刺五加对蛛网膜下腔出血患者血浆内皮素含量的影响

目的观察刺五加对蛛网膜下腔出血(SAH)患者血浆内皮素(ET)的作用,进一步探讨刺五加防治SAH后脑血管痉挛(CVS)的作用机制.方法将SAH患者44例,随机分为刺五加组(20例)和SAH对照组(24例),应用放射免疫分析方法,测定刺五加组不同时期血浆中ET含量,并与SAH对照组和正常对照组(20例)比较.结果SAH对照组于用药前及用药后2h、7d、14d血浆ET含量分别为68.38±15.41、60.45±11.35、56.83±9.32、55.25±8.21,均明显高于正常对照组42.12±6.37(P<0.01,P<0.05);刺五加组用药后2h、7d和14d血浆ET含量分别为42.30±13.45、46.52±10.36、48.31±9.17,与SAH对照组同期比较,明显降低(P<0.01,P<0.05);刺五加组用药后不同时期血浆ET含量明显低于用药前(P<0.01).结论刺五加能明显降低SAH后增高了的血浆ET水平,从而预防和治疗SAH后CVS,保障脑组织的血液供给.     

不同剂量尼莫地平防治蛛网膜下腔出血后脑血管痉挛的疗效观察

目的　探讨应用尼莫地平防治蛛网膜下腔出血(SAH)后脑血管痉挛(CVS)的最佳剂量。方法对30例原发性SAH患者分别给予尼莫地平大剂量(1~2mg/h, 12例)、中剂量(0. 5~0. 8mg/h, 12例)、小剂量(0. 2~0 .4mg/h, 6例)治疗。用经颅多普勒(TCD)检测SAH患者脑动脉的收缩峰速度,观察各组CVS发生的情况。结果　大剂量组与中剂量组用药后的脑动脉血流速度相比差异无显著性(P>0. 05),大、中剂量组与小剂量组用药后的脑动脉血流速度相比差异均有显著性(P<0.05 ~0. 01);大、中剂量组治疗后与治疗前的脑动脉血流速度相比差异均有显著性(均P<0. 05),小剂量组治疗前后的脑动脉血流速度相比差异无显著性(P>0 .05)。结论　大、中剂量尼莫地平对SAH后CVS均有较好的防治作用,而小剂量尼莫地平则不能有效防治CVS。     

经颅多普勒对蛛网膜下腔出血导致血管痉挛的临床研究

目的研究实时床旁经颅多普勒(transcranial doppler,TCD)在蛛网膜下腔出血(subarachnoid hemorrhage,SAH)中对脑血管痉挛(cerebral vasospasm,CVS)的预警和治疗指导作用。方法采用前瞻性研究TCD实时监测180例CT确诊SAH患者大脑中动脉(middle cerebral artery,MCA)的动脉平均峰值流速(mean blood velocity,Vm)、搏动指数(pulsatility index,PI)、阻力指数(resistance index,RI)和血流频谱,自身健侧作为正常对照,对符合CVS诊断标准的使用尼莫地平进行治疗,观察疗效。结果与健侧相比,出血侧PI、RI增大,Vd、Vm减小,其中以Vd减小较明显,与健侧相比有显著差异意义(P0.01),Vs与健侧相比无显著差异(P0.05);CVS组与非CVS组相比Vm明显增加,差异有统计学意义(P0.001)。监测SAH后出现血管痉挛52例(28.89%),经尼莫地平治疗均获得缓解。结论采用TCD监测SAH患者脑血流变化,其对血流的监测为临床诊断和个性化治疗SAH后CVS提供参考依据,经TCD的预警和干预明显提高了SAH的疗效。     

法舒地尔治疗蛛网膜下腔出血后脑血管痉挛有效性和安全性的临床评价——Ⅳ期临床试验报告

目的 法舒地尔治疗蛛网膜下腔出血(SAH)后脑血管痉挛(CVS)的临床疗效和安全性.方法 74家医院共收治2 092例动脉瘤性SAH患者,进行Ⅳ期临床试验.所有病例术后均静脉滴注法舒地尔30 mg/次,每日3次,共14d.观察治疗前与后第3、7和14天患者的临床表现及神经系统评分、血生化、经颅多普勒(TCD)的有效性和安全性.结果 用药后14d患者的临床表现明显改善,TCD显示CVS的缓解率为94.36％(P=0.0000),大脑中动脉平均流速降至正常.总有效率91.21％.均未发现任何不良反应,主要血化验指标未见异常.结论 静脉法舒地尔治疗SAH后CVS非常有效并具有安全性和可靠性;是治疗和预防CVS的一种新方法.     

