Brain Advance Access published online on September 12, 2007
Brain, doi:10.1093/brain/awm218
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Stereoelectroencephalography in presurgical assessment of MRI-negative epilepsy
1INSERM, U 751, Laboratoire de Neurophysiologie et Neuropsychologie, Marseille, F-13000, 2Aix Marseille Université, Faculté de Médecine, Marseille, F-13000, 3Assistance Publique Hôpitaux de Marseille, Hôpital La Timone, Service de Neurophysiologie Clinique, Marseille, F-13005, 4Assistance Publique Hôpitaux de Marseille, Hôpital La Timone, Service d’Anatomie Pathologique, Marseille, F-13005, 5Assistance Publique Hôpitaux de Marseille, Hôpital La Timone, Service de Neurochirurgie, Marseille, F-13005 and 6Assistance Publique Hôpitaux de Marseille, Hôpital La Timone, Service de Neuroradiologie, Marseille, F-13005, France
Correspondence to:
Dr Aileen McGonigal, Laboratoire de Neurophysiologie et Neuropsychologie, INSERM U 751 & Service de Neurophysiologie Clinique, CHU Timone, Marseille, France, 27 boulevard Jean Moulin 13005 Marseille France E-mail: aileenmcg{at}hotmail.com
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Summary |
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According to most existing literature, the absence of an MRI lesion is generally associated with poorer prognosis in resective epilepsy surgery. Delineation of the epileptogenic zone (EZ) by intracranial recording is usually required but is perceived to be more difficult in ‘MRI negative’ cases. Most previous studies have used subdural recording and there is relatively less published data on stereoelectroencephalography (SEEG). The objective of this study was to report the experience of our group in using SEEG in presurgical evaluation, comparing its effectiveness in normal and lesional MRI cases. One hundred consecutive patients undergoing SEEG for presurgical assessment were studied. Forty-three patients out of one hundred (43%) had normal MRI and 57 (57%) had lesional MRI. Successful localization was achieved with no difference between these two groups, in 41/43 (95%) normal MRI and in 55/57 (96%) lesional MRI cases (P = 1.00). Surgery was proposed in 84/100 patients and contraindicated in 16/100 with no significant difference between lesional and MRI-negative groups (P > 0.05). At 1 year follow-up, 11/20 (55%) of those having undergone cortectomy in the MRI-negative group and 21/40 (53%) in the lesional MRI group were entirely seizure free (P > 0.05) and these proportions were maintained at 2 years follow-up. Significant improvement in seizure control (ILAE outcome groups 1–4) was achieved in >90% cases with no difference between groups (P > 0.05). Of MRI-negative cases that underwent surgery, 10/23 (43%) had focal cortical dysplasia. This series showed that SEEG was equally effective in the presurgical evaluation of MRI-negative and lesional epilepsies.
Key Words: stereoelectroencephalography (SEEG); depth electrodes; intracranial EEG; epilepsy surgery
Abbreviations: OP, opercular frontal cortex; DLPF9/46, dorsolateral prefrontal cortex, Brodmann area 9/46; PSMA, preSMA; CG 24, cingulate cortex Brodmann 24; TP, temporal pole; STG, superior temporal gyrus; Am, amygdala; MTG, middle temporal gyrus
Received March 20, 2007. Revised July 29, 2007. Accepted August 20, 2007.
