Respiratory syncytial virus-associated seizures in Korean children, 2011–2016 / 소아과

PURPOSE: Respiratory syncytial virus (RSV) infection can cause various neurological complications. This study aimed to investigate the RSV-associated neurologic manifestations that present with seizures. METHODS: We retrospectively reviewed the medical records of patients aged less than 15 years with laboratory-confirmed RSV infections and seizures between January 2011 and December 2016 in a regional hospital in South Korea. RESULTS: During this period, 1,193 patients with laboratory-confirmed RSV infection were identified. Of these, 35 (35 of 1,193, 2.93%; boys, 19; girls, 16; mean age: 20.8±16.6 months) presented with seizure. Febrile seizure was the most common diagnosis (27 of 35, 77.1%); simple febrile seizures in 13 patients (13 of 27, 48.1%) and complex febrile seizures in 14 (14 of 27, 51.9%). Afebrile seizures without meningitis or encephalopathy were observed in 5 patients (5 of 35, 14.3%), seizures with meningitis in 2 (2 of 35, 5.7%), and seizure with encephalopathy in 1 (1 of 35, 2.9%) patient. Lower respiratory symptoms were not observed in 8 patients. In a patient with encephalopathy, brain diffusion-weighted magnetic resonance imaging revealed transient changes in white matter, suggesting cytotoxic edema as the mechanism underlying encephalopathy. Most patients recovered with general management, and progression to epilepsy was noted in only 1 patient. CONCLUSION: Although febrile seizures are the most common type of seizure associated with RSV infection, the proportion of patients with complex febrile seizures was higher than that of those with general febrile seizures. Transient cytotoxic edema may be a pathogenic mechanism in RSV-related encephalopathy with seizures.

A new mosaic der(18)t(1;18)(q32.1;q21.3) with developmental delay and facial dysmorphism / 소아과

We report the case of a 22-month-old boy with a new mosaic partial unbalanced translocation of 1q and 18q. The patient was referred to our Pediatric Department for developmental delay. He showed mild facial dysmorphism, physical growth retardation, a hearing disability, and had a history of patent ductus arteriosus. White matter abnormality on brain magnetic resonance images was also noted. His initial routine chromosomal analysis revealed a normal 46,XY karyotype. In a microarray-based comparative genomic hybridization (aCGH) analysis, subtle copy number changes in 1q32.1-q44 (copy gain) and 18q21.33-18q23 (copy loss) suggested an unbalanced translocation of t(1;18). Repeated chromosomal analysis revealed a low-level mosaic translocation karyotype of 46,XY,der(18)t(1;18)(q32.1;q21.3)[12]/46,XY[152]. Because his parents had normal karyotypes, his translocation was considered to be de novo. The abnormalities observed in aCGH were confirmed by metaphase fluorescent in situ hybridization. We report this patient as a new karyotype presenting developmental delay, facial dysmorphism, cerebral dysmyelination, and other abnormalities.

Increased Levels of Interleukine-6, Interleukine-8, Interleukine-10 in Cerebrospinal Fluid in Children with Aseptic Meningitis / 대한소아신경학회지

PURPOSE: Cytokines play important roles on the expression of various neuronal inflammatory disease and insults. The purpose of this study was to evaluate the levels of interleukine (IL)-6, IL-8, IL-10 in cerebrospinal fluid (CSF) in children with aseptic meningitis and compare them with those of the patients having other acute neurological symptoms. METHODS: We retrospectively reviewed the medical records of the children who admitted in the pediatric department of Hanyang University Guri Hospital for acute neurological symptoms and had CSF examinations from September 2012 to July 2013. We classified them into six groups as acute encephalopathy, epilepsy, febrile convulsion, headache, infantile fever, and meningitis. We analyzed the clinical and laboratory data from them. RESULTS: A total of 87 CSFs of the patients were available. The levels of CSF IL-6, IL-8, and IL-10 were significantly increased in the group with aseptic meningitis group as compared to the other groups (P<0.05). CSF IL-6 (r=0.576, P=0.000), IL-8 (r=0.329, P=0.003), and IL-10 (r=0.523, P=0.000) were all significantly correlated with CSF White bood cell (WBC) count. Among the patients with aseptic meningitis, CSF enterovirus positive patients (CSF entero+) showed significantly increased IL-6, IL-8, IL-10 levels than CSF enterovirus negative patients (CSF entero-) (P<0.05). In addition, the CSF entero+ and the increase of IL-10 were significantly correlated (x2=6.827, P=0.033). CONCLUSION: In patients with aseptic meningitis, the CSF IL-6, IL-8 and IL-10 were more expressed than in other neurological disease group. Among them, the enteroviral meningitis may be more related with IL-6, IL-8 and IL-10 expression than in other causes of aseptic meningitis.

