The DOI matches its Crossref record; 146 of the 146 references it cites were found in a registry or an index.
Drug-Resistant Epilepsy: Multiple Hypotheses, Few Answers
Open accessAbstract
Epilepsy is a common neurological disorder that affects over 70 million people worldwide. Despite the recent introduction of new antiseizure drugs (ASDs), about one-third of patients with epilepsy have seizures refractory to pharmacotherapy. Early identification of patients who will become refractory to ASDs could help direct such patients to appropriate non-pharmacological treatment, but the complexity in the temporal patterns of epilepsy could make such identification difficult. The target hypothesis and transporter hypothesis are the most cited theories trying to explain refractory epilepsy, but neither theory alone fully explains the neurobiological basis of pharmacoresistance. This review summarizes evidence for and against several major theories, including the pharmacokinetic hypothesis, neural network hypothesis, intrinsic severity hypothesis, gene variant hypothesis, target hypothesis, and transporter hypothesis. The discussion is mainly focused on the transporter hypothesis, where clinical and experimental data are discussed on multidrug transporter overexpression, substrate profiles of ASDs, mechanism of transporter upregulation, polymorphisms of transporters, and the use of transporter inhibitors. Finally, future perspectives are presented for the improvement of current hypotheses and the development of treatment strategies as guided by the current understanding of refractory epilepsy.
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Cites
Early Identification of Refractory Epilepsy
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Cited by
Altered composition of the gut microbiome in patients with drug-resistant epilepsy
Peng, A., Qiu, X., Lai, W., Li, W., Zhang, L., Zhu, X., He, S., Duan, J., & Chen, L. (2018) · Epilepsy Research · doi:10.1016/j.eplepsyres.2018.09.013 · Cited by 247
Matrix Metalloproteinase-Mediated Blood-Brain Barrier Dysfunction in Epilepsy
Rempe, R. G., Hartz, A. M. S., Soldner, E. L. B., Sokola, B. S., Alluri, S. R., Abner, E. L., Kryscio, R. J., Pekcec, A., Schlichtiger, J., & Bauer, B. (2018) · The Journal of Neuroscience · doi:10.1523/jneurosci.2751-17.2018 · Cited by 162
Self-citationDysfunction of ABC transporters at the blood-brain barrier: Role in neurological disorders
Gil-Martins, E., Barbosa, D. J., Silva, V., Remião, F., & Silva, R. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107554 · Cited by 152
Gut bacterial dysbiosis in children with intractable epilepsy
Lee, K., Kim, N., Shim, J. O., & Kim, G.-H. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm10010005 · Cited by 70
Bypassing the Blood–Brain Barrier: Direct Intracranial Drug Delivery in Epilepsies
Gernert, M., & Feja, M. (2020) · Pharmaceutics · doi:10.3390/pharmaceutics12121134 · Cited by 68
Metadata
- Authors
- Tang, F., Hartz, A. M. S., & Bauer, B.
- Venue
- Frontiers in Neurology
- Publisher
- Frontiers Media SA
- Published
- 2017-07-06
- Volume
- 8
- Pages
- 301-301
- ISSN
- 1664-2295 (ISSN-L)
- OpenAlex
- W2726666234
- Cited by
- 482
- References
- 146
- FWCI
- 26.50
- Type
- journal article
- Language
- en
- Open access
- gold
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