洛伐他汀对颈动脉粥样硬化斑块、血脂及血清C-反应蛋白水平的影响

目的 观察洛伐他汀对脑梗死患者颈动脉粥样硬化斑块、血脂及血清C-反应蛋白(CRP)水平的影响.方法 120例脑梗死合并颈动脉粥样硬化斑块患者随机分为洛伐他汀组和对照组.两组在低脂饮食的基础上,洛伐他汀组口服洛伐他汀20 mg每日1次,共6个月;观察两组治疗8周及 6个月时颈动脉粥样硬化斑块积分、血清CRP及血脂水平的变化.结果 (1)治疗6个月时,洛伐他汀组颈动脉粥样硬化斑块积分(4.20±3.77) 明显低于治疗前(4.77±2.31)及对照组(6.86±1.89)(均P<0.05);(2)治疗8周时,洛伐他汀组血清CRP水平[(6.37±2.16)mg/L]明显低于治疗前 [(16.35±5.18)mg/L] 及对照组[(16.30±4.84)mg/L](均P<0.05);(3)与治疗前及对照组比较,治疗8周及6个月时,洛伐他汀组血总胆固醇、三酰甘油及低密度脂蛋白胆固醇水平明显降低,高密度脂蛋白胆固醇明显升高(均P<0.05).结论 长期服用洛伐他汀可稳定甚至缩小颈动脉粥样硬化斑块,降低CRP及血脂水平,有助于预防脑卒中复发.     

脑梗死与颈动脉粥样硬化的关系

目的探讨脑梗死与颈动脉粥样硬化的关系。方法选取100例脑梗死患者进行颈动脉多普勒超声检查。结果颈动脉粥样硬化斑块与脑梗死部位存在同侧相关性,有软斑块、混合斑块的病人脑梗死的发生率较有扁平斑块、硬斑块的病人脑梗死的发生率明显增高(P<0.05)。腔隙性梗死在各种斑块的病人中发生率无明显差异。结论颈动脉粥样硬化斑块脱落是脑梗死的病因,颈动脉超声可以发现颈动脉粥样硬化斑块,是一种易于重复的无创性诊断方法。     

急性脑梗死患者颈动脉粥样硬化斑块与IL-6及CRP的关系

目的分析急性脑梗死患者颈动脉粥样硬化斑块性质与白细胞介素-6(IL-6)、C反应蛋白(CRP)表达水平的关系。方法选择急性脑梗死患者95例(观察组)为研究对象,根据颈动脉彩色多普勒超声检测结果分为不稳定斑块组(29例)、稳定斑块组(31例)及无斑块组(35例),选择同时期健康人30例为正常对照组,测定4组研究对象血清中IL-6、CRP的水平并进行比较。结果观察组CRP(4.80±2.16)mg/L和IL-6(209.54±75.60)pg/mL水平显著高于正常对照组的(2.43±0.51)mg/L和(103.34±8.99)pg/mL(P0.05)。不稳定斑块组CRP、IL-6水平均高于稳定斑块组、无斑块组和对照组(P0.05);稳定斑块组高于无斑块组和对照组(P0.05)。CRP、IL-6水平与动脉粥样硬化斑块的不稳定性呈正相关(rCRP=0.740,rIL-6=0.924,均P0.05)。结论急性脑梗死患者颈动脉粥样硬化斑块性质与IL-6、CRP表达水平密切相关,可能在预测脑血管病的发生及防治中起重要作用。     

