发作性睡病诊断和治疗指南解读——诊断方法的评估

<正>发作性睡病的临床表现主要包括白天无法遏制的睡眠、猝倒发作,可以伴有入睡性幻觉、睡眠麻痹等夜间睡眠障碍和其它症状。伴有典型猝倒的发作性睡病的诊断通常并不困难,因为猝倒发作有一定特异性,在其它疾病中很少见到。而不伴有猝倒的发作性睡病的诊断是比较困难的,因为嗜睡缺乏特异性,可以见于多种疾病。嗜睡通常是发作性睡病的首发症状,而猝倒有可能在几个月到几年后才出现。所以发     

发作性睡病昼夜节律的研究进展

发作性睡病（Narcolepsy）是一种严重的睡眠－觉醒障碍疾病,发病年龄通常跨度较大,从儿童时期到50岁均可发病,在我国以儿童、青少年时期发病最为常见［1－2］。发作性睡病主要表现为白天反复发作无法遏制的睡眠和夜间睡眠障碍,可伴或不伴猝倒发作［3］。根据是否伴有猝倒发作,可分为发作性睡病1型与2型。目前已证实1型（又称猝倒型）患者脑脊液中下丘脑分泌素（Hypocretin,Hcrt）,又称为食欲素（Orexin）含量显著下降或缺乏［4］。     

发作性睡病的最新研究进展

正发作性睡病(Narcolepsy)是一种慢性神经系统疾病,以严重的不可抗拒的白天嗜睡和睡眠异常-唤醒模式作为其最重要特点,分为两型:1型即Hcrt缺乏综合征,既往称为猝倒型发作性睡病(Narcolepsy with Cataplexy),以脑脊液中Hcrt-1水平显著下降为重要指标;2型,既往称为非猝倒型发作性睡病(Narcolepsy without Cataplexy),通常脑脊液中     

发作性睡病伴异态睡眠1例报告

正发作性睡病(Narcolepsy)是一种睡眠障碍疾病,临床表现为睡眠-觉醒节律不稳定、发作性猝倒、睡瘫、入睡前或醒前幻觉~([1,2])。既往研究发现发作性睡病患者中快速眼球运动睡眠行为异常(REM sleep behavior disorder,RBD)发生率较高~([3]),治疗猝倒发作的药物也可引起或加重RBD,说明发作性睡病和RBD可能为共患病关系。我们报道1例我中心诊治的发作性睡病合并RBD及NREM期异态睡眠的患者,对     

发作性睡病1型的免疫学研究进展

<正>发作性睡病是一类以日间过度思睡、猝倒发作和夜间睡眠障碍为主要特征的慢性睡眠障碍,可伴有体重增加,入睡前幻觉和心理障碍等临床表现~([1])。根据国际睡眠障碍第三版(ICSD-3)的分类,发作性睡病被分为两型~([1]):1型,伴猝倒发作,患者脑脊液中下丘脑分泌素-1(Hypocretin-1,Hcrt-1)水平有明显下降; 2型,不伴猝倒发作,脑脊液中Hcrt-1水平无明显下降。人类外侧下丘脑有大约70000个生产Hcrt-1的神经元,此类神经元在1型发作性睡病患者脑内有90%～     

发作性睡病的药物和行为心理治疗

自1975年在法国召开了第1次发作性睡病国际研讨会以来,对发作性睡病的研究已历时37载.发作性睡病通常被认为是一类终身性疾病[1-2],已证实发作性睡病伴猝倒发作型的特征性病理改变为下丘脑分泌素能神经元的选择性缺失[1].发作性睡病主要表现为白天反复发作无法遏制的睡眠、夜间睡眠不安、猝倒发作以及睡瘫、睡眠幻觉等.由于对发作性睡病长久以来一直存在严重误诊误治的现象,导致很多患者症状出现数年后才得以明确诊断和治疗.随着近年来临床上对本病的认识越来越清楚,发作性睡病患者的早期诊断有望实现.早期治疗对于帮助患者改善疾病症状、回归正常生活、减轻不良预后,具有十分重要的意义.     

