生酮饮食治疗癫痫儿童的随机对照研究

目的通过随机对照研究,评估生酮饮食治疗难治性癫痫的疗效。方法回顾性分析145例难治性癫痫儿童的临床资料。年龄2～16岁：癫痫每天均发作（或每周至少发作7次）;使用两种或两种以上抗癫痫药物治疗无效。前期未采用生酮饮食。2001年12月一2006年7月,在治疗年轻癫痫病人的医疗中心进行研究。实验组病儿随机接受生酮饮食,立即或者每隔3个月进行评估;对照组不接受治疗。家属和调查者均了解分组情况。与对照组相比,3个月后记录早期放弃情况,评估治疗中癫痫发作频率。主要的评价指标是发作减少,分析治疗方法。治疗耐受性可通过3个月后调查问卷评估。研究注册于ClinicalTrials．gov网站,编号：NCT00564915。结果实验组73例,对照组72例。103例病儿数据可用于分析,其中54例接受生酮饮食,49例不接受治疗。未完成观察的病例中,16例不接受治疗,16例未能提供有效数据,10例在3个月观察期内放弃治疗（其中6例不耐受）。3个月后,实验组基线癫痫平均发作率（62％）低于对照组（136．9％）,降低75％（95％CI为42．4％～107．4％,P〈0．0001）。与对照组4例（6％）病儿相比,实验组28例（38％）癫痫发作减少50％以上（P〈0．0001）,5例（7％）癫痫发作减少90％以上（P=0．0582）。两组在缓解全身症状或局部症状方面无差别。最常见的副作用为便秘、呕吐、无力、饥饿。结论研究表明：生酮饮食适用于难治性癫痫儿童的治疗。     

生酮饮食联合抗癫痫药物对难治性癫痫的疗效评价

目的评价生酮饮食(KD)联合抗癫痫药物对难治性癫痫的疗效。方法对77例难治性癫痫患者在原有药物不变的基础上添加KD治疗3个月。观察癫痫临床发作频率的改变,判断疗效。比较有效组和无效组患者的临床资料,分析影响KD疗效的因素。结果在KD治疗后,完全控制16例(20.8%),显著有效14例(18.2%),有效12例(15.6%),无效35例(45.5%);KD添加治疗的总有效率为54.5%,保留率为76.6%。KD添加治疗无效组合用药物种类、智能障碍比例及睡眠障碍比例均明显高于有效组;而痉挛发作比例则明显低于有效组(均P0.05)。结论 KD联合抗癫痫药物治疗难治性癫痫总体有效,尤其是痉挛发作类;对伴有智能障碍、睡眠障碍及合用药物种类偏多者疗效欠佳。     

生酮饮食治疗对人体各系统影响

正癫痫是儿科系统常见病,据中国卫生部及抗癫痫协会统计数据显示,0~14岁儿童癫痫发病率为151/10万,患病率为3.45‰,经过各种抗癫痫药物治疗,虽70%~80%患儿可治愈,仍有20%~30%患儿发作得不到控制,成为难治性癫痫,需要寻求其他治疗手段~[1]。生酮饮食(KD)用于难治性癫痫治疗在国外已有90余年历史,通过让癫痫患者进食脂肪/(蛋白质+碳水化合物)重量比为4∶1的饮食来控制癫痫发作(饮     

胼胝体切开术对儿童难治性癫痫术后认知功能的影响

目的探讨胼胝体切开术对儿童难治性癫痫患儿术后认知功能的影响。方法 2016年4月至2018年10月在解放军第988中心医院儿科、神经外科门诊及病房收治的47例儿童难治性癫痫患儿根据治疗方式分为手术组(25例)及对照组(22例);手术组行胼胝体切开术,术后继续给予抗癫痫药物治疗;对照组仅给予抗癫痫药物治疗。6个月后根据治疗前后癫痫发作频率的变化评价效果;治疗前和治疗后6个月时采用韦氏儿童智力量表对患儿进行认知功能的评测。结果①术后6个月,手术组总体有效率(92.00%)明显高于对照组(63.64%),差异有统计学意义(P0.05);②与术前相比,手术组术后智商(IQ)、操作评分及言语评分均明显提高,差异有统计学意义(P0.05)。结论胼胝体切开术对儿童难治性癫痫患儿治疗有效;并且对患儿的认知功能有明确改善。     

