The Calgary Comprehensive Epilepsy Program

Through its strong academic and clinical arms, the Calgary Comprehensive Epilepsy Program (CEP) focuses on achieving the best outcomes for patients suffering from epilepsy. This is accomplished through new developments in clinical research, quality improvement initiatives, and comprehensive, interdisciplinary clinical care. The interdisciplinary team includes a highly skilled group of specialists in epilepsy comprising neurologist epileptologists, epilepsy neurosurgeons, neuropsychiatrists, clinical psychologists, neuropsychologists, neuroradiologists, nuclear medicine specialists, clinical assistant physicians, nurses, EEG technologists, clinical neurophysiologists and administrative staff.

The research team has strong collaborations with the Hotchkiss Brain Institute (HBI), the O’Brien Institute for Public Health, and the Alberta Children’s Hospital Research Institute. The team includes basic scientists (HBI), health outcomes and health services researchers, and advanced imaging researchers. The CEP clinical research team also continues to have strong collaborations with, and support from, the Brain and Mental Health Research Clinics; an initiative partially funded by DCNS.

As a tertiary care centre, the CEP provides care for a wide breadth of persons with epilepsy, including those with complex epilepsies, and those requiring complex surgical investigations and interventions. Complex and surgical adult and pediatric cases are discussed weekly in multidisciplinary conferences in conjunction with pediatric epilepsy colleagues.

Core clinical facilities available at the CEP include:

• State-of-the-art neurophysiologic assessment, including long-term video-EEG monitoring, day-time video-EEG monitoring, 24-hour ambulatory EEG monitoring, intracranial EEG using multiple modalities of implantation and electrodes, electrocorticography, functional brain mapping, and intraoperative monitoring and evoked potentials. Analysis of high frequency oscillations (HFOs) is available and automated detection of HFOs has been developed to facilitate EEG source localization.
• Advanced functional imaging includes PET, SPECT, functional MRI with capacity for mapping of cortical function, voxel-based relaxometry and arterial spin labeling, as well as EEG-fMRI interictal and ictal studies.
• The EEG laboratory operates at four hospital sites and the Seizure Monitoring Unit (SMU) operates at the Foothills Medical Centre and the South Health Campus. Continuous video-EEG monitoring is provided at all hospital sites for diagnostic purposes in hospitalized patients, and for seizure management in critically ill patients at all four adult sites in the Calgary Zone.
• Neuropsychologists, clinical psychologists and neuropsychiatrists focusing on epilepsy provide care to patients in the CEP.
• The CEP registry increasingly encompasses neurosurgical, genetics and clinic datasets. In particular the clinic dataset is being incorporated into routine care by providing one-page clinical summaries for every patient, which includes measures of well-being, mental health and clinical aspects. These summaries are made available at the time of patient encounters to facilitate and ensure comprehensive care.
• Epilepsy surgery for drug-resistant epilepsy is guided by scalp and intracranial EEG. Surgical techniques include subdural and depth electrodes, robotic  and frame-based stereo-EEG, cortical mapping, the entire breadth of procedures for cortical resection and disconnections,and neuromodulation including vagus nerve stimulation and deep brain stimulation.  MR guided Laser Interstitial Thermal Therapy (Mrg-LITT), a minimally invasive technique for lesioning epileptic foc, is the newest addtion.

Research and Leadership

The CEP houses world-class research teams in prediction models, health services research and outcomes research (Dr. Samuel Wiebe and Dr. Colin Josephson), genomics (Dr. Karl Martin Klein), and in advanced imaging in epilepsy (Dr. Paolo Federico). Members of the CEP serve in leadership positions in organizations such of the Canadian League Against Epilepsy, the International League Against Epilepsy (ILAE), the North American Commission of the ILAE, the Latin American Commission of the ILAE, the Commission on Diagnostics of the ILAE, and the Task Forces on Big Data, epilepsy in the elderly, and guidelines of the ILAE.

Important initiatives spearheaded this year by Dr. Wiebe as president of the International League Against Epilepsy include:

1. the development and publication of the Competencies-Based Curriculum for Education in Epileptology. This systematically developed curriculum and learning objectives are now being used internationally to develop a large variety of educational tools, including distance learning, that can lead to an Assessment-Based Certificate in Epileptology in countries around the world.
2. Creation of the ILAE Academy, a comprehensive portal for online education in epilepsy;
3. Creation of ILAE Councils on Education, Congresses, Publications and Global Outreach.
4. Producing, in collaboration with the WHO and the International Bureau for Epilepsy, the first Global Report on Epilepsy.
5. Creation of the Next Generation Initiative in Epilepsy to engage early career professionals in the field of epilepsy.

Dr. Federico has started his two-year term as President of the Canadian League Against Epilepsy. He is also the chair of Neuroimaging Task Force of the International League Against Epilepsoy. As chair, he has organized an on-line neuroimaging course that is freely available to all ILAE members. He is also organizing a three-month web-based course on basic and advanced topics related to neuroimaging in epilepsy.

