Aim: 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.
Methods: 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.
Results: 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.
Conclusion: The presented data corroborate the hypothesis that reelin might be involved in human heterotopic nodular formation.