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Updated: Jun 2, 2026
Large-scale Three-dimensional Imaging of Cellular Organization in the Mouse Neocortex
Published on: September 5, 2018
Polymicrogyria includes fusion of the molecular layer and decreased neuronal populations but normal cortical laminar
Alexander R Judkins1, Daniel Martinez, Pamela Ferreira
1Department of Pathology, The Children's Hospital of Philadelphia, Pennsylvania.
Abstract:
Malformations of cortical development are frequently identified in surgical resections for intractable epilepsy. Among the more frequently identified are cortical dysplasia, pachygyria, and polymicrogyria. The pathogenesis of these common developmental anomalies remains uncertain. Polymicrogyria is particularly vexing because there are multiple described forms (2, 4, and 6 layers) that have been attributed to multiple etiologies (e.g. ischemic, genetic, infectious, and toxic). We reviewed the pathology in 19 cases and performed cortical laminar analysis in 10 of these cases. Our data indicate that a defining feature of polymicrogyriais fusion of the molecular layer and that most often there is a well-defined gray matter-white matter junction. Unexpectedly, the cortical laminae were normally positioned, but there were reduced neuronal populations within these laminae, particularly in the subgranular layers. On the basis of these data, we propose that the categorization of polymicrogyria according to the number of lamina is artificial and should be abandoned, and polymicrogyria should be defined according to the presence or absence of coexisting neuropathological features. Furthermore, our data indicate that polymicrogyria is not a cell migration disorder, rather it should be considered a postmigration malformation of cortical development.
Insights
Polymicrogyria, a brain malformation linked to epilepsy, is redefined as a postmigration disorder. This finding challenges the traditional classification based on cortical layers, suggesting a focus on coexisting neuropathological features instead.
Area of Science:
- Neuroscience
- Developmental Biology
- Neuropathology
Background:
- Malformations of cortical development, including polymicrogyria, are common in epilepsy surgery.
- The underlying causes and classification of polymicrogyria remain unclear, with multiple etiologies proposed.
- Existing classifications based on the number of cortical layers (e.g., 2, 4, 6) are problematic.
Purpose of the Study:
- To investigate the neuropathological features of polymicrogyria.
- To re-evaluate the current classification system for polymicrogyria.
- To determine the developmental stage at which polymicrogyria occurs.
Main Methods:
- Pathological review of 19 surgical epilepsy resection cases.
- Cortical laminar analysis in 10 of these cases.
- Detailed examination of gray matter-white matter junctions and neuronal populations.
Main Results:
- Polymicrogyria is characterized by fusion of the molecular layer and a distinct gray matter-white matter junction.
- Cortical laminae are normally positioned, but exhibit reduced neuronal populations, especially in subgranular layers.
- Findings suggest polymicrogyria is not a cell migration disorder.
Conclusions:
- The classification of polymicrogyria by the number of laminae is artificial and should be abandoned.
- Polymicrogyria should be defined by the presence of coexisting neuropathological features.
- Polymicrogyria is a postmigration malformation of cortical development, not a cell migration disorder.
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