원저접수번호 :09-029(2 차 -0710) 이화여자대학교목동병원신경과 Peri-ictal Heart Rate Changes in Patients With Localization-Related Epilepsy Eun Hye Jeong, MD, Won Sup Kim, PhD, Hyeran Yang, MD, Youngshin Yoon, MD, Kyu Sun Lee, MD, Kyoung-Gyu Choi, MD, PhD, Kee-Duk Park, MD, PhD, Hyang Woon Lee, MD, PhD Department of Neurology, Ewha Womans University School of Medicine and Ewha Medical Research Institute, Seoul, Korea Background: Epileptic seizures can be associated with changes in autonomic functions. This study evaluated heart rate (HR) changes at the transition from the preictal to the ictal state in patients with epileptic seizures, and investigated whether peri-ictal HR changes can help to predict electroencephalography (EEG) seizures prior to their onset. Methods: We retrospectively studied 94 seizures in 33 patients who underwent video-eeg monitoring with scalp EEG and electrocardiography. The existence and initial timing of HR changes relative to the onset of EEG seizures were determined by analyzing consecutive RR-interval changes in 10-minute recordings. We evaluated the correlation between the peri-ictal HR changes and the type of localization-related epilepsy. Results: Peri-ictal HR changes were documented in 70.2% (66/94) of all seizures, of which 62 were tachycardia (66.0%) and 4 were bradycardia (4.3%). Peri-ictal tachycardia occurred significantly with seizures as an ictal manifestation, more often in seizures with a right hemispheric onset than in those with a left hemispheric onset (77.4% vs. 50%, p=0.016). Peri-ictal HR changes were observed much earlier in seizures of mesial temporal lobe epilepsy (TLE) than in those of extratemporal lobe epilepsy ( 54.4 s vs. 6.7 s, p<0.001). Conclusions: Peri-ictal HR changes were observed in 70.2% of seizures, 94% of which were tachycardia. These changes could be helpful in predicting seizure onset, especially in mesial TLE. J Korean Neurol Assoc 28(3):179-185, 2010 Key Words: Epileptic seizures, Autonomic, Heart rate, Ictal, Electrocardiography 서론 간질발작 (epileptic seizure) 은발작의주된증상으로여러 Received February 11, 2010 Revised May 13, 2010 Accepted May 13, 2010 *Hyang-Woon Lee, MD, PhD Department of Neurology, Ewha Womans University School of Medicine and Ewha Medical Research Institute, 911-1, Mok-dong, Yangcheon-gu, Seoul 158-710, Korea Tel: +82-2-2650-2673 Fax: +82-2-2650-2652 E-mail: leeh@ewha.ac.kr * These two authors (E.H.J and W.S.K) were