生酮饮食的抗癫(痫)机制研究进展

生酮饮食用于癫(痫)治疗已达90年之久,引进我国也已10余年.生酮饮食临床疗效已得到一致认可,但其抗癫(痫)机制至今仍不明确.该文从离子通道、神经递质、神经保护、腺苷及mTOR通路、免疫因素的角度来阐述其可能的抗癫(痫)机制.     

Angelman综合征的临床和脑电图特征

目的 探讨儿童Angelman综合征(AS)的临床和脑电图特征,加强对本病的认识.方法 14例患儿均接受录像脑电图、头颅MRI/CT及基因学检查;11例进行了遗传代谢病相关检查(血乳酸、血氨、尿氨基酸和有机酸筛杳等);8例接受智力测查.随访时间1～3年.结果 本组就诊时年龄8个月～3岁7个月,其中男4例,女10例,他们的临床特征表现为下颌突出、嘴阔大、肤色白、毛发黄、虹膜色淡,阵发性发笑,站立不能或走路不稳,语言落后.本组中被诊断癫癎12例,其中10例出现非惊厥样癫癎持续状态;同时有肌阵挛发作、不典型失神发作、非惊厥样癫癎持续状态9例;单纯肌阵挛发作、强直阵挛发作和复杂部分性发作各1例;病初发热惊厥4例.8例患儿脑电图提示清醒及睡眠期阵发中高波幅(2.5～3 Hz)棘波、棘慢波;4例双导频繁阵发中高波幅2～3 Hz慢波,夹杂少量尖波;2例脑电图正常.全部病例均被遗传学检查确诊,其中母源性染色体15q11-13缺失12例,父源性单亲二倍体1例,印迹缺损1例.结论 AS患儿具有较为突出的临床特点及特殊面容,多数患儿具有特征性的脑电图表现.15q11-13区域存在异常是确诊的依据.     

热性感染相关性癫(癎)综合征的研究进展

国外学者报道了一组既往正常的儿童,在发热后出现难治性部分性癫(癎)或癫(癎)持续状态,预后存在认知功能障碍以及药物抵抗性癫(癎)的临床病例,将其命名为热性感染相关性癫(癎)综合征.目前该病病因不明,病情危重,预后差,脑脊液、脑活检和神经影像学未见特异性改变,尚无明确有效的治疗方法,有报道生酮饮食可能有效.该文就热性感染相关性癫(癎)综合征的临床特点进行综述.     

癫(间)156例的临床及脑电图分析

我院1996年10月～2002年10月根据临床和脑电图(EEG)确诊为儿童癫(间)156例,现分析如下.     

两种生酮饮食方案治疗儿童难治性癫(癎)的随机对照研究

目的 评估按需和按时服用生酮饮食(ketogenic diet,KD)两种方案的疗效和安全性.方法 采用随机数字表法将60例难治性癫(癎)患儿随机分成按需服用KD组和按时服用KD组,每组30例.全量服用KD后连续72 h每6小时监测血酮、血糖和尿酮,比较两组患儿酮症状态的稳定性.记录发作频率并确定起效时间,分别在治疗后4周、12周、24周、48周评估两组患儿的疗效及安全性.结果 治疗4周后,按需服用KD组与按时服用KD组发作完全缓解率分别为33.3％ (10/30)与30.0％ (9/30),两组疗效相当(P＞0.05).按需服用KD组治疗有效病例平均起效时间为(6.18±2.42)d,而按时服用KD组有效病例平均起效时间为(8.63±2.63)d,两组比较差异有统计学意义(P＜0.05).治疗后12周、24周和48周,按需服用KD组发作完全缓解率分别为30.0％(9/30)、34.8％(8/23)和36.8％ (7/19);按时服用KD组发作完全缓解率分别为33.3％ (10/30)、30.4％ (7/23)和44.4％ (8/18),两组比较差异无统计学意义(P＞0.05).1年后,按需服用KD组和按时服用KD组治疗保留率分别为63.3％ (19/30)与60.0％ (18/30),两组比较差异无统计学意义(P＞0.05).治疗过程中,按需服用KD组与按时服用KD组的不良反应主要为可治疗的胃肠道反应和代谢紊乱.结论 按需服用KD和按时服用KD两种治疗方案均基本安全有效,按需服用方案更易达到酮症状态,起效更迅速,较易被患儿接受.因此在临床实施过程中可根据患儿的饮食习惯,灵活安排进食时间以提高治疗的依从性.     