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Introduction |
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TopSummaryIntroductionPatients and methodsResultsDiscussionSupplementary materialAppendixReferences |
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Current practice in epilepsy resective surgery generally relies heavily on the identification of radiologically visible lesions considered likely to be responsible for the epilepsy (Polkey, 2004
). The absence of a lesion visualized by MRI has been previously shown to relate to poorer prognosis in resective epilepsy surgery, both for temporal (Berkovich et al., 1995) and extra-temporal cases (Zentner et al., 1996; Smith et al., 1997; Mosewich et al., 2000; Jeha et al., 2007). Despite major advances in neuroimaging, MRI-negative cases still account for up to a quarter of all those presenting for pre-surgical evaluation (Berg et al., 2003). Although some authors previously considered it unhelpful to pursue presurgical assessment in this situation (Scott et al., 1999), it is however increasingly recognized that certain MRI-negative cases, while among the most challenging in terms of presurgical assessment, are indeed surgically treatable with satisfactory and sometimes excellent outcomes (Alarcon et al., 2006). This has been highlighted in a number of recent series (Cukiert et al., 2001; Siegel et al., 2001; Hong et al., 2002; Chapman et al., 2005; Cohen-Gadol et al., 2005; Lee et al., 2005; Alarcon et al., 2006). The possibility of avoiding invasive monitoring in certain cases of MRI-negative focal epilepsy has been proposed (Wennberg, 2005), particularly in carefully selected cases of temporal lobe epilepsy (Sylaja et al., 2004) and the ultimate goal may indeed be to achieve ‘totally non-invasive investigation’ in as many patients as possible (Knowlton, 2004). However the need for intracranial recording in the vast majority of MRI-negative cases is generally accepted (Lee et al., 2005). Successful determination of the epileptogenic zone (EZ) is generally considered to be more difficult in MRI negative cases, which is almost certainly a contributing factor to the poorer surgical outcome observed in many (Siegel et al., 2001; Blume et al., 2004). Most recent studies have been based on the majority of patients being investigated with invasive monitoring using subdural grids, subdural strips or a combination of subdural recording and some depth electrodes. The majority of these previous series of MRI-negative cases focus on those patients who were ultimately selected for surgery, that is, those in whom localization by these means of intracranial recording was successful; there is therefore a relative paucity of data on the overall yield of intracranial exploration in such cases.
Stereoelectroencephalography (SEEG) (Bancaud et al., 1965; Talairach et al., 1974; Chauvel et al., 1987) differs in certain respects from other intracranial recording methods such as subdural grids. In particular, deep structures and buried cortex, which are not readily accessible by subdural or cortical methods of recording, can be accessed, and EEG data is obtained simultaneously from superficial and deep brain structures. As the precise position of each electrode contact is determined, a dynamic three-dimensional temporo-spatial picture of epileptic activity may be reconstructed. This aspect makes SEEG ideally suited to the study of the relations between structures involved in seizure production and propagation, and, building on the initial concept proposed by Bancaud et al. (1965), has made possible the development of the now widely accepted network model of seizure organization (Chauvel et al., 1987; Wendling et al., 2003; Bartolomei et al., 2005). From this point of view the role of SEEG in presurgical assessment continues to evolve (Bartolomei et al., 2005 [1]). The SEEG exploration is well tolerated by the majority of patients and overall complication rates of SEEG are reported as being of the order of 5% (Guenot et al., 2001; Cossu et al., 2005). This compares similarly to recent studies using predominantly subdural mats or strips (Alarcon et al., 2006), and is somewhat less than studies of subdural grids showing overall complication rates of around 13% even for recent series from a major centre (Hamer et al., 2002). The perception by some authors that depth electrodes are ‘more invasive’ than subdural methods of recording (Alarcon et al., 2006) (and therefore less desirable than subdural recording) could therefore be questioned.
The SEEG method was developed before the era of magnetic resonance imaging and as such the original cases explored were indeed ‘MRI-negative’ as often no structural imaging was available. We wish in particular to pose the question of whether SEEG is equally as effective in MRI-negative cases as in cases with lesional MRI. Our aim is to report the experience of our group in using SEEG in the context of pre-surgical evaluation, examining the clinical usefulness of this method in localizing the epileptogenic zone, influencing clinical decision-making regarding surgery, and subsequent surgical outcome.
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Patients and methods |
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From February 2000 to May 2006, 100 consecutive patients underwent SEEG in the Epilepsy Unit, Hôpital de la Timone, Marseille, France. This centre is specialist in surgical assessment and receives tertiary referrals from other epilepsy surgery centres as well as direct referrals from primary and secondary care centres. All of these patients were referred for consideration of surgical treatment for drug-resistant partial epilepsy.
