应重视帕金森病认知功能障碍

认知功能障碍是帕金森病常见的非运动症状,影响患者生活质量、增加家属负担。帕金森病认知功能障碍包括帕金森病轻度认知损害和帕金森病痴呆。本文拟对国内外帕金森病认知功能障碍发病机制、临床表现、诊断标准和药物治疗研究进展进行概述。     

帕金森病轻度认知损害

轻度认知损害是帕金森病最为常见的非运动症状之一,是影响帕金森病患者日常生活活动能力的主要因素.轻度认知损害是介于正常老龄化与痴呆之间的过渡阶段,一般生活能力保持良好、发生轻度认知损害的帕金森病患者被称为帕金森病轻度认知损害,其临床特征可表现为不同认知领域损害,如工作记忆和(或)注意力、执行能力、言语、记忆力及视空间能力障碍等.在本文中,我们通过文献复习从流行病学、病理学、临床表现特点,以及辅助检查及诊断标准等方面对帕金森病轻度认知损害进行概述.     

帕金森病相关认知功能障碍

帕金森病认知功能障碍起病隐匿,是帕金森病常见非运动症状,包括帕金森病轻度认知损害和帕金森病痴呆,尤以执行功能障碍突出,亦可见视空间能力、记忆力和言语功能等认知域损害。主要危险因素包括男性、高龄、低受教育程度、严重运动症状、基线认知功能较差和白天过度嗜睡。主要病理改变是脑组织路易小体形成,也可见阿尔茨海默病样病理改变。脑脊液总α-突触核蛋白和β-淀粉样蛋白1~42水平降低作为生物学标志物的价值尚存争议。相关基因研究较少且无法获得肯定结论。PET显像发现多巴胺能通路和乙酰胆碱能通路均参与帕金森病认知功能障碍的发生;MRI研究发现皮质及皮质下结构萎缩与帕金森病认知功能障碍有关。嗅觉障碍可能是帕金森病认知功能障碍的预测因素之一。帕金森病痴呆与路易体痴呆具有共同的生物学特性,二者鉴别诊断困难。胆碱酯酶抑制剂和美金刚有助于改善临床症状,应注意个体化治疗。认知行为疗法具有潜在临床价值,尚待更多研究。     

帕金森病认知障碍相关生物学指标的研究进展

正帕金森病(Parkinson’s disease,PD)是一种以中脑黑质多巴胺能神经元变性、缺失和路易体形成为病理特征的中枢神经系统变性疾病,除了典型的运动症状之外,常伴发多种非运动症状,其中认知功能障碍是帕金森病最常见的非运动症状之一,分为帕金森病轻度认知功能障碍(Mild cognitive impairment in PD,PD-MCI)和帕金森病痴呆(Dementia in PD,PD-D)两类。调查研究显示,大约20%的PD患者存在轻度     

帕金森病痴呆相关临床研究进展

帕金森病是临床常见的神经变性病,以运动症状和非运动症状为主要临床特征。帕金森病痴呆是其中常见的非运动症状,发生率和病残率较高,治疗效果不理想。近年国际上关于帕金森病痴呆的基础与临床研究取得新进展。本文拟从临床视角对帕金森病痴呆的流行病学特征、神经心理学特征、预测因素、诊断及药物治疗进展进行综述,以期有助于推动国内帕金森病痴呆的研究。     

伴有认知障碍帕金森病患者的楔前叶影像学研究进展

正帕金森病(PD)是仅次于Alzheimer's病(AD)的第二大常见的神经系统变性疾病。PD主要表现在运动症状,表现为静止性震颤、运动迟缓、肌强直和姿势步态障碍。近年来人们越来越多的注意到痴呆、抑郁和睡眠障碍等非运动症状,也是PD患者常见的主诉,它们对患者生活质量的影响甚至超过运动症状。PD患者以每年10%的速度进展为PD痴呆(PDD)[1],PD认知下降作为常见的非运动症状,给患者本人     

正电子发射断层扫描成像在帕金森病认知功能障碍中的研究进展

近年来,帕金森病的认知功能障碍得到医学界的广泛关注.流行病学调查显示,约70％的帕金森病患者会出现不同程度的认知功能损害[1].随着疾病的进展,帕金森病痴呆(Parkinson's disease dementia,PDD)的发病率约为30％[2].尽管认知功能障碍不是导致帕金森病患者死亡的直接原因,但是会间接导致病死率的增加;同时,该症状具有进展性和致残性,会降低帕金森病患者的生活自理能力和社会功能,极大地影响患者及其家属的生活质量,并长期增加家庭护理的投入和社会的经济负担[3-4].因此,寻找可以用于早期评估、诊断及监测帕金森病患者认知功能障碍的客观方法,为疾病的治疗决策和预后判断提供依据,具有重要的临床和科研意义.     

帕金森病认知和行为障碍

认知障碍是帕金森病(PD)常见症状,即使在PD早期也能检测到轻微的认知损害[1].与阿尔茨海默病(AD)相比,PD认知损害具有其特征,主要表现为执行功能(即计划、组织、思维、判断及问题解决)损害和视空间障碍,最终会进入痴呆状态.与AD相似,PD出现认知障碍至发展为痴呆前常有数年的过渡阶段,称之为PD轻度认知障碍(PD-MCI).PD痴呆(PDD)的诊断多年来缺乏统一的诊断标准,许多文献借用美国精神障碍诊断和统计手册第四版(DSM-Ⅳ)中AD的诊断标准作为PDD诊断的参考,实际上并不恰当,因为PDD和AD的认知损害各有特点.     

帕金森病合并轻度认知损害研究新进展

轻度认知损害(MCI)是帕金森病(PD)常见的一种非运动症状,近半数患者可进展为帕金森病痴呆(PDD),严重影响患者生活质量、增加了致残率和病死率。当前,PD合并MCI (PD-MCI)的患病率高而检出率低,且缺乏有效的治疗手段,因而识别MCI潜在的危险因素、寻找可靠的临床生物标志物以及制定合理的诊断标准尤为重要。研究者们从流行病学、神经影像学、神经心理学、分子生物学等多个角度进行探索,致力于阐明其病理生理机制,实现PD患者认知损害的精准预测,为PD-MCI的预防、早期诊断和疗效评估提供科学有效的线索。     

帕金森病合并快速眼动睡眠行为障碍与认知功能相关性的研究进展

<正>帕金森病(PD)的主要临床特征为静止性震颤、肌强直、运动迟缓及姿势步态异常,除了典型的运动症状外,PD患者还伴随众多非运动症状。认知功能障碍是PD不可忽略的非运动症状之一,PD早期即可出现认知功能受损[1]。近年来的研究显示,快速眼动睡眠行为障碍(RBD)可能是PD患者认知功能障碍的又一危险因素,为认知功能障碍提供早期识别和干预的机会,进而延缓PD痴呆(PD with dementia,PDD)     

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.