肥大性下橄榄核变性

肥大性下橄榄核变性(HOD)为一种特殊类型的跨突触神经元变性,是小脑齿状核-中脑红核-延髓下橄榄核神经元联系环路受损而引起的下橄榄核神经元的继发性变性改变.其主要病理变化包括神经元肥大、空泡样变性和胶质细胞增生,特征性病理表现基于以下两点:(1)与神经元溃变不同,肥大性下橄榄核变性被称为"跨突触变性",即下位神经元损伤引发的上位神经元的数量、结构和功能改变.     

帕金森病早期生物学标记物研究新进展

帕金森病(PD)是中老年人常见的中枢神经系统变性疾病,≥65岁人群患病率约为1%.以黑质多巴胺能神经元变性缺失和残存神经元出现特征性包涵体--路易小体(LB)为主要病理改变.     

神经元核内包涵体的研究进展

神经元核内包涵体(neuronal intranulear inclusions,NIIs)是遗传性神经变性疾病的一种重要的病理表现,尤其在三核苷酸重复疾病(triplet repeat disease)中更被视为特征性的病理表现,尽管分子遗传学研究已证实基因突变导致的三核苷酸重复的异常扩增引起了相应的临床疾病,但三核苷酸重复引起神经变性的发病机制尚不明确,越来越多的学者认为神经元核内包涵体的出现不是一个孤立的事件,尽管对其在神经变性中的作用还存在很大争议,神经元核内包涵体的研究可能对神经变性的机制提供重要线索,本文主要综述神经元核内包涵体可能的形成机制及其在神经变性疾病中的意义.     

帕金森病炎症反应及姜黄素抗炎作用的实验研究

帕金森病( Parkinson's disease,PD) 是一种常见于中老年人的中枢神经系统变性疾病.以静止性震颤、肌强直、运动迟缓及姿态反射障碍为临床特征.病理表现为选择性黑质多巴胺能神经元变性缺失,残余多巴胺能神经元内出现嗜酸性包涵体(Lewy 小体)、纹状体多巴胺(DA) 含量下降.帕金森病的发病原因尚未完全清楚,但已有多项研究认为免疫炎性机制可能参与了帕金森病神经变性的发病过程[1-2].     

甲基强的松龙对急性脊髓损伤神经元保护作用的实验研究

目的探讨甲基强的松龙对急性脊髓损伤(ASCI)后神经元是否具有保护作用。方法大鼠随机分为2组，即模型组和正常对照组(N组)，模型组建立脊髓半横断损伤模型后又分两组，即激素治疗组(M组)，腹腔注射甲基强的松龙(MP)；模型对照组(B组)术后不做处理。每组大鼠观察损伤后3d、7d、15d和30d。取脊髓损伤部位标本做光镜病理组织学检查，观察正常神经元和变性神经元的数量变化。结果(1)B组在ASCI早期脊髓损伤区的灰白质被明显的破坏，有出血及坏死，可见多量空泡状细胞和溃变的神经纤维，部分组织液化。在损伤灶内见正常神经元及神经纤维的数量稀少，多数神经元呈现不同程度的变性乃至坏死。随着时间的延长，神经元数量进一步减少，胶质细胞增生形成疤痕，或者液化形成囊腔。病变常常累及对侧组织，而M组的脊髓损伤区组织结构的变化与B组基本相同。(2)在ASCI后3d，M组的正常神经元数量少于B组，变性神经元数量与B组相近；在损伤7d以后，随着时间的延长，B组的变性神经元数量减少的同时，正常神经元的数量稍有减少，而M组的变性神经元数量减少的同时，正常神经元数量有所增加。结论(1)MP对ASCI后的继发性组织结构破坏无明显的改善作用；(2)MP在ASCI早期能促使神经元的死亡，但在后期能增加正常神经元的数量，其机理有待于进一步研究。     

内质网应激在帕金森病中的作用

<正>帕金森病(PD)是仅次于阿尔茨海默病(AD)的年龄相关性神经变性病,主要的临床症状为运动迟缓、肌肉僵直、静止性震颤和姿势不稳;其神经变性特征为进行性黑质致密部(SNc)多巴胺能(DA)神经元变性、缺失、以及神经元内出现由α-共核蛋白(α-synuclein)组成的Lewy小体的形成。虽然家族性PD有一些基因突变基础,但大多数原发性PD病因不明,有多种机制参与DA神经元变性,包括线粒体功能障碍、氧化     

轴突变性在帕金森病发病中的作用

帕金森病(PD)是常见的中枢神经系统变性疾病,目前认为PD的主要病理变化是黑质多巴(dopamine,DA)能神经元的凋亡,因此研究重点集中在DA能神经元凋亡机制昨治疗方面,而轴突变性被认为是神经元死亡的佯随产物,长期未受到重视.     