equally contributed to this paper as first authors. This work was supported by Basic Science Research Program through the National Research Foundation (NRF) funded by the Ministry of Education, Science and Technology (NRF-2009-007- 2164 and NRF-2009-006-5721 to H.W.L), and by the Korea Healthcare technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (A091329 to W.S.K.). 가지자율신경계증상을흔히동반한다. 발작발생전이나발생중, 혹은발생직후에나타날수있는자율신경계증상으로는심혈관계, 호흡계, 위장관계, 피부 비뇨기계, 성적인증상들이있는데이중에서특히심혈관계증상인돌연사 (sudden unexpected death in epilepsy, SUDEP) 는간질환자의주된사망원인이라는점에서주목을받아왔다. 1 이전연구에의하면발작중빈맥 (ictal tachycardia) 이 41~ 99% 로가장흔한심혈관계증상이며, 2-10 발작중서맥 (ictal bradycardia) 은 7% 미만으로훨씬적었다. 5,6,8 왼쪽섬엽피질 (insular cortex) 을자극하면서맥과감압반응 (depressor response) 이뚜렷하게나타나는반면, 오른쪽섬엽피질자극시에는빈맥과승압효과 (pressor effect) 가관찰되어오른쪽뇌가교감기능에좀더우세하다는연구가있었으며, 11 이는경동맥내아모바르비탈 (amobarbital) 주입시왼쪽뇌반구의비활성화때문 J Korean Neurol Assoc Volume 28 No. 3, 2010 179
에빈맥이생겼다는연구와일치하였다. 12,13 그러나좌우대뇌반구사이에발작중심박수변화 (ictal heart rate change) 에차이가없는연구도있었다. 10,14 무증상발작 (subclinical seizure) 이있는환자를대상으로한연구에서측두엽에서발생하는발작에서빈맥이더유의하게관찰되었다는점은발작시나타나는심박수의증가가발작중발생하는운동증상이나발작전에느끼는심리적인스트레스때문이아니라간질로인해중추성자율신경계, 특히측두엽부위가직접활성화되면서발생하는증상으로추정한다. 9 이전의실험적연구들에서편도핵 (amydala) 이심박수와리듬조절에핵심적인역할을할것으로생각했으나측두엽간질 (temporal lobe epilepsy, TLE) 환자에게심부전극 (depth electrode) 을이용한연구에서편도핵이심박수조절에제한적인역할을하는것으로나타나발작방전 (ictal discharge) 이변연계 (limbic system) 까지광범위하게포함될때심박수변화가생기는것으로추측한다. 15-17 지금까지대부분의연구들에서발작중심박수변화는측두엽중에서특히내측측두엽부분과밀접한연관성을보였다. 8-10,14 본연구에서는국소관련간질 (localization-related epilepsy) 환자들의발작전부터발작상태까지나타나는 (from the preictal to the ictal state) 심박수변화를분석하고, 심박수변화가발작발생 (seizure onset) 의국소화혹은편측성 (localization or lateralization) 과관계있는지알아보고자하였다. 또이심박수변화를경련의조기발견의임상지표로서가치가있는지알아보았다. 대상과방법 Table 1. Baseline characteristics of the patients and number of seizures related with localization, lateralization and types of seizure Mesial TLE (N=10) Neocortical TLE (N=4) Extratemporal (N=19) Age (year) 31.5±15.2 41.0±22.0 21.6±17.2 Sex (M:F) 2:8 2:2 7:12 Lateralization of seizure Right 6 4 21 31 Left 10 6 30 46 Bilateral 2 0 15 17 Types of seizure Subclinical 3 4 17 24 Simple partial 2 2 18 22 Complex partial 12 3 27 42 Secondary generalized 1 1 4 6 18 10 66 94 The data were expressed as mean±standard deviation or as a number. TLE; temporal lobe epilepsy, N; number of patients, M; male, F; female. 용한뇌파검사에서발작초점이내측측두엽을시사하는소견이관찰되는경우에해당하며총 10명에서 18개의발작을관찰하였다. 