KCNT1基因突变相关难治性癫痫五例

目的 分析KCNT1基因突变患者的分子遗传学特征及临床特点。方法 分析广东三九脑科医院癫痫中心经全外显子二代测序发现的5例KCNT1基因阳性患者的临床资料,对KCNT1基因阳性患者的分子遗传学特征及临床特点进行分析总结。结果 所有5例KCNT1基因阳性癫痫患者均为错义突变,其中例2、例4、例5为新生突变,例1及例3为来源自母亲的杂合突变,其中例5新生突变患者(c.1038C>G p.F346L)合并有Y染色体异常,表现为超雄综合征(47,XYY)。5例患者中例1、例2及例3突变位点一致(c.1193G>A p.R398Q),但其中例1及例2临床表型为常染色体显性遗传夜间额叶癫痫(ADNFLE),例3为婴儿癫痫伴游走性局灶性发作(EIMFS),且3例突变位点一致的患者中例1及例2合并有自闭症。5例患者中例1患者的母亲及外婆有癫痫病史,其余4例无癫痫家族史。所有患者均有精神运动发育迟缓。5例患者的癫痫起病年龄为生后1月龄～36月龄,其中例1、例2及例4临床表型为ANDFLE、例3及例5临床表型为EIMFS。5例患者均使用2种以上抗癫痫药物,其中例2及例3添加生酮饮食治疗,例2及...     

良性家族性婴儿癫痫的临床特点

目的 探讨良性家族性婴儿癫痫(BFIE)的临床特点.方法 回顾性分析1例PRRT2基因突变和双侧额区放电的BFIE患者的临床资料,并进行文献复习.结果 BFIE主要临床表现为局灶性癫痫发作,PRRT2为主要致病基因.发作间歇期EEG多无异常,局灶性放电部位多为额区.本病预后良好,多数抗癫痫药物对本病有效.结论 婴儿期以...     

SCN2A基因突变致癫痫三例

目的探讨SCN2A基因不同位点突变致癫痫的临床特点。方法收集河北省儿童医院神经内科2019年1月-2019年12月收治的SCN2A基因突变阳性致癫痫患儿资料,并进行临床分析。结果共收集3例SCN2A基因突变阳性致癫痫患儿,突变类型均为杂合突变。例1患儿生后2d起病,发作形式为阵挛发作、局灶性发作,诊断为良性家族性新生儿婴儿癫痫;突变基因型c.2426AG(p.K809R),为家族遗传性突变,使用丙戊酸、托吡酯胶囊、苯巴比妥钠后发作控制。例2患儿生后30h起病,发作形式为局灶性发作,痉挛发作,诊断为婴儿游走性部分性癫痫,婴儿痉挛,发育性癫痫性脑病;突变基因型c.4391CT(p.T1464I),为自发突变,使用托吡酯及ACTH治疗后发作逐渐减停。例3患儿1岁3月龄起病,发作形式为强直发作,诊断为全面性癫痫伴热性惊厥附加征;突变基因型c.1711C T(p.R571C),遗传自父亲,未使用抗癫痫药物。结论本组病例提示SCN2A基因应作为婴幼儿期良性癫痫、癫痫性脑病、智力、运动发育落后、孤独症等疾病的候选筛查基因之一。     

良性家族性婴儿癫痫的临床特征及遗传学研究

目的探讨我国良性家族性婴儿癫痫(BFIE)的临床特征及致病基因谱。方法收集10例BFIE患儿的临床资料,通过靶向捕获二代测序发现可疑致病性突变基因,并经Sanger测序验证基因突变来源。结果 10例患儿起病年龄2～14月龄(中位年龄为5月龄),表现为部分性发作或部分继发全面性发作。6例患儿起病初期呈丛集性发作。9例予抗癫痫药物治疗,服药后发作易控制,1例未用抗癫痫药未再发作。随访8～18个月,均于2岁以内停止。10例患儿均有基因突变,9例为家族遗传性突变,1例为新生突变。6例PRRT2基因突变、2例SCN2A基因突变和2例KCNQ2基因突变。除1例PRRT2基因突变位点(c.439GC)已报道,余9例为未报道的新突变。结论婴儿起病的BFIE多表现为部分性发作或部分继发全面性发作,抗癫痫药物治疗多可短期控制;PRRT2、SCN2A、KCNQ2基因为致病基因,突变位点和方式多样。     

