血清炎性标志物与缺血性脑血管病的关系

目的 比较急性脑梗死、短暂性脑缺血发作(TIA)、陈旧脑梗死患者和健康对照者血清炎性标志物白细胞介素-6(IL-6)、高敏C反应蛋白(hsCRP)、基质金属蛋白酶-9(MMP-9)和组织金属蛋白酶抑制物-1(TIMP-1)水平.方法 收集作者医院急性脑梗死患者56例,TIA患者46例,陈旧脑梗死患者56例,对照组30名,采用ELISA法测定其血IL-6、MMP-9和TIMP-1水平,采用免疫比浊法测定其血hsCRP水平.结果 急性脑梗死和TIA组IL-6水平均高于陈旧脑梗死和对照组 (P<0.05).各组间hsCRP水平比较差异均有统计学意义(P<0.05),水平由高至低依次为急性脑梗死组、TIA组、对照组和陈旧脑梗死组.急性脑梗死组和TIA组MMP-9水平高于陈旧脑梗死和对照组(P<0.05).TIA、急性脑梗死和陈旧脑梗死组TIMP-1水平均高于对照组(P<0.05).IL-6水平(OR=20.525,95%CI:2.623～160.58,P=0.004)和hsCRP(OR=1.878, 95%CI:1.138～3.100, P=0.014)是脑卒中患者预后不佳的独立危险因素.结论 TIA与急性脑梗死患者炎性标志物水平升高,其中IL-6和hsCRP水平升高是患者预后不佳的独立危险因素.     

急性脑梗死患者超早期血清基质金属蛋白酶水平与磁共振改变的相关性

目的 研究急性脑梗死患者超早期血清基质金属蛋白酶(MMPs)水平与磁共振(MR)改变的相关性.方法 对47例发病6 h内的急性脑梗死患者进行头颅MR检查和血清MMP-2、MMP-9及MMP-13水平检测.结果 脑梗死患者血清MMP-2、MMP-9及MMP-13的水平分别为(242.70 ±78.42)ng/ml、(113.40±108.65)rig/ml及(84.31±47.62)VS/ml.血清MMP-2、MMP-13水平与MR改变无相关性(均P＞0.05),MMP-9水平与MR的平均通过时间图(r=0.371,P=0.026)、达峰时间图(r=0.379,P=0.023)、脑血流量图(r=0.447,P=0.006)的异常体积及大血管闭塞(r=0.416,P=0.004)有正相关性.结论 血清MMP-9水平在急性脑梗死超早期与脑MR改变呈正相关,而血清MMP-2及MMP-13水平与脑MR改变无相关性.提示MMP-9参与了急性缺血性脑损害的病理过程.     

急性脑梗死患者血清MMP-3 MMP-9水平变化及意义

目的探讨急性脑梗死患者血清基质金属蛋白酶-3(MMP-3)、MMP-9水平的变化及其临床意义。方法采用ELISA试验检测并比较78例急性脑梗死患者发病24h内和50例健康体检者的血清MMP-3、MMP-9水平。结果急性脑梗死患者血清MMP-3、MMP-9水平分别为(89.6±23.1)ng/mL、(285.3±78.4)ng/mL,均高于健康体检者的(15.3±3.3)ng/mL、(78.6±15.7)ng/mL,差异有统计学意义(P0.05)。急性脑梗死患者血清MMP-3、MMP-9水平与疾病严重程度关系密切,病情越重,两者表达水平越高(P0.05)。急性脑梗死患者血清MMP-3、MMP-9水平表达呈正相关关系(r=0.453,P0.05)。结论急性脑梗死患者血清MMP-3、MMP-9水平明显升高,且水平随病情的加重而升高,两者联合检测可用于急性脑梗死的早期检测。     

