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Pharmacoresistant epilepsy

Argelia Rosillo -de la Torre, Luisa Rocha, Hermelinda Salgado-Ceballos, Perla E García Casillas, Gabriel Luna-Bárcenas
BACKGROUND: Pharmacoresistant epilepsy is a disabling neuronal disorder with harmful consequences that impact patient quality of life. Although psychiatric comorbidities are frequently present in patients with epilepsy, they are more common in those patients with pharmacoresistant epilepsy. Despite medical advances, the current existing therapeutic strategies for pharmacoresistant seizure control are not available for all patients and/or present disadvantages. Moreover, the conventional drug therapies for psychiatric comorbidities have several adverse effects...
October 13, 2016: Mini Reviews in Medicinal Chemistry
Marie Hully, Juliette Ropars, Laurence Hubert, Nathalie Boddaert, Marlene Rio, Mathieu Bernardelli, Isabelle Desguerre, Valerie Cormier-Daire, Arnold Munnich, Pascale de Lonlay, Louise Reilly, Claude Besmond, Nadia Bahi-Buisson
Mutations in ATP1A3 are involved in a large spectrum of neurological disorders, including rapid onset dystonia parkinsonism (RDP), alternating hemiplegia of childhood (AHC), and cerebellar ataxia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS), with recent descriptions of overlapping phenotypes. In AHC, a few familial cases of autosomal dominant inheritance have been reported, along with cases of de novo sporadic mutations. In contrast, autosomal dominant inheritance has frequently been associated with RDP and CAPOS...
October 10, 2016: Neurogenetics
Katrina Ducis, Jian Guan, Michael Karsy, Robert J Bollo
Epilepsy is a common disease in the pediatric population, and the majority of cases are controlled with medications and lifestyle modification. For the children whose seizures are pharmacoresistant, continued epileptic activity can have a severely detrimental impact on cognitive development. Early referral of children with drug-resistant seizures to a pediatric epilepsy surgery center for evaluation is critical to achieving optimal patient outcomes. There are several components to a thorough presurgical evaluation, including a detailed medical history and physical examination, noninvasive testing including electroencephalogram, magnetic resonance imaging (MRI) of the brain, and often metabolic imaging...
July 2016: Translational pediatrics
Ayelet Zerem, Kazuhiro Haginoya, Dorit Lev, Lubov Blumkin, Sara Kivity, Ilan Linder, Cheryl Shoubridge, Elizabeth Emma Palmer, Michael Field, Jackie Boyle, David Chitayat, William D Gaillard, Eric H Kossoff, Marjolaine Willems, David Geneviève, Frederic Tran-Mau-Them, Orna Epstein, Eli Heyman, Sarah Dugan, Alice Masurel-Paulet, Ame'lie Piton, Tjitske Kleefstra, Rolph Pfundt, Ryo Sato, Andreas Tzschach, Naomichi Matsumoto, Hirotomo Saitsu, Esther Leshinsky-Silver, Tally Lerman-Sagie
OBJECTIVE: IQSEC2 is an X-linked gene associated with intellectual disability (ID) and epilepsy. Herein we characterize the epilepsy/epileptic encephalopathy of patients with IQSEC2 pathogenic variants. METHODS: Forty-eight patients with IQSEC2 variants were identified worldwide through Medline search. Two patients were recruited from our early onset epileptic encephalopathy cohort and one patient from personal communication. The 18 patients who have epilepsy in addition to ID are the subject of this study...
September 26, 2016: Epilepsia
Antonio Gambardella, Angelo Labate, Pierangelo Cifelli, Gabriele Ruffolo, Laura Mumoli, Eleonora Aronica, Eleonora Palma
Mesial temporal lobe epilepsy (MTLE) is frequently associated with hippocampal sclerosis (Hs), possibly caused by a primary brain injury that occurs a long time before the appearance of neurological symptoms. MTLE-Hs is, however, a heterogeneous condition that evolves with time, involving both environmental and genetic components. Recent experimental studies emphasize that drugs or drug combinations that target modulation and circuitry reorganization of the epileptogenic networks favorably modify the complex molecular and cellular alterations underlying MTLE...
September 19, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Bo Jin, Jing Wang, Jian Zhou, Shuang Wang, Yuguang Guan, Shuhua Chen
This study aimed to determine the long-term surgical outcome of pharmacoresistant epilepsy caused by focal cortical dysplasia (FCD) and to identify the important predictors of the favorable surgical outcome. The study retrospectively analyzed the data of pharmacoresistant epilepsy patients with histologically proven FCD in our epilepsy center from May 2010 to December 2014. It included 120 patients with a mean follow-up of 34.6 months. Survival analysis and multivariate regression with Cox proportional hazards model were used to evaluate the rate, stability, and predictors of seizure freedom...
