No major role of common SV2A variation for predisposition or levetiracetam response in epilepsy.


:Levetiracetam (LEV), a newer antiepileptic drug (AED) useful for several epilepsy syndromes, binds to SV2A. Identifying genetic variants that influence response to LEV may allow more tailored use of LEV. Obvious candidate genes are SV2A, SV2B and SV2C, which encode the only known binding site, synaptic vesicle protein 2 (SV2), with LEV binding to the SV2A isoform. SV2A is an essential protein as homozygous SV2A knockout mice appear normal at birth but fail to grow, experience severe seizures and die by 3 weeks. We addressed characterising AED response issues in pharmacogenetics and whether variation in these genes associates with response to LEV in two independent cohorts with epilepsy. We also investigated whether variation in these three genes associated with epilepsy predisposition in two larger cohorts of patients with various epilepsy phenotypes. Common genetic variation in SV2A, encoding the actual binding site of LEV, was fully represented in this study whereas SV2B and SV2C were not fully covered. None of the polymorphisms tested in SV2A, SV2B or SV2C influence LEV response or predisposition to epilepsy. We found no association between genetic variation in SV2A, SV2B or SV2C and response to LEV or epilepsy predisposition. We suggest this study design may be used in future pharmacogenetic work examining AED or LEV efficacy. However, different study designs would be needed to examine common variation with minor effect sizes, or rare variation, influencing AED or LEV response or epilepsy predisposition.


Epilepsy Res


Epilepsy research


Lynch JM,Tate SK,Kinirons P,Weale ME,Cavalleri GL,Depondt C,Murphy K,O'Rourke D,Doherty CP,Shianna KV,Wood NW,Sander JW,Delanty N,Goldstein DB,Sisodiya SM




Has Abstract


2009-01-01 00:00:00














  • Effects of eugenol on granule cell dispersion in a mouse model of temporal lobe epilepsy.

    abstract::Granule cell dispersion (GCD), a structural abnormality, is characteristic of temporal lobe epilepsy (TLE). Eugenol (EUG) is an essential component of medicinal herbs and is suggested to exert anticonvulsant activity. However, it is unclear whether EUG ameliorates the abnormal morphological changes in granule cells in...

    journal_title:Epilepsy research

    pub_type: 杂志文章


    authors: Jeong KH,Lee DS,Kim SR

    更新日期:2015-09-01 00:00:00

  • Involvement of α4β2 nicotinic acetylcholine receptors in working memory impairment induced by repeated electroconvulsive seizures in rats.

    abstract::A role of cholinergic nervous system in the behavioral impairments induced by repeated ECS is not understood. The α4β2 nicotinic acetylcholine receptor (nAChR) agonist ABT-418, but not the α7 nAChR agonist, significantly ameliorated the impairment of spontaneous alternation behavior in the Y-maze test. And, repeated E...

    journal_title:Epilepsy research

    pub_type: 杂志文章


    authors: Hidaka N,Suemaru K,Kato Y,Araki H

    更新日期:2013-03-01 00:00:00

  • Excitability changes in freeze-induced neocortical microgyria.

    abstract::A freezing probe was placed on the skull of postnatal day (PN) 1 rats to induce formation of a cerebrocortical microsulcus. Experimental studies were performed on PN days 21-24. At that time point, Nissl-stained sections revealed the presence of a microsulcus similar to that described in human dysplastic cortex. Immun...

    journal_title:Epilepsy research

    pub_type: 杂志文章


    authors: Hablitz JJ,DeFazio T

    更新日期:1998-09-01 00:00:00

  • Increased neurokinin-1 receptor availability in temporal lobe epilepsy: a positron emission tomography study using [(11)C]GR205171.

    abstract:PURPOSE:Activation of the neurokinin-1 (NK1) receptor by neuropeptide substance P (SP) induces and maintains epileptic activity in various experimental models of epilepsy. The primary objective of this study was to investigate whether neurobiological changes linked to NK1-SP receptor system are associated with hyperexc...

    journal_title:Epilepsy research

    pub_type: 杂志文章


    authors: Danfors T,Åhs F,Appel L,Linnman C,Fredrikson M,Furmark T,Kumlien E

    更新日期:2011-11-01 00:00:00

  • Multietiological determinants of psychopathology and social competence in children with epilepsy.

