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Akshanth R Polepally, Richard C Brundage, Rory P Remmel, Ilo E Leppik, Page B Pennell, James R White, R Eugene Ramsay, Brett M Kistner, Angela K Birnbaum
OBJECTIVE: The objectives of this study were to investigate the effect of age on pharmacokinetic parameters of lamotrigine (LTG) and estimate parameter variability. METHODS: Patients (>18 years old) who were already on a steady-state dose of LTG therapy with no interacting comedications were enrolled. Patients with significant cardiac disease, severe kidney dysfunction, or moderate-to-severe liver dysfunction were excluded. Fifty milligrams of a stable-labeled intravenous LTG formulation (SL-LTG) replaced 50 mg of a patient's normal daily oral LTG dose...
August 12, 2018: Epilepsia
Ruth Ottman, Catharine Freyer, Heather C Mefford, Annapurna Poduri, Daniel H Lowenstein
Genomic findings are emerging rapidly in 2 large, closely related epilepsy research consortia: the Epilepsy Phenome/Genome Project and Epi4K. Disclosure of individual results to participants in genomic research is increasingly viewed as an ethical obligation, but strategies for return of results were not included in the design of these consortia, raising complexities in establishing criteria for which results to offer, determining participant preferences, managing the large number of sites involved, and covering associated costs...
August 10, 2018: Epilepsia
Sharon Samueli, Anastasia Dressler, Gudrun Gröppel, Theresa Scholl, Martha Feucht
Tuberous sclerosis complex (TSC) is the most common cause of West syndrome (WS). Currently available treatment options are ineffective in the majority of affected infants and/or associated with potential serious side effects. Based on the assumption that mTOR overactivation results in increased neuroexcitability in TSC, mTOR inhibitors have been studied as antiseizure therapy. As a result, everolimus recently received approval for the adjunctive treatment of patients aged ≥2 years with refractory TSC-associated focal and secondary generalized seizures...
August 10, 2018: Epilepsia
Martha Sajatovic, Kari Colon-Zimmermann, Mustafa Kahriman, Edna Fuentes-Casiano, Hongyan Liu, Curtis Tatsuoka, Kristin A Cassidy, Samden Lhatoo, Douglas Einstadter, Peijun Chen
OBJECTIVE: Despite advances in care, many people with epilepsy have negative health events (NHEs) such as accidents, emergency department visits, and poor quality of life. "Self-management for people with epilepsy and a history of negative health events" (SMART) is a novel group format epilepsy self-management intervention. A community participatory approach informed the refinement of SMART, which was then tested in a 6-month randomized controlled trial of SMART (n = 60) versus waitlist control (WL, n = 60)...
August 10, 2018: Epilepsia
Ezequiel Gleichgerrcht, Brent Munsell, Sonal Bhatia, William A Vandergrift, Chris Rorden, Carrie McDonald, Jonathan Edwards, Ruben Kuzniecky, Leonardo Bonilha
OBJECTIVE: We evaluated whether deep learning applied to whole-brain presurgical structural connectomes could be used to predict postoperative seizure outcome more accurately than inference from clinical variables in patients with mesial temporal lobe epilepsy (TLE). METHODS: Fifty patients with unilateral TLE were classified either as having persistent disabling seizures (SZ) or becoming seizure-free (SZF) at least 1 year after epilepsy surgery. Their presurgical structural connectomes were reconstructed from whole-brain diffusion tensor imaging...
August 10, 2018: Epilepsia
Bo Zhang, Jia Zou, Lirong Han, Brennan Beeler, Joseph L Friedman, Elizabeth Griffin, Yue-Shan Piao, Nicholas R Rensing, Michael Wong
OBJECTIVE: Microglial abnormalities have been reported in pathologic specimens from patients with tuberous sclerosis complex (TSC), a genetic disorder characterized by epilepsy, intellectual disability, and autism. However, the pathogenic role of microglia in epilepsy in TSC is poorly understood, particularly whether microglia defects may be a primary contributor to epileptogenesis or are secondary to seizures or simply epiphenomena. In this study, we tested the hypothesis that Tsc1 gene inactivation in microglia is sufficient to cause epilepsy in mouse models of TSC...
