吡仑帕奈治疗局灶性癫痫的研究进展

吡仑帕奈为第三代新型抗癫痫发作药物，通过非竞争性抑制α-氨基-3-羟基-5-甲基-4-异恶唑啉丙酸受体来发挥其抗癫痫发作作用。多个国家已批准用于≥4岁局灶性癫痫患者（伴或不伴继发全面性发作）的单药及添加治疗。该文总结了吡仑帕奈治疗局灶性癫痫患者的作用机制、药代动力学、疗效及不良反应等的相关文献，以期为临床医师治疗局灶性癫痫提供更多的药物选择，从而更好地为临床上合理化用药提供依据。 [国际神经病学神经外科学杂志, 2023, 50(4): 85-89]     

拉考沙胺和吡仑帕奈单药治疗癫痫的研究进展

抗癫痫发作药物(Antiseizure medications,ASMs)在癫痫患者的治疗中起着重要的作用,因为大多数患者需要长期的抗惊厥治疗。由于高达30%的患者对药物治疗不耐受,因此需要选择新的治疗。单药治疗是新诊断癫痫治疗的金标准,如果第一次治疗不成功,可以选择第二次单药治疗。拉考沙胺(Lacosamide,LCM)和吡仑帕奈(Perampanel,PER)是第三代新型ASMs,最新被批准用于局灶性癫痫的单药治疗。PER对α-氨基-3-羟基-5-甲基4-异恶唑丙酸(AMPA)受体具有独特的和选择性的作用模式。LCM通过选择性地增强电压门控钠通道的慢失活来发挥作用。文章对拉考沙胺和吡仑帕奈的作用机制、药物代谢动力学,以及作为单药治疗在癫痫患者中的有效性及安全性等方面作一综述,以期为临床医师提供用药参考,利于癫痫的个体化治疗。     

吡仑帕奈治疗儿童难治性癫痫的研究进展

吡仑帕奈是第三代新型抗癫痫药,自其上市,已经在许多国家广泛用于治疗各种儿童癫痫,并取得较好疗效。本文综述了吡仑帕奈在儿童难治性癫痫治疗方面的临床疗效、不良反应、认知功能影响等,有助于临床医生更全面地了解吡仑帕奈在儿童癫痫治疗方面的临床特点,尽可能大地在控制发作和降低不良反应间取得平衡,以更好地治疗癫痫患儿。     

第三代新型抗癫痫药吡仑帕奈在癫痫治疗中的研究进展

吡仑帕奈是第三代新型抗癫痫药物(AEDs),也是首个治疗癫痫的高度选择性非竞争性α-氨基-3-羟基-5-甲基-4-异喃恶唑丙酸(α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid,AMPA)型谷氨酸受体拮抗剂。现已在许多国家广泛用于治疗各种癫痫,并取得较好疗效。文章对吡仑帕奈在癫痫治疗方面的临床用法、药物代谢动力学、临床疗效和不良反应等作一综述,以帮助临床医生更全面地了解吡仑帕奈临床特点,利于癫痫的个体化治疗。     

新型抗癫痫药物的研究进展

癫痫常需多种药物联合治疗。目前,拉科酰胺,依佐加滨,吡仑帕奈和醋酸艾司利卡西平等新型抗癫痫药物不断被应用到临床试验中。本文对近年应用于临床新药的作用机制、临床评价、安全性、药代动力学、药效学、注意事项及药物相互作用方面的研究进展进行综述。     

吡仑帕奈治疗儿童难治性癫痫的疗效和安全性研究

目的评估吡仑帕奈在儿童难治性癫痫患者中的有效性、安全性与耐受性。方法回顾性分析2020年1月—2021年1月在苏州大学附属儿童医院就诊的34例难治性癫痫患儿的病历资料,通过对比患儿的基线情况与吡仑帕奈添加治疗后第4、8、12、24、36、48周的癫痫发作情况,来评估吡仑帕奈的疗效与不良反应。结果患儿添加吡仑帕奈治疗时的平均年龄为(8.1±4.1)岁,男女性别比为1∶1。吡仑帕奈添加治疗后,第4、8、12、24、36、48周的有效率分别为37.5%、46.7%、50.0%、47.4%、53.8%、42.9%,不良反应发生率为32.4%,药物保留率为88.2%。结论吡仑帕奈治疗难治性癫痫具有良好的有效性、安全性与耐受性。个性化治疗和较好的基线发作控制水平或许可以提高吡仑帕奈治疗的有效性和药物保留率。     

托吡酯治疗癫痫的临床疗效及安全性的观察

目的　观察及评价托吡酯对各型癫痫的临床疗效及安全性。方法　对 1998年 12月至2 0 0 0年 12月在我院确诊的 14 2例癫痫患者中的 93例采用托吡酯添加治疗、4 9例单药治疗 ,经 8周加量期和 12周稳定期观察后进行评价。结果　添加治疗组及单药治疗组总有效率分别为 79%和84 % ,完全控制率分别为 2 8%和 4 1%。成人有效剂量为 10 0～ 2 0 0mg/d ,儿童 3～ 5mg·kg-1·d-1。不良反应较轻 ,耐受性良好。结论　托吡酯是一种广谱、有效及安全的新型抗癫痫药 ,可作为一线抗癫痫药添加或单独使用。     

托吡酯治疗各型癫癎的疗效与安全性观察

目的 观察托吡酯（TPM)对成人和儿童各型癫痫的临床效果与安全性。方法 用开放性试验方法对100例癫痫患者进行了添加、添加转单药以及首诊单药的托吡酯治疗；以加用托吡酯前3个月的平均月发作频率为基准，与用托吡酯进入稳定期后的月平均发作频率进行比较，按常规计算发作减少百分比的中位值和有效率百分比。结果 托吡酯无论在添加治疗、添加转单药以及单药治疗上均有明显疗效。添加组70％患者的发作减少，添加转单药组发作减少者占78％，而单药组发作减少者占86％。其抗癫痫谱广，可用于单纯部分性发作伴或不伴全面性发作、复杂部分性发作伴或不伴全面性发作、婴儿痉挛以及Lennox—Gastaut综合征。托吡酯的不良反应以中枢神经系统最常见，但导致治疗中断的不良反应少见，本组仅3例因不良反应而中断治疗。结论 托吡酯是广谱抗癫痫药，疗效肯定，无耐药性，无严重不良反应，即既可用于添加治疗也可作为单药治疗。     

托吡酯添加治疗转换为单药治疗癫痫56例疗效观察

目的 观察添加托吡酯(TPM)治疗有效的癫痫患者转换为TPM单药治疗的疗效。方法 对56例添加TPM治疗有效并持续6个月以上的患者，逐渐减、停合用的抗癫痫药，转换为TPM单药治疗。结果 转换成功32例(57．1％)，完全控制13例，显效15例，有效4例，恶化4例，中途退出20例；不良反应减少14例次(35．8％)。结论 添加TPM治疗有效且稳定的非难治性癫痫患者大多数可成功转换为TPM单药治疗，而难治性癫痫患者转换为TPM单药治疗的成功率较低。     

托吡酯治疗难治性癫癎32例分析

目的观察托吡酯治疗难治性癫痫的疗效与安全性。方法对32例难治性癫痫患者加用托吡酯治疗进行临床观察研究。结果15例患者发作频度减少≥50％,8例患者发作频度减少到26％～49％,疗效较佳;各种类型癫痫之间发作减少差异不显著;与不同抗癫痫药物合用疗效无差异。结论托吡酯是一种有效的广谱抗癫痫药,能与常用抗癫痫药合用。     

Cultural Identity and Experiences of Prejudice and Discrimination of Afghan and Iranian Immigrant Youth

In culturally diverse and immigrant receiving societies, immigrant youth can be subject to prejudice and discrimination. Such experiences can impact on immigrant youth’s cultural identity and influence their psychosocial outcomes. This paper presents findings of a study that examined cultural identity and experiences of prejudice and discrimination among Afghan (N = 9) and Iranian (N = 17) immigrant youth in Canada. The study had a prospective, comparative, longitudinal qualitative design. Data was gathered through focus groups, interviews, journals and field logs. Four main themes emerged on participants’ experiences of prejudice and discrimination: (a) societal factors influencing prejudice; (b) personal experiences of discrimination; (c) fear of disclosure and silenced cultural identity; and (d) resiliency and strength of cultural identity. Drawing from Rosenberg’s (Conceiving the self, Basic Books, New York, 1979) self-concept framework and Romero and Roberts (J. Adolesc., 21:641–656, 1998) distinction between prejudice and discrimination, results indicated that youth’s extant and presenting cultural identity were affected. Inclusive policies and practices are needed to promote youth integration in multicultural and immigrant receiving settings.

