Dipole analysis in a case with tumor-related epilepsy

Brain & Development 21 (1999) 483±487

Original article

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Dipole analysis in a case with tumor-related epilepsy Harumi Yoshinaga a,*, Tomoyuki. Nakahori a, Junri Hattori a, Tomoyuki Akiyama a, Eiji Oka a, Susumu Tomita b, Mizuho Aoi b, Takasi Ohmoto b, Keiichi Miyamoto c a

Department of Child Neurology, Okayama University Medical School, Okayama, Japan b Department of Neurosurgery, Okayama University Medical School, Okayama, Japan c Central Electronics Company, Japan

Received 27 October 1998; received in revised form 12 April 1999; accepted 21 May 1999

Abstract In order to evaluate the effectiveness of presurgical dipole analysis of interictal spikes as a non-invasive technique for the determination of epileptogenic area, we compared the results of this method with those of electrocorticography (ECoG) localization in the diagnosis of a patient with tumor-related epilepsy. A preoperative MRI revealed a temporal lobe tumor on the right side. The individual dipoles estimated from the interictal spikes were located mainly in the anterolateral region of the right temoral lobe, although some were located in the mesial side. The ECoG recorded frequent spikes in the anterolateral region of the right temporal lobe consistent with the location estimated by dipole analysis. After surgery, the patient suffered from residual seizures. Therefore, the residual epileptogenic area was examined by dipole analysis using a four-layered head model instead of the previous three-layered head model. As a result, the dipole analysis was able to pinpoint the epileptic focus in the area directly adjacent to the resected area, and in the mesial temporal lobe. In conclusion, EEG dipole analysis appears to hold promise as a non-invasive presurgical evaluation technique for locating epileptogenic areas as well as for postsurgical evaluation of residual epileptic focus. q 1999 Elsevier Science B.V. All rights reserved. Keywords: Tumor epilepsy; Dipole analysis; Four-layered head model; Dysembryoplastic neuroepithelial tumor; Electrocorticography

1. Introduction Focal excision of the epileptic focus in the treatment of intractable epilepsy is clinically bene®cial. In particular, this is the most effective method for the treatment of tumorrelated epilepsy [1]. For the detection and localization of the epileptogenic area, various non-invasive techniques have been tried, instead of invasive techniques such as electrocorticography (ECoG) and the implantation of electrodes. Of these, the clinical effectiveness of dipole localization analysis with EEG and MEG has been reported [2,3]. However, clinical application of dipole source localization for the determination of the extents of residual epileptogenic area remaining after surgery has not yet been reported. This may be due to differential conductivity of the brain following lesionectomy.

* Corresponding author. Dr. Harumi Yoshinaga, Department of Child Neurology, Okayama University Medical School, 2-5-1 Shikatacho, Okayama, 700-8558, Japan. Tel.: 1 81-86-235-7372; fax: 1 81-86-2357377. E-mail address: [email protected] (H. Yoshinaga)

Therefore, we decided to evaluate this technique by comparing its results with those attained by electrocorticography on a patient with tumor-related epilepsy. The extent of residual epileptogenic area after surgery was also determined by dipole analysis using a four-layered head model [4] instead of a three-layered model [5].

2. Subject and methods The subject of this study was a 17-year-old boy who had suffered complex partial seizures from the age of 3 onward. CT performed when the boy was 4 years of age revealed the presence of a space occupying lesion on the right temporal side. At the age of 14, a stereotactic biopsy of the tumor was performed and pathologic examination revealed it to be a dysembryoplastic neuroepithelial tumor (DNT). Because of increased seizure frequency, he was admitted to the department of neurosurgery of the Okayama University Hospital for the purpose of tumor resection. After surgery, he enjoyed a short seizure-free period but was soon readmitted due to a relapse of symptoms.

