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Background: Abnormalities in white matter development may influence development of autism spectrum disorder in tuberous sclerosis complex (TSC). Our goals for this study were as follows: (1) use data from a longitudinal neuroimaging study of tuberous sclerosis complex (TACERN) to develop optimized linear mixed effects models for analyzing longitudinal, repeated diffusion tensor imaging metrics (fractional anisotropy, mean diffusivity) pertaining to select white matter tracts, in relation to positive Autism Diagnostic Observation Schedule–Second Edition classification at 36 months, and (2) perform an exploratory analysis using optimized models applied to all white matter tracts from these data. Methods: Eligible participants (3-12 months) underwent brain magnetic resonance imaging (MRI) at repeated time points from ages 3 to 36 months. Positive Autism Diagnostic Observation Schedule–Second Edition classification at 36 months was used. Linear mixed effects models were fine-tuned separately for fractional anisotropy values (using fractional anisotropy corpus callosum as test outcome) and mean diffusivity values (using mean diffusivity right posterior limb internal capsule as test outcome). Fixed effects included participant age, within-participant longitudinal age, and autism spectrum disorder diagnosis. Results: Analysis included data from n = 78. After selecting separate optimal models for fractional anisotropy and mean diffusivity values, we applied these models to fractional anisotropy and mean diffusivity of all 27 white matter tracts. Fractional anisotropy corpus callosum was related to positive Autism Diagnostic Observation Schedule–Second Edition classification (coefficient = 0.0093, P =.0612), and mean diffusivity right inferior cerebellar peduncle was related to positive Autism Diagnostic Observation Schedule–Second Edition classification (coefficient = –0.00002071, P =.0445), though these findings were not statistically significant after multiple comparisons correction. Conclusion: These optimized linear mixed effects models possibly implicate corpus callosum and cerebellar pathology in development of autism spectrum disorder in tuberous sclerosis complex, but future studies are needed to replicate these findings and explore contributors of heterogeneity in these models. [ABSTRACT FROM AUTHOR]

Tuberous sclerosis complex is a multisystem genetic syndrome often affecting the central nervous system. The purpose of the current study was to identify topographical patterns in the distribution specific to epileptogenic (n = 37) and nonepileptogenic (n = 544) tubers throughout the brain for a cohort of 23 tuberous sclerosis complex patients with a history of seizures. Tubers localized to the inferior parietal lobes, middle frontal lobes, middle temporal lobes, or central sulcus regions were associated with a high frequency of epileptogenic tubers. Epileptogenic tubers occurred statistically more frequently within the inferior parietal lobe and within the central sulcus region in children younger than 1 or between 1 and 3 years old, respectively. Results imply seizure activity in tuberous sclerosis complex patients can be associated with the location of cortical tubers.

Tuberous sclerosis complex is an autosomal dominant genetic disorder that confers a high risk for neurodevelopmental disorders, such as autism spectrum disorder and intellectual disability. Studies have demonstrated specific delays in visual reception skills that may predict the development of autism spectrum disorder and intellectual disability. Based on evidence for alterations in the retinogeniculate pathway in animal models of tuberous sclerosis complex, we asked whether children with tuberous sclerosis complex demonstrate alterations in early visual processing that may undermine the development of higher-level visual behaviors. Pattern-reversal visual evoked potentials were recorded in infants with tuberous sclerosis complex (n = 16) and typically developing infants (n = 18) at 12 months of age. Infants with tuberous sclerosis complex demonstrated remarkably intact visual evoked potentials even within the context of intellectual disability and epilepsy. Infants with tuberous sclerosis complex show intact visual cortical processing, suggesting that delays in visually mediated behaviors in tuberous sclerosis complex may not be rooted in early visual processing deficits.