Quality of Care

The CEP has developed a thriving quality of care program that systematically evaluates clinical care and patient outcomes in the SMU and in the epilepsy clinics. This year, the CEP database has expanded significantly in scope and aims to promote patient outcomes through integrating clinical, EEG, MRI, genomic, and electronic health records data. Additionally, funding has been secured to create a multicentre consortium on epilepsy clinical data, led by Drs. Josephson and Wiebe, using the CEP clinical database model and structure.

Highlights

• The CEP, like every other programme has had to adapt to the unique circumstances of the COVID-19 pandemic. Outpatient clinic, inpatient consultations, seizure monitoring unit, and inpatient and outpatient EEG laboratory services, have followed rigorously the guidelines of our health authorities to prevent COVID-19 spread. At the same time, we have continued to provide all services listed above, with the necessary restrictions, including telemedicine, physical distancing, decreased patient density in seizure monitoring units, freeing up beds for pandemic emergencies, covering back-up call for epilepsy, and adapting our EEG protocols for safe practices. Not least, we are mindful of the important toll the pandemic takes on the well-being and mental health of our patients and our staff and are mindful to provide the necessary support.
• The CEP held a very successful third Banff International Epilepsy Symposium in February 2020 on the topic of “Epilepsy Care in the 21st Century: Precision Medicine and Novel Surgical Techniques.” In addition to our local speakers, the one-day symposium featured renowned international researchers  Heather Mefford (USA), Nathan Fountain (USA), and Fabrice Bartolomei (France). A successful Western Epilepsy Workshop was held after the Banff symposium, organized by the Calgary Epielpsy Programme, featuring lively case presentations from colleagues across Western Canada.
• The 2019 Mary Anne Lee Memorial lecturer in epilepsy was Dr. Robert Gross from Emory University, who spoke about “The New Era of Minimally Invasive Surgery.”
• The CEP held its annual epilepsy research retreat, in conjunction with the HBI, with presentations by trainees and prizes for best trainee presentations.
• Dr. Paolo Federico is conducting a clinical trial looking for a new indication for ibuprofen and nifedipine to prevent postictal hypoperfusion.
• Dr. Federico was awarded a six-year CIHR operating grant for the project “Improving epilepsy surgery outcome by mapping high frequency oscillations. The application was ranked 2nd out of 57 applications reviewed.
• Dr. Walter Hader has implemented the first MR guided laser interstitial thermal therapy (MRg-LITT) treatment for intractable epilepsy secondary to mesial temporal sclerosis was performed in Calgary in February, 2020.  The LITT program was recently established as a result of a philanthropic joint venture between the Alberta Children’s Hospital Foundation and Calgary Health Trust in support of the Epilepsy surgery program.  The Mrg-LITT procedure is performed in an all inclusive Epilepsy Surgery Suite,  the Seamen MR Centre, housing an IMRIS 3T intraoperative MRI, ROSA robotic assistant and Visualase Laser Platform.
• Dr. Fady Girgis joined the neurosurgery epilepsy team, with a focus on functional neurosurgery and neurostimulation.
• Drs. Sophia Macrodimitris and Ruby Sharma run a successful cognitive behavioural therapy program for epilepsy patients with anxiety and depression, and they offer much needed psychological support for epilepsy patients. They train psychology practicum students through the University of Calgary and residents through the Calgary Clinical Psychology Residency Program. They also provide support for patients with functional neurological symptom disorder (Conversion Disorder) presenting as epileptic seizures. Dr. Joanne Stephen provides psychological services for epilepsy patients at the South Health Campus.
• Drs. Lisa Partlo and Kim Goddard use standardized procedures for neuropsychological testing in epilepsy patients across hospitals, providing a uniquely strong team for our CEP. Drs. Brienne McLean and Aaron Mackie, neuropsychiatrists affiliated to the CEP, provide invaluable support to our many patients with psychiatric comorbidities.

There are important developments in pediatric epilepsy this year:

• Dr. Julia Jacobs from Freiburg, Germany is now the director of the pediatric epilepsy program
• Dr. Pierre Levan, also from Freiburg, is now a member of the Alberta Children’s Hospital Institute and the Hotchkiss Brain Institute to continue his work on advanced imaging in epilepsy.

In the basic sciences, the Hotchkiss Brain Institute continues to be a strong partner in various fronts:

• Dr. Cam Teskey’s CIHR-funded research program discovered that a severe hypoperfusion/hypoxic event follows a seizure, which has implications for postictal behavioural dysfunction including paralysis, memory disturbances and Sudden Unexpected Death in Epilepsy.
• Dr. Quentin Pittman’s lab employs multiple approaches to investigate neuronal function from the entire organism to the single cell.

This year we will welcome two Epilepsy and EEG fellows in the adult program —Dr. Guillermo Delgado Garcia from Mexico, and Dr. Laura Gill, from British Columbia. The paediatric epilepsy programme will also welcome Dr. Marvin Braun as an epilepsy fellow later during this term.

