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.     

生酮饮食治疗儿童难治性癫痫

儿童难治性癫痫(intractable/refractory epilepsy)是指经2种或2种以上抗癫痫药物正规治疗,仍不能完全控制发作的癫痫[1-2],也称为小儿药物难治性癫痫。生酮饮食(ketogenic diet,KD)是目前治疗儿童难治性癫痫的重要方法之一。KD是一种模拟禁食状态下代谢过程的高脂肪、     

生酮饮食对难治性癫痫患儿脂类代谢水平的影响

目的 研究生酮饮食（KD）对难治性癫痫患儿脂类代谢的影响,并通过血脂的变化评估经KD治疗的患儿发生动脉粥样硬化的风险。方法 收集2013~2017年行KD治疗的47例难治性癫痫患儿的临床资料,检测患儿治疗前及治疗3个月后的血脂水平,包括甘油三酯（TG）、总胆固醇（TC）、高密度脂蛋白（HDL）和低密度脂蛋白（LDL）;计算LDL/HDL比值、动脉硬化指数（AI）、血浆致动脉硬化指数（AIP）和血脂综合指数（LCI）,来评估动脉粥样硬化的风险。结果 KD治疗3个月后,患儿TG、TC水平较治疗前轻度升高,HDL水平较治疗前略有下降,但差异均无统计学意义（P > 0.05）;患儿LDL水平在KD治疗3个月后明显高于治疗前（P < 0.05）。KD治疗3个月后,患儿LDL/HDL比值、AI、AIP和LCI数值与治疗前相比均有上升,但仅LDL/HDL比值在患儿治疗前后比较差异有统计学意义（P < 0.05）。结论 KD治疗会引起LDL水平升高,动脉粥样硬化指标LDL/HDL比值升高,提示KD治疗可能会增加动脉粥样硬化发生风险。     

生酮饮食治疗儿童全面性发育迟缓的前瞻性研究

目的观察生酮饮食(KD)对全面性发育迟缓(GDD)患儿神经行为发育、情绪和社会行为及生活能力的影响。方法采用前瞻性病例对照研究,对住院的GDD患儿随机分为KD治疗组和常规治疗组,最终常规治疗组37例和KD治疗组40例纳入研究。两组患儿均进行综合康复训练,KD治疗组在此基础上给予生酮饮食改良Atkins治疗方案。治疗前及治疗后3、6、9个月对两组患儿进行Gesell发育量表、中国幼儿情绪性及社会性发展量表(CITSEA)/Achenbach儿童行为量表(CBCL)、婴儿-初中学生社会生活能力量表(S-M量表)评估,比较2组之间神经行为发育、情绪和社会行为及生活能力的改善情况。结果治疗后3、6、9个月两组患儿Gesell评分比较,在适应性、精细动作、言语3个能区的评分,KD治疗组改善情况优于常规治疗组(P0.05);治疗后3、6、9个月两组患儿CITSEA/CBCL评分比较,KD治疗组改善情况亦优于常规治疗组(P0.05);治疗后9个月KD治疗组S-M量表评分改善情况优于常规治疗组(P0.05)。KD治疗期间,6例患儿出现腹泻症状,1例出现轻度泌尿系结石。结论 KD治疗可改善GDD患儿的神经行为发育及情绪和社会行为,且不良反应少。     

Outpatient initiation of the ketogenic diet in children with pharmacoresistant epilepsy: An effectiveness,safety and economic perspective

