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、     

生酮饮食治疗儿童难治性癫痫的进展

儿童难治性癫痫是指经2种以上抗癫痫药物的正规治疗,发作仍不能完全控制的癫痫。而生酮饮食(KD)作为一种特殊饮食(高脂肪、低碳水化合物、适量蛋白质的饮食),是治疗儿童难治性癫痫的重要方法。实施KD前,需排除某些代谢性疾病。虽然KD的治疗机制尚未完全明确,但已取得一定的临床疗效。多种因素影响KD的疗效。KD治疗中的不良反应大多为一过性,经积极预防和处理,一般预后良好。     

生酮饮食治疗结节性硬化症相关癫痫的研究进展

结节性硬化症(TSC)是一种遗传性多系统疾病,由 TSC1或 TSC2基因突变引起,发病率为1/14 000～1/6 000。TSC的神经系统表现包括癫痫、发育迟滞、精神异常和神经功能缺损等,其中癫痫最为常见,占80%～90%,其中55%～62%为药物难治性癫痫。TSC相关癫痫严重影响TSC患者的临...     

生酮饮食在儿童癫痫治疗中的应用进展

用含脂肪比例高、蛋白质和碳水化合物比例低的饮食配方，通过脂肪分解代谢产生酮体模拟身体对饥饿的反应治疗癫痫等疾病，这种饮食治疗方法称为生酮饮食疗法。目前生酮饮食治疗癫痫的确切机制尚不清楚。有关生酮饮食治疗儿童难治性癫痫的疗效，系统分析显示无发作的病例达到15．6％（95％CI为10．4％-20．8％），33％（95％CI为24．3％-41．8％）病例获得发作减少50％以上的效果。且该方法不良反应少。因此成为儿童难治性癫痫治疗的主要方法之一。本文就生酮饮食的可能机制、高效、适应证及禁忌证等进行介绍。     

生酮饮食添加治疗儿童癫痫性痉挛临床和随访研究

目的：初步了解生酮饮食（ ketogenic diet,KD）添加治疗对儿童癫痫性痉挛的短期疗效、不良反应及依从性。方法对2012年7月至2014年12月在我院接受KD添加治疗的20例癫痫性痉挛患儿,总结其临床特点,并临床随访。结果20例癫痫性痉挛患儿,男14例,女6例,年龄10个月至8岁2个月,＜1岁2例,～3岁10例,～6岁5例,＞6岁3例。隐源性癫痫12例,围生期脑损伤6例,先天性脑发育畸形及重症病毒性脑炎后遗症各1例。20例患儿均以痉挛发作为主要发作形式,其中7例患儿同时伴随其他发作形式,包括部分性发作泛化全身、阵挛发作、强直发作、不典型失神、不典型失神持续状态。19例患儿诊断为婴儿痉挛症或晚发性癫痫性痉挛,1例诊断为Lennox-Gaustaut综合征。20例患儿病程最短11 d,最长7年9个月。1例患儿因口服抗癫痫药物后短期（11 d）出现较严重肝功损害,予KD治疗,余患儿均为难治性癫痫。20例患儿中6例完全缓解,占30％,1例患儿癫痫发作明显改善,达Engel分级Ⅱ级。12例患儿大运动能力进步,6例患儿同时出现语言能力进步。主要不良反应为消化道症状和代谢紊乱,均较轻微,无严重不良反应。治疗疗程＞6个月者8例,其中4例仍继续治疗,其余12例因短期治疗无效、饮食不耐受、腹泻、治疗过程中饮食控制欠佳及复发等原因终止治疗。结论 KD添加治疗对癫痫性痉挛治疗有效,短期内尚未观察到严重不良反应。还需要加强长期管理,改善饮食配方,提高优质脂肪比例,对更大样本进行更长时间临床观察,为癫痫性痉挛患儿提供更好的治疗方案及更多治疗选择。     

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。     

生酮饮食在基因突变所致难治性癫痫中应用及疗效的研究进展

遗传因素是难治性癫痫的重要病因。多数情况下,基因突变导致的癫痫无法被现有的抗癫痫药物所控制。生酮饮食通过多靶点作用机制控制癫痫发作,在基因突变所致难治性癫痫中应用广泛。该文就生酮饮食在能量代谢、离子通道、哺乳动物雷帕霉素靶蛋白(mTOR)信号通路以及部分其他罕见病四个方面共23种基因突变所致难治性癫痫中应用及疗效的研究...     