发作性睡病免疫学机制

发作性睡病是一种严重的睡眠障碍,其中猝倒型患者下丘脑大量Hypocretin(Hcrt)/Orexin能神经元缺失可能是自身免疫性因素选择性破坏下丘脑Hcrt能神经元所致。流行病学调查资料显示,发作性睡病发病率升高与甲型H1N1流感病毒感染、疫苗接种、化脓性链球菌感染密切相关;而且遗传因素(HLA-DQB1*0602、P2RY11基因多态性)和自身免疫性因素(TCR-α基因多态性、肿瘤坏死因子-α)亦参与其中。大剂量静脉滴注免疫球蛋白可暂时改善猝倒发作症状,但针对下丘脑Hcrt能神经元自身抗体或T细胞反应的治疗措施尚无确凿证据。随着对发作性睡病病因学研究的深入,其免疫学研究将是未来的热点领域。     

发作性睡病免疫学机制

发作性睡病是一种严重的睡眠障碍,其中猝倒型患者下丘脑大量 Hypoeretin （ Hcrt）/Orexin能神经元缺失可能是自身免疫性因素选择性破坏下丘脑Hcrt能神经元所致。流行病学调查资料显示,发作性睡病发病率升高与甲型H1N1流感病毒感染、疫苗接种、化脓性链球菌感染密切相关;而且遗传闲素（（HLA-DOB1＊0602、P2RY11基囚多态性）和自身免疫性因素（TCR-α基因多态性、肿瘤坏死因子-α）亦参与其中。大剂量静脉滴注免疫球蛋白可暂时改善猝倒发作症状,但针对下丘脑Hcrt能神经元自身抗体或T细胞反应的治疗措施尚无确凿证据。随着对发作性睡病病因学研究的深入,其免疫学研究将是未来的热点领域。     

发作性睡病研究

正发作性睡病(narcolepsy)是1880年由格里诺(Gelineau)首创的一个术语,是一种慢性睡眠障碍,可分为两类:1型发作性睡病(NT1)和2型发作性睡病(NT2)。NT1的特征是白天过度嗜睡、猝倒、入睡前幻觉和睡眠瘫痪,其原因是下丘脑中产生食欲素(一种与觉醒相关的神经肽)的神经元显著减少。除了猝倒外,NT2与NT1表现出大部分相同的症状。此外,大约90%的小儿发作性睡病患者会有夜间睡眠紊乱,其特征是夜间反复觉醒导致睡眠碎片化和整体睡眠质量下降。发作性睡病的一系列症状对患者来说是一个极大的挑战,可能会对他们的身心健康产生负面影响~([1])。一、流行病学调查     

发作性睡病猝倒发作视频-脑电图-肌电图监测与分析

目的通过对猝倒过程进行动态视频-脑电图-肌电图监测,全面解析猝倒发作动态演变的临床过程和脑电图特征。方法共6例伴典型猝倒发作的1型发作性睡病患者(其中2例为猝倒持续状态),行夜间多导睡眠图监测和日间多次睡眠潜伏期试验;通过情感刺激诱发猝倒发作,动态视频-脑电图-肌电图监测猝倒过程,分析特征性脑电图改变。结果共记录到6例患者的14个全面性猝倒发作事件。根据猝倒过程中临床表现和肌电图特征将猝倒发作分为4期,即诱发期、对抗期、无张力期和恢复期,其中对抗期初期脑电图可见阵发性高同步化θ节律,可能是猝倒发作的特征性脑电图改变。结论全面性猝倒发作分为4期,代表复杂而动态的临床和神经电生理学改变过程。阵发性高同步化θ节律可能是猝倒发作的重要机制。     

Differences in diffusion tensor imaging changes between narcolepsy with and without cataplexy

ObjectiveThe distinctive clinical finding of Type 1 narcolepsy compared to Type 2 is the presence of cataplexy. Several neuroimaging studies have also reported abnormalities in narcolepsy patients with or without cataplexy. However, there are conflicting results to differentiate them. In this study, we aimed to clarify the white matter changes in narcolepsy patients both with and without cataplexy and compared them with healthy adults to evaluate microstructural differences in the brain.MethodsEleven narcolepsy patients with cataplexy (NC), 12 narcolepsy patients without cataplexy (NOC) and healthy age- and gender-matched controls (N = 16) were studied. Whole-brain diffusion tensor imaging (DTI) was obtained and tract-based spatial statistics were used to localize white matter abnormalities.ResultsCompared with the healthy controls, both NC and NOC patients exhibited significant fractional anisotropy (FA) decreases in the bilateral cerebellar hemispheres, bilateral thalami, the corpus callosum and left anterior-medial temporal white matter. Compared with the controls, the NC patients' FA values were also decreased in the midbrain. No significant correlations were found between FA values and clinical-polysomnographic variables.ConclusionThis DTI study has demonstrated white matter abnormalities in the midbrain–brainstem regions as a distinctive finding of narcolepsy patients with cataplexy. Involvement of bilateral temporal lobes with greater changes on the left lobe is also a supporting finding of patients with cataplexy. DTI changes in the midbrain–brainstem and bilateral temporal lobes can be signs of different pathological mechanisms in these patients.     

