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Denson G Fujikawa
Ketamine is currently being used as an anesthetic/antiepileptic drug in refractory status epilepticus. To validate its use, 2 clinical trials are recruiting patients. However, preclinical studies of its use in chemically induced status epilepticus in rodents have shown that it is remarkably neuroprotective, through N-methyl-d-aspartate-receptor blockade, even when given after the onset of status epilepticus. Human studies have shown that status epilepticus-induced brain damage can be caused by a glutamate analogue and that it occurs in the same brain regions as in the animal studies...
February 19, 2019: Epilepsia
Michal B Juda, Alexandra K Brooks, Albert E Towers, Gregory G Freund, Robert H McCusker, Andrew J Steelman
OBJECTIVE: Viral encephalitis increases the risk for developing seizures and epilepsy. Indoleamine 2,3-dioxygenase 1 (Ido1) is induced by inflammatory cytokines and functions to metabolize tryptophan to kynurenine. Kynurenine can be further metabolized to produce kynurenic acid and the N-methyl-d-aspartate receptor agonist quinolinic acid (QuinA). In the present study, we sought to determine the role of Ido1 in promoting seizures in an animal model of viral encephalitis. METHODS: C57BL/6J and Ido1 knockout mice (Ido1-KO) were infected with Theiler's murine encephalomyelitis virus (TMEV)...
February 15, 2019: Epilepsia
Cristina Filipescu, Stanislas Lagarde, Isabelle Lambert, Francesca Pizzo, Agnès Trébuchon, Aileen McGonigal, Didier Scavarda, Romain Carron, Fabrice Bartolomei
We investigated the effect of electrical stimulation of the medial pulvinar (PuM) in terms of its effect on temporal lobe seizures. Eight patients with drug-resistant temporal lobe epilepsy undergoing stereoelectroencephalographic exploration were included. All had at least one electrode exploring the PuM. High-frequency (50 Hz) stimulations of the PuM were well tolerated in the majority of them. During diagnostic stimulation to confirm the epileptogenic zone, 19 seizures were triggered by stimulating the hippocampus...
February 14, 2019: Epilepsia
Rup K Sainju, Deidre N Dragon, Harold B Winnike, Marcus B Nashelsky, Mark A Granner, Brian K Gehlbach, George B Richerson
OBJECTIVE: Severe periictal respiratory depression is thought to be linked to risk of sudden unexpected death in epilepsy (SUDEP) but its determinants are largely unknown. Interindividual differences in the interictal ventilatory response to CO2 (hypercapnic ventilatory response [HCVR] or central respiratory CO2 chemosensitivity) may identify patients who are at increased risk for severe periictal hypoventilation. HCVR has not been studied previously in patients with epilepsy; therefore we evaluated a method to measure it at bedside in an epilepsy monitoring unit (EMU) and examined its relationship to postictal hypercapnia following generalized convulsive seizures (GCSs)...
February 12, 2019: Epilepsia
Cato M Drion, Lieneke Kooijman, Eleonora Aronica, Erwin A van Vliet, Wytse J Wadman, Pascal Chameau, Jan A Gorter
OBJECTIVE: Inhibition of the mammalian target of rapamycin (mTOR) pathway could be antiepileptogenic in temporal lobe epilepsy (TLE), possibly via anti-inflammatory actions. We studied effects of the mTOR inhibitor rapamycin and the anti-inflammatory compound curcumin-also reported to inhibit the mTOR pathway-on epileptogenesis and inflammation in an in vitro organotypic hippocampal-entorhinal cortex slice culture model. METHODS: Brain slices containing hippocampus and entorhinal cortex were obtained from 6-day-old rat pups and maintained in culture for up to 3 weeks...
February 12, 2019: Epilepsia
Robert A McGovern, Paul Ruggieri, Juan Bulacio, Imad Najm, William E Bingaman, Jorge A Gonzalez-Martinez
OBJECTIVE: To examine the true incidence of hemorrhage related to stereo-electroencephalography (SEEG) procedures. To analyze risk factors associated with the presence of different types of hemorrhage in SEEG procedures. METHODS: This was a retrospective, single-center observational study examining every SEEG implantation performed at our center from 2009 to 2017. This consisted of 549 consecutive SEEG implantations using a variety of stereotactic and imaging techniques...
February 12, 2019: Epilepsia
Rachel Rolinski, Alison Austermuehle, Edythe Wiggs, Shubhi Agrawal, Leigh N Sepeta, William D Gaillard, Kareem A Zaghloul, Sara K Inati, William H Theodore
OBJECTIVE: To assess the ability of functional MRI (fMRI) to predict postoperative language decline compared to direct cortical stimulation (DCS) in epilepsy surgery patients. METHODS: In this prospective case series, 17 patients with drug-resistant epilepsy had intracranial monitoring and resection from 2012 to 2016 with 1-year follow-up. All patients completed preoperative language fMRI, mapping with DCS of subdural electrodes, pre- and postoperative neuropsychological testing for language function, and resection...
