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Pharmacoresistant epilepsy

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https://www.readbyqxmd.com/read/29152735/6%C3%A2-hz-corneal-kindling-in-mice-triggers-neurobehavioral-comorbidities-accompanied-by-relevant-changes-in-c-fos-immunoreactivity-throughout-the-brain
#1
Giulia Albertini, Laura Walrave, Thomas Demuyser, Ann Massie, Dimitri De Bundel, Ilse Smolders
OBJECTIVE: Besides seizures, patients with epilepsy are affected by a variety of cognitive and psychiatric comorbidities that further impair their quality of life. The present study provides an in-depth characterization of the behavioral alterations induced by 6 Hz corneal kindling. Furthermore, we correlate these behavioral changes to alterations in c-Fos protein expression throughout the brain following kindling. METHODS: Adolescent male Naval Medical Research Institute (NMRI) mice were kindled via repetitive subconvulsive 6 Hz corneal stimulations until they reached the fully kindled state (defined as 10 consecutive generalized seizures)...
November 20, 2017: Epilepsia
https://www.readbyqxmd.com/read/29140112/a-2017-review-of-pharmacotherapy-for-treating-focal-epilepsy-where-are-we-now-and-how-will-treatment-develop
#2
Andreas Schulze-Bonhage
Focal epilepsy is the most common type of epilepsy with approximately 30 million patients affected worldwide. There is a major challenge to develop new antiepileptic treatments as currently approximately one third of patients remain uncontrolled under our best standards of care. Areas covered: An overview is given on first- and second generation antiepileptic drugs and their mechanisms of action, and on recent new strategies for antiepileptic targets, including drugs aiming at disease modification. Expert opinion: Newer antiepileptic drugs have enabled a better tolerated and individualized treatment for many patients...
November 15, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/29130506/animal-models-of-acquired-epilepsy-insights-into-mechanisms-of-human-epileptogenesis
#3
Albert J Becker
In many patients who suffer from epilepsies, recurrent epileptic seizures do not start at birth but develop later in life. This holds particularly true for epilepsies with a focal seizure origin including focal cortical dysplasias (FCDs) and temporal lobe epilepsy (TLE). TLE most frequently has its seizure onset in the hippocampal formation. Hippocampal biopsies of pharmacoresistant TLE patients undergoing epilepsy surgery for seizure control most frequently reveal the damage pattern of hippocampal sclerosis, i...
November 12, 2017: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/29122665/in-vitro-screening-of-dual-flavonoid-combinations-for-reversing-p-glycoprotein-mediated-multidrug-resistance-focus-on-antiepileptic-drugs
#4
Ana Ferreira, Adriana O Santos, Amílcar Falcão, Gilberto Alves
The combined use of different P-glycoprotein (P-gp) inhibitors may be a relevant approach to the synergistic and safer inhibition of the P-gp-mediated drug efflux. Herein, we aimed to explore dual combinations of the flavonoids baicalein, (-)-epigallocatechin gallate, kaempferol, quercetin and silymarin to reverse the interference of P-gp on the intracellular accumulation of antiepileptic drugs (AEDs). The intracellular accumulation of rhodamine 123 (a classic P-gp substrate) and of several commonly used AEDs (carbamazepine, phenytoin, oxcarbazepine) or their metabolites (carbamazepine-10,11-epoxide and licarbazepine) was evaluated in MDCK-MDR1 cells in the presence and absence of individual flavonoids and their combinations...
November 6, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29105058/verbal-memory-decline-from-hippocampal-depth-electrodes-in-temporal-lobe-surgery-for-epilepsy
#5
Hanna Ljung, Arto Nordlund, Maria Strandberg, Johan Bengzon, Kristina Källén
OBJECTIVE: To explore whether patients with refractory mesial temporal lobe epilepsy risk aggravated verbal memory loss from intracranial electroencephalography (EEG) recording with longitudinal hippocampal electrodes in the language-dominant hemisphere. METHODS: A long-term neuropsychological follow-up (mean 61.5 months, range 22-111 months) was performed in 40 patients after ictal registration with left hippocampal depth electrodes (study group, n = 16) or no invasive EEG, only extracranial registration (reference group, n = 24)...
November 3, 2017: Epilepsia
https://www.readbyqxmd.com/read/29097316/quantitative-surface-analysis-of-combined-mri-and-pet-enhances-detection-of-focal-cortical-dysplasias
#6
Yee-Leng Tan, Hosung Kim, Seunghyun Lee, Tarik Tihan, Lawrence Ver Hoef, Susanne G Mueller, Anthony James Barkovich, Duan Xu, Robert Knowlton
OBJECTIVE: Focal cortical dysplasias (FCDs) often cause pharmacoresistant epilepsy, and surgical resection can lead to seizure-freedom. Magnetic resonance imaging (MRI) and positron emission tomography (PET) play complementary roles in FCD identification/localization; nevertheless, many FCDs are small or subtle, and difficult to find on routine radiological inspection. We aimed to automatically detect subtle or visually-unidentifiable FCDs by building a classifier based on an optimized cortical surface sampling of combined MRI and PET features...