中央被盖束梗死继发双侧肥大性下橄榄核变性1例报告及文献复习

<正>肥大性下橄榄核变性(hypertrophic olivary degeneration,HOD)是一种由于小脑齿状核-中脑红核-下橄榄核神经元环路(又称Guillain-Mollaret三角)受损而引起的下橄榄核神经元继发性变性改变。此环路任何部分受损都可引起单侧或双侧HOD,其病理特征是胞浆的空泡变性、橄榄核体积的增大以及星形胶质细胞增生。除原发病引起的症状外,HOD患     

帕金森病相关转录因子Nurr1在多巴胺能神经元中的作用

<正>黑质多巴胺能神经元对于运动控制、药物成瘾、学习记忆等功能的调控至关重要[1]。中脑多巴胺能神经元的变性死亡是帕金森病(Parkinson's disease,PD)发生的主要病理特征之一。近年来研究发现核相关受体因子(nuclear receptor related factor1,Nurr1)蛋白对于多巴胺能神经元的发育分化、存活和变性具有重要意义。本文将对Nurr1在神经系统的表达、转录因子功能、在多巴胺能神经元的发育以及PD发病与干     

维生素D依赖型钙结合蛋白D28k及MC6蛋白异常与C型尼曼-皮克病小鼠神经元骨架病理改变

目的探讨C型尼曼-皮克病(NPC)小鼠模型神经元病变时,维生素D依赖型钙结合蛋白D28k(calbindin D28k)和MC6蛋白异常表达与神经元细胞骨架病变之间的相关性。方法利用免疫组化、免疫荧光标记以及免疫印迹等方法检测NPC1小鼠和野生型对照组小鼠(各8只)脑组织不同部位神经元变性过程中calbindin D28k及MC6蛋白表达,细胞骨架蛋白抗有丝分裂活化蛋白激酶-2(MAP2)和神经丝(neurofilament,NF)的病理变化。结果NPC1小鼠4周龄时,calbindin D28k表达为0·68±0·32,稍微高于野生型小鼠(0·53±0·20,P=0·665),以后5~8周龄的连续变化0·71±0·33,1·22±0·73均低于对照组的1·20±0·47和2·28±1·42(P=0·34,0·045)。NPC1鼠小脑浦肯野神经元发生变性早期,calbindin D28k蛋白表达增高,晚期表达降低。小脑白质、脑干、基底节和部分大脑中出现异常calbindin D28k蛋白颗粒和MC6蛋白。异常的MC6蛋白与calbindin D28k高度共表达。相同部位的神经元NF也明显病理改变。浦肯野神经元则没有发现MC6以及MAP2、NF病理改变。结论calbindin D28k在NPC1小鼠神经元变性早期可能有短暂的神经元保护作用。随着病程发展calbindin D28k表达异常,并与MC6蛋白密切相关。两者均与神经元细胞骨架结构破坏明显相关。浦肯野细胞变性与MC6和MAP2、NF关系不大。由此推测calbindin D28k参与NPC1小鼠模型神经元细胞骨架病变机制;同时,浦肯野神经元变性、死亡的途径与其他的神经元可能不同。     

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.     

Diagnostic Difficulties and Treatment Implications

Summary: Differentiation between types of epileptic seizures has been aided in recent years by the introduction of intensive neurodiagnostic techniques and the development of increasingly detailed classification systems. Paradoxically, these developments have not simplified the task of matching the appropriate antiepileptic drug to a particular seizure type. It is reasonable to assume that anticonvulsant drugs will have different effects on different types of seizures, but faulty, circular reasoning can enter the picture if one also assumes that responses of seizures to different drugs signify different seizure types. There are several examples of differential diagnoses that can fall prey to this problem, including the diagnosis between partial seizures with secondary generalization and generalized tonic-clonic seizures, and the diagnosis between complex partial seizures and absence seizures with automatisms, among others. Considerations of etiology in future classification systems can further complicate the problem: should one then choose an anticonvulsant drug on the basis of individual seizure type or on the basis of the type of epilepsy? Ramifications of this issue extend even to the drug approval process. Official sanction is not given for use of a drug for a seizure type not included in the original efficacy studies, even if later scientific evidence shows that seizure type to be related to a type that is included. New trials must be undertaken. These problems arise from how we choose to classify seizures.     

