대한임상신경생리학회지 9(2):63~68,2007 ISSN 1229-6414 Controversies in Clinical Neurophysiology 간질치료에서뇌파의임상적유용성에관한논란 : 긍정적관점에서 가톨릭대학교의과대학신경과학교실 손영민 김영인 Young-Min Shon, M.D., Yeong In Kim, M.D. Department of Neurology, The Catholic University of Korea, Seoul, Korea The EEG plays an important diagnostic role in epilepsy and provides supporting evidence of a seizure disorder as well as assisting with classification of seizures and epilepsy syndromes. There are a variety of electroclinical syndromes that are really defined by the EEG such as Lennox-Gastaut syndrome, benign rolandic epilepsy, childhood absence epilepsy, juvenile myoclonic epilepsy and also for localization purposes, it is vitally important especially for temporal lobe epilepsy. The sensitivity of first routine EEG in diagnosis of epilepsy has been known about 20-50%, but this proportion rises to 80-90% if sleep EEG and repetitive recording should be added. Convincing evidences suggest that the EEG may also provide useful prognostic information regarding seizure recurrence after a single unprovoked attack and following antiepileptic drug (AED) withdrawal. Moreover, patterns in the EEG make it possible to disclose an ictal feature of nonconvulsive status epilepticus, separate epileptic from other non-epileptic episodes and clarify the clues predictive of the cause of the encephalopathy (i.e., triphasic waves in metabolic encephalopathy). Therefore, regardless of its low sensitivity and other pitfalls, EEG should be considered not only in the situation of new onset episode such as a newly developed, unprovoked seizure or a condition manifesting decreased mentality from obscure origin, but also as a barometer of the long-term outcome following AED withdrawal. Key words: Electroencephalogram (EEG), usefulness, diagnostic, predictive value 서 론 간질은다른질환과달리외래에서환자의증상을직접관찰하는것이매우어렵기때문에환자나보호자로부터병력청취를통해간질발작의형태를확인하는것이가장중요하며, 동반되는신경학적진찰이나 EEG 의이상은진단에많은도움을줄수있다. EEG 는간질진단에가장중요한객관적검사로서, 발작파나서파자체의발견이간질의진단을뒷받침할뿐아니라, 3 Hz 극서파복합체 (3 Hz spike-and-wave complex) 와같은특정한증후군의진단에결정적인역할을하며, 국소간질에서간질병소를추정하는데큰도움을준다. 1 Copyright 2007 by the Korean Society for Clinical Neurophysiology 63
손영민 김영인 그러나, EEG 의진단적한계점도명확히알려져있기때문에간질의정확한진단을위해서는여러가지정보를종합적으로분석할수있는임상의의능력이강조된다. 저자는이번종설의한축인 EEG 의임상적중요성에대한지지적입장에서, 증례분석과기존의연구를고찰하여실제임상상황에서 EEG 의긍정적역할에대해언급하고자한다. 본론임상에서간질의진단에도움을주는실제상황들 1. EEG 가특징적인간질증후군의진단에도움을주는경우주로소아간질증후군중간질뇌병증 (epileptic encephalopathy) 에속하는부류중에서 Lennox-Gastaut 증후군, Landau-Kleffner증후군, electrical status epilepticus of slow wave sleep (ESES) 등이해당되며, 이들은대개특징적인뇌파소견 ( 예를들어 ESES 는 continuous spike wave during slow wave sleep 이특징적으로보임 ) 을가지고있다. 