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Neuroscience Bulletin 2023年第11期39卷 1605-1622页

作者： Zhijuan Zhang Hui Zhang Ana Antonic‑Baker patrick kwan Yin Yan Yuanlin Ma Department of Neurology Chongqing Key Laboratory of NeurologyThe First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Chongqing Emergency Medical Center The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Neuroscience Central Clinical SchoolMonash UniversityMelbourneAustralia

Epilepsy is a common,chronic neurological disorder that has been associated with impaired neurodevelopment and *** chemokine receptor CXCR5 is involved in seizures via an unknown ***,we first determined the expression pattern and distribution of the CXCR5 gene in the mouse brain during different stages of development and the brain tissue of patients with ***,we found that the knockdown of CXCR5 increased the susceptibility of mice to pentylenetetrazol-and kainic acid-induced seizures,whereas CXCR5 overexpression had the opposite ***5 knockdown in mouse embryos via viral vector electrotransfer negatively influenced the motility and multipolar-to-bipolar transition of migratory *** a human-derived induced an in vitro multipotential stem cell neurodevelopmental model,we determined that CXCR5 regulates neuronal migration and polarization by stabilizing the actin cytoskeleton during various stages of *** experiments demonstrated that the knockdown of CXCR5 induced neuronal hyperexcitability,resulting in an increased number of ***,our results suggested that CXCR5 deficiency triggers seizure-related electrical activity through a previously unknown mechanism,namely,the disruption of neuronal polarity.

关键词： Epilepsy CXCR5 Embryonic neurogenesis Pluripotent stem cells Intrauterine electroporation F-actin Neuronal polarity Neuronal migration

Practical considerations of dietary therapies for epilepsy in adults

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Acta Epileptologica 2021年第1期3卷 101-107页

作者： Neha Kaul John-Paul Nicolo Terence J.O’Brien patrick kwan Department of Nutrition and Dietetics Alfred Hospital55 Commercial RoadMelbourneVIC 3004Australia Department of Allied Health(Clinical Nutrition) Royal Melbourne HospitalParkvilleAustralia Departments of Neurosciences and Neurology Alfred Hospital and Monash UniversityMelbourneAustralia Departments of Medicine and Neurology Royal Melbourne HospitalUniversity of MelbourneMelbourneAustralia Chongqing Key Laboratory of Neurology The First Affiliated HospitalChongqing Medical UniversityChongqingChina

Despite the increasing number of anti-seizure medications becoming available,the proportion of patients with drug-resistant epilepsy remains *** therapy for epilepsy is well-established practice in paediatric care,but relatively underutilised in ***,international recommendations have been published to guide the treatment of adults receiving dietary therapy for *** review focuses on the specific aspects of care unique to the management of adults receiving dietary therapy for epilepsy,including patient selection,diet composition,initiation,monitoring and cessation of dietary *** emphasise the need for a multidisciplinary team approach with appropriately trained neurologists and dietitians to provide holistic care while the patients are receiving dietary *** research should focus on the optimal diet composition and meeting the psychosocial needs of adults with epilepsy to maximise efficacy and adherence to dietary treatment.

关键词： Ketogenic diet Epilepsy Diet Drug-resistant epilepsy Nutrition

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大麻二酚在癫痫治疗中的研究进展

中华神经科杂志 2019年第7期52卷 586-591页

作者：李臻王雁 kwan patrick 青岛大学附属医院神经内科 266000 澳大利亚墨尔本皇家医院神经内科305000

在难治性癫痫尤其是Dravet综合征和Lennox-Gastaut综合征的治疗方面,大麻中的抗惊厥成分——大麻二酚显示出良好的疗效和安全性。然而,其作用机制以及与其他药物之间的相互作用尚不明确,对于已经应用多种抗癫痫药物的难治性癫痫患者,大... 详细信息

在难治性癫痫尤其是Dravet综合征和Lennox-Gastaut综合征的治疗方面,大麻中的抗惊厥成分——大麻二酚显示出良好的疗效和安全性。然而,其作用机制以及与其他药物之间的相互作用尚不明确,对于已经应用多种抗癫痫药物的难治性癫痫患者,大麻二酚的应用使其治疗更见曙光但也更加复杂化。本文将重点综述大麻二酚的相关作用机制研究及其在难治性癫痫治疗中的临床研究进展。

关键词：癫痫大麻大麻二酚抗癫痫药物

癫痫发作控制不佳患者进一步规范治疗的疗效评估——前瞻性研究

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癫痫发作控制不佳患者进一步规范治疗的疗效评估——前瞻性研究

SiRNA-mediated ankyrin-G silence modulates the expression of voltage-gated Na channels in murine hippocampal HT22 cells

中华医学会神经病学分会第十次全国脑电图与癫痫诊治进展高...

