Pilocarpine에 의한 간질 중첩증 동물 모델에서 MK 801이 뇌 손상, 자발적 경련 발생 및 태상 섬유 발아에 미치는 영향

황규은(Gyu Eun Whoang),안인철(Ren Zhe An),임혜경(Hae Hyung Lim),이건수(Keon Su Lee) 대한소아신경학회 2001 대한소아신경학회지 Vol.9 No.1

목적: Pilocarpine 동물 모델을 이용하여 NMDA 수용체 길항제인 MK 801이 뇌 손상, 태상 섬유 발아 및 자발성 반복성 경련에 미치는 영향을 관찰하고, 또한 간질발생에서 위의 여러 인자간의 상호 작용 및 역할에 대해 알아보고자 하였다. 방법: 52마리의 생후 7-8주된 몸무게 180-240g 되는 수컷 Sprague-Dawley 종의 흰쥐를 ketamine/xylazine을 복강내 마취 후 고정 장치를 사용하여 뇌의 F3, P3, F4, P4 부위에 전극을 부착시켰다. Pilocarpine(360㎎/㎏)을 복강내에 주사한 흰쥐의 70%(70/100)에서 주사 후 10분에서 40분 사이에 경련이 유발되었으며, 1시간 이내에 경련이 유발되지 않으면 Pilocarpine(175㎎/㎏)을 재차 투여한 경우 86.6%(26/30)의 동물에서 경련이 유발되었다. 결과: MK 801 치료군과 대조군의 두 군으로 나누어 실험한 결과 다음과 같은 결과를 얻었다. 1) MK 801 치료군에서 평균 경련 지속시간은 62.00±6.80분이었고, 대조군에서는 평균 61.10±7.37분으로 두 군에서 의미있는 차이는 없었다(P>0.05). 2)경련 지속 상태 후 24시간, 72시간, 6주에 H & E 염색으로 해마 부위의 세포 괴사를 관찰한 결과, MK 801 치료군에서는 신경 세포 괴사가 관찰되었다. 3) 경련 지속 후 6주에 대조군은 자발성 반복성 경련이 70%(7/10)에서 발생한 반면, MK 801 치료군에서는 한 마리도 발생하지 않았다. 4) 평균 태상 섬유 발아 점수가 대조군에서는 2.05±0.47으로 치료군의 0.40±0.31에 비하여 의미 있는 차이를 보였다(P<0.05). 결론: 본 연구 결과 MK 801은 자발성 반복성 경련의 발생과 태상 섬유 발아의 발생을 차단하는 작용이 있고, 자발성 반복성 경련의 발생과 태상 섬유 발아의 발생은 NMDA 수용체 활성화와 관련이 있으며, NMDA 수용체 활성화는 간질 발생에 중요한 역할을 할 것으로 사료된다. Purpose: We investigated the effect on MK 801 on the development on brain damage, spontaneous recurrent seizures and mossy fiber sprouting in the pilocarpine induced status epilepticus animal model. Methods: Fifty two adult Sprague Dawley male rats(180-240gm) were studied under ketamine/xylazine(87㎎/13㎎/㎏, IP) anesthesia and were implanted at the F3, P3, F4, P4 areas for recording EEG. With a single intraperitoneal(IP) administration of pilocarpine hydrochloride(360㎎/㎏), 70% developed status epilepticus(SE). When SE was not induced within 1 hour after injection of pilocarpine, the second dose of pilocarpine(175㎎/㎏, IP) was injected, with 86.6% of success. Results: All studied animals were divided into two large groups, one group was treated with NMDA receptor antagonist, the other was control group. The mean duration of SE was 62.00±6.80 minutes in the MK 801(1㎎/㎏, IP, 30 minutes after SE) treated group, and 61.10±7.37 minutes in the control group without any signigicant differences(P>0.05). Neuronal loss(necrosis dominantly) was observed at CA1 and CA3 areas in the control group, with more loss after 6 weeks than 24 or 72 hrs specimens. However, there was no neuronal loss in MK 801 treated group. The protective effect of MK 801 for neuronal injury suggested the glutamate receptor activation was involved in the neuronal injury induced by repeated seizure attack. Spontaneous recurrent seizures(SRS) were observed 70% of animals in the control group, but there were no SRS observed in the MK 801 treated group. The mean scores of mossy fiber sprouting were significantly higher in the control group(2.05±0.47) than MK 801 treated group(0.4±0.32)(P<0.05). Conclusion: These results suggested that SRS and mossy fiber sprouting were associated with NMDA receptor activation, and NMDA receptor activation had a key role in the epilepsy development.

