Objective Narcolepsy type 1 （NT1） is known to be associated with low levels of hypocretin-1 （Hcrt-1） in cerebrospinal fluid （CSF）. The standard method for Hcrt-1 measurement is radioimmunoassay （RIA） with imported reagents， but this antibody-dependent method is limited to radiation safety-certified lab， gradual radioactivity degradation， and slow turn-around time. The purpose of this study is to explore a non-radioactive， faster， and antibody independent domestic method in China for Hcrt-1 detection. Methods Repeated testing of cerebrospinal fluid from 14 clinically diagnosed NT1 patients and 10 non-narcolepsy patients was performed using liquid chromatography-tandem mass spectrometry （LC-MS/MS）technology，including the establishment and optimization of fundamental methodological procedures. The main steps involved the addition of non-radioactive isotope-labeled internal standards to the cerebrospinal fluid， followed by solid-phase extraction， mass spectrometry signal acquisition， and quantitative analysis. The results were then compared with the corresponding radioimmunoassay（RIA） findings. Results The LC-MS/MS method showed faster speed， and good linearity across a wider range of synthesized standard（5~2 500 pg/ml）， and good repeatability. Although this absolute-quantitation-based LC-MS/MS method and RIA method have different reading values in Hcrt-1 quantitation， they both can segregate NT1 group from non-NT1 group well. Conclusion Although larger cohorts are needed to set up a standard method in China，LC-MS/MS method is proved to be an easier， safer， faster， and possibly more accurate method for Hcrt-1 quantitation and detection for NT1 diagnosis.
Narcolepsy ; Radioimmunoassay

Narcolepsy（NP） is a rare central sleep disorder， and it is categorized into narcolepsy type1 （NT1） and narcolepsy type2（NT2）.The main clinical symptoms of NP include daytime lethargy， cataplexy induced by emotions， and sleep paralysis， with a peak onset during adolescence （with an age of 8‒12 years）. At present， the pathogenesis of NP remains unclear and is associated with various factors such as human leucocyte antigen （HLA）， infection， and epigenetic silencing， and the selective loss of hypocretin neurons in the hypothalamus is the key pathophysiological mechanism of NP. Pharmacological intervention is currently the main treatment method， and diagnostic delay can be as long as more than 10 years， which not only affects the social activities， academic performance， and work of patients， but also leads to mental health issues such as anxiety and depression. This article reviews the latest research findings in the epidemiology， pathogenesis， and treatment of NT1 and clarifies the deficiencies and controversies in current research， so as to provide new ideas and directions for subsequent studies.
Narcolepsy ; Cataplexy

Objective The efficacy and safety of pitolisant in the treatment of adult narcolepsy have been confirmed in clinical trials abroad， but there is a lack of data on the application of pitolisant in Chinese patients. The aim of this study is to investigate the efficacy and safety of pitolisant in the treatment of adult narcolepsy in China.Methods A total of 30 subjects were enrolled in this study and were given individualized titration once a day for 8 weeks. Epworth Somnolence Scale （EES） and daily cataplexy rate （DCR） were used as the primary outcome measures，and Clinical Global Impression-Severity scale（CGI-S） and Clinical Global Impression of Change Scale （CGI-C） were used as the secondary outcome measures；safety indicators included adverse event （AE） records and laboratory examination.Results The results showed that there were significant improvements in ESS score and number of cataplexy attacks after medication. At the end of treatment，ESS score was reduced by（7.63±4.79）（P<0.001）. For all subjects， the average daily number of cataplexy attacks was 0.83 at baseline，which was reduced significantly to （0.39±0.82）after 3 weeks of pitolisant treatment and（0.38±0.79）after 5 weeks of pitolisant treatment（P<0.05）. After the treatment ended， the median CGI-S score of excessive daytime sleepiness （EDS） improved from "severe" at baseline to "mild"（P<0.001）， and the CGI-S score of cataplexy improved from "mild" at baseline to "basically normal"（P<0.001）. Most AEs were mild and did not receive any drug treatment， and there were no significant changes in other laboratory markers used to monitor the general condition of the subjects before and after treatment. Conclusion Pitolisant has good efficacy and safety in the treatment of EDS and cataplexy in Chinese adults with narcolepsy.
Narcolepsy ; Histamine ; Cataplexy

Humans ; Cataplexy/drug therapy* ; Sleep, REM ; Dopamine ; Narcolepsy/drug therapy*