또한흔한특발간질 (idiopathic epilepsy) 중에서양성롤란딕간질 (benign rolandic epilepsy, BRE), 소아기결신 Box. 1) 증례 1 14세남자가 11세경부터시작한이상한행동을주소로내원하였다. 환자본인은기억하지못하는동안자주멍한표정을짓고, 입맛을다시며불러도반응이없는시기가관찰되었고그횟수는일정하지않았으나매일여러번나타난적도있었다고한다. 고개가한쪽으로돌아가기도하지만대발작으로진행하지는않았다. 과거력에서열성경련이 2세경에 3회있었고, 주의력결핍과다행동장애 (attention-deficit hyperactivity disorder, ADHD) 로진단받은적이있으나특별한치료는하지않았다고한다. 병력을종합해서 oroalimentary automatism without aura를보이는복합부분발작으로판단하여안쪽관자엽간질 (mesial TLE) 의가능성을염두에두고 EEG, MRI, 그리고 SPECT를하였다. EEG에서는아래그림과같이전형적인 3 Hz spike-and-wave complex가약 15~20초가량자주관찰되었고, MRI와 SPECT는정상이었다. 이환자는청소년기결신간질 (JAE) 로진단하였고, valproate 단독요법 (1,000 mg/day) 으로현재 2년이상경련이소실된상태이다. 64 J Korean Society for Clinical Neurophysiology / Volume 9 / December, 2007
간질치료에서뇌파의임상적유용성에관한논란 : 긍정적관점에서 2) 증례 2 19세여자가의식소실을동반하며쓰러진상태로발견되어응급실로내원하였다. 전날수면이부족한상태였고, 약간의어지럼증과심계항진 (palpitation) 을느끼면서의식을잃었으며, 발견당시에는경련성운동 (convulsive movement) 는없었고, 10분후의식을되찾았으나경련후두통 (postictal headache) 이심하게동반되었다. 과거력에서열성경련이나두부외상, 뇌염등은없었다고하며, 이연령에흔한혈관미주신경실신 (vasovagal syncope) 의가능성을먼저염두에두고, 간질발작의감별을위해검사를하였다. EEG 결과다음과같이빠른, 전반예파서파복합체 (generalized, fast polyspike and wave pattern) 가나타났고, 추가적인병력청취에서약 2년전부터피곤할경우한달에수회의빈도로주로새벽이나아침에양어깨와손의움찔거림이수초간있다가소실되었다고하였다. MRI는정상이었다. 이환자는청소년기근육간대경련간질 (JME) 로진단하였고, lamotrigine 단독요법 (200 mg/day) 으로현재 1년이상경련이소실된상태이다. 간질 (childhood absence epilepsy, CAE), 청소년기결신간질 (juvenile absence epilepsy, JAE) 및청소년기근육간대경련간질 (juvenile myoclonic epilepsy) 에서는특징적뇌파소견이관찰되며, 어떤경우는병력청취나다른임상정보가모호한경우, 진단에결정적인역할을할수도있다 ( 증례 1, Box). 2-4 2. 발작과거짓발작의감별많은경우에발작당시의병력정보는제한되는경우가흔하며, 특히발작의초기부분을알수없는경우가많다. 이러한경우에뇌파소견은환자의진단에큰도움을줄수있 다 ( 증례 2, Box). 3. 국소간질에서간질병소의예측 Blume 등은 104 명의관자엽간질환자중 99명 (95%) 에서간질병소와같은쪽에서발작간극파 (interictal spikes) 가우세하게관찰되었다고하며, 그비율이 75% 이상이되면거의모든환자 (79/80, 98.8%) 에서간질병소의편측화 (lateralization) 가가능하다고하였다. 또한국소적느린델타활동 (delta slow activity) 이관찰된환자중 90% 이상에서간질병소쪽으로편측화되었다고하였다. 5 즉, 간질병소의위치파악에도움을줌으로써, 이후의치료계획수립에 J Korean Society for Clinical Neurophysiology / Volume 9 / December, 2007 65
손영민 김영인 Figure 1. A case of non-convulsive status epilepticus which shows an ictal onset from right central area. A 52-year-old female who had suffered a large right middle cerebral artery ischemic infarction (5 years before) was referred to the department of neurology for the management of the altered mentality and decreased responsiveness. After intravenous loading of valproate (1,500 mg/day), her mental status was markedly improved. 큰도움을줄수있다. 4. 의식저하가있는환자들에서비경련간질지속증 (nonconvulsive status epilepticus, NCSE) 의확인여러가지내과질환이동반되거나혹은그렇지않은상황에서반응이느려지거나, 의식이저하되어외래로의뢰되는환자들중드물지않게 EEG 에서 NCSE 나삼상파 (triphasic wave), PLEDs (periodic lateralized epileptiform discharges) 등의중요한소견이있는경우가많고, 이는진단뿐만아니라향후치료에결정적인역할을한다 (Fig. 1). 