重症肌无力患者外周血干扰素—γ和白细胞介素—10分泌性T细？…

目的 探讨重症肌无力（ＭＧ）患者乙酰胆碱受体（ＡＣｈＲ）特异性Ｔ细胞免疫应答及其国酰胆碱受体抗体间的关系。及该类Ｔ细胞在胸腺瘤切除前后的变化。方法 采用酶联免疫斑点技术在１５例ＭＧ患者和１０例其他神经疾病（ＯＮＤ）患者中,检测在ＡＣｈＲ等不同抗原特异干扰素－γ分泌性Ｔｈ１细胞和白细胞介素－１０（ＩＬ－１０）分泌笥ＺＴｈ２细胞数。结果 ＡＣｈＲＡｂ阳性组ＭＧ患者外周血ＡＣｈＲ特异性ＩＦＮ－γ、ＩＬ＿     

THE T CELL REPERTOIRE TO ACETYLCHOLINE RECEPTOR SUBUNITS IN MYASTHENIA GRAVIS AND CONTROLS

（１）目的：多数重症肌无力（ＭＧ）患者可见作为烟碱样乙酰胆碱受体（ｎＡＣｈＲ）抗体（Ａｂ）升高基础的抗原特异性辅助性Ｔ细胞（Ｔｈ）增多，本研究目的在于探讨此类细胞的可能作用。（２）方法：设重症肌无力、其它神经科患者和正常对照三组。用体外测试的免疫酶点法，即以电鳗的ＡＣｈＲα－，β－，γ－，和δ－亚单位作为特异性抗原以及ＰＰＤ和与多发性硬化相关的髓鞘碱性蛋白作为非特异性抗原，于抗原刺激后计数分泌γ干扰素（ＩＦＮ－γ）的Ｔｈ１细胞数。测定周围血中针对这些抗原的Ｔ细胞亚群计数。（３）结果：ＭＧ患者识别ＡＣｈＲ四种亚单位的Ｔ细胞数均增高，依次为：１／２５０００，１／５９０００，１／８３０００和１／２５０００个细胞。６５％ＭＧ患者的Ｔ细胞主要识别α－亚单位，有些则主要识别γ－和δ－亚单位。少数ＭＧ患者测不到对任何亚单位起反应的Ｔ细胞。（４）结论：ＭＧ患者中，ＡＣｈＲ的四种亚单位均为通过分泌ＩＦＮγ的Ｔｈ１样细胞自身免疫攻击的靶。     

重症肌无力患者胸腺及外周血白细胞介素和干扰素—γ分泌细胞的检测

目的 研究重症肌无力（ＭＧ）胸腺以及外周血辅助性Ｔ细胞（Ｔｈ）,包括Ｔｈ１和Ｔｈ２亚群的免疫功能。方法 利用酶联免疫斑点（ＥＬＩＳＰＯＴ）法检测２０例ＭＧ患者胸腺及外周血乙酰胆碱受体（ＡＣｈＲ）特异反应性白细胞介素－２（ＩＬ－２）、白细胞介素－４（ＩＬ－４）、白细胞介素－１０（ＩＬ－１０）、干扰素－γ（ＩＦＮ－γ）分泌细胞数。结果 ＭＧ患者胸腺ＡＣｈＲ特异反应性ＩＬ－２、ＩＬ－４、ＩＬ－１０、ＩＦＮ－γ分泌细胞数均增高,外周血ＡＣｈＲ特异反应性ＩＬ－１０、ＩＦＮ－分泌细胞数增高,外周血与胸腺间ＡＣｈＲ特异反应性ＩＬ－４、ＩＬ－１０分泌细胞数呈正相关,３例ＭＧ患者在治疗后,外周血ＡＣｈＲ特异反应性ＩＬ－２、ＩＬ－４、ＩＦＮ－γ分泌细胞数均下降,ＩＬ－１０分泌细胞数则１例降低,２例增高。结论 ＭＧ胸腺及外周血存在着     