血浆同型半胱氨酸水平与动脉粥样硬化和脑梗死的关系

目的 探讨血浆同型半胱氨酸(Hcy)水平与颈动脉粥样硬化和脑梗死关系.方法 2005-05～2006-02收治的91例脑梗死住院患者被列入研究对象.根据病灶大小分3组大片梗死21例,小片梗死44例,腔隙性梗死26例.根据颈动脉彩超检测结果将研究对象分为颈动脉斑块组34例,无颈动脉斑块组57例.全部患者测定血浆Hcy、血清叶酸、VitB12水平.分析血浆Hcy水平与脑梗死的危险因素、病灶大小、颈动脉粥样硬化斑块及血清叶酸、VitB12的关系.结果 血浆Hcy水平(1)与高血压、糖尿病、血脂、性别、年龄各指标无明显相关关系.(2)与脑梗死病灶大小无关.(3)与颈动脉粥样硬化斑块有关,有斑块34例,血浆Hcy(20.73±9.31)μmol/L,无斑块57例,血浆Hcy (15.46±11.4) μmol/L,前者高于后者(P＜0.05).(4)与血清叶酸、VitB12水平呈负相关(r1s=-0.264,r2s=-0.16,P＜0.05).结论 血浆Hcy水平与脑梗死病灶大小无关;Hcy水平升高与颈动脉粥样硬化斑块密切相关;与血清叶酸、VitB12水平呈负相关.高血浆Hcy血症可能是颈动脉粥样硬化的危险因素,但与脑梗死关系不明确.     

急性脑梗死患者血清内脂素含量的变化及对颈动脉粥样硬化斑块形成和稳定性的影响

目的观察急性脑梗死(ACI)患者血清内脂素水平,探讨其与颈动脉粥样硬化斑块形成和稳定性的关系。方法对68例ACI患者及45例健康人群(对照组)进行颈动脉彩色多普勒超声检查,根据血管超声检查颈动脉粥样硬化斑块结果,对ACI患者分组并检测血清内脂素水平。结果 68例ACI患者中,稳定斑块组31例,不稳定斑块组25例,无斑块形成(无斑块组)12例;3组内脂素水平分别为(28.25±8.06)μg/L、(34.25±8.75)μg/L、(16.58±6.02)μg/L,对照组为(14.56±6.12)μg/L;不稳定斑块组高于稳定斑块组,稳定斑块组高于无斑块组及对照组,组间比较差异有统计学意义(P0.05)。结论血清内脂素与ACI患者颈动脉粥样硬化斑块的形成及不稳定性的形成关系密切。     

血清尿酸、超敏C-反应蛋白与腔隙性脑梗死患者颈动脉粥样硬化程度的相关分析

研究背景中青年脑梗死患者呈逐年增加趋势,病因尚不明确。通过对中青年腔隙性脑梗死患者血清尿酸、超敏C反应蛋白水平及颈动脉内中膜厚度(IMT)的测定,探讨血清尿酸、超敏C反应蛋白与颈动脉粥样硬化程度的相关性。方法采用经颅多普勒超声分别测量186例诊断明确的腔隙性脑梗死患者舒张末期颈总动脉远端、颈总动脉分叉处和颈内动脉近端内中膜厚度;以1.00mm≤IMT<1.20mm为颈动脉内中膜增厚,存在突入血管腔回声结构或突入血管腔血流异常缺损或局部IMT≥1.20mm为颈动脉粥样硬化斑块形成;并分析血清尿酸、超敏C反应蛋白水平与颈动脉粥样硬化程度间的相关性。结果腔隙性脑梗死组患者血清尿酸、超敏C反应蛋白水平及内中膜厚度均高于正常对照组(P=0.000),颈动脉内中膜增厚组、粥样硬化斑块形成组与颈动脉内膜正常组之间差异有统计学意义(均P<0.01);血清尿酸和超敏C反应蛋白水平与内中膜厚度呈线性正相关关系(r=0.923,P=0.000;r=0.955,P=0.008)。结论血清尿酸和超敏C反应蛋白参与了粥样硬化斑块的形成,并在不伴高血压等危险因素的腔隙性脑梗死首次发病机制中起重要作用。     

脑梗死患者颈动脉粥样硬化斑块稳定性与血清C反应蛋白水平的关系

目的探讨脑梗死患者颈动脉粥样硬化斑块的稳定性与血清C反应蛋白(CRP)水平的关系。方法对112例颈内动脉系统脑梗死患者进行颈动脉彩色多普勒超声检查,明确粥样硬化斑块类型,同时测定血清CRP水平。结果脑梗死患者中不稳定斑块组、稳定斑块组、无斑块组血清CRP水平比较差异有统计学意义(P<0.01)。结论血清CRP水平可反映脑梗死患者颈动脉粥样硬化斑块的稳定性。     

