血浆同型半胱氨酸与脑梗死及颈动脉粥样硬化相关性的研究

目的探讨同型半胱氨酸水平与脑梗死、颈动脉粥样硬化的关系。方法将508例分为脑梗死组368例和对照组140例,测定血浆同型半胱氨酸水平与糖尿病、高血压、年龄、性别、血脂等各指标间的关系;同时做颈动脉彩色多普勒超声检查,比较脑梗死组与对照组、颈动脉硬化组与颈动脉正常组同型半胱氨酸水平变化。结果脑梗死组与对照组血浆同型半胱氨酸水平升高分别为309例和23例,各占84.2%和16.4%,同型半胱氨酸水平分别为(25.33±5.66)umol/L和(12.52±3.16)umol/L,两组比较有统计学意义(P<0.001)。脑梗死组中伴颈动脉粥样硬化的患者血浆同型半胱氨酸水平明显高于颈动脉正常者(P<0.001)。结论高同型半胱氨酸血症是脑梗死独立的危险因素,与颈动脉粥样硬化及斑块形成有关。     

高同型半胱氨酸血症在脑梗死氧化应激和炎症损伤机制中的作用

目的 探讨高同型半胱氨酸血症(Hhcy)在脑梗死发病机制中的作用.方法 选取急性脑梗死患者,根据血浆总同型半胱氨酸(tHcy)水平,将其分为Hhcy组和非Hhcy(Nhhcy)组,除外脑血管疾病和肝肾甲状腺疾病患者40例作为对照.分别测血浆tHcy、血清丙二醛(MDA)、白细胞介素-8(IL-8)水平,并研究其相关性.结果 病例组tHcy(μmol/L,下同)、MDA(nmol/L,下同)、IL-8(ng/ml,下同)水平分别为19.97、4.41±0.84、0.23±0.08,显著高于对照组的9.83、3.24±0.64、0.12±0.08,t值分别为8.139,8.021,7.767(均P＜0.01);病例组中Hhcy患者的tHcy、MDA、IL-8水平分别为24.40、4.70±0.76、0.25±0.07,显著高于Nhhcy患者的10.33、3.76±0.61、0.16±0.06,t值分别为13.213,6.543,6.520(P＜0.01).tHcy水平与MDA、IL-8水平具有相关性(P＜0.01).结论 Hhcy在脑梗死发病机制中的作用可能与其参与氧化应激反应和炎症损伤过程有关.     

高同型半胱氨酸血症及相关因子与脑梗死相关性的研究

目的 :研究高同型半胱氨酸血症及N5N10 亚甲基四氢叶酸还原酶 (methylenetetrahydrofolatereductase ,MTHFR)基因、叶酸和维生素B12 与脑梗死的关系。方法 :PCR RFLP技术检测 5 4例脑梗死患者及 3 0例对照的MTHFR基因型 ;高效液相色谱法测定空腹及蛋氨酸负荷后血浆tHcy水平 ;化学发光法测定血清叶酸和维生素B12 浓度。结果 :患者组中MTHFR基因T/T型及T等位基因频率、空腹及负荷后tHcy水平显著高于对照组 ;而血清叶酸和维生素B12 水平低于对照组。结论 :MTHFR基于突变、高同型半胱氨酸血症及叶酸、维生素B12 缺乏与脑卒中发病有关。     

胱硫醚β合酶基因突变及负荷后同型半胱氨酸水平与青年脑梗死

目的　研究胱硫醚β合酶(CBS)基因T833C突变对蛋氨酸负荷试验(MLT)后血浆同型半胱氨酸(Hcy)水平的影响及其对青年脑梗死的致病作用。方法　采用高压液相色谱法测定血浆空腹同型半胱氨酸(Fhcy)及负荷后同型半胱氨酸(Phcy)水平,选取Fhcy水平正常的75例青年脑梗死患者和52例正常对照者。利用扩增阻滞突变体系法检测CBST833C基因型。结果　病例组Phcy水平和负荷前后Hcy水平的差值均高于对照组;病例组和其负荷后高同型半胱氨酸血症(PHhcy)组CBS基因C/C、C/T型和C等位基因频率分别高于对照组和病例组负荷后非高同型半胱氨酸血症(NPHhcy)组;病例组、对照组和PHhcy青年脑梗死患者组CBSC/C型者Phcy水平依次高于C/T型和T/T型者;NPHhcy青年脑梗死患者CBSC/C型者Phcy水平高于T/T型者,C/T型显著高于T/T型者。结论　CBST833C基因突变可能是Phcy水平异常升高的遗传原因,并间接导致青年脑梗死发生的重要遗传危险因素。     

