β-干扰素对多发性硬化患者趋化因子mRNA表达的影响

目的　观察干扰素 β 1b(IFNβ 1b)在体外对多发性硬化 (MS)患者趋化因子mRNA表达的影响。方法　取MS患者外周血 ,分离单个核细胞 (MNC) ,以其他非炎性神经系统疾病 (OND)及健康人 (HC)为对照组。MNC在完全培养基中分别与自身抗原髓鞘碱性蛋白 (MBP)、对照抗原AChR及不加抗原组 ,加或不加药物IFNβ 1b共同培养 ,3d后收集细胞 ,涂片 ,用地高辛标记的寡核苷酸探针进行原位杂交 (ISH) ,检测C C趋化因子单核细胞炎性蛋白 1α/ β(MIP 1α/ β)、单核细胞趋化蛋白 1(MCP 1 )和正常T细胞表达及分泌的调节活化因子 (RANTES)mRNA的表达。结果　MBP刺激的MIP 1α及自发产生的MIP 1αmRNA均受到IFN β 1b的抑制 ,但差异无显著意义 (P >0 0 5)。RANTESmRNA的表达受到IFNβ 1b的抑制 ,在MBP诱导下无药物处理时为 30 2± 1 5 0 (细胞数 / 1 0 5,下同 ) ,有药物处理为 1 1 1± 5 3 ,差异有显著意义 (P <0 0 1 ) ;在无抗原诱导下无药物处理时为 1 8 5± 3 3 ,有药物处理为 5 1± 3 2 ,差异亦有显著意义 (P <0 0 1 )。IFNβ 1b在 1 0U/ml浓度下 ,可对MBP刺激的MCP 1mRNA的表达产生抑制作用 (分别为 1 58 4± 1 0 4 3和 63 2± 36 9,差异有显著性意义 ,P <0 0 1 ) ,而对自发产生的MCP 1mRNA作用不明显 ;对MBP刺激     

单纯多发性肌炎肌肉组织中趋化因子的表达

目的 探讨趋化因子单核细胞趋化蛋白－1（MCP－1）、巨噬细胞炎症蛋白－1α（MIP－1α）和调节活化正常T细胞表达分泌的因子（RANTES）在单纯多发性肌炎（SPM）受累肌肉组织中的表达状况,并着重分析它们与SPM病期、病情的关系。方法 采用免疫组织化学LAB法,观察这些趋化因子蛋白在SPM受累肌肉组织中的表达状况,结合图像分析处理系统定量其表达水平。结果 这些趋化因子蛋白在SPM中均有表达;MCP－1在慢性组和病情较重组表达显著增加（均P＜0．01）,MIP－1α在病情较轻的慢性患者中表达显著增加（P＜0．05）,RANTES在不同病期组的表达无显著性差异（均P＞0．05）。结论 MCP－1可能不但在SPM病程的慢性进展中起较大作用,而且与病情严重程度有关,可作为病情进展或恶化的一个指标;MIP－1α则可能参与了疾病的持续发展;RANTES在SPM发病过程中可能只是机体对炎性损伤的一种普遍性反应。     

多发性硬化患者IFN-γ及IL-10分泌性T细胞的变化

目的　通过计数促炎症性细胞因子IFN γ及抗炎症性细胞因子IL 10分泌性T细胞数目 ,观察多发性硬化 (MS)患者此两类细胞因子 (CK)的变化。方法　采用酶联免疫斑点 (Elispot)技术检测MS患者、其他神经疾病 (OND)患者及正常对照组 (NC)外周血 (PB)及脑脊液 (CSF)中MBP及其他抗原反应性IFN γ和IL 10分泌性T细胞数目 ,并对活动期与缓解期MS及甲基强的松龙 (MP)冲击疗法前后MS患者PB中两种CK分泌性T细胞数目进行了比较。结果　活动期MS患者PB及CSF中IFN γ及IL 10分泌性T细胞数目较OND及NC组明显增多 (P <0 0 5) ,CSF中MBP反应性T细胞差异更为显著 (P <0 0 1)。MS患者PB中IL 10分泌性T细胞数在缓解期较活动期明显升高 (P <0 0 5)。MP治疗后IFN γ分泌性T细胞数目明显减少 ,而IL 10分泌细胞数目明显增多 (P <0 0 1)。结论　在MS发病机制中IFN γ起促进作用 ,而IL 10有保护作用 ,是促、抗炎症性CK的比值而非按顺序的表达决定MS的活动性。MP疗法的部分机制可能是调节CK网络的平衡     