蛛网膜下腔出血后脑血管痉挛的肿瘤坏死因子-α基因启动子相关遗传易感性分析

目的 探讨蛛网膜下腔出血(SAH)后脑血管痉挛(CVS)与肿瘤坏死因子-α基因(TNF-α)启动子相关遗传易感性。方法 经临床确诊SAH患者168例,采用TCD检测和评定SAH患者CVS情况,分为CVS(-)组84例和CVS(+)组84例,另选84名正常成年人作为对照组,应用聚合酶链反应和序列特异性引物-PCR(SSP-PCR)方法对TNF-α基因启动子区5个位点进行基因分型, 用EPI 和EH 等软件分析各位点等位基因、基因型及其组间差异。结果 CVS(+)组与CVS(-)组Hunt-Hess分级构成比有明显差异(P<0.05)。38GG基因型和-863CC基因型是SAH后发生CVS的易感因素(P均<0.05)。多因素Logistic回归分析发现-238G/A、-863C/A基因型和Hunt-Hess分级为与脑血管痉挛有关的危险因素(P<0.05)。CVS(+)组与CVS(-)组年龄、性别、高血压病史及CT Fisher分级构成比均无明显差异(P均>0.05)。结论 TNF-α基因启动子区多态性可能是影响SAH患者发生CVS的高危因素。     

尼莫地平预防创伤性蛛网膜下腔出血所致的脑血管痉挛

本文观察尼莫地平预防创伤性蛛网膜下腔出血(SAH)所致的脑血管痉挛(CVS)。将创伤性SAH病人136例分为两组,尼莫地平组(65例)于伤后24小时内给予尼莫地平治疗,对照组(71例)采用一般综合治疗各三周。结果提示尼莫地平组死亡率(24.6％)、CVS发生率(26.1％)分别低于对照组(33.8％和36.6％),说明尼莫地平预防创伤性SAH所致的CVS有效。     

腰穿置管脑脊液持续引流防治创伤性蛛网膜下腔出血后脑血管痉挛

目的 观察腰穿置管脑脊液（CSF）持续引流防治蛛网膜下腔出血（SAH）后脑血管痉挛（CVS）的疗效。方法 将SAH患者88例，随机分两组。对照组（48例）采用常规治疗加腰穿。治疗组（40例）采用常规治疗加腰穿置管CSF持续引流。结果 治疗组CSF压力和细胞学检查恢复正常时间较对照组快（P〈0．05），不同时间痉挛指数及脑梗死、死亡的例数、再出血发生率明显低于对照组（P〈0．05）。两组间疗效评价采用出院时GOS评定，显示两组间有明显差别（P〈0．05）。结论 腰穿置管CSF持续引流防治SAH后CVS疗效确切，能促进神经功能的尽快恢复，减少并发症。     

动脉瘤性蛛网膜下腔出血并发脑血管痉挛患者血清血管内皮生长因子表达的变化

目的:探讨动脉瘤性蛛网膜下腔出血(SAH)并发脑血管痉挛(CVS)与血清血管内皮生长因子(VEGF)表达的关系.方法:27例动脉瘤性SAH患者为试验组(SAH组),再依据是否并发不同程度CVS分为:无CVS亚组(11例),轻度CVS亚组(9例)、中度CVS亚组(4例)和重度CVS亚组(3例);另设10名健康体检者为对照组.采用ELISA法检测血清VEGF水平.结果:SAH各时间点各组血清VEGF水平为①SAH组发病第1天起即明显高于对照组;②无CVS组不增高.SAH后第1、3、5、7天时血清VEGF水平为①轻度CVS组与中度CVS组相同时间点比较,差异无统计学意义;②重度CVS组明显高于轻度和中度CVS组.SAH后出现脑梗死患者血清VEGF水平明显高于未出现脑梗死患者.结论:SAH后出现CVS患者和出现脑梗死的患者血清VEGF水平明显增高,血清VEGF水平能反映脑血管痉挛的程度.     

经颅多普勒超声检查对蛛网膜下腔出血后脑血管痉挛的诊断价值

目的探讨经颅多普勒超声(TCD)检查对蛛网膜下腔出血(SAH)后脑血管痉挛(CVS)的诊断价值。方法应用TCD对30例SAH患者脑血流状况进行动态监测,并结合临床表现、头颅影像学资料进行分析。结果经TCD证实,本组17例(56.7%)发生CVS,其中10例无症状,7例出现CVS症状。头颅CTFisher分级中,Ⅲ、Ⅳ级SAH患者中CVS的发生率明显高于Ⅰ、Ⅱ级(均P<0.05)。结论TCD监测是早期发现SAH后CVS的一种敏感的检查手段。     

醒脑静治疗蛛网膜下腔出血临床分析

目的探讨醒脑静治疗蛛网膜下腔出血(SAH)的方法和疗效。方法随机将50例SAH患者分为醒脑静组(25例)和对照组组(25例)。对照组应用常规药物包括尼莫地平,醒脑静组在常规药物治疗基础上加用醒脑静治疗。行经颅多普勒(TCD)动态检测大脑中动脉、颈内动脉颅外段的平均血流速度及脉动指数,评定治疗效果。结果醒脑静组的脑血管痉挛(CVS)发病率明显低于对照组(P<0.05),持续时间也明显缩短(P<0.05)。第7d及第10d时醒脑静组平均血流速度(VMCA)较对照组有明显降低(P<0.05),2组间脉动指数(PI)值无明显差异(P>0.05)。结论醒脑静可显著降低SAH患者的大脑中动脉血流速度(MCA),降低CVS发生的频率,缩短CVS持续时间,减弱CVS的强度,认为醒脑静治疗对防治CVS有显著作用。     

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 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.     