    abstract::The purpose of this investigation was to inquire into the multietiological determinants of psychopathology and social competence in children with epilepsy. The relationship between behavioral functioning as assessed by the Child Behavior Checklist and a variety of biological, psychosocial, medication and demographic r...

    journal_title:Epilepsy research

    pub_type: 杂志文章


    authors: Hermann BP,Whitman S,Hughes JR,Melyn MM,Dell J

    更新日期:1988-01-01 00:00:00

  • Preclinical characterization of MDL 27,192 as a potential broad spectrum anticonvulsant agent with neuroprotective properties.

    abstract::The compound 5-(4-chlorophenyl)-2,4-dihydro-4-ethyl-3H-1,2,4-triazol-3-one (MDL 27,192) was evaluated in a variety of rodent models to assess its anticonvulsant profile and its potential neuroprotective activity. MDL 27,192 demonstrated anticonvulsant activity in a wide range of epilepsy models that are genetically-ba...

    journal_title:Epilepsy research

    pub_type: 杂志文章


    authors: Kehne JH,Kane JM,Chaney SF,Hurst G,McCloskey TC,Petty MA,Senyah Y,Wolf HH,Zobrist R,White HS

    更新日期:1997-04-01 00:00:00

  • The hippocampus participates in a pharmacological rat model of absence seizures.

    abstract:OBJECTIVE:Using the gamma-butyrolactone (GBL) model of absence seizures in Long-Evans rats, this study investigated if 2.5-6 Hz paroxysmal discharges (PDs) induced by GBL were synchronized among the thalamocortical system and the hippocampus, and whether inactivation of the hippocampus affected PDs. METHODS:Local fiel...

    journal_title:Epilepsy research

    pub_type: 杂志文章


    authors: Arcaro J,Ma J,Chu L,Kuo M,Mirsattari SM,Stan Leung L

    更新日期:2016-02-01 00:00:00

  • The wada test: prediction of focus lateralization by asymmetric and symmetric recall.

    abstract:PURPOSE:The intracarotid amytal test is commonly used as a predictor of memory dysfunctioning after anterior temporal lobe resection (ATL) for intractable epilepsy. Asymmetry in memory scores can provide focus lateralizing information. In this study the predictive value of a set of Wada test parameters was analyzed, in...

    journal_title:Epilepsy research

    pub_type: 临床试验,杂志文章


    authors: Alpherts WC,Vermeulen J,van Veelen CW

    更新日期:2000-05-01 00:00:00

  • Levetiracetam: an improvement of attention and of oral fluency in patients with partial epilepsy.

    abstract:PURPOSE:The aim of the present study is to verify whether patients with partial epilepsy receiving levetiracetam (LEV) as an add-on treatment show an improvement in cognitive function. METHODS:A neuropsychological battery of tests was administered to 35 patients with partial epilepsy before the assumption of LEV and a...

    journal_title:Epilepsy research

    pub_type: 杂志文章


    authors: Piazzini A,Chifari R,Canevini MP,Turner K,Fontana SP,Canger R

    更新日期:2006-03-01 00:00:00

  • The applications of time-frequency analyses to ictal magnetoencephalography in neocortical epilepsy.

    abstract:PURPOSE:Ictal magenetoencephalographic (MEG) discharges convey significant information about ictal onset and propagation, but there is no established method for analyzing ictal MEG. This study sought to clarify the usefulness of time-frequency analyses using short-time Fourier transform (STFT) for ictal onset and propa...

    journal_title:Epilepsy research

    pub_type: 杂志文章


    authors: Yagyu K,Takeuchi F,Shiraishi H,Nakane S,Sueda K,Asahina N,Kohsaka S,Umeoka S,Usui N,Baba K,Saitoh S

    更新日期:2010-08-01 00:00:00

  • Effect of valproic acid on sodium currents in cortical neurons from patients with pharmaco-resistant temporal lobe epilepsy.

    abstract::In a selected group of temporal lobe epilepsy patients with seizures refractory to pharmacological treatment, pharmacological seizure control can be attained by surgical resection of the epileptic zone. We investigated to what extent pharmaco-resistance is reflected in a reduced response at the cellular level, in neur...

