Coherence analysis using MEG provides superior lateralization of a site of epileptogenicity in cases of TLE when compared to the more commonly used ECD method. The analysis is not limited by an absence of epileptiform activity during the course of the study and, because of its ability to identify higher synchronization of activity in the seizure onset zone (Arnhold et al., 1999
; Mormann et al., 2000
; Bartolomei et al., 2004
), the method is applicable in all patients undergoing investigation for partial epilepsy. In fact, one third of patients in this study were excluded from analysis by the ECD method for lack of epileptiform activity. Identification of class I outcomes using either method was similar when these indeterminate results were excluded from analysis in the case of the ECD method. When included, the ability of the ECD method to identify a class I outcome fell from 87% to 50%. Similarly, because of the indeterminacy problem, the sensitivity of the ECD methodology was found to be 41% as compared to 73% with coherence analysis. The specificities for each method are low indicating that neither provides sufficient exclusionary information in assessing the laterality of focal temporal epileptogenicity.
Although coherence analysis correctly identified an Engel class I outcome in 20 (67%) of 30 cases, it incorrectly identified a putative site of epileptogenicity corresponding to that determined by standard investigation in three cases (7, 10, and 21) that had achieved suboptimal results (i.e., Engel class II, III) assuming that a sufficient resection had been performed. Furthermore, it provided misleading information regarding the laterality of epileptogenicity in another six cases that achieved optimal results (i.e., Engel class Ia). In a large retrospective review of 455 patients with partial epilepsy of both temporal and extratemporal origin, an average sensitivity of MEG for specific epileptic activity, using the ECD method was 76.3% with the exclusion of indeterminate cases (Stefan et al., 2003
). This was not, however, a final confirmation of epileptic focality amenable to surgical resection and, therefore, was not fully verifiable in accordance with surgical outcome. Of 109 patients with TLE who did undergo resection in the latter study, ECD analysis identified the corresponding lobe in 94 (86.2%) cases. Engel class I and II categories were grouped together and regarded as a successful outcome and no numerical distribution between the categories was provided. A similar grouping of class I and II outcomes in the current study yields six more cases, four with class Ib-d and two with class II outcomes, for a total of 28 cases. Of this total, ECD analysis achieved a match rate of 64% and coherence analysis, 79%. Apart from the disparity in study populations (i.e., 28 vs 109 cases), the relative distributions of class I and II outcomes and the manner of case selection may account for differences between the two studies.
A limitation of this MEG study was the lack of information regarding coherence variability during different states of arousal (i.e., wakeful, drowsy, asleep) and the lack of standardization of measures in these states. Interictal spike discharges are more common during drowsiness and light sleep. One would expect the yield of ECD MEG analysis and perhaps the magnitude of coherence to be greater in the latter condition. Intersubject variability in arousal during recording may have affected ECD measures adversely to bring about lower sensitivity in this study. Run-to-run variability, however, did not seem to bear this out. Moreover, coherence analysis remained the application with the greater yield for the same interval of recording. Postictal recording with its greater likelihood of spike discharge may be a further consideration in this argument that would ostensibly improve yield with both analyses (Oishi et al., 2002
From a clinical perspective, the ability to salvage data in the absence of concurrent epileptiform activity bears considerable practical importance; however, its place in the investigation of TLE must be examined alongside other applications serving to do the same. Innovative postprocessing of MR imaging applications and electrographic approaches have been developed in order to better establish the laterality of TLE preoperatively. Volumetric assessment of the medial temporal structures (Jack et al., 1990
; Cendes et al., 1993
; Kim et al., 1994
) has been used, for some time, as a quantitative measure to establish the laterality of an epileptic focus as volume reduction of the hippocampus, in particular, has been shown to coincide with the location of the focus. However, in 15 – 30% of mTLE cases, no distinct asymmetry in volume can be established (Jackson et al., 1994
; Paesschen, 1997
; Carne et al., 2004
). An increase in signal intensity in both T2-weighted and fluid-attenuated inversion recovery (FLAIR) images (Jack et al., 1996
) has also provided lateralizing information and a recent study of mean and standard deviation of FLAIR signal intensity (Jafari-Khouzani et al., 2010
) has indicated accurate lateralization in 98% of proven mTLE cases. There is evidence, however, of cases in which MTS was identified by MR imaging but no mTLE was found. This has been specifically noted in familial mTLE in which upwards of 34% of asymptomatic first degree relatives of patients with mTLE were found to have MTS (Kobayashi et al., 2003
). The application of texture analysis in MR imaging to mTLE has also shown promise over that of volumetry (Yu et al., 2001
; Bonilha et al., 2003
; Jafari-Khouzani et al., 2010
) The apparent diffusion coefficient (ADC) is significantly reduced in mTLE with diffusion-weighted MR imaging (O'Brien et al., 2007
); however, in certain cases without distinct lateralizing features identified by conventional MR imaging, no difference in ADC has been identified between the temporal lobes (Wehner et al., 2007
). Other imaging modalities, particularly functional studies, have therefore been used in a complementary fashion to arrive at a more accurate predictive standard in the case of TLE. Subtraction ictal SPECT coregistered to MRI (SISCOM) may be of use in localizing epileptic foci (Spanaki et al., 1999
), sometimes obviating the need for intracranial electrode placement (Tan, 2008
). Positron emission tomography (PET) of serotonin (HT1A
) receptor uptake binding may be reduced in TLE (Didelot et al., 2008
) even in the absence of distinct pathological change (Merlet et al., 2004
). ECD source localization has been adopted in a similar capacity with favorable postoperative outcomes reported when the resection volume included or was proximate to ellipsoidal volumes containing a cluster of dipoles (Fischer et al., 2005
The use of MEG in the investigation of TLE does offer unique information toward the lateralization of the epileptic focus in cases where ambiguity exists in determining which of the two temporal lobes is epileptogenic after completion of standard study. This appears to be particularly the case with the application of coherence analysis as was seen with significant interhemispheric differences in coherence in the present study. A match rate of 76.9% was achieved for class I outcomes. However, in TLE cases without MTS, of which there were 19 in this study, a match rate of only 58% was achieved. With coherence analysis identified as the better predictor of laterality in TLE, its overall sensitivity may be established in a prospective study that includes all clinical outcomes. Additionally, further insight might be obtained in specific cases where coherence analysis fails to adequately achieve acceptable lateralization and disagrees with the accrued data from standard investigation that has suggested otherwise (i.e., case 14). Two cases were noted in our study population to have had particularly poor outcomes (i.e., class IIIa). Each had widespread hemispheric changes on MR imaging. In case 10, coherence analysis identified network activity more distributed in the frontotemporal region and in case 14, symmetric bitemporal coherence was apparent. Such cases may indeed deserve closer scrutiny in order to avoid suboptimal postoperative outcomes.
At the present time, there is no single investigational modality that can reliably identify the location of an epileptic focus in those cases of TLE in which there appears to be ambiguity regarding the side of ictal onset. In fact, each modality, including MEG, may provide misleading information that improperly lateralizes the focus. With continuing improvements in these individual applications, however, and their proper use in a complementary fashion, more dependable lateralization of temporal lobe epileptogenicity in the more challenging cases may be possible. The application of MEG coherence analysis offers advantages over that of the ECD method but still falls short of providing the needed predictive strength for concluding laterality. Progress along these lines, however, may ultimately arrive at an investigational model sufficiently robust to circumvent the need for extraoperative ECoG in the majority of patients.