0387-7604/99/$ - see front matter q 1999 Elsevier Science B.V. All rights reserved. PII: S 0387-760 4(99)00058-3

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H. Yoshinaga et al. / Brain & Development 21 (1999) 483±487

2.1. Dipole analysis Using EEG analyzer CDT 1000 (Central Electronics Company, Japan), dipole estimation was performed for several individual spikes at 20 ms sampling time which included the negative apex of the spike. The estimation was performed using a one-dipole model. This method estimates localization based on least-squares modeling. The actual potential ®eld distribution recorded from the 21 scalp electrode, Umeas, was compared with the calculated ®eld distribution, Ucal, for a properly chosen equivalent current dipole. Thus the locations and vector moments of a current dipole were iteratively changed until the squared difference between Ucal and Umeas became minimal. We evaluated the goodness of ®t for the calculated dipole by means of ``dipolarity'', which was de®ned as follows: D ˆ 100 £

r   1 2 jUmeas 2 Ucal j2 =jUmeas j2

In an ideal case the dipolarity is 100%, however in practice it is usually less due to noise, electrode misalignment, and non-dipole components of the electric source. Since previous computer simulations have shown that a disk formed dipole source with a diameter of 1 cm in the cortex resulted in a dipolarity larger than 98% in the presence of back ground EEG, in the present study a dipolarity larger than 98% was adopted to indicate a concentrated source [6]. Three-layered realistically shaped model was used for presurgical investigation and four-layered one was used post surgically. The former head model takes into consideration the conductivity of the scalp, skull, and brain as well as the patient's head shape in construction of the head model (scalp-skull-brain model, SSB model) [5]. The outer scalp shell was measured using a semispherical helmet equipped with 64 sensors. The helmet could be tilted, and the horizontal plane of the coordinate system was thus adjusted to correspond to the orbitomeatal plane. The shapes of the remaining two shells, skull and brain, were obtained from consecutive 5 mm horizontal CT images in a plane parallel to the orbitomeatal plane. The CT images were scanned with an image scanner and digitized in the computer using an automatic edge detection program delineating the outer and inner surfaces of the skull bone. The shapes of the scalp, skull and brain were three-dimensionally reconstructed from the CT images into the SSB head model using triangular meshes. The conductivity ratio was chosen to be 1:1/ 80:1 respectively for scalp, skull and brain. The latter is more advanced, in that it takes into account a fourth variable, namely, empty space in the brain ®lled with cerebrospinal ¯uid (scalp-skull-liquor-brain model, SSLB model) [4,5]. Four-layered head model was made in the same way as the three-layered one. The conductivity ratio was 1:1/ 80:1:3 respectively for scalp, skull, brain, and liquor. Details

of these analytical methods have been reported in previous studies [4,5]. 2.2. Subdural electrodes ECoG was performed during surgery with 10 siliconeembedded strips placed in the subdural space from the lateral side of the right temporal lobe to its base. Unfortunately, postoperative ECoG could not be performed because the patient refused to grant permission for this procedure. 3. Results 3.1. Preoperative MRI and scalp EEG The center column of Fig. 1 shows preoperative MRI. It reveals an extensive heterogeneous isointense to hypointense mass lesion with poorly de®ned borders, in the lateral side to mesial side of the right temporal lobe. There was no abnormality observed in the hippocampus on MRI. Presurgical scalp EEGs revealed frequent interictal spikes with maximum intensity at the right anterior temporal electrode with propagation to the adjacent area. Ten of these interictal spikes were analyzed individually 3.2. Preoperative spike dipoles As shown in the upper row in Fig. 2, most individual dipoles were located at the anterolateral sides of the right temporal lobe, while some dipoles were scattered toward the posterior and mesial sides of the main dipole locations. 3.3. The intrasurgical ECoG The frequency of interictal spikes on ECoG is shown in Fig. 3. The ECoG recorded more frequent spikes at the anterolateral region of the right temporal lobe consistent with the location estimated by dipole analysis. However, a few spikes were recorded in the other regions of the right temporal lobe, such as the upper and the posterior regions. Subsequently, the lesion was resected, including the tip of the temporal lobe but not including mesial temporal lobe. The resection area was decided according to ECoG and MRI ®ndings, while the dipole ®ndings were not taken into consideration. Therefore, the hippocampus was not removed. Histological analysis of the pathological features led to the diagnosis of a dysembryoplastic neuroepithelial tumor. 3.4. Post surgical MRI Postsurgical MRI are shown in the right column of Fig. 1. After the resection, a large empty space in the brain was ®lled with cerebrospinal ¯uid and a part of the mesial temporal lobe remained.

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Fig. 1. Center column. A presurgical MRI shows a lesion in the lateral to mesial side of the right temporal lobe. Right column. Postsurgical MRI study shows a cavity in the lateral side to mesial side of the right temporal lobe (note that a part of the mesial temporal lobe remains). Note that the left and right are reversed in the upper row and lower row in order to correspond to Fig. 2, which shows the dipole analysis.

