Literature review and protocol for a prospective multicentre cohort study on multimodal prediction of seizure recurrence after unprovoked first seizure.

INTRODUCTION: Epilepsy is a common neurological disorder characterised by recurrent seizures. Almost half of patients who have an unprovoked first seizure (UFS) have additional seizures and develop epilepsy. No current predictive models exist to determine who has a higher risk of recurrence to guide treatment. Emerging evidence suggests alterations in cognition, mood and brain connectivity exist in the population with UFS. Baseline evaluations of these factors following a UFS will enable the development of the first multimodal biomarker-based predictive model of seizure recurrence in adults with UFS. METHODS AND ANALYSIS: 200 patients and 75 matched healthy controls (aged 18-65) from the Kingston and Halifax First Seizure Clinics will undergo neuropsychological assessments, structural and functional MRI, and electroencephalography. Seizure recurrence will be assessed prospectively. Regular follow-ups will occur at 3, 6, 9 and 12 months to monitor recurrence. Comparisons will be made between patients with UFS and healthy control groups, as well as between patients with and without seizure recurrence at follow-up. A multimodal machine-learning model will be trained to predict seizure recurrence at 12 months. ETHICS AND DISSEMINATION: This study was approved by the Health Sciences and Affiliated Teaching Hospitals Research Ethics Board at Queen's University (DMED-2681-22) and the Nova Scotia Research Ethics Board (1028519). It is supported by the Canadian Institutes of Health Research (PJT-183906). Findings will be presented at national and international conferences, published in peer-reviewed journals and presented to the public via patient support organisation newsletters and talks. TRIAL REGISTRATION NUMBER: NCT05724719.

Sequential Semiology of Seizures and Brain Perfusion Patterns in Patients with Drug-Resistant Focal Epilepsies: A Perspective from Neural Networks.

Ictal semiology and brain single-photon emission computed tomography have been performed in approaching the epileptogenic zone in drug-resistant focal epilepsies. The authors aim to describe the brain structures involved in the ictal and interictal epileptogenic network from sequential semiology and brain perfusion quantitative patterns analysis. A sequential representation of seizures was performed (n = 15). A two-level analysis (individual and global) was carried out for the analysis of brain perfusion quantification and estimating network structures from the perfusion indexes. Most of the subjects started with focal seizures without impaired consciousness, followed by staring, automatisms, language impairments and evolution to a bilateral tonic-clonic seizure (temporal lobe and posterior quadrant epilepsy). Frontal lobe epilepsy seizures continued with upper limb clonus and evolution to bilateral tonic-clonic. The perfusion index of the epileptogenic zone ranged between 0.439-1.362 (mesial and lateral structures), 0.826-1.266 in dorsolateral frontal structures and 0.678-1.507 in the occipital gyrus. The interictal epileptogenic network proposed involved the brainstem and other subcortical structures. For the ictal state, it included the rectus gyrus, putamen and cuneus. The proposed methodology provides information about the brain structures in the neural networks in patients with drug-resistant focal epilepsies.

Surgical Outcome in Extratemporal Epilepsies Based on Multimodal Pre-Surgical Evaluation and Sequential Intraoperative Electrocorticography.

OBJECTIVE: to present the postsurgical outcome of extratemporal epilepsy (ExTLE) patients submitted to preoperative multimodal evaluation and intraoperative sequential electrocorticography (ECoG). SUBJECTS AND METHODS: thirty-four pharmaco-resistant patients with lesional and non-lesional ExTLE underwent comprehensive pre-surgical evaluation including multimodal neuroimaging such as ictal and interictal perfusion single photon emission computed tomography (SPECT) scans, subtraction of ictal and interictal SPECT co-registered with magnetic resonance imaging (SISCOM) and electroencephalography (EEG) source imaging (ESI) of ictal epileptic activity. Surgical procedures were tailored by sequential intraoperative ECoG, and absolute spike frequency (ASF) was calculated in the pre- and post-resection ECoG. Postoperative clinical outcome assessment for each patient was carried out one year after surgery using Engel scores. RESULTS: frontal and occipital resection were the most common surgical techniques applied. In addition, surgical resection encroaching upon eloquent cortex was accomplished in 41% of the ExTLE patients. Pre-surgical magnetic resonance imaging (MRI) did not indicate a distinct lesion in 47% of the cases. In the latter number of subjects, SISCOM and ESI of ictal epileptic activity made it possible to estimate the epileptogenic zone. After one- year follow up, 55.8% of the patients was categorized as Engel class I-II. In this study, there was no difference in the clinical outcome between lesional and non lesional ExTLE patients. About 43.7% of patients without lesion were also seizure- free, p = 0.15 (Fischer exact test). Patients with satisfactory seizure outcome showed lower absolute spike frequency in the pre-resection intraoperative ECoG than those with unsatisfactory seizure outcome, (Mann- Whitney U test, p = 0.005). CONCLUSIONS: this study has shown that multimodal pre-surgical evaluation based, particularly, on data from SISCOM and ESI alongside sequential intraoperative ECoG, allow seizure control to be achieved in patients with pharmacoresistant ExTLE epilepsy.