February 11, 2019: Epilepsia
Elizabeth Thiele, Eric Marsh, Maria Mazurkiewicz-Beldzinska, Jonathan J Halford, Boudewijn Gunning, Orrin Devinsky, Daniel Checketts, Claire Roberts
OBJECTIVE: Patients with Lennox-Gastaut syndrome (LGS) who completed 1 of 2 randomized, double-blind, placebo-controlled trials of add-on cannabidiol (CBD) (GWPCARE3, NCT02224560 or GWPCARE4, NCT02224690) were invited to enroll in an open-label extension (OLE) study evaluating the long-term safety and efficacy of CBD (GWPCARE5, NCT02224573). Herein we present an interim analysis of the safety, efficacy, and patient-reported outcomes from this trial. METHODS: Patients received a pharmaceutical formulation of highly purified CBD oral solution (Epidiolex; 100 mg/mL), titrated from 2...
February 11, 2019: Epilepsia
Olga Taraschenko, Howard S Fox, Sean J Pittock, Anastasia Zekeridou, Maftuna Gafurova, Ember Eldridge, Jinxu Liu, Shashank M Dravid, Raymond Dingledine
OBJECTIVE: Seizures develop in 80% of patients with anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis, and these represent a major cause of morbidity and mortality. Anti-NMDAR antibodies have been linked to memory loss in encephalitis; however, their role in seizures has not been established. We determined whether anti-NMDAR antibodies from autoimmune encephalitis patients are pathogenic for seizures. METHODS: We performed continuous intracerebroventricular infusion of cerebrospinal fluid (CSF) or purified immunoglobulin (IgG) from the CSF of patients with anti-NMDAR encephalitis or polyclonal rabbit anti-NMDAR IgG, in male C57BL/6 mice...
February 11, 2019: Epilepsia
Xiaozhen You, Ashley N Zachery, Eleanor J Fanto, Gina Norato, Sierra C Germeyan, Eric J Emery, Leigh N Sepeta, Madison M Berl, Chelsea L Black, Edythe Wiggs, Kareem Zaghloul, Sara K Inati, William D Gaillard, William H Theodore
OBJECTIVE: We aimed to predict language deficits after epilepsy surgery. In addition to evaluating surgical factors examined previously, we determined the impact of the extent of functional magnetic resonance imaging (fMRI) activation that was resected on naming ability. METHOD: Thirty-five adults (mean age 37.5 ± 10.9 years, 13 male) with temporal lobe epilepsy completed a preoperative fMRI auditory description decision task, which reliably activates frontal and temporal language networks...
February 11, 2019: Epilepsia
Ravindra Arya, Brian Ervin, J Adam Wilson, Anna W Byars, Leonid Rozhkov, Jason Buroker, Paul S Horn, Craig Scholle, Hisako Fujiwara, Hansel M Greiner, James L Leach, Douglas F Rose, Francesco T Mangano, Tracy A Glauser, Katherine D Holland
OBJECTIVE: We studied age-related dynamics of information sharing among cortical language regions with electrocorticographic high-gamma modulation during picture-naming and story-listening tasks. METHODS: Seventeen epilepsy patients aged 4-19 years, undergoing extraoperative monitoring with left-hemispheric subdural electrodes, were included. Mutual information (MI), a nondirectional measure of shared information, between 16 pairs of cortical regions of interest, was computed from trial-averaged 70-150 Hz power modulations during language tasks...
February 11, 2019: Epilepsia
Chayanin Tangwiriyasakul, Suejen Perani, Eugenio Abela, David W Carmichael, Mark P Richardson
Recent evidence suggests that three specific brain networks show state-dependent levels of synchronization before, during, and after episodes of generalized spike-wave discharges (GSW) in patients with genetic generalized epilepsy (GGE). Here, we investigate whether synchronization in these networks differs between patients with GGE (n = 13), their unaffected first-degree relatives (n = 17), and healthy controls (n = 18). All subjects underwent two 10-minute simultaneous electroencephalographic-functional magnetic resonance imaging (fMRI) recordings without GSW...
February 7, 2019: Epilepsia
Stephen W Kruse, Kyle G Dayton, Benton S Purnell, Jared I Rosner, Gordon F Buchanan
OBJECTIVE: Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in patients with refractory epilepsy. Although the mechanisms for SUDEP are incompletely understood, seizure-induced respiratory arrest (S-IRA) has been strongly and consistently implicated. A body of evidence indicates that serotonin (5-HT), a modulator of breathing, plays a critical role in SUDEP. Because the 5-HT and norepinephrine (NE) systems interact in many biologic processes and NE is known to modulate breathing and seizures, we hypothesized that NE may play a role in S-IRA and SUDEP...
February 5, 2019: Epilepsia
Michael Tan, Ray Boston, Mark J Cook, Wendyl J D'Souza
OBJECTIVE: There remains a paucity of knowledge regarding specific epilepsy-related risk factors for accidents and injuries in people with epilepsy. Injury studies in people with epilepsy are overrepresented, with tertiary based populations that are prone to bias from severe disease. This study aims to assess the contribution of epilepsy-related risk factors to injuries in a community-based cohort. METHODS: We performed a retrospective nested case-control study on patients recruited into the Tasmanian Epilepsy Register (TER) from July 1, 2001 to June 30, 2002...
