Evaluation of nerve cell distribution in cerebral cortex--a proposal for a new method applied to patients with epilepsy.

Microdysgenesis is a microscopic malformation of cortical development (MCD) associated with epilepsy, but its significance in epileptogenesis is debated. This is partly since the histopathological aberrations associated with microdysgenesis can also be found in normal brains. We here report a method for objective analysis of one criterion for microdysgenesis, irregular cortical nerve cell distribution. Tissue from the lateral temporal lobe from two epilepsy patients was compared with tissue from two post-mortem controls. An expansion/shrinkage factor was calculated to determine the change in tissue size during cutting and mounting. Neurons were identified and the positions of their nucleoli were marked and stored. The spatial distribution of neurons was analysed using distance to nearest neighbouring neuron and Voronoi tessellation. Specimens from the epilepsy patients expanded markedly during mounting compared with controls. Epilepsy specimens had shorter mean distances to nearest neighbour than controls and smaller Voronoi tessellation areas than controls. Both measurements suggest more densely packed neurons in epilepsy specimens. This pilot study describes a new objective method for identification of cortical neurons and their spatial distribution. Voronoi tessellation and distance to nearest neighbouring neuron might provide robust methods for objective analysis of cortical nerve cell distribution. The yield of such comparisons might be improved if each cortical layer is analysed separately.