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Background Infantile epileptic spasms syndrome (IESS) is a rare but severe condition affecting children early and is usually secondary to an identifiable brain disorder. It is related to psychomotor deterioration in childhood and epilepsy in adult life. Treatment is challenging as infantile spasms may not respond to most antiseizure medication, and relapse is frequent.

Purpose Vigabatrin has proven efficacy in the treatment of infantile spasms, but it carries the risk of irreversible visual field constriction. The incidence of vigabatrin-induced visual field constriction seems to depend on the extent of vigabatrin exposure. The aim of this study was to evaluate whether the therapeutic effect of vigabatrin is maintained in patients with infantile spasms receiving a short vigabatrin course followed by switching to another antiepileptic drug. Methods Patients with infantile spasms responsive to initial vigabatrin treatment were divided into a vigabatrin switch group (n=25) and a vigabatrin maintenance group (n=41). In the former group, vigabatrin was switched to other drugs within 6 months of spasm remission. The rate of seizure recurrence at 6 and 12 months from spasm remission was compared between the two groups. Results No statistically significant differences were found between the vigabatrin switch and maintenance groups in the age of onset, presence of concomitant seizures, time from spasm onset to vigabatrin treatment, time from vigabatrin treatment initiation to spasm remission, or vigabatrin dose at spasm remission. The number of patients with seizure recurrence at 12 months after spasm remission was 3 (3/25, 12%) in the vigabatrin switch group and 10 (10/41, 24.4%) in the vigabatrin maintenance group. The seizure recurrence rate at 12 months from spasm remission was not significantly different between groups. Conclusion A short course of vigabatrin could be considered in patients with infantile spasms who are responsive to initial vigabatrin treatment, since spasm remission was maintained after switching to other drugs.

Purpose Mutations in the cyclin-dependent kinase-like 5 (CDKL5) gene are associated with epileptic encephalopathy and severe cognitive impairment. We aim to characterize the association between this gene and treatment efficacy. Methods We retrospectively analyzed 10 patients who were treated at Severance Children's Hospital for epileptic encephalopathy who were subsequently diagnosed with a CDKL5 mutation using next-generation sequencing. Results Electroencephalography (EEG) results showed generalized pattern abnormalities in 60% (6/10) of patients with CDKL5 mutations. We analyzed the effects of three treatments, namely antiepileptic drugs (AEDs), ketogenic diet (KD), and steroids. A more than 50% reduction in seizures was observed in 12% (1/8) of patients treated with clobazam. KD treatment proved ineffective in most cases. In addition, a more than 50% reduction in seizures was observed in 57% (4/7) of patients treated with steroids. EEG analysis of patients treated effectively with steroids revealed that 75% (3/4) showed hypsarrhythmia and 25% (1/4) showed focal epileptiform. Conclusion In this study, as in other studies, AEDs and KD did not effectively control seizures in most patients with a CDKL5 mutation. However, steroid therapy reduced the frequency of seizures in patients who also exhibited hypsarrhythmia. This suggests that steroid treatment is helpful in cases of hypsarrhythmia with CDKL5 mutations.

Purpose To investigate the effect of vigabatrin (VGB) as a therapeutic agent for patients with infantile spasms (IS), compare risk factors for treatment response, and review safety of VGB by assessing its side effects. Methods Among 35 patients admitted to the Department of Pediatric Neurology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea who received initial monotherapy with VGB under diagnosis of IS, 23 patients who met our inclusion criteria were enrolled and their medical records were retrospectively reviewed. Results Of these 23 patients, average age at diagnosis was 7.26±4.8 months and average age at spasms was 6.20±3.8 months. Average treatment lag was 1.09±1.8 months. Thirteen patients (56.5%) achieved seizure free status. There was no ophthalmic complication among patients. Remission of hypsarrhythmia at 3 and 6 months after treatment was a good prognostic factor (P=0.026 and P=0.004, respectively). Conclusion VGB is effective enough to become a first-line drug for children with IS. Better prognosis can be expected in patients with clinical remission of hypsarrhythmia on electroencephalography after treatment initiation using VGB compared to those who do not have such remission. Regular eye examination and follow-up check-up are also needed in parallel with the use of VGB.

