急性缺血性脑卒中TOAST分型与血浆D-二聚体的相关研究

目的探讨不同亚型急性缺血性脑卒中患者血浆D-二聚体含量的变化及其意义。方法 107例急性缺血性脑卒中患者按照TOAST标准进行病因学分型,大动脉粥样硬化性脑卒中(large-artery athero-sclerosis,LAA),小动脉闭塞性脑卒中或腔隙性脑卒中(small artery occlusion,SAO),心源性脑栓塞(cardio-embolism,CE),其他确定原因引起的缺血性脑卒中(stroke of other demonstrated etiology,SOE)和不明原因的缺血性脑卒中(stroke of undemomtrated etiology,SUE)。用酶联免疫吸附试验检测急性缺血性脑卒中患者发病后1、7和14d时血浆D-二聚体含量,并与65例对照者进行比较。结果在急性缺血性脑卒中亚型组血浆D-二聚体含量显著高于对照组(P0.05);在急性期(第1d)增高,在高峰期(第7d)较急性期明显增高,在恢复期(第14d)下降至急性期水平,仍明显高于正常值;在急性缺血性脑卒中组中CE组血浆D-二聚体含量最高,显著高于其他各亚型组(P0.05);LAA组血浆D-二聚体含量也显著高于SAO组、SUE组和SOE组(P0.05).结论在急性缺血性脑卒中血浆D-二聚体含量升高明显,不同亚型的升高程度不同,这对于临床早期分型诊断并及时给予相应治疗具有重要意义。     

穿支动脉性脑梗死早期神经功能恶化的研究

<正>国际上缺血性卒中分型中急性脑卒中Org 10172治疗实验(Trial of Org 10172 in Acute Treatment,TOAST)分型是目前应用最广泛的病因学分型。根据缺血性卒中(ischemic stroke,IS)的病因分型各型大致分为以下几类:大动脉粥样硬化(large-artery athero-sclerosis,LAA)、心源性栓塞(cardioembolism,CE)、小动脉闭塞(small-artery occlusion lacunar,SAA)、其他病因(stroke of other determined etiology,     

青年缺血性脑卒中的病因及发病机制研究进展

正缺血性脑卒中(ischemic stroke,IS)是发病率高、致残率高、复发率高的一种疾病。最近的一项全球性疾病负担调查结果显示,到2010年IS已成为全球负担最严重的疾病,全球范围每年因IS致死人数高达590万[1]。近年来,随着环境的恶化,饮食结构的不合理,生活方式的改变,及生活节奏的加快,缺血性脑卒中的发病呈现年轻化趋势[2]。青年缺血性脑卒中是指发病时患者年龄在45岁以下的成年人群发生的     

一氧化氮合酶家族及其基因多态性与缺血性脑卒中

脑卒中是一种多因素的复杂疾病,其遗传机制尚不完全明确。脑卒中又分为缺血性脑卒中和出血性脑卒中,其中缺血性脑卒中(ischemic stroke,IS)约占脑卒中的80%,是致残率和致死率最高的疾病之一。流行病学研究证实,脑卒中的发生与多个环境因素相关,其中吸烟、血脂异常、糖尿病、     

血浆VEGF在缺血性脑卒中的表达及影响

目的探讨血浆血管内皮生长因子(VEGF)在缺血性脑卒中以及其不同亚型中的表达水平和临床意义。方法纳入171例缺血性脑卒中病人作为脑卒中组,分为4个亚型:(1)动脉血栓性脑梗死(ATBI,n=34);(2)小动脉病变(SAD,n=45);(3)心源性脑梗死(CE,n=49);(4)其他类型(OT,n=43)。同时以年龄和性别匹配的健康人群作为对照组(n=171)。采用酶联免疫吸附试验(ELISA)检测脑卒中后1 d、3 d、7 d、14 d、90 d血浆VEGF的水平并分析。结果与对照组相比,脑卒中组卒中后1 d血浆VEGF水平开始上升,持续至90 d;血浆VEGF水平在4种脑卒中亚型中均显著上升(P0.05)。CE亚型病人VEGF水平与NIHSS评分呈正相关(r=0.843,P0.05)。与卒中后90 d疗效良好的病人比较,脑卒中组、SAD和CE亚型疗效不良的病人VEGF水平显著上升(P0.05),ATBI亚型反而显著下降(P0.05),OT亚型无差异(P0.05)。结论血浆VEGF水平在所有脑卒中病人中均会增加,与各亚型的预后存在不同的相关性。     

重视关联分析在缺血性脑卒中遗传学研究中的作用

脑卒中是导致人类死亡的三大疾病之一,其发病率、致残率和病死率极高.大约80%的脑卒中为缺血性脑卒中(ischemic stroke,IS).越来越多的证据表明,遗传因素在IS发病中发挥重要作用.     

