抗癫药物的作用机制与用药

癫(癎)是一种常见病、多发病,药物治疗是最重要的手段.采用现代有效的抗癫(癎)药物,可使约80%患者的癫(癎)发作获得控制.然而,到目前为止仍无一种药物能控制所有发作类型或癫(癎)综合征.正确选择抗癫(癎)药物,是疗效的保证.除按照癫(癎)发作类型和综合征选择外,还要参考抗癫(癎)药物的作用机制.     

癫(癎)患儿预后与相关因素的远期随访研究

目的 分析影响癫(癎)患儿预后的相关因素,为癫(癎)的诊治和预后评估提供依据.方法 回顾性分析2003年1-12月在北京大学第一医院儿科门诊就诊的290例癫(癎)患儿的临床资料,随访患儿发作、用药、智力及精神运动发育等情况,以至少1年无发作为疗效控制指标.结果 ①经正规抗癫(癎)药物治疗,57.9%患儿发作控制满意,多数可以正常学习或生活;(②各型癫(癎)均有控制发作的可能,不同发作类型癫(癎)的控制率不同;③起病年龄越早,特别是1岁内起病者发作控制较差;④原发性癫(癎)控制率明显高于症状性或隐源性癫(癎),症状性癫(癎)预后最差;⑤大部份病例经单药治疗可以控制发作,2种药物治疗未控制者,再添加药物进行治疗,控制率无明显提高.结论 儿童癫痫的预后大多良好,有下列情况者预后差:①起病年龄小,尤其是1岁者;②同时有多种发作形式;③症状性癫(癎).     

癫癎患儿的认知障碍

超过1/3的癫癎患儿存在不同程度的认知障碍,引起癫癎认知障碍的因素较多,癫癎基础疾病、癫癎临床或电的发作、抗癫癎药物、外科手术等均可影响认知功能。相对成人而言,儿童癫癎的认知障碍有其特殊性,需要更多的关注和研究。     

难治性癫(癎)与多药转运体关系的研究进展

儿童癫癎是儿科神经系统常见的一种发作性疾病,其中20%～30%为难治性癫癎(IE).儿童IE的发病机制尚不明确,国内外研究认为可能与不同作用机制的多种抗癫癎药耐药有关,与多药耐药基因表达异常有关.目前研究多药转运体抗癫癎药物耐药机制最多的有p-糖蛋白、多药耐药相关蛋白,二者是存在于细胞膜上的蛋白质趟家族,属于ATP依赖的膜转运蛋白.研究显示IE患者颞叶脑组织及慢性癫癎动物模型中p-糖蛋白、多药耐药相关蛋白等多药转运体过度表达,它们通过利用分解ATP所释放的能量,以主动转运的方式将大量抗癫癎药物转运到大脑毛细血管内皮细胞之外,降低治疗药物在细胞内的水平,从而产生耐药.现就多药转运体的结构、分布、功能及其与癫癎耐药的关系作一综述.     

努力提高小儿癫痫的诊断水平

小儿癫癎不仅是小儿神经系统的常见病、多发病,也是可以治疗的疾病。小儿时期癫癎的发生率相当于成人的10倍～15倍,而且其临床表现复杂多样,在国内外癫癎分类上,众多的癫癎发作类型,癫癎及癫癎综合征,几乎在小儿时期都可以见到。同时经过合理、规范治疗,小儿癫癎的控制率可达到80％左右,且其中大多数患儿是可以治愈的。必须指出的是小儿癫癎的正确诊断是合理治疗的根本保     

以癫(癎)发作为主要表现的甲状腺功能亢进症

目的 探讨甲状腺功能亢进症(甲亢)伴癫(癎)样发作的临床特点及发病机制.方法 总结本院2例住院甲亢患儿,均为女童.1例3岁7个月患儿出现高代谢症状9个月余,未给予正规治疗出现抽搐发作;另1例12岁患儿已诊断甲亢并口服抗甲亢药物,症状好转后自行停药,1周后出现抽搐发作.2例患儿的发作形式均为全面性强直-阵挛发作.根据患儿临床表现、实验室检查、治疗及转归,同时回顾性分析PUBMED检索及中文医学期刊全文数据库,从1975年至今国内外相关文献报道共18例甲亢伴癫(癎)样发作患儿(年龄3～18岁;男7例,女11例).结果 甲亢伴发癫(癎)样发作形式主要为全面性强直一阵挛发作,共18例;2例青春期患者表现为肌阵挛发作.其中有3种临床表现形式:8例(8/20例,占40%)以癫(癎)样发作为首发症状,分别在首发症状出现1个月～2 a才确诊为甲亢;癫(癎)样发作为继发症状9例(9/20例,占45%),在确诊为甲亢2个月～4 a出现癫(癎)样发作,多为甲亢控制欠佳或中断药物时发生;癫(癎)患者并甲亢时癫(癎)样发作加重3例(3/20例,占15%),均在青春期合并甲亢时发作次数明显增加.结论 甲亢可引起癫(癎)样发作,其发作与甲状腺激素水平升高关系密切;甲亢与癫(癎)可能存在某些共同的免疫发病机制.     

癫癎儿童心理状态及影响因素的调查研究

目的评估癫癎儿童的心理状态,分析影响癫癎儿童心理状态的可能因素。方法采用儿少心理健康量表(MHS-CA)对113例癫癎儿童和114例正常儿童进行心理状态评定及比较。癫癎组儿童填写患儿一般情况和癫癎病情及治疗情况调查表。正常对照组儿童填写儿童一般情况调查表。分析影响癫癎儿童心理状态的可能因素。结果癫癎儿童在认知、思维、情绪、意志行为、个性特征上的心理健康状态均低于对照组儿童,差异有统计学意义(P0.05)。多因素logistic回归分析显示家庭教育方式、家庭关系、癫癎发作频率、癫癎发作持续时间、近6个月EEG癎样放电、抗癫癎药物使用种数为影响癫癎儿童心理状态的危险因素。结论癫癎儿童较正常儿童存在更广泛的心理健康问题。家庭生活环境差、癫癎控制不佳及多种抗癫癎药物应用是影响癫癎儿童心理状态的危险因素;改善家庭生活环境,尽量控制癫癎发作及使用单药治疗有助于改善癫癎患儿心理状态。     

癫发作的分类

阐述2001年癫(癎)发作分类新建议对癫(癎)发作类型重新划分的新观点及术语、概念的变化,并对一些新列入的发作类型进行r简单的介绍.新建议中的癫(癎)发作类型主要是依据其病理生理机制和解剖基础的分类,是集病因、治疗和预后为一体的诊断实体,可以对癫(癎)综合征的诊断起补充作用,或在不能作出癫(癎)综合征诊断时,单独进行诊断.现对国际抗癫(癎)联盟2001年与1981年提出的癫(癎)发作分类进行比较.     

小儿结节性硬化症合并癫癎的随访研究

目的：调查结节性硬化症（TSC）合并癫癎的治疗转归及癫癎反复发作的高危因素。方法：回顾性分析我院66例TSC患儿的资料。结果：66例TSC患儿中,随访47例,随访时间为7个月至9.3年,平均4.5±2.6年。患儿现在年龄7.7±4.1岁,癫癎发作类型：40%有婴儿痉挛症,51%有强直性发作,32%有部分性发作,强直-阵挛性发作占6%,多灶性发作、失张力发作、不典型失神发作、抑制性运动发作各占2%。目前使用抗癫癎药1.9±0.86种,中位数1种。26%仍然癫癎发作,70%无发作,4%死亡。手术治疗3例,均在继续用药,随访1.5年以上,无发作。应用非条件logistic回归方法分析,发现起病年龄（RR=1.8, 95% CI 1.0～3.2, P=0.050）、抗癫癎药的种类(RR=4.8, 95% CI 1.2～18.6, P=0.024)、强直发作(RR=0.003, 95% CI 0.0～0.2, P=0.04)、性别(RR=0.016, 95% CI 0.0～0.5, P=0.017）是癫癎反复发作的高危因素。30例7岁以上儿童57%例可以上普通学校, 10%上特殊学校; 33%因为智力、言语发育落后不能上学。结论：对TSC合并癫癎进行抗癫癎治疗可以达到大部分无发作。癫癎发作起病年龄早、强直发作、需要多种抗癫癎药是癫癎反复发作的高危因素。［中国当代儿科杂志,2009,11（12）：996-998］     

