Epileptic encephalopathy (EE) is a devastating pediatric disease that features medically resistant seizures, which can contribute to global developmental delays. Despite technological advancements in genetics, the neurobiological mechanisms of EEs are not fully understood, leaving few therapeutic options for affected patients. In this review, we introduce the most common EEs in pediatrics (i.e., Ohtahara syndrome, Dravet syndrome, and Lennox-Gastaut syndrome) and their molecular mechanisms that cause excitation/inhibition imbalances. We then discuss some of the essential molecules that are frequently dysregulated in EEs. Specifically, we explore voltage-gated ion channels, synaptic transmission-related proteins, and ligand-gated ion channels in association with the pathophysiology of Ohtahara syndrome, Dravet syndrome, and Lennox-Gastaut syndrome. Finally, we review currently available antiepileptic drugs used to treat seizures in patients with EEs. Since these patients often fail to achieve seizure relief even with the combination therapy, further extensive research efforts to explore the involved molecular mechanisms will be required to develop new drugs for patients with intractable epilepsy.

Neurodiagnostic investigation requirements are expanding for diagnostic and therapeutic purposes in children, especially in those with developmental delay/intellectual disability (DD/ID). Thus, determination of optimal sedatives to achieve successful sedation and immobility without further neurological compromise is important in children with DD/ID. The purpose of this study is to assess the effectiveness and adverse reactions of chloral hydrate (CH) for brain magnetic resonance imaging (B-MRI) in children with DD/ID compared to those with normal intelligence (NI). We performed a retrospective chart review of children aged from 1 day to 12 years who required elective sedation using CH for B-MRI. About 730 cases (415 with DD/ID and 315 with NI) of CH sedation were conducted for B-MRI. Children with DD/ID showed a higher failure rate (22%) than did those with NI (6%); additional CH and prolonged sedation time were required. There was no difference in incidence of adverse reactions between DD/ID and NI groups (p = 0.338). Older or heavier children with DD/ID (p = 0.036 and p = 0.013, respectively), as well as those diagnosed with epilepsy or neuropsychiatric disorders showed higher risk of sedation failure (p < 0.001 for each). In conclusion, CH was a suboptimal sedative drug for children with DD/ID compared with those with NI. Other alternative or supplementary sedatives should be taken into consideration especially for those vulnerable groups.

18p deletion (18p-) syndrome is a rare chromosome abnormality that has a wide range of phenotypes, with short stature, intellectual disability, and facial dysmorphism being the main clinical features. Here, we report the first case in Korea of a 16-year-old male adolescent with 18p- syndrome resulting from de novo unbalanced whole-arm translocation between chromosomes 13 and 18 (45, XY, der(13;18)(q10:q10)). Three rare clinical findings were discovered that had not been reported in the previous literature; morbid obesity without other hormonal disturbances, rib cage deformity leading to the direct compression of the liver, and lumbar spondylolisthesis at the L5-S1 level. This case expands the phenotypic spectrum of 18p- syndrome and highlights the importance of considering chromosomal analysis, since this syndrome can be easily overlooked in a clinical setting, especially without distinctive symptoms of other organs, due to its nonspecific but typical features of short stature and mild intellectual disability with a mildly dysmorphic face. Moreover, since not all cases of 18p- syndrome with unbalanced translocation (13;18) show the same phenotype, multidisciplinary examinations and follow-up seem to be important to monitor evolving and developing clinical manifestations and to predict prognosis in advance associated with the specific genes of 18p breakpoint regions.

Choosing optimal anti-seizure medication (ASM) is very important in pediatric patients with epilepsy who attend school, especially children with an intellectual disability (ID). Levetiracetam (LEV) has proven to be an effective, safe, generally well-tolerated, broad-spectrum ASM in children. In the context of increasing use of LEV in school-aged children with epilepsy and ID, we evaluate relevant clinical data, including efficacy, safety, and tolerability in children with epilepsy and an intellectual disability (ID) or normal intelligence (NI). We performed a retrospective chart review of children and included 298 pediatric patients with epilepsy who were treated with LEV with NI (147) and ID (151). After 6 months, 96% of NI and 83% of ID subjects had a seizure reduction rate greater than 50% (p = 0.031). The tolerability of LEV was generally good, with 75% retention rates at 2 years in both groups and only minor side effects (under 15%). The retention rates of patients with NI and ID were 76% and 74%, respectively (p = 0.597). Thus, LEV showed considerable efficacy with minimal side effects and high retention rates and is an easily maintained and safe treatment option for pediatric epilepsy with ID. However, better-designed research studies are needed to clearly elucidate the efficacy and safety of LEV in children with epilepsy and ID.

Partial deletion of the long arm (q) in chromosome 21 is an extremely rare condition with various phenotypes, including microcephaly, neurodevelopmental delay, dysmorphic features, and epileptic seizures. Neonatal hypoxic-ischemic encephalopathy (HIE) is an encephalopathy associated with a hypoxic-ischemic event in the brain where seizures usually occur in the earliest days of life. Neonatal encephalopathy is a distinct entity resulting from metabolic disorders, congenital infections or genetic abnormalities that could often mimic HIE features, leading to a misdiagnosis of HIE. Here, we present a case of a newborn who was initially misdiagnosed with HIE due to HIE-like features, and eventually was diagnosed to have a de novo ring chromosome 21 with 21q microdeletion. Clinical findings, including severe hypotonia with respiratory/feeding difficulties and intractable seizures, and radiologic findings of ischemic encephalopathy were discovered. Subsequent atypical findings of the clinical presentation ultimately led to her undergoing genetic testing confirming that she had a neonatal encephalopathy with a genetic abnormality. Our case highlights the importance of identifying non-HI neonatal encephalopathy by careful and structured evaluation for current history with a clinical course and a multidisciplinary approach including genetic testing, to provide an accurate diagnosis, treat curable inherited disorders, and develop future genetic counseling.

This retrospective study was performed to determine the seroprevalence of hepatitis A virus (HAV) in children and adolescents with hematologic malignancies after the completion of chemotherapy and hematopoietic cell transplantation (HCT). Of 97 enrolled patients, 60 (61.9%) were seropositive for HAV. The seroprevalences in patients undergoing chemotherapy and HCT were 60.3% (41/68) and 65.5% (19/29), respectively (P = 0.628). No significant factors associated with seropositivity for HAV after chemotherapy and HCT were identified. Anti-HAV tests and HAV re-vaccinations can be considered in children and adolescents with underlying hematologic malignancies after chemotherapy and HCT based on the anti-HAV results.