细胞焦亡与缺血性脑卒中的关系研究进展

缺血性脑卒中(ischemic stroke,IS)是一种严重危害人类健康的疾病,其发病机制仍不清楚,治疗方法有限,迫切需要探索新的干预方法。细胞焦亡是近年来发现的一种促炎性调控细胞死亡,参与了IS的发病机制,抑制细胞焦亡可减轻IS后脑损伤。现就细胞焦亡的发生机制、其参与IS的发病机制以及靶向细胞焦亡治疗IS的研究进展进行综述。     

基质金属蛋白酶-9基因多态性与缺血性脑卒中的相关性

目的探讨基质金属蛋白酶-9(matrix metalloproteinases-9,MMP-9)基因多态性与缺血性脑卒中的相关性。方法运用多重小测序技术(multiplex SNa Pshot)分析粤西地区251例缺血性脑卒中患者和96例健康对照组MMP-9基因(rs3787268、rs3918241、rs3918242)的多态性分布,并分析与缺血性脑卒中的相关性。结果 (1)与对照组相比,病例组rs3787268基因型频率有统计学差异(P=0.042),在隐性模型中A/A基因型的个体患病风险升高(OR=2.21,P=0.046);(2)rs3918242基因型频率亦有统计学差异(P=0.007),在显性模型中,携带T基因型的个体患病风险升高(OR=2.14,P=0.009);(3)其中rs3787268在大动脉粥样硬化(large artery atherosclerosis,LAA)亚型组的基因型分布与对照组相比有统计学差异(P=0.039),而非LAA亚型中无统计学差异;rs3918242在LAA亚型组的基因型和等位基因频率与对照组相比分别有统计学差异(P=0.009,P=0.047),在非LAA亚型中无统计学差异。结论 MMP-9基因rs3787268和rs3918242多态位点突变可能与中国粤西地区汉族人群缺血性脑卒中的发病风险相关;并主要可能增加了LAA型脑卒中的发病风险。     

颅内分支动脉粥样硬化病的研究进展

正1989年Louis Caplan首次提出分支动脉粥样硬化病(Branch atheromatous disease,BAD)这个概念,用来描述由于动脉粥样硬化引起颅内深穿支动脉开口处的严重狭窄或闭塞,从而导致的急性缺血性脑卒中。这是1个被忽略的、未充分研究与利用的概念,近年来在日本等亚洲地区进行了较多的研究。尽管缺血性脑卒中(ischemic stroke,IS)的治     

脑微出血与不同亚型缺血性脑卒中的关系及预后分析

目的探讨脑微出血(CMBs)与不同亚型缺血性脑卒中的关系及预后。方法收集2014年3月~2016年5月期间就诊我院,并确诊为缺血性脑卒中的患者116例,根据中国缺血性脑卒中亚型(CISS)标准分为5种亚型,即大动脉粥样硬化型卒中(LAA)、心源性卒中(CS)、其他病因型(OE)、穿支动脉疾病型(PAD)和病因不确定型(UE)。每个亚型分为CMBs组和非CMBs组,比较各组血清相关指标,采用Logistic回归分析每种亚型伴CMBs的影响因素,采用NIHSS评分评价每种亚型伴CMBs的预后情况。结果 PAD组同型半胱氨酸(Hcy)水平(23.32±2.79)μmol/L,明显高于LAA(20.64±3.11)μmol/L、CS(20.7±2.63)μmol/L、OE(18.92±2.91)μmol/L和UE(17.63±3.06)μmol/L,差异具有统计学意义(P0.05)。OE组和LAA组糖化血红蛋白(Hb A1)水平(7.60±0.25和7.11±0.32)明显高于CS组(5.03±0.11)、PAD组(5.10±0.11)和UE组(4.99±0.12),差异具有统计学意义(P0.05);而OE和LAA两组间、CS、PAD和UE三组间Hb A1水平差异不明显(P0.05)。长期饮酒是CS和PAD伴CMBs的独立危险因素;Hcy是每种亚型伴CMBs的独立危险因素;Hb A1是PAD、LAA伴CMBs的独立危险因素。结论 Hcy、Hb A1和长期饮酒是缺血性脑卒中伴CMBs的独立危险因素。不同亚型缺血性脑卒中伴CMBs的预后差异不明显。     

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.     

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.     

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.     

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.     

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.     

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.     

Treatment Considerations in Anticonvulsant Monotherapy

Summary: The long-standing practice of polypharmacy in treating epilepsy is giving way to use of monotherapy. Monotherapy can improve seizure control as well as reduce the risk of serious idiosyncratic reactions, dose-related side effects, and complex drug interactions. Monotherapy also offers improved compliance and cost-effectiveness. The basis of monotherapy is accurate diagnosis and assessment of the patient's seizure type(s), followed by selection of a single appropriate anticonvulsant drug. Many patients currently treated with multiple anticonvulsants can be successfully converted to monotherapy with a carefully monitored program in which troublesome and redundant drugs are gradually withdrawn from the therapeutic regimen.