Search

Evidence of the importance of early childhood development (ECD) has transformed child health monitoring and screening tools. Development of the Korean Developmental Screening Test for Infants and Children (K-DST) has expanded the applications of child health screening to a large number of infants and children in Korea and is contributing to the early detection of neurodevelopmental disorders and delivery of timely interventions. The previous screening tool (Korean Ages and Stages Questionnaire) raised some concerns, as its lack of consideration of the cultural background of the Korean population can lead to inaccurate or imprecise diagnoses. The K-DST, a tailored tool for Korean infants and children, is a simple and cost-efficient solution for child health monitoring and screening. This review focuses on the development and role of the K-DST in ensuring ECD. Here we review use of the K-DST for ECD screenings and discuss the best strategy for its use in other countries.

The artificial intelligence (AI)-based genetic diagnostic program has been applied to genome sequencing to facilitate the diagnostic process. The objective of the current study was to evaluate the experience and level of satisfaction of participants using an AI-based diagnostic program for rare pediatric genetic diseases. The patients with neurodevelopmental disorders or hearing impairments, their guardians, and their physicians from 16 tertiary general hospitals were enrolled. The study period was from April 2020 to March 2021. A survey was designed to assess their experience and level of satisfaction. A total of 30 physicians and 243 patients and guardians (199 neurodevelopmental disorders and 44 hearing impairments) completed the survey. DNA samples of the subjects were collected through buccal swabs or blood collection: 211 subjects (86.8%) through buccal swab and 29 subjects (11.9%) through blood collection. Average turnaround time for result receipt was 57.54 ± 32.42 days. For the sampling method, 193 patients and guardians (81.1%) and 28 physicians (93.3%) preferred buccal swab. The level of satisfaction of the 2 groups participating in the AI-based diagnostic program was 8.31 ± 1.71 out of 10 in the patient and guardian group and 8.42 ± 1.23 in the physician group. Clinicians, patients, and guardians are satisfied with the AI-based diagnostic program in general. With an increase in AI-based precision medicine solutions, the evaluation of the user's satisfaction with appropriate provision will help improve personal health care., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: PHF21A , along with EXT2 and ALX4 , is one of the causative genes of Potocki-Shaffer syndrome (PSS), a rare contiguous disorder involving chromosome region11p11.2. PHF21A has been associated with intellectual developmental disorders and craniofacial anomalies and suggested as a candidate for more extended phenotypes. However, variants in PHF21A and its associated phenotypes are yet to be fully explored, since reports on cases with variants affecting this gene are few worldwide. We present a novel heterogeneous variant in PHF21A in a 26-year-old Korean female., Methods: The patient's clinical manifestations were recorded and physical examination, cognitive assessment, brain imaging, metabolic screening, and cytogenetic testing including whole exome sequencing were pursued., Results: Whole exome sequencing identified a de novo nonsense variant c.1171A>T (p.Lys391Ter), affecting the AT-hook domain. The patient showed an extended phenotypic spectrum along with intellectual developmental disorders and craniofacial anomalies, such as attention-deficit hyperactivity disorder, epilepsy, overgrowth, and hypotonia. Variants affecting the AT-hook domain are few in PSS, however, the phenotypic spectrum of the patient was in line with previously reported cases., Conclusion: This case further reinforced and adds to the extended data on the phenotypes associated with PHF21A haploinsufficiency., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 by S. Karger AG, Basel.)

Background: The diagnostic yield of whole-exome sequencing (WES) varies from 30%-50% among patients with mild to severe neurodevelopmental delay (NDD)/intellectual disability (ID). Routine retrospective reanalysis of undiagnosed patients has increased the total diagnostic yield by 10-15%. Here, we performed proband-only WES of 1065 patients with NDD/ID and applied a prospective, daily reanalysis automated pipeline to patients without clinically significant variants to facilitate diagnoses., Methods: The study included 1065 consecutive patients from 1056 nonconsanguineous unrelated families from 10 multimedical centers in South Korea between April 2018 and August 2021. WES data were analyzed daily using automatically updated databases with variant classification and symptom similarity scoring systems., Results: At the initial analysis, 402 patients from 1056 unrelated families (38.0%, 402/1,056 families) had a positive genetic diagnosis. Daily prospective, automated reanalysis resulted in the identification of 34 additional diagnostic variants in 31 patients (3%), which increased our molecular diagnostic yield to 41% (433/1056 families). Among these 31 patients, 26 were diagnosed with 23 different diseases that were newly discovered after 2019. The time interval between the first analysis and the molecular diagnosis by reanalysis was 1.2 ± 0.9 years, which was shorter in the patients enrolled during the latter part of the study period., Conclusion: Daily updated databases and reanalysis systems enhance the diagnostic performance in patients with NDD/ID, contributing to the rapid diagnosis of undiagnosed patients by applying the latest molecular genetic information., (© 2022. The Author(s).)

Background and Purpose: Cerebral visual impairment (CVI) is an underdiagnosed condition in children, and its assessment tools have focused on older children. We aimed to develop a parental questionnaire for cerebral visual impairment (PQCVI) for screening CVI in young children., Methods: The PQCVI comprised 23 questions based on a modified version of Houliston and Dutton's questionnaire for older children. The PQCVI with neurocognitive function tests was applied to 201 child-parent pairs with typically developing children younger than 72 months (age 32.4±20.1 months, mean±standard deviation). The children were classified into six age groups. The normative data, cutoff scores, and internal reliability were assessed and item analysis was performed. We referred to the total score for all questions as the cerebral visual function (CVF) score., Results: The normative data showed that the CVF score and the scores corresponding to ventral-stream and dorsal-stream visual functions plausibly increased with age. The scores rapidly reached 90% of their maximum values up to the age of 36 months, after which they increased slowly. Cronbach's alpha for all questions across all age groups was 0.97, showing excellent consistency. The item difficulty and item discrimination coefficients showed that the questions were generally adequate for this age stage., Conclusions: The PQCVI items produced reliable responses in children younger than 72 months. The rapid increase in scores before the age of 3 years supports the importance of early identification of CVI. Following additional clinical verification, the PQCVI may be useful for CVI screening., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2021 Korean Neurological Association.)

