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Pharmacoresistant epilepsy

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https://www.readbyqxmd.com/read/28320117/use-of-social-media-to-assess-the-effectiveness-of-vagal-nerve-stimulation-in-dravet-syndrome-a-caregiver-s-perspective
#1
Rushna Ali, Mona Elsayed, Manpreet Kaur, Ellen Air, Naznin Mahmood, Jules Constantinou, Jason Schwalb
BACKGROUND: Dravet syndrome (DS) is a rare genetic epilepsy syndrome which is particularly pharmacoresistant. Vagus nerve stimulation (VNS) is commonly used in the treatment of DS as an adjunct to medical therapy. A meaningful assessment of post-surgical outcomes with VNS is difficult given the rarity of the condition. OBJECTIVE: In a novel approach, we used social media to contact patients with DS to gather data on post-surgical seizure reduction and overall satisfaction with VNS...
April 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28317156/synthesis-and-anticonvulsant-properties-of-new-3-3-diphenyl-2-5-dioxo-pyrrolidin-1-yl-acetamides-and-3-3-diphenyl-propionamides
#2
Jolanta Obniska, Anna Rapacz, Sabina Rybka, Małgorzata Góra, Paweł Żmudzki, Krzysztof Kamiński
The focused library of new amides derived from 3,3-diphenyl-2,5-dioxo-pyrrolidin-1-yl-acetic acid (2a-t) and 3,3-diphenyl-propionic acid (3a-t) as potential anticonvulsant agents was synthesized. The final products were obtained in the amidation reaction of the given carboxylic acid (2, 3) with appropriate secondary amines in the presence of carbonyldiimidazole (CDI) as a coupling reagent. The initial anticonvulsant screening was performed in mice intraperitoneally (i.p.) using the "classical" maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) seizure models, whereas the acute neurological toxicity was determined applying the rotarod test...
March 20, 2017: Archiv der Pharmazie
https://www.readbyqxmd.com/read/28303498/validation-of-a-preclinical-drug-screening-platform-for-pharmacoresistant-epilepsy
#3
Melissa L Barker-Haliski, Kristina Johnson, Peggy Billingsley, Jennifer Huff, Laura J Handy, Rizvana Khaleel, Zhenmei Lu, Matthew J Mau, Timothy H Pruess, Carlos Rueda, Gerald Saunders, Tristan K Underwood, Fabiola Vanegas, Misty D Smith, Peter J West, Karen S Wilcox
The successful identification of promising investigational therapies for the treatment of epilepsy can be credited to the use of numerous animal models of seizure and epilepsy for over 80 years. In this time, the maximal electroshock test in mice and rats, the subcutaneous pentylenetetrazol test in mice and rats, and more recently the 6 Hz assay in mice, have been utilized as primary models of electrically or chemically-evoked seizures in neurologically intact rodents. In addition, rodent kindling models, in which chronic network hyperexcitability has developed, have been used to identify new agents...
March 16, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28295557/parachlorophenylalanine-induced-5-ht-depletion-alters-behavioural-and-brain-neurotransmitters-levels-in-6-hertz-psychomotor-seizure-model-in-mice
#4
Kausar Jahan, Krishna K Pillai, Divya Vohora
The present study was designed to investigate the role of serotonin and other neurotransmitters namely dopamine (DA), histamine, noradrenaline (NA), glutamate and γ-amino-butyric acid (GABA) in the 6-hertz (6 Hz) induced psychomotor seizures in Swiss albino mice. Parachlorophenylalanine (PCPA, 300 mg/kg/day, i.p for 3 days) treated mice were given 6 Hz stimulation. Sodium valproate (SVP) [200 mg/kg/day, p.o for 3 days] was used as a reference anti-epileptic drug. The behavioral changes induced by 6Hz including increased rearing and grooming, Straub's tail, behavioral arrest, stun position etc were amplified by PCPA...
March 10, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/28290134/animal-models-of-seizures-and-epilepsy-past-present-and-future-role-for-the-discovery-of-antiseizure-drugs
#5
Wolfgang Löscher
The identification of potential therapeutic agents for the treatment of epilepsy requires the use of seizure models. Except for some early treatments, including bromides and phenobarbital, the antiseizure activity of all clinically used drugs was, for the most part, defined by acute seizure models in rodents using the maximal electroshock and subcutaneous pentylenetetrazole seizure tests and the electrically kindled rat. Unfortunately, the clinical evidence to date would suggest that none of these models, albeit useful, are likely to identify those therapeutics that will effectively manage patients with drug resistant seizures...
