Doublecortin expression in focal cortical dysplasia in epilepsy.
OBJECTIVE
Doublecortin (DCX) is a microtubule-associated protein with regulatory roles in radial and tangential migration of neurons during cortical development. In normal adult cortex there is restricted expression, and DCX is widely used as a marker of neurogenesis. Imperfect corticogenesis is thought to underpin many focal cortical pathologies in epilepsy surgical series, including focal cortical dysplasia (FCD). The aim was to study DCX expression patterns in such lesions compared to normal developing and mature cortex.


METHODS
Cases of FCD types Ia (13) and IIb (4), pediatric hippocampal sclerosis (HS) (5), temporal lobe sclerosis (5), glioneuronal tumors (5), gray matter heterotopia (3), and control tissues (16) from a wide age range [20 gestational weeks (GW) to 85 years] were studied using immunohistochemistry to DCX.


RESULTS
In controls and all epilepsy cases, perinuclear labeling of small round cells (SRCs) and satellite perineuronal cells was observed in both postmortem and surgical tissues. In FCD Ia up to the age of 4 years, prominent DCX-positive (DCX(+)), immature cells were present along the junction of layers I and II, with processes extending into the molecular layer. These cell types were not a significant feature in other pathologies, which showed multipolar DCX(+) cells or labeling of dysmorphic cells throughout the cortex.


CONCLUSIONS
Persistent cellular DCX expression is confirmed in normal adult cortex. Characteristic expression patterns in layer II of FCD Ia could indicate delayed or abnormal cortical maturation rather than ongoing cytogenesis. This could be indicative of enhanced local cortical plasticity as well as a potential diagnostic feature of this type of pathology.
Srikandarajah
Nisaharan
N
Department of Clinical and Experimental Epilepsy, Institute of Neurology, Queen Square, London, United Kingdom.
Martinian
Lillian
L
Sisodiya
Sanjay M
SM
Squier
Waney
W
Blumcke
Ingmar
I
Aronica
Eleonora
E
Thom
Maria
M
D000293:Adolescent; D000328:Adult; D000818:Animals; D001344:Autopsy; D015153:Blotting, Western; D054443:Cell Migration Assays / Q000706:statistics & numerical data; D002648:Child; D002675:Child, Preschool; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D004827:Epilepsy / Q000235:genetics / Q000276:immunology / Q000601:surgery; D005260:Female; D005455:Fluorescent Antibody Technique; D018507:Gene Expression Regulation, Developmental; D015726:Giant Cells / Q000276:immunology / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D054220:Malformations of Cortical Development / Q000235:genetics* / Q000276:immunology / Q000601:surgery; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D019579:Neocortex / Q000254:growth & development / Q000473:pathology* / Q000601:surgery; D055495:Neurogenesis / Q000235:genetics; D009474:Neurons / Q000276:immunology / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics / Q000276:immunology; D014402:Tuberous Sclerosis / Q000235:genetics* / Q000276:immunology / Q000601:surgery
C000714328:DCX protein, human; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides