Overview

Epilepsy affects approximately 50 million people worldwide. Up to 30 per cent of patients with focal epilepsy have persistent, disabling seizures that are resistant to conventional treatment. Uncontrolled epilepsy is harmful to the brain, has devastating socio-economic consequences, and is associated with increased risk of injury and sudden death. Surgery is the most effective treatment for drug-resistant focal childhood epilepsy.

Magnetic resonance imaging (MRI) has revolutionized the evaluation and management of drug-resistant epilepsy by allowing the reliable detection of the structural lesion associated with certain focal epilepsies, thus leading to increased rates of successful resective surgery. Multiple studies have shown that the most important predictor for favorable post-surgical outcome is the complete resection of the abnormality detected on pre-operative MRI. However, despite technical improvements in MR hardware and sequences, in up to 50 percent of patients with drug-resistant focal epilepsy have a best-practice MRI that is unremarkable and thus unable to show the potential surgical target.

Our research focuses on the use of advanced MRI techniques to improve the understanding and treatment epilepsy due to focal lesions.

Publications

Functional connectome contractions in temporal lobe epilepsy: Microstructural underpinnings and predictors of surgical outcome.
Epilepsia
Larivière S and Weng Y and Vos de Wael R and Royer J and Frauscher B and Wang Z and Bernasconi A and Bernasconi N and Schrader DV and Zhang Z and Bernhardt BC
DOI: 10.1111/epi.16540
PubMed: 32452574
05/2020

Multiscale Structure-Function Gradients in the Neonatal Connectome
Cerebral Cortex
Larivi{\`e}re, S. and Vos De Wael, R. and Hong, S.-J. and Paquola, C. and Tavakol, S. and Lowe, A.J. and Schrader, D.V. and Bernhardt, B.C.
DOI: 10.1093/cercor/bhz069
2020

Targeting age-related differences in brain and cognition with multimodal imaging and connectome topography profiling
Human Brain Mapping
Alexander J. Lowe and Casey Paquola and Reinder Vos de Wael and Manesh Girn and Sara Lariviere and Shahin Tavakol and Benoit Caldairou and Jessica Royer and Dewi V. Schrader and Andrea Bernasconi and Neda Bernasconi and R. Nathan Spreng and Boris C. Bernhardt
DOI: 10.1002/hbm.24767
08/2019

GP.04 Prevalence and determinants of seizure action plans in a pediatric epilepsy population
Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques
M Chiu and S Peinhof and M Borhani and C DeGuzman and C Siu and B Kuzeljevic and D Schrader and L Huh and MB Connolly
DOI: 10.1017/cjn.2019.80
06/2019

Targeting Age-Related Differences in Brain and Cognition with Multimodal Imaging and Connectome Topography Profiling
Lowe AJ and Paquola C and Vos de Wael R and Girn M and Lariviere S and Tavakol S and Caldairou B and Royer J and Schrader DV and Bernasconi A and Bernasconi N and Spreng RN and Bernhardt BC
DOI: 10.1101/601146
04/2019

Brain Morphometry: Epilepsy
Neuromethods
Dewi S. Schrader and Neda Bernasconi and Andrea Bernasconi
DOI: 10.1007/978-1-4939-7647-8_18
02/2018

Multimodal MRI profiling of focal cortical dysplasia type II
Neurology
Seok-Jun Hong and Boris C. Bernhardt and Benoit Caldairou and Jeffery A. Hall and Marie C. Guiot and Dewi Schrader and Neda Bernasconi and Andrea Bernasconi
DOI: 10.1212/wnl.0000000000003632
01/2017

Multimodal MRI profiling of focal cortical dysplasia type II
Neurology
Hong, S.-J. and Bernhardt, B.C. and Caldairou, B. and Hall, J.A. and Guiot, M.C. and Schrader, D. and Bernasconi, N. and Bernasconi, A.
DOI: 10.1212/WNL.0000000000003632
2017

Whole-brain MRI phenotyping in dysplasia-related frontal lobe epilepsy
Neurology
Seok-Jun Hong and Boris C. Bernhardt and Dewi S. Schrader and Neda Bernasconi and Andrea Bernasconi
DOI: 10.1212/wnl.0000000000002374
01/2016

Whole-brain MRI phenotyping in dysplasia-related frontal lobe epilepsy
Neurology
Hong, S.-J. and Bernhardt, B.C. and Schrader, D.S. and Bernasconi, N. and Bernasconi, A.
DOI: 10.1212/WNL.0000000000002374
2016

MRI-based lesion profiling of epileptogenic cortical malformations
Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
Hong, S.-J. and Bernhardt, B.C. and Schrader, D. and Caldairou, B. and Bernasconi, N. and Bernasconi, A.
DOI: 10.1007/978-3-319-24571-3_60
2015