Prior to selection for SEEG, a phase of thorough non-invasive pre-surgical assessment was carried out, including detailed clinical history focussing particularly on seizure semiology, and a period of surface video-electroencephalographic (EEG) recording, to permit analysis of habitual seizures and interictal EEG. All patients underwent MRI that was interpreted by experienced neuroradiologists as well as being reviewed by the epilepsy team.
The MRI specifications evolved during the study period. From 2000 to 2005, the MRI protocol consisted of: transverse diffusion images, transverse T2-weighted images, coronal T1-weighted inversion recovery images, coronal fluid-attenuated inversion recovery (FLAIR) images and a three-dimensional T1-weighted acquisition (Raybaud et al., 2001). Acquisition plans were referred to the bi-hippocampal plane for the transverse acquisitions and to the AC–PC plane for the coronal and axial acquisition. Reconstructions of the 3D T1 images were adapted to the type of epilepsy. MRI examinations were performed on a 1.5-Tesla Symphony machine (Siemens Medical Systems, Erlangen, Germany), with a 4-channel head coil being used from 2000 to 2005; from January 2006 onwards a 12-channel head coil was used. In this latter part of the study period the multi-channel head coil allowed the use of matrix acquisition, isotropic 1 mm 3D T1 images, with reasonable acquisition time especially for inversion-recovery, FLAIR and 3D sequences (overall MRI examination lasting approximately 25 min).
A different neuroradiologist was responsible for overseeing technical parameters and for interpreting the images before and after August 2004.
Functional neuroimaging was also performed in all cases, including single photon emission computerized tomography (SPECT) and/or positron emission tomography (PET). Some patients also underwent magnetic resonance spectroscopy (MRS) (Guye et al., 2005) and/or functional MRI with language activation (fMRI). In 32/43 (74%) of the MRI-negative and 38/57 (66%) of the lesional MRI cases, high-resolution EEG (HR-EEG) with source localization was carried out; some patients also had magnetoencephalography (MEG) within the context of a research protocol. Neuropsychology assessment was routinely performed.
We identified patients as ‘MRI negative’ from data collected retrospectively and prospectively in a database. This group was defined as those patients in whom standard quality structural cerebral MRI as defined above was considered to be normal by the neuroradiologist and the epilepsy team, at the time of decision to pursue invasive recording. This included re-review of standard MRI and/or repeated imaging in the light of obviously focal abnormalities on functional imaging or after video-EEG recording and the assumption made about the likely EZ location. The obvious limitations of the term ‘MRI-negative’ are acknowledged and will be discussed later.
Forty-three of the 100 cases were thus considered to have normal MRI and 57/100 to have lesional MRI.
Most cases also underwent additional morphometric analysis of cortical anatomy performed using raw MRI data within a computer model research tool (Mangin et al., 2004), at the time of planning the electrode implantation. In some this data pointed to the possibility of a subtle cortical anomaly, in which cases the planned SEEG implantation took account of this. Research using this as yet unvalidated tool is ongoing and more detailed descriptions of these cases will be reported separately at a later date. In the course of comprehensive presurgical evaluation, non-invasive investigations were therefore directed at obtaining as much information as possible that might help with formulating the eventual hypotheses of seizure organization, including the extensive search for any lesion that might be related to the epileptogenic zone.
Patients were selected for SEEG exploration depending on the conclusion following non-invasive investigations: where the ensemble of non-invasive data led to the formulation of a single hypothesis regarding the likely localization and extent of the EZ, and where no contraindications were present, surgery was carried out directly without invasive recording. Indeed of all cortectomies performed for epilepsy in the same time period, approximately two-thirds were carried out without prior SEEG exploration (the majority of these being ‘lesional MRI’ cases). However where a surgical decision was not able to be made based purely on non-invasive data (in other words where non-invasive data were unable to distinguish between 2 or more clearly formulated hypotheses), SEEG exploration was proposed, with the planned electrode implantation designed to refute or confirm these hypotheses. SEEG was thus performed on 
20% of all patients undergoing video-EEG recording in the context of possible pre-surgical evaluation during this time period. This step of patient selection for SEEG and planning of electrode position, based on the hypotheses formulated from all available non-invasive data, forms a crucial part of the investigation process and likely determines to a large extent the eventual likelihood of successful exploration.