Risk Factors for Cystic Periventricular Leukomalacia in Very Low Birth Weight Infants

PURPOSE: In the present study, we aimed to determine the risk factors for the development of cystic periventricular leukomalacia (CPVL) in very low birth weight (VLBW) infants. METHODS: We reviewed the medical records of 309 infants weighing less than 1,500 g who were admitted to the neonatal intensive care unit at Hanyang University Medical Center, Seoul from April 2007 to December 2012. Thirty-nine infants died within 28 days of birth. Of the remaining 270 infants, 21 with CPVL established by cranial ultrasonography, and 63 without CPVL, who were matched for gestational age, were enrolled in this study. Univariate and multivariate analyses of maternal, perinatal, and neonatal risk factors for CPVL were performed through retrospective assessment of data collected from the medical records. RESULTS: Necrotizing enterocolitis (NEC > or =stage II: 42.9% vs. 9.5%, P=0.002), culture-proven sepsis (66.7% vs. 34.9%, P=0.021), hypotension with sepsis (33.3% vs. 6.3%, P=0.004), and severe intraventricular hemorrhage (> or =grade III: 61.9% vs. 22.2%, P=0.002) were associated with the development of CPVL on univariate analysis. Using multivariate logistic regression analysis, two variables were found to be statistically significant independent risk factors: NEC (> or =stage II: adjusted OR, 5.12; 95% CI, 1.219-21.514; P=0.026) and hypotension with sepsis (adjusted OR, 8.23; 95% CI, 1.194-56.713; P=0.032). CONCLUSION: NEC (> or =stage II) and hypotension with sepsis were associated with an increased risk of developing CPVL in VLBW infants.

Blood Urea Nitrogen Concentration and Aggressive Parenteral Amino Acid Administration in Extremely Low Birth Weight Infants during the First Week / 대한주산의학회잡지

PURPOSE: Early administration of parenteral amino acids has been shown to limit catabolism and improve growth in extremely low birth weight infants (ELBWI). This study aimed to evaluate the relationship between an earlier aggressive administration of amino acids and blood urea nitrogen (BUN). METHODS: We retrospectively analyzed the medical records of all ELBWI who were born and admitted to Hanyang University Hospital from March 2007 to December 2009. The high initial dose group received > or =3.0 g/kg/d amino acids, while the lower initial dose group did not received a minimum of > or =3.0 g/kg/d parenteral AA at < or =3 days of age. RESULTS: There were no differences in gestational age, birth weight and sex between the groups. Mean fluid intake and total calories during the first 48 hours of life were similar between two groups. There is no correlation between amino acid intake and BUN level in ELBWI during study period. However, gestational age showed a significant negative correlation with BUN level in ELBWI on day 3 and 7. CONCLUSION: An earlier, more aggressive administration of amino acids was safe and well-tolerated. There is no correlation between amino acid intake and BUN level in ELBWI infants within 7 days of life.

A Case of Cervical Disc Herniation with Paresthesia in Both Arms and Tic Mimicking Motions / 대한소아신경학회지

Intervertebral disc herniation is rare in children and is reportedly related with disc calcification and traumatic injury. We report an 8 years old girl, who complained of tingling sensation in both arms and intentional tic like neck stretching for about 1 month. She had got unnoticed whiplash Injury 2 weeks before symptoms. She also had been taking lessons for taekwondo for one and half year. Physical examination was unremarkable. Her symptoms got aggravated over the next 4 weeks. Plain vertebral x-ray showed no abnormalities, but cervical spinal MRI revealed disc central herniations at C 5-6 and C 6-7 levels. We concluded that her paresthesia and tic like motion were related with cervical disc herniation from hyperflexion neck injury.