February 5, 2019: Epilepsia
Meng Wang, David A Greenberg, William C L Stewart
OBJECTIVE: Genetic generalized epilepsy (GGE) consists of epileptic syndromes with overlapping symptoms and is considered to be largely genetic. Previous cosegregation and association studies have pointed to malic enzyme 2 (ME2) as a candidate susceptibility gene for adolescent-onset GGE. In this article, we present new evidence supporting ME2's involvement in GGE. METHODS: To definitively test ME2's influence on GGE, we used 3 different approaches. First, we compared a newly recruited GGE cohort with an ethnically matched reference sample from 1000 Genomes Project, using an efficient test of association (POPFAM+)...
February 4, 2019: Epilepsia
Herbert Schulz, Ann-Kathrin Ruppert, Federico Zara, Francesca Madia, Michele Iacomino, Maria S Vari, Ganna Balagura, Carlo Minetti, Pasquale Striano, Amedeo Bianchi, Carla Marini, Renzo Guerrini, Yvonne G Weber, Felicitas Becker, Holger Lerche, Claudia Kapser, Christoph J Schankin, Wolfram S Kunz, Rikke S Møller, Karen L Oliver, Susannah T Bellows, Saul A Mullen, Samuel F Berkovic, Ingrid E Scheffer, Hande Caglayan, Ugur Ozbek, Per Hoffmann, Sara Schramm, Despina Tsortouktzidis, Albert J Becker, Thomas Sander
Juvenile myoclonic epilepsy (JME) is a common syndrome of genetic generalized epilepsies (GGEs). Linkage and association studies suggest that the gene encoding the bromodomain-containing protein 2 (BRD2) may increase risk of JME. The present methylation and association study followed up a recent report highlighting that the BRD2 promoter CpG island (CpG76) is differentially hypermethylated in lymphoblastoid cells from Caucasian patients with JME compared to patients with other GGE subtypes and unaffected relatives...
February 4, 2019: Epilepsia
Srinivasan Tupal, Carl L Faingold
OBJECTIVE: Prevention of sudden unexpected death in epilepsy (SUDEP) is a critical goal for epilepsy therapy. The DBA/1 mouse model of SUDEP exhibits an elevated susceptibility to seizure-induced death in response to electroconvulsive shock, hyperthermia, convulsant drug, and acoustic stimulation. The serotonin hypothesis of SUDEP is based on findings that treatments which modify serotonergic function significantly alter susceptibility to seizure-induced sudden death in several epilepsy models, including DBA/1 mice...
February 4, 2019: Epilepsia
Yasuo Nakai, Ayaka Sugiura, Erik C Brown, Masaki Sonoda, Jeong-Won Jeong, Robert Rothermel, Aimee F Luat, Sandeep Sood, Eishi Asano
OBJECTIVE: The strength of presurgical language mapping using electrocorticography (ECoG) is its outstanding signal fidelity and temporal resolution, but the weakness includes limited spatial sampling at an individual patient level. By averaging naming-related high-gamma activity at nonepileptic regions across a large number of patients, we provided the functional cortical atlases animating the neural dynamics supporting visual-object and auditory-description naming at the whole brain level...
February 1, 2019: Epilepsia
McKenna Kelly, Meredith Park, Ivana Mihalek, Anne Rochtus, Marie Gramm, Eduardo Pérez-Palma, Erika Takle Axeen, Christina Y Hung, Heather Olson, Lindsay Swanson, Irina Anselm, Lauren C Briere, Frances A High, David A Sweetser, Saima Kayani, Molly Snyder, Sophie Calvert, Ingrid E Scheffer, Edward Yang, Jeff L Waugh, Dennis Lal, Olaf Bodamer, Annapurna Poduri
OBJECTIVE: To characterize the phenotypic spectrum associated with GNAO1 variants and establish genotype-protein structure-phenotype relationships. METHODS: We evaluated the phenotypes of 14 patients with GNAO1 variants, analyzed their variants for potential pathogenicity, and mapped them, along with those in the literature, on a three-dimensional structural protein model. RESULTS: The 14 patients in our cohort, including one sibling pair, had 13 distinct, heterozygous GNAO1 variants classified as pathogenic or likely pathogenic...
January 25, 2019: Epilepsia
Isabell Brikell, Qi Chen, Ralf Kuja-Halkola, Brian M D'Onofrio, Kelsey K Wiggs, Paul Lichtenstein, Catarina Almqvist, Patrick D Quinn, Zheng Chang, Henrik Larsson
OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) affects 10%-30% of individuals with epilepsy, yet concerns remain regarding the safety of ADHD medication in this group. The objective of this study was to examine the risk of acute seizures associated with ADHD medication in individuals with epilepsy. METHODS: A total of 21 557 individuals with a seizure history born between 1987 and 2003 were identified from Swedish population registers. Within this study population, we also identified 6773 youth (<19 years of age) who meet criteria for epilepsy, and 1605 youth with continuous antiepileptic drug (AED) treatment...
January 25, 2019: Epilepsia
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