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。     

The ketogenic diet in refractory childhood epilepsy

OBJECTIVE: To report the efficacy and tolerability of the ketogenic diet (KD) in refractory paediatric epilepsy. METHODS: Twenty-six consecutive children were treated with the classical KD from 1996 to 2001. The epilepsy syndromes included symptomatic generalized epilepsy (15), idiopathic generalized epilepsy (4), symptomatic partial epilepsy (1) and unclassified epilepsy (6). One child was lost to follow up. RESULTS: Median age at initiation of the KD was 6.1 years. Median duration of the treatment was 9 months. Twelve children (48%) were treated for >12 months; one still remains on the KD. Four children (16%) became seizure-free. Five children (20%) had 50-99% reduction in seizures, seven (28%) had <50% reduction in seizures and eight (36%) had no improvement. Age, seizure-type and aetiology did not predict response. The medications were decreased in 33% of the children. The KD was discontinued in 64% of the children because of poor efficacy and in 12% because of side-effects. Problems during initiation of the KD included asymptomatic hypoglycaemia (24%) and vomiting (12%). Later complications included poor growth (20%), hyperlipidaemia (16%), hypercalcuria (8%), hypocarnitaemia (8%), constipation (8%), pancreatitis (4%) and decreased bone density (4%). There were no deaths. A 3-month trial of the KD costs A3879 dollars. The first 12 months cost A7275 dollars with a cost of A4528 dollars each year, thereafter. CONCLUSIONS: The KD is an effective treatment for some children with refractory epilepsy, being generally well tolerated and rarely associated with side-effects. Response is not necessarily predicted by age, syndrome or aetiology. A prospective study of the KD is presently underway.     

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??The ketogenic diet??KD?? has been used in the treatment of epilepsy in China mainland since 2004. Indications include glucose transporter protein 1??GLUT-1?? deficiency??pyruvate dehydrogenase deficiency??PDHD???? myoclonus astatic epilepsy ??Doose syndrome???? tuberous sclerosis complicated with epilepsy??Rett syndrome??Dravet syndrome??infant spasms??Landau Kleffner syndrome??Lafora disease??and super-refractory status epilepticus. The contraindications include fat metabolic pathway inborn errors??porphyrins diseases??and patients who are not able to cooperate with. The KD therapy complications are less??and by conservative treatment most are reversible. Transition from ordinary diet to KD often lasts 1—2 weeks?? 2??1—4??1 diet can produce ketosis of clinical therapeutic effect. It is recommended that KD might be tried at least for three months. Good responders should maintain the therapy for 2 years or so. It often takes 2 to 3 months for KD to turn back to normal diet. KD therapy should be combined with close follow-up and essessment??and it is considered safe in clinical practice.     

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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.     

