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A unified hypothesis of SUDEP: Seizure-induced respiratory depression induced by adenosine may lead to SUDEP but can be prevented by autoresuscitation and other restorative respiratory response mechanisms mediated by the action of serotonin on the periaqueductal gray
Carl L. Faingold, Hua-Jun Feng
doi : 10.1111/epi.17521
Sudden unexpected death in epilepsy (SUDEP) is a major cause of death in people with epilepsy (PWE). Postictal apnea leading to cardiac arrest is the most common sequence of terminal events in witnessed cases of SUDEP, and postconvulsive central apnea has been proposed as a potential biomarker of SUDEP susceptibility.
Ketamine as advanced second-line treatment in benzodiazepine-refractory convulsive status epilepticus in children
Silvia Buratti, Emanuele Giacheri, Antonella Palmieri, Jessica Tibaldi, Giacomo Brisca, Antonella Riva, Pasquale Striano, Maria Margherita Mancardi, Lino Nobili, Andrea Moscatelli
doi : 10.1111/epi.17550
Status epilepticus (SE) is one of the most common neurological emergencies in children. To date, there is no definitive evidence to guide treatment of SE refractory to benzodiazepines.
Neurostimulation in generalized epilepsy: A systematic review and meta-analysis
Zulfi Haneef, Henry C. Skrehot
doi : 10.1111/epi.17524
There are three neurostimulation devices available to treat generalized epilepsy: vagus nerve stimulation (VNS), deep brain stimulation (DBS), and responsive neurostimulation (RNS). However, the choice between them is unclear due to lack of head-to-head comparisons.
Associations between testing and treatment pathways in lesional temporal or extratemporal epilepsy: A census survey of NAEC center directors
Christopher W. Beatty, Stephanie M. Ahrens, Kristen H. Arredondo, Anto I. Bagić, Shasha Bai, Kevin E. Chapman, Michael A. Ciliberto, Dave F. Clarke, Mariah Eisner, Nathan B. Fountain, Jay R. Gavvala, M. S. Perry, Kyle C. Rossi, Lily C. Wong-Kisiel, Susan T. Herman, Adam P. Ostendorf, the NAEC Center Director Study Group
doi : 10.1111/epi.17512
The evaluation to determine candidacy and treatment for epilepsy surgery in persons with drug-resistant epilepsy (DRE) is not uniform. Many non-invasive and invasive tests are available to ascertain an appropriate treatment strategy. This study examines expert response to clinical vignettes of magnetic resonance imaging (MRI)–positive lesional focal cortical dysplasia in both temporal and extratemporal epilepsy to identify associations in evaluations and treatment choice.
A phase 1 open-label trial evaluating focused ultrasound unilateral anterior thalamotomy for focal onset epilepsy
Vibhor Krishna, Jesse Mindel, Francesco Sammartino, Cady Block, Alok Kumar Dwivedi, Jamie J. Van Gompel, Nathan Fountain, Robert Fisher
doi : 10.1111/epi.17535
Focused ultrasound ablation (FUSA) is an emerging treatment for neurological and psychiatric diseases. We describe the initial experience from a pilot, open-label, single-center clinical trial of unilateral anterior nucleus of the thalamus (ANT) FUSA in patients with treatment-refractory epilepsy.
Cost-effectiveness of cenobamate for focal seizures in people with drug-resistant epilepsy
Vicki Laskier, Kenneth K. Agyei-Kyeremateng, Alex E. Eddy, Dilip Patel, Stuart Mulheron, Samuel James, Rhys H. Thomas, Josemir W. Sander
doi : 10.1111/epi.17506
This study was undertaken to estimate the cost-effectiveness of add-on cenobamate in the UK when used to treat drug-resistant focal seizures in adults who are not adequately controlled with at least two prior antiseizure medications, including at least one used adjunctively.
Levetiracetam as a first-line antiseizure medication in WHO grade 2 glioma: Time to seizure freedom and rates of treatment failure
Sam Fairclough, John Goodden, Paul Chumas, Ryan Mathew, Melissa Maguire
doi : 10.1111/epi.17508
The high seizure burden seen in World Health Association (WHO) grade 2 gliomas is well documented. This study aims to identify factors that influence the probability of seizure freedom (12 months of seizure remission) and treatment failure (antiseizure medication [ASM] cessation or introduction of an alternative) in patients with WHO grade 2 glioma.
Perampanel as precision therapy in rare genetic epilepsies
Andreea Nissenkorn, Gerhard Kluger, Susanne Schubert-Bast, Allan Bayat, Marya Bobylova, Paolo Bonanni, Berten Ceulemans, Antonietta Coppola, Carlo Di Bonaventura, Martha Feucht, Anne Fuchs, Gudrun Gröppel, Gali Heimer, Brigitte Herdt, Sviatlana Kulikova, Konstantin Mukhin, Stefania Nicassio, Alessandro Orsini, Maria Panagiotou, Milka Pringsheim, Burkhard Puest, Olga Pylaeva, Georgia Ramantani, Maria Tsekoura, Paolo Ricciardelli, Tally Lerman Sagie, Brigit Stark, Pasquale Striano, Andreas van Baalen, Matthias De Wachter, Emanuele Cerulli Irelli, Claudia Cuccurullo, Celina von Stülpnagel, Angelo Russo
doi : 10.1111/epi.17530
Perampanel, an antiseizure drug with α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist properties, may have a targeted effect in genetic epilepsies with overwhelming glutamate receptor activation. Epilepsies with loss of γ-aminobutyric acid inhibition (e.g., SCN1A), overactive excitatory neurons (e.g., SCN2A, SCN8A), and variants in glutamate receptors (e.g., GRIN2A) hold special interest.