难治性癫(癎)耐药的分子生物学机制

癫(癎)是儿科常见病、多发病.虽然大多数癫(癎)患儿经过目前正规临床药物治疗后可以获得满意的控制,但仍约有20%～30%发作得不到有效控制而成为难治性癫(癎).其治疗困难的原因一方面与其发病机制复杂有关,另一方面则是由于多药耐受,即对不同化学结构、不同作用方式的临床常用的多种抗癫(癎)药物(anti-epileptic drugs,AED)产生耐药性.癫(癎)多药耐受的原因有:病变或癫(癎)发作造成药物作用靶点的改变,使AED的敏感性减低;多药耐受基因及其编码药物转运体蛋白如P糖蛋白、多药耐药相关蛋白、穹隆体主蛋白等多种蛋白过度表达,使AED通过血脑屏障时被主动泵出增加,局部的AED达不到有效浓度;谷胱甘肽转移酶活性增高加快了脑内药物的降解速度,从而降低了脑组织局部药物浓度等都参与了癫(癎)多药耐受的发生.     

Neonatal epilepsy and inborn errors of metabolism]

Metabolic disorders constitute an important cause of neurologic disease, including neonatal epilepsy. Epilepsy rarely dominates the clinical presentation, which is more frequently associated with other neurologic symptoms, such as hypotonia and/or vigilance disturbances. In most cases, epilepsy secondary to inherited metabolic disorders presents with polymorphic clinical and electrographic features that are difficult to classify into precise epileptic syndromes. However, specific types of seizures, such as myoclonic seizures or distinctive electroencephalographic patterns, such as suppression burst patterns, epileptic syndrome or early myoclonic encephalopathy, may suggest a specific metabolic disease. The aim of this article is to help clinicians in reviewing potential metabolic diagnoses and approaching metabolic evaluations.     

伴高热惊厥史的儿童癫痌病例分析

分析伴高热惊厥史的癫痌患儿的临床特点,探讨高热惊厥脑损伤及其与颞叶癫痌的关系。 方法对1996～1999年本院儿科神经病房480例住院癫痌患儿进行回顾性分析,包括首发年龄、家族史、持续时 间、癫痌发作类型、神经影像学及脑电图改变等。结果115例(23.9％)患儿有前期高热惊厥史。伴高热惊厥史 的患儿癫痌发作早且易于出现癫痌持续状态。与无高热惊厥史的患儿相比,伴高热惊厥史的患儿强直-阵挛发作 较多,复杂部分性发作较少。408例患儿曾行影像学检查,4例提示有海马硬化者均无高热惊厥史。在伴高热惊厥史 的癫痌患儿中脑电图局灶起源的异常放电显著低于无高热惊厥史的癫痌患儿。有6.08％(7/115)伴高热惊厥史的癫 痌惠儿和6.84％(25/365)无高热惊厥史的癫痌患儿脑电图表现为单纯颞叶异常放电,二组相比无明显差异。结论 在癫痌患儿中,高热惊厥可能伴有脑损伤,且可能与后期的癫痌发生有关,伴高热惊厥史者不一定发展为颞叶癫痌。     

