[PS12-2D-K] Histopathologic Features Indicating Possible Pathomechanisms Underlying Neurological Disorders of Infants and Children
Histopathological examination of human CNS tissue, obtained at the time of lesion resection or autopsy, may provide information that indicates pathophysiological mechanisms or the associated molecular genetic background underlying neurological disorders affecting infants and children. For example, focal cortical dysplasia type II and hemimegalencephaly share some histological characteristics, including the presence of dysmorphic neurons and balloon cells. In relation to this, recent genetic analyses of these two disorders have revealed somatic mutations involving the MTOR (Nakashima M, et al. Ann Neurol 2015) and other molecules associated with the signal pathway. Children with hypothalamic hamartoma often have characteristic gelastic seizures. With regard to the pathophysiology of this malformation, a recent physiological and morphological study using needle biopsy specimens has revealed that the Ca2+ permeability of neurons via AMPA receptors is aberrantly elevated, and that the neuronal nuclei show loss of ADAR2 immunoreactivity (Kitaura H, et al. Epilepsia 2017). Whole-exome sequencing analysis of families with affected siblings showing unique early-onset neurodegenerative encephalopathy has revealed biallelic TBCD mutations, and autopsy of the affected brain has demonstrated characteristic morphologic features of degeneration, including cactus and somatic sprout formation in the residual Purkinje cells (Miyake N, et al. Am J Hum Genet 2016). Thus, an integrated approach involving various methodologies may be crucial for a better understanding of the pathomechanisms of these disorders. Indeed, histopathological information may validate the significance of the findings obtained from other examinations, and may also demonstrate cellular vulnerability that is relevant to the clinical phenotype of the patients.