36 research outputs found
Molecular Genetics of Drug-resistance in Epilepsies
Nearly one-third of newly diagnosed patients with epilepsy remain unresponsive to antiepileptic drugs (AEDs), etiopathogenesis of which is poorly understood. The genes encoding the proteins that regulate the pharmacokinetics such as P-glycoprotein [ABCBI], major vault protein [MVP gene] and drug metabolizing enzymes [ABCB1, ABCG2, MVP, CYP2C9, CYP2C19, CYP3A4, CYP3A5, EPHX1, UGT1A1, UGT2B7], and pharmacodynamics such as sodium channels [SCN1A, SCN2A] and GABA receptors [GABRA1, GABRA6, GABRB2, GABRG2] of AEDs are under intense investigation to unravel the mysteries of AED-resistance. However, till today, a consistent and reliable result that could help the clinician either to predict drug resistance or to overcome it has not been forthcoming. The discrepant results may be related to variations in the definition of drug-resistance, heterogeneous patient populations, ethnic variations in the frequency distribution of single nucleotide polymorphisms (SNPs) and the selection of SNPs. Understanding of these limitations of existing studies, hopefully, will help in designing better studies. Nearly one-third of newly diagnosed patients with epilepsy remain unresponsive toantiepileptic drugs (AEDs), etiopathogenesis of which is poorly understood. The genesencoding the proteins that regulate the pharmacokinetics such as P-glycoprotein[ABCBI], major vault protein [MVP gene] and drug metabolizing enzymes [ABCB1,ABCG2, MVP, CYP2C9, CYP2C19, CYP3A4, CYP3A5, EPHX1, UGT1A1, UGT2B7],and pharmacodynamics such as sodium channels [SCN1A, SCN2A] and GABAreceptors [GABRA1, GABRA6, GABRB2, GABRG2] of AEDs are under intenseinvestigation to unravel the mysteries of AED-resistance. However, till today, aconsistent and reliable result that could help the clinician either to predict drugresistanceor to overcome it has not been forthcoming. The discrepant results may berelated to variations in the definition of drug-resistance, heterogeneous patientpopulations, ethnic variations in the frequency distribution of single nucleotidepolymorphisms (SNPs) and the selection of SNPs. Understanding of these limitationsof existing studies, hopefully, will help in designing better studies.CorrespondenceNearly one-third of newly diagnosed patients with epilepsy remain unresponsive to antiepileptic drugs (AEDs), etiopathogenesis of which is poorly understood. The genes encoding the proteins that regulate the pharmacokinetics such as P-glycoprotein [ABCBI], major vault protein [MVP gene] and drug metabolizing enzymes [ABCB1, ABCG2, MVP, CYP2C9, CYP2C19, CYP3A4, CYP3A5, EPHX1, UGT1A1, UGT2B7], and pharmacodynamics such as sodium channels [SCN1A, SCN2A] and GABA receptors [GABRA1, GABRA6, GABRB2, GABRG2] of AEDs are under intense investigation to unravel the mysteries of AED-resistance. However, till today, a consistent and reliable result that could help the clinician either to predict drug resistance or to overcome it has not been forthcoming. The discrepant results may be related to variations in the definition of drug-resistance, heterogeneous patient populations, ethnic variations in the frequency distribution of single nucleotide polymorphisms (SNPs) and the selection of SNPs. Understanding of these limitations of existing studies, hopefully, will help in designing better studies. Nearly one-third of newly diagnosed patients with epilepsy remain unresponsive toantiepileptic drugs (AEDs), etiopathogenesis of which is poorly understood. The genesencoding the proteins that regulate the pharmacokinetics such as P-glycoprotein[ABCBI], major vault protein [MVP gene] and drug metabolizing enzymes [ABCB1,ABCG2, MVP, CYP2C9, CYP2C19, CYP3A4, CYP3A5, EPHX1, UGT1A1, UGT2B7],and pharmacodynamics such as sodium channels [SCN1A, SCN2A] and GABAreceptors [GABRA1, GABRA6, GABRB2, GABRG2] of AEDs are under intenseinvestigation to unravel the mysteries of AED-resistance. However, till today, aconsistent and reliable result that could help the clinician either to predict drugresistanceor to overcome it has not been forthcoming. The discrepant results may berelated to variations in the definition of drug-resistance, heterogeneous patientpopulations, ethnic variations in the frequency distribution of single nucleotidepolymorphisms (SNPs) and the selection of SNPs. Understanding of these limitationsof existing studies, hopefully, will help in designing better studies.Correspondenc
Epilepsy surgery in India
This review traces the evolution of epilepsy surgery in India from the
beginning to the present state. During the last one and half decades,
