The objective was to define the role of excessive heterotopic white matter neurons beneath focal cortical dysplasias (FCD) for their contribution to epileptic circuitry. Synaptic plexi can be identified by synaptophysin immunoreactivity. Other neuronal markers can distinguish the origin of these neurons from the fetal subplate zone or by radial migration by using calretinin reactivity for GABAergic inhibitory interneurons or lack of calretinin expression by radial migratory excitatory neurons. Synaptophysin, calretinin and NeuN antibodies were applied to paraffin sections of surgical resections of epileptic foci in 16 infants, children and adolescents, ages 3 months to 17 years, with focus on subcortical axonal networks: 10 FCD I and 6 FCD II. Ten normal fetal brains of 18-22 gestational weeks, 6 of 37-41 weeks and 8 postnatal brains of infants and children at autopsy, and also white matter beneath normal cortex of surgical cases provided controls.
Subcortical and deep white matter in FCD exhibited excessive neurons, mostly scattered, but focally clustered and mainly at the depths of sulci. White matter neurons were reactive for NeuN and MAP2, but rarely for calretinin. Elaborate axonal plexi showed connections between heterotopic neurons and also with overlying cortex. Axons were oriented randomly and frequently projected to and entered the cortex; subcortical axons of controls ran parallel to cortex. In the grey matter of FCD Ia and some cases of FCD II, radial layers of synapses alternated with micro-columns of neurons. The significance is that subcortical white matter neurons in FCD have elaborate synaptic plexi that probably contribute to epileptic circuitry. They are not derived from the subplate zone, hence contribute to excitatory rather than inhibitory networks. They also help explain indistinct grey/white MRI boundaries in FCD.
Conflictsof Interest:
None.