Protective Effect of Hypoxic Preconditioning on Hypoxic-Ischemic Injured Newborn Rats

Brief episodes of cerebral hypoxia-ischemia cause transient ischemic tolerance to subsequent ischemic events that are otherwise lethal. This study was conducted to evaluate the protective effect of hypoxic preconditioning on hypoxic-ischemic injury in the neonatal rat and the persistence of a protective window after hypoxic preconditioning. The rats were preconditioned with hypoxia (8% oxygen, 92% nitrogen) for three hours, subjected to ischemia using ligation of the right common carotid artery, and then exposed to another three hours of hypoxia. Using proton magnetic resonance spectroscopy, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) staining, and morphologic scores, this study shows that hypoxic preconditioning 6-hr to 1-day before hypoxic-ischemic injury increases survival rates and has neuroprotective effects against subsequent hypoxic-ischemic injury. The mechanism of the protective effects of hypoxic preconditioning in the newborn rat brain may involve downregulation of apoptotic cell death.

Effect of Prophylactic Ibuprofen in Preterm Infants Less than 1,250 g in Birth Weight

PURPOSE: Ibuprofen is used for prevention and treatment of patent ductus arteriosus as an alternative drug of indomethacin in very premature infants. We aimed to determine the effect of prophylactic ibuprofen on patent ductus arteriosus and clinical outcomes in preterm infants less than 1,250 g. METHODS: A retrospective review of 39 preterm infants who were admitted to our neonatal intensive care unit from November 2009 to July 2010 was performed. Patients were divided into a prophylactic group (n=13) and a matched historical control group (n=26), where prophylactic ibuprofen were administrated within 24 hours after birth. The rate of ductal closure, side-effects of drug treatment and clinical outcomes were compared between two groups. RESULTS: Comparison of the prophylactic and control groups revealed no significant differences in the rate of ductal closure (69.2% vs 77.7%, P=0.825) and surgical ligation (23.1% vs 30.8%, P=0.719). Occurrence of bowel perforation was more frequent in the prophylactic group than the control group, but was not significant (30.8% vs 11.5%, P=0.194). The frequency of intraventricular hemorrhage (grade> or =3) and other outcomes did not differ between the groups. CONCLUSION: Ibuprofen prophylaxis in preterm infants did not decrease the rate of ductal closure, the need for surgical ligation and the incidence of intraventricular hemorrhage. Further studies are needed to investigate the beneficial effect and associated adverse events attributed to ibuprofen prophylaxis.

Effect of Low Versus High Parenteral Amino Acid Supplementation on Liver Unctions in Premature Infants / 대한주산의학회잡지

PURPOSE: To study the safety of more aggressive parenteral amino acid supplementation on liver functions during parenteral nutrition in preterm infants. METHODS: Medical records of preterm infants (n=58) treated in the neonatal intensive care unit from 2004 through 2008 with birth weight less than 2,000 g and exposure to parenteral nutrition (PN) for more than 7 days were reviewed. Patients were divided into two groups; low amino acid intake group (LAA, n=32) admitted from January 2004 to May 2006 and high amino acid intake group (HAA, n=26) admitted from June 2006 to July 2008. The incidence of cholestasis was compared between the two groups and the liver functions in infants with cholestasis were evaluated. RESULTS: Mean protein intake was significantly higher in HAA (1.0+/-0.2 g/kg/day vs 2.1+/-0.6 g/kg/day, P=0.001). But there were no differences in the incidence and duration of cholestasis between the groups. And peak total bilirubin (T.bil), peak direct bilirubin (D.bil), peak alanine aminotransferase (ALT), peak asparate aminotransferase (AST), and peak alkaline phosphatase (ALP) in infants with cholestasis were not significantly different. CONCLUSION: Aggressive parenteral amino acid supplementation in preterm infants were not associated significantly with the liver functions in this study.

Multiple Congenital Anomalies in a Neonate of a Diabetic Mother

Maternal diabetes is known to have teratogenic effects which increase the risk for congenital anomalies, such as caudal dysplasia, cardiac defects, hydronephrosis, and small left colon syndrome. Infants of diabetic mothers have a 10-fold higher frequency of anomalies in the central nervous system and a 5-fold higher frequency of congenital heart defects. However, jejunal atresia combined with multiple anomalies of the face, ears, and hands has rarely been reported. Herein we report a neonate born to a diabetic mother, who had hemifacial microsomia, displacement of the lacrimal ducts, polydactyly of the right hand, microtia of the right ear and proximal jejunal atresia presenting as bile regurgitation on the 1st day of life.

