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Estimation of prevalence and incidence of narcolepsy and idiopathic hypersomnia (IH) is challenging owing to symptomatic overlap, underdiagnosis, and misdiagnosis, and epidemiological data are lacking in Asian populations. We estimated the prevalence and incidence of narcolepsy and IH in Japan. The Japan Medical Data Center (JMDC) database includes healthcare claims data for employed individuals ≤74 years of age. Narcolepsy and IH cases were defined by ≥2 diagnosis codes within 12 months, or a multiple sleep latency test with ≥1 diagnosis code within 12 months. Estimated point-prevalences of diagnosed narcolepsy and IH were calculated for December 31, 2019. Incidences of narcolepsy and IH were estimated for the period January 1, 2014 to December 31, 2019. Of 7,075,869 individuals enrolled in the database on December 31, 2019, 6,110,751 (86.4 %) had ≥12 months' continuous enrollment and were eligible for inclusion in the prevalence population. Age-sex standardized overall prevalences of narcolepsy and IH were 37.5 (95 % confidence intervals 35.9–39.1) and 7.7 (7.0–8.4) per 100,000 persons, respectively. Prevalence for both conditions peaked at age 20–29 years and declined with increasing age. Age-sex standardized overall incidences of narcolepsy and IH were 5.1 (4.8–5.4) and 1.2 (1.0–1.5) per 100,000 person-years, respectively. Narcolepsy and IH incidences peaked in the 10–19 and 20–29 years age groups then declined with increasing age. This claims-based study provides updated estimates for the prevalence and incidence of narcolepsy in Japan, and the first estimates for prevalence and incidence of IH in Japan. [Display omitted] • There is a paucity of data on the epidemiology of narcolepsy and IH in Japan. • Here we report the first epidemiological data on idiopathic hypersomnia in Japan. • Narcolepsy and idiopathic hypersomnia are rare in Japan in people aged ≤74 years. • Prevalence and incidence were similar to those from the United States and Europe. • Robust estimates for those aged >74 years are needed. [ABSTRACT FROM AUTHOR]

Narcolepsy is a chronic disorder that requires lifelong management; however, few studies have evaluated disease burden of narcolepsy. We estimated the healthcare burden of narcolepsy in Japan using data from the Japan Medical Data Center health insurance claims database. This was a retrospective analysis of clinical burden, healthcare resource utilization, and costs among incident narcolepsy cases and matched controls identified between January 1, 2014 and December 31, 2019. Of the 1317 incident cases; 889 (with 1778 controls) were analyzed for healthcare burden, 626 (with 1252 controls) for clinical journey, and 439 (no controls) for treatment patterns. The most common baseline comorbidity was non-narcolepsy sleep disorder (41.6 % cases vs 3.0 % controls), including insomnia (28.5 % vs 2.6 %) and sleep apnea (10.8 % vs 0.3 %; both p < 0.001). The most common nonsleep disorder comorbidities were depression (35.0 % vs 2.6 %), anxiety (30.4 % vs 2.7 %), and headache/migraine (18.1 % vs 5.5 %; all p < 0.001). Compared to controls, narcolepsy cases had more prescription claims in the year following index date (82.8 % vs 9.5 %; p < 0.001), higher rates of outpatient (2291.8 vs 674.9 visits/100 person-years; p < 0.001) and inpatient claims (56.8 vs 5.1/100 person-years; p < 0.001), and longer hospital stays (mean 2.9 vs 0.5 days; p < 0.001). Similarly, median HCRU costs were higher in cases than controls (total annual healthcare costs, $2531 vs $266; community pharmacy claims, $826 vs $47 per person; and outpatient claim costs, $1053 vs $188 per person year). Narcolepsy carries a substantial comorbidity burden, a high rate of medication prescribing, and high healthcare resource use in Japan. [Display omitted] • This study provides much-needed information on the burden of narcolepsy in Japan. • Narcolepsy has a substantial burden of sleep and non-sleep-related comorbidities. • Medication prescribing rates were high for people with narcolepsy. • Healthcare resource utilization and medical costs were high compared with controls. [ABSTRACT FROM AUTHOR]