基质金属蛋白酶-9基因多态与急性脑梗死

目的 探讨基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)基因多态及血清水平与急性脑梗死的关系.方法 对2006年1月至2007年5月期间在我院神经内科住院的急性脑梗死患者101例和我院体检中心健康体检者114名进行研究,采用ELISA法测定血清MMP-9水平,同时采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法 分析MMP-9基因启动子C-1562T多态.结果 脑梗死患者组48 h内血清MMP-9水平为(138.9±121.8)ng/ml,而对照组为(18.4±4.6)ng/ml,两组差异有统计学意义(t=9.93,P=0.00).脑梗死组CT基因型患者外周血MMP-9水平为(113.3±66.6)ng/ml.而CC基因型患者外周血MMP-9水平为(148.6±104.9)ng/ml,两者相比差异无统计学意义(t=1.22,P=0.21).脑梗死组CT+TT基因型频率13.9%,对照组为13.2%,两者比较差异无统计学意义(χ2=0.02,P=0.88),T等位基因频率在脑梗死组为6.9%,对照组为7.5%,两者比较差异也无统计学意义(χ2=0.04,P=0.83).结论 MMP-9基因启动子-1562位点的多态与MMP-9基因表达和脑梗死没有明确的关系.MMP-9基因启动子C-1562T的多态与缺血性脑血管疾病的关系有待进一步研究.     

急性脑梗死内脏脂肪素、基质金属蛋白酶-9动态变化及相关研究

目的研究急性脑梗死患者血清内脏脂肪素(visfatin)与基质金属蛋白酶-9(MMP-9)的动态变化及其相关性,探讨二者在脑梗死发生发展中的作用。方法 157例急性脑梗死患者组(ACI)和70例健康对照组,根据颈动脉彩超将脑梗死组分为无斑块组(NP)43例、稳定斑块组(SP)55例和不稳定斑块组(VP)59例3个亚组。应用双抗体夹心酶联免疫法(ELISA),分别测定对照组和急性脑梗死组发病48 h内、第14天血清visfatin及MMP-9水平,并测定血压、血脂、空腹血糖及体重指数,进行相关分析。结果急性脑梗死患者入院48 h内、第14天血清visfatin及MMP-9水平4组比较差异均有显著性意义(P<0.05)。Visfatin水平与体重指数(r=0.235,P=0.032)和血糖(r=0.351,P=0.026)呈正相关;MMP-9水平与脑梗死体积(r=0.372,P=0.012)、入院NIHSS评分(r=0.243,P=0.010)、血糖(r=0.365,P=0.025)及血压(P<0.05)呈正相关;Visfatin及MMP-9呈正相关(r=0.221,P=0.018)。大梗死灶血清MMP-9明显高于小梗死灶(P<0.05)。结论脑梗死患者血清visfatin与MMP-9水平均升高,二者相互作用,可能在动脉粥样硬化、斑块形成及脑梗死的发生发展中起重要作用。     

急性脑梗死患者血清IL-35、MMP-9与颈动脉粥样硬化斑块稳定性的关系

目的探讨急性脑梗死患者血清白细胞介素-35(IL-35)、基质金属蛋白酶9(MMP-9)与颈动脉粥样硬化斑块稳定性的关系。方法选择急性脑梗死患者89例,应用彩色多普勒超声检查颈动脉斑块,根据颈动脉粥样硬化斑块稳定性分为易损斑块组和稳定斑块组。采用酶联免疫吸附法检测患者血清IL-35、MMP-9水平,并分析IL-35、MMP-9与斑块稳定性的关系。结果颈动脉粥样硬化易损斑块组的患者41例,稳定斑块组的患者48例。易损斑块组血清IL-35水平(17.89±7.21 ng/ml)明显高于稳定斑块组(9.08±3.45 ng/ml)(P<0.05)。MMP-9水平易损斑块组(430.36±72.78 ng/ml)亦显著高于稳定斑块组(305.16±45.63 ng/ml)(P<0.01),差异均有统计学意义。结论脑梗死患者血清IL-35、MMP-9水平可能与颈动脉斑块稳定性有关。     

