帕金森病和快速眼球运动睡眠期行为障碍的共同发病机制研究进展

帕金森病是中老年人高发的一种神经退行性疾病, 其前驱期可持续数年至数十年, 疾病前驱期标志物是早期识别或诊断帕金森病的重要依据。快速眼球运动睡眠期行为障碍(RBD)是帕金森病的特征性临床前驱症状, 且与帕金森病具有一些相同的发病机制, 部分机制在RBD转化为帕金森病的过程中进行性发展, 可能成为有价值的帕金森病前驱期标志物。文中对帕金森病与RBD的共同发病机制进行综述, 以期为帕金森病的临床早期诊断和治疗提供一些思路。     

帕金森病前驱期非运动症状的相关研究进展

正帕金森病是常见的神经退行性病变,早期诊断及干预可以有效改善帕金森病患者的预后。2015年国际运动障碍学会强调了帕金森病前驱期的重要性,在帕金森病前驱期中患者已经出现中枢或周围神经病理性改变,患者可表现为不同程度的非运动症状和体征,但有限的运动症状仍不足以作出帕金森病的诊断。了解目前帕金森病前驱期非运动症状的特点及可能的生物标记物,将有助于临床医生更早的甄别可疑的帕金森病患者,而本文就近期国内外帕金森病前驱期主要的非运动症状(嗅觉减退、睡眠障碍、认知功能下降、神经精神症状及自主神经功能障碍)特点及可能发生机制的相关文章进行分类叙述,旨在提高临床医生对帕金森病前驱期非运动症状的关注及加强相关临床回顾性或前瞻性研究。     

帕金森病前驱期α-突触核蛋白生物标志物的研究进展

帕金森病（PD）是最常见的神经退行性疾病之一,临床诊断的PD患者已出现实质性、不可逆的神经退行性病变,临床上通过多巴胺能药物对症治疗并不能阻止疾病进展和降低致残率。近年来,帕金森病研究关口前移,众多研究在其前驱期探索神经保护疗法,以期延缓与阻止疾病进展。在此类型研究中,如何大范围准确筛选、检测、识别PD前驱期患者是目前所面临的难题。α-突触核蛋白是PD的标志性蛋白,本文以α-突触核蛋白为切入点,阐述其在PD发病过程中的重要理论地位,整合近年来已报道的PD前驱期患者脑脊液、组织、粪便中α-突触核蛋白的检测特异性,整理各研究所采用的检测方法及其优缺点,为临床进一步探索该标志物提供参考。     

蓝斑损伤介导帕金森病疼痛病理机制的研究进展

帕金森病是常见的中枢神经系统退行性病变,疼痛是帕金森病比较常见的非运动症状, 患病率在 40%～85%。疼痛症状使帕金森病患者的生活质量受到严重影响,且它的机制错综复杂。在 帕金森病神经退行性病变过程中,蓝斑区域神经元丢失程度更大且更早于黑质致密部。蓝斑包含中枢 神经系统中最大的去甲肾上腺素能神经元群,去甲肾上腺素能神经元群在整个大脑中提供广泛的神经 来支配参与疼痛的内在控制。现综述蓝斑损伤介导帕金森病疼痛的病理机制研究进展。     

帕金森病影像学研究进展

<正>帕金森病(Parkinson’s Disease,PD)是一种中枢神经系统退行疾病,临床上以静止性震颤、肌僵硬、运动迟缓为主要特征。国内外学者近年发现,PD患者在出现典型的临床症状之前,即可表现某些影像学异常[1]。对PD患者进行脑成像研究,可能对阐明PD病理生理机制的和早期诊断提供帮助。     

外周组织中α-突触核蛋白作为帕金森病生物标志物的研究进展

帕金森病(PD)是以黑质多巴胺能神经元变性丢失和路易小体形成为特征的神经系统退行性疾病,由于缺乏特异性生物标志物,其早期诊断准确率受限.α-突触核蛋白(α-syn)是构成路易小体的关键蛋白,α-syn不仅存在于中脑多巴胺能神经元,还在皮肤、唾液腺等外周组织中广泛分布,并且外周神经系统α-syn病理改变可能早于中枢神经系...     

帕金森病患者认知功能评定及护理对策探讨

帕金森病(Parkinson's disease PD) 是以运动障碍为主要特征的神经系统退行性病变, 是老年期常见病,常伴有认知功能障碍和抑郁症状[1].目前, 多数学者认为PD患者伴发抑郁症状会影响认知功能[2],影响患者的生活质量和生存年限.本文用神经心理学方法评定帕金森病患者认知功能,并探讨其护理对策,现报道如下.     

基于体素的形态学分析在阿尔茨海默病及轻度认知障碍中的应用

<正>阿尔茨海默病(Alzheimer’s disease,AD)是一种进行性的神经退行性病变,是引起老年人痴呆最常见的疾病,占老年痴呆患者的50%～60%~([1])。据统计,2015年报道全球现有痴呆患者4680万,预计到2050年达1.3亿~([2])。轻度认知障碍(mild cognitive impairment,MCI)是介于正常衰老和轻度痴呆之间的不稳定的认知损害阶段,在此阶段患者认知功能下降,但尚未对日常生活状态造成很大的影响。据统计,每年约10%～15%的MCI转化为AD,随着人口老龄化程度的加剧,这一比例仍会继续增加~([3])。随着影像技术的发展,结构磁共振成像已经作为AD的生物学标志物之一被引入新的诊断标准,并被广泛应用于临床~([4]),早期诊断MCI并采取适     

帕金森病血液生物标志物的研究进展

帕金森病(PD)是仅次于阿尔茨海默病的第二大神经变性疾病,在中老年人群中较常见,其发病率随着年龄的增长而增高。然而在现阶段帕金森病的诊断主要依据患者的临床症状以及医生的自身经验。因此,需要寻找可检测的生物标志物对帕金森病进行诊断和病情进展的跟踪。本文对近年来主要的潜在帕金森病血生物标志物的研究进展进行综述。     

细胞移植治疗帕金森病移植细胞的选择与调控

帕金森病(Parkinson disease,PD)是以中脑多巴胺(DA)神经元丢失为特征的中机神经系统退行性疾病.近年来,干细胞移植技术、体外培养诱导分化技术日渐成熟,为神经细胞脑内移植治疗神经系统退行性病变提供更广阔的前景.本文主要从移植细胞的来源和移植的调控方面对近年来国内外神经细胞脑内移植治疗帕金森病的新进展进...     

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.     

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.     

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.     

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.     

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.     

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.     

Special Pharmacokinetic Considerations in Children

Summary: Pediatric patients have greater degrees of pharmacokinetic variability and unpredictability than adults. This variability results from the effects of pharmacogenetics, age and growth, prior and current comedication, and disease. Newborns with seizures have the least predictable dosage requirements, and their needs change as drug-eliminating mechanisms mature in the neonatal period. Infants have the highest relative capacities to eliminate antiepileptics of any age group and require the largest relative doses. In addition to age-related trends, children demonstrate the same drug-specific, pharmacokinetic phenomena that adults do, including nonlinear phenytoin elimination, nonlinear valproate binding, and autoinduction of carbamazepine. Intercurrent illness and drug interactions further modify the age-related pharmacokinetic patterns in children and make dosage requirements even more unpredictable. Recent studies have shown that febrile illness can affect drug elimination, sometimes decreasing drug levels by 50% or more. Intermittent treatment with benzodiazepines administered either orally or rectally can be an important adjunct and help minimize this type of problem for children with marginally controlled epilepsy. Intermittent benzodiazepines are also helpful for children who have febrile seizures and who need only occasional antiepileptic protection.