Infantile spasms is an epileptic encephalopathy characterized by a profoundly abnormal electroencephalograph pattern called hypsarrhythmia, clinical seizures consisting of spasms, and developmental delays or regression. It is now widely accepted that infantile spasms must be treated early and urgently to decrease the negative developmental effects. Generally agreed upon first-line treatment options are hormonal therapy or vigabatrin, with all other therapies considered second-line. Much debate continues as to the most efficacious hormonal therapy (adrenocorticotropic hormone [ACTH] vs corticosteroids), and no study has yet successfully put this question to rest. Existing data suggest that these hormonal therapies are equally effective. The studies comparing corticosteroids with ACTH are not all randomized or controlled, many are retrospective, and they have been underpowered to answer the question definitively. This issue is also important due to the significant rise in the cost of ACTH therapy. Delays in obtaining ACTH and training time for families due to the need for injections rather than oral administration can potentially prolong the time that a child experiences hypsarrhythmia and spasms, thus potentially affecting long-term developmental outcome. Li et al. provide a meta-analysis of multiple randomized controlled trials that have compared the various forms of hormonal therapies, namely prednisolone/prednisone and ACTH, evaluating their comparative efficacy in cessation of hypsarrhythmia and spasms, and adverse event profile. While each of these studies was randomized and controlled, the outcomes between different hormonal therapies were not always powered to detect a difference between the various hormonal therapies (notably the United Kingdom Infantile Spasms Study). The authors found no difference in efficacy or side effects between hormonal therapies. Each therapy also worked within the same time frame and neither was superior at the 14-day time point. They comment that there may be a difference in efficacy between highand low-dose corticosteroids. A number of limitations in the studies included in this meta-analysis are discussed, including heterogeneous dosing, pretreatment with other antiseizure drugs, and insufficient power, as well as heterogeneity of the underlying infantile spasms etiology. Lumping prednisone and prednisolone together should be viewed with caution, as there is some evidence that infants less effectively convert prednisone into the active metabolite, prednisolone, which could lead to lower effectiveness in the low-dose prednisone versus high-dose prednisolone studies. Other prospective, non-randomized studies have noted a bias in treatment choice depending on the child’s developmental status; those with developmental delays are less likely to receive standard therapy. Additionally, studies that have demonstrated ACTH to have higher efficacy may have been skewed by the fact that patients without developmental disability were more likely to receive ACTH. While this meta-analysis does not definitively answer the question of which hormonal therapy to use, it does provide additional support for equipoise between ACTH and highdose prednisolone. In a healthcare system that is becoming ever more expensive, having a drastically cheaper treatment with equal efficacy is highly desirable. Unanswered questions include whether developmental outcomes correlate with the different hormonal therapies and whether combination therapy, namely with vigabatrin plus hormonal therapy, should be considered as a treatment option. Preclinical studies to explore the underlying mechanisms of infantile spasms will be key to expanding and refining treatment options. Pursuing randomized

中文翻译：

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用于婴儿痉挛症的皮质类固醇和促肾上腺皮质激素：我们是否更接近平衡？

婴儿痉挛症是一种癫痫性脑病，其特征在于称为高度心律失常的严重异常脑电图模式、由痉挛组成的临床癫痫发作以及发育迟缓或退化。现在人们普遍认为，婴儿痉挛症必须及早紧急治疗，以减少对发育的负面影响。普遍同意的一线治疗选择是激素治疗或氨己烯酸，所有其他治疗都被视为二线治疗。关于最有效的激素疗法（促肾上腺皮质激素 [ACTH] 与皮质类固醇）的争论仍在继续，目前还没有研究成功地解决了这个问题。现有数据表明，这些激素疗法同样有效。比较皮质类固醇与 ACTH 的研究并非都是随机或对照的，许多是回顾性的，他们没有能力明确回答这个问题。由于 ACTH 治疗费用的显着增加，这个问题也很重要。由于需要注射而不是口服给药而延迟获得 ACTH 和家庭训练时间可能会延长儿童出现心律失常和痉挛的时间，从而可能影响长期发育结果。李等人。提供对多个随机对照试验的荟萃分析，这些试验比较了各种形式的激素疗法，即泼尼松龙/泼尼松和 ACTH，评估它们在停止超速心律失常和痉挛方面的比较疗效以及不良事件概况。虽然这些研究中的每一项都是随机对照的，不同激素疗法之间的结果并不总是能够检测各种激素疗法之间的差异（特别是英国婴儿痉挛症研究）。作者发现激素疗法在疗效或副作用方面没有差异。每种疗法也在相同的时间范围内起作用，并且在 14 天的时间点都没有优势。他们评论说，高剂量和低剂量皮质类固醇之间的疗效可能存在差异。讨论了本荟萃分析中包括的研究中的许多局限性，包括异质剂量、其他抗癫痫药物的预处理、效力不足以及婴儿痉挛症潜在病因的异质性。应谨慎看待将泼尼松和泼尼松龙混在一起，因为有一些证据表明婴儿将泼尼松转化为活性代谢物泼尼松龙的效率较低，这可能导致低剂量泼尼松与高剂量泼尼松龙研究的有效性较低。其他前瞻性、非随机研究指出，根据儿童的发育状况，治疗选择存在偏差；那些发育迟缓的人不太可能接受标准治疗。此外，由于没有发育障碍的患者更有可能接受 ACTH，因此证明 ACTH 具有更高疗效的研究可能存在偏差。虽然这项荟萃分析没有明确回答使用哪种激素治疗的问题，但它确实为 ACTH 和高剂量泼尼松龙之间的平衡提供了额外的支持。在变得越来越昂贵的医疗保健系统中，非常需要具有同等功效的便宜得多的治疗方法。悬而未决的问题包括发育结果是否与不同的激素疗法相关，以及是否应将联合疗法，即氨己烯酸加激素疗法视为一种治疗选择。探索婴儿痉挛症潜在机制的临床前研究将是扩大和完善治疗方案的关键。追求随机 探索婴儿痉挛症潜在机制的临床前研究将是扩大和完善治疗方案的关键。追求随机 探索婴儿痉挛症潜在机制的临床前研究将是扩大和完善治疗方案的关键。追求随机