scholarly journals Virtual resection predicts surgical outcome for drug-resistant epilepsy

Brain ◽  
2019 ◽  
Vol 142 (12) ◽  
pp. 3892-3905 ◽  
Author(s):  
Lohith G Kini ◽  
John M Bernabei ◽  
Fadi Mikhail ◽  
Peter Hadar ◽  
Preya Shah ◽  
...  

Abstract Patients with drug-resistant epilepsy often require surgery to become seizure-free. While laser ablation and implantable stimulation devices have lowered the morbidity of these procedures, seizure-free rates have not dramatically improved, particularly for patients without focal lesions. This is in part because it is often unclear where to intervene in these cases. To address this clinical need, several research groups have published methods to map epileptic networks but applying them to improve patient care remains a challenge. In this study we advance clinical translation of these methods by: (i) presenting and sharing a robust pipeline to rigorously quantify the boundaries of the resection zone and determining which intracranial EEG electrodes lie within it; (ii) validating a brain network model on a retrospective cohort of 28 patients with drug-resistant epilepsy implanted with intracranial electrodes prior to surgical resection; and (iii) sharing all neuroimaging, annotated electrophysiology, and clinical metadata to facilitate future collaboration. Our network methods accurately forecast whether patients are likely to benefit from surgical intervention based on synchronizability of intracranial EEG (area under the receiver operating characteristic curve of 0.89) and provide novel information that traditional electrographic features do not. We further report that removing synchronizing brain regions is associated with improved clinical outcome, and postulate that sparing desynchronizing regions may further be beneficial. Our findings suggest that data-driven network-based methods can identify patients likely to benefit from resective or ablative therapy, and perhaps prevent invasive interventions in those unlikely to do so.

2020 ◽  
Author(s):  
Florian Missey ◽  
Evgeniia Rusina ◽  
Emma Acerbo ◽  
Boris Botzanowski ◽  
Romain Carron ◽  
...  

AbstractIn patients with focal drug-resistant epilepsy, electrical stimulation from intracranial electrodes is frequently used for the localization of seizure onset zones and related pathological networks. The ability of electrically stimulated tissue to generate beta and gamma range oscillations, called rapid-discharges, is a frequent indication of an epileptogenic zone. However, a limit of intracranial stimulation is the fixed physical location and number of implanted electrodes, leaving numerous clinically and functionally relevant brain regions unexplored. Here, we demonstrate an alternative technique relying exclusively on nonpenetrating surface electrodes, namely an orientation-tunable form of temporally-interfering (TI) electric fields to target the CA3 of the mouse hippocampus which focally evokes seizure-like events (SLEs) having the characteristic frequencies of rapid-discharges, but without the necessity of the implanted electrodes. The orientation of the topical electrodes with respect to the orientation of the hippocampus is demonstrated to strongly control the threshold for evoking SLEs. Additionally, we demonstrate the use of square waves as an alternative to sine waves for TI stimulation. An orientation-dependent analysis of classic implanted electrodes to evoke SLEs in the hippocampus is subsequently utilized to support the results of the minimally-invasive temporally-interfering fields. The principles of orientation-tunable TI stimulation seen here can be generally applicable in a wide range of other excitable tissues and brain regions, overcoming several limitations of fixed electrodes which penetrate tissue.


2019 ◽  
Vol 61 (1) ◽  
pp. 67-75 ◽  
Author(s):  
Pei-Wen Zhu ◽  
You Chen ◽  
Ying-Xin Gong ◽  
Nan Jiang ◽  
Wen-Feng Liu ◽  
...  

