Altered patterns of catecholaminergic fibers in focal cortical dysplasia in two patients with partial seizures

Abstract

We present the histologic study of two patients who underwent cerebral cortex resection for partial seizures linked with cortical dysplasia. The distinction of areas of seizure origin from areas of seizure propagation was made according to stereoelectroencephalographic criteria. Samples of epileptogenic tissue were studied by using cytoarchitectonic and immuno-histochemical stainings. We mapped the catecholaminergic afferents by employing antisera directed against tyrosine hydroxylase and dopamine-β-hydroxylase enzymes. The epileptic activity was correlated with the underlying patterns of cytoarchitectonic and immunohistochemical changes. The neuropathological features were focal and consisted of large neurons dispersed through all but the first cortical layer (associated in one case to giant glial cells), of variable disturbance of lamination, of neuronal ectopia in the white matter and of moderate proliferation of small glial cells. Areas of seizure onset coincided with that of dysplastic zones. Both laminar distribution and density of catecholaminergic fibers were altered in the dysplastic cortices (area of seizure onset) and there was an increase in the density of tyrosine hydroxylase-immunoreactive fibers in the surrounding areas of seizure propagation. Our results indicate that these developmental epileptogenic lesions were associated with abnormal neuronal circuitry. They provide evidence at the structural level of the increase in tyrosine hydroxylase activity previously reported in spiking areas of human epileptogenic cerebral cortex and they suggest that catecholamines may contribute toward limiting seizure activity propagation.