• Clinical and Experimental Pediatrics
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• v.51 no.2
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• pp.162-169
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• 2008

Purpose : Oxcabarzepine (OXC), newly recommended antiepileptic drug, has been prescribed for patients with partial seizures and generalized tonic clonic seizures in Korea from 1999. There are limited reports about an efficacy of OXC therapy in epileptic children in Korea. This study evaluated the efficacy and safety of OXC in the light of our experience. Methods : The patients, who had visited the pediatric neurology clinic of Korea University Guro Hospital from January 2001 to December 2006, were included. The data of 144 patients who were administrated OXC as monotherapy or polytherapy, was summarized retrospectively and we evaluated the efficacy and safety of OXC. Results : After 6 months of OXC therapy, 77 patients (53.5%, n=144) achieved seizure freedom, 48 patients (33.3%) experienced >50% improvement. After 12 months of OXC therapy, cessation of seizure was observed in 88 patients (61.1%, n=133), and 27 patients (18.8%) manifested an improvement. Monotherapy group showed superior efficacy to polytherapy one. The frequent side effects of OXC were drowsiness (20.1%), headache (12.5%), dizziness (9.7%) and rash (8.3%). They did not related to patient's age or sex, and dosage of OXC. Twenty four patients (16.7%) experienced hyponatremia, but which were neither symptomatic nor significant one. Conclusion : The efficacy and safety of OXC in our patients were excellent and had less significant side effects than established international one. We expect this report contributes toward OXC therapy in epileptic children.

• Korean Journal of Psychosomatic Medicine
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• v.28 no.1
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• pp.63-71
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• 2020

Objectives : The aim of this study was to investigate the impact of clinical and psychological factors on the parental stress of children and adolescents with epilepsy. Methods : Children and adolescents with epilepsy (n=90, age range=6-17 years) completed questionnaires on epilepsy-related variables, children's depressive symptoms (Children's Depression Inventory, CDI), children's anxiety (Revised Children's Manifest Anxiety Scale, RCMAS) and performed the scale for children's intelligence (IQ). Parents who have children and adolescents with epilepsy completed questionnaires on parental stress (Questionnaire on Resources and stress, QRS), parental anxiety (State-Trait Anxiety Inventory, STAI), children's attention problems (Abbreviated Conners Parent Rating Scale Revised, CPRS), and children's behavioral problems (Korean Child Behavior Checklist, K-CBCL). Stepwise regression analysis was performed to determine the significant predictive variables that affect parental stress. Results : In the correlational analysis, duration of seizure treatment (r=0.253, p=0.016), children's IQ (r=-0.544, p<0.001), children's attention problems (r=0.602, p<0.001), children's depressive symptoms (r=0.335, p=0.002), children's anxiety (r=0.306, p=0.004), children's behavioral problems (r=0.618, p<0.001), and parental anxiety (r=0.478, p<0.001), showed a significant correlation with parental stress. Children's behavioral problem (β=0.241, p=0.010), children's IQ (β=-0.472, p<0.001), and parental anxiety (β=0.426, p<0.001) were significantly related to the parental stress (Adjusted R²=0.619). Conclusions : Clinicians should pay attention to children's intelligence and behavioral problems and parental anxiety, which affect parental stress with children and adolescents with epilepsy.

• Clinical and Experimental Pediatrics
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• v.52 no.2
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• pp.199-204
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• 2009

Purpose : Seizure associated with fever may indicate the presence of underlying inherited metabolic diseases. The present study was performed to investigate the presence of underlying metabolic diseases in patients with complex febrile seizures, using analyses of urine organic acids. Method : We retrospectively analyzed and compared the results of urine organic acid analysis with routine laboratory findings in 278 patients referred for complex febrile seizure. Results : Of 278 patients, 132 had no abnormal laboratory findings, and 146 patients had at least one of the following abnormal laboratory findings: acidosis (n=58), hyperammonemia (n=55), hypoglycemia (n=21), ketosis (n=12). Twenty-six (19.7 %) of the 132 patients with no abnormal findings and 104 (71.2%) of the 146 patients with statistically significant abnormalities showed abnormalities on the organic acid analysis (P<0.05). Mitochondrial respiratory chain disorders (n=23) were the most common diseases found in the normal routine laboratory group, followed by PDH deficiency (n=2) and ketolytic defect (n=1). In the abnormal routine laboratory group, mitochondrial respiratory chain disorder (n=29) was the most common disease, followed by ketolytic defects (n=27), PDH deficiency (n=9), glutaric aciduria type II (n=9), 3-methylglutaconic aciduria type III (n=6), biotinidase deficiency (n=5), propionic acidemia (n=4), methylmalonic acidemia (n=2), 3-hydroxyisobutyric aciduria (n=2), orotic aciduria (n=2), fatty acid oxidation disorders (n=2), 2-methylbranched chain acyl CoA dehydrogenase deficiency (n=2), 3-methylglutaconic aciduria type I (n=1), maple syrup urine disease (n=1), isovaleric acidemia (n=1), HMG-CoA lyase deficiency (n=1), L-2-hydroxyglutaric aciduria (n=1), and pyruvate carboxylase deficiency (n=1). Conclusion : These findings suggest that urine organic acid analysis should be performed in all patients with complex febrile seizure and other risk factors for early detection of inherited metabolic diseases.

• Clinical and Experimental Pediatrics
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• v.51 no.4
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• pp.415-419
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• 2008

Purpose : Herbal medicine is thought to be widely used by children with epilepsy, but there have been few studies. This study aimed to investigate the perceptions and the actual conditions of usage of herbal medicine by children with epilepsy. Methods : From July to August 2007, three hundred seventy eight questionnaires were completed by parents of epileptic children who visited pediatric neurology clinic of Korea University hospital and Kwangmyung-Sungae hospital. Demographic data and patterns of usage of herbal medicine were investigated. Results : Among 378 patients, sixty five (17.2%) reported using herbal medicine. Major reasons for using herbal medicine were 'to enhance general health' and 'belief that it has fewer side effects'. Majority of respondents did not notify their physician about using herbal medicine because 'they did not need to share this with doctor' and 'they thought their doctor would disapprove'. After taking herbal medicine, 33.3% of patients reported that it did not benefit their seizure but they felt healthier. Usage of herbal medicine was significantly related to number of AEDs (antiepileptic drugs), duration of AED treatment, association with psychosomatic disorders and motivation by other people or by mass media. Conclusion : Considerable numbers of epileptic children were using herbal medicine during treatment with AED and did not inform their physician about usage of it. Physicians should be aware of benefits and harms of herbal medicine and actively intervene in the usage of herbal medicine by epileptic patients.

• Tuberculosis and Respiratory Diseases
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• v.65 no.6
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• pp.471-475
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• 2008

Background: In order to achieve a maintenance level and to prevent hemorrhagic complications, regular monitoring of the INR is mandatory for patients on oral anticoagulation therapy (OAT). A point-of-care instrument for INR monitoring is convenient for users, but the accuracy of the results has been controversial, and so this calls for exact evaluation of the point-of-care instrument that is used for INR monitoring. Methods: From Aug 2007 through Feb 2008, 85 patients on OAT among the all the patients who were admitted to Soonchunhyang University Bucheon Hospital were involved in this study. Parallel measurements of the PT INR were performed using a CoaguChek-XS and, a CA-7000 laboratory reference instrument and the results were analyzed. In addition, the patients' clinical data, including the diagnosis and the frequency and interval of the INR measurements, were also analyzed. Results: Of the 85 patients, 25 were admitted more than once to undergo INR testing and the mean interval between testing was 8.6 weeks with 39% and 38% of the tests being less than INR 2 units with using the CoaguChek-XS and the reference method, respectively. The coefficients of variation of CoaguChek-XS were 4.50 and 2.45 for the high and low INR patients, respectively. An excellent correlation was found between the two methods with a $R^2$ of 0.966 (p<0.001). Through Bland-Altman analysis, the mean INR difference between the two methods was 0.13 with the limit of agreement being -0.47~+0.72 with a 95% confidence interval. CoaguChek-XS was shown to overestimate the INR value for patients with an increasing INR, as compared to the reference method. Conclusion: CoaguChek-XS demonstrated great precision and accuracy for patients on OAT when compared to the laboratory INR results. Accordingly, the instrument should help to monitor the INR in the patients on OAT.

• Investigative Magnetic Resonance Imaging
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• v.18 no.4
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• pp.332-340
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• 2014

Purpose : A relative increase in deoxyhemoglobin levels in hypoperfused tissue can cause prominent hypointense signals in the draining veins (PHSV) within areas of impaired perfusion in susceptibility-weighted imaging (SWI). The purpose of this study is to evaluate the usefulness of SWI in patients with acute cerebral infarction by evaluating PHSV within areas of impaired perfusion and to investigate the usefulness of PHSV in predicting prognosis of cerebral infarction. Materials and Methods: In 18 patients with acute cerebral infarction who underwent brain MRI with diffusion-weighted imaging and SWI and follow-up brain MRI or CT, we reviewed the presence and location of the PHSV within and adjacent to areas of cerebral infarction qualitatively and measured the signal intensity difference ratio of PHSVs to contralateral normal appearing cortical veins quantitatively on SWI. The relationship between the presence of the PHSV and the change in the extent of infarction in follow-up images was analyzed. Results: Of the 18 patients, 10 patients showed progression of the infarction, and 8 patients showed little change on follow- up imaging. On SWI, of the 10 patients with progression 9 patients showed peripheral PHSV and the newly developed infarctions corresponded well to area with peripheral PHSV on initial SWI. Only one patient without peripheral PHSV showed progression of the infarct. The patients with infarction progression revealed significantly higher presence of peripheral PHSV (p=0.0001) and higher mean signal intensity difference ratio (p=0.006) comparing to the patients with little change. Conclusion: SWI can demonstrate a peripheral PHSV as a marker of penumbra and with this finding we can predict the prognosis of acute infarction. The signal intensity difference of PHSV to brain tissue on SWI can be used in predicting prognosis of acute cerebral infarction.

• Clinical and Experimental Pediatrics
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• v.50 no.7
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• pp.686-693
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• 2007

Purpose : Mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil (MMF), is a potent inhibitor of inosine-monophosphate dehydrogenase (IMPDH), a new immunosuppressive drug used. It was reported that MPA protected neurons after excitotoxic injury, induced apoptosis in microglial cells. However, the effects of MPA on hypoxic-ischemic (HI) brain injury has not been yet evaluated. Therefore, we examined whether MPA could be neuroprotective in perinatal HI brain injury using Rice-Vannucci model (in vivo) and in rat brain cortical cell culture induced by hypoxia (in vitro). Methods : Cortical cells were cultured using a 18-day-pregnant Sprague-Dawley (SD) rats and incubated in 1% $O_2$ incubator for hypoxia. MPA ($10{\mu}g/mL$) before or after a HI insult was treated. Seven-day-old SD rat pups were subjected to left carotid occlusion followed by 2 hours of hypoxic exposure (8% $O_2$). MPA (10 mg/kg) before or after a HI insult were administrated intraperitoneally. Apoptosis was measured using western blot and real-time PCR for Bcl-2, Bax, caspase-3. Results : H&E stain revealed increased brain volume in the MPA-treated group in vivo animal model of neonatal HI brain injury. Western blot and real-time PCR showed the expression of caspase-3 and Bax/Bcl-2 were decreased in the MPA-treated group In in vitro and in vivo model of perinatal HI brain injury, Conclusion : These results may suggest that the administration of MPA before HI insult could significantly protect against perinatal HI brain injury via anti-apoptotic mechanisms, which offers the possibility of MPA application for the treatment of neonatal HI encephalopathy.