Distribution of neurochemical abnormalities in patients with narcolepsy with cataplexy: An in vivo brain proton MR spectroscopy study

Narcolepsy with cataplexy is characterised by excessive daytime sleepiness, sudden drops of muscle tone triggered by emotions, termed cataplexy, disrupted nocturnal sleep and other dissociated rapid eye movement (REM) sleep phenomena. Narcolepsy has been linked to a loss of hypothalamic neurons producing hypocretins, neuropeptides implicated in the regulation of the arousal system. Neuroimaging and neurometabolic studies have shown the pathophysiological involvement of other brain structures such as cerebral cortex and thalamus, but, overall with inconsistent results.We investigated, by using an advanced quantitative MR technique, proton MR spectroscopy (¹H-MRS), the distribution of brain neurochemical abnormalities in narcolepsy with cataplexy patients. Single voxel ¹H-MRS study was performed in the thalamus, hypothalamus, and parietal–occipital cortex of hypocretin deficient, narcolepsy with cataplexy patients, HLA-DQB1*0602-positive, drug free. No significant changes were detected in the thalamus and parietal–occipital cortex of the patients. On the other hand, the neuronal marker N-acetyl-aspartate was reduced in the hypothalamus of narcolepsy with cataplexy patients compared to controls.These ¹H-MRS findings further support that in narcolepsy with cataplexy patients, the hypothalamus is the primary site of neural lesions. The absence of ¹H-MRS neurodegenerative changes in the thalamus and cerebral cortex suggests that the abnormalities detected in these brain regions by other neuroimaging techniques are likely of functional nature.     

Diagnosing narcolepsy with cataplexy on history alone: challenging the International Classification of Sleep Disorders (ICSD‐2) criteria

Background and purpose: The second version of the International Classification of Sleep Disorders suggests narcolepsy with cataplexy can be diagnosed on history alone. Patients: Five patients with a history supportive of narcolepsy/cataplexy. Method: Case review following clinical investigation. Results: None of the five patients had a diagnosis of narcolepsy/cataplexy on the basis of objective testing using polysomnography (PSG) and multiple sleep latency testing (MSLT). Conclusion: PSG and MSLT should always be used in conjunction with a comprehensive history taken by an experienced sleep physician to support a diagnosis of narcolepsy with cataplexy and to exclude other conditions that may mimic narcolepsy.     

Narcolepsy and obesity: remission of severe cataplexy with sibutramine

An overweight patient (body mass index of 34 kg/m(2)) with narcolepsy associated with cataplexy is described. Polysomnography did not indicate obstructive sleep apnea. Her obesity was treated with sibutramine, a norepinephrine, serotonin and dopamine reuptake inhibiting medication and her severe cataplexy remitted. Clinicians must be aware that sibutramine may suppress cataplexy when evaluating excessive daytime sleepiness in an overweight patient taking this anti-obesity medication. Therefore a negative history of cataplexy in these cases may be misleading and narcolepsy may be overlooked in the differential diagnosis. Sibutramine should be discontinued before polysomnography and multiple sleep latency testing but may be a useful medication in the management of obese narcoleptic patients with cataplexy. With the discovery of decreased hypocretin 1 levels in humans with narcolepsy, a neuropeptide that modulates sleep and feeding, the association between narcolepsy and obesity requires more attention.     

HLA DR2 in narcolepsy with sleep-onset REM periods but not cataplexy.

