Epilepsy Research RSS feed: Current Issue. Epilepsy Research provides for rapid publication of high quality articles in both experimental and clinical epileptology. It is intended to provide a forum for the many disciplines involved, such as neurology, neurosurgery, neurophysiology, neuropharmacology, neurochemistry, neuroanatomy, neuropathology, neuroendocrinology, neurotoxicology, neurogenetics, neuroimaging, neuropsychology, neuropsychiatry, molecular neurobiology, clinical chemistry and child neurology. As such the journal will publish original papers from any of these areas or studies of a multidisciplinary nature. Clinical and experimental research papers adopting fresh conceptual approaches to the study of epilepsy and its treatment are encouraged. The overriding criteria for publication are novelty, significant clinical or experimental relevance, and interest to a multidisciplinary audience in the broad arena of epilepsy. http://www.epires-journal.com/?rss=yesElsevier Inc.en © 2009 Published by Elsevier Inc. All rights reserved. Epilepsy Research0920-1211881January 2010 © 2009 Published by Elsevier Inc. All rights reserved. healthpermissions@elsevier.comhttp://www.epires-journal.com/article/PIIS0920121109003672/abstract?rss=yesEditorial Board10.1016/S0920-1211(09)00367-2Epilepsy Research 88, 1 (2010)2010-01-01Epilepsy Research2010-01-01881S0920-1211(09)X0011-2CO3CO3http://www.epires-journal.com/article/PIIS0920121109003714/abstract?rss=yesEditorial Board10.1016/S0920-1211(09)00371-4Epilepsy Research 88, 1 (2010)2010-01-01Epilepsy Research2010-01-01881S0920-1211(09)X0011-2iiiiiihttp://www.epires-journal.com/article/PIIS0920121109002435/abstract?rss=yesSummary: Use of medication with a desired effect on the central nervous system (as with anti-epileptic drugs) in children will undoubtedly cause concern about neurodevelopment. Data are emerging to suggest an effect of anticonvulsants on the developing brain of the unborn child when administered to mothers with epilepsy. This obviously requires detailed evaluation, especially when considering the risks of epilepsy itself. In the child with epilepsy, many of the early onset epilepsies are associated with developmental compromise as part of their clinical profile, and therefore determining the relative effects of the underlying cause, seizures and medication can be difficult. Although data are available with regard to some anti-epileptic drugs (AEDs) they remain lacking particularly in the very young with regard to efficacy as well as neurodevelopmental effects of the newer anti-epileptic drugs. Ongoing evaluation is required to ensure the best clinical practice in each individual.Neurodevelopmental effects of anti-epileptic drugsJ. Helen Cross10.1016/j.eplepsyres.2009.08.015Epilepsy Research 88, 1 (2010)2010-01-01Epilepsy Research2010-01-01881S0920-1211(09)X0011-2Review110http://www.epires-journal.com/article/PIIS0920121109002630/abstract?rss=yesSummary: Epilepsy, the most common neurological disorder in young humans, has its highest incidence during the first year of life. Antiepileptic drugs (AEDs) which are used to treat seizures in infants, children and pregnant women target ion channels, neurotransmitters and second messenger systems in the brain. The same targets regulate brain processes essential both for propagation of seizures and for brain development, learning, memory and emotional behavior.Here we review adverse effects of AEDs in the developing mammalian brain. In addition, we discuss mechanisms explaining adverse effects of AEDs in the developing mammalian brain including interference with cell proliferation and migration, neurogenesis, axonal arborization, synaptogenesis, synaptic plasticity and physiological apoptotic cell death.Antiepileptic drugs and brain developmentChrysanthy Ikonomidou, Lechoslaw Turski10.1016/j.eplepsyres.2009.09.019Epilepsy Research 88, 1 (2010)2010-01-01Epilepsy Research2010-01-01881S0920-1211(09)X0011-2Review1122http://www.epires-journal.com/article/PIIS0920121109002642/abstract?rss=yesSummary: Mitochondrial oxidative stress and dysfunction are contributing factors to various neurological disorders. Recently, there has been increasing evidence supporting the association between mitochondrial oxidative stress and epilepsy. Although certain inherited epilepsies are associated with mitochondrial dysfunction, little is known about its role in acquired epilepsies such as temporal lobe epilepsy (TLE). Mitochondrial oxidative stress and dysfunction are emerging as key factors that not only result from seizures, but may also contribute to epileptogenesis. The occurrence of epilepsy increases with age, and mitochondrial oxidative stress is a leading mechanism of aging and age-related degenerative disease, suggesting a further involvement of mitochondrial dysfunction in seizure generation. Mitochondria have critical cellular functions that influence neuronal excitability including production of adenosine triphosphate (ATP), fatty acid oxidation, control of apoptosis and necrosis, regulation of amino acid cycling, neurotransmitter biosynthesis, and regulation of