A Novel Noninvasive Approach Based on SPECT and EEG for the Location of the Epileptogenic Zone in Pharmacoresistant Non-Lesional Epilepsy.

Background and objectives: The aim of this study is to propose a methodology that combines non-invasive functional modalities electroencephalography (EEG) and single photon emission computed tomography (SPECT) to estimate the location of the epileptogenic zone (EZ) for the presurgical evaluation of patients with drug-resistant non-lesional epilepsy. Materials and Methods: This methodology consists of: (i) Estimation of ictal EEG source imaging (ESI); (ii) application of the subtraction of ictal and interictal SPECT co-registered with MRI (SISCOM) methodology; and (iii) estimation of ESI but using the output of the SISCOM as a priori information for the estimation of the sources. The methodology was implemented in a case series as an example of the application of this novel approach for the presurgical evaluation. A gold standard and a coincidence analysis based on measures of sensitivity and specificity were used as a preliminary assessment of the proposed methodology to localize EZ. Results: In patients with good postoperative evolution, the estimated EZ presented a spatial coincidence with the resection site represented by high values of sensitivity and specificity. For the patient with poor postoperative evolution, the methodology showed a partial incoherence between the estimated EZ and the resection site. In cases of multifocal epilepsy, the method proposed spatially extensive epileptogenic zones. Conclusions: The results of the case series provide preliminary evidence of the methodology's potential to epileptogenic zone localization in non-lesion drug-resistant epilepsy. The novelty of the article consists in estimating the sources of ictal EEG using SISCOM result as a prior for the inverse solution. Future studies are necessary in order to validate the described methodology. The results constitute a starting point for further studies in order to support the clinical reliability of the proposed methodology and advocate for their implementation in the presurgical evaluation of patients with intractable non-lesional epilepsy.

Relation of Structural and Functional Changes in Auditory and Visual Pathways after Temporal Lobe Epilepsy Surgery.

Auditory and visual pathways may be affected as a consequence of temporal lobe epilepsy surgery because of their anatomical relationships with this structure. The purpose of this paper is to correlate the results of the auditory and visual evoked responses with the parameters of tractography of the visual pathway, and with the state of connectivity between respective thalamic nuclei and primary cortices in both systems after the surgical resection of the epileptogenic zone in drug-resistant epileptic patients. Tractography of visual pathway and anatomical connectivity of auditory and visual thalamus-cortical radiations were evaluated in a sample of eight patients. In general, there was a positive relationship of middle latency response (MLR) latency and length of resection, while a negative correlation was found between MLR latency and the anatomical connection strength and anatomical connection probability of the auditory radiations. In the visual pathway, significant differences between sides were found with respect to the number and length of tracts, which was lower in the operated one. Anatomical connectivity variables and perimetry (visual field defect index) were particularly correlated with the latency of P100 wave which was obtained by quadrant stimulation. These results demonstrate an indirect functional modification of the auditory pathway and a direct traumatic lesion of the visual pathway after anterior temporal lobectomy in patients with drug resistant epilepsy.

What We Know About the Brain Structure-Function Relationship.

How the human brain works is still a question, as is its implication with brain architecture: the non-trivial structure–function relationship. The main hypothesis is that the anatomic architecture conditions, but does not determine, the neural network dynamic. The functional connectivity cannot be explained only considering the anatomical substrate. This involves complex and controversial aspects of the neuroscience field and that the methods and methodologies to obtain structural and functional connectivity are not always rigorously applied. The goal of the present article is to discuss about the progress made to elucidate the structure–function relationship of the Central Nervous System, particularly at the brain level, based on results from human and animal studies. The current novel systems and neuroimaging techniques with high resolutive physio-structural capacity have brought about the development of an integral framework of different structural and morphometric tools such as image processing, computational modeling and graph theory. Different laboratories have contributed with in vivo, in vitro and computational/mathematical models to study the intrinsic neural activity patterns based on anatomical connections. We conclude that multi-modal techniques of neuroimaging are required such as an improvement on methodologies for obtaining structural and functional connectivity. Even though simulations of the intrinsic neural activity based on anatomical connectivity can reproduce much of the observed patterns of empirical functional connectivity, future models should be multifactorial to elucidate multi-scale relationships and to infer disorder mechanisms.