13 - Congenital disorders of cerebral cortical development

Summary

Developmental malformations of the cerebral cortex represent a heterogeneous group of disorders that are individually rare, but that collectively account for a large number of cases of epilepsy, mental retardation and other cognitive disorders. Though many of the disorders discussed in this chapter have been known for decades, our view of them has been revolutionized in recent years. Two recent major advances facilitated our understanding of these disorders. First is the use of non-invasive brain imaging techniques, particularly MRI, in clinical neurological practice (Osborn et al., 1988). This has enabled accurate diagnosis of disorders of cortical development, which had only been diagnosed by post mortem examinations in the past. Improved imaging techniques have also led to the recognition of new clinical entities and the recognition of mendelian inheritance of many cortical malformations. Second are the advances in molecular genetics, which have allowed identification of genes responsible for inherited diseases using methods of positional cloning (Walsh, 1999). Identification of genes responsible for cortical malformations has led to molecular diagnosis in many cases. Furthermore, genes identified as responsible for human disorders have provided us with important clues to understand the mechanisms of normal brain development.

With these advances in our knowledge, the traditional classification scheme of cortical malformations, which is solely based on morphological abnormalities, has been reassessed. Several attempts have recently been made to classify the disorders of cortical development, reflecting new insights into their pathogenesis. A classification based on the time that the derangement is presumed to have occurred has been proposed (van der Knaap & Valk, 1988). Another classification system devised by Barkovich et al., (1996) is based on a combination of embryology, genetics, imaging and pathology. Because our understanding of these disorders is still incomplete, any classification is somewhat provisional. In this chapter, the disorders are categorized according mainly to the disturbed developmental process. As our knowledge about their pathogenesis evolves, the classification systems will inevitably be modified and refined.

Normal development of the cerebral cortex

The neurons of the cerebral cortex are formed in the ventricular zone, which consists of a specialized proliferative region along the wall of the lateral ventricles. The postmitotic neurons then leave the ventricular zone and migrate over considerable distances to reach the cortex.