Background: Based on the reports of low prevalence and severity of pediatric severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, the Korean government has released new SARS-CoV-2 infection response and treatment guidelines for children under the age of 12 years. The government has further directed school reopening under strict preventive measures. However, there is still considerable concern on the impact of school reopening on community transmission of Coronavirus disease 2019 (COVID-19). In the present study, we aimed to evaluate the appropriateness of these directives and the severity of SARS-CoV-2 infections in children as compared to adults using sufficient national sample data., Methods: In the present study, we evaluated the severity of SARS-CoV-2 infection in pediatric patients as compared to adults by analyzing the length of hospital stays (LOS), medical expenses, and hospital and intensive care unit (ICU) admission rates. A multivariate linear regression analysis was carried out to examine the effects of COVID-19 patients that the characteristics on the LOS and medical expenses, and multivariate logistic regression analysis were performed to identify COVID-19 characteristics that affect hospital and ICU admission rates and to prove the low SARS-CoV-2 infection severity in pediatric patients., Results: The hospitalization period for children aged 0-9 was 37% shorter and that of patients aged 10-19 years was 31% shorter than those of older age groups ( P < 0.001). The analysis of the medical expenses by age showed that on average, medical expenses for children were approximately 4,900 USD lower for children than for patients over 80 years of age. The linear regression analysis also showed that patients who were 0-9 years old spent 87% and those aged 10-19 118% less on medical expenses than those aged 70 and over, even after the correction of other variables ( P < 0.001). The probability of hospitalization was the lowest at 10-19 years old (odds ratio [OR], 0.05; 95% confidence interval [CI], 0.03-0.09), and their ICU admission rate was also the lowest at 0.14 (OR, 0.14; 95% CI, 0.08-0.24). On the other hand, the likelihood of hospitalization and ICU admission was the highest in children aged 0-9 years, and among patients under the age of 50 years in general., Conclusion: This study demonstrated the low severity of SARS-CoV-2 infection in younger patients (0-19 years) by analyzing the LOS, medical expenses, hospital, and intensive care unit admission rates as outcome variables. As the possibility to develop severe infection of coronavirus at the age of 10-19 was the lowest, a mitigation policy is also required for middle and high school students. In addition, children with underlying diseases need to be protected from high-risk infection environments., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2021 The Korean Academy of Medical Sciences.)

Background: Coronavirus disease 2019 (COVID-19) has spread around the globe, and it is important to determine the risk factors of death in the general population. Our study aimed to determine the risk factors of death and severe illness requiring supplemental oxygen therapy based on the demographic and clinical characteristics of COVID-19 patients in Korea., Methods: In this study, we used data provided by the Korea Disease Control and Prevention Agency (KDCA) and analyzed a total of 5,068 patients with COVID-19, excluding 19 pregnant women and 544 individuals with missing data. We performed logistic regression analysis to determine the impact of early symptoms on survival and severe disease. Logistic regression models included sex, age, number of comorbidities, symptoms on admission, blood pressure, heart rate, and body temperature as explanatory variables, and death and oxygen therapy as outcome variables., Results: Logistic regression analyses revealed that the male sex, older age (≥ 60 years), higher number of comorbidities, presence of symptoms on admission, heart rate ≥ 120 bpm, and body temperature ≥ 37.5°C presented with higher risk of in-hospital death and oxygen therapy requirement. Conversely, rhinorrhea and headache were associated with a low risk of death and oxygen therapy requirement. The findings showed that cough, sputum, and fever were the most common symptoms on admission, while 25.3% of patients with COVID-19 were asymptomatic., Conclusion: COVID-19 patients with high-risk early symptoms on admission, such as dyspnea and altered mental status, and those without low-risk symptoms of rhinorrhea and headache should be included in priority treatment groups., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2021 The Korean Academy of Medical Sciences.)

EVIDENCE, an automated variant prioritization system, has been developed to facilitate whole exome sequencing analyses. This study investigated the diagnostic yield of EVIDENCE in patients with suspected genetic disorders. DNA from 330 probands (age range, 0-68 years) with suspected genetic disorders were subjected to whole exome sequencing. Candidate variants were identified by EVIDENCE and confirmed by testing family members and/or clinical reassessments. EVIDENCE reported a total 228 variants in 200 (60.6%) of the 330 probands. The average number of organs involved per patient was 4.5 ± 5.0. After clinical reassessment and/or family member testing, 167 variants were identified in 141 probands (42.7%), including 105 novel variants. These variants were confirmed as being responsible for 121 genetic disorders. A total of 103 (61.7%) of the 167 variants in 95 patients were classified as pathogenic or probably to be pathogenic before, and 161 (96.4%) variants in 137 patients (41.5%) after, clinical assessment and/or family member testing. Factor associated with a variant being regarded as causative includes similar symptom scores of a gene variant to the phenotype of the patient. This new, automated variant interpretation system facilitated the diagnosis of various genetic diseases with a 42.7% diagnostic yield., (© 2020 The Authors. Clinical Genetics published by John Wiley & Sons Ltd.)

Background: Most developmental screening tools in Korea are adopted from foreign tests. To ensure efficient screening of infants and children in Korea, a nationwide screening tool with high reliability and validity is needed., Purpose: This study aimed to independently develop, standardize, and validate the Korean Developmental Screening Test for Infants and Children (K-DST) for screening infants and children for neurodevelopmental disorders in Korea., Methods: The standardization and validation conducted in 2012-2014 of 3,284 subjects (4-71 months of age) resulted in the first edition of the K-DST. The restandardization and revalidation performed in 2015-2016 of 3.06 million attendees of the National Health Screening Program for Infants and Children resulted in the revised K-DST. We analyzed inter-item consistency and test-retest reliability for the reliability analysis. Regarding the validation of K-DST, we examined the construct validity, sensitivity and specificity, receiver operating characteristic curve analysis, and a criterion-related validity analysis., Results: We ultimately selected 8 questions in 6 developmental domains. For most age groups and each domain, internal consistency was 0.73-0.93 and test-retest reliability was 0.77-0.88. The revised K-DST had high discriminatory ability with a sensitivity of 0.833 and specificity of 0.979. The test supported construct validity by distinguishing between normal and neurodevelopmentally delayed groups. The language and cognition domain of the revised K-DST was highly correlated with the K-Bayley Scales of Infant Development-II's Mental Age Quotient (r=0.766, 0.739), while the gross and fine motor domains were highly correlated with Motor Age Quotient (r=0.695, 0.668), respectively. The Verbal Intelligence Quotient of Korean Wechsler Preschool and Primary Scales of Intelligence was highly correlated with the K-DST cognition and language domains (r=0.701, 0.770), as was the performance intelligence quotient with the fine motor domain (r=0.700)., Conclusion: The K-DST is reliable and valid, suggesting its good potential as an effective screening tool for infants and children with neurodevelopmental disorders in Korea.

Aim: To evaluate the long-term effects of nutritional improvement following percutaneous endoscopic gastrostomy (PEG) tube feeding stratified by previous feeding method and to assess the impact of underlying muscle tone on the outcomes of the nutritional intervention., Methods: Neurologically impaired children who underwent PEG tube insertion and nutritional intervention provided by a pediatric nutritional support team were enrolled. We measured anthropometric variables, laboratory parameters, and nutritional intake at baseline, 6 months after PEG insertion, and the last visit. We evaluated the percent ideal body weight (PIBW), body mass index (BMI)-for-age z -score, and percentiles and calculated the ratios of calorie intake compared to required requirement (CIR) and protein intake compared to recommended requirement (PIR)., Results: The PIBW and BMI-for-age z -score improved during the first 6 months ( p = 0.003 and p = 0.005, respectively). The CIR ( p = 0.015) and PIR ( p = 0.004) increased during the study period. The baseline BMI and PIBW of the previous nasogastric tube feeding group were better than those of the oral feeding group ( p = 0.02 and p = 0.03, respectively). The BMI-for-age z -score, PIBW, CIR, and PIR improved in the hypertonic group ( p = 0.03, 0.02, 0.03, and 0.01, respectively)., Conclusion: PEG tube feeding and active nutritional intervention improved the nutritional status of neurologically impaired children immediately after PEG insertion. The nutritional requirements might vary by the muscle tonicity.