生酮饮食添加治疗难治性癫(癇)36例

目的 观察生酮饮食(KD)添加治疗儿童难治性癫(癇)的临床疗效、保留率、不良反应及其对认知功能的影响,并比较住院治疗组与门诊治疗组不同实施方案的临床疗效及保留率.方法 选择2012年5月至2013年10月在郑州大学第三附属医院河南省小儿脑瘫康复治疗中心接受添加治疗的36例难治性癫(癇)患儿,包括住院治疗组及门诊治疗组,住院治疗组KD方案采用经典模式,即启动时禁食,脂肪和蛋白质、碳水化合物比例为4∶1;门诊治疗组KD方案无需禁食,脂肪和蛋白质、碳水化合物比例由1∶1逐渐升高至4∶1,疗效的评估以KD添加治疗前癫(癇)发作频率为基线,通过家长记录癫(癇)日记,了解癫(癇)发作的频率、类型、每次发作持续时间、发作程度变化,并于添加KD治疗前及KD治疗3、6、12个月行Gesell发育量表评定.结果 住院治疗组KD治疗3、6、12个月总有效率分别为60.0％、45.0％、40.0％,保留率分别为80.0％、55.0％、40.0％,完全控制率30.0％;门诊治疗组3、6、12个月总有效率分别为37.5％、25.0％、18.8％,保留率分别为62.5％、37.5％、18.8％,完全控制率12.5％;住院治疗组与门诊治疗组临床疗效比较差异有统计学意义(P＜0.05),保留率比较差异无统计学意义(P＞0.05);住院治疗组短期不良反应主要表现为胃肠道反应,长期不良反应为肾结石1例,门诊治疗组不良反应多轻微;36例难治性癫(癇)患儿认知功能改善共9例,住院治疗组6例,门诊治疗组3例,五大能区发育商多组间比较大运动(F=3.287,P=0.025)及适应性能区(F=8.335,P=0.000)差异有统计学意义.结论 KD添加治疗儿童难治性癫(癇)住院治疗与门诊治疗均安全有效;住院治疗组的疗效较门诊治疗组好,2组保留率相当;提高患者依从性仍是KD治疗成败的重要因素;KD治疗对难治性癫(癇)患儿的认知功能有所改善,主要表现在大运动及适应性能区.     

儿童板层型灰质异位症伴癫(痫)发作三例并文献复习

目的 观察并探讨板层型灰质异位症伴癫(痫)发作儿童的临床表现、脑电图及影像学特点.方法 收集板层型灰质异位症的癫(痫)患儿病例资料3例,对其临床表现、影像学及脑电图特点进行回顾性分析,并电话随访其治疗及预后情况.结果 本研究中板层型灰质异位症患儿均为女性,均伴有反复癫(痫)发作,并伴有一定程度发育落后或学习困难;影像学均呈典型的“双皮质征”改变;其癫(痫)发作形式复杂,以全面发作或复杂部分性发作为主,可混合不典型失神发作或失张力发作,发作前有恐惧、腹痛等先兆,脑电图呈多灶性改变,以枕、顶、颞叶最显著;3例患儿均为联合用药治疗,脑电图改变及临床发作均有好转趋势.结论 对儿童期反复癫(痫)发作伴有一定智力缺陷的女性患儿需注意是否为板层型灰质异位症,磁共振发现“双皮质征”改变为确诊依据,其癫(痫)发作早期治疗可有较好的效果,抗癫(痫)治疗建议联合用药.     

小儿枕叶癫(癎)35例临床与脑电图分析

目的 分析小儿枕叶癫(癎)的临床特点及脑电图资料,以提高诊断水平.方法 对1997-09-2006-06成都市儿童医院收治的35例枕叶癫(癎)患儿的临床表现和脑电图进行分析.结果 1 097例癫(癎)患儿中,枕叶癫(癎)35例(3.2%),男23例,女12例,确诊时病程1d至6年,平均1年5个月.其中早发型儿童良性枕叶癫(癎)(EB-OS)13例,晚发型儿童枕叶癫(癎)(LOS)16例,症状性枕叶癫(癎)6例.EBOS组发病年龄(4.08±2.19)岁,以运动性发作多见,占84.6%(11/13);LOS组发病年龄(7.28±3.92)岁,视觉症状占56.3%(9/16)、偏头痛症状56.3%(9/16);症状性枕叶癫(癎)组发病年龄(1.51±0.76)岁,均为运动性发作.脑电图特征为发作间期一侧或双侧枕叶的高幅棘波、棘慢波或尖波发放,闭眼出现,睁眼消失.结论 小儿枕叶癫(癎)临床表现复杂多样,容易误诊,应熟悉临床特点,重视视觉症状,结合发作间期脑电图枕叶放电特征,可作出正确诊断.     