Background Infantile spasm (IS) is characterized by spasm seizure, hypsarrhythmia in EEG, and psychomotor retardation. It is refractory to conventional antiepileptic drugs (AEDs). As firstline therapy for IS, adrenocorticotropic hormone (ACTH) has side effects, such as infection and hypertension. This study aims to evaluate the efficacy and tolerability of magnesium sulfate combined with ACTH treatment by open-label clinical trial. Methods An open-label clinical study was designed. According to inclusion and exclusion criteria, objects were inpatients with IS. A total of 55 patients with IS were enrolled. After clinical data collection, standard magnesium sulfate combined with ACTH was given to the patients for 2 weeks. Efficacy and safety were assessed regularly. The evaluation parameters of efficacy included change of spasm seizure frequency and EEG after treatment. During administration process, vital signs were monitored, laboratory items were tested regularly, and adverse events were daily recorded by guardian. Results After treatment of magnesium sulfate combined with ACTH for 2 weeks, seizure control efficiency was 78.18%(43/55), and the improvement rate of EEG was 55.77% (29/52), wherein 25 patients (45.45%) acquired seizure free, 6 patients (11.54%) presented normal in EEG examination. There were no statistical differences of the effect of different onset ages (≤ 4 months, > 4 months) on seizure control efficiency rate (χ2 = 0.595, P = 0.441) and EEG improvement rate (χ2 = 1.325, P = 0.250), the effect of different courses of disease (≤ 2 months, > 2 months) on seizure control efficiency rate (Fisher's exact test: P = 0.735) and EEG improvement rate ( χ2 = 2.668, P = 0.102), and the effect of different etiologies (idiopathic or cryptogenic IS, symptomatic IS) on seizure control efficiency rate (Fisher's exact test: P = 1.000) and EEG improvement rate ( χ2 = 2.215, P = 0.145). No adverse events, such as hypertension, occurred. After long-term (1 month, 3 months and 12 months) follow-up for 29 patients, seizure free rate remained roughly unchanged (χ2 = 0.945, P = 0.815). Conclusions For patients with IS, magnesium sulfate combined with ACTH treatment is effective and well tolerated. doi: 10.3969/j.issn.1672-6731.2014.11.009

Objective To explore the possible correlation between the genetic variations of the melanocortin receptors (MCRs, including MC2R, MC3R and MC4R) and adrenocorticotropic hormone (ACTH) responsiveness in patients with infantile spasms, and to investigate the function of single nucleotide polymorphism (SNP) found in this study. Methods Direct sequencing method was used to test variations and polymorphisms in the promoter and coding regions of the MC2R, MC3R and MC4R gene. Haplotypes were structured by using SHEsis and Haploview3.32 programs to analyze the distribution frequencies of polymorphism genotypes, alleles and structured haplotypes in Chinese patients with infantile spasms and normal controls. The association between ACTH responsiveness and genetic variations was also assessed. Results Four SNPs were identified in the MC2R promoter region, one of which was new ⁃found locus named ⁃ 2T > C. Three SNPs (rs1893220, rs2186944 and ⁃ 2T > C) showed a significant difference between the cases and controls (P = 0.04, 0.02, 0.01). The common haplotype TCCT may give protection against the development of infantile spasms (P = 0.00). Besides, TCCT carriers were more sensitive to ACTH therapy than non⁃carriers (P = 0.00). The in vitro study proved that the translational efficiency of TCCT promoter in MC2R gene was four times higher than that of TCCC promoter (P = 0.00). MC2R expression assay showed a 5⁃fold increase in the TCCT promoter in presence of ACTH, compared with that in absence of ACTH (P = 0.00). However, responsiveness to ACTH in expression by TCCC promoter showed only 1.50⁃fold increase after ACTH stimulation (P > 0.05). The SNP rs11872992 in MC4R gene was related to the development of infantile spasms, as the efficiency of TC genotype in cases was lower than that of normal controls (P = 0.00). The ACTH therapy results of T⁃allele⁃carriers were better than that of non⁃T⁃allele⁃carriers (P = 0.01). The difference of SNP distribution frequencies in MC3R gene was not statistically significant (P > 0.05). Conclusion The study revealed an association between polymorphism in MCRs (MC2R and MC4R) promoter and the development of infantile spasms, and ACTH responsiveness in patients with infantile spasms. These findings may provide a clue for clinicians to find an early predictive marker for the responsiveness to ACTH and improve the understanding of pathogenesis in infantile spasms. DOI：10.3969/j.issn.1672⁃6731.2012.05.012