精神分裂症外周血致炎性细胞因子、酪氨酸羟化酶基因表达水平

目的：检测精神分裂症患者致炎性细胞因子白介素1β（IL-1β）,肿瘤坏死因子α（TNF-α）和酪氨酸羟化酶（TH）基因表达水平。方法：采用逆转录聚合酶链反应和半定量技术,分别检测39例精神分裂症患者,25名同胞和30名正常对照外周血单个核细胞IL-1β、TNF-α和TH基因表达水平。结果：患者组与同胞组IL-1β、TNF-α、TH基因表达水平差异均无显著性（P均〉0.05）;患者组与正常对照组、同胞组与正常对照组的IL-1β、TNF-α、TH基因表达水平差异均有显著性（P〈0.01或〈0.05）。结论：精神分裂症患者可能存在致炎性细胞因子和儿茶酚胺类神经递质的过度表达,且可能受遗传影响。     

急性发作精神分裂症患者血清前炎性因子与临床特征的关系

目的分析血清前炎性因子水平与急性发作精神分裂症患者临床特征间的关系,探索前炎性因子在疾病发生机制中可能的作用。方法共纳入急性发作的精神分裂症患者105例（患者组）,健康对照50名（对照组）。采用酶联免疫（ELISA）法检测所有研究对象血清IL-1B、IL-6和TNF—的浓度;使用阳性和阴性症状量表（PANSS）评定患者的精神病理症状。在比较患者组与对照组血清前炎性因子浓度差异的同时,分析其与患者临床特征的关系。结果（1）患者组与对照组相比,血清IL-1β[12.3（2．8,15．0）ng／L比7．9（1．3,9．9）ng／L]、TNF—α[151．6（58．9,186．8）ng／L比108．9（37．0,132．3）ng／L]的差异有统计学意义（P〈0．05）;（2）按照性别、发作次数、病程、家族史、精神病理症状对患者组进行分层,首发患者血清IL－1β、TNF－α[水平高于复发患者;病程小于5年患者血清TNF－α水平高于病程超过5年的患者;家族史阳性患者IL－6水平高于阴性患者;以阳性症状为主患者的TNF—α水平高于以阴性症状为主的患者,差异均有统计学意义（P〈0．05）;（3）患者组血清IL－1β与IL－6（r=0．49,P〈0．01）、TNF－α（r=0．30,P〈0．01）呈正相关;对照组血清IL－1β水平与IL－6（r=0．55,P〈0．01）、TNF—α（r=0．34,P=0．02）呈正相关。结论急性发作的精神分裂症患者存在免疫激活,免疫激活程度与疾病的临床特征有关;免疫异常可能在疾病发生过程中起关键作用。     

多发家系精神分裂症肿瘤坏死因子α基因启动子多态性与其血浆水平的关系

目的探讨多发家系精神分裂症患者肿瘤坏死因子d基因启动子（TNF—α）区-308A／G位点基因多态性与血浆水平的关系。方法纳入51个多发精神分裂症家系（血亲同胞中有≥2例同胞符合美国精神障碍诊断与统计手册第4版精神分裂症诊断标准的患者，且血亲父母健在）222人完成遗传学研究用诊断会谈及遗传学研究用家属会谈表；分为患者组（98例）、父母组（94名）及正常同胞组（30名）。非血亲健康对照组（40名，以下简称对照组）。用聚合酶链反应特异序列引物法检测基因型。用酶联免疫吸附法检测TNF—α血浆浓度。统计分析采用X^2检验、t检验、传递不平衡检验及关联分析。结果（1）患者、父母、正常同胞及对照组基因型均以G／G为多，分别为80％、81％、90％及85％，A／G分别为20％、19％、10％及15％，未检出A／A基因型；等位基因A的频度分别为10％、10％、5％及8％；等位基因G分别为90％、90％、95％及92％；4组间基因型及等位基因频度分布的差异均无统计学意义（P〉0．05）。（2）TNF—αP区-308A等位基因在精神分裂症患者中存在传递小平衡性（McNemarx。=3．85，P〈0．05），相对风险分析（RR）呈负相关（RR=0．44，XRR^2=3．846，P〈0．05）。（3）患者、父母、正常同胞及对照组G／G型TNF—α血浆浓度分别为（61±29）ng／L、（68±29）ng／L、（80±23）ng／L和（73±32）ng／L；A／G型分别为（64±21）ng／L、（79±40）ng／L、（95±46）ng／L和（81±35）ng／L；各组两型间TNF—α浓度的差异均无统计学意义（P均〉0．05）。结论TNF—αP区-308A等位基因在精神分裂症患者中的传递频率较低；-308A等位基因与精神分裂症存在相关性，但与TNF—α血浆水平变化无直接关系。     