2군은신피질측두엽간질 (neocortical TLE) 환자로 MRI 에서측두엽의곁고랑 (collateral sulcus) 외측에병소가있거나뇌파검사에서발작초점이내측측두엽이아닌측두전극에있는경우로정하였으며총 4명에서 10개의발작이보였다. 3군은측두엽외간질 (extratemporal lobe epilepsy) 환자로 MRI 상측두엽이아닌다른뇌영역에간질병소가있거나뇌파검사에서발작초점이측두엽외의다른뇌영역에있는경우, 즉 1군과 2군을제외한모든국소관련간질환자를포함하며총 19명으로구성되었고 66개의발작을확인하였다 (Table 1). 1. 대상 2. 뇌파와심전도기록 본연구는 2005 년 7월부터 2009 년 9월까지본원간질모니터링실 (epilepsy monitoring unit) 에입원하여두피전극 (scalp electrode) 을이용하여비디오-뇌파검사 (video-eeg monitoring) 를시행한 393 명의환자들을후향적으로조사하여뇌파에서발작이관찰된국소관련간질환자 40명에서 127 개의발작을관찰하였다. 잡파 (artifact) 때문에심전도분석이어려운경우를제외하고총 33명의환자에서관찰된 94개의발작에서뇌파와심전도를분석하였고이환자들의뇌자기공명영상 (magnetic resonance imaging, MRI) 을확인하였다. 임상양상, 뇌파및 MRI 분석결과를토대로환자를 3개그룹으로분류하였는데 1 군은내측측두엽간질 (mesial TLE) 환자로 MRI 에서해마에국소화병변이관찰되거나나비전극 (sphenoidal electrode) 을이 뇌파는 Telefactor digital video-eeg (Beehive Millennium, Grass-Telefactor, Long Island, USA) 를이용하여기록하였다. 뇌파전극은 9 mm gold cup mid-hole 을사용하였고 international 10-10 system 에따라서전극을부착하였으며임상양상및 MRI 소견에서측두엽간질이의심되는경우에는나비전극을추가하였다. 뇌파데이터는 400 Hz의표본추출 (sampling rate) 로저장하였으며, 1~70 Hz 의 band-pass filter 를사용하였다. 뇌파와함께심전도를동시에기록하였는데심전도전극은앞가슴좌우측 5번째늑간에각각하나씩총 2개의전극을이용하여기록하였다. 180 대한신경과학회지제 28 권제 3 호, 2010
3. 뇌파와심전도분석 뇌파전공인신경과전문의가육안검사를통해뇌파를분석하였다. 뇌파변화시점을발작시작 (ictal onset) 시점으로정하였고, 발작기의뇌파변화는국소적인율동방전 (rhythmic discharges) 혹은반복적인극예파 (repetitive spikes or sharp waves) 출현, 또는발작간뇌파 (interictal EEG) 와확연하게구분되는 electrodecremental response 등이 3초이상지속되고이러한뇌파변화가점차진행되는양상을보일때로정의하였다. 심전도는발작시작전후각각 5분 ( 총 10분 ) 동안데이터를추출하여분석하였다 (Fig. 1-B). 측정한심전도에서시간에따른심박수변화를분석하기위해 R-wave 를다음과같은방법으로추출하였다. (i) 1 Hz 고주파통과여과 (high pass filtering) 를통해저주파성분제거, (ii) 심전도신호의표준편차를구하고표준편차의 1.5~2.0 배값을문턱값 (threshold value) 으로결정, (iii) 정의한문턱값보다큰영역에서 RR 간격의일차미분에의한영점교차 (zero-crossing) 를이용하여 R 시점 (t i) 을추출하고, 18 (iv) 육안검사로심전도패턴과추출한 R 시점 (t i) 간의일치도를확인하여움직임혹은간질발작에의한잡파지점을제거하였으며 (v) R i(t i)=t i-t i-1 로 t i 시점에서의 RR 간격을정의하였다 (Fig. 1-C). 발작시심박수변화를관찰한대부분의연구에서임의의시간구간을정하고심박수를계산및비교분석하였다. 10,14 그러나발작시심박수변화시점은환자마다다를수있고, 정해진시간구간에대한분석은시간에따른평균효과로인해유용한정보를잃을수있다. 8 따라서본연구에서는심박수변화시점및심박수변화여부를시간에따른 RR 간격의연속적인변화추적을통해추출하고자하였다. 기저심박수 (baseline heart rate) 의기준은아직까지명확하지않다. 기존연구에서는발작시작시점으로부터약 60초전후의임의의시간간격으로정의하고사용하였다. 6.10,14 본연구에서는가능한한평소심박수변동을충분히반영하기위해평균기저 RR (baseline RR:B_RR) 을발작시작시점으로부터 300 초전부터 200 초간추출한 RR 간격의평균으로비교적넓게정의하였다. 추출한불연속적인 RR 간격, R i(t i), 시계열을연속적이고정규화 (normalization, 혹은 Z score 라고함 ) 한 RR 간격시계열데이터 Z(t) 를다음식 (1) 과같이정의하였다. 19 여기서 R(t) 는불연속적인 R i(t i) 을스플라인보간법 (spline (1) interpolation) 을이용하여 10 ms 간격의연속데이터로전환한시계열값, 20 B_RR 은위에서언급한평균기저 RR 간격, SD는기저 RR 간격들의표준편차값을의미한다. Z(t) 값은기저와각시점에서의 RR 간격의차이가기저의변동 ( 표준편차값 ) 의비를의미한다. 