血清抗apoA-1IgG、MMP-9与急性脑梗死患者颈动脉粥样硬化的相关分析

目的探讨抗载脂蛋白A1抗体(Anti-apolipoprotein A-1 Ig G,抗apo A-1 Ig G)、基质金属蛋白酶9(metalloproteinase-9,MMP-9)与急性脑梗死患者颈动脉粥样硬化的相关性。方法选择急性脑梗死患者120例,采用彩色多普勒超声检测患者颈部血管,观察颈动脉内-中膜厚度(Intima-median thickness,IMT)及斑块性质,并分为4组:IMT正常组(颈动脉正常组)、IMT增厚组、稳定斑块组、不稳定斑块组,其中后3组为颈动脉粥样硬化组。用ELISA方法检测抗apo A-1 Ig G、MMP-9的表达水平。结果颈动脉粥样硬化组的抗apo A-1 Ig G、MMP-9的表达水平明显高于颈动脉正常组(P0.05);4组中由1组到4组的抗apo A-1 Ig G、MMP-9的表达水平依次升高(P0.01);分别以IMT、斑块稳定性为因变量,以动脉粥样硬化相关的危险因素作为自变量做Logistic回归分析,结果示抗apo A-1 Ig G、MMP-9是颈动脉粥样硬化、斑块不稳定的独立危险因素[抗apo A-1 Ig G(μg/ml)OR=23.226,95%CI 4.204~128.305,P0.01,MMP-9(ng/ml)OR=2.287,95%CI 0.890~5.872,P0.05;抗apo A-1 Ig G(μg/ml)OR=3.301,95%CI 1.212~8.991,P0.01,MMP-9(ng/ml)OR=2.345,95%CI 1.129-4.871,P0.05]。抗apo A-1 Ig G、MMP-9血清水平与颈动脉粥样硬化程度呈正相关(抗apo A-1 Ig G:r=0.407,P0.01;MMP-9:r=0.316,P0.01)。结论抗apo A-1 Ig G、MMP-9是脑梗死患者颈动脉粥样硬化的独立危险因素,与脑梗死患者颈动脉粥样硬化程度呈正相关。检测二者的浓度可能成为发现早期动脉粥样硬化的方法。     

老年男性2型糖尿病急性脑梗死患者血清基质金属蛋白酶-2,3,9的动态变化及临床意义

目的研究合并2型糖尿病的老年男性急性脑梗死患者血清基质金属蛋白酶-2(MMP-2)、MMP-3、MMP-9水平的动态变化和临床意义。方法将急性脑梗死患者分为糖尿病脑梗死组和非糖尿病脑梗死组。对照者分为糖尿病对照组和健康对照组。ELISA法检测急性脑梗死后24 h、48 h、3 d、5 d和14 d血清MMP-2,3,9水平。比较两个脑梗死组血清MMP-2,3,9水平,分析急性脑梗死后24 h血清MMP-2,3,9水平与糖化血红蛋白(HbA1c)、空腹血糖(FBG)、甘油三酯(TG)、总胆固醇(CH)、临床神经功能缺损程度评分(CNFDS)及CNFDS的预后总积分的相关性。结果糖尿病脑梗死组血清MMP-2,3,9水平在各时间点均显著高于非糖尿病脑梗死组(均P0.05)。糖尿病脑梗死组血清MMP-2,3,9达峰值的时间均早于非糖尿病脑梗死组。第14 d非糖尿病脑梗死组血清MMP-2,3,9均降至基础水平,而糖尿病脑梗死组血清MMP-2,3,9仍高于基础水平。非糖尿病脑梗死组CNFDS预后总积分显著高于糖尿病脑梗死组(P=0.000)。相关分析显示急性脑梗死后24 h血清MMP-2,3,9水平与HbA1c均成正相关(r=0.132,r=0.205,r=0.352;均P0.05),与CNFDS的预后总积分均成负相关(r=-0.226,r=-0.496,r=-0.571;均P0.05),MMP-2,3,9与CNFDS、FBG、TG、CH均无明显的相关性(均P0.05)。结论 2型糖尿病增加急性脑梗死患者血清MMP-2,3,9的表达,影响神经功能的恢复。     

