醋酸纤维素聚合物栓塞实验性宽颈动脉瘤影像学研究

目的观察非粘附性液体栓塞剂醋酸纤维素聚合物（CAP）栓塞实验性宽颈动脉瘤的影像学效果。方法家猪7只，将静脉袋端-侧吻合于颈总动脉建立侧方宽颈动脉瘤模型。动脉瘤制作后1-3d行CAP结合球囊再塑形技术栓塞。栓塞术后1个月行造影复查。结果7只动物共制作10个动脉瘤。对8个动脉瘤行栓塞，除在1个动脉瘤模型中微导管破裂导致载瘤动脉闭塞以外，余7个动脉瘤均获完全栓塞并保留载瘤动脉；栓塞术后1个月复查造影显示动脉瘤无再通，载瘤动脉保留率降至62．5％。结论CAP结合球囊再塑形技术能够实现完全栓塞宽颈动脉瘤并保留载瘤动脉的影像学效果。     

醋酸纤维素聚合物栓塞实验性宽颈动脉瘤的组织学研究

目的观察实验性宽颈动脉瘤被非黏附性液体栓塞剂醋酸纤维素聚合物(CAP)栓塞后的组织学变化。方法犬3只,将颈外动脉和股深动脉结扎建立动脉残端性宽颈动脉瘤模型,随即向动脉瘤腔内注射CAP(注射时用血管夹夹闭动脉瘤颈)。3周后取动脉瘤标本做电镜检查。结果3只动物共制作12个动脉瘤,7个用CAP栓塞。扫描电镜显示瘤体内的CAP团块与动脉瘤内膜紧密贴合,有4个动脉瘤的瘤颈被较完整的新生内皮细胞覆盖。透射电镜显示瘤壁存在轻度炎症,瘤腔被CAP及纤维组织充填。结论宽颈动脉瘤被CAP栓塞后能够达到组织学上表现为瘤颈内皮化和瘤腔纤维化的解剖愈合。     

兔颈总动脉动脉瘤中药白芨胶栓塞研究

目的 探讨动脉瘤中药白芨胶液体栓塞的可行性。方法 应用显微外科技术建立10只兔颈总动脉侧壁动脉瘤。将超微导管插至动脉瘤腔并进行中药白芨胶液体栓塞，通过数字减影血管造影及组织病理标本观察栓塞前后瘤腔及载瘤动脉发生的血流动力学改变。结果 栓塞后即刻血管造影显示7只瘤腔全部闭塞，3只瘤腔大部被白芨栓塞。栓塞后半年组织病理标本示10只动脉瘤瘤腔均完全闭塞，8只动脉瘤远端载瘤动脉通畅，2只动脉瘤远端载瘤动脉闭塞。未见血管壁明显炎症及远端组织缺血表现。结论 应用中药白芨胶栓塞动脉瘤具有可行性。     

负载VEGF聚合物修饰铂金微弹簧圈栓塞动脉瘤模型的研究

目的 探讨负载血管内皮生长因子(VEGF)的聚合物修饰铂金微弹簧圈对动脉瘤的栓塞效果. 方法 健康雌性SD大鼠54只采用随机数字表法分为普通铂金微弹簧罔组、聚合物涂层修饰组和负载VEGF组,每组各18只.分别将各组弹簧圈片断植入大鼠右侧颈总动脉,在弹簧圈远端将颈总动脉结扎后恢复血流,则颈总动脉残端形成囊状动脉瘤,弹簧圈片断位于动脉瘤囊内.于术后15d、30 d和90 d每组取6只大鼠,将包含有弹簧圈的一段动脉切下,同时切取普通铂金微弹簧圈组大鼠左侧一段颈总动脉作为空白对照组.HE染色观察标本内皮细胞的增殖和纤维化程度；免疫组织化学染色检测血管性假血友病因子(vwf)的表达；Western blotting检测动脉瘤局部VEGF的释放情况. 结果 术后10d、30 d、90 d时负载VEGF组动脉瘤组织纤维化分级明显高于普通铂金微弹簧圈组,术后30d时负载VEGF组纤维化分级高于聚合物涂层修饰组,差异均有统计学意义(P＜0.05)；免疫组织化学染色检测显示负载VEGF组铂金微弹簧圈在栓塞动脉瘤模型后很快形成血栓并机化,动脉瘤腔内完全被纤维化的组织填塞,并且纤维化的组织中有呈vwf阳性表达的新生小血管形成,另外3组均未观察到vwf呈阳性表达的新生血管；Western blotting结果显示负载VEGF组在术后15d、30 d时动脉瘤壁组织中VEGF因子水平明显高于其他组,而90 d时VEGF因子水平明显低于其他组. 结论 负载VEGF的聚合物修饰铂金微弹簧圈可在动脉瘤腔内缓慢释放VEGF,刺激动脉瘤内细胞增生,促进血栓机化,形成致密的纤维化组织,达到更快、更完全地闭塞动脉瘤的效果.     

两种线栓法制作小鼠大脑中动脉栓塞模型的比较

目的通过颈总动脉和颈外动脉两种栓塞途径插入线栓在小鼠身上建立短暂性大脑中动脉栓塞（MCAO）模型，比较分析两种模型实验动物的术后存活率、行为学、梗死体积、脑水肿程度以及神经细胞凋亡情况，从而筛选出更为可行有效的脑梗死模型建立方法。 方法42只C57BL/6雄性小鼠，体质量20~22 g，按照随机数字表法分为假手术组（6只）、MCAO模型颈外动脉插线组（18只，颈外组）、MCAO模型颈总动脉插线组（18只，颈总组）。颈外组从颈外动脉剪口插入线栓栓塞大脑中动脉起始部制备小鼠大脑中动脉栓塞模型，颈总组从颈总动脉剪口插入线栓栓塞大脑中动脉起始部制备小鼠大脑中动脉栓塞模型，假手术组结扎与模型组同侧颈总动脉相同，但不插入线栓。颈外组和颈总组缺血1 h、假手术组颈总动脉结扎1 h，其后拔出线栓解除结扎，同时再灌注24 h，其后采用Longa神经功能评分，灌流取脑TTC染色，计算梗死体积并测出脑组织含水量，观察神经细胞凋亡情况，从而进行比较分析。 结果颈外组和颈总组小鼠均出现脑卒中表现、神经功能评分升高、出现脑水肿、有明显梗死体积以及神经细胞凋亡，假手术组未出现与之相对的明显表征。颈总组与颈外组相比，梗死体积和脑水肿程度接近，神经细胞凋亡数量基本一致，差异无统计学意义（P>0.05）；颈总组相对颈外组，神经功能评分较高，死亡率较高，差异具有统计学意义（P<0.05）。 结论两种栓塞途径所造成的脑梗死比较结果一致，但考虑到部分实验需要长期给药观察，颈外动脉栓塞途径实验动物存活率更高，所以推荐采用颈外动脉插线方法制作大脑中动脉栓塞模型。     

自制白芨液态栓塞剂栓塞兔动脉瘤模型研究

目的观察自制白芨液态栓塞剂对兔颅内动脉瘤的栓塞效果.方法从白芨中提取液态栓塞剂,对19侧兔颈总动脉动脉瘤模型进行栓塞实验.结果DSA示模型动脉瘤栓塞中未发生栓塞剂外溢及黏管现象.栓塞后3周,病理显示瘤颈口出现内皮细胞生长.结论自制的白芨液态栓塞剂栓塞效果满意.     

支架辅助弹簧圈栓塞基底动脉分叉部宽颈动脉瘤

目的探讨支架辅助弹簧圈栓塞基底动脉分叉部动脉瘤的有效性和安全性。方法回顾性分析2003年5月至2012年9月我科按照基底动脉分叉部动脉瘤不同形态采用不同支架技术治疗的23例动脉瘤患者的临床资料。这23例均为囊性宽颈动脉瘤,其中采用单侧支辅助弹簧圈栓塞16例,单侧支架＋微导管或微导丝辅助栓塞2例,双侧支架辅助栓塞5例。结果23例动脉瘤均成功栓塞。术后即刻栓塞结果：Raymond Ⅰ级9例,Ⅱ级4例,Ⅲ级10例。术中动脉瘤破裂1例,手术后6d死亡。22例患者出院时改良Rankin评分为0～1分。16例患者进行影像学随访1～46月,平均13．5月,其中动脉瘤不显影10例,改善2例,稳定3例,复发1例;无再出血及新发神经功能障碍。结论支架辅助弹簧圈栓塞治疗基底动脉分又部宽颈动脉瘤安全、有效。     

