Jung Hye Byeon

Rufinamide as an adjuvant treatment in children with Lennox-Gastaut syndrome

PURPOSE To evaluate the efficacy of rufinamide as an add-on treatment in children and adolescents with Lennox-Gastaut syndrome (LGS). METHODS The study was an open-label, observational clinical trial of rufinamide as an add-on treatment in intractable LGS patients. This intent-to-treat trial included 4 weeks of scheduled titrated doses and a 12-week maintenance phase with a target dose of 20-40 mg/kg rufinamide, adjusted according to its effectiveness and tolerability after a baseline period of 4 weeks. The primary outcome was measured by the seizure-reduction rate according to individual seizure type over the 12-week maintenance period. RESULTS One hundred and twenty-eight patients with LGS who were determined to be unresponsive to one or more antiepileptic drugs or dietary therapy were enrolled. Of the 128 patients enrolled, 112 (87.5%) completed the study. After add-on rufinamide treatment, 46 patients (35.9%) achieved a more than 50% reduction in seizure frequency and 10 (7.8%) patients became seizure-free. When we identified those who responded with an at least 50% reduction in seizure frequency, 39.4% of the responders reported reductions in convulsive seizures, 36.4% in drop attacks, 33.3% in myoclonic seizures, and 20.0% in epileptic spasms. Overall, 32.8% of patients reported adverse effects, which were mostly mild and transient in nature. The most common adverse effects were fatigue (15 patients, 11.7%) and poor appetite (9 patients, 7.0%). Twenty-one (16.4%) patients experienced an increased seizure frequency. CONCLUSIONS Rufinamide appears to be a safe and effective adjuvant treatment for many cases of intractable LGS.

Enterovirus 71-related encephalomyelitis: usual and unusual magnetic resonance imaging findings

IntroductionMost enterovirus (EV) 71 infections manifest as mild cases of hand–foot–mouth disease (HFMD)/herpangina with seasonal variations, having peak incidence during the summer. Meanwhile, EV 71 may involve the central nervous system (CNS), causing severe neurologic disease. In many cases, enteroviral encephalomyelitis involves the central midbrain, posterior portion of the medulla oblongata and pons, bilateral dentate nuclei of the cerebellum, and the ventral roots of the cervical spinal cord, and the lesions show hyperintensity on T2-weighted and fluid-attenuation inversion recovery (FLAIR) images. Our goal was to review usual and unusual magnetic resonance (MR) findings in CNS involvement of enteroviral infection.MethodsAmong consecutive patients who had HFMD and clinically suspected encephalitis or myelitis and who underwent brain or spinal MR imaging, five patients revealed abnormal MR findings. Diffusion-weighted and conventional MR and follow-up MR images were obtained. From cerebrospinal fluid, stool, or nasopharyngeal swabs, EV 71 was confirmed in all patients.ResultsMR imaging studies of two patients showed hyperintensity in the posterior portion of the brainstem on T2-weighted and FLAIR images, which is the well-known MR finding of EV 71 encephalitis. The remaining three cases revealed unusual manifestations: leptomeningeal enhancement, abnormal enhancement along the ventral roots at the conus medullaris level without brain involvement, and hyperintensity in the left hippocampus on T2/FLAIR images.ConclusionEV 71 encephalomyelitis shows relatively characteristic MR findings; therefore, imaging can be helpful in radiologic diagnosis. However, physicians should also be aware of unusual radiologic manifestations of EV 71.

Increased Serum Interleukin-5 and Vascular Endothelial Growth Factor in Children With Acute Mycoplasma Pneumonia and Wheeze

Acute mycoplasma pneumonia may be accompanied by wheeze in some children considered not to have asthma. The aim of the present study was to evaluate cytokine secretion in children with acute mycoplasma pneumonia and wheeze. We studied 58 patients with mycoplasma pneumonia (12 with wheeze, Group 1; 46 without wheeze, Group 2) and 36 patients of non‐mycoplasma pneumonia (Group 3). Serum levels of interleukin (IL)‐4, IL‐5, interferon (IFN)‐γ, and vascular endothelial growth factor (VEGF) were measured using an enzyme‐linked immunosorbent assay kits. The mean ± SD IL‐5 level of Group 1 was 97.1 ± 73.0 pg/ml, which was significantly higher than that of Group 2 (28.2 ± 32.2 pg/ml) and that of Group 3 (35.7 ± 42.0 pg/ml). The mean ± SD VEGF level of Group 1 was 687.5 ± 385.8 pg/ml, which was significantly higher than that of Group 2 (310.0 ± 251.9 pg/ml) and that of Group 3 (402.3 ± 279.5 pg/ml). No significant differences in serum levels of IL‐4, IFN‐γ, and IgE were observed between the groups. Our results show that children with mycoplasma pneumonia and wheeze have significantly higher serum levels of IL‐5 and VEGF. These increased immune responses may be associated with the pathophysiological mechanisms by which the Mycoplasma pneumoniae contribute to the development of wheeze during acute mycoplasma pneumonia. Pediatr Pulmonol. 2009; 44:423–428.

A study on the menstruation of Korean adolescent girls in Seoul

Purpose Westernized eating habits have been associated with early-age menstruation, which increases the incidence of dysmenorrhea and premenstrual syndrome among adolescent girls. We therefore surveyed changes in menarche timing and the general menstrual characteristics of adolescent girls in Seoul, Korea. Methods We surveyed 538 teenage girls who visited our hospital between July and November 2007. Items explored included age at menarche, general menstrual characteristics, occurrence of premenstrual syndrome and treatment thereof, and an association between present dysmenorrhea and a family history of the condition. Results Average age at menarche was 12.6 years, with 29% (n=156) subjects beginning menstruation at age 12 years. The prevalence of dysmenorrhea was 82% (n=435). The main symptoms were abdominal (53.2%) and lower back pain (34.2%), and 15.2% of girls who experienced such symptoms required medication. Present dysmenorrhea, and a family history thereof, were statistically correlated (P<0.05). In addition, 58.8% (n=316) of teenage girls had symptoms of premenstrual syndrome. The most frequent psychological symptoms were fatigue (36.4%) and nervousness (38.7%), whereas the most common physical symptom was menstrual cramps (46.5%). Most subjects (87.6%) tolerated the symptoms of premenstrual syndrome without medication; 11.4% took medicines including painkillers; but only 0.1% of subjects visited a doctor. Conclusion The average age at menarche in Korean girls was 12.6 years, thus younger than in the past. Most teenage girls experienced dysmenorrhea and premenstrual syndrome, but few consulted a doctor. Organized treatment plans are required to manage menstrual problems in teenage girls.

Comparison of cytokine responses in nasopharyngeal aspirates from children with viral lower respiratory tract infections.

Aim: To determine whether nasopharyngeal aspirates (NPAs) cytokine response is different according to the causative viruses in children with lower respiratory tract infections (LRTI).

Attention deficit hyperactivity disorder in epileptic children

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.

Epilepsy in children with a history of febrile seizures

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.

Association between sensitization to mold and impaired pulmonary function in children with asthma

Purpose Recent data indicate that sensitization to mold contributes to the severity and persistence of asthma. In this study, we investigated the relationships between sensitization to mold and lung function parameters in children with asthma. Methods We retrospectively reviewed clinical data from 551 asthmatic subjects. We selected subjects who met clinical diagnostic criteria of asthma. Their spirometry, methacholine challenge tests, and measurements of blood eosinophils, serum IgE, eosinophil cationic protein (ECP) and fractional exhaled nitric oxide (FeNO) results were included. Skin prick testing (SPT) results with 13 common aeroallergens in Korea including house dust mites, animal dander, pollen, cockroach and mold were reviewed. Subjects were divided into 3 groups according to their SPT results. Subjects who showed no positive result to any aeroallergen were designated as group 1 (non-sensitized). Group 2 represented subjects who were sensitized to aeroallergens other than mold (other allergen-sensitized) and group 3 included subjects who were sensitized to mold allergens (mold-sensitized). Results Among the 551 asthmatic subjects, 67 (12.2%) were sensitized to mold and 366 (66.4%) were sensitized to other aeroallergens. The log mean IgE levels were higher in groups 2 (5.96±1.14 IU/mL) and 3 (5.81±0.97 IU/mL) compared to group 1 (3.88±1.68 IU/mL). Blood eosinophils, ECP and FeNO concentrations were significantly higher in groups 2 and 3, but no significant difference was found between the 2 groups. The mean FEV1 value was significantly lower in group 3 (86.9±12.1%pred) than in groups 2 (92.0±14.8%pred) and 1 (93.4±15.4%pred). The log mean methacholine PC20 was significantly lower in group 3 (0.08±1.91 mg/mL) than in groups 2 (1.31±1.69 mg/mL) and 1 (2.29±1.66 mg/mL). Conclusions We observed a differential association between mold and other aeroallergen sensitization, and severity of asthma. Sensitization to mold is associated with lower lung function and increased airway hyper-responsiveness in children with asthma. Mold sensitization could be an important factor determining asthma severity particularly airflow limitation in children.

Application of array-based comparative genomic hybridization to pediatric neurologic diseases.

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 with an atypical phenotype: identification of TWIST microdeletion by array CGH

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 of 46,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.