cytosolic Ca2+ homeostasis. Mitochondria are the primary site of reactive oxygen species (ROS) production making them uniquely vulnerable to oxidative stress and damage which can further affect cellular macromolecule function, the ability of the electron transport chain to produce ATP, antioxidant defenses, mitochondrial DNA stability, and synaptic glutamate homeostasis. Oxidative damage to one or more of these cellular targets may affect neuronal excitability and increase seizure susceptibility. The specific targeting of mitochondrial oxidative stress, dysfunction, and bioenergetics with pharmacological and non-pharmacological treatments may be a novel avenue for attenuating epileptogenesis.Mitochondria, oxidative stress, and temporal lobe epilepsySimon Waldbaum, Manisha Patel10.1016/j.eplepsyres.2009.09.020Epilepsy Research 88, 1 (2010)2010-01-01Epilepsy Research2010-01-01881S0920-1211(09)X0011-2Review2345http://www.epires-journal.com/article/PIIS0920121109002873/abstract?rss=yesSummary: Brivaracetam (ucb 34714; BRV), a new antiepileptic drug (AED) candidate, is a pyrrolidone derivative displaying a markedly higher affinity than levetiracetam (LEV; Keppra®) to the synaptic vesicle protein SV2A, shown to be the brain-specific binding site of LEV. The higher affinity for SV2A correlates significant antiepileptic activity in animal epilepsy models in vitro and in vivo. Since many AEDs act upon inhibiting neuronal Na+ currents, this study explored putative activity of BRV on the properties of these currents. Voltage-activated Na+ currents were recorded by whole-cell patch-clamp on neuronal somas of rat neocortical neurons, grown in dissociated cell culture for up to 12 days. BRV, dissolved at the desired final concentration (between 0.2μM and 1mM) was applied by a multi-barrel pipette system near the soma of the recorded neuron. BRV produced a concentration-dependent inhibition of voltage-dependent Na+ currents with IC50 values of 41μM at the holding potential of −100mV, and of 6.5μM at the holding potential of −60mV. The voltage-dependence of activation and the kinetics of fast inactivation were not modified in the presence of BRV (30μM). Conversely, the recovery from fast inactivation was significantly slower and the voltage of half-maximal inactivation was shifted toward hyperpolarized value after BRV perfusion in a concentration-dependent manner. Furthermore, BRV (30μM) induced a significant use-dependent block at 50Hz stimulation frequency. These results indicate that BRV is able to modulate the voltage-activated Na+ inflow in cortical neurons, which conceivably might contribute to the antiepileptic activity of this drug.Brivaracetam (ucb 34714) inhibits Na+ current in rat cortical neurons in cultureCristina Zona, Massimo Pieri, Irene Carunchio, Livia Curcio, Henrik Klitgaard, Doru Georg Margineanu10.1016/j.eplepsyres.2009.09.024Epilepsy Research 88, 1 (2010)2010-01-01Epilepsy Research2010-01-01881S0920-1211(09)X0011-2Research Papers4654http://www.epires-journal.com/article/PIIS0920121109002861/abstract?rss=yesSummary: Objective: The etiopathogenesis of temporal lobe epilepsy (TLE) and its subgroups – mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) and TLE with antecedent febrile seizures (TLE-FS) – is poorly understood. It has been proposed that the water channel aquaporin-4 (AQP4) and the potassium channel Kir4.1 (KCNJ10 gene) act in concert to regulate extracellular K+ homeostasis and that functional alterations of these channels influence neuronal excitability. The current study was designed to identify variants of the AQP4 and KCNJ10 genes associated with TLE and subgroups of this condition.Material and methods: We included 218 Norwegian patients with TLE and 181 ethnically matched healthy controls. An association study was established in which all TLE patients were compared with healthy controls. Additionally, subgroups of 56 MTLE-HS patients were compared with 162 TLE patients without HS, and 102 TLE-FS patients were compared with 105 TLE without FS.Results: We found eight single SNPs, seven in KCNJ10 and one between KCNJ10 and KCNJ9, associated with TLE-FS (nominal p-values from 0.009 to 0.041). Seven of the SNPs segregate into one large haplotype block expanding from KCNJ10 to KCNJ9, including the region interposed those genes. One haplotype was overrepresented in the TLE-FS cases (nominal p-value 0.014). These results were confirmed by explorative multivariate analysis indicating that a combination of SNPs from KCNJ10, the region between KCNJ10 and KCNJ9, and the AQP4 gene is associated with TLE-FS. For the TLE cohort as a whole, explorative multivariate analysis indicated a combination of SNPs from the KCNJ10 and AQP4 genes in association with TLE.Conclusion: Variations in the AQP4 and the KCNJ10/KCNJ9 region are likely to be associated with TLE, particularly TLE-FS, supporting the suggestion that perturbations of water and K+ transport are involved in the etiopathogenesis of TLE.Variants of the genes encoding AQP4 and Kir4.1 are associated with subgroups of patients with temporal lobe epilepsyKjell Heuser, Erlend A. Nagelhus, Erik