Focal cortical dysplasias in autism spectrum disorders
Open accessAbstract
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.
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Somatic activating mutations in the PI3K/AKT pathway are associated with hemimegalencephaly and focal cortical dysplasia syndromes marked by cortical dyslamination, dysmorphic neurons and loss of radial neuronal orientation.
“Somatic activating mutations in the PI3K/AKT pathway are associated with hemimegalencephaly and focal cortical dysplasia syndromes that are marked by cortical dyslamination, dysmorphic neurons and loss of radial neuronal orientation [50, 105, 106].”
From The ASD Living Biology: from cell proliferation to clinical phenotype (2019) · cites this paper as [106]
Cortical dysplasia and heterotopia of misplaced neurons can be detected in ASD individuals, and in some cases both occur in the same person.
“Disorganized cortical structure (dysplasia) and nodules of misplaced neurons (heterotopia) can be detected in individuals with ASD; in some cases dysplasia and heterotopia are observed concomitantly in the same individual [59, 339, 379].”
From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [59]
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- Authors
- Casanova, M. F., El-Baz, A. S., Kamat, S. S., Dombroski, B. A., Khalifa, F., Elnakib, A., Soliman, A., Allison-McNutt, A., & Switala, A. E.
- Affiliations
- University of Louisville (US)
- Corresponding author
- Casanova, Manuel F
- Venue
- Acta Neuropathologica Communications
- Published
- 2013-10-11
- Volume
- 1
- Issue
- 1
- Pages
- 67-67
- ISSN
- 2051-5960 (ISSN-L)
- PMC
- PMC3893372
- OpenAlex
- W2155740914
- Cited by
- 150
- References
- 68
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 7 · 2023: 9 · 2022: 15 · 2021: 14 · 2020: 7 · 2019: 11 · 2018: 11 · 2017: 20 · 2016: 15 · 2015: 17 · 2014: 15 · 2013: 1
- FWCI
- 8.74
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Acta Neuropathologica Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Autism Speaks
- Autism Research Institute
- National Institutes of Health
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD065279, R01 HD-65279)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Fetal and Pediatric Neurological Disorders
- Keywords
- focal cortical dysplasia, autism spectrum disorder, cortical thinning, neuronal morphometry, pyramidal neurons, interneurons, granulometry, cortical development, frontal lobe, seizures, sensory disturbances
- MeSH terms
- Adolescent, Algorithms, Cerebral Cortex, Child, Child Development Disorders, Pervasive, Child, Preschool, Humans, Image Processing, Computer-Assisted, Neurons, Organ Size, Cell Size, Malformations of Cortical Development, Young Adult
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