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Pharmacoresistant epilepsy

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https://www.readbyqxmd.com/read/29789377/polyamine-modulation-of-anticonvulsant-drug-response-a-potential-mechanism-contributing-to-pharmacoresistance-in-chronic-epilepsy
#1
Niklas Michael Beckonert, Thoralf Opitz, Julika Pitsch, Patrício Soares da Silva, Heinz Beck
Despite the development of numerous novel anticonvulsant drugs, approximately 30% of epilepsy patients remain refractory to antiepileptic drugs (AEDs). Many established and novel AEDs reduce hyperexcitability via voltage- and use-dependent inhibition of voltage-gated Na+ channels. For the widely-used anticonvulsant carbamazepine (CBZ), use-dependent block of Na+ channels is significantly reduced both in experimental and human epilepsy. However, the molecular underpinnings of this potential cellular mechanism for pharmacoresistance have remained enigmatic...
May 22, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29786811/-50-percent-of-patients-who-had-epilepsy-surgery-are-seizure-free
#2
Anna Edelvik, Ingrid B Olsson, Tove Hallbook, Kristina Malmgren
About one third of patients with epilepsy do not become seizure-free despite medication. For some, resective epilepsy surgery is the treatment of choice. There are three randomized controlled trials, with positive results at a follow-up of 1-2 years: two on temporal lobe resections on adults and young people and one on all types of epilepsy surgery on children. Since 1990 all epilepsy surgery procedures in Sweden are reported to the Swedish Epilepsy Surgery Register, now with data on almost 1500 patients. Two years after surgery about 50% of adults and children are seizure-free, and another 10% have been so during the last year...
May 22, 2018: Läkartidningen
https://www.readbyqxmd.com/read/29782369/neuroimaging-in-epilepsy
#3
Meneka Kaur Sidhu, John S Duncan, Josemir W Sander
PURPOSE OF REVIEW: Epilepsy neuroimaging is important for detecting the seizure onset zone, predicting and preventing deficits from surgery and illuminating mechanisms of epileptogenesis. An aspiration is to integrate imaging and genetic biomarkers to enable personalized epilepsy treatments. RECENT FINDINGS: The ability to detect lesions, particularly focal cortical dysplasia and hippocampal sclerosis, is increased using ultra high-field imaging and postprocessing techniques such as automated volumetry, T2 relaxometry, voxel-based morphometry and surface-based techniques...
May 17, 2018: Current Opinion in Neurology
https://www.readbyqxmd.com/read/29753683/evaluating-resective-surgery-targets-in-epilepsy-patients-a-comparison-of-quantitative-eeg-methods
#4
Michael Müller, Kaspar Schindler, Marc Goodfellow, Claudio Pollo, Christian Rummel, Andreas Steimer
BACKGROUND: Quantitative analysis of intracranial EEG is a promising tool to assist clinicians in the planning of resective brain surgery in patients suffering from pharmacoresistant epilepsies. Quantifying the accuracy of such tools, however, is nontrivial as a ground truth to verify predictions about hypothetical resections is missing. NEW METHOD: As one possibility to address this, we use customized hypotheses tests to examine the agreement of the methods on a common set of patients...
May 10, 2018: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/29750337/lamotrigine-resistant-corneal-kindled-mice-a-model-of-pharmacoresistant-partial-epilepsy-for-moderate-throughput-drug-discovery
#5
Zachery Koneval, Kevin M Knox, H Steve White, Melissa Barker-Haliski
OBJECTIVE: Despite numerous treatments for epilepsy, over 30% of patients remain resistant to available antiseizure drugs (ASDs). Thus, there is a strong need for more effective ASDs for these individuals. Early ASD discovery has historically relied on acute in vivo seizure models (maximal electroshock, subcutaneous pentylenetetrazol, 6 Hz), which lack the pathophysiology that defines chronic epilepsy. Etiologically relevant rodent models of pharmacoresistant epilepsy exist (eg, phenytoin (PHT)- and lamotrigine (LTG)-resistant amygdala-kindled rat and focal kainic acid mouse), but these models are resource- and labor-intensive and thus unsuitable for frontline ASD discovery...
