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Drug resistant epilepsy

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https://www.readbyqxmd.com/read/28810185/outcome-of-treatment-changes-in-patients-with-drug-resistant-chronic-epilepsy-a-tertiary-center-experience
#1
E Martínez-Lizana, F Gil-Lopez, A Donaire, J Aparicio, A Brandt, M Carreño
BACKGROUND: Previous studies suggest that changing patients' anti-epileptic drug regimen can reduce the frequency of seizures. The approval of new anti-epileptic drugs with different modes of action during the last decades has provided multiple options for the treatment of epilepsy, although the efficacy of these new drugs is controversial. We aimed to determine the effects of adding or changing to a previously untried anti-epileptic drug, including recently approved drugs, on the frequency of seizures in patients with drug-resistant epilepsy...
July 29, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28807787/trigeminal-nerve-stimulation-induces-fos-immunoreactivity-in-selected-brain-regions-increases-hippocampal-cell-proliferation-and-reduces-seizure-severity-in-rats
#2
Beniamina Mercante, Paolo Enrico, Gabriele Floris, Marina Quartu, Marianna Boi, Maria Pina Serra, Paolo Follesa, Franca Deriu
Sites and mechanisms by which trigeminal nerve stimulation (TNS) exerts beneficial effects on symptoms of drug-resistant epilepsy and depression are still unknown. Effects of short-term TNS on brain regions involved in the physiopathology of these disorders were investigated in this study. Forty male rats were assigned to 3 groups: TNS (undergoing electrical stimulation of the left infraorbitary nerve via surgically implanted cuff electrodes); Sham (undergoing surgical procedure but without a stimulation); Naïve rats...
August 11, 2017: Neuroscience
https://www.readbyqxmd.com/read/28804898/epilepsy-surgery-of-low-grade-epilepsy-associated-neuroepithelial-tumors-a-retrospective-nationwide-italian-study
#3
Marco Giulioni, Gianluca Marucci, Veronica Pelliccia, Francesca Gozzo, Carmen Barba, Giuseppe Didato, Flavio Villani, Giancarlo Di Gennaro, Pier Paolo Quarato, Vincenzo Esposito, Alessandro Consales, Matteo Martinoni, Gianfranco Vornetti, Corrado Zenesini, Carlo Efisio Marras, Nicola Specchio, Luca De Palma, Raffaele Rocchi, Flavio Giordano, Giovanni Tringali, Paolo Nozza, Gabriella Colicchio, Guido Rubboli, Giorgio Lo Russo, Renzo Guerrini, Paolo Tinuper, Francesco Cardinale, Massimo Cossu
OBJECTIVE: To analyze the attitude and results of Italian epilepsy surgery centers in the surgical management of "low grade epilepsy associated neuroepithelial tumors" (LEATs). METHODS: We conducted a retrospective study enrolling 339 consecutive patients with LEATs who underwent surgery between January 2009 and June 2015 at eight Italian epilepsy surgery centers. We compared demographic, clinical, pathologic, and surgical features of patients with favorable (Engel class I) and unfavorable (Engel class II, III, and IV) seizure outcome...
August 14, 2017: Epilepsia
https://www.readbyqxmd.com/read/28804872/lacosamide-in-the-treatment-of-patients-with-epilepsy-and-intellectual-disabilities-a-long-term-study-of-136-patients
#4
Stefan Böttcher, Martin T Lutz, Thomas Mayer
OBJECTIVE: This study aimed to analyze the retention rate of lacosamide (LCM) in patients with epilepsy and intellectual disabilities (IDs), to identify factors influencing retention rate, and to investigate the LCM retention rate with and without concomitant sodium channel blocker (SCB). We hypothesized that the retention rate of LCM with concomitant SCB would be lower than without SCB. METHODS: Using the Kaplan-Meier estimator, we conducted a monocentric, retrospective, observational, open-label study to evaluate LCM retention rates in patients with IDs and drug-resistant epilepsy...