September 8, 2016: Journal of Neurology
Bo Jin, Shan Wang, Linglin Yang, Chunhong Shen, Yao Ding, Yi Guo, Zhongjin Wang, Junming Zhu, Shuang Wang, Meiping Ding
OBJECTIVE: This study first aimed to establish the prevalence and predictors of subclinical seizures in patients with epilepsy undergoing video electroencephalographic monitoring, then to evaluate the relationship of sleep/wake and circadian pattern with subclinical seizures. METHODS: We retrospectively reviewed the charts of 742 consecutive patients admitted to our epilepsy center between July 2012 and October 2014. Demographic, electro-clinical data and neuroimage were collected...
August 28, 2016: International Journal of Neuroscience
Yaohua Li, Cheng Huang, Peimin Feng, Yanping Jiang, Wei Wang, Dong Zhou, Lei Chen
Evidence suggest that overexpression of hypoxia-inducible factor-1α (HIF-1α) is linked to multidrug resistance of epilepsy. Here we explored whether aberrant expression of HIF-1α is regulated by miRNAs. Genome-wide microRNA expression profiling was performed on temporal cortex resected from mesial temporal lobe epilepsy (mTLE) patients and age-matched controls. miRNAs that are putative regulator of HIF-1α were predicted via target scan and confirmed by real-time quantitative polymerase chain reaction (RT-qPCR)...
2016: Scientific Reports
Neha Kinariwalla, Arjune Sen
There have been many studies exploring quality of life as well as the impact of epilepsy on the affected individual. However, epilepsy affects more than the patients themselves, and there seems to be a paucity of data regarding the impact of epilepsy beyond the person with epilepsy (PWE). In particular, it is uncertain what the impact of epilepsy on marriage may be. We therefore performed a narrative review to evaluate work measuring the psychosocial effect of epilepsy on marriage. We reviewed the literature on epilepsy and marriage by searching PubMed (Medline) and EMBASE and thoroughly examining relevant bibliographies...
October 2016: Epilepsy & Behavior: E&B
Inuka Kishara Gooneratne, Alexander L Green, Patricia Dugan, Arjune Sen, Angelo Franzini, Tipu Aziz, Binith Cheeran
For patients with pharmacoresistant focal epilepsy in whom surgical resection of the epileptogenic focus fails or was not feasible in the first place, there were few therapeutic options. Increasingly, neurostimulation provides an alternative treatment strategy for these patients. Vagal nerve stimulation (VNS) is well established. Deep brain stimulation (DBS) and cortical responsive stimulation (CRS) are newer neurostimulation therapies with recently published long-term efficacy and safety data. In this literature review, we introduce these therapies to a non-specialist audience...
November 2016: Journal of Neurology, Neurosurgery, and Psychiatry
Mariangela Cantore, Marcello Leopoldo, Francesco Berardi, Roberto Perrone, Nicola Antonio Colabufo
P-glycoprotein is an ATP-binding cassette transporter involved in drug absorption, distribution and excretion. It pumps a wide range of xenobiotic compounds out of the cells and plays a crucial role in Multi Drug Resistance. Moreover, recent studies have demonstrated that changes in P-gp function and/or expression at the blood brain barrier are implicated in the pathogenesis of neurological disorders such as therapy-refractory epilepsy, Alzheimer's and Parkinson's disease. In the last decades the studies have been addressed to the discovery of potent P-gp inhibitors able to revert pharmacoresistance and to the development of PET tracers to detect P-gp activity and expression for an early diagnosis and therapy monitoring of neurodegenerative disease...
August 10, 2016: Current Pharmaceutical Design
Maria Feldmann, Matthias Koepp
Resistance to antiepileptic drugs (AED) remains a major problem in clinical epileptology. This pharmacoresistance is independent of the choice of AEDs. Different hypotheses have been proposed to explain the neurobiological basis for pharmacoresistance in epilepsy. The transporter hypothesis is the mostly investigated theory. Hereby, overexpression of multidrug efflux transporters such as P-glycoprotein (Pgp) at the blood-brain-barrier (BBB) is thought to be involved in pharmacoresistance in epilepsy by extruding AEDs from their target site...
August 10, 2016: Current Pharmaceutical Design
Pl Bozhinov, S Bojinova
PURPOSE: To determine the frequency and the course of hypertensive disorders in pregnant women with epilepsy (PWWE). MATERIALS AND METHODS: The survey is prospective and covers 206 PWWE during the period 1997-2012 year, monitored and treated in Risk Pregnancy Clinic of University Hospital - Pleven. All the patients (PWWE) are with clinically established etiology and prescription of epilepsy, type of seizures and their frequency. EEG records, ultrasound of fetus and cardiotocograph monitoring were conducted...
2016: Akusherstvo i Ginekologii︠a︡
Catherine M Sweeney-Reed, Tino Zaehle, Jürgen Voges, Friedhelm C Schmitt, Lars Buentjen, Klaus Kopitzki, Alan Richardson-Klavehn, Hermann Hinrichs, Hans-Jochen Heinze, Robert T Knight, Michael D Rugg
The data presented here comprise clinical, neuropsychological, and intrathalamic electrophysiological data from 7 patients with pharmacoresistant focal epilepsy and are related to the article "Pre-stimulus thalamic theta power predicts human memory formation" C.M. Sweeney-Reed, T. Zaehle, J. Voges, F.C. Schmitt, L. Buentjen, K. Kopitzki, et al. (2016) [1]. The patients participated in a memory paradigm after receiving electrodes implanted in the DMTN due to the surgical approach taken in electrode insertion for deep brain stimulation of the anterior thalamic nucleus...
