Role of cortical dysplasia in epileptogenesis following prolonged febrile seizure.
OBJECTIVE
Hippocampal sclerosis, characterized by prominent neuronal loss and reactive gliosis, is the most common pathology in human temporal lobe epilepsy (TLE). Although prolonged febrile convulsion (FC) is a risk factor of TLE, it is not clear whether FC provokes hippocampal sclerosis and subsequent TLE. Given that underlying brain lesions, such as cortical dysplasia (CD), in the immature brain predispose patients to FC, CD may link FC and TLE. However, the role of CD in epileptogenesis after FC is also unclear. Here, we investigated whether inborn CD increases the risk of later epilepsy induced by prolonged FC using a rat model.


METHODS
Experimental CD was induced by in utero exposure of methylazoxymethanol (MAM). Rat pups from MAM-treated or control rats were then subjected to prolonged FC. We examined morphologic changes in the hippocampi with respect to neuronal loss, reactive gliosis, and synaptogenesis, and evaluated spontaneous recurrent seizures (SRS) by long-term video-EEG (electroencephalography).


RESULTS
The MAM+FC group had a significantly lower hippocampal neuronal density in the CA1 and dentate hilus than other control groups. A robust increase in glial cells and synaptic reorganization was also detected in the MAM+FC groups. Furthermore, later SRS occurred in all rats in the MAM+FC group and in 50% and 25% of the rats in the FC-only and MAM-only group, respectively. The frequency and total duration of SRS was highest in the MAM+FC group.


CONCLUSIONS
Our results suggest that preexisting CD in the immature brain augments the proepileptogenic effects of prolonged FC, leading to TLE.
Park
Kyung-Il
KI
Department of Neurology, Seoul Paik Hospital, Inje University College of Medicine, Seoul, South Korea.
Chu
Kon
K
Jung
Keun-Hwa
KH
Kim
Jin-Hee
JH
Kang
Kyung-Muk
KM
Lee
Soon-Tae
ST
Park
Hee-Kwon
HK
Kim
Manho
M
Lee
Sang Kun
SK
Roh
Jae-Kyu
JK
D000818:Animals; D004195:Disease Models, Animal; D004569:Electroencephalography / Q000379:methods / Q000706:statistics & numerical data; D004833:Epilepsy, Temporal Lobe / Q000209:etiology* / Q000503:physiopathology; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D054220:Malformations of Cortical Development / Q000139:chemically induced / Q000503:physiopathology*; D008746:Methylazoxymethanol Acetate / Q000031:analogs & derivatives; D019599:Mossy Fibers, Hippocampal / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012598:Sclerosis / Q000473:pathology / Q000503:physiopathology; D003294:Seizures, Febrile / Q000139:chemically induced / Q000151:congenital* / Q000503:physiopathology*; D013569:Synapses / Q000473:pathology
D008746:Methylazoxymethanol Acetate; C030667:methylazoxymethanol