生酮饮食对海藻酸致癎大鼠空间学习记忆能力和GluR5表达的影响

目的 探讨生酮饮食对大鼠空间学习记忆能力的影响和其可能的抗癫癎机制.方法 以海藻酸(kainic acid,KA)致癎幼鼠为研究对象,按是否经KA致癎和饮食处理不同分为海藻酸+正常饮食组(KA+ND)、海藻酸+生酮饮食组(KA+KD)、生理盐水+正常饮食组(NS+ND)和生理盐水+生酮饮食组(NS+KD).观察各组动物癫癎行为的变化;经Morris水迷宫对大鼠的空间学习和记忆能力及对已存储信息的再摄取能力进行评价并用Western Blot法检测海马海藻酸受体(CluR5)的表达.结果 KA+KD组动物自发性反复惊厥的次数(1.40±1.03)明显少于KA+ND组(7.36±3.75),四组动物找到平台的潜伏期随实验进行呈缩短趋势(F=30.86,P＜0.001),各组动物间潜伏期比较差异无统计学意义(F=1.04,P＞0.05).KA+KD组大鼠海马CluR5的表达(189.38±40.03)明显高于KA+ND组(128.79±46.51,t=2.79,P＜0.05).结论 酮食疗法对KA致癎大鼠确有抗癫癎作用,其抗癫癎机制可能与增加幼年大鼠CA1区中间神经元CluR5的表达,使海马内抑制性突触传递增强,进而阻止癫癎活动扩散有关.生酮饮食对大鼠的空间学习和记忆能力无明显影响.     

生酮饮食对海藻酸致癎大鼠空间学习记忆能力和GluR_5表达的影响

目的探讨生酮饮食对大鼠空间学习记忆能力的影响和其可能的抗癫癎机制。方法以海藻酸(kainicacid,KA)致疒间幼鼠为研究对象,按是否经KA致疒间和饮食处理不同分为海藻酸 正常饮食组(KA ND)、海藻酸 生酮饮食组(KA KD)、生理盐水 正常饮食组(NS ND)和生理盐水 生酮饮食组(NS KD)。观察各组动物癫癎行为的变化;经Morris水迷宫对大鼠的空间学习和记忆能力及对已存储信息的再摄取能力进行评价并用WesternBlot法检测海马海藻酸受体(GluR5)的表达。结果KA KD组动物自发性反复惊厥的次数(1.40±1.03)明显少于KA ND组(7.36±3.75),四组动物找到平台的潜伏期随实验进行呈缩短趋势(F=30.86,P<0.001),各组动物间潜伏期比较差异无统计学意义(F=1.04,P>0.05)。KA KD组大鼠海马GluR5的表达(189.38±40.03)明显高于KA ND组(128.79±46.51,t=2.79,P<0.05)。结论酮食疗法对KA致疒间大鼠确有抗癫疒间作用,其抗癫疒间机制可能与增加幼年大鼠CA1区中间神经元GluR5的表达,使海马内抑制性突触传递增强,进而阻止癫疒间活动扩散有关。生酮饮食对大鼠的空间学习和记忆能力无明显影响。     

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??Objective To evaluate the effect of ketogenic diet??KD?? in patients with Dravet syndrome??DS??. Methods The seizures??electroencephalogram??EEG?? and cognitive function of 46 DS patients receiving treatment of KD from January 2007 to November 2015 in Department of Pediatrics were analyzed retrospectively. Modified Johns Hopkins protocol was used to initiate KD??and urinary ketone bodies were daily monitored in the patients to maintain the state of ketosis. The effect was evaluated by Engel outcome scale. The EEG?? cognition??language??and motor function of the patients were assessed. Results Totally 46 DS patients??25 boys??21 girls?? received treatment of KD more than 12 weeks??and among them 29??63.0%?? patients were maintained on the diet more than 24 weeks??16??34.8%?? patients more than 48 weeks. Nine patients were seizure free. The seizures in 25 patients were reduced over 50%??and the KD effect was observed within 2 weeks in them.At the end of 12 weeks of treatment with KD??46 patients achieved ?? ?? ?? ?? grade effect??accounting for 19.6%??9/46 cases????13.0%??6/46 cases????21.7%??10/46 cases????and 45.7%??21/46 cases?? respectively according to Engel scale. The background rhythm of EEG showed obvious improvement in 6 patients??andinterictal seizure discharge frequency decreased significantly. Cognitive function of 15 patients was improved. Language was enhanced in 8 patients. Motor function was improved in 8 patients. The main adverse reactions of KD in the treatment process were mainly gastrointestinal symptoms and metabolic disorders. Conclusion KD treatment in Dravet syndrome has many advantages??such as fast acting?? being effective in more than half of the DS patients and tolerable adverse reactions. Drug resistant DS patients are suggested to receive KD treatment.     

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.