1、Ictal tachycardia: its discriminating potential between temporal and extratemporal seizure foci發作性心動過速：顳葉及顳葉外致癇灶間的潛在差別A wide variety of CNS lesions have been associated with changes in heart rate (HR). However, in epileptic patients their value to lateralize seizure onset remains controversial. This

2、 study aims to assess if HR changes associated with partial onset seizures could be useful in lateralizing seizure onset.許多中樞神經系統病灶與心率變化相關。但是，在癲癇患者中，他們對于發作開始定側價值仍然是有爭議的。這研究旨在評估是否與部分發作開始相關的心率變化在發作開始定側方面是有用的。We analysed HR changes on 100 seizures from 38 consecutive patients (mean age: 27.5 years) adm

3、itted for video-EEG telemetry monitoring. We evaluated the RR interval 30 seconds before the seizure onset and 10, 20 and 120 seconds after the onset. We assessed whether there was a correlation between HR changes and seizure type, left/right differences and different semiological components for eac

4、h seizure.我們分析了行視頻腦電監測的38例連續患者（平均年齡：27.5）100次發作心率變化。我們評估了發作開始前30秒R-R間期以及發作開始后10秒、20秒以及120秒R-R間期。我們評估了心率變化與發作類型，左右側差別，每次發作不同的癥狀學表現之間是否有相關性。We recorded 100 seizures. Three non-lateralized seizures were excluded from the analysis; 63/97 (65%) had left hemisphere onset, mainly from the temporal lobe (57

5、.7%). The mean baseline HR was 77 beats per minute Ictal tachycardia (HR: 107.06 beats per minute) was detected in 32 seizures, with ictal onset from the mesial temporal lobe structures in 23/32; 16/32 occurred during the first 10 seconds and 16/32 during the next 20 seconds from the seizure onset i

6、ndependently of the site of origin. Among the different semiological components for each seizure, only dystonic posturing and automatism correlated with HR increments. We did not find bradycardia in our series.我們記錄了100次發作。三次非單次發作從分析中被排除。63/97（65%）有左側半球區起始發作，主要來自顳葉（57.7%）。平均基線心率是每分鐘77次，觀察到32次發作中有發作性心

7、動過速（HR：107.06次/分），這32次發作中有23次發作開始來源于顳葉內側結構，這32次發作中有16次發生在起源區獨立癲癇發作開始第一個10秒，剩余16次發生在接下來20秒。在每次發作的不同癥狀學表現中，僅僅姿勢性肌張力障礙和自動癥與心率增量相關。在我們的研究中我們沒有發現心動過緩。Ictal tachycardia occurs most frequently with seizures arising from the mesial temporal lobe and it may not reliably predict the lateralization of seizure

8、onset.發作性心動過速最常發生于顳葉內側起始區發作，并且它可能無法可靠地預測發作開始區的定側。Key words: heart rate; epilepsy; ictal onset.關鍵詞：心率、癲癇、發作期開始 INTRODUCTION背景介紹The putative role of the cerebral hemispheres in modu-lating the autonomic cardiac balance is still poorly un-derstood. Along with other higher cortical functions, hemispheri

9、c lateralization in cardiac autonomic con-trol has been suggested based upon the observation of heart rate and/or blood pressure changes following brain lesions, but these changes do not directly reflect the intrinsic cardiac sympathovagal regulation1. Such differences may result from different left

10、/right cere-bral hemispheric influences upon the brainstem auto-nomic centers and can be evaluated by cerebral inac-tivation or stimulation2. Such changes have been re-ported following a wide variety of brain lesions includ-ing stroke, epilepsy, cerebral trauma, encephalitis and brain tumors.大腦半球在調節

11、自主神經心臟平衡方面上的假定的作用仍被理解地很差。與其他更高級的皮質功能一起，大腦半球在心臟自主神經控制方面上的定側被認為是建立在腦損傷后心率或血壓變化基礎之上，但是這些變化不能直接反應固有的心臟交感迷走調節。這些不同可能源于左/右側大腦半球對腦干自主神經中心不同影響以及能夠被腦失活或刺激所評估。這些變化被報道說發生在各種各樣的腦損傷后包括卒中，癲癇，腦外傷，腦炎和腦部腫瘤。In epileptic patients most of these disturbances, seen primarily in the form of tachycardia, could be drug rela

