学习障碍患儿血清BDNF水平的研究

目的探讨学习障碍血清脑源性神经营养因子(BDNF)水平的变化,及其与学习障碍病理基础的关系。方法患者组为22例未治疗过且不共患其他疾病的学习障碍患儿,对照组为16例年龄性别匹配正常儿童,以瑞文标准推理测验(SPM)测定智商,BDNF采用酶联夹心免疫吸附法检测。结果LD患者血清BDNF浓度为:平均(4.603±3.620)ng/ml高于对照组(1.843±0.728)ng/ml(t=3.326,P=0.003<0.01)。边缘智商组(4.523±4.618)ng/ml,与正常对照组比较差异有非常显著性(P=0.008<0.01)。结论学习障碍患儿血清BDNF浓度高于正常儿童,边缘智商者升高更明显。     

伴与不伴学习困难的注意缺陷多动障碍患儿认知特点的比较

目的　探讨伴与不伴学习困难 (LD)注意缺陷多动障碍 (ADHD)患儿认知特点的异同。方法　运用韦氏儿童智力量表 (C WISC)、韦氏记忆量表、数字划消测验、Stroop测验和瑞文标准推理测验 ,对 66例仅患ADHD患儿 (ADHD组 )和 2 9例合并LD的ADHD患儿 (ADHD +LD组 )的智力、记忆力、注意力及执行功能进行比较。结果　 (1 )ADHD组的平均年龄 [(9 5± 2 0 )岁 ]小于ADHD +LD组[(1 1 3± 2 3)岁 ] ,差异有显著性 (P <0 0 5) ;(2 )ADHD组在C WISC中仅注意 /不分心因子分 [(1 0 2±1 3)分 ]高于ADHD +LD组 [(96± 1 3)分 ] ,差异有显著性 (P =0 0 2 8) ,其余各项测验结果两组间的差异均无显著性 (P >0 0 5)。结论　ADHD +LD组注意 /不分心因子受损更严重 ,其余认知模式与ADHD组相似。     

注意缺陷/多动障碍儿童临床特征与单胺类神经递质研究

目的：探讨注意缺陷/多动障碍（ADHD）儿童的临床特征及血清单胺类神经递质水平的变化。方法：对32例ADHD儿童（研究组）和46名正常儿童（对照组）测评Piers-Harris儿童自我意识量表（PHCSS）、儿童焦虑性情绪障碍筛查表（SCRED）、儿童冲动量表（BIS）等,对其中30例ADHD儿童及36名正常儿童测量血清5-羟色胺（5-HT）、多巴胺（DA）、肾上腺素等的含量。结果：研究组PHCSS评分低于对照组（P〈0.01）;研究组SCRED和BIS评分均高于对照组（P〈0.001）。研究组血清5-HT低于对照组（P=0.002）。血清5-HT水平与冲动总分（r=-0.273）呈负相关;血清DA水平与运动分呈正相关（r=0.541）。结论：ADHD儿童具有多动、冲动、自我意识低等临床特征。而血清5-HT水平降低可能与ADHD的冲动控制困难特征有关。     

双相障碍与脑源性神经营养因子外周血mRNA和蛋白表达相关性的研究

目的 探讨脑源性神经营养因子(BDNF)外周血mRNA表达和血清蛋白水平与双相障碍、双相躁狂和双相抑郁的关系.方法 应用TaqMan探针及荧光实时定量逆转录-聚合酶链反应方法,检测并比较双相障碍组(61例)、双相躁狂组(29例)、双相抑郁组(32例)和对照组(61名)外周血白细胞BDNF基因的mRNA表达水平的差异;采用酶联免疫吸附方法测定血清BDNF浓度;应用17项汉密尔顿抑郁量表(HAMD17)和Young氏躁狂量表(YMRS)评定患者抑郁症状严重程度和躁狂症状的严重程度,采用Pearson相关分析分析BDNF基因mRNA表达水平和血清蛋白浓度与HAMD17和YMRS评分的关系.结果 (1)双相障碍组BDNF基因mRNA相对表达水平(0.0077±0.0019)较对照组(0.0096±0.0028)下降(t=-3.74,P＜0.01);双相躁狂组(0.0081±0.0023)、双相抑郁组(0.0073±0.0024)与对照组3组间BDNF基因mRNA相对表达水平的差异有统计学意义(F=7.55,P＜0.01),且双相躁狂组和双相抑郁组均低于对照组(P＜0.05或P＜0.01).(2)双相障碍组BDNF血清蛋白浓度低于对照组(t=-2.90,P＜0.01);双相躁狂组、双相抑郁组与对照组3组间BDNF血清蛋白浓度的差异有统计学意义(F=4.21,P＜0.05);双相躁狂组和双相抑郁组BDNF血清蛋白浓度均低于对照组(P均＜0.05),但双相躁狂组与双相抑郁组比较差异无统计学意义(P＞0.05).(3)双相躁狂组BDNF基因mRNA表达水平及血清蛋白浓度与YMRS评分未见相关(P＞0.05),双相抑郁组BDNF基因mRNA表达水平及血清蛋白浓度与HAMD17评分未见相关(P＞0.05).结论 双相障碍与BDNF水平下调可能相关,这种下降贯穿于躁狂相和抑郁相,而且BDNF的变化不会因双相障碍患者极性的变化而处于两极状态.     

