOR]

Previous studies in narcolepsy, an autoimmune disorder affecting hypocretin (orexin) neurons and recently associated with H1N1 influenza, have demonstrated significant associations with five loci. Using a well-characterized Chinese cohort, we refined known associations in TRA@ and P2RY11-DNMT1 and identified new associations in the TCR beta (TRB@; rs9648789 max P = 3.7×10−9 OR 0.77), ZNF365 (rs10995245 max P = 1.2×10−11 OR 1.23), and IL10RB-IFNAR1 loci (rs2252931 max P = 2.2×10−9 OR 0.75). Variants in the Human Leukocyte Antigen (HLA)- DQ region were associated with age of onset (rs7744020 P = 7.9×10−9 beta −1.9 years) and varied significantly among cases with onset after the 2009 H1N1 influenza pandemic compared to previous years (rs9271117 P = 7.8×10−10 OR 0.57). These reflected an association of DQB1*03:01 with earlier onset and decreased DQB1*06:02 homozygosity following 2009. Our results illustrate how genetic association can change in the presence of new environmental challenges and suggest that the monitoring of genetic architecture over time may help reveal the appearance of novel triggers for autoimmune diseases. [ABSTRACT FROM AUTHOR]

Type 1 narcolepsy, a disorder caused by a lack of hypocretin (orexin), is so strongly associated with human leukocyte antigen (HLA) class II HLA-DQA1 ∗ 01:02-DQB1 ∗ 06:02 (DQ0602) that very few non-DQ0602 cases have been reported. A known triggering factor for narcolepsy is pandemic 2009 influenza H1N1, suggesting autoimmunity triggered by upper-airway infections. Additional effects of other HLA-DQ alleles have been reported consistently across multiple ethnic groups. Using over 3,000 case and 10,000 control individuals of European and Chinese background, we examined the effects of other HLA loci. After careful matching of HLA-DR and HLA-DQ in case and control individuals, we found strong protective effects of HLA-DPA1 ∗ 01:03-DPB1 ∗ 04:02 (DP0402; odds ratio [OR] = 0.51 [0.38–0.67], p = 1.01 × 10 −6 ) and HLA-DPA1 ∗ 01:03-DPB1 ∗ 04:01 (DP0401; OR = 0.61 [0.47–0.80], p = 2.07 × 10 −4 ) and predisposing effects of HLA-DPB1 ∗ 05:01 in Asians (OR = 1.76 [1.34–2.31], p = 4.71 × 10 −05 ). Similar effects were found by conditional analysis controlling for HLA-DR and HLA-DQ with DP0402 (OR = 0.45 [0.38–0.55] p = 8.99 × 10 −17 ) and DP0501 (OR = 1.38 [1.18–1.61], p = 7.11 × 10 −5 ). HLA-class-II-independent associations with HLA-A ∗ 11:01 (OR = 1.32 [1.13–1.54], p = 4.92 × 10 −4 ), HLA-B ∗ 35:03 (OR = 1.96 [1.41–2.70], p = 5.14 × 10 −5 ), and HLA-B ∗ 51:01 (OR = 1.49 [1.25–1.78], p = 1.09 × 10 −5 ) were also seen across ethnic groups in the HLA class I region. These effects might reflect modulation of autoimmunity or indirect effects of HLA class I and HLA-DP alleles on response to viral infections such as that of influenza. [ABSTRACT FROM AUTHOR]

Narcolepsy is a rare brain disorder that reflects a selective loss or dysfunction of orexin (also known as hypocretin) neurons of the lateral hypothalamus. Narcolepsy type 1 (NT1) is characterized by excessive daytime sleepiness and cataplexy, accompanied by sleep-wake symptoms, such as hallucinations, sleep paralysis and disturbed sleep. Diagnosis is based on these clinical features and supported by biomarkers: evidence of rapid eye movement sleep periods soon after sleep onset; cerebrospinal fluid orexin deficiency; and positivity for HLA-DQB1*06:02. Symptomatic treatment with stimulant and anticataplectic drugs is usually efficacious. This Review focuses on our current understanding of how genetic, environmental and immune-related factors contribute to a prominent (but not isolated) orexin signalling deficiency in patients with NT1. Data supporting the view of NT1 as a hypothalamic disorder affecting not only sleep-wake but also motor, psychiatric, emotional, cognitive, metabolic and autonomic functions are presented, along with uncertainties concerning the 'narcoleptic borderland', including narcolepsy type 2 (NT2). The limitations of current diagnostic criteria for narcolepsy are discussed, and a possible new classification system incorporating the borderland conditions is presented. Finally, advances and obstacles in the symptomatic and causal treatment of narcolepsy are reviewed. [ABSTRACT FROM AUTHOR]

Type 1 narcolepsy, an autoimmune disease affecting hypocretin (orexin) neurons, is strongly associated with HLA-DQB1*06:02. Among polymorphisms associated with the disease is single-nucleotide polymorphism rs2305795 (c.*638G>A) located within the P2RY11 gene. P2RY11 is in a region of synteny conserved in mammals and zebrafish containing PPAN, EIF3G and DNMT1 (DNA methyltransferase 1). As mutations in DNMT1 cause a rare dominant form of narcolepsy in association with deafness, cerebellar ataxia and dementia, we questioned whether the association with P2RY11 in sporadic narcolepsy could be secondary to linkage disequilibrium with DNMT1. Based on genome-wide association data from two cohorts of European and Chinese ancestry, we found that the narcolepsy association signal drops sharply between P2RY11/EIF3G and DNMT1, suggesting that the association with narcolepsy does not extend into the DNMT1 gene region. Interestingly, using transethnic mapping, we identified a novel single-nucleotide polymorphism rs3826784 (c.596-260A>G) in the EIF3G gene also associated with narcolepsy. The disease-associated allele increases EIF3G mRNA expression. EIF3G is located in the narcolepsy risk locus and EIF3G expression correlates with PPAN and P2RY11 expression. This suggests shared regulatory mechanisms that might be affected by the polymorphism and are of relevance to narcolepsy. [ABSTRACT FROM AUTHOR]