Bergqvist A G Christina, Schall Joan I, Gallagher Paul R, Cnaan Avital, Stallings Virginia A
Division of Neurology, The Children's Hospital of Philadelphia, Pennsylvania 19104, USA.
Epilepsia. 2005 Nov;46(11):1810-9. doi: 10.1111/j.1528-1167.2005.00282.x.
The ketogenic diet (KD) is a 90% fat diet that is an effective treatment for intractable epilepsy. Rapid initiation of the KD requires hospital admission because of the complexity of the protocol and frequent mild and moderate adverse events. The purpose of the study was to compare the efficacy of a gradual KD initiation with the standard KD initiation preceded by a 24- to 48-h fast.
Children ages 1 to 14 years with intractable epilepsy were randomized to a fasting initiation (FAST-KD) or gradual initiation (GRAD-KD). Baseline seizure activity was recorded daily for 28 days before admission and continued for the 3-month duration of the study. Effectiveness was measured in two ways: (a) the proportion of subjects with >50% reduction in target seizure type from baseline to 3-month evaluation, and (b) percentage reduction in the frequency of the target seizure type from baseline to 3-month evaluation. Blood glucose was assessed q4 to 6h, and weights, electrolytes, hydration status, vomiting, acid balance, need for interventions (citric acid and sodium citrates (Bicitra) and IV fluids) were assessed daily. Fisher's exact tests were used to examine the association between protocol and occurrence of adverse events, and longitudinal mixed-effects models were used to look for trends in tolerability data over time.
Forty-eight subjects, 24 in each arm, were randomized. In the FAST-KD protocol, 58% of the children had >50% reduction in the target seizure type at 3 months, and 21% were seizure free. In the GRAD-KD protocol, 67% had a >50% reduction at 3 months, and 21% were seizure free. The two protocols were equivalent in efficacy (p = 0.033). At 3 months, the FAST-KD median percentage seizure reduction rate was 78% (ranging from 100% reduction to 73% increase in seizures per week) and was 94% (ranging from 100% reduction to 161% increase in seizures per week) for the GRAD-KD protocol. By using a logarithmic transformed percentage reduction rate and an equivalence limit difference of 20%, the efficacy of the two protocols was equivalent (p = 0.0002). Children in the GRAD protocol lost significantly less weight (p = 0.006), and had fewer and less-severe episodes of hypoglycemia (p < 0.001), fewer treatments for acidosis (citric acid and sodium citrates) (p < 0.04) and dehydration (IV fluids) (p < 0.04), but no difference in vomiting was noted.
These data suggest that in children with intractable epilepsy, a gradual initiation results in fewer adverse events and is tolerated better overall while maintaining the efficacy of the KD.
生酮饮食（KD）是一种脂肪含量为90%的饮食，是治疗难治性癫痫的有效方法。由于方案的复杂性以及频繁出现的轻中度不良事件，快速启动生酮饮食需要住院治疗。本研究的目的是比较逐步启动生酮饮食与先进行24至48小时禁食再启动标准生酮饮食的疗效。
将1至14岁的难治性癫痫儿童随机分为禁食启动组（FAST-KD）或逐步启动组（GRAD-KD）。入院前每天记录28天的基线癫痫发作活动，并在研究的3个月期间持续记录。疗效通过两种方式衡量：（a）从基线到3个月评估时目标癫痫发作类型减少>50%的受试者比例，以及（b）从基线到3个月评估时目标癫痫发作类型频率的减少百分比。每4至6小时评估一次血糖，每天评估体重、电解质、水化状态、呕吐情况、酸碱平衡以及干预措施（柠檬酸和柠檬酸钠（枸橼酸合剂）及静脉输液）的需求。采用Fisher精确检验来检查方案与不良事件发生之间的关联，并使用纵向混合效应模型来观察耐受性数据随时间的趋势。
48名受试者被随机分组，每组24人。在FAST-KD方案中，58%的儿童在3个月时目标癫痫发作类型减少>50%，21%无癫痫发作。在GRAD-KD方案中，67%的儿童在3个月时减少>50%，21%无癫痫发作。两种方案疗效相当（p = 0.033）。3个月时，FAST-KD方案癫痫发作减少率的中位数百分比为78%（每周癫痫发作减少100%至增加73%），GRAD-KD方案为94%（每周癫痫发作减少100%至增加161%）。通过使用对数转换后的减少率百分比和20%的等效限值差异，两种方案的疗效相当（p = 0.0002）。GRAD方案中的儿童体重减轻明显较少（p = 0.006），低血糖发作次数更少且程度更轻（p < 0.001），酸中毒（柠檬酸和柠檬酸钠）治疗次数更少（p < 0.04），脱水（静脉输液）治疗次数更少（p < 0.04），但呕吐情况无差异。
这些数据表明，对于难治性癫痫儿童，逐步启动生酮饮食导致的不良事件较少，总体耐受性更好，同时保持了生酮饮食的疗效。
Zotero 插件