Transcranial direct current stimulation for focal status epilepticus or lateralized periodic discharges in four patients in a critical care setting
Robert S. Fisher, Ryan J. McGinn, Erica L. Von Stein, Teresa Q. Wu, Kurt Y. Qing, Adam Fogarty, Babak Razavi, Chitra Venkatasubramanian
doi : 10.1111/epi.17514
Transcranial direct current stimulation (tDCS) has been advocated for various neurological conditions, including epilepsy. A 1–4-mA cathodal current applied to the scalp over a seizure focus can reduce spikes and seizures. This series of four patients with focal status epilepticus is among the first case series to demonstrate benefit of tDCS in the critical care setting.
Preclinical pharmacokinetics and tolerability of a novel meglumine-based parenteral solution of topiramate and topiramate combinations for treatment of status epilepticus
Chris Rundfeldt, Pavel Klein, Detlev Boison, Alexander Rotenberg, Raimondo D'Ambrosio, Cliff Eastman, Benton Purnell, Madhuvika Murugan, Howard P. Goodkin, Wolfgang Löscher
doi : 10.1111/epi.17520
For an antiseizure medication (ASM) to be effective in status epilepticus (SE), the drug should be administered intravenously (i.v.) to provide quick access to the brain. However, poor aqueous solubility is a major problem in the development of parenteral drug solutions.
Medical and surgical treatment of epilepsy in older adults: A national survey
Nafisa Husein, Timothé Langlois-Thérien, Bastien Rioux, Colin B. Josephson, Nathalie Jetté, Mark R. Keezer
doi : 10.1111/epi.17516
There are no clinical guidelines dedicated to the treatment of epilepsy in older adults. We investigated physician opinion and practice regarding the treatment of people with epilepsy aged 65 years or older. We also sought to study how our opinion and practice varied between geriatricians, general neurologists, and epilepsy neurologists (i.e., epileptologists).
Impact of regulatory restrictions on the use of valproic acid in women of childbearing age: An Italian study
Lidia Di Vito, Stefania Mazzoni, Laura Maria Beatrice Belotti, Elisabetta Poluzzi, Elisa Baldin, Corrado Zenesini, Francesca Bisulli, Paolo Tinuper, Barbara Mostacci
doi : 10.1111/epi.17526
Due to significant risks to the offspring after intrauterine exposure, the European Medicines Agency issued recommendations in 2014 and 2018 restricting the use of valproate (VPA) in women of childbearing age (WOCA). We aimed to evaluate their impact in the Emilia-Romagna region (ERR) of Northern Italy.
A core outcome set for childhood epilepsy treated with ketogenic diet therapy (CORE-KDT study): International parent and health professional consensus
Jennifer H. Carroll, J. Helen Cross, Mary Hickson, Emma Williams, Val Aldridge, Avril Collinson
doi : 10.1111/epi.17513
Ketogenic diet therapy (KDT) can result in benefits (seizure-related and non-seizure-related) for children with drug-resistant epilepsy. However, clinical trials report a wide range of outcomes, making synthesis of evidence difficult, and do not adequately reflect parent views on important outcomes for their child.
In-hospital and home-based long-term monitoring of focal epilepsy with a wearable electroencephalographic device: Diagnostic yield and user experience
Jaiver Macea, Miguel Bhagubai, Victoria Broux, Maarten De Vos, Wim Van Paesschen
doi : 10.1111/epi.17517
The aim is to report the performance of an electroencephalogram (EEG) seizure-detector algorithm on data obtained with a wearable device (WD) in patients with focal refractory epilepsy and their experience.
Semiautomatic interictal electric source localization based on long-term electroencephalographic monitoring: A prospective study
Laurent Spinelli, Amir G. Baroumand, Serge Vulliemoz, Shahan Momjian, Gregor Strobbe, Pieter van Mierlo, Margitta Seeck
doi : 10.1111/epi.17460
Electric source imaging (ESI) of interictal epileptiform discharges (IEDs) has shown significant yield in numerous studies; however, its implementation at most centers is labor- and cost-intensive.
Relative entropy is an easy-to-use invasive electroencephalographic biomarker of the epileptogenic zone
Vojtech Travnicek, Petr Klimes, Jan Cimbalnik, Josef Halamek, Pavel Jurak, Benjamin Brinkmann, Irena Balzekas, Chifaou Abdallah, François Dubeau, Birgit Frauscher, Greg Worrell, Milan Brazdil
doi : 10.1111/epi.17539
High-frequency oscillations are considered among the most promising interictal biomarkers of the epileptogenic zone in patients suffering from pharmacoresistant focal epilepsy. However, there is no clear definition of pathological high-frequency oscillations, and the existing detectors vary in methodology, performance, and computational costs.
A region-specific modulation of sleep slow waves on interictal epilepsy markers in focal epilepsy
Cong Chen, Yunling Wang, Lingqi Ye, Jiahui Xu, Wenjie Ming, Xiaochen Liu, Lingli Hu, Hongyi Ye, Cenglin Xu, Yi Wang, Zhongjing Wang, Yao Ding, Junