Aetiopathogenesis of infantile epileptic spasms syndrome and mechanisms of action of adrenocorticotrophin hormone/corticosteroids in children: A scoping review.

IF 3.8 2区医学 Q1 CLINICAL NEUROLOGY

Developmental Medicine and Child Neurology Pub Date : 2025-02-28 DOI:10.1111/dmcn.16273

Emily A Innes, Velda X Han, Shrujna Patel, Michelle A Farrar, Deepak Gill, Shekeeb S Mohammad, Russell C Dale

{"title":"Aetiopathogenesis of infantile epileptic spasms syndrome and mechanisms of action of adrenocorticotrophin hormone/corticosteroids in children: A scoping review.","authors":"Emily A Innes, Velda X Han, Shrujna Patel, Michelle A Farrar, Deepak Gill, Shekeeb S Mohammad, Russell C Dale","doi":"10.1111/dmcn.16273","DOIUrl":null,"url":null,"abstract":"Aim: To review the aetiopathogenesis of infantile epileptic spasms syndrome (IESS) and mechanisms of action of adrenocorticotrophin hormone (ACTH)/corticosteroids established in humans.Method: MEDLINE, PubMed, and Embase were systematically searched from inception to December 2023 to identify studies related to IESS aetiology and treatment response. Mechanistic themes were identified and through consensus meetings refined and grouped into five overarching hypotheses.Results: Five hypotheses were generated from 17 mechanistic themes: (1) gene and epigenetic regulation altering expression of 'vulnerability' genes; (2) stress and hypothalamic-pituitary-adrenal axis activation; (3) neuroinflammation and altered immune function; (4) altered neuronal transmission and pathways; and (5) dysfunction of metabolic pathways.Interpretation: The evidence that ACTH/corticosteroids alter these processes remains limited. It is plausible that these processes interact with one another, rather than existing independently, and affect maturational and regulatory processes in the central nervous system, consistent with proposals that IESS is a neurodevelopmental disorder. Understanding how ACTH/corticosteroids work in IESS may facilitate disease-modifying treatments and improve neurodevelopmental outcomes.","PeriodicalId":50587,"journal":{"name":"Developmental Medicine and Child Neurology","volume":" ","pages":""},"PeriodicalIF":3.8000,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Developmental Medicine and Child Neurology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/dmcn.16273","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Aim: To review the aetiopathogenesis of infantile epileptic spasms syndrome (IESS) and mechanisms of action of adrenocorticotrophin hormone (ACTH)/corticosteroids established in humans.

Method: MEDLINE, PubMed, and Embase were systematically searched from inception to December 2023 to identify studies related to IESS aetiology and treatment response. Mechanistic themes were identified and through consensus meetings refined and grouped into five overarching hypotheses.

Results: Five hypotheses were generated from 17 mechanistic themes: (1) gene and epigenetic regulation altering expression of 'vulnerability' genes; (2) stress and hypothalamic-pituitary-adrenal axis activation; (3) neuroinflammation and altered immune function; (4) altered neuronal transmission and pathways; and (5) dysfunction of metabolic pathways.

Interpretation: The evidence that ACTH/corticosteroids alter these processes remains limited. It is plausible that these processes interact with one another, rather than existing independently, and affect maturational and regulatory processes in the central nervous system, consistent with proposals that IESS is a neurodevelopmental disorder. Understanding how ACTH/corticosteroids work in IESS may facilitate disease-modifying treatments and improve neurodevelopmental outcomes.

查看原文本刊更多论文

目的：综述婴儿癫痫痉挛综合征（IESS）的发病机制以及肾上腺皮质激素（ACTH）/皮质类固醇在人类中的作用机制：方法：系统检索了从开始到 2023 年 12 月的 MEDLINE、PubMed 和 Embase，以确定与 IESS 病因学和治疗反应相关的研究。确定了机制主题，并通过共识会议加以完善，归纳为五个总体假设：从 17 个机理主题中产生了五个假设：(1) 基因和表观遗传调控改变了 "易感性 "基因的表达；(2) 压力和下丘脑-垂体-肾上腺轴激活；(3) 神经炎症和免疫功能改变；(4) 神经元传递和通路改变；以及 (5) 代谢通路功能障碍：ACTH/皮质类固醇改变这些过程的证据仍然有限。这些过程相互影响，而不是独立存在，并影响中枢神经系统的成熟和调节过程，这与 IESS 是一种神经发育障碍的说法是一致的。了解促肾上腺皮质激素/皮质类固醇如何在 IESS 中起作用，可能有助于改变疾病的治疗和改善神经发育的结果。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Developmental Medicine and Child Neurology 医学-临床神经学

CiteScore

7.80

自引率

13.20%

发文量

338

审稿时长

3-6 weeks

期刊介绍： Wiley-Blackwell is pleased to publish Developmental Medicine & Child Neurology (DMCN), a Mac Keith Press publication and official journal of the American Academy for Cerebral Palsy and Developmental Medicine (AACPDM) and the British Paediatric Neurology Association (BPNA). For over 50 years, DMCN has defined the field of paediatric neurology and neurodisability and is one of the world’s leading journals in the whole field of paediatrics. DMCN disseminates a range of information worldwide to improve the lives of disabled children and their families. The high quality of published articles is maintained by expert review, including independent statistical assessment, before acceptance.