OBJECTIVE: To study the association between timing and characteristics of the first electroencephalography (EEG) with epileptiform discharges (ED-EEG) and epilepsy and neurodevelopment at 24 months in infants with tuberous sclerosis complex (TSC). METHODS: Patients enrolled in the prospective Epileptogenesis in a genetic model of epilepsy - Tuberous sclerosis complex (EPISTOP) trial, had serial EEG monitoring until the age of 24 months. The timing and characteristics of the first ED-EEG were studied in relation to clinical outcome. Epilepsy-related outcomes were analyzed separately in a conventionally followed group (initiation of vigabatrin after seizure onset) and a preventive group (initiation of vigabatrin before seizures, but after appearance of interictal epileptiform discharges [IEDs]). RESULTS: Eighty-three infants with TSC were enrolled at a median age of 28 days (interquartile range [IQR] 14-54). Seventy-nine of 83 patients (95%) developed epileptiform discharges at a median age of 77 days (IQR 23-111). Patients with a pathogenic TSC2 variant were significantly younger (P-value .009) at first ED-EEG and more frequently had multifocal IED (P-value .042) than patients with a pathogenic TSC1 variant. A younger age at first ED-EEG was significantly associated with lower cognitive (P-value .010), language (P-value .001), and motor (P-value .013) developmental quotients at 24 months. In the conventional group, 48 of 60 developed seizures. In this group, the presence of focal slowing on the first ED-EEG was predictive of earlier seizure onset (P-value .030). Earlier recording of epileptiform discharges (P-value .019), especially when multifocal (P-value .026) was associated with higher risk of drug-resistant epilepsy. In the preventive group, timing, distribution of IED, or focal slowing, was not associated with the epilepsy outcomes. However, when multifocal IEDs were present on the first ED-EEG, preventive treatment delayed the onset of seizures significantly (P-value <.001). SIGNIFICANCE: Early EEG findings help to identify TSC infants at risk of severe epilepsy and neurodevelopmental delay and those who may benefit from preventive treatment with vigabatrin.

Brigham and Women's Hospital Harvard Medical School Boston Massachusetts USA

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

Child Neurology Unit Neuroscience and Neurorehabilitation Department Bambino Gesù Children's Hospital Rome Italy

Department of Child Neurology Brain Centre University Medical Centre 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 Development and Regeneration Section Pediatric Neurology Catholic University of Leuven Leuven Belgium

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

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

Department of Pediatric Neurology Reference Centre for Rare Epilepsies Necker Enfants Malades Hospital Imagine Institute INSERM U1163 University Paris Descartes Paris France

Department of Pediatrics Medical University Vienna Vienna Austria

Department of University of Amsterdam Amsterdam The Netherlands

Diagnose und Behandlungszentrum für Kinder und Jugendliche Vivantes Klinikum Neuköln Berlin Germany

Institute of Heat Engineering Warsaw University and Technology Warsaw Poland

Neuroscience Unit Queensland Children's Hospital Brisbane Australia

Pediatric Neurology Unit University Hospital Brussel Brussels Belgium

Stichting Epilepsie Instellingen Nederland Zwolle The Netherlands

Transition Technologies Warsaw Poland

University of Queensland School of Clinical Medicine Brisbane Australia

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