血管内新型液体栓塞剂CAP的实验研究

目的　研制一种血管内治疗颅内动脉瘤的液体栓塞剂—醋酸纤维素聚合物（ＣＡＰ） 。方法　寻找自制ＣＡＰ溶液的最佳配比; 在１２ 只家兔右侧股动脉内注入此溶液, 观察栓塞效果和组织病理变化。结果　表明ＣＡＰ溶液最佳配比为２５０ｍｇＣＡＰ、３ｍｌ ＤＭＳＯ和８００ｍｇＢｉ２Ｏ３ 。此溶液易于通过微导管, 不产生粘堵, 凝固约需５ 分钟; 并且具有组织相容性好、无毒副作用和栓塞血管腔完全牢固持久的优点。结论　ＣＡＰ是一种较理想且有开发前景的液体栓塞材料     

生物可吸收聚合物弹簧圈结合碱性成纤维细胞生长因子栓塞鼠动脉瘤模型

目的评价生物可吸收聚合物弹簧圈Matrix结合碱性成纤维细胞生长因子(bFGF)栓塞鼠颈动脉瘤模型的效果和作为药物递送系统的可行性。方法64只SD大鼠随机分成4组:假手术组、GDC组、Matrix组和bFGFMatrix组,每组各16只。GDC和Matrix被切成10mm长的片段,分别将GDC、Matrix和bFGFMatrix片段植入鼠结扎的颈总动脉(CCA)囊,栓塞后2周和4周处死动物并分析组织病理学资料。结果栓塞后2周和4周,Matrix组和bFGFMatrix组的CCA腔充满明显细胞增生,新生内膜形成和管壁增厚纤维化,增生组织主要由胶原纤维、成纤维细胞、平滑肌细胞和内皮细胞构成。Matrix组和bFGFMatrix组的CCA管腔面积均明显小于GDC组(P<0.05),bFGFMatrix组血管腔增生组织厚度/血管直径的比率明显大于Matrix组(P<0.05)和GDC组(P<0.05),Matrix组也大于GDC组(P<0.05)。结论Matrix能够诱导动脉瘤内细胞反应和纤维化,促进动脉瘤闭塞,而且可以作为药物递送系统,递送生物活性物质进一步增强动脉瘤的愈合。     

雌激素缺乏对大鼠颅内动脉瘤形成的影响

目的 建立雌激素缺乏的颅内动脉瘤模型,并在此基础上初步研究雌激素缺乏对颅内动脉瘤形成、生长的影响及其可能机制. 方法 雌性Wistar大鼠30只按随机数字表法分为实验组(切除双侧卵巢+颅内动脉瘤模型)、实验对照组(切除双侧卵巢旁与其大小相当的一块脂肪+颅内动脉瘤模型)、空白对照组(每组各10只).大鼠去势模型或腹部假手术模型制作后2周用猪胰弹性蛋白酶滴加到颈外动脉及分叉处动脉壁周围,在颈外动脉距分叉处约1.5 mm位点用两根手术线结扎颈外动脉,在两根线之间剪断颈外动脉,使颈外动脉的盲段形成颈内动脉的一个动脉瘤.动脉瘤模型制作6周后取右心房全血2mL,离心取上清液后于-20℃冰箱保存,用于检测大鼠血清中雌激素的含量,同时游标卡尺测量颅内动脉瘤长度和直径,并取实验组及实验对照组的颅内动脉瘤组织和空白对照组相应的一段颈外动脉组织用于常规组织切片染色. 结果 实验组血清中雌激素水平为(105.00±12.96)pmol/L,实验对照组为(178.50±25.96)pmol/L,空白对照组为(180.40±18.70)pmol/L,实验组与实验对照组及空白对照组组间比较差异有统计学意义(P<0.05).实验组颅内动脉瘤长度扩张率为(131.31±6.63)%,直径扩张率为(125.10±5.49)%,实验对照组为(109.90±3.44)%和(106.82±2.49)%,比较差异有统计学意义(P<0.05).结论 雌激素缺乏对颅内动脉瘤的形成、生长有一定的促进作用.本研究使用肓段法结合酶消化法制作颅内动脉瘤模型简便可行.     

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.     

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.     

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.