뇌성마비 환자에서의 뇌유발전위 평가

노혜미(Hye Mi Rhou),이건수(Keon Su Lee),안인철(Ren Zhe An) 대한소아신경학회 1999 대한소아신경학회지 Vol.7 No.2

목 적 : 뇌성마비는 주산기부터 영유아기 사이의 미숙한 뇌에 발생한 손상에 의해 초래되는 동작과 자세의 질환으로 소아장애의 주원인으로 방사선학적 검사법을 이용한 뇌손상 부위의 정확한 해부학적 진단과 뇌유발전위 검사법과 같은 신경생리 검사를 이용한 뇌기능 평가가 가능해졌다. 따라서 본 연구에서는 뇌성마비 환아에서 뇌유발전위 검사의 평가 결과 및 뇌파와 뇌전산화단층촬영이나 자기공명영상기술 결과와의 상관성에 대해 조사하였다. 방 법 : 충남대학교 병원 소아과 및 재활의학과에서 병력 및 이학적 소견으로 뇌성마비를 진단 받은 환아 중 1995년 7월부터 1999년 6월까지 뇌유발전위 검사를 시행받았던 환아 86명을 대상으로 의무기록을 검토하여 뇌유발전위 검사 결과를 조사하였으며 뇌성마비의 유형, 뇌파 및 방사선학적 검사 결과와의 통계적 상관성을 분석하였다. 결 과 : 1) 대상 환아의 뇌성마비 임상형은 강직형 85%, 무정위형 3.5%, 혼합형 3.5%, 임상형이 정확히 명기되지 않았던 예가 8.1%였다. 2) 뇌유발전위 검사결과 시각유발전위 검사 29.47%, 청각유발전위 검사 18.8%, 정중신경유발전위 검사 37.8%, 경골신경유발전위 검사 52.7%에서 비정상 소견을 보였다. 3) 뇌파 검사, 자기공명영상술, 뇌전산화촬영 결과와 뇌유발전위 검사 결과는 통계학적으로 유의한 상관성이 없었다(P>0.05). 결 론 : 뇌유발전위 검사는 비침습적인 신경 검사로써 뇌파 검사나 방사선학적 검사와의 독립적으로 뇌성마비 환아에서 향후 신경학적 발달 경과와 감각 장애의 조기 진단과 치료에 도움이 될 것으로 사료된다. Purpose : Cerebral palsy is a group of conditions characterized by nonprogressive motor and posture dysfunction developing during perinatal period due to brain damage. Combined sensory and cognitive disorders can evolve the secondary mental retardation or speech disorder. Brain evoked potential can evaluate the visual, auditory, somatosensory neuropathway, and the response of frontal, temporal, occipital lobe. We studied the usefulness of brain pvoked votential as a tool in the early diagnosis and treatment of sensory disorders in cerebral palsy. Methods : We retrospectively reviewed the records of 86 cerebral palsy patients who were practiced brain evoked potential study in Chungnam National University Hospital from July, 1995 to June, 1999. We analyzed the visual, auditory, somatosensory evoked potential result and the correlations between the electroencephalography, radiologic brain imaging study and the brain evoked potential. Results : 1) Clinical types of cerebral palsy were spastic type(85.0%), athetoid type(3.5%), mixed type(3.5%) and the remaining cases did not manifest any one the types above. 2) Abnormal evoked potential fingings were 25 cases(29.4%) in visual evoked potential, 16 cases(18.8%) in auditory evoked potential, 28 cases(37.8%) in median nerve evoked potential, 39 cases(52.7%) in tibial nerve evoked potential. 3) Electroencephalography, radiologic brain imaging study manifested no statistically significant correlations with the brain evoked potential result(P>0.05). Conclusion : As a noninnvasive neurophysiologic study, Brain evoked potential is a useful method predicting neurologic developmental progress and helpful to early diagnosis of sensory disorder in cerebral palsy patients.