5-羟色胺转运体基因多态与共患学习困难的儿童注意缺陷多动障碍的相关性

目的探讨共患学习困难(LD)的注意缺陷多动障碍(ADHD)患儿与5-羟色胺转运体(5-HTT)基因连锁多态区(5-HTTLPR)和第2内含子17 bp数目可变的顺向重复(stin2.VNTR)的关联关系。方法对126例共患LD的ADHD患儿和198例不共患LD的ADHD患儿的5-HTTLPR和stin2.VNTR两种多态进行检测,并采用传递不平衡检测(TDT)和单体型分析方法进行关联分析。结果(1)TDT检测:5-HTTLPR多态的S等位基因在共患LD的ADHD和ADHD混合型(ADHD-C)核心家系中优先传递(X2=5.831和5.281,P=0.015和0.020);所有家系均未观察到stin2.VNTR多态中的任何等位基因有传递不平衡现象(均P>0.05);(2)单体型分析:5-HTT基因与共患LD的ADHD和ADHD-C相关联(X2=11.391和13.343,v=3,P=0.010和P=0.004);单体型L／12在共患LD的ADHD和ADHD-C核心家系中传递较少(X2=10.317和8.948,v=1,P=0.001和0.003),而单体型L／10在共患LD的ADHD核心家系中传递较多(X2=4.065,v=1,P=0.044)。结论5-HTT基因可能与共患LD的ADHD相关联,其中主要为共患LD的ADHD-C亚型。     

重复经颅磁刺激对注意缺陷多动障碍儿童临床症状及血清脑源性神经营养因子的影响

目的:探讨高频重复经颅磁刺激(rTMS)对注意缺陷多动障碍(ADHD)儿童临床症状及血清脑源性神经营养因子(BDNF)水平的影响。方法:30例ADHD患儿随机分为真、伪刺激组;两组在接受盐酸哌甲酯控释片(18 mg/d)治疗的同时分别给予真、伪高频(10 Hz)rTMS治疗4周,刺激部位为右侧前额叶皮质;治疗前后采用中文版ADHD斯诺佩评估量表第4版(SNAP-IV)-父母版评估患儿症状和检测血清BDNF水平,并进行治疗前后比较。结果:治疗前两组SNAP-IV评分差异无统计学意义;治疗后,两组SNAP-IV总分及各分量表分明显降低(P均0.01);真刺激组多动冲动分明显低于伪刺激组(P0.05);治疗后两组血清BDNF水平明显升高(P0.05或P0.01),但治疗前后两组间血清BDNF水平比较差异无统计学意义;真刺激组SNAP-IV评分与血清BDNF水平无相关。结论:高频rTMS联合盐酸哌甲酯控释片相较于单用盐酸哌甲酯控释片治疗ADHD的多动冲动症状可能存在优势;但对血清BDNF水平无明显影响。     

重症肌无力患者抑郁障碍与皮质醇昼夜节律的关联性分析

目的 观察重症肌无力(Myasthenia gravis,MG)伴抑郁障碍患者皮质醇(COR)昼夜节律变化,探讨MG患者抑郁障碍与COR昼夜节律之间的关联性.方法 根据HAMD-24抑郁量表评分将43例MG患者分为伴抑郁组、不伴抑郁组,采用电化学发光法检测各组8:00、16:00、24:00外周血COR水平,并将所得结果与正常对照组(n=38)进行比较.同时比较不同Osserman分型与正常对照组的日平均COR水平及HAMD-24评分结果.结果 (1)MG伴抑郁组、不伴抑郁组及正常对照组COR水平均随时间点的不同而不同(F =2.824,P=0.036);其中,MG伴抑郁组各个时间点COR水平均高于正常对照组(P =0.009 ＜0.005);(2) MG不同Osserman分型组HAMD-24项评分不同(x2=62.268,P=0.000),日平均COR水平比较无统计学意义(x2=3.332,P=0.343).结论 MG伴抑郁障碍患者COR水平高于正常对照组;与正常对照组相比,MG伴抑郁障碍组还表现出COR昼夜节律的紊乱.     