多发性硬化患者趋化因子MCP—1的表达及意义

目的 测定急性期多发性硬化(MS)患者血清及脑脊液中的趋化因子MCP—1的浓度变化，并对其结果作初步探讨。方法 用ELISA法检测20例急性期MS患者，20例其他神经系统疾患的血清/脑脊液中的趋化因子MCP—1的浓度。结果 急性期MS患者血清及脑脊液中的趋化因子MCP—1的浓度与对照组相比均下降。结论 急性期MS患者血清及脑脊液中的趋化因子MCP—1的浓度下降可能与T细胞的不同反应性有关，趋化因子可能参与MS的发病过程。     

脑脊液髓鞘碱性蛋白抗体检测对格林-巴利综合征的临床价值

目的探讨格林-巴利综合征（GBS）中枢神经髓鞘的免疫性损伤。方法GBS患者20例，神经系统其它疾病组（OND）20例，非神经系统疾病手术者33例。以酶联免疫吸附法检测73份脑脊液（CSF）中髓鞘碱性蛋白IgG（MBP－IgG）。结果GBS患者、OND患者和非神经系统疾病手术者CSF中MBP－IgG阳性率分别为55％、30％和9.1％。GBS患者CSF中MBP-IgG阳性率与发病天数有关。结论部分GBS有中枢神经髓鞘的免疫性损害，证实GBS是自身免疫性脱髓鞘病。     

趋化因子在实验性自身免疫性神经炎中的动态表达

目的 探讨趋化因子在实验性自身免疫性神经炎（EAN）中的作用。方法 用兔坐骨神经匀浆免疫Wistgr大鼠．观察免疫后大鼠的发病情况和病理改变，通过免疫组化测定趋化因子在坐骨神经中的动态表达。结果 EAN大鼠于免疫后第9天开始出现症状．第15天症状达高峰，病理表现为炎性细胞浸润和脱髓鞘。趋化因子MCP-1表达在第9天达高峰，随后逐渐下降．前后时相点相比差异均有显著性（P〈0．05），且与对照组相比差异也有显著性（P〈0．001）。趋化因子MIP—1α和RANTES的表达有着相似的动态变化，在第15天疾病高峰期表达最高．随后逐渐下降，且与对照组相比差异有显著性（P〈0．001）。结论 趋化因子MCP-1在EAN发病早期可能起一定作用，MIP-1α和RANTES可能与EAN的病情进展有关。     

sIL-2R、mIL-2R及TNF-α在多发性硬化症免疫学发病机制中的作用

目的探讨可溶性白细胞介素-2受体（sIL－2R）、膜白细胞介素-2受体（mIL－2R）和肿瘤坏死因于-α（TNF－α）与多发性硬化（MS）免疫学发病机制、病程及病情的关系。方法采用ELkA法检测了临床确诊的48例MS患者血清、28例CSF中sIL－ZR水平，用免疫荧光法检测28例MS患者血中mIL－2R的表达，用生物活性测定法检测28例MS患者PBMCs体外诱生TNF－α水平。结果MS患者组激素治疗前血清及CSF中sIL－1R和血中TNF－α水平显著高于对照组（NC组）（P＜0．01），其中急性复发组MS显著高于缓解组（P＜0．01）；治疗后血清SIL－2R及TNF－α水平较治疗前显著下降（P＜0．01），且二者水平仍显著高于NC组（P＜0.01）。而缓解组TNF－α水平低于NC组（P＜0．05）。MS组血中mIL－2R表达，急性复发期MS患者显著高于缓解期（P＜0．01）及NC组（P＜0．01），缓解期MS患者则又显著低于NC组（P＜0．01）。MS患者血中sIL－2R及TNF－α水平与病情显著相关而与病程无关，sIL－2R与TNF－α显著相关。结论sIL－2R，mIL－2R、TNF－α在MS免疫发病中可能起重要作用，为探讨MS免疫发病机制进一步提供了理论依据。     

