The pathology of incipient polymicrogyria

Brain Dev. 2017 Jan;39(1):23-39. doi: 10.1016/j.braindev.2016.06.005. Epub 2016 Jul 9.


Objective: To characterise the early tissue changes of post encephaloclastic polymicrogyria in the human fetus.

Methods: We identified and reviewed the clinical histories and autopsy pathology of post ischemic fetal cerebral cortical injury at less than 30weeks gestational age (GA). The histology of local cortical abnormalities was examined with neuronal, glial, microglial and vascular immunohistochemical markers.

Results: We identified eight cases ranging from 18 to 29weeks GA: 5 cases show full thickness cortical infarcts and 3 show periSylvian post-ischemic necrosis of the cerebral cortex. The maximal age is less than 10weeks after injury. There are abnormalities in gross fissuration as early as one month after injury. Disruption of the pia limitans was associated with a microglial and glial response and full thickness cortical injury. Macrophages were often seen accumulating deep to abnormal cortex. Hyperplasia of the subpial granular cell layer was universal in perilesional cortex. Cajal Retzius neuron hyperplasia, aggregation, and both superficial and deep displacement were noted. Where there was loss and dispersal of early cortical pyramidal neurons there was usually no pseudolaminar necrosis. Radial glia by 18weeks GA showed altered growth patterns and lateral branching. Altered migration of primitive elements was often prominent. Particularly prior to 20weeks GA subadjacent subplate neurons showed striking hypertrophy.

Conclusions: The array of histological changes encompasses all tissue elements of the affected brains, early in the evolution polymicrogyria. Although subpial alterations were ubiquitous, not all changes are referable to alterations in the pia limitans. The role of the necroinflammatory response in the genesis of abnormal cytoarchitecture deserves further study.

Keywords: Fetal; Malformation; Polymicrogyria; Porencephaly; Schizencephaly.

MeSH terms

  • Brain / embryology*
  • Brain / metabolism
  • Brain / pathology*
  • Cerebral Infarction / embryology
  • Cerebral Infarction / metabolism
  • Cerebral Infarction / pathology
  • Humans
  • Immunohistochemistry
  • Macrophages / metabolism
  • Macrophages / pathology
  • Neuroglia / metabolism
  • Neuroglia / pathology
  • Polymicrogyria / embryology*
  • Polymicrogyria / metabolism
  • Polymicrogyria / pathology*