Authors :
Presenting Author: Sam Cen, MD – Schulich school of medicine and dentistry
Kalene van Engelen, Bsc – Genetic counselor, Division of Genetics, Department of Paediatrics, Western University, London, ON; Rochelle Sorzano, Bsc – Research coordinator, Division of Neurology, Department of Paediatrics,, London Health Sciences Centre; Denait Haile Haile, Bsc – Research asistant, ivision of Neurology, Department of Paediatrics, London Health Sciences Centre, London, ON; andrea Andrade, MD – Co-investigator, Department of pediatrics, Schulich School of Dentistry and Medicine, Western University, London, ON; Narayan Prasad, MD – Co-investigator, Department of pediatrics, Schulich School of Dentistry and Medicine, Western University, London, ON; Tugce Balci, MD – Co-principal investigator, Department of genetics, Schulich School of Dentistry and Medicine, Western University, London, ON; Maryam Nabavi Nouri, MD – Co-principle investigator, Department of pediatrics, Schulich School of Dentistry and Medicine, Western University, London, ON
Rationale:
The diagnostic care of children with drug-resistant epilepsy (DRE) typically follows nonuniform protocols. A timely diagnosis can inform management, as seen in at least a quarter of genetic and almost all autoimmune diagnoses. The objective of this study is to offer a unanimous diagnostic approach and to report on the prevalence of genetic diagnoses and anti-neuronal antibodies in a prospective cohort of children with DRE.Methods:
PAGE is a prospective cohort study that investigates the utility of combined genetic and autoimmune testing in a cohort of children with newly diagnosed DRE. Participants are offered (a) comprehensive genetic testing (microarray and panel or exome), (b) genetic counselling, and (c) panel-based neural antibody testing using tissue indirect immunofluoresence and fixed cell-based assay at their first visit. Families also complete baseline, follow-up treatment, and satisfaction questionnaires.
Results:
We have 43 participants enrolled (median: 7 years, range: 0-20 years); 51% (n=22) were female. Developmental epileptic encephalopathy was diagnosed in 18% (7/38) of patients. Diagnostic yield was 37% (14/38) for genetic testing and 5% (2/37) for autoimmune testing. Those with a genetic diagnosis had a lower age of onset of seizures (1.7 vs 4.4 years), with the most common diagnosis being SCN1A-related disorder. Changes in seizure management, clinical care, and prognosis based on genetic results occurred in 90% of cases. In those with positive autoimmune results (n=2), results were reported as weakly positive for GAD65, which was clinically insignificant. None of these patients had a clinical picture of autoimmune encephalitis. In follow-up surveys, 90% of participants reported satisfaction with testing offered and 86% agreed that genetic counselling improved their disease understanding.Conclusions:
This study provides novel insights into the benefits of timely genetic and autoimmune testing in the pediatric DRE diagnostic pathway. While we found no cases of autoimmune-associated epilepsy in this cohort, clinical impact, as well as increased patient and family satisfaction from genetic counseling, warrants consideration for improved diagnostic guidelines for pediatric DRE.
Funding:
This study has been funded by a grant from the Academic Medical Organization of Southwestern Ontario (AMOSO), as well as funding support from the Department of Pediatrics at London Health Sciences Institute and Schulich School of Medicine and Dentistry, University of Western Ontario.