August 14, 2017: Epilepsia
https://www.readbyqxmd.com/read/28801717/vitamin-b6-is-essential-for-serine-de-novo-biosynthesis
#5
Rúben J Ramos, Mia L Pras-Raves, Johan Gerrits, Maria van der Ham, Marcel Willemsen, Hubertus Prinsen, Boudewijn Burgering, Judith J Jans, Nanda M Verhoeven-Duif
Pyridoxal 5'-phosphate (PLP), the metabolically active form of vitamin B6, plays an essential role in brain metabolism as a cofactor in numerous enzyme reactions. PLP deficiency in brain, either genetic or acquired, results in severe drug-resistant seizures that respond to vitamin B6 supplementation. The pathogenesis of vitamin B6 deficiency is largely unknown. To shed more light on the metabolic consequences of vitamin B6 deficiency in brain, we performed untargeted metabolomics in vitamin B6-deprived Neuro-2a cells...
August 11, 2017: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/28799516/antiepileptic-drugs-in-clinical-development-differentiate-or-die
#6
Gaetano Zaccara, D Schmidt
BACKGROUND: Animal models when carefully selected, designed and conducted, are important parts of any translational drug development strategy. However, research of new compounds for patients with drug-resistant epilepsies is still based on animal experiments, mostly in rodents, which are far from being a model of chronic human epilepsy and have failed to differentiate the efficacy of new compounds versus standard drug treatment. Objective The objective was identification and description of compounds in clinical development in 2016...
August 9, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28799513/ketogenic-diets-in-the-treatment-of-epilepsy
#7
Maurizio Elia, Joerg Klepper, Baerbel Leiendecker, Hans Hartmann
BACKGROUND: Although a larger number of antiepileptic drugs became available in the last decades, epilepsy remains drug-resistant in approximately a third of patients. Ketogenic diet (KD), first proposed at the beginning of the last century, is complex and has anticonvulsant effects, yet not completely understood. Over the last decades, different types of ketogenic diets (KDs) have been developed, namely classical KD and modified Atkins diet (MAD). They offer an effective alternative for children and adults with drug-resistant epilepsies...
August 9, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28799509/update-on-pharmacological-treatment-of-progressive-myoclonus-epilepsies
#8
Edoardo Ferlazzo, Dorothee Kasteleijn-Nolst Trenite, Gerrit-Jan de Haan, Felix Felix Nitschke, Saija Ahonen, Sara Gasparini, Berge A Minassian
BACKGROUND: Progressive myoclonus epilepsies (PMEs) are a group of rare inherited diseases featuring a combination of myoclonus, seizures and variable degree of cognitive impairment. Despite extensive investigations, a large number of PMEs remain undiagnosed. In this review, we focus on the current pharmacological approach to PMEs. METHODS: References were mainly identified through PubMed search until February 2017 and backtracking of references in pertinent studies...
August 9, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28799177/racemic-and-enantiopure-forms-of-3-ethyl-3-phenylpyrrolidin-2-one-adopt-very-different-crystal-structures
#9
Arcadius V Krivoshein, Sergey V Lindeman, Tatiana V Timofeeva, Victor N Khrustalev
3-Ethyl-3-phenylpyrrolidin-2-one (EPP) is an experimental anticonvulsant based on the newly proposed α-substituted amide group pharmacophore. These compounds show robust activity in animal models of drug-resistant epilepsy and are thus promising for clinical development. In order to understand pharmaceutically relevant properties of such compounds, we are conducting an extensive investigation of their structures in the solid state. In this article, we report chiral high-performance liquid chromatography (HPLC) separation, determination of absolute configuration of enantiomers, and crystal structures of EPP...
August 11, 2017: Chirality
https://www.readbyqxmd.com/read/28799062/long-term-epilepsy-associated-tumor-in-the-amygdala-of-a-16-year-old-boy-report-of-a-rare-case-having-intranuclear-filaments
#10
Yoon Jin Cha, Dong-Seok Kim, Seung-Koo Lee, Hoon-Chul Kang, Se Hoon Kim
The term "long-term epilepsy-associated tumor (LEAT)" encompasses brain lesions associated with drug-resistant epilepsy over a long duration (≥2 years). Notably, some LEATs do not fit into any of the classifications of the World Health Organization (WHO). Herein, we report a LEAT that occurred in the left amygdala of a 16-year-old patient with intractable epilepsy. Histological examination of the resected amygdala revealed diffusely infiltrating tumor cells in the cortex. Perineuronal satellitosis and perivascular aggregation of tumor cells were apparent, along with mild nuclear enlargement and cytologic atypia...
August 10, 2017: Brain Tumor Pathology
https://www.readbyqxmd.com/read/28792706/lack-of-association-between-slc6a11-genetic-polymorphisms-and-drug-resistant-epilepsy-in-chinese-han-population
#11
Y Y Xie, J Qu, L Zhou, N Lv, J E Gong, Y Z Cao, L L Long, H Y Long, B Xiao
BACKGROUND: Epilepsy is one of the most common chronic neurological diseases. A recent study has implicated that the genetic variants of the SLC6A11 gene encoding GAT-3, an astrocytic GABA transporter, may influence the efficacy of antiepileptic drugs (AEDs) in the Korean population. METHODS: This study aims to investigate the possible associations between SLC6A11 gene and drug resistance in Chinese epilepsy patients. Genomic DNA from 240 drug resistant epilepsy (DRE) patients and 336 drug responsive epilepsy patients was tested for the polymorphisms using Illumina GoldenGate assay...
July 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/28775328/inhibition-of-glutamate-decarboxylase-gad-by-ethyl-ketopentenoate-ekp-induces-treatment-resistant-epileptic-seizures-in-zebrafish
#12
Yifan Zhang, Michiel Vanmeert, Aleksandra Siekierska, Annelii Ny, Jubi John, Geert Callewaert, Eveline Lescrinier, Wim Dehaen, Peter A M de Witte, Rafal M Kaminski
Epilepsy is a chronic brain disorder characterized by recurrent seizures due to abnormal, excessive and synchronous neuronal activities in the brain. It affects approximately 65 million people worldwide, one third of which are still estimated to suffer from refractory seizures. Glutamic acid decarboxylase (GAD) that converts glutamate into GABA is a key enzyme in the dynamic regulation of neural network excitability. Importantly, clinical evidence shows that lowered GAD activity is associated with several forms of epilepsy which are often treatment resistant...
August 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28774708/epileptologist-s-view-laser-interstitial-thermal-ablation-for-treatment-of-temporal-lobe-epilepsy
#13
Joon Y Kang, Michael R Sperling
A procedure called laser interstitial thermal ablation has been utilized to treat drug resistant epilepsy. With this technique, a probe is stereotactically inserted into a target structure responsible for seizures, such as mesial temporal lobe, hypothalamic hamartoma, or a small malformation of cortical development, and the tip is then heated by application of laser energy to ablate structures adjacent to the probe tip. This procedure has the advantage of selectively targeting small lesions responsible for seizures, and is far less invasive than open surgery with shorter hospitalization, less pain, and rapid return to normal activities...
July 25, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28755545/stereo-electroencephalography-identifies-n2-sleep-and-spindles-in-human-hippocampus
#14
Nicolas Carpentier, Thierry Cecchin, Laurent Koessler, Valérie Louis-Dorr, Jacques Jonas, Jean-Pierre Vignal, Marc Carpentier, William Szurhaj, Patrice Bourgin, Louis Maillard
OBJECTIVES: To describe the hippocampal stereo-electroencephalogram during sleep according to sleep stages (including N2 sleep) and cycles, together with the hippocampal spindles. METHODS: All patients with drug-resistant focal epilepsy undergoing intra-hippocampal implantation between August 2012 and June 2013 at Nancy University Hospital were screened. Six patients with explored hippocampus devoid of pathological features were analyzed. During one night, we identified continuous periods of successive N2, N3 and REM sleep for two full cycles...
July 8, 2017: Clinical Neurophysiology: Official Journal of the International Federation of Clinical Neurophysiology
https://www.readbyqxmd.com/read/28751143/n-alkyl-1-1-biphenyl-2-sulfonamide-derivatives-as-novel-broad-spectrum-anti-epileptic-drugs-with-efficacy-equivalent-to-that-of-sodium-valproate
#15
Tomoyuki Tanaka, Nana Yajima, Tomoko Kiyoshi, Yoshiki Miura, Seiji Iwama
In order to develop phenyl sulfonamides as a novel class of anti-epileptic drugs (AED) for both general and partial seizure, we initiated in vivo screening of our chemical library in the mice MES and sc-PTZ models and found compounds 1 and 2 as lead compounds. Optimization of 1 and 2 led to the discovery of compound 21, which showed potent anticonvulsant effect in MES, scPTZ and rat amygdala kindling models. These findings indicate that compound 21 could be a useful new broad spectrum AED like sodium valproate and provide an opportunity to struggle current therapy-resistant epilepsy...
