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Purpose: Video electroencephalography (vEEG) monitoring of patients with unilateral mesial temporal sclerosis (uMTS) may show concordant or discordant seizure onset in relation to magnetic resonance imaging (MRI) evidence of MTS. Contralateral seizure usually leads to an indication of invasive monitoring. Contralateral seizure onset on invasive monitoring may contraindicate surgery. We evaluated long-term outcome after anteromesial temporal lobectomy (AMTL) in a consecutive series of uMTS patients with concordant and discordant vEEG findings, uniformly submitted to AMTL on the MRI evidence of MTS side without invasive monitoring.
Methods: We compared surgical outcome of all uMTS patients undergoing vEEG monitoring between January 1999 and April 2005 in our service. Discordant cases were defined by at least one seizure onset contralateral to the MRI evidence of MTS. Good surgical outcome was considered as Engel's class I. We also evaluated ictal SPECT concordance to ictal EEG and surgical outcome.
Results: Fifty-four patients had concordant (C) and 22 had discordant (D) scalp EEG and MRI. Surgical outcome was similar in both groups (C = 74% versus D = 86%). Duration of follow-up was comparable in both groups: C = 56.1 ± 20.7 months versus D = 59.8 ± 21.2 months (p = 0.83, nonsignificant).Discordant single-photon emission computed tomography (SPECT) results did not influence surgical outcome.
Discussion: Surgical outcome was not influenced by contralateral vEEG seizure onset or contralateral increased flow on ictal SPECT. Although vEEG monitoring should still be performed in these patients, to rule out psychogenic seizures and extratemporal seizure onset, a potentially risky procedure such as invasive monitoring may not only not be indicated in this patient population, but may also lead to patients erroneously being denied surgery.
Unilateral mesial temporal sclerosis (uMTS) is a surgically remediable syndrome (McIntosh et al., 2001). When presurgical video electroencephalography (vEEG) yields concordant data—electrographic seizure onset on the same side of the lesion—patients are referred for surgical treatment without further testing. Problems arise when noninvasive vEEG monitoring data shows EEG seizure-onset contralaterally to the magnetic resonance imaging (MRI) evidence of MTS (Williamson et al., 1993; King et al., 1997; Diehl & Lüders, 2000).
Discordant vEEG-MRI data may be associated with worse postoperative seizure control (Jack et al., 1992; Schulz et al., 2000), but this is not a consistent finding (Hirsch et al., 1991; Sirven et al., 1997). Discordant MRI-vEEG data on presurgical evaluation in uMTS can indicate either a contralateral structural epileptogenic abnormality, not detected by MRI (Babb, 1991) or false vEEG lateralization, resulting from rapid contralateral ictal activity spread, not necessarily determining a worse surgical outcome (Mintzer et al., 2004). Different interpretations of this phenomenon may influence surgical decision in these cases. Ictal SPECT studies could contribute to address ictal vEEG false lateralization.
uMTS patients with discordant MRI-noninvasive vEEG data usually undergo invasive monitoring to determine seizure onset side (Diehl & Lüders, 2000; Spencer, 2002). If contralateral seizure onset is seen in invasive studies, surgery may be contraindicated (Lieb et al., 1981; So et al., 1989; Hirsch et al., 1991; Sirven et al., 1997; Diehl & Lüders, 2000). Resective surgery on the MTS side, regardless of discordant MRI-vEEG data is also a justifiable option, since lesion resection is the most important prognostic factor for a seizure-free outcome (Berkovic et al., 1995).
We compared long-term surgical outcome in a consecutive series of uMTS patients with concordant and discordant MRI-noninvasive vEEG monitoring, uniformly submitted to temporal lobe resection on the lesion side, without invasive studies. We also analyzed the contribution of ictal SPECT studies in predicting surgical outcome in vEEG-MRI discordant cases.
