载脂蛋白AI在帕金森病发病中的作用及临床价值

<正>帕金森病(Parkinson’s disease,PD)是一种与年龄相关的进行性神经系统变性疾病,是中老年人最常见的运动障碍疾病,在60岁以上人群中帕金森病发病率约2%。它的病理学特征主要为黑质纹状体中多巴胺能神经元变性缺失和存活神经元中路易氏小体形成,α-突触核蛋白是路易氏小体的主要成分。PD患者出现运动障碍症状时,其大脑黑质中已大约有30%~50%的多巴胺能神经元缺失[1],随着病情进     

丘脑底核功能解剖的研究进展

帕金森病是一种常见的慢性中老年神经系统变性疾病。其主要病理特征为中脑黑质纹状体系统多巴胺能神经元变性缺失和路易小体形成,临床主要表现为静止性震颤、运动迟缓、肌强直、姿势和步态异常等运动症状及一系列非运动症状。目前,帕金森病多采用对症治疗,治疗方法主要为内科药物、外科手术及其他辅助康复相结合的综合治疗方法,以减缓临床症状。因为丘脑底核是帕金森病患者接受脑深部电刺激术采用最多的核团,所以本文对丘脑底核深部电刺激术治疗帕金森病进行综述,主要讨论丘脑底核的解剖、定位和神经环路等。     

帕金森病相关基因研究进展

帕金森病(Parkinson's disease,PD)是仅次于阿尔茨海默病的高发性神经元变性疾病,其病理学上以黑质致密层和蓝斑核神经元变性以及路易小体(Lewy bodies,LBs)的形成为特点.     

以记忆力下降、震颤及幻视为主要表现的痴呆临床诊断分析1例

<正>路易体痴呆(dementia with Lewy bodies,DLB)和帕金森病痴呆(Parkinson disease dementia,PDD)具有共同病理学改变,包括路易小体形成等,两者均属于"路易小体疾病谱系"~([1])。然而研究发现,除了路易小体形成,两者均存在类似阿尔茨海默病(Alzheimer’s disease,AD)的病理学改变,即β-淀粉样蛋白(amyloid-βpeptide,Aβ)沉积,且研究     

帕金森病运动症状及其发生机制研究进展

<正>帕金森病(Parkinson's disease,PD),又称震颤麻痹(paralysis agitans),是由英国医生James Parkinson(1817年)首先描述,是一种中老年人常见的运动障碍疾病,以黑质多巴胺能神经元变性缺失和路易小体(Lewy body)形成为病理特征,临床表现为静止性震颤、动作徐缓、肌强直和姿势步态异常等。     

家族性帕金森病致病基因的研究进展

帕金森病(Parkinson disease,PD)是1817年由英国医生James Parkinson首先描述,是一种中老年人常见的神经变性疾病,主要病理特征为黑质多巴胺能神经元变性、缺失和路易小体形成,临床表现为静止性震颤、肌肉强直、运动迟缓、姿势步态异常等,病因及发病机制十分复杂,目前尚未完全明确。PD大多数为散发性,约有10%～15%的PD患者有家族史。目前,已发现了16个与PD发病有关的致病基因     

磁共振波谱在帕金森病中应用

一、概述 帕金森病由英国医生James Parkinson (1817)首先描述,是一种中老年人常见的运动障碍疾病,以黑质多巴胺能神经元变性性缺失及黑质和蓝斑区路易小体形成为病理特征.起病缓慢,只有黑质多巴胺能神经元缺失到一定程度,才出现临床症状,Fearnley[1]等认为帕金森患者从多巴胺神经元开始丢失到症状出现潜伏期大约5年,动物及人体研究已证实帕金森患者症状前期脑中已存在生化、病理的改变,此时头颅CT和MRI在病变部位仍无明显特征表现,故大多数患者能明确诊断时已经是中晚期.因此能否早期诊断亚临床期和临床前期帕金森病人对治疗和预后具有重大意义.     

帕金森病痴呆的临床特征及治疗进展

帕金森病（Parkinson disease，PD）是一种中老年常见的神经系统变性疾病，其主要的病理特征是黑质多巴胺能神经元的变性死亡和残存神经元内路易小体（Lewy body）形成。部分PD患者在疾病的晚期会出现痴呆的表现。临床上将与路易小体有关的痴呆分为：PD痴呆（Parkinson disease withdementia, PDD） 和路易体痴呆（dementia with Lewy bodies,，DLB），据研究大多数诊断为PD的患者会出现PDD；而在所有痴呆患者中，DLB大约占了20％，仅次于阿尔茨海默病（Alzheimer disease，AD）。这三者尤其是前两者在病理学、临床表现以及神经生物学上有很大的重叠，难以鉴别。本文就PDD以及其与DLB、AD的鉴别及联系的最新研究作一综述。     

帕金森病痴呆与路易体痴呆

帕金森病(PD)是一种常见的神经系统变性疾病。其主要病理特征是黑质多巴胺能神经元的变性死亡和残存神经元内路易体(LB)形成。部分PD患者在疾病进展中并发痴呆表现,称帕金森病痴呆(PDD)和路易体痴呆(DLB)都具synuclein蛋白此特征性病理改变,两者在认知、精神症状和锥体外系症状上很相似,在病理学、临床表现上有很大重叠。本文就PDD与DLB、阿尔茨海默病(AD)、PD的鉴别及联系的最新研究作一综述。     

帕金森病的蛋白质组学研究进展

帕金森病(PD)作为一种较为常见的中老年人神经变性疾病,65岁以上人群发病率为l%～2%,其主要特征为中脑黑质区多巴胺能神经元的选择性脱失死亡和路易小体的形成.该病病因和发病机制目前尚不清楚,且疾病的早期诊断和治疗均有一定的困难.     