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.     

Anticonvulsant Drugs and Cognitive Function: A Review of the Literature

Summary: Alterations of cognitive function are separate from disturbances of behavior seen in association with epilepsy. The nature of the cognitive disability may to a certain extent depend on the seizure type. Partial seizures, mainly derived from a temporal lobe focus, impair memory tasks, while generalized seizures seem to have more effect on attentional abilities. A number of studies, reviewed in this paper, suggest that anticonvulsant drugs further impair cognitive function. Maximal impairments are seen in patients receiving polytherapy: rationalization of polytherapy improves cognitive abilities. Studies in children and adults have allowed differentiation of the effects of various commonly used antiepileptic agents. Maximal cognitive deficits are seen with. phenytoin, while phenobarbital and sodium valproate induce moderate disturbances, and carbamazepine seems relatively free from such toxicity. Further research is needed on the interrelationship between types of seizure disorders, types of anticonvulsant medications, and cognitive function.     

Dextromethorphan: Cellular Effects Reducing Neuronal Hyperactivity

Summary: Dextromethorphan is a dextrorotary morphinan without affinity for opioid receptors, commonly used as an antitussive medication. During the past 5 years, interest in the compound and its demethylated derivative, dextrorphan, has been revived because additional neuroprotective and an-tiepileptic properties were found in in vitro studies, animal experiments, and a few clinical cases. Both morphinans are able to inhibit N -methyl-D-aspartate (NMDA) receptor channels and voltage-operated calcium and sodium channels with different potencies. The inhibition of the NMDA receptor is believed to be the predominant mechanism of action responsible for the anticonvulsant and neuroprotective properties of the compounds.     

Effects of NMD A- and AMPA-Receptor Antagonists on Different Forms of Epileptiform Activity in Rat Temporal Cortex Slices

Summary: Lowering extracellular magnesium induces different patterns of epileptiform activity in rat hippocampus and entorhinal cortex. Short recurrent epileptiform discharges in the hippocampus are stable over time, whereas seizurelike events (SLEs) in the entorhinal cortex, the subiculum, and the neighboring neocortex develop into late recurrent discharges which are not blocked by clinically employed antiepileptic drugs. We tested the sensitivity of the different epileptiform discharge patterns to. /V-methyl-D-aspartate (NMDA)- and non-NMDA-receptor antagonists. As NMDA-receptor antagonist we used dextrorphan, ket-amine, and 2-aminophosphonovalerate (2APV); as α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)-receptor antagonist we employed the quinoxaline derivative glutamate 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). The findings show that the different patterns of epileptiform activity, including the late recurrent discharges, are sensitive to all NMDA-receptor antagonists. However, when dextrorphan was employed to suppress seizure-like events, later recurrent discharges did not develop during the remaining time course of the experiment. CNQX reversibly suppressed recurrent discharges in the hippocampus and SLEs in the entorhinal cortex. However, late recurrent discharges become insensitive to CNQX, even at a high concentration of 60 μM m. This finding suggests a prominent role for NMDA receptors in the generation of late recurrent discharges.     

Pediatric Epilepsy Surgery

Summary: The use of implantable arrays of epidural electrodes has made it possible to carry out extraoperative electrocorticography (ECoG) and functional localization in the awake child. This has permitted cortical excisions that are determined by criteria similar to those obtained during surgical procedures performed under local anesthesia in adults. In addition, the method also permits simultaneous ECoG and video monitoring during the child's symptomatic seizures, providing additional important localizing information that is impractical to obtain in operations under local anesthesia. We report our experience with 75 children, ages 5 months to 15 years, whom we have managed with epidural electrode arrays. The method of extraoperative ECoG is described and illustrative cases are presented to demonstrate its feasibility and utility in children. In addition, we call attention to gliomas as a common cause of chronic focal seizures in children. Of 49 children undergoing resection and followed for from 1 to 14 years (mean of 5.8 years), 32 (65%) are either seizure free or have had a significant reduction in seizure frequency that has unambiguously improved their quality of life. The results are analyzed further by relating the surgical outcome to each of the pathologic entities that caused the seizures. This analysis reveals the variety of neurological conditions that commonly cause intractable focal seizure disorder in children and distinguishes those pathologic entities in which the seizure disorder is apt to respond to surgical intervention from those that will not.