吡哆醇依赖性癫(癎)的临床及乙醛脱氢酶7家庭成员A1基因突变分析

目的 分析1例吡哆醇依赖性癫(癎)(PDE)的临床诊治过程及乙醛脱氢酶7家庭成员A1(ALDH7A1)基因突变特征.方法 对1例以早期癫(癎)起病的PDE患儿行临床诊治观察、神经电生理及神经影像学检查、以及ALDH7A1基因突变分析.结果 患儿出生2个月出现反复癫(癎)发作,多种抗癫(癎)药均不能控制发作,多次住院过程中在抗癫(癎)药治疗基础上给予吡哆醇静脉滴注使发作控制,出院后仅用抗癫(癎)药而未用吡哆醇维持治疗,癫(癎)发作分别在吡哆醇撤药后13 d、14 d及38 d出现复发,减停抗癫(癎)药物后仅单纯口服吡哆醇使发作完全控制.治疗前后多次EEG正常,头颅MRI检查正常.ALDH7A1基因检测发现1对新的复合杂合突变,第5外显子c.410G＞ A(p.G137E)和第11内含子IVS11 +1G＞A剪切位点突变,其父携带G137E突变,其母携带IVS11 +1G＞A突变.结论 本例癫(癎)发作早期起病、经吡哆醇治疗有效、撤药后复发临床提示了PDE的可能,ALDH7A1基因分析最终确诊了国内第1例PDE,本例携带的2个基因突变位点均为国际未报道的新位点.     

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.     

获得性癫(癎)失语综合征4例

目的 探讨获得性癫(癎)失语综合征(LKS)的临床特征及治疗反应.方法 通过对4例LKS患儿临床表现、EEG特征、治疗效果观察,并通过电话及门诊复诊随访其预后.结果 4例患儿均予丙戊酸钠口服溶液及激素治疗,3～6个月抽搐发作控制,失语明显好转,EEG提示不同程度改善.结论 LKS是一少见的年龄依赖性癫(癎)综合征,以失语和癫(癎)发作为主要表现,可伴有行为异常,EEG以颞区为主的样放电,睡眠期可泛化全导,抗癫(癎)药物可控制癫(癎)发作,但对失语疗效欠佳,早期足量激素治疗对失语疗效明显.该病预后较好.     

特发性儿童枕叶癫癎21例临床分析

目的总结特发性儿童枕叶癫癎的临床表现及脑电图特点,以提高临床诊断水平。方法回顾性分析2000—2007年广西医科大学第一附属医院收治的21例确诊为特发性儿童枕叶癫癎患儿的临床表现及脑电图特点。结果起病年龄5个月至14岁;发作性呕吐11例,眼球偏转11例,头偏转8例,发作后头痛8例,口咽部自动症5例,眼睑扑动6例,黑蒙5例,视物模糊3例,视幻觉2例;继发半侧肢体抽搐5例,继发全身性发作7例,21例头颅影像学检查均正常。所有病例发作间期脑电图均有癎样放电,闭眼出现,睁眼消失。随访1～5年,其中早发型儿童良性枕叶癫癎(EBOS)12例,晚发型儿童良性枕叶癫癎(LOS)9例,EBOS对多种抗癫癎药物(AEDS)反应较好,12例EBOS患儿中11例单药治疗完全控制发作,1例患儿两种AEDS联合应用可以完全控制发作,IOS对AEDS治疗反应稍差,9例LOS患儿中有2例未完全控制。结论特发性儿童枕叶癫癎是一组较具特征表现的癫癎综合征,掌握临床表现及脑电图特点,常可做出正确诊断。     

异丙酚持续静滴治疗小儿癫癎持续状态的临床观察

目的总结异丙酚持续静滴治疗小儿癫癎持续状态的疗效.方法对2001年4月至2003年10月唐山工人医院儿科8例继发性癫癎持续状态患儿的治疗进行分析,本组8例均为常规抗癫癎药物不能控制的继发性癫癎所致癫癎持续状态.在使用常规止惊药物失败后开始异丙酚静滴.结果8例患儿全部抽搐停止.结论癫癎持续状态是儿科急症之一,如何在短时间内控制癫癎持续状态是治疗成败的关键,在正确常规治疗无逆转时,应用异丙酚持续静滴可以有效控制癫癎持续状态且未见严重不良反应.     