癫痫共病抑郁的机制及临床诊疗

本文目的是探讨癫痫共病抑郁的可能机制及临床诊疗。癫痫是一种常见的、慢性的、致残性的神经疾病,癫痫患者生活质量下降,存在明显的负性情绪,常伴发各种精神疾病。癫痫与抑郁具有共同的神经生物学基础,可能存在共同的发病机制。本文从癫痫共病抑郁的发病机制、临床诊断及治疗方面予以总结归纳。     

沙盘游戏疗法在地中海贫血患儿心理干预中的应用

本文目的是对沙盘游戏疗法在地中海贫血患儿心理干预中的应用进行综述,以期为地中海贫血患儿的心理康复提供参考。地中海贫血是以珠蛋白生成障碍为主要特征的遗传性疾病,由于长期输血治疗,患儿存在较多的心理和行为问题。沙盘游戏疗法作为一种有效、实用的儿童心理治疗方法,对提高地中海贫血患儿的康复效果、改善生存质量有重要的临床意义。     

Efficacy and Effectiveness of Child and Adolescent Psychotherapy and Pharmacotherapy

Decades of intervention research have produced a rich body of evidence on the effects of psychotherapies and pharmacotherapies with children and adolescents. Here we summarize and critique that evidence. We review findings bearing on the efficacy of psychosocial treatments and medications under controlled experimental conditions. We also report evidence, where available, on the effectiveness of both classes of treatment with clinically referred youth treated in real-world clinical contexts. In general, the large body of evidence on efficacy contrasts sharply with the small base of evidence on effectiveness. Addressing this gap through an enriched research agenda could contribute importantly to linking scientific inquiry and clinical practice—to the benefit of both ventures. This is one element of a multifaceted agenda for future research and for synthesis of research, which will require the interplay of multiple disciplines related to child and adolescent mental health.     

小胶质细胞和少突胶质细胞前体的培养和鉴定

目的 探讨新生大鼠脑组织小胶质细胞(MG)和少突胶质细胞(OL)前体的分离和体外培养方法 . 方法 取新生2 d SD大鼠脑组织,体外原代培养混合胶质细胞7 d后,分别采用"改良振荡伴差速贴壁"法和"营养缺失伴振荡"法纯化培养MG和OL前体,并分别应用免疫荧光染色异凝集素-B4(IB4)和OL前体标记物(O4)进行鉴定.结果 混合胶质细胞培养7 d后呈明显三层增长,其中MG位于上层,星型胶质细胞位于底层,两者之间为2型少突星型(O2A)祖细胞.纯化培养后OL前体胞体呈小圆形,有双极或三极突起,MG则以阿米巴形、圆形居多,或边缘呈毛刺状.免疫荧光染色IB4显示绿色荧光,MG纯度达到90%以上.免疫荧光染色O4显示棕黄色荧光,OL前体纯度达到95%以上. 结论 采用"改良振荡伴差速贴壁"法以及"营养缺失伴振荡"法分别成功获取大量纯度高、活力好的MG和OL前体.     

发作性睡病与异态睡眠的诊治

本文目的是探讨发作性睡病与异态睡眠的诊断与治疗。发作性睡病被漏诊和误诊的几率较高,危害较大,共患异态睡眠比例高。文章从发作性睡病临床特征、REM睡眠的作用、发作性睡病与异态睡眠(睡眠瘫痪、睡眠幻觉、快眼动睡眠期行为障碍)共病特征及治疗这四个方面进行了讨论。     

Neurological and neuropsychological consequences of electrical and lightning shock:review and theories of causation

Injuries from lightning and electrical injuries involve multiple systems of the body, however neurological symptoms are very widely reported. A disabling neuropsychological syndrome is also noted.This paper presents a comprehensive review of neurological and neuropsychological symptoms. Partial theories of causation for these injuries have been advanced, however, there is no convincing explanation for both delay in onset of symptoms and also the genesis of the neuropsychological syndrome. A theory of causation is proposed which satisfies both these constraints.This theory suggests circulating hormones such as cortisol, together with nitric oxide and oxidant free radicals from glutamatergic hyper-stimulation, act on tissues remote from the injury path including the hippocampus.This theory opens a research path to explore treat-ment options.     