伴自杀未遂双相障碍患者的血清脑源性神经营养因子水平

目的 分析伴自杀未遂的双相障碍（BD）患者与不伴自杀未遂患者及健康人群间血清BDNF水平的差异,探讨BDNF在预防BD患者自杀中的作用.方法 采用DSM-IV轴Ⅰ障碍用临床定式检查（患者版）（SCID-I/P）对临床诊断为心境障碍的患者进行评佑.纳入111例BD患者（26例有自杀未遂史）及41例健康对照.使用汉密尔顿抑郁量表（HAMD-17）及杨氏躁狂量表（YMRS）评估患者症状严重程度;使用酶联免疫吸附测定法测定所有研究对象的血清BDNF水平.结果 伴自杀未遂的BD患者血清BDNF水平（13.8±7.4） ng/ml显著低于无自杀未遂患者（18.7±11.9） ng/ml及健康对照组（26.0±12.9）ng/ml（F=9.371,P＜0.01）;伴自杀未遂的BD患者抑郁发作次数显著多于不伴自杀未遂患者,在控制抑郁发作次数后,两组间血清BDNF水平差异消失（P=0.236）;伴自杀未遂的BD患者血清BDNF水平和抑郁发作次数有相关性的倾向（r=-0.388,P=0.068）,与HAMD-17得分呈负相关（r=-0.585,P＜0.01）.结论 本研究提示BDNF在BD及BD患者自杀未遂的病理生理机制中起重要作用;伴自杀未遂的BD患者血清BDNF水平可能与抑郁发作次数、抑郁严重程度相关;通过有效治疗来提高BDNF水平可能通过减少抑郁发作次数,降低抑郁严重程度来降低自杀风险.     

注意缺陷多动障碍患儿可乐定激发试验的研究

目的探讨注意缺陷多动障碍(ADHD)患儿血清生长激素(GH)和催乳素(PRL)水平在可乐定激发前后的变化.方法将47例ADHD患儿按年龄分为儿童组(35例),青少年组(12例),并按症状分为注意障碍亚组(21例)和多动-混合亚组(26例);采用放射免疫分析法,于可乐定激发试验前、激发后120min、180min测定GH及PRL水平的变化,并与10名正常儿童(对照组)进行比较.结果(1)儿童组、青少年组与对照组间血清GH、PRL水平在试验各时点的差异均无显著性(P＞0.05).表现形式为,可乐定激发后120min时,三组GH水平均高于激发前,PRL均低于激发前;激发后180min时,儿童组和对照组GH下降,青少年组持续上升;儿童组PRL下降,青少年组和对照组回升.(2)ADHD多动-混合亚组120min时的GH水平[(12.26±6.63)μg/L]高于注意障碍亚组[(6.16±4.59)μg/L;t=3.58,P=0.01)].结论有多动、冲动行为ADHD患儿的肾上腺受体对可乐定激发更敏感.     

神经病理性疼痛患者血清BDNF,5-HT水平

目的 研究神经病理性疼痛(NP)患者的血清脑源性神经营养因子(BDNF)和5-羟色胺(5-HT)水平变化及其焦虑、抑郁状况,探索NP可能的生化机制和临床心理特征.方法 在精神专科医院门诊和综合医院神经科门诊收集NP患者(NP组)35例,同期收集健康对照者(对照组)42人,进行血清采集和量表评定,用ELISA法测其血清BDNF和5-HT浓度,采用疼痛视觉模拟评分法(VAS)、Zung抑郁自评量表(SDS)和Zung焦虑自评量表(SAS)评估研究对象的疼痛强度、抑郁和焦虑水平.结果 NP组BDNF血清浓度显著低于对照组,差异有统计学意义(t=2.157,P=0.034),两组5-HT血清浓度的差异无统计学意义(t=-0.315,P=0.754);对照组BDNF与5-HT血清浓度呈正相关(r=0.461,P=0.004).VAS与5-HT浓度呈负相关(r=-0.326,P=0.021);NP组SDS、SAS评分均高于对照组(t=2.058,P=0.039;t=2.568,P=0.011),VAS分与SAS及SDS评分均呈正相关(r=0.502,P=0;r=0.346,P=0.018);SDS分、SAS分与BDNF、5-HT浓度水平均无相关性.结论 BDNF可能在神经病理性疼痛发生的生化机制中起一定作用;NP患者的焦虑、抑郁症状明显,但主要表现为疼痛感所致的继发性状态,与NP的生化机制无相关性.     

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.