帕金森病患者基础PRL水平与并发痴呆及抑郁关系的研究

目的探讨帕金森病(PD)患者基础血浆泌乳素(prolactin,PRL)水平及与PD伴随的痴呆及抑郁的关系。方法测定167名在我院体检的正常老人(正常对照组)及113例PD患者(PD组)基础血浆PRL水平,并采用汉密顿抑郁量表(HAMD)、简明智能状况评价量表(MMSE)把PD患者分别划为痴呆组和非痴呆组及伴发抑郁组和非抑郁组,同时筛选同期我科收治的阿尔茨海默病(AD)患者20例及心理门诊治疗的功能性抑郁症患者50例(功能性抑郁组)。分别比较各组的PRL水平。结果PD组者的基础血浆PRL平均水平为(9.44±4.07)μg/L,与正常对照组[(9.76±3.97)μg/L]比较无统计学差异;PD伴发抑郁组平均PRL水平为(8.75±4.12)μg/L,与PD非抑郁组[(10.52±3.97)μg/L]、功能性抑郁组[(9.52±5.17)μg/L]比较均无统计学差异;PD伴发痴呆组平均PRL水平为[(5.26±4.90)μg/L],明显低于PD非痴呆组[(10.19±5.19)μg/L]及AD组[(7.85±4.25)μg/L]。结论PD患者出现痴呆时其基础血浆PRL水平降低。PD患者可能有DA、Ach、5HT能神经递质平衡的紊乱。     

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。     

进展性脑梗死患者血浆纤维蛋白原水平监测的临床意义

目的探讨进展性脑梗死患者血浆纤维蛋白原水平的变化及其与疾病进展间的关系。方法随机选取进展性脑梗死患者36例,非进展性脑梗死患者30例,健康体检者30例,通过检测不同组别之间血浆纤维蛋白原的水平。结果进展性脑梗死患者血浆纤维蛋白原的平均水平为（5．16±1．13）g,非进展性脑梗死患者血浆纤维蛋白原的平均水平为（3．71±0．52）g,健康体检者血浆纤维蛋白原的平均水平为（1．21±0．67）g。3组之间比较差异有统计学意义（P〈0．05）。结论进展性脑梗死患者血浆纤维蛋白原的水平明显高于其他2组,说明血浆纤维蛋白原的水平对于脑梗死疾病的进展有一定的关系。     

奎硫平与氯丙嗪对血清催乳素的影响

目的:探讨奎硫平与氯丙嗪对精神分裂症患者血清催乳素(PRL)的影响及血清PRL水平与药物疗效的相互关系。方法:对191例精神分裂症患者分别以奎硫平或氯丙嗪治疗。以阳性与阴性症状量表(PANSS)进行评估,同时测血清PRL浓度,于治疗前及治疗8周时各测1次。结果:经8周治疗,氯丙嗪组血清PRL(680.23±90.26)μg/L,显著高于奎硫平组(124.24±13.56)μg/L(P<0.001)。奎硫平组男女患者血清PRL水平差异无显著性(P>0.05);氯丙嗪组女性血清PRL(785.72±15.81)μg/L,显著高于男性的(557.75±99.23)μg/L(P<0.05),两组患者血清PRL浓度与PANSS减分率均无显著相关。结论:奎硫平对精神分裂症患者血清PRL水平基本无影响,氯丙嗪可明显升高患者血清PRL水平。血清PRL水平与药物疗效无显著相关。     

ω-3多不饱和脂肪酸对慢性轻度应激抑郁症大鼠糖水摄入量及脑单胺类递质的影响

目的探讨鱼油中的ω-3多不饱和脂肪酸（ω-3PUFA）对慢性轻度应激（CMS）抑郁症大鼠模型糖水摄入量及脑单胺类递质的影响，并探讨其可能的神经生化机制。方法雄性Sprague—Dawley大鼠41只，随机分为CMS组（32只）和正常组（9只），CMS组共CMS刺激8周，自实验第4周末起，随机分为ω-3PUFA组（8只）、阳性对照组（氯米帕明组，8只）和2个阴性对照组[橄榄油组（8只）和生理盐水组（8只）]。实验每周进行1次糖水消耗量的测定，实验第8周末采增高效液相色谱技术测定海马及前额叶皮质的5-羟色胺（5-HT）、去甲肾上腺素（NE）、多巴胺（DA）及其代谢产物的水平。结果（1）实验第8周末，ω-3PUFA组糖水摄入量[（10．25±1．55）g]均高于橄榄油组[（5．98±1．83）g]及生理盐水组[（4．65±1．17）g]，P=0．010和P=0．008；与氯米帕明组[（13．27±1．27）g]的差异无统计学意义（P〉0．05）。（2）ω-3PUFA组海马5-HT[（0．11±0．03）μg／g]、5-羟吲哚乙酸（5-HIAA）[（0．14±0．04）μg/g]及NE水平[（0．47±0．14）μg／g]均分别明显低于橄榄油组[（0．24±0．04）μg／g]、[（0．25±0．02）μg／g]、[（0．88±0．09）μg／g]及生理盐水组[（0．30±0．10）μg／g]、[（0．35±0．02）μg／g]、[（1．02±0．05）μg／g]，DA水平[（0．09±0．06）斗g／g]高于橄榄油组[（0．02±0．00）μg／g]，差异均有统计学意义（P均〈0．05）。（3）与橄榄油组相比，ω-3PUFA组前额叶5-HT水平[（0．08±0．01）μg／g]降低、DA水平[（0．04±0．00）μg／g]升高，差异均有统计学意义（P均〈0．05）。前额叶和海马所有单胺类递质的水平与氯米帕明组的差异均无统计学意义（P均〉0．05）。结论ω-3PUFA能够明显缓解慢性轻度应激大鼠糖水摄入量的降低，多种单胺类递质可能参与了该现象的作用机制。     

