EEG and Neuroimaging Characteristics of Neonatal Onset Genetic Epilepsy
Abstract number :
3.371
Submission category :
12. Genetics / 12A. Human Studies
Year :
2022
Submission ID :
2204281
Source :
www.aesnet.org
Presentation date :
12/5/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:24 AM
Authors :
Amanda Sandoval Karamian, MD – University of Utah; Tianjia Zhu, MS – Children's Hospital of Philadelphia; Hao Huang, PhD – Children's Hospital of Philadelphia; Shavonne Massey, MD – Children's Hospital of Philadelphia; Mark Fitzgerald, MD, PhD – Children's Hospital of Philadelphia; Ingo Helbig, MD – Children's Hospital of Philadelphia; Nicholas Abend, MD – Children's Hospital of Philadelphia
Rationale: Genetic etiologies are increasingly identified in neonates presenting with seizures and comprise a growing subset of neonatal onset epilepsy. The relationship between EEG and imaging characteristics and outcomes in neonatal onset genetic epilepsy remain unclear, although there is increasing evidence that white matter structure is abnormal in some forms of genetic epilepsy. Neonates undergoing rapid myelination afford a unique population to determine whether recurrent seizures are associated with abnormal white matter development in early life epilepsy.
Methods: This was a retrospective single-center case-control study of term neonates who underwent brain MRI from 2011-2021. Cases were neonates with genetic epilepsy. Controls were healthy neonates with normal MRI. EEG background and seizure burden were systematically assessed by a central reader. Neonatal presentation severity was categorized as mild, moderate, or severe based on neurological examination and EEG background scoring using previously established scales. Presence of developmental delay and use of antiseizure medications was obtained from chart review. White matter is being assessed via tract based spatial statistics of diffusion tensor imaging (DTI) for quantitative fractional anisotropy (FA) and mean diffusivity (MD) of the genu and splenium of the corpus callosum, cingulum, and corticospinal tracts. FA and MD of the specified tracts is being compared between cases and controls using multivariable linear regression models, adjusting for GA and PMA at time of MRI.
Results: Nineteen neonates with genetic epilepsy and 40 unmatched healthy controls met inclusion criteria. Pathogenic variants in KCNQ2 were the most common, occurring in 10 (53%) of cases. Pathogenic variants in SCN2A, KCNQ3, and TCF4 were identified in one neonate each. Six neonates had no etiology identified on current genetic testing and had no other etiology identified after extensive evaluation. Neonatal presentation severity was mild in 12 cases (63%), moderate in 7 cases (37%) and severe in none. Of the 12 neonates with mild presentation severity, 8 (67%) had typical development and 4 (33%) had developmental delay. Of the 7 neonates with moderate presentation severity, 5 (71%) had developmental delay and 2 (29%) had typical development. The median total number of seizures on EEG was 4 (IQR 3, 9.5; range 2-44) and the median total duration of seizures of 4.5 minutes (IQR 2.9, 8.3; range 1.1-48.6). DTI was obtained and undergoing analysis with comparison of FA and MD in major white matter tracts between cases with neonatal onset genetic epilepsy and healthy control neonates with normal MRI.
Conclusions: Neonatal genetic epilepsy has a range of phenotypic presentations and outcomes, and KCNQ2 is the most common pathogenic variant. These neonates have a wide range of seizure exposure, therefore allowing subsequent analyses comparing seizure burden to white matter development. Further analyses will determine whether white matter microstructure is abnormal in these neonates compared to healthy controls.
Funding: PERF/AES Research and Training Fellowship for Clinicians Award
Genetics