Taubøll, Ulf Indahl, Paul R. Berg, Sigbjørn Lien, Sigve Nakken, Leif Gjerstad, Ole Petter Ottersen10.1016/j.eplepsyres.2009.09.023Epilepsy Research 88, 1 (2010)2010-01-01Epilepsy Research2010-01-01881S0920-1211(09)X0011-2Research Papers5564http://www.epires-journal.com/article/PIIS092012110900285X/abstract?rss=yesSummary: Purpose: To characterize the clinical features and molecular genetic background in a family with various epilepsy phenotypes including febrile seizures, childhood absence epilepsy, and possible temporal lobe epilepsy.Methods: Clinical data were collected. DNA and RNA were extracted from peripheral blood. A genome-wide microsatellite marker scan was performed and regions with a multipoint location score ≥1.5 were fine mapped. Functional candidate genes identified from databases and by comparing gene expression profiles of genes between affected and unaffected individuals were sequenced. Copy number variation was evaluated with array-based comparative genomic hybridization.Results: The seizure phenotype was benign. Inheritance was consistent with an autosomal dominant model and reduced penetrance. The highest two-point LOD score of 2.8 was identified at marker D17S1606 in a 37cM interval on chromosome 17q12-q24. Loci on 5q11.2 and on 18p11-q11, showed LOD scores ≥1.5 after fine mapping. Sequencing of nine ion-channel genes and two (RPIP8 and SLC25A39) differentially expressed genes from 17q12-q24, as well as IMPA2 from 18p11-q11 did not reveal a pathogenic alteration. No clinically relevant copy number variation was identified.Conclusions: Our findings suggest complex inheritance of seizure susceptibility in the family with contribution from three loci, including a possible new locus on chromosome 17q. The underlying molecular defects remain unknown.Suggestive evidence for a new locus for epilepsy with heterogeneous phenotypes on chromosome 17qAuli Sirén, Anne Polvi, Lyne Chahine, Malgorzata Labuda, Sarah Bourgoin, Anna-Kaisa Anttonen, Maria Kousi, Kari Hirvonen, Kalle O.J. Simola, Eva Andermann, Asta Laiho, Juhani Soini, Matti Koivikko, Reijo Laaksonen, Massimo Pandolfo, Anna-Elina Lehesjoki10.1016/j.eplepsyres.2009.09.022Epilepsy Research 88, 1 (2010)2010-01-01Epilepsy Research2010-01-01881S0920-1211(09)X0011-2Research Papers6575http://www.epires-journal.com/article/PIIS0920121109002848/abstract?rss=yesSummary: Focal cortical dysplasias (FCDs) represent a prominent cause of pharmacologically intractable epilepsy. In FCD, the decrease of parvalbumin immunoreactive (PV+) inhibitory interneurons has been repeatedly documented. Here, we wanted to show whether another interneuronal population, the calretinin immunoreactive (CR+) neurons, exhibits any change in human FCD. We also investigated samples of morphologically normal temporal neocortex resected together with sclerotic hippocampus (nHSTN), where decrease of PV+ interneurons was previously documented as well. Brain tissue from 24 patients surgically treated for pharmacoresistant epilepsy was examined. Calretinin immunoreactivity was qualitatively evaluated and the density of CR+ neuronal profiles was quantified. As a control, post-mortem acquired neocortical samples of nine patients without any brain affecting disease were used.CR+ neurons were located predominantly in superficial cortical layers both in controls and pathological samples. Similarly, the morphology of CR+ neurons was unaffected in pathological samples. The overall density of CR+ neurons was significantly decreased in FCD type I (to approximately 70% of control values) and even more in FCD type II (to approximately 50% of controls). In nHSTN, no change compared to controls was found in CR+ neuronal density. Our results may contribute to the better understanding of the role of individual interneuronal populations in epileptogenesis.Calretinin immunoreactivity in focal cortical dysplasias and in non-malformed epileptic cortexFilip Barinka, Rastislav Druga, Petr Marusic, Pavel Krsek, Josef Zamecnik10.1016/j.eplepsyres.2009.09.021Epilepsy Research 88, 1 (2010)2010-01-01Epilepsy Research2010-01-01881S0920-1211(09)X0011-2Research Papers7686http://www.epires-journal.com/article/PIIS0920121109002629/abstract?rss=yesSummary: We conducted a search for white matter changes (WMCs) in 13 Unverricht-Lundborg disease patients and compared the prevalence of WMCs in these patients to age-matched long-term epileptics and healthy controls. ULD patients had significantly more T2-weighted high-intensity signals on MRI than control subjects, due to the increased prevalence of these signals in the basal ganglia. Interestingly, ULD patients with the basal ganglia changes were overweight. Basal ganglia T2-weighted high-intensity signals are novel findings in ULD.T2-weighted high-intensity signals in the basal ganglia as an interesting image finding in Unverricht-Lundborg diseaseMiikka Korja, Edoardo Ferlazzo, Merja Soilu-Hänninen, Adriana Magaudda, Reijo Marttila, Pierre Genton, Riitta Parkkola10.1016/j.eplepsyres.2009.09.018Epilepsy Research 88, 1 (2010)2010-01-01Epilepsy Research2010-01-01881S0920-1211(09)X0011-2Short Communication8791