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https://www.readbyqxmd.com/read/29771456/serum-serotonin-levels-in-patients-with-epileptic-seizures
#1
Arun Murugesan, M R Sandhya Rani, Johnson Hampson, Bilal Zonjy, Nuria Lacuey, Carl L Faingold, Daniel Friedman, Orrin Devinsky, Rup K Sainju, Stephan Schuele, Beate Diehl, Maromi Nei, Ronald M Harper, Lisa M Bateman, George Richerson, Samden D Lhatoo
Profound cardiovascular and/or respiratory dysfunction is part of the terminal cascade in sudden unexpected death in epilepsy (SUDEP). Central control of ventilation is mediated by brainstem rhythm generators, which are influenced by a variety of inputs, many of which use the modulatory neurotransmitter serotonin to mediate important inputs for breathing. The aim of this study was to investigate epileptic seizure-induced changes in serum serotonin levels and whether there are potential implications for SUDEP...
May 17, 2018: Epilepsia
https://www.readbyqxmd.com/read/29768152/effect-of-cannabidiol-on-drop-seizures-in-the-lennox-gastaut-syndrome
#2
Orrin Devinsky, Anup D Patel, J Helen Cross, Vicente Villanueva, Elaine C Wirrell, Michael Privitera, Sam M Greenwood, Claire Roberts, Daniel Checketts, Kevan E VanLandingham, Sameer M Zuberi
BACKGROUND: Cannabidiol has been used for treatment-resistant seizures in patients with severe early-onset epilepsy. We investigated the efficacy and safety of cannabidiol added to a regimen of conventional antiepileptic medication to treat drop seizures in patients with the Lennox-Gastaut syndrome, a severe developmental epileptic encephalopathy. METHODS: In this double-blind, placebo-controlled trial conducted at 30 clinical centers, we randomly assigned patients with the Lennox-Gastaut syndrome (age range, 2 to 55 years) who had had two or more drop seizures per week during a 28-day baseline period to receive cannabidiol oral solution at a dose of either 20 mg per kilogram of body weight (20-mg cannabidiol group) or 10 mg per kilogram (10-mg cannabidiol group) or matching placebo, administered in two equally divided doses daily for 14 weeks...
May 17, 2018: New England Journal of Medicine
https://www.readbyqxmd.com/read/29722352/epilepsy
#3
REVIEW
Orrin Devinsky, Annamaria Vezzani, Terence J O'Brien, Nathalie Jette, Ingrid E Scheffer, Marco de Curtis, Piero Perucca
Epilepsy affects all age groups and is one of the most common and most disabling neurological disorders. The accurate diagnosis of seizures is essential as some patients will be misdiagnosed with epilepsy, whereas others will receive an incorrect diagnosis. Indeed, errors in diagnosis are common, and many patients fail to receive the correct treatment, which often has severe consequences. Although many patients have seizure control using a single medication, others require multiple medications, resective surgery, neuromodulation devices or dietary therapies...
May 3, 2018: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/29710173/preventing-sudden-unexpected-death-in-epilepsy
#4
Orrin Devinsky, Philippe Ryvlin, Daniel Friedman
No abstract text is available yet for this article.
April 16, 2018: JAMA Neurology
https://www.readbyqxmd.com/read/29619247/cardiac-arrhythmia-and-neuroexcitability-gene-variants-in-resected-brain-tissue-from-patients-with-sudden-unexpected-death-in-epilepsy-sudep
#5
Daniel Friedman, Kasthuri Kannan, Arline Faustin, Seema Shroff, Cheddhi Thomas, Adriana Heguy, Jonathan Serrano, Matija Snuderl, Orrin Devinsky
Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related mortality in young adults. The exact mechanisms are unknown but death often follows a generalized tonic-clonic seizure. Proposed mechanisms include seizure-related respiratory, cardiac, autonomic, and arousal dysfunction. Genetic drivers underlying SUDEP risk are largely unknown. To identify potential SUDEP risk genes, we compared whole-exome sequences (WES) derived from formalin-fixed paraffin embedded surgical brain specimens of eight epilepsy patients who died from SUDEP with seven living controls matched for age at surgery, sex, year of surgery and lobe of resection...