간질 환아의 혈청 지질에 관한 연구

이건수,안인철 충남대학교 의과대학 지역사회의학연구소 1999 충남의대잡지 Vol.26 No.2

Purpose : To assess the changes of treatment of phenobarbital, carbamazepine, valproic acid and polytherapy on serum lipids in epileptic children. Method : We determined serum levels of total cholesterol(TC), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), and triglycerides in 50 healthy children and in 80 children with epilepsy who had been receiving phenobarbital(9 patients), carbamazepine(20 patients), valproic acid(30 patients), or polytherapy (21 patients) Results : In the group receiving phenobarbital, mean TC, HDL-C and LDL-C levels were significantly higher than in the control group. In the group receiving carbamazepine, mean TC levels were significantly higher than in the control group. In the group receiving valproic acid, mean triglyceride and HDL-C levels were significantly lower than in the control group, but mean LDL-C/HDL-C ratio were significantly higher than in the control group. In the group receiving polytherapy, mean TC and LDL-C levels were significantly higher than in the control group. In neither group did mean TG/HDL-C ratio differs significantly from the corresponding control groups. Conclusion : Our results suggest long-term treatment of anticonvulsants significantly modify serum lipids in epileptic children.

신경세포 이주장애에 관한 연구

이건수,안인철 충남대학교 의과대학 지역사회의학연구소 1999 충남의대잡지 Vol.26 No.1

25 cases under 15 years of age with neuronal migration disorders were observed at the department of Pediatrics at Chungnam National University Hospital during a period of 6 years from January, 1992 to December, 1997. The results were as follows: 1. The peak incidence of age was 5 to 10 years(40.3%). The sex ratio of male to female was 1.8 : 1. 2. The types of neuronal migration disorders were cortical dysplasia (36%), lissencephaly(28%), schizencephaly(16%), heterotopia(12%) and megalencephaly(8%) in order of frequency. 3. The clinical findings were seizure(76%), delayed development(48%), delayed speech(32%), mental retardation(24%) and motor deficit(20%) in order of frequency. 4. The locations of disorder were frontal lobe(72%), parietal lobe(60%), temporal lobe(40%) and occipital Iobe(32%) in order of frequency. 5. The abnormal EEG findings were 17 cases(68%). Among these cases, focal abnormalities were 5 cases(29.4%), general abnormalities were 11 cases(64.7%) and abnormal background was 1 case(5.9%). 6. The seizure types were generalized seizure(63.2%), partial seizure (31.6%) and mixed seizure (5.3%) in order of frequency. 7. The patients with larger size of lesions had more delayed development, delayed speech and mental retardation.