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).     

3例MECP2重复综合征临床分析和文献复习

MECP2重复综合征(MDS)是儿科少见病,主要表现为运动发育落后、语言缺失或落后、反复感染、严重智力障碍、癫癎、孤独症样表现及婴儿早期肌张力低下等。该文3例患儿均为男孩,病例1、2首发表现为运动发育落后、语言缺失或落后,病例3首发表现为反复感染,查体均有肌张力均低下、病理征均阴性。病例1有全身强直-阵挛发作,脑电图示局灶性发作,予奥卡西平、左乙拉西坦、氯硝基安定联合抗癫癎治疗,癫癎发作控制。病例3出现过失神发作1次及点头发作3次,发作间期多次脑电图正常,未予抗癫癎治疗。3例患儿的反复感染随年龄增长得到改善,语言及智力改善不明显。微阵列比较基因组杂交技术(aCGH)检测发现3例患儿的X染色体存在MECP2基因重复,确诊为MDS。对于发育落后伴反复感染、癫癎发作的患儿,应考虑到MDS可能,早期行aCGH检测有助于诊断。     

以癫痫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-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%）以癫痫样发作为首发症状,分别在首发症状出现1个月-2a才确诊为甲亢;癫痫样发作为继发症状9例（9/20例,占45%）,在确诊为甲亢2个月-4a出现癫痫样发作,多为甲亢控制欠佳或中断药物时发生;癫痫患者并甲亢时癫痫样发作加重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。结论甲亢可引起癫痫样发作,其发作与甲状腺激素水平升高关系密切;甲亢与癫痫可能存在某些共同的免疫发病机制。     

癫癎患儿共患注意缺陷多动障碍的临床分析

目的：评估癫癎患儿共患注意缺陷多动障碍（ADHD）的共患率,探讨引起癫癎患儿共患ADHD的相关危险因素。方法：选取符合癫癎和癫癎综合征诊断标准、年龄在6～15岁的患儿256例,调查癫癎患儿与ADHD的共患率及危险因素。结果：192例患儿完成系统评定。ADHD的共患率为42.2%。首次发作年龄越早,抗癫癎药物治疗时程越长及多种抗癫癎药物联合应用者癫癎共患ADHD的共患率越高;Lennox-Gastaut 综合征和全身强直-阵挛发作型癫癎及脑电图提示多病灶起源的癫癎患儿ADHD共患率较高。结论：ADHD在癫癎患儿中的共患率较高。癫癎患儿共患ADHD相关的危险因素包括：癫癎的首次发作年龄、癫癎发作类型、癫癎综合征的类型、脑电图特征及抗癫癎药物的使用。     

癫持续状态

癫(癎)持续状态是指持续抽搐超过30 min或在2次意识不清之间的连续惊厥发作.癫(癎)持续状态是临床急症,以全身强直阵挛性发作最为常见.控制癫(癎)持续状态时,采用静脉注射应用药物,可迅速控制惊厥发作,减少和避免脑损伤.癫(癎)持续状态经急救而停止发作后,应进行病因治疗以防止癫(癎)持续状态复发.     

Brain malformations associated to Aldh7a1 gene mutations: Report of a novel homozygous mutation and literature review

Background

The ALDH7A1 gene is known to be responsible for autosomal recessive pyridoxine-dependent epilepsy (OMIM 266100). The phenotypic spectrum of ALDH7A1 mutations is very heterogeneous ranging from refractory epilepsy and neurodevelopmental delay, to multisystem neonatal disorder.

Pyridoxine-dependent seizures: long-term follow-up of two cases with clinical and MRI findings,and pyridoxine treatment

Pyridoxine-dependency is a rare autosomal recessive disorder causing a severe seizure disorder of neonatal onset. There are a few reports including neuroimaging studies, such as cranial CT and MRI, and one report with longitudinal MRI findings in two cases with pyridoxine-dependent seizures (PDS). We report long-term follow-up of two siblngs with PDS in the light of clinical, EEG, CT and MRI findings, and pyridoxine treatment. The first patient, an 8-year-old female who had neonatal seizures, has sequential cranial CT and MRIs which are normal except for mega cistema magna thus far. She still has mild mental retardation, although the accurate diagnosis was made when she was 6 years old and pyridoxine treatment was initiated. The second patient, a 1-year-old female, who is the younger sibling of the first patient, presented with neonatal seizures and PDS was diagnosed immediately, with resulting pyridoxine treatment (10 mg/kg/day). She is now neurologically normal, seizure-free, and has sequential normal CT and MRIs. These patients show rather benign clinical courses.     

