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More Than Spikes: On the Added Value of Non-linear Intracranial EEG Analysis for Surgery Planning in Temporal Lobe Epilepsy.

ABSTRACT: Epilepsy surgery can be a very effective therapy in medication refractory patients. During patient evaluation intracranial EEG is analyzed by clinical experts to identify the brain tissue generating epileptiform events. Quantitative EEG analysis increasingly complements this approach in research settings, but not yet in clinical routine. We investigate the correspondence between epileptiform events and a specific quantitative EEG marker. We analyzed 99 preictal epochs of multichannel intracranial EEG of 40 patients with mixed etiologies. Time and channel of occurrence of epileptiform events (spikes, slow waves, sharp waves, fast oscillations) were annotated by a human expert and non-linear excess interrelations were calculated as a quantitative EEG marker. We assessed whether the visually identified preictal events predicted channels that belonged to the seizure onset zone, that were later resected or that showed strong non-linear interrelations. We also investigated whether the seizure onset zone or the resection were predicted by channels with strong non-linear interrelations. In patients with temporal lobe epilepsy (32 of 40), epileptic spikes and the seizure onset zone predicted the resected brain tissue much better in patients with favorable seizure control after surgery than in unfavorable outcomes. Beyond that, our analysis did not reveal any significant associations with epileptiform EEG events. Specifically, none of the epileptiform event types did predict non-linear interrelations. In contrast, channels with strong non-linear excess EEG interrelations predicted the resected channels better in patients with temporal lobe epilepsy and favorable outcome. Also in the small number of patients with seizure onset in the frontal and parietal lobes, no association between epileptiform events and channels with strong non-linear excess EEG interrelations was detectable. In contrast to patients with temporal seizure onset, EEG channels with strong non-linear excess interrelations did neither predict the seizure onset zone nor the resection of these patients or allow separation between patients with favorable and unfavorable seizure control. Our study indicates that non-linear excess EEG interrelations are not strictly associated with epileptiform events, which are one key concept of current clinical EEG assessment. Rather, they may provide information relevant for surgery planning in temporal lobe epilepsy. Our study suggests to incorporate quantitative EEG analysis in the workup of clinical cases. We make the EEG epochs and expert annotations publicly available in anonymized form to foster similar analyses for other quantitative EEG methods.

SUBMITTER: Muller M

PROVIDER: S-EPMC8793863 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Patients with drug-resistant temporal lobe epilepsy often undergo intracranial EEG recording to capture multiple seizures in order to lateralize the seizure onset zone. This process is associated with morbidity and often ends in postoperative seizure recurrence. Abundant interictal (between-seizure) data are captured during this process, but these data currently play a small role in surgical planning. Our objective was to predict the laterality of the seizure onset zone using interictal intracranial EEG data in patients with temporal lobe epilepsy. We performed a retrospective cohort study (single-centre study for model development; two-centre study for model validation). We studied patients with temporal lobe epilepsy undergoing intracranial EEG at the University of Pennsylvania (internal cohort) and the Medical University of South Carolina (external cohort) between 2015 and 2022. We developed a logistic regression model to predict seizure onset zone laterality using several interictal EEG features derived from recent publications. We compared the concordance between the model-predicted seizure onset zone laterality and the side of surgery between patients with good and poor surgical outcomes. Forty-seven patients (30 female; ages 20-69; 20 left-sided, 10 right-sided and 17 bilateral seizure onsets) were analysed for model development and internal validation. Nineteen patients (10 female; ages 23-73; 5 left-sided, 10 right-sided, 4 bilateral) were analysed for external validation. The internal cohort cross-validated area under the curve for a model trained using spike rates was 0.83 for a model predicting left-sided seizure onset and 0.68 for a model predicting right-sided seizure onset. Balanced accuracies in the external cohort were 79.3% and 78.9% for the left- and right-sided predictions, respectively. The predicted concordance between the laterality of the seizure onset zone and the side of surgery was higher in patients with good surgical outcome. We replicated the finding that right temporal lobe epilepsy was harder to distinguish in a separate modality of resting-state functional MRI. In conclusion, interictal EEG signatures are distinct across seizure onset zone lateralities. Left-sided seizure onsets are easier to distinguish than right-sided onsets. A model trained on spike rates accurately identifies patients with left-sided seizure onset zones and predicts surgical outcome. A potential clinical application of these findings could be to either support or oppose a hypothesis of unilateral temporal lobe epilepsy when deciding to pursue surgical resection or ablation as opposed to device implantation.