儿童精神分裂症患者微小躯体异常与脑室扩大关系的研究

目的探讨儿童精神分裂症患者微小躯体异常（MPAs）与脑室扩大的关系。方法对168例儿童精神分裂症患者（患者组）进行躯体异常量表（WS）评定，并将患者分为MPAs明显组（WS总分≥4分，85例）和MPAs不明显组（WS总分≤3分，83例）。用阳性和阴性症状量表（PANSS）评定患者组的精神症状；用CT测量患者的脑室（脑室值用哈氏值、三脑室宽度、脑室指数、侧脑室体部指数、侧脑室宽度指数、前角指数表示），并与40名健康儿童（对照组）进行对照。结果（1）患者组哈氏值[（5．37±0．53）cm]和三脑室宽度[（3．83±1．21cm）]均大于对照组[分别为（4．94±0．34）cm和（3．16±0．41）cm]，腩室指数（1．55±0．18）和前角指数（3．52±0．31）小于对照组（分别为1．65±0．22和3．77±0．34），均P〈0．01。（2）MPAs明显组哈氏值[（5．50±0．54）cm]和三脑室宽度[（4．10±1．32）cm]大于MPAs不明显组[分别为（5．24±0．49）cm和（3．55±1．01）cm]和对照组，前角指数（3．47±0．30）小于MPAs不明显组（3．57±0．31）和对照组，脑室指数（1．55±0．18）小于对照组。（3）MPAs不明显组哈氏值大于对照组，脑室指数和前角指数小于对照组，均P〈0．01和P〈0．05。（4）患者组WS总分与哈氏值（r=0．263）及三脑室宽度（r=0．287）存在正相关，与前角指数存在负相关（r=-0．178）；患者组的WS总分与阴性症状分呈正相关（r=0．247）；患者组的阴性症状分与哈氏值（r=0．375）和三脑室宽度（r=0．161）呈正相关，与脑室指数（r=-0．159）和前角指数（r=-0．191）呈负相关（均P〈0．01和P〈0．05）。结论儿童精神分裂症患者存在显著的MPAs和脑室扩大，MPAs与脑室扩大之间有明显的相关。     

免疫球蛋白对吉兰-巴雷综合征患者血液白细胞介素-12和肿瘤坏死因子-α水平的影响

目的探讨免疫球蛋白对吉兰-巴雷综合征（GBS）患者血液白细胞介素（IL）-12和肿瘤坏死因子（TNF）-α水平的影响。方法采用酶联免疫吸附（ELISA）法检测大剂量免疫球蛋白静脉输注（IVIG）治疗GBS患者前后血液IL-12和TNF-α水平变化,并与健康对照组进行比较。结果47例GBS患者IL-12和TNF-α水平IVIG治疗前分别为（39．74±8．86）、（815．17±170．84）pg／mL,治疗后分别为（18．93±4．21）、（453．21±146．75）pg／mL,治疗前后差异均有统计学意义（P〈0．05）。IL-12与TNF-α水平呈正相关。结论IVIG治疗可下调GBS患者IL-12与TNF-α水平。     

偏执型分裂症外周血IL-1β、TNF-α和酪氨酸羟化酶mRNA表达水平与临床症状的关系

目的检测偏执型精神分裂症患者白介素-1β、肿瘤坏死因子-α和酪氨酸羟化酶（TH）的基因表达水平,探讨其与临床症状的关系。方法采用RT-PCR和半定量技术,分别检测39例偏执型精神分裂症患者和30例正常对照外周血单个核细胞IL-1β、TNF-α和TH的基因表达水平,同时应用PANSS量表评定偏执型精神分裂症患者临床症状。结果研究显示病例组的IL-1β、TNF-α、TH基因表达水平均显著高于正常对照组（P〈0.01）。且同时发现IL-1β（r=0.420）、TNF-α（r=0.430）基因表达水平与PANSS量表的一般病理症状分显著相关（P〈0.01）。结论偏执型精神分裂症患者可能存在致炎性细胞因子和儿茶酚胺类神经递质的过度表达;致炎性细胞因子可能参与偏执型精神分裂症一般病理症状的形成。     

