阿尔茨海默病和血管性痴呆的载脂蛋白E基因多态性研究

目的探讨载脂蛋白E(ApoE)基因与中国昆明地区汉族人阿尔茨海默病(AD)和血管性痴呆(VD)是否存在关联。方法运用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析方法对58例无亲缘关系的中国昆明地区AD患者、10例VD患者及96例健康老年人,进行ApoE基因变异检测,并进行统计分析。结果AD组、VD组ApoEε3/ε4基因型频率及ε4等位基因频率高于健康对照组,差异比较有统计学意义(P<0.05)。结论ε4基因可能是AD和VD的危险因素。     

载脂蛋白E基因多态性与Alzheimer病和血管性痴呆的关系

目的 探讨载脂蛋白E(ApoE)基因多态性与Alzheimer病(AD)和血管性痴呆(VD)的关系.方法 用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测79例AD患者(AD组)、85例VD患者(VD组)及156名健康老年人(正常对照组)ApoE基因型和等位基因频率.结果 ApoEε3/ε4基因型及ε4等位基因频率AD组分别为25.3%及17.7%,VD组分别为25.9%及20.5%,正常对照组分别为10.9%及5.7%;AD组及VD组ApoEε3/ε4基因型及ε4等位基因频率显著高于正常对照组(均P＜0.01).结论 ApoEε4等位基因可能是AD和VD共同的危险因素.     

心血管危险因子与迟发性阿尔茨海默病行为和精神症状间的相关性研究

目的研究心血管危险因子载脂蛋白E(ApoE)、载脂蛋白C-Ⅰ(ApoC-Ⅰ)以及低密度脂蛋白受体相关蛋白(LRP)与汉族迟发性阿尔茨海默病(LOAD)发生行为和精神症状(BPSD)之间的相关性。方法应用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)技术或直接通过PCR方法,分析了136例LOAD(伴BPSD者79例,无伴BPSD者57例)及150名健康老年人的ApoE、ApoC-Ⅰ与LRP基因型。结果①与对照组比较,BPSD组ApoEε4等位基因及ε4基因型出现的频率增高(P<0·001),而ApoEε3等位基因出现频率降低(P<0·001),ApoC-ⅠH2等位基因出现的频率增高(P<0·05);无BPSD组亦出现了ApoEε4等位基因及ε4基因型频率的增高(P<0·05)。②在BPSD组和无BPSD组中,前者ApoEε4等位基因及基因型出现的频率高于后者(P<0·05),而其ApoEε3等位基因频率则低于后者(P=0·001);前者ApoC-ⅠH2等位基因出现的频率高于后者(P=0·005),而其ApoC-ⅠH1等位基因频率则低于后者(P=0·005);③LRP各等位基因出现频率在3组间均无显著性差异(P>0·05)。结论ApoEε4及ApoC-ⅠH2等位基因是LOAD出现BPSD的遗传危险因子,ApoEε3及ApoC-ⅠH1等位基因则可能有保护效应;此研究未能证明LRP基因C766T多态性与LOAD出现BPSD有相关关系。     

散发性阿尔茨海默病与ApoE及LRP基因3号外显子C/T多态性的关联分析

目的探讨载脂蛋白E(ApoE)基因与低密度脂蛋白受体相关蛋白(LRP)基因3号外显子C/T多态性在散发性阿尔茨海默病(SAD)发病中的作用。方法应用聚合酶链反应和限制性片段长度多态性方法,检测了56例SAD患者和75例正常老年人的ApoE基因多态性和LRP基因3号外显子C/T多态性,并对SAD与ApoE和LRP各基因型及等位基因进行了关联分析。结果与对照组比较,SAD患者等位基因ε4频率显著升高(x2=11.36,P<0.01),SAD患者与等位基因ε4均呈正关联(OR=3.29,CI1.36～7.95)。SAD患者与LRP等位基因C呈正关联(OR=1.83,P<0.05),与等位基因T呈负关联(OR=0.55,P<0.05)。结论ApoE等位基因ε4和LRP等位基因C可能是SAD发病的危险因素,ApoE和LRP基因多态性与SAD之间有密切相关性。     

载脂蛋白E基因多态性与老年人认知功能相关性研究

目的 研究载脂蛋白E(ApoE)基因多态性与老年人认知功能之间的相关性。方法 采用简易精神状态检查(MMSE)对134例住院患者作认知功能评分,分为MMSE≤23组和MMSE≥24组,做ApoE的基因分型鉴定并进行比较。结果 MMSE≥24组,ApoEε3/ε3型占77.8％,MMSE≤23组,ApoEε3/ε3型占52.1％。ApoEε4/ε3型频率(28.8％)和ApoE ε4等位基因频率(17.6％)均高于MMSE≥24组,两组相比有显著性差异(P<0.01)。在MMSE≤23组中男女患者相比ApoEε4等位基因频率和年龄均无显著性差异(P>0.05),而女性患者在MMSE≤23组中的人数比男性患者多,有显著性差异(P>0. 05)。结论 无痴呆老年人的认知功能与ApoE基因型存在关联性,ApoEε4等位基因是对老年认知功能产生有害影响的因素,可能不是AD所特有的。ApoEε4等位基因频率分布无性别差异。     