Background: Suboptimal intake of magnesium become prevalent due to the modern diet of processed food low in magnesium. Magnesium may modulate seizure activity by antagonizing excitatory calcium influx through the N-methyl-D-aspartate receptor. Although hyponatremia has been reported to be common in febrile seizures, the most common form of seizure, little is known about the status of serum ionized magnesium. We therefore investigated the status of serum ionized magnesium (iMg 2+ ) in children with febrile seizures and compared with controls., Methods: We included all patients from 1 to 6 years old who had presented with febrile seizure to the pediatric emergency department at the Korea University Guro Hospital from July 2016 to February 2017. The control group comprised patients admitted to the hospital with febrile respiratory tract infections, but with no history of febrile seizure. Clinical data, blood tests, and electroencephalogram (EEG) results were reviewed using the patients' medical records., Results: A total of 133 patients with febrile seizure and 141 control patients were analyzed in the present study. As a result, hypomagnesemia (< 0.50 mmol/L) was more common in patients with febrile seizure than in controls (42.9% vs. 6.9%, p < 0.001) and it was an independent risk factor for febrile seizure (OR, odds ratio = 22.12, 95% CI = 9.23-53.02, P < 0.001). A receiver operating curve analysis revealed that serum iMg 2+ levels < 0.51 mmol/L predicted the presence of febrile seizures with a sensitivity of 45.1% and a specificity of 92.6% (AUC, area under the curve = 0.731, 95% confidence interval = 0.671-0.791). When the patients with febrile seizure were divided in terms of a serum iMg 2+ concentration of 0.51 mmol/L, there was no difference in clinical features., Conclusions: Hypomagnesemia was more common and serum iMg 2+ level was lower in patients with febrile seizures than in controls. However, further evidence is needed for the causal relationship between low magnesium and febrile convulsions.

Objectives: Recently, conflicting results have been reported regarding the necessity of routine lumbar puncture in children less than 12 months of age with simple febrile seizure. The aims of this study were to evaluate the results of lumbar puncture in children younger than 60 months of age with febrile seizure and to reassess the need for lumbar puncture in children younger than 12 months with simple febrile seizure., Methods: A retrospective chart review was performed in patients younger than 60 months who presented with febrile seizure and underwent lumbar puncture from January 2005 to January 2015., Results: A total of 1249 patients presenting with febrile seizure were admitted. Of these, 816 met inclusion criteria for presenting with simple febrile seizure. Lumbar puncture was performed in 75 patients (9.2%; age, mean ± SD, 12.05 ± 9.13 months; male/female, 31/44), who were reviewed. Sixty-six (88.0%) of 75 patients were younger than 12 months. Five patients (6.7%) showed pleocytosis in cerebrospinal fluid, and 4 of them were younger than 1 year of age. Three patients (4.0%) had bacterial meningitis and were 4, 8, and 12 months. Streptococcus pneumoniae (2 patients) and Klebsiella pneumoniae (1 patient) were isolated in cerebrospinal fluid. Nobody had neurologic signs suggesting bacterial meningitis, and all of them completed scheduled immunizations and were up-to-date., Conclusion: Lumbar puncture should be considered in every child younger than 12 months of age with a simple febrile seizure owing to lack of abnormal neurologic sign even if immunization is up-to-date.

Background and Purpose: Febrile seizures (FS) are the most common type of seizure during childhood, reportedly occurring in 2-5% of children aged 6 months to 5 years. However, there are no national data on the prevalence of FS in Korea. This study determined the prevalence, incidence, and recurrence rates of FS in Korean children using national registry data., Methods: The data were collected from the Korea National Health Insurance Review and Assessment Service for 2009-2013. Patients with febrile convulsion as their main diagnosis were enrolled. The overall prevalence of FS in more than 2 million children younger than 5 years was estimated, and the incidence and recurrence rates of FS were determined for children born in 2009., Results: The average prevalence of FS in children younger than 5 years based on hospital visit rates in Korea was 6.92% (7.67% for boys and 6.12% for girls). The prevalence peaked in the second to third years of life, at 27.51%. The incidence of FS in children younger than 5 years (mean 4.5 years) was 5.49% (5.89% for boys and 5.06% for girls). The risk of first FS was highest in the second year of life. The overall recurrence rate was 13.04% (13.81% for boys and 12.09% for girls), and a third episode of FS occurred in 3.35%., Conclusions: Our study determined the overall prevalence of FS using data for the total population in Korea. The prevalence was comparable to that reported for other countries. Patients with three episodes of FS need to be monitored carefully., Competing Interests: The authors have no financial conflicts of interest., (Copyright © 2018 Korean Neurological Association.)

Purpose: To evaluate the usefulness of the Korean Developmental Screening Test (K-DST) for infants and children for developmental delay assessment., Methods: This study was based on retrospective studies of the results of the K-DST, Preschool Receptive-Expressive Language Scale (PRES), Sequenced Language Scale for Infants (SELSI), Childhood Autism Rating Scale (CARS), Modified Checklist for Autism in Toddlers (M-CHAT), electroencephalography, magnetic resonance imaging, and extensive tests conducted in 209 of 1,403 patients, of whom 758 underwent the K-DST at the Korea University Guro Hospital between January 2015 and December 2016 and 645 were referred from local clinics between January 2015 and June 2016., Results: Based on the K-DST results, the male children significantly more frequently required further or follow-up examination than the female children in most test sections, except for gross motor. The male children had notably lower mean scores than the female children. The PRES/SELSI results showed that when more further or follow-up evaluations were required in the K-DST communication section, significantly more problems in language delay or disorder emerged. When further or follow-up evaluation was required in the cognitive section in the CARS/M-CHAT, the possibility of autism increased significantly. A child tended to score low in the CARS test and show autism when further or follow-up evaluation was recommended in the K-DST., Conclusion: This study demonstrated the usefulness of the K-DST as a screening test early in the development of infants and children in Korea. Data of normal control groups should be examined to determine the accuracy of this investigation., Competing Interests: Conflict of interest: No potential conflict of interest relevant to this article was reported.