3.5. Post surgical spike dipole Dipoles estimated using residual spikes in post operative EEG recording are shown in the lower row of Fig. 2. Compared with MRI images (Fig. 1), dipole locations are consistent with the residual lesion including those in the right mesial temporal lobe.

4. Discussion In this case, individual dipole analysis of spikes showed the existence of several scattered dipoles located in the tumor itself in addition to the main dipole location. In 1996, we reported an epileptic patient with a small hamartoma showed concentrated dipole locations adjacent to a cystic lesion detected by MRI without other scattered dipole locations [7]. Based on our present ®ndings and those of our 1996 report, we conclude that small homogenous tumors have a discrete focus situated in the peripheral area of the tumor, not in the tumor itself, while larger lesions have several foci which result in the scattered locations estimated by the dipole analysis and subdural electrode recordings. The existence of the epileptogenic area in the tumor structure itself is abnormal [1,7]. However, DNT have characteristic intracortical nodules [8], so that the normal cortex is included in the large mass and this could be as the epilepto-

Fig. 2. Upper row: presurgical dipole analysis. Each dot shows the dipole of eight individual spikes which showed acceptable dipoles with the dipolarity threshold set at 98%. Most dipoles were clustered at the anterolateral side of the right temoral lobe, while some were observed on the mesial side. Lower row: postsurgical dipole analysis. Although dipoles were scattered, they were concentrated at the mesial ridges of the cavity.

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Fig. 3. Frequency of interictal spikes on ECoG: solid circles, one or more spikes/10 s; shaded circles, one or more spikes/50 s; open circles, no spikes. The eight of ten electrode strips were placed parallel to the silvian ®ssure (the left column) and the other two were placed vertical to the ®ssure, covering the mesial temporal and the temporal base (the right colum). The electrode contacts in the vicinity of the silvian ®ssure were relatively quiet. In contrast, the frequency of interictal spikes increased the lower and more anteriorly located the electrodes were, peaking at the ®nal anterior electrode.

genic area. Thus, the results of dipole analysis might differ according to the pathology of the tumor. In the case presented herein, there was a good correlation between the results of dipole analysis and the results of subdural electrode recording. Shindo et al. recently reported that the estimated foci by EEG dipoles are located more toward the mesial side than indicated by ECoG in some patients [3]. However, Shindo et al. used a single-layered head model, so the differential conductivity of the head was not taken into account. Actually, in our previous reports, it was con®rmed that the dipole locations estimated by singlelayered head model were situated more deeply than those estimated by three-layered head model [9,10]. Lantz et al. also mentioned the limits of EEG dipole accuracy in the temporal area, and they emphasized that the temporal area is a part of the brain that ®ts quite poorly with the spherical head model [11]. However, our method uses a three-layered head model and takes into account the individual cranial structure based on CT scan data. Therefore, problems arising from inadequate compensation for individual cranial structure are considerably less with our method than with past methods which were far from physiologically precise. Additionally, in this report, we were able to con®rm the accuracy of dipole analysis using a more advanced four-layered head model [4], for cases in which surgery results in empty cavities in the brain.

Currently, subdural electrocorticography (ECoG) and the placement of depth electrodes are considered the most accurate methods for presurgical localization of epileptogenic areas in epileptic patients. However, these methods involve risk, and safety considerations limit the number of intracranial electrodes which can be placed, which can result in a large sampling error. In the case reported herein, it is unfortunate that electrodes were not placed in the areas where the dipoles were located, namely, the mesial temporal lobe. Dipole analysis might help focus intracranial electrodes and reduce sampling error. It was regrettable that the results of dipole analysis are not taken into consideration for the decision of the surgical procedure. This case indicates that further careful presurgical evaluation is warranted when the discrepancy is observed between the dipole results and the other presurgical ®ndings. In the future, greater emphasis on the dipole analysis would be expected. In summary, EEG dipole appears to have potential value as a non-invasive presurgical and postsurgical diagnostic technique. References [1] Cascino GD. Epilepsy and brain tumors: implications for treatment. Epilepsia 1990;31(Suppl 3):S37±S44. [2] Boon P, D'Have M, Vandekerckhove T, Achten E, Adam C, Clem-

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