6 새로발생된간질에서 EEG 의역할새로발생된간질발작환자에서첫번째 EEG 상발작파를발견하는경우는 12~56% 까지다양하게보고되어있으나, 반복검사를통해민감도는증가될수있다. Salinsky 등은 429 명의성인간질환자들로부터 1,201 개의 EEG 를분석한결과첫번째 EEG 에서발작파가나타난경우는 29% 에불과 했으나, 4회검사시 90% 까지나타날수있다고하였다. 7 Ebersole 과 Pedley 에의하면성인보다소아연령대에서, 간질이어릴때발생될수록, 발작파가흔히관찰되는특정간질증후군인경우 (BRE, ESES 등 ), 수면박탈을시도하거나, 뇌파촬영시간을늘릴수록, 그리고주로심부보다대뇌겉질쪽에간질병소가있을수록발작파가잘관찰되었다고하였다. 8 간질발작의재발여부를예측할때 EEG 의역할간질의재발여부를예측하는데 EEG 의역할은중요하다. Van Donselaar 등은 1회의발작이후치료받지않은 157 명을 2년간추적조사한결과첫발작당시 EEG 에서이상이있었던 41명 (26%) 중 83% 가재발한반면, EEG 가정상이던환자중 12% 만이재발하였다고하였다. 9 그리고그외의많은연구에서간질발작의예후파악에 EEG 의중요성에대해보고해왔다 (Table 1). 66 J Korean Society for Clinical Neurophysiology / Volume 9 / December, 2007
간질치료에서뇌파의임상적유용성에관한논란 : 긍정적관점에서 Table 1. EEG predictors of recurrence after the first unprovoked seizure Study Age IEDs Non-IED abnormality Any abnormality Annegers (1986) Mixed NR NR + Hopkins (1988) Adults 0 0 0 Shinnar (1990) Children 0 NR + Hauser (1990) Mixed + (generalized IED only) 0 0 FIRST group (1993) Mixed + NR NR Van Donselaar (1992) Adults + + + IED; interictal epileptiform discharge, +; factor associated with increased risk, 0; factor not associated with increased risk, NR; effect of factor not reported Table 2. Personal recommendations for an ideal follow-up of EEG during management of epilepsy Generally, how frequently would you check EEG? 1) In cases of well controlled epilepsy with the normal previous EEG: Not necessary to check follow-up EEG. Consider at the time of drug withdrawal. 2) In cases of poorly controlled epilepsy with the normal previous EEG: At the physician s discretion, it may be done before and after a drug change (maybe at least 3 months apart from the next exam). 3) In cases of well controlled epilepsy with the abnormal previous EEG: Do not need to check follow-up EEG, but you may perform semiannual examination. 4) In cases of poorly controlled epilepsy with the abnormal previous EEG: At the physician s discretion, it may be examined during a drug change or dose adjustment. In cases of intractable epilepsy, how frequently would you check EEG? At the physician s discretion, it may be examined during a drug change or dose adjustment. How frequently would you check EEG in cases of first unprovoked seizure? 1) In cases with normal EEG and normal imaging study: Not necessary to check follow-up EEG, but you may consider semiannual follow-up EEG. 2) In cases with normal EEG but abnormal imaging study (relevant lesion): Perform EEG at the time of starting anti-epileptic drug medication, the drug withdrawal, and in cases with the recurrent seizures Should an EEG be performed before the withdrawal of anti-epileptic drug? 1) In case with the latest normal EEG: Do not need to check follow-up EEG, but you may consider it for comparison with the next EEG in case of a relapse of epileptic seizure. 