雷帕霉素添加治疗结节性硬化症合并难治性癫痫的临床疗效观察

目的分析雷帕霉素添加治疗结节性硬化症(Tuberous sclerosis complex,TSC)合并难治性癫痫的临床疗效及安全性,为该病的临床治疗提供科学依据。方法回顾性分析2017年12月—2019年12月在河南省人民医院就诊的TSC合并难治性癫痫患儿,满足纳入标准共22例患儿,其中男11例、女11例,平均年龄(27.91±36.92)月龄,在服用抗癫痫药物治疗的同时添加雷帕霉素治疗,随访至少1年,观察使用雷帕霉素治疗前后癫痫发作频率的改变。结果雷帕霉素添加治疗结节性硬化合并难治性癫痫患儿6个月后平均癫痫发作频率减少率为52.1%,治疗12个月后平均癫痫发作频率减少率为51.2%,并可以维持无癫痫发作天数,添加雷帕霉素治疗前后差异性具有统计学意义(P0.05)。结论雷帕霉素在添加治疗TSC合并难治性癫痫中能降低癫痫的发作频率,并增加无癫痫发作天数,不良反应为轻/中度,在定期随访下雷帕霉素对儿童具有一定的安全性。     

生酮饮食在儿童难治性癫痫中的应用进展

生酮饮食作为治疗难治性癫痫患者的方法之一,其疗效越来越得到大众的认可。由于抗癫痫药物治疗对身心的不良影响,饮食疗法已成为改善难治性癫痫患者生活质量的重要方法。生酮饮食疗法(kctogcnic diet thcrapics,KDTs)结合了多种有益机制为癫痫的治疗提供了广泛的益处,不仅有可能抑制癫痫发作,还可能改变癫痫病程。特别是对于许多儿童难治性癫痫患儿,KDTs为提高患者生活质量带来了希望,并明显降低了癫痫的发作频率。本文将对生酮饮食疗法在治疗儿童难治性癫痫中的应用进行综述。     

胼胝体切开术对难治性癫痫患者认知功能的影响

目的 探讨胼胝体切开术对难治性癫痫患者认知功能的影响.方法 46例难治性癫痫患者按是否接受胼胝体切开术治疗分为手术组(24例)及对照组(22例);手术组给予胼胝体切开术及抗癫痫药物治疗,对照组仅给予抗癫痫药物治疗;6个月后根据治疗前后发作频率的变化评价疗效,治疗前及治疗后6个月时采用韦氏智力量表及事件相关电位P300评价两组患者的认知功能.结果 (1)手术组总有效率(83.3％)显著高于对照组(9.1％)(P＜0.01);(2)与术前比较,手术组术后智商(IQ)、言语及操作评分均明显提高(P＜0.05 ～0.01),P300潜伏期明显缩短、波幅明显提高(均P＜0.01);对照组IQ及P300潜伏期及波幅与治疗前比较差异无统计学意义.结论 胼胝体切开术可有效地治疗难治性癫痫,同时也改善患者的认知功能.     