May 11, 2018: Epilepsia
https://www.readbyqxmd.com/read/29676681/frameless-robot-assisted-stereoelectroencephalography-in-children-technical-aspects-and-comparison-with-talairach-frame-technique
#6
Taylor J Abel, René Varela Osorio, Ricardo Amorim-Leite, Francois Mathieu, Philippe Kahane, Lorella Minotti, Dominique Hoffmann, Stephan Chabardes
OBJECTIVE Robot-assisted stereoelectroencephalography (SEEG) is gaining popularity as a technique for localization of the epileptogenic zone (EZ) in children with pharmacoresistant epilepsy. Here, the authors describe their frameless robot-assisted SEEG technique and report preliminary outcomes and relative complications in children as compared to results with the Talairach frame-based SEEG technique. METHODS The authors retrospectively analyzed the results of 19 robot-assisted SEEG electrode implantations in 17 consecutive children (age < 17 years) with pharmacoresistant epilepsy, and compared these results to 19 preceding SEEG electrode implantations in 18 children who underwent the traditional Talairach frame-based SEEG electrode implantation...
April 20, 2018: Journal of Neurosurgery. Pediatrics
https://www.readbyqxmd.com/read/29672844/longitudinal-positron-emission-tomography-imaging-of-glial-cell-activation-in-a-mouse-model-of-mesial-temporal-lobe-epilepsy-toward-identification-of-optimal-treatment-windows
#7
Duc-Loc Nguyen, Catriona Wimberley, Charles Truillet, Benoit Jego, Fabien Caillé, Géraldine Pottier, Raphaël Boisgard, Irène Buvat, Viviane Bouilleret
OBJECTIVE: Mesiotemporal lobe epilepsy is the most common type of drug-resistant partial epilepsy, with a specific history that often begins with status epilepticus due to various neurological insults followed by a silent period. During this period, before the first seizure occurs, a specific lesion develops, described as unilateral hippocampal sclerosis (HS). It is still challenging to determine which drugs, administered at which time point, will be most effective during the formation of this epileptic process...
April 19, 2018: Epilepsia
https://www.readbyqxmd.com/read/29653328/a-pragmatic-study-on-efficacy-tolerability-and-long-term-acceptance-of-ketogenic-diet-therapy-in-74-south-indian-children-with-pharmacoresistant-epilepsy
#8
Neena Baby, Kollencheri Puthenveettil Vinayan, Nivedita Pavithran, Arun Grace Roy
PURPOSE: Significant challenges exist for Ketogenic Diet (KD) programs in many populations, mainly due to the variations in local dietary preferences. Here we report a single center experience of KD therapy in a cohort of South Indian children with pharmaco-resistant epilepsies. METHODS: Children aged 0-18 years, enrolled in the KD program for pharmacoresistant epilepsies of Amrita institute of Medical Sciences, Kochi, Kerala, India (2010 - 2015) were included in this pragmatic study...
March 21, 2018: Seizure: the Journal of the British Epilepsy Association
https://www.readbyqxmd.com/read/29618099/surgical-treatment-of-extratemporal-epilepsy-results-and-prognostic-factors
#9
Daniel Delev, Bernhard Oehl, Bernhard J Steinhoff, Julia Nakagawa, Christian Scheiwe, Andreas Schulze-Bonhage, Josef Zentner
BACKGROUND: Surgery is a widely accepted option for the treatment of pharmacoresistant epilepsies of extratemporal origin. OBJECTIVE: To analyze clinical and epileptological results and to provide prognostic factors influencing seizure outcome. METHODS: This retrospective single-center study comprises a consecutive series of 383 patients, most of whom had an identifiable lesion on MRI, who underwent resective surgery for extratemporal epilepsy...
March 30, 2018: Neurosurgery
https://www.readbyqxmd.com/read/29605667/epitools-a-software-suite-for-presurgical-brain-mapping-in-epilepsy-intracerebral-eeg
#10
S Medina Villalon, R Paz, N Roehri, S Lagarde, F Pizzo, B Colombet, F Bartolomei, R Carron, C-G Bénar
BACKGROUND: In pharmacoresistant epilepsy, exploration with depth electrodes can be needed to precisely define the epileptogenic zone. Accurate location of these electrodes is thus essential for the interpretation of Stereotaxic EEG (SEEG) signals. As SEEG analysis increasingly relies on signal processing, it is crucial to make a link between these results and patient's anatomy. Our aims were thus to develop a suite of software tools, called "EpiTools", able to i) precisely and automatically localize the position of each SEEG contact and ii) display the results of signal analysis in each patient's anatomy...