2018: NPJ Genomic Medicine
https://www.readbyqxmd.com/read/29588980/novel-bandlike-signal-abnormality-suggestive-of-heterotopia-in-patient-with-a-kcnq1-frameshift-mutation
#6
Priyanka Sabharwal, Orrin Devinsky, Timothy M Shepherd
Malformations of cortical development are associated with epilepsy and cognitive dysfunction, and can occur in patients with SCN1A ion channel mutations. We report a novel and subtle bandlike subcortical heterotopia on integrated positron emission tomography-magnetic resonance imaging ( PET-MRI) in a patient with treatment-resistant epilepsy due to a de novo KCNQ1 frameshift mutation. Our case highlights the potential for other channel mutations to cause both epilepsy and cortical malformations. Further scrutiny of high contrast resolution MRI studies is warranted for patients with KCNQ1 and other epilepsy genes to further define their extended phenotype...
December 2017: Epilepsia Open
https://www.readbyqxmd.com/read/29574705/a-comprehensive-approach-to-identifying-repurposed-drugs-to-treat-scn8a-epilepsy
#7
Talia A Atkin, Chani M Maher, Aaron C Gerlach, Bryant C Gay, Brett M Antonio, Sonia C Santos, Karen M Padilla, JulieAnn Rader, Douglas S Krafte, Matthew A Fox, Gregory R Stewart, Slavé Petrovski, Orrin Devinsky, Matthew Might, Steven Petrou, David B Goldstein
OBJECTIVE: Many previous studies of drug repurposing have relied on literature review followed by evaluation of a limited number of candidate compounds. Here, we demonstrate the feasibility of a more comprehensive approach using high-throughput screening to identify inhibitors of a gain-of-function mutation in the SCN8A gene associated with severe pediatric epilepsy. METHODS: We developed cellular models expressing wild-type or an R1872Q mutation in the Nav 1.6 sodium channel encoded by SCN8A...
April 2018: Epilepsia
https://www.readbyqxmd.com/read/29540584/randomized-dose-ranging-safety-trial-of-cannabidiol-in-dravet-syndrome
#8
Orrin Devinsky, Anup D Patel, Elizabeth A Thiele, Matthew H Wong, Richard Appleton, Cynthia L Harden, Sam Greenwood, Gilmour Morrison, Kenneth Sommerville
OBJECTIVE: To evaluate the safety and preliminary pharmacokinetics of a pharmaceutical formulation of purified cannabidiol (CBD) in children with Dravet syndrome. METHODS: Patients aged 4-10 years were randomized 4:1 to CBD (5, 10, or 20 mg/kg/d) or placebo taken twice daily. The double-blind trial comprised 4-week baseline, 3-week treatment (including titration), 10-day taper, and 4-week follow-up periods. Completers could continue in an open-label extension. Multiple pharmacokinetic blood samples were taken on the first day of dosing and at end of treatment for measurement of CBD, its metabolites 6-OH-CBD, 7-OH-CBD, and 7-COOH-CBD, and antiepileptic drugs (AEDs; clobazam and metabolite N -desmethylclobazam [N-CLB], valproate, levetiracetam, topiramate, and stiripentol)...
March 14, 2018: Neurology
https://www.readbyqxmd.com/read/29530966/author-response-underestimation-of-sudden-deaths-among-patients-with-seizures-and-epilepsy
#9
Orrin Devinsky, Daniel Friedman, Jocelyn Y Cheng, Ellen Moffatt, Anthony Kim, Zian H Tseng
No abstract text is available yet for this article.
