Prospective Quantitative Neuroimaging Analysis of Putative Temporal Lobe Epilepsy

Purpose: A prospective study of individual and combined quantitative imaging applications for lateralizing epileptogenicity was performed in a cohort of consecutive patients with a putative diagnosis of mesial temporal lobe epilepsy (mTLE). Methods: Quantitative metrics were applied to MRI and nuclear medicine imaging studies as part of a comprehensive presurgical investigation. The neuroimaging analytics were conducted remotely to remove bias. All quantitative lateralizing tools were trained using a separate dataset. Outcomes were determined after 2 years. Of those treated, some underwent resection, and others were implanted with a responsive neurostimulation (RNS) device. Results: Forty-eight consecutive cases underwent evaluation using nine attributes of individual or combinations of neuroimaging modalities: 1) hippocampal volume, 2) FLAIR signal, 3) PET profile, 4) multistructural analysis (MSA), 5) multimodal model analysis (MMM), 6) DTI uncertainty analysis, 7) DTI connectivity, and 9) fMRI connectivity. Of the 24 patients undergoing resection, MSA, MMM, and PET proved most effective in predicting an Engel class 1 outcome (\u3e80% accuracy). Both hippocampal volume and FLAIR signal analysis showed 76% and 69% concordance with an Engel class 1 outcome, respectively. Conclusion: Quantitative multimodal neuroimaging in the context of a putative mTLE aids in declaring laterality. The degree to which there is disagreement among the various quantitative neuroimaging metrics will judge whether epileptogenicity can be confined sufficiently to a particular temporal lobe to warrant further study and choice of therapy. Prediction models will improve with continued exploration of combined optimal neuroimaging metrics

Quantitative MRI in refractory temporal lobe epilepsy: relationship with surgical outcomes

Medically intractable temporal lobe epilepsy (TLE) remains a serious health problem. Across treatment centers, up to 40% of patients with TLE will continue to experience persistent postoperative seizures at 2-year follow-up. It is unknown why such a large number of patients continue to experience seizures despite being suitable candidates for resective surgery. Preoperative quantitative MRI techniques may provide useful information on why some patients continue to experience disabling seizures, and may have the potential to develop prognostic markers of surgical outcome. In this article, we provide an overview of how quantitative MRI morphometric and diffusion tensor imaging (DTI) data have improved the understanding of brain structural alterations in patients with refractory TLE. We subsequently review the studies that have applied quantitative structural imaging techniques to identify the neuroanatomical factors that are most strongly related to a poor postoperative prognosis. In summary, quantitative imaging studies strongly suggest that TLE is a disorder affecting a network of neurobiological systems, characterized by multiple and inter-related limbic and extra-limbic network abnormalities. The relationship between brain alterations and postoperative outcome are less consistent, but there is emerging evidence suggesting that seizures are less likely to remit with surgery when presurgical abnormalities are observed in the connectivity supporting brain regions serving as network nodes located outside the resected temporal lobe. Future work, possibly harnessing the potential from multimodal imaging approaches, may further elucidate the etiology of persistent postoperative seizures in patients with refractory TLE. Furthermore, quantitative imaging techniques may be explored to provide individualized measures of postoperative seizure freedom outcome

The ENIGMA-Epilepsy working group: Mapping disease from large data sets

Epilepsy is a common and serious neurological disorder, with many different constituent conditions characterized by their electro clinical, imaging, and genetic features. MRI has been fundamental in advancing our understanding of brain processes in the epilepsies. Smaller‐scale studies have identified many interesting imaging phenomena, with implications both for understanding pathophysiology and improving clinical care. Through the infrastructure and concepts now well‐established by the ENIGMA Consortium, ENIGMA‐Epilepsy was established to strengthen epilepsy neuroscience by greatly increasing sample sizes, leveraging ideas and methods established in other ENIGMA projects, and generating a body of collaborating scientists and clinicians to drive forward robust research. Here we review published, current, and future projects, that include structural MRI, diffusion tensor imaging (DTI), and resting state functional MRI (rsfMRI), and that employ advanced methods including structural covariance, and event‐based modeling analysis. We explore age of onset‐ and duration‐related features, as well as phenomena‐specific work focusing on particular epilepsy syndromes or phenotypes, multimodal analyses focused on understanding the biology of disease progression, and deep learning approaches. We encourage groups who may be interested in participating to make contact to further grow and develop ENIGMA‐Epilepsy

