- Overview
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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
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A WORLDWIDE ENIGMA STUDY ON EPILEPSY-RELATED GRAY AND WHITE MATTER COMPROMISE ACROSS THE ADULT LIFESPAN
bioRxiv
DOI: 10.1101/2024.03.02.583073
2024Expanding the molecular and phenotypic spectrum of CTLA-4 insufficiency
Pediatric Allergy and Immunology
DOI: 10.1111/pai.14077
2024Associations of Cerebral Blood Flow Patterns with Gray and White Matter Structure in Patients with Temporal Lobe Epilepsy
Neurology
DOI: 10.1212/WNL.0000000000209528
2024Cerebral perfusion alterations in temporal lobe epilepsy: Structural underpinnings and network disruptions
Alexander Ngo and Jessica Royer and Raúl Rodríguez-Cruces and Ke Xie and Jordan DeKraker and Hans Auer and Shahin Tavakol and Jack Lam and Dewi Schrader and Roy W. R. Dudley and Andrea Bernasconi and Neda Bernasconi and Birgit Frauscher and Sara Larivière and Boris C. Bernhardt
DOI: 10.1101/2023.08.22.553552
08/2023Multimodal mapping of regional brain vulnerability to focal cortical dysplasia
Brain
DOI: 10.1093/brain/awad060
2023All hands on deck: A multidisciplinary approach to SARS-CoV-2-associated MIS-C,Tout le monde sur le pont: une approche multidisciplinaire du SRAS-CoV-2 associe au SIME
Paediatrics and Child Health (Canada)
DOI: 10.1093/pch/pxac018
2022KCNQ2 R144 variants cause neurodevelopmental disability with language impairment and autistic features without neonatal seizures through a gain-of-function mechanism
eBioMedicine
Miceli, F. and Millevert, C. and Soldovieri, M.V. and Mosca, I. and Ambrosino, P. and Carotenuto, L. and Schrader, D. and Lee, H.K. and Riviello, J. and Hong, W. and Risen, S. and Emrick, L. and Amin, H. and Ville, D. and Edery, P. and de Bellescize, J. and Michaud, V. and Van-Gils, J. and Goizet, C. and Willemsen, M.H. and Kleefstra, T. and M?ller, R.S. and Bayat, A. and Devinsky, O. and Sands, T. and Korenke, G.C. and Kluger, G. and Mefford, H.C. and Brilstra, E. and Lesca, G. and Milh, M. and Cooper, E.C. and Taglialatela, M. and Weckhuysen, S.
DOI: 10.1016/j.ebiom.2022.104130
2022All hands on deck: A multidisciplinary approach to SARS-CoV-2-associated MIS-C
Paediatrics and Child Health (Canada)
Lopez, A.A. and Patel, M. and Rayment, J.H. and Tam, H. and Roberts, A. and Laskin, S. and Tucker, L. and Biggs, C.M. and Ahmed, M.A. and Barakauskas, V. and Galanis, E. and Goldfarb, D. and Halparin, J. and Harris, K.C. and Kissoon, N. and Lawrence, S. and McGuffin, D. and Meckler, G. and Noel, K. and Schrader, D. and Sherwood, M. and Singh, A. and Vercauteren, S.
DOI: 10.1093/pch/pxab110
2022Connectomic profiling and Vagus nerve stimulation Outcomes Study (CONNECTiVOS): A prospective observational protocol to identify biomarkers of seizure response in children and youth
BMJ Open
Siegel, L. and Yan, H. and Warsi, N. and Wong, S. and Suresh, H. and Weil, A.G. and Ragheb, J. and Wang, S. and Rozzelle, C. and Albert, G.W. and Raskin, J. and Abel, T. and Hauptman, J. and Schrader, D.V. and Bollo, R. and Smyth, M.D. and Lew, S.M. and Lopresti, M. and Kizek, D.J. and Weiner, H.L. and Fallah, A. and Widjaja, E. and Ibrahim, G.M.
DOI: 10.1136/bmjopen-2021-055886
2022Seizure action plans in the pediatric population with epilepsy: Uptake, determinants, and parental interest in a mobile application
Epilepsy and Behavior
Chiu, M. and Peinhof, S. and De Guzman, C. and Borhani, M. and Siu, C. and Kuzeljevic, B. and Schrader, D. and Huh, L. and Connolly, M.B.
