X刀治疗垂体腺瘤的疗效与方法学初探

目的总结50例X刀治疗垂体腺瘤的治疗和临床、内分泌、影像复查资料,评价X刀治疗垂体腺瘤的临床疗效,探讨X刀治疗垂体腺瘤的方法学.方法用X刀对PRL腺瘤36例,GH腺瘤5例,混合性腺瘤4例,无功能性腺瘤5例治疗.肿瘤治疗剂量19.48±3.36Gy,等中心数1.24±0.68个/例,视交叉受重＜8～9Gy.结果随访12～62月,平均32.6月,14例闭经患者恢复月经,共26例月经恢复正常,25例停止溢乳,3例患者溢乳减轻,5例患者受孕,6例患者肢端肥大改善,临床有效率96%.影像学复查肿瘤消失35例,坏死缩小12例,肿瘤控制率100%.在治疗后3～6月,可出现肿瘤坏死缩小,随时间的延长,肿瘤消失率增加,但大体积病变,肿瘤消失困难.结论X刀是一种垂体腺瘤的安全、有效的治疗手段.推荐无功能腺瘤＞12-13Gy,分泌性腺瘤20-30Gy.分次立体定向放射治疗是X刀治疗垂体腺瘤的新课题和努力方向.     

功能性垂体腺瘤伽玛刀治疗后激素水平变化与肿瘤体积变化的相关性

目的 探讨功能性垂体腺瘤伽玛刀治疗后激素水平变化与肿瘤体积变化的相关性。方法 收集2012年1月至2015年1月行伽玛刀治疗的功能性垂体腺瘤72例,其中生长激素（GH）腺瘤32例,泌乳素（PRL）腺瘤40例。伽玛刀治疗前、治疗后1.5年测定激素水平及肿瘤体积。结果 伽玛刀治疗后1.5年,GH腺瘤激素水平较治疗前明显下降（P<0.05）,GH腺瘤体积较治疗前明显缩小（P<0.05）。伽玛刀治疗后1.5年,PRL腺瘤激素水平较治疗前明显下降（P<0.05）,PRL腺瘤体积较治疗前明显缩小（P<0.05）。伽玛刀治疗后1.5年,GH腺瘤激素水平变化与肿瘤体积变化呈明显正相关（r=0.947,P<0.05）。伽玛刀治疗后1.5年,PRL腺瘤激素水平变化与肿瘤体积变化呈明显正相关（r=0.963,P<0.05）。结论 本文结果提示功能性垂体腺瘤伽玛刀治疗后激素水平的变化能反映肿瘤体积的变化,激素水平变化的测定对肿瘤的体积变化的测量具有一定的指导意义。     

侵袭性垂体腺瘤的病理特点初探

目的通过回顾性分析垂体腺瘤的影像学资料及病理学资料,探讨垂体腺瘤的侵袭性。方法回顾性分析59例垂体腺瘤的影像学资料及病理学资料。结果影像结果:侵袭性垂体腺瘤33例,非侵袭性垂体腺瘤26例。肿瘤3 cm 20例,均为侵袭性垂体腺瘤;肿瘤3 cm 39例,其中13例为侵袭性垂体腺瘤,26例为非侵袭性垂体腺瘤。病理结果:PRL腺瘤8例,其中侵袭性腺瘤5例,非侵袭性腺瘤3例;GH腺瘤6例,其中侵袭性腺瘤3例,非侵袭性腺瘤3例;TSH腺瘤2例,均为侵袭性腺瘤;ACTH腺瘤2例,均为非侵袭性腺瘤;混合性腺瘤28例,其中侵袭性腺瘤13例,非侵袭性腺瘤15例;无分泌功能腺瘤13例,其中侵袭性腺瘤10例,非侵袭性腺瘤3例。Ki-67截断值:33例侵袭性腺瘤中23例3%,10例3%;26例非侵袭性腺瘤均3%。结论侵袭性垂体腺瘤的诊断应综合考虑影像学、病理结果及术中所见。垂体腺瘤的侵袭可能与其分泌激素类型无关,发生侵袭的机制仍需进一步深入研究。     

