Chronic unlimited recording electrocorticography–guided resective epilepsy surgery: technology-enabled enhanced fidelity in seizure focus localization with improved surgical efficacy

Abstract

Object Epilepsy surgery is at the cusp of a transformation due to the convergence of advancements in multiple technologies. Emerging neuromodulatory therapies offer the promise of functionally correcting neural instability and obviating the need for resective or ablative surgery in select cases. Chronic implanted neurological monitoring technology, delivered as part of a neuromodulatory therapeutic device or as a stand-alone monitoring system, offers the potential to monitor patients chronically in their normal ambulatory setting with outpatient medication regimens. This overcomes significant temporal limitations, pharmacological perturbations, and infection risks inherent in the present technology comprising subacute percutaneous inpatient monitoring of presurgical candidates in an epilepsy monitoring unit. Methods As part of the pivotal study for the NeuroPace Responsive Neurostimulation (RNS) System, the authors assessed the efficacy of the RNS System to control seizures in a group of patients with medically refractory epilepsy. Prior to RNS System implantation, these patients were not candidates for further resective surgery because they had temporal lobe epilepsy with bilateral temporal sources, frontal lobe reflex epilepsy with involvement of primary motor cortex, and occipital lobe epilepsy with substantial involvement of eloquent visual cortex. Without interfering with and beyond the scope of the therapeutic aspect of the RNS System study, the authors were able to monitor seizure and epileptiform activity from chronically implanted subdural and depth electrodes in these patients, and, in doing so, they were able to more accurately localize the seizure source. In 5 of these study patients, in whom the RNS System was not effective, the notion of resective surgery was revisited and considered in light of the additional information gleaned from the chronic intracranial recordings obtained from various permutations of electrodes monitoring sources in the frontal, temporal, parietal, and occipital lobes. Results Through long-term analysis of chronic unlimited recording electrocorticography (CURE) from chronically implanted electrodes, the authors were able to further refine seizure source localization and sufficiently increase the expected likelihood of seizure control to the extent that 4 patients who had previously been considered not to be candidates for surgery did undergo resective surgery, and all have achieved seizure freedom. A fifth patient, who had a double-band heterotopia, underwent surgery but did not achieve significant seizure reduction. Conclusions Chronic unlimited recording electrocorticography–guided resective epilepsy surgery employs new monitoring technology in a novel way, which in this small series was felt to improve seizure localization and consequently the potential efficacy of resective surgery. This suggests that the CURE modality could improve outcomes in patients who undergo resective surgery, and it may expand the set of patients in whom resective surgery may be expected to be efficacious and therefore the potential number of patients who may achieve seizure freedom. The authors report 4 cases of patients in which this technique and technology had a direct role in guiding surgery that provided seizure freedom and that suggest this new approach warrants further study to characterize its value in presurgical evaluation. Clinical trial no.: NCT00572195 (ClinicalTrials.gov).

Temporal behavior of seizures and interictal bursts in prolonged intracranial recordings from epileptic canines

“…This conclusion is supported by the work of DiLorenzo et al, who found that a group of patients who were poorly localized during acute implantation were well localized after chronic implantation of a neuromodulatory device and developed seizure freedom following resection of their chronically localized network. It is also possible that the emergence of other seizure patterns after months of chronic electrode implantation could be due to secondary epileptogenesis, although data from King‐Stephens, DiLorenzo, and significant relapse rates after resection of well‐localized unilateral temporal lobe seizure during acute intracranial recordings argue against this conclusion . The recurrence of early seizure types later in our canine recordings suggests that the initial seizure types are likely not a transient result of tissue reaction postimplantation.…”

“…One recent study analyzing 82 patients who were implanted chronically with the NeuroPace Responsive Neurostimulator System (RNS) demonstrates that an accurate representation of the spatial and temporal variability of seizures in these patients requires at least 30 days of continuous monitoring . Another study demonstrates that this prolonged monitoring may reveal patients to have well‐localized seizures and be good surgical candidates, although this was not apparent during the standard inpatient iEEG monitoring period …”

Intracranial EEG fluctuates over months after implanting electrodes in human brain

“…Seizure onset localization relies on identifying subtle electrographic changes that are spatially distinct, so any changes in spatial variability may interfere with the localization procedure. Of interest, there is evidence that patients who appear to have multifocal onset seizures immediately after electrode implantation during standard clinical evaluation localize to one predominant area in the chronic steady state, eventually resulting in seizure-free outcome after surgery 45 . This provides at least circumstantial evidence that the chronic steady state may better reflect a patient’s baseline than alterations of the network from implantation.…”

Chronic ambulatory electrocorticography from human speech cortex

“…Recently, several reports have highlighted the diagnostic power of the RNS System, using chronic ECoG recorded by the device to characterize longitudinal dynamics of epileptiform activity (DiLorenzo et al, 2014; King-Stephens et al, 2015; Mackow et al, 2016; Smart et al, 2013). Here, we extend the research applications of the RNS System by recording fine-grained physiological responses from eloquent cortex over long periods of time.…”

“…The neurostimulator detects abnormal patterns of activity and responds by delivering brief, imperceptible pulses of electrical current to inhibit seizure activity. Although the RNS System is a clinical tool, the availability of chronic ECoG in ambulatory patients offers an unprecedented opportunity to study longitudinal patterns of brain activity (Anderson et al, 2015; DiLorenzo et al, 2014; King-Stephens et al, 2015; Smart et al, 2013; Spencer et al, 2016). However, the ability of the RNS System to record physiological responses from eloquent cortical regions has not been reported.…”