CHD2基因突变致癫痫患者九例

目的 探讨CHD2基因突变致癫痫患儿临床表型及基因型特点。方法 分析2017年01月-2022年07月河北省儿童医院神经内科收治的CHD2基因突变相关性癫痫患儿。并查阅万方、中国知网(CNKI)、PubMed、Uptodate等数据库,结合相关文献进行总结。结果 本研究共收集9例CHD2基因突变阳性患儿,其中自发突变5例,母源性突变4例。9例患儿局灶性发作起病6例,全面性发作起病3例,1例患儿符合LGS诊断,1例患儿符合眼睑肌阵挛综合征诊断。7例患儿伴有轻到中度的发育障碍。9例患儿共发现8个基因突变位点,其中错义突变5个,移码突变3个,突变多集中在SNF2相关解旋酶/ATP酶结构域;其中7个突变位点尚未报道。7例患儿应用丙戊酸钠治疗有效。结论(1)CHD2基因突变多以局灶性发作起病,丙戊酸治疗有效;(2)自发突变起病更早,均伴有轻到中度的发育障碍;(3)CHD2基因致病性突变多集中在SNF2相关解旋酶/ATP酶结构域。     

钾离子通道基因变异相关婴儿癫痫性脑病临床表型与基因变异特点分析

目的 分析总结钾离子通道基因变异相关婴儿癫痫性脑病的临床和基因变异特点。方法与结果 采用第二代测序技术对2016年7月至2020年1月湖南省儿童医院收治的11例钾离子通道基因变异相关癫痫性脑病患儿行基因检测,Sanger测序验证变异类型其及来源。临床表型包括婴儿癫痫伴游走性局灶性发作（4例）、大田原综合征（2例）、婴儿痉挛症（2例）和非特异性癫痫性脑病（3例）;新发基因变异8/11例、遗传变异3/11例（均来自母亲）;变异类型为KCNQ2基因变异（5例）、KCNT1基因变异（4例）、KCNB1基因变异（2例）。采取多种抗癫痫发作药物联合治疗,部分患儿辅助生酮饮食（3例）。平均随访19个月,3例完全无发作、1例有效、7例无效,11例均遗留智力发育迟缓和运动障碍。结论 钾离子通道基因变异是婴儿癫痫性脑病的常见遗传性病因,可引起不同临床表型,基因检测可协助病因诊断,并为精准治疗提供依据。     

婴儿癫痫伴游走性局灶性发作的遗传学研究进展

婴儿癫痫伴游走性局灶性发作(EIMFS)是一类罕见的难治性癫痫综合征, 脑电图特征性表现为游走性。近年来, 随着该综合征越来越多的致病基因被发现, 极大地拓宽了人们对该综合征病理生理机制的认识和理解。本文现系统归纳目前国内外已报道的与EIMFS相关的致病基因, 以期拓展临床医生对该综合征的认识及提高鉴别诊断能力。     

左乙拉西坦添加治疗成人难治性癫痫部分性发作的临床疗效和脑电图分析

<正>评价新型抗癫痫药物左乙拉西坦(LEV)添加治疗成人难治性癫痫部分性发作的临床疗效,及其对脑电图(EEG)的影响,报道如下。1对象与方法1.1研究对象1.1.1纳入标准(1)临床诊断为难治性部分性癫痫,即符合国际抗癫痫联盟(ILAE)分类标准[1],明确诊断为部分性发作,伴或不伴有继发全面性发作,稳定服用一种或一种以上一线抗癫痫药物且治疗效果欠佳者;(2)年龄为18~     

发育性及癫痫性脑病的遗传学研究进展

发育性及癫痫性脑病是一组疾病的总称,其持续频繁癫痫发作伴发作间期异常放电严重影响患儿大脑的发育和成熟,且抗癫痫药物难以控制其发作,可导致认知功能和运动发育落后。近来随着基因2代测序技术发展迅速,发现某些离子通道型基因发生突变可导致发育性及癫痫性脑病,对疾病的早期诊断及干预有重要作用。本文主要对发育性及癫痫性脑病相关离子通道类基因做一综述。     

具有中央颞区棘波的小儿良性癫痫

小儿良性局灶性癫痫指的是临床具有局灶性发作的表现 ,发生在某一特定的年龄阶段 ,脑电图有特征性表现 ,抗癫痫药物治疗反应良好 ,预后较好的一组癫痫综合征。小儿良性局灶性癫痫的发病机制一般认为与遗传因素密切相关 ,目前已确定了几种类型癫痫基因突变的部位及突变形式。由于基因调控异常 ,使离子通道转运、神经递质或其受体功能障碍 ,导致正处于发育阶段的大脑神经元之间兴奋与抑制环路平衡紊乱 ,局部神经元的兴奋性异常增高 ,因此出现癫痫发作。小儿大脑具有较强的可塑性 ,随年龄的增长与神经介质及其受体的发育 ,大脑内部逐渐进行神经…     