热性感染相关性癫痫综合征亚急性期的序贯治疗及转归

目的 回顾性分析热性感染相关性癫痫综合征(Fever infection related epilepsy symdrome,FIRES)患儿在亚急性期(急性期生命体征平稳后至病后6个月)的序贯治疗及转归。方法 18例患儿采取高压氧、神经康复及对症处理,就患儿的气管封堵、惊厥、生酮饮食、神经功能障碍等进行综合治疗及管理,评估这些治疗的有效性,以优化亚急性期的治疗方案。结果 ①气管切开:14例患儿气管切开,13例顺利封堵切开的气管; ②惊厥:8例患儿急性期后持续无癫痫发作,10例在亚急性期不同时间出现再发惊厥或者惊厥无缓解,其中通过调整抗癫痫方案后4例无发作,4例明显好转,2例仍存在难治性惊厥发作; ③生酮饮食:急性期所有患儿均进行了生酮饮食治疗。亚急性期呈现生酮值不理想,消化道出血患儿不耐受等不同问题,2例低风险患儿停用生酮饮食后惊厥无复发,1例停用后出现惊厥复发,恢复生酮饮食后控制惊厥,余维持原生酮饮食不变; ④神经功能障碍:所有病例均接受高压氧及康复综合治疗,2例病情极其严重患儿仍为醒状昏迷,其余16例患儿均恢复意识。恢复意识的16例患儿中2例患儿神经功能基本恢复同龄儿童的水平,余14例患儿都存在不同程度的认知、语言障碍,2例伴有明显的情绪异常,除1例患儿有运动障碍,其余患儿除协调平衡功能欠佳,未遗留运动系统严重问题。结论 FIRES有共同的发病特点,但转归各有不同,亚急性的综合治疗措施,优化综合治疗流程,最大可能减小患儿并发症,减轻患儿神经系统后遗症。     

难治性颞叶癫痫术后急性发作对远期预后的预测价值

目的探讨药物难治性颞叶癫痫术后急性发作对远期预后的影响。方法回顾性分析我院自2009年6月-2010年6月收治的52例药物难治性颞叶癫痫患者的临床资料,所有患者均接受外科治疗,术后定期门诊或电话随访。根据术后7天患者有无急性发作,分为2组,分为实验组(复发),对照组(未复发)。将2组患者随访资料、远期预后(5年)等进行对比分析。结果实验组癫痫控制满意率为35.0%,对照组控制满意率为68.8%,实验组明显低于对照组,差异有统计学意义(χ2=5.683,P=0.017)。在多元Logistic回归分析结果中,复发次数、术前使用抗癫痫药物数量、术后脑电图,术后急性发作与术前习惯性发作相似是影响远期预后的独立影响因子。结论难治性颞叶癫痫术后急性发作对患者远期预后存在影响,已明确的影响因子包括:复发次数、术前抗癫痫药≥3种,术后脑电图及术后急性发作与术前习惯性发作相似。     

结节性硬化症患儿癫痫预后的危险因素分析

目的探讨影响结节性硬化症(TSC)患儿进展为难治性癫痫的危险因素。方法根据近1年内有无癫痫发作及药物控制情况,将83例合并癫痫的TSC患儿分为难治性癫痫组和癫痫控制组,比较两组患儿的临床资料、脑电图(EEG)和头颅MRI检查差异,并通过多因素Logistics回归分析确定影响难治性癫痫进展的独立危险因素。结果与癫痫控制组患儿相比,难治性癫痫组患儿中,癫痫首次发作年龄<2岁、新生儿癫痫、智商评分<70、婴儿痉挛史、合并林-戈综合征、自闭症、癫痫持续状态、使用抗癫痫药物≥3种的患儿显著升高。而难治性癫痫组患儿的EEG呈全面型的患儿比例显著高于癫痫控制组,磁共振(MRI)显示皮质结节≥3个的患儿比例也显著高于癫痫控制组(P<0.001)。多因素Logistics回归分析显示癫痫首次发作年龄<2岁(OR=1.243,95%CI:1.114~1.672,P=0.036)、合并自闭症(OR=3.892,95%CI:1.241~9.351,P=0.008)和大脑皮质结节≥3个(OR=1.905,95%CI:1.101~3.288,P=0.021)是影响难治性癫痫的独立危险因素。结论癫痫首发年龄小于2岁、合并自闭症和脑皮质结节数目超过3个是影响TSC患儿难治性癫痫进展的独立危险因素,对于此类TSC患儿应早期采取干预措施以预防或延缓难治性癫痫的进展。     

