Frontiers in Neurology (Oct 2020)

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,
  • Romina Moavero,
  • Paolo Curatolo,
  • Bernhard Weschke,
  • Kate Riney,
  • Kate Riney,
  • Martha Feucht,
  • Pavel Krsek,
  • Rima Nabbout,
  • Anna C. Jansen,
  • Konrad Wojdan,
  • Konrad Wojdan,
  • Dorota Domanska-Pakieła,
  • Magdalena Kaczorowska-Frontczak,
  • Christoph Hertzberg,
  • Cyrille H. Ferrier,
  • Sharon Samueli,
  • Barbora Benova,
  • Eleonora Aronica,
  • Eleonora Aronica,
  • David J. Kwiatkowski,
  • Floor E. Jansen,
  • Sergiusz Jóźwiak,
  • Sergiusz Jóźwiak,
  • Sabine Van Huffel,
  • Lieven Lagae

DOI
https://doi.org/10.3389/fneur.2020.582891
Journal volume & issue
Vol. 11

Abstract

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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.

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