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*

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

No abstract available.
Disorders of Excessive Somnolence ; Humans ; Metoclopramide ; Parkinsonian Disorders

BACKGROUND AND OBJECTIVES: We aimed to evaluate effects of endonasal dilators (END) on sleep quality in patients with obstructive sleep apnea (OSA) by improving nasal airflow. MATERIALS AND METHODS: In 13 patients with OSA, changes of total nasal volume (TNV) and minimal cross-sectional area (MCA) before and after END use were evaluated. The change in peak nasal inspiratory flow (PNIF) was also measured. Subjects completed Epworth Sleepiness Scale questionnaire before and 2 weeks after END use. Finally, changes in apnea-hypopnea index (AHI), respiratory distress index (RDI), oxygen desaturation index (ODI), sleep time, sleep position and loudness of snoring (in decibels) were obtained by repetitive portable polysomnography. RESULTS: After END use, TNV (11.4±3.1 cm3 to 19.4±5.7 cm3) and MCA (0.7±0.2 cm2 to 0.9±0.1 cm2) increased significantly (p=0.001). PNIF also increased significantly after END (147.3±39.5 to 194.6±57.6 liter/min, p=0.001). Among 11 patients undergoing 2-week follow-up, 7 reported improvement in daytime sleepiness. Although AHI, RDI and ODI showed no statistically significant change before and after END (p>0.05), the proportion of subjects sleeping in the supine position increased from 38.0 to 44.5%. CONCLUSION: END may be an effective adjunctive tool for patients with OSA with the potential to improve nasal airflow and daytime sleepiness.
Disorders of Excessive Somnolence ; Follow-Up Studies ; Humans ; Nasal Cavity ; Oxygen ; Polysomnography ; Sleep Apnea Syndromes ; Sleep Apnea, Obstructive ; Snoring ; Supine Position

Disorders of Excessive Somnolence ; Humans ; Parkinson Disease ; complications ; REM Sleep Behavior Disorder ; therapy ; Restless Legs Syndrome ; therapy ; Sleep Apnea, Obstructive ; therapy ; Sleep Wake Disorders ; 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

INTRODUCTIONPatients with obstructive sleep apnoea (OSA) often present with excessive daytime sleepiness (EDS) as measured by the Epworth Sleepiness Scale (ESS). However, the relationship between EDS and OSA severity as measured by the apnoea-hypopnoea index (AHI) remains inconsistent. We hypothesise that this may be due to the usage and equal weightage of apnoea and hypopnoea events used in determining AHI and that apnoea and hypopnoea load as measured by their total durations may be a better metric to use. We sought to investigate if apnoea or hypopnoea load can display better correlation with ESS.

MATERIALS AND METHODSRetrospective analysis of 821 patients with AHI ≥5, who underwent in-laboratory polysomnogram for suspected OSA from January 2015-December 2015, was performed. Objective factors on polysomnogram were correlated with ESS.

RESULTSESS was correlated with age (r = -0.148, <0.001), number of apnoeas (r = 0.096, = 0.006), apnoea load (r = 0.102, = 0.003), apnoea index (r = 0.075, = 0.032), number of desaturations (r = 0.081, = 0.020), minimum SpO (r = -0.071, = 0.041), time SpO <85% (r = 0.075, = 0.031) and REM sleep duration (r = 0.099, = 0.004). Linear regression analysis found age ( <0.001), apnoea load ( = 0.005), REM ( = 0.021) and stage 1 sleep duration ( = 0.042) as independent factors correlated to ESS. The apnoea load calculated using duration in apnoea correlate with ESS in patients with severe OSA by AHI criteria compared to the mild category.

CONCLUSIONAHI does not correlate with ESS. Younger age, longer apnoea, stage 1 and REM sleep were independently related to higher ESS though the correlations were weak. Apnoea load should be taken into account when determining OSA severity.

Adult ; Age Factors ; Disorders of Excessive Somnolence ; diagnosis ; etiology ; physiopathology ; Female ; Humans ; Male ; Middle Aged ; Polysomnography ; methods ; Retrospective Studies ; Severity of Illness Index ; Singapore ; Sleep Apnea Syndromes ; physiopathology ; Sleep Apnea, Obstructive ; complications ; diagnosis ; physiopathology ; Sleep, REM ; physiology ; Statistics as Topic