Early development and epilepsy in tuberous sclerosis complex: A prospective longitudinal study

Abstract

AimTo characterize early changes in developmental ability, language, and adaptive behaviour in infants diagnosed with tuberous sclerosis complex (TSC), and determine whether clinical features of epilepsy influence this pathway.MethodProspective, longitudinal data were collected within the Early Development in Tuberous Sclerosis (EDiTS) Study to track development of infants with TSC (n = 32) and typically developing infants (n = 33) between 3 and 24 months of age. Questionnaire and observational measures were used at up to seven timepoints to assess infants' adaptive behaviour, developmental ability, language, and epilepsy.ResultsA significant group by age interaction effect showed that infants with TSC had lower adaptive functioning at 18 to 24 months old (intercept = 88.12, slope estimate = −0.82, p < 0.001) and lower developmental ability scores from 10 months old (intercept = 83.33, slope estimate = −1.44, p < 0.001) compared to typically developing infants. Early epilepsy severity was a significant predictor of these emerging developmental (R2 = 0.35, p = 0.004, 95% confidence interval [CI] –0.08 to −0.01) and adaptive behaviour delays (R2 = 0.34, p = 0.004, 95% CI –0.05 to −0.01]). Lower vocabulary production (intercept = −1.25, slope = −0.12, p < 0.001) and comprehension scores (intercept = 2.39, slope estimate = −0.05, p < 0.001) in infants with TSC at 24 months old were not associated with epilepsy severity.InterpretationDivergence of developmental ability and adaptive functioning skills occur in infants with TSC from 10 and 18 months, respectively. Associations between early epilepsy severity and impaired development supports the importance of early intervention to reduce seizure severity.

Early therapeutic intervention guided by electroencephalography surveillance in infants with tuberous sclerosis complex

“…Differences were evident already at 6 months of age both in cognitive and motor areas, and at 12 months in the language area. Despite different psychological tests, these data correlate with the results presented by Lindsay et al 2 The results of these studies support the need for the early identification of infants at high risk of neurocognitive delay or ASD development to implement early intervention.…”

“…However, identifying a need in care or facilities is meaningless if there is nothing suitable to meet those needs, whether due to funding or availability, and I have to concur with Fortune et al's own conclusion that poor management of transition may contribute to poor health outcomes, decreased opportunities to participate in the community, and decreased quality of life. 2 provided further evidence of the integral relationship between seizures and neurodevelopmental outcomes in infants with TSC. They tracked longitudinal changes in adaptive functioning, developmental abilities, and language using selected diagnostic tests, such as the Vineland Adaptive Behavior Scales, the Mullen Scales of Early Learning, and the MacArthur-Bates Communicative Development Inventories respectively, aiming to identify the beginning of developmental delay in these different spheres and how this delay is associated with the severity of epilepsy.…”

“…To make the picture even more complicated, several studies have consistently reported the huge variability in disease severity and motor function trajectories since early ambulatory stages. 2 While factors like the co-occurrence of learning difficulties and the involvement of dystrophin isoforms expressed in the brain can further impact on the rate and the peak of motor function achievements, 3 improvements in attention and cognitive abilities can also contribute to the observed gains in gross motor skills in the youngest male children with DMD. There is also a wide variability in the way and timescale when different functional skills like raising from floor, running or climbing stairs, continue to improve, plateau, or decline.…”

“…Unfortunately, in the study by Lindsay et al, 2 the authors did not include data on autism-related traits and their relationship to neurodevelopment in individuals with TSC. In another study from the EPISTOP trial, Moavero et al 4 prospectively evaluated 82 infants with TSC (aged 6-24 months) using a detailed neuropsychological assessment (Bayley Scales of Infant Development and Autism Diagnostic Observation Schedule).…”