March 13, 2018: Neurology
https://www.readbyqxmd.com/read/29492970/national-association-of-medical-examiners-position-paper-recommendations-for-the-investigation-and-certification-of-deaths-in-people-with-epilepsy
#10
Owen Middleton, Daniel Atherton, Elizabeth Bundock, Elizabeth Donner, Daniel Friedman, Dale Hesdorffer, Heather Jarrell, Aileen McCrillis, Othon J Mena, Mitchel Morey, David Thurman, Niu Tian, Torbjörn Tomson, Zian Tseng, Steven White, Cyndi Wright, Orrin Devinsky
Sudden unexpected death of an individual with epilepsy can pose a challenge to death investigators, as most deaths are unwitnessed, and the individual is commonly found dead in bed. Anatomic findings (eg, tongue/lip bite) are commonly absent and of varying specificity, thereby limiting the evidence to implicate epilepsy as a cause of or contributor to death. Thus it is likely that death certificates significantly underrepresent the true number of deaths in which epilepsy was a factor. To address this, members of the National Association of Medical Examiners, North American SUDEP Registry, Epilepsy Foundation SUDEP Institute, American Epilepsy Society, and the Centers for Disease Control and Prevention constituted an expert panel to generate evidence-based recommendations for the practice of death investigation and autopsy, toxicological analysis, interpretation of autopsy and toxicology findings, and death certification to improve the precision of death certificate data available for public health surveillance of epilepsy-related deaths...
March 2018: Epilepsia
https://www.readbyqxmd.com/read/29491347/author-correction-low-frequency-transcranial-electrical-stimulation-does-not-entrain-sleep-rhythms-measured-by-human-intracranial-recordings
#11
Belen Lafon, Simon Henin, Yu Huang, Daniel Friedman, Lucia Melloni, Thomas Thesen, Werner Doyle, György Buzsáki, Orrin Devinsky, Lucas C Parra, Anli Liu
It has come to our attention that we did not specify whether the stimulation magnitudes we report in this Article are peak amplitudes or peak-to-peak. All references to intensity given in mA in the manuscript refer to peak-to-peak amplitudes, except in Fig. 2, where the model is calibrated to 1 mA peak amplitude, as stated. In the original version of the paper we incorrectly calibrated the computational models to 1 mA peak-to-peak, rather than 1 mA peak amplitude. This means that we divided by a value twice as large as we should have...
February 28, 2018: Nature Communications
https://www.readbyqxmd.com/read/29457829/species-specific-susceptibility-to-cannabis-induced-convulsions
#12
Benjamin J Whalley, Hong Lin, Lynne Bell, Thomas Hill, Amesha Patel, Roy A Gray, C Elizabeth Roberts, Orrin Devinsky, Michael Bazelot, Claire M Williams, Gary J Stephens
BACKGROUND AND PURPOSE: Numerous claims are made for cannabis' therapeutic utility upon human seizures, but concerns persist about risks. A potential confounder is the presence of both Δ9 -tetrahydrocannabinol (THC), variously reported to be pro- and anticonvulsant, and cannabidiol (CBD), widely confirmed as anticonvulsant. Therefore, we investigated effects of prolonged exposure to different THC/CBD cannabis extracts on seizure activity and associated measures of endocannabinoid (eCB) system signalling...
February 19, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29454104/functional-brain-connectivity-is-predictable-from-anatomic-network-s-laplacian-eigen-structure
#13
Farras Abdelnour, Michael Dayan, Orrin Devinsky, Thomas Thesen, Ashish Raj
How structural connectivity (SC) gives rise to functional connectivity (FC) is not fully understood. Here we mathematically derive a simple relationship between SC measured from diffusion tensor imaging, and FC from resting state fMRI. We establish that SC and FC are related via (structural) Laplacian spectra, whereby FC and SC share eigenvectors and their eigenvalues are exponentially related. This gives, for the first time, a simple and analytical relationship between the graph spectra of structural and functional networks...