Cognitive Dysfunction Associated with Antiepileptic Drug Therapy

Summary: Epilepsy is frequently associated with cognitive dysfunction. However, the reasons for this correlation are unclear. Possible influential factors include patient age; duration, frequency, etiology, and type of seizures; hereditary factors; psychosocial issues; and antiepileptic drug (AED) therapy. Whereas many of these factors are beyond the physician's control, AED therapy is one element that can be addressed in treatment decisions by recognizing the potential cognitive effects of particular AEDs. For example, phenobarbital impairs memory and concentration; phenytoin affects attention, problem solving ability, and performance of visuomotor tasks. In contrast, carbamazepine may affect concentration, while valproate would appear to have minimal effects on cognition. Moreover, cognitive effects of AEDs are amplified with coadministration of multiple anticonvulsants (polytherapy). A review of studies on the cognitive effects of monotherapy with AEDs, as opposed to those of polytherapy, provides evidence that drug-related cognitive dysfunction can be reversed if patients are switched to a simpler therapeutic regimen. Future research should be directed toward developing reliable measures for assessing and monitoring cognition, and understanding the particular cognitive side effects of each AED. Physicians also need to revise their opinions about which side effects are "tolerable" for epileptic patients.     

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.     

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.     

Carbamazepine Efficacy in Adults With Partial and Generalized Tonic-Clonic Seizures

Summary: Carbamazepine and phenytoin are drugs of choice in initial monotherapy for adult partial and secondarily generalized tonic-clonic seizures. These designations reflect the results of the Veterans Administration Epilepsy Cooperative Study Group of 1985. An earlier comparative study of carbamazepine and phenytoin by Ramsay and associates found both drugs equally effective in controlling new-onset seizures. Among the advantages of carbamazepine is that it causes relatively few cognitive and dysmorphic side effects. Its disadvantages are its unavailability in parenteral formulation and its metabolic autoinduction. The latter must be compensated for by planned dosage increases to maintain therapeutic plasma steady-state levels during the first 2 or 3 months of treatment. Carbamazepine is judged a drug of choice in the treatment of these secondarily generalized tonic-clonic seizures, and the drug of choice in children, adolescents, and women susceptible to the dysmorphic side effects associated with other anticonvulsant agents.     

Etiologic and Preventive Aspects of Epilepsy in the Child–Bridging the Gap Between Laboratory and Clinic

Summary: Four broad categories of basic phenomena are pertinent to developing ways to prevent epilepsy. These include mechanisms of epileptogenesis, ictal initiation and temporary entrainment by the seizure discharge of normally functioning brain, seizure propagation, and control mechanisms that function both to restrain the cascade of epileptic events culminating in a seizure and to arrest the epileptic event and restore the interictal state. In newborns and children, hypoxia-ischemia is a major factor leading to epileptogenesis, and several schemes are proposed to classify, quantify, and prevent hypoxic-ischemic encephalopathy. Control mechanisms must be better understood in order to develop prophylactic recommendations for epilepsy, and an experimental model of "kindling antagonism" may increase our understanding of these. Programs of prevention of seizures in children will evolve only if basic researchers and clinicians work productively together to develop an adequate understanding of factors important in epileptogenesis and antiepileptogenic control mechanisms.     

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.     

Predisposing and Causative Factors in Childhood Epilepsy

Summary: We review information from large studies of defined populations, examining the role of known factors and especially of prenatal and perinatal factors in contributing to nonfebrile seizure disorders of early childhood. We depend especially, but not exclusively, on the recently completed analyses from the Collaborative Perinatal Project of the National Institute of Neurological and Communicative Disorders and Stroke, the NCPP. About 4% of children in the NCPP who had at least one non-febrile nonsymptomatic seizure by the age of 7 years had a previous seizure during acute neurologic illness, such as meningitis or during the acute illness after trauma. Many such seizures should potentially be preventable. Of children with seizures, 10% had had a neonatal seizure and 13% had had a febrile seizure. Among the hundreds of prenatal and perinatal factors explored as predictors of childhood seizure disorders, the principal predictors identified were congenital malformations of the fetus, cerebral and noncerebral; family history of certain neurologic disorders; and neonatal seizures. In agreement with the British National Child Development Study, labor and delivery factors in the NCPP appeared to contribute very little to childhood seizure disorders. Maldevelopment, rather than damage at birth to an initially intact nervous system, appeared to be the more common mechanism. Most seizure disorders of early childhood remained unexplained by the large set of prenatal and perinatal characteristics examined.