항경련제 투여 소아의 성장 양상

박성식(Swong Shik Park),이정임(Jung Im Lee),배상남(Sang Nam Bae),남상욱(Sang Ook Nam),박희주(Hee Ju Park) 대한소아신경학회 2001 대한소아신경학회지 Vol.9 No.1

목적: 간질로 진단받고 항경련제로 치료중인 환아들을 대상으로 항경련제가 성장에 미치는 영향을 알아보기 위해 본 연구를 실시하였다. 방법: 1996년 1월부터 1999년 7월까지 부산대학교병원 소아과 외래를 방문하거나 입원한 소아중 간질로 진단받은 환아 331명을 대상으로 후향적으로 병력지를 통해 체중, 신장 및 두위가 측정되었고, 이후 변화가 관찰 가능한 219명을 대상으로 하였으며 모든 대상 환아 각각에 대한 1998년 개정된 한국 소아 및 청소년 신체 발육 표준치의 체중, 신장 및 두위의 평균을 대조군으로 하였다. 항경련제 치료 시작할 당시의 체중, 신장 및 두위를 측정하고 각각의 변화를 성별, 치료 시작할 당시의 연령, 치료 기간, 간질의 원인 및 형태, 약물 치료방법에 따라 분석하여 항경련제가 성장에 미치는 영향을 알아보았다. 결과: 항경련제 치료 시작할 당시의 체중, 신장은 대조군과 비교하여 차이가 없었으나 치료 시작할 당시의 두위는 대조군과 비교시 작았다.(P<0.05). 특히 치료 시작할 당시 연령으로 비교시 1-6에 군에서 작았으며(P<0.005), 간질의 형태에 따라 나누었을 때 증후성 간질에서 작았다(P<0.001). 치료 이후 체중, 신장, 두위의 증가는 성별, 치료 시작할 당시의 연령, 치료기간, 간질의 원인 및 형태, 약물 치료방법에 따라 대조군과 차이가 없었다. 결론: 간질 소아의 항경련제 투여에 따른 체중 신장과 두위의 변화는 정상 소아와 비교하여 차이가 없었다. Purpose: This study was performed to investigate the growth pattern of epileptic children on medication with anticonvulsants. Methods: We measured the weight, height and head circumference of 219 epileptic children on medication with anticonvulsants through the review of the medical records, compared these with those of the control group as means of Standard Measurement of Body Growth for Korean Children and Adolescence reformed at 1998 and analyzed this data according to sex, age at the start of medication, duration of medication, the cause of epilepsy, the type of seizure and the number of anticonvulsants. Results: The weight and height at the start of medication with anticonvulsants had no difference from those of the control group according to sex, age at the state of medication, the cause of epilepsy, the type of seizure and the number of anticonvulsants, but the head circumference at the start of medication was smaller than that of the control group(P<0.05), especially in children aged 1 to 6 years(P<0.005) and in children with symptomatic epilepsy(P<0.001). The increase of weight, height and head circumference had no difference from those of the control according to sex, age, duration of medication, the cause of epilepsy, the type of seizure and the number of anticonvulsants. Conclusion: The increase of weight, height and head circumference of epileptic children on medication with anticonvulsants had no difference from those of normal children.

항경련제 복용 환자에서 항핵항체 양상

박필환 ( Pil Whan Park ),김신규 ( Thin Kyou Kim ) 대한류마티스학회 2002 대한류마티스학회지 Vol.9 No.4

Objective: This study set out to determine the antinuclear antibody (ANA) frequency and fluorescence pattern, as well as the incidence of drug-induced lupus (DIL) in patients on long term medications with anticonvulsants. Methods: Sera from 200 patients on medications with anticonvulsants for at least 6 months and from 105 healthy controls were tested by indirect immunofluorescence on immunotype (IT)-1 cells, and the medical records were retrospectively reviewed. The patients included 72 on valproic acid, 24 on phenytoin, 75 on carbamazepine, and 29 patients on two or more anticonvulsants. Results: ANA were positive in 3 of the 105 normal controls (3%). Twenty nine percent of patients on valproic acid, 26% on phenytoin, 8% on carbamazepine, and 34% on two or more different anticonvulsants were positive for ANA. The cytoskeletal pattern was prominent in patients on valproic acid and the speckled pattern in phenytoin. Most were of low titers. Conclusion: Long-term ingestion of valproic acid and phenytoin were shown to influence ANA, while carbamazepine was not. No definite relationship was observed between ANA positivity and DIL. However, positive ANA indicates effects of anticonvulsants on the immune system, and therefore progression to DIL cannot be ruled out. Therefore, patients on long-term medications with anticonvulsants should be regularly tested for ANA.