Ketogenic diet in pediatric epilepsy patients with gastrostomy feeding

Ketogenic diet is effective in the control of intractable seizures. Poor compliance is a major limiting factor. In one study, only 50% of children receiving the oral ketogenic diet remained on the diet after 1 year. Twelve children with static encephalopathy and intractable symptomatic epilepsy were given the ketogenic diet via gastrostomy tube. Mean age was 3 years (range, 7 months to 6.5 years). Mean seizure frequency at baseline was 199/month. Seizure frequency after 12 and 18 months of diet was compared with baseline. After 12 months on the diet, the number of antiepileptic drugs was compared with baseline. Median seizure reduction at 1 year and 18 months was 61% and 66%, respectively (P = 0.02). Individually, six patients had 90% seizure reduction, one had 75% reduction, three had 50% reduction, and two patients did not improve. Mean antiepileptic drugs at baseline was 2.8; at 12 months 1.6 (49% reduction). Three patients had weight loss. Two patients discontinued the diet at 13 months and 21 months, respectively, because of diarrhea and weight loss. Compliance with diet was 100% during treatment. This study suggests that the ketogenic diet via gastrostomy feeding tube is safe and effective in children with intractable seizures and ensures compliance.     

The Effect of the Ketogenic Diet on the Vascular Structure and Functions in Children With Intractable Epilepsy

ObjectiveWe aimed to determine the midterm effect of a ketogenic diet on serum lipid levels, carotid intima-media thickness, and the elastic properties of the carotid artery and the aorta in patients with intractable epilepsy.MethodsA total of 52 children aged between 12 months and 18 years with intractable epilepsy who started the ketogenic diet from September 2014 to September 2015 were included into this prospective study. Carotid intima-media thickness and the elastic properties of the carotid artery and the aorta were assessed by echocardiography in all cases before beginning of the ketogenic diet and after at least 12 months on the ketogenic diet.ResultsTwenty-one patients at the third month and 25 patients at the first year of the ketogenic diet were seizure free. A reduction of greater than 90% in the seizure frequency was achieved in three patients at the sixth month and in five patients at the first year of the treatment. The serum levels of total cholesterol, low-density lipoprotein, and triglyceride were increased significantly at a median of 12.6 months (range: 12 to 13.5 months) of the ketogenic diet treatment, whereas serum levels of high-density lipoprotein did not change. Carotid intima-media thickness, aortic and carotid strain, the stiffness index, distensibility, and elastic modulus did not change after 12 months of the ketogenic diet therapy.ConclusionOlive oil–based ketogenic diet appears to have no disturbing effect on the carotid intima-media thickness and the elastic properties of the aorta and the carotid artery in epileptic children, although it may be associated with increased concentrations of serum lipids.     

Ketogenic diet in adolescents and adults with epilepsy

PurposeThe ketogenic diet is an alternative treatment for patients with refractory epilepsy. Most studies to date report dietary response in children. There are limited data evaluating the efficacy of the ketogenic diet in adults. This is a report of the long-term outcome in a largely adult population of patients treated with the ketogenic diet for epilepsy.MethodTwenty-nine adult and adolescent patients (mean age 32 years, range 11–51) were initiated on the ketogenic diet and followed until diet discontinuation. Clinical response and adverse effects were noted during the duration of the diet.ResultsFifty-two percent of patients had a significant reduction in seizure frequency on the ketogenic diet, including 45% with ≥50% reduction in seizure frequency. Thirty-one percent had no improvement, seven percent were unable to successfully initiate the diet, and 10% had a >50% increase in seizure frequency. The diet was continued for a mean of 9 months (range 0.13–35 months), with five patients completing ≥23 months. There was a trend toward better response and better tolerability/longer duration in patients with symptomatic generalized epilepsy. The diet was generally well-tolerated, but undesired weight loss and constipation were the most frequent adverse effects.ConclusionThe ketogenic diet can be used safely in the adult and adolescent population, with a response rate similar to those seen in children. Patient with symptomatic generalized epilepsy may be particularly good candidates for this type of dietary treatment.     

