吸烟与青年脑大动脉粥样硬化性狭窄的相关性分析

目的探讨吸烟与青年缺血性卒中患者脑大动脉粥样硬化性狭窄的相关性。方法2002～2004年于我院神经内科行血管造影检查的青年(18～49岁)脑卒中(包括短暂性脑缺血发作及脑梗死)患者93例,其中73例患者可能存在颅内或颅外大动脉粥样硬化性狭窄作为狭窄组,20例患者无大动脉狭窄作为无狭窄组,对两组患者的吸烟及其他危险因子进行调查。研究变量包括:人口学因子(如年龄、性别)、既往病史(包括高血压、糖尿病、长期吸烟及饮酒史)、实验室检测因子(血浆三酰甘油、高密度脂蛋白、低密度脂蛋白、同型半胱氨酸及血纤维蛋白原)。结果单变量分析发现,两组患者的长期吸烟率、高密度脂蛋白降低率、同型半胱氨酸及三酰甘油的升高率、高密度脂蛋白、纤维蛋白原水平间差别均无显著性意义(P＞0．05)。多变量Logistic回归分析发现,长期吸烟(OR=4．367, 95% CI 1．028-18．554,P=0．046)及血三酰甘油水平升高(OR=3．274,95% CI 1．083-9．900,P=0．036)与青年卒中患者脑大动脉粥样硬化性狭窄的发生有关。结论长期吸烟及血三酰甘油水平升高可能是青年卒中患者脑大动脉粥样硬化性狭窄的独立危险因子,应进行大样本的队列研究加以证实。     

缺血性脑卒中患者颅内/外脑大动脉粥样硬化性狭窄的分布及其预测因素

目的探讨缺血性脑卒中患者脑动脉粥样硬化性狭窄的分布及其预测因素。方法对行数字减影血管造影(DSA)的连续的297例动脉粥样硬化性缺血性脑卒中患者进行分组,具有颅内/外大动脉狭窄(狭窄率＞50%)的241例患者作为狭窄组,未发现狭窄或轻度狭窄(≤50%)的56例患者作为小动脉闭塞对照组。按照狭窄部位又将狭窄组分3种模式:颅内与颅外狭窄并存(Ⅰ组,n=92)、单纯颅内动脉狭窄(Ⅱ组,n=102)及单纯颅外动脉狭窄组(Ⅲ组,n=47)。记录所有患者的常规危险因素如年龄、性别、高血压、糖尿病、长期吸烟、长期饮酒及血液学指标如血浆同型半胱氨酸(Hcy)、三酰甘油(TG)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)及纤维蛋白原(Fib)水平等。结果经多变量Logistic逐步回归分析,血浆Hcy水平升高〔OR为3．79,95% CI为(1．79,8．03)〕、长期吸烟〔OR为2．79,95% CI为(1．58,4．93)〕及高龄〔OR为1．34,95% CI为(1．13,1．59)〕是脑大动脉病变的独立预测因素;对于不同的狭窄分布,血浆Hcy水平升高(OR分别为Ⅰ组3．41,Ⅱ组4．49,Ⅲ组2．42)及长期吸烟(OR分别为Ⅰ组3．79,Ⅱ组4．40)几乎是所有狭窄模式的重要预测因子。其他危险因素中,高龄为Ⅰ组(OR为2．41)、Fib为Ⅰ组(OR为2．66)和Ⅲ组(OR为2．89)、TG升高(OR为1．77)为Ⅱ组的独立预测因子。结论颅内、外脑大动脉粥样硬化性病变的危险因子不同,可以部分解释中国患者颅内病变多于颅外病变的特点。高同型半胱氨酸血症及长期吸烟对颅内动脉病变的影响大于颅外,高纤维蛋白原血症为颅外动脉病变的特殊预测因子。     

中国包头市城镇居民脑血管狭窄的流行病学

目的发现人群中脑动脉粥样硬化病变的分布和颅内、颅外动脉狭窄的患病率。方法采用分层抽样的方法,随机抽取研究对象2482人,用标准的问卷收集资料,包括姓名、年龄、性别、吸烟状况、高血压病史、糖尿病史、高脂血症史、心脏病史,测量血压,检测血糖、血脂并进行颈动脉彩色超声和经颅多普勒(TCD)检查。结果筛查的2482人的应答率为2360人,占95%,所有2360人中,颅内动脉狭窄的患病率是8.1%,颅内外动脉狭窄的患病率是9.2%。颅内动脉狭窄的影响因素中,性别(P=0.01)、高血压(P=0.04)、糖尿病(P=0.00)在颅内动脉狭窄组和无狭窄组差异有统计学意义,其余各因素无显著性差异。颈动脉粥样硬化病变(包括内膜增厚,1个或多个斑块形成,管腔狭窄或闭塞)发生率33.4%。结论颈动脉和颅内动脉粥样硬化病变在中老年健康人群中是普遍存在的,在没有任何自觉症状的正常人群中就已经有颅内血管的狭窄,联合应用颈部血管彩色超声和TCD会发现更多的狭窄或动脉粥样硬化病变。     

