替莫唑胺联合放疗对体外原代培养的胶质瘤细胞Ki-67表达的影响

目的探讨替莫唑胺同步放化疗对脑神经胶质瘤病人生存质量的影响以及放疗联合替莫唑胺处理对体外原代培养胶质瘤细胞Ki-67表达的影响。方法 2013年10月至2016年8月收治恶性脑神经胶质瘤114例,分为对照组(n=57)与观察组(n=57)。所有病人均接受手术治疗。对照组术后4周接受安慰剂+放疗;观察组在放疗基础上采用替莫唑胺同步化疗。对照组和观察组术中各留取两份肿瘤组织,一份4 h后直接测定Ki-67表达情况。对照组另一份经放疗处理后测定Ki-67表达情况。观察组另一份经过替莫唑胺放、化疗处理后测定Ki-67表达。结果治疗前,观察组和对照组生存质量评分分别为(32.67±3.32)分、(32.69±3.29)分,两组无统计学差异(P0.05)。治疗后,观察组和对照组生存质量评分分别为(43.40±3.26)分、(38.37±5.99)分,较治疗前均明显增高(P0.05),而且,观察组增加更明显(P0.05)。两组不良反应总发生率无统计学差异(P0.05)。放、化疗两处理前,观察组和对照组Ki-67阳性表达率分别为71.93(41/57)、73.68(42/57),两组无统计学差异(P0.05)。放、化疗两处理前,观察组Ki-67阳性表达率(24.56%,14/57)明显低于对照组(43.68%,25/57;P0.05)。结论替莫唑胺同步放化疗可显著改善脑神经胶质瘤病人生存质量,可能与降低Ki-67表达水平有关。     

脑转移瘤治疗方法的对比研究

目的比较手术结合全脑放疗、X-刀和X-刀结合全脑放疗治疗单发脑转移瘤的效果。方法回顾分析我院自1996年2月至2000年4月间经手术结合放射治疗的脑转移瘤84例、X-刀和X-刀结合全脑放疗治疗的脑转移瘤102例,从中选择符合条件的脑转移瘤患者86例,分成3组:手术结合全脑放疗组36例;X-刀组32例;X-刀结合全脑放疗组18例。从临床症状变化,生存时间,局部控制率,肿瘤脑远隔部位生长率,因中枢神经系统病变死亡率等方面比较三种方法的疗效。结果手术结合全脑放疗组、X-刀组和X-刀结合全脑放疗组的临床有效率分别为86.1%(31/36),87.5%(28/32)和88.9%(16/18);中位生存时间分别为54周,50周和51周;1年生存率分别为47.2%(17/36),43.8%(14/32)和44.4%(8/18)。1年肿瘤局部控制率分别为83.3%(30/36),78.1(25/32)和77.8%(14/18)。因中枢神经系统病变死亡率分别为26.7%(8/30),30%(6/20)和28.6%(4/14),三组之间无明显差异(P>0.05)。肿瘤脑远隔部位发生率分别为13.9%(5/36),37.5%(12/32)和11.1%(2/18),X-刀组明显高于其他两组(P<0.05)。结论对于单发脑转移瘤,单纯X-刀可以获得与手术结合全脑放疗和X-刀结合全脑放疗相同的生存时间、局部控制率;全脑放疗可降低肿瘤脑远隔部位生长率,但对生存时间和局部控制率无明显影响。     

脑恶性胶质瘤术后联合放化疗的疗效观察

目的通过对比观察脑恶性胶质瘤术后替莫唑胺胶囊联合外放射治疗的疗效及安全性。方法选择2004年7月至2006年1月收治的55例术后病理证实为脑恶性胶质瘤的病人,按照完全随机分组的原则分为3组:替莫唑胺胶囊联合外放射治疗组21例、125I或131I内放疗组15例和单纯替莫唑胺胶囊化疗组19例。观察病人的无进展生存时间、总生存时间以及药物的安全性。结果实验组的平均无进展生存时间为(56.33±3.36)周,对照组分别为(44.83±4.55)周和(41.5±3.95)周(P<0.05)。实验组的平均总生存时间为(59.27±3.19)周,对照组分别为(50.19±4.80)周和(47.65±3.97)周(P<0.05)。实验组仅有1个病人表现为白细胞减少,经减量处理后好转。结论术后替莫唑胺胶囊联合外放射治疗胶质瘤的效果要好于单纯内放疗或化疗,病人对联合治疗有较好的耐受性。     

