Heterotopic reelin in human nodular heterotopia: a neuropathological study

The extracellular matrix glycoprotein reelin plays a crucial role in the control of neuronal migration and during development is expressed by Cajal-Retzius cells in the marginal zone. The purpose of this study was to investigate the possible involvement of reelin in the pathogenesis of human nodular heterotopia, a malformation of cortical development frequently associated with focal drug-resistant epilepsy.

Five patients presenting with subcortical nodular heterotopia and referred for epilepsy surgery, after a comprehensive presurgical investigation, were considered. The surgical specimens were studied by combining immunohistochemistry, double immunofluorescence, and in situ hybridisation procedures.

The selected cases were characterised by the presence of multiple nodules presenting in the core cell-free zones, reminiscent of the cortical molecular layer. In all cases, small reelin-positive cells, without typical Cajal-Retzius cell features, were distributed inside the nodules and localised in these cell body-sparse regions.

The presented data corroborate the hypothesis that reelin might be involved in human heterotopic nodular formation.