Relationship Between Epileptic Activity and Developmental Outcome in KCNQ2-Related Epilepsy - 12/06/23

Doi : 10.1016/j.pediatrneurol.2023.03.004

Dídac Casas-Alba, MD, PhD ^a,^b,^c,^⁎ , Anna Aguilar, BS ^a,^b, Itziar Alonso, MD ^a, María Teresa García, MD ^d, Maria Roberta Cilio, MD, PhD ^e, Carmen Fons, MD, PhD ^a,^b,^f,^⁎
BIO-KCNQ2-Spanish Study Group^{^†}
Membership of the BIO-KCNQ2-Spanish Study Group is provided in the Acknowledgements.
Javier López-Pisón, Luis Gutiérrez-Solana, Fernando Ferragut, María Luz Ruiz-Falcó, Víctor Soto-Insuga, Elena González, Tamara Pablos, María José Mas, Sara Hernández, María Vázquez-López, Patricia Fuentes-Pita, Sergio Aguilera-Albesa, Rocío Sánchez-Carpintero, Montserrat Garcia-Puig, Deyanira García-Navas, Helena Alarcón-Martínez, Candelaria González, Rocío Calvo, Ana Extraviz, Jordi Muchart, Francesc Palau, Judith Armstrong, Dèlia Yubero, Carlos Eduardo Valera, Verónica González, Mar O'’Callaghan, Ariadna Borràs, Àngels García-Cazorla, Óscar Casis, Amaia Alquiza, Ainhoa Rodríguez de Yurre, Álvaro Villarroel

^a Pediatric Neurology Department, Hospital Sant Joan de Déu, Full Member of ERN EpiCare, Barcelona University, Barcelona, Spain
^b Institut de Recerca Sant Joan de Déu, Barcelona, Spain
^c Department of Genetic Medicine, Pediatric Institute of Rare Diseases (IPER), Hospital Sant Joan de Déu, Barcelona University, Barcelona, Spain
^d Pediatric Neurology Unit, Hospital Infantil Universitario Miguel Servet, Zaragoza, Spain
^e Division of Pediatric Neurology, Saint-Luc University Hospital, Catholic University of Louvain, Brussels, Belgium
^f Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, Madrid, Spain

^∗Communications should be addressed to: Dr. Fons; Chief of the Pediatric Neurology Department; Hospital Sant Joan de Déu; Member of ERN EpiCare; Barcelona University; Barcelona, Spain; Hospital Sant Joan de Déu; Pº Sant Joan de Déu, 2; Esplugues Barcelona 08950, Spain.Chief of the Pediatric Neurology DepartmentHospital Sant Joan de DéuMember of ERN EpiCareBarcelona University; Barcelona, Spain; Hospital Sant Joan de DéuPº Sant Joan de Déu, 2Esplugues Barcelona08950Spain^∗∗Dr. Casas-Alba; Pediatric Neurology Department; Hospital Sant Joan de Déu; Full Member of ERN EpiCare; Barcelona University; Barcelona, Spain; Hospital Sant Joan de Déu; Pº Sant Joan de Déu, 2; Esplugues Barcelona 08950, Spain.Pediatric Neurology DepartmentHospital Sant Joan de DéuFull Member of ERN EpiCareBarcelona UniversityBarcelona, Spain; Hospital Sant Joan de DéuPº Sant Joan de Déu, 2Esplugues Barcelona08950Spain

Abstract

Background

We aim to describe a cohort of patients with KCNQ2-related epilepsy and evaluate the relationship between epileptic activity and developmental outcome. This topic is relevant for the selection of clinical end points in future clinical trials, since cessation of seizures may or may not be the most important outcome.

Methods

This retrospective cohort study of children with self-limited (familial) neonatal epilepsy and developmental and epileptic encephalopathy due to pathogenic variants in KCNQ2 was conducted between 2019 and 2021. We collected clinical, therapeutic, and genetic information. Available electroencephalographic recordings were reviewed by a neurophysiologist. Gross motor function was determined using the Gross Motor Function Classification System (GMFCS). The Vineland Adaptive Behavior Composite standard score (ABC SS) was used to measure adaptive functioning.

Results

Among 44 children (mean age 8.1 ± 4.0 years, 45.5% were male), 15 of 44 had S(F)NE, and 29 of 44 had DEE. Delayed seizure freedom was more frequent in DEE than in S(F)NE (P = 0.025), but no correlation was observed between age at seizure freedom and developmental outcome in patients with DEE. Multifocal interictal epileptiform abnormalities at epilepsy onset were more frequent in DEE than in S(F)NE (P = 0.014), and were associated with higher GMFCS (P = 0.027) and lower ABC SS (P = 0.048) in patients with DEE. Disorganized background activity at follow-up was more frequent in DEE than in S(F)NE (P = 0.001), and was associated with higher GMFCS levels (P = 0.009) and lower ABC SS (P = 0.005) in patients with DEE.

Conclusions

This study shows a partial correlation between epileptic activity and developmental outcome in KCNQ2-related epilepsy.

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Keywords : KCNQ2, Self-limited (familial) neonatal epilepsy, Developmental and epileptic encephalopathy, Gross Motor Function Classification System, Vineland Adaptive Behavior Scales

Plan

Introduction

Materials and Methods

Description of the cohort

Comparison between epileptic activity and developmental outcome

Discussion

	The Vineland Adaptive Behavior Composite score (ABC SS) was used to measure adaptive functioning.
	Author contributions: D.C.-A. contributed to conception or design of the work, data collection, data analysis and interpretation, drafting the article, critical revision of the article, and final approval of the version to be published. A.A. contributed to data collection, drafting the article, critical revision of the article, and final approval of the version to be published. I.A. contributed to data collection, review of EEG recordings, critical revision of the article, and final approval of the version to be published. M.T.G. contributed to data collection, critical revision of the article, and final approval of the version to be published. M.R.C. contributed to data analysis and interpretation, critical revision of the article, and final approval of the version to be published. C.F. contributed to conception or design of the work, data collection, data analysis and interpretation, drafting the article, critical revision of the article, and final approval of the version to be published.
	Conflicts of interest: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.