Patients with multilobar epileptic localization that comprises the temporal lobes and surrounding areas, including the orbitofrontal cortex, the insular cortex, and the parietooccipital regions, have been described as temporal plus epilepsies (TPE) [
Despite advances in multimodal techniques which include MEG/EEG source imaging and fMRI, to define the epileptic zones we still do not have the technology to reliably identify the epileptic network without invasive data. In patients with intracranial recordings, the epileptic zone could be localized by the presence of persistent high frequency oscillations (HFOs). HFOs have been reported as excellent markers for the epileptogenic zone. Removal of cortical areas generating HFOs has been related to better postsurgical outcome than removing the seizure onset zone [
The methodology for detection of HFO and differentiation of ictal HFO versus physiological HFO is not clear. Several studies reported detection of ictal HFO with multiple band frequency analysis using different methods. One study defined ictal HFO using power spectral HFO activity during 400 ms [
The authors started using ictal HFO mapping as part of the presurgical evaluation since January 2014. We used a power spectral analysis of ictal HFO on 40-millisecond segments, synchronized with direct visualization of the standard intracranial EEG data. We compared the direct visual determination of the ictal EEG changes with the ictal HFO mapping. The surgical decision included the HFO mapping data if the epilepsy team considered resection of those areas safe and potentially beneficial for the patient.
This is a review of consecutive patients admitted to the University of South Alabama Epilepsy Monitoring Unit (SouthCEP) between January 2014 and October 2015, with suspected temporal lobe epilepsy and intracranial electrode placement to localize the epileptic zone and/or functional mapping prior resection. The typical implantation for most patients included between 30 and 64 channels including one or two 4- to 6-contact strips in the posterior orbitofrontal region, along with anterior and inferior temporal, 4- to 6-contact strips in the nondominant hemisphere, or, less commonly, a 32-contact lateral temporal grid plus anterior and inferior temporal strips in the dominant side. Additional electrodes were implanted based on noninvasive data that included scalp video EEG monitoring, scalp EEG source imaging, PET, Wada, neuropsychological testing, and 3T-MRI. Interictal and ictal EEG was recorded using the Neuvo system (Compumedics Ltd., Abbotsford, Victoria, Australia), which acquires raw data at 10 kHz and then applies a software second-order Infinite Impulse Response (IIR) Butterworth low-pass filter at 40% of the sampling frequency. For a sampling rate of 500 Hz, the resulting cutoff frequency is 200 Hz. The patient’s antiepileptic medications were stopped during the intracranial monitoring in order to record sufficient seizures.
The ictal onsets were defined by initial visual inspection characterized by a clear change from the ongoing background rhythms, not explained by artifact or physiologic changes [
The implanted electrodes positions were obtained by manual digitization of the leads using a head CT scan after implantation and later overlaid onto an image of three-dimensional (3D) reconstructed brain images using the patient’s own coregistered magnetic resonance imaging (MRI). A segment of the EEG data containing a typical seizure was then coregistered with the image data. The EEG was displayed in a common reference average montage with a constant baseline correction and filter settings (CURRY 7; Compumedics Ltd., Abbotsford, Victoria, Australia).
Fifteen consecutive intracranial subdural implanted patients, with initial diagnosis of temporal lobe epilepsy, were analyzed for presence of early ictal extratemporal involvement in addition to the temporal lobes using the HFO mapping model described above. Four of these patients showed evidence of extratemporal involvement at the onset of the clinical seizures. The clinical data and HFO findings of the four patients with evidence extratemporal involvement at the onset were summarized in Table
Clinical features, imaging correlation, and ictal HFO data.