DOI: 10.1016/j.yebeh.2021.107860
2021Multicenter Validation of a Deep Learning Detection Algorithm for Focal Cortical Dysplasia
Neurology
Gill, R.S. and Lee, H.-M. and Caldairou, B. and Hong, S.-J. and Barba, C. and Deleo, F. and D'Incerti, L. and Mendes Coelho, V.C. and Lenge, M. and Semmelroch, M. and Schrader, D.V. and Bartolomei, F. and Guye, M. and Schulze-Bonhage, A. and Urbach, H. and Cho, K.H. and Cendes, F. and Guerrini, R. and Jackson, G. and Hogan, R.E. and Bernasconi, N. and Bernasconi, A.
DOI: 10.1212/WNL.0000000000012698
2021ILAE Neuroimaging Task Force Highlight: harnessing optimized imaging protocols for drug-resistant childhood epilepsy
Epileptic Disorders
Larivière, S. and Federico, P. and Chinvarun, Y. and Jackson, G. and Morgan, V. and Rampp, S. and Vaudano, A.E. and Wang, I. and Cendes, F. and Boelman, C.G. and Bernasconi, A. and Bernasconi, N. and Bernhardt, B.C. and Schrader, D.V.
DOI: 10.1684/epd.2021.1312
2021Rapid Implementation of Virtual Health in a Pediatric Neurology Practice During COVID-19.
The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques
Lee J and Schrader D and Boelman C and Huh L and Connolly MB
DOI: 10.1017/cjn.2020.241
PubMed: 33148364
11/2020Functional 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, D.V. and Zhang, Z. and Bernhardt, B.C.
DOI: 10.1111/epi.16540
2020Multiscale Structure-Function Gradients in the Neonatal Connectome
Cerebral Cortex
Larivière, 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
2020GP.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
06/2019Targeting age-related differences in brain and cognition with multimodal imaging and connectome topography profiling
Human Brain Mapping
Lowe, A.J. 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, D.V. and Bernasconi, A. and Bernasconi, N. and Spreng, R.N. and Bernhardt, B.C.
DOI: 10.1002/hbm.24767
2019Functional connectome contractions in temporal lobe epilepsy: Microstructural underpinnings and associations to surgical outcome
bioRxiv
Larivière, S. and Weng, Y. and de Wael, R.V. and Frauscher, B. and Wang, Z. and Bernasconi, A. and Bernasconi, N. and Schrader, D.V. and Zhang, Z. and Bernhardt, B.C.
DOI: 10.1101/756494
2019Brain morphometry: Epilepsy
Neuromethods
DOI: 10.1007/978-1-4939-7647-8_18
2018Multimodal 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
2017Whole-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
2016MRI-based lesion profiling of epileptogenic cortical malformations
Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
DOI: 10.1007/978-3-319-24571-3_60
2015Automated 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
20144D CT angiography more closely defines intracranial thrombus burden than single-phase CT angiography
American Journal of Neuroradiology
Frölich, 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
2013Advances 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
2011Epilepsy with occipital features in children: Factors predicting seizure outcome and neuroimaging abnormalities
European Journal of Paediatric Neurology
Schrader, D. and Shukla, R. and Gatrill, R. and Farrell, K. and Connolly, M.
DOI: 10.1016/j.ejpn.2010.08.005
2011Cingulate 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
2009Urgent, resective surgery for medically refractory, convulsive status epilepticus
European Journal of Paediatric Neurology
Schrader, D.V. and Steinbok, P. and Connolly, M.
DOI: 10.1016/j.ejpn.2008.01.011
2009The role of neurosurgery in status epilepticus
Neurocritical Care
Ng, Y.-T. and Bristol, R.E. and Schrader, D.V. and Smith, K.A.
DOI: 10.1007/s12028-007-0038-4
2007Identification and characterization of two neurogenic zones in interface organotypic hippocampal slice cultures
Neuroscience
Chechneva, O. and Dinkel, K. and Schrader, D. and Reymann, K.G.
DOI: 10.1016/j.neuroscience.2005.07.058
2005 - Research
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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.GrantsSickKids Foundation - New Investigator Grant 2016 "Connectome informed simulations of pediatric epilepsy surgery"
Research Group MembersVesna Popovska, Research Director, Pediatric Neurology & Neurosurgery
Sara Singh, Research Study Assistant
A strong case for virtual health in pediatric neurology
Dr. James Lee and colleagues found that virtual health in a pediatric neurology setting during the COVID-19 pandemic provided reliable, accessible and efficient patient care.
