Trial Information

Longitudinal Study to Identify Early Biomarkers of Autism Spectrum Disorder (ASD) in Infants With Tuberous Sclerosis Complex (TSC)

This is a five-year multi-site study using MRI and EEG technologies to identify
developmental precursors of Autism Spectrum Disorder in patients with Tuberous Sclerosis
Complex (TSC). The study will be enrolling infants at five TSC centers throughout the
country, including Boston Children's Hospital, Cincinnati Children's Hospital Medical
Center, University of Alabama at Birmingham, University of Texas at Houston and University
of California Los Angeles. The main goal of this study is to identify early signs of autism
in children with TSC looking at the brain through MRI/diffusion tensor imaging, EEG and
behavioral/neuropsychological methods. Eligible infants between the ages of 3-9 months will
be evaluated longitudinally at regular visit intervals up to 3 years of age.

Study Objectives

1. To characterize the developmental precursors of ASD in a large number of TSC infants
using a prospective multi-center design: Infants with TSC will be evaluated
longitudinally at ages 3, 6, 9, 12, 18, 24 and 36 months. At each age, children will
undergo standardized evaluations, using cognitive and adaptive measures. At age 24 and
36 months, formal assessment for autism will be performed. Clinical data including
medication use, seizure history, EEG activity, genotypic variation, and co-morbidities
will be recorded to determine if specific clinical factors modify the course of
development.

2. To identify biomarkers with advanced diffusion tensor imaging (DTI) that help predict
development of ASD in TSC infants: The investigators hypothesize that decreased white
matter integrity performed annually for each of the first 3 years of life, including
DTI sequences with tractography. Radial, axial, and mean diffusivity and fractional
anisometry will be calculated for each time point and change over time correlated with
development of ASD to determine relative risk. Individual measures at each time point
will be compared between ASD and non-spectrum groups to assess the individual impact of
each measure and timing.

3. To identify biomarkers with quantitative EEG that help predict development of ASD in
TSC infants: The investigators hypothesize that altered functional connectivity, as
measured by qEEG coherence and high frequency oscillations, will correlate with
development of ASD in TSC. Quantitative EEG (qEEG), EEG coherence/gamma frequency
(30-50Hz), and high frequency oscillations encompassing both ripples (80-250H) and fast
ripples (250-500 Hz) will be measured at each time point. Changes over time will be
correlated with development of ASD to determine relative risk, as will comparison of
individual measures between the two groups. EEG findings will also be correlated with
MR results obtained to further couple functional connectivity as measured by EEG with
structural connectivity measured by DTI.