All patients gave their informed consent prior to exploration. SEEG recordings were performed using intracerebral multiple contact electrodes (10 to 15 contacts, length: 2 mm, diameter: 0.8 mm, 1.5 mm apart) placed intracranially according to Talairach's stereotactic method (Talairach et al., 1992). The positioning of electrodes was established in each patient based upon available non-invasive information and hypotheses about the localization of the epileptogenic zone. The implantation accuracy was peri-operatively controlled by telemetric X-ray imaging. A post-operative computerized tomography (CT) scan without contrast was used to verify the absence of bleeding and the location of each recording lead. Following the recording period of 3–9 days, intracerebral electrodes were then removed and an MRI performed, permitting visualization of the trajectory of each electrode. Finally, CT-scan/MRI data fusion was performed to anatomically and precisely locate each contact along the electrode trajectory (see Bartolomei et al., 2004 for further description).
Statistical analysis was performed in order to compare the data between the two groups using an analysis of variance (ANOVA) for quantitative data and Chi square (or Fisher's exact test when appropriate) for qualitative data. A P-value <0.05 was considered to be statistically significant.
Follow-up information was determined from out-patient visits, patient telephone calls and telephone calls to referring physicians.
Localization and organization of epileptogenic zone as defined by SEEG
The EZ is defined as the region of primary organization of seizures (Bancaud et al., 1965). Seizure onset recorded using SEEG is often characterized by a high frequency low amplitude rapid discharge (beta and gamma range) (Bancaud et al., 1965; Wendling et al., 2003), often preceded by changes in pre-ictal activity (repetitive spikes and/or slow wave activity in the same region) (Gavaret et al., 2004), and followed or not by more clonic activity. However other patterns of ictal discharge also exist. The temporal relation of the electrical and clinical changes is crucial, in that by definition ictal discharge always occurs prior to the onset of clinical ictal symptoms and signs, in order to be confident that the region of seizure onset has been correctly identified. Where a seizure occurs without clear SEEG evidence of an ictal discharge preceding the first clinical sign, it can thus be concluded that no electrode has been placed within the appropriate structure involved in the EZ. In some such circumstances the EZ cannot fully delineated.
Surgical strategy based on SEEG findings
Identification of the eventual cortical region to be resected may be a complex process, requiring consideration of the whole electroclinical picture (non-invasive and invasive data). This takes account of not only the EZ as defined by SEEG but also the irritative zone (IZ) (characterized by the region of interictal spikes as well as consideration of PET and SPECT data) and the lesional zone (LZ) (characterized by EEG features of interictal slow wave activity, and also reflected in MRI, PET and SPECT abnormalities). Definition by SEEG is clearly dependent upon the position of electrodes, the sampling of particular brain regions and systems having been chosen according to the hypotheses formulated following the non-invasive phase of assessment. The planned resection is informed by the exact position of SEEG electrodes, which are stereotaxically placed and whose location can be reconstructed using the patient's 3D MRI. A zone or region is not defined by a single electrode; estimation must be made of the extent of activity, based on the activity in adjacent electrodes and knowledge of the electrophysiological patterns of activity and propagation in different cerebral systems or structures (Talairach et al., 1974).
The ‘MRI-negative’ (n = 43) and ‘lesional MRI’ (n = 57) groups were broadly similar in the proportion of males/females, age range, duration of epilepsy and the number of electrodes implanted, with no statistically significant difference (Table 1). The MRI-negative group had proportionally more bilateral implantations (P = 0.02).
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The provisional localizations of epilepsy as determined following non-invasive investigation, and prior to SEEG, are shown in Table 2.
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The group was notably heterogeneous. The majority of MRI-negative cases were extra-temporal and frontal lobe epilepsies accounted for 60% of this group (26/43). Conversely, 40% of the lesional group consisted of temporal lobe epilepsies compared with 12% in the normal MRI group. This is likely to partly reflect the various aetiologies implicated in the different groups; for example many of the temporal lobe epilepsy cases showed some radiological evidence of temporal lesion associated with other non-concordant data, necessitating intracranial exploration.