    journal_title:Epilepsy research

    pub_type: 杂志文章


    authors: Vreugdenhil M,van Veelen CW,van Rijen PC,Lopes da Silva FH,Wadman WJ

    更新日期:1998-09-01 00:00:00

  • The NMDA antagonist MK-801 suppresses behavioral seizures, augments afterdischarges, but does not block development of perforant path kindling.

    abstract::The role of N-methyl-D-aspartate (NMDA) in the development and expression of kindled seizures was assessed using a crossover design. Rats were stimulated once daily in the perforant path for 10 consecutive days 30 min following daily administration of saline or the NMDA antagonist MK-801 (1.0 mg/kg) (phase I). Five to...

    journal_title:Epilepsy research

    pub_type: 杂志文章


    authors: Gilbert ME

    更新日期:1994-02-01 00:00:00

  • The long-term retention of pregabalin in a large cohort of patients with epilepsy at a tertiary referral centre.

    abstract::Pregabalin (PGB) is a new antiepileptic drug (AED) which is a structural, non-functional analogue of gamma-aminobutyric acid. It acts at presynaptic calcium channels to modulate neurotransmitter release in the CNS. While the efficacy and tolerability of PGB have been demonstrated in several randomised controlled trial...

    journal_title:Epilepsy research

    pub_type: 杂志文章


    authors: Yuen AW,Singh R,Bell GS,Bhattacharjee A,Neligan A,Heaney DC,Duncan JS,Sander JW

    更新日期:2009-12-01 00:00:00

  • Designing a new proof-of-principle trial for treatment of partial seizures to demonstrate efficacy with minimal sample size and duration-a case study.

    abstract::The ideal proof-of-principle study design provides a strong efficacy signal over the shortest duration, while exposing the fewest patients possible. Data from a large database (Pfizer Inc) which studied add-on pregabalin for the treatment of partial seizures was used to model how duration of baseline, post-randomizati...

    journal_title:Epilepsy research

    pub_type: 杂志文章,随机对照试验


    authors: French JA,Cabrera J,Emir B,Whalen E,Lu F

    更新日期:2013-09-01 00:00:00

  • Increased gamma-hydroxybutyric acid receptors in thalamus of a genetic animal model of petit mal epilepsy.

    abstract::The distribution and kinetics of specific binding sites for gamma-hydroxybutyrate (GHB), a naturally occurring compound known to produce absence-like seizures, was studied in the brains of Wistar rats with spontaneous, bilaterally synchronous spike wave discharges (SWDs), a model of petit mal epilepsy, and non-epilept...

    journal_title:Epilepsy research

    pub_type: 杂志文章


    authors: Snead OC 3rd,Hechler V,Vergnes M,Marescaux C,Maitre M

    更新日期:1990-11-01 00:00:00

  • Experimental secondarily generalized convulsive status epilepticus induced by D,L-homocysteine thiolactone.

    abstract::Secondarily generalized convulsive status epilepticus was induced by intraperitoneal (i.p.) injection of D,L-homocysteine thiolactone to rats with actively epileptogenic cobalt lesions in motor cortex. This induced focal motor seizures which secondarily generalized. Control animals not treated with antiepileptic drugs...

    journal_title:Epilepsy research

    pub_type: 杂志文章


    authors: Walton NY,Treiman DM

    更新日期:1988-03-01 00:00:00

  • Increasing structural atrophy and functional isolation of the temporal lobe with duration of disease in temporal lobe epilepsy.

    abstract:BACKGROUND:Due to pharmacoresistant seizures and the underutilization of surgical treatments, a large number of temporal lobe epilepsy (TLE) patients experience seizures for years or decades. The goal of this study was to generate a predictive model of duration of disease with the least number of parameters possible in...

    journal_title:Epilepsy research

    pub_type: 杂志文章


    authors: Morgan VL,Conrad BN,Abou-Khalil B,Rogers BP,Kang H

    更新日期:2015-02-01 00:00:00

  • Inhibition of different GABA transporter systems is required to attenuate epileptiform activity in the CA3 region of the immature rat hippocampus.

    abstract::GABA transporters (GATs) are an essential element of the GABAergic system, which regulate excitability in the central nervous system and are thus used as targets for anticonvulsive therapy. However, in the immature nervous system the functions of the GABAergic system and the expression profile of GATs are distinct fro...

