DENDRITIC MORPHOLOGY IN EPILEPTOGENIC CORTEX FROM TRPE PATIENTS, REVEALED BY INTRACELLULAR LUCIFER-YELLOW MICROINJECTION AND CONFOCAL LASER-SCANNING MICROSCOPY

Biopsy material was obtained from cortical epileptogenic zones (eight temporal, one occipital, one parietal and one frontal) of eleven patients aged 1.5-47 years with therapy-resistant partial epilepsy (TRPE) undergoing epilepsy surgery. Control autopsy material (two temporal, two occipital, one parietal and one frontal) was removed from six neurologically healthy cases within 6-10 hours postmortem delay. In each specimen, 100-300 pyramidal and nonpyramidal neurons were visualized by intracellular Lucifer Yellow microinjection. Single neurons were imaged using CLSM generated serial optical sections; 2-D reconstruction of each neuron was made using z-projection of serial optical images, and 3-D reconstructions and rotations were computerized. Neuronal maps from TRPE biopsies, compared to control autopsies, show markedly increased numbers of dendritic abnormalities of single pyramidal and non-pyramidal neurons in layers I, II-III, V-VII, and in the subcortical white matter. The abnormalities include: (1) increased number of non-pyramidal cells in layer I; (2) many pyramidal cells with two or three dendrites originating apically, rather than one single apical dendrite, in layers II-III; (3) atypical orientation of oblique apical and basal dendrites in pyramidal neurons of layers II-VII; (4) increased number of atypical 'dinosaur-like' and fusiform cells in layers V-VII; (5) numerous neurons in the white matter. These abnormalities may be etiological in cases with early onset, and predisposing in cases with late onset.