August 5, 2018: Epilepsia
Yin Jiang, Chun-Lei Han, Huan-Guang Liu, Xiu Wang, Xin Zhang, Fan-Gang Meng, Jian-Guo Zhang
OBJECTIVE: Although abnormal hippocampal structure and impaired spatial memory have been revealed in a pilocarpine rat model of temporal lobe epilepsy (TLE), the brain functional network changes are still unclear. The aim of the present study was to investigate the changes of brain functional connectivity related to the hippocampus and the associated memory impairment in a pilocarpine model of TLE. METHODS: Functional magnetic resonance imaging signals were recorded in pilocarpine-treated rats and controls by using a 7...
August 2, 2018: Epilepsia
Vicente Villanueva, Javier Montoya, Ascension Castillo, José Á Mauri-Llerda, Pau Giner, Francisco J López-González, Anna Piera, Pedro Villanueva-Hernández, Vicente Bertol, Alejandro Garcia-Escrivá, Juan J Garcia-Peñas, Iñigo Garamendi, Patricia Esteve-Belloch, Juan J Baiges-Octavio, Júlia Miró, Mercè Falip, Mercedes Garcés, Asier Gómez, Francisco J Gil-López, Mar Carreño, Juan J Rodriguez-Uranga, Dulce Campos, Macarena Bonet, Rosa Querol, Albert Molins, Diego Tortosa, Javier Salas-Puig
OBJECTIVE: To analyze the effectiveness and tolerability of perampanel across different seizure types in routine clinical care of patients with idiopathic generalized epilepsy (IGE). METHODS: This multicenter, retrospective, 1-year observational study collected data from patient records at 21 specialist epilepsy units in Spain. All patients who were aged ≥12 years, prescribed perampanel before December 2016, and had a confirmed diagnosis of IGE were included. RESULTS: The population comprised 149 patients with IGE (60 with juvenile myoclonic epilepsy, 51 generalized tonic-clonic seizures [GTCS] only, 21 juvenile absence epilepsy, 10 childhood absence epilepsy, 6 adulthood absence epilepsy, and one Jeavons syndrome)...
July 31, 2018: Epilepsia
Alexandra Rohracher, Georg Zimmermann, Vicente Villanueva, Iñigo Garamendi, Josemir W Sander, Tim Wehner, Rohit Shankar, Elinor Ben-Menachem, Martin J Brodie, Max C Pensel, Giancarlo Di Gennaro, Aude Maurousset, Adam Strzelczyk, Sylvain Rheims, Attila Rácz, Katja Menzler, Vicente Bertol-Alegre, Irene García-Morales, Francisco Javier López-González, Manuel Toledo, Katherine J Carpenter, Eugen Trinka
OBJECTIVE: To pool observational data on the routine use of perampanel to obtain information on real-world outcomes and data in populations typically underrepresented in clinical trials. METHODS: Individual-level data of people with epilepsy treated with perampanel at 45 European centers were merged into a single dataset. Prespecified outcomes were: 1-year retention rate, 1-year seizure freedom rate (duration ≥6 months), and incidence of treatment-emergent adverse events (TEAEs)...
July 25, 2018: Epilepsia
Gudrun Kalss, Alexandra Rohracher, Markus Leitinger, Georg Pilz, Helmut F Novak, Caroline Neuray, Rudolf Kreidenhuber, Julia Höfler, Giorgi Kuchukhidze, Eugen Trinka
Brivaracetam (BRV) is a high-affinity synaptic vesicle glycoprotein 2A ligand that is structurally related to levetiracetam (LEV). Compared to LEV, its affinity to the ligand is >10%-30% higher. Due to its more lipophilic characteristics, it might have a quicker penetration across the blood-brain barrier and potentially also a stronger anticonvulsant effect. Thus, we aimed to explore its usefulness in the treatment of status epilepticus (SE). We retrospectively assessed treatment response and adverse events in adjunctive treatment with intravenous BRV in patients with SE from January 2016 to July 2017 at our institution...