AChRAb阳性和阴性重症肌无力患者IL—4和IFN—γ…

将行胸腺切除术的重症肌无力（ＭＧ）患者分成乙酰胆碱受体抗体（ＡＣｈＲＡｂ）阳性和阴性２组，采用免疫酶点法检测其外周血、骨髓和胸腺白细胞介素４－（ＩＬ－４）分泌细胞和干扰素－γ（ＩＦＮ－γ）分泌细胞的数量，结果表明ＡＣｈＲＡｂ阳性组其外周血和骨髓中ＩＬ－４和ＩＦＮ－γ分泌细胞数量均显著高于ＡＣｈＲＡｂ阴性组（Ｐ〈０．０５），而胸腺细胞两组间差异无显著性意义（Ｐ〉０．０５）。提示ＩＬ－４和ＩＦＮ－γ在     

重症肌无力患者外周血乙酰胆碱受体特异性T细胞sIL—2R,IFN—γ,IL— …

目的 了解ＭＧ患者的乙酰胆碱受体（ＡＣｈＲ）特异性细胞免疫应答。方法 采用酶联免疫吸附试验（ＥＬＩＳＡ）检测３０例ＭＧ患者２０名健康对照者经ＡＣｈＲ刺激后外周血单核细胞（ＰＢＭＣ）辅助性Ｔ细胞１（Ｔｈ１）相关的干扰素（ＩＦＮ）－γ，辅助性Ｔ细胞（Ｔｈ２）相关的白细胞介素（ＩＬ）－４及与细胞免疫活化密切要关的可溶性白细胞介素－２受体（ｓＩＬ－２Ｒ）的分泌，用逆转录－聚合酶链反应（ＲＴ－ＰＣＲ）结合狭     

急性脑梗死和Alzheimer病脑脊液高水平髓鞘素抗原B细胞免疫应答

目的确认急性脑梗死（ＡＣＩ）和Ａｌｚｈｅｉｍｅｒ病（ＡＤ）对髓鞘素碱性蛋白（ＭＢＰ）、髓鞘素结合糖蛋白（ＭＡＧ）和含脂质蛋白（ＰＬＰ）的Ｂ细胞免疫应答。方法采用酶联免疫斑点技术检测了ＡＣＩ、临床可能ＡＤ和其它神经疾病（ＯＮＤ）对照组患者外周血和脑脊液（ＣＳＦ）中ＭＢＰ、ＭＡＧ和ＰＬＰ抗体分泌细胞。结果ＡＣＩ、ＡＤ和ＯＮＤ患者外周血中均可检出ＩｇＧ、ＩｇＡ、ＩｇＭ三种表型ＭＢＰ、ＭＡＧ、ＰＬＰ抗体分泌细胞，无显著差异。但ＡＣＩ和ＡＤ患者ＣＳＦ中ＩｇＧ型ＭＢＰ、ＭＡＧ和ＰＬＰ抗体分泌细胞均呈显著性增高。结论ＡＣＩ急性脑缺血损伤和ＡＤ神经变性可能导致体内Ｂ细胞激活及ＣＮＳ内髓鞘素反应性Ｂ细胞免疫应答，其病理意义有待探讨。     

