Synaptogenesis in hemimegalencephaly: the numerical density of asymmetric and symmetric synapses in the cerebral cortex.

Abstract

Specimens of cerebral cortex were prepared for electron microscopy from cortical resections performed for the treatment of intractable seizures in four cases of hemimegalencephaly (HME). Morphometric analyses were performed to determine mean cortical thickness, the numerical density of synapses (NV, contacts per mm3) and the number of synapses in a column of cortex beneath 1 mm2 of pial surface. The NV were calculated separately for asymmetric and symmetric synapses as well as for axospinous, axodendritic and axosomatic contacts. Four cases of Rasmussen's encephalitis served as controls, with tissue being sampled from a region distant to the site of the inflammatory lesion without obvious necrosis. The NV of synapses did not differ significantly between HME cases and controls. The proportions or asymmetric and symmetric synapses were similar in both groups, as were the proportions of axospinous, axodendritic and axosomatic contacts. However, there was a significant increase in mean cortical thickness in HME cases (130%, P < 0.05). Consequently, there was a significant increase in the total number of synapses in a column of cortex (126%, P < 0.05). In HME the cerebral cortex is characterized by synaptic dysgenesis. Although synaptic density per unit volume of tissue appears relatively normal, the increased thickness and volume of the cerebral cortex provides for an increase in the total number of synapses in a given cytoarchitectonic area.