# | Age/gender | Interictal EEG | Ictal EEG onset | 3T-MRI | Aura | Semiology | Ictal HFO mapping |
---|---|---|---|---|---|---|---|
1 | 24 y/F | R-frontal and temporal spikes | R-temporal rhythmic theta | Normal | No | Confusion, late head turn to left and left arm posturing | Right anterior frontal and right mesial temporal |
2 | 31 y/F | Left and right temporal spikes | R-orbitofrontal followed by bitemporal | Normal | No | Generalized tonic seizure without warning | Right orbitofrontal propagating to bilateral temporal lobes |
3 | 39 y/F | Left temporal spikes | Left anterior temporal | Larger Left hippocampus | No | Staring | Left posterior orbitofrontal region with rapid propagation to mesial temporal and subsequent lateral temporal cortex |
4 | 27 y/M | Left temporal spikes | Left anterior temporal | Normal | Metallic smell and vision distortion | Staring followed by GTC | Left mesial temporal with rapid propagation to the posterior orbitofrontal region and subsequent lateral temporal cortex |
Patient three had previous selective amygdalectomy sparing the hippocampus and failed to control her seizures. This patient was implanted for reoperation and was included in this analysis. All patients had a consistent seizure onset and initial propagation pattern of cortical ictal HFO activation in all the recorded seizures. Electrodes with inconsistent HFO activation were not considered ictal HFOs. Patient one had strong suggestion of frontal lobe involvement in addition to temporal lobe seizures by noninvasive diagnostic data. HFO mapping confirmed the extratemporal involvement at the onset of the seizures. There was no imaging or scalp EEG evidence of extratemporal involvement in the remainder of three patients. Two patients had a clear onset of ictal HFO activity in the frontal lobe before the temporal lobe (Figures
This synchronized ictal EEG on patient three at the onset of a typical seizure. The top EEG depicts interictal HFO evolving to ictal pattern. The bottom EEG only shows focal slowing at the onset but the ictal HFO is obscured by the filter.
Comparison of HFO activity using a wide band (1–200 Hz) versus a ripple band (80–200 Hz).
Dynamic representation of the ictal HFO activity demonstrated a back and forth sequential activation between the temporal lobe and the orbitofrontal region. This pattern of dynamic activity between the frontal and temporal lobe was not seen in the remaining eleven patients with isolated temporal lobe epilepsy (Figure
HFO mapping of initial ictal activity at the orbitofrontal and mesial temporal ictal activity of a typical seizure. The EEG data on top depicts the time window where the HFO power was calculated. The bottom image on the left side displays the graphic bar power on each EEG channel and the right side represents the localization onto a 3D model based on the patient’s own MRI.
Resection of the ictal HFO at the onset of the seizure and the initial propagation region was associated with seizure freedom in all patients; follow-up period ranged from 12 to 25 months.
The epileptic network is very complex and frequently involves more than one lobe. Cortical HFO represents a relatively small area of local network activity before it is spread to a larger cortical area. Physiologic oscillations with similar frequency properties exist throughout the cortex, not related to the epileptic network, which are under the control of the thalamic pacemaker activity. Therefore only HFO activity with sustained evolution is included in this analysis. The sequential display in a short time window allows a topographical assessment of the cortical areas involved during the ictal HFO activity. This data helps us understand the epileptic network better. Consistent with previous published data, ictal HFOs can be found in distant areas from the main ictal zone [
In patients with multilobar involvement, the ictal zone concept does not explain well the ictal phenomenon. The data found in these small series support the idea of a complex epileptic network involving distant areas, particularly the orbitofrontal region and the temporal lobe, at times with minimal or no clinical manifestations of the multilobar involvement. Recording and analyzing intracranial EEG data with a standard filter band (1–70 Hz) and low sampling rate may prevent correct identification of the ictal HFO activity. ACNS recommends a sampling rate at least three times the high frequency filter to record a reliable activity [
Intracranial ictal HFO mapping can be useful to detect ictal cortical activation areas. With adequate sampling rate and a wide filter band (1–200 Hz), focal ictal HFO activity at the onset of the seizure could be detected. This small series supports that previous publications about disabling or resecting ictal onset HFO activity are important to stop seizures. Finally, posterior orbitofrontal seizure onset may manifest as temporal epilepsy without other clinical manifestations and may be responsible for surgical failure in some cases.
Juan G. Ochoa has been a Speaker for Compumedics. The authors confirm that they have read the journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.
None of the authors has any additional conflict of interests to disclose.
The authors thank Michael Wagner, Ph.D. degree holder, for his help with the technical aspects of EEG recording and HFO detection.