From the ECRI-Penn Medicine Evidence-based Practice Center (J.R.T., M.W., A.Y.T.), ECRI, Plymouth Meeting, PA; Department of Pediatrics (Division of Neurology) (S.K.K., N.S.A., S.L.M.), Children's Hospital of Philadelphia; Departments of Neurology and Pediatrics (S.K.K., N.S.A., S.L.M.), University of Pennsylvania Perelman School of Medicine; Department of Anesthesia & Critical Care (N.S.A.), University of Pennsylvania Perelman School of Medicine; Department of Biostatistics, Epidemiology and Informatics (N.S.A.), University of Pennsylvania Perelman School of Medicine; and Division of Neurology (A.Y.T.), Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA.
Neurology. 2023 Jan 3;100(1):e16-e27. doi: 10.1212/WNL.0000000000201026. Epub 2022 Oct 21.
Early life epilepsies are common and often debilitating, but no evidence-based management guidelines exist outside of those for infantile spasms. We conducted a systematic review of the effectiveness and harms of pharmacologic and dietary treatments for epilepsy in children aged 1-36 months without infantile spasms.
We searched EMBASE, MEDLINE, PubMed, and the Cochrane Library for studies published from January 1, 1999, to August 19, 2021. Using prespecified criteria, we identified studies reporting data on children aged 1-36 months receiving pharmacologic or dietary treatments for epilepsy. We did not require that studies report etiology-specific data. We excluded studies of neonates, infantile spasms, and status epilepticus. We included studies administering 1 of 29 pharmacologic treatments and/or 1 of 5 dietary treatments reporting effectiveness outcomes at ≥ 12 weeks. We reviewed the full text to find any subgroup analyses of children aged 1-36 months.
Twenty-three studies met inclusion criteria (6 randomized studies, 2 nonrandomized comparative studies, and 15 prestudies/poststudies). All conclusions were rated low strength of evidence. Levetiracetam leads to seizure freedom in some infants (32% and 66% in studies reporting seizure freedom), but data on 6 other medications were insufficient to permit conclusions about effectiveness (topiramate, lamotrigine, phenytoin, vigabatrin, rufinamide, and stiripentol). Three medications (levetiracetam, topiramate, and lamotrigine) were rarely discontinued because of adverse effects, and severe events were rare. For diets, the ketogenic diet leads to seizure freedom in some infants (rates 12%-37%), and both the ketogenic diet and modified Atkins diet reduce average seizure frequency, but reductions are greater with the ketogenic diet (1 RCT reported a 71% frequency reduction at 6 months for ketogenic diet vs only a 28% reduction for the modified Atkins diet). Dietary harms were not well-reported.
Little high-quality evidence exists on pharmacologic and dietary treatments for early life epilepsies. Future research should isolate how treatments contribute to outcomes, conduct etiology-specific analyses, and report patient-centered outcomes such as hospitalization, neurodevelopment, functional performance, sleep quality, and patient and caregiver quality of life.
This systematic review was registered in PROSPERO (CRD42021220352) on March 5, 2021.
婴儿痉挛症以外，针对 1-36 月龄儿童的早期癫痫的循证医学管理指南仍匮乏，而早发性癫痫较为常见，且常导致残疾。我们进行了一项系统综述，旨在评估针对 1-36 月龄儿童的癫痫的药物和饮食治疗的有效性和危害。
我们在 EMBASE、MEDLINE、PubMed 和 Cochrane 图书馆中检索了 1999 年 1 月 1 日至 2021 年 8 月 19 日发表的研究。我们使用预设标准，筛选了报告了针对 1-36 月龄儿童接受癫痫药物或饮食治疗的数据的研究。我们不要求研究报告病因特异性数据。我们排除了新生儿、婴儿痉挛症和癫痫持续状态的研究。我们纳入了报告 12 周及以上有效性结局的使用 29 种药物中的 1 种或 5 种饮食中的 1 种治疗的研究。我们查阅全文以找到任何针对 1-36 月龄儿童的亚组分析。
23 项研究符合纳入标准（6 项随机研究、2 项非随机对照研究和 15 项预研究/后研究）。所有结论的证据质量均为低强度。左乙拉西坦可使部分婴儿癫痫发作停止（在报告癫痫发作停止的研究中分别为 32%和 66%），但其他 6 种药物的数据不足以得出有效性结论（托吡酯、拉莫三嗪、苯妥英钠、氨己烯酸、鲁拉西酮和司替戊醇）。3 种药物（左乙拉西坦、托吡酯和拉莫三嗪）因不良反应而停药的情况很少见，严重事件也很少见。对于饮食，生酮饮食可使部分婴儿癫痫发作停止（发生率为 12%-37%），生酮饮食和改良阿特金斯饮食均可降低平均癫痫发作频率，但生酮饮食的降低幅度更大（1 项 RCT 报告生酮饮食在 6 个月时的频率降低 71%，而改良阿特金斯饮食仅降低 28%）。饮食相关危害的报告并不完善。
针对早发性癫痫的药物和饮食治疗的高质量证据很少。未来的研究应分离治疗方法如何对结局产生影响，进行病因特异性分析，并报告以患者为中心的结局，如住院、神经发育、功能表现、睡眠质量以及患者和照顾者的生活质量。
本系统综述于 2021 年 3 月 5 日在 PROSPERO（CRD42021220352）注册。