즉, 임의의시점에서 Z >2 이면 B_RR 과그시점의 RR 간격차이가 2SD 이상임을의미한다. 위의식으로정의한 Z(t) 는시간에따라변하므로정확한심박수변화시점을찾기위해, 20초간격의 sliding moving window 방법을이용하여 smoothing 한값을 Z s(t) 로정의하였다 (Fig. 1-D). 빈맥및서맥여부는발작시작 100 초전부터발작후 100 초사이에 Z s 값이최소 20초이상 -2보다작은지점이존재하면빈맥이존재, 2보다큰지점이존재하면서맥이존재하는것으로판단했다. 이기준은 RR 간격과 B_RR 차이가 2SD 이상일때를심박수변화로정의한 Garcia 등이사용한기준과같다. 14 빈맥혹은서맥이존재한경우, Z s 값이각각 -1 혹은 1을통과하는시점을빈맥혹은서맥의발생시점으로정의하였다 (Fig. 1-D). 모든계산은 MatLab 7.3.0 (MathWorks, MA, USA) 에서직접프로그램을작성하여실행하였다. 4. 통계적분석 A B C D 통계분석은 SPSS 13.0 을이용하여명목변수는 chi-square Figure 1. An example of peri-ictal tachycardia in a 17-year old male patient with right mesial TLE associated with ipsilateral hippocampal sclerosis. The black dashed line at t=0 means ictal onset and black dotted line means ictal offset. (A) EEG time sequence in FT10 electrode by 10-10 international EEG system. (B) ECG time sequence. (C) Discrete RR intervals, R i(t), sequence. (D) The smooth Z(t) function, Z s(t). The arrow is pointed that RR interval was significantly decreased at 39.49 sec before the EEG seizure onset. The dark and light gray shadow area means Z s <1.0 and Z s <2.0 respectively. J Korean Neurol Assoc Volume 28 No. 3, 2010 181
Table 2. Peri-ictal heart rate changes related to hemispheric lateralization Seizures with no significant Tachycardia Bradycardia HR changes Right 24 (77.4%) a 0 (0%) 7 (22.6%) 31 Left 23 (50%) a 4 (8.7%) 19 (41.3%) 46 Bilateral 15 (88.2%) 0 (0%) 2 (11.8%) 17 a p=0.016 by χ 2 test, HR; heart rate. Table 3. Peri-ictal heart rate changes related to localization of seizure Seizures with no significant Tachycardia Bradycardia HR changes Mesial TLE 9 (50%) 2 (11.1%) 7 (38.9%) 18 Neocortical TLE 7 (70%) 1 (10%) 2 (20%) 10 Extratemporal 46 (69.7%) 1 (1.5%) 19 (28.8%) 66 TLE; temporal lobe epilepsy, HR; heart rate. A 결과 본연구에서는총 94 개의발작을발작초점의편측성 B (lateralization) 과발작의유형 (seizure types) 에따라각각분 석한결과, 왼쪽에서발생한발작이가장많았고 (46/94), 오른 C 쪽 (31/94), 양쪽 (17/94) 의순서였으며, 발작의유형은임상증상없이뇌파에서만경련이관찰되는무증상발작 (subclinical seizure) (24/94), 단순부분발작 (simple partial seizure) (22/94), D 복합부분발작 (complex partial seizure) (42/94), 이차전신발작 (secondary generalized seizure) (6/94) 으로나타났다 (Table 1). 