Behavioural and neuropsychological problems in refractory paediatric epilepsies

The associated behavioural and neuropsychological profiles were studied in 573 children with refractory epilepsy, admitted in our residential Rehabilitation and Epilepsy Unit during the period 1984-2000. The aim of this study was to look for possible correlations between epileptic categories and behavioural profiles. The most frequent neuro-behavioural correlates in the different epilepsy categories were pervasive disorders (48/573=8%), attentional problems (43/573=7.5%), loss of self-esteem (n=49 or 9%) and self-induction of seizures (n=34 or 7%). Pervasive disorders were significantly more frequent in secondary generalised epilepsies. In 86/573 children (15%), mental decline due to epileptic process itself was observed. As expected this was seen in all patients with Lennox-Gastaut syndrome, West syndrome, severe myoclonic epilepsy of infancy and in continuous spikes and slow waves during slow wave sleep. The only behavioural problem that was more frequent in females was self-induction of seizures.     

Abnormal circadian rhythm in patients with GRIN1-related developmental epileptic encephalopathy

GRIN1 encodes the obligate subunit (GluN1) of glutamate N-methyl-d-aspartate receptor (NMDAr). Pathogenic variants in GRIN1 are a well-known cause of infantile encephalopathy characterized by profound developmental delay (DD), variable epileptic phenotypes, and distinctive behavioral abnormalities. Recently, GRIN1 has also been implicated in the pathogenesis of polymicrogyria (PMG).We investigated two patients presenting with severe intellectual disability (ID), epilepsy, stereotyped movements, and abnormal ocular movements. They showed distinctive circadian rhythm alterations and sleep-wake patterns anomalies characterized by recurrent cyclic crying or laughing spells. Genetic analysis led to the identification of two distinct de novo variants in GRIN1 affecting the same amino acid residue of an important functional protein domain.Recent advances in circadian rhythm and sleep regulation suggest that abnormal GluN1 function might play a relevant pathogenetic role for the peculiar behavioral abnormalities observed in GRIN1 patients. Our cases highlight the relevance of circadian rhythm abnormalities in epileptic children as a clue toward GRIN1 encephalopathy and expand the complex phenotypic spectrum of this severe genetic disorder.     

The clinical use of dynamic EEG in childhood]

A-EEG is an important recent technologic innovation in EEG recording that facilitates long-term monitoring. The system consists of a miniature cassette tape recorder and a video play-back unit, which permits the taped EEG to be reviewed (Brain Spy CH24, Micromed). Because it is extremely lightweight and portable, the system permits unrestricted activity during recording. On the other hand, this predisposes the recording to more artifacts than are seen in routine recordings. We examined 103 patients, aged 3 months-24 years, between July 1988 and July 1990. Patients were divided into three groups: group 1 included 61 subjects with evidence of epilepsy and clinically definite seizures; group 2 included 29 patients with recurrent episodes that were not clearly epileptic (suspected "pseudo epileptic"); group 3 included 13 subjects with psychiatric disorders. We found that the clinical utility of A-EEG in epileptic children was: 1) obtain better clinical and EEG characterization and circadian distribution of seizures in 17 cases (28%); 2) quantify epileptiform generalized abnormalities and their variations during the sleep in 6 cases (10%); 3) verify the efficacy of specific drug treatment such as Bzd and ACTH in 12 cases (20%). The role of A-EEG in non-epileptic children with pseudoseizures was to establish the epileptic or non epileptic nature of some ictal events by detecting EEG seizure patterns in 11 cases (38%). As to regard the group 3, A-EEG has permitted to study sleep architecture and REM sleep measures, especially in depressed children compared to normal children. We discuss advantages, drawbacks and clinical applications of A-EEG in child neurology and psychiatry vs conventional EEG.     

