Epilepsy research
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The present study aimed to investigate whether Na(+),K(+)-ATPase activity and phosphorylation state of the catalytic α subunit are altered by pentylenetetrazol (PTZ)-induced seizures. PTZ (30, 45 or 60 g/kg, i.p.) was administered to adult male Swiss mice, and Na(+),K(+)-ATPase activity and phosphorylation state were measured in the cerebral cortex 15 min after PTZ administration. Na(+),K(+)-ATPase activity significantly decreased after PTZ-induced seizures (60 mg/kg). ⋯ A significant positive correlation between Na(+),K(+)-ATPase activity and latency to myoclonic jerks and generalized seizures was found. Conversely, a strong negative correlation between Ser943 phosphorylation and latency to generalized seizures was detected. Given the role of Na(+),K(+)-ATPase as a major regulator of brain excitability, Ser943 at Na(+),K(+)-ATPase α subunit may represent a potentially valuable new target for drug development for seizure disorders.
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In a recent genome-wide association study for partial epilepsies in the European population, a common genetic variation has been reported to affect partial epilepsy only modestly. However, in complex diseases such as partial epilepsy, multiple factors (e.g. single nucleotide polymorphisms, microRNAs, metabolic and epigenetic factors) may target different sets of genes in the same pathway, affecting its function and thus causing the disease development. In this regard, we hypothesize that the pathways are critical for elucidating the mechanisms underlying partial epilepsy. ⋯ Traditional studies on genome-wide association have not revealed strong associations in epilepsies, since these single nucleotide polymorphisms are not shared by most of the patients. Our results suggest that it is more effective to incorporate the functional effect of a single nucleotide polymorphism on the gene product, protein-protein interaction networks and functional enrichment tools into genome-wide association studies. These can then be used to determine leading molecular pathways, which cannot be detected through traditional analyses. We hope that this type of analysis brings the research community one step closer to unraveling the complex genetic structure of epilepsies.
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Lennox-Gastaut syndrome (LGS) is a severe epileptic encephalopathy with complex etiology. To explore possible genetic predispositions and causes of LGS, we have searched for copy number variants (CNVs). ⋯ There is a high frequency of rare CNVs in adult patients with LGS-like epilepsy. The phenotypes of these background disorders may be obscured by the effects of intractable seizures and massive antiepileptic drug treatment. Previously, syndromic disorders were primarily identified by their clinical features; however, a genome wide approach with identification of the genotype might shed light on the phenotype.
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Refractory status epilepticus (RSE) occurs when status epilepticus (SE) fails to respond to appropriate therapy with typical antiepileptic drugs (AEDs). Animal studies have shown ketamine to be a highly efficacious agent in this setting, but very few case reports describe use of ketamine in human SE or RSE. We report a retrospective review of 11 patients who were treated for RSE with ketamine infusion in addition to other standard AEDs over a nine-year period. ⋯ Six of the seven patients (85%) who required vasopressors during early treatment for RSE were able to be weaned from vasopressors during ketamine infusion. No acute adverse effects were noted. These findings suggest that ketamine may be a safe and efficacious adjunctive agent in the treatment of RSE.
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To analyze trends in utilization of pre-surgical evaluations including video-EEG (VEEG) monitoring, intracranial EEG (IEEG) monitoring, and epilepsy surgery from 1998 to 2009 in the U.S. ⋯ Despite the increase in VEEG monitoring, the availability of guideline and evidences demonstrating benefits of epilepsy surgery was not associated with a greater employment of surgery over time. Nevertheless, access to pre-surgical evaluations and epilepsy surgery is no longer limited to large medical centers.