분석한총 94 개발작중 66 개 (70.2%) 에서발작전후심박수변 Figure 2. An example of peri-ictal bradycardia in a 68-year old female patient with left neocortical TLE with gliosis in left superior temporal gyrus. (A) EEG time sequence in T7 electrode by 10-10 international EEG system. (B) ECG time sequence. (C) Discrete RR intervals, R i(t), sequence. (D) The smooth Z(t) function, Z s(t). The down directed arrow depicts the time point of bradycardia initiation. RR interval was significantly increased at 76.06 sec before the EEG seizure onset. The dark and light gray shadow area means Z s <1.0 and Z s <2.0 respectively. About 33 sec after ictal onset, R i and Z s couldn t be calculated because of severe artifacts caused by seizure and movements. test를이용하였고, 그룹간평균값비교에는일원분산분석 (one-way ANOVA) 을이용하였으며사후분석 (post-hoc analysis) 은 Scheffe 법을이용하였다. 추출한빈맥및서맥의재검토를위해기저 RR 간격과빈맥및서맥발생지점의 RR 간격비교는 student t-test 를이용하였다. 모든분석에서 p-value 가 0.05 미만인경우에통계적으로유의한것으로판정하였다. 화 (peri-ictal heart rate change) 를관찰하였으며, 추출한 66 개발작에서발작전후심박수변화시점과기저심박수사이에통계적으로의미있는차이가있었다 (p<10-5 ). 간질증후군분류에따른세군에서각왼쪽, 오른쪽반구및양쪽에간질병소가있는경우로나누어보았고또한발작의유형에따라나누어비교해보면 Table 1과같다. 발작전후의심박수변화는발작전에비해심박수가유의하게빨라진즉, RR 간격이감소된빈맥을보인경우 (Fig. 1) 와, 심박수가유의하게느려진즉, RR 간격이증가된서맥 (Fig. 2) 및유의한심박수변화또는 RR 간격의변화가없는 (Fig. 3) 세가지경우로분류하였다. 경련발작후빈맥을보인경우는전체발작중 66.0% (62/94) 였고, 서맥은전체의 4.3% (4/94) 에서관찰되었으며, 나머지 29.8% (28/94) 에서는유의한심박수변화가없었다. 발작과함께관찰되는심박수변화중빈맥이가장많이관찰되었으며, 오른쪽반구에서발작이발생하는경우에빈맥이더많이관찰되었다 (Table 2). 서맥은전체발작중 4개에서만관찰되었는데 4개발작모두왼쪽반구에서발생하였다. 발작발생의위치에따라심박수변 182 대한신경과학회지제 28 권제 3 호, 2010
Table 4. Peri-ictal heart rate changes related to types of seizure Seizures with no significant Tachycardia Bradycardia HR changes Subclinical 9 (37.5%) 1 (4.2%) 14 (58.3%) 24 Simple partial 19 (86.4%) 0 (0%) 3 (13.6%) 22 Complex partial 29 (69.0%) 3 (7.1%) 10 (23.8%) 42 Secondary generalized 5 (83.3%) 0 (0%) 1 (16.7%) 6 HR; heart rate. Table 5. Temporal relation between peri-ictal heart rate changes and EEG seizure onset Seizures with no significant T( Z s =1) Tachycardia Bradycardia HR changes mean (s) a Mesial TLE 9/18 (50%) 2/18 (11.1%) 7/18 (38.9%) -54.4 b Neocortical TLE 7/10 (70%) 1/10 (10%) 2/10 (20%) -17.5 Extratemporal 46/66 (69.7%) 1/66 (1.5%) 19/66 (28.8%) -6.7 b a p<0.001 by one-way ANOVA, b significant values by post-hoc analysis (Scheffe test); mesial TLE > extratemporal lobe epilepsy. TLE; temporal lobe epilepsy, HR; heart rate. T( Z s =1) is a time interval (expressed in seconds) between peri-ictal heart rate change and EEG seizure onset. 화에차이가있는지알아보기위해세군을비교하였으나유의한차이는없었다 (Table 3). 발작의유형에따라분석해보면무증상발작을제외한나머지유형에서모두빈맥이유의하게관찰되었으나, 단순부분발작, 복합부분발작및이차전신발작간에심박수변화의유의한차이는없었다 (Table 4). 