West syndrome associated with Down syndrome: Case report and literature review

West syndrome is the most frequent cause of epilepsy in Down syndrome. West syndrome is often associated with poor long-term prognosis in most of children. We report a girl with West syndrome associated with Down syndrome which occurred at 8 months of age for repetitive flexor spasms and electroencephalography (EEG) showed hypsarrhythmia. She had Down syndrome facies, microcephaly, psychomotor development delay and axial hypotonia. Computed tomography of the brain was normal. Her karyotype was 47, XX, +21. Phenobarbital therapy was immediately effective with good clinical control of seizures, while the EEG monitored after one month was unchanged. At 2 years of age, the patient had hypertonic status epilepticus following a lung infection. The EEG showed a persistence of hypsarrhythmia. Sodium valproate and hydrocortisone therapy was effective with good seizure control but her psychomotor development was severely impaired. After a follow-up of 7 years, the patient presents growth retardation, microcephaly, severe psychomotor development delay, generalized hypotonia and tetraparesis. Knowledge of West syndrome in Down syndrome allows the early detection and prompt management of this neurological complication in order to optimize psychomotor development and improve the quality of life of these children.     

Self induced photosensitive epilepsy

The authors report a case of a 12-year-old girl who had rare self induced photosensitive epilepsy. She used to move her right hand over the right eye while simultaneously rubbing the forehead since the age of 8. During these episodes she was lost in herself. Lately these episodes were followed by brief spell of unconsciousness. The EEG examination, in its third attempt, revealed bilateral multiple symmetric spikes on photic stimulation. She admitted that she often induced the episode herself and derived pleasure out of it. She responded well to Sodium valproate     

幼儿发育落后间断抽搐8个月

该文报道1 例因发育落后及癫癎而诊断为母性苯丙酮尿症(phenylketonuria, PKU)的患儿。患儿男,1 岁8 个月时就诊,发育落后,1 岁出现癫癎,毛发黑,头围小,发育商为43,脑MRI 扫描显示白质髓鞘化发育落后,双侧侧脑室增宽,枕骨大孔狭窄。染色体核型正常,血液氨基酸、酯酰肉碱谱及尿液有机酸正常。家族史调查发现患儿母亲自幼智力落后,学习困难,毛发色泽发黄,26 岁结婚,婚前常规检查未见异常。患儿母亲于28 岁来院检查,血液氨基酸分析发现血液苯丙氨酸显著增高(916.54 μmol/L,正常值20~120 μmol/L),苯丙氨酸羟化酶(PAH)基因c.611A>G(p.Y204C)纯合突变,为PAH 缺陷导致的PKU 患者。患儿为c.611A>G杂合突变携带者,血液苯丙氨酸正常。患儿父亲健康,PAH 基因未检出突变。建议对于不明原因智力障碍的患儿需进行详细的家族史调查,对智力障碍的父母更需进行详细的临床及代谢分析,以发现亲代疾病导致的儿童脑损害,如母性PKU。     

CHD2基因突变相关癫痫临床表型谱研究（附18例报告）

目的　研究CHD2基因突变相关癫痫的临床表型特点。方法　收集2014年1月至2019年3月在北京大学第一医院就诊的18例CHD2基因突变癫痫患儿，总结其临床表型特点。结果　18例患儿癫痫发作中位起病年龄为26.5月龄。病程中出现的发作类型包括全面强直阵挛发作11例，肌阵挛发作7例，局灶性发作5例，失张力发作4例，不典型失神4例，肌阵挛-失张力发作3例，痉挛发作2例。16例患儿发作间期脑电图监测到异常放电，8例监测到临床发作，2例脑电图正常。15例患儿有不同程度的运动、智力发育落后，7例有孤独症样表现。癫痫综合征诊断符合癫痫伴肌阵挛-失张力发作2例，Lennox-Gastaut综合征2例，热性惊厥附加症2例，婴儿痉挛症1例。末次随访年龄为3岁5月龄至18岁，其中10例发作控制半年以上，丙戊酸和左乙拉西坦是治疗CHD2基因突变相关癫痫的有效药物。结论　CHD2基因突变相关癫痫发作类型多样，GTCS和肌阵挛发作常见；多数患儿存在发育落后；半数以上患儿癫痫发作可控制。     