生酮饮食抗癫(疒间)机制的研究进展

生酮饮食(ketogenic diet,KD)是一种高脂低糖低蛋白饮食,直接引发酮体、脂肪酸升高以及糖酵解抑制等全身性变化.癫疒间发病机制主要与离子通道、神经递质和神经细胞损伤等相关.该文着重从癫(疒间)发生的角度阐述KD所引发的全身性变化,通过调控离子通道的开放和关闭,调节兴奋性和抑制性神经递质的平衡,增加能量代谢、减少氧自由基的生成和促进神经细胞再生等方式发挥抗癫疒间作用.     

15q11-13缺失型Angelman综合征17例遗传学诊断及临床特点

目的 对临床诊断的Angelman综合征(AS)患儿进行遗传学诊断和临床特点分析.方法 利用MS-PCR、STR家系连锁分析和染色体核型分析,对17例临床诊断AS的患儿(其中男7例,女10例,年龄8个月～5岁)进行遗传学诊断.依据国际诊断标准,分析15q11-13缺失型AS患儿的相关表型特点.结果 (1)17例确诊为15q11-13缺失型AS.(2)患儿出生情况无明显异常.所有的患儿均有不同程度的运动和语言发育迟缓,以语言发育落后更为显著,并伴有特征性的快乐行为.(3)AS的经常性表现:癫癎(15例),异常脑电图(14例),发生率约80%～90%,只有35%的患儿(6例)存在小头畸形.(4)与AS较为关联的表现:平枕/枕骨凹陷(12例),下颌突出(10例),宽嘴和齿缝稀疏(13例),频繁流口水(8例),过多的嘴部动作(9例),肤色及发色浅淡(13例),运动时屈曲手臂(9例),睡眠障碍(9例)等,发生率47%～77%.＞2岁年龄组患儿的AS相关性表现的发生率均高于≤2岁年龄组患儿.结论 联合应用MS-PCR、STR连锁分析和染色体核型分析,确诊17例患儿为15q11-13缺失型AS.我国15q11-13缺失型AS患儿的临床表现与国际诊断标准基本一致,惟小头畸形比率低于白种人,可能存在人种表型差异.随着年龄的增长AS相关性表现更为明显.     

Long-standing fever and Angelman syndrome: report of two cases

Abstract:   An 8-month-old girl and a 20-month-old boy who presented with motor and developmental delay and long-standing fever are presented. The patients were diagnosed as Angelman syndrome with fluorescence in situ hybridization (FISH) analysis. Despite extensive clinical and laboratory examinations, no inflammatory or infectious origin for the fever was found. It was considered that the long-standing fever observed in these cases was due to hypothalamic dysfunction for thermoregulation.     

Angelman�ۺ����ٴ����Ե�ͼ����?

目的分析Angelman综合征(AS)的临床及脑电图(EEG)特征,提高临床对本病早期而准确的认识。方法分析2006年1月至2009年11月北京大学第一医院儿科神经门诊、病房及EEG监测室8例经遗传学确诊的AS患儿临床及EEG特征,并对治疗及预后进行随访。结果 8例中男6例,女2例。均存在全面发育特别是语言发育延迟、运动障碍、表情快乐并伴与环境不相适应的笑,部分患儿有异常的特征性面部表现。均有癫痫发作,起病年龄为6个月至2岁,发作包括热性惊厥、不典型失神发作、部分性发作、肌阵挛发作、部分继发全面性发作,3例有癫痫持续状态。EEG监测年龄为1岁7个月至7岁,图形特征为醒睡各期前头部、后头部及广泛性δ及θ节律性阵发或连续发放,慢波在多部位之间常呈游走性,并见夹杂棘波、棘慢波,5例棘慢波以后头部突出。均经遗传学检测而确诊,其中7例为来源于母源染色体15q11-13的大片段缺失。2例影像学证实有脑白质发育异常。随访时年龄为2岁5个月至9岁3个月,随访时间1～8年。癫痫治疗主要为丙戊酸单药或联合其他抗癫痫药,3例发作控制,4例发作明显减少,1例无改善。随访时5例能独立行走但不稳,1例仅能说简单词汇,7例语言始终无发育。...     

