Classification system for malformations of cortical development

TLDR

The recent advances in the molecular biology of cortical development and the identification of new malformations have made older classification schemes obsolete. The authors propose a revised classification of malformations of cortical development that is organized by the developmental stage—cell proliferation, neuronal migration, or cortical organization—at which the defect first occurs. This system is built on known developmental steps, pathological features, genetics, and neuroimaging, and it reduces the number of specific disorders to limit future revisions while providing detailed tables for individual malformations. By eliminating the distinction between diffuse and focal/multifocal malformations, the new framework reflects shared underlying mechanisms and gives clinicians a practical, imaging‑based tool that enhances conceptual understanding without requiring brain biopsy.

Abstract

The many recent discoveries concerning the molecular biologic bases of malformations of cortical development and the discovery of new such malformations have rendered previous classifications out of date. A revised classification of malformations of cortical development is proposed, based on the stage of development (cell proliferation, neuronal migration, cortical organization) at which cortical development was first affected. The categories have been created based on known developmental steps, known pathologic features, known genetics (when possible), and, when necessary, neuroimaging features. In many cases, the precise developmental and genetic features are uncertain, so classification was made based on known relationships among the genetics, pathologic features, and neuroimaging features. A major change since the prior classification has been the elimination of the separation between diffuse and focal/multifocal malformations, based on the recognition that the processes involved in these processes are not fundamentally different; the difference may merely reflect mosaicism, X inactivation, the influence of modifying genes, or suboptimal imaging. Another change is the listing of fewer specific disorders to reduce the need for revisions; more detail is added in other smaller tables that list specific malformations and malformation syndromes. This classification is useful to the practicing physician in that its framework allows a better conceptual understanding of the disorders, while the component of neuroimaging characteristics allows it to be applied to all patients without necessitating brain biopsy, as in pathology-based classifications.