This study aimed to determine the burden of narcolepsy in terms of direct medical costs and comorbidities and compare it with the respective burden of schizophrenia, epilepsy, and ulcerative colitis as controls. Patients diagnosed with narcolepsy (at least once based on the International Statistical Classification of Diseases and Related Health Problems, 10th Revision, code G47.4) between April 2017 and March 2022 were identified on the health insurance claims database compiled by JMDC Inc. Patients with schizophrenia (F20), epilepsy (G40), and ulcerative colitis (K51) were matched as controls. Direct medical costs (including inpatient, outpatient, and medication costs) and comorbidities were analyzed. We identified 4,594 patients with narcolepsy (≥18 years), 18,376 with schizophrenia, 18,376 with epilepsy, and 4,594 with ulcerative colitis. The total annual direct medical cost per person with narcolepsy was 349,188 JPY. The cost for narcolepsy was less than that for schizophrenia, epilepsy, and ulcerative colitis. Several comorbidities, such as sleep apnea, attention deficit hyperactivity disorder (ADHD), and obesity were more prevalent in the narcolepsy group. The total direct cost for narcolepsy was approximately three times higher than the national medical expense for people aged 15–44 years (122,000 JPY in 2020), but lower than the total cost for all control diseases. The patients with narcolepsy were also likely to have comorbidities that affected their burden. These findings can contribute to future discussions on medical expense assistance programs for patients with narcolepsy. • We determined the medical costs and comorbidities of narcolepsy, based on claims data. • The direct medical cost of narcolepsy was higher than the national medical expense. • Patients with narcolepsy have a wide range of comorbidities. [ABSTRACT FROM AUTHOR]

The objectives of this study were to describe prevalence, incidence, and medications among patients who were diagnosed with narcolepsy in Japan using a claims database. Patients diagnosed with narcolepsy were identified from January 2010 to December 2019 using an employment-based health insurance claims database compiled by JMDC Inc. The prevalence and incidence of narcolepsy were estimated annually in the overall population and by age and sex among employees and their dependents aged < 75 years. Medications, examined for each quarter in the overall population, were modafinil, methylphenidate, pemoline, tricyclic antidepressants, selective serotonin reuptake inhibitors, and serotonin-norepinephrine reuptake inhibitors. We identified 1539 patients with narcolepsy. The overall annual prevalence increased from 5.7 to 18.5/100,000 persons in 2010 and 2019, respectively. Large increases were found from 2010 to 2019 in patients aged 20–29 years and 10–19 years, with the highest prevalence in 2019 (9.7–37.5/100,000 persons and 5.0–27.1/100,000 persons). The overall incidence slightly increased from 3.6 to 4.3/100,000 person-year from 2010 to 2019, and the highest incidence was found in patients aged 20–29 years and 10–19 years (5.8–11.3/100,000 person-year, and 3.8–7.4/100,000 person-year from 2010 to 2019, respectively). Methylphenidate and modafinil were commonly prescribed in 2010 (27.3–38.9% and 17.5–45.5%, respectively). Methylphenidate prescriptions declined during the 10 years, whereas modafinil prescriptions increased (15.6–17.1% and 43.8–45.8% in 2019, respectively). The estimated prevalence and incidence of narcolepsy appeared to increase from 2010 to 2019, especially in teenagers and 20-year olds. [ABSTRACT FROM AUTHOR]

