Long-term negative impact of an inappropriate first antiepileptic medication on the efficacy of a second antiepileptic medication in mice

Abstract : Childhood absence epilepsy (CAE) is one of the most frequent epilepsies in infancy. The first-line recommended therapy for CAE is based on the prescription of the narrow-spectrum ethosuximide and the broad-spectrum valproic acid, which have similar efficacy in the first 12 months. Nevertheless, some antiepileptic drugs (AEDs) may worsen seizure duration and type in this syndrome. In line with this, we have encountered a case of identical twins with CAE and early exposure to different antiseizure drugs leading to divergent outcomes. From this, we hypothesized that the first AED to treat CAE may determine the long-term prognosis, especially in the developing brain, and that some situations leading to drug resistance may be explained by use of an inappropriate first AED. Therefore, we investigated this hypothesis by using a genetic mouse model of absence epilepsy (BS/Orl). Mice received a first appropriate or inappropriate AED followed by the same appropriate AED. Our data demonstrate that an inappropriate first AED has a negative impact on the long-term efficacy of a second appropriate AED. This work supports the necessity to effectively diagnose epileptic syndromes prior to medication use, particularly in children, in order to prevent the deleterious effects of an inappropriate initial AED.
Complete list of metadatas

Cited literature [6 references]  Display  Hide  Download

https://hal-univ-rennes1.archives-ouvertes.fr/hal-01833892
Contributor : Laurent Jonchère <>
Submitted on : Monday, September 3, 2018 - 4:19:14 PM
Last modification on : Thursday, July 11, 2019 - 1:02:06 AM
Long-term archiving on : Tuesday, December 4, 2018 - 7:22:29 PM

File

Pawluskimanuscript.pdf
Files produced by the author(s)

Identifiers

Citation

Jodi L Pawluski, Mathieu Kuchenbuch, Sarah Hadjadj, Gabriel Dieuset, Nathalie Costet, et al.. Long-term negative impact of an inappropriate first antiepileptic medication on the efficacy of a second antiepileptic medication in mice. Epilepsia, Wiley, 2018, 59 (7), pp.e109-e113. ⟨10.1111/epi.14454⟩. ⟨hal-01833892⟩

Share

Metrics

Record views

412

Files downloads

87