OBJECTIVES: Previous studies have shown that periodic limb movements in sleep (PLMS) could be one of risk factors for cardiovascular morbidity. The purpose of this study was to investigate the association between PLMS and blood pressure changes during sleep. METHODS: We analyzed data from 358 adults (176 men and 182 women) aged 18 years and older who were free from sleep apnea syndrome (Respiratory Disturbance Index < 5) and sleep disorders such as REM sleep behavior disorder or narcolepsy. Demographic characteristics, polysomnography records, and clinical variable data including blood pressure, body mass index, alcohol, smoking, and current medications were collected. In addition, self-report questionnaires including the Beck Depression Index, Epworth Sleepiness Scale and Pittsburgh Sleep Quality Index were completed. Blood pressure change from bedtime to awakening was compared between the two periodic limb movement index (PLMI) groups [low PLMI (PLMI ≤ 15) and high PLMI (PLMI > 15)]. Blood pressure change patterns were compared using repeated measures analysis of variance. RESULTS: Systolic blood pressure in the high PLMI group was lower than that in the low PLMI group (p = 0.036). These results were also significant when adjusted for gender and age, but were not statistically significant when adjusted for BMI, alcohol, smoking, anti-hypertension medication use and sleep efficiency (p = 0.098). Systolic blood pressure dropped by 9.7 mm Hg in the low PLMI group, and systolic blood pressure in the high PLMI group dropped by 2.9 mm Hg. There was a significant difference in delta systolic blood pressure after sleep between the two groups in women when adjusted for age, BMI, alcohol, smoking, antihypertensive medication use and sleep efficiency (p = 0.023). CONCLUSION: PLMS was significantly associated with a decreasing pattern in nocturnal BP during sleep, and this association remained significant in women when adjusted for age, BMI, alcohol, smoking, antihypertension medication use and sleep efficiency related to blood pressure. We suggest that PLMS may be associated with cardiovascular morbidity.
Adult ; Blood Pressure ; Body Mass Index ; Depression ; Extremities ; Female ; Humans ; Hypertension ; Male ; Narcolepsy ; Polysomnography ; REM Sleep Behavior Disorder ; Risk Factors ; Sleep Apnea Syndromes ; Sleep Wake Disorders ; Smoke ; Smoking

OBJECTIVE: The Epworth Sleepiness Scale is a measure used for the diagnosis of sleep disorders including obstructive sleep apnea (OSA) syndrome, insomnia, and narcolepsy. Although a Korean version has been developed (the KESS), Korean lifestyle such as the floor culture and low driving rates has not been considered. We aim to develop and validate a modified KESS (mKESS) that reflects the Korean lifestyle. METHODS: The sample consisted of 795 healthy participants and 323 OSA patients. The mKESS was developed by modifying several questions to concern the floor culture (questions 1, 2, 6, and 7) and low driving rates (question 8). Feasibility of the modification was tested by comparing the KESS and mKESS using paired samples t-test and by examining internal consistency reliability. Then, mKESS scores of the OSA patients and general participants were compared to test its validity. RESULTS: Questions 1, 2, 7, and 8 were significantly different when comparing the performances of the general population on both scales. Especially, the mean scores on question 8 were significantly different in the non-driver group, but not in the driver group. Cronbach’s alpha of the mKESS was relatively higher than that of the KESS. Total mKESS scores of the OSA patients were significantly higher than that of the general population. CONCLUSION: The mKESS is more universally applicable for the clinical evaluation of people that live in Korea. Results support that the mKESS can be administered to measure the average daytime sleep propensity of the Korean population as an alternative to the KESS.
Diagnosis ; Healthy Volunteers ; Humans ; Korea ; Life Style* ; Narcolepsy ; Sleep Apnea, Obstructive ; Sleep Initiation and Maintenance Disorders ; Sleep Wake Disorders ; Weights and Measures

Narcolepsy is characterized by excessive daytime sleepiness, cataplexy, sleep paralysis and hypnagogic hallucinations. Only a few studies have focused on non-rapid eye movement (NREM) and REM parasomnias in narcolepsy. We report a narcolepsy without cataplexy patient presenting parasomnia as an initial symptom. A 18-year-old boy was admitted to hospital for abnormal behavior of sitting up during sleep over 2 years. He had a symptom of lethargy without cataplexy and subjective excessive daytime sleepiness, but his family found him often asleep during daytime. He underwent 3 times of polysomnography (PSG) including 1 multiple sleep latency test (MSLT) after the last PSG. The last PSG showed 1 episode of abrupt sitting. Three sleep REM onset period was observed in MSLT which was not detect in PSG. Parasomnia as an initial symptom of narcolepsy is a rare clinical entity. The MSLT may be useful in the evaluation of patients with parasomnia and unexplained hypersomnia.
Adolescent ; Cataplexy ; Disorders of Excessive Somnolence ; Eye Movements ; Hallucinations ; Humans ; Lethargy ; Male ; Narcolepsy ; Parasomnias ; Polysomnography ; Sleep Arousal Disorders ; Sleep Paralysis

