Influence of seizures on early development in tuberous sclerosis complex

Abstract

Objective Epilepsy is commonly seen in Tuberous Sclerosis Complex (TSC). The relationship between seizures and developmental outcomes has been reported, but few studies have examined this relationship in a prospective, longitudinal manner. The objective of the study was to evaluate the relationship between seizures and early development in TSC. Methods Analysis of 130 patients ages 0–36 months with TSC participating in the TSC Autism Center of Excellence Network, a large multicenter, prospective observational study evaluating biomarkers predictive of autism spectrum disorder (ASD), was performed. Infants were evaluated longitudinally with standardized evaluations, including cognitive, adaptive, and autism-specific measures. Seizure history was collected continuously throughout, including seizure type and frequency. Results Data were analyzed at 6, 12, 18, and 24 months of age. Patients without a history of seizures performed better on all developmental assessments at all time points compared to patients with a history of seizures and exhibited normal development at 24 months. Patients with a history of seizures not only performed worse, but developmental progress lagged the non-seizing group. All patients with a history of infantile spasms performed worse on all developmental assessments at 12, 18, and 24 months. Higher seizure frequency correlated with poorer outcomes on developmental testing at all time points, but particularly at 12 months and beyond. Patients with higher seizure frequency during infancy continued to perform worse developmentally through 24 months. A logistic model looking at the individual impact of infantile spasms, seizure frequency, and age of seizure onset as predictors of developmental delay revealed that age of seizure onset was the most important factor in determining developmental outcome. Conclusions Results of this study further define the relationship between seizures and developmental outcomes in young children with TSC. Early seizure onset in infants with TSC negatively impacts very early neurodevelopment, which persists through 24 months of age.

Scalp EEG spikes predict impending epilepsy in TSC infants: A longitudinal observational study

“…4,[11][12][13] We recognize that this study did not incorporate the neuroimaging findings for this cohort, which also may be a contributing factor to the cognitive decline in some of the participants. Our data suggest that there is a specific association between severity of epilepsy and comorbid conditions, including developmental delay, reported previously in retrospective and prospective series.…”

Utility of the Autism Observation Scale for Infants in Early Identification of Autism in Tuberous Sclerosis Complex

“…We recently published a study of the TACERN cohort that specifically evaluated the temporal relationship between seizures and early development 35 . Seizures were seen in approximately 73% of the children with the majority of the children developing seizures prior to 12 months of age (average age of seizure onset 5.6 ± 3.9 months).…”

A clinical update on tuberous sclerosis complex‐associated neuropsychiatric disorders (TAND)

“…Factors related to a higher risk for ID, including greater tuber load (Asato & Hardan, 2004), early onset of seizures, especially infantile spasms (Capal et al, 2017; Humphrey et al, 2014; Joinson et al, 2003; van Eeghen, Chu-Shore, et al, 2012), poor seizure control (Goh et al, 2005; van Eeghen, Chu-Shore, et al, 2012), and use of more antiepileptic medications likely reflecting more problematic seizure control (van Eeghen, Chu-Shore, et al, 2012), have all been examined. There may also be a dose-dependent effect of seizure activity on the development of ID.…”