October 31, 2017: NeuroImage
https://www.readbyqxmd.com/read/29064093/focal-cortical-malformations-in-children-with-early-infantile-epilepsy-and-pcdh19-mutations-case-report
#7
Mary Kurian, Christian M Korff, Emmanuelle Ranza, Andrea Bernasconi, Anja Lübbig, Srishti Nangia, Gian Paolo Ramelli, Gabriele Wohlrab, Douglas R Nordli, Thomas Bast
In this case report we assess the occurrence of cortical malformations in children with early infantile epilepsy associated with variants of the gene protocadherin 19 (PCDH19). We describe the clinical course, and electrographic, imaging, genetic, and neuropathological features in a cohort of female children with pharmacoresistant epilepsy. All five children (mean age 10y) had an early onset of epilepsy during infancy and a predominance of fever sensitive seizures occurring in clusters. Cognitive impairment was noted in four out of five patients...
October 24, 2017: Developmental Medicine and Child Neurology
https://www.readbyqxmd.com/read/29060814/passive-functional-mapping-guides-electrical-cortical-stimulation-for-efficient-determination-of-eloquent-cortex-in-epilepsy-patients
#8
R Prueckl, C Kapeller, J Gruenwald, H Ogawa, K Kamada, M Korostenskaja, J Swift, J Scharinger, W Cho, G Edlinger, C Guger
Electrical cortical stimulation (ECS) is often used in presurgical evaluation procedures for patients suffering from pharmacoresistant epilepsy. Real-time functional mapping (RTFM) is an alternative brain mapping methodology that can accompany traditional functional mapping approaches like ECS. In this paper, we present a combined RTFM/ECS system that aims to exploit the common ground and the advantages of the two procedures for improved time/effort effectiveness, patients' experience and safety. Using the RTFM and ECS data from four patients who suffer epilepsy, we demonstrate that the RTFM-guided ECS procedure hypothetically reduces the number of electrical stimulations necessary for eloquent cortex detection by 40%...
July 2017: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28961159/in-vitro-assessment-of-the-effect-of-antiepileptic-drugs-on-expression-and-function-of-abc-transporters-and-their-interactions-with-abcc2
#9
Gurpreet Kaur Grewal, Samiksha Kukal, Neha Kanojia, Krateeka Madan, Luciano Saso, Ritushree Kukreti
ABC transporters have a significant role in drug disposition and response and various studies have implicated their involvement in epilepsy pharmacoresistance. Since genetic studies till now are inconclusive, we thought of investigating the role of xenobiotics as transcriptional modulators of ABC transporters. Here, we investigated the effect of six antiepileptic drugs (AEDs) viz. phenytoin, carbamazepine, valproate, lamotrigine, topiramate and levetiracetam, on the expression and function of ABCB1, ABCC1, ABCC2 and ABCG2 in Caco2 and HepG2 cell lines through real time PCR, western blot and functional activity assays...
September 29, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28959876/ultrasound-assisted-awake-epilepsy-surgery-for-type-iib-focal-cortical-dysplasia-in-eloquent-areas
#10
Matteo Martinoni, Gianluca Marucci, Stefano Meletti, Lilia Volpi, Roberto Michelucci, Marco Giulioni
INTRODUCTION: Focal cortical dysplasia (FCD) type IIb is a frequent cause of pharmacoresistant epilepsy. However, intraoperative identification of the pathological tissue still remains a challenge despite the use of neuronavigation, particularly when it lies in eloquent areas. CASE REPORT: We here report a case of intraoperative identification of a right frontal FCD type IIB through ultrasound assisted neuronavigation during awake surgery in a patient with drug-resistant epilepsy...
September 28, 2017: Journal of Neurosurgical Sciences
https://www.readbyqxmd.com/read/28956955/a-resurging-boom-in-new-drugs-for-epilepsy-and-brain-disorders
#11
Iyan Younus, Doodipala Samba Reddy
Epilepsy is one of the most common neurological diseases affecting approximately 50 million people worldwide. Despite many advances in epilepsy research, nearly a third of patients with epilepsy have refractory or pharmacoresistant epilepsy. Despite the approval of a dozen antiepileptic drugs (AEDs) over the past decade, there are no agents that halt the development of epilepsy. Thus, newer and better AEDs that can prevent refractory seizures and modify the disease are needed for curing epilepsy. Areas covered: In this article, we highlight the recent advances and emerging trends in new and innovative drugs for epilepsy and seizure disorders...
