In recording and analyzing multiple seizures, we found ictal MEG to be superior to scalp EEG for lateralization and localization. The eight patients’ initial ictal MEG onsets were identified by examining the spectral power in multiple overlapping bandwidths with STFT. The earliest consistent change in spectral power was then further evaluated with ICA of the signal to be certain at least one consistent source could be discerned above the background noise level. The spectral power changes in the MEG initial ictal onset could be detected even when scalp EEG did not show clear ictal onset. In most prior studies of ictal MEG localization, patients had complex partial seizures with either minimal clinical change, subtle changes such as arrest of activity, brief lapse of consciousness, or no identifiable clinical change (Stefan et al., 1992
; Manoharan et al., 2007
; Shiraishi et al., 2001
). During seizures with minimal visually observable movement, patients may nonetheless make subtle head movements that could blur source localizations if included in the ictal onset signal. Because our system recorded continuous head localization (CHL), we were able to identify precisely the time point when the patient began head movement near the clinical onset of simple and complex partial seizures. This capability allowed us to study two additional kinds of ictal events: brief tonic seizures with short time duration between ictal signal onset and movement, and seizures with focal MEG signal onset but rapid propagation to paroxysmal bilateral high amplitude diffuse discharges.
This study represents a progression in technique in analyzing ictal MEG, relying upon analysis of change in spectral power over time at ictal onset rather than at a single time point (e.g., spike peak) with a source localization algorithm. Prior studies of ictal MEG onset used the single ECD model, which can localize a single discrete source when the signal to noise ratio (SNR) is fairly high. We found ictal onset patterns varied considerably from patient to patient but included low amplitude faster frequency rhythmic discharges, the leading edge of which is more detectable using spectral analysis. In this study, we evaluated the spectral power at ictal onset to discover the frequency bandwidth that showed the earliest signal change that also demonstrated good SNR evaluated with principal component analysis (PCA) and/or independent component analysis (ICA). This bandwidth often required high pass filter setting greater than the conventional 1 Hz.
We did not find a significant difference between the ECD model and the extended source localizations algorithms that we used. The lack of difference may be because we chose to look very early in the ictal onset at the first detectable change in spectral power. At this time point the ictal source may still be fairly focal and reasonably well-modeled with the standard ECD algorithm.
Ictal MEG represents a potential advantage over interictal MEG in defining the seizure onset zone. This is particularly true in nonlesional and multi-lesional patients, which comprise a large group of children with intractable epilepsy. In pediatric intractable partial epilepsy, interictal discharges are often multifocal or diffuse; interictal MEG source localizations in these cases are often bilateral. In our study, there were three patients who had bilateral independent and diffuse interictal discharges based on MEG source localization, as well as one patient with interictal discharges with widespread sources throughout one hemisphere (see ). In these cases we found ictal MEG source localization, in addition to the other noninvasive presurgical testing, contributed to the surgical plan, whereas interictal MEG source localization would have argued more for avoidance of resective surgery or a hemispheric procedure. These results were validated by good lobar and often sublobar concordance with the SOZ determined by ICEEG.
Recent studies regarding MEG, EEG or MEG/EEG simultaneous source localization have been compared to ICEEG recordings to confirm accuracy, since the intracranial EEG is considered the gold standard (Stefan et al., 1992
; Otsubo et al., 2001a
; RamachandranNair et al., 2007
; Wheless et al., 1999
). In our patient sample, ictal MEG proved better than interictal MEG in showing concordance with ICEEG of the SOZ at the sub-lobar level. We also followed the surgery and surgical outcome as another means for estimating the predictive value of ictal MEG onset. Lobar concordance between interictal and ictal MEG resulted in excellent seizure outcome.
There are several limitations to this study. Even though we recorded and evaluated ictal MEG in 20 patients, when we applied the requirement of ECoG confirmation of SOZ and at least 6 months post-surgical follow-up, our study population became eight patients. So our overall conclusions, though very positive, must remain modest and describe potential clinical benefit of recording ictal MEG. Also the study is limited by its retrospective design. Since several noninvasive tests are used to make the surgical plan, it is not possible at this time to determine the exact contribution of ictal MEG data to the plan for the craniotomy location, grid placement or eventual resection. There may always be limitations to the value of ictal MEG onset localization, the most important of which relates to undersampling of seizures and seizure types (Sanker et al., 2005
; Gelžinienė et al., 2008
). In children with multiple seizure types and bilateral interictal MEG discharges, we demonstrated a relatively poor seizure outcome. This is a consequence of multiple factors, including the inability to safely resect the SOZs in patients with multiple seizure types, which may begin independently bilaterally or involve eloquent areas in some patients. The MEG recording length and the need for strict head immobility to establish an adequate SNR remain significant limitations, especially in the pediatric population.
We found that initial ictal MEG onset provides useful additional information for surgical evaluation. Although capturing seizures during MEG recording is challenging, the source localization for the initial ictal MEG onset is a very useful tool for presurgical evaluation for medically intractable epilepsy patients, especially in our pediatric population, many of whom had “nonlesional” epilepsy based on anatomical MR imaging. Ictal MEG demonstrated good concordance with the SOZ as defined by the current gold standards: ICEEG and surgical outcome. A prospective design in a larger number of patients may better define the role of ictal MEG in surgical planning. Further study is needed to determine the role of ictal MEG in replacing intracranial recording in selected patients.