Early Predictors and Clinical Correlates of Autism in Tuberous Sclerosis Complex

Abstract.

Tuberous Sclerosis Complex (TSC) is a neurocutaneous autosomal dominant disorder involving mutations of the TSC1 or TSC2 genes. It is characterized by the presence of benign tumors throughout the body, including the brain where they are known as cortical tubers. TSC symptoms may take time to develop and vary considerably from minimally affected people with normal intelligence and no seizures to severely affected people with profound retardation. Particularly, between 17% and 61% of children with TSC exhibit autism spectrum disorder (ASD) symptoms. However, there remains an unclear association between tuber load, tuber location and neurological outcomes. Other mechanisms than the tubers are likely to contribute to the pathogenesis of autism in individuals with TSC. Particularly, differences in normal-appearing white matter and miswiring of neuronal connections that are independent of the tubers may actually be the root cause of neurological symptoms in TSC.

Here we investigate macro-structural and micro-structural brain alterations in TSC and their correlation with autism. This research may enable the development of a set of quantitative imaging biomarkers for early prediction of later risk of ASD.

Selected related publications


Peters JM, Prohl AK, Tomas-Fernandez X, Taquet M, Scherrer B, Prabhu SP, Lidov HG, Singh JM, Jansen FE, Braun KP, Sahin M, Warfield SK, Stamm A,  Tubers are neither static nor discrete: Evidence from serial diffusion tensor imaging,  Neurology,  85(18),  2015,  1536-45,  PMID26432846,  PMC4642145
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Peters JM *, Taquet M *, Prohl AK, Scherrer B, Van Eeghen AM, Prabhu SP, Sahin M, Warfield SK,  Diffusion Tensor Imaging and Related Techniques in Tuberous Sclerosis Complex: Review and Future Directions,  Future Neurology,  8(5),  2013,  583-597,  PMID24489482,  PMC3904372,  NIHMS537965
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* Authors contributed equally
Lewis WW, Sahin M, Scherrer B, Peters JM, Suarez RO, Vogel-Farley VK, Jeste SS, Gregas MC, Prabhu SP, Nelson CA, Warfield SK,  Impaired Language Pathways in Tuberous Sclerosis Complex Patients with Autism Spectrum Disorders,  Cereb Cortex,  23(7),  2013,  1526-1532,  PMID22661408,  PMC3673171
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Peters JM, Sahin M, Vogel-Farley VK, Jeste SS, Nelson CA, Gregas MC, Prabhu SP, Scherrer B, Warfield SK,  Loss of white matter microstructural integrity is associated with adverse neurological outcome in tuberous sclerosis complex,  Acad Radiol,  19(1),  2012,  17-25,  PMID22142677,  PMC3343770,  NIHMS338007
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Scherrer B, Sahin M, Stamoulis C, Prabhu S, Akhondi-Asl A, Warfield SK,  Globally impaired network of anatomical connectivity in tuberous sclerosis complex patients with autism spectrum disorders,  Proc. the 20th International Symposium on Magnetic Resonance in Medicine (ISMRM),  Melbourne, Australia,  2012
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ISMRM Magna Cum Laude Merit Award
Akhondi-Asl A, Hans A, Scherrer B, Peters JM, Warfield SK,  Whole brain connectivity analysis using resting state functional MRI in pediatric TSC patients,  Proc. the 20th International Symposium on Magnetic Resonance in Medicine (ISMRM),  Melbourne, Australia,  2012
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