The difference in case-mix also reflects evolution of the referral pattern to our service with more of the extra-temporal and MRI negative cases having been explored in the latter part of the study period. For example in approximately the first half of the series, only 15 of the 56 patients explored from 2000 to 2002 were considered to have normal imaging (27%). In the second half of the series however, 28/44 (64%) patients explored from 2003 to 2006 had normal imaging.
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Results |
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Localization of the epileptogenic zone (EZ) with SEEG
The results show that the vast majority of patients in the present series had successful localisation of the EZ using SEEG. This was not significantly different between the MRI-negative and lesional MRI groups (Table 3).
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The type of organization of the EZ varied between cases. Most showed unilateral organization involving several structures that were not necessarily contiguous but known to be closely functionally connected (for example, see Fig. 1). Some cases had bilateral organisation, involving bilateral homotopic regions at seizure onset. Only rarely did we observe very local organization restricted to closely neighbouring structures. By definition, no localization differed greatly from the provisional pre-SEEG diagnosis, as electrode placement had been chosen to confirm or refute the main hypotheses of EZ localization; if these hypotheses had been completely wrong then the SEEG would have been entirely non-conclusive. The localization of the EZ for each patient as determined by SEEG is given in the Tables A1 and A2 of the Appendix.
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One patient in the lesional MRI group did not have SEEG recording due to the complication of a haematoma at the time of electrode implantation (discussed later). Only three inconclusive results were obtained following SEEG recording, two in the MRI-negative group and one in the lesional MRI group. In each of these cases, although the EZ was not felt to have been adequately defined in its totality, there was however sufficient indication of multi-focality to make further attempts at SEEG localization inadvisable as eventual surgical treatment would be contraindicated. One patient in the series (normal MRI group) underwent two SEEG explorations: the first had partially localised the EZ but showed that some seizures arose outside the structures explored; the second SEEG showed conclusive evidence of a bifocal organization.
Complications of SEEG
Three complications occurred in this series of 100 cases, of which 2 led to a neurological deficit. One patient developed a local haematoma at an electrode site that caused a focal motor upper limb deficit. The deficit partially resolved over several months. One other patient developed an intracranial haematoma at the time of implantation requiring abandonment of the procedure; no further attempt was made and no SEEG recording was carried out in this single case. This patient has a residual moderate hemiparesis. The third patient developed an extradural haemorrhagic collection at the first attempt at implantation, requiring surgical intervention. This particular patient had previously had very mild functional abnormalities of blood clotting attributed to sodium valproate. A second successful implantation was subsequently performed.
Decision following SEEG
As the EZ could be satisfactorily defined in the majority of both MRI-negative and lesional MRI cases, a high yield of either focal localization or clear evidence of multi-focality leading to surgical contraindication was obtained in this series (Table 3). In some cases with a unilateral EZ, surgery was also considered contraindicated due to major involvement of functional cortex. The SEEG was therefore clinically useful in making a definitive treatment decision in the majority of cases in both groups (Table 4), allowing some form of surgical treatment to be offered in 79% of the normal MRI group and 88% of the lesional MRI group, with no statistically significant difference between these (Chi square P = 0.55).
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The surgical treatment offered depended upon the characteristics of each case. The majority of cases were suitable for tailored cortical resection. In some patients a gamma knife (GK) radiosurgical procedure was proposed (see Tables A1 and A2 for details of these cases, e.g. radiosurgical anterior callostomy; treatment of a surgically inaccessible region such as the insula; patient preference in some TLE cases).
Four patients who were considered suitable for conventional surgery subsequently chose to delay surgical treatment or declined intervention. In two of these this was due to a relative improvement in epilepsy control and in one due to other health problems; one patient no longer wished to pursue surgical treatment.
