超早期静脉溶栓治疗急性脑梗死

目的 评价应用尿激酶静脉内溶栓治疗急性脑梗死的有效性和安全性。方法 应用注射用国产尿激酶治疗急性脑梗死16例，用法：尿激酶150万U溶人生理盐水150ml内，30min滴完。分别在溶栓前、溶栓后2h、24h、3d、7d、14d时间点，采用欧洲卒中量表(ESS)对神经功能缺损进行评价。结果 75％(12例)的患者ESS分值在溶栓后24h内迅速增加。截止溶栓后14d，ESS分值仅有1例无变化，2例下降。其中时间窗＜4h者ESS分值增加的速度明显高于4—6h，而后者又明显高于＞6h。本组非症状性脑内出血2例(12．5％)，症状性脑内出血1例(6．25％)；全身性出血4例(25％)；死亡率1例(6．25％)，死因为脑内出血；再瘫痪1例。结论 本研究提示尿激酶治疗急性脑梗死有效，如能严格掌握溶栓时间窗及适应症，可以提高治疗的安全性。     

急性脑梗塞(6h以内)静脉溶栓双盲对照临床分析

目的 :评价尿激酶对急性脑梗塞静脉溶栓的疗效及安全性。方法 :为随机、双盲、安慰剂对照临床试验 ,凡符合入选标准的患者 (随机按照编号给药 ) ,胰肠尿激酶 15 0万 U溶于生理盐水 10 0～ 15 0 ml内 ,30分钟内滴完 ,以后静点低分子右旋糖苷 5 0 0 mg/ d,共 10天 ,2 4h后加用口服水溶性阿司匹林 10 0 mg/ d,共 10天 ,以后改为维持量5 0 mg/ d。神经功能评价采用欧洲卒中量表 (ESS) ,并记录在下列时间点 :溶栓前 ,溶栓后 2 h,2 4h,3d,7d,14d,30 d和90 d。结果 :符合入选标准的共 38例 ,年龄 35～ 72岁 ,其中发病后 3h以内溶栓的 13例 ,3～ 6 h溶栓者 2 5例。 15 0万 U治疗组 14例 ,10 0万 U治疗组 13例 ,安慰剂对照组 11例。溶栓后 2 4h内 ESS分值增加显著。 15 0万 U治疗组 2周内ESS分值明显高于 10 0万 U组 (P<0 .0 5 ) ,后者又明显高于安慰组 (P<0 .0 1) ;90天时 ,15 0万 U与 10 0万 U治疗组无显著差异 ,但治疗组明显高于安慰剂组 (P<0 .0 1) ,3～ 6 h内溶栓的病例 ,各组 ESS分值增加速度不如 3h内溶栓的ESS值增加明显。结果提示 ,ESS分值的上升高度与溶栓时间窗密切相关。本组死亡率为 5 .6 2 %(2 / 38)。结论 :尿激酶静脉溶栓治疗急性脑梗塞 (6 h)以内有效。目前是治疗急性脑梗塞唯一有效的方法。     

小剂量尿激酶治疗急性脑梗死36例临床观察

目的探讨小剂量尿激酶静脉溶栓治疗(发病6～72h内)急性脑梗死疗效和安全性。方法符合入选标准的36例病人予以静滴尿激酶30万U×5d。结果溶栓后各时间点与溶栓前比较PC、APTT、PT、FP无明显差异性(P<0.05);溶栓后各时间点ESS积分逐渐上升,第30d以后的ESS积分较溶栓前均有显著性差异;溶栓后第90dBarthel指数≥95分(完全恢复和基本完全恢复)26例(72.2%)。结论小剂量尿激酶静脉溶栓治疗急性脑梗死安全、有效,远期疗效比近期更好。     

尿激酶治疗脑梗死的疗效观察

目的观察尿激酶静脉溶栓治疗急性脑梗死的疗效。方法对46例符合入选的早期急性脑梗死(<6 h)的患者随机分为溶栓组和对照组,溶栓组24例,对照组22例。溶栓组给予尿激酶100万~150万U加入生理盐水100~200 mL中静滴30 min。24 h头颅CT证实无脑出血者用丁咯地尔200 mg静滴,1次/d,连续14 d。对照组应用丁咯地尔200 mg,1次/d,连续14 d。2组患者均辅以脑代谢药、血塞通、胞二磷胆碱、丹参川芎嗪等。结果静脉溶栓组疗效明显优于对照组。溶栓有效率95.8%,对照组有效率86.4%。结论尿激酶静脉溶栓治疗急性脑梗死疗效显著,值得推广应用。     

急性脑梗死超早期尿激酶静脉溶栓治疗体会

目的观察中等剂量尿激酶在急性脑梗死超早期静脉溶栓治疗的有效性和安全性。方法选择发病在6h内的急性脑梗死患者47例,随机分为治疗组23例,对照组24例,治疗组一次性应用尿激酶75万～100万U静脉溶栓治疗。观察溶栓后1d、7d、14d2组神经功能缺损评分（NIHSS）变化。以溶栓后出血转化、24h内再梗死及死亡等作为安全指标。结果 2组治疗前后NIHSS评分比较差异有统计学意义（P〈0.01）,治疗组24h内出血转化1例,对照组再梗死1例,死亡1例。结论中等剂量尿激酶静脉溶栓治疗超早期急性期脑梗死临床疗效显著、安全。     