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&#177;0．57）ng／L]、．89&#177;0．36）ng／L，IL-2（4．3&#177;1．5）ng／L，IL-6（13．3&#177;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&#177;0．83）ng／L]及IL-6[（97．5&#177;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。     

精神分裂症患者血清催乳素和生长激素水平与奎硫平、氟哌啶醇治疗关系的对照研究

目的研究精神分裂症患者血清催乳素(PRL)、生长激素(GH)的基础水平与正常人的差异,以及奎硫平、氟哌啶醇治疗前后PRL、GH的变化。方法采用放射免疫法检测126例精神分裂症患者(包括奎硫平组62例和氟哌啶醇组64例)治疗前和治疗8周后PRL、GH水平,观察这2种药物对PRL、GH的影响及比较两者的差异,并与65名健康者进行对照分析。结果 126例精神分裂症患者的基础PRL、GH水平与对照组比较无显著性差异(P>0．05),奎硫平组治疗后PRL和GH均无显著改变(P>0．05)。氟哌啶醇组治疗后PRL值为(96．20±41．12)μg/L,较治疗前的(20．39±11．26)μg/L显著升高(P<0．01),女性升高更明显,为男性的 2．6倍。氟哌啶醇组治疗后GH值为(1．72±1．32)μg/L,较治疗前的(2．41±11．26)μg/L显著降低(P<0．01)。结论奎硫平治疗精神分裂症患者,对PRL及GH无明显影响,更适合生长期的青少年患者和药物性溢乳、乳房发育患者。     

精神分裂症患者脑源性神经营养因子水平及其与临床症状的关系

目的探讨脑源性神经营养因子（BDNF）在精神分裂症病理生理机制中的可能作用。方法采用横断面病例一对照研究设计。患者组为48例精神分裂症患者，其中发病后从未治疗组31例，停止治疗组17例。正常对照组（以下简称对照组）为与患者组性别、年龄匹配的41名健康人。对患者组用阳性和阴性症状量表（PANSS）评定病情严重程度。血浆BDNF浓度用酶联免疫吸附试验测定。用多变量方差分析比较组间差异。结果从未治疗组[（4．5±2．2）μg/L]和停药组患者[（3．9±1．4）μg/L]血浆BDNF浓度均低于对照组[（6．5±2．2）μg/L]（F检验，P〈0．01）；而从未治疗组与停止治疗组的差异无统计学意义（P〉0．05）。患者组的血浆BDNF浓度与PANSS阴性症状因子分（r=-0．509；P〈0．01）及总病期呈负相关（r=-0．426；P〈0．01），与发病年龄、PANSS阳性因子分、总分的相关性均无统计学差异。结论精神分裂症患者BDNF浓度低于正常；BDNF可能是参与精神分裂症病理生理机制的一种重要物质。     

阿立哌唑治疗奋乃静所致高催乳素血症的临床研究

目的探讨阿立哌唑治疗奋乃静所致高催乳素血症的疗效及安全性。方法将60例奋乃静所致高催乳素血症的精神分裂症患者,随机分为两组,在维持原奋乃静治疗的同时,分别加阿立哌唑（30例）及安慰剂（30例）治疗,疗程6周。分别于治疗前、治疗6周末检测血清催乳素（PRL）水平、评定简明精神病量表（BPRS）及副反应量表（TESS）,同时观察高催乳素血症临床症状变化情况。结果（1）治疗6周末,阿立哌唑组PRL（26.1±6.9）μg/L较治疗前（79.5±19.8）μg/L下降（P=0.000）,安慰剂组PRL（76.0±24.1）μg/L与治疗前（80.2±17.6）μg/L无显著性差异（P=0.227）;（2）治疗6周末,阿立哌唑组PRL下降值（53.4±16.8）μg/L高于安慰剂组（4.2±18.5）μg/L,差异有显著性（P=0.000）;（3）两组不良反应总体发生率均低,对原有奋乃静治疗的疗效均无不良影响。结论阿立哌唑可安全、有效治疗奋乃静所致的高催乳素血症。     

帕金森病患者的事件相关电位研究

为探讨帕金森病（PD）患者认识功能障碍的电生理改变，分别对32例PD非痴呆患者，30例PD痴呆患者及28例健康人的事件相关电位（ERP）进行了分析。结果显示PD痴呆患者N2，P3潜伏期明显延长（P＜0．05），P3。潜伏期与其简易精神状态量表评分存在显著位负相关（P＜0．05）．另外，0对PD痴呆患者ERP及CT的对比研究表明，PD痴呆患者ERP阳性检出率高于CT。认为ERP能客观地反映出PD痴呆患者认知功能的损害．     

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.     

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.     

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.