颈动脉粥样硬化与不同类型脑梗死的关系

目的探讨颈动脉粥样硬化与腔隙性脑梗死和非腔隙性脑梗死的关系。方法用彩色多普勒超声仪对45例腔隙性脑梗死者（腔梗组）、114例非腔隙性梗死者（非腔梗组）及39例非脑梗死者（对照组）进行颈动脉探查,观察颈动脉内膜-中层厚度（IMT）、粥样斑块的形态、数量并计算斑块积分。结果三组中非腔梗组颈动脉粥样硬化程度最严重,颈动脉斑块总体检出率（97%）最高,平均每例颈动脉斑块检出个数（2.50±1.63）最多（P〈0.01）,其次为腔梗组（P〈0.05）。三组各型斑块构成比比较差异具有统计学意义（P〈0.05）。非腔梗组中病灶侧不稳定斑块检出率高于非病灶侧（P〈0.01）。结论颈动脉粥样硬化与脑梗死及其类型有关,利用超声技术检测颈动脉时各个指标要综合考虑,药物干预颈动脉粥样硬化应被重视。     

彩色多普勒超声在脑血管病颈动脉粥样硬化诊断中的应用

目的总结脑血管病患者颈动脉粥样硬化的特点,观察彩色多普勒超声诊断颈动脉粥样硬化的价值。方法脑血管病患者210例(观察组),其中短暂性脑缺血发作(TIA)患者68例,动脉粥样硬化性梗死(AI)患者72例,腔隙性梗死(LI)患者70例,同期住院非脑血管病患者200例(对照组),应用彩色多普勒超声检测各组颈总动脉内-中膜厚度、动脉粥样硬化斑块数、斑块类型及斑块部位,并进行比较。结果 TIA、LI、AI患者单发及多发斑块发生率均高于对照组,差异有统计学意义(P0.05)。TIA、LI、AI患者软斑块、硬斑块发生率均高于对照组(P0.05),扁平斑块发生率低于对照组(P0.05)。观察组斑块多见于颈动脉分叉处,其次为颈内动脉起始处。结论 TIA、AI与颈动脉粥样硬化关系密切,及时多普勒超声检查有助于预测脑血管疾病分型。     

可溶性CD40L水平对急性脑梗死患者颈动脉粥样硬化斑块稳定性的影响

目的探讨可溶性CD40L水平对急性脑梗死患者颈动脉粥样硬化斑块稳定性的影响。方法选取急性脑梗死患者69例(观察组),以健康体检者28例为对照组,应用酶联免疫法测量血清可溶性CD40L水平,并行彩色多普勒检查,测定颈动脉内-中膜厚度(IMT)、有无斑块及计算Crouse积分,比较2组颈动脉粥样硬化斑块、血清可溶性CD40L水平,根据超声结果分为稳定斑块组、不稳定斑块组,比较2组血清可溶性CD40L水平,分析可溶性CD40L水平与颈动脉粥样硬化斑块稳定性的关系。结果观察组血清可溶性CD40L浓度(7.97±2.42)μg/L,高于对照组(P0.05)。观察组检出粥样硬化斑块91个,其中不稳定斑块62个(68.13%)。不稳定斑块组血清可溶性CD40L水平高于稳定斑块组(P0.05)。观察组IMT增厚、Crouse积分高于对照组(P0.05)。血清可溶性CD40L水平与IMT、Crouse积分呈正相关。结论急性脑梗死患者血清可溶性CD40L水平明显升高,可能为预测缺血性脑血管事件的重要指标,可溶性CD40L越高,颈动脉粥样硬化斑块的稳定性越差,通过影响斑块稳定性参与了急性脑梗死的发生。     

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.