Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0848771 (neurological disability)
 928 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tubers are cerebral cortical developmental malformations associated with epilepsy and autism in tuberous sclerosis complex (TSC). The disparity between tuber number and severity of neurological impairment often observed in TSC led us to hypothesize that microscopic structural abnormalities distinct from tubers may occur in TSC. Serial frontal to occipital lobe sections were prepared from five postmortem TSC brain specimens. Sections were probed with cresyl violet stain or NeuN antibodies to define cytoarchitectural abnormalities and phospho-S6 (Ser235/236) antibodies to define mammalian target of rapamycin complex 1 (mTORC1) pathway activation. Tubers identified in all specimens (mean, 5 tubers per brain specimen) were defined by abnormal cortical lamination, dysmorphic neurons, and giant cells (GCs) and exhibited robust phospho-S6 immunolabeling. Histopathological analysis of non-tuber cortices demonstrated that 32% of the sections exhibited microscopic cytoarchitectural alterations, whereas 68% of the sections did not. Four types of morphological abnormalities were defined including: (1) focal dyslamination, (2) heterotopic neurons, (3) small collections of giant cells (GCs) and neurons we termed "microtubers", (4) isolated GCs we termed "sentinel" cells. When compared with control cortex, phospho-S6 labeling was enhanced in microtubers and sentinel cells and in some but not all areas of dyslamination. There are microscopic cytoarchitectural abnormalities identified in postmortem TSC brain specimens that are distinct from tubers. mTORC1 cascade activation in these areas supports a widespread effect of TSC1 or TSC2 mutations on brain development. Tubers may represent the most dramatic developmental abnormality in TSC; however, more regionally pervasive yet subtle abnormalities may contribute to neurological disability in TSC.
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PMID:Cytoarchitectural alterations are widespread in cerebral cortex in tuberous sclerosis complex. 2232 61

Tuberous sclerosis complex (TSC) 1 or TSC2 is mutated in most TSC patients. TSC2 mutations are more frequently associated with worse outcomes, earlier age at seizure onset, more severe intellectual disability, and higher tuber load than TSC1. The degree of white matter involvement is thought to be associated with the severity of neurological impairment. At present, genotype-phenotype correlations and relationship between tuber burden and neurological disability in TSC are debatable. We presented a 43-year-old patient with TSC2 mutation, whose symptom was only incomplete quadrantic visual field deficit in spite of multiple brain tubers. The visual field deficit was thought to be due to a small lesion in the upper medial part of the optic radiation revealed by diffusion tensor imaging. Her brain tubers showed normal findings in magnetic resonance spectroscopy. Our case suggested that neurological and neuropsychiatric manifestations of TSC are affected by the quality rather than number of the lesions. In addition, MRS may be useful to identify the correlation between brain tubers and neurological disability in TSC patients.
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PMID:Diffusion tensor imaging and magnetic resonance spectroscopy in a patient with adult onset tuberous sclerosis complex. 2912 21