수종 항경련제가 고양이 척수 후각 세포의 activity에 미치는 효과

고상돈,신홍기,김기순,김태영 한양대학교 의과대학 1993 한양의대 학술지 Vol.13 No.1

The present study was undertaken to investigate effects of a few anticonvulsants on the dorsal horn cell activities, to elucidate their mechanism of action and to examine whether these anticonvulsants have spinal and/or supraspinal actions. Spontaneous activities and the responses of wide dynamic range (WDR) cells to mechanical stimulations and graded electrical stimulations of the afferent nerve were extracellulary recorded in the normal and spinal cats before and after the intravenous administration of diphenylhydantoin (15-30mg/kg, DPH), carbamazepine (15-30mg/kg, CBZ) and valproic acid (15-30mg/kg, VA). Also studied were the effects of picrotoxin and strychnine on the anticonvulsant-induced changes in the dorsal horn cell activities. All the anticonvulsants tested inhibited dose-dependently the response of WDR cell to afferent signals. The resposes of WDR cell to pinch and C-fiber stimulation were more strongly inhibited than those to brush and A-fiber stimulation. Strychnine (0.5mg/kg), not picrotoxin (0.5mg/kg) strongly blocked an inhibitory effect of DPH on all the reponses of WDR cells except C-fiber response. In the spinal animal, approximately two-third of DPH-induced inhibition was maintained. The anticonvulsants also markedly inhibited spontaneous activities of the cat spinal neurons. These results lead to the conclusion that in the lumbar segment of the cats spinal cord most of anticonvulsant-induced inhibitions of the responses of WDR cell to afferent signals were mediated through glycine receptors at both the spinal and supraspinal sites.

간질 환아에서 항경련제의 임의 중단 후 관찰된 임상 소견

임근희(Keun Hee Lim),이은실(Eun Sil Lee),문한구(Han Ku Moon) 대한소아신경학회 1999 대한소아신경학회지 Vol.7 No.1

목 적 : 본 연구는 간질 환아 중 보호자나 환아가 임의로 항경련제의 복용을 중단한 후 추적 관찰된 경우에서 임의 중단 후 발생한 경련은 어떤 형태로 나타나며, 임의 중단이 간질 중첩증의 발생과 직접적인 인과관계가 있는지에 대해 알아보기 위하여 시행되었다. 방 법 : 1995년 1월부터 1997년 6월까지 2년 6개월 동안 영남대학교 부속병원 소아과 소아신경클리닉에서 추적 관찰되고 있던 간질 환아 425명 중 항경련제의 복용을 갑자기 임의 중단했던 72명, 88증례를 대상으로 항경련제의 임의 중단 후 간질 의 종류 및 항경련제의 종류에 따른 경련의 발생 여부와 발생한 경련의 형태와 정도를 분석하고, 임의 중단과 간질 중첩증의 발생과의 연관성을 의무 기록지를 검토하는 후향적 연구로 시행하였다 결 과 : 1) 항경련제가 임의 중단된 88 증례 중 추적시 기존 경련 재발군에 속한 경우가 42례(47.7%), 경련의 발생이 없던 군이 18례(20.5%) 그리고 14례(16.0%)는 경련 횟수 증가군에 속했으며, 경련 횟수나 정도의 변화가 없던 경우가 3례(3.4%), 경련의 횟수나 정도가 감소한 경우가 2례(2.3%)였다. 2) 임의 중단 후 기존 경련 재발, 경련 횟수 증가, 경련 정도 악화 및 간질 중첩증의 소견을 보인 경우는 국소 간질의 경우 71례 중 55례(77.5%), 전신성 간질의 경우 17례 중 9례(52.9%)로서 국서 간질에서 많았으며(P=0.041), 이와 같은 소견이 임의 중단 4주 이내에 관찰된 예는 국소 간질의 경우 55례 중 36례(65.5%), 전신성 간질의 경우는 9례 중 3례(30.0%)로서 이 역소 국소 간질에서 많았으나 통계학적으로는 유의하지 않았다(P=0.137). 3) 항경련제별로 임의 중단 후 기존 경련의 개발, 횟수 증가, 경련 정도의 악화 및 간질 중첩증 발생의 소견을 보인 경우는 carbamazepine 사용군 26례 중 18례(69.2%), phenobarbital 사용군은 16례 중 15례(93.8%), 다약제군의 34례 중 24례(70.6%)였으나 통계학적으로 유의한 차이를 얻을 수 없었고(P=0.143), 이러한 소견이 임의 중단 4주 이내에 발생한 예에서 약제간의 차이도 유의하지 않았다(P=0.122). 4) 간질 중첩증은 4명, 4례(4.5%)에서 발생하였으며 모두 국소 간질 환아였고 항경련제의 임의 중단 4개월(2례), 5개월(1례), 23개월(1례) 후에 발생하였다. 결 론 : 간질 환아에서 항경련제의 복용이 임의로 중단되는 경우가 많으므로 이에 대한 환아 및 부모의 교육이 강화되어야 하겠다. 간질 환아의 간질 중첩증의 발생기전에 대해 항경련제의 임의 중단 외의 다른 요인에 보다 많은 연구가 필요할 것으로 생각된다. 간질 환아에서 항경련제의 처방 후 효과 뿐만 아니고 역효과에 대해서도 세심항 관찰이 필요하다고 생각된다. Purpose : The effects of arbiturary acute anticonvulsants withdrawal in epileptic children were studied and relationship between status epilepticus and anticonvulsant withdrawal was analysed. Methods : Medical records of 88 withdrawal episodes in 72 active epileptic children were analysed retrospectively according to the types of epilepsies, anticonvulsants. Results : 1) When followed up after withdrawal, 42 cases(47.7%) had a recurrence of habitual seizure, 18 cases(20.5%) had no seizure and increased seizure frequency were found in 14 cases(16.0%). Three cases(3.4%) had no change in seizure frequency or severity and in 2 cases(2.3%) the frequency or severity of seizure were decreased after withdrawal. 2) Recurrence of habitual seizure, increased seizure frequency, more intense seizure or status epilepticus were noted in 55 of 71 withdrawal episodes in focal epilepsies(77.5%), in 9 of 7 withdrawal episodes(52.9%) in generalized epilepsies(P=0.041). These changes occurred in 36 of 55 cases(65.5%) in focal epilepsies, 3 of 9 cases(30.0%) in generalized epilepsies within 4 weeks after withdrawal(P=0.137). 3) Recurrence of habitual seizure, increased seizure frequency, development of more intense seizure or status epilepticus were found in 18 of 26 cases(69.2%) in carbamazepine monotherapy, 15 of 16 cases(93.%) in phenobarbital monotherapy, 24 of 34 cases(70.6%) in polypharmacy(P=0.143). These changes occurred in 14 of 18 cases(77.8%) in carbamazepine monotherapy, 7 of 15 cases(46.7%) in phenobarbital monotherapy and 18 of 24 cases(75.0%) in polypharmacy within 4 weeks after withdrawal(P=0.122). 4) Four cases(4.5%) of status epilepticus occurred in 4 patients with focal epilepsies at 4 months(2 cases), 5 months, 23 months later after acute anticonvulsant withdrawal. Conclusion : Arbiturary acute anticonvulsants withdrawal in epileptic children wrer more common than expectation and councelling to avoid arbiturary anticonvulsant withdrawal must be entensified. Approximately half of the cases with anticonvulsant withdrawal showed a recurrence of habitual seizure abd status epilepticus occurred in 4.5% of cases only. Other factors besides acute anticonvulsant withdrawal must be investigated to clarify the underlying mechanism of status epilepticus. A quarter of cases showed no seizure and even decrease in seizure frequency or severity after anticonvulsant withdrawal. These results suggest more considerated prescription of anticonvulsant is needed in practice.