血浆同型半胱氨酸与脑梗死的临床观察

目的观察脑梗死病人血浆同型半胱氨酸与脑梗死的关系及其临床意义.方法 79例急性脑梗死患者和同期39例对照者采用荧光偏振免疫分析法测定空腹血浆同型半胱氨酸,采用化学发光法测定叶酸和维生素B12.结果血浆同型半胱氨酸(Hcy)>15 μmol/L者,脑梗死组为57例,占71.25%.对照组为5例,占12.5%.两组平均t-Hcy分别为22.40±11.23 μmol/L和11.89±2.50 μmol/L,差异有极显著性(χ2＝36.87,P<0.01).叶酸水平两组分别为4.73±1.83 ng/mL与(6.77±4.29)ng/mL,(t＝3.62, P<0.01);维生素B12水平两组分别为5.59±0.73 pg/mL与5.96±0.56 pg/mL,(t＝2.78, P<0.01);差异均有极显著性.结论脑梗死病人血浆同型半胱氨酸水平是升高的,而叶酸和维生素B12水平呈下降.     

高同型半胱氨酸血症致脑梗死病例特点研究

目的探讨高同型半胱氨酸血症脑梗死患者病例特点,为进一步对脑梗死的综合干预提供依据。方法对90例脑梗死患者根据血浆同型半胱氨酸水平分为高同型半胱氨酸血症脑梗死组(Hhcy脑梗死组)60例及同型半胱氨酸正常脑梗死组(nHcy脑梗死组)30例,将其临床特点、血脂水平、血浆纤维蛋白原水平及影像学特点进行回顾性分析。结果 Hhcy脑梗死组患者中男性、吸烟及饮酒者均多于nhcy脑梗死组,血浆Hcy及低密度脂蛋白(LDL-C)水平高于nhcy脑梗死组,并且均有统计学差异(P<0.05)。相关性分析显示Hcy水平与性别相关(r=0.257,P=0.015)。Hhcy脑梗死组病情进展患者比例、复发性脑梗死患者比例、病灶多发者比例均高于nhcy脑梗死组(P<0.05);两组神经功能缺损程度、梗死面积无差别。结论高同型半胱氨酸血症脑梗死发病以男性多见,临床上病情容易进展,脑血管事件再发风险高,影像学上以多发梗死病灶多见。血浆同型半胱氨酸增高对于神经功能缺损程度、脑梗死面积无明显影响。     

蛋氨酸负荷试验在糖尿病周围神经病变中的临床意义

目的评估蛋氨酸负荷试验(MLT)与糖尿病周围神经病变的关系。方法选空腹血浆同型半胱氨酸(Fhcy)水平在正常范围(≤15 mmol/L)内的103例2型糖尿病患者,分为糖尿病周围神经病变(DPN )组和无糖尿病神经病变(DPN-)组,另50例健康体检者作为对照(CON)组,于MLT后行Hcy(Phcy)测定,按体重0.1g/kg口服蛋氨酸,并测取服药前后4 h血同型半胱氨酸(Hcy)及糖化血红蛋白(HbAlc)、甘油三酯(TG)、胆固醇(TC)等水平。结果Phcy水平DPN 组[(37.3±1.3)mmol/L]明显高于DPN-组[(25.0±1.2)mmol/L]及CON组[(9.8±1.4)mmol/L,P<0.01];餐后2 h血糖(PPG)、TG水平均DPN 组高于DPN-组及CON组,差异有统计学意义(P<0.05),而叶酸(FA)、维生素B12(Vit B12)水平则DPN 组低于DPN-组及CON组(P<0.01)。结论高Hcy(Hhcy)及低FA、VitB12水平与2型DM患者伴发周围神经病变相关,在DPN 组患者中进行MLT检查有助于Hhcy血症及早发现。     