Surgical outcome
As the time course of post-operative evolution of GK treatment differs markedly from that of cortectomy, and as the numbers with adequate follow-up are small, the results of the 10 patients who underwent a GK procedure have been separated from the analysis of outcome. We therefore report outcome data on 60 of the original 100 explored patients, who have undergone resective cortectomy and in whom at least 1 year follow-up is available (20 in the MRI negative group and 40 in the lesional MRI group).
Outcome has been assessed using the International League Against Epilepsy (ILAE) classification (Wieser et al., 2001), with a score assigned at the 1-year and 2-year post-operative assessment based on presence or absence of seizures and their frequency relative to the pre-operative status. Class 1 outcome is defined as complete seizure freedom with no auras [therefore being equivalent to the ‘1a’ outcome of the Engel classification (Engel et al., 1993)]. Range of duration of follow-up was 6–55 months (mean 28 months) in the MRI negative group and 6–67 months (mean 38 months) in the lesional MRI group. The relatively shorter follow-up for the MRI-negative cases reported here relates to the fact that the majority of the MRI negative cases were explored in the latter part of the 6-year study period, many during 2005 and 2006. As this difference in follow-up period is significant between the two groups, we have chosen to compare all patients at the same post-operative time intervals of 1 and 2 years (Tables 5 and 6), accepting that the numbers are obviously smaller in the normal MRI group at the 2-year assessment. The most recent follow-up data for each patient is also listed in Tables A1 and A2 of the Appendix.
The present results indicate that there is no significant difference between the MRI-negative and lesional MRI groups, in the proportion of cases that are seizure free or that have had significant improvement following surgery (Tables 5 and 6), either at 1 or at 2 years post-cortectomy. Seizure freedom rates (Class I ILAE) are 55% in the MRI-negative group and 53% in the lesional MRI group at 1 year, while more than 90% of patients in each group have had significant improvement in seizure control (ILAE outcome groups 1–4). These proportions remain similar at the 2-year follow-up.
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Histopathology
Of 67 patients having undergone cortectomy, histopathology results were available in 23/25 MRI negative patients having undergone cortectomy and in 40/42 operated lesional MRI patients. In addition, one patient in the lesional MRI group who underwent GK radiosurgery had had a prior biopsy of the lesion (DNET). In four operated patients, histopathological analysis was not available for technical reasons (for example in cases of temporal lobe resection using aspiration of mesial structures). Histopathology data are therefore provided for a total of 64 patients.
Ten out of 23 patients of the MRI-negative group (43%) proved to have Taylor's type focal cortical dysplasia (FCD) (Table 7). Two MRI-negative patients had pathological evidence of hippocampal sclerosis despite the absence of definite imaging abnormality. Eleven MRI-negative cases showed evidence of gliotic change but no specific evidence of tumour, dysplasia or neuronal migration disorder.
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Discussion |
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TopSummaryIntroductionPatients and methodsResultsDiscussionSupplementary materialAppendixReferences |
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This study reports our group's experience of using SEEG in a consecutive series of pre-surgical epilepsy patients requiring invasive exploration, comprising a high proportion of MRI-negative cases. The present study illustrates that, combined with thorough non-invasive assessment, SEEG can be equally effective in MRI-negative and lesional MRI cases. Given the high proportion of clinically useful results obtained following SEEG, particularly the large number in whom some form of surgical treatment could be offered (79% in the normal MRI group and 88% in the lesional MRI group), it seems that patient selection for exploration in this series was satisfactory. This is an important aspect given the risks of invasive exploration as well as issues of cost-effectiveness. The patient population presented here reflects a complete series of consecutively explored patients, representative of our centre's practice as it has evolved over a 6-year period; other aspects of investigation have also necessarily evolved over the same period, notably MRI. The case-mix is therefore heterogeneous and comprises a high proportion of cases that can be considered complex (e.g. presence of extensive lesion; extra-temporal cases with normal MRI) including patients referred from other epilepsy surgery centres. Indeed, surgery had previously been considered contraindicated by other epilepsy surgery teams in 10 of the operated cases presented here. That subsequent resective surgery could be offered to the majority of patients in the present study may seem evident, given that patients were indeed selected with this ultimate goal; however such a rate of subsequent surgical treatment has not automatically been found in some previous series. For example Siegel and colleagues (2001) achieved localization of the EZ in 37/43 patients (86%), using mainly subdural grids, but only 25/43 patients (58%) were deemed to have a ‘focal’ epilepsy likely to be amenable to surgical treatment. The authors acknowledged that it is important to try to further reduce the failure rate due to ‘sampling error’ of the exploration.