Background and Purpose: Lacosamide (LCM) is an antiepileptic drug that enhances the slow inactivation of sodium channels and modulates collapsin response mediator protein-2. LCM was recently demonstrated to exert a neuroprotective effect in a murine model of traumatic brain injury and status epilepticus. Assuming the same underlying excitotoxicity-related brain injury mechanism, we hypothesized that LCM would have a neuroprotective effect in hypoxic-ischemic brain injury., Methods: We divided rats into three groups at each testing session: pre- or postfed with LCM, fed with normal saline, and sham. A hypoxic-ischemic brain injury was induced by subjecting 7-day-old rats to right carotid artery coagulation followed by 2.5 h of exposure to 8% oxygen. The animals were killed on postnatal day 12 to evaluate the severity of brain damage. Open field testing was also performed between week 2 and week 6, and the Morris water maze test was performed in week 7 after hypoxia-ischemia., Results: The incidence of liquefactive cerebral infarction was lower in rats prefed with LCM at 100 mg/kg/dose, with the mortality rate being higher at higher doses (200 and 300 mg/kg/dose). The infarct areas were smaller in LCM-prefed rats in several brain regions including the hemisphere, hippocampus, cortex, and striatum. Spatial learning and memory function were better in LCM-prefed rats (p<0.05). No effect was observed in postfed rats., Conclusions: This study suggests that LCM pretreatment exerts a neuroprotective effect on hypoxia-ischemia in neonatal rats. The obtained results suggest that LCM pretreatment could be used as an effective neuroprotective method for neonates under hypoxic-ischemic conditions including heart surgery., Competing Interests: The authors have no financial conflicts of interest., (Copyright © 2017 Korean Neurological Association)

Purpose: We investigated the number of test takers of the Korean-Developmental Screening Test (K-DST) in a single children's hospital within a year, according to age, referral rate, and follow-up percentage., Methods: For this study, 4,062 children who visited and received K-DST at Woorisoa Children's Hospital between January and December 2015 were enrolled. Seven test sets were used according to the Korean National Health Screening Program for infants and children in the following age groups: 4 to 6, 9 to 12, 18 to 24, 30 to 36, 42 to 48, 54 to 60, and 66 to 71 months. The results of the K-DST were categorized into 4 groups as follows: further evaluation (<-2 standard deviation [-2SD]), follow-up test (-2SD to -1SD), peer level (-1SD to 1SD), and high level (>1SD)., Results: The test participants' population and follow-up population were concentrated before the age of 24 months (2,532, 62.3%). The children most commonly referred for further evaluation were those in the 30- to 41-month age group. A mismatch was found between the results of the K-DST and the additional questions. Most of the infants and children with suspicious developmental delays showed catch-up development in their follow-up tests (43 of 55, 78.2%)., Conclusion: The use of K-DST should be encouraged, especially among children aged over 24 months. Multiple-choice question format for the additional questions is recommended to avoid confusion. We suggest a nationwide study to evaluate and revise the K-DST., Competing Interests: No potential conflict of interest relevant to this article was reported.

Background: Benign convulsions with gastroenteritis (CwG) are defined as afebrile convulsions accompanying symptoms of gastroenteritis without evidence of laboratory derangement. Although the main pathogen has been known as rotavirus, since the introduction of rotavirus vaccine, associated viruses with CwG may have changed. Thus, we evaluated the viral association of CwG for patients admitting for recent 2.5 years., Methods: All patients hospitalized for CwG between November 2012 and May 2015 were included in our study. Stool specimens were tested with reverse transcription polymerase chain reaction for detecting norovirus and astrovirus and with enzyme immunoassay for rotavirus and enteric adenovirus. Clinical data was gathered via chart review., Results: Fifty patients were included. Except four patients who failed to collect stool samples, 46 patients were tested. Causative diarrheal viruses were detected in 38 patients and they were 29 norovirus, four rotavirus, four adenovirus, and one astrovirus. Norovirus was commonly identified during the months of November and December. No difference of the clinical characteristics and laboratory value was noted according to the number of seizure episodes., Conclusions: Norovirus is a common pathogen in CwG. Understanding the viral associations can facilitate recognition of CwG.

Ictal tachycardia and bradycardia are common arrhythmias; however, ictal sinus pause and asystole are rare. Ictal arrhythmia is mostly reported in adults with temporal lobe epilepsy. Recently, ictal arrhythmia was recognized as a major warning sign of sudden unexpected death in epilepsy. We present an interesting case of a child with ictal sinus pause and asystole. A 27-month-old girl was hospitalized due to 5 episodes of convulsions during the past 2 days. Results of routine electroencephalography (EEG) were normal, but she experienced brief generalized tonic seizure for 3 days. During video-monitored EEG and echocardiography (ECG), she showed multiple myoclonic seizures simultaneously or independently, as well as frequent sinus pauses. After treatment with valproic acid, myoclonus and generalized tonic seizures were well controlled and only 2 sinus pauses were seen on 24-hour Holter ECG monitoring. Sinus dysfunction should be recognized on EEG, and it can sometimes be treated successfully with only antiepileptic medication., Competing Interests: No potential conflict of interest relevant to this article was reported.

Chromosome 11q13 deletion syndrome has been previously reported as either otodental syndrome or oculo-oto-dental syndrome. The otodental syndrome is characterized by dental abnormalities and high-frequency sensorineural hearing loss, and by ocular coloboma in some cases. The underlying genetic defect causing otodental syndrome is a hemizygous microdeletion involving the FGF3 gene on chromosome 11q13.3. Recently, a new form of severe deafness, microtia (small ear) and small teeth, without the appearance of eye abnormalities, was also reported. In this report, we describe a 1-year-old girl presenting with ptosis of the left upper eyelid, right auricular deformity, high-arched palate, delayed dentition, simian line on the right hand, microcephaly, and developmental delay. In this patient, we identified a deletion in the chromosome 11q13.2-q13.3 (2.75 Mb) region by using an array-comparative genomic hybridization analysis. The deletion in chromosome 11q13 results in a syndrome characterized by variable clinical manifestations. Some of these manifestations involve craniofacial dysmorphology and require a functional workup for hearing, ophthalmic examinations, and long-term dental care., Competing Interests: No potential conflict of interest relevant to this article was reported.

Background and Purpose: Childhood absence epilepsy (CAE) is one of the most common types of pediatric epilepsy. It is generally treated with ethosuximide (ESM), valproic acid (VPA), or lamotrigine (LTG), but the efficacy and adverse effects of these drugs remain controversial. This study compared initial therapy treatment outcomes, including VPA-LTG combination, and assessed clinical factors that may predict treatment response and prognosis., Methods: Sixty-seven patients with typical CAE were retrospectively enrolled at the Korea University Medical Center. We reviewed patients' clinical characteristics, including age of seizure onset, seizure-free interval, duration of seizure-free period, freedom from treatment failure, breakthrough seizures frequency, and electroencephalogram (EEG) findings., Results: The age at seizure onset was 7.9±2.7 years (mean±SD), and follow-up duration was 4.4±3.7 years. Initially, 22 children were treated with ESM (32.8%), 23 with VPA (34.3%), 14 with LTG (20.9%), and 8 with VPA-LTG combination (11.9%). After 48 months of therapy, the rate of freedom from treatment failure was significantly higher for the VPA-LTG combination therapy than in the three monotherapy groups (p=0.012). The treatment dose administrated in the VPA-LTG combination group was less than that in the VPA and LTG monotherapy groups. The shorter interval to loss of 3-Hz spike-and-wave complexes and the presence of occipital intermittent rhythmic delta activity on EEG were significant factors predicting good treatment response., Conclusions: This study showed that low-dose VPA-LTG combination therapy has a good efficacy and fewer side effects than other treatments, and it should thus be considered as a firstline therapy in absence epilepsy.