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Mesial temporal lobe epilepsy (TLE) associated with HS is a surgical remediable syndrome, with 64%–93% (McIntosh et al., 2001) patients being rendered seizure-free after standard anteromesial temporal lobectomy. The MRI finding of uMTS is a potent predictor of surgical success in patients with medically refractory mesial TLE (Baulac et al., 1994; Berkovic et al., 1995). There is a high concordance of MRI, interictal and ictal EEG data in these cases (Cascino et al., 1996). In cases where presurgical evaluation indicates concordant MRI, interictal, and ictal EEG findings, surgery is indicated, with good surgical outcome, obviating invasive monitoring studies. Difficulties arise when noninvasive vEEG monitoring, and to a lesser extent, interictal EEG findings yield discordant MRI and electroencephalographic data. In approximately 3%–19% of MTS cases, noninvasive vEEG recordings show contralateral, bilateral, or ambiguous seizure onset (Williamson et al., 1993; Ebner & Hoppe, 1995; King et al., 1997). In some centers, patients with discordant ictal EEG and MRI data are submitted to chronic semiinvasive or invasive vEEG monitoring with ovale foramen, depth, or subdural electrodes. Patients with discordant vEEG and imaging data after invasive monitoring may be denied surgery for fear of poor surgical results.
Surgical results in patients with discordant findings on MRI and scalp vEEG is difficult to ascertain. Although some studies have suggested a worse surgical outcome compared to concordant cases (Jack et al., 1992; Schulz et al., 2000; Tonini et al., 2004), other studies suggest that surgical result may not be worse in this group (Hirsch et al., 1991; Baulac et al., 1994; Sirven et al., 1997; Schiller et al., 1998; Hardy et al., 2003; Mintzer et al., 2004; Jeong et al., 2005). Most studies that suggest a poorer outcome in the discordant group have included patients that had not undergone MRI, nonlesional TLE cases, TLE secondary to other etiologies, bilateral MTS, as well as cases with extratemporal seizure onset (Jack et al., 1992; Schulz et al., 2000; Tonini et al., 2004). Moreover, all studies incur in a selection bias, in which patients with discordant data after invasive monitoring could be denied surgery. Thus, surgical outcome in patients with discordant ictal EEG-MRI data cannot be precisely evaluated by these studies.
Determination of ictal EEG onset may be controversial, since subtle initial ictal changes can be subjective and examiner-dependent. In this study, we found a higher proportion of discordant cases than what is usually reported in other studies. If we had used a more stringent criterion to define discordant cases, as those where both initial ictal EEG changes and full ictal development were seen contralaterally to the MRI evidence of MTS in at least one seizure, results would not be different. Of the 13 of 22 cases in the discordant group fulfilling this more stringent definition (Table 2, cases 3, 4, 7, 10, 11, 12, 13, 16, 17, 18, 20, 21, and 22), all cases had good surgical outcome (Engel's class Ia, nine cases; class Ib, two cases; and class Ic, two cases). Our subgroup analysis further corroborated the fact that the degree of discordance, measured by the proportion of contralateral onset seizures in each patient does not appear to indicate that a particular subgroup has a worse surgical outcome. The three patients with an unfavorable surgical outcome appeared to be randomly distributed in three different discordant subgroups. Of note, the only discordant case with the most unfavorable surgical outcome (case 8, Engel's class IVa)—the other two unfavorable outcome discordant patients were classes IIa and IIc (almost without seizures)—was classified in the least discordant group, with only one seizure originating contralaterally to the MRI evidence of MTS. Also, if we consider the most discordant subgroup of patients in the ictal SPECT analysis (ictal-EEG during SPECT injection seizure and SPECT discordant from MRI lesion side), all three cases in this category had a good surgical outcome (Engel's class Ia in all cases).
In this series, the finding of bilateral concordant or even discordant interictal EEG activity did not influence outcome. Although the discordant interictal EEG subgroup had a slightly worse surgical outcome, this difference was not statistically significant.