Neurologic Complications Associated with Respiratory Syncytial Virus Infection in Childhood / 대한소아신경학회지

PURPOSE: Respiratory syncytial virus(RSV) mainly brings about respiratory complication, but it can also be related to neurologic complication. We have studied clinical aspect and incidence of neurologic complication associated with RSV infection. METHODS: We reviewed the medical records of 732 children with RSV infection who were admitted to the department of pediatrics, Hanyang University hospital from November 2002 to June 2007 and studied on existence of neurologic complication, age, sex, clinical symptom, characteristics of seizure, and laboratory findings. RESULTS: Neurologic complications were occurred in 52 patients(7.1%) among 732 patients. Among them, 14 patients(1.9%) had seizure and 38 patients(5.2%) had alteration of mental status such as drowsy, lethargy. Age distribution of patients with neurologic complication was from 1 month to 5 years(mean 16.4 months). There were 30 boys and 22 girls. Among 14 patients who had seizure, 2 patients had convulsion disorder, 3 patients had febrile convulsion, and 9 patients had no seizure before. Their age distribution was from 1 months to 4 years(mean 18.4 months) and there were 8 boys and 6 girls. All of 14 patients showed generalized tonic clonic seizure and durations were from 30sec to 15 min(mean 4.4 min). All of the investigations were normal. None of 52 patients had recurrence and neurologic sequelae. CONCLUSION: It is important to know that RSV can cause CNS complications because we know how many patients infected by RSV. RSV-related seizure can be considered as benign seizure which does not need any long-term antiepileptic medication.

Study on the Prognosis According to Clinical Patterns and Laboratory Findings in Children with Acute Encephalopathy / 대한소아신경학회지

PURPOSE:Acute encephalopathy is defined as diffuse interference of brain functions due to neuronal dysfunction by generalized or multifocal insults. In this study, we investigated the relationship between the prognosis and other factors such as clinical patterns, laboratory findings, electroencephalographic and radiologic findings in children with acute encephalopahty. METHODS:We carried out a retrospective review on the medical records of 43 patients who were initially diagnosed as encephalopathy from January 1995 to June 2004. We excluded the patients diagnosed as mumps meningitis, Reye syndome and neonatal hypoxic ischemic encephalopathy. RESULTS: 1) The morality rate was 50% in the patients below 1 year old at the admission, but all the patients above 10 years old were survived. 2) The morality rate was 40% in the patients with alert mental status at the admission and one patient with comatous mental status died. 3) The morality rate of the patients without seizures at the admission(35.7%) was higher than that of the patients with seizures(10.3%). But there was no statistical significance. 4) In the patients with abnormal liver function tests, the mortality rate(40%) was singnificantly higher than that of the patients with normal liver functions(7.1%, P value <0.05) 5) Only 5 patients(20%) among 25 patients who took both EEG's and imaging studies were taken showed abnormalities at the same locations in both studies. But there was no significant relationship between the mortality rate and EEG and the radiologic findings. CONCLUSION:In this study, we could not find out the statistically significant relationship between the prognosis and other factors such as age, consciousness levels, the presence of seizures at the admission, and electroencephalographic and radiologic abnormalities. But the patients with abnormal liver functions at the admission showed statistically significant higher mortality rates than patients with normal liver function.

Factors Associated with Care-giver Burden of Pediatric Epilepsy Patients

BACKGROUND: Pediatric epilepsy can result in a heavy burden of illness for the family and the role of family caregivers is becoming more important for the management of the disease. However, there are only few studies about care-giver burden of pediatric epilepsy. This study examined the factors which may influence care-giver burden of pediatric epilepsy patients METHODS: We surveyed 87 care-givers of pediatric epilepsy patients. The demographic and social data of the care-givers, along with the social and clinical data of the patients were obtained. The Korean version of the Burden Interview (KBI) and the Korean version of the Beck Depression Inventory (KBDI) were used. The relationship between the demographic and social data of care-givers, the clinical factors of the patients and KBI score were evaluated. RESULTS: Of the 87 participants, sixty-nine (79.3%) were the mothers. The mean age of caregivers was 41.3 years and the mean score on the KBI was 20.2 (+/-16.8) points. The mean age of the patients was 11.1 years and 48 patients (55.8%) were male. The number of antiepileptic drugs prescribed, severity of the disease and school record had a significant correlation with KBI in a multivariate linear regression analysis. CONCLUSIONS: We suggest that in addition to the strict control of the seizure, that the consideration for the academic functions of pediatric patients is also important for reducing care-giver burden in the treatment of pediatric epilepsy.