12、ted3 and have been reported following both complex partial seizures (CPS) and simple partial seizures (SPS). Furthermore, the association between heart rate (HR) changes and sudden unexpected death in epileptic patients (SUDEP) has been suggested by case reports of patients with temporal lobe epilep

13、sy and unexpected death46 . Pathological cases, as well as animal models proposed to explain SUDEP, sug-gest that diffuse extratemporal and/or bilateral mesial temporal damage in epileptic patients could interfere with descending forebrain pathways that have influ-ence on cardiovascular regulation,

14、accounting for HR variability. Nevertheless, its semiological value to lat-eralize seizure onset remains controversial in epileptic patients.在癲癇患者中大多數紊亂主要見于心動過速的形成中，可能是藥物相關性的，被報道出現在復雜部分發作和簡單部分發作之后。另外，心率變化和癲癇猝死之間的關系是通過顳葉癲癇患者和猝死的案例報道表明的。病理報道，同動物模型一樣，被用來解釋癲癇猝死，表明癲癇患者中彌漫性顳葉外或雙側顳葉內側損害干擾前腦下行通路，前腦下行通路能夠對心血

15、管調節有影響，對心率變異性作出解釋。然而，它對發作起始區定側的癥狀學價值在癲癇患者中仍然是有爭議的。It is well known that 2530% of epileptic patients are not adequately controlled with medical therapy and these represent the group of refractory patients7. For some of these patients epilepsy surgery is considered, and a thorough work up is used in o

16、rder to identify the epileptogenic zone. Clinical semiology is one of the parameters used for such lateralization, although the lateralizing value for some of the clinical manifesta-tions remains controversial.眾所周知，25-30%癲癇患者不能被醫學治療充分控制，且這些代表難治性患者一組。這些患者中有一部分可以考慮手術，全面工作被用來確定致癇灶。臨床癥狀學被用于這樣定側參數之一，盡管一些

17、臨床表現的定側價值仍然是有爭議的。The objective of the present study was to evalu-ate if heart rate changes associated with partial onset seizures could be helpful in lateralizing ictal onset.當前研究的目的是為了評估與部分發作起始相關的心率變化在發作起始定側上是否是有幫助的。MATERIALS AND METHODS材料和方法We analysed HR changes on 100 consecutive CPS from 38 epi

18、leptic patients referred to our center for video-EEG monitoring. Most of these cases were ad-mitted to our unit to define suitability for epilepsy surgery. All patients studied had no history or evidence of an active cardiovascular disease, diabetes, uremia or any other disorder that might affect th

19、e autonomic ner-vous system. In order to be included in the study, base-line heart rate had to be below 120 bpm, and patients had to be on no other medication than antiepileptic drugs (AEDs).我們分析了視頻腦電監測中心選取的38例癲癇患者100次連貫性復雜部分發作的心率變化。大多是病例被承認進入我們單元來確定手術是否適合。受試者沒有活動性心血管病，糖尿病，尿毒癥或者可能影響自主神經系統的任何一種紊亂的既往史

20、或者證據。這項研究的入選標準是基線心率是低于120次/分，且患者除了抗癲癇藥以外沒有其他治療。Scalp EEG was performed with electrodes applied following the 1020 International System, plus two additional sphenoidal electrodes. Electrodes monitor-ing eye movements and chest electrodes for EKG leads were also used. One patient was also recorded wit

21、h in-dwelling depth electrodes. All patients had a negative brain MRI ruling out the presence of a progressive lesion.頭皮腦電采用應用電極安裝，履行10-20國際系統，加上2個額外的蝶骨電極。監測眼動電極以及心電圖的胸腔電極也被使用。一名患者也用顱內深部電極記錄。所有患者腦部MRI陰性，排除了進行性病灶的存在。We measured the RR interval for the 60 seconds that preceded the seizure onset and th

22、ereafter at 10, 20 and 120 seconds after ictal onset. Ictal onset was defined both clinically and electrographically. From the electrographical point of view we classified tem-poral onset seizures as mesial or neocortical, based on the patterns recently described by Pacia and Eber-sole8. The first o

23、f these patterns, accepted as a mesial pattern, is characterized by a regular 59 Hz activ-ity localized over subtemporal and/or anterior tem-poral areas. The second pattern, highly associated with neocortical temporal lobe onset, is character-ized by low-voltage, high-frequency discharges in the bet

24、a and gamma range with slow and irregular corti-cal rhythms following seizure onset. This activity can be focal or regional temporal. Semiological analyses included the presence and type of aura, type of au-tomatisms, dystonic posturing and the presence of sec-ondarily generalized tonicclonic seizur

25、e. Only those seizures without motor manifestations at the onset were considered for analysis in order to rule out their influence upon heart rate.我們測量了發作開始前60秒R-R間期，隨之發走開始后10秒，20秒，120秒R-R間期。發作開始是通過臨床和腦電圖來確定的。從腦電圖觀點來看，我們將顳葉起始區發作分類為內側或新皮層，基于被Pacia and Eber-sole近來所描述的模式。這些模式中第一個模式，作為內側模式被接受，是由定位在顳葉下或前

26、顳區的規律5-9Hz活動為特征的。第二個模式，與新皮層顳葉起始高度相關，是以和范圍的低電壓高頻放電以及緊跟發作起始的規律皮層節律為特征的。這一活動可能是局灶的或某區顳葉。癥狀學分析包括先兆的存在和類型，自動癥的類型，姿勢性肌張力障礙以及繼發全身強直陣攣發作的存在。僅僅那些在起始時沒有運動臨床表現的發作才被用作分析，目的是為了排除運動對心率的影響。A mean baseline HR was estimated (B-HR) and thereafter at 10, 20 and 120 seconds after seizure on-set. Mean differences compar

27、ed to B-HR were as-sessed with a non-parametric variable test (Wisconsin test). B-HR 2SD was used to define significance at a P level 0.05. This value was used to examine each particular seizure, assessing if it produced ictal HR changes. Finally, we attempted to correlate HR changes and left/right

28、side differences, electrograph-ical onset and the semiological components for each seizure.平均基線心率被評估，隨之發作開始后10秒，20秒以及120秒心率被評估。與基線心率相比較，平均差別被沒有參數的變量分析所評估。基線心率2標準差被用作定義一個P0.05的重要性。這一價值被用作監測每一種特定類型，評估是否產生發作性心率變化。最后，我們試圖將心率變化和左/右側差別，每次發作腦電圖上發作開始以及癥狀學表現相關聯。RESULTS結果We included 38 patients (18 male and 2

29、0 female, mean age: 27.6 years, range: 353 years). Eleven patients had a single seizure whereas 27 had multiple seizures during the recording. All patients had consistent HR changes from seizure to seizure. General physical and neurologic examinations were unremarkable ex-cept for eight out of 37. A

30、ll patients were exposed to AED therapy with plasma levels within the therapeutic range. (See Table 1 for demographic information.)我們包括38例患者（18名男性以及20名女性，平均年齡27.6歲，范圍3-53歲）。在記錄期11名患者有單一發作，而27名患者有多種發作。所有患者從發作到發作有持續的心率變化。一般生理學和神經學檢查是不起眼的，除了37例特例。所有患者在抗癲癇藥物治療且血漿水平在治療范圍內。Brain MRI detected morphologic a

31、lteration in 25 out of 37 cases. In 23 cases focal lesions were doc-umented, including hippocampal sclerosis (n D 16), sequelae from previous surgery for cerebral neoplasm (n D 2) or trauma (n D 1) and gray matter heterotopy (n D 4).腦部MRI發現：37例中25例有形態學上的改變。23例中局灶性病灶被記錄到，包括海馬硬化（16例），腦部腫瘤先前手術的后遺癥（2例），

32、腦外傷（1例），灰質異位（4例）。We were able to lateralize seizure focus in 97 seizures, thus excluding the other three, for statisti-cal analysis. The mean B-HR was 77 bpm, and the mean HR at 10, 20 and 120 seconds after seizure on-set was 88.8, 95.1 and 93.5 bpm, respectively. The mean HR was significantly modif

33、ied from baseline at 10 ( P D 0:001), 20 ( P D 0:003) and 120 ( P D 0:002) seconds.我們能夠給97次發作致癇灶定側，因此為了統計分析，排除了其他3次發作。平均基礎心率是77次/分，發作開始后10秒、20秒、120秒平均心率分別是88.8,95.1,93.5次/分，在發作后10秒，20秒，120秒時的平均心率是從基線處作了重大調整。（ 分別是P=0.001,P=0.003,P=0.002）HR was raised in 32 seizures (32.9%), half of them within the fi

34、rst 10 seconds from seizure onset and the remaining within the first 20 seconds. We found no ic-tal bradycardia or interictal heart rate disorders in our patients. Analysis of HR at 120 seconds from ictal on-set showed changes only in those cases with secondar-ily tonicclonic activity.心率增快出現在32次發作中（