September 2016: Data in Brief
Wolfgang Löscher
Epilepsy, a prevalent neurological disease characterized by spontaneous recurrent seizures (SRS), is often refractory to treatment with anti-seizure drugs (ASDs), so that more effective ASDs are urgently needed. For this purpose, it would be important to develop, validate, and implement new animal models of pharmacoresistant epilepsy into drug discovery. Several chronic animal models with difficult-to-treat SRS do exist; however, most of these models are not suited for drug screening, because drug testing on SRS necessitates laborious video-EEG seizure monitoring...
August 8, 2016: Neurochemical Research
B Schmeiser, T Hammen, B J Steinhoff, J Zentner, A Schulze-Bonhage
OBJECT: The intention of our study was to identify predictive characteristics for long-term seizure control and running down phenomenon after surgical treatment of pharmacoresistant mesiotemporal lobe epilepsy (mTLE) with and without associated cortical dysplasia. MATERIALS AND METHODS: Our study comprises a consecutive series of 458 patients who underwent surgical treatment for intractable mTLE at the Epilepsy Center Freiburg. Data evaluated included semiology, duration and frequency of seizures, results of presurgical diagnostics including video-EEG monitoring, MRI, PET and SPECT as well as postoperative seizure outcome...
October 2016: Epilepsy Research
Wafaa Moustafa M Abo El Fotoh, Sameh Abd Allah Abd El Naby, Mona Salah El-Din Habib, Abeer Ahmed ALrefai, Zeinab A Kasemy
PURPOSE: Despite the advances in the pharmacological treatment of epilepsy, pharmacoresistance still remains challenging. Understanding of the pharmacogenetic causes is critical to predict drug response hence providing a basis for personalized medications. Genetic alteration in activity of drug target and drug metabolizing proteins could explain the development of pharmacoresistant epilepsy. So the aim of this study was to explore whether SCN1A c.3184 A/G (rs2298771) and CYP3A5*3 (rs776746) polymorphisms could serve as genetic based biomarkers to predict pharmacoresistance among Egyptian epileptic children...
October 2016: Seizure: the Journal of the British Epilepsy Association
Catherine M Sweeney-Reed, Harim Lee, Stefan Rampp, Tino Zaehle, Lars Buentjen, Juergen Voges, Martin Holtkamp, Hermann Hinrichs, Hans-Jochen Heinze, Friedhelm C Schmitt
The relationships between interictal epileptiform discharges (IEDs) in the anterior (ANT) and dorsomedial nuclei (DMNT) of the thalamus and electro-clinical parameters in pharmacoresistant focal epilepsy patients receiving intrathalamic electrodes for deep brain stimulation (DBS) were investigated. Thalamus-localized IEDs (LIEDs) and surface EEG (sEEG)-IEDs were evaluated in eight patients who underwent ANT-DBS. Occurrence and frequency of ANT- and DMNT-LIEDs and pre-operative sEEG-IEDs were examined with respect to seizure onset location and seizure outcome following ANT-DBS...
October 2016: Journal of Neurology
Stephanie M Miller, Susan M Sullivan, Zoe Ireland, Kirat K Chand, Paul B Colditz, S Tracey Bjorkman
Seizures are a common manifestation of hypoxic-ischaemic brain injury in the neonate. In status epilepticus models alterations to GABAA R subunit expression have been suggested to contribute to 1) abnormal development of the GABAergic system, 2) why seizures become self-sustaining and 3) the development of pharmacoresistance. Detailed investigation of GABAA R subunit protein expression after neonatal hypoxia-ischaemia (HI) is currently insufficient. Using our pig model of HI and subsequent spontaneous neonatal seizures, we investigated changes in protein expression of the three predominant α-subunits of the GABAA R; α1 , α2 and α3 ...
July 26, 2016: Journal of Neurochemistry
Florent Marguet, Hager Barakizou, Abdellah Tebani, Lenaig Abily-Donval, Stéphanie Torre, Fethi Bayoudh, Sami Jebnoun, Marie Brasseur-Daudruy, Stéphane Marret, Annie Laquerriere, Soumeya Bekri
Pyridoxine-dependent epilepsy (PDE) is a pharmacoresistant epileptogenic encephalopathy controlled by pyridoxine supplementation at pharmacological doses. Despite supplementation, the long-term outcome is often poor possibly because of recurrent seizures and developmental structural brain abnormalities. We report on five patients with PDE from three unrelated families. The diagnosis was confirmed by ALDH7A1 sequencing, which allowed for the characterization of two homozygous variations [NM_001182.3:c.1279G > C - p...
July 20, 2016: Metabolic Brain Disease
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