Nuclear imaging for localization and surgical outcome prediction in epilepsy: A review of latest discoveries and future perspectives

BackgroundEpilepsy is one of the most common neurological disorders. Approximately, one-third of patients with epilepsy have seizures refractory to antiepileptic drugs and further require surgical removal of the epileptogenic region. In the last decade, there have been many recent developments in radiopharmaceuticals, novel image analysis techniques, and new software for an epileptogenic zone (EZ) localization.ObjectivesRecently, we provided the latest discoveries, current challenges, and future perspectives in the field of positron emission tomography (PET) and single-photon emission computed tomography (SPECT) in epilepsy.MethodsWe searched for relevant articles published in MEDLINE and CENTRAL from July 2012 to July 2022. A systematic literature review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis was conducted using the keywords “Epilepsy” and “PET or SPECT.” We included both prospective and retrospective studies. Studies with preclinical subjects or not focusing on EZ localization or surgical outcome prediction using recently developed PET radiopharmaceuticals, novel image analysis techniques, and new software were excluded from the review. The remaining 162 articles were reviewed.ResultsWe first present recent findings and developments in PET radiopharmaceuticals. Second, we present novel image analysis techniques and new software in the last decade for EZ localization. Finally, we summarize the overall findings and discuss future perspectives in the field of PET and SPECT in epilepsy.ConclusionCombining new radiopharmaceutical development, new indications, new techniques, and software improves EZ localization and provides a better understanding of epilepsy. These have proven not to only predict prognosis but also to improve the outcome of epilepsy surgery

Cognitive functional MRI in temporal lobe epilepsy

Anterior temporal lobe resections (ATLR) provide an effective treatment option for patients with medically refractory temporal lobe epilepsy (TLE) rendering up to 70% of them seizure free. The goal of epilepsy surgery is to remove the brain areas generating the seizures without causing neuropsychological deficits such as language or memory dysfunction. Furthermore up to 60% of patients with TLE suffer from emotional disturbances following surgery. The principle aim of the work presented in this thesis was to improve presurgical evaluation of patients with TLE by using cognitive functional MRI (fMRI) to non-invasively localise brain areas that are essential for processing cognitive function such as language and memory function and emotional and social behaviour. 150 consecutive patients and 40 healthy controls were included in our experiments. Different fMRI paradigms for the evaluation of cognitive functions have been implemented on a 3 Tesla scanner. All subjects underwent language and memory fMRI and standard neuropsychological assessment; those patients who proceeded to have temporal lobe surgery were reinvestigated 4 months following ATLR. We studied the efficiency of reorganisation of language and memory function due to the underlying disease and in particular following ATLR. Amygdala fMRI was used to investigate potential implications on emotional and social outcome. A major part of the work included in this thesis has concentrated on the use of fMRI for the exploration and prediction of postoperative complications such as language and memory impairment but also emotional disturbances. When used in concert with other MR imaging modalities the results of these methods can be used to improve surgical strategies tailored to individual patients with regard to functional outcome, by virtue of definition of epileptic cerebral areas that need to be resected and eloquent areas that need to be spared

Computational modelling in source space from scalp EEG to inform presurgical evaluation of epilepsy