儿童孤独症谱系障碍与癫癎共患病的研究

目的探讨儿童孤独症谱系障碍(ASD)与癫癎的相关性。方法选取ASD患儿190例,采用自编问卷、儿童孤独症评定量表和孤独症行为量表对儿童ASD与癫癎相关问题进行调查。结果 190例ASD患儿中,20例(10.5%)曾有癫癎发作,12例(6.3%)被诊断为癫癎。有癫癎发作的ASD儿童1岁前出现体格发育问题及听力问题的比例较无癫癎发作的ASD儿童显著增高(P0.05);被诊断为癫癎的患儿及正接受癫癎治疗的患儿1岁前出现体格发育问题的比例显著增高(P0.05)。有癫癎发作的ASD儿童其感觉反应能力和行为能力较无癫癎发作的ASD儿童差(P0.05)。癫癎治疗对ASD儿童行为有正向影响(P0.05)。结论儿童ASD与癫癎患病有显著关联,可根据儿童1岁前生长发育状况、感觉反应能力和行为能力及有无癫癎发作评估二者共患的可能性。     

Topiramate as a new antiepileptic drug in epileptic children in Iran

Objective It is known that current antiepileptic drugs cannot control seizures in 20–30% of patients. The aim of this study was to evaluate the efficacy and safety of topiramate (TPM) as add-on therapy in intractable epileptic children in Iran. Methods As a quasi- experimental (before and after) study, 42 iranian children aged 1–15 years, 28 boys and 14 girls with refractory seizures seeking treatment were recruited to be subjects of this study. Results Type of seizures of those 42 epileptic children were as follows: L.G.S. (n=14), idiopathic epilepsy (n=8), symptomatic epilepsy (n=16) and progressive myoclonic epilepsy (n=4). At the end of three months of treatment in which topiramate was used concomitantly with previous AED, 17% became seizure free, 26% had more than 50% reduction of seizure frequency and 5% of them had increasing seizures. Therefore, the drug is statistically significant in seizures reduction. The efficacy of the drug was statistically significant in idiopathic and symptomatic epilepsy. The author’s did not notice any serious side effects such as: hematologic abnormality, hepatotoxicity and nephrotoxicity. Conclusion This study supports efficacy and safety of TPM in controlling of intractable epilepsy in children and indicates the drug should be considered as an add-on therapy in the management of refractory epileptic syndromes.     

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??Children??especially young children with epilepsy have unique eletro-clinical characteristics that are different from those of adults. To fully understand the characteristics of epileptic seizures in childhood has an important value for proper classification and localization of epileptogenic zone. In addition??epilepsy in children with developmental and early acquired lesions usually present generalized patterns of seizures and epileptiform discharges??which is common in young children and may cause a delay surgical intervention that result in the children developmental delay of psychomotor. Being familiar with the electro-clinical features of epileptic pathology in children is crucial for selecting the appropriate surgical candidates.     

Prolactin and cortisol levels in various paroxysmal disorders in childhood

The hormonal response of the anterior pituitary to various epileptic and nonepileptic events in children was studied. Postictal serum prolactin and cortisol levels were measured in 17 children with epilepsy, 23 with febrile seizures, and 10 with syncope or breath-holding spells. The levels were compared with those of 30 children with nonspecific fever, and 23 afebrile children served as control subjects. Significantly higher (P less than .01) prolactin levels (26.5 +/- 3.3 ng/mL, mean +/- SEM) were found in the epileptic group, compared with levels in children with febrile seizures (13.2 +/- 1.0 ng/mL), fever (11.2 +/- 0.9 ng/mL), syncope (7.3 +/- 0.9 ng/mL), and the control group (7.9 +/- 0.6 ng/mL). In contrast, serum cortisol levels were nonspecifically elevated in the epileptics and patients with febrile seizures or fever only. These findings suggest that elevated prolactin levels may be found after epileptic seizures and much less after febrile seizures, but not after breath-holding spells or syncopal events. Cortisol secretion appears to be nonselectively triggered by all stressful events, such as epileptic and febrile seizures, and fever. Elevated prolactin levels (greater than 15 ng/mL) associated with seizures may help in differentiating epileptic from febrile seizures or syncope.