Prediction of Neurodevelopment in Infants With Tuberous Sclerosis Complex Using Early EEG Characteristics

Jessie De Ridder; Mario Lavanga; Birgit Verhelle; Jan Vervisch; Katrien Lemmens; Katarzyna Kotulska; Romina Moavero; Paolo Curatolo; Bernhard Weschke; Kate Riney; Martha Feucht; Pavel Krsek; Rima Nabbout; Anna C Jansen; Konrad Wojdan; Dorota Domanska-Pakieła; Magdalena Kaczorowska-Frontczak; Christoph Hertzberg; Cyrille H Ferrier; Sharon Samueli; Barbora Benova; Eleonora Aronica; David J Kwiatkowski; Floor E Jansen; Sergiusz Jóźwiak; Sabine Van Huffel; Lieven Lagae

doi:10.3389/fneur.2020.582891

Prediction of Neurodevelopment in Infants With Tuberous Sclerosis Complex Using Early EEG Characteristics

Front Neurol. 2020 Oct 16:11:582891. doi: 10.3389/fneur.2020.582891. eCollection 2020.

Authors

Jessie De Ridder¹, Mario Lavanga², Birgit Verhelle¹, Jan Vervisch¹, Katrien Lemmens¹, Katarzyna Kotulska³, Romina Moavero^{4

5}, Paolo Curatolo⁴, Bernhard Weschke⁶, Kate Riney^{7

8}, Martha Feucht⁹, Pavel Krsek¹⁰, Rima Nabbout¹¹, Anna C Jansen¹², Konrad Wojdan^{13

14}, Dorota Domanska-Pakieła³, Magdalena Kaczorowska-Frontczak³, Christoph Hertzberg¹⁵, Cyrille H Ferrier¹⁶, Sharon Samueli⁹, Barbora Benova¹⁰, Eleonora Aronica^{17

18}, David J Kwiatkowski¹⁹, Floor E Jansen¹⁶, Sergiusz Jóźwiak^{3

20}, Sabine Van Huffel², Lieven Lagae¹

Affiliations

¹ Pediatric Neurology, Department of Development and Regeneration, University of Leuven KU Leuven, Leuven, Belgium.
² Department of Electrical Engineering (ESAT), STADIUS Centre for Dynamical Systems, Signal Processing and Data Analytics, KU Leuven, Leuven, Belgium.
³ Department of Neurology and Epileptology, The Children's Memorial Health Institute, Warsaw, Poland.
⁴ Child Neurology and Psychiatry Unit, Systems Medicine Department, Tor Vergata University, Rome, Italy.
⁵ Child Neurology Unit, Neuroscience and Neurorehabilitation Department, "Bambino Gesù" Children's Hospital, Rome, Italy.
⁶ Department of Child Neurology, Charité University Medicine Berlin, Berlin, Germany.
⁷ Neuroscience Unit, Queensland Children's Hospital, Brisbane, QLD, Australia.
⁸ University of Queensland School of Clinical Medicine, Brisbane, QLD, Australia.
⁹ Department of Pediatrics, Medical University Vienna, Vienna, Austria.
¹⁰ Department of Paediatric Neurology, Charles University, Second Faculty of Medicine, Motol University Hospital, Prague, Czechia.
¹¹ Department of Pediatric Neurology, Reference Centre for Rare Epilepsies, Imagine Institute, Necker- Enfants Malades Hospital, University Paris Descartes, Paris, France.
¹² Pediatric Neurology Unit, Universitair Ziekenhuis Brussel, Brussels, Belgium.
¹³ Transition Technologies, Warsaw, Poland.
¹⁴ Institute of Heat Engineering, Warsaw University and Technology, Warsaw, Poland.
¹⁵ Diagnose und Behandlungszentrum für Kinder und Jugendliche, Vivantes Klinikum Neuköln, Berlin, Germany.
¹⁶ Department of Child Neurology, Brain Centre, University Medical Centre Utrecht, Utrecht, Netherlands.
¹⁷ Department of (Neuro)Pathology, Amsterdam Universitair Medisch Centrum, University of Amsterdam, Amsterdam, Netherlands.
¹⁸ Stichting Epilepsie Instellingen Nederland (SEIN), Heemstede, Netherlands.
¹⁹ Harvard Medical School, Brigham and Women's Hospital, Boston, MA, United States.
²⁰ Department of Child Neurology, Medical University of Warsaw, Warsaw, Poland.

Abstract

Tuberous Sclerosis Complex (TSC) is a multisystem genetic disorder with a high risk of early-onset epilepsy and a high prevalence of neurodevelopmental comorbidities, including intellectual disability and autism spectrum disorder (ASD). Therefore, TSC is an interesting disease model to investigate early biomarkers of neurodevelopmental comorbidities when interventions are favourable. We investigated whether early EEG characteristics can be used to predict neurodevelopment in infants with TSC. The first recorded EEG of 64 infants with TSC, enrolled in the international prospective EPISTOP trial (recorded at a median gestational age 42 4/7 weeks) was first visually assessed. EEG characteristics were correlated with ASD risk based on the ADOS-2 score, and cognitive, language, and motor developmental quotients (Bayley Scales of Infant and Toddler Development III) at the age of 24 months. Quantitative EEG analysis was used to validate the relationship between EEG background abnormalities and ASD risk. An abnormal first EEG (OR = 4.1, p-value = 0.027) and more specifically a dysmature EEG background (OR = 4.6, p-value = 0.017) was associated with a higher probability of ASD traits at the age of 24 months. This association between an early abnormal EEG and ASD risk remained significant in a multivariable model, adjusting for mutation and treatment (adjusted OR = 4.2, p-value = 0.029). A dysmature EEG background was also associated with lower cognitive (p-value = 0.029), language (p-value = 0.001), and motor (p-value = 0.017) developmental quotients at the age of 24 months. Our findings suggest that early EEG characteristics in newborns and infants with TSC can be used to predict neurodevelopmental comorbidities.

Keywords: EEG; TAND profile; autism (ASD); biomarker; neurodeveloment; tuberous sclerosis complex (TSC).

Copyright © 2020 De Ridder, Lavanga, Verhelle, Vervisch, Lemmens, Kotulska, Moavero, Curatolo, Weschke, Riney, Feucht, Krsek, Nabbout, Jansen, Wojdan, Domanska-Pakieła, Kaczorowska-Frontczak, Hertzberg, Ferrier, Samueli, Benova, Aronica, Kwiatkowski, Jansen, Jóźwiak, Van Huffel and Lagae.