In our study, we selected a homogeneous group of uMTS patients, without other MRI lesions or extratemporal ictal onset. Groups differed only in the presence or absence of seizure onset in contralateral temporal region on surface EEG. All patients were submitted to a standard surgical procedure, by the same surgeon, regardless of concordant or discordant noninvasive vEEG data. Although five patients decided not to undergo surgery and seven patients were operated by different surgeons, and thus not included in this study, this did not lead to a selection bias, since the proportion of concordant and discordant cases was similar in the operated and not operated groups: 2 of 12 (16.7%) discordant cases in the not operated cases, compared with 22 of 77 (28.6%) of discordant cases in the study group.
Contralateral seizure onset may represent a false lateralization, where scalp electrodes detect contralateral spread of ictal activity (“burned-out hippocampus theory”) (Mintzer et al., 2004). Conversely, this may indicate true seizure onset in the contralateral temporal region, arising from structural lesions not identified by MRI on the contralateral mesial temporal structures (Babb, 1991; Diehl & Lüders, 2000). Surgical outcome should be poorer in the discordant group in this latter scenario.
In our study, surgical outcome was similar in both groups, suggesting that false lateralization is probably the underlying scenario in most discordant cases. In this study, discordant cases had even a slightly (12%) better surgical outcome than concordant cases. Both groups were very similar in terms of demographic and clinical data, suggesting that they represent homogeneous samples of the larger population of patients with unilateral MRI evidence of MTS. We did not perform a more detailed volumetric or histopathologic analysis to evaluate if discordant cases are associated with a more severe hippocampal volume loss or cell loss.
Discordant cases may display a denser interhemispheric connection, possibly through the anterior commissure, that might contribute to a faster interhemispheric spread of ictal activity in these cases, leading to false lateralization.
With our current sample size of 77 patients, the study was only powered to detect a 37% difference in outcome between groups. In order to achieve an 80% power, a sample size of approximately 240 patients would be needed. However, the discordant EEG group had an excellent surgical outcome, well within the range of concordant uMTS cases, making a type II error less likely. Another strength of this study is that both concordant and discordant groups were followed for a mean of approximately five years, making it unlikely that good outcome might represent an initial, but not sustained surgical result over time.
Ictal SPECT studies could noninvasively solve the issue of false lateralization: ipsilaterally increased flow, despite contralateral seizure onset would suggest false lateralization. Conversely, contralaterally increased flow, discordant with the MRI evidence of MTS could suggest true contralateral seizure onset. Our data suggests that this is not the case: despite relatively low numbers, surgical outcome did not differ in cases where ictal SPECT showed increased flow ipsi or contralaterally to the lesion. In these cases, ictal SPECT may also indicate seizure spread and not seizure onset. Although false lateralization on ictal SPECT occurs less commonly than with ictal EEG, it should not be interpreted as an indicator of poor surgical outcome in these cases.
Pathology data further supports these findings, confirming MRI diagnosis in almost all cases in both groups. The finding of HS associated with heterotopic gray matter in two cases and lack of HS in another two cases in the concordant group did not modify surgical outcome of the concordant group as a whole.
The findings in this study should not be interpreted as indicative that vEEG monitoring is not useful in patients with uMTS. Nonepileptic psychogenic seizures cannot adequately ruled out without vEEG monitoring. Also, this study did not analyze surgical outcome of patients with unilateral MRI evidence of MTS who showed extratemporal seizure onset on ictal EEG.
Memory decline can be a concern in temporal lobe resection, especially in discordant cases, where bilateral hippocampal dysfunction may occur. All our discordant cases underwent sodium amytal testing to ensure adequate memory reserve in the contralateral temporal structures. Further studies should address the risk of memory decline in concordant and discordant cases.
Our findings suggest that unilateral MRI evidence of MTS with seizure onset in the contralateral temporal region have a similar surgical success rate as fully concordant uMTS cases. Potentially risky invasive or semiinvasive studies (Diehl & Lüders, 2000; Velasco et al., 2006) not only may not be indicated in these cases, but it also may lead to erroneous contraindication of a surgical procedure with a high success rate in this subgroup of mesial TLE patients with discordant ictal EEG and MRI findings.