March 13, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28281007/seizure-outcomes-of-temporal-lobe-epilepsy-surgery-in-patients-with-normal-mri-and-without-specific-histopathology
#6
Jugoslav Ivanovic, Pål G Larsson, Ylva Østby, John Hald, Bård K Krossnes, Jan G Fjeld, Are H Pripp, Kristin Å Alfstad, Arild Egge, Milo Stanisic
BACKGROUND: Seizure outcome following surgery in pharmacoresistant temporal lobe epilepsy patients with normal magnetic resonance imaging and normal or non-specific histopathology is not sufficiently presented in the literature. METHODS: In a retrospective design, we reviewed data of 263 patients who had undergone temporal lobe epilepsy surgery and identified 26 (9.9%) who met the inclusion criteria. Seizure outcomes were determined at 2-year follow-up. Potential predictors of Engel class I (satisfactory outcome) were identified by logistic regression analyses...
March 9, 2017: Acta Neurochirurgica
https://www.readbyqxmd.com/read/28264441/effect-of-oxidative-stress-on-abc-transporters-contribution-to-epilepsy-pharmacoresistance
#7
REVIEW
Gurpreet Kaur Grewal, Samiksha Kukal, Neha Kanojia, Luciano Saso, Shrikant Kukreti, Ritushree Kukreti
Epilepsy is a neurological disorder affecting around 1%-2% of population worldwide and its treatment includes use of antiepileptic drugs to control seizures. Failure to respond to antiepileptic drug therapy is a major clinical problem and over expression of ATP-binding cassette transporters is considered one of the major reasons for pharmacoresistance. In this review, we have summarized the regulation of ABC transporters in response to oxidative stress due to disease and antiepileptic drugs. Further, ketogenic diet and antioxidants were examined for their role in pharmacoresistance...
February 27, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28259063/to-what-extent-does-depression-influence-quality-of-life-of-people-with-pharmacoresistant-epilepsy-in-argentina
#8
Laura Scévola, Mercedes Sarudiansky, Alejandra Lanzillotti, Silvia Oddo, Silvia Kochen, Luciana D'Alessio
INTRODUCTION: Depression is the most frequent psychiatric co-morbidity in patients with epilepsy. Lifetime prevalence of depression is reported more frequently in temporal lobe epilepsy and is estimated at 35%. This co-morbidity appears to be related with various mechanisms. The aim of this study was to determine the quality of life (QoL) of patients with pharmacoresistant epilepsy with and without co-morbid depression in an Argentinean population. METHODS: Patients admitted to the video-EEG monitoring unit during the period 2010-2013 went through a standardized psychiatric assessment using SCID-I (Structured Clinical Interview for Axis I diagnoses of DSM-IV), BDI II (Beck Depression Inventory) GAF (Global assessment of functioning), and Q LES Q-SF (for quality of life)...
February 28, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28229367/inhibition-of-mtor-pathway-by-rapamycin-decreases-p-glycoprotein-expression-and-spontaneous-seizures-in-pharmacoresistant-epilepsy
#9
Xiaosa Chi, Cheng Huang, Rui Li, Wei Wang, Mengqian Wu, Jinmei Li, Dong Zhou
The mammalian target of rapamycin (mTOR) has been demonstrated to mediate multidrug resistance in various tumors by inducing P-glycoprotein (P-gp) overexpression. Here, we investigated the correlation between the mTOR pathway and P-gp expression in pharmacoresistant epilepsy. Temporal cortex specimens were obtained from patients with refractory mesial temporal lobe epilepsy (mTLE) and age-matched controls who underwent surgeries at West China Hospital of Sichuan University between June 2014 and May 2015. We established a rat model of epilepsy kindled by coriaria lactone (CL) and screened pharmacoresistant rats (non-responders) using phenytoin...
February 22, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28206669/characterization-of-focal-cortical-dysplasia-with-balloon-cells-by-layer-specific-markers-evidence-for-differential-vulnerability-of-interneurons
#10
Julia M Nakagawa, Catharina Donkels, Susanne Fauser, Andreas Schulze-Bonhage, Marco Prinz, Josef Zentner, Carola A Haas
OBJECTIVE: Focal cortical dysplasia (FCD) is a major cause of pharmacoresistant focal epilepsy. Little is known about the pathomechanisms underlying the characteristic cytoarchitectural abnormalities associated with FCD. In the present study, a broad panel of markers identifying layer-specific neuron subpopulations was applied to characterize dyslamination and structural alterations in FCD with balloon cells (FCD 2b). METHODS: Pan-neuronal neuronal nuclei (NeuN) and layer-specific protein expression (Reelin, Calbindin, Calretinin, SMI32 (nonphosphorylated neurofilament H), Parvalbumin, transducin-like enhancer protein 4 (TLE4), and Vimentin) was studied by immunohistochemistry on paraffin sections of FCD2b cases (n = 22) and was compared to two control groups with (n = 7) or without epilepsy (n = 4 postmortem cases)...
February 16, 2017: Epilepsia
https://www.readbyqxmd.com/read/28188677/5-hydroxytryptamine1a-receptor-density-in-the-hippocampus-of-patients-with-temporal-lobe-epilepsy-is-associated-with-disease-duration
#11
N C Fonseca, H P G Joaquim, L L Talib, S Vincentiis, W F Gattaz, K D Valente
BACKGROUND AND PURPOSE: To date, no study has evaluated the association between serotonin receptor density and clinical variables in patients with temporal lobe epilepsy caused by hippocampal sclerosis (TLE-HS) using hippocampal tissue. We evaluated 5-hydroxytryptamine1A receptor (5-HT1AR) density in hippocampal tissue from patients with TLE-HS. METHODS: We analyzed the hippocampal tissue of 34 patients with pharmacoresistant unilateral TLE-HS. 5-HT1AR density was measured using semiquantitative western blotting...
February 11, 2017: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/28111749/progress-report-on-new-antiepileptic-drugs-a-summary-of-the-thirteenth-eilat-conference-on-new-antiepileptic-drugs-and-devices-eilat-xiii
#12
REVIEW
Meir Bialer, Svein I Johannessen, René H Levy, Emilio Perucca, Torbjörn Tomson, H Steve White
The Thirteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XIII) took place in Madrid, Spain, on June 26-29, 2016, and was attended by >200 delegates from 31 countries. The present Progress Report provides an update on experimental and clinical results for drugs presented at the Conference. Compounds for which summary data are presented include an AED approved in 2016 (brivaracetam), 12 drugs in phase I-III clinical development (adenosine, allopregnanolone, bumetanide, cannabidiol, cannabidivarin, 2-deoxy-d-glucose, everolimus, fenfluramine, huperzine A, minocycline, SAGE-217, and valnoctamide) and 6 compounds or classes of compounds for which only preclinical data are available (bumetanide derivatives, sec-butylpropylacetamide, FV-082, 1OP-2198, NAX 810-2, and SAGE-689)...
January 23, 2017: Epilepsia
https://www.readbyqxmd.com/read/28109992/acute-and-spontaneous-seizure-onset-zones-in-the-intraperitoneal-kainic-acid-model
#13
Phillip Connell, Arezou Bayat, Sweta Joshi, Mohamad Z Koubeissi
OBJECTIVE: Hippocampal monitoring is often used in the intraperitoneal kainic acid (KA) seizure model for detection and quantification of early ictal activity. Here, we investigated extra-hippocampal seizure onset zones (SOZs) in this model. METHODS: Eight male Sprague Dawley rats implanted with depth electrodes were continuously recorded during intraperitoneal KA injections until status epilepticus (SE) was induced. Another group of four rats was monitored chronically up to two weeks after emergence of spontaneous recurrent seizures...
January 18, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28109652/epilepsy-in-patients-with-grin2a-alterations-genetics-neurodevelopment-epileptic-phenotype-and-response-to-anticonvulsive-drugs
#14
C von Stülpnagel, M Ensslen, R S Møller, D K Pal, S Masnada, P Veggiotti, E Piazza, M Dreesmann, T Hartlieb, T Herberhold, E Hughes, M Koch, C Kutzer, K Hoertnagel, J Nitanda, M Pohl, K Rostásy, T B Haack, K Stöhr, G Kluger, I Borggraefe
OBJECTIVE: To delineate the genetic, neurodevelopmental and epileptic spectrum associated with GRIN2A alterations with emphasis on epilepsy treatment. METHODS: Retrospective study of 19 patients (7 females; age: 1-38 years; mean 10.1 years) with epilepsy and GRIN2A alteration. Genetic variants were classified according to the guidelines and recommendations of the American College of Medical Genetics (ACMG). Clinical findings including epilepsy classification, treatment, EEG findings, early childhood development and neurodevelopmental outcome were collected with an electronic questionnaire...
January 14, 2017: European Journal of Paediatric Neurology: EJPN
https://www.readbyqxmd.com/read/28087827/neuropsychological-outcome-following-frontal-lobectomy-for-pharmacoresistant-epilepsy-in-adults
#15
Robyn M Busch, Darlene P Floden, Lisa Ferguson, Shamseldeen Mahmoud, Audrina Mullane, Stephen Jones, Lara Jehi, William Bingaman, Imad M Najm
OBJECTIVE: This retrospective cohort study characterized cognitive and motor outcomes in a large sample of adults who underwent frontal lobe resections for treatment of pharmacoresistant epilepsy. METHODS: Ninety patients who underwent unilateral frontal lobe resection for epilepsy (42 language-dominant hemisphere/48 nondominant hemisphere) between 1989 and 2014 completed comprehensive preoperative and postoperative neuropsychological evaluations that included measures of verbal and nonverbal intellectual functioning, attention/working memory, processing speed, language, executive functioning, verbal and visual memory, and motor functioning...
