脑血管病患者血浆同型半胱氨酸水平及MTHFR基因多态性分析

目的探讨血浆同型半胱氨酸(homocysteine Hcy)水平与脑血管病的关系及其水平升高的遗传和营养因素.方法对130例脑梗死和77例脑出血患者及65例正常对照者采用高效液相色谱(HPLC)法检测血浆Hcy水平、放射免疫法测定叶酸、VitB12水平,运用多聚酶链反应-限制性内切酶片段长度多态性技术(PCR-RFLP)分析亚甲基四氢叶酸还原酶(methylenetetrahydrofolate reductase MTHFR)基因多态性,并加以对照分析.结果脑梗死组、脑出血组血浆Hcy水平分别为19.87±11.67 μmol/L、20.15±10.12 μmol/L,均显著高于对照组11.41±3.28 μmol/L(P<0.01);而脑梗死组与脑出血组间无显著差异(P>0.05).MTHFR有三种基因型,脑梗死组、脑出血组和对照组C/C型基因频率分别为0.39、0.46、0.53,C/T型分别为0.35、0.31、0.30,T/T型分别为0.26、0.23、0.17,T等位基因频率分别为0.43、0.39、0.32,各基因型及等位基因频率无显著差异(P>0.05).各组中T/T基因型血浆Hcy水平与C/C型比较差异有显著性(P<0.01),而病例组中C/T型血浆Hcy水平与C/C型相比亦有显著差异(P<0.01).脑梗死组与脑出血组叶酸、VitB12水平显著低于正常对照组(P<0.01).结论血浆Hcy水平升高是脑血管病的主要危险因素.MTHFR基因677位点碱基C→T突变可能是血浆Hcy水平升高的主要影响因素,但与脑血管病的直接关系有待进一步研究,而叶酸 VitB12与Hcy水平也有关联.     

血浆同型半胱氨酸水平及MTHFR基因多态性与中青年脑卒中的相关研究

目的探讨中青年脑卒中与血浆同型半胱氨酸(homocysteine Hcy)水平及亚甲基四氢叶酸还原酶(methylenetetrahydrofolate reductase MTHFR)基因多态性的关系.方法利用多聚酶链反应-限制性内切酶片段长度多态性技术(PCR-PFLP)分析73例中青年脑卒中患者及134例老年脑卒中患者与27例中青年及38例老年正常对照人群MTHFR基因突变情况,并应用高效液相色谱(HPLC)法检测其血浆Hcy水平、放射免疫法测定叶酸、VitB2水平加以对照分析.结果中青年脑卒中组血浆Hcy水平(22.36±10.99μmol/L)及老年脑卒中组血浆Hcy水平(19.41±10.32μmol/L)均高于各自对照组(11.49±5.05μmol/L)及(12.26±5.24μmol/L),差异有显著性(P＜0.01),且中青年脑卒中组中血浆Hcy升高的比例(58%)显著高于老年脑卒中组(43%)(x2=4.69,P＜0.05).MTHFR有三种基因型,中青年脑卒中组及对照组C/C型C/T型T/T型分别为(0.25、0.44、0.31)及(0.52、0.32、0.16),两组相比差异有显著性(x2=8.51,P＜0.05);而老年脑卒中组及对照组分别为(0.35、0.46、0.19)及(0.52、0.32、0.16),两组相比无显著差异(x2=3.96,P＞0.05).各组MTHFR的T/T基因型血浆Hcy水平与C/C型比较有显著差异(P＜0.01),两脑卒中组MTHFR的C/T基因型血浆Hcy水平与C/C型比较也有显著差异(P＜0.05),且叶酸VitB12水平较各自对照组显著下降(P＜0.01),老年脑卒中组较中青年组叶酸水平降低更显著(P＜0.05).结论血浆Hcy水平升高是脑血管病的重要危险因索,MTHFR基因突变及叶酸VitB12变化均是血浆Hcy升高的重要影响因素,对于中青年患者意义更大.     