Purpose: Foreign body (FB) ingestion is common in children, and button battery (BB) ingestion has been increasing in recent years. This study was to identify factors related to outcomes of FB ingestion, particularly BBs in the stomach. We evaluated whether the current recommendations are appropriate and aimed to suggest indications for endoscopic removal of BB in the stomach in young children., Methods: We investigated patient age, shape, size, location of FBs, spontaneous passage time and resulting complications among 76 children. We observed types, size, location of BB and outcomes, and analyzed their associations with complications., Results: Coins and BB were the two most common FBs. Their shapes and sizes were not associated with the spontaneous passage time. Size, spontaneous passage time, and age were also not associated with any specific complications. For BB ingestion, all 5 cases with lithium batteries (≥1.5 cm, 3 V) presented moderate to major complications in the esophagus and stomach without any symptoms, even when the batteries were in the stomach and beyond the duodenum, while no complications were noted in 7 cases with alkaline batteries (<1.5 cm, 1.5 V) (p=0.001). All endoscopies were conducted within 24 hours after ingestion., Conclusion: The type and voltage of the battery should be considered when determining whether endoscopy is required to remove a BB in the stomach. For lithium battery ingestion in young children, urgent endoscopic removal might be important in order to prevent complications, even if the child is asymptomatic and the battery is smaller than 2 cm.

Purpose: Febrile seizure, the most common type of pediatric convulsive disorder, is a benign seizure syndrome distinct from epilepsy. However, as epilepsy is also common during childhood, we aimed to identify the prognostic factors that can predict epilepsy in children with febrile seizures., Methods: The study comprised 249 children at the Korea University Ansan Hospital who presented with febrile seizures. The relationship between the subsequent occurrence of epilepsy and clinical factors including seizure and fever-related variables were analyzed by multivariate analysis., Results: Twenty-five patients (10.0%) had additional afebrile seizures later and were diagnosed with epilepsy. The subsequent occurrence of epilepsy in patients with a history of febrile seizures was associated with a seizure frequency of more than 10 times during the first 2 years after seizure onset (P<0.001). Factors that were associated with subsequent occurrence of epilepsy were developmental delay (P<0.001), preterm birth (P=0.001), multiple seizures during a febrile seizure attack (P=0.005), and epileptiform discharges on electroencephalography (EEG) (P=0.008). Other factors such as the age at onset of first seizure, seizure duration, and family history of epilepsy were not associated with subsequent occurrence of epilepsy in this study., Conclusion: Febrile seizures are common and mostly benign. However, careful observation is needed, particularly for prediction of subsequent epileptic episodes in patients with frequent febrile seizures with known risk factors, such as developmental delay, history of preterm birth, several attacks during a febrile episode, and epileptiform discharges on EEG.

Background and Purpose: Benign childhood epilepsy with centrotemporal spikes (BCECTS) is the most common pediatric focal epilepsy syndrome and typically has positive clinical outcomes. However, a few patients experience recurrent seizures, and therefore, require treatment with antiepileptic drugs (AEDs). This study aimed to identify risk factors associated with poor response to initial AED therapy in BCECTS patients., Methods: We retrospectively reviewed the files of 57 patients who were diagnosed with BCECTS between January 2008 and September 2013. Patients not being treated with AEDs have been excluded. We placed the patients into two groups: (1) patients using 1 AED, and (2) patients using 2 AEDs. Clinical characteristics were then collected from the medical records., Results: Of the 57 patients, 41 (72%) were successfully treated with 1 AED, and 16 (28%) required 2 AEDs to control seizures. Multiple logistic regression analysis indicated that seizure onset prior to age 5 (odds ratio [OR]: 5.65, 95% confidence interval [CI]: 1.41-22.68) and history of febrile seizures (OR: 4.97, 95% CI: 1.06-23.36) were independent risk factors for poor response to initial therapy (p<0.05). Response to AEDs was not associated with the presence of focal slowing or generalized epileptiform discharges on EEG, abnormalities on MRI of the brain, frequency of afebrile seizures before drug therapy, or family history of febrile seizures or epilepsy., Conclusions: This study revealed that 28% of patients with BCECTS experienced poor responses to initial AED therapy. Factors predicting poor response to the initial AED included onset of seizures prior to age 5 and history of febrile seizures.

Purpose: Meningitis is among the most common infections affecting the central nervous system. It can be difficult to determine the exact pathogen responsible for the infection and patients are often treated with empiric antibiotics. This study was conducted to identify the most common clinical characteristics of enteroviral meningitis in children and evaluate the diagnostic efficacy of reverse transcriptase-polymerase chain reaction (RT-PCR) for early detection of an enterovirus., Methods: We analyzed the medical records of children admitted to Korea University Medical Center and diagnosed with meningitis on the basis of cerebrospinal fluid (CSF) analysis and RT-PCR from CSF and other samples from January 2010 to August 2013., Results: A total of 333 patients were enrolled and classified into four groups based on diagnosis: enteroviral meningitis (n=110), bacterial meningitis (n=23), other viral meningitis (n=36), and unknown etiology (n=164). Patients with bacterial meningitis were younger than those in the other groups (P<0.001). Pleocytosis in CSF was similar across all groups. Of patients in the enteroviral meningitis group, 92.7% were diagnosed based on RT-PCR findings. Mean length of hospital stay for patients with enteroviral meningitis was 6.08 days, which was significantly shorter than that for patients with meningitis of bacterial etiology (19.73 days, P<0.001)., Conclusion: Diagnosis of enteroviral meningitis before viral culture results are available is possible using RT-PCR. Accurate diagnosis reduces the length of hospital stay and helps to avoid unnecessary empiric antibiotic treatment.

Background: Prolonged febrile seizures (FS) have both acute and long-lasting effects on the developing brain. Because FS are often associated with peripheral infection, we aimed to develop a preclinical model of FS that simulates fever and immune activation in order to facilitate the implementation of targeted therapy after prolonged FS in young children., Methods: The innate immune activator lipopolysaccharide (LPS) was administered to postnatal day 14 rat (200 μg/kg) and mouse (100 μg/kg) pups 2-2.5 h prior to hyperthermic seizures (HT) induced by hair dryer or heat lamp. To determine whether simulation of infection enhances neuronal excitability, latency to seizure onset, threshold temperature and total number of seizures were quantified. Behavioral seizures were correlated with electroencephalographic changes in rat pups. Seizure-induced proinflammatory cytokine production was assessed in blood samples at various time points after HT. Seizure-induced microglia activation in the hippocampus was quantified using Cx3cr1(GFP/+) mice., Results: Lipopolysaccharide priming increased susceptibility of rats and mice to hyperthemic seizures and enhanced seizure-induced proinflammatory cytokine production and microglial activation., Conclusions: Peripheral inflammation appears to work synergistically with hyperthermia to potentiate seizures and to exacerbate seizure-induced immune responses. By simulating fever, a regulated increase in body temperature from an immune challenge, we developed a more clinically relevant animal model of prolonged FS.