Dental management of gingival overgrowth in children on antiepileptic drug therapy: Case reports

Mi So Lee,Jea-gon Kim,Yeon-mi Yang,Dae-woo Lee Asia Association for Disability and Oral Health 2020 대한장애인치과학회지 Vol.16 No.1

Anticonvulsants commonly used as a treatment for epilepsy frequently cause undesired gingival enlargement. Phenytoin is the most well-known anticonvulsant that induces gingival enlargement. As an alternative, sodium valproate can be considered; it is used less frequently but can also cause gingival enlargement. We present case reports of two patients that experienced druginduced gingival enlargement due to anticonvulsants. The first case was a 13-year-old girl who was referred for gingival enlargement. She had Lennox-Gastaut syndrome and was taking anticonvulsants. The gingiva of her entire dentition was overgrown and completely covered the crowns of all teeth. After a gingivectomy under general anesthesia, the gingival enlargement improved, but severe-to-moderate gingival enlargement remained due to need for continued treatment for intractable epilepsy. The second case was an 11-year-old boy who was diagnosed with pachygyria scoliosis and had been taking sodium valproate. He had severe generalized fibrous drug-induced gingival enlargement with poor oral hygiene. The gingival status did not improve remarkably despite regular intensive professional tooth cleaning, but the pathological changes of teeth and gingiva did not progress significantly for at least 3 years. In conclusion, when gingival enlargement is induced by anticonvulsants, changing the medication should first be considered and adapted, if possible. It is very important for patients to undergo regular checkups and professional tooth cleaning and for guardians to adhere to oral hygiene instruction to improve oral status.

외상성 뇌손상과 출혈성 뇌졸중 환자의 간질발생에 대한 보고

위훈,길은영,양충용,주민철,신용일 최신의학사 2004 最新醫學 Vol.47 No.1

항경련제가 갑상선기능에 미치는 영향

서은숙,이동환,문경상 순천향의학연구소 1998 Journal of Soonchunhyang Medical Science Vol.4 No.1

Object: Many studies on the effect of long-term treatment with anticonvulsant on thyroid function in children have been reported. Because the mechanism and metabolism of each drugs are different, the effect of anticonvulsants on thyroid function is controversial. And it has been reported that competitive binding with serum protein, increased intrahepatic excretion and more recently effects on hypothalamus and pituitary gland make changes in thyroid hormones. Therefore, we checked T₃, T₄, TSH levels of the patients who have been taking anticonvulsants for more than 1 years, in order to the influence of carbamazepine and valproic acid on thyroid function. Method: 38 patients (male 18, female 18) who have been diagnosed as epilepsy during the period of Jan 1996 to Dec 1996 at SoonChunHyang University Hospital, and being treated with anticonvulsant, the serum levels of triiodothyronine(T₃) thyroxine(T₄) and TSH were measured were measured by RIA. Result: Of these 38 patients, 18 were males and 18 were females. The mean age of the patients was 9.46 ±3.86(2 to 17 years old) years old. In 10 cases were treated with valproic acid, in 7 cases received carbamazepine and in 11 cases were treated with combined therapy. In valproic acid treated group, T₃, T₄, TSH levels were 145.05±25.34ng/dl, 8.86±2.17㎍/dl, 2.73±0.86 μU/ml respectively. In Carbamazepine treated group. T₃, T₄, TSH levels were group, T₃, T₄, TSH levels were 162.06 ±26.78ng/dl, 9.66 ±4.18㎍/dl 2.01 ±0.78 μU/ml respectively. Although the levels of T₃, T₄, TSH were within normal range, they were relatively decreased compared to the control group. The carbamazepine treated group was revield lower T₃, T₄ levels compared to those treated with valproic acid, but we couldn't find out statistical significance. Conclusion: In our study we found out long-term treatment with anticonvulsants including carbamzepine and valproic acid had effects on thyroid function and follow-up test with larger group of patients should be proceeded.