Study Objectives: We evaluated the risk of traumatic injury in patients with narcolepsy compared to the general population., Methods: We conducted a population-based matched cohort study using a Japanese health insurance claims database. For each patient with narcolepsy, up to 5 individuals from the general population without narcolepsy were matched by variables such as sex, age, and cohort entry month. The primary outcome was traumatic injury, and the secondary outcome was fracture. The study population was followed for up to 5 years from the cohort entry date. We estimated crude incidence rates, adjusted incidence rate differences, adjusted hazard ratios, and their 95% confidence intervals (CIs) for study outcomes using crude and multivariable Poisson and Cox regression models., Results: We included 2,451 patients with narcolepsy (mean age, 30.3 years; male, 58.0%) and 10,591 matched individuals (mean age, 30.6 years; male, 58.4%). Crude incidence rate of traumatic injury was 11.4 per 100 person-years for patients with narcolepsy compared with 6.2 per 100 person-years for matched individuals (adjusted incidence rate difference, 6.2 excess events per 100 person-years [95% CI, 4.9-7.4]; adjusted hazard ratio, 1.8 [95% CI, 1.5-2.2]). Crude incidence rate of fracture was 2.3 per 100 person-years for patients with narcolepsy compared with 1.3 per 100 person-years for matched individuals (adjusted incidence rate difference, 1.2 excess events per 100 person-years [95% CI, 0.7-1.7]; adjusted hazard ratio, 1.7 [95% CI, 1.4-2.1])., Conclusions: Narcolepsy was associated with increased risk of traumatic injury. For patients with narcolepsy, optimized approaches to injury prevention should be considered., Citation: Zheng Y, Fukasawa T, Masuda S, Takeuchi M, Kawakami K. Narcolepsy and risk of traumatic injury: a population-based matched cohort study. J Clin Sleep Med. 2024;20(10):1657-1662., (© 2024 American Academy of Sleep Medicine.)

Background: The minimum narcolepsy criteria "mean sleep latency (MSL) ≤8 min and ≥2 sleep onset rapid eye movement (REM) periods (SOREMPs) on polysomnography (PSG) and the multiple sleep latency test (MSLT)," according to The International Classification of Sleep Disorders, Third Edition (ICSD-3), are not specific to narcolepsy. Recently, the characteristic sleep stage sequences preceding SOREMPs in narcolepsy have received attention, but their diagnostic utility remains unclear.Methods: We retrospectively reviewed PSG/MSLT records and chart data for 102 Japanese patients with hypersomnia and at least one SOREMP. We examined the sporadic rates of two sleep stage sequences preceding the SOREMPs-wakefulness or stage 1 to REM (W/S1→R) and stage 2 to REM (S2→R)-comparing these between patient groups with narcolepsy type 1 (N = 28), narcolepsy type 2 (N = 19), and other hypersomnia (N = 55). We also examined the utility of three simple indices using the occurrence of W/S1→R SOREMPs for distinguishing between narcolepsy and other hypersomnia in patients who satisfied the minimum narcolepsy criteria.Results: W/S1→R SOREMPs were significantly more frequent in narcolepsy than in other hypersomnia, and this tendency was also observed even in the patients who satisfied the minimum narcolepsy criteria. The three indices had moderate sensitivities and specificities for distinguishing between narcolepsy and other hypersomnia in patients satisfying the minimum narcolepsy criteria.Conclusions: The W/S1→R pattern was observed significantly more frequently in narcolepsy than in other hypersomnia, suggesting it may help with differentiating narcolepsy from other hypersomnia in patients demonstrating the narcolepsy criteria, although its ability to do so may be modest. [ABSTRACT FROM AUTHOR]

Background: Narcolepsy (NA) is a sleep disorder characterized by excessive daytime sleepiness and an increased propensity of rapid eye movement sleep. If left untreated, NA can lead to academic underachievement or job loss because of dozing off or mistakes caused by inattentiveness due to sleepiness. Purpose: Although untreated narcolepsy patients may suffer from many social disadvantages due to excessive daytime sleepiness, mostly it takes a long time to receive a definitive diagnosis of the disorder. This retrospective study investigated factors related to the period until definitive diagnosis among patients with narcolepsy in Japan. Methods: We enrolled 181 consecutive patients (108 men, 73 women; mean age 37.6 ± 16.6 years old; narcolepsy with cataplexy/narcolepsy without cataplexy = 131:50). Multivariate logistic regression analysis was performed with period until definitive diagnosis as the dependent variable and descriptive clinical variables as the independent variables. Results: The mean period until receiving the diagnosis among the participants was 9.9 ± 10.1 years. More than half of the patients first learned about the disorder from information provided by the media. Multivariate logistic analysis indicated that adult onset ( p < 0.01), onset in 1995 or later ( p < 0.001), and first learning about the disorder from a sleep disorder specialist physician or a general practitioner ( p < 0.001) were associated with a time taken for receiving a definitive diagnosis less than or equal to the median value (7 years). Conclusion: Improving access to information about the concept of the disorder and the medical institutions specialized in sleep disorders, especially via the Internet, would be necessary to promote early diagnosis of the disorder. [ABSTRACT FROM AUTHOR]