Review and meta-analysis of the phenomenology and clinical characteristics of mania in children and adolescents

OBJECTIVE: Using predetermined criteria for study quality and methods, a literature review and meta-analysis of seven reports about pediatric bipolar disorder (BPD) was conducted to determine if there is a consistent picture of the phenomenology and clinical characteristics of BPD in children and adolescents. METHODS: Searches were conducted in MedLine and PsycINFO using the terms mania, BPD, children and adolescents, and was limited to published articles in peer-reviewed journals. Seven reports were selected that met the following criteria: a systematic method for the elicitation and reporting of symptoms and clinical characteristics of subjects; subjects were interviewed by a trained researcher or clinician; ages 5-18 years; use of a diagnostic system, either DSM or RDC for categorization; a consensus method for the establishment of the diagnosis of BPD. RESULTS: Most DSM-IV symptoms of mania were common in the children and adolescents with BPD with the most common symptoms being increased energy, distractibility, and pressured speech. On average, four of five bipolar cases also showed threshold levels of irritable mood and grandiosity, and more than 70% of all cases showed elated/euphoric mood, decreased need for sleep, or racing thoughts. Roughly 69% of cases also showed poor judgment, whereas only half of bipolar cases demonstrated flight of ideas, and slightly more than one-third showed hypersexuality or psychotic features. CONCLUSIONS: The clinical picture that emerges is that of children or adolescents with periods of increased energy (mania or hypomania), accompanied by distractibility, pressured speech, irritability, grandiosity, racing thoughts, decreased need for sleep and euphoria/elation.     

Design and pharmacological activity of glycinamide and N-methoxy amide derivatives of analogs and constitutional isomers of valproic acid

A series of glycinamide conjugates and N-methoxy amide derivatives of valproic acid (VPA) analogs and constitutional isomers were synthesized and evaluated for anticonvulsant activity. Of all compounds synthesized and tested, only N-methoxy-valnoctamide (N-methoxy-VCD) possessed better activity than VPA in the following anticonvulsant tests: maximal electroshock, subcutaneous metrazol, and 6-Hz (32-mA) seizure tests. In mice, the ED₅₀ values of N-methoxy-VCD were 142 mg/kg (maximal electroshock test), 70 mg/kg (subcutaneous metrazol test), and 35 mg/kg (6-Hz test), and its neurotoxicity TD₅₀ was 118 mg/kg. In rats, the ED₅₀ of N-methoxy-VCD in the subcutaneous metrazol test was 36 mg/kg and its protective index (PI = TD₅₀/ED₅₀) was > 5.5. In the rat pilocarpine-induced status epilepticus model, N-methoxy-VCD demonstrated full protection at 200 mg/kg, without any neurotoxicity. N-Methoxy-VCD was tested for its ability to induce teratogenicity in a mouse strain susceptible to VPA-induced teratogenicity and was found to be nonteratogenic, although it caused some resorptions. Nevertheless, a safety margin was still maintained between the ED₅₀ values of N-methoxy-VCD in the mouse subcutaneous metrazol test and the doses that caused the resorptions. On the basis of these results, N-methoxy-VCD is a good candidate for further evaluation as a new anticonvulsant and central nervous system drug.     

Long-term health and socioeconomic consequences of childhood and adolescent-onset of narcolepsy

ObjectivesThere is limited information about the long-term consequences of childhood- and adolescent-onset narcolepsy on educational and social factors. Here, we estimate the long-term socioeconomic consequences and health care costs of narcolepsy.MethodsThe prospective cohort study included Danish individuals with narcolepsy onset in childhood or adolescence, diagnosed between 1994 and 2015. Health care costs and socioeconomic data were obtained from nationwide administrative and health registers. One hundred seventy-one patients were compared with 680 controls (mean index age, 15.2 years; SD, 3.4 years) matched for age, gender, and other sociodemographic characteristics.ResultsComparing the narcolepsy patient and control groups at age 20 years we found: (1) no differences in parental educational level; (2) patients had a significantly lower educational level than controls; (3) patients had significantly lower grade-point averages; (4) patients had a lower employment rate and lower-income, even when transfer payments were considered; and (5) patients' initial health care costs were higher. Patients had a higher mortality rate than controls, although the difference was not statistically significant.ConclusionNarcolepsy is associated with a significant influence on educational level, grading, social outcome, and welfare consequences. The development of narcolepsy is independent of parental social level.