间质内放疗、外照射、X-刀治疗脑胶质瘤及转移瘤疗效的对比研究

目的:分析后装192铱(192Ir)间质内放射治疗脑胶质瘤和转移瘤病人56例,探讨后装192Ir间质内放疗的疗效及影响疗效的因素.方法:用后装192Ir间质内放射治疗方法,治疗56例脑胶质瘤和转移瘤(胶质瘤54例,转移瘤2例)病人,全部病人均随访2年以上,依随访结果进行分析,并以同期行外照射治疗的89例和X-刀治疗的42例脑胶质瘤病人为对照,统计分析192Ir间质内放射治疗的疗效.结果:行后装192Ir间质内放疗后,除11例间质内放疗前CT检查证实无肿瘤残存者外(术中置管2组),余45例中,肿瘤消失1例,缩小30例,有效率为68.9%,长期随访,1年内死亡8例,生存48例(85.7%),2年生存42例(75.0%),3年生存22例(39.3%).平均生存期(MST)为28个月.而外照射组1、2、3、生存率分别为70.8%、51.7%和19.5%,MST为19个月.间质内放疗组1、2、3年生存率显著高于外照射组(P＜0.05～0.01).X-刀治疗组1年生存率为78.6%(33/42),2年生存率为68.2%,X-刀治疗组与间质内放疗组相比较,两者无显著性差异.结论:间质内放疗具有疗程短、放疗反应轻、并发症少、疗效佳、经济等优点,其疗效明显优于外照射;与X-刀治疗效果大致相同,但其具较X-刀经济、易于推广等优点.     

小剂量抗精神病药联合心理疗法治疗躯体化障碍的疗效观察

目的观察小剂量抗精神病药联合心理疗法治疗躯体化障碍的临床效果。方法选取2015-05—2016-08我院诊治的躯体化障碍患者70例,采用随机数字法分为对照组(n=35)和观察组(n=35)。对照组采用心理疗法治疗,观察组联合小剂量利培酮治疗,比较2组临床疗效及安全性。结果观察组治疗后2周、4周、6周及8周HAMA17评分、HAMA评分,均显著低于对照组(P0.05);观察组不良反应发生率为8.57%,与对照组的11.43%比较差异无统计学意义(P0.05)。结论躯体化障碍患者在心理疗法基础上联合小剂量抗精神病药治疗效果理想,安全性较高,值得推广应用。     

X刀治疗多发脑转移瘤的临床研究

目的探讨X-刀治疗多发脑转移瘤的预后因素及X-刀在多发脑转移瘤治疗中的作用.方法在4种预后因素(年龄、治疗前KPS评分、有无远处转移、颅外病灶控制情况)相同或相似的条件下,配对选择两组病例.X-刀加全脑放疗组和常规放疗组各53例.常规放疗组采用全脑照射30～40Gy/3～4周.在X-刀加全脑放疗组中,X-刀治疗采用单次照射40例,分次照射13例,单次靶区平均周边剂量为20Gy.分次照射方法为4～12Gy/次,2次/周,总剂量为15～30Gy.结果KPS评分,颅外肿瘤病变稳定,以及颅内转移灶的数目是影响多发脑转移瘤病人预后的重要因素.中位生存期均有明显差异.在死因分析中,X-刀加全脑放疗组死于脑转移的比例为27%,比常规放疗组的51%低(P＜0.05).但两组病例的放射并发症的发生率相似.结论对于多发脑转移瘤,X-刀加全脑放疗在提高局部控制率,延长生存期和提高生存质量方面均优于单纯放射治疗.     

