High-frequency oscillations, extent of surgical resection, and surgical outcome in drug-resistant focal epilepsy

Abstract

Purpose: Removal of areas generating high-frequency oscillations (HFOs) recorded from the intracerebral electroencephalography (iEEG) of patients with medically intractable epilepsy has been found to be correlated with improved surgical outcome. However, whether differences exist according to the type of epilepsy is largely unknown. We performed a comparative assessment of the impact of removing HFO-generating tissue on surgical outcome between temporal lobe epilepsy (TLE) and extratemporal lobe epilepsy (ETLE). We also assessed the relationship between the extent of surgical resection and surgical outcome.

Methods: We studied 30 patients with drug-resistant focal epilepsy, 21 with TLE and 9 with ETLE. Two thirds of the patients were included in a previous report and for these, clinical and imaging data were updated and follow-up was extended. All patients underwent iEEG investigations (500 Hz high-pass filter and 2,000 Hz sampling rate), surgical resection, and postoperative magnetic resonance imaging (MRI). HFOs (ripples, 80-250 Hz; fast ripples, >250 Hz) were identified visually on a 5-10 min interictal iEEG sample. HFO rates inside versus outside the seizure-onset zone (SOZ), in resected versus nonresected tissue, and their association with surgical outcome (ILAE classification) were assessed in the entire cohort, and in the TLE and ETLE subgroups. We also tested the correlation of resected brain hippocampal and amygdala volumes (as measured on postoperative MRIs) with surgical outcome.

Key findings: HFO rates were significantly higher inside the SOZ than outside in the entire cohort and TLE subgroup, but not in the ETLE subgroup. In all groups, HFO rates did not differ significantly between resected and nonresected tissue. Surgical outcome was better when higher HFO rates were included in the surgical resection in the entire cohort and TLE subgroup, but not in the ETLE subgroup. Resected brain hippocampal and amygdala volumes were not correlated with surgical outcome.

Significance: In TLE, removal of HFO-generating areas may lead to improved surgical outcome. Less consistent findings emerge from ETLE, but these may be related to sample size limitations of this study. Size of resection, a factor that was ignored and that could have affected results of earlier studies did not influence results.

Figure 1

Axial (left), sagittal (middle), and coronal (right) MRI views of a patient with extratemporal lobe epilepsy. The first row shows the postoperative MRI with the right frontal surgical cavity and the registered intracerebral electrodes. The electrodes were implanted in the right supplementary motor area (green), through the lesion (red), and in the anterior cingulate gyrus (blue). The views below show only part of the electrodes. The second row shows in red the right frontal surgical cavity painted with the Display software (MNI, Montreal, Canada). Epilepsia © ILAE

Figure 2

Axial (left), coronal (middle), and sagittal (right) brain MRI views in a patient with temporal lobe epilepsy. The two upper rows of the figure illustrate the trajectories of the depth electrodes on the postexplantation MRI. The electrodes targeted the head of the hippocampus (red), the posterior hippocampus (green), and the orbitofrontal cortex (blue). The third row shows the automatic segmentation of the amygdala and hippocampus obtained after registration of the preoperative MRI with the postoperative MRI. The bottom row shows in red the left anterior temporal surgical cavity painted with Display software. Epilepsia © ILAE

Figure 3

Boxplots illustrating ratios between HFOs in removed and nonremoved contacts for patients with a favorable surgical outcome (ILAE classes 1–3) and those with a poor outcome (ILAE classes 4–6), in the entire cohort (graph at the top) and in the TLE and ETLE subgroups (graphs at the bottom). Note that the results in the entire cohort are influenced mainly by the TLE subgroup, which is more than twice as large as the ETLE subgroup (21 vs. 9 patients). Symbol (*) indicates statistically significant differences. R, ripples; FR, fast ripples. Epilepsia © ILAE