Role of cortical dysplasia in epileptogenesis following prolonged febrile seizure

Authors: Park, Kyung-Il¹; Chu, Kon; Jung, Keun-Hwa; Kim, Jin-Hee²; Kang, Kyung-Muk²; Lee, Soon-Tae; Park, Hee-Kwon; Kim, Manho; Lee, Sang Kun; Roh, Jae-Kyu

Source: Epilepsia, Volume 51, Number 9, September 2010 , pp. 1809-1819(11)

Publisher: Wiley-Blackwell

Abstract:

Summary Purpose: 

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. Discussion: 

Our results suggest that preexisting CD in the immature brain augments the proepileptogenic effects of prolonged FC, leading to TLE.

Keywords: Hippocampal sclerosis; Temporal lobe epilepsy; Febrile convulsion; Cortical dysplasia; Synaptogenesis; Epileptogenesis

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1528-1167.2010.02676.x

Affiliations: 1: Department of Neurology, Seoul Paik Hospital, Inje University College of Medicine, Seoul, South Korea 2: Department of Neurology, Stroke & Stem Cell Laboratory in Clinical Research Institute, Stem Cell Research Center, Seoul, South Korea

Publication date: 2010-09-01

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