血管紧张素转换酶基因多态性与高血压合并脑血管病的关系

目的　研究血管紧张素转换酶 (ACE)基因多态性和高血压合并脑血管病的关系。方法　应用PCR方法检测正常对照者 (6 6人 )、高血压 (4 0例 )、高血压脑梗死 (5 4例 )、腔隙性脑梗死 (4 5例 )、高血压合并脑出血 (33例 )患者的ACE基因插入 /缺失 (I/D)多态性 ,同时测定 6例脑梗死患者急性期和恢复期血浆血管紧张素Ⅱ (AngⅡ )水平。结果　高血压患者的ACE基因型及等位基因频率和正常对照组及高血压合并不同脑血管病患者比较无显著差异 (P >0 0 5 ) ,高血压合并不同脑血管病患者的ACE基因型及等位基因频率和正常对照组比较无显著差异 ,但高血压合并脑出血组的ACE基因型及等位基因频率较其他组高 ;脑梗死患者急性期血浆AngⅡ水平显著高于恢复期 (P <0 0 5 )。结论　高血压合并脑出血的发病可能与ACE基因I/D多态性有关 ,血浆AngⅡ水平升高可能是脑梗死患者急性期血压升高的因素之一     

高血压性脑出血与血管紧张素转换酶基因多态性及血清水平关系的研究

目的：探讨原发性高血压（EH）,高血压性脑出血（CH）与血管紧张素转换酶（ACE）基因I／D多态性及血清ACE水平的相互关系。方法：对正常人（NC组）29例,EH组28例和CH组31例提取白细胞DNA,检测ACE基因型,等位基因和血清水平。结果：88例中不同ACE基因型血清ACE水平有显著性差异（DD＞ID＞II,P＜0．01）,EH组DD基因及D基因频率与NC组比较无显著性差异（P＜0．05）,CH组血清ACE水平和D基因频率显著高于NC组及EH组（P＜0．01）,其DD型的血清ACE水平也高于后二者（P＜0．05）,结论：ACE基因多态性及其血清水平与EH无关,而与CH呈正相关,D基因可能为高血压病患者脑出血发病的相对危险因素。     

血管紧张素转换酶基因插入/缺失多态性与原发性高血压合并缺血性脑卒中关系的Meta分析

目的研究血管紧张素转换酶(ACE)基因插入/缺失(I/D)多态性与原发性高血压(EH)合并缺血性脑卒中(IS)(EH+IS)的关系。方法检索1997年1月～2010年10月4个中国著名科技期刊全文数据库和Medline中收录的有关ACE基因I/D多态性与EH+IS的病例对照研究的文献,按纳入、排除标准选择文献,并采用RevMan 5.0软件进行Meta分析。结果共纳入12项病例对照研究,其中EH+IS患者1068例,EH患者1225例。Meta分析结果表明,EH人群携带D等位基因和DD基因型者发生IS的危险性分别明显高于I等位基因和非DD基因型者,合并OR分别为1.50(95%CI:1.33～1.70)和1.83(95%CI:1.32～2.55);而携带II基因型者发生IS危险性要低于非II基因型者,合并OR为0.63(95%CI:0.53～0.76)。结论 ACE基因I/D多态性与EH人群IS的发病有密切关系,D等位基因和DD基因型是IS的危险因素。     

血管紧张素转换酶基因多态性与白族脑血管病患者的相关性研究

目的研究血管紧张素转换酶(ACE)基因插入/缺失多态性与云南大理白族脑血管病患者的相关性。方法应用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)技术,对73例白族脑血管病(ICVD)组患者(其中脑梗死40例,脑出血33例)和43例性别年龄相匹配的白族健康对照组进行ACE基因型检测和基因插入/缺失多态性分析;并进行ACE基因双向测序。结果(1)脑梗死组的DD基因型频率和D等位基因频率明显高于对照组(P<0.05);(2)脑出血组与对照组相比较,未发现DD基因型频率和D等位基因频率有明显差异(P>0.05);(3)脑血管组内伴高血压与不伴高血压,伴糖尿病与不伴糖尿病,伴血脂异常与血脂正常者相比较,未发现DD基因型频率和D等位基因频率有显著差异(P>0.05);(4)D等位基因和I等位基因其核苷酸序列和长度与国内外文献报道无明显差别。结论(1)ACE基因插入/缺失多态性与脑梗死的发生有关联性,DD基因型和D等位基因是脑梗死患者的高危因素;(2)ACE基因插入/缺失多态性与脑出血发生未发现有关联性;(3)脑血管病的其他相关危险因素如高血压,糖尿病,血脂与ACE基因多态性可能无关联;(4)ACE基因16内含子...     

血管紧张素转换酶基因定量性状位点多态性与脑血管病的关系研究

目的:研究血管紧张素转换酶(ACE)基因定量性状位点:16内含子插入/缺失(I/D)和3’非翻译区4656(CT)23多态性与高血压、脑血管病的关系。方法:对54例动脉粥样硬化性血栓性脑梗塞(ACI)、45例腔隙性脑梗塞、33例脑出血、40例高血压患者及66例正常对照者以多聚酶链反应-扩增片段长度多态性(PCR-AFLP)方法分析ACE基因I/D多态性、以多聚酶链反应-变性梯度凝胶电泳(PCR-DGGE)方法检测4656(CT)23多态性。结果:各受试组之间比较,仅ACI患者ACE基因I/D等位基因频率(0.546/0.454)分布与对照人群(0.674/0.326)显著不同(X2=4.114,P<0.05),而高血压、脑出血及腔隙性脑梗死患者与对照人群无显著差别;D等位基因决定高水平血AT-Ⅱ。本受试人群中未发现3'非翻泽区4656(CT)23多态现象。结论:ACE D等位基因并非高血压的危险因素,而是ACI发病的遗传性危险因素;中国人3’非翻译区可能无4656(CT)23多态性。     