Objective: Perinatal hypoxic-ischemic encephalopathy (HIE) and prolonged febrile seizures (pFS) are common neurologic problems that occur during childhood. However, there is insufficient evidence from experimental studies to conclude that pFS directly induces hippocampal injury. We studied cognitive function and histological changes in a rat model and investigated which among pFS, HIE, or a dual pathologic effect is most detrimental to the health of children., Methods: A rat model of HIE at postnatal day (PD) 7 and a pFS model at PD10 were used. Behavioral and cognitive functions were investigated by means of weekly open field tests from postnatal week (PW) 3 to PW7, and by daily testing with the Morris water maze test at PW8. Pathological changes in the hippocampus were observed in the control, pFS, HIE, and HIE+pFS groups at PW9., Results: The HIE priming group showed a seizure-prone state. The Morris water maze test revealed a decline in cognitive function in the HIE and HIE+pFS groups compared with the pFS and control groups. Additionally, the HIE and HIE+pFS groups showed significant hippocampal neuronal damage, astrogliosis, and volume loss, after maturation. The pFS alone induced minimal hippocampal neuronal damage without astrogliosis or volume loss., Conclusion: Our findings suggest that pFS alone causes no considerable memory or behavioral impairment, or cellular change. In contrast, HIE results in lasting memory impairment and neuronal damage, gliosis, and tissue loss. These findings may contribute to the understanding of the developing brain concerning conditions caused by HIE or pFS.

X-linked Charcot-Marie-Tooth disease (CMTX1) results from numerous mutations in the GJB1 gene encoding the gap junction protein connexin32 (Cx32) and is one of the commonest forms of inherited neuropathy. Owing to the expression of Cx32 not only in Schwann cells but also in oligodendrocytes, a subset of CMT1X patients develops central nervous system (CNS) clinical manifestations in addition to peripheral neuropathy. While most GJB1 mutations appear to cause peripheral neuropathy through loss of Cx32 function, the cellular mechanisms underlying the CNS manifestations remain controversial. A novel start codon GJB1 mutation (p.Met1Ile) has been found in a CMT1X patient presenting with recurrent episodes of transient encephalomyelitis without apparent signs of peripheral neuropathy. In order to clarify the functional consequences of this mutation, we examined the cellular expression of two different constructs cloned from genomic DNA including the mutated start codon. None of the cloned constructs resulted in detectable expression of Cx32 by immunocytochemistry or immunoblot, although mRNA was produced at normal levels. Furthermore, co-expression with the other major oligodendrocyte connexin, Cx47, had no negative effect on GJ formation by Cx47. Finally, lysosomal and proteasomal inhibition in cells expressing the start codon mutant constructs failed to recover any detection of Cx32 as a result of impaired protein degradation. Our results indicate that the Cx32 start codon mutation is equivalent to a complete loss of the protein with failure of translation, although transcription is not impaired. Thus, complete loss of Cx32 function is sufficient to produce CNS dysfunction with clinical manifestations.

Metachromatic leukodystrophy (MLD) is an autosomal recessive disease caused by a deficiency in arylsulfatase A (ARSA). However, decreased ARSA activity is also observed in pseudodeficiency (PD). To distinguish between MLD and PD, we performed gene mutation and sulfatide analyses by using dried blood spots (DBSs) from seven Korean individuals who underwent an analysis of ARSA activity. DNA was extracted from DBSs, and PCR-direct sequencing of ARSA was performed. The cDNA obtained was analyzed to confirm a novel mutation. Of the seven subjects, three were confirmed as having MLD, one was confirmed as having MLD-PD, one was confirmed as having PD, and the remaining two were obligate heterozygotes. We verified the novel pathogenic variant c.1107+1delG by performing familial and cDNA analyses. Sulfatide concentrations in DBSs were analyzed and were quantified by using ultra-performance liquid chromatography and tandem mass spectrometry, respectively. Total sulfatide concentration was inversely correlated with ARSA activity (Spearman's coefficient of rank correlation, P=0.929, P=0.0025). The results of this mutational and biochemical study on MLD will increase our understanding of the genetic characteristics of MLD in Koreans.

Background and Purpose: Many parents express worries about potential negative side effects of antiepileptic drugs (AED) on cognition, behavior, mood, and academic achievement. We aimed to evaluate parents' subjective feelings about cognitive or behavioral changes in their children and their quality of life after antiepileptic drug (AED) discontinuation., Methods: A modified questionnaire based on the Korean-Quality of Life in Childhood Epilepsy and the Korean-Child Behavior Checklist was answered by parents whose children were seizure-free over the course of 1 month after AED discontinuation. All children were seizure-free for at least 2 years before AED withdrawal., Results: Fifty-eight eligible patients (mean age, 14.1 ± 4.5 years) were examined. Except valproate in cognition (p = 0.03), parents did not feel significant change after discontinuation of different drugs. They felt improvement of behavior in generalized epilepsy (p = 0.04) and better quality of life in children less than 6 year of age at diagnosis of epilepsy (p = 0.02)., Conclusions: We propose that factors such as earlier age at diagnosis of epilepsy or type of epilepsy might influence parents' subjective feelings about their children's well-being after drug discontinuation, rather than the drug itself.

Objective: To prospectively evaluate the neuropsychological effect of levetiracetam (LVT) in comparison with carbamazepine (CBZ) and its efficacy and tolerability as a monotherapy in children with focal epilepsy., Methods: A total of 121 out of 135 screened children (4-16 years) were randomly assigned to LVT or CBZ groups in a multicenter, parallel-group, open-label trial. The study's primary endpoints were defined as the end of 52 weeks of treatment, followed by analysis of changes observed in a series of follow-up neurocognitive, behavioral, and emotional function tests performed during treatment in the per protocol population. Drug efficacy and tolerability were also analyzed among the intention-to-treat (ITT) population (ClinicalTrials.gov, number NCT02208492)., Results: Eighty-one patients (41 LVT, 40 CBZ) from the randomly assigned ITT population of 121 children (57 LVT, 64 CBZ) were followed up to their last visit. No significant worsening or differences were noted between groups in neuropsychological tests, except for the Children's Depression Inventory (LVT -1.97 vs CBZ +1.43, p = 0.027, [+] improvement of function). LVT-treated patients showed an improvement (p = 0.004) in internalizing behavioral problems on the Korean Child Behavior Checklist. Seizure-free outcomes were not different between the 2 groups (CBZ 57.8% vs LVT 66.7%, p = 0.317)., Conclusions: Neither LVT nor CBZ adversely affected neuropsychological function in pediatric patients. Both medications were considered equally safe and effective as monotherapy in children with focal epilepsy., Classification of Evidence: This study provides Class II evidence that in patients with pediatric focal epilepsy, LVT and CBZ exhibit equivalent effects on neuropsychological function., (© 2015 American Academy of Neurology.)