surgical treatment of epilepsies has made resurgence in this country
and at present a few centers have very active and sustained epilepsy
surgery programs. Within a 14-year period, the R. Madhavan Nayar Center
for Comprehensive Epilepsy Care, Trivandrum, has undertaken over 1000
epilepsy surgeries. However, in the whole country, annually, not more
than 200 epilepsy surgeries are currently being performed. This number
is a miniscule when compared to the number of potential surgical
candidates among the vast population of India. The enormous surgical
treatment gap can only be minimized by developing many more epilepsy
surgery centers in different parts of our country
An overview of pre-surgical evaluation
The success of an epilepsy surgery program depends upon the early identification of potential surgical candidates and selecting from them, ideal candidates for surgery, who are destined to have a post-operative seizure-free outcome without any unacceptable neurological deficits. Since epilepsy surgery centers in resource-poor countries will lack the full range of state-of-the-art technologies usually available in resource-rich countries to perform pre-surgical evaluation, cost-effectively utilization of the locally available investigative facilities to select the surgical candidates becomes challenging. In the present era of rapid electronic communications and telemedicine, it has become possible for epilepsy surgery centers to pool their technological and human resources and to partner with centers nationally and internationally in implementing pre-surgical evaluation strategies
Molecular Genetics of Drug-resistance in Epilepsies
Nearly one-third of newly diagnosed patients with epilepsy remain unresponsive to antiepileptic drugs (AEDs), etiopathogenesis of which is poorly understood. The genes encoding the proteins that regulate the pharmacokinetics such as P-glycoprotein [ABCBI], major vault protein [MVP gene] and drug metabolizing enzymes [ABCB1, ABCG2, MVP, CYP2C9, CYP2C19, CYP3A4, CYP3A5, EPHX1, UGT1A1, UGT2B7], and pharmacodynamics such as sodium channels [SCN1A, SCN2A] and GABA receptors [GABRA1, GABRA6, GABRB2, GABRG2] of AEDs are under intense investigation to unravel the mysteries of AED-resistance. However, till today, a consistent and reliable result that could help the clinician either to predict drug resistance or to overcome it has not been forthcoming. The discrepant results may be related to variations in the definition of drug-resistance, heterogeneous patient populations, ethnic variations in the frequency distribution of single nucleotide polymorphisms (SNPs) and the selection of SNPs. Understanding of these limitations of existing studies, hopefully, will help in designing better studies. Nearly one-third of newly diagnosed patients with epilepsy remain unresponsive toantiepileptic drugs (AEDs), etiopathogenesis of which is poorly understood. The genesencoding the proteins that regulate the pharmacokinetics such as P-glycoprotein[ABCBI], major vault protein [MVP gene] and drug metabolizing enzymes [ABCB1,ABCG2, MVP, CYP2C9, CYP2C19, CYP3A4, CYP3A5, EPHX1, UGT1A1, UGT2B7],and pharmacodynamics such as sodium channels [SCN1A, SCN2A] and GABAreceptors [GABRA1, GABRA6, GABRB2, GABRG2] of AEDs are under intenseinvestigation to unravel the mysteries of AED-resistance. However, till today, aconsistent and reliable result that could help the clinician either to predict drugresistanceor to overcome it has not been forthcoming. The discrepant results may berelated to variations in the definition of drug-resistance, heterogeneous patientpopulations, ethnic variations in the frequency distribution of single nucleotidepolymorphisms (SNPs) and the selection of SNPs. Understanding of these limitationsof existing studies, hopefully, will help in designing better studies.CorrespondenceNearly one-third of newly diagnosed patients with epilepsy remain unresponsive to antiepileptic drugs (AEDs), etiopathogenesis of which is poorly understood. The genes encoding the proteins that regulate the pharmacokinetics such as P-glycoprotein [ABCBI], major vault protein [MVP gene] and drug metabolizing enzymes [ABCB1, ABCG2, MVP, CYP2C9, CYP2C19, CYP3A4, CYP3A5, EPHX1, UGT1A1, UGT2B7], and pharmacodynamics such as sodium channels [SCN1A, SCN2A] and GABA receptors [GABRA1, GABRA6, GABRB2, GABRG2] of AEDs are under intense investigation to unravel the mysteries of AED-resistance. However, till today, a consistent and reliable result that could help the clinician either to predict drug resistance or to overcome it has not been forthcoming. The discrepant results may be related to variations