Dr. Karl Martin Klein runs a research program on epilepsy genetics and genomics, as well as precision medicine. Consenting patients provide a blood or saliva sample of which DNA is extracted, stored and analyzed. Details on the patients’ epilepsy are documented in a database that is linked to the CEP database. His group has recently established somatic DNA extraction from brain cells that remain on depth electrodes used for intracranial video EEG monitoring and also from LITT probes (laser surgery).

These samples allow the identification of somatic mutations i.e. genetic variants that occur during development and are only present in the brain. DNA samples and phenotypic information are used in local and international collaborative projects to identify new genes for epilepsy in multiplex families with epilepsy, patients with epileptic encephalopathies and common epilepsies and to characterize the associated phenotype. The combination of the genetic data with the detailed prospective data in the CEP database also allows to address pharmacogenomic questions.

Dr. Klein coordinates an international consortium (RAISE-GENIC, funded by the ERA PerMed Cofound) which aims to develop tools that help physicians to select the anti-seizure drug with the best chance of success. This collaborative effort involves additional PIs at the University of Calgary (Dr. Colin Josephson) and three European countries (Germany, Finland, Belgium) and uses big data strategies to integrate clinical data, raw EEG and raw MRI data as well as exome sequencing data.

Dr. Colin Josephson leads the big data and data linkage initiatives within the CEP. He has made important inroads in linking granular clinical data with raw imaging and EEG data. Linkage with genetic data and administrative health records is an ongoing project. Dr. Josephson’s research has resulted in milestone publications related to predictive models and clinical-epidemiological aspects of epilepsy utilizing machine learning and traditional statistical models. These contributions have been published in flagship journals such as JAMA Neurology, Journal of Nuerology, Neurosurgery and Psychiatry, and Epilepsia. Additionally, Dr. Josephson leads the Canada-wide epilepsy registry initiative (CANOE) which is closer now to being implemented. Dr. Josephson also serves in several Task Forces of the International League Against Epilepsy including Epilepsy and driving and Big Data.

Dr. Billie Au (Medical Genetics), Dr. JP Appendino (Pediatrics) and Dr. Karl Martin Klein have established the Genetic Epilepsy Clinic for patients with unsolved genetic epilepsies.

Dr. Wiebe continues to lead the overall CEP. Dr. Paolo Federico is lead of the SMU and EEG laboratories. Dr. Colin Josephson is the leader of the epilepsy clinics. Drs. Shaily Singh and Colin Josephson are the co-directors of education and fellowships. Dr. Karl Martin Klein overviews clinical assistants and Dr. William Murphy overviews clinical trials.

Dr. Wiebe chairs the Clinical Research Unit for the Cumming School of Medicine, and is serving his third year as president of the International League Against Epilepsy.

Members

Adult Epileptology: Dr. Paolo Federico, Dr. Alexandra Hanson, Dr. Colin Josephson, Dr. Brain Klassen, Dr. Karl Martin Klein, Dr. William Murphy, Dr. Andrea Salmon, Dr. Shaily Singh, Dr. Samuel Wiebe

Pediatric Epileptology: Dr. Juan Pablo Appendino, Dr. Alice Ho, Dr. Morris Scantlebury, Dr. Julia Jacobs

Neurosurgery: Dr. Walter Hader, Dr. Yves Starreveld, Dr. Fady Girgis

Neuropsychiatry: Dr. Aaron Mackie, Dr. Brienne McLean

Clinical psychology: Dr. Sophia Macrodimitris, Dr. Ruby Sharma, Dr. Joanne Stephen

Adult Neuropsychology: Dr. Lisa Partlo, Dr. Kim Goddard, Dr. Linette Savage

Psychometrists: Danielle Croft, Gerry Ceballos, Ryan Kasper

Neuro-Intensive Care: Dr. Julie Krom

Pediatric Neuropsychology: Brian Brooks, Marsha Vasserman, Naddley Desire, Sandra Mish, Taryn Fay-McClymont, William MacAllister

Adult Neuroradiology: Dr. James Scott

Nuclear Medicine: Dr. Christine Molnar, Dr. Leonard Numerow, Dr. Ruban Gnanakumar

Pediatric Neuroradiology: Dr. Xing-Chang Wei

Basic Science: Dr. Cam Teskey, Dr. Quentin Pitmann, Dr. Pierre Levan

Clinical Assistants: Dr. Reynaldo Avendano, Dr. Salma Hanna. This year we bid Adieu to both Drs. Avendano and Hanna. We wish them success in their new endeavours. We will be welcoming two new clinical assistants to the epilepsy program.

Adult Epilepsy Fellows: We will be welcoming Dr. Guillermo Delgado Garcia from Mexico, and Dr. Laura Gill, from British Columbia

Pediatric Epilepsy Fellows: The Paediatric program will be welcoming Dr. Marvin Braun

Epilepsy Nurses: Meliza Camerino, Amira Jivraj, Jackie Martini, Michele Zulinick, Andrea Palmer, Wendy Chen

Dietician: Shannon Josey