Purpose: The aim of this study was to identify the different influencing patterns of demographic and epilepsy-related variables on various aspects of psychosocial function in pediatric epilepsy., Method: Five hundred ninety-eight patients with pediatric epilepsy between the ages of 4 and 18 years (boys=360, 60% and girls=238, 40%) and their parents participated in the study. Parents completed the Social Maturity Scale (SMS), the Korean version of the Child Behavior Checklist (K-CBCL), and the Korean version of the Quality of Life in Childhood Epilepsy Questionnaire (K-QOLCE) to assess daily living function, behavior, and quality of life. The Children's Global Assessment Scale (CGAS) was completed by clinicians to assess general adaptive function. Demographic variables, such as age and sex of child, and epilepsy-related clinical variables, including seizure type, seizure frequency, duration of epilepsy, and number of medications, were obtained from medical records., Results: Demographic and epilepsy-related clinical variables had a strong influence (22-32%) on the cognition-related domain such as general adaptive function, school/total competence, and quality of life for cognitive function while a comparatively smaller effect (2-16%) on the more psychological domain including behavioral, emotional, and social variables. Younger age, shorter duration of illness, and smaller number of medications showed a strong positive impact on psychosocial function in pediatric epilepsy, particularly for adaptive function, competence, and quality-of-life aspects., Conclusion: Given the wide range of impact of demographic and clinical variables on various facets of psychosocial functions, more specific understanding of the various aspects of factors and their particular pattern of influence may enable more effective therapeutic approaches that address both the medical and psychological needs in pediatric epilepsy., (Copyright © 2014 Elsevier Inc. All rights reserved.)

X-linked Charcot-Marie-Tooth disease (CMTX1) is a clinically heterogeneous hereditary motor and sensory neuropathy with X-linked transmission. Common clinical manifestations of CMTX1 disease, as in other forms of Charcot-Marie-Tooth (CMT) disease, are distal muscle wasting and weakness, hyporeflexia, distal sensory disturbance, and foot deformities. Mutations in the connexin-32 gene (gap junction protein β1 [GJB1]) are responsible for CMTX1 disease. In this report, we describe a patient with CMTX1 disease presenting with recurrent attacks of transient and episodic acute demyelinating encephalomyelitis (ADEM)-like symptoms without previous signs of lower extremity weakness or foot deformities; the patient, as well as his asymptomatic mother, exhibited a novel GJB1 mutation (p.Met1Ile). Differential diagnosis of recurrent and transient ADEM-like illness, if unexplained, should include the possibility of CMTX1 disease., (Copyright © 2014 by the American Academy of Pediatrics.)

Purpose: This study was to evaluate the relationship of 25(OH)D3 levels with anticonvulsant use and other possible factors in epileptic children and adolescents., Materials and Methods: We studied 143 patients with epilepsy (90 boys, 53 girls; 11.21±4.49 years), who had been treated with anticonvulsants for more than 1 year. Patients who had taken multiple vitamins before the blood test and those who have the limitation of physical activity (wheelchair-bound) were excluded from the study. We evaluated the difference in vitamin D status according to the type and number of anticonvulsants taken and other factors such as gender, age, intelligence and seizure variables., Results: For patients with mental retardation or developmental delay, 25(OH)D3 levels were lower than the levels in patients with normal intelligence quotient levels (p=0.03). 25(OH)D3 levels were lower in patients who had taken anticonvulsants for more than 2 years as compared to those who had taken them for less than 2 years (p=0.03). Those taking oxcarbazepine had significantly lower vitamin D levels than patients taking valproic acid (p=0.01). However, no effects of number of anticonvulsants taken were detectable. More than two-thirds of the patients were diagnosed with osteopenia or osteoporosis in patients showing either vitamin D insufficiency or deficiency., Conclusion: The possibility of vitamin D deficiency can be considered in pediatric patients taking anticonvulsants if they have mental retardation or developmental delay or if they have been taking anticonvulsants for more than 2 years or taking hepatic enzyme inducing drugs.

Introduction: Respiratory syncytial virus (RSV) is a common pathogen causing acute respiratory infection in children. Herein, we describe the incidence and clinical and magnetic resonance imaging (MRI) findings of RSV-related encephalitis, a major neurological complication of RSV infection., Methods: We retrospectively reviewed the medical records and imaging findings of the patients over the past 7 years who are admitted to our medical center and are tested positive for RSV-RNA by reverse transcriptase PCR. In total, 3,856 patients were diagnosed with RSV bronchiolitis, and 28 of them underwent brain MRI for the evaluation of neurologic symptoms; 8 of these 28 patients had positive imaging findings. Five of these 8 patients were excluded because of non-RSV-related pathologies, such as subdural hemorrhage, brain volume loss due to status epilepticus, periventricular leukomalacia, preexisting ventriculomegaly, and hypoxic brain injury., Results: The incidence of RSV-related encephalitis was as follows: 3/3,856 (0.08 %) of the patients are positive for RSV RNA, 3/28 (10.7 %) of the patient underwent brain MRI for neurological symptom, and 3/8 (37.5 %) of patients revealed abnormal MR findings. The imaging findings were suggestive of patterns of rhombenmesencephalitis, encephalitis with acute disseminated encephalomyelitis, and limbic encephalitis. They demonstrated no diffusion abnormality on diffusion-weighted image and symptom improvement on the follow-up study., Conclusion: Encephalitis with RSV bronchiolitis occurs rarely. However, on brain MRI performed upon suspicion of neurologic involvement, RSV encephalitis is not infrequently observed among the abnormal MR findings and may mimic other viral and limbic encephalitis. Physicians should be aware of this entity to ensure proper diagnosis and neurologic care of RSV-positive patients.

Purpose: Array comparative genomic hybridization (array-CGH) is a technique used to analyze quantitative increase or decrease of chromosomes by competitive DNA hybridization of patients and controls. This study aimed to evaluate the benefits and yield of array-CGH in comparison with conventional karyotyping in pediatric neurology patients., Materials and Methods: We included 87 patients from the pediatric neurology clinic with at least one of the following features: developmental delay, mental retardation, dysmorphic face, or epilepsy. DNA extracted from patients and controls was hybridized on the Roche NimbleGen 135K oligonucleotide array and compared with G-band karyotyping. The results were analyzed with findings reported in recent publications and internet databases., Results: Chromosome imbalances, including 9 cases detected also by G-band karyotyping, were found in 28 patients (32.2%), and at least 19 of them seemed to be causally related to the abnormal phenotypes. Regarding each clinical symptom, 26.2% of 42 developmental delay patients, 44.4% of 18 mental retardation patients, 42.9% of 28 dysmorphic face patients, and 34.6% of 26 epilepsy patients showed abnormal array results., Conclusion: Although there were relatively small number of tests in patients with pediatric neurologic disease, this study demonstrated that array-CGH is a very useful tool for clinical diagnosis of unknown genome abnormalities performed in pediatric neurology clinics.