Project description:Planning surgery for patients with medically refractory epilepsy often requires recording seizures using intracranial EEG. Quantitative measures derived from interictal intracranial EEG yield potentially appealing biomarkers to guide these surgical procedures; however, their utility is limited by the sparsity of electrode implantation as well as the normal confounds of spatiotemporally varying neural activity and connectivity. We propose that comparing intracranial EEG recordings to a normative atlas of intracranial EEG activity and connectivity can reliably map abnormal regions, identify targets for invasive treatment and increase our understanding of human epilepsy. Merging data from the Penn Epilepsy Center and a public database from the Montreal Neurological Institute, we aggregated interictal intracranial EEG retrospectively across 166 subjects comprising >5000 channels. For each channel, we calculated the normalized spectral power and coherence in each canonical frequency band. We constructed an intracranial EEG atlas by mapping the distribution of each feature across the brain and tested the atlas against data from novel patients by generating a z-score for each channel. We demonstrate that for seizure onset zones within the mesial temporal lobe, measures of connectivity abnormality provide greater distinguishing value than univariate measures of abnormal neural activity. We also find that patients with a longer diagnosis of epilepsy have greater abnormalities in connectivity. By integrating measures of both single-channel activity and inter-regional functional connectivity, we find a better accuracy in predicting the seizure onset zones versus normal brain (area under the curve = 0.77) compared with either group of features alone. We propose that aggregating normative intracranial EEG data across epilepsy centres into a normative atlas provides a rigorous, quantitative method to map epileptic networks and guide invasive therapy. We publicly share our data, infrastructure and methods, and propose an international framework for leveraging big data in surgical planning for refractory epilepsy.

Project description:In temporal lobe epilepsy (TLE), the epileptogenic focus is focal and unilateral in the majority of patients. A key characteristic of focal TLE is the presence of subclinical epileptiform activity in both the ictal and contralateral "healthy" hemisphere. Such interictal activity is clinically important, as it may reflect the spread of pathology, potentially leading to secondary epileptogenesis. The role played by white matter pathways in this process is unknown.We compared three interhemispheric white matter tracts (anterior commissure, fornix, and tapetum) to determine the pathway most associated with the presence of contralateral interictal spikes. Forty patients with unilateral left or right TLE were categorized based on the presence or absence of contralateral interictal spikes. Analyses of variance (ANOVAs) were run on diffusion properties from each tract.The analyses revealed that patients with left TLE and with bilateral interictal spikes had lower fractional anisotropy (FA) and higher mean diffusivity (MD) in the tapetum. Patients with right TLE did not show this effect. No significant associations with bilateral activity were observed for the other tracts. Blood oxygen level-dependent (BOLD) functional connectivity data revealed that homotopic lateral, not mesial, temporal areas were reliably correlated in bilateral patients, independent of ictal side.Our results indicate that, among the tracts investigated, only the tapetum was associated with contralateral epileptiform activity, implicating this structure in seizures and possible secondary epileptogenesis. We describe two mechanisms that might explain this association (the interruption of inhibitory signals or the toxic effect of carrying epileptiform signals toward the healthy hemisphere), but also acknowledge other rival factors that may be at work. We also report that patients with TLE with bilateral spikes had increased lateral bitemporal lobe connectivity. Our current results can be seen as bringing together important functional and structural data to elucidate the basis of contralateral interictal activity in focal, unilateral epilepsy. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

Project description:EEG source imaging is becoming widely used for the evaluation of medically refractory focal epilepsy. The validity of EEG source imaging has been established in several studies comparing source imaging to the surgical resection cavity and subsequent seizure freedom. We present a cohort of 87 patients and compare EEG source imaging of both ictal and interictal scalp EEG to the seizure onset zone on intracranial EEG. Concordance of EEG source imaging with intracranial EEG was determined on a sublobar level and was quantified by measuring the distance between the source imaging result and the centroid of the active seizure onset zone electrodes. The EEG source imaging results of a subgroup of 26 patients with high density 76-channel EEG were compared with the localization of three experienced epileptologists. Of 87 patients, 95% had at least one analysis concordant with intracranial EEG and 74% had complete concordance. There was a higher rate of complete concordance in temporal lobe epilepsy compared to extratemporal (89.3 and 62.8%, respectively, P = 0.015). Of the total 282 analyses performed on this cohort, higher concordance was also seen in temporal discharges (95%) compared to extratemporal (77%) (P = 0.0012), but no difference was seen comparing high-density EEG with standard (32-channel) EEG. Subgroup analysis of ictal waveforms showed greater concordance for ictal spiking, compared with rhythmic activity, paroxysmal fast activity, or obscured onset. Median distances from the dipole and maximum distributed source to a centroid of seizure onset zone electrodes were 30.0 and 32.5 mm, respectively, and the median distances from dipole and maximum distributed source to nearest seizure onset zone electrode were 22.8 and 21.7, respectively. There were significantly shorter distances in ictal spiking. There were shorter distances in patients with Engel Class 1 outcome from surgical resection compared to patients with worse outcomes. For the subgroup of 26 high-density EEG patients, EEG source localization had a significantly higher concordance (92% versus 65%), sensitivity (57% versus 35%) and positive predictive value (60% versus 36%) compared with epileptologist localization. Our study demonstrates good concordance between ictal and interictal source imaging and intracranial EEG. Temporal lobe discharges have higher concordance rates than extratemporal discharges. Importantly, this study shows that source imaging has greater agreement with intracranial EEG than visual review alone, supporting its role in surgical planning.

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More Than Spikes: On the Added Value of Non-linear Intracranial EEG Analysis for Surgery Planning in Temporal Lobe Epilepsy.

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