Fertility in Prader-Willi syndrome: a case report with Angelman syndrome in the offspring

We report on a 32-y-old woman with Prader-Willi syndrome (PWS) and her daughter with Angelman syndrome (AS). PWS in the mother was confirmed as due to a deletion of 15q11-q13, and molecular analysis in the neonate indicated an inherited maternal deletion of the same region. Features of AS in early infancy, such as jerky movements, feeding problems and poor sleep, were observed. At 5 mo of age, a triphasic high voltage EEG pattern was reported. Conclusions: This case confirms the non-Mendelian inheritance of PWS and AS and, in addition to previous reports, provides evidence of fertility in PWS women. We recommend the provision of information regarding fertility in females with PWS to parents, guardians and individuals with PWS, and frequent EEG monitoring for early AS diagnosis. Given the different genetic aetiologies for PWS and AS, cytogenetic and molecular genetic analysis is strongly indicated for counselling and risk estimation.     

The EEG in early diagnosis of the Angelman (Happy Puppet) syndrome

An EEG study has been carried out on 19 children (including siblings in 3 families) with clinical features of Angelman syndrome. The age at time of the first EEG ranged from 11 months to 11 years with the majority under 5 years. Six children had no history of seizures at the time of the first EEG. One or more of the following EEG abnormalities were seen in all patients: 1. Persistent rhythmic 4–6/s activities reaching more than 200 V not associated with drowsiness. 2. Prolonged runs of rhythmic 2–3/s activity (200–500 V) often more prominent anteriorly, sometimes associated with discharges (ill-defined spike/wave complexes). 3. Spikes mixed with 3–4/s components usually more than 200 V mainly posteriorly and facilitated by, or only seen with, eye closure. Two and sometimes three of these EEG features could be present in the same record particularly at a young age. The appearance of discharges mixed with slow components on eye closure was the commonest finding seen at some stage in 17 patients (aged from 11 months to over 12 years). The EEG features of Angelman syndrome appear to be sufficiently characteristic to help identify patients at an early age before the clinical features become obvious and at a time when genetic counselling may be particularly important.     

An Angelman syndrome clinic: Report on 24 patients

Objective : Angelman syndrome (AS) is a rare congenital neurodevelopmental disorder with complex genetic aetiology. Diagnosis may be difficult and there is severe life-long disability. An AS clinic was commenced in Sydney, Australia, in 1993 with the aim of gathering information about the natural history of AS, management issues and parental concerns. Methodology : Patients were referred from metropolitan Sydney, rural New South Wales and interstate. A questionnaire, history, physical examination and diagnostic tests were undertaken. Results : In the first year, 24 patients with AS were assessed. There were 11 males and 13 females, whose ages ranged from 3 to 30 years. The mean age of diagnosis was 12.8 years. The diagnosis was made by neurologists in four cases, by clinical geneticists in three cases, by paediatricians in two cases and 15 cases were diagnosed at the AS clinic. A clear history of epilepsy was obtained in 19 (79%) and in 15 of these patients the age of onset was during the first 4 years of life. An EEG had been performed in 21 patients, and in two the EEG was reported as normal. Fifteen of the patients (62.5%) could walk independently and in this cohort there was a significant sex difference in walking: 10/11 males compared to 5/13 females (P >0.01). Five patients (21%) were in full-time permanent care. Genetic testing with appropriate DNA probes from chromosome 15(q11-13), complete in 20 families, showed deletion in 12 patients (60%), uniparental disomy in 1 (5%) and no detectable abnormality in 7 (35%). Conclusions : The diagnosis of AS should be considered in any patient with severe developmental disability particularly if there is a movement disorder and lack of speech. The control of epilepsy is a major management problem. Further research is needed to establish the frequency and type of seizures, the reponse to anticonvulsants and to determine if improvement can be expected with age. The mobility of patients should be assessed regularly, to determine the most appropriate options for intervention.     

Angelman综合征发病机制、分型及治疗进展

Angelman综合征(AS)是以严重发育迟缓、智力低下、语言障碍、共济失调、癫痫发作、愉快表情为特征的神经遗传性疾病。成年AS患者生活质量低下,对家庭及社会造成极大负担。目前已知AS有4种基因型,不同基因型患者的临床表现存在差异。文章综述近年对AS发病机制、基因缺陷分型、治疗的研究进展。     

生酮饮食抗癫痫机制的研究进展

生酮饮食（ketogenic diet,KD）是一种高脂低糖低蛋白饮食,直接引发酮体、脂肪酸升高以及糖酵解抑制等全身性变化。癫痫发病机制主要与离子通道、神经递质和神经细胞损伤等相关。该文着重从癫痫发生的角度阐述KD所引发的全身性变化,通过调控离子通道的开放和关闭,调节兴奋性和抑制性神经递质的平衡,增加能量代谢、减少氧自由基的生成和促进神经细胞再生等方式发挥抗癫痫作用。