February 14, 2017: Neurology
https://www.readbyqxmd.com/read/28076316/changes-of-thyroid-hormonal-status-in-patients-receiving-ketogenic-diet-due-to-intractable-epilepsy
#16
Engin Kose, Orkide Guzel, Korcan Demir, Nur Arslan
BACKGROUND: Ketogenic diet (KD), which is high in fat and low in carbohydrates, mimics the metabolic state of starvation and is used therapeutically for pharmacoresistant epilepsy. It is known that generation of triiodothyronine (T3) from thyroxine (T4) decreases during fasting periods. The aim of this study was to evaluate the thyroid function of children receiving KD for at least 1 year due to drug-resistant epilepsy. METHODS: A total of 120 patients [63 males, 52...
January 11, 2017: Journal of Pediatric Endocrinology & Metabolism: JPEM
https://www.readbyqxmd.com/read/28064458/label-free-multiphoton-microscopy-reveals-altered-tissue-architecture-in-hippocampal-sclerosis
#17
Ortrud Uckermann, Roberta Galli, Susann Leupold, Roland Coras, Matthias Meinhardt, Susanne Hallmeyer-Elgner, Thomas Mayer, Alexander Storch, Gabriele Schackert, Edmund Koch, Ingmar Blümcke, Gerald Steiner, Matthias Kirsch
The properties and structure of tissue can be visualized without labeling or preparation by multiphoton microscopy combining coherent anti-Stokes Raman scattering (CARS), addressing lipid content, second harmonic generation (SHG) showing collagen, and two-photon excited fluorescence (TPEF) of endogenous fluorophores. We compared samples of sclerotic and nonsclerotic human hippocampus to detect pathologic changes in the brain of patients with pharmacoresistant temporomesial epilepsy (n = 15). Multiphoton microscopy of cryosections and bulk tissue revealed hippocampal layering and micromorphologic details in accordance with reference histology: CARS displayed white and gray matter layering and allowed the assessment of axonal myelin...
January 2017: Epilepsia
https://www.readbyqxmd.com/read/28053048/identifying-new-antiepileptic-drugs-through-genomics-based-drug-repurposing
#18
Nasir Mirza, Greame J Sills, Munir Pirmohamed, Anthony G Marson
Currently available antiepileptic drugs (AEDs) fail to control seizures in 30% of patients. Genomics-based drug repurposing (GBR) offers the potential of savings in the time and cost of developing new AEDs. In the current study, we used published data and software to identify the transcriptomic signature of chornic temporal lobe epilepsy and the drugs that reverse it. After filtering out compounds based on exclusion criteria, such as toxicity, 36 drugs were retained. 11 of the 36 drugs identified (>30%) have published evidence of the antiepileptic efficacy (for example, curcumin) or antiepileptogenic affect (for example, atorvastatin) in recognised rodent models or patients...
January 4, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28031219/preoperative-automated-fibre-quantification-predicts-postoperative-seizure-outcome-in-temporal-lobe-epilepsy
#19
Simon S Keller, G Russell Glenn, Bernd Weber, Barbara A K Kreilkamp, Jens H Jensen, Joseph A Helpern, Jan Wagner, Gareth J Barker, Mark P Richardson, Leonardo Bonilha
Approximately one in every two patients with pharmacoresistant temporal lobe epilepsy will not be rendered completely seizure-free after temporal lobe surgery. The reasons for this are unknown and are likely to be multifactorial. Quantitative volumetric magnetic resonance imaging techniques have provided limited insight into the causes of persistent postoperative seizures in patients with temporal lobe epilepsy. The relationship between postoperative outcome and preoperative pathology of white matter tracts, which constitute crucial components of epileptogenic networks, is unknown...
January 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28017578/drug-development-for-refractory-epilepsy-the-past-25-years-and-beyond
#20
REVIEW
Ambica Golyala, Patrick Kwan
Despite the exponential growth of approved antiepileptic drugs (AEDs) over the past 25 years, epilepsy remains uncontrolled in approximately a third of patients. This article summarises the clinical trials and properties of the AEDs developed over this period, and reviews the pre-clinical and clinical development paradigms of modern AEDs. We discuss possible reasons for the apparent failure to develop more efficacious compounds. We also review the current regulatory frameworks for drug approval in the United States and Europe, and the changes on the horizon...
January 2017: Seizure: the Journal of the British Epilepsy Association
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