Background Neuroimaging studies revealed that trigeminal neuralgia was related to alternations in brain anatomical function and regional function. However, the functional characteristics of network organization in the whole brain is unknown. Purpose The aim of the present study was to analyze potential functional network brain-activity changes and their relationships with clinical features in patients with trigeminal neuralgia via the voxel-wise degree centrality method. Material and Methods This study involved a total of 28 trigeminal neuralgia patients (12 men, 16 women) and 28 healthy controls matched in sex, age, and education. Spontaneous brain activity was evaluated by degree centrality. Correlation analysis was used to examine the correlations between behavioral performance and average degree centrality values in several brain regions. Results Compared with healthy controls, trigeminal neuralgia patients had significantly higher degree centrality values in the right lingual gyrus, right postcentral gyrus, left paracentral lobule, and bilateral inferior cerebellum. Receiver operative characteristic curve analysis of each brain region confirmed excellent accuracy of the areas under the curve. There was a positive correlation between the mean degree centrality value of the right postcentral gyrus and VAS score (r = 0.885, P < 0.001). Conclusions Trigeminal neuralgia causes abnormal brain network activity in multiple brain regions, which may be related to underlying disease mechanisms.


2011 ◽  
Vol 6 (1) ◽  
pp. 57 ◽  
Author(s):  
Xiao-Ting Hao ◽  
Patrick Kwan ◽  
◽  

Drug-resistant epilepsy remains a major clinical challenge. Diverse criteria have been used to define drug resistance by different researchers, making it difficult or even impossible to compare the results across different studies. To improve patient care and facilitate clinical research, the International League Against Epilepsy (ILAE) recently proposed a consensus definition to define drug-resistant epilepsy. This is the failure of adequate trials of two tolerated, appropriately chosen and used antiepileptic drug schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom. This article outlines the framework of the consensus definition, explains how to apply it in practice and discusses the future development of its use.


2021 ◽  
Author(s):  
Kiran Seunarine ◽  
Xiaosong He ◽  
Martin Tisdall ◽  
Christopher Clark ◽  
Danielle S Bassett ◽  
...  

Network control theory provides a framework by which neurophysiological dynamics of the brain can be modelled as a function of the structural connectome constructed from diffusion MRI. Average controllability describes the ability of a region to drive the brain to easy-to-reach neurophysiological states whilst modal controllability describes the ability of a region to drive the brain to difficult-to-reach states. In this study, we identify increases in mean average and modal controllability in children with drug-resistant epilepsy compared to healthy controls. Using simulations, we purport that these changes may be a result of increased thalamocortical connectivity. At the node level, we demonstrate decreased modal controllability in the thalamus and posterior cingulate regions. In those undergoing resective surgery, we also demonstrate increased modal controllability of the resected parcels, a finding specific to patients who were rendered seizure free following surgery. Changes in controllability are a manifestation of brain network dysfunction in epilepsy and may be a useful construct to understand the pathophysiology of this archetypical network disease. Understanding the mechanisms underlying these controllability changes may also facilitate the design of network-focussed interventions that seek to normalise network structure and function.


2019 ◽  
Author(s):  
Adam Li ◽  
Chester Huynh ◽  
Zachary Fitzgerald ◽  
Iahn Cajigas ◽  
Damian Brusko ◽  
...  

AbstractOver 15 million epilepsy patients worldwide do not respond to drugs. Successful surgical treatment requires complete removal, or disconnection of the seizure onset zone (SOZ), brain region(s) where seizures originate. Unfortunately, surgical success rates vary between 30%-70% because no clinically validated biological marker of the SOZ exists. We develop and retrospectively validate a new EEG marker - neural fragility. We validate this new marker in a retrospective analysis of 91 patients by using neural fragility of the annotated SOZ as a metric to predict surgical outcomes. Fragility predicts 43/47 surgical failures with an overall prediction accuracy of 76%, compared to the accuracy of clinicians being 48% (successful outcomes). In failed outcomes, we identify fragile regions that were untreated. When compared to 20 EEG features proposed as SOZ markers, fragility outperformed in predictive power and interpretability suggesting neural fragility as an EEG fingerprint of the SOZ.One Sentence SummaryNeural fragility, an intracranial EEG biomarker for the seizure onset zone in drug-resistant epilepsy, predicts surgical outcomes with high accuracy.


