Abstracts

Rationale: Some patients with extensive deep white matter heterotopia do not have severe epilepsy. Axons from heterotopia do not extend through U-fibres to cortex, except transmantle dysplasias. The proteoglycan keratan sulfate (KS) in dorsal and ventral median septa of fetal spinal cord and brainstem repels growing glutamatergic axons, thus prevent aberrant decussations, though facilitates GABAergic commissural axons. KS also might be expressed in the cortex and U-fibre layer. Methods: Immunocytochemical demonstration of KS in neocortex of surgical resections and autopsies was studied in 28 normal brains: 12 fetuses and neonates 9-42wk gestational age (GA); 13 infants, children and adolescents; an additional 6 patients with focal cortical dysplasias (FCD). Results: From 9-15wk GA no KS is seen in the cortical plate. At 19wk GA reactivity is detected in the molecular zone. At 28-38wk GA patchy granular reactivity appears in cortical extracellular matrix and also is adherent to neuronal somata and dendritic trunks but not distal dendritic spines. It increases in intensity and becomes more localized to deep cortex and U-fibres by term but is still immature in neonates. In FCD of children, U-fibre reactivity was discontinuous and also occurred in cytoplasm of scattered reactive astrocytes. Conclusions: This proteoglycan barrier of the U-fibre layer isolates deep white matter heterotopia and impedes their participation in cortical epileptic networks. Thalamocortical projections develop before the barrier is formed. Adhesion of KS to neuronal somatic membranes during fetal and postnatal life likely selectively repels glutamatergic but enables GABAergic axons, explaining why axosomatic synapses normally are inhibitory. Funding: Alberta Children's Hospital Research Institute