X—刀治疗垂体腺瘤47例报告

我院自1997年11月～2000年9月,对47例垂体腺瘤病人采用了X－刀治疗,近期效果较为满意,现报告如下：1　对象与方法1．1　临床资料　男25例,女22例,发病年龄17～80岁,病程3个月～5年,随访时间6个月～3年。根据临床、实验室检查和影像学检查,诊断泌乳素（PRL）腺瘤19例,生长激素（GH）腺瘤10例,无功能腺瘤8例,促肾上腺皮质激素（ACTH）腺瘤6例,混合性（GH＋PRL）腺瘤4例,手术后PRL瘤残留2例,GH腺瘤残留1例。CT及MRI示肿瘤直径5～47mm。1．2　治疗方法及剂量　用面膜固定在CT定位下（使用美国toplame公司的X－线立体…     

经单鼻孔蝶窦入路神经内镜下切除垂体腺瘤

目的 介绍经单鼻孔蝶窦入路神经内镜下切除垂体腺瘤的经验及体会。方法 对16例垂体腺瘤病人采用经单鼻孔蝶窦入路行神经内镜下垂体腺瘤切除术，其中微腺瘤3例，大腺瘤12例，巨型腺瘤1例。功能性腺瘤14例，其中PRL腺瘤6例，GH腺瘤4例，混合性（PRL GH）腺瘤4例；无功能性腺瘤2例。结果 内镜下全切除肿瘤14例，近全切1例，大部切除1例；无死亡，无脑出血、视神经损伤、脑脊液鼻漏及其他鼻腔并发症发生；2例术后出现一过性多尿，经治疗术后1周恢复正常。随访3-6个月，原有症状均有所改善，异常增高的激素水平均降至正常，MRI检查显示下一例肿瘤复发。结论 内镜下经单鼻孔蝶窦入路垂体腺瘤切除术具有深部照明好，鼻腔结构损伤小，切除肿瘤彻底，术后并发症少，病人恢复快等优点。     

侵袭海绵窦垂体腺瘤的伽玛刀治疗

目的 评价伽玛刀治疗侵袭海绵窦垂体腺瘤的疗效和内分泌激素变化,并分析了治疗后主要的并发症.方法 选择了自1995年9月至2006年1月收治的并获得完全随访资料的128例侵袭海绵窦垂体腺瘤患者,肿瘤直径1.0～4.8 cm(平均3.04 cm),既往手术63例,具有放疗史22例.PRL腺瘤56例,GH腺瘤19例,ACTH腺瘤2例,FSH腺瘤1例,混合性腺瘤22例,无功能性腺瘤28例.采用Leksell立体定位系统,边缘剂量12～35 Gy(平均19.56 Gy).等剂量线45%～50%.平均随访时间34个月.结果 大部分病人均可耐受伽玛刀治疗,急性并发症很少出现.晚期并发症主要表现为视力下降和垂体功能低下.伽玛刀治疗后,肿瘤消失的为4例,肿瘤缩小的为94例,肿瘤大小无变化的26例,4例患者治疗后肿瘤增大,总的肿瘤控制率为96.87%.同时对于功能性腺瘤,于治疗后11例激素水平恢复正常,58例患者激素水平较治疗前下降.结论 伽玛刀治疗侵袭性垂体腺瘤是一种安全、有效的治疗方法.     

催乳素释放肽受体在不同类型垂体瘤的表达及其与血泌乳素水平的相关性

目的探讨催乳素释放肽受体(PrRP-R)在不同类型的垂体瘤中的表达及其与术前泌乳素(PRL)水平、垂体瘤侵袭性之间的关系.方法收集19例垂体瘤标本,其中泌乳素(PRL)腺瘤5例、生长激素(GH)腺瘤6例、促肾上腺皮质激素(ACTH)腺瘤4例、其他4例.根据Hardy-Knosp分级标准,侵袭性腺瘤13例,非侵袭性腺瘤6例.采用半定量RT-PCR方法检测垂体瘤中PrRP-RmRNA的表达,RIA法检测术前血PRL水平.结果19例腺瘤中均有PrRP-RmRNA的表达,在PRL、GH、ACTH腺瘤中的表达量之间无统计学差别(P＞0.05).在侵袭性腺瘤和非侵袭性腺瘤中的表达量分别为(0.69±0.31)、(1.02±0.74),两者之间无统计学差异(P＞0.05).PrRP-R表达量与病人术前PRL水平不具相关性(r=0.189,P＞0.05).结论PrRP-R表达与病人术前PRL水平不相关且与肿瘤的侵袭无关,需进一步研究PrRP-R在PRL分泌中的作用.     