高同型半胱氨酸血症与脑梗死复发的关系

目的探讨高同型半胱氨酸血症(Hhcy)与脑梗死复发的关系。方法按血浆同型半胱氨酸(Hcy)水平,将139例急性脑梗死患者分为Hhcy组(42例,血Hcy≥15μmol/L)和非Hhcy(NHhcy)组(97例,血Hcy<15μmol/L)。给予入组者抗血小板治疗,以及控制已知的脑血管病危险因素等治疗;随访5年,观察两组脑梗死复发率及死亡率,分析影响脑梗死复发的危险因素。结果 Hhcy组脑梗死复发率(38.1%)和死亡率(19.0%)明显高于NHhcy组(15.5%,6.1%)(P<0.05～0.01)。Logistic回归分析显示,脑梗死复发与Hhcy(OR=1.110,95%CI:1.051～1.171,P<0.01)及糖尿病(OR=4.816,95%CI:1.693～13.697,P<0.01)有关。结论 Hhcy是脑梗死复发的独立危险因素之一。     

高同型半胱氨酸血症对急性脑梗死近期预后的影响

目的:探讨高同型半胱氨酸血症(Hhcy)对急性脑梗死近期预后的影响,以期为脑梗死干预治疗奠定理论基础。方法:测定121例急性脑梗死患者和52例健康对照者空腹血浆总同型半胱氨酸,以此结果将患者分为Hhcy组和非Hhcy组,对两组患者神经功能缺损和日常生活能力进行追踪观察。结果:Hhcy和非Hhcy组患者发病3天内神经功能缺损和发病第7、14天神经功能缺损和日常生活能力评分无显著差异(P>0.05);发病第30、90、180天,Hhcy组神经功能缺损评分显著高于非Hhcy组,而日常生活能力评分显著低于非Hhcy组(P<0.05)。结论:Hhcy不利于急性脑梗死患者近期康复。     

胱硫醚β合酶基因突变对中青年缺血性卒中/TIA再发影响的随访研究

目的 研究胱硫醚β合酶(CBS)基因T833C突变对中青年缺血性卒中/TIA再发的影响.方法 对中青年缺血性卒中/TIA患者,采用高压液相色谱法测定血浆总同型半胱氨酸(tHcy)水平,采用扩增阻滞突变体系法(PCR-ARMS)技术检测CBS T833C基因型,跟踪观察5年内中青年缺血性卒中/TIA的后发事件.结果 再发组CBS基因C/C、C/T型和C等位基因频率分别高于非再发组(P<0.05),两组不同基因型血浆tHcy水平比较,再发组中C/C型分别高于C/T和T/T型,C/T高于T/T型(P<0.01);非再发组中C/C和C/T型分别高于T/T型(P<0.01);相同C/T型血浆tHcy水平比较,再发组高于非再发组(P<0.01).结论 CBS T833C基因突变可能是引起高同型半胱氨酸血症(Hhcy)间接导致中青年缺血性卒中/TIA患者再发的重要遗传危险因素.     

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.     

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.     

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.     

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.     

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.     

Special Pharmacokinetic Considerations in Children

Summary: Pediatric patients have greater degrees of pharmacokinetic variability and unpredictability than adults. This variability results from the effects of pharmacogenetics, age and growth, prior and current comedication, and disease. Newborns with seizures have the least predictable dosage requirements, and their needs change as drug-eliminating mechanisms mature in the neonatal period. Infants have the highest relative capacities to eliminate antiepileptics of any age group and require the largest relative doses. In addition to age-related trends, children demonstrate the same drug-specific, pharmacokinetic phenomena that adults do, including nonlinear phenytoin elimination, nonlinear valproate binding, and autoinduction of carbamazepine. Intercurrent illness and drug interactions further modify the age-related pharmacokinetic patterns in children and make dosage requirements even more unpredictable. Recent studies have shown that febrile illness can affect drug elimination, sometimes decreasing drug levels by 50% or more. Intermittent treatment with benzodiazepines administered either orally or rectally can be an important adjunct and help minimize this type of problem for children with marginally controlled epilepsy. Intermittent benzodiazepines are also helpful for children who have febrile seizures and who need only occasional antiepileptic protection.