July 25, 2018: Epilepsia
Alexandra Rohracher, Gudrun Kalss, Caroline Neuray, Julia Höfler, Judith Dobesberger, Giorgi Kuchukhidze, Rudolf Kreidenhuber, Cristina Florea, Aljoscha Thomschewski, Helmut F Novak, Georg Pilz, Markus Leitinger, Eugen Trinka
In refractory status epilepticus (SE), γ-aminobutyric acidergic drugs become less effective and glutamate plays a major role in seizure perpetuation. Data on the efficacy of perampanel (PER) in treatment of refractory SE in humans are limited. Here, we present a single-center case series of patients with refractory SE who received PER orally in an intensive care unit. We retrospectively analyzed treatment response, outcome, and adverse effects of all patients with refractory SE in our Neurological Intensive Care Unit who received add-on PER between September 2012 and February 2018...
July 25, 2018: Epilepsia
Patrizia Aracri, Marco de Curtis, Greta Forcaia, Laura Uva
OBJECTIVE: The key factors that promote the termination of focal seizures have not been fully clarified. The buildup of neuronal synchronization during seizures has been proposed as one of the possible activity-dependent, self-limiting mechanisms. We investigate if increased thalamo-cortical coupling contributes to enhance synchronization during the late phase of focal seizure-like events (SLEs) generated in limbic regions. METHODS: Recordings were simultaneously performed in the nucleus reuniens of the thalamus, in the hippocampus and in the entorhinal cortex of the isolated guinea pig brain during focal bicuculline-induced SLEs with low voltage fast activity at onset...
July 23, 2018: Epilepsia
Prasanna Jayakar, Anuj Jayakar, Mark Libenson, Alexis Arzimanoglou, Bertil Rhydenhag, J Helen Cross, Sanjiv Bhatia, Laura Tassi, Deepak Lachhwani, William D Gaillard
OBJECTIVE: We aimed to investigate the current practices guiding surgical resection strategies involving epileptogenic zones (EZs) near or in eloquent cortex (EC) at pediatric epilepsy surgery centers worldwide. METHODS: A survey was conducted among 40 respondents from 33 pediatric epilepsy surgery centers worldwide on the weight assigned to diagnostic tests used to define the EZ and EC, how EC is viewed, and how surgeries are planned for foci near or in eloquent cortex...
July 22, 2018: Epilepsia
Lora D Weidner, Pavitra Kannan, Nicholas Mitsios, Sun J Kang, Matthew D Hall, William H Theodore, Robert B Innis, Jan Mulder
OBJECTIVE: The role of neuroinflammation in mesial temporal lobe epilepsy (MTLE), and how it relates to drug resistance, remains unclear. Expression levels of the inflammatory enzymes cyclooxygenase (COX)-1 and COX-2 have been found to be increased in animal models of epilepsy. Knowing the cellular expression of COX-1 and COX-2 is the key to understanding their functional role; however, only 3 studies have investigated COX-2 expression in epilepsy in humans, and there are no reports on COX-1...
July 21, 2018: Epilepsia
Martin Salinsky, Victoria S S Wong, Paul Motika, Justin Meuse, Joseph Nguyen
OBJECTIVE: To determine the frequency and yield of neuroimaging in patients with known seizure disorders presenting to the emergency department (ED) with recurrent (nonindex) seizures. METHODS: We reviewed 822 consecutive ED visits for nonindex seizures at the Oregon Health & Science University and the VA Portland Health Care System. For each visit, we abstracted details of the clinical presentation, whether neuroimaging was obtained, the results of neuroimaging, and the results of previous neuroimaging studies, when available...