in the definition of drug-resistance, heterogeneous patient populations, ethnic variations in the frequency distribution of single nucleotide polymorphisms (SNPs) and the selection of SNPs. Understanding of these limitations of existing studies, hopefully, will help in designing better studies. Nearly one-third of newly diagnosed patients with epilepsy remain unresponsive toantiepileptic drugs (AEDs), etiopathogenesis of which is poorly understood. The genesencoding the proteins that regulate the pharmacokinetics such as P-glycoprotein[ABCBI], major vault protein [MVP gene] and drug metabolizing enzymes [ABCB1,ABCG2, MVP, CYP2C9, CYP2C19, CYP3A4, CYP3A5, EPHX1, UGT1A1, UGT2B7],and pharmacodynamics such as sodium channels [SCN1A, SCN2A] and GABAreceptors [GABRA1, GABRA6, GABRB2, GABRG2] of AEDs are under intenseinvestigation to unravel the mysteries of AED-resistance. However, till today, aconsistent and reliable result that could help the clinician either to predict drugresistanceor to overcome it has not been forthcoming. The discrepant results may berelated to variations in the definition of drug-resistance, heterogeneous patientpopulations, ethnic variations in the frequency distribution of single nucleotidepolymorphisms (SNPs) and the selection of SNPs. Understanding of these limitationsof existing studies, hopefully, will help in designing better studies.Correspondence</p
Focal cortical resections for the treatment of extratemporal epilepsies in children
Children with lesion-related extratemporal epilepsies with suboptimal seizure control should be identified early and referred for presurgical evaluation before irreversible deterioration in cognitive or psychosocial functions ensues due to long-standing disabling seizures and chronic antiepileptic drug-related side effects. The success of epilepsy surgery depends upon the accurate preoperative localization of the epileptogenic zone and its complete resection. Children with medically refractory lesional epilepsies belong to different categories depending upon the degree of complexity involved in the presurgical evaluation to define their epileptogenic zone. While some patients, such as those with tumoral epilepsy syndrome, can be selected for surgery by simple noninvasive presurgical evaluation strategy, others with malformations of cortical development and those with multiple lesions often require complex and invasive means to define their epileptogenic zone. Recent advances in structural and functional imaging have obviated the need of invasive monitoring in the majority. These advances along with improvement in surgical techniques have made resective surgery safer and more effective. Prospective comprehensive follow-up studies are needed to evaluate the long-term seizure, cognitive, psychosocial, educational and occupational outcomes of surgically treated children with extratemporal epilepsies
Idiopathic intracranial hypertension: Are false localising signs other than abducens nerve palsy acceptable?
Electro-clinical characteristics and postoperative outcome of medically refractory tumoral temporal lobe epilepsy
Idiopathic intracranial hypertension: Are false localising signs other than abducens nerve palsy acceptable?
Drug resistance in epilepsy and the ABCB1 gene: The clinical perspective
Multidrug resistance is one of the most serious problems in the
treatment of epilepsy that is likely to have a complex genetic and
acquired basis. Various experimental data support the hypothesis that
over-expression of antiepileptic drug (AED) transporters may play a
pivotal role in drug resistance. However, key questions concerning
their functionality remain unanswered. The idea that P-glycoprotein,
encoded by the ABCB1 gene, might mediate at least part of the drug
resistance was met with both enthusiasm and skepticism. As in oncology,
initial optimism has been clouded subsequently by conflicting results.
The first study reporting a positive association between genetic
variation in the P-glycoprotein and multidrug-resistant epilepsy was
published in 2003. Since then, several other genetic association
studies have attempted to verify this result. However, taken overall,
the role of P-glycoprotein in drug resistance in epilepsy still remains
uncertain. We intend to critically review the inherent problems
associated with epilepsy pharmacogenetic studies in general and with
ABCB1 polymorphisms studies in particular. The lessons learnt from the
ABCB1 studies can help us to guide future association genetics studies
to investigate AED resistance, and thereby taking us closer to the
cherished dream of personalized AED therapy