Dataset Information

Reproducibility of interictal spike propagation in children with refractory epilepsy.

ABSTRACT: OBJECTIVE:Interictal spikes are a characteristic feature of invasive electroencephalography (EEG) recordings in children with refractory epilepsy. Spikes frequently co-occur across multiple brain regions with discernable latencies, suggesting that spikes can propagate through distributed neural networks. The purpose of this study was to examine the long-term reproducibility of spike propagation patterns over hours to days of interictal recording. METHODS:Twelve children (mean age 13.1 years) were retrospectively studied. A mean ± standard deviation (SD) of 47.2 ± 40.1 hours of interictal EEG recordings were examined per patient (range 17.5-166.5 hours). Interictal recordings were divided into 30-minute segments. Networks were extracted based on the frequency of spike coactivation between pairs of electrodes. For each 30-minute segment, electrodes were assigned a "Degree Preference (DP)" based on the tendency to appear upstream or downstream within propagation sequences. The consistency of DPs across segments ("DP-Stability") was quantified using the Spearman rank correlation. RESULTS:Regions exhibited highly stable preferences to appear upstream, intermediate, or downstream in spike propagation sequences. Across networks, the mean ± SD DP-Stability was 0.88 ± 0.07, indicating that propagation patterns observed in 30-minute segments were representative of the patterns observed in the full interictal window. At the group level, regions involved in seizure generation appeared more upstream in spike propagation sequences. SIGNIFICANCE:Interictal spike propagation is a highly reproducible output of epileptic networks. These findings shed new light on the spatiotemporal dynamics that may constrain the network mechanisms of refractory epilepsy.

SUBMITTER: Tomlinson SB

PROVIDER: S-EPMC6488404 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Reproducibility of interictal spike propagation in children with refractory epilepsy.

Tomlinson Samuel B SB Wong Jeremy N JN Conrad Erin C EC Kennedy Benjamin C BC Marsh Eric D ED

Epilepsia 20190421 5

<h4>Objective</h4>Interictal spikes are a characteristic feature of invasive electroencephalography (EEG) recordings in children with refractory epilepsy. Spikes frequently co-occur across multiple brain regions with discernable latencies, suggesting that spikes can propagate through distributed neural networks. The purpose of this study was to examine the long-term reproducibility of spike propagation patterns over hours to days of interictal recording.<h4>Methods</h4>Twelve children (mean age ...[more]

PMID: 31006860

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Project description:ObjectiveThis study was undertaken to evaluate the influence that subject-specific factors have on intracranial interictal epileptiform discharge (IED) rates in persons with refractory epilepsy.MethodsOne hundred fifty subjects with intracranial electrodes performed multiple sessions of a free recall memory task; this standardized task controlled for subject attention levels. We utilized a dominance analysis to rank the importance of subject-specific factors based on their relative influence on IED rates. Linear mixed-effects models were employed to comprehensively examine factors with highly ranked importance.ResultsAntiseizure medication (ASM) status, time of testing, and seizure onset zone (SOZ) location were the highest-ranking factors in terms of their impact on IED rates. The average IED rate of electrodes in SOZs was 34% higher than the average IED rate of electrodes outside of SOZs (non-SOZ; p < .001). However, non-SOZ electrodes had similar IED rates regardless of the subject's SOZ location (p = .99). Subjects on older generation (p < .001) and combined generation (p < .001) ASM regimens had significantly lower IED rates relative to the group taking no ASMs; newer generation ASM regimens demonstrated a nonsignificant association with IED rates (p = .13). Of the ASMs included in this study, the following ASMs were associated with significant reductions in IED rates: levetiracetam (p < .001), carbamazepine (p < .001), lacosamide (p = .03), zonisamide (p = .01), lamotrigine (p = .03), phenytoin (p = .03), and topiramate (p = .01). We observed a nonsignificant association between time of testing and IED rates (morning-afternoon p = .15, morning-evening p = .85, afternoon-evening p = .26).SignificanceThe current study ranks the relative influence that subject-specific factors have on IED rates and highlights the importance of considering certain factors, such as SOZ location and ASM status, when analyzing IEDs for clinical or research purposes.

Project description:Neurosurgical intervention is the best available treatment for selected patients with drug resistant epilepsy. For these patients, surgical planning requires biomarkers that delineate the epileptogenic zone, the brain area that is indispensable for the generation of seizures. Interictal spikes recorded with electrophysiological techniques are considered key biomarkers of epilepsy. Yet, they lack specificity, mostly because they propagate across brain areas forming networks. Understanding the relationship between interictal spike propagation and functional connections among the involved brain areas may help develop novel biomarkers that can delineate the epileptogenic zone with high precision. Here, we reveal the relationship between spike propagation and effective connectivity among onset and areas of spread and assess the prognostic value of resecting these areas. We analysed intracranial EEG data from 43 children with drug resistant epilepsy who underwent invasive monitoring for neurosurgical planning. Using electric source imaging, we mapped spike propagation in the source domain and identified three zones: onset, early-spread and late-spread. For each zone, we calculated the overlap and distance from surgical resection. We then estimated a virtual sensor for each zone and the direction of information flow among them via Granger causality. Finally, we compared the prognostic value of resecting these zones, the clinically-defined seizure onset zone and the spike onset on intracranial EEG channels by estimating their overlap with resection. We observed a spike propagation in source space for 37 patients with a median duration of 95 ms (interquartile range: 34-206), a spatial displacement of 14 cm (7.5-22 cm) and a velocity of 0.5 m/s (0.3-0.8 m/s). In patients with good surgical outcome (25 patients, Engel I), the onset had higher overlap with resection [96% (40-100%)] than early-spread [86% (34-100%), P = 0.01] and late-spread [59% (12-100%), P = 0.002], and it was also closer to resection than late-spread [5 mm versus 9 mm, P = 0.007]. We found an information flow from onset to early-spread in 66% of patients with good outcomes, and from early-spread to onset in 50% of patients with poor outcome. Finally, resection of spike onset, but not area of spike spread or the seizure onset zone, predicted outcome with positive predictive value of 79% and negative predictive value of 56% (P = 0.04). Spatiotemporal mapping of spike propagation reveals information flow from onset to areas of spread in epilepsy brain. Surgical resection of the spike onset disrupts the epileptogenic network and may render patients with drug resistant epilepsy seizure-free without having to wait for a seizure to occur during intracranial monitoring.

Dataset Information

Reproducibility of interictal spike propagation in children with refractory epilepsy.

Publications

Reproducibility of interictal spike propagation in children with refractory epilepsy.

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