scholarly journals Early patterns of functional brain development associated with autism spectrum disorder in tuberous sclerosis complex

2019 ◽  
Vol 12 (12) ◽  
pp. 1758-1773 ◽  
Author(s):  
Abigail Dickinson ◽  
Kandice J. Varcin ◽  
Mustafa Sahin ◽  
Charles A. Nelson ◽  
Shafali S. Jeste
Keyword(s):  
Autism Spectrum Disorder ◽  
Brain Development ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Functional Brain

scholarly journals Early white matter development is abnormal in tuberous sclerosis complex patients who develop autism spectrum disorder

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Anna K. Prohl ◽  
◽  
Benoit Scherrer ◽  
Xavier Tomas-Fernandez ◽  
Peter E. Davis ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
White Matter ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Neural Circuits ◽  
Diffusion Tensor ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Fiber Bundles ◽  
The Brain

Abstract Background Autism spectrum disorder (ASD) is prevalent in tuberous sclerosis complex (TSC), occurring in approximately 50% of patients, and is hypothesized to be caused by disruption of neural circuits early in life. Tubers, or benign hamartomas distributed stochastically throughout the brain, are the most conspicuous of TSC neuropathology, but have not been consistently associated with ASD. Widespread neuropathology of the white matter, including deficits in myelination, neuronal migration, and axon formation, exist and may underlie ASD in TSC. We sought to identify the neural circuits associated with ASD in TSC by identifying white matter microstructural deficits in a prospectively recruited, longitudinally studied cohort of TSC infants. Methods TSC infants were recruited within their first year of life and longitudinally imaged at time of recruitment, 12 months of age, and at 24 months of age. Autism was diagnosed at 24 months of age with the ADOS-2. There were 108 subjects (62 TSC-ASD, 55% male; 46 TSC+ASD, 52% male) with at least one MRI and a 24-month ADOS, for a total of 187 MRI scans analyzed (109 TSC-ASD; 78 TSC+ASD). Diffusion tensor imaging properties of multiple white matter fiber bundles were sampled using a region of interest approach. Linear mixed effects modeling was performed to test the hypothesis that infants who develop ASD exhibit poor white matter microstructural integrity over the first 2 years of life compared to those who do not develop ASD. Results Subjects with TSC and ASD exhibited reduced fractional anisotropy in 9 of 17 white matter regions, sampled from the arcuate fasciculus, cingulum, corpus callosum, anterior limbs of the internal capsule, and the sagittal stratum, over the first 2 years of life compared to TSC subjects without ASD. Mean diffusivity trajectories did not differ between groups. Conclusions Underconnectivity across multiple white matter fiber bundles develops over the first 2 years of life in subjects with TSC and ASD. Future studies examining brain-behavior relationships are needed to determine how variation in the brain structure is associated with ASD symptoms.

scholarly journals Early developmental pathways to autism spectrum disorder in tuberous sclerosis complex

2016 ◽  
Vol 2 (2) ◽  
pp. 84-93 ◽  
Author(s):  
Charlotte Tye ◽  
Kandice Varcin ◽  
Patrick Bolton ◽  
Shafali Spurling Jeste
Keyword(s):  
Autism Spectrum Disorder ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Developmental Trajectories ◽  
Genetic Disorder ◽  
Familial Risk ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Content Type ◽  
Cascading Effects

Purpose – Tuberous sclerosis complex (TSC) is a genetic disorder with a high prevalence of autism spectrum disorder (ASD), yet no single genetic, neurological or neurophysiological risk marker is necessary or sufficient to increase risk for ASD. This paper aims to discuss the utility of adopting a developmental perspective. Design/methodology/approach – The increasing number of TSC infants presenting with abnormalities prenatally provides a unique opportunity to study risk pathways to ASD from birth. Here, the authors review findings to date that support the investigation of infants with TSC to further our understanding of typical and atypical development. Findings – Evidence has accumulated from studies of infants at familial risk for ASD (“baby siblings”) to suggest that early markers of ASD are present in the first year of life. The early waves of prospective studies of infants with TSC indicate dynamic changes in developmental trajectories to ASD and are likely to provide insight into cascading effects of brain “insult” early in development. Emerging evidence of phenotypic and biological homology between syndromic and idiopathic cases of ASD supports the notion of a convergence of risk factors on a final common pathway in ASD. Originality/value – The delineation of brain-based biomarkers of risk, prediction and treatment response in TSC will be critical in aiding the development of targeted intervention and prevention strategies for those infants at high risk of poorer developmental outcomes.

scholarly journals Language predictors of autism spectrum disorder in young children with tuberous sclerosis complex

2020 ◽  
Vol 103 ◽  
pp. 106844 ◽  
Author(s):  
Alexandra Schoenberger ◽  
Jamie K. Capal ◽  
Annie Ondracek ◽  
Paul S. Horn ◽  
Donna Murray ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Young Children ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Autism Spectrum ◽  
Spectrum Disorder

scholarly journals Early Clinical Predictors of Autism Spectrum Disorder in Infants with Tuberous Sclerosis Complex: Results from the EPISTOP Study

2019 ◽  
Vol 8 (6) ◽  
pp. 788 ◽  
Author(s):  
Romina Moavero ◽  
Arianna Benvenuto ◽  
Leonardo Emberti Gialloreti ◽  
Martina Siracusano ◽  
Katarzyna Kotulska ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Infant Development ◽  
Genetic Model ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
Spectrum Disorder ◽  
Clinical Markers ◽  
Clinical Predictors

Autism spectrum disorder (ASD) is highly prevalent in subjects with Tuberous Sclerosis Complex (TSC), but we are not still able to reliably predict which infants will develop ASD. This study aimed to identify the early clinical markers of ASD and/or developmental delay (DD) in infants with an early diagnosis of TSC. We prospectively evaluated 82 infants with TSC (6–24 months of age), using a detailed neuropsychological assessment (Bayley Scales of Infant Development—BSID, and Autism Diagnostic Observation Schedule—ADOS), in the context of the EPISTOP (Long-term, prospective study evaluating clinical and molecular biomarkers of EPIleptogenesiS in a genetic model of epilepsy—Tuberous SclerOsis ComPlex) project (NCT02098759). Normal cognitive developmental quotient at 12 months excluded subsequent ASD (negative predictive value 100%). The total score of ADOS at 12 months clearly differentiated children with a future diagnosis of ASD from children without (p = 0.012). Atypical socio-communication behaviors (p < 0.001) were more frequently observed than stereotyped/repetitive behaviors in children with ASD at 24 months. The combined use of BSID and ADOS can reliably identify infants with TSC with a higher risk for ASD at age 6–12 months, allowing for clinicians to target the earliest symptoms of abnormal neurodevelopment with tailored intervention strategies.

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