March 29, 2018: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/29605572/decreased-ghrelin-and-des-acyl-ghrelin-plasma-levels-in-patients-affected-by-pharmacoresistant-epilepsy-and-maintained-on-the-ketogenic-diet
#11
Maddalena Marchiò, Laura Roli, Carmela Giordano, Tommaso Trenti, Azzurra Guerra, Giuseppe Biagini
BACKGROUND & AIMS: The gastric hormones ghrelin and des-acyl ghrelin have been found to be altered in patients treated with antiepileptic drugs. However, it is unknown if these hormones could be modified by other antiepileptic treatments, such as the ketogenic diet. Especially, a reduction in ghrelin levels could be relevant in view of the growth retardation observed under ketogenic diet treatment. For this reason we aimed to determine the changes in ghrelin and des-acyl ghrelin plasma levels in children affected by refractory epilepsy and treated with the ketogenic diet up to 90 days...
March 23, 2018: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/29600809/radiosurgery-versus-open-surgery-for-mesial-temporal-lobe-epilepsy-the-randomized-controlled-rose-trial
#12
Nicholas M Barbaro, Mark Quigg, Mariann M Ward, Edward F Chang, Donna K Broshek, John T Langfitt, Guofen Yan, Kenneth D Laxer, Andrew J Cole, Penny K Sneed, Christopher P Hess, Wei Yu, Manjari Tripathi, Christianne N Heck, John W Miller, Paul A Garcia, Andrew McEvoy, Nathan B Fountain, Vincenta Salanova, Robert C Knowlton, Anto Bagić, Thomas Henry, Siddharth Kapoor, Guy McKhann, Adriana E Palade, Markus Reuber, Evelyn Tecoma
OBJECTIVE: To compare stereotactic radiosurgery (SRS) versus anterior temporal lobectomy (ATL) for patients with pharmacoresistant unilateral mesial temporal lobe epilepsy (MTLE). METHODS: This randomized, single-blinded, controlled trial recruited adults eligible for open surgery among 14 centers in the USA, UK, and India. Treatment was either SRS at 24 Gy to the 50% isodose targeting mesial structures, or standardized ATL. Outcomes were seizure remission (absence of disabling seizures between 25 and 36 months), verbal memory (VM), and quality of life (QOL) at 36-month follow-up...
March 30, 2018: Epilepsia
https://www.readbyqxmd.com/read/29588990/time-to-push-the-age-limit-epilepsy-surgery-in-patients-60-years-or-older
#13
Vineet Punia, Ahmed Abdelkader, Robyn M Busch, Jorge Gonzalez-Martinez, William Bingaman, Imad Najm, Andrey Stojic
Objective: To summarize the existing literature on resective epilepsy surgery (RES) in older adults (≥60 years old) and examine seizure and neuropsychological outcomes in a single-center large cohort of older adults undergoing RES and their comparison to a consecutive, younger (25- to45-year-old) adult population who underwent RES in routine clinical practice. Methods: First, a comprehensive literature review was performed. Then, we identified older adults who underwent RES at our center (2000-2015)...
March 2018: Epilepsia open
https://www.readbyqxmd.com/read/29565791/animal-models-of-status-epilepticus-and-temporal-lobe-epilepsy-a-narrative-review
#14
Nikita Nirwan, Preeti Vyas, Divya Vohora
Temporal lobe epilepsy (TLE) is the chronic and pharmacoresistant form of epilepsy observed in humans. The current literature is insufficient in explicating the comprehensive mechanisms underlying its pathogenesis and advancement. Consequently, the development of a suitable animal model mimicking the clinical characteristics is required. Further, the relevance of status epilepticus (SE) to animal models is dubious. SE occurs rarely in people; most epilepsy patients never experience it. The present review summarizes the established animal models of SE and TLE, along with a brief discussion of the animal models that have the distinctiveness and carries the possibility to be developed as effective models for TLE...
March 22, 2018: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/29563872/the-metabotropic-purinergic-p2y-receptor-family-as-novel-drug-target-in-epilepsy
#15
REVIEW
Mariana Alves, Edward Beamer, Tobias Engel
Epilepsy encompasses a heterogeneous group of neurological syndromes which are characterized by recurrent seizures affecting over 60 million people worldwide. Current anti-epileptic drugs (AEDs) are mainly designed to target ion channels and/or GABA or glutamate receptors. Despite recent advances in drug development, however, pharmacoresistance in epilepsy remains as high as 30%, suggesting the need for the development of new AEDs with a non-classical mechanism of action. Neuroinflammation is increasingly recognized as one of the key players in seizure generation and in the maintenance of the epileptic phenotype...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29554343/stereoelectroencephalography-guided-laser-ablations-in-patients-with-neocortical-pharmacoresistant-focal-epilepsy-concept-and-operative-technique
#16
Louis Ross, Ahsan M Naduvil, Juan C Bulacio, Imad M Najm, Jorge A Gonzalez-Martinez
BACKGROUND: Laser ablation surgery has had encouraging results in the treatment of multiple intracranial diseases including primary and metastatic brain tumors, radiation necrosis, and epilepsy. The use of the stereoelectroencephalography (SEEG) method in combination with laser thermocoagulation therapy with the goal of modulating epileptic networks in patients with neocortical nonlesional phamacoresistant epilepsy has not been previously described. OBJECTIVE: To describe the novel methodological and conceptual aspects related to SEEG-guided laser ablations in patients with magnetic resonance imaging (MRI)-negative pharmacoresistant neocortical focal epilepsy...
