Hypersomnias of central origin are defined as the inability to maintain wakefulness and alertness during the major waking episodes of the day， with the manifestation of irrepressible drowsiness or even unprovoked sleep attacks. This spectrum of disorders mainly includes narcolepsy type 1， narcolepsy type 2， idiopathic hypersomnia， and Kleine-Levin syndrome. Currently， the clinical diagnosis of hypersomnias of central origin mainly depends on subjective medical history， sleepiness scales， and electrophysiological assessments， and these conventional diagnostic methods are easily affected by confounding factors. A reduction in the level of hypocretin-1 in cerebrospinal fluid （CSF） is the gold standard for the diagnosis of narcolepsy type 1， while there is still a lack of specific and Objective laboratory markers for the other subtypes， resulting in the high rates of diagnostic delay and misdiagnosis. As Objective and quantifiable indicators for pathophysiological processes， biomarkers have an important clinical value in the early screening， precise phenotyping， and longitudinal monitoring of hypersomnias of central origin， as well as in the development of targeted therapies for this group of sleep disorders. This article systematically reviews the research advances in biomarkers associated with hypersomnias of central origin from the five dimensions of polysomnography and daytime functional assessment， peripheral serology， cerebrospinal fluid， neuroimaging， and autonomic nervous function， in order to provide a theoretical framework and evidence-based support for constructing a precise diagnosis and treatment system for these disorders.
Narcolepsy

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

Narcolepsy （NP） is a rare nervous system disease with the typical symptoms of excessive daytime sleepiness， cataplexy， sleep paralysis， and hypnagogic hallucination. The pathophysiological mechanism of NP remains unclear， and it is currently believed that NP is an immune-related disease closely associated with HLA-DQB1*06∶02 genotype and it can be triggered by environmental factors such as infection and vaccination， while the precise neural pathways leading to degeneration/apoptosis of orexin neurons in the lateral hypothalamic area remain unknown. In recent years， an increasing number of evidence has revealed the association between sleep disturbance and gut microbiota， and in particular， the microbiota-gut-brain axis plays an important role in sleep regulation. This article systematically reviews the regulatory mechanism of gut microbiota in the central nervous system and discusses the potential interaction between gut microbiota and NP， in order to provide new perspectives for both mechanistic research and clinical management of NP.
Narcolepsy

This article reports the complete screening-diagnosis-rehabilitation process for an Air Force non-commissioned officer diagnosed with narcolepsy（NP） comorbid with obstructive sleep apnea （OSA） and REM sleep behavior disorder（RBD）.The patient attended the hospital due to uncontrollable daytime sleep for 3 years and one episode of cataplexy，and a confirmed diagnosis was made based on polysomnography， multiple sleep latency test （MSLT）， and imaging examination， with the exclusion of organic lesions. As for treatment， since the patient showed no response to venlafaxine alone， the treatment regimen was switched to a comprehensive regimen of behavioral interventions， traditional Chinese medicine syndrome differentiation， and pitolisant. Based on this case report and the literature review， it is proposed that the armed forces should introduce a modern diagnostic and therapeutic mode integrating routine screening （Epworth Sleepiness Scale and MSLT）， multidisciplinary dynamic assessment， and individualized comprehensive care， in order to provide evidence-based guidance for the early identification， diagnosis， and treatment of sleep disorders in military personnel.
Narcolepsy ; Polysomnography

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*

Niemann-Pick disease type C (NP-C) is a rare autosomal recessive neurovisceral lysosomal lipid storage disorder. The clinical manifestations of the disorder are variable. This report describes the case of a 27-month-old girl with NP-C whose condition had been misdiagnosed as spastic cerebral palsy (CP). She had spasticity, particularly at both ankles, and gait disturbance. Magnetic resonance imaging of the brain revealed findings suspicious of sequelae from a previous insult, such as periventricular leukomalacia, leading to the diagnosis of CP. However, she had a history of hepatosplenomegaly when she was a fetus and her motor development had deteriorated, with symptoms of vertical supranuclear gaze palsy, cataplexy, and ataxia developing gradually. Therefore, NP-C was considered and confirmed with a genetic study, which showed mutation of the NPC1 gene. Thus, if a child with CP-like symptoms presents with a deteriorating course and NP-C-specific symptoms, NP-C should be cautiously considered.
Ankle ; Ataxia ; Brain ; Cataplexy ; Cerebral Palsy ; Child ; Child, Preschool ; Diagnosis ; Female ; Fetus ; Gait ; Humans ; Infant, Newborn ; Leukomalacia, Periventricular ; Magnetic Resonance Imaging ; Muscle Spasticity ; Niemann-Pick Diseases ; Paralysis

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

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