立体定向放射外科加血脑屏障开放化疗治疗脑深部胶质瘤

目的 研究和评价应用立体定向放射外科加血脑屏障开放、颈动脉灌注化疗治疗脑深部和重要功能区胶质瘤(GDEBA)。方法 对50例患者进行治疗，肿瘤体积19．72cm^3～135．56cm^3，平均43．28cm^3，先行X-刀治疗，术后3～7天行血脑屏障开放、颈动脉卡铂灌注(400mg/次)，4周后重复化疗。结果 随访3月～2．7年，显示24例(48％)肿瘤消失，14例(28％)缩小，6例(12％)保持稳定。6例(12％)肿瘤再生长。在随访超过2年的患者中，存活率为72．7％。死亡5例(10％)。结论 采用X-刀加BBB开放、颈动脉灌注化疗治疗GDEBA是一种微侵袭和风险小的方法，能够延长病人生命，改善生存质量和预后。     

百忧解联合尼莫地平治疗血管性抑郁症的临床研究

目的　探讨百忧解对血管性抑郁症的治疗效果。方法　将血管性抑郁症患者 68例随机分为百忧解治疗组 (n =3 8)和对照组 (n =3 0 ) ,在治疗前和治疗后 4周、8周分别用汉密尔顿抑郁量表 (HAMD)评价疗效。结果　治疗 4周、8周后 ,治疗组抑郁症状改善者明显高于对照组 (P <0 0 5 )结论　百忧解联合尼莫地平治疗血管性抑郁症有较好疗效 ,而且耐受性好。     

齐拉西酮联合心理干预在青少年精神分裂症中的应用效果

目的探讨齐拉西酮联合心理干预在青少年精神分裂症中的临床疗效。方法选取2014年1月~2016年12月医院收治青少年精神分裂症患者90例,随机分为对照组(n=45)和观察组(n=45)。对照组采用齐拉西酮治疗,观察组在对照组的基础上联合心理干预治疗,采用阳性和阴性症状量表(PANSS)对两组治疗效果进行评估。结果观察组治疗后有效率为94.1%,对照组为67.6%,两组差异有统计学意义(P0.05);治疗后,观察组治疗后阳性量表、阴性量表、一般病理及量表总分均低于对照组(P0.05)。结论青少年精神分裂症患者在齐拉西酮基础上联合心理干预治疗效果理想,值得推广应用。     

X-刀在脑转移瘤的补救治疗中的临床研究

目的 研究X-刀在脑转移瘤补救治疗中的价值。方法 应用X-刀治疗脑转移瘤233例,其中12例为行2次或3次X-刀治疗,重复行X-刀治疗的标准为复发的肿瘤部位分散或在以前行立体定向放射治疗的体积以外,KPS70分。第1次靶区平均周边剂量为20Gy(17～30Gy),肿瘤平均体积2.2ml(0.3～20.1ml);第2次靶区平均周边剂量为18Gy(15～30Gy),肿瘤平均体积2.4ml(0.4～12.5ml);第3次靶区平均周边剂量为15Gy,肿瘤平均体积1.2ml(0.4～6.8ml)。结果 本组病人中,第1次X-刀治疗35个病灶,1～2次治疗的中位时间为59周(5～104周),第2次治疗36个病灶,第3次治疗3个病灶。这12个病人中,在治疗过程中全部接受全脑放疗,全脑放疗的剂量为30～36Gy。实际第1次X-刀治疗的中位生存期82周,第2次X-刀治疗 的中位生存期21周。随访中有84％的病人获得影像学资料,90％局部控制,10％在疾病过程中进展,局部控制20周的占94.3％。生存质量提高者占91.7％(11/12)。12例接受X-刀治疗的病人有9例(75％)死亡,其中8例(89％)死于颅内病变,1(11％)例死于系统性疾病,中枢系统的死因为出现癌性脑膜炎或颅内多发转移。结论 SRS治疗后出现其他部位的颅内转移的脑转移瘤的患者,X-刀治疗可作为一种较好的补救治疗措施,延长生存期,提高生存质量。     

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.     

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.