地塞米松对MS的IFN-γ及IL-10分泌性T细胞的影响

目的　检测多发性硬化 (MS)患者外周血单个核细胞在地塞米松 (Dex)影响下的 IFN- γ和 IL- 10的分泌细胞水平。方法　采用酶联免疫斑点技术 (EL ISPOT)检测体外培养的外周血单个核细胞 (MNC)在 CNS髓鞘素抗原 MBP刺激下的地塞米松对照试验 ,检测 IFN -γ和 IL - 10分泌性 T细胞水平 ,并与其他神经疾病 (OND)组及健康对照组的检测结果进行对比。结果　显示 MS患者 IFN- γ分泌细胞水平高于对照组 ,Dex使 MS患者 IFN- γ分泌细胞减少 ,对 IL- 10分泌细胞无明显影响。结论　MS患者存在 Th1/ Th2细胞因子的失衡 ,Dex能抑制 MS Th1类细胞因子 IFN- γ,其治疗作用可能与此有关。     

钾通道阻滞剂对多发性硬化患者细胞因子分泌的影响

目的研究多发性硬化(multiple sclerosis,MS)患者髓鞘反应性CD4+T淋巴细胞分泌γ干扰素(INF-γ)和白细胞介素-4(IL-4)的水平,并探讨钾通道阻滞剂对其分泌的影响。方法采用酶联免疫斑点方法(ELISPOT)对12例急性期MS患者、12例缓解期MS患者(经INF--β1b治疗)和10名健康对照的CD4+T淋巴细胞在有无髓鞘抗原和钾通道阻滞剂作用下分泌细胞因子INF-γ和IL-4的变化进行比较。结果 MS急性期外周血CD4+T细胞以分泌IFN-γ为主;MS急性期及缓解期的CD4+T淋巴细胞经髓鞘碱性蛋白(MBP)刺激后分泌IFN-γ的水平较未加抗原组均增高(P<0.05),加入Kv1.3通道阻滞剂海葵毒素(Stichodactyla helianthustoxin,SHK)后,MS急性期和缓解期的MBP反应CD4+T淋巴细胞IFN-γ分泌明显减低(P<0.05),而对IL-4无明显影响。结论 Kv1.3钾通道阻滞剂SHK能减少MS患者MBP反应CD4+T细胞分泌IFN-γ,提示髓鞘反应性CD4+T细胞上Kv1.3通道有可能作为治疗MS的新靶点。     

地塞米松对MS的IFN-γ-10分泌性T细胞的影响

目的检测多发性硬化(MS)患者外周血单个核细胞在地塞米松(Dex)影响下的IFN-γ和IL-10的分泌细胞水平.方法采用酶联免疫斑点技术(ELISPOT)检测体外培养的外周血单个核细胞(MNC)在CNS髓鞘素抗原MBP刺激下的地塞米松对照试验,检测IFN-γ和IL-10分泌性T细胞水平,并与其他神经疾病(OND)组及健康对照组的检测结果进行对比.结果显示MS患者IFN-γ分泌细胞水平高于对照组,Dex使MS患者IFN-γ分泌细胞减少,对IL-10分泌细胞无明显影响.结论MS患者存在Th1/Th2细胞因子的失衡,Dex能抑制MSTh1类细胞因子IFN-γ,其治疗作用可能与此有关.     

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.     

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 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.     

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.     

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.