Ketogenic diet in patients with myoclonic-astatic epilepsy.

For more than 80 years, the ketogenic diet has been used as an alternative to antiepileptic drugs for patients with refractory epilepsy. Myoclonic-astatic epilepsy in early childhood is one of the malignant epilepsy syndromes that often proves refractory to antiepileptic drugs treatment. Objective. In this prospective study we assess the efficacy and tolerability of the ketogenic diet in patients with myoclonic-astatic epilepsy. Material and methods. Between March 1, 1990 and August 31, 2004, 30 patients who met diagnostic criteria of myoclonic-astatic epilepsy were seen at our department. Eleven of them were placed on the ketogenic diet using the Hopkins protocol and were followed for a minimum of 18 months. Results. The children had previously received a mean of 5.2 different antiepileptic drugs and were on a mean of 2.2 antiepileptic drugs when the diet was started. Eighteen months after initiating the diet, six of the patients (54.5%) remained on the diet. Two patients (18%) were seizure-free, two (18%) had a 75-99% decrease in seizures, and the remaining two children (18%) had a 50% to 74% decrease in seizures. The first two patients were tapered off the diet after remaining seizure-free, without antiepileptic drugs for several years. In the two patients who had sporadic seizures, antiepileptic drugs were reduced to one, and in the last two the seizure frequency was significantly reduced. No differences in seizure control were found when compared for age, sex, or seizure type. Five of our patients discontinued the ketogenic diet in less than 3 months (four because of lack of effectiveness and one because of persistent vomiting). Conclusion. The ketogenic diet is a promising therapy for patients with myoclonic-astatic epilepsy, with over half the children showing a > 50% reduction in seizures, and seizure-freedom in 18%. In drug resistant cases of myoclonic-astatic epilepsy, the diet should be considered early in the course of this syndrome and not as a last resort.     

Efficacy of the Atkins diet as therapy for intractable epilepsy

The ketogenic diet is effective for treating seizures in children with epilepsy. The Atkins diet can also induce a ketotic state, but has fewer protein and caloric restrictions, and has been used safely by millions of people worldwide for weight reduction. Six patients, aged 7 to 52 years, were started on the Atkins diet for the treatment of intractable focal and multifocal epilepsy. Five patients maintained moderate to large ketosis for periods of 6 weeks to 24 months; three patients had seizure reduction and were able to reduce antiepileptic medications. This provides preliminary evidence that the Atkins diet may have a role as therapy for patients with medically resistant epilepsy.     

Experience in the use of the ketogenic diet as early therapy

The ketogenic diet has traditionally been considered an anticonvulsant therapy of last resort, despite excellent efficacy and limited side effects. We hypothesized that the ketogenic diet would have similar results in patients with new-onset epilepsy. A retrospective study was conducted of patients started on the ketogenic diet since 1994. Thirteen of 460 (2.8%) patients were started on the ketogenic diet as early (zero or one prior anticonvulsant) therapy for seizures. Of those remaining on the diet, 60% (6 of 10) had a > 90% seizure reduction at 6 months and 100% (6 of 6) had a > 90% reduction at 12 months. Patients with infantile spasms were as likely to achieve > 50% seizure reduction at 6 months as patients with other seizure types (75% vs 60%; P = .6). The ketogenic diet can be a valuable therapy before epilepsy becomes intractable. In the 13 patients reported, efficacy without side effects was achieved similarly to that with patients with intractable epilepsy.     

