Hormonal Therapy for Infantile Spasms: A Systematic Review and Meta-Analysis

Abstract

ObjectiveThe limitations of adrenocorticotrophic hormone (ACTH) treatment for infantile spasms (ISs), such as high costs, limited availability, and adverse effects (AEs), make it necessary to explore whether corticosteroids are optimal alternatives. Many other compelling treatments have gone through trials due to the suboptimal effectiveness of hormonal therapy. A systematic review and meta-analysis were performed to evaluate the effectiveness and safety of hormonal therapy for patients with ISs.MethodsEMBASE, Ovid MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and online registers were searched through April 2021 for randomized controlled trials (RCTs).ResultsA total of 19 RCTs (N = 1,279) were included. There was no significant difference in the effectiveness of oral corticosteroids and ACTH in electro-clinical response (risk ratio [RR] = 0.85, 95% CI 0.41–1.76). Low-dose ACTH had similar effectiveness in electro-clinical response compared to usual-dose group (RR = 0.94, 95% CI 0.60–1.47) but conferred a lower risk of AEs (RR = 1.71, 95% CI 1.08–2.71). ACTH was more beneficial in controlling spasms than vigabatrin (VGB) (RR = 1.31, 95% CI 1.05–1.64) for patients without tuberous sclerosis complex (TSC). All RCTs were connected through network meta-analysis, and we found that ketogenic diet (KD), zonisamide, methylprednisolone, or combined treatment of hormonal therapy with topiramate (TPM) or pyridoxine was not different in electro-clinical response compared to usual-dose ACTH.ConclusionOur analysis showed that oral corticosteroids could be optional alternatives when ACTH is not applicable, and ACTH is more beneficial for patients without TSC. Moreover, low-dose ACTH is recommended due to comparative effectiveness but lower risk of AEs. However, due to the high heterogeneity of included patients and treatment protocols, these results must be interpreted with caution. RCTs with multicentric involvement and larger sample size are needed for solid evaluation of other alternative treatments.

Corticosteroids in childhood epilepsies: A systematic review

“…The reoccurrence of seizures after a period of seizure freedom was extracted, if possible, from the studies. Because structured meta-analysis for epileptic spasms exists, no analysis was performed on this cohort (5,6). The PRISMA flowchart is shown in Supplementary Figure 1.…”

“…In 1958, Sorel and Dusaucy-Bauloye first reported a marked improvement in 21 patients with epileptic spasms treated with ACTH (4). Since then, corticosteroids have evolved into an essential component of the standard therapy of epileptic spasms backed up by evidence of randomized controlled trials (RCTs) (5,6). Nevertheless, for other childhood epilepsies, various treatment algorithms exist that encompass several steroids including prednisolone, adrenocorticotrophin hormone (ACTH), methylprednisolone, hydrocortisone, and the novel neurosteroid ganaxolone as well as a multifold of protocols .…”

An Epilepsy-Associated Mutation of Salt-Inducible Kinase 1 Increases the Susceptibility to Epileptic Seizures and Interferes with Adrenocorticotropic Hormone Therapy for Infantile Spasms in Mice

“…Although the relevance between the SIK1 mutation and autistic behaviors has been uncovered in SIK1-MT mice, the effect of the SIK1 mutation on epilepsy remains enigmatic. In addition, considering the role of SIK1 in ACTH signaling, it would be intriguing to investigate the effect of ACTH on SIK1-MT mice because ACTH is the first-line drug for infantile spasms [ 16 , 17 , 18 ]. In the present study, we investigated the effect of the C-terminal truncated mutation of SIK1 on epilepsy by inducing seizures in SIK1-MT mice.…”

“…PKA phosphorylates a serine at position 577 (S577) of SIK1 [6,7]. Phosphorylated SIK1 upregulates the cAMP response element binding (CREB) protein 2 of 16 and downregulates the myocyte enhancer factor 2 (MEF2) functions by phosphorylating cAMP-regulated transcriptional co-activators (CRTC) and the class IIa histone deacetylases (HDAC), respectively [8,9].…”

Finding the best: Corticosteroids for the treatment of west syndrome

“…Recent systematic reviews and meta-analyses demonstrated that the efficacy of high-dose oral prednisolone is comparable to ACTH for the electro-clinical remission of infantile spasms in WS. [ 3 4 ] In addition, low-dose ACTH was found to have comparable effectiveness but a lower incidence of adverse effects. Thus, high-dose oral prednisolone is currently widely used as the first-choice medication for the treatment of WS as the short-, medium-, and long-term seizure, and development outcomes have been found to be similar compared to ACTH.…”