October 23, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28950818/inflammation-and-epilepsy-preclinical-findings-and-potential-clinical-translation
#12
Gaetano Terrone, Alessia Salamone, Annamaria Vezzani
BACKGROUND: The lack of treatments which can prevent epilepsy development or improve disease prognosis represents an unmet and urgent clinical need. The development of such drugs requires a deep understanding of the mechanisms underlying disease pathogenesis. In the last decade, preclinical studies in models of acute seizures and of chronic epilepsy highlighted that neuroinflammation arising in brain areas of seizure onset and generalization is a key contributor to neuronal hyper-excitability underlying seizure generation...
September 25, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28950221/spontaneous-seizure-remission-following-status-epilepticus-in-drug-resistant-epilepsy-due-to-focal-cortical-dysplasia
#13
Nadine Girard, Eric Guedj, Patrick Chauvel, Fabrice Bartolomei, Aileen McGonigal
We describe a patient with chronic pharmacoresistant epilepsy related to right parietal focal cortical dysplasia (FCD), who became seizure-free following an episode of convulsive status epilepticus (SE). Magnetic resonance imaging (MRI) and fludeoxyglucose positron emission tomography (FDG-PET) were performed before and after SE. Longitudinal MRI scans showed a stable appearance of the FCD with no new signal change. However, diffusion tensor imaging showed altered white matter fiber tract orientation in posterior cortices, especially in proximity to the lesion, at 3 years post-SE...
September 20, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28941835/pharmacoresistance-with-newer-anti-epileptic-drugs-in-mesial-temporal-lobe-epilepsy-with-hippocampal-sclerosis
#14
Michael S Pohlen, Jingxiao Jin, Ronnie S Tobias, Atul Maheshwari
This study aims to evaluate the overall prognosis, prognostic factors, and efficacy of treatment in patients with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) who have access to third generation anti-epileptic drugs but not to epilepsy surgery. Eighty-five MTLE-HS patients were retrospectively placed into a seizure-free (seizure-free for >1year) or drug-resistant group, and the two groups were compared on the basis of age, sex, age at onset of seizures, duration of epilepsy, side of lesion, handedness, EEG findings, history of CNS infection, history of febrile convulsions, history of head trauma, history of cognitive impairment, family history of seizures, number of current anti-epileptic drugs (AEDs), total number of AED trials, and presence of individual AEDs...
November 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28926841/beneficial-combination-of-lacosamide-with-retigabine-in-experimental-animals-an-isobolographic-analysis
#15
Jarogniew J Luszczki, Mirosław Zagaja, Barbara Miziak, Maria W Kondrat-Wrobel, Katarzyna Zaluska, Paula Wroblewska-Luczka, Piotr Adamczuk, Stanislaw J Czuczwar, Magdalena Florek-Luszczki
BACKGROUND/AIM: To isobolographically determine the types of interactions that occur between retigabine and lacosamide (LCM; two third-generation antiepileptic drugs) with respect to their anticonvulsant activity and acute adverse effects (sedation) in the maximal electroshock-induced seizures (MES) and chimney test (motor performance) in adult male Swiss mice. METHODS: Type I isobolographic analysis for nonparallel dose-response effects for the combination of retigabine with LCM (at the fixed-ratio of 1:1) in both the MES and chimney test in mice was performed...
September 20, 2017: Pharmacology
https://www.readbyqxmd.com/read/28919879/automated-online-quantification-method-for-18-f-fdg-positron-emission-tomography-ct-improves-detection-of-the-epileptogenic-zone-in-patients-with-pharmacoresistant-epilepsy
#16
Vanessa Cristina Mendes Coelho, Marcia E Morita, Barbara J Amorim, Celso Darío Ramos, Clarissa L Yasuda, Helder Tedeschi, Enrico Ghizoni, Fernando Cendes
AIMS: To assess the validity of an online method to quantitatively evaluate cerebral hypometabolism in patients with pharmacoresistant focal epilepsy as a complement to the visual analysis of the (18)F-FDG positron emission tomography (PET)/CT exam. METHODS: A total of 39 patients with pharmacoresistant epilepsy and probable focal cortical dysplasia [22 patients with frontal lobe epilepsy (FLE) and 17 with temporal lobe epilepsy (TLE)] underwent a presurgical evaluation including EEG, video-EEG, MRI, and (18)F-FDG PET/CT...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28919768/ictal-heart-rate-changes-and-the-effects-of-vagus-nerve-stimulation-for-patients-with-refractory-epilepsy
#17
Wei Chen, Fan-Gang Meng
Vagus nerve stimulation (VNS) shows long-term efficiency worldwide in most pharmacoresistant patients with epilepsy; however, there are still a small number of patients who are non-responders to VNS therapy. It has been shown that VNS treatment outcomes for drug-resistant epilepsy may be predicted by preoperative heart-rate variability measurements and that patients with epilepsy with ictal tachycardia (IT) during seizures have good responses to VNS. However, few studies have reported the efficacy of VNS in patients with epilepsy with ictal bradycardia (IB) or normal heart rate (HR), and none have explored the possible mechanisms of VNS efficacy based on different HR types...