血清MMP-9和TIMP-1与脑梗死后认知障碍的关系

目的研究血清基质金属蛋白酶-9(Matrix Metalloproteinase-9,MMP-9)和组织金属蛋白酶抑制剂-1(Tissue Inhibitor of Metalloproteinase-1,TIMP-1)水平与脑梗死后认知功能障碍的关系。方法陈旧脑梗死患者根据简易智力状态量表(Mini-Mental State Examination,MMSE)评分分为认知障碍组(小于等于26分)、对照组(大于26分)和健康受试者。通过ELISA法测定血清MMP-9和TIMP-1水平。结果认知障碍组42例,MMSE评分21.50±4.88。对照组81例,MMSE评分28.75±0.96。与健康受试者相比,认知障碍组和对照组患者血清MMP-9及TIMP-1水平均显著升高(P<0.01,P<0.01);与对照组比较,认知障碍组患者血清TIMP-1显著升高(P=0.049),而MMP-9水平无显著差异。Logistic回归显示年龄(OR=1.096,P<0.001,95%CI1.043¹.152)、MMP-9(OR=0.33,P=0.035,95%CI 0.1181.152)、MMP-9(OR=0.33,P=0.035,95%CI 0.118⁰.926)和TIMP-1(OR=4.99,P=0.004,95%CI1.6880.926)和TIMP-1(OR=4.99,P=0.004,95%CI1.688¹4.741)是认知功能障碍的独立危险因素。相关分析显示,MMP-9和TIMP-1水平均与美国国立卫生研究院卒中量表(National Institute of Health Stroke Scale,NIHSS)(r=0.27,P=0.003;r=0.24,P=0.008)和改良Rankin评分(modified Rankin Scale,mRS)(r=0.25,P=0.01;r=0.23,P=0.02)呈正相关。结论陈旧脑梗死患者中存在认知障碍者血清MMP-9水平降低且TIMP-1水平升高,有望成为预测梗死后认知障碍的生化标志物。     

基质金属蛋白酶-12血清水平及启动子区-82A/G多态性与急性动脉粥样硬化性脑梗死的关系

目的 探讨基质金属蛋白酶-12(MMP-12)血清水平及启动子基因- 82A/G多态性与动脉粥样硬化性脑梗死的关系.方法 对608例动脉粥样硬化脑梗死和374名健康体检者进行研究,采用ELISA法测定血清MMP-12蛋白水平,同时采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法分析MMP-12基因启动子区- 82A/G多态性.结果 脑梗死组患者48 h内血清MMP-12为(17.36±9.12) ng/ml,对照组为(17.42±7.70) ng/ml,两组比较差异无统计学意义(t=0.047,P=0.962).脑梗死组AG+ GG基因型频率为7.6％,与对照组的5.9％基因型频率比较差异无统计学意义(x2 =0.281,P=0.584),G等位基因频率在两组间分别为3.8％和2.9％,两组比较差异同样无统计学意义(x2=0.746,P=0.374).结论 MMP-12血清水平及基因启动子- 82位点的多态与MMP-12基因表达和脑梗死没有相关性.     

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.     

Hepatic Considerations in the Use of Antiepileptic Drugs

Summary: Virtually all of the major antiepileptic drugs (AEDs) can cause hepatotoxicity, although fatal hepatic reactions are rare. The mechanisms, incidences, and risk profiles for such reactions differ from drug to drug. With carbamazepine and phenytoin, hepatotoxicity may be due to drug hypersensitivity. Although the profiles of patients at risk have not been well-defined for these two antiepileptic drugs, it would appear from reports in the literature that older adolescents and adults are at higher risk than children of developing serious or fatal hepatotoxicity. Once hepatotoxicity develops, mortality rates are 10–38% with phenytoin and 25% for carbamazepine. The risk profile for valproate fatal hepatotoxicity has been more clearly defined. Those at primary risk of fatal hepatic dysfunction are children under the age of 2 years who are receiving multiple anticonvulsants and also have significant medical problems in addition to severe epilepsy. The risk is considerably lower for patients over the age of 2 years on valproate monotherapy. In contrast to the risk profile with other AEDs, adults receiving valproate as monotherapy have the lowest risk of hepatotoxicity. Fatal hepatic dysfunction coincident with valproate may be the result of aberrant drug metabolism. Concomitant use of AEDs that induce microsomal P450 enzymes (e.g., phenytoin and phenobarbital) may enhance the production of a toxic metabolite, and hence the greater risk of hepatotoxicity with polypharmacy.     