BackgroundChildren with pharmacoresistant epilepsy usually receive ketogenic diet (KD) as an inpatient, which makes it an expensive treatment.ObjectiveTo compare the effectiveness, safety, and costs of outpatient versus inpatient initiated KD.DesignRetrospective observational non-inferiority study.Patients/settingPatients (1–18 years of age) who started KD either inpatient or outpatient.Main outcome measuresEffectiveness was defined as ≥50% seizure reduction. Safety was measured by the numbers of emergency visits and complications. Economic impact was analyzed by calculating total costs of treatment.Statistical analysesNon-inferiority of outpatient initiation was tested using 95% confidence intervals of the differences in effectiveness and safety endpoints between groups with non-inferiority margins of 10%. Nonparametric bootstrap techniques were used to derive a 95% confidence interval for the mean difference in total costs between the groups.ResultsHundred and five patients started KD in the period 2001 to 2017: 43 inpatient and 62 outpatient. At three months, the KD was effective in 61% of outpatients versus 63% of inpatients. The KD was considered safe in 36% of the outpatients, as compared to 29% in the inpatients. Outpatient initiation was shown to be non-inferior to inpatient initiation in terms of safety. Total health care costs of outpatient initiation were € 2901, as compared to € 8195 of inpatient initiation per patient (mean difference € 5294, 95% CI; -€ 7653 to -€ 2935).ConclusionsOur study suggests that outpatient KD initiation is no worse than inpatient initiation in terms of effectiveness and safety, while carrying lower health care costs.     

外科手术治疗儿童难治性癫痫及临床评估

国际抗癫痫联盟(ILEA)下属的癫痫外科组委会于1998年成立了儿童癫痫外科分会,着手制定推荐儿童癫痫患者手术治疗的适应证,并探讨和推广正规的术前评估方法。可见儿童癫痫外科与成人之间存在很大差别[1]。     

Angelman综合征8例回顾性临床分析

目的 分析Angelman综合征(AS)的临床表现、脑电图(EEG)特征以及基因结果,探讨生酮饮食(KD)对AS难治性癫(痫)的近期疗效.方法 回顾性分析2012年1月至2013年12月复旦大学附属儿科医院神经科诊断的8例AS患儿的临床表现及EEG特征,并对治疗及预后进行随访.结果 8例AS患儿中男4例,女4例.临床均(100％)表现为大笑或愉快时微笑、全面发育迟滞和运动障碍,4例患儿头围偏小或小头畸形.7例患儿(88％)有癫(痫)发作且发作形式多种,主要为肌阵挛、不典型失神、失张力和部分继发全面性发作等,癫(痫)发病年龄6个月～2岁9个月,4例(57％)有肌阵挛持续状态.EEG特征为前头部、后头部或广泛性δ及θ节律性发放,慢波多呈游走性,并夹杂棘波、棘慢波,棘慢波多在后头部突出.所有患儿采用基因组DNA甲基化特异性多重连接探针扩增技术(MS-MLPA)进行检测,其中6例患儿(75％)证实存在染色体15q11PWS/AS相关区域基因的拷贝数缺失.7例患儿为多种抗癫(痫)药物联合治疗,6例(86％)为药物难治性癫(痫),3例患儿给予KD治疗,治疗1个月时2例有效,1例无效,3个月时1例发作完全缓解,1例有效,1例无效.结论 AS具有相对特征性的临床和EEG表现,结合基因检查可帮助诊断,癫(痫)发生率高,肌阵挛持续状态多见,且多为药物难治性癫(痫),KD可作为AS难治性癫(痫)治疗的选择.     

A pilot study of 1 versus 3 days of dexamethasone as add-on therapy in children with streptococcal pharyngitis

BACKGROUND: Studies in adults, but not in children, have shown a beneficial effect of one dose of steroid on the severity and duration of throat pain in acute pharyngitis. The effectiveness of longer steroid treatment has not been evaluated in children. METHODS: We performed a randomized, double-blind, 3-arm, placebo-controlled trial to estimate the effectiveness of one dose versus 3 daily doses of oral dexamethasone in the treatment of 4- to 21-year-old patients with group A beta-hemolytic streptococcal (GABHS) pharyngitis. Participants used the Wong-Baker FACES scale to rate their symptoms at enrollment and twice daily for 5 days. Patient-completed diaries and telephone interviews provided follow-up data. Primary end points-severity of throat pain, improvement in general condition and improvement in activity level-were evaluated by survival analysis. RESULTS: Ninety patients were enrolled. For each end point, we rejected the null hypothesis of a common survival experience for the 3 study arms. With the exception of 2 days for throat pain in participants receiving one dose of dexamethasone, the median time to improvement for all end points was 1 day for both arms of dexamethasone and 2 days for placebo. There was no difference between study arms in return to a clinical setting for symptoms related to GABHS pharyngitis or absenteeism from work/school. No patient experienced complications related to GABHS pharyngitis in the 30 days after enrollment. CONCLUSIONS: In this pilot study, children with GABHS pharyngitis who receive dexamethasone as add-on therapy have a more rapid improvement in general condition and level of activity and, for those receiving 3 daily doses of dexamethasone, in resolution of throat pain.     

