Cortical Malformations


Cortical malformations are structural abnormalities of the cerebral cortex that occur when there is a disruption in the normal processes of cortical development caused by interruption of the normal developmental sequences. The development of the cerebral cortex can be divided into 3 stages; cell proliferation, cell migration, and cortical organization. Abnormalities at any of these stages, be they environmental or genetic in origin, may cause disruption of neuronal circuitry and predispose to a variety of clinical consequences, the most common of which is epileptic seizures.

Classification system for malformations of cortical development organizes a myriad of conditions according to one of three major underlying mechanisms:

  1. abnormal neuronal and glial proliferation or apoptosis proliferation
  2. abnormal neuronal migration
  3. abnormal postmigrational development

Abnormal cell proliferation or apoptosis

These conditions include those due to disorders of neuronal and/or glial proliferation or apoptosis and occur between the second and fourth months of gestation. They can be further divided into three categories: reduced proliferation or accelerated apoptosis (congenital microcephalies); increased proliferation or decreased apoptosis (megalencephalies); and abnormal proliferation (focal and diffuse dysgenesis and dysplasia).

Abnormal migration

In normal brain development, neurons form in the periventricular region, located around fluid-filled cavities (ventricles) near the center of the brain. Between the third and fifth month of gestation, the neurons migrate outward to form the exterior of the brain (cerebral cortex) in six onion-like layers. Malformations that occur during this time can be divided into one of four subcategories: malformations that occur during the initiation of migration (periventricular heterotopias); generalized abnormalities of transmantle migration (lissencephalies); localized abnormalities of transmantle migration (subcortical heterotopia); and abnormalities due to abnormal terminal migration/defects in pial limiting membrane (cobblestone malformations).

Abnormal postmigrational development

Neuronal organization, which is dependent on normal neuronal migration, starts at 22 weeks of gestation and continues until 2 years of age. During this process neurons differentiate into several cell types (pyramidal cells, stellate cells), organizing into horizontal laminar aggregates and vertical columns, which leads to the formation of the normal cortical cytoarchitectonic pattern. Disorders of cortical organization result in abnormalities of gyral formation and cortical organization. Malformations that occur during this time include polymicrogyria, schizencephaly, focal cortical dysplasia, and postmigrational microcephaly.