Evolution of electroencephalogram in infants with tuberous sclerosis complex and neurodevelopmental outcome: a prospective cohort study

Abstract

Aim To describe the evolution of electroencephalogram (EEG) characteristics in infants with tuberous sclerosis complex (TSC) and the relationship with neurodevelopmental outcome at 24 months. Method Eighty‐three infants were enrolled in the EPISTOP trial and underwent serial EEG follow‐up until the age of 24 months (males n=45, females n=37, median age at enrolment 28d, interquartile range 14–54d). Maturation of the EEG background and epileptiform discharges were compared between the TSC1 and TSC2 variants and between preventive and conventional groups respectively. Results Children with TSC2 more frequently had a slower posterior dominant rhythm (PDR) at 24 months (51% vs 11%, p=0.002), a higher number of epileptiform foci (median=8 vs 4, p=0.003), and a lower fraction of EEGs without epileptiform discharges (18% vs 61%, p=0.001) at follow‐up. A slower PDR at 24 months was significantly associated with lower cognitive (median=70 vs 80, p=0.028) and motor developmental quotients (median=70 vs 79, p=0.008). A higher fraction of EEGs without epileptiform discharges was associated with a lower probability of autism spectrum disorder symptoms (odds ratio=0.092, 95% confidence interval=0.009–0.912, p=0.042) and higher cognitive (p=0.004), language (p=0.002), and motor (p=0.001) developmental quotients at 24 months. Interpretation TSC2 is associated with more abnormal EEG characteristics compared to TSC1, which are predictive for neurodevelopmental outcome.

Bumetanide Effects on Resting-State EEG in Tuberous Sclerosis Complex in Relation to Clinical Outcome: An Open-Label Study

“…We found lower alpha-band power in TSC compared to TDC—an observation that has been described also in ASD ( Kulandaivel and Holmes, 2011 ; Tierney et al, 2012 ; Wang et al, 2013 ; Bruining et al, 2020 ) and in attention deficit and hyperactivity disorder ( Deiber et al, 2020 ). Furthermore, in TSC studies, it has been associated with delayed cognitive and motor development ( Dickinson et al, 2019 ; De Ridder et al, 2021 ). Albeit the link between network-level E/I balance and alpha power remains uncertain, computational models have related decreasing alpha power to increasing inhibitory connections or inhibitory signaling ( Poil et al, 2020 ; Bruining et al, 2020 ).…”

Epileptogenesis in tuberous sclerosis complex-related developmental and epileptic encephalopathy

“… 34 Moreover, longitudinal observational studies provide evidence of early epileptiform EEG activity in infants with TSC. 37 , 38 …”

“… 34 , 100 Several clinical studies have had promising results in support of the value of EEG-based biomarkers of epileptogenesis and co-occurring NDDs. 38 , 135–141 …”