Floppy Infant에 관한 연구

이건수,안인철 충남대학교 의과대학 지역사회의학연구소 1999 충남의대잡지 Vol.26 No.1

16 cases with floppy infant syndrome were observed at the department of Pediatrics at Chungnam National University Hospital during a period of ll years from January, 1986 to December, 1996. The results were as follows: 1. The incidences of disease were Werdnig-Hoffman disease(W-H-D, 7 cases), Guillain-Barre syndrome(GBS, 3 cases), congenital muscular dystrophy(2 case), congenital myasthenia gravis (2 cases), congenital myotonic dystrophy(1 case) and neonatal myasthenia gravis(1 case) in order of frequency. 2. The sex ratio of male to female was 1.3 : 1. 3. The main symptoms and signs were decreased muscle tone(93.8%), decreased tendon reflex (75%), dysphagia(75%), respiratory distress(75%), abnormal traction response(68.8%), abnormal vertical response(68.8%), weak crying(62.5%), poor head control(62.5%), frog leg posture(62.5%) and fasciculation(31.3%) in order of frequency. 4. The EMG findings of W-H-D and GBS were increased amplitude and duration. The EMG findings of congenital muscular dystrophy and congenital myasthenia gravis were reduced amplitude and duration. The EMG findings of congenital myotonic dystrophy and neonatal myasthenia gravis were normal. 5. The ceatine kinase(CK) levels of W-H-D, GBS, congenital myasthenia gravis and neonatal myasthenia gravis were normal. The CK levels of congenital muscular dystrphy and congenital myotonic dystropohy were increased.

항경련제 투여 환아의 간기능 변화

황치관,이건수,안인철 충남대학교 의과대학 지역사회의학연구소 2000 충남의대잡지 Vol.27 No.1

Routine liver function test is done in epileptic children receiving antiepileptic drugs to prevent hepatotoxicity induced by these drugs. The abnormalities of liver function test are rarely seen, but these abnormalities accompanied by the clinical manifestation of hepatotoxicity are seldomly seen. This study carried out in order to assess the efficacy of routine liver function test in epileptic children. We examed the changes of the serum level of aspartate transferase(AST), alanine aminotransferase(ALT), total bilirubin, total protein, albumine, alkaline phosphatase(ALP) before and after antiepileptic drug medication in 60 epileptic children who had been receiving valproic acid(n=25명), ethosuximide(n=6명), carbamazepine(n=4명), valproic acid and carbamazepine(n= 14명), and other polytherapy(n=11명) for 3months or more. Results are as follows ; 1) The difference in each groups according to age, duration of treatment, and drug plasma concentration was not found. 2) AST was within normal range in any group, but decreased after valproic acid, ethosuximide, carbamazepine, and other polytherapy treatment. 3) ALT was within normal range in any group, but decreased after valproic acid treatment. 4) Total bilirubin, total protein, albumin, and ALP were within normal range in any groups. 5) Y-GT was within normal range, but the values were increasing tendency in polytherapy groups. 6) No clinical significant menifestations had developed during study period in any groups. The result suggest that the routine liver function test itself can not be the indicator of hepatotoxicity, and that the liver function test exammed when the clinical symptoms appear is more effective than the routine liver function test.

심초음파를 이용한 태아심장 기형의 평가

진병로,안인철,이윤이,길홍량 충남대학교 의과대학 지역사회의학연구소 1999 충남의대잡지 Vol.26 No.1

Congenital heart disease is the most common congenital malformation and its incidence is 8/1000 live birth, and contributes to significant perinatal morbidities and mortalities. With the advancement of echocardiogrphic equipment and technique, it is enable to detect the heart anomalies in utero. We performed 94 fetal (93 mothers) echocardiographic examinaton. 10 confirmed and 3 unconfirmed cardiac anomalies were identified. The common cardiac anomalies were ventricular septal defect(4), tetralogy of Fallot(2), and tricuspid valve regurgitation(2). The common indications of fetal echocardiography were as follows: family history of congenital heart disease(26), suspection by obstericians(24), fetal arrhythmia(13), and other organ anomaly(7). But the relative yield of indication were; suspected by obstericians 33.3%, other organ anomaly 14.3%, family history of congenital heart disease 7.6%, and fetal arrhythmia 7.6%. The false positive result was only 1 case of ventricular septal defect, which was normal in postnatal examination. The mean maternal age was 27years 5months in confirmed cases and 25years 5month s in unconfirmed cases. The fetal echocardiographic study for cardiac anomalies is reliable and accurate method in selected indicated groups, but systematic approach for screening method and identified cardiac anomalies would be needed.