In terms of surgical outcome in the present study, over 50% of the operated patients in each group became completely seizure free and over 90% of each group had significant improvement in seizure control, with no significant difference between groups. We chose to use the ILAE method of classification in which ‘Group 1’ patients are strictly seizure-free with no auras. If the Engel method of classification is used to assess outcome in the present study, 13/20 in the MRI-negative group (65%) and 24/40 in the lesional group (60%) have Class I outcome. It is indeed recognized that studies using Engel's classification tend to report higher rates of ‘seizure freedom’ than those using other forms of classification (Tellez-Zenteno et al., 2005). Comparison with other studies is therefore clearly difficult given the issues of heterogeneous patient groups, different methods of exploration and different surgical outcome measures used. We also acknowledge the importance of longer term follow-up, particularly in view of recent reports of high rates of relapse in patients with normal MRI following frontal lobe surgery (Jeha et al., 2007). Recognizing these limitations of possible comparison, the seizure freedom rate of 55% (or 65% Engel's Class I) obtained in the present MRI-negative group compares well with overall rates of between 40 and 50% patients in Engel Class I found in the majority of other studies of MRI-negative cases comprising mixed temporal and extra-temporal cases (Siegel et al., 2001; Blume et al., 2004; Lee et al., 2005; Tellez-Zenteno et al., 2005). However the high rates of seizure-freedom found in the present study for MRI negative cases are particularly notable considering that three quarters of these were extra-temporal epilepsies, as previous authors have reported poorer outcomes in MRI-negative extra-temporal cases than either ‘non-lesional’ temporal epilepsies or extra-temporal epilepsies with lesional MRI (Blume et al., 2004; Tellez-Zenteno et al., 2005; Alarcon et al., 2006). In terms of the lesional MRI group, while comparison with other studies remains difficult as mentioned above, outcome is in keeping with previous series of mixed temporal and extra-temporal cases that have undergone intracranial recording (Siegel et al., 2001; Lee et al., 2005; Alarcon et al., 2006). Lesional cases requiring intracranial exploration are a different population from those that can be operated directly. In such cases in the present study the SEEG was performed in order to define the extent of the EZ and its relation to the lesion and to decide whether an absolute surgical contraindication existed. In some, the results of the exploration were such that a partial resection was proposed with the consideration that, although the chances of obtaining complete seizure freedom were low, the possibility of significantly improving very disabling epilepsy merited surgical intervention.
Earlier SEEG series (Bancaud et al., 1965; Talairach et al., 1974, 1992) demonstrated surgical outcomes comparable with many modern series; in effect these were cases that were correctly localized independently of structural imaging abnormalities. This aspect was also recently illustrated in a study of cerebral dysplastic lesions that were successfully localized using SEEG, with the majority of patients having been investigated before the era of modern brain imaging (Chassoux et al., 2000). An important feature of earlier SEEG series was a relatively high proportion of extra-temporal epilepsy cases, in contrast to the general emphasis on temporal lobe surgery in recent decades. The role of SEEG in the context of modern pre-surgical evaluation has evolved, taking account of the great advances made in non-invasive investigations (particularly MRI), and the method is always used within the context of a full non-invasive work-up leading to clear hypotheses to be tested by intracranial electrode placement. This process of formulating and testing hypotheses is essentially the same whether or not a visible lesion is present.
