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%～     

猝倒型发作性睡病患者的神经影像学研究进展

猝倒型发作性睡病是一种睡眠-觉醒障碍疾病,发病可能与免疫、遗传、环境、感染、中枢神经系统退行性病变等因素有关,近年来神经影像学技术的发展促进了我们对猝倒型发作性睡病生物学机制的理解。该文汇总了猝倒型发作性睡病患者最新的神经影像学进展,以期阐明该病可能的神经影像学特征。     

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     

老年性发作性睡病的研究进展

发作性睡病(narcolepsy)是一种多在青少年时期起病且持续终生不加重的慢性睡眠障碍性疾病[1].发作性睡病这一概念于1880年由法国内科医师Gelineauin[1]首次提出,典型临床表现为四联征:日间过度嗜睡、猝倒、睡眠瘫痪、睡眠幻觉.     

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.     

以发作性双眼睑无力、头颈颤搐为表现伴快速动眼睡眠期行为障碍的发作性睡病1例报告及文献复习

发作性睡病(narcolepsy)是一种以不可控制的睡眠发作为主要临床表现的睡眠障碍性疾病,可伴有猝倒、睡眠相关性幻觉、睡眠瘫痪,也可伴有快速眼球运动睡眠行为障碍( rapid-eye-movement sleep behavior disorder,RBD)、周期性肢体运动障碍等夜间睡眠障碍.猝倒发作症状复杂多样,容...     

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     

Epilepsy and anomalies of neuronal migration: MRI and clinical aspects

Neuronal migration disorders are the result of disturbed brain development. In such disorders, neurons are abnormally located. In diagnosing these conditions, magnetic resonance imaging is superior to any other imaging technique. This enables us to improve our knowledge of the clinical correlates of neuronal migration. With reference to migrational disorder, a retrospective study of all 303 patients with epileptic seizures referred for magnetic resonance imaging during a 3-year period was performed, 13 patients (aged 12-41, mean age 27) were identified. They represent 4.3% of the entire study group. Of the patients with known epilepsy, 6.7% and of the mentally retarded, 13.7% had migrational disorders. Four patients had schizencephaly as the dominant finding, one was classified as hemimegalencephaly, 2 had isolated heterotopias, and 6 had localized pachy- and/or poly-microgyria. The clinical pictures are complex. Ectopias of grey matter are recognised foci of epilepsy, but from an epileptological and a clinical viewpoint little attention has been given to these disorders. The present study shows that malmigration is not rare in epilepsy patients, especially not in the mentally retarded.     

Classification of methods in transcranial Electrical Stimulation (tES) and evolving strategy from historical approaches to contemporary innovations

Transcranial Electrical Stimulation (tES) encompasses all methods of non-invasive current application to the brain used in research and clinical practice. We present the first comprehensive and technical review, explaining the evolution of tES in both terminology and dosage over the past 100 years of research to present day. Current transcranial Pulsed Current Stimulation (tPCS) approaches such as Cranial Electrotherapy Stimulation (CES) descended from Electrosleep (ES) through Cranial Electro-stimulation Therapy (CET), Transcerebral Electrotherapy (TCET), and NeuroElectric Therapy (NET) while others like Transcutaneous Cranial Electrical Stimulation (TCES) descended from Electroanesthesia (EA) through Limoge, and Interferential Stimulation. Prior to a contemporary resurgence in interest, variations of transcranial Direct Current Stimulation were explored intermittently, including Polarizing current, Galvanic Vestibular Stimulation (GVS), and Transcranial Micropolarization. The development of these approaches alongside Electroconvulsive Therapy (ECT) and pharmacological developments are considered. Both the roots and unique features of contemporary approaches such as transcranial Alternating Current Stimulation (tACS) and transcranial Random Noise Stimulation (tRNS) are discussed. Trends and incremental developments in electrode montage and waveform spanning decades are presented leading to the present day. Commercial devices, seminal conferences, and regulatory decisions are noted. We conclude with six rules on how increasing medical and technological sophistication may now be leveraged for broader success and adoption of tES.     

Hepatic Considerations in the Use of Antiepileptic Drugs

Summary: Virtually all of the major antiepileptic drugs (AEDs) can cause hepatotoxicity, although fatal hepatic reactions are rare. The mechanisms, incidences, and risk profiles for such reactions differ from drug to drug. With carbamazepine and phenytoin, hepatotoxicity may be due to drug hypersensitivity. Although the profiles of patients at risk have not been well-defined for these two antiepileptic drugs, it would appear from reports in the literature that older adolescents and adults are at higher risk than children of developing serious or fatal hepatotoxicity. Once hepatotoxicity develops, mortality rates are 10–38% with phenytoin and 25% for carbamazepine. The risk profile for valproate fatal hepatotoxicity has been more clearly defined. Those at primary risk of fatal hepatic dysfunction are children under the age of 2 years who are receiving multiple anticonvulsants and also have significant medical problems in addition to severe epilepsy. The risk is considerably lower for patients over the age of 2 years on valproate monotherapy. In contrast to the risk profile with other AEDs, adults receiving valproate as monotherapy have the lowest risk of hepatotoxicity. Fatal hepatic dysfunction coincident with valproate may be the result of aberrant drug metabolism. Concomitant use of AEDs that induce microsomal P450 enzymes (e.g., phenytoin and phenobarbital) may enhance the production of a toxic metabolite, and hence the greater risk of hepatotoxicity with polypharmacy.     