屏氧酶-1基因多态性和脑梗死的相关性研究

目的 探讨屏氧酶-1（PON-1）基因192位Gin—Arg（Q／R192）多态性与脑梗死的关系。方法 采用聚合酶链式反应（PCR）-限制件片段长度多态性方法测定375例脑梗死患者（脑梗死组）和339名健康普查者及非心脑血管疾病患者（对照组）的PON-1 Q／R192基因多态性,进行基因型分析;并对各基因型与血脂水平关系进行比较。结果 在研究的总人群中,PON-1 Q／R1923种基冈型频率分别为QQ13．6％、QR44．0％、RR42．4％;PON-1 Q／R192皋因型和等位基因频率分布在脑梗死组与对照组之间差异无显著性（P〉0．05）;各基因型之间血脂水：乎差异无显著性（P〉0．05）。结论 未发现PON-1 Q／R192基因多态性与脑梗死存在相关关系。     

急性脑梗死患者颅内动脉硬化及其危险因素的分析

目的研究急性脑梗死患者颅内动脉狭窄或闭塞的发生率和分布特点,以及与动脉硬化危险因素之间的关系。方法根据有无颅内动脉狭窄或闭塞,将122例急性脑梗死患者分为颅内动脉狭窄或闭塞组和无颅内动脉狭窄或闭塞组。分析颅内动脉狭窄的比例和各支动脉狭窄或闭塞的比例,分析症状性颅内动脉狭窄或闭塞的比例;比较两组年龄、性别、高血压病、糖尿病、吸烟、饮酒、血脂、血同型半胱氨酸、糖化血红蛋白等危险因素的差异;分析各支动脉狭窄或闭塞与以上危险因素的关系。结果 122例研究对象中,有颅内动脉狭窄或闭塞患者55例(45.1%),其中有症状性颅内动脉狭窄或闭塞患者36/55例(65.4%),多支动脉狭窄51/55例(92.7%)。颅内动脉狭窄或闭塞组的年龄(67.29±10.92)岁大于无颅内动脉狭窄或闭塞组(63.28±11.20)岁,差异有统计学意义(P0.05)。大脑后动脉狭窄或闭塞患者患有糖尿病比例(58.1%)较无大脑后动脉狭窄或闭塞患者(16.7%)明显增高,差异有统计学意义(P=0.011)。结论急性脑梗死患者存在颅内动脉狭窄或闭塞的比例较高,颅内动脉狭窄或闭塞与年龄有关,大脑后动脉狭窄与糖尿病关系密切。     

缺血性卒中患者颅内外血管狭窄率研究

目的:研究缺血性卒中患者颅内外血管狭窄或闭塞的发生率,并对其相关病因进行分析。方法:对经CT/MRI/DWI诊断的缺血性卒中患者的人口构成情况进行登记,了解其相关危险因素。并经TCD和/或MRA了解其颅内外血管狭窄或闭塞的情况。结果:579例缺血性卒中患者中,颅内外血管狭窄的发生率为70.98%(411/579例);411例大动脉狭窄或闭塞患者中,以大脑中动脉狭窄或闭塞最常见(64.48%),其次为颈内动脉(50.36%)。大动脉狭窄或闭塞的主要原因为动脉粥样硬化,引起动脉粥样硬化的危险因素的发病率依次为:高血压病(77.24%),吸烟(63.68%)。通过Logistic回归分析发现,糖尿病、高血压、吸烟是血管狭窄的主要相关危险因素(P值均<0.05)。结论:国内缺血性卒中患者颅内外血管狭窄或闭塞的发生率高,其主要病因为动脉粥样硬化,糖尿病是大动脉狭窄或闭塞的最主要危险因素。     

2型糖尿病患者基质金属蛋白酶-12基因多态性与缺血性卒中的相关性研究

目的探讨2型糖尿病患者基质金属蛋白酶12(MMP-12)基因多态性与缺血性卒中的相关性。方法选择2013年1月至2015年12月在本科治疗的217例2型糖尿病合并缺血性卒中患者作为病例组,按照TOAST分型结果将病例组患者分为大动脉粥样硬化性卒中(LAA)组88例和非大动脉粥样硬化性卒中(n-LAA)组129例,选择同期在我院体检的无缺血性卒中的2型糖尿病患者100例作为对照组,采用聚合酶链反应-限制性内切酶分析(PCR-RFLP)法比较MMP-12(-82 A/G)和MMP-12(-1082 A/G)基因型多态性在各组间的差异。结果病例组和n-LAA组MMP-12(82 A/G)基因型和等位基因与对照组比较,差异均无统计学意义(P0.05)。LAA组(G/G+A/G)基因型频率显著高于对照组(22.73%vs 11.00%,P=0.031);G等位基因频率也高于对照组(18.18%vs 10.05%,P=0.033)。n-LAA组MMP-12(-1082 A/G)基因型和等位基因与对照组比较,差异均无统计学意义(P0.05)。病例组和LAA组(G/G+A/G)基因型频率均显著高于对照组(33.64%vs 22.00%,P=0.036;37.50%vs 22.00%,P=0.020);两组G等位基因频率也均高于对照组(25.58%vs 17.00%,P=0.017;30.68%vs 17.00%,P=0.002)。多因素Logistic回归分析结果显示MMP-12-82A/G等位基因G和MMP-12-1082A/G等位基因G均是2型糖尿病患者发生LAA的危险因素(OR=1.107,95%CI 1.010-1.371,P=0.031;OR=1.285,95%CI 1.142-1.817,P=0.010)。结论对于2型糖尿病患者,MMP-12基因-82位点G等位基因和-1082位点G基因多态性与大动脉粥样硬化性卒中密切相关。     