    journal_title:Epilepsy research

    pub_type: 杂志文章


    authors: Sharopov S,Chen R,Sun H,Kolbaev SN,Kirischuk S,Luhmann HJ,Kilb W

    更新日期:2014-02-01 00:00:00

  • Topiramate and zonisamide prevent paradoxical intoxication induced by carbamazepine and phenytoin.

    abstract::The mechanisms of paradoxical aggravation of epileptic seizures induced by selected antiepileptic drugs (AEDs) remain unclear. The present study addressed this issue by determining the seizure-threshold doses of carbamazepine (CBZ) and phenytoin (PHT), as well the dose-dependent effects of CBZ, PHT, and carbonic anhyd...

    journal_title:Epilepsy research

    pub_type: 杂志文章


    authors: Yamamura S,Hamaguchi T,Ohoyama K,Sugiura Y,Suzuki D,Kanehara S,Nakagawa M,Motomura E,Matsumoto T,Tanii H,Shiroyama T,Okada M

    更新日期:2009-04-01 00:00:00

  • The role of SLC2A1 in early onset and childhood absence epilepsies.

    abstract::Early Onset Absence Epilepsy constitutes an Idiopathic Generalized Epilepsy with absences starting before the age of four years. Mutations in SLC2A1, encoding the glucose transporter, account for approximately 10% of EOAE cases. The role of SLC2A1 mutations in absence epilepsies with a later onset has not been assesse...

    journal_title:Epilepsy research

    pub_type: 杂志文章


    authors: Muhle H,Helbig I,Frøslev TG,Suls A,von Spiczak S,Klitten LL,Dahl HA,Brusgaard K,Neubauer B,De Jonghe P,Tommerup N,Stephani U,Hjalgrim H,Møller RS

    更新日期:2013-07-01 00:00:00

  • Assessment of the neuropsychiatric comorbidities in Chinese children with epilepsy using the MINI-KID tool.

    abstract::This study aimed to assess neuropsychiatric comorbidities and analyze risk factors in Chinese children with epilepsy. Children with epilepsy aged between 6 and 16 years from the Children's Hospital of Fudan University were included. Children with asthma and typically developing children were matched for age and gender...

    journal_title:Epilepsy research

    pub_type: 杂志文章


    authors: Li T,Zhou H,Li Y,Li C,Zhang Y,Zhou Y,Wang Y

    更新日期:2018-02-01 00:00:00

  • Interictal HM-PAO SPECT: a routine investigation in patients with medically intractable complex partial seizures?

    abstract::Single photon emission computed tomography (SPECT) is increasingly being used as an adjunctive technique in the localisation of epileptogenic foci prior to surgery. As yet, few studies have been undertaken to establish the clinical associations of areas of reduced cerebral perfusion. Sixty-three consecutive patients (...

    journal_title:Epilepsy research

    pub_type: 杂志文章


    authors: Duncan S,Gillen G,Adams FG,Duncan R,Brodie MJ

    更新日期:1992-10-01 00:00:00

  • Remacemide HCl and its metabolite, FPL 12495AA, limit action potential firing frequency and block NMDA responses of mouse spinal cord neurons in cell culture.

    abstract::The novel anticonvulsant, remacemide HCl [(+/-)-2-amino-N-(1-methyl-1,2-diphenylethyl)acetamide monohydrochloride; FPL12924AA], and a desglycinated metabolite [(+/-)-1-methyl-1,2-diphenylethylamine monohydrochloride; FPL 12495AA] reversibly limited sustained high-frequency repetitive firing (SRF) of sodium-dependent a...

    journal_title:Epilepsy research

    pub_type: 杂志文章


    authors: Wamil AW,Cheung H,Harris EW,McLean MJ

    更新日期:1996-02-01 00:00:00

  • Long-term safety and efficacy following conversion to eslicarbazepine acetate monotherapy in adults with focal seizures.

    abstract:OBJECTIVE:To assess the long-term safety and efficacy of eslicarbazepine acetate (ESL) monotherapy in adults with focal seizures (FS). METHODS:Study 050 was a long-term, multicenter, open-label (OL) safety extension of two conversion-to-ESL monotherapy studies in adults with refractory FS. After participating in Study...