Medicolegal Problems in Pediatric Area / 소아과

PURPOSE: Medicolegal problems start when the patient asserts the mistake of doctor and doctor does not accept it. The purpose of this study is to assess the actual condition of medicolegal problems and to provide solutions of medicolegal problems in the pediatric field. METHODS: There is not official statistical data about medicolegal problems in our country. We gathered data of legal insurance program of Korean Medical Association (KMA) and court cases and other fragmentary data. RESULTS: Between 1981 and 1995, of total 2, 338 cases reported to legal problem insurance program of KMA, most common ones were 748 cases of obstetrics and gynecology. Pediatric case was ranked at the 5th, 74 cases (3.1%). According to analysis of 41 medicolegal cases' after 1990, maltreatment of patient had the highest incidence of 14 cases, injection and medication were related to 12 cases, misdiagnosis was 9 cases, patient management were related to 4 cases, and others were 2 cases. The trial result of the medicolegal cases was that 31 cases were compensated, and 8 cases were defeated, and 2 cases were still in the process. CONCLUSION: The aspect of medical legal problem has the tendency of radicalism and systematization. This brings an economic destitution in the patient and gives damage to a doctor. In order to reduce medicolegal problem, doctor should offer a duty of explanation and efforts to his best to satisfy patient and endeavor to make an intimate doctor-patient relationship.

DNA Methylation Change of IL-4 Gene from T Cell in Allergic Children / 소아과

PURPOSE: An understanding of the immunological process is required if primary prevention of atopic diseases is to be developed in early childhood. But, it is too hard to distinguish atopy from nonatopy under the age of two clinically, because the expression of phenotype and cytokines is vague in early childhood. We evaluated DNA methylation changes at Th2 interleukin-4 gene in peripheral blood from atopic children. METHODS: We selected 15 allergic children (mild: eight, moderate to severe: seven) and seven normal controls by using family allergy scores and clinical histories. We measured Total IgE and Der f II specific IgE levels and cultured peripheral blood mononuclear cells with Der f II stimulation and extracted DNA from Der f II specific T cells. We examined the change of CpG methylation in DNA from atopic and nonatopic children. RESULTS: In T cells from normal children, IL-4 DNA were predominantly methylated; otherwise, CpG demethylation occurred in Der f II specific T cells from allergic children. CONCLUSION: IL-4 DNA methylation changes occurred in T genes from allergic children and DNA methylation assay in early childhood.

The Study on the Clinical Significance of the Finger Extension Reflex in Early Infancy

The finger extension reflex was performed to the 419 normal infants without CNS abnormalities that visited to the well baby clinic and out-patient department, and so to the patients with CNS abnormalities on the brain sonography and brain CT under the age of 2 months from May 1992 to September 1993 in the department of pediatrics, Hanyang university hospital. The results were summerized as follows 1) The positive rates of the finger extension reflex according to age in month on the normal infants from birth to 8 months of age were 100%, 100%, 100%, 72.3%, 57.1%, 28.6%, 17.5%, 6.3% and 0% respectively, and the reflex was almost lost after the age of 5 months. 2) Of 21 patients with brain pathology on the brain sonography and/or brain CT, the finger extension reflexes were absent on two patients with grade 3~4 intraventricular hemorrhage, one with hypoxic brain damage and one with severe brain parenchymal hemorrhage, partially responded on two patients with brain edema and one with moderate-sized brain parenchymal hemorrhage, and completely responded on 11 patients with mild intracranial hemorrhage, two with hydrocephalus and one with aneurysm of Galen vein. 3) Because there were no cases with localized brain pathology, we couldn't find the differences of the finger extension reflexes associated with the location of brain pathology. In conclusion, we found that the finger extension reflex may be lost from 3 months through 6 months of age. With further study of normal premature babies and more infants with brain pathology, we may use the finger extension reflex as one of the primitive reflexes and predict severe CNS abnormalities.