This is the author accepted manuscript. The final version is available on open access from Elsevier via the DOI in this recordObjective: The effectiveness of intracranial electroencephalography (iEEG) to inform epilepsy surgery depends on where iEEG electrodes are implanted. This decision is informed by noninvasive recording modalities such as scalp EEG. Herein we propose a framework to interrogate scalp EEG and determine epilepsy lateralization to aid in electrode implantation. Methods: We use eLORETA to map source activities from seizure epochs recorded from scalp EEG and consider 15 regions of interest (ROIs). Functional networks are then constructed using the phase-locking value and studied using a mathematical model. By removing different ROIs from the network and simulating their impact on the network’s ability to generate seizures in silico, the framework provides predictions of epilepsy lateralization. We consider 15 individuals from the EPILEPSIAE database and study a total of 62 seizures. Results were assessed by taking into account actual intracranial implantations and surgical outcome. Results: The framework provided potentially useful information regarding epilepsy lateralization in 12 out of the 15 individuals (p=0.02, binomial test). Conclusions: Our results show promise for the use of this framework to better interrogate scalp EEG to determine epilepsy lateralization. Significance: The framework may aid clinicians in the decision process to define where to implant electrodes for intracranial monitoring.Medical Research CouncilEpilepsy Research UKEngineering and Physical Sciences Research Council (EPSRC)Wellcome TrustEngineering and Physical Sciences Research Council (EPSRC)Innovate UKEuropean Union’s Horizon 2020Alzheimer's SocietyMedical Research Counci

Disrupted Functional Brain Connectivity in Partial Epilepsy: A Resting-State fMRI Study

Examining the spontaneous activity to understand the neural mechanism of brain disorder is a focus in recent resting-state fMRI. In the current study, to investigate the alteration of brain functional connectivity in partial epilepsy in a systematical way, two levels of analyses (functional connectivity analysis within resting state networks (RSNs) and functional network connectivity (FNC) analysis) were carried out on resting-state fMRI data acquired from the 30 participants including 14 healthy controls(HC) and 16 partial epilepsy patients. According to the etiology, all patients are subdivided into temporal lobe epilepsy group (TLE, included 7 patients) and mixed partial epilepsy group (MPE, 9 patients). Using group independent component analysis, eight RSNs were identified, and selected to evaluate functional connectivity and FNC between groups. Compared with the controls, decreased functional connectivity within all RSNs was found in both TLE and MPE. However, dissociating patterns were observed within the 8 RSNs between two patient groups, i.e, compared with TLE, we found decreased functional connectivity in 5 RSNs increased functional connectivity in 1 RSN, and no difference in the other 2 RSNs in MPE. Furthermore, the hierarchical disconnections of FNC was found in two patient groups, in which the intra-system connections were preserved for all three subsystems while the lost connections were confined to intersystem connections in patients with partial epilepsy. These findings may suggest that decreased resting state functional connectivity and disconnection of FNC are two remarkable characteristics of partial epilepsy. The selective impairment of FNC implicated that it is unsuitable to understand the partial epilepsy only from global or local perspective. We presumed that studying epilepsy in the multi-perspective based on RSNs may be a valuable means to assess the functional changes corresponding to specific RSN and may contribute to the understanding of the neuro-pathophysiological mechanism of epilepsy

Stereo-Encephalographic Presurgical Evaluation of Temporal Lobe Epilepsy: An Evolving Science

Drug-resistant epilepsy is present in nearly 30% of patients. Resection of the epileptogenic zone has been found to be the most effective in achieving seizure freedom. The study of temporal lobe epilepsy for surgical treatment is extensive and complex. It involves a multidisciplinary team in decision-making with initial non-invasive studies (Phase I), providing 70% of the required information to elaborate a hypothesis and treatment plans. Select cases present more complexity involving bilateral clinical or electrographic manifestations, have contradicting information, or may involve deeper structures as a part of the epileptogenic zone. These cases are discussed by a multidisciplinary team of experts with a hypothesis for invasive methods of study. Subdural electrodes were once the mainstay of invasive presurgical evaluation and in later years most Comprehensive Epilepsy Centers have shifted to intracranial recordings. The intracranial recording follows original concepts since its development by Bancaud and Talairach, but great advances have been made in the field. Stereo-electroencephalography is a growing field of study, treatment, and establishment of seizure pattern complexities. In this comprehensive review, we explore the indications, usefulness, discoveries in interictal and ictal findings, pitfalls, and advances in the science of presurgical stereo-encephalography for temporal lobe epilepsy