Vascular Malformations and Epilepsy: Clinical Considerations and Basic Mechanisms

Summary: Vascular malformations (VMs) are associated with epilepsy. The natural history of the various VMs, clinical presentation, and tendency to provoke epilepsy determine treatment strategies. Investigations have probed the mechanisms of epileptogenesis associated with these lesions. Electrophysiologic changes are associated with epileptogenic cortex adjacent to VMs. Putative pathophysiologic mechanisms of epileptogenesis include neuronal cell loss, glial proliferation and abnormal glial physiology, altered neurotransmitter levels, free radical formation, and aberrant second messenger physiology.     

Neonatal Seizures: Problems in Diagnosis and Classification

Summary: The clinical identification of neonatal seizures is critical for the recognition of brain dysfunction; however, diagnosis is often difficult because of the poorly organized and varied nature of these behaviors. Current classification systems are limited in their ability to communicate motor, autonomic, and electroencephalo-graphic features of seizures precisely and to provide a basis for uniform effective diagnosis, therapy, and determination of prognosis. Recent investigations of neonates, utilizing bedside electroencephalographic/polygraphic/ video monitoring techniques, have provided the basis for improved diagnosis and classification of seizures in the newborn. These studies have demonstrated that not all clinical phenomena currently considered to be seizures require electrocortical epileptiform activity for their initiation or elaboration. In addition, the specific clinical character of the phenomena considered to be seizures, the clinical state of the infant, and the character of the EEG indicate the probable pathophysiological mechanisms involved and suggest probable etiologies, prognosis, and therapy. Similarities between animal models that demonstrate reflex physiology and neonates with motor automatisms and tonic posturing suggest that these clinical behaviors may not be epileptic in origin but, rather, primitive movements of progression and posture mediated by brainstem mechanisms. Although not all clinical behaviors currently considered to be neonatal seizures may have similar pathophysiological mechanisms, they are clinically significant because they all indicate brain dysfunction.     

Valproate Monotherapy in the Management of Generalized and Partial Seizures

Summary: For decades, therapeutic tradition has promoted the concept of polypharmacy in the management of epilepsy. In recent years, however, studies have shown that, for most patients, monotherapy can provide comparable or better seizure control than administration of multiple anticonvulsants, while diminishing the potential for adverse reactions, drug interactions, and poor compliance. Valproate is an important monotherapeutic agent that is highly effective in the control of idiopathic primary and secondarily generalized epilepsies, and partial seizures that do not generalize. Comparative studies have found that valproate is at least as effective as phenytoin and carbamazepine in the treatment of generalized and partial seizures. Given the similar efficacy, other factors such as pharmacokinetics and side effects may therefore determine anticonvulsant selection for monotherapy.     

Carbamazepine Efficacy and Utilization in Children

Summary: Carbamazepine is effective for preventing partial and generalized tonic-clonic seizures in children. Although absence epilepsies are more common in children than adults, an estimated 80% of children with epilepsy have seizure types or epilepsies that are potentially responsive to carbamazepine. The differential diagnosis of ictal staring is an especially important issue in children because absence and atypical absence seizures are more prevalent in children than adults. Age-related pharmacokinetic differences and drug interactions are major considerations in children. On average, children have higher clearance rates of carbamazepine, shorter half-lives, and higher ratios of carbamazepine-10, 11-epoxide to carbamazepine than adults. In addition, children with severe epilepsy are more likely to require multiple-drug therapy, which can lead to complex drug interactions. When carbamazepine is administered along with valproate, drug protein binding interactions can cause intermittent side effects.     

Un nouveau cadre conceptuel de travail pour la psychiatrie

In an attempt to place psychiatric thinking and the training of future psychiatrists more centrally into the context of modern biology, the author outlines the beginnings of a new intellectual framework for psychiatry that derives from current biological thinking about the relationship of mind to brain. The purpose of this framework is twofold. First, it is designed to emphasize that the professional requirements for future psychiatrists will demand a greater knowledge of the structure and functioning of the brain than is currently available in most training programs. Second, it is designed to illustrate that the unique domain which psychiatry occupies within academic medicine, the analysis of the interaction between social and biological determinants of behavior, can best be studied by also having a full understanding of the biological components of behavior.