Disrupted white matter connectivity and organization of brain structural connectomes in tuberous sclerosis complex patients with neuropsychiatric disorders using diffusion tensor imaging

AbstractObjectiveTuberous sclerosis complex (TSC) is a genetic neurocutaneous syndrome with variable and unpredictable neurological comorbidity that includes epilepsy, intellectual disability (ID), autism spectrum disorder, and neurobehavioral abnormalities. The degree of white matter involvement is believed to be associated with the severity of neurological impairment. The goal of the present study was to evaluate diffusion characteristics of tubers, white matter lesions, and brain structural network alterations in TSC patients using diffusion tensor imaging (DTI), graph theoretical analysis (GTA), and network-based statistical (NBS) analysis.Materials and methodsForty-two patients with a definitive diagnosis of TSC were recruited for this study. All patients underwent brain DTI examination using a 3  T magnetic resonance imaging system. Mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD) values, and fractional anisotropy (FA) mapping in 52 tubers and white matter lesions were measured and compared with those of contralateral normal regions. GTA was performed on the inter-reg ional connectivity matrix, and NBS analysis was used to identify the significance of any connected subnetworks evident in the set of altered connections. For neurological severity subgrouping, a neurological severity score was assigned to TSC patients including those with ID, seizure, autism, and ot her neuropsychiatric disorders (NPDs).ResultsSignificantly higher MD, AD, and RD,...
Source: Magnetic Resonance Materials in Physics, Biology and Medicine - Category: Materials Science Source Type: research

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Tuberous sclerosis complex (TSC) represents the prototypic monogenic disorder of the mammalian target of rapamycin (mTOR) pathway dysregulation. It provides the rational mechanistic basis of a direct link between gene mutation and brain pathology (structural and functional abnormalities) associated with a complex clinical phenotype including epilepsy, autism, and intellectual disability. So far, research conducted in TSC has been largely neuron-oriented. However, the neuropathological hallmarks of TSC and other malformations of cortical development also include major morphological and functional changes in glial cells invo...
Source: Frontiers in Neurology - Category: Neurology Source Type: research
Abstract OBJECTIVE: Tuberous sclerosis complex (TSC) is a genetic neurocutaneous syndrome with variable and unpredictable neurological comorbidity that includes epilepsy, intellectual disability (ID), autism spectrum disorder, and neurobehavioral abnormalities. The degree of white matter involvement is believed to be associated with the severity of neurological impairment. The goal of the present study was to evaluate diffusion characteristics of tubers, white matter lesions, and brain structural network alterations in TSC patients using diffusion tensor imaging (DTI), graph theoretical analysis (GTA), and network...
Source: Magma - Category: Radiology Authors: Tags: MAGMA Source Type: research
CONCLUSION: Congenital SEGA can follow a relatively benign course with a lower growth rate compared with published literature. Frequent neuroimaging surveillance is recommended for congenital SEGA with volumes exceeding 500 mm3. IMPACT: Congenital SEGA occur in 9.2% of paediatric patients with tuberous sclerosis complex.There are few published cases of congenital SEGA to date. This case series of ten patients adds to our experience seen in a tertiary referral hospital over 10 years.Congenital SEGA can follow a relatively benign course with a lower growth rate compared with published literature.Congenital SEGA w...
Source: Pediatric Research - Category: Pediatrics Authors: Tags: Pediatr Res Source Type: research
ConclusionsOur results indicate thatTsc1 haploinsufficiency in MGE-derived inhibitory cells upregulates mTORC1 activity in these interneurons, reduces their synaptic inhibition of pyramidal cells, and alters contextual fear discrimination and spatial working memory. Thus, selective dysregulation of mTORC1 function in Nkx2.1-expressing inhibitory cells appears sufficient to impair synaptic inhibition and contributes to cognitive deficits in theTsc1 mouse model of TSC.
Source: Molecular Autism - Category: Molecular Biology Source Type: research
Authors: Uysal SP, Sahin M Abstract Tuberous sclerosis complex (TSC) is an autosomal dominant, multisystem disorder that is characterized by cellular and tissue dysplasia in With the advent of genetic and molecular techniques, mutations in TSC1 or TSC2 genes were discovered to be responsible for mTOR overactivation, which is the underlying mechanism of pathogenesis. TSC is a highly heterogenous clinical entity with variable presentations and severity of disease. The brain, heart, skin, eyes, kidneys, and lungs are commonly involved in this syndrome, with the neurologic symptoms comprising a significant source of mo...
Source: Turkish Journal of Medical Sciences - Category: General Medicine Tags: Turk J Med Sci Source Type: research
AbstractTuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by epilepsy, intellectual disability, and benign tumors of the brain, heart, skin, and kidney. Animal models have contributed to our understanding of normal and abnormal human brain development, but the construction of models that accurately recapitulate a human pathology remains challenging. Recent advances in stem cell biology with the derivation of human-induced pluripotent stem cells (hiPSCs) from somatic cells from patients have opened new avenues to the study of TSC. This approach combined with gene-editing tools such as CRISPR/C...
Source: Molecular Autism - Category: Molecular Biology Source Type: research
ConclusionsDifferent types of glial cells have both cell autonomous effects and interactions with neurons and other cells that are involved in the pathophysiology of the neurological phenotype of TSC. Targeting glial-mediated mechanisms may represent a novel therapeutic approach for epilepsy and TAND in TSC patients.
Source: Journal of Neurodevelopmental Disorders - Category: Neurology Source Type: research
Tuberous sclerosis complex (TSC) is a neurogenetic disorder associated with epilepsy, intellectual disabilities, and autistic behaviors. These neurological symptoms result from synaptic dysregulations, which s...
Source: Molecular Brain - Category: Neuroscience Authors: Tags: Research Source Type: research
[´╗┐Neuropsychiatric manifestations in Tuberous Sclerosis Complex (TSC): diagnostic guidelines, TAND concept and therapy with mTOR inhibitors´╗┐]. Z Kinder Jugendpsychiatr Psychother. 2018 Aug 06;:1-14 Authors: Waltereit R, Feucht M, de Vries MC, Huemer J, Roessner V, de Vries PJ Abstract Neuropsychiatric manifestations in Tuberous Sclerosis Complex (TSC): diagnostic guidelines, TAND concept and therapy with mTOR inhibitors Abstract. Tuberous sclerosis complex (TSC), albeit a rare autosomal-dominant multisystem disease with an incidence of 1:6,000, is one of the most important monogenetic disorders in ...
Source: Zeitschrift fur Kinder- und Jugendpsychiatrie und Psychotherapie - Category: Child Development Tags: Z Kinder Jugendpsychiatr Psychother Source Type: research
We report the molecular diagnosis of TSC in individuals exhibiting extreme intra-familial variability, including the incidental diagnosis of asymptomatic family members. Exome sequencing was performed in three families, with probands referred for epilepsy, autism, and absent speech (Family 1); epileptic spasms (Family 2); and connective tissue disorders (Family 3.) Pathogenic variants inTSC1 orTSC2 were identified in nine individuals, including relatives with limited or no medical concerns at the time of testing. Of the nine individuals reported here, six had post-diagnosis examinations and three met clinical diagnostic cr...
Source: Neurogenetics - Category: Genetics & Stem Cells Source Type: research
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