35、32.9%），他們中一半出現在發作開始起的第一個10秒內，剩余一半出現在接下來的20秒內。在我們的患者中我們沒有看到發作性心動過緩或者發作間期心率紊亂。發作開始起120秒時的心率分析顯示變化僅僅出現在繼發強直-陣攣活動的那些病例中。1、HR changes in relation to hemispheric lateralization與大腦半球定側相關的心率變化Sixty-five percent of the seizures lateralized to the left hemisphere and the remaining to the right. Con-sidering o

36、nly those seizures with ictal HR changes, 10/32 (31.2%) were right-sided and 22/32 (68.8%) left-sided. These percentages were also seen for those seizures without HR changes.We found no statistical differences between both groups in relation to lateral-ization (Fig. 1).65%的發作定側在左側大腦半球，剩余定側在右側大腦半球。考慮

37、到僅僅伴有發作性心率變化的那些發作，10/32（31.2%）是定側在右側的，22/32（68.8%）是定側在左側的。這些百分比也見于那些沒有心率變化的發作中。與定側相關的組組之間我們沒有發現統計學差異。Ictal tachycardia does not lateralize seizure onset發作性心動過速沒有定側發作起始2、HR changes related to seizure focus與致癇灶相關的心率變化Seizure onset defined by ictal EEG findings was as follSeizure onset defined by ictal

38、 EEG findings was as follows: 41/97 seizures were extratemporal and 56/97 had temporal onset. In the latter group, 40/56 had elec-trographic patterns suggestive of mesial temporal on-set, whereas the onset was defined as neocortical in the remaining 16.通過發作期腦電圖發現定義的發作起始如下：97次發作41次是顳葉外，56次是顳葉起始。在后面這組

39、中，56次發作中有40次被認為是顳葉內側起始的腦電圖模式，然而剩余16次發作起始被定義為新皮層。Considering the relationship between seizures with HR changes and seizure onset, we found that the ma-jority of these seizures (25/32) had temporal onset. Looking for differences between mesial and neocor-tical origin, we found that the mesial group wa

40、s re-sponsible for changes in 23/25 (92%).考慮到心率變化和發作開始間的關系，我們發現這些發作中大多數（25/32）是顳葉起始。查看內側和新皮層起源之間的差別，我們發現內側組對在25次發作中有23次（92%）心率變化負有責任。The analysis of those seizures without HR changes showed that 34/65 (52.3%) had an extratemporal focus and 31/65 (47.7%) a temporal one, without a signifi-cant differe

41、nce between mesial and neocortical onset.沒有心率變化的那些發作分析顯示65次發作34次（52.3%）有一個顳葉外病灶，65次發作31次（47.7%）有一個顳葉病灶，在內側和新皮層起始之間沒有重大差別。In summary, the only difference statistically signif-icant was the one that linked temporal lobe onset and HR changes (Fig. 2).總而言之，統計學上惟一重大不同是顳葉起始和心率變化之間的聯系。3、HR changes related

42、to semiological findings與癥狀學發現相關的心率變化We found that 17/32 (53.1%) seizures with HR changes had a clear aura, 28/32 (87.5%) automatisms and 19/32 (59.4%) dystonia. A similar analysis for those seizures without HR changes showed an aura in 23/65 (35.4%), automatisms in 29/65 (44.6%) and dystonia in 14/

43、65 (21.5%) (Fig. 3).我們發現了32次伴有心率變化的發作17次（53.1%）有一個清晰的先兆，這32次中28次（87.5%）有自動癥，這32次中19次（59.4%）有肌張力障礙。沒有心率變化的那些發作的一個相似分析顯示65次發作中23次（35.4%）有一個先兆，65次發作中有29次（44.6%）有自動癥以及65次發作中有14次（21.5%）有肌張力障礙。Finally, we found no association between HR changes and age, sex or pharmacological therapy ad-ministered.最后，我們發現

44、心率變化和年齡，性別或者管理的藥理學治療沒有關系。DISCUSSION討論One of the most striking findings in the present study is the significant percentage of partial onset seizures presenting with increased HR as an ictal manifesta-tion. Moreover, these changes seem to have a more robust association with partial seizures arising fr

45、om the temporal lobe, especially from mesial structures. However, our findings failed to support a positive cor-relation between cardiac changes and side of the ic-tal discharge suggesting that, although present in some cases, they have no predictive value to assess lateral-ization.當前研究最突出的發現之一是呈現增快

46、的心率作為一個發作性臨床表現的部分起始發作占了重大百分比。而且，這些變化似乎與起源于顳葉尤其是內側結構的部分發作部分發作有更密切關系。但是，我們的發現沒能支持心臟變化和發作期放電一側之間的正性相關，這表明盡管一些病例有呈現相關性，但是我們的發現表明他們沒有評估定側的預測價值。Although in the present study we observed no dif-ferences between left-sided onset with or without HR changes, we have to recognize that these figures might refle

47、ct a sample bias, given that 65% of the anal-ysed seizures were left-sided in origin. Furthermore, our results showed that 78% of the seizures with ic-tal tachycardia were seen in patients with temporal lobe epilepsy, especially those with electrographic on-set from mesial structures, which accounts

48、 for 92% of the events with temporal onset. This finding, along with the presence of automatisms and dystonia, semio-logical features mostly seen with mesial temporal lobe epilepsy, reached statistical significance.盡管在當前研究我們發現左側半球起始發作伴或不伴心率變化之間沒有區別，但是我們不得不承認這些數據可能反映一個樣本偏倚，考慮到被分析的發作中65%是左側起源。另外，我們的結果

49、顯示伴有發作性心動過速的發作中78%見于顳葉癲癇患者，尤其是那些腦電圖起始于內側結構的患者，這為92%的顳葉起始事件作出了解釋。這一發現，與自動癥和肌張力障礙存在一起，癥狀學特征更多見于顳葉內側癲癇，達到了統計學意義。Our findings agree with several other reports, in spite of the fact that different methods were used to evaluate the relationship between seizures and HR changes. Li et al.4 observed tachycar

50、dia in 39% of their patients with CPS from temporal lobe epilepsy, but found no differences regarding lateralization. Sim-ilar conclusions were reported by Galimberti et al.6. Blumhardt and his group9 have also seen sinus tachy-cardia in 92% of their patients with temporal lobe epilepsy, whereas Mar

51、shall et al.10 observed a similar incidence rate in video-EEG evaluation of CPS. Con-trary to the present study, the possibility to lateralize seizure onset has been proposed through both clinical and experimental studies. Fang et al.11 found that the electrical stimulation of the right hypothalamus

52、 trig-gers a significant cardioacceleration in dogs, whereas the stimulation of the left hypothalamus resulted only in a moderate response. Asymmetrical autonomic in-nervation of the heart and lateralization of cardiac sympathetic outflow in the brainstem has also been re-cently suggested by Hachins

53、ki et al.12 using a stroke animal model. They found that right hemispheric in-farcts produced a greater increase in sympathetic nerve discharge, plasma norepinephrine, and duration of the QT interval of the EKG. In studies performed during an intracarotid amytal test, both Hachinskis1 and Zam-rinis2

54、 groups found an increased HR after the inacti-vation of the left hemisphere by an intracarotid injec-tion of amobarbital, whereas a reduction in HR was seen after inactivation of the right hemisphere. Thisobservation provides support for the hypothesis that the autonomic response might be disinhibi

55、ted with le-sions in the contralateral hemisphere5. Given that the major effects of an intracarotid amobarbital injection are in the distribution of the ipsilateral anterior and middle cerebral arteries, the changes in HR appear to be produced by a suprabulbar inactivation, so it does not represent

56、a discrete focus, similar to what happens during a seizure. In addition, these reports were done with a small number of subjects, so that changes could be not statistically significant. Oppenheimer et al.13 suggested a right-sided dominance for sympathetic ef-fects in humans by stimulation of the in

57、sular cortex. However, simple observation of the HR or blood pres-sure level may not be an accurate method for assess-ing cardiac sympathovagal balance. In a recent report by Swartz and colleagues14 based on patients under-going electroconvulsive therapy (ECT), they showed a significant and more per

58、sistent HR elevation with right than with left side stimulation. This observation agrees with the predominantly right-sided mechanisms that mediate sympathetic cardioacceleration and with the theory that the cardioacceleratory sinoatrial heart node is innervated by a greater number of sympathetic fi

59、bers arising from the right side of the brain14. It is im-portant to consider that these HR changes can result from a summation of effects. The seizures triggered by ECT are linked not only to ictal discharges that in-volve widespread cortical areas, but also to endocrine mechanisms, such as epinephrine liberation. This un-derlying pathophysiological process is rather different from the one seen with CPS, where seizures