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Pharmacoresistant epilepsy

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https://www.readbyqxmd.com/read/27875747/new-model-of-pharmacoresistant-seizures-induced-by-3-mercaptopropionic-acid-in-mice
#1
Andrea Enrique, Sofía Goicoechea, Rocío Castaño, Facundo Taborda, Luisa Rocha, Sandra Orozco, Elena Girardi, Luis Bruno Blanch
About 30% of the patients with epilepsy do not respond to clinically established anticonvulsants, despite having effective concentrations of the antiepileptic drug in plasma. Therefore, new preclinical models of epilepsy are needed to identify more efficacious treatments. We describe here a new drug-resistant seizure model in mice to be used at the early stages of pre-clinical trials. This model consists in inducing daily generalized seizures for 23 consecutive days by administration of 3-mercaptopropionic acid (MP)...
October 27, 2016: Epilepsy Research
https://www.readbyqxmd.com/read/27871881/targeting-brain-and-peripheral-plasticity-of-the-lipidome-in-acute-kainic-acid-induced-epileptic-seizures-in-mice-via-quantitative-mass-spectrometry
#2
Raissa Lerner, Julia Post, Sebastian Loch, Beat Lutz, Laura Bindila
Epilepsy is a highly common chronic neurological disorder, manifested in many different types, affecting ~1% of the worldwide human population. The molecular mechanisms of epileptogenesis has not yet been clarified, and pharmacoresistance exhibited by 30-40% of epilepsy patients remains a major obstacle in medical care. Growing evidence indicates a role of lipid signalling pathways in epileptogenesis, thus lipid signals emerge as potential biomarkers for the onset and evolving course of the epileptic disorder, as well as potential therapeutic agents and targets...
November 15, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27864845/activity-of-the-anticonvulsant-lacosamide-in-experimental-and-human-epilepsy-via-selective-effects-on-slow-na-channel-inactivation
#3
Dominik Holtkamp, Thoralf Opitz, Isabelle Niespodziany, Christian Wolff, Heinz Beck
OBJECTIVE: In human epilepsy, pharmacoresistance to antiepileptic drug therapy is a major problem affecting ~30% of patients with epilepsy. Many classical antiepileptic drugs target voltage-gated sodium channels, and their potent activity in inhibiting high-frequency firing has been attributed to their strong use-dependent blocking action. In chronic epilepsy, a loss of use-dependent block has emerged as a potential cellular mechanism of pharmacoresistance for anticonvulsants acting on voltage-gated sodium channels...
November 19, 2016: Epilepsia
https://www.readbyqxmd.com/read/27859041/increased-subcortical-oligodendroglia-like-cells-in-pharmacoresistant-focal-epilepsy-in-children-correlate-with-extensive-epileptogenic-zones
#4
Satoru Sakuma, William C Halliday, Ruka Nomura, Shiro Baba, Yosuke Sato, Kazuo Okanari, Midori Nakajima, Elysa Widjaja, Cyrus Boelman, Ayako Ochi, O Carter Snead, James T Rutka, James Drake, Steven Miller, Hiroshi Otsubo
OBJECTIVE: Cortical resections in epilepsy surgery tend to involve multiple lobes in children, compared to adults, partly due to underlying pathology. Oligodendroglia-like cells (OLCs) have been observed in surgical specimens from children with pharmacoresistant epilepsy. We hypothesize that OLCs recruit multiple-lobe epileptogenic zones in pediatric pharmacoresistant focal epilepsy. METHODS: We examined the surgical specimens from 30 children who underwent epilepsy surgery (1...
November 8, 2016: Epilepsia
https://www.readbyqxmd.com/read/27852771/reduced-efficacy-of-the-kcc2-cotransporter-promotes-epileptic-oscillations-in-a-subiculum-network-model
#5
Anatoly Buchin, Anton Chizhov, Gilles Huberfeld, Richard Miles, Boris S Gutkin
: Pharmacoresistant epilepsy is a chronic neurological condition in which a basal brain hyperexcitability results in paroxysmal hypersynchronous neuronal discharges. Human temporal lobe epilepsy has been associated with dysfunction or loss of the potassium-chloride cotransporter KCC2 in a subset of pyramidal cells in the subiculum, a key structure generating epileptic activities. KCC2 regulates intraneuronal chloride and extracellular potassium levels by extruding both ions. Absence of effective KCC2 may alter the dynamics of chloride and potassium levels during repeated activation of GABAergic synapses due to interneuron activity...
November 16, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27837191/age-associated-physiological-and-pathological-changes-at-the-blood-brain-barrier-a-review
#6
REVIEW
Franciska Erdő, László Denes, Elizabeth de Lange
The age-associated decline of the neurological and cognitive functions becomes more and more serious challenge for the developed countries with the increasing number of aged populations. The morphological and biochemical changes in the aging brain are the subjects of many extended research projects worldwide for a long time. However, the crucial role of the blood-brain barrier (BBB) impairment and disruption in the pathological processes in age-associated neurodegenerative disorders received special attention just for a few years...
November 11, 2016: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/27816896/simultaneous-seeg-meg-eeg-recordings-overcome-the-seeg-limited-spatial-sampling
#7
Martine Gavaret, Anne-Sophie Dubarry, Romain Carron, Fabrice Bartolomei, Agnès Trébuchon, Christian-George Bénar
During presurgical evaluation of pharmacoresistant partial epilepsies, stereoelectroencephalography (SEEG) records interictal and ictal activities directly but is inherently limited in spatial sampling. In contrast, scalp-EEG and MEG are less sensitive but provide a global view on brain activity. Therefore, recording simultaneously these three modalities should provide a better understanding of the underlying brain sources by taking advantage of the different sensitivities of the three recording techniques...