Narcolepsy patients often access the Internet using key words mostly consisting of common symptoms in order to further learn about their disease. Although information from diverse sources floods the Internet, the quality of narcolepsy-related information appears to have improved, and harmful information does not often enter the top access rankings. Narcolepsy patients consider the information available on the Internet as being useful and wish to know more about new treatments, drugs, and the situation of other narcolepsy patients. The time from the onset of the symptoms to a definitive diagnosis has been significantly shorter in patients using the Internet compared to those who have not used it (8.8 vs 19.8 years). From this point of view, we believe that the Internet plays an important role in improving the quality of life of narcolepsy patients. Patients often desire information regarding the hereditary nature of the disease and ways to deal with their disease. There is a need to accurately assess what kind of information patients are looking for and to provide reliable information. [ABSTRACT FROM AUTHOR]

We report two cases of young adults sleepwalking. The first was a 19-year-old man whose episode occurred at the end of the first sleep stage 4. The second patient, a 28-year-old man, had episodes after the first and/or second slow wave sleep. Neither patient had epileptic discharges on a polysomnogram. Sleepwalking is diagnosed in only one percent of patients who are seen in our sleep clinic; this rate is lower than that of narcolepsy. In Japan, there have been few case reports of adult sleepwalking. We report these cases to further the study of sleep medicine, in particular of sleepwalking, in Japan. [ABSTRACT FROM AUTHOR]

We report on the association study of the tumor necrosis factor receptor 2 (TNFR2) gene with human narcolepsy. A single-nucleotide polymorphism in TNFR2, which is involved in an amino acid substitution [methionine(M)/arginine(R)] at position 196, was investigated in 149 Japanese narcoleptic patients and 204 healthy individuals as controls. Results reveal that the frequency of the TNFR2--196R allele significantly increased in the patients as compared with that in the controls (P50.029), suggesting that TNFR2 is likely associated with the susceptibility to narcolepsy. In addition, the analyses of the relationship of TNFR2 and TNF-a with the susceptibility to narcolepsy indicate the possibility that an additive effect on the susceptibility to the disorder lies between TNFR2--196R and TNF-a(--857T) alleles. [ABSTRACT FROM AUTHOR]

Objective The association between narcolepsy and rapid eye movement (REM)-related obstructive sleep apnea (OSA) has not been reported. This study aimed to examine the prevalence of REM-related OSA in narcolepsy patients. Methods From January 2013 to April 2018, 141 adult patients were diagnosed with narcolepsy using nocturnal polysomnography and the multiple sleep latency test. The prevalence of REM-related OSA in narcolepsy patients was retrospectively reviewed. Three criteria were used to determine REM-related OSA: Definition #1, an overall apnea-hypopnea index (AHI) ≥5 and AHI during REM (AHIREM)/AHI during non-rapid eye movement (NREM) (AHINREM) ≥2; Definition #2, an overall AHI ≥5 and AHI REM /AHI NREM ≥2 and AHI NREM <15; and Definition #3, an overall AHI ≥5 and AHI REM /AHI NREM ≥2 and AHI NREM <8 plus an REM sleep duration >10.5 minutes. Results Of the 141 narcolepsy patients, 26 were diagnosed with narcolepsy with cataplexy (NA-CA) and 115 with narcolepsy without cataplexy (NA w/o CA). Seventeen patients with NA-CA and 39 with NA w/o CA had OSA. According to Definition #1, the prevalence of REM-related OSA was 47.1% and 41.0%, respectively, in OSA patients with NA-CA and NA w/o CA; according to Definition #2, the respective prevalence was 47.1% and 38.5%, while that according to Definition #3 was 41.2% and 25.6%. No significant differences were found in the prevalence of REM-related OSA for each definition. Conclusion A high prevalence of REM-related OSA was confirmed in adult narcolepsy patients with OSA. Compared to previous reports, we noted a high frequency of REM-related OSA satisfying the relatively strict Definition #3. These results might reflect the pathophysiological characteristics of narcolepsy.