2017: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/28917501/personalized-translational-epilepsy-research-novel-approaches-and-future-perspectives-part-i-clinical-and-network-analysis-approaches
#18
REVIEW
Felix Rosenow, Natascha van Alphen, Albert Becker, Andreas Chiocchetti, Ralf Deichmann, Thomas Deller, Thomas Freiman, Christine M Freitag, Johannes Gehrig, Anke M Hermsen, Peter Jedlicka, Christian Kell, Karl Martin Klein, Susanne Knake, Dimitri M Kullmann, Stefan Liebner, Braxton A Norwood, Diana Omigie, Karlheinz Plate, Andreas Reif, Philipp S Reif, Yvonne Reiss, Jochen Roeper, Michael W Ronellenfitsch, Stephanie Schorge, Gerhard Schratt, Stephan W Schwarzacher, Joachim P Steinbach, Adam Strzelczyk, Jochen Triesch, Marlies Wagner, Matthew C Walker, Frederic von Wegner, Sebastian Bauer
Despite the availability of more than 15 new "antiepileptic drugs", the proportion of patients with pharmacoresistant epilepsy has remained constant at about 20-30%. Furthermore, no disease-modifying treatments shown to prevent the development of epilepsy following an initial precipitating brain injury or to reverse established epilepsy have been identified to date. This is likely in part due to the polyetiologic nature of epilepsy, which in turn requires personalized medicine approaches. Recent advances in imaging, pathology, genetics and epigenetics have led to new pathophysiological concepts and the identification of monogenic causes of epilepsy...
September 13, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28917498/personalized-translational-epilepsy-research-novel-approaches-and-future-perspectives-part-ii-experimental-and-translational-approaches
#19
REVIEW
Sebastian Bauer, Natascha van Alphen, Albert Becker, Andreas Chiocchetti, Ralf Deichmann, Thomas Deller, Thomas Freiman, Christine M Freitag, Johannes Gehrig, Anke M Hermsen, Peter Jedlicka, Christian Kell, Karl Martin Klein, Susanne Knake, Dimitri M Kullmann, Stefan Liebner, Braxton A Norwood, Diana Omigie, Karlheinz Plate, Andreas Reif, Philipp S Reif, Yvonne Reiss, Jochen Roeper, Michael W Ronellenfitsch, Stephanie Schorge, Gerhard Schratt, Stephan W Schwarzacher, Joachim P Steinbach, Adam Strzelczyk, Jochen Triesch, Marlies Wagner, Matthew C Walker, Frederic von Wegner, Felix Rosenow
Despite the availability of more than 15 new "antiepileptic drugs", the proportion of patients with pharmacoresistant epilepsy has remained constant at about 20-30%. Furthermore, no disease-modifying treatments shown to prevent the development of epilepsy following an initial precipitating brain injury or to reverse established epilepsy have been identified to date. This is likely in part due to the polyetiologic nature of epilepsy, which in turn requires personalized medicine approaches. Recent advances in imaging, pathology, genetics, and epigenetics have led to new pathophysiological concepts and the identification of monogenic causes of epilepsy...
September 13, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28890320/neuropsychologist-s-re-view-resective-versus-ablative-amygdalohippocampectomies
#20
REVIEW
Juri-Alexander Witt, Christian Hoppe, Christoph Helmstaedter
Pharmacoresistant mesial temporal lobe epilepsy (mTLE) represents the major indication for epilepsy surgery. Since epilepsy surgery is an elective treatment option, preserving cognition is a high priority. Given the essential role of temporomesial structures in declarative long-term memory formation, surgical treatment for mTLE is primarily associated with a risk of material-specific memory decline, but other cognitive domains may be affected as well. The major determinants for the neuropsychological outcome are the functional integrity of surgically affected tissues, the functional reserve capacities of the remnant brain, the postoperative seizure outcome, as well as the quantitative and qualitative changes of antiepileptic drugs...
September 1, 2017: Epilepsy Research
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