발작발생과심박수변화간의시간관계를알아보기위해발작기뇌파발생시점과심박수변화가생기는시점사이의시간차를측정하여평균값을비교해보았더니내측측두엽간질에서발작기뇌파발생 54.4 초전부터심박수변화가생겼고, 신피질측두엽간질에서 17.5 초, 측두엽외간질에서는발작기뇌파발생 6.7 초전부터심박수변화가나타나, 내측측두엽간질에서측두엽외간질보다심박수변화가통계적으로유의하게더빨리발생하였다 (Table 5). 고찰 본연구에서는간질발작과관련된심박수변화를알아보기위해국소관련간질환자 33명에서관찰한 94개의발작을분석하였다. 그결과, 전체발작의 66.0% 에서빈맥이관찰되었고전체의 4.3% 에서서맥이관찰되었으며, 발작의 41~99% 에서빈맥이동반되었고, 2-10 7% 미만에서서맥이동반되었던 5,6,8 기존보고들과비슷한결과를보였다. 간질병소의편측성 (lateralization) 즉, 발작이어느반구에서발생하였는지에따라빈맥이관찰되는정도에차이가있었는데오른쪽반구에서발작이발생한경우에빈맥이더많이관찰되었다. 간질발작과관련된심박수변화를좌우반구에따라 A B C D Figure 3. No significant heart rate change in a 12-year old male patient with right frontal lobe epilepsy without any brain lesion on MRI. (A) EEG time sequence in F8 electrode by 10-10 international EEG system. (B) ECG time sequence. (C) Discrete RR intervals, R i(t), sequence. (D) The smooth Z(t) function, Z s(t). There is no significant change of RR intervals before and after the seizure onset. 분석한기존연구에서서로상이한결과를보였다. 한연구에서는측두엽간질과측두엽외간질모두에서오른쪽반구에서발작이발생한경우에왼쪽보다심박수증가가더뚜렷하다고하였으나, 8 그밖의연구들에서는좌우반구에따른심박수변화의차이가없다고하였다. 10,14 그러나오른쪽에서발작이발생한경우에빈맥이유의하게더많이관찰되었고서맥이관찰된 4개발작모두왼쪽에서발생한본연구결과는섬엽피질을자극할때오른쪽에서빈맥이유의하게관찰되고, 11 경동맥내아모바르비탈주입시왼쪽반구의비활성화로인해빈맥이유발된다는 12,13 연구결과와일치하므로오른쪽반구가교감신경계조절 J Korean Neurol Assoc Volume 28 No. 3, 2010 183
에우세한기능을한다는사실을지지한다. 발작발생의위치와심박수변화간의관계를알아본많은연구에서측두엽간질이측두엽외간질보다유의하게심박수변화가많이발생한다고하였으며, 2,3,8,9,10,14 특히내측측두엽간질에서신피질측두엽간질보다유의하게심박수변화가많이관찰된다는사실을알수있었다. 8,10,14 그러나본연구에서는측두엽간질을내측측두엽간질과신피질측두엽간질로나누어서측두엽외간질과그룹간비교를해본결과발작발생의위치선정 (localization) 에따른유의한심박수변화의차이가없었는데이는연구에포함된내측측두엽간질의발작수가전체발작의 19% 에불과하였고, 측두엽외간질의발작이 70% 로상대적으로많아, 선택오차 (selection bias) 가결과에영향을주었을가능성이있다. 또한발작의유형과심박수변화간의관계를알아본결과, 무증상발작을제외한나머지유형에서모두빈맥이유의하게관찰되었으나유형에따른의미있는심박수변화의차이는없었다. 관련된기존연구들을살펴보면비전신발작혹은부분발작에비해전신발작에서발작시심박수증가혹은심전도의이상소견이많이관찰되었다. 7,21 또다른연구에서무증상발작과부분발작및전신발작으로나누어비교했을때전신발작에서심전도의이상소견이더많이나타나지는않았으나분석에포함된전신발작의수가적었기때문에결과를명확하게해석할수없었다. 6 본연구에서도발작의유형에따른심박수의유의한차이는없는것으로보였으나, 전신발작으로나타난발작의수가다른유형에비해현저히적었다는점이결과에영향을미칠수도있다. 본연구에서발작발생과심박수변화발생의시간관계를알아보기위해시간차의평균값을구해그룹간비교를해본결과, 내측측두엽간질의경우발작기뇌파발생시점보다심박수변화가평균 54.4 초먼저나타났으나측두엽외간질에서는발작기뇌파발생보다 6.7 초전에발생하는것으로나타났다. 이는다른연구에서측두엽간질의경우심박수변화가발작기뇌파발생시점보다평균 13.7 초앞서관찰되는반면측두엽외간질은발작기뇌파발생보다평균 8.2 초전에발생한다는결과와비슷하다. 8 또다른연구에서는측두엽간질중에서도내측측두엽간질의경우심박수변화가발작기뇌파발생보다평균 5초선행하며외측측두엽 (lateral temporal) 간질은발작기뇌파발생시점과심박수변화가생기는시점이거의일치하여본연구와유사한결과를보였다. 10 이는간질방전 (epileptic discharge) 이측두엽중에서도특히내측측두엽과밀접한관련이있는자율신경조절중추를자극하여심박수변화가나타나는것으로추정된다. 따라서이러 한심박수변화는특히내측측두엽간질의경우뇌파변화가생기기전에발작시작을예측하는데도움이될수있지만이와관련된연구가많지않으므로후속연구가필요하다. 