July 13, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28749594/seizure-activity-per-se-does-not-induce-tissue-damage-markers-in-human-neocortical-focal-epilepsy
#16
Laura Rossini, Rita Garbelli, Vadym Gnatkovsky, Giuseppe Didato, Flavio Villani, Roberto Spreafico, Francesco Deleo, Giorgio Lo Russo, Giovanni Tringali, Francesca Gozzo, Laura Tassi, Marco de Curtis
Objective The contribute of recurring seizures to the progression of epileptogenesis is debated. Seizure-induced brain damage is not conclusively demonstrated both in humans and in animal models of epilepsy. We evaluated the expression of brain injury biomarkers on post-surgical brain tissue obtained from 20 patients with frequent seizures and a long history of drug-resistant focal epilepsy. Methods The expression patterns of specific glial, neuronal and inflammatory molecules was evaluated by immunohistochemistry in the core of type II focal cortical dysplasias (FCD-II), at the FCD boundary (perilesion) and in the adjacent normal-appearing area included in the epileptogenic region...
July 27, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28749544/combined-electroencephalography-functional-magnetic-resonance-imaging-and-electrical-source-imaging-improves-localization-of-pediatric-focal-epilepsy
#17
Maria Centeno, Tim M Tierney, Suejen Perani, Elhum A Shamshiri, Kelly St Pier, Charlotte Wilkinson, Daniel Konn, Serge Vulliemoz, Frédéric Grouiller, Louis Lemieux, Ronit M Pressler, Christopher A Clark, J Helen Cross, David W Carmichael
OBJECTIVE: Surgical treatment in epilepsy is effective if the epileptogenic zone (EZ) can be correctly localized and characterized. Here we use simultaneous electroencephalography-functional magnetic resonance imaging (EEG-fMRI) data to derive EEG-fMRI and electrical source imaging (ESI) maps. Their yield and their individual and combined ability to (1) localize the EZ and (2) predict seizure outcome were then evaluated. METHODS: Fifty-three children with drug-resistant epilepsy underwent EEG-fMRI...
July 27, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28748348/impact-of-genetic-polymorphisms-on-phenytoin-pharmacokinetics-and-clinical-outcomes-in-the-middle-east-and-north-africa-region
#18
REVIEW
Renée Dagenais, Kyle John Wilby, Hazem Elewa, Mary H H Ensom
BACKGROUND: Genetic polymorphisms are known to influence outcomes with phenytoin yet effects in the Middle East and North Africa region are poorly understood. OBJECTIVES: The objective of this systematic review was to evaluate the impact of genetic polymorphisms on phenytoin pharmacokinetics and clinical outcomes in populations originating from the Middle East and North Africa region, and to characterize genotypic and allelic frequencies within the region for genetic polymorphisms assessed...
July 26, 2017: Drugs in R&D
https://www.readbyqxmd.com/read/28740261/sustained-efficacy-of-closed-loop-electrical-stimulation-for-long-term-treatment-of-absence-epilepsy-in-rats
#19
Gábor Kozák, Antal Berényi
Closed-loop brain stimulation is a promising alternative to treat drug-resistant epilepsies. In contrast to optogenetic interventions, transcranial electrical stimulation (TES) does not require cellular modification of neurons to be effective, and it is less invasive compared to deep brain stimulation. Furthermore, on-demand TES of targeted brain regions allows the potential for normal function of these networks during interictal periods, a possibility that is eliminated by resective surgical treatment approaches...
July 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28737479/evaluation-of-brivaracetam-a-new-drug-to-treat-epilepsy
#20
Jasmina R Milovanović, Slobodan M Janković, Ana Pejčić, Miloš Milosavljević, Valentina Opančina, Vesela Radonjić, Zoran Protrka, Marina Kostić
High prevalence of therapy-resistant epilepsy demands development of anticonvulsants with new mechanisms of action. Brivaracetam is an analogue of levetiracetam which binds to the synaptic vesicle protein 2A (SV2A) and decreases release of excitatory neurotransmitters. Areas covered: Relevant published studies were searched for by predefined strategy in MEDLINE, EBSCO and SCINDEKS electronic databases. Brivaracetam is effective as adjunctive therapy for uncontrolled partial-onset seizures with or without secondary generalization in patients 16 years and older with epilepsy...
July 28, 2017: Expert Opinion on Pharmacotherapy
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