In this study, we evaluated cortical thinning using surface-based analysis in two groups of MTLE patients defined by the distribution and orientation of their interictal spike ECDs. This is the first study that investigates cortical thinning in relation to electrophysiological parameters in patients with epilepsy. We found that there is significant cortical thinning in patients with posterior-lateral/widespread source distribution as compared to patients with antero-medial source distribution.
There were two types of dipole distributions in our study: localized and distributed. This distinction is a modification of the classification proposed by Ebersole (Ebersole, 1991
; Ebersole et al., 2008
). Patients with frequent spikes and a varied dipole orientation demonstrate a widespread pattern of cortical thinning that goes beyond the temporal lobe, with pronounced atrophy of structures of the limbic system as well as frontal, and parietal lobe. These results are consistent with previous studies that showed that patients with antero-mesial dipole localization have limited propagation of epileptic discharges and therefore have good surgical outcomes, whereas patients with widespread dipole distribution have widespread cortical involvement of pathophysiology and may have an unfavorable surgical outcome (Iwasaki et al., 2002
). Based on these findings, grouping patients based on source dipole distribution and orientation demonstrates important differences in the pathophysiology of MTLE. Temporal lobectomies in these patients may potentially result in a poorer surgical outcome since they have more distant cortical involvement, even though the clinical manifestation of patients in both groups is similar. Future studies with larger numbers of patients and examination of postsurgical clinical information are needed to test this hypothesis, as not all patients of our study subsequently underwent surgery. Furthermore, a spatial correlation between scattered ECDs and the multifocal cortical thinning in group B was not performed due to the relatively low number of patients.
Our study extends the results of previous studies that suggested MTLE affects not only mesiotemporal structures but also a more distant cortical network (Duzel et al., 2006
; McDonald et al., 2008
; Mueller et al., 2009
). One possible explanation for distant cortical abnormality is the existence of dual pathology that includes both an extrahippocampal structural lesion as well as hippocampal sclerosis. Due to the strict selection according to seizure semiology and the absence of neocortical structural abnormalities in the MRI scans, additional lateral lesions appear unlikely in our patients. Possible dual pathologies are furthermore believed to be of little importance in MTLE (Spencer and Huh, 2008
). An alternative possibility is that distant cortical thinning is a secondary effect of recurrent seizures or status epilepticus, which was accounted for by using duration of epilepsy and age as a nuisance regressor in the current analysis. Based on the regression, duration of epilepsy does have an effect on cortical thinning, but the cortical thinning effect remains significant for the comparison of both groups when the effect of duration and age of the patients is accounted for.
We have utilized cortical surface-based analysis in this study rather than voxel based morphometry (VBM). Cortical parcellation and reconstruction can be performed accurately and nearly automatically (Dale et al., 1999
). Cortical surface-based analysis is objectively performed by using this technique, and the use of a spherical coordinate transformation offers more accurate gyral alignments across subjects than volumetric measurements, which improves the ability to compare cortical thicknesses across groups (Fischl et al., 1999b
). Mueller et al. (Mueller et al., 2009
; Mueller et al., 2006
) compared two groups of MTLE patients divided by the presence or absence of HS and found no significant difference in their cortical thickness using VBM (Mueller et al., 2006
), whereas surface based analysis demonstrated a different pattern of cortical thinning in MTLE with HS in comparison to MTLE without HS (Mueller et al., 2009
). However, it was not differentiated for the affected side or the duration of epilepsy.
This study could address left TLE patients exclusively, due to low numbers of right TLE. The cortical thinning pattern in right TLE, however, has been shown to be distinct from right TLE patients (Ahmadi et al., 2009
; Bonilha et al., 2007
), which suggests that the correlation of epileptic discharges might also be different. We plan to include more right TLE patients in a future study to determine if a similar correlation of epileptic discharges and the cortical thinning exists.
In our study only three out of 19 patients had HS on MRI. This most probably reflects a selection bias in patients with MTLE referred to the MEG service prior to possible surgery. We note that MTLE patients with HS often have surgery without any further evaluation such as MEG. Since this is a retrospective study, the lack of patient with HS is a potential source of bias in our patient selection criteria. However, patients with HS also may fail surgery (Spencer and Huh, 2008
), and the causes of this failure is still unclear. We hope to include patients with HS in a future study to determine whether source analysis might also be helpful in these patients.
So far, the presence of HS is becoming recognized as a prognostic factor concerning favorable outcome after surgery (Spencer and Huh, 2008
). Our study suggests that an electrophysiological marker may be useful in the absence of gross structural lesions such as HS in predicting the anatomic extent of involvement in patients, who have clinical manifestations of MTLE. However, the presence of HS in both MEG-groups supports that the presence of HS alone may not be a solely useful parameter to subdivide MTLE patients with respect to surgical outcome, although larger numbers of patients with and without HS are needed to support this hypothesis. Neurophysiologic source analysis complements structural imaging and may have implications for the selection of patients, extent of procedures, and prediction of prognosis in patients with TLE. In conjunction with intracranial EEG recordings, the described analysis may provide additional information leading to a more informed decision regarding the likely success of resective surgery.