Saethre–Chotzen syndrome is a very rare autosomal dominant congenital disorder characterized by craniosynostosis and acrocephalosyndactyly. It is caused by a mutation in TWIST1, located on chromosome 7p21. A shortage of functional TWIST1 protein affects the development and maturation of cells in the skull, face, and limbs. The patient described in this report displayed craniofacial features classic for Saethre–Chotzen syndrome, including craniosynostosis, low-set ears, small pinna with prominent crura, a high-arched palate, and a simian crease on the left hand. He did not have the limb anomalies commonly seen in patients with Saethre–Chotzen syndrome, and the results of conventional chromosome analysis were normal. However, results of a microarray-based comparative genomic hybridization (array CGH) study confirmed the karyotype of46,XY.7p21.1p15.3(15,957,375-20,331,837)x1, a region that includes TWIST1. Subsequent fluorescent in situ hybridization analysis confirmed this result. No other chromosome was involved in the rearrangement. This case illustrates the important contribution of array CGH to the identification of TWIST microdeletions, even in a patient not showing the phenotype typical of Saethre–Chotzen syndrome.

We investigated the neuroprotective effects of human placental extracts (HPE) and the effects of HPE on recovery of cognitive and behavioral function on hypoxic-ischemic brain injury in the newborn rat. The right common carotid arteries of 7-day-old rats were coagulated, and rats were then exposed to 8% oxygen. Immediately before and again at three times after the hypoxia-ischemia (pre-treatment group), and immediately after and three times again after hypoxia-ischemia (post-treatment group), the rats were intraperitoneally injected with HPE (0.1, 0.25, or 0.5 mL/10 g/dose). No-treatment rats received saline only. On postnatal day 12, brains were removed and gross morphological damage was evaluated. To quantify the severity of brain injury, bilateral cross-sectional areas of the anterior commissural and posterior hippocampal levels were analyzed with NIH Image. Assessments of the open field activity levels at 2, 4, 6 and 8 week and, the Morris water maze test at 8 weeks after hypoxia-ischemia were carried out according to standard methods. HPE pre-treatment decreased the incidence of liquefactive cerebral infarction, at an optimally neuroprotective dose of 0.5 mL/10 g/dose (P<0.05). In the Morris water maze test, the group injected with HPE at 0.5 mL/10 g/dose concentration showed shorter escape latencies than the no-treatment group (P<0.05). These findings support a protective effect of the HPE treatment on neuronal integrity and cognitive function following hypoxic-ischemic brain injury. Injected at an appropriate dose prior to exposure, HPE may significantly reduce or prevent hypoxic-ischemic injury in the immature brain., (Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

To compare the cognitive and behavioral effects of lamotrigine (LTG) to carbamazepine (CBZ) as monotherapy for pediatric epilepsy. A multicenter, randomized, open-label, parallel-group clinical trial was conducted in children with partial-onset seizures. LTG or CBZ was prescribed as monotherapy for previously untreated children and titrated over 8 weeks, followed by maintenance for 24 weeks. Outcome measures were change in cognition and behavior in a combined analysis of standardized measures from screening to the end of the maintenance phase, as well as antiepileptic efficacy and tolerability. A total of 67 children completed the study, including 32 of 43 (74.4%) treated with LTG and 35 of 41 (85.4%) treated with CBZ. Seizure-free outcomes did not differ between the intent-to-treat populations (53.5% LTG, 56.1% CBZ; p=0.81). There were no statistically significant differences in the intelligence of the two groups after treatment. Externalizing behavior problems improved in the CBZ group (p<0.05). However, there were no significant differences between the two groups in terms of externalizing behavior. The parents' report on the Conner scale showed an improvement in the CBZ group compared to the LTG group (p<0.05). LTG and CBZ showed similar efficacy and cognitive effects in treating childhood partial epilepsy. However, CBZ showed more benefits in improving externalizing behaviors., (Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Purpose: We conducted a prospective, multicenter, open label trial to evaluate the effectiveness of oxcarbazepine (OXC) oral suspension as monotherapy for children newly diagnosed with partial seizures., Methods: This trial included a two- to eight-week titration and stabilization period to achieve effective target doses and a 24-week maintenance phase. The primary outcome measure was the seizure-free rate over six months, while a secondary measure was the change in cognition and behavior from screening to the end of the maintenance phase. The effectiveness of OXC was compared in intellectually normal versus intellectually impaired children (intelligence quotient <70)., Results: We enrolled 171 patients and analyzed 168 as the per-protocol (PP) group (3 patients had protocol violations). The mean age of the PP group was 8.4±2.7 years. The maintenance dose of OXC was 24.9±8.0mg/kg/day. Of the 168 patients included in the efficacy analysis, 122 (72.6%) completed the study and 94 (56.0%) became seizure-free after the OXC treatment. Comparing the efficacy of OXC for intellectually normal and intellectually impaired patients, 79 (56.8%) of the 139 intellectually normal patients and 15 (51.7%) of the 29 intellectually impaired patients became seizure-free (P=0.61). After treatment, intelligence scale scores improved in intellectually normal patients compared to the intellectually impaired children (P<0.05). Social problems quantified by behavior scales improved in intellectually impaired patients compared to intellectually normal children (P<0.05)., Conclusions: OXC is effective and well-tolerated as monotherapy in children with partial seizures. There was no difference in the effectiveness of OXC between intellectually normal and intellectually impaired children., (Copyright © 2012 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

It is well-known that the prevalence of attention deficit hyperactivity disorder (ADHD) is higher in epileptic children than in the general pediatric population. The aim of this study was to compare the accompaniment of ADHD in epileptic children with well-controlled seizures and no significant intellectual disability with that in healthy controls. We included epileptic children between the ages of 6 and 12 yr visiting our clinic for six consecutive months and controls without significant medical or psychiatric illnesses. We excluded patients with intellectual disability or persistent seizures during the recent three months. The diagnosis of ADHD was based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV). After exclusion of 84 patients, we enrolled 102 (54.8%) children (mean age, 9.4 ± 2.0 yr). Seven (7 of 102, 6.9%) were diagnosed with ADHD. As compared to control group (4 of 110, 3.6%), there was no difference in ADHD accompaniment (P = 0.29). No difference was observed in ADHD accompaniment according to seizure type and epilepsy syndrome. In conclusion, the accompaniment of ADHD in epileptic children with well-controlled seizures and no intellectual disability may not differ from that of the general pediatric population.