March 14, 2018: Operative Neurosurgery (Hagerstown, Md.)
https://www.readbyqxmd.com/read/29550061/lesion-focused-radiofrequency-thermocoagulation-of-bottom-of-sulcus-focal-cortical-dysplasia-type-iib-conceptional-considerations-with-regard-to-the-epileptogenic-zone
#17
Jörg Wellmer
Small bottom-of-sulcus focal cortical dysplasias (BOS-FCD) type IIb are intrinsically epileptogenic lesions often responsible for pharmacoresistant epilepsy. They are increasingly well demarcated in vivo from surrounding cortex and white matter by 3 T magnetic resonance imaging (MRI). These facts and frequent seizure freedom after just narrow resections allow questioning the classical concept of epilepsy surgery in which the epileptogenic lesion is generally considered only one part of the epileptogenic zone and the resection volume categorically has to exceed lesion limits...
May 2018: Epilepsy Research
https://www.readbyqxmd.com/read/29526578/cannabidiol-for-treatment-of-refractory-childhood-epilepsies-experience-from-a-single-tertiary-epilepsy-center-in-slovenia
#18
David Neubauer, Mirjana Perković Benedik, Damjan Osredkar
PURPOSE: Refractory epilepsies in children present a major burden for patients and their families. Cannabidiol (CBD) has been suggested as a potential treatment for refractory epilepsies. The aim of this study was to evaluate the effectiveness of add-on therapy with CBD for the treatment of refractory childhood epilepsies. METHOD: Patients with childhood-onset refractory epilepsy, treated at the tertiary epilepsy center of the University Children's Hospital Ljubljana, Slovenia, were included in the study...
April 2018: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/29490292/top3b-a-novel-candidate-gene-in-juvenile-myoclonic-epilepsy
#19
Marwa Daghsni, Saida Lahbib, Mohamed Fradj, Marwa Sayeb, Wided Kelmemi, Lilia Kraoua, Mariem Kchaou, Faouzi Maazoul, Slim Echebbi, Nadia Ben Ali, Sonia Abdelhak, Ridha M'rad
Juvenile myoclonic epilepsy (JME) is characterized by seizures, severe cognitive abnormalities, and behavior impairments. These features could evolve over time and get worse, especially when the encephalopathy is pharmacoresistant. Thus, genetic studies should provide a better understanding of infantile epilepsy syndromes. Herein, we investigate the genetics of JME in a consanguineous family analyzing the copy number variations detected using over 700 K SNP arrays. We identified a 254-kb deletion in the 22q11...
2018: Cytogenetic and Genome Research
https://www.readbyqxmd.com/read/29476662/new-clinicopathological-associations-and-histoprognostic-markers-in-ilae-types-of-hippocampal-sclerosis
#20
Ana Laura Calderon-Garcidueñas, Bertrand Mathon, Pierre Lévy, Anne Bertrand, Karima Mokhtari, Véronique Samson, Valérie Thuriès, Virginie Lambrecq, Vi-Huong Michel Nguyen, Sophie Dupont, Claude Adam, Michel Baulac, Stéphane Clémenceau, Charles Duyckaerts, Vincent Navarro, Franck Bielle
Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is a heterogeneous syndrome. Surgery results in seizure freedom for most pharmacoresistant patients, but the epileptic and cognitive prognosis remains variable. The 2013 International League Against Epilepsy (ILAE) histopathological classification of hippocampal sclerosis (HS) has fostered research to understand MTLE-HS heterogeneity. We investigated the associations between histopathological features (ILAE types, hypertrophic CA4 neurons, granule cell layer alterations, CD34 immunopositive cells) and clinical features (presurgical history, postsurgical outcome) in a monocentric series of 247 MTLE-HS patients treated by surgery...
February 24, 2018: Brain Pathology
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