MRI Findings in a Cohort of Pediatric Epilepsy Patients Undergoing Whole-Exome Sequencing
Abstract number :
1.238
Submission category :
5. Neuro Imaging / 5A. Structural Imaging
Year :
2021
Submission ID :
1826740
Source :
www.aesnet.org
Presentation date :
12/9/2021 12:00:00 PM
Published date :
Nov 22, 2021, 06:56 AM
Authors :
Bo Gong, MD, MSc. - BC Children's Hospital; Cyrus Boelman, MD – Neurologist/Epileptologist, BC Children's Hospital; Anita Datta, MD – Neurologist/Epileptologist, BC Children's Hospital; Mary Connolly, MBBCH – Neurologist/Epileptologist, BC Children's Hospital; Makabongwe Tshuma, MBChB – Pediatric Neuroradiologist, BC Children's Hospital; Michelle Demos, MD – Neurologist/Epileptologist, BC Children's Hospital
Rationale: There has been increased application of targeted whole-exome sequencing (WES) in the diagnosis of early-onset pediatric epilepsy. This study examines the magnetic resonance imaging (MRI) findings in pediatric epilepsy patients who undergo WES, and investigates whether these MRI findings have value in predicting the diagnostic yield of WES.
Methods: WES was performed on a cohort of 180 pediatric patients at our institution with early-onset epilepsy of unknown cause, with the WES results and clinical features published previously (Demos M, Front Neurol. 2019. PubMed ID: 31164858). The MRI images and reports of these patients were retrospectively analyzed. The study was approved by a local Clinical Research Ethics Board.
Results: MRI results were available for 178 patients, among whom 58 patients received a definitive/likely WES genetic diagnosis, 21 patients a possible genetic diagnosis, and 98 patients no genetic diagnosis. Each patient had 1 - 9 MRI exams (median: 2) with a median interval of 28 months between the MRI exams. The timing of the first MRI exam ranged from day 1 of life to 200.5 months (median 24.0 months); the intervals between the seizure onset to the first MRI exam ranged from 0 to 190.0 months (median: 8.0 months).
Among the 178 patients, 98 patients’ MRI exams were reported as normal, 18 patients with findings of unclear significance, and 61 patients with abnormal findings. In 25 out of 98 patients who had abnormal MRI results (41%), one or more key MRI findings were not present on the first MRI exam and only emerged in subsequent MRI exams. The most common abnormal MRI findings included cortical malformation (23 patients), myelination abnormality (20 patients), parenchymal volume loss (19 patients), and hippocampal sclerosis (8 patients).
Compared with patients with normal MRI results, patients with abnormal MRI results were more likely to receive a definitive/likely genetic diagnosis instead of receiving no genetic diagnosis (patients with normal MRI results: 27.6% received a definitive/likely genetic diagnosis vs. 61.2% received no genetic diagnosis; patients with abnormal MRI results: 42.6% and 44.3%, respectively, with a sensitivity of 44.8%. The likelihood of receiving a definitive/likely genetic diagnosis among patients with a particular MRI finding is: 60.0% for myelination abnormality, 52.6% for parenchymal volume loss, 37.5% for hippocampal sclerosis, and 30.4% for cortical malformation.
Conclusions: Early-onset pediatric epilepsy patients with abnormal MRI results are more likely to receive a definitive/likely WES genetic diagnosis, but the sensitivity is low. Furthermore, due to developmental changes, key MRI findings are often not present on the initial MRI exams. Therefore, early use of WES provides unique diagnostic value, complementing the diagnostic roles of MRI and other clinical tests in pediatric patients with early-onset epilepsy.
Funding: Please list any funding that was received in support of this abstract.: Canada Excellence Research Chair and Leading Edge Endowment funds, the Rare Disease Foundation, Grocholski Foundation and the Alva Foundation.
Neuro Imaging