尿激酶溶栓联合脑保护剂治疗急性脑梗死的疗效观察

目的评价尿激酶联合脑保护剂对急性脑梗死(6～12h)静脉溶栓的疗效及安全性。方法 凡符合入组标准的患者接受尿激酶75万~125万U溶于生理盐水100~200ml内,20min内滴完,随后静滴25％硫酸镁极化液、低分子右旋糖酐、丹参、20％甘露醇、胞二磷胆碱、七叶皂甙及尼莫通或口服尼莫地平等脑细胞保护剂,治疗前及治疗后2h、24h、7d、14d进行神经功能缺损评分及疗效评价。结果 起病6～12h的急性脑梗死尿激酶溶栓后不同时间神经功能缺损评分及有效率和总有效率与对照组比较有显著性差异(P<0.01),虽6h内溶栓组比6～12h溶栓组疗效好,24h溶栓组后神经功能缺损评分均高于6～12h溶栓组(P<0.05),但2周后疗效评价二组间却无显著性差异(P>0.05)。结论起病6~12h的急性脑梗死并非溶栓治疗的绝对禁区,只要合理选择病例,及早联合使用脑保护剂,同样能获得理想的疗效。     

改良尿激酶静脉溶栓方案治疗急性脑梗死的疗效观察

目的探讨改良尿激酶静脉溶栓方案治疗急性脑梗死的临床疗效。方法 90例急性脑梗死患者分为改良组(30例)和对照组(60例),改良组采用尿激酶50万U 15min内静滴完,继以尿激酶50万U 45min内静滴完;对照组采用尿激酶100万U 30min内静滴完。在溶栓前、溶栓后1h、24h、14d进行美国国立卫生研究院卒中量表(NIHSS)评分,观察14d时改良的Rankin残障(mRS)评分及再闭塞的发生率。结果溶栓后1h2组NIHSS分数均迅速降低,差异无统计学意义(P0.05),改良组14dNIHSS评分为3.9±2.4,对照组5.1±3.3;14d时mRS≤2者,改良组20例(67%),对照组28例(47%);再闭塞发生率,改良组2例(7%),对照组13例(22%);2组比较差异均有统计学意义(P0.05)。结论改良尿激酶溶栓方案治疗急性脑梗死临床效果确切,早期再闭塞发生率显著减少。     

尿激酶溶栓治疗急性脑梗死52例疗效分析

目的 观察尿激酶溶栓治疗急性脑梗死的临床疗效。方法 将104例急性脑梗死病人随机分为治疗组和对照组。治疗组应用尿激酶50万U加入100ml生理盐水中静滴,1次/d,连用3d,之后尿激酶20万U加入生理盐水100ml静滴,1次/d,连用4d,共治疗7d;对照组给予尿激酶75万U加入生理盐水100ml静滴,1/2h滴完;两组均同时给予肠溶阿司匹林片0.lg/(次·d),并给子脱水、改善微循环等综合治疗。治疗4周后进行神经功能缺失评分及凝血功能、血流变比较,判定疗效。结果 治疗4周后神经功能缺失评分及凝血功能、血流变指标分析,治疗组与对照组相比差异有显著性。结论 尿激酶溶栓治疗急性脑梗死疗效确切,简单易行,副作用小,值得临床推广应用。     

尿激酶静脉溶栓治疗急性脑梗死34例临床疗效分析

目的 评价应用尿激酶静脉溶栓治疗急性脑梗死的有效性和安全性.方法 治疗组34例静脉滴注尿激酶100万U(体质量≤50公斤)或150万U(体质量＞50公斤)溶于生理盐水100ml或150ml中,半小时内滴完;对照组30例按常规治疗,并分别在溶栓前、溶栓后24h、1周、3周时间点,采用脑卒中患者神经功能缺损评分表进行评价.结果 治疗组总有效率为91.17%,对照组总有效率为66.66%,2组比较差异有非常显著性(P＜0.01);不同剂量尿激酶治疗前、治疗后24h、1周及3周神经功能缺损评分比较差异无显著性(P＞0.05).结论 尿激酶静脉溶栓治疗急性脑梗死剂量为100万U(体质量≤50公斤)或150万U(体质量＞50公斤)较符合治疗剂量个体化原则,且安全、有效.     

贴敷式局部亚低温并用尿激酶治疗急性脑梗死

目的评价局部亚低温治疗急性脑梗死的临床疗效。方法本研究为随机、配对对照的临床研究。符合入选标准的62例患者分为2组:对照组仅接受尿激酶100万U溶栓治疗,低温组在尿激酶100万U溶栓治疗的同时加用局部亚低温治疗。采用欧洲卒中量表(ESS)评价神经功能缺失状态。结果发病3h内给予溶栓治疗的低温组患者在溶栓后7d始ESS评分显著高于对照组患者。发病3~6h给予溶栓治疗的低温组患者在溶栓后24h始ESS评分显著高于对照组患者。结论局部亚低温并用溶栓治疗的效果优于单用溶栓治疗,局部亚低温治疗急性闭塞性脑血管病安全有效。     

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.     

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.     

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.     

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.     

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.     

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.