Secondary Corpus Callosum Abnormalities Associated with Antiepileptic Drugs in Temporal Lobe Epilepsy

Abstract

Epilepsy is more than a grey-matter disorder affecting large white matter connections of the brain with seizure generation and propagation. The mechanism for such changes remains unclear. The purpose of this study was to investigate the microstructural changes in the corpus callosum in temporal lobe epilepsy (TLE) patients and whether these abnormalities are related to antiepileptic drug (AED) therapy. Ten TLE patients receiving AED therapy, ten TLE patients with no therapy and ten controls were included in the study. The regions of interest in the corpus callosum were outlined to each Witelson region (WR). Fractional anisotrophy (FA), apparent diffusion coefficient (ADC), three main diffusivity values (λ1, λ2, λ3) and tractography were acquired from each WR. DTI indices of these tracts and each WR were compared between the three subject groups and correlates examined with clinical variables that included duration of epilepsy, gender, AED type and AED therapy exposure. In TLE subjects with receiving AED therapy significantly (p<0.05) decreased FA and increased ADC values of corpus callosum were obtained when compared to the other groups. There was no significant relationship between AED type and DTI indices. Analysis of eigen values in the splenium of corpus callosum (WR7) showed λ1 values were significantly decreased in relation to AED medication duration (p<0.05). FA values of rostrum and corpus showed a reduction with duration of epilepsy. TLE is associated with abnormal integrity of corpus callosum white matter tracts. AED therapy may cause additional damage on secondary degeneration and medication time effects especially on the splenium of corpus callosum.

Rapid discontinuation of sodium channel–blocking antiseizure drugs evokes focal edema in the splenium corporis callosi: A matched case‐control study

“…This allowed us to evaluate the relation of the dose‐reduction rates of all anticonvulsants and to correlate them with the presence of FESCC. Furthermore, we investigated relative diffusion restriction in the splenium corporis callosi as a quantitative, objective measure of focal edema, which to our knowledge has not been done in the context of FESCC . This analysis lent further support to the role of sodium channel blocker dose‐change rates in the pathophysiology of FESCC.…”

White matter alterations in MR-negative temporal and frontal lobe epilepsy using fixel-based analysis

“…Fibre atrophy in the splenium of the corpus callosum, apparent from the reduction of all three observed parameters, is more probably the result of the drug treatment and seizures. DTI-based studies have shown that WM bundles of the splenium of the corpus callosum are more prone to structural abnormalities as a consequence of antiepileptic drug usage and they are also associated with seizure frequency, resulting in secondary WM degeneration 53,[60][61][62][63] . Moreover, callosal fibres, cingulum bundles, inferior longitudinal fasciculus, arcuate fasciculus, and uncinate fasciculus have been reported to be associated with different seizure propagation directions (antero-posterior and medio-lateral spread), suggesting that a decrease in fibre microstructure parameters in these tracts is driven by seizure propagation rather than being a cause of seizures 54 .…”

White matter structural connectivity changes correlate with epilepsy duration in temporal lobe epilepsy

“…Fourth, use of antiepileptic drugs (Gunbey et al, 2011) and heterogeneity in TLE etiology (Scanlon et al, 2013) have also been shown to affect DTI. Earlier age of onset has also been associated with decreased hippocampal volumes (Trenerry et al, 1993).…”