Psychostimulants are a broad class of sympathomimetic drugs that include drugs of abuse, such as illegal substances, as well as therapeutic drugs, such as methylphenidate and modafinil. The common effect of psychostimulants is to improve motivation, mood, movement, energy, wakefulness, arousal, anorexia and attention. Methylphenidate and modafinil are psychostimulants used in the treatment of attention deficit hyperactivity disorder and narcolepsy. They have also been found to be effective for treating certain cognitive disorders that result in secondary depression or profound apathy, obesity, cancer-related fatigue as well as in specific treatment-resistant depressions as an augmentation therapy with antidepressants. Psychostimulants are also used in an non-medical manner, such as cognitive and/or performance enhancers in healthy population. However, the most limiting adverse effect of psychostimulants is their vulnerability to psychological and physical dependence. Therefore, the abuse and misuse of stimulants, including methylphenidate and modafinil, for the purpose of neuroenhancement is an issue of concern throughout the world including Korea. Although several recent studies have reported on the cognitive and performance enhancement effects of methylphenidate and modafinil in healthy population, psychostimulants should be administered with discretion in the light of their potential adverse effects and the lacks of long-standing efficacy.
Anorexia ; Antidepressive Agents ; Apathy ; Arousal ; Attention Deficit Disorder with Hyperactivity ; Depression ; Fatigue ; Korea ; Methylphenidate ; Motivation ; Narcolepsy ; Obesity ; Street Drugs ; Sympathomimetics ; Wakefulness

OBJECTIVE: This study was conducted to identify differences between people with narcolepsy and the normal control of delta and theta activity using electroencephalogram (EEG) spectrum analysis of nocturnal polysomnography (PSG). METHODS: Seven narcolepsy patients and seven age-sex matched normal controls underwent PSG and multiple sleep latency tests. Participants' non-rapid eye movement (NREM) sleep EEGs in PSG was analyzed using a Fast Fourier Transform technique. RESULTS: While NREM delta activity of people with narcolepsy declined during the first three periods of NREM, there was no change during the 4th period of NREM. The increase in NREM theta activity also lasted until the 3rd period of NREM but did not occur during the 4th period of NREM. In comparing sleep parameters, REM sleep latency in the narcolepsy group was significantly shorter than in controls. CONCLUSION: These results suggest that people with narcolepsy are likely to have a delta and theta activity-related sleep disturbance mechanism in NREM sleep.
Electroencephalography ; Eye Movements ; Fourier Analysis ; Humans ; Narcolepsy* ; Polysomnography* ; Sleep, REM ; Spectrum Analysis

OBJECTIVES: Periodic limb movement disorder (PLMD) has been debated with regard to its clinical significance and diagnostic criteria. The current diagnostic criterion for PLMD in adults has been changed from periodic limb movement index (PLMI) > 5/ hour to PLMI > 15/hour by the International Classification of Sleep Disorders (ICSD). In this study, we aimed to investigate the changes in polysomnographic sleep variables according to PLMI and to determine the relevance of the diagnostic criterion for PLMD. METHODS: Out of 4195 subjects who underwent standard polysomnography, we selected 666 subjects (370 males and 296 females, aged 47.1 ± 14.8) who were older than 17 years and were not diagnosed with primary insomnia, sleep apnea, narcolepsy, or REM sleep behavior disorder. Subjects were divided into three groups according to PLMI severity: group 1 (PLMI ≤ 5), group 2 (5 < PLMI ≤ 15), and group 3 (PLMI > 15). Demographic and polysomnographic sleep variables and Epworth sleepiness scale (ESS) were compared among the three groups. RESULTS: There were significant differences among the three groups in age and gender. Sleep efficiency (SE) and stage 3 sleep percentage in group 1 were significantly higher than those in groups 2 and 3. The wake after sleep onset (WASO) score in group 1 was significantly lower than those in groups 2 and 3. However, there were no significant differences in SE, stage 3 sleep percentage, or WASO between groups 2 and 3. Sleep latency (SL) in group 1 was significantly lower than that in group 3, but there was no difference in SL between group 2 and group 3. ESS score in group 1 was significantly higher than that in group 3, but there was no difference between group 2 and group 3. Partial correlation analysis adjusted by age showed that PLMI was significantly related to SE and WASO. CONCLUSION: This study suggests that PLMI influences polysomnographic sleep variables. In addition, we found the individuals who did not have PLMD but had PLMI > 5 were not different in polysomnographic sleep variables from the individuals who had PLMD according to the current criterion. These results raise questions about the relevance of the current diagnostic criterion of PLMD.
Adult ; Classification ; Extremities* ; Female ; Humans ; Male ; Narcolepsy ; Nocturnal Myoclonus Syndrome ; Polysomnography ; REM Sleep Behavior Disorder ; Sleep Apnea Syndromes ; Sleep Initiation and Maintenance Disorders ; Sleep Wake Disorders