Automated detection of cortical dysplasia type II in MRI-negative epilepsy
Neurology
Hong, S.-J. and Kim, H. and Schrader, D. and Bernasconi, N. and Bernhardt, B.C. and Bernasconi, A.
DOI: 10.1212/WNL.0000000000000543
2014

4D CT angiography more closely defines intracranial thrombus burden than single-phase CT angiography
American Journal of Neuroradiology
Fr{\"o}lich, A.M.J. and Schrader, D. and Klotz, E. and Schramm, R. and Wasser, K. and Knauth, M. and Schramm, P.
DOI: 10.3174/ajnr.A3533
2013

Epilepsy with occipital features in children: Factors predicting seizure outcome and neuroimaging abnormalities
European Journal of Paediatric Neurology
Dewi Schrader and Ruchika Shukla and Renee Gatrill and Kevin Farrell and Mary Connolly
DOI: 10.1016/j.ejpn.2010.08.005
01/2011

Advances in MRI for 'cryptogenic' epilepsies
Nature Reviews Neurology
Bernasconi, A. and Bernasconi, N. and Bernhardt, B.C. and Schrader, D.
DOI: 10.1038/nrneurol.2010.199
2011

Cingulate Lesions Presenting With Epileptic Spasms
Journal of Clinical Neurophysiology
Dewi Schrader and Lisa Langill and Ash Singhal and Paul Steinbok and Mary B. Connolly
DOI: 10.1097/wnp.0b013e3181baaacf
10/2009

Urgent, resective surgery for medically refractory, convulsive status epilepticus
European Journal of Paediatric Neurology
Dewi V. Schrader and Paul Steinbok and Mary Connolly
DOI: 10.1016/j.ejpn.2008.01.011
01/2009

Cingulate lesions presenting with epileptic spasms
Journal of Clinical Neurophysiology
Schrader, D. and Langill, L. and Singhal, A. and Steinbok, P. and Connolly, M.B.
DOI: 10.1097/WNP.0b013e3181baaacf
2009

The role of neurosurgery in status epilepticus.
Neurocritical care
Ng YT and Bristol RE and Schrader DV and Smith KA
DOI: 10.1007/s12028-007-0038-4
PubMed: 17657660
01/2007

Functional connectome contractions in temporal lobe epilepsy: microstructural underpinnings and associations to surgical outcome
Sara Larivière and Yifei Weng and Reinder Vos de Wael and Birgit Frauscher and Zhengge Wang and Andrea Bernasconi and Neda Bernasconi and Dewi V. Schrader and Zhiqiang Zhang and Boris C. Bernhardt
DOI: 10.1101/756494

Research

Connectome-informed simulations of pediatric epilepsy surgery
Background

Surgery is the most effective treatment for drug-resistant childhood epilepsy. Yet, ~30 per cent of patients show post-surgical seizure recurrence and many suffer from cognitive side effects. So far, an outcome cannot be reliably predicted for a given patient prior to intervention.

Objectives

1) Integrate preoperative MRI markers and data on the actual surgery for more effective prediction;

2) analyze brain change from pre- to postoperative time points, mapping alterations of non-resected areas; 3) simulate network reorganization using connectome models.
Hypothesis. Combining preoperative markers of patient anatomy with with models that simulate consequences of surgery will yield high accuracy in predicting clinical and cognitive outcomes.

Methods

In children that will undergo epilepsy surgery, we will obtain MRI and neurocognitive data shortly before surgery, 6 months after surgery (and 12 months after surgery. We will overlay resection extent (from postoperative MRI) with preoperative MRI features (atrophy, gliosis, myelin), testing whether anomalies outside the resection margin predict seizure relapse. In addition, fMRI pattern analysis will localize regions critical for language/memory function, testing whether their resection relates to postoperative cognitive decline. Mixed-effects models will map MRI feature change, assessing surgical consequences. Connectome-based models will be devised to predict downstream degeneration and functional reorganization after surgery in non-resected areas. Supervised learners will predict outcomes based on preoperative data and simulations.

Expected Results

Empirical studies on surgical consequences will help build effective in silico models that optimize outcome prediction, improving clinical decision-making in >10,000 children with drug-resistant seizures in Canada.
Improved detection of Focal Cortical Dysplasia.
Focal cortical dysplasia (FCD) is the most common cause of surgically-treatable, extra-temporal epilepsy. Unfortunately, the findings of FCD on MRI are often subtle and can be easily overlooked. We are using advanced MRI techniques to improve the detection of focal cortical dysplasia, allowing us to offer the life changing benefits of epilepsy surgery to more patients.

Grants

SickKids Foundation - New Investigator Grant 2016 "Connectome informed simulations of pediatric epilepsy surgery"