高原地区藏族ACE基因I/D多态性与脑出血的关系研究

目的探讨血管紧张素转化酶(ACE)基因插入/缺失(I/D)多态性与高原地区世居藏族脑出血的相关性。方法收集青海地区高原世居藏族脑出血患者52例(男27例,女25例)为病例组,与之年龄、性别、居住地相匹配的同期体检的世居健康藏族51例(男28例,女23例)为对照组,收集一般资料。利用聚合酶链式反应(PCR)检测所有样本的ACE基因I/D多态性。结果病例组ACE基因型:DD型9例(17.31%),II型21例(40.38%),ID型22例(42.31%);等位基因频率:D等位基因38.46%,I等位基因61.54%;对照组ACE基因型:DD型10例(19.61%),II型19例(37.26%),ID型22例(43.13%);等位基因频率:D等位基因41.18%,I等位基因58.82%。两组间基因型、等位基因比较无显著性差异(基因型χ~2为0.14,等位基因χ~2为0.16,P0.05)。结论ACE基因I/D多态性与青海高原地区藏族脑出血无相关性,ACE基因I/D多态性可能不是高原世居藏族人群脑出血的遗传易感因素。     

血管紧张素转换酶基因多态性与中国人Binswanger病的关系

目的 探讨血管紧张素转换酶（ACE）基因多态性与中国人汉族Binswanger病（BD）及其危险因素的关系。方法 应用聚合酶链反应技术（PCR）测定111例中国汉族BD、98例高血压病患者和102名正常对照者ACE基因插入／缺失（I／D）多态性,用比色法测定血清ACE水平,调查BD孤危险因素及家族史。结果 BD组DD型基因频率为0．64,高于高血压病组的0．31（P＜0．01）和正常对照组的0．17（P＜0．01）,且D等位基因亦明显高于高血压病组和正常对照组（P＜0．01）。BD组中MRI所见轻（I）、中（Ⅱ）、重（Ⅲ）三度的DD型基因频率和D等位基因亦高于对照组（P＜0．01）。BD组血清ACE水平明显高于正常对照组（P＜0．01）。其中DD基因型血清ACE水平又高于同组DI基因和II基因（P＜0．01）。ACE基因型分布与BD患者的年龄、性别、体重指数、收缩压、舒张压、总胆固醇、甘油三脂等差异无显著性意义。结论 ACE基因缺失多态性可能是中国人汉族BD独立危险因素,循环ACE活性与基因缺失多态性相关。     

血管紧张素转换酶基因多态性与高血压腔隙性脑梗死关联性的研究

目的 研究血管紧张素转换酶（ACE）基因插入／缺失（I／D）多态性与高血压腔隙性脑梗死的关系。方法 （1）应用聚合酶链反应（PCR）方法扩增50例正常人、49例高血压无并发症患、30例高血压腔隙性脑梗死患的ACE基因上287Bp片段，根据插入（I）或／缺失（D）来判断其多态性。（2）用CT或MRI诊断腔隙性脑梗死。结果 （1）腔隙性脑梗死组与健康对照组相比，其D等位基因及DD基因型显升高。微量蛋白尿组与健康对照组相比，其D等位基因及DD基因型显升高。（2）腔隙性脑梗死组与高血压无并发症组相比，其D等位基因及DD基因型显升高。（3）高血压无并发症组与健康对照组相比，ACE基因型和等位基因频率无显性差异。结论 ACE基因多态性与高血压腔隙性脑梗死患有关联性，DD基因型提示可能与高血压腔隙性脑梗死有关。     

血管紧张素转换酶基因DD基因型与脑出血的相关性研究

目的探讨血管紧张素转换酶(ACE)基因多态性分布与高血压脑出血发病的关系。方法应用聚合酶链反应方法检测200名健康人(NT)及80例高血压合并脑出血患者ACE I/D基因多态性。结果脑出血患者的DD基因型及D等位基因频率和正常对照组比较差异有显著意义(P＜0．05)。结论ACE基因DD基因型和D等位基因携带者可能是高血压合并脑出血的易感因素。     

血管紧张素原、血管紧张素转换酶基因多态性 与脑卒中相关性研究

目的　探讨血管紧张素原基因 (AGT)的M2 35T基因多态性、血管紧张素转换酶 (ACE)基因的插入 (I) /缺失 (D)多态性与中国汉族人脑卒中发病的相关性。方法　采用PCR法和PCR RFLR法检测 10 0例脑卒中患者 (脑梗死患者 72例 ,脑出血患者 2 8例 )以及 10 0例正常人ACE(I/D)和AGT(M2 35T)的基因多态性。结果　在脑卒中患者中ACE的纯合插入 (I)基因型和I等位基因频率增加 (x2 =4 17,P =0 0 4 1) ,AGT基因的 2 35TT基因型和T等位基因频率明显增加 (x2 =2 6 79,P <0 0 0 1)。结论　同期监测AGT及ACE基因多态性是一项对急性脑血管病风险因素分子水平的检测方法 ,这对筛选脑卒中高危人群并早期采取干预对策 ,防治脑卒中有一定意义。     

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.     

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.     

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.     

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.     

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.     

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.