To determine the association of HLA DR2 in patients with narcolepsy without cataplexy, a case-control study was performed. Patients receiving the diagnosis of narcolepsy without cataplexy had excessive daytime sleepiness (EDS) and polysomnographic findings consistent with narcolepsy but no clinical evidence of cataplexy. Of 28 patients identified, 12 agreed to return for HLA typing. Respondents did not differ from nonrespondents in demographic, clinical, or sleep laboratory data. The comparison group was 503 individuals, those 30 years and older, on the Michigan Kidney Transplant Registry. The odds ratio obtained from logistic regression indicated a strong association between narcolepsy without cataplexy and HLA DR2. To control for potential confounding variables, multivariate models were constructed to explore the joint effects of HLA DR2 and each one of the covariates (age, sex, and race), their possible combinations, and the effect of all three covariates. The odds ratios decreased minimally and the association between the disease and HLA DR2 remained significant.     

Childhood narcolepsy with partial facial cataplexy: A diagnostic dilemma

Sixteen percent of adults ultimately diagnosed with having narcolepsy/cataplexy experienced symptoms before the age of ten years, 4.5% even before the age of five years [1]. The symptomatology in childhood narcolepsy/cataplexy can differ significantly from adults and can lead to misinterpretations and misdiagnosis. Standard diagnostic tools (polysomnography and multiple sleep latency test) can give false negative results and do not exclude the disorder. The decision to determine hypocretins in cerebrospinal fluid (CSF) should be made as early as possible in children. Here, we present a case of a five-year-old girl with acute onset of narcolepsy/cataplexy after a closed head trauma. The first symptoms were excessive daytime sleepiness, partial facial cataplexy and a serious behavioral disorder. Hypocretin-1 level (Hrt-1) in CSF was undetectable.     

Intravenous high-dose immunoglobulin treatment in recent onset childhood narcolepsy with cataplexy

We report on the outcome of intravenous high-dose immunoglobulin (IVIg) treatment in four children with narcolepsy and cataplexy, in whom the early diagnosis and the extreme disease severity were indications for this potentially efficacious therapy. One of four patients showed an objective and persistent improvement in clinical features during and after IVIg treatment. Our data partially support the recent report of the efficacy of IVIg treatment in early diagnosed narcolepsy with cataplexy and support the need for a controlled multicenter clinical trial on IVIg in narcolepsy.     

Narcolepsy: a review of evidence for autoimmune diathesis

Sporadic narcolepsy with cataplexy is a disabling disease that is strongly associated with the major histocompatibility class II allele HLA DQB1*0602 and is characterized by profound reduction in the cerebrospinal fluid (CSF) concentration of hypocretin 1 levels. This article provides a comprehensive review of the evidence that neurologic autoimmunity is the pathogenic basis of narcolepsy with cataplexy. Despite this evidence, specific antibody markers for narcolepsy have been elusive. Clinical trials using intravenous immunoglobulin infusions in recent onset narcolepsy with cataplexy have led to improvement in cataplexy in some patients. Future research must focus on elucidation of immune markers and early ameliorative treatments for narcolepsy.     

Narcolepsy: A review of evidence for autoimmune diathesis

Sporadic narcolepsy with cataplexy is a disabling disease that is strongly associated with the major histocompatibility class II allele HLA DQB1*0602 and is characterized by profound reduction in the cerebrospinal fluid (CSF) concentration of hypocretin 1 levels. This article provides a comprehensive review of the evidence that neurologic autoimmunity is the pathogenic basis of narcolepsy with cataplexy. Despite this evidence, specific antibody markers for narcolepsy have been elusive. Clinical trials using intravenous immunoglobulin infusions in recent onset narcolepsy with cataplexy have led to improvement in cataplexy in some patients. Future research must focus on elucidation of immune markers and early ameliorative treatments for narcolepsy.     

氟西汀治疗发作性睡病的猝倒发作

目的观察氟西汀(即百优解,fluoxetine)对发作性睡病(narcolepsy)猝倒(cataplexy)发作的治疗效果并探讨其剂量选择.方法随机选择入组之前6个月内未接受任何针对性治疗的发作性睡病患者30例.治疗开始前1周,由患者详细记录相关的临床表现和各种症状的出现频率,单独选用氟西汀20～40 mg/d,早餐后顿服.于用药的第1、2、4、6周根据患者猝倒发作次数的减少情况评价疗效.结果氟西汀对猝倒发作有良好的治疗作用,多数患者的有效治疗剂量在20～40 mg/d之间.治疗前后相比,患者的猝倒发作次数平均减少了78.83%(P ＜0.01).毒副作用少而轻且多数能在治疗过程中自行消失.结论氟西汀是治疗猝倒发作有效而安全的药物,完全可以替代三环类抗抑郁剂.