Removing interictal fast ripples on electrocorticography linked with seizure freedom in children

Abstract

Background: Fast ripples (FR, 250-500 Hz) detected with chronic intracranial electrodes are proposed biomarkers of epileptogenesis. This study determined whether resection of FR-containing neocortex recorded during intraoperative electrocorticography (ECoG) was associated with postoperative seizure freedom in pediatric patients with mostly extratemporal lesions.

Methods: FRs were retrospectively reviewed in 30 consecutive pediatric cases. ECoGs were recorded at 2,000 Hz sampling rate and visually inspected for FR, with reviewer blinded to the resection and outcome.

Results: Average age at surgery was 9.1 ± 6.7 years, ECoG duration was 11.8 ± 8.1 minutes, and postoperative follow-up was 27 ± 4 months. FRs were undetected in 6 ECoGs with remote or extensive lesions. FR episodes (n = 273) were identified in ECoGs from 24 patients, and in 64% FRs were independent of spikes, sharp waves, voltage attenuation, and paroxysmal fast activity. Of these 24 children, FR-containing cortex was removed in 19 and all became seizure-free, including 1 child after a second surgery. The remaining 5 children had incomplete FR resection and all continued with seizures postoperatively. In 2 ECoGs, the location of electrographic seizures matched FR location. FR-containing cortex was found outside of MRI and FDG-PET abnormalities in 6 children.

Conclusion: FRs were detected during intraoperative ECoG in 80% of pediatric epilepsy cases, and complete resection of FR cortex correlated with postoperative seizure freedom. These findings support the view that interictal FRs are excellent surrogate markers of epileptogenesis, can be recorded during brief ECoG, and could be used to guide future surgical resections in children.

Figure 1 Example of interictal fast ripples (FR) during intraoperative electrocorticography (patient 17) Note the split screen on the left with no filter settings at 30 mm/s paper speed, and on the right with FR filter settings of 240 and 500 Hz at the maximally allowed 338 mm/s paper speed. The 2 events of interictal FR measured 338 and 342 Hz at electrode 14 on the grid (A14), occurred independently of spikes and sharp waves on the strip (B1-8), and appeared adjacent to paroxysmal fast activity elsewhere on the grid (A1-20).

Figure 2 An illustrative case (patient 26) This is a 16-year-old patient with 4 years of intractable epilepsy described as visual blurring and distortion. His video-EEG did not show clear electrographic onset during all stereotypical events (not shown), and his head MRI (A) showed a lesion over the right occipital region. His ¹⁸fluoro-deoxyglucose PET (FDG-PET) (B) showed hypometabolism over the right occipital region, and the coregistration of MRI and FDG-PET (C) demonstrated hypometabolism limited to the lesion. At surgery, the occipital lesion is seen in the surgical field (D). A 4 × 5 macroelectrode grid was placed over the surgical field (E), with a 1 × 4 macroelectrode strip off the surgical field (not shown) in the right frontal region as “control.” Intraoperative electrocorticography showed intermittent slowing, attenuation, and sharp waves superimposed with paroxysmal fast activity (G, left screen, no filters, no notch filter, time scale 30 mm/s, referential montage to contralateral frontal scalp electrode). After the lesion was resected (F), interictal fast ripples (FRs) (G, right screen, 240-Hz high-pass filter and 500-Hz low-pass filter, time scale 338 mm/s, referential montage to contralateral frontal scalp electrode) were seen first over A19 (E, shaded red) in the parietal region, with quick propagation to adjacent A20 and A15 superiorly, and A18 inferiorly, and importantly not found in the “control” frontal lobe. Thus the occipital lesion was resected but the parietal region containing FR remained. The patient's seizures returned in 3 months with similar semiology of visual distortion and blurring, again without electrographic changes in a second video-EEG. A second surgery 10 months after the first resection revealed similar electrocorticography, and FR was again found in the right parietal region. This FR-containing region was resected in the second surgery, and patient has been seizure-free for 20 months since the second resection, now off all antiepileptic drugs. Final pathology showed dysembryoplastic neuroepithelial tumor in the first resected specimen, and residual tumor in the second resected specimen.