晚发型癫痫性痉挛患儿临床特征及生酮饮食近期疗效分析

目的 分析晚发型癫痫性痉挛患儿临床特征、诊断和治疗。方法 回顾性收集2012年3月至2013年12月在复旦大学附属儿科医院神经科收治的晚发型癫痫性痉挛患儿的临床资料、EEG及抗癫痫药物治疗情况,并评估生酮饮食（KD）的近期疗效。结果 ①18例晚发型癫痫性痉挛患儿进入分析,均经长程视频EEG监测到癫痫性痉挛发作,男13例,女5例,年龄2~10岁（中位年龄5.5岁）。癫痫起病年龄1~8岁（中位年龄3岁）;病程1~72个月（中位病程9个月）。②首次发作为癫痫性痉挛4例（22.2%）,其他发作类型14例（77.8%）。③发作间期EEG呈典型高度失律4例(22.2%)。④7例为症状性癫痫（病毒性脑炎后遗症4例,围生期脑损伤3例）,另11例病因不明,18例均有不同程度精神运动发育落后。⑤在电-临床综合征分类上,符合晚发型婴儿West综合征4例,Lennox-Gastaut综合征4例。⑥18例在抗癫痫药物治疗期间随访3~24个月,抗癫痫药物治疗末次随访时单药治疗2例,多种抗癫痫药物治疗16例;4例维持无发作,14例（77.8%）为药物难治性癫痫。8例药物难治性癫痫患儿接受KD治疗,治疗3个月末完全无发作3例,有效2例,无效3例,有效率62.5%(5/8),完全无发作率37.5%(3/8)。8例均能耐受KD且均未观察到明显的不良事件。结论 儿童晚发型癫痫性痉挛发作不仅见于West综合征,也可见于其他癫痫性脑病,EEG缺乏特征性高度失律,多为药物难治性癫痫,KD治疗安全且具有一定的近期疗效。     

The ketogenic diet in children with Glut1 deficiency syndrome and epilepsy

The effects of a long-term ketogenic diet in children with Glut1 deficiency syndrome on metabolism are unknown. Our results indicate a characteristic effect of a long-term ketogenic diet on glucose and lipid homeostasis in Glut1 deficiency syndrome. Although serum lipids and apolipoproteins reflect a proatherogenic lipoprotein profile, adipocytokine constellation is not indicative of enhanced cardiovascular risk.     

Lorazepam in the treatment of refractory neonatal seizures. A pilot study

Seven neonatal patients with severe seizures unresponsive to conventional anticonvulsant therapy were treated with lorazepam. Immediate cessation of seizure activity occurred in all patients within five minutes. Although seizures recurred in two infants eight hours later, frequency and severity diminished. There were no apparent significant side effects attributed to the medication.     

Glucose transporter type 1 deficiency: a study of two cases with video-EEG

Glucose transporter type 1 (GLUT1) deficiency is an inborn error of glucose transport. Clinical manifestations are presumed secondary to reduced glucose transport across the blood brain barrier, and include seizures, abnormal tone, developmental delay and hypoglycorrhachia. A high index of suspicion is important as GLUT1 deficiency is a potentially treatable cause of mental retardation. We studied two affected children by continuous video-EEG in order to better understand the cause of the clinical manifestations and improvement on a ketogenic diet. The EEG was characterized by generalized paroxysmal 2–2.5 Hz spike-wave discharges, although normal EEGs were also obtained. Atypical absence seizures were the most prominent clinical seizure. Epileptiform activity and clinical seizures occurred in both children while acutely ketotic and non-ketotic, but were markedly more frequent in one child when non-ketotic. Discharges were not associated with a reduction in substrate for brain metabolism in the blood at that time. Conclusion Atypical absence seizures are common in glucose transporter type 1 deficiency and should alert the clinician to the possibility of this treatable disorder when present in a young child with developmental delay. Our data suggest that the therapeutic mechanism of the ketogenic diet in this disorder is more complicated than simply delivering ketones as an alternative substrate for brain metabolism. Received: 28 September 1998 / Accepted: 12 May 1999     

