This study compared neuromagnetic spike localization in patients with TLE before and after surgery, and found a positive correlation between MEG spike localization and epileptogenic area. Patients without neocortical lesion showing AT localization became seizure free and spike free after ATL, whereas some patients with non-AT localization had residual seizures and/or residual spikes, although the other patients became seizure free and spike free after ATL. Patients with neocortical lesion showing lobar localization suggested that the epileptogenic area was more extensive than the MR lesion.
Correlation between postoperative seizure outcome and magnetoencephalography spikes
The present study found that AT localization of the interictal MEG spikes indicated excellent seizure outcome in patients without neocortical lesion. Previously, anterior temporal spikes in scalp EEG and MEG were found to be highly specific to medial TLE (7,18–20). Classification of temporal lobe MEG spikes into anterior temporal horizontal (ATH), anterior temporal vertical (ATV), and posterior temporal vertical (PTV) dipoles (18,19) and comparison with ECoG findings showed that dominant ATH and ATV dipoles were correlated with seizure onset from the medial temporal structures, whereas PTV dipoles were correlated with onset from the lateral temporal neocortex or nonlocalized onset. Investigation of the relation between the dipole pattern and clinical diagnosis found that patients with medial TLE showed ATH or ATV dipoles, whereas patients with nonlesional TLE (no MRI abnormalities) showed dipoles localized on the anterior medial or posterior lateral temporal lobe (20). In the present study, all five patients with AT localization, corresponding to ATH or ATV dipoles, had hippocampal sclerosis and achieved excellent seizure outcome after ATL.
The spike dipole location was not totally included in the surgical resection in our patients with AT localization. However, the patients became seizure free and spike free after ATL. The spike dipole area is not identical to the epileptogenic area, but is usually more extensive, suggesting that the MEG spikes may be a remote propagation phenomenon distant from the epileptogenic area (2,30). The epileptogenic area in patients with medial TLE may have a strong tendency to propagate medial temporal spikes over the anterior temporal lobe. Thus AT localization indicates a possible epileptogenic area in the medial temporal structures, and complete resection of the MEG spike area in the lateral neocortex may be unnecessary. No MEG spikes were detected in the medial temporal structures, possibly because of the limitations of the method, as discussed later.
Non-AT localization implies that the epileptogenic area is located in the posterior or extratemporal lobe. Posterior temporal dipoles may indicate a lateral TLE or nonlocalizable focus (18). We agree that these dipoles indicate posterior temporal activity. However, four of our six patients with posterior temporal dipoles became seizure free after ATL. Therefore, lateral temporal epileptogenicity is difficult to determine based only on the MEG spike localization. This study had a relatively small patient population with homogeneous surgical outcome [i.e., all except one patient belonged to the good-outcome group (class I or II)], so no statistical difference in seizure outcome could be identified. A longer follow-up period is needed to evaluate the actual outcome of patients with non-AT localization, because late seizure recurrence is likely in patients with hippocampal sclerosis compared with other etiologies (31,32). Patients with non-AT localization should undergo further presurgical evaluations, such as intracranial EEG, to improve the seizure outcome.
The non-AT dipoles disappeared in three patients, but persisted in the other three patients on follow-up MEG at 12 months after ATL. This result suggests two possible mechanisms generating the non-AT dipoles: remote propagation from the medial temporal structures; and extended epileptogenic area. Disappearance of the interictal spikes might be due to insufficient sampling time. However, the non-AT dipoles were obviously reduced in the two patients with excellent seizure outcome; thus we believe that the non-AT localization was caused by remote activity propagated from the medial temporal epileptogenic area, and removal of the medial structures resulted in spike disappearance. Interictal cortical spikes can be propagated from the primary leading region near the epileptogenic area to remote secondary regions (4). Interictal spike propagations from deep to superficial temporal, anterior to posterior temporal, and temporal to frontal lobes were observed in spike-averaging studies (2,3). In these cases, the leading spike preceding the most prominent non-AT dipole may be detected by intensive analysis of MEG spikes (18,19).
The persistent residual spiking in the other three patients suggests that the anterior temporal resection did not include part of the epileptogenic area (i.e., the remnant of the posterior hippocampus or other neocortical area). How this activity is associated with in situ seizure generation is unknown. The residual epileptogenicity causing the interictal spikes might not have been sufficient to cause clinical seizures in the two patients with excellent outcome (33). However, postoperative interictal spikes detected at 6 to 12 months' follow-up examination were correlated with residual seizures in previous studies (34,35). Further investigation with a longer follow-up period is needed to assess the relation of residual MEG spike with seizure outcome.
Non-AT localization was related to residual seizures after ATL in our cases 10 and 11, who both had frontal lobe dipoles. Unfavorable seizure outcome after ATL was predicted by incomplete resection of the extratemporal spike area, indicated by implanted grid electrodes (8) and scalp EEG (6). Persistent spike activity was observed postoperatively in one patient, but not in the other patient. Sampling time may have been insufficient in the latter case; thus non-AT localization, especially the coexistence of frontal spikes, may suggest unfavorable seizure outcome in patients with TLE.
The perilesional irritable area was successfully localized by MEG in our patients with neocortical lesion, as found previously (20). Additionally, we found extensive spike localization in two patients. The intracranial EEG study revealed participation of the medial temporal structures in seizure generation in both cases, and histologic examination showed coexistence of hippocampal sclerosis in one patient. Thus an extensive epileptogenic area may be suggested when a significant number of dipoles are localized remote from the lesion. Lesion localization may indicate favorable seizure outcome after lesionectomy, whereas intensive presurgical evaluations are desirable in patients with lobar localization to improve seizure outcome.
Sensitivity of neuromagnetic spike localization
MEG does not always detect all interictal spike sources of patients, because of the limited sensitivity. Radial currents to the scalp (i.e., gyral cortical activity in the lateral cortex) may not be detected by MEG (18,19). In contrast, tangential currents in the superior or basal temporal plane and temporal tip are often localized by MEG. Deep sources (i.e., medial temporal spikes) may not be detected by MEG (20,30,36). In the present study, no medial temporal dipole was localized, even in the patient with hippocampal sclerosis and excellent seizure outcome. We believe that the present MEG study detected predominantly neocortical spikes tangential to the scalp.
Short sampling time MEG may overlook interictal spikes. The recording time is limited in current MEG technology compared with conventional EEG (20,37). In this study, sufficient interictal spikes were obtained in 16 (67%) of 24 patients. This sensitivity agrees with that (73%) of the previous study of TLE (17). Oral barbiturate was used to induce the sleep state to increase interictal spike density in this study (38). However, insufficient spike sampling does not exclude the presence of epileptic activity. No interictal spike was detected by postoperative MEG in two of our three patients with residual seizures (cases 10 and 14). Induced light sleep and decreased antiepileptic medication may be useful to increase the density of interictal spikes (20).
Limitation of source-estimation accuracy in magnetoencephalography
We applied single ECD modeling, assuming that all neuronal activity can be represented as a point generator. However, this model has limited capacity to accommodate extended or multiple generators (18,19). The size of the cortical area required to generate detectable MEG spikes is unknown (18). Nevertheless, in this study, spike localization characterized the dominant irritative site for each patient, which was correlated with the postoperative findings. Thus we believe that single ECD modeling is clinically useful to localize epileptic activity.
Spike dipoles were estimated on the single-spike basis in the present study, so background brain noise might affect the source estimation accuracy. Sleep induction and the high-pass filtering technique were used to improve the signal-to-noise ratio of the spike component. We believe that these techniques provide source localization accuracy acceptable for clinical use.