TY - JOUR
T1 - Early epileptiform EEG activity in infants with tuberous sclerosis complex predicts epilepsy and neurodevelopmental outcomes
AU - De Ridder, Jessie
AU - Verhelle, Birgit
AU - EPISTOP Consortium
AU - Vervisch, Jan
AU - Lemmens, Katrien
AU - Kotulska, Katarzyna
AU - Moavero, Romina
AU - Curatolo, Paolo
AU - Weschke, Bernhard
AU - Riney, Kate
AU - Feucht, Martha
AU - Krsek, Pavel
AU - Nabbout, Rima
AU - Jansen, Anna C.
AU - Wojdan, Konrad
AU - Domanska-Pakieła, Dorota
AU - Kaczorowska-Frontczak, Magdalena
AU - Hertzberg, Christoph
AU - Ferrier, Cyrille H.
AU - Samueli, Sharon
AU - Benova, Barbora
AU - Aronica, Eleonora
AU - Kwiatkowski, David J.
AU - Jansen, Floor E.
AU - Jóźwiak, Sergiusz
AU - Lagae, Lieven
AU - Anink, J.
AU - Benvenuto, A.
AU - Blazejczyk, M.
AU - Bongaarts, A.
AU - Borkowska, J.
AU - Breuillard, D.
AU - Chmielewski, D.
AU - Dabrowska, M.
AU - Emberti Gialloreti, L.
AU - Giannikou, K.
AU - Głowacka-Walas, J.
AU - Hamieh, L.
AU - Haręza, A.
AU - Hulshof, H.
AU - Iyer, A.
AU - Janssen, B.
AU - Jaworski, J.
AU - Lehmann, K.
AU - Leusman, A.
AU - Maćkowiak, N.
AU - Mills, J. D.
AU - Muehlebner, A.
AU - Sadowski, K.
AU - Scheldeman, C.
AU - Scholl, T.
N1 - Publisher Copyright:
© 2021 International League Against Epilepsy
PY - 2021/5
Y1 - 2021/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85103249570&partnerID=8YFLogxK
U2 - 10.1111/epi.16892
DO - 10.1111/epi.16892
M3 - Article
C2 - 33778971
AN - SCOPUS:85103249570
SN - 0013-9580
VL - 62
SP - 1208
EP - 1219
JO - Epilepsia
JF - Epilepsia
IS - 5
ER -