脑血栓形成与亚甲基四氢叶酸还原酶基因多态性的关系

目的　探讨中国汉族人群脑血栓形成与亚甲基四氢叶酸还原酶 (MTHFR)基因多态性及血浆同型半胱氨酸 (Hcy)水平的关系。 方法　利用聚合酶链反应 限制性内切酶长度多态性 (PCR RFLP)方法分析脑血栓形成患者 (75例 )与健康人群 (62名 )的MTHFR基因突变的情况。采用高效液相色谱法测定血浆Hcy水平 ,并加以对照分析。 结果　脑血栓形成组与对照组MTHFR基因型频率CC、CT、TT型分别为 0 41、0 35、0 2 4及 0 58、0 2 3、0 1 9,两组相比差异无显著意义 (P =0 1 37)。患者组与对照组MTHFR的T等位基因频率分别为 0 41和 0 31 ,两组相比差异无显著意义 (P =0 0 67)。脑血栓形成组与对照组血浆Hcy水平分别为 (1 8 3± 7 2 ) μmol/L与 (1 3 6± 5 8)μmol/L ,二者比较差异有显著意义 (P <0 0 0 1 )。两组中MTHFR基因TT型者Hcy水平与CC型比较差异有显著意义 (P <0 0 5) ,Hcy水平与叶酸呈负相关 (患者组 :r =- 0 31 ,P <0 0 1 ;对照组 :r =- 0 2 8,P <0 0 5)。结论　血浆Hcy水平升高是脑血栓形成的危险因素之一 ,MTHFR基因突变可能是血浆Hcy升高的主要影响因素     

抑郁症患者MTHFR基因多态性的研究

目的:探讨抑郁症患者5,10-亚甲基四氢叶酸还原酶(MTHFR)基因多态性与抑郁症发病的相关性。方法:将94例抑郁症患者作为研究组,选98名身心健康正常人为对照组,用荧光偏振免疫法检测血清同型半胱氨酸水平,运用聚合酶链反应-限制性内切酶片段长度多态性分析技术(PCR-RFLP)检测MTHFR基因C677T多态性。入组时对患者组进行汉密尔顿抑郁量表(HAMD)评定。结果:研究组患者血清同型半胱氨酸水平显著高于对照组[(16.72±3.94)μmol/L,(10.99±3.51)μmol/L;P<0.05],研究组高同型半胱氨酸血症发生率显著高于对照组[(41.5%,14.3%)(χ2=14.89,P<0.05)]。患者组与对照组基因型频率和等位基因频率分布差异有统计学意义(P<0.05)。患者组和对照组TT基因型血清同型半胱氨酸浓度均较CT型、CC型高,且患者组TT基因型HAMD评分也比后两者高(P<0.05)。结论:TT基因型可能是抑郁症发病的重要危险因素之一,它可能是通过影响血清同型半胱氨酸水平而影响抑郁症的严重程度。     

2型糖尿病合并脑梗死患者MTHFR C677T基因多态性及血清Hcy水平的相关性研究

目的探讨MTHFR C677T基因多态性、同型半胱氨酸(Hcy)水平对2型糖尿病患者发生脑梗死的影响。方法采用病例-对照研究。随机选取422例研究对象,分为正常对照组(n=111)、脑梗死组(n=155)、2型糖尿病合并脑梗死组(n=156)。PCR-芯片法测定MTHFR基因型,循环酶法检测血清Hcy水平。运用SPSS25.0软件比较各组间MTHFR基因型分布情况及不同基因型患者的Hcy水平。结果各实验组和正常对照组相比,MTHFR基因型分布、等位基因T频率差异均具有统计学意义(x~2=7.023～7.52,P0.05;x~2=3.875～6.262,P0.05)。糖尿病合并脑梗死组和脑梗死组相比,MTHFR基因型分布差异无统计学意义(x~2=1.761,P=0.415),但Hcy水平差异有统计学意义(P0.001)。其中糖尿病合并脑梗死组TT型患者血浆Hcy水平显著低于脑梗死组(P0.001)。结论 MTHFR基因多态性可能为脑梗死的危险因素。TT型糖尿病合并脑梗死患者相对于该基因型单纯脑梗死患者Hcy水平更低。     

血浆同型半胱氨酸及其酶基因多态性与老年脑梗死的关系

目的探讨血浆同型半胱氨酸(Hcy)及其代谢酶N~(5,10-)亚甲基四氢叶酸还原酶(MTHFR)和胱硫醚β合成酶(CBS)基因多态性与老年脑梗死的关系。方法应用高效液相色谱荧光法、聚合酶链限制性内切酶片段长度多态性分析和扩增阻滞突变体系法对61例首次发病的老年脑梗死患者和57例对照者血浆Hcy浓度、MTHFR及CBS基因型进行检测。结果脑梗死组血浆Hcy浓度[(13·07±3·96)μmol/L]显著高于对照组[(11·51±3·90)μmol/L](P<0·05);两组间基因型分布、纯合子频率和等位基因频率无差异;血浆Hcy浓度在MTHFR C677T、CBS G919A、CBS T833C各突变位点的纯合子、杂合子和野生型间差异无显著性;Logistic多元回归及相关分析表明血浆Hcy浓度升高是脑梗死的独立危险因素。结论老年患者MTHFR和CBS基因突变不产生高Hcy血症;血浆Hcy浓度升高是老年脑梗死的独立危险因素;单纯MTHFR和CBS突变不能被确定为老年脑梗死的独立遗传危险因素。     