    journal_title:Epilepsy research

    pub_type: 杂志文章,多中心研究,随机对照试验


    authors: Chung S,Sinha SR,Shah A,Stern JM,Cheng H,Jung J,Grinnell T,Blum D

    更新日期:2019-07-01 00:00:00

  • Genetic linkage studies in familial frontal epilepsy: exclusion of the human chromosome regions homologous to the El-1 mouse locus.

    abstract::Familial frontal epilepsy has been recently described in six pedigrees. All families reported show autosomal dominant inheritance with incomplete penetrance. Affected individuals develop predominantly nocturnal seizures with frontal lobe semiology. In 1959, a genetic mouse model for partial epilepsy, the El mouse, was...

    journal_title:Epilepsy research

    pub_type: 杂志文章


    authors: Lopes-Cendes I,Phillips HA,Scheffer IE,Mulley JC,Desbiens R,Andermann E,Cendes F,Verret S,Andermann F,Berkovic SF

    更新日期:1995-11-01 00:00:00

  • Benzodiazepine modulation of GABA(A) receptor opening frequency depends on activation context: a patch clamp and simulation study.

    abstract::Benzodiazepines (BDZs) are GABA(A) receptor modulators with anxiolytic, hypnotic, and anticonvulsant properties. BDZs are understood to potentiate GABA(A) receptor function by increasing channel opening frequency, in contrast to barbiturates, which increase channel open duration. However, the in vitro evidence demonst...

    journal_title:Epilepsy research

    pub_type: 杂志文章


    authors: Bianchi MT,Botzolakis EJ,Lagrange AH,Macdonald RL

    更新日期:2009-08-01 00:00:00

  • GC-MS-Based metabolomics discovers a shared serum metabolic characteristic among three types of epileptic seizures.

    abstract:OBJECTIVE:Understanding the overall and common metabolic changes of seizures can provide novel clues for their control and prevention. Here, we aim to investigate the global metabolic feature of serum for three types of seizures. METHODS:We recruited 27 patients who had experienced a seizure within 48h (including 11 w...

    journal_title:Epilepsy research

    pub_type: 杂志文章


    authors: Wang D,Wang X,Kong J,Wu J,Lai M

    更新日期:2016-10-01 00:00:00

  • Modeling epileptogenesis and temporal lobe epilepsy in a non-human primate.

    abstract::Here we describe a new non-human primate model of temporal lobe epilepsy (TLE) to better investigate the cause/effect relationships of human TLE. Status epilepticus (SE) was induced in adult marmosets by pilocarpine injection (250mg/kg; i.p.). The animals were divided in 2 groups: acute (8h post-SE) and chronic (3 and...

    journal_title:Epilepsy research

    pub_type: 杂志文章


    authors: Perez-Mendes P,Blanco MM,Calcagnotto ME,Cinini SM,Bachiega J,Papoti D,Covolan L,Tannus A,Mello LE

    更新日期:2011-09-01 00:00:00

  • Antiepileptic drugs trials: neonates and infants.

    abstract::Special issues are related to AED testing in several populations. Pharmacokinetics, pharmacodynamics and underlying neurochemistry and developing systems require specific testing in appropriate infants with refractory seizures. EEG monitoring is an essential part of seizure definition and recognition, making it a nece...

    journal_title:Epilepsy research

    pub_type: 杂志文章,评审


    authors: Pellock J

    更新日期:2006-01-01 00:00:00

  • Epilepsy phenotype associated with a chromosome 2q24.3 deletion involving SCN1A: Migrating partial seizures of infancy or atypical Dravet syndrome?

    abstract::The deletion of a sodium channel gene cluster located on chromosome 2q24.3 is associated with variable epilepsy phenotypes, including Dravet syndrome and migrating partial seizures of infancy. Although SCN1A is considered as the major contributor to the epilepsy phenotype, the role of other sodium channel genes that m...

    journal_title:Epilepsy research

    pub_type: 杂志文章


    authors: Lim BC,Hwang H,Kim H,Chae JH,Choi J,Kim KJ,Hwang YS,Yum MS,Ko TS

    更新日期:2015-01-01 00:00:00