@article{f50bc82c2f044da68e7a86af26dbf8eb,
title = "Scalp EEG spikes predict impending epilepsy in TSC infants: A longitudinal observational study",
abstract = "Objective: To determine if routine electroencephalography (EEG) in seizure-naive infants with tuberous sclerosis complex (TSC) can predict epilepsy and subsequent neurocognitive outcomes. Methods: Forty infants 7 months of age or younger and meeting the genetic or clinical diagnostic criteria for tuberous sclerosis were enrolled. Exclusion criteria included prior history of seizures or treatment with antiseizure medications. At each visit, seizure history and 1-hour awake and asleep video-EEG, standardized across all sites, were obtained until 2 years of age. Developmental assessments (Mullen and Vineland-II) were completed at 6, 12, and 24 months of age. Results: Of 40 infants enrolled (mean age of 82.4 days), 32 completed the study. Two were lost to follow-up and six were treated with antiepileptic drugs (AEDs) due to electrographic seizures and/or interictal epileptiform discharges (IEDs) on their EEG studies prior to the onset of clinical seizures. Seventeen of the 32 remaining children developed epilepsy at a mean age of 7.5 months (standard deviation [SD] = 4.4). Generalized/focal slowing, hypsarrhythmia, and generalized/focal attenuation were not predictive for the development of clinical seizures. Presence of IEDs had a 77.3% positive predictive value and absence a 70% negative predictive value for developing seizures by 2 years of age. IEDs preceded clinical seizure onset by 3.6 months (mean). Developmental testing showed significant decline, only in infants with ongoing seizures, but not infants who never developed seizures or whose seizures came under control. Significance: IEDs identify impending epilepsy in the majority (77%) of seizure-naive infants with TSC. The use of a 1-hour awake and asleep EEG can be used as a biomarker for ongoing epileptogenesis in most, but not all, infants with TSC. Persistent seizures, but not history of interictal epileptiform activity or history of well-controlled seizures, correlated with low scores on the Vineland and Mullen tests at 2 years of age.",
keywords = "biomarker, epileptiform discharges, seizure outcome, tuberous sclerosis complex",
author = "Wu, {Joyce Y.} and Monisha Goyal and Peters, {Jurriaan M.} and Darcy Krueger and Mustafa Sahin and Hope Northrup and Au, {Kit S.} and Sarah O{\textquoteright}Kelley and Marian Williams and Pearson, {Deborah A.} and Ellen Hanson and Byars, {Anna W.} and Jessica Krefting and Mark Beasley and Gary Cutter and Nita Limdi and Bebin, {E. Martina}",
note = "Funding Information: This study was supported by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health (P20 NS 080199 and U01 NS 082320). Table 3 details participants' names, locations, roles, and contributions. J.Y.W. was also supported by the NINDS/NIH (R01 NS 82649), and the Today's and Tomorrow's Children Fund from UCLA Mattel Children's Hospital at the University of California Los Angeles. M.S. was also supported by the Senior Investigator award from Boston Children's Translational Research Program. This study also utilized clinical research facilities and resources supported by the National Center for Advancing Translational Sciences of the National Institutes of Health grant (UL1TR001881, 8UL1TR000077) and National Institute of Child Health and Development (U54HD090255). Author contributions: Drs. Wu, Goyal, Peters, Krueger, Sahin, Northrup, Cutter, Limdi, and Bebin all contributed equally to the study design and concept, analysis, and interpretation of the results. Drs. Au, O'Kelley, Williams, Pearson, Hanson, Byers, Beasley, and Jessica Krefting were involved in data acquisition, and analysis and interpretation of the data. The statistical analyses were completed by Dr Nita Limdi and Dr Mark Beasley, both affiliated with the University of Alabama at Birmingham. Funding Information: This study was supported by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health (P20 NS 080199 and U01 NS 082320). Table 3 details participants' names, locations, roles, and contributions. J.Y.W. was also supported by the NINDS/NIH (R01 NS 82649), and the Today's and Tomorrow's Children Fund from UCLA Mattel Children's Hospital at the University of California Los Angeles. M.S. was also supported by the Senior Investigator award from Boston Children's Translational Research Program. This study also utilized clinical research facilities and resources supported by the National Center for Advancing Translational Sciences of the National Institutes of Health grant (UL1TR001881, 8UL1TR000077) and National Institute of Child Health and Development (U54HD090255). Author contributions: Drs. Wu, Goyal, Peters, Krueger, Sahin, Northrup, Cutter, Limdi, and Bebin all contributed equally to the study design and concept, analysis, and interpretation of the results. Drs. Au, O'Kelley, Williams, Pearson, Hanson, Byers, Beasley, and Jessica Krefting were involved in data acquisition, and analysis and interpretation of the data. The statistical analyses were completed by Dr Nita Limdi and Dr Mark Beasley, both affiliated with the University of Alabama at Birmingham. Publisher Copyright: {\textcopyright} 2019 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy.",
year = "2019",
month = dec,
day = "1",
doi = "10.1111/epi.16379",
language = "English (US)",
volume = "60",
pages = "2428--2436",
journal = "Epilepsia",
issn = "0013-9580",
publisher = "Wiley-Blackwell",
number = "12",
}