본연구에서는국소관련간질환자에서발작전후의심박수변화에대해분석한결과, 다수의발작에서심박수변화가동반되었고이는대부분빈맥의형태로관찰되었으며특히오른쪽반구에서발작이발생한경우에유의하게심박수변화가뚜렷하였다. 또한내측측두엽간질의경우측두엽외간질보다심박수변화가더빨리나타나므로발작시작을예측하는데심박수변화의관찰이도움이될것으로생각한다. 하지만발작발생의위치 (localization) 및발작의유형과심박수변화간의관련성은기존연구와결과가일치하지않아후속연구가필요하다. 또한본연구에서는국소관련간질환자만을대상으로하였지만향후전신간질 (generalized epilepsy) 환자를포함한대규모연구를통하여심장과뇌, 그리고자율신경계의조절과관련된상호관계를규명할수있을것이다. REFERENCES 1. Baumgartner C, Lurger S, Leutmezer F. Autonomic symptoms during epileptic seizures. Epileptic Disord 2001;3:103-116. 2. Marshall DW, Westmoreland BF, Sharbrough FW. Ictal tachycardia during temporal lobe seizures. Mayo Clin Proc 1983;58:443-446. 3. Blumhardt LD, Smith PE, Owen L. Electrocardiographic accompaniments of temporal lobe epileptic seizures. Lancet 1986;1:1051-1056. 4. Keilson MJ, Hauser WA, Magrill JP. Electrocardiographic changes during electrographic seizures. Arch Neurol 1989;46:1169-1170. 5. Schernthaner C, Lindinger G, Potzelberger K, Zeiler K, Baumgartner C. Autonomic epilepsy-the influence of epileptic discharges on heart rate and rhythm. Wien Klin Wochenschr 1999;111:392-401. 6. Zijlmans M, Flanagan D, Gotman J. Heart rate changes and ECG abnormalities during epileptic seizures: prevalence and definition of an objective clinical sign. Epilepsia 2002;43:847-854. 7. Opherk C, Coromilas J, Hirsch LJ. Heart rate and EKG changes in 102 seizures: analysis of influencing factors. Epilepsy Res 2002;52:117-127. 8. Leutmezer F, Schernthaner C, Lurger S, Potzelberger K, Baumgartner C. Electrocardiographic changes at the onset of epileptic seizures. Epilepsia 2003;44:348-354. 9. Weil S, Arnold S, Eisensehr I, Noachtar S. Heart rate increase in otherwise subclinical seizures is different in temporal versus extratemporal seizure onset: support for temporal lobe autonomic influence. Epileptic Disord 2005; 7:199-204. 10. Di Gennaro G, Quarato PP, Sebastiano F, Esposito V, Onorati P, Grammaldo LG, et al. Ictal heart rate increase precedes EEG discharge in drugresistant mesial temporal lobe seizures. Clin Neurophysiol 2004;115:1169-1177. 11. Oppenheimer SM, Gelb A, Girvin JP, Hachinski VC. Cardiovascular effects of human insular cortex stimulation. Neurology 1992;42:1727-1732. 12. Zamrini EY, Meador KJ, Loring DW, Nichols FT, Lee GP, Figueroa RE, et al. Unilateral cerebral inactivation produces differential left/right heart 184 대한신경과학회지제 28 권제 3 호, 2010
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