2) In case with the latest abnormal EEG: Consider to perform EEG owing to the high risk of recurrence of epileptic seizure in case of the persisting abnormal findings in the latest EEG. 항경련제의중단을고려할때 EEG 의역할 결 론 항경련제투여이후경련이소실되어약물을끊는경우, 감량당시의 EEG 가비정상이면재발될확률은 35~70% 정도이다. Shinnar 등은첫번째간질발생당시의나이가늦을수록, 발작파나서파가관찰될수록그리고항경련제투여로초기에비해뇌파가호전될수록재발의가능성이높다고하였다. 10 그외에도 JME, 2차전신간질이동반된부분간질, 영상검사에서병변이확인된경우, EEG 에서국소서파가관찰되는경우, 발작의빈도가잦을수록재발의위험도가증가된다고한다. 11 이상의모든부분들을종합적으로고려하여, 합리적으로 EEG 를할수있는판단의근거를만들어실제상황에서적용해볼수있는개인적인권고안을제시하고자한다 (Table 2). 결론적으로우리는상대적으로낮은민감도와여러가지제약에도불구하고, 일반적인임상상황에서 EEG 가매우중요한간질의진단방법임을확인할수있었다. 비록최근 MRI, PET, SPECT 등의영상검사를활발히적용하고있지만, 간질진단에 EEG 의위치는여전히굳건하게자리매김할것으로보인다. MEG, 고밀도전극 EEG (highdensity electrode EEG), current source modeling 등의새로운기술을접목한다면향후더높은진단적유용성을보일것으로확신한다. J Korean Society for Clinical Neurophysiology / Volume 9 / December, 2007 67
손영민 김영인 REFERENCE 1. Binnie CD SH. Modern electroencephalography: its role in epilepsy management. Clin Neurophysiol 1999;110:1671-1697. 2. King MA, Newton MR, Jackson GD, et al. Epileptology of the first-seizure presentation: a clinical, electroencephalographic, and magnetic resonance imaging study of 300 consecutive patients. Lancet 1998;352:1007-1011. 3. Holmes MD, Kutsy RL, Ojemann GA, et al. Interictal, unifocal spikes in refractory extratemporal epilepsy predict ictal origin and postsurgical outcome. Clin Neurophysiol 2000; 111:1802-1808. 4. Kellaway P. The electroencephalographic features of benign centrotemporal (rolandic) epilepsy of childhood. Epilepsia 2000;41:1053-1056. 5. Blume WT, Borghesi JL. Interictal indices of temporal seizure origin. Ann Neurol 1993;34:703-709. 6. Granner, M.A. and Lee, S.I. Nonconvulsive status epilepticus: EEG analysis in a large series. Epilepsia 1994;35:42-47. 7. Salinsky M, Kanter R, Dasheiff RM. Effectiveness of multiple EEGs in supporting the diagnosis of epilepsy: an operational curve. Epilepsia 1987;28(4):331-4. 8. Ebersole JS and Pedley TA, Current Practice of Clinical EEG, 2003:504. 9. van Donselaar CA, Schimsheimer RJ, Geerts AT, Declerck AC. Value of the electroencephalogram in adult patients with untreated idiopathic first seizures. Arch Neurol 1992;49:231-237. 10. Shinnar S, Berg AT, Moshe SL, et al. Risk of seizure recurrence following a first unprovoked seizure in childhood: a prospective study. Pediatrics 1990;85(6):1076-85. 11. Berg AT, Shinnar S, Levy SR, et al. Two-year remission and subsequent relapse in children with newly diagnosed epilepsy. Epilepsia 2001;42(11):1553-1562. 68 J Korean Society for Clinical Neurophysiology / Volume 9 / December, 2007