Author(s):  
Christos Koutlis

In this work the objective is to detect brain connectivity changes during epileptic seizures using methods of multivariate time series analysis on scalp multi-channel EEG. Different brain regions represented by the electrode positions interact in terms of Granger causality and these directed connections formulate the brain network at a certain time window. The numerous proposed network features are believed to capture the information of many network characteristics. The ability of a single network feature of the brain network to detect the transition of brain activity from preictal to ictal is examined. The connectivity of the brain is estimated by 13 Granger causality indices on 7 epochs from multivariate time series (19 channels per epoch) at 15 time windows of 20 seconds (5 min in total) before seizure and during the seizure. The characteristics of the networks are estimated by 379 network features. Finally, the discrimination task (preictal vs. ictal) for each network feature is evaluated by the area under receiver operating characteristic curve (AUROC).


Epilepsia ◽  
2019 ◽  
Vol 60 (4) ◽  
pp. 593-604 ◽  
Author(s):  
Shahin Tavakol ◽  
Jessica Royer ◽  
Alexander J. Lowe ◽  
Leonardo Bonilha ◽  
Joseph I. Tracy ◽  
...  

2016 ◽  
Vol 23 (2) ◽  
pp. 152-168 ◽  
Author(s):  
Stefanie Robel

Epilepsy is among the most prevalent chronic neurological diseases and affects an estimated 2.2 million people in the United States alone. About one third of patients are resistant to currently available antiepileptic drugs, which are exclusively targeting neuronal function. Yet, reactive astrocytes have emerged as potential contributors to neuronal hyperexcitability and seizures. Astrocytes react to any kind of CNS insult with a range of cellular adjustments to form a scar and protect uninjured brain regions. This process changes astrocyte physiology and can affect neuronal network function in various ways. Traumatic brain injury and stroke, both conditions that trigger astroglial scar formation, are leading causes of acquired epilepsies and surgical removal of this glial scar in patients with drug-resistant epilepsy can alleviate the seizures. This review will summarize the currently available evidence suggesting that epilepsy is not a disease of neurons alone, but that astrocytes, glial cells in the brain, can be major contributors to the disease, especially when they adopt a reactive state in response to central nervous system insult.


US Neurology ◽  
2010 ◽  
Vol 06 (02) ◽  
pp. 122
Author(s):  
Xiao-Ting Hao ◽  
Patrick Kwan ◽  
◽  

Drug-resistant epilepsy remains a major clinical challenge. Diverse criteria have been used to define drug resistance by different researchers, making it difficult or even impossible to compare the results across different studies. To improve patient care and facilitate clinical research, the International League Against Epilepsy (ILAE) recently proposed a consensus definition to define drug-resistant epilepsy. This is the failure of adequate trials of two tolerated, appropriately chosen and used antiepileptic drug schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom. This article outlines the framework of the consensus definition, explains how to apply it in practice, and discusses the future development of its use.


Author(s):  
Brittany H. Scheid ◽  
John M. Bernabei ◽  
Ankit N. Khambhati ◽  
Jay Jeschke ◽  
Danielle S. Bassett ◽  
...  

AbstractDespite the success of responsive neurostimulation (RNS) for epilepsy, clinical outcomes vary significantly and are hard to predict. The ability to forecast clinical response to RNS therapy before device implantation would improve patient selection for RNS surgery and could prevent a costly and ineffective intervention. Determining and validating biomarkers predictive of RNS response is difficult, however, due to the heterogeneity of the RNS patient population and clinical procedures; large, multi-center datasets are needed to quantify patient variability and to account for stereotypy in the treatment paradigm of any one center. Here we use a distributed, cloud-based pipeline to analyze a federated dataset of intracranial EEG recordings, collected prior to RNS surgery, from a retrospective cohort of 30 patients across three major epilepsy centers. Based on recent work modelling the controllability of distributed brain networks, we hypothesize that broader brain network connectivity, beyond the seizure onset zone, can predict RNS response. We demonstrate how intracranial EEG recordings can be leveraged through network analysis to uncover biomarkers that predict response to RNS therapy. Our findings suggest that peri-ictal changes in synchronizability, a global network metric shown to accurately predict outcome from resective epilepsy surgery, can distinguish between good and poor RNS responders under the current RNS therapy guidelines (area under the receiver operating characteristic curve of 0.75). Furthermore, this study also provides a proof-of-concept roadmap for multicenter collaboration where practical considerations impede sharing datasets fully across centers.


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