作者：郝晓婷鄢波 patrick kwan 周东四川大学华西医院神经内科墨尔本大学墨尔本皇家医院香港中文大学威尔士亲王医院

目的在中国的发展相对落后的地区,有41%的癫痫患者没有接受规范的治疗。尽管新型抗癫痫药物不断研发,但仍有70%左右的中国患者发作没有达到临床无发作。近期关于ILAE耐药癫痫专家共识的研究表明,很多发作未得到控制的患者,并不是真正的...

目的在中国的发展相对落后的地区,有41%的癫痫患者没有接受规范的治疗。尽管新型抗癫痫药物不断研发,但仍有70%左右的中国患者发作没有达到临床无发作。近期关于ILAE耐药癫痫专家共识的研究表明,很多发作未得到控制的患者,并不是真正的耐药。本研究针对中国西部发展相对落后区域的癫痫患者,经过进一步适当剂量,评价癫痫发作的控制情况是否得到进一步改善。方法该研究为前瞻性研究,根据ILAE对于耐药癫痫的专家共识,癫痫预后分为"临床无发作","耐药癫痫"和"无法分类"三种类型。在基线期,对所有患者进行耐药性分析,纳入标准为:1、基线期耐

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Acta Epileptologica 2019年第1期1卷 23-30页

作者： Guanzhong Ni Xiaoting Hao Xiaodong Cai Jiaming Qin Liemin Zhou patrick kwan Ziyi Chen Department of Neurology National Key Clinical Department and Key Discipline of Neurologythe First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina. Department of Neurology West China HospitalSichuan UniversityChengduChina. Department of Neurology the Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhouChina. Department of Neurology the Seventh Affiliated HospitalSun Yat-sen UniversityGuangzhouChina. Department of Neurology Royal Melbourne HospitalUniversity of MelbourneMelbourneAustralia.

Background:Voltage-gated sodium channels are the targets of many commonly used antiepileptic ***1.6,encoded by Scn8a,increased in chronic mesial temporal epilepsy animal models and co-localized with Ankyrin-G,encoded by *** hypothesized that inhibition of Ank3 transcription by siRNA decrease the expression of ***:We characterized expression of the target genes in hippocampal neuron HT22 cells by Real *** melt peak in the resolution curve of Scn1a,Scn8a and Ank3 were all ***3 transcription was interfered and the relative Ank3 mRNA levels of the three interfered groups compared to GAPDH were 0.89±0.13,0.52±0.07 and 0.26±0.05 while that of the negative control group was 1.01±0.08(P<0.05).When Ank3 transcription was inhibited by siRNA,the relative mRNA levels of Scn8a decreased in the three groups(0.91±0.09,0.33±0.06 and 0.25±0.05),compared to the negative control group(1.10±0.09).Tested by Western blotting,protein levels of ankyrinG and Nav1.6 decreased after ***-G in negative control group,group1,group2 and group1+2 were 0.813±0.051,0.744±0.041,0.477±0.055 and 0.351±0.190 respectively(P<0.01)while Nav1.6 were 0.934±0.036,0.867±0.078,0.498±0.070 and 0.586±0.180(P<0.01).The quantity analysis of immunofluorescence showed significant decrease of ankyrin-G and Nav1.6(Student’s test,P=0.046 and 0.016 respectively).Conclusion:We therefore concluded that in HT22 cells the expression of Nav1.6 was down-regulated by Ank3 RNA interference.

关键词： Nav1.1 Nav1.6 Ankyrin-G Hippocampal neurons HT22

鼠海马神经元锚蛋白对电压门控钠离子通道的调控研究

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鼠海马神经元锚蛋白对电压门控钠离子通道的调控研究

Generalized polyspike train:an EEG biomarker of drug-resistant idiopathic generalized epilepsy

中华医学会神经病学分会第十次全国脑电图与癫痫诊治进展高...

作者：陈子怡倪冠中秦家明 patrick kwan 周列民中山大学附属第一医院 The Royal Melbourne Hospital The University of Melbourne

背景与目的癫痫药物抗性的形成机制中"靶点假说"假设常见抗癫痫药物的靶点发生结构或者功能的改变,导致药物无法如期作用。电压门控钠离子通道是常见抗癫痫药物的靶点。本课题组的前期研究发现癫痫大鼠模型进入慢性自发发作期后电压门...

