Role of glyoxalase I gene polymorphisms in late-onset epilepsy and drug-resistant epilepsy

Background. Epilepsy is one of the most common neurological disorders with about 30% treatment failure rate. An interindividual variations in efficacy of antiepileptic drugs (AEDs) make the treatment of epilepsy challenging, which can be attributed to genetic factors such as ATP-Binding Cassette sub-family B, member1 (ABCB1) gene polymorphisms. Objective. The main objective of the present study is to evaluate the association of ABCB1 C1236T, G2677T, and C3435T polymorphisms with treatment response among Tunisian epileptic patients. Materials and Methods. One hundred epileptic patients, originated from north of Tunisia, were recruited and categorized into 50 drug-resistant and 50 drug-responsive patients treated with antiepileptic drugs (AEDs) as per the International League Against Epilepsy. DNA of patients was extracted and ABCB1 gene polymorphisms studied using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results. The C1236T, G2677T, and C3435T polymorphisms were involved into AED resistance. Significant genotypic (C1236T TT (p≤0.001); G2677T TT (p=0.001); C3435T TT (p≤0.001)) and allelic associations (C1236T T (3.650, p≤0.001); G2677TT (1.801, p=0.044); C3435T T (4.730, p≤0.001)) with drug resistance epilepsy (DRE) were observed. A significant level of linkage disequilibrium (LD) was also noted between ABCB1 polymorphisms. Patients with the haplotypes CT and TT (C1236T-G2677T); GT, TC, and TT (G2677T-C3435T); CT and TT (C1236T-C3435T); CTT, TTC, TGT, and TTT (C1236T-G2677T-C3435T) were also significantly associated to AED resistance. Conclusions. The response to antiepileptics seems to be modulated by TT genotypes, T alleles, and the predicted haplotypes for the tested SNPs in our population. Genetic analysis is a valuable tool for predicting treatment response and thus will contribute to personalized medicine for Tunisian epileptic patients.

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Role of P-glycoprotein inhibitors in children with drug-resistant epilepsy

Acta Neurologica Scandinavica ◽

10.1111/ane.12778 ◽

2017 ◽

Vol 136 (6) ◽

pp. 639-644 ◽

Cited By ~ 5

Author(s):

H. A. Elkhayat ◽

R. H. Aly ◽

I. A. Elagouza ◽

R. H. El-Kabarity ◽

Y. I. Galal

Keyword(s):

Drug Resistant ◽

P Glycoprotein ◽

Drug Resistant Epilepsy ◽

Glycoprotein Inhibitors

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The Ketogenic Diet in the Treatment of Childhood Epilepsy

European Neurological Review ◽

10.17925/enr.2010.05.01.88 ◽

2010 ◽

Vol 5 (1) ◽

pp. 88

Author(s):

J Helen Cross ◽

Keyword(s):

Ketogenic Diet ◽

Evidence Base ◽

Drug Resistant ◽

Older Children ◽

Efficacy Evaluation ◽

Anti Epileptic Drug ◽

Drug Resistant Epilepsy ◽

Randomised Controlled

The ketogenic diet has been used for the treatment of drug-resistant epilepsy in childhood for almost 100 years. This aside, it is only over the past decade that renewed interest has led to a further evidence base for efficacy, evaluation of optimal implementation and wider discussion of possible mechanisms of action. Randomised controlled data have now demonstrated the diet to be as effective as any newer anti-epileptic drug (AED) in drug-resistant epilepsy. Implementation can be challenging, and is resource-intensive, but successful use can lead to improved quality of life with most immediate side effects alleviated by dietary manipulation. However, data are still required on the choice of optimal candidates and the role of alternative diets in older children.

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Faculty Opinions recommendation of Role of magnetoencephalography and stereo-electroencephalography in the presurgical evaluation in patients with drug-resistant epilepsy.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.734934015.793555811 ◽

2019 ◽

Author(s):

Robert Greenwood

Keyword(s):

Drug Resistant ◽

Presurgical Evaluation ◽

Drug Resistant Epilepsy

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Refractory Epilepsy: Mechanisms of Pharmacoresistance

10.48091/uwyg8998 ◽

2021 ◽

pp. 99-110

Author(s):

Ariel Le ◽

Makenzie Thomas ◽

Brady Stallman ◽

Kathryn Meadows ◽

Vidya Bhargava

Keyword(s):

Blood Brain Barrier ◽

Refractory Epilepsy ◽

Treatment Options ◽

Brain Barrier ◽

Drug Resistant ◽

Blood Brain ◽

Anti Epileptic Drug ◽

Drug Resistant Epilepsy ◽

Protein Transporters

Refractory or drug-resistant epilepsy is a complex and debilitating disorder that impacts over one-third of people diagnosed with epilepsy. Many studies have suggested a variety of possible hypotheses for drug-resistant epilepsy, including the degeneration of neural networks, alterations of anti-epileptic drug (AED) targets, intrinsic severity/frequency of seizures, and genetic predisposition to pharmacoresistance. However, extensive research suggests that the overexpression of efflux protein transporters in brain tissue is the most viable hypothesis. Specifically, the overexpression of P-glycoproteins (P-gps) at the blood brain barrier proves the most compelling mechanism to discuss further. Studying the mechanisms of these transporters provides critical insight for new ways to combat pharmacoresistance. Thus, this review evaluates the co-administration of P-gp inhibitors with AEDs as a promising, yet relatively unexplored, treatment option for refractory epilepsy. This review specifically considers Tariquidar (TQD) the most promising P-gp inhibitor for refractory epilepsy treatment. This work aims to evaluate the role of P-gp overexpression in refractory epilepsy, consolidate current research about potential treatment options, and identify discrepancies or gaps in the literature related to P-gp inhibitory treatments for refractory epilepsy. It was concluded that, as a result of increased drug efflux processes at the blood brain barrier, overexpression of P-gp is the leading cause of pharmacoresistance. By inhibiting the activity of these proteins with the drug Tariquidar, an effective treatment for refractory epilepsy may become a reality.

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