The definition of ‘MRI negative’ is somewhat controversial, as the ability to detect subtle lesions varies according to the techniques used, this being itself an area of extremely rapid current development (Knowlton, 2004; Koepp and Woemann, 2005). Overall, more advanced techniques may show abnormalities in around half of patients in whom conventional MRI is negative, but such abnormalities may not be concordant with other patient data (Koepp and Woermann, 2005). In addition, lack of large series of surgical outcome data means that the clinical implications of advanced imaging techniques, when used to identify potentially operable lesions in epilepsy patients with conventionally normal imaging, are somewhat unclear: ever more sensitive imaging methods carry the risk of increasingly identifying clinically innocuous lesions for which surgery may be unhelpful or even detrimental (Koepp and Woemann, 2005) and results must always be interpreted in the light of the clinical picture and other investigation findings. There are therefore likely to be natural limits to the ability of better imaging techniques alone to improve epilepsy surgical outcome and the need for invasive recording in certain cases is likely to persist. Better knowledge of seizure organisation has been suggested as an essential step to future progress in epilepsy surgery (Bartolomei et al., 2005 [1]; Luders and Schuele, 2006). In addition clearer indications of whether some cases are better suited to certain methods of exploration could help improve patient selection for invasive exploration.
It is of interest that 43% of the MRI-negative cases for whom histopathology results were available showed focal dysplasia, as it is well-known that small dysplastic lesions may be difficult to detect using conventional high-resolution MRI (Duncan, 1997; Lee et al., 2001; Knowlton, 2004; Lüders and Schuele, 2006). Several previous studies have found a high incidence of cortical dysplasia in patients with normal MRI who have subsequently been operated (Hong et al., 2002; Cossu et al., 2005; Lee et al., 2005; Nobili et al., 2006; Jeha et al., 2007). All cases of cortical dysplasia in the present study, whether associated or not with a visible lesion, had significant improvement in seizure frequency following surgery. Indeed of the eight patients with focal cortical dysplasia and adequate follow up in the MRI-negative group, 6/8 were seizure free at 1 year. Of these eight normal MRI cases with FCD, seven had frontal lobe epilepsy and one had occipito-temporal epilepsy. While these numbers are small, these results are in marked contrast to a recent study of operated FLE cases explored using subdural grids (Jeha et al., 2007), in which 11/12 patients with normal MRI plus malformations of cortical development (MCD) relapsed following surgery (the majority relapsing within the first six post-operative months), thus leading to the authors’ conclusion that such patients formed the group with the overall worst surgical prognosis. The results of the present study may therefore offer an alternative to this rather pessimistic view. Our findings seem much closer to the findings of an Italian SEEG study (Nobili et al., 2006), which found very good rates of persistent seizure freedom in a group of frontal lobe epilepsy patients: of nine who had normal imaging and evidence of dysplasia on histopathology, six became seizure-free following surgery. It is known that dysplasias are often located in regions that are difficult to satisfactorily record using subdural techniques, such as mesial cerebral structures and the fundus of sulci, and the advantage of SEEG in permitting direct intralesional recording in such cases has been documented (Chassoux et al., 2000). In our cases of focal dysplasia, characteristic interictal surface and depth EEG abnormalities were often present, in keeping with previous observations (Chassoux et al., 2000; Gavaret et al., 2006; Lüders and Schuele, 2006). Finding better ways of identifying the group of likely radiologically ‘invisible’ cortical dysplasias may therefore represent a reasonable target in terms of future study, and the particular role of SEEG in exploring this group merits further study.
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Supplementary material |
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TopSummaryIntroductionPatients and methodsResultsDiscussionSupplementary materialAppendixReferences |
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Supplementary material is available at Brain online.
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Appendix |
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TopSummaryIntroductionPatients and methodsResultsDiscussionSupplementary materialAppendixReferences |
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Acknowledgements |
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The authors would like to thank Professor Charles Raybaud, Neuroradiology Department, Hôpital de la Timone, Marseille for his work in MRI interpretation. Aileen McGonigal gratefully acknowledges financial support received from the Glasgow Neuroscience Foundation and the European Federation of Neurological Societies as well as an Entente Cordiale bursary.
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References |
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TopSummaryIntroductionPatients and methodsResultsDiscussionSupplementary materialAppendixReferences |
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