Investigation of the Relationship between Anticonvulsants for Seizures and Genes Using Artificial Intelligence Modeling and Topic Analysis

김광남,김광현 계명대학교 자연과학연구소 2024 Quantitative Bio-Science Vol.43 No.1

Epilepsy is a neurological disorder characterized by recurrent seizures, and anticonvulsant medications are the mainstay of treatment. However, individual responses vary substantially. Identifying the underlying genetic factors that influence anticonvulsant responses remains a challenge. This study investigated the relationship between anticonvulsants and related genes using artificial intelligence (AI) modeling. We used a comprehensive dataset of anticonvulsant medications and genetic profiles. The XGBoost model and ontology method were developed to elucidate the complex interplay between these factors and predict individual responses to anticonvulsant treatment. The interpretability of the predictive model and ontology analysis facilitated the identification of specific genes and their interactions that contribute to anticonvulsant efficacy. The model performance was evaluated using metrics like area under the curve (AUC), accuracy, sensitivity, and specificity. AI modeling was used to analyze the main features of gene interactions for enzymes, ion channels, cytochromes, and kinases in order of importance. Serine/threonine kinase and drug resistance showed a strong correlation coefficient of 0.93. Three topics were identified on the principal component plane by grouping salient genes, such as SCN and CYP, with each relevant gene predicted by each topic (anticonvulsant). Based on modeling, the AUCmax, accuracy, sensitivity, and specificity were 0.84, 0.89, 0.77, and 0.97, respectively. The findings of this study could revolutionize personalized medicine approaches for epilepsy by providing a deeper understanding of the genetic basis of anticonvulsant responses and facilitating the development of targeted treatment strategies.

Vitamin D Levels in Children and Adolescents with Antiepileptic Drug Treatment

백정현,은백린,서영호,김건하,김미경 연세대학교의과대학 2014 Yonsei medical journal Vol.55 No.2

Purpose: This study was to evaluate the relationship of 25(OH)D3 levels with anticonvulsantuse 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 patientswho 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 osteoporosisin patients showing either vitamin D insufficiency or deficiency. Conclusion: The possibility of vitamin D deficiency can be considered in pediatric patients takinganticonvulsants if they have mental retardation or developmental delay or if they have been taking anticonvulsants for more than 2 years or taking hepatic enzymeinducing drugs.

Seizures after Spontaneous Intracerebral Hemorrhage

Woo, Kwang-Moo,Yang, Seung-Yeob,Cho, Keun-Tae The Korean Neurosurgical Society 2012 Journal of Korean neurosurgical society Vol.52 No.4

Objective : In patients with spontaneous intracerebral hemorrhage (ICH), the risk factors for seizure and the effect of prophylactic anticonvulsants are not well known. This study aimed to determine the risk factor for seizures and the role for prophylactic anticonvulsants after spontaneous ICH. Methods : Between 2005 and 2010, 263 consecutive patients with spontaneous ICH were retrospectively assessed with a mean follow-up of 19.5 months using medical records, updated clinical information and, when necessary, direct patient contact. The seizures were classified as early (within 1 week of ICH) or late (more than 1 week after ICH). The outcomes were measured with the Glasgow Outcome Scale at discharge and the modified Rankin Scale (mRS) at both 2 weeks and discharge. Results : Twenty-two patients (8.4%; 9 patients with early seizures and 13 patients with late seizures) developed seizures after spontaneous ICH. Out of 263 patients, prophylactic anticonvulsants were administered in 216 patients. The prophylactic anticonvulsants were not associated with a reduced risk of early (p=0.094) or late seizures (p=0.326). Instead, the factors associated with early seizure were cortical involvement (p<0.001) and younger age (60 years or less) (p=0.046). The risk of late seizure was increased by cortical involvement (p<0.001) and communicating hydrocephalus (p=0.004). The prophylactic anticonvulsants were associated with a worse mRS at 2 weeks (p=0.024) and at last follow-up (p=0.034). Conclusion : Cortical involvement may be a factor for provoked seizures. Although the incidence of early seizures tended to decrease in patients prescribed prophylactic anticonvulsants, no statistical difference was found.