脑梗死后癫痫患者血清细胞因子水平的改变

目的研究脑梗死后癫痫患者血清细胞因子水平的改变。方法应用放射免疫法检测87例脑梗死后癫痫患者（脑梗死癫痫组）和75名健康体检者（正常对照组）的血清肿瘤坏死因子α（TNF-α），白细胞介素（IL）-2和IL-6水平。结果脑梗死癫痫组血清TNF-α[（2．5±0．57）ng／L]、．89±0．36）ng／L，IL-2（4．3±1．5）ng／L，IL-6（13．3±11．1）ng／L]（均P〈0.01）。结论脑梗死后癫痫患者的血清细胞因子TNIL-2[2（9、0±0．83）ng／L]及IL-6[（97．5±13．1）ng／L]水平明显高于正常对照组[TNF-α（0F-α、IL-2及IL-6水平显著升高，提示细胞因子可能在脑梗死后癫痫的发病中起重要作用。     

肿瘤坏死因子α对大鼠平滑肌细胞增殖及syndecan-4蛋白表达的影响

目的 观察肿瘤坏死因子α（TNF—α）对大鼠胸主动脉血管平滑肌细胞（VSMC）增殖和syndecan-4蛋白表达的影响。方法 体外培养大鼠胸主动脉VSMC，1、10、20、100ng／mL的TNF—α分别作用并设立对照组（不采取干预措施）进行比较，采用MTS／PES法确定VSMC的增殖状态，利用Western blot蛋白免疫印迹法测定syndecan-4蛋白表达。结果 各组细胞增殖率分别为对照组1．001±0．064，TNF—α 1ng／mL组1．082±0．272，10ng／mL组1．125±0．198，20ng／mL组1．566±0．060，100ng／mL组1．215±0．231。统计分析显示低至1ng／mL的TNF-α仍能明显刺激大鼠VSMC的增殖（与对照组比较，P〈0．05），其中以TNF—α 20ng／mL组细胞增殖最显著。TNF-α对VSMC的syndecan-4蛋白的表达有显著的增强作用（与对照组比较，P〈0．05），其中也以20ng／mL组增强作用最显著。结论 TNF-α对体外培养大鼠VSMC增殖和syndecan-4蛋白表达均有显著的促进作用。     

利培酮与舒必利对精神分裂症男性老年患者血清催乳素水平影响的对照研究

目的 探讨利培酮和舒必利对精神分裂症男性老年患者血清催乳素（PRL）水平的影响。方法 将51例精神分裂症男性老年患者随机分为利培酮组[（3．7±0、9）mg／d，24例]和舒必利组[（800±156）mg／d，27例]，采用酶联免疫方法测定两组治疗前后的PRL水平，并与25名正常男性老年人（对照组）进行对照。结果 （1）治疗前，患者组PRL水平[（26±11）彬L]与对照组[（24±14）μg／L]的差异无统计学意义，利培酮组[（26±11）μg/L]与舒必利组[（28±12）μg/L]的差异亦无统计学意义（均P〉0．05）。（2）治疗后，患者组PRL水平[（149±59）μg/L]高于治疗前（t=14．53，P〈0．01）；利培酮组[（118±47）μg/L]和舒必利组[（196±73）μg/L]亦均高于治疗前，其中舒必利组高于利培酮组（均P〈0．01）。结论 利培酮和舒必利均能升高精神分裂症男性老年患者的PRL水平，其中以舒必利更为显著。     

c-Jun在颅内动脉瘤中的表达及对MMP-9表达调控作用的研究

目的检测c-Jun在颅内动脉瘤中的表达及探讨其对基质金属蛋白酶-9（MMP-91表达调控的意义。方法对15例颅内动脉瘤标本和6例非脑血管病患者的正常脑血管应用免疫组化SP法和实时荧光定量RT-PCR法分别检测脑血管壁组织内c-Jun免疫活性和MMP-9mRNA的表达水平。结果c-Jun免疫活性在颅内动脉瘤壁组织内为1．92±0．51，正常脑血管壁内为0．17±0．41，二者有显著性差异（P〈0．01）。动脉瘤壁组织中MMP-9mRNA的表达是正常血管的10．06倍（P〈0．01）。颅内动脉瘤壁组织内c-Jun的免疫活性和MMP-9mRNA的表达呈正相关（r=．818，P〈0．001）。结论活化后的c-Jun可能通过其结构域内MMP-9结合位点启动MMP-9大量转录而参与颅内动脉瘤的发病机制。     

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.     

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.     

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.     

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.     

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.     

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.     

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.