May 15, 2018: NeuroImage
https://www.readbyqxmd.com/read/29449429/heterogeneous-origins-of-human-sleep-spindles-in-different-cortical-layers
#14
Donald J Hagler, István Ulbert, Lucia Wittner, Loránd Erőss, Joseph R Madsen, Orrin Devinsky, Werner Doyle, Dániel Fabó, Sydney S Cash, Eric Halgren
Sleep spindles are a cardinal feature in human NREM sleep and may be important for memory consolidation. We studied the intracortical organization of spindles in men and women by recording spontaneous sleep spindles from different cortical layers using linear microelectrode arrays. Two patterns of spindle generation were identified using visual inspection, and confirmed with factor analysis. Spindles (10-16 Hz) were largest and most common in upper and middle channels, with limited involvement of deep channels...
March 21, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29446753/correction-measurements-and-models-of-electric-fields-in-the-in-vivo-human-brain-during-transcranial-electric-stimulation
#15
Yu Huang, Anli A Liu, Belen Lafon, Daniel Friedman, Michael Dayan, Xiuyuan Wang, Marom Bikson, Werner K Doyle, Orrin Devinsky, Lucas C Parra
No abstract text is available yet for this article.
February 15, 2018: ELife
https://www.readbyqxmd.com/read/29424352/dna-dope-gemini-surfactants-complexes-at-low-surface-charge-density-from-structure-to-transfection-efficiency
#16
Lukáš Hubčík, Dominika Galliková, Petra Pullmannová, Ľubica Lacinová, Zdena Sulová, Mária Hanulová, Sergio S Funari, Ferdinand Devínsky, Daniela Uhríková
DNA condensation, structure and transfection efficiency of complexes formed by gemini surfactants alkane-α,ω-diyl-bis(dodecyldimethylammonium bromide)s (CnGS12, n = 3, 6 and 12 is the number of alkane spacer carbons), dioleoylphosphatidylethanolamine (CnGS12/DOPE = 0.3 mol/mol) and DNA at low surface charge density were investigated through different techniques. Small angle X-ray diffraction showed a condensed lamellar phase with marked dependence of DNA-DNA distance on (+/-) charge ratio. High ionic strength of hydrating medium screens the interaction DNA - CnGS12/DOPE and complexed DNA represented maximally ~ 45-60% of total DNA in the solution as derived from fluorescence and UV-VIS spectroscopy...
January 2018: General Physiology and Biophysics
https://www.readbyqxmd.com/read/29391596/superficial-slow-rhythms-integrate-cortical-processing-in-humans
#17
Milan Halgren, Daniel Fabó, István Ulbert, Joseph R Madsen, Lorand Erőss, Werner K Doyle, Orrin Devinsky, Donald Schomer, Sydney S Cash, Eric Halgren
The neocortex is composed of six anatomically and physiologically specialized layers. It has been proposed that integration of activity across cortical areas is mediated anatomically by associative connections terminating in superficial layers, and physiologically by slow cortical rhythms. However, the means through which neocortical anatomy and physiology interact to coordinate neural activity remains obscure. Using laminar microelectrode arrays in 19 human participants, we found that most EEG activity is below 10-Hz (delta/theta) and generated by superficial cortical layers during both wakefulness and sleep...