经颅多普勒超声和颈动脉超声检测无脑缺血症状的2型糖尿病患者颅内外动脉粥样硬化病变

目的 分析无脑缺血症状的2型糖尿病患者颅内动脉粥样硬化性狭窄和颅外颈动脉粥样硬化病变的发生频率及分布特征,并探讨其危险因素.方法 对94例无脑缺血症状的2型糖尿病住院患者用经颅多普勒超声(TCD)和颈动脉超声判断颅内外动脉粥样硬化病变,颅内动脉只分析狭窄,颅外动脉病变包括颈动脉斑块及狭窄.分析各危险因素的影响.结果 55例(58.5%)有颅内外动脉粥样硬化病变.22例(23.4%)发现有颅内动脉狭窄,明显高于颅外颈动脉狭窄或闭塞(3/94,3.2%,χ~2=16.66,P＜0.01).大脑中动脉是颅内最常受累的动脉(狭窄率17.0%),占狭窄动脉数的58.5%.48例(51.0%)有颅外颈动脉粥样斑块或狭窄.Logistic多元回归分析显示糖尿病病程和合并高血压是颅内外动脉粥样硬化病变的独立危险因素.结论 无脑缺血症状的2型糖尿病住院患者,半数以上有颅内外动脉粥样硬化改变,且与糖尿病病程及合并高血压有关,提示对上述高危患者应常规进行超声检测.     

环指蛋白213基因单核苷酸多态性与中国汉族缺血性卒中相关性研究

目的探讨环指蛋白213(RNF213)基因P.R4810K(G>A)单核苷酸多态性与中国汉族缺血性卒中的关系。方法纳入2013年6月~2013年12月入住郑州大学第一附属医院神经内科汉族缺血性脑卒中患者,所有患者均行血管影像学检查,包括磁共振血管成像(MRA)或者CT血管成像(CTA),分为颅内大动脉狭窄或闭塞亚组(intracranial major artery stenosis/occlusion,ICASO)及无颅内大动脉狭窄或闭塞亚组(non-ICASO),同时选取性别、年龄与缺血性脑卒中组相匹配的健康汉族人为对照组。通过聚合酶链式反应及直接测序方法行多态性位点分析。结果共纳入285例中国汉族缺血性脑卒中患者,其中139例(48.8%)存在不同程度颅内动脉狭窄或者闭塞,146例(51.2%)无颅内大动脉狭窄或闭塞。RNF213基因P.R4810K多态性在缺血性卒中组、ICASO亚组、非ICASO亚组、正常对照组的发生率分别为0.35%(1/285)、0.72%(1/139)、0(0/146)、0.33%(1/300)。和对照组相比,RNF213基因P.R4810K多态性与缺血性卒中组差异无统计学意义(P=1,odds ratio[OR]1.053,95%confidence interval[CI]0.066~16.912),与合并颅内大动脉狭窄或者闭塞亚组间差异同样无统计学意义(P=0.533,OR 2.167,95%CI 0.135~34.894)。结论 RNF213基因P.R4810K单核苷酸多态性与中国汉族缺血性脑卒中及存在ICASO的缺血性脑卒中患者的易患性无相关性,但需在较大样本中进一步验证。     

青、老年脑梗死患者的危险因素及病因分析

目的探讨青、老年脑梗死的危险因素及病因特点。方法对我院2007年1月至2009年12月在我院收治的785例脑梗死病例资料进行分析,患者按年龄分为青年组（≤45岁;n=80）和老年组（≥65岁;n=705）,就高血压病、糖尿病／葡萄糖耐量异常（IGT）、高脂血症、心脏病、中枢神经系统感染、高同型半胱氨酸血症（HCY）、颅内外动脉狭窄或闭塞、烟雾病等危险因素进行分析和比较。结果危险因素分析显示老年脑梗死患者高血压病、糖尿病／IGT的发生率显著高于青年患者（P〈0．01）;两组患者高脂血症、心脏病史的发生率无显著差异（P〉0．05）。病因分析中枢神经系统感染、HCY、颅内外动脉狭窄或闭塞以及烟雾病的发生率显著高于老年患者（P〈0．05）。结论高血压病、糖尿病／IGT是导致老年人发生脑梗死的主要高危因素;而HCY、中枢神经系统感染、烟雾病、颅内外动脉狭窄或闭塞则为导致青年脑梗死发生的重要病因。控制好这些危险因素以及病因治疗,对脑梗死的预防和预后具有重要的临床价值。     

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.     

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.