Denervation study of synapses of organ of corti of old world monkeys

Fine structural characteristics of synapses in the spiral organ of Corti were examined, with reference to differences between inner and outer haircell systems, and to location of neurons of origin of efferent axons. Surgical interruption of crossed olivocochlear bundle, of vestibular nerve, of facial nerve, and excision of superior cervical ganglia were used to determine the pathways of efferent axons. Interruption of the vestibular nerve near the brainstem results in degeneration of all efferent terminals on outer hair cells. Mid-line lesions at, and caudal to, the facial colliculus result in degeneration of about half of these efferent terminals. Efferent synaptic bulbs to the inner hair-cell system are small, of the order of one micron, and form type 2 junctions with afferent dendrites. They tend to have more large dense-core vesicles (about 80 nm) than the large efferent terminals of the outer hair-cell system, and appear to be the terminals of axons in the habenula perforata, which exhibit varicosities laden with large dense core vesicles. The varicosities are unaffected by excision of the superior cervical ganglia. So far as our material can reveal, it appears that the varicosities in the habenula perforata do not survive vestibular root interruption, nor do the efferent processes in the internal spiral bundle or at the base of inner hair cells. Most interestingly, the afferent processes of the inner hair-cell system, as identified for example by their relation to pre-synaptic bodies in the inner hair cells, are subject to a trans-synaptic reaction after severance of the vestibular root. They undergo a dramatic cytological transformation, characterized by increase of volume, engorgement with microtubules, microfilaments, microvesicles of various sizes, and clusters of lysosomes. Thus, both the efferent and afferent terminals of the inner hair-cell system show marked cytological differences from the corresponding terminals of the outer hair cell system.     

Mechanism of action of tubocurarine on nicotinic cholinoreceptors of neurons of the sympathetic ganglia of rats

Tubocurarine (Tc) effect on membrane currents elicited by acetylcholine (ACh) was studied in isolated superior cervical ganglion neurons of rat using patch-clamp method in the whole-cell recording mode. The "use-dependent" block of ACh current by Tc was revealed in the experiments with ACh applications, indicating that Tc blocked the channels opened by ACh. Mean lifetime of Tc-open channel complex, tau, was found to be 9.8 +/- 0.5 s (n = 7) at -50 mV and 20-24 degrees C. tau exponentially increased with membrane hyperpolarization (e-fold change in tau corresponded to the membrane potential shift by 61 mV). Inhibition of the ACh-induced current by Tc (3-30 microM/1) was completely abolished by membrane depolarization to the level of 80-100 mV. Inhibition of ACh-induced current was augmented at increased ACh doses. It is concluded that the open channel block produced by Tc is likely to be the only mechanism for Tc action on nicotinic acetylcholine receptors in superior cervical ganglion neurons of rat.     

The effect of age of onset of PD on risk of dementia

Background Dementia occurs in the majority of patients with Parkinson’s disease (PD). Late onset of PD has been reported to be associated with a higher risk for dementia. However, age at onset (AAO) and age at baseline assessment are often correlated. The aim of this study was to explore whether AAO of PD symptoms is a risk factor for dementia independent of the general effect of age. Methods Two community-based studies of PD in New York (n = 281) and Rogaland county, Norway (n = 227) and two population-based groups of healthy elderly from New York (n = 180) and Odense, Denmark (n = 2414) were followed prospectively for 3–4 years and assessed for dementia according to DSM-IIIR. All PD and control cases underwent neurological examination and were followed with neurological and neuropsychological assessments. We used Cox proportional hazards regression based on three different time scales to explore the effect of AAO of PD on risk of dementia, adjusting for age at baseline and other demographic and clinical variables. Findings In both PD groups and in the pooled analyses, there was a significant effect of age at baseline assessment on the time to develop dementia, but there was no effect of AAO independent of age itself. Consistent with these results, there was no increased relative effect of age on the time to develop dementia in PD cases compared with controls. Interpretation This study shows that it is the general effect of age, rather than AAO that is associated with incident dementia in subjects with PD. Received in revised form: 22 December 2005     

Limits of deinstitutionalization--perspectives of relatives of psychiatric patients

After a hopeful beginning, the social process of the reintegration of those with severe mental illness has come to a standstill. I am led to wonder whether "the community" really wants to live together with people suffering from severe mental illness, and if so, how closely? As long as the medical treatment of mental illness provided by the general practitioners is fundamentally deficient, as they are not able to prescribe the necessary interventions--such as out-patient psychiatric nursing, and service providers in the out-patient sector are content with offering increasingly intensive forms of care for the less seriously ill at the cost of the Social Welfare System--the reintegration of those with serious mental illness remains an illusion--which is mainly to the benefit of providers of residential care in homes and hostels.     

Summary of Legislation of 1933 of interest to the Department of Mental Hygiene

Psychiatric Quarterly -