A Study on the Serum Level of Phenytoin after Intravenous Administration of Loading Dose

PURPOSE: Phenytoin is effectively and widely used drug for the treatment of status epilepticus and patient with ongoing seizure by intravenous infusion. It is generally recommended to maintain serum concentration above 10microgram/ml for the sustained effective anticonvulsant effect. This study was designed to know the optimal time to begin oral maintenance therapy after initial intravenous infusion. METHODS: Total 17 patients with status epilepticus and ongoing seizure who were admitted to the pediatric department of Han Yang University during the period from July 1993 to September 1995 were enrolled in this study and serum level was monitored at 2, 6 and 12 hours after the intravenous phenytoin infusion of loading dose, 20mg/kg of body weight by enzyme multiplict immunoassay technic. Student t-test was used for statistical analysis and P value below 0.05 interpreted as statistically significant. RESULTS: 1) The subjects were 5 boys and 12 girls, average age was 7.6 years old and age distribution was from 3 months to 15 years old. 2) The serum concentration ranged from 9.42microgram/ml to 43.98microgram/ml (24.04+/-8.97microgram/ml) after 2 hours, 8.82microgram/ml to 33.95microgram/ml (18.62+/-6.43microgram/ml) after 6 hours, and 7.20microgram/ml to 31.38microgram/ml (14.97+/-6.58microgram/ml) after 12 hours. 3) There was no significant differences of average serum concentration and the decline of serum concentration by time between patients over and below 2 years of age and both sexes. 4) The average decrease in serum phenytoin concentration per hour was 0.91microgram/ml. 5) The average maintenance duration of therapeutic serum level after initial infusion of loading dose was 22.4 hours. CONCLUSIONS: The average maintenance duration of therapeutic serum level after initial infusion of loading dose was 22.4 hours, hence it would be appropriate to administer maintenance dose of phenytoin if the serum level at 2 hours after loading dose is satisfactory.

A Case of Paroxysmal Kinesigenic Choreoathetosis

No abstract available.

A Study on Prognostic Factors in Children with Encephalopathy

To elucidate the clinical characteristics-especially its clinical pattern and outcome-of children with encephalopathy, we carried out a retrospective review on medical records of 45 patients who were initially diagnosed as encephalopathy except mumps meningitis, Reye's syndome and neonatal hypoxic ischemic encephalopathy at the Department of pediatrics, Hanyang University children's hospital from Jaunary 1986 to February 1994. The results were summarized as follows: 1) Twenty five were male and twenty were female with male to female ratio 1.3:l. 2) There were no association with death rate and conscious level, abnormal liver function test, and sugar level in CSF on admission. 3) Death rate (33.3%) of group with seizure was higher than that (13.3%) of group without seizure on admission, but there was no statistical significance (p=0.28). 4) Death rate (7.5%) of group (l) which initial therapy started before 12hours was lower than that (43.4%) of group (ll) which initial therapy started after 12hours, but there was no statistical significance (p=0.09). However complete recovery rate (66.7%) of the former group was higher than that (26.7%) of the latter group with statistical significance (p<0.05). Therefore, early diagnosis and treatment before 12hours was essential to recovery and good prognosis in childern with acute encephalopathy.

Study on Serum Level of Phenobarbital after Intravenous Administration of Loading Dose

PURPOSE: To learn the changes of phenobarbital serum level after intravenous administration of loading dose and to determine the optimal time of maintenance therapy to support therapeutic concentration. METHODS: A total of 24 patients, who were admitted to the pediatric ward for treatment of ongoing and recurrent seizure, were enrolled in this study from November, 1994 to August, 1996. None of them had taken other anticonvulsants before and their age varied from 8 days old to 7 years old. Loading dose of 20mg per kg of phenobarbital was administered intravenously, and sequential plasma samples were obtained at 2, 6, and 12 hours after administration. RESULTS: The mean serum concentration of phenobarbital was 23.65 (11.53-36.81) microgram/ml after 2 hours, 22.78 (10.97-35.29) microgram/ml after 6 hours and 20.79 (9.79-33.01) microgram/ml after 12 hours. We divided the patients into 2 groups by the 12-hour levels, group A : therapeutic level (>20 microgram/ml), and group B : subtherapeutic level. The mean 12-hour level in group A was 25.39 (20.13-33.01) microgram/ ml and 16.24 (9.79-19.48) microgram/ml in group B. The mean 2-hour level in group A was 28.30 microgram/ml and 19.00 microgram/ml in group B (P<0.05). The mean decline rate of serum phenobarbital level was 0.34 microgram/ml/hr in group A and 0.29 microgram/ml/hr in group B. And there was no significant difference between the two groups. CONCLUSION: It is usually effective to begin maintenance therapy 12 hours after loading dose, but in cases where 2-hour serum level of phenobarbital is below 20 microgram/ml, it is better to begin maintenance therapy earlier.