垂体腺瘤的γ-刀治疗

目的评价γ-刀治疗垂体腺瘤的疗效及患者激素水平的变化,以及治疗后的主要并发症。方法对1995年9月-2004年12月经γ-刀治疗并获得完全随访的312例垂体腺瘤患者(包括手术后104例,放射治疗后35例,173例直接采用γ-刀治疗)的临床资料及疗效进行回顾性分析,其中非功能性垂体腺瘤78例,功能性垂体腺瘤234例(催乳素腺瘤124例、生长激素腺瘤37例、促肾上腺皮质激素腺瘤12例、促甲状腺激素腺瘤1例、卵泡刺激素腺瘤8例和混合性腺瘤52例)。根据患者临床症状改善程度、治疗前后肿瘤直径变化及内分泌功能等综合评价疗效。平均随访30.50个月。结果γ-刀治疗后肿瘤完全消失25例(8.01%),缩小152例(48.72%),大小无变化129例(41.35%),增大6例(1.92%),总的肿瘤控制率为98.08%(306/312)。功能性垂体腺瘤患者中77例(32.91%)激素分泌水平恢复正常,102例(43.59%)较治疗前下降,55例(23.50%)无明显改变。γ-刀治疗的晚期并发症主要有视力下降(5例)和垂体功能低下(8例)。结论γ-刀治疗垂体腺瘤患者安全、有效。     

垂体腺病的X刀治疗

目的观察分析X刀对垂体腺瘤的治疗效果.方法对1997年1月至2000年6月应用Radionic公司头部X刀系统,治疗的垂体腺瘤患者随访54例,单次治疗32例,分次治疗22例.其中54例获得影象学复查,36例获得血激素水平复查.随访期3个月到32个月,平均13.2个月.结果肿瘤缩小达55.6%,无一例肿瘤增大;临床症状改善率72.2%,无临床症状加重着.血激素水平恢复正常达30.6%.结论X刀治疗垂体腺瘤安全、有效,无明显副作用,SRT治疗后血激素水平恢复正常率高于SRS治疗,但血激素水平恢复时间长于SRS治疗.     

神经肽Y在人垂体腺瘤中组织学和分子生物学变化的研究

目的 探讨NPY在人垂体腺瘤细胞中的位置和表达,不同类型中的特点.方法 收集我院神经外科经手术和病理确诊的垂体腺瘤57例.免疫电镜研究NPY在垂体腺瘤细胞中的位置.免疫组化和RT-PCR检测NPY的表达.结果 (1)免疫电镜:NPY主要位于胞质的分泌颗粒中,其次位于粗面内质网和细胞基质中.(2)免疫组化:NPY在垂体腺瘤中总体表达的结果为59.6%(34/57);促性腺瘤91.7%,GH腺瘤和ACTH腺瘤均为66.7%,零细胞腺瘤和混合性腺瘤均为50%,PRL腺瘤为25%,它们间的差异有统计学意义(P=0.04).(3)RT-PCR:NPY mRNA在垂体腺瘤中均表达,其差异有统计学意义(P<0.01);促性腺瘤最高是PRL腺瘤的9.3倍、无功能腺瘤5.8倍、GH腺瘤2.7倍,其余组间的差异无统计学意义.结论 (1)人垂体腺瘤中存在NPY.(2)垂体腺瘤中的确有NPY表达,不同类型中的表达各有差异;促性腺瘤表达最高,PRL腺瘤表达最低.(3)为今后深入探讨NPY在垂体腺瘤中的作用奠定了基础.     

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.