Distribution of cortical interneurons in grey matter heterotopia in patients with epilepsy.
OBJECTIVE
Grey matter heterotopia are well-defined malformations of the cortex often associated with severe epilepsy. Defects have been identified in genes, including DCX and FLN1, that influence radial migration of postmitotic cells from the ventricular zone to the cortical plate. A proportion of cortical gamma-aminobutyric acid (GABA)-containing interneurons may arise from the ganglionic eminence of the ventral telencephalon. We aimed to identify the subtypes and localisation of interneurons within grey matter heterotopia relative to cortex.


METHODS
By using quantitative immunohistochemistry, we studied the density and distribution of interneurons within six cases of grey matter heterotopia in postmortem tissue from patients with epilepsy.


RESULTS
In many cases, a suggestion of focal rudimentary laminar arrangement and small reelin-positive cells was identified within the heterotopia. Immunohistochemistry for glutamic acid decarboxylase(65/57), parvalbumin, calbindin, and calretinin showed inhibitory neurons of all subtypes represented within the heterotopia, and of normal morphology. The mean densities of interneurons were overall similar to those of the overlying cortex, but the interneurons showed less organisation and were more randomly orientated compared with cortex.


CONCLUSIONS
Interneurons within heterotopia probably arise from the ventricular zone, but their abnormal local organization may influence the epileptogenicity of these lesions.
Department of Clinical and Experimental Epilepsy, Institute of Neurology, University College London, London, United Kingdom. M.Thom@ion.ucl.ac.uk
Maria
M
Thom
Lillian
L
Martinian
John G
JG
Parnavelas
Sanjay M
SM
Sisodiya
D000293:Adolescent; D000328:Adult; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism; D002452:Cell Count; D002540:Cerebral Cortex / Q000002:abnormalities* / Q000378:metabolism / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D002828:Choristoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004827:Epilepsy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007395:Interneurons / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009419:Nerve Tissue Proteins; D009421:Nervous System Malformations / Q000378:metabolism / Q000473:pathology; D000091042:Reelin Protein; D012697:Serine Endopeptidases; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; D005680:gamma-Aminobutyric Acid; C000717127:RELN protein, human; D012697:Serine Endopeptidases