Difficulties in assessing the effect of strychnine on the outcome of non-ketotic hyperglycinaemia. Observations on sisters with a mild T-protein defect

Sisters with a mild variant of non-ketotic hyperglycinaemia resulting from a defect in the T-protein of the glycine cleavage system had different clinical outcomes. The older sister was ascertained at 6 months of age because of mental retardation. She received only brief treatment with sodium benzoate from 11–15 months and at 15 years of age is profoundly retarded and has epilepsy. The younger sister was diagnosed 36h after birth, was treated with strychnine, sodium benzoate and arginine from the neonatal period and at 27 months of age is only moderately retarded and free of seizures. The possible role of strychnine in the improved outcome is discussed.Abbreviations NKH non-ketotic hyperglycinaemia - CSF cerebrospinal fluid     

Precocious puberty connected with a hamartoma. Treatment with medroxyprogesterone. 2 cases

2 cases of precocious puberty, a boy diagnosed at age 22 months and a girl at 40 months, were treated with farlutal (medroxyprogesterone) orally. The boy had excessive appetite and penile development at 16 months. Upon examination at 22 months, his bone age was 10 years, and his height and weight were above the third standard deviation. Fractional gas encephalography showed a hamartoma 10 mm in diameter. 3 tablets of farlutal daily were prescribed from 4 years of age to 7 1/2 years. The girl, a twin, had breast development and pubic hair at 3 years, and was examined at 3 years 4 months when she was over the second standard deviation in height and weight, although her twin was below the mean. She also had a hamartoma visible by fractional encephalography. She menstruated at 3 years 11 months and began taking farlutal 20 mg/day, which was increased to 40 mg/day from 4 years to 8 years of age. Pubertal development was arrested by medroxyprogesterone in both children, but bone age was not affected.     

Epidemiology of absence epilepsy. I. Concept and incidence

An epidemiological study of absence epilepsy is presented. The study comprised a series of cases from a Swedish population, aged 0-15 years, selected on the basis of EEG criteria. All children with regular and symmetrical 3 (2-4) Hz spike-and-slow-wave complexes, recorded for the first time during the period 1978-1982, were included. A total of 134 children fulfilled the inclusion criteria, and of these, 108 (80.6%) had absences alone or in combination with general tonic-clonic seizures (GTCS); 11 (8.2%) had absences combined with other seizures; 15 (11.2%) had other types of seizures only. The mean annual incidence of absence epilepsy was 7/100,000 for children aged 0-15 years. Of these, 6.3/100,000 had absences alone or in combination with GTCS. The cumulative incidence of absence epilepsy was 98/100,000. The mean age of onset was 7 years.     

Behavioral problems in Indian children with epilepsy

Objective

To assess prevalence of behavioral problems in children with epilepsy.

Methods

This was a cross-sectional study of children with epilepsy, and normal controls enrolled between July 2013 to June 2015. Child Behavior Checklist (CBCL) was used as a tool to assess the behavior based on parents reported observation.

Results

There were 60 children with epilepsy in 2-5 years and 80 in 6-14 years age groups, and 74 and 83 unaffected controls, respectively. Mean CBCL scores for most of the domains in children of both age groups were significantly higher than controls. Clinical range abnormalities were mainly detected in externalizing domain (23.3%) in 2-5 years, and in both internalizing (21.2%) and externalizing (45%) domains in children of 6-14 years. Younger age of onset, frequency of seizures and duration of disease had significant correlation with behavioral problems in both the age groups. Antiepileptic drug polytherapy was significantly associated with internalizing problems in older children.

Conclusion

Age at onset, frequency of seizures and duration of disease were found to be significantly associated with occurrence of behavioral problems.