阿耳茨海默性痴呆与血管性痴呆的ApoE基因多态性研究

目的探讨ApoE基因在阿耳茨海默性痴呆（Alzheimer-typedementia,AD）与血管性痴呆（Vasculardementia,VD）患者当中的分布情况,以找出中国人的特点,评价ApoE基因检测在早期预测性诊断中的作用,比较AD与VD在ApoE基因多态性方面的异同。方法采用PCR-RFLP方法,对41例AD、35例VD和30例对照进行ApoE基因型测定。结果小于70岁的AD患者,其ε4等位基因频率大大高于同龄VD组患者和同龄对照组（P＜0.01和P＜0.05）。而≥70岁的AD患者ε4频率明显低于70岁以下AD患者（P＜0.01）。结论（1）ApoEε4与散发性AD之间具有明显相关性,其基因型以4/3为主,而ε4/4相对于国外文献报道要少。（2）AD组ε4等位基因频率高于VD组（P＜0.05）。（3）评价AD发病危险时,年龄因素不容忽视,70岁以下ε4携带者可能具有更高的AD发病危险性。     

低密度脂蛋白受体相关蛋白基因两种多态性与阿尔茨海默病的关系

目的　探讨低密度脂蛋白受体相关蛋白 (LRP)基因两种多态性与阿尔茨海默病(Alzheimerdisease,AD)的相关情况。方法　应用分子生物学技术 ,在 42例患者和 40名正常人中观察LRP基因、ApoE基因多态性的分布 ,进行关联分析。结果　AD与LRP基因上游区域 5′端插入序列多态性无关联 ;AD与LRP基因外显子 3多态中的等位基因C正关联 (RR =2 .36 2 ,P <0 .0 5 ) ,与基因型C/C正关联 (RR =2 .710 ,P <0 .0 5 ) ;AD与ApoE基因ε4等位基因正关联 (RR =3.194,P <0 .0 1) ,与ε4/ 3基因型正关联 (RR =3.148,P <0 .0 5 ) ,但与ε4/ 2基因型无关 ;无ApoEε4等位基因的AD与LRPC/C基因型正关联 (RR =6 .842 ,P <0 .0 5 ) ,有ApoEε4等位基因的AD患者与LRPC/C基因型无关联(RR =1.85 7,P >0 .0 5 )。结论　ApoEε4是AD发病的风险因子 ;LRP基因多态性与AD正关联是由于LRP基因C/C型在患者中过表达所致 ;LRP基因C/C型是无ApoEε4的AD患者发病的风险因子。     

蒙古族Alzheimer病患者载脂蛋白E基因多态性研究

目的探讨载脂蛋白E(ApoE)基因多态性与蒙古族Alzheimer病(AD)的关系。方法用聚合酶链反应及基因测序技术检测106例蒙古族AD患者和100名正常对照者的ApoE基因的基因型和等位基因频率,并进行比较。结果 AD组中有ApoEε4基因型频率(31.1%)显著高于正常对照组(17.0%)(χ2=5.591,P=0.018;OR=2.207,95%CI:1.136～4.289);ε4等位基因的频率显著高于正常对照组(χ2=4.27,P=0.039;OR=1.841,95%CI:1.026～3.304);两组ApoEε2、ε3等位基因频率的差异无统计学意义。结论ApoE基因ε4等位基因可能是蒙古族人群患AD的遗传性危险因素。     

8-羟基鸟嘌呤糖苷酶1、载脂蛋白酶E基因多态性与阿尔茨海默病相关性研究

目的 探讨河南汉族人群8-羟基鸟嘌呤糖苷酶1(OGG1)、载脂蛋白酶E(ApoE)基因多态性与阿尔茨海默病的相关性.方法 采用聚合酶链反应(PCR)及基因测序检测126例正常对照组和58例阿尔茨海默病患者OGG1基因第326位Ser/Ser、Ser/Cys、Cys/Cys基因型多态分布及ApoE e2、e3、ε4基因型多态分布.结果 与对照组比较,AD组OGG1基因的3种基因型分布总体差异有统计学意义(x2＝6.337,P＝0.042),G等位基因频率高于健康对照组(χ2＝ 6.447,P＝0.011);AD组ApoE等位基因ε4频率显著升高,呈正关联(χ2＝ 11.722,OR＝2.872,95％CI＝ 1.542 ～5.351,P＝0.001).ApoEε4等位基因不影响OGG1基因型或等位基因的分布频率(P＞0.05).经年龄分层后,AD组OGG1基因分布无差异性(P＞0.05),ApoE基因在大于70岁组分布有差异性(x2＝14.163,P＝0.001).结论 河南汉族人群中,OGG1 G等位基因可能是AD发病的独立于ApoE之外的危险因素,与年龄无相关性;ApoEε4等位基因是散发性AD的主要危险因素,并与年龄有相关性,ε3等位基因是AD的保护因素.     

老年性痴呆患者载脂蛋白E基因多态性与淀粉样β蛋白前体16-17外显子表达的相关性及意义

目的探讨老年性痴呆(AD)患者血清载脂蛋白E(ApoE)基因多态性和淀粉样β蛋白前体16-17(β-APP16-17)外显因子表达相关性及其临床意义。方法选取2018-02—2019-08在郑州市第二人民医院诊治的32例AD患者纳入研究组,随机选取同期门诊或健康体检的老年自愿者32例纳入正常组,均接受聚合酶链反应-限制性片段长度多态性(PCR-RFLP)检测和相对定量竞争RNA扩增聚合酶链反应(RT-PCR)检测,对比分析2组检测结果。结果研究组ApoE基因型频率整体高于正常组(P<0.05);ApoEε4等位基因携带者的β-APP16-17表达水平高于ε2、ε3等位基因,但差异无统计学意义(P>0.05);2组有无ApoEε4等位基因间App16-17水平无显著性差异(P>0.05)。结论ApoEε4基因是AD发生的重要危险因子,其等位基因对患者的β-APP16-17表达影响不明显,但在目前发现的基因片段中,该基因的表达可为下一步的临床诊治提供新方向。     

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.