血浆同型半胱氨酸水平及其代谢酶N5,N10亚甲基四氢叶酸脱氢还原酶基因多态性与Binswanger病的关系

目的探讨血浆同型半胱氨酸(Hcy)水平及其相关代谢酶N5,N10亚甲基四氢叶酸脱氢还原酶(MTHFR)基因多态性与Binswanger病(BD)的关系。方法应用荧光极化免疫法测定77例BD患者和71名健康体检者(健康对照组)的血浆Hcy水平,采用多聚酶链反应限制性片段长度多态性检测MTHFR基因C677T多态性。结果BD组患者血浆Hcy水平为(19.83±2.23)μmol/L,显著高于健康对照组的(13.03±3.79)μmol/L(P<0·01)。BD组和健康对照组间MTHFR各基因型分布和等位基因频率比较差异无显著性(均P>0·05)。各基因型之间血浆Hcy含量差异亦无显著性(均P>0·05)。结论BD患者血浆Hcy水平明显高于健康人,高Hcy血症可能参与了BD的发病过程;而MTHFR基因多态性与BD可能无明显关系。     

亚甲基四氢叶酸还原酶(MTHFR)C677T基因多态性与血管性认知功能障碍相关性的研究

目的 探讨亚甲基四氢叶酸还原酶(MTHFR) C677T突变基因与血管性认知功能障碍(VCI)的关系.方法 采用酶联免疫法测定血浆同型半胱氨酸(Hcy)浓度,应用聚合酶链反应-限制性内切酶片段长度多态性技术检测143例VCI患者、122例无认知损害脑梗死患者及140例正常对照的MTHFR C677T基因型.结果 (1)VCI组、脑梗死组和对照组的血浆同型半胱氨酸(Hcy)平均水平分别为(12.257±3.595) μmol/L、(11.028 ±3.198)μmol/L、(9.784±3.074) μmol/L,两病例组Hcy水平明显高于正常对照组(P＜0.05);(2)3组研究对象的TT基因型分布有明显差异(x2=19.464,P＜0.01),CT型及CC型分布无差异(P＞0.05);VCI组及脑梗死组的T等位基因发生频率明显高于正常对照组(P＜0.05),相对危险度分别为1.79和1.47;(3)VCI组、脑梗死组及正常对照组中,MTHFR基因有C677T突变者(尤其TT型者)血浆Hcy水平均显著高于无基因突变者.结论 血浆Hcy水平升高是VCI和脑梗死共同的致病基础;MTHFR C677T基因突变致血浆Hcy水平升高可能是VCI发病的重要遗传因素.     

脑动脉狭窄与同型半胱氨酸和MTHFR基因多态性的关系

目的探讨血浆同型半胱氨酸(Hcy)和5,10-亚甲基四氢叶酸还原酶(MTHFR)两个常见突变位点与脑动脉狭窄的关系。方法选择年龄、性别匹配的病例组80例,对照组55例,采用荧光偏振免疫法(FPIA)测定血浆Hcy水平,聚合酶链反应-限制片段长度多态性(PCR-RFLP)技术进行基因分型。结果病例组和对照组血浆Hcy水平分别为17.18μmol/L和12.54μmol/L,差别显著(P<0.05)。血浆Hcy水平与血管狭窄数目无关。两组MTHFR677TT及T等位基因频率差异均显著(P<0.05),1298AC/CC及C等位基因频率、677CT/1298AC频率均无显著差异。各组内677TT Hcy水平显著高于677CT或677CC型,A1298C突变对Hcy水平无明显影响。结论677TT突变可引起血浆Hcy水平显著升高,与脑动脉狭窄密切相关。A1298C突变对血浆Hcy水平及脑动脉狭窄无显著影响。     

亚甲基四氢叶酸还原酶基因多态性与脑梗死的关系

目的 再一次探讨亚甲基四氢叶酸还原酶(MTHFR)基因多态性及血浆同型半胱氨酸(Hcy) 与脑梗死的相关性.方法 采用聚合酶链反应-限制性内切酶长度多态性(PCR-RFLP)方法分析脑梗死病人(260例)与健康人群(242例)的MTHFR基因突变的情况.利用高效液相色谱法测定血浆Hcy水平,并加以对照分析.结果 脑梗死组与对照组MTHFR基因型比较无统计学意义(P=0.140).2组MTHFR的T等位基因频率相比亦无统计学意义(P=0.061).2组Hcy水平比较差异有统计学意义(P＜0.001),Hcy水平与叶酸呈负相关.结论 进一步证实血浆Hcy水平升高是脑梗死的独立危险因素,MTHFR基因突变可能是Hcy升高的主要影响因素.     

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.