Intraoperative fast ripples independently predict postsurgical epilepsy outcome: Comparison with other electrocorticographic phenomena

Abstract

In the surgical management of epilepsy, the resection of cortex exhibiting interictal fast ripples (250–500 Hz) on electrocorticography has been linked to postoperative seizure-freedom. Although fast ripples appear to accurately identify the epileptogenic zone—the minimum tissue that must be removed at surgery to achieve seizure-freedom—it has not been established that fast ripples are a superior biomarker in comparison with multimodal presurgical neuroimaging and other electrocorticography abnormalities. Hence, in the prediction of postoperative seizure-freedom, we compared the value of fast ripples with other intraoperative electocorticography abnormalities including focal slowing, paroxysmal fast activity, intermittent spike discharges, continuous epileptiform discharges, focal attenuation, and intraoperative seizures, as well as complete resection of the lesion defined by MRI and other neuroimaging. In a cohort of 60 children with lesional epilepsy and median postsurgical follow-up exceeding 4 years, who underwent resective epilepsy surgery with intraoperative electrocorticography, we evaluated the extent to which removal of each intraoperative electrocorticography abnormality impacts time to first postoperative seizure using the Kaplan-Meier method and Cox proportional hazards regression. Secondly, we contrasted the predictive value of resection of each competing electrocorticography abnormality using standard test metrics (sensitivity, specificity, positive predictive value, and negative predictive value). In contrast with all other intraoperative electrocorticography abnormalities, fast ripples demonstrated the most favorable combination of positive predictive value (100%) and negative predictive value (76%) in the prediction of postoperative seizures. Among all candidate electrocorticography features, time to first postoperative seizure was most strongly associated with incomplete resection of fast ripples (hazard ratio = 19.8, p <0.001). In multivariate survival analyses, postoperative seizures were independently predicted by incomplete resection of cortex generating fast ripples (hazard ratio = 25.4, 95%CI 6.71 – 96.0, p < 0.001) and focal slowing (hazard ratio = 5.79, 95%CI 1.76 – 19.0, p = 0.004), even after adjustment for the impact of an otherwise complete resection. All children with incomplete resection of interictal FR-generating cortex exhibited postoperative seizures within six months. Notably, this cohort included many patients with large resections and thus limited opportunity to exhibit unresected fast ripples. Future study in a cohort with small resection volume, or a clinical trial in which resection margins are guided by fast ripple distribution, would likely yield a more precise estimate of the risk posed by unresected fast ripples. With a high detection rate during brief intraoperative electrocorticography and favorable positive and negative predictive value, interictal fast ripple characterization during surgery is a feasible and useful adjunct to standard methods for epilepsy surgery...

Treatment of infantile spasms

“…Despite the added challenge of surgical evaluation of IS, functional outcomes following even large resections in infancy tend to be quite favorable, reflecting greater neuroplasticity in this age group. In the effort to refine the identification of the epileptogenic zone—the minimum volume of brain resection required to achieve enduring seizure freedom—advances in neuroimaging such as PET/MRI coregistration and the identification of localizing biomarkers such as fast ripples will hopefully yield higher response rates and superior functional outcomes.…”

Phase‐amplitude coupling between interictal high‐frequency activity and slow waves in epilepsy surgery

“…As the sampling rate of digital recording systems have recently improved, investigators have described the value of interictal high‐frequency activity at >80 Hz (HFA >80 Hz ) for localizing the EZ. Specifically, resection of recording sites showing frequent episodes of HFA during invasive monitoring has been associated with excellent seizure outcome . However, whether preresection interictal HFA can inform postresection clinical outcome, independently of the effects of resection size, SOZ on ictal recording, and neuroimaging data, remains an open question …”

“…Specifically, resection of recording sites showing frequent episodes of HFA during invasive monitoring has been associated with excellent seizure outcome. [9][10][11][12][13][14][15][16] However, whether preresection interictal HFA can inform postresection clinical outcome, independently of the effects of resection size, SOZ on ictal recording, and neuroimaging data, remains an open question. 16 To evaluate whether interictal coupling between HFA and slow waves could be used as a preoperative electrographic biomarker, we examined whether a modulation index (MI) was associated with postoperative success rates in 123 patients with drug-resistant focal epilepsy.…”

Interrater reliability in visual identification of interictal high‐frequency oscillations on electrocorticography and scalp EEG

“…Animal and human studies have identified a disproportionate burden of high‐frequency oscillations (HFOs) in the seizure‐onset zones, and multiple studies have linked favorable postsurgical seizure outcomes to the resection of cortical sites showing interictal HFOs, especially fast ripples (Rs; ≥250 Hz), on electrocorticography (ECoG) . In contrast to ECoG, the identification of HFOs with noninvasive scalp electroencephalography (EEG) has proven more challenging.…”

“…Given the high prevalence, morbidity, and mortality of intractable epilepsy, 1 the identification of a biomarker of the epileptogenic zone-and more generally, intractability -would be of great utility in the evaluation and treatment of epilepsy Animal and human studies have identified a disproportionate burden of high-frequency oscillations (HFOs) in the seizure-onset zones, 2,3 and multiple studies have linked favorable postsurgical seizure outcomes to the resection of cortical sites showing interictal HFOs, especially fast ripples (Rs; ≥250 Hz), on electrocorticography (ECoG). [4][5][6][7] In contrast to ECoG, the identification of HFOs with noninvasive scalp electroencephalography (EEG) has proven more challenging. Although several studies have linked beta, gamma, and ripple activity to hypsarrhythmia 8 and epileptic spasms 9,10 in West syndrome, and to the seizure-onset zones in focal epilepsy, 11 it is only recently that fast ripples (FRs) have been identified with the use of subdermal scalp electrodes in adults with epilepsy, 12 and with the use of standard scalp electrodes in children with epilepsy.…”