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??Abstract??Objective To evaluate the compliance and safety of the ketogenic diet ??KD?? in children with intractable epilepsy. Methods This was a prospective??open-label study of intractable epilepsy patients treated with the classic KD with a lipid-to-nonlipid ratio 4??1.83 of cases??49 males and 34 females????who were managed and followed-up through multidisciplinary KD special group from May 2011 to December 2012.The variables related to the compliance and safety were also analyzed. Results ??At 5 days??3 and 6 months after initiation??92.8%??77/83????70.7%??53/75????and 57.1%??32/56?? patients remained on the diet.??The main causes to stop the treatment of 26 cases included poor efficacy accounting for 27%??7/26????the children??s rejection for KD accounting for 19%??5/26????a poor compliance of parents accounting for 15%??4/26????the infection and accidental death 12%??3/26??.The cause of treatment discontinued was the noncompliance of the patients or the parents in the early days?? inefficiency and the infection were the main causes to stop the therapy in the near future?? the stopping of treatment according to abnormal nutrition indicators in long-term.??The side effect was drowsiness??fatigue??intolerance of gastrointestinal tract and abnormal blood lipids in the early days.The tolerance of gastrointestinal tract got better in the near future?? and the main side effect was the abnormal blood lipids in this period. Three dead cases were not relative with KD. Conclusion The KD is a safe and effective alternative therapy for intractable childhood epilepsy.Multidisciplinary KD special group is beneficial to children with KD treatment.     

Efficacy and safety of felbamate in children with refractory epilepsy

BackgroundDespite the introduction of multiple new antiepileptic drugs in the past two decades, many patients with epilepsy continue to experience uncontrolled seizures or significant side effects.AimTo present our experience with felbamate therapy in children with drug-resistant epilepsy.MethodsWe retrospectively reviewed the medical charts and video-EEG recordings of all patients receiving felbamate until May 2012. Efficacy was determined according to seizure frequency during the week prior to treatment initiation and the week after the maximal dosage of felbamate was reached.ResultsFifty patients (34 boys) aged 4 months to 17 years (mean – 5.5 years) were identified. Nearly third of the patients had Lennox–Gastaut syndrome. Mean epilepsy duration was 3.4 years (range – 1 month to 13 years). The mean number of previous antiepileptic drugs was 7.5. The mean duration of follow-up was 1.1 years. Seizure frequency decreased by at least 50% in 29 (58%) patients. Side effects were reported in 22 (44%) patients, none of them included aplastic anemia or liver failure. In the responder group, the maximal dose of felbamate was lower and the patients were older compared to non-responders.ConclusionsDespite current recommendations, felbamate is initiated following multiple AEDs. Based on its efficacy and safety data, earlier initiation of felbamate is recommended in children with refractory epilepsy.     

PET、EEG和MRI对儿童难治性癫癎病灶定位的对比研究

目的　探讨正电子发射断层扫描 (PET)、脑电图 (EEG)和磁共振成像 (MRI)在儿童难治性癫疒间 病灶定位方面的诊断价值。方法　对 2 2例难治性癫疒间 患儿分别进行 18F FDGPET、EEG和MRI检查 ,并对癫疒间 病灶的检出率及一致性进行比较。结果　PET显像异常率 90 9% (2 0例 ) ,其中低代谢灶 7例 ,高代谢灶 12例 ,低代谢灶和高代谢灶共存 1例。EEG异常率 81 8% (18例 ) ,在病灶诊断上与PET完全一致为 36 .4 % ,部分一致为36 .4 % ,完全不一致为 2 7.2 %。MRI异常率占 4 0 % ,与PET完全一致为 2 5 % ,完全不一致为 75 %。MRI与PET、EEG比较完全一致率 2 0 % ,部分一致率 5 % ,完全不一致率 75 %。结论　PET显像对儿童难治性癫疒间 病灶的探测敏感性高于EEG和MRI ,在病灶诊断上PET与EEG一致性高于PET与MRI。