October 25, 2016: Epilepsy Research
https://www.readbyqxmd.com/read/27816354/invasive-epilepsy-surgery-evaluation
#8
Stjepana Kovac, Vejay N Vakharia, Catherine Scott, Beate Diehl
Intracranial EEG (iEEG) recordings are widely used for the work up of pharmacoresistant epilepsy. Different iEEG recording techniques namely subdural grids, strips, depth electrodes and stereoencephalography (SEEG) are available with distinct limitations and advantages. Epilepsy centres mastering multiple techniques apply them in an individualised patient approach. These tools are used to map the seizure onset zone which is pivotal in approximating the epileptogenic zone, i.e. the zone which is indispensable for the generation of seizures and when resected will render the patient seizure free...
October 21, 2016: Seizure: the Journal of the British Epilepsy Association
https://www.readbyqxmd.com/read/27816260/the-abcc2-c-24c-t-polymorphism-increases-the-risk-of-resistance-to-antiepileptic-drugs-a-meta-analysis
#9
REVIEW
Long Qian, Shu Fang, Yuan-Liang Yan, Shuang-Shuang Zeng, Zhi-Jie Xu, Zhi-Cheng Gong
Several studies examined a possible link between multidrug resistance-associated protein 2 (ABCC2) gene variants and the risk of resistance to antiepileptic drugs (AEDs) in epilepsy, but the results were contradictory. In this study, a meta-analysis was conducted to assess the relevance of ABCC2 common variants (c.-24C>T, c.1249G>A, c.3972C>T) with the response risk of AEDs. We searched Embase, PubMed, the Cochrane Library and CNKI databases for case-control studies published through May 2016 that evaluated the role of ABCC2 gene variants in pharmacoresistance to AEDs...
November 2, 2016: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/27815406/estimating-risk-of-word-finding-problems-in-adults-undergoing-epilepsy-surgery
#10
Robyn M Busch, Darlene P Floden, Brigid Prayson, Jessica S Chapin, Kevin H Kim, Lisa Ferguson, William Bingaman, Imad M Najm
OBJECTIVE: This retrospective, observational study examined the frequency and magnitude of change in naming ability as a function of side/site of epilepsy surgery and identified predictive factors to assist clinicians in identifying patients at low, moderate, or high risk of postoperative naming decline. METHODS: A total of 875 adults with pharmacoresistant epilepsy (454 left/421 right; 763 temporal/87 frontal/25 posterior quadrant) met inclusion criteria and completed the Boston Naming Test before and after surgery...
November 4, 2016: Neurology
https://www.readbyqxmd.com/read/27788449/epilepsy-surgery-in-the-posterior-part-of-the-brain
#11
Alexandra Liava, Roberto Mai, Francesco Cardinale, Laura Tassi, Giuseppe Casaceli, Francesca Gozzo, Massimo Cossu, Lino Nobili, Laura Castana, Ivana Sartori, Giorgio Lo Russo, Stefano Francione
Posterior cortex epilepsy surgery is rarely performed and is associated with a high number of surgical failures, partly because accurate localization of the epileptogenic zone in the posterior part of the brain is extremely difficult. We present the characteristics as well as the surgical outcome and its determinants of a cohort of 208 consecutive patients (adults/children: 125/83) operated on for drug-resistant posterior cortex epilepsy at the "Claudio Munari" Epilepsy Surgery Centre, Milan between May 1996 and May 2013 (mean postsurgical follow-up: 9...
November 2016: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/27779300/-results-of-vagal-nerve-stimulation-in-patients-with-pharmacoresistant-epilepsy-in-a-national-epilepsy-referral-centre
#12
P Roldan-Ramos, L A Reyes-Figueroa, J Rumia, E Martinez-Lizana, A Donaire, M Carreno-Martinez
AIM: To describe clinical results and complications derived from vagal nerve stimulation therapy in drug resistant epileptic patients unsuitable for other surgical treatments, since the first implant in an epilepsy national referral centre. PATIENTS AND METHODS: A retrospective analysis of the patients implanted in our centre was held. Data related to baseline characteristics of their epilepsy and therapy complications was collected. RESULTS: 32 new implants in 31 patients are included, mean age of 34 years, 29...
November 1, 2016: Revista de Neurologia
https://www.readbyqxmd.com/read/27739360/nanotechnology-as-potential-strategy-for-the-treatment-of-pharmacoresistant-epilepsy-and-comorbid-psychiatric-disorders
#13
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
https://www.readbyqxmd.com/read/27726050/mosaicism-in-atp1a3-related-disorders-not-just-a-theoretical-risk
#14
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
https://www.readbyqxmd.com/read/27709099/preoperative-evaluation-and-surgical-decision-making-in-pediatric-epilepsy-surgery
#15
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
https://www.readbyqxmd.com/read/27665735/the-molecular-and-phenotypic-spectrum-of-iqsec2-related-epilepsy
#16
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...
November 2016: Epilepsia
https://www.readbyqxmd.com/read/27659220/pharmacological-modulation-in-mesial-temporal-lobe-epilepsy-current-status-and-future-perspectives
#17
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
https://www.readbyqxmd.com/read/27632178/a-longitudinal-study-of-surgical-outcome-of-pharmacoresistant-epilepsy-caused-by-focal-cortical-dysplasia
#18
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...
December 2016: Journal of Neurology
https://www.readbyqxmd.com/read/27569054/prevalence-and-predictors-of-subclinical-seizures-during-scalp-video-eeg-monitoring-in-patients-with-epilepsy
#19
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
https://www.readbyqxmd.com/read/27554040/aberrant-expression-of-mir-153-is-associated-with-overexpression-of-hypoxia-inducible-factor-1%C3%AE-in-refractory-epilepsy
#20
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
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