We present a comprehensive multi-omic analysis of the EPISTOP prospective clinical trial of early intervention with vigabatrin for pre-symptomatic epilepsy treatment in Tuberous Sclerosis Complex (TSC), in which 93 infants with TSC were followed from birth to age 2 years, seeking biomarkers of epilepsy development. Vigabatrin had profound effects on many metabolites, increasing serum deoxycytidine monophosphate (dCMP) levels 52-fold. Most serum proteins and metabolites, and blood RNA species showed significant change with age. Thirty-nine proteins, metabolites, and genes showed significant differences between age-matched control and TSC infants. Six also showed a progressive difference in expression between control, TSC without epilepsy, and TSC with epilepsy groups. A multivariate approach using enrollment samples identified multiple 3-variable predictors of epilepsy, with the best having a positive predictive value of 0.987. This rich dataset will enable further discovery and analysis of developmental effects, and associations with seizure development in TSC.

Amsterdam UMC University of Amsterdam Department of Pathology Amsterdam Neuroscience Amsterdam The Netherlands

Chalfont Centre for Epilepsy Chalfont St Peter UK

Child Neurology and Psychiatry Unit Systems Medicine Department Tor Vergata University Rome Italy

Department of Child Neurology Brain Center University Medical Center Utrecht Utrecht The Netherlands

Department of Child Neurology Charité University Medicine Berlin Berlin Germany

Department of Child Neurology Medical University of Warsaw Warsaw Poland

Department of Clinical and Experimental Epilepsy UCL Queen Square Institute of Neurology London UK

Department of Development and Regeneration Section Pediatric Neurology University Hospitals KU Leuven Leuven Belgium

Department of Internal Medicine Erasmus MC Rotterdam Netherlands

Department of Medicine Brigham and Women's Hospital Boston MA USA

Department of Medicine Harvard Medical School and Division of Signal Transduction Beth Israel Deaconess Medical Center Boston MA USA

Department of Neurology and Epileptology member of ERN EPICARE The Children's Memorial Health Institute Warsaw Poland

Department of Paediatric Neurology Motol University Hospital 2nd Medical Faculty Charles University Prague Czech Republic

Department of Pathology and Molecular Medicine Motol University Hospital 2nd Medical Faculty Charles University Prague Czech Republic

Department of Pathology University Medical Center Utrecht Utrecht The Netherlands

Department of Pediatric Neurology Reference Centre for Rare Epilepsies Necker Enfants Malades Hospital Université Paris cité Imagine Institute Paris France

Developmental Neurology Bambino Gesù Children's Hospital IRCCS Rome Italy

Diagnose und Behandlungszentrum für Kinder Vivantes Klinikum Neukölln Berlin Germany

Epilepsy Service Department of Pediatrics and Adolescent Medicine Medical University of Vienna Member of ERN EpiCARE Vienna Austria

GenomeScan Leiden The Netherlands

International Institute of Molecular and Cell Biology Warsaw Poland

Neurogenetics Research Group Vrije Universiteit Brussel Brussels Belgium

Neurosciences Unit Queensland Children's Hospital South Brisbane Queensland Australia

Proteome Factory AG Berlin Germany

School of Medicine University of Queensland St Lucia Queensland Australia

Stichting Epilepsie Instellingen Nederland Heemstede the Netherlands Utrecht The Netherlands

Transition Technologies Science Warsaw Poland

Warsaw University of Technology Institute of Heat Engineering Warsaw Poland

Warsaw University of Technology The Institute of Computer Science Warsaw Poland

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Molecular EPISTOP, a comprehensive multi-omic analysis of blood from Tuberous Sclerosis Complex infants age birth to two years