重症肌无力患者外周血乙酰胆碱受体特异性T细胞sIL-2R、IFN-γ、IL-4的表达和转录

目的了解ＭＧ患者的乙酰胆碱受体（ＡＣｈＲ）特异性细胞免疫应答。方法采用酶联免疫吸附试验（ＥＬＩＳＡ）检测３０例ＭＧ患者和２０名健康对照者经ＡＣｈＲ刺激后外周血单核细胞（ＰＢＭＣ），辅助性Ｔ细胞１（Ｔｈ１）相关的干扰素（ＩＦＮ）γ、辅助性Ｔ细胞２（Ｔｈ２）相关的白细胞介素（ＩＬ）４及与细胞免疫活化密切相关的可溶性白细胞介素２受体（ｓＩＬ２Ｒ）的分泌，用逆转录聚合酶链反应（ＲＴＰＣＲ）结合狭缝印迹杂交检测ＩＦＮγ、ＩＬ４的信息核糖核酸（ｍＲＮＡ）转录。结果总ＭＧ患者组ＩＦＮγ显著高于健康对照组，尤以急性ＭＧ患者组（１４例）更明显，且其升高与其ｍＲＮＡ转录水平一致。虽然这两组ＭＧ患者的ｓＩＬ２Ｒ亦明显高于健康对照组，但患者组的ＩＬ４表达及其ｍＲＮＡ转录与健康对照组相比差异无显著意义。结论ＭＧ患者有Ｔｈ１和Ｔｈ２的失衡，ＭＧ患者有ＡＣｈＲ特异性细胞免疫活化，Ｔｈ１的细胞因子ＩＦＮγ可能作为效应因子参与了ＭＧ的发病。     

TGF－β高调在鼻腔给予AChR抑制EAMG中起重要作用

用放射标记的ｃＤＮＡ寡核苷酸探针，使用原位杂交技术检测表达γ干扰素（ＩＦＮ－γ）、白细胞介素４（ＩＬ－４）和转移生长因子β（ＴＧＦ－β）ｍＲＮＡ的单个核细胞（ＭＮＣ）。结果表明，实验性自身免疫性重症肌无力（ＥＡＭＧ）对照组大鼠窝和腹股沟淋巴结（ＰＩＬＮ）的ＭＮＣ乙酰胆碱受体（ＡＣｈＲ）诱导的ＩＦＮ－γ、ＩＬ－４ＴＧＦ－βｍＲＮＡ表达细胞数明显增高，与给予ＰＢＳＣＦＡ注射组比较差异显著。鼻腔耐受组与ＥＡＭＧ对照组相比，某些淋巴器官中ＡＣｈＲ诱导的ＩＦＮ－γ、ＩＬ－４数降低，ＡＣｈＲ诱导的ＴＧＦ－β细胞明显上调。提示ＩＦＮ－γ、ＩＬ－４和ＴＧＦ－β与ＥＡＭＧ的发病有关，而ＴＧＦ－β高调在鼻腔ＡＣｈＲ耐受ＥＡＭＧ中起重要作用。     

急性脑梗死和Alzheimer病脑脊液高水平髓鞘素抗原B细胞免 …

目的 确认急性脑梗死对髓鞘素碱性蛋白（ＭＢＰ）,髓鞘素结合糖蛋白（ＭＡＧ）和含脂质蛋白（ＰＬＰ）的Ｂ细胞免疫应答。方法 采用酶联免疫斑点技术检测了ＡＣＩ,临床可能ＡＤ和其它神经疾病（ＯＮＤ）对照组患者外周血和脑脊液（ＣＳＦ）中ＭＢＰ,ＭＡＧ和ＰＬＰ抗体分泌细胞。     

重症肌无力患者血清IgG-乙酰胆硷受体抗体亚型研究

目的 探讨重症肌无力（ＭＧ）患者血清ＩｇＧ－乙酰胆硷受体抗体（ＡＣｈＲＡｂ）亚型的分布规律及其临床意义。方法 采用ＡＢＣ－ＥＬＩＳＡ法检测４３例ＭＧ组和２５例临床对照组、２０例正常对照组血清中ＩｇＧ－ＡＣｈＲＡｂ亚型ＩｇＧ１－４。结果 ＭＧ组与两对照组相比ＩｇＧ１和ＩｇＧ４亚型抗体无显著差别,ＩｇＧ２亚型抗体显著升高（Ｐ〈０．０５）,ＩｇＧ３亚型抗体显著降低（Ｐ〈０．０５）;ＭＧ组各临床类型间各亚型抗体无显著差别。结论 ＩｇＧ－ＡＣｈＲＡｂ亚型以ＩｇＧ２活性为主,但未显示与ＭＧ临床类型有关。     

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.     

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.     

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.     

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.     

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.     

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.     

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.