Cortical malformations are being increasingly recognized as a significant cause of developmental delay, focal neurological deficit, refractory epilepsy and mental retardation. Many of these malformations present in the neonatal period or infancy. Proper diagnosis and rational classification of these disorders is essential for prognosis, genetic testing and counseling, and investigation of the underlying olecular causes.
Table 1.: Stage of brain development correlates with the brain malformation pathology.
Stage of brain development | Time | Pathology |
| | |
Dorsal induction | 3-7w | Neural tube defects |
Ventral induction | 5-w | Holoprosencephaly |
NeuronaMil glial proliferation | 8-18w | Micro-Megalencephaly |
Migration | 12-20w | Lissencephaly and heterotopia |
Organization | > 24w | Poly-microgyria, dysplasia |
Myelination | >24w.-2yr. | Hypo-dysmyelination |
Although cerebral cortical development is an extremely complex process, it can be divided into three broad and overlapping steps: cell proliferation, neuronal migration, and cortical organization.
1. Neuronal and glial proliferation or apoptosis.
Cell proliferation is the process that takes place in the germinal zones of the developing prosencephalon. The germinal matrix is expanded through series of cell divisions in which the doughter cells re-enter the cell cycle as progenitors.
Eventually, asymmetric division begins: neuroblasts (predominantly) and glial precursors are generated.
2. Neuronal migration.
The neuroblasts attach to glial cells that span the developing hemisphere from the germinal zone to the pia mater, and start migrating along the radial glial cells. (Figs. 1 , 2 , 3).
The neuroblasts detach from the glial cells when they reach the proper layer of the developing cerebral cortex. (Fig. 4).
3. Cortical organization.
The molecular mechanisms of cortical organization are those of neurite extension, synaptogenesis and neuronal maturation. These mechanisms are not completely understood yet. The classification scheme of malformations of cortical development is based on whether these disorders are the result of abnormal neuronal and glial proliferation or apoptosis, abnormal neuronal migration, or abnormal cortical organization. Proper diagnosis and rational classification of these disorders is essential for prognosis, genetic testing and counselling, and investigation of the underlying molecular causes.
Characteristics that correlate with and enforce this system of classification can be identified by MR imaging.