Vascular Malformations and Epilepsy: Clinical Considerations and Basic Mechanisms

Summary: Vascular malformations (VMs) are associated with epilepsy. The natural history of the various VMs, clinical presentation, and tendency to provoke epilepsy determine treatment strategies. Investigations have probed the mechanisms of epileptogenesis associated with these lesions. Electrophysiologic changes are associated with epileptogenic cortex adjacent to VMs. Putative pathophysiologic mechanisms of epileptogenesis include neuronal cell loss, glial proliferation and abnormal glial physiology, altered neurotransmitter levels, free radical formation, and aberrant second messenger physiology.     

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.     

Carbamazepine Efficacy and Utilization in Children

Summary: Carbamazepine is effective for preventing partial and generalized tonic-clonic seizures in children. Although absence epilepsies are more common in children than adults, an estimated 80% of children with epilepsy have seizure types or epilepsies that are potentially responsive to carbamazepine. The differential diagnosis of ictal staring is an especially important issue in children because absence and atypical absence seizures are more prevalent in children than adults. Age-related pharmacokinetic differences and drug interactions are major considerations in children. On average, children have higher clearance rates of carbamazepine, shorter half-lives, and higher ratios of carbamazepine-10, 11-epoxide to carbamazepine than adults. In addition, children with severe epilepsy are more likely to require multiple-drug therapy, which can lead to complex drug interactions. When carbamazepine is administered along with valproate, drug protein binding interactions can cause intermittent side effects.     

Neonatal Seizures: Problems in Diagnosis and Classification

Summary: The clinical identification of neonatal seizures is critical for the recognition of brain dysfunction; however, diagnosis is often difficult because of the poorly organized and varied nature of these behaviors. Current classification systems are limited in their ability to communicate motor, autonomic, and electroencephalo-graphic features of seizures precisely and to provide a basis for uniform effective diagnosis, therapy, and determination of prognosis. Recent investigations of neonates, utilizing bedside electroencephalographic/polygraphic/ video monitoring techniques, have provided the basis for improved diagnosis and classification of seizures in the newborn. These studies have demonstrated that not all clinical phenomena currently considered to be seizures require electrocortical epileptiform activity for their initiation or elaboration. In addition, the specific clinical character of the phenomena considered to be seizures, the clinical state of the infant, and the character of the EEG indicate the probable pathophysiological mechanisms involved and suggest probable etiologies, prognosis, and therapy. Similarities between animal models that demonstrate reflex physiology and neonates with motor automatisms and tonic posturing suggest that these clinical behaviors may not be epileptic in origin but, rather, primitive movements of progression and posture mediated by brainstem mechanisms. Although not all clinical behaviors currently considered to be neonatal seizures may have similar pathophysiological mechanisms, they are clinically significant because they all indicate brain dysfunction.     

Valproate Monotherapy in the Management of Generalized and Partial Seizures

Summary: For decades, therapeutic tradition has promoted the concept of polypharmacy in the management of epilepsy. In recent years, however, studies have shown that, for most patients, monotherapy can provide comparable or better seizure control than administration of multiple anticonvulsants, while diminishing the potential for adverse reactions, drug interactions, and poor compliance. Valproate is an important monotherapeutic agent that is highly effective in the control of idiopathic primary and secondarily generalized epilepsies, and partial seizures that do not generalize. Comparative studies have found that valproate is at least as effective as phenytoin and carbamazepine in the treatment of generalized and partial seizures. Given the similar efficacy, other factors such as pharmacokinetics and side effects may therefore determine anticonvulsant selection for monotherapy.     

Un nouveau cadre conceptuel de travail pour la psychiatrie

In an attempt to place psychiatric thinking and the training of future psychiatrists more centrally into the context of modern biology, the author outlines the beginnings of a new intellectual framework for psychiatry that derives from current biological thinking about the relationship of mind to brain. The purpose of this framework is twofold. First, it is designed to emphasize that the professional requirements for future psychiatrists will demand a greater knowledge of the structure and functioning of the brain than is currently available in most training programs. Second, it is designed to illustrate that the unique domain which psychiatry occupies within academic medicine, the analysis of the interaction between social and biological determinants of behavior, can best be studied by also having a full understanding of the biological components of behavior.