背景与目的癫痫药物抗性的形成机制中"靶点假说"假设常见抗癫痫药物的靶点发生结构或者功能的改变,导致药物无法如期作用。电压门控钠离子通道是常见抗癫痫药物的靶点。本课题组的前期研究发现癫痫大鼠模型进入慢性自发发作期后电压门控钠离子通道Nav1.6和锚蛋白ankyrin-G增加并共表达于海马CA1区。本研究对鼠海马神经元细胞株的ankyrin-G编码基因进行RNA干扰,检测干扰后电压门控钠离子通道不同亚单位的表达是否进而受影响。方法:以siRNA片段-lipofectamine

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Generalized polyspike train:an EEG biomarker of drug-resista...

Ⅲ期临床试验非盲延期阶段联合使用吡仑帕奈的局灶性癫痫患者的四年药物安全性、耐受性及发作结局:307号研究

第六届CAAE脑电图与神经电生理大会

作者： Yanping Sun Udaya Seneviratne Piero Perucca Zhibin Chen Kee Meng Tan Terence J O' Brien Wendyl D' Souza patrick kwan The Affiliated Hospital of Qingdao University The Royal Melbourne Hospital The University of Melbourne St.Vincent's Hospital Melbourne The University of Melbourne The School of Clinical Sciences at Monash Health Monash University The Alfred Hospital The Central Clinical School Monash University

Objective:To identifyclinical and EEG biomarkers of drug resistance in adults With idiopathic generalized epilepsy(IGE).Methods:We conducted a case-control study consisting of a discovery cohort and a replication cohort independently assessed at two different *** each centre patients with IGE phenotype and generalized spike-wave discharges on EEG were classified as drug-resistant or *** changes were classified

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癫痫杂志 2020年第1期6卷 63-69页

作者： Gregory L Krauss Emilio Perucca patrick kwan 覃英杰(译) 熊维希(审) 慕洁(审) 不详

评估307号研究(临床试验验证码:NCT00735397)Ⅲ期非盲延期阶段(OLEx)联合使用吡仑帕奈的局灶性癫痫患者的药物安全性、耐受性及痫性发作结局。患者在完成任一III期双盲试验后均可进入非盲延期阶段(Open-labelextension,OLEx)。对所有OLE... 详细信息

评估307号研究(临床试验验证码:NCT00735397)Ⅲ期非盲延期阶段(OLEx)联合使用吡仑帕奈的局灶性癫痫患者的药物安全性、耐受性及痫性发作结局。患者在完成任一III期双盲试验后均可进入非盲延期阶段(Open-labelextension,OLEx)。对所有OLEx队列中有同样最小吡伦帕奈暴露剂量的局灶性癫痫和继发全面性癫痫(Secondarily generalized seizures,SGS)的患者进行药物安全性及耐受性和痫性发作结局(每28 d中位痫性发作减少率、反应率和无发作率)的分析。另外,针对OLEx的早期失访进行了额外的敏感性分析。从1480例双盲试验中随机分组的患者共纳入1218例。大部分患者(65.4%~80.9%)仅用吡仑帕奈12 mg,每日一次,进行治疗,并在相同剂量下完成长期的检测,或是相对基线联合使用少量抗癫痫药物(AEDs)。长期的药物安全性及耐受性结果与双盲研究一致。导致超过1%的患者研究中断治疗的紧急不良反应事件(Treatment-emergent adverse events,TEAEs)包括眩晕、易激、疲劳。有临床意义的TEAEs稳定期为4年。所有队列中患者的痫性发作结局随时间持续改善。对于接受3年(n=436)、4年(n=78)药物治疗的患者28 d中位痫性发作减少率分别为62%、70.6%,相应的50%反应率为59.6%、67.9%。最大28 d中位痫性发作减少率发生于基线水平的SGS患者,接受3年(n=190)、4年(n=28)药物治疗分别为88.0%和100.0%。在这些队列中分别有40.0%和53.6%的患者达到了无SGS。排除早期失访后的28 d中位痫性发作减少率结果类似。长期吡仑帕奈联合用药(≤4年)不会导致新的药物安全性及耐受性问题,并且可以很大程度地减少痫性发作,特别是基线水平的SGS患者。