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.     

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.     

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.     

Treatment Considerations in Anticonvulsant Monotherapy

Summary: The long-standing practice of polypharmacy in treating epilepsy is giving way to use of monotherapy. Monotherapy can improve seizure control as well as reduce the risk of serious idiosyncratic reactions, dose-related side effects, and complex drug interactions. Monotherapy also offers improved compliance and cost-effectiveness. The basis of monotherapy is accurate diagnosis and assessment of the patient's seizure type(s), followed by selection of a single appropriate anticonvulsant drug. Many patients currently treated with multiple anticonvulsants can be successfully converted to monotherapy with a carefully monitored program in which troublesome and redundant drugs are gradually withdrawn from the therapeutic regimen.     

Anticonvulsant Drugs and Cognitive Function: A Review of the Literature

Summary: Alterations of cognitive function are separate from disturbances of behavior seen in association with epilepsy. The nature of the cognitive disability may to a certain extent depend on the seizure type. Partial seizures, mainly derived from a temporal lobe focus, impair memory tasks, while generalized seizures seem to have more effect on attentional abilities. A number of studies, reviewed in this paper, suggest that anticonvulsant drugs further impair cognitive function. Maximal impairments are seen in patients receiving polytherapy: rationalization of polytherapy improves cognitive abilities. Studies in children and adults have allowed differentiation of the effects of various commonly used antiepileptic agents. Maximal cognitive deficits are seen with. phenytoin, while phenobarbital and sodium valproate induce moderate disturbances, and carbamazepine seems relatively free from such toxicity. Further research is needed on the interrelationship between types of seizure disorders, types of anticonvulsant medications, and cognitive function.     

Dextromethorphan: Cellular Effects Reducing Neuronal Hyperactivity

Summary: Dextromethorphan is a dextrorotary morphinan without affinity for opioid receptors, commonly used as an antitussive medication. During the past 5 years, interest in the compound and its demethylated derivative, dextrorphan, has been revived because additional neuroprotective and an-tiepileptic properties were found in in vitro studies, animal experiments, and a few clinical cases. Both morphinans are able to inhibit N -methyl-D-aspartate (NMDA) receptor channels and voltage-operated calcium and sodium channels with different potencies. The inhibition of the NMDA receptor is believed to be the predominant mechanism of action responsible for the anticonvulsant and neuroprotective properties of the compounds.     

Effects of NMD A- and AMPA-Receptor Antagonists on Different Forms of Epileptiform Activity in Rat Temporal Cortex Slices

Summary: Lowering extracellular magnesium induces different patterns of epileptiform activity in rat hippocampus and entorhinal cortex. Short recurrent epileptiform discharges in the hippocampus are stable over time, whereas seizurelike events (SLEs) in the entorhinal cortex, the subiculum, and the neighboring neocortex develop into late recurrent discharges which are not blocked by clinically employed antiepileptic drugs. We tested the sensitivity of the different epileptiform discharge patterns to. /V-methyl-D-aspartate (NMDA)- and non-NMDA-receptor antagonists. As NMDA-receptor antagonist we used dextrorphan, ket-amine, and 2-aminophosphonovalerate (2APV); as α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)-receptor antagonist we employed the quinoxaline derivative glutamate 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). The findings show that the different patterns of epileptiform activity, including the late recurrent discharges, are sensitive to all NMDA-receptor antagonists. However, when dextrorphan was employed to suppress seizure-like events, later recurrent discharges did not develop during the remaining time course of the experiment. CNQX reversibly suppressed recurrent discharges in the hippocampus and SLEs in the entorhinal cortex. However, late recurrent discharges become insensitive to CNQX, even at a high concentration of 60 μM m. This finding suggests a prominent role for NMDA receptors in the generation of late recurrent discharges.     

Pediatric Epilepsy Surgery

Summary: The use of implantable arrays of epidural electrodes has made it possible to carry out extraoperative electrocorticography (ECoG) and functional localization in the awake child. This has permitted cortical excisions that are determined by criteria similar to those obtained during surgical procedures performed under local anesthesia in adults. In addition, the method also permits simultaneous ECoG and video monitoring during the child's symptomatic seizures, providing additional important localizing information that is impractical to obtain in operations under local anesthesia. We report our experience with 75 children, ages 5 months to 15 years, whom we have managed with epidural electrode arrays. The method of extraoperative ECoG is described and illustrative cases are presented to demonstrate its feasibility and utility in children. In addition, we call attention to gliomas as a common cause of chronic focal seizures in children. Of 49 children undergoing resection and followed for from 1 to 14 years (mean of 5.8 years), 32 (65%) are either seizure free or have had a significant reduction in seizure frequency that has unambiguously improved their quality of life. The results are analyzed further by relating the surgical outcome to each of the pathologic entities that caused the seizures. This analysis reveals the variety of neurological conditions that commonly cause intractable focal seizure disorder in children and distinguishes those pathologic entities in which the seizure disorder is apt to respond to surgical intervention from those that will not.