July 18, 2018: Epilepsia
Natasha E Schoeler, Costin Leu, Simona Balestrini, Jonathan M Mudge, Charles A Steward, Adam Frankish, Mary-Anne Leung, Mark Mackay, Ingrid Scheffer, Ruth Williams, Josemir W Sander, J Helen Cross, Sanjay M Sisodiya
OBJECTIVE: With the exception of specific metabolic disorders, predictors of response to ketogenic dietary therapies (KDTs) are unknown. We aimed to determine whether common variation across the genome influences the response to KDT for epilepsy. METHODS: We genotyped individuals who were negative for glucose transporter type 1 deficiency syndrome or other metabolic disorders, who received KDT for epilepsy. Genotyping was performed with the Infinium HumanOmniExpressExome Beadchip...
July 16, 2018: Epilepsia
Christian Vollmar, Iris Stredl, Matthias Heinig, Soheyl Noachtar, Jan Rémi
OBJECTIVE: To evaluate the necessity of recording ictal electroencephalography (EEG) in patients with temporal lobe epilepsy (TLE) considered for resective surgery who have unilateral temporal interictal epileptiform discharges (IEDs) and concordant ipsitemporal magnetic resonance imaging (MRI) pathology. To calculate the necessary number of recorded EEG seizure patterns (ESPs) to achieve adequate lateralization probability. METHODS: In a retrospective analysis, the localization and lateralization of interictal and ictal EEG of 304 patients with lesional TLE were analyzed...
July 15, 2018: Epilepsia
Steve A Gibbs, Paola Proserpio, Stefano Francione, Roberto Mai, Massimo Cossu, Laura Tassi, Lino Nobili
Sleep-related hypermotor epilepsy (SHE) is an epilepsy syndrome that is characterized by the occurrence of sleep-related hypermotor seizures of variable complexity and duration. Seizures usually arise in the frontal lobe, but extrafrontal seizure onset zones are well described. To identify clinically relevant ictal features of SHE that could distinguish a frontal from an extrafrontal onset zone, we conducted a retrospective analysis of seizure characteristics in 58 patients with drug-resistant SHE (43 frontal and 15 extrafrontal) who underwent video-stereo-electroencephalographic recordings and became seizure-free after epilepsy surgery...
July 15, 2018: Epilepsia
Hongying Ma, Shenglei Feng, Xuejun Deng, Li Wang, Sheng Zeng, Cheng Wang, Xixiang Ma, Hao Sun, Rui Chen, Shiyue Du, Jinglin Mao, Xianwei Zhang, Cong Ma, Hong Jiang, Luoying Zhang, Beisha Tang, Jing Yu Liu
OBJECTIVE: To identify the causative gene of autosomal dominant paroxysmal kinesigenic dyskinesia and benign familial infantile seizures (PKD/BFIS) in a large Chinese family and explore the potential pathogenic mechanism of a PRRT2 (proline-rich transmembrane protein 2) variant. METHODS: Genetic testing was performed via whole exome sequencing. Western blotting and immunofluorescence were used to analyze the protein expression level and subcellular localization of the PRRT2 mutant in HeLa cells and N2A cells...
July 15, 2018: Epilepsia
Rod C Scott, Liset Menendez de la Prida, J Matt Mahoney, Katja Kobow, Raman Sankar, Marco de Curtis
The brain is a complex system composed of networks of interacting elements, from genes to circuits, whose function (and dysfunction) is not derivable from the superposition of individual components. Epilepsy is frequently described as a network disease, but to date, there is no standardized framework within which network concepts applicable to all levels from genes to whole brain can be used to generate deeper insights into the pathogenesis of seizures or the associated morbidities. To address this shortcoming, the Neurobiology Commission of the International League Against Epilepsy dedicated a Workshop on Neurobiology of Epilepsy (XIV WONOEP 2017) with the aim of formalizing network concepts as they apply to epilepsy and to critically discuss whether and how such concepts could augment current research endeavors...
July 15, 2018: Epilepsia
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