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Pharmacoresistant epilepsy

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https://www.readbyqxmd.com/read/28206669/characterization-of-focal-cortical-dysplasia-with-balloon-cells-by-layer-specific-markers-evidence-for-differential-vulnerability-of-interneurons
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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...
January 13, 2017: Neurology
https://www.readbyqxmd.com/read/28076316/changes-of-thyroid-hormonal-status-in-patients-receiving-ketogenic-diet-due-to-intractable-epilepsy
#7
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
#8
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
#9
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
#10
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
#11
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...
December 6, 2016: Seizure: the Journal of the British Epilepsy Association
https://www.readbyqxmd.com/read/28005041/-outcomes-of-surgical-treatment-of-patients-with-pharmacoresistant-epilepsy
#12
V V Krylov, A B Gekht, I S Trifonov, A V Lebedeva, I L Kaimovsky, M V Sinkin, E V Grigor'eva, M N Grishkina, L V Shishkina, O O Kochetkova
AIM: To evaluate the results of surgical treatment of patients with pharmacoresistant epilepsy. MATERIAL AND METHODS: Examination and surgical treatment of 61 patients with pharmacoresistant forms of symptomatic epilepsy were performed from 01.01.14 to 01.05.16. RESULTS AND CONCLUSION: The results confirmed the safety and efficacy of the surgical treatment of pharmacoresistant epilepsy. After 12 months, seizures were controlled in 69% of operated patients...
2016: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/27933950/structure-activity-relationship-drug-metabolism-and-pharmacokinetics-properties-optimization-and-in-vivo-studies-of-new-brain-penetrant-triple-t-type-calcium-channel-blockers
#13
Romain Siegrist, Davide Pozzi, Gaël Jacob, Caterina Torrisi, Kilian Colas, Bertrand Braibant, Jacques Mawet, Thomas Pfeifer, Ruben de Kanter, Catherine Roch, Melanie Kessler, Olivier Corminboeuf, Olivier Bezençon
Despite the availability of numerous antiepileptic drugs, 20-30% of epileptic patients are pharmacoresistant with seizures not appropriately controlled. Consequently, new strategies to address this unmet medical need are required. T-type calcium channels play a key role in neuronal excitability and burst firing, and selective triple T-type calcium channel blockers could offer a new way to treat various CNS disorders, in particular epilepsy. Herein we describe the identification of new 1,4-benzodiazepines as brain penetrant and selective triple T-type calcium channel blockers...
December 8, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27918961/the-promise-of-subtraction-ictal-spect-co-registered-to-mri-for-improved-seizure-localization-in-pediatric-epilepsies-affecting-factors-and-relationship-to-the-surgical-outcome
#14
Catherine Stamoulis, Nishant Verma, Himanshu Kaulas, Jonathan J Halford, Frank H Duffy, Phillip L Pearl, S Ted Treves
OBJECTIVE: Ictal SPECT is promising for accurate non-invasive localization of the epileptogenic brain tissue in focal epilepsies. However, high quality ictal scans require meticulous attention to the seizure onset. In a relatively large cohort of pediatric patients, this study investigated the impact of the timing of radiotracer injection, MRI findings and seizure characteristics on ictal SPECT localizations, and the relationship between concordance of ictal SPECT, scalp EEG and resected area with seizure freedom following epilepsy surgery...
January 2017: Epilepsy Research
https://www.readbyqxmd.com/read/27875747/new-model-of-pharmacoresistant-seizures-induced-by-3-mercaptopropionic-acid-in-mice
#15
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
#16
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 have 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...
February 2017: 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
#17
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...
January 2017: Epilepsia
https://www.readbyqxmd.com/read/27859041/increased-subcortical-oligodendroglia-like-cells-in-pharmacoresistant-focal-epilepsy-in-children-correlate-with-extensive-epileptogenic-zones
#18
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...
December 2016: Epilepsia
https://www.readbyqxmd.com/read/27852771/reduced-efficacy-of-the-kcc2-cotransporter-promotes-epileptic-oscillations-in-a-subiculum-network-model
#19
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
#20
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...
January 2017: Journal of Cerebral Blood Flow and Metabolism
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