February 1, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29365066/structural-brain-abnormalities-in-the-common-epilepsies-assessed-in-a-worldwide-enigma-study
#18
Christopher D Whelan, Andre Altmann, Juan A Botía, Neda Jahanshad, Derrek P Hibar, Julie Absil, Saud Alhusaini, Marina K M Alvim, Pia Auvinen, Emanuele Bartolini, Felipe P G Bergo, Tauana Bernardes, Karen Blackmon, Barbara Braga, Maria Eugenia Caligiuri, Anna Calvo, Sarah J Carr, Jian Chen, Shuai Chen, Andrea Cherubini, Philippe David, Martin Domin, Sonya Foley, Wendy França, Gerrit Haaker, Dmitry Isaev, Simon S Keller, Raviteja Kotikalapudi, Magdalena A Kowalczyk, Ruben Kuzniecky, Soenke Langner, Matteo Lenge, Kelly M Leyden, Min Liu, Richard Q Loi, Pascal Martin, Mario Mascalchi, Marcia E Morita, Jose C Pariente, Raul Rodríguez-Cruces, Christian Rummel, Taavi Saavalainen, Mira K Semmelroch, Mariasavina Severino, Rhys H Thomas, Manuela Tondelli, Domenico Tortora, Anna Elisabetta Vaudano, Lucy Vivash, Felix von Podewils, Jan Wagner, Bernd Weber, Yi Yao, Clarissa L Yasuda, Guohao Zhang, Nuria Bargalló, Benjamin Bender, Neda Bernasconi, Andrea Bernasconi, Boris C Bernhardt, Ingmar Blümcke, Chad Carlson, Gianpiero L Cavalleri, Fernando Cendes, Luis Concha, Norman Delanty, Chantal Depondt, Orrin Devinsky, Colin P Doherty, Niels K Focke, Antonio Gambardella, Renzo Guerrini, Khalid Hamandi, Graeme D Jackson, Reetta Kälviäinen, Peter Kochunov, Patrick Kwan, Angelo Labate, Carrie R McDonald, Stefano Meletti, Terence J O'Brien, Sebastien Ourselin, Mark P Richardson, Pasquale Striano, Thomas Thesen, Roland Wiest, Junsong Zhang, Annamaria Vezzani, Mina Ryten, Paul M Thompson, Sanjay M Sisodiya
Progressive functional decline in the epilepsies is largely unexplained. We formed the ENIGMA-Epilepsy consortium to understand factors that influence brain measures in epilepsy, pooling data from 24 research centres in 14 countries across Europe, North and South America, Asia, and Australia. Structural brain measures were extracted from MRI brain scans across 2149 individuals with epilepsy, divided into four epilepsy subgroups including idiopathic generalized epilepsies (n =367), mesial temporal lobe epilepsies with hippocampal sclerosis (MTLE; left, n = 415; right, n = 339), and all other epilepsies in aggregate (n = 1026), and compared to 1727 matched healthy controls...
February 1, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29336036/the-incidence-and-significance-of-periictal-apnea-in-epileptic-seizures
#19
Nuria Lacuey, Bilal Zonjy, Johnson P Hampson, M R Sandhya Rani, Anita Zaremba, Rup K Sainju, Brian K Gehlbach, Stephan Schuele, Daniel Friedman, Orrin Devinsky, Maromi Nei, Ronald M Harper, Luke Allen, Beate Diehl, John J Millichap, Lisa Bateman, Mark A Granner, Deidre N Dragon, George B Richerson, Samden D Lhatoo
OBJECTIVE: The aim of this study was to investigate periictal central apnea as a seizure semiological feature, its localizing value, and possible relationship with sudden unexpected death in epilepsy (SUDEP) pathomechanisms. METHODS: We prospectively studied polygraphic physiological responses, including inductance plethysmography, peripheral capillary oxygen saturation (SpO2 ), electrocardiography, and video electroencephalography (VEEG) in 473 patients in a multicenter study of SUDEP...
March 2018: Epilepsia
https://www.readbyqxmd.com/read/29336029/sudden-unexpected-death-in-epilepsy-in-patients-treated-with-brain-responsive-neurostimulation
#20
Orrin Devinsky, Daniel Friedman, Robert B Duckrow, Nathan B Fountain, Ryder P Gwinn, James W Leiphart, Anthony M Murro, Paul C Van Ness
OBJECTIVE: To study the incidence and clinical features of sudden unexpected death in epilepsy (SUDEP) in patients treated with direct brain-responsive stimulation with the RNS System. METHODS: All deaths in patients treated in clinical trials (N = 256) or following U.S. Food and Drug Administration (FDA) approval (N = 451) through May 5, 2016, were adjudicated for SUDEP. RESULTS: There were 14 deaths among 707 patients (2208 postimplantation years), including 2 possible, 1 probable, and 4 definite SUDEP events...
March 2018: Epilepsia
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