关键词：抗癫痫药物局灶性痫性发作长期安全性及耐受性吡仑帕奈继发全面性痫性发作

口服左乙拉西坦即刻预防儿童热性惊厥的多中心随机对照研究

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发育医学电子杂志 2015年第2期3卷 96-102页

作者：胡琳燕邹丽萍钟建民高蕾赵建波肖农周红赵锰石秀玉刘玉洁鞠俊张玮娜杨小凡 patrick kwan 中国人民解放军总医院儿童医学中心北京100853 江西省儿童医院神经内科南昌330006 首都医科大学附属北京儿童医院神经内科北京100045 重庆医科大学附属儿童医院神经康复科重庆400014 北京新世纪儿童医院儿科北京100045 Departments of Medicine and Neurology Royal Melbourne Hospital University of Melbourne Department of Medicine and Therapeutics Chinese University of Hong Kong

目的热性惊厥(febrile seizure,FS)是最常见的儿童惊厥性疾病,也是全球儿科急诊最常见的就诊原因之一。本研究即为寻求一种新的、安全有效的方法来预防FS的发生。方法共115例入组前6个月内有过至少2次或2次以上的FS发作患儿,按2∶1的比... 详细信息

目的热性惊厥(febrile seizure,FS)是最常见的儿童惊厥性疾病,也是全球儿科急诊最常见的就诊原因之一。本研究即为寻求一种新的、安全有效的方法来预防FS的发生。方法共115例入组前6个月内有过至少2次或2次以上的FS发作患儿,按2∶1的比例随机分配至左乙拉西坦(Levetiracetam,LEV)组及对照组。在发热初始,LEV组给予LEV片15~30 mg/(kg·d),口服,每天2次,连续服用1周,然后每2天减半量,直到第2周结束时停药;当体温>38.5℃时口服退热药,并根据当地儿科医生建议对症处理。主要效应指标是在随访的48周内与发热相关的惊厥频率以及FS再发率,次要指标是两组医疗费用比较。结果意向性分析显示LEV组78例经历了148次发热事件,其中11例经历了15次FS再发。对照组中37例经历了64次发热事件,19例经历了32次FS再发。两组间差异有显著性。使用LEV预防FS再发的医疗费用明显低于对照组。在48周的随访期间,仅一例发生比较严重的嗜睡,未发现其他的严重不良发应。结论口服LEV即刻预防儿童FS安全有效,并可减少医疗资源的浪费。

关键词：热性惊厥儿童左乙拉西坦预防

Second malignant neoplasms in childhood cancer survivors in a tertiary paediatric oncology centre in Hong Kong, China

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Chinese Medical Journal 2011年第22期124卷 3686-3692页

作者： SUN Wai-fun CHENG Frankie Wai-tsoi LEE Vincent LEUNGWing-kwan SHING Ming-kong YUEN patrick Man-pan LI Chi-kong Department of Paediatrics and Adolescent Medicine Pamela Youde Nethersole Eastern Hospital Hong Kong China

Background Childhood cancer survivors were at risk of development of second malignant neoplasms. The aim of this study is to evaluate the incidence, risk factors and outcome of second malignant neoplasms in childhood cancer survivors in a tertiary paediatric oncology centre in Hong Kong, China. Methods We performed a retrospective review of patients with childhood cancer treated in Children＇s Cancer Centre in Prince of Wales Hospital, Hong Kong, China between May 1984 and June 2009. Case records of patients who developed second malignant neoplasms were reviewed. Results Totally 1374 new cases aged less than 21-year old were treated in our centre in this 25-year study period. Twelve cases developed second malignant neoplasms with 10-year and 20-year cumulative incidence of 1.3% （95% confidence interval 0.3%-2.3%） and 2.9% （95% confidence interval 1.1%-4.7%） respectively. Another 4 cases were referred to us from other centres for the management of second malignant neoplasms. In this cohort of 16 children with second malignant neoplasms, the most frequent second malignant neoplasms were acute leukemia or myelodysplastic syndrome （n--6） and central nervous system tumor （n=4）. Median interval between diagnosis of primary and second malignant neoplasms was 7.4 years （range 2.1-13.3 years）. Eight patients developed second solid tumor within the previous irradiated field. Radiotherapy significantly increased the risk of development of second solid tumor in patients with acute lymphoblastic leukemia （P=0.027）. Seven out of 16 patients who developed second malignant neoplasms had a family histo＇ry of cancer among the first or second-degree relatives. Nine patients died of progression of second malignant neoplasms, mainly resulted from second central nervous system tumor and osteosarcoma. Conclusions Cumulative incidence of second cancer in our centre was comparable to western countries. Radiotherapy was associated with second solid tumour among patients with acute lymphoblast

关键词： second neoplasm oncology paediatric