Uncontrolled epilepsy is not necessarily the same as drug-resistant epilepsy: Differences between populations with newly diagnosed epilepsy and chronic epilepsy

Hao, Xiaoting; Goldberg, Danielle; Kelly, Kevin; Stephen, Linda J.; Kwan, Patrick; Brodie, Martin J.

doi:10.1016/j.yebeh.2013.06.019

Cited by 66 publications

(46 citation statements)

References 15 publications

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“…The efficacy of these medications varies in function of etiology. Despite the relatively large number of AEDs available to treat convulsive syndromes, up to 30% of patients are resistant to the pharmacotherapies currently available [134, 135, 136] and some are not candidates for surgery. Therefore, therapeutic interventions are still sought for such epilepsies unresponsive to the available treatments.…”

Section: The Cb1r-nmdar Complexmentioning

confidence: 99%

Endocannabinoid control of glutamate NMDA receptors: the therapeutic potential and consequences of dysfunction

et al. 2016

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Glutamate is probably the most important excitatory neurotransmitter in the brain. The glutamate N-methyl-D-aspartate receptor (NMDAR) is a calcium-gated channel that coordinates with G protein-coupled receptors (GPCRs) to establish the efficiency of the synaptic transmission. Cross-regulation between these receptors requires the concerted activity of the histidine triad nucleotide-binding protein 1 (HINT1) and of the sigma receptor type 1 (σ1R). Essential brain functions like learning, memory formation and consolidation, mood and behavioral responses to exogenous stimuli depend on the activity of NMDARs. In this biological context, endocannabinoids are released to retain NMDAR activity within physiological limits. The efficacy of such control depends on HINT1/σ1R assisting in the physical coupling between cannabinoid type 1 receptors (CB1Rs) and NMDARs to dampen their activity. Subsequently, the calcium-regulated HINT1/σ1R protein tandem uncouples CB1Rs to prevent NMDAR hypofunction. Thus, early recruitment or a disproportionate cannabinoid induced response can bring about excess dampening of NMDAR activity, impeding its adequate integration with GPCR signaling. Alternatively, this control circuit can apparently be overridden in situations where bursts of NMDAR overactivity provoke convulsive syndromes. In this review we will discuss the possible relevance of the HINT1/σ1R tandem and its use by endocannabinoids to diminish NMDAR activity and their implications in psychosis/schizophrenia, as well as in NMDAR-mediated convulsive episodes.

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Section: The Cb1r-nmdar Complexmentioning

confidence: 99%

Endocannabinoid control of glutamate NMDA receptors: the therapeutic potential and consequences of dysfunction

et al. 2016

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“…In accordance with a recent Task Force of the ILAE Commission on Therapeutic Strategies, drug-resistant patients (our group of 31 patients) were considered if they were not seizure free even after adequate trial with two, three or more tolerated, appropriately chosen AED schedules was instituted. [13,14] Genotyping procedure Genomic DNA was obtained from peripheral blood samples using a Zymo Beads Genomic DNA kit (Zymo Research). The ABCB1 genotypes were determined by PCR-RFLP (polymerase chain-restriction fragment length polymorphism) assay.…”

Section: Patients and Controlsmentioning

confidence: 99%

ABCB1 gene polymorphisms is not associated with drug-resistant epilepsy in Romanian children

Butilă

Sin

Szabo

et al. 2015

Revista Romana De Medicina De Laborator

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“…15,16 Inclusion of patients with pseudo drug resistance can also potentially explain discrepancies across studies in reported outcomes of treatment changes in patients considered to be drug-resistant. Agreement between expert pairs in applying ILAE criteria for categorization of treatment outcome was generally high, as reported in an earlier pilot study by other investigators.…”

Section: Discussionmentioning

confidence: 99%

Validated outcome of treatment changes according to International League Against Epilepsy criteria in adults with drug‐resistant focal epilepsy

et al. 2019

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Summary Objective Although many studies have attempted to describe treatment outcomes in patients with drug‐resistant epilepsy, results are often limited by the adoption of nonhomogeneous criteria and different definitions of seizure freedom. We sought to evaluate treatment outcomes with a newly administered antiepileptic drug (AED) in a large population of adults with drug‐resistant focal epilepsy according to the International League Against Epilepsy (ILAE) outcome criteria. Methods This is a multicenter, observational, prospective study of 1053 patients with focal epilepsy diagnosed as drug‐resistant by the investigators. Patients were assessed at baseline and 6, 12, and 18 months, for up to a maximum of 34 months after introducing another AED into their treatment regimen. Drug resistance status and treatment outcomes were rated according to ILAE criteria by the investigators and by at least two independent members of an external expert panel (EP). Results A seizure‐free outcome after a newly administered AED according to ILAE criteria ranged from 11.8% after two failed drugs to 2.6% for more than six failures. Significantly fewer patients were rated by the EP as having a “treatment failure” as compared to the judgment of the investigator (46.7% vs 62.9%, P < 0.001), because many more patients were rated as “undetermined outcome” (45.6% vs 27.7%, P < 0.001); 19.3% of the recruited patients were not considered drug‐resistant by the EP. Significance This study validates the use of ILAE treatment outcome criteria in a real‐life setting, providing validated estimates of seizure freedom in patients with drug‐resistant focal epilepsy in relation to the number of previously failed AEDs. Fewer than one in 10 patients achieved seizure freedom on a newly introduced AED over the study period. Pseudo drug resistance could be identified in one of five cases.

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Uncontrolled epilepsy is not necessarily the same as drug-resistant epilepsy: Differences between populations with newly diagnosed epilepsy and chronic epilepsy

Cited by 66 publications

References 15 publications

Endocannabinoid control of glutamate NMDA receptors: the therapeutic potential and consequences of dysfunction

Endocannabinoid control of glutamate NMDA receptors: the therapeutic potential and consequences of dysfunction

ABCB1 gene polymorphisms is not associated with drug-resistant epilepsy in Romanian children

Validated outcome of treatment changes according to International League Against Epilepsy criteria in adults with drug‐resistant focal epilepsy

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