Reddy Doodipala S
Department of Molecular Biomedical Sciences, North Carolina State University, College of Veterinary Medicine, Raleigh, NC 27606, USA.
Drugs Today (Barc). 2002 Oct;38(10):657-75. doi: 10.1358/dot.2002.38.10.820139.
Infantile spasms is an age-specific epileptic syndrome in infants and young children. Although the exact mechanism is unknown, adrenocorticotrophic hormone (ACTH) has been the mainstay for the therapeutic management of infantile spasms and other developmental epilepsies. Clinical benefits of ACTH in infantile spasms could partially relate to its stimulatory effects on the release of adrenocorticosteroids and neurosteroids. Glucocorticoids, pyridoxine and ketogenic diet therapy have all been used for the treatment of refractory infantile spasms. Recent studies indicate that several newer anticonvulsant agents, which are positive allosteric modulators of GABA(A) receptors, are as effective as ACTH in acutely controlling infantile spasms. The efficacy of agents that enhance GABA-mediated inhibition (such as vigabatrin and benzodiazepines) for rapid and complete abolition of infantile spasms has been demonstrated in several clinical studies. Ganaxolone, a novel neuroactive steroid has, however, demonstrated outstanding efficacy and better tolerability in children with intractable infantile spasms. Zonisamide, topiramate, deoxycorticosterone and neurosteroids are emerging as effective treatment approaches. These new antiepileptic drugs represent a potential nonhormonal approach for infantile spasms, but additional studies are needed to verify their efficacy and tolerability. Future studies will hopefully identify rational antiseizure drugs that not only control infantile spasms but also abrogate its risk on the development of the brain.
婴儿痉挛症是婴幼儿期特有的一种癫痫综合征。尽管确切机制尚不清楚，但促肾上腺皮质激素（ACTH）一直是婴儿痉挛症及其他发育性癫痫治疗管理的主要手段。ACTH对婴儿痉挛症的临床益处可能部分与其对肾上腺皮质类固醇和神经甾体释放的刺激作用有关。糖皮质激素、吡哆醇和生酮饮食疗法都已用于治疗难治性婴儿痉挛症。最近的研究表明，几种新型抗惊厥药物，即γ-氨基丁酸A（GABA(A)）受体的正变构调节剂，在急性控制婴儿痉挛症方面与ACTH一样有效。在几项临床研究中已证实，增强GABA介导的抑制作用的药物（如氨己烯酸和苯二氮䓬类药物）在快速、完全消除婴儿痉挛症方面的疗效。然而，新型神经甾体甘氨酰环己酮在难治性婴儿痉挛症患儿中已显示出卓越的疗效和更好的耐受性。唑尼沙胺、托吡酯、脱氧皮质酮和神经甾体正成为有效的治疗方法。这些新型抗癫痫药物代表了一种治疗婴儿痉挛症的潜在非激素方法，但还需要更多研究来验证其疗效和耐受性。未来的研究有望确定合理的抗癫痫药物，这些药物不仅能控制婴儿痉挛症，还能消除其对大脑发育的风险。
