High‐frequency electroencephalographic oscillations correlate with outcome of epilepsy surgery

Abstract

Objective-High-frequency oscillations (HFOs) in the intracerebral electroencephalogram (EEG) have been linked to the seizure onset zone (SOZ). We investigated whether HFOs can delineate epileptogenic areas even outside the SOZ by correlating the resection of HFO-generating areas with surgical outcome.Methods-Twenty patients who underwent a surgical resection for medically intractable epilepsy were studied. All had presurgical intracerebral EEG (500Hz filter and 2,000Hz sampling rate), at least 12-month postsurgical follow-up, and a postsurgical magnetic resonance imaging (MRI). HFOs (ripples, 80 -250Hz; fast ripples, >250Hz) were identified visually during 5 to 10 minutes of slow-wave sleep. Rates and extent of HFOs and interictal spikes in resected versus nonresected areas, assessed on postsurgical MRIs, were compared with surgical outcome (Engel's classification). We also evaluated the predictive value of removing the SOZ in terms of surgical outcome.Results-The mean duration of follow-up was 22.7 months. Eight patients had good (Engel classes 1 and 2) and 12 poor (classes 3 and 4) surgical outcomes. Patients with a good outcome had a significantly larger proportion of HFO-generating areas removed than patients with a poor outcome. No such difference was seen for spike-generating regions or the SOZ.Interpretation-The correlation between removal of HFO-generating areas and good surgical outcome indicates that HFOs could be used as a marker of epileptogenicity and may be more accurate than spike-generating areas or the SOZ. In patients in whom the majority of HFOgenerating tissue remained, a poor surgical outcome occurred.Thirty percent to 40% of patients with focal epilepsy are medically intractable, 1 and for some, surgical removal of epileptogenic areas is the best option to gain seizure freedom. Intracranial electroencephalographic (iEEG) investigations are indicated for patients in whom noninvasive methods fail to identify a single focal seizure generator. CIHR Author Manuscript CIHR Author Manuscript CIHR Author ManuscriptiEEG is used to define the seizure onset zone (SOZ). 3 Removal of the SOZ alone, however, does not always predict the surgical benefit. 4,5 It is uncertain whether the outcome can be improved by removing areas of interictal spiking, often more widespread than the SOZ. 6,7 Intracranial studies also have limitations, as their results depend on electrode location and type of implantation (intracortical vs subdural). For instance, iEEG electrodes only record neuronal activity in their direct vicinity and are blind for other areas, 8 making it hard to judge whether the activity at seizure onset really represents the seizure generator or is the result of propagation from else-where. Thus the actual focus and its extent may be missed, leading to unsuccessful surgery.Microelectrode-recorded high-frequency oscillations (HFOs), ripples (80 -250Hz), and fast ripples (FRs, 250 -500Hz), were found predominantly in epileptogenic tissue. 9 -11 They can also be recorded with macroelectrodes duri...

Advances of Intracranial Electroencephalography in Localizing the Epileptogenic Zone

“…Subsequent studies have demonstrated that HFOs can be reliably recorded using commercially-available macroelectrodes, both subdural and depth electrodes, with the highest rates during slow-wave NREM sleep. They were found to be an independent epilepsy marker both in neocortical epilepsy and mTLE [17][18][19][20][21][22]. The regions showing high rates of interictal or ictal HFOs spatially colocalize with the SOZ or EZ, and resection of areas with higher interictal or ictal HFO rates have been significantly associated with a better surgical outcome (Table 1).…”

Mechanisms of physiological and epileptic HFO generation

“…The close relationship between hippocampal fast ripples and individual cell bursting is now widely accepted in the field (Bikson et al, 2003a;Engel et al, 2009;Köhling and Staley, 2011). A major reason to focus at their mechanisms is linked with their potential diagnostic value: if fast ripples are biomarkers of abnormal and enhanced forms of neuronal synchronization, then their detection can be used to closely delineate the epileptogenic territories and to eventually identify candidate areas for resection in combinations with other clinical variables (Jacobs et al, 2010;Zijlmans et al, 2012).…”

Ictal and interictal high frequency oscillations in patients with focal epilepsy

“…HFOs seem better markers for the SOZ than epileptic spikes and do not depend on the underlying pathology (Jacobs et al, 2008(Jacobs et al, , 2009a. Finally, removal of HFO generating tissue is related to good surgical outcome, more than spikes and the SOZ are (Jacobs et al, 2010), which supports their relation to epileptogenic tissue and potential clinical importance. The current hypothesis is that HFOs result from misconnected or disinhibited neuronal networks leading to highly synchronized neuronal activity over an area of brain tissue, which in turn results in seizure genesis after other areas or networks get involved (Bragin et al, 2004a;Engel et al, 2009;Ogren et al, 2009).…”