Focal cortical dysplasias in autism spectrum disorders

• Published in: Acta neuropathologica communications Vol. 1; no. 1; p. 67
• Main Authors: Casanova, Manuel F, El-Baz, Ayman S, Kamat, Shweta S, Dombroski, Brynn A, Khalifa, Fahmi, Elnakib, Ahmed, Soliman, Ahmed, Allison-McNutt, Anita, Switala, Andrew E
• Format: Journal Article
• Language: English
• Published: London BioMed Central 11.10.2013; BioMed Central Ltd
• Subjects: Adolescent; Algorithms; Biomedical and Life Sciences; Biomedicine; Cell Size; Cerebral cortex; Cerebral Cortex - pathology; Child; Child Development Disorders, Pervasive - complications; Child Development Disorders, Pervasive - pathology; Child, Preschool; Development and progression; Dysplasia; Equipment and supplies; Humans; Image processing; Image Processing, Computer-Assisted; Malformations of Cortical Development - complications; Malformations of Cortical Development - pathology; Neurology; Neurons; Neurons - pathology; Neurosciences; Organ Size; Pathology; Pervasive developmental disorders; Physiological aspects; Young Adult; Frontal lobe; Cortical width; Malformations of cortical development; Autistic spectrum disorder
• ISSN: 2051-5960; 2051-5960
• DOI: 10.1186/2051-5960-1-67

Background Previous reports indicate the presence of histological abnormalities in the brains of individuals with autism spectrum disorders (ASD) suggestive of a dysplastic process. In this study we identified areas of abnormal cortical thinning within the cerebral cortex of ASD individuals and examined the same for neuronal morphometric abnormalities by using computerized image analysis. Results The study analyzed celloidin-embedded and Nissl-stained serial full coronal brain sections of 7 autistic (ADI-R diagnosed) and 7 age/sex-matched neurotypicals. Sections were scanned and manually segmented before implementing an algorithm using Laplace’s equation to measure cortical width. Identified areas were then subjected to analysis for neuronal morphometry. Results of our study indicate the presence within our ASD population of circumscribed foci of diminished cortical width that varied among affected individuals both in terms of location and overall size with the frontal lobes being particularly involved. Spatial statistic indicated a reduction in size of neurons within affected areas. Granulometry confirmed the presence of smaller pyramidal cells and suggested a concomitant reduction in the total number of interneurons. Conclusions The neuropathology is consistent with a diagnosis of focal cortical dysplasia (FCD). Results from the medical literature (e.g., heterotopias) and our own study suggest that the genesis of this cortical malformation seemingly resides in the heterochronic divisions of periventricular germinal cells. The end result is that during corticogenesis radially migrating neuroblasts (future pyramidal cells) are desynchronized in their development from those that follow a tangential route (interneurons). The possible presence of a pathological mechanism in common among different conditions expressing an autism-like phenotype argue in favor of considering ASD a “sequence” rather than a syndrome. Focal cortical dysplasias in ASD may serve to explain the high prevalence of seizures and sensory abnormalities in this patient population.