The pathology of incipient polymicrogyria

Area of Science:

• Neuroscience
• Developmental Biology
• Pathology

Background:

• Post-encephaloclastic polymicrogyria is a severe developmental brain malformation.
• Understanding early fetal brain injury is crucial for diagnosing and managing congenital neurological disorders.

Purpose of the Study:

• To characterize the early histological tissue changes in fetal polymicrogyria resulting from ischemic injury.
• To investigate the cellular and tissue responses in the developing human fetal brain following early cortical injury.

Main Methods:

• Review of clinical histories and autopsy pathology of fetal cerebral cortical injury cases (<30 weeks gestational age).
• Histological examination using immunohistochemical markers for neuronal, glial, microglial, and vascular components.
• Analysis of tissue changes at various time points post-injury, up to 10 weeks.

Main Results:

• Identified eight cases (18-29 weeks GA) with full-thickness cortical infarcts or periSylvian cortical necrosis.
• Observed gross fissuration abnormalities within one month of injury.
• Documented disruption of pia limitans, microglial/glial responses, macrophage accumulation, and subpial granular cell layer hyperplasia.
• Noted Cajal Retzius neuron alterations, altered radial glia growth, and hypertrophy of subplate neurons prior to 20 weeks GA.

Conclusions:

• The histological changes in early polymicrogyria involve all brain tissue elements.
• Subpial alterations are common but not solely due to pia limitans changes.
• The role of the necroinflammatory response in abnormal brain cytoarchitecture requires further investigation.