Efficacy and safety of the ketogenic diet in Chinese children

ObjectiveTo evaluate the efficacy and safety of the ketogenic diet (KD) treatment of refractory childhood epilepsy in China and determine which children are more likely to respond.MethodsBetween 2004 and 2011, we prospectively enrolled 317 children with refractory epilepsy for the KD treatment in Shenzhen Children's Hospital and followed up for at least a year. Outcome was measured by seizure frequencies before and after the diet, change in anticonvulsant use and adverse effects. We also evaluated influences of different variables (starting age, duration of epilepsy and underlying conditions) on the outcome.ResultsIntent-to-treat analysis showed that after 3, 6 and 12 months, 62.8%, 42.0% and 24.3% remained on the diet, 35.0%, 26.2% and 18.6% showed >50% seizure reduction, including 20.8%, 13.6% and 10.7% seizure free, respectively. Starting age may influence efficacy. The ≥10 age group showed worse response than the <10 age group, though the difference was statistically significant (p = 0.039) at 3 month only. Other variables such as duration of epilepsy at the start of the diet, seizure types and aetiologies showed no significant influence on efficacy. Frequently reported complications included GI disturbance, food refusal and hypoproteinaemia.ConclusionsThe KD is a safe and efficacious therapy for intractable childhood epilepsy in Chinese children. The influence of age on efficacy is worth further investigation.     

A pilot study of the modified Atkins diet for Sturge-Weber syndrome

The modified Atkins diet (MAD) is a dietary treatment for epilepsy which does not restrict fluids or calories. This theoretically makes the MAD safer than the ketogenic diet for children with Sturge-Weber syndrome (SWS). Five children aged 4-18 years with SWS and at least monthly intractable seizures were started prospectively on the MAD for 6 months. All children had urinary ketosis and seizure improvement, including 3 with > 50% seizure reduction.     

Ketogenic diet effects on neurobehavioral development of children with intractable epilepsy: A prospective study

ObjectiveThis study aimed to determine the impact of a ketogenic diet (KD) on neurobehavioral development when used to treat children with intractable epilepsy, confirming the efficacy of the KD, as well as the correlation between early electroencephalography (EEG) changes in the early stage with treatment efficacy.MethodsWe enrolled 42 children who were starting treatment for intractable epilepsy with the classic KD protocol. The total development quotient as well as the development quotients for adaptability, gross motor movements, fine motor movements, language, and individual–social interaction on the Gesell developmental scales were assessed before and after 3, 6, 12, and 18 months of KD treatment. The efficacy assessment was based on changes in seizure frequency after KD as recorded by the parents. We conducted 24-h video-EEG before and after 1 month of KD treatment.ResultsDevelopmental quotients of five energy regions in the Gesell developmental scales assessment were used to compare adaptability (P1 = 0.000), gross motor movements (P2 = 0.010), and fine motor movements (P3 = 0.000); the results showed significant differences. After KD treatment at different time points, 69.0%, 54.8%, 40.5%, and 33.3% patients, respectively, achieved a ≥ 50% reduction in seizure frequency. The reduction of epileptiform discharges in the awake state after 1 month of KD treatment correlated with the efficacy after 3 months of KD treatment.ConclusionsKetogenic diet treatment tends to be associated with improved neurobehavioral development, and more significant improvement can be obtained with prolonged treatment. The KD is safe and effective in treating children with intractable epilepsy. Early EEG changes correlate with clinical efficacy, to a certain degree.     

The importance of parental expectations of cognitive improvement for their children with epilepsy prior to starting the ketogenic diet

Although the success rates and complications of various treatment options for children with intractable epilepsy have been described, the actual expectations of parents for these treatments are less clear. Since 1998, parents at our institution have written their goals in a letter before starting their children on the ketogenic diet. One hundred consecutive letters were evaluated. The most common first goal was seizure improvement, second was anticonvulsant reduction, and third was cognitive improvement. Ninety percent requested improvement in cognition or alertness. These expectations were either met or exceeded at 6 months in 52-60% of children. Achieving or surpassing parental expectations for cognitive improvement correlated with longer diet duration (P=0.04), but meeting goals for seizure or anticonvulsant reduction did not. Cognitive improvement (P<0.001) and >90% seizure reduction (P=0.04) at 6 months positively correlated with longer eventual diet duration. Expectations for cognitive improvement need to be discussed prior to beginning the ketogenic diet.