Saturday, May 22, 2010: 10:45 AM
Grand Ballroom AB Level 5 (Philadelphia Marriott Downtown)
9:45 AM
J. Wegiel
,
Developmental Neurobiology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY
I. Kuchna
,
Developmental Neurobiology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY
K. Nowicki
,
Developmental Neurobiology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY
H. Imaki
,
Developmental Neurobiology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY
J. Wegiel
,
Developmental Neurobiology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY
E. Marchi
,
Developmental Neurobiology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY
S. Y. Ma
,
Developmental Neurobiology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY
A. Chauhan
,
Neurochemistry, NYS Institute for Basic Research in Developmental Disabilities, Staten Island, NY
V. Chauhan
,
Neurochemistry, NYS Institute for Basic Research in Developmental Disabilities, Staten Island, NY
I. Cohen
,
Psychology, NYS Institute for Basic Research in Developmental Disabilities, Staten Island, NY
E. London
,
Psychology, NYS Institute for Basic Research in Developmental Disabilities, Staten Island, NY
W. T. Brown
,
Human Genetics, NYS Institute for Basic Research in Developmental Disabilities, Staten Island, NY
T. Wisniewski
,
Developmental Neurobiology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY
Background: An emerging theory of autism-related encephalopathy integrates evidence of (a) abnormal acceleration of brain growth in early childhood (Redcay and Courchesne 2005), (b) minicolumn pathology (Casanova et al 2002, 2006), (c) curtailed neuronal development (Bauman and Kemper 1985), brain-structure-specific delays of neuronal growth in early childhood, and desynchronization of neuronal development.
Objectives: The aims of this study were to detect the patterns of focal qualitative developmental brain defects, including the type, topography and severity of changes, and to identify the structures and brain regions that are prone to developmental alterations in autism.
Methods: Formalin-fixed brain hemispheres of 13 autistic (4–60 years of age) and 14 age-matched control subjects were embedded in celloidin and cut into 200-μm-thick coronal sections, which were stained with cresyl violet and used for neuropathological evaluation.
Results: Thickening of the subependymal germinal matrix and subependymal nodular dysplasias in two autistic children were indicative of active neurogenesis. Subcortical, periventricular, hippocampal and cerebellar heterotopias were detected in the brains of four autistic subjects (31%) reflecting abnormal neuronal migration. Multifocal cerebral dysplasias seen in the neocortex (31%), in the entorhinal cortex (15%), in the cornu Ammonis (31%) and in the dentate gyrus (15%) reflect frequent developmental distortions of brain cytoarchitecture. Cerebellar floculonodular dysplasia detected in six subjects (46%) and hypoplasia in one case indicate local failure of cerebellar development in 54% of the autistic subjects. Dystrophy with calcification and focal damage within meninges, cortex and white matter was present in all examined brains of autistic and control subjects.
Conclusions: Detection of focal dysplasia in one control subject and of a broad spectrum of focal qualitative neuropathological developmental changes in 12 of 13 (92%) examined brains of autistic subjects indicates a multi-regional dysregulation of neurogenesis, neuronal migration and maturation in autism. This may contribute to the heterogeneity of the observed clinical phenotype.