Etiology of narcolepsy-cataplexy involves multiple genetic and environmental factors. While the human leukocyte antigen (HLA)-DRB1*15:01-DQB1*06:02 haplotype is strongly associated with narcolepsy, it is not sufficient for disease development. To identify additional, non-HLA susceptibility genes, we conducted a genome-wide association study (GWAS) using Japanese samples. An initial sample set comprising 409 cases and 1562 controls was used for the GWAS of 525,196 single nucleotide polymorphisms (SNPs) located outside the HLA region. An independent sample set comprising 240 cases and 869 controls was then genotyped at 37 SNPs identified in the GWAS. We found that narcolepsy was associated with a SNP in the promoter region of chemokine (C-C motif) receptor 1 (CCR1) (rs3181077, P=1.6×10(-5), odds ratio [OR]=1.86). This rs3181077 association was replicated with the independent sample set (P=0.032, OR=1.36). We measured mRNA levels of candidate genes in peripheral blood samples of 38 cases and 37 controls. CCR1 and CCR3 mRNA levels were significantly lower in patients than in healthy controls, and CCR1 mRNA levels were associated with rs3181077 genotypes. In vitro chemotaxis assays were also performed to measure monocyte migration. We observed that monocytes from carriers of the rs3181077 risk allele had lower migration indices with a CCR1 ligand. CCR1 and CCR3 are newly discovered susceptibility genes for narcolepsy. These results highlight the potential role of CCR genes in narcolepsy and support the hypothesis that patients with narcolepsy have impaired immune function., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Reports on undetectable cerebrospinal fluid level of orexin A (hypocretin-1) in a nacroleptic-cataplexic patient in Japan found negative for human leukocyte antigen-class II. Daytime sleepiness; Hypnagogic hallucinations; Results of diagnostic nocturnal polysomnography and multiple latency tests.

Narcolepsy is a chronic hypersomnia involving excessive daytime sleepiness and cataplexy. Some susceptibility genes and environmental factors suggest that post-infectious immunological alterations underlie its pathophysiology. To investigate the immunological alterations in narcolepsy patients, we examined cytokines. Nine healthy controls and twenty-one narcolepsy patients with cataplexy were studied. All subjects were positive for the HLA-DRB1(∗)1501-DQB1(∗)0602 allele. Age-, sex-, and body mass index -matched healthy controls were selected. Plasma samples were separated using EDTA-2K-coated blood collection tubes. Bioplex Pro Human Cytokine 17-Plex Assays were used to measure plasma cytokines. Elevations of interleukin (IL)-6, IL-8, granulocyte- colony stimulating factor (G-CSF), and tumor necrosis factor-alpha were found in the narcolepsy group compared with healthy controls (p<0.05). G-CSF values were significantly correlated with the disease duration in narcolepsy patients (r=0.426, p<0.05). IL-8 and G-CSF play major roles in neutrophil activation in respiratory diseases. Since environmental factors including infection are reportedly associated with narcolepsy onset, elevated IL-8 and G-CSF may be involved in the pathophysiology of narcolepsy., (Copyright © 2014 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

Objectives: (1) To examine criterion validity of the Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) using obstructive sleep apnea (OSA), periodic limb movement disorder (PLMD), rapid eye movement sleep behavior disorder (RBD), and narcolepsy as criterion standard. (2) To summarize the evidence for criterion validity of the ESS for the diagnosis of OSA by a meta-analysis that combines the current and previous studies. (3) To investigate the determinants of the PSQI and ESS scores., Methods: The PSQI and ESS as well as the Hospital Anxiety and Depression Scale (HADS), which measures anxiety and depression levels, were administered to 367 patients consecutively referred to a sleep clinic. They underwent overnight polysomnography (PSG) and the multiple sleep latency test if narcolepsy was suspected., Results: The area under the receiver operating characteristic curves for the ESS and PSQI (and its subscale) were <0.9, meaning that these questionnaires were not highly accurate for predicting the four sleep disorders. The meta-analysis found that the ESS had no value in identifying OSA. The variable that most strongly influenced PSQI or ESS scores was the HADS score., Conclusion: The PSQI and ESS should no longer be used as a screening or diagnostic instrument for the four PSG-defined sleep disorders, especially in a low-risk population., (Copyright © 2014 Elsevier B.V. All rights reserved.)