• Journal of Life Science
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• v.31 no.3
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• pp.257-265
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• 2021

Heterotrimeric kinesin-2 is a molecular motor protein of the kinesin superfamily (KIF) that moves along a microtubule plus-end directed motor protein. It consists of three different motor subunits (KIF3A, KIF3B, and KIF3C) and a kinesin-associated protein 3 (KAP3) that form a heterotrimeric complex. Heterotrimeric kinesin-2 interacts with many different binding proteins through the cargo-binding domain of the KIF3s. The activity of heterotrimeric kinesin-2 is regulated to ensure that the cargo is directed to the right place at the right time. How this regulation occurs, however, remains in question. To identify the regulatory proteins for heterotrimeric kinesin-2, we performed yeast two-hybrid screening and found a specific interaction with creatine kinase B (CKB), which is the brain isoform of cytosolic creatine kinase enzyme. CKB bound to the cargo-binding domain of KIF3A but did not interact with the KIF3B, KIF5B, or KAP3 in the yeast two-hybrid assay. The carboxyl (C)-terminal region of CKB is essential for the interaction with KIF3A. Another protein kinase, CaMKIIa, interacted with KIF3A, but GSK3a did not interact with KIF3A in the yeast two-hybrid assay. KIF3A interacted with GST-CKB-C but not with GSK-CKB-N or GST alone. When co-expressed in HEK-293T cells, CKB co-localized with KIF3A and co-immunoprecipitated with KIF3A and KIF3B but not KIF5B. These results suggest that the CKB-KIF3A interaction may regulate the cargo transport of heterotrimeric kinesin-2 under energy-compromised conditions in cells.

• Journal of Life Science
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• v.33 no.1
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• pp.1-7
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• 2023

Intracellular cargo transport is mediated by molecular motor proteins, such as kinesin and cytoplasmic dynein. Kinesins make up a large subfamily of molecular motors. Kinesin-1 is a plus-end-directed molecular motor protein that moves various cargoes, such as organelles, protein complexes, and mRNAs, along a microtubule track. It consists of the kinesin superfamily protein (KIF) 5A, 5B, and 5C (also called kinesin heavy chains) and kinesin light chains (KLCs). Kinesin-1 interacts with many different binding proteins through its carboxyl (C)-terminal region of KIF5s and KLCs, but their binding proteins have not yet been fully identified. In this study, a yeast two-hybrid assay was used to identify the proteins that interact with the KIF5A specific C-terminal region. The assay revealed an interaction between KIF5A and glutamate-rich 4 (ERICH4). ERICH4 bound to the KIF5A specific the C-terminal region but did not interact with the C-terminal region of KIF5B or KIF3A (a motor protein of kinesin-2). In addition, KIF5A did not interact with another isoform, ERICH1. Glutathione S-transferase (GST) pull-downs showed that KIF5A interacts with GST-ERICH4 and GST-ERICH4-amino (N)-terminal but not with GST-ERICH4-C or GST alone. When co-expressed in HEK-293T cells, ERICH4 co-localized with KIF5A and co-immunoprecipitated with KIF5A and KLC but not KIF3B. Together, our findings suggest that ERICH4 is capable of binding to KIF5A and that it may serve as an adaptor protein that links kinesin-1 with cargo.

• Journal of Life Science
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• v.32 no.3
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• pp.189-195
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• 2022

Kinesin-2 comprises two subfamilies of the heterotrimeric or homodimeric motors found in mammalian cells. Heterotrimeric kinesin-2 consists of kinesin superfamily proteins (KIFs) 3A and 3B and kinesin-associated protein 3 (KAP3), which is a molecular motor protein that moves along microtubules. It plays diverse roles in cargo transport, including anterograde trafficking in cilia, and interacts with many different cargoes and proteins, but their binding proteins have not yet been fully identified. In this study, the yeast two-hybrid assay was used to identify the proteins that interact with the cargo-binding domain (CBD) of KIF3A, and an interaction between KIF3A and brain expressed X-linked 2 (Bex2) was found. Bex2 bound to the CBD-containing C-terminal tail region of KIF3A but did not interact with the same region of KIF3B or KIF5A (a motor protein of kinesin-1). KIF3A interacted with another isoform, Bex1, but did not interact with Bex3. In addition, glutathione S-transferase (GST) pull-downs showed that KIF3A specifically interacts with GST-Bex1 and GST-Bex2 but not with GST alone. When co-expressed in HEK-293T cells, Bex2 co-localized with KIF3A and co-immunoprecipitated with KIF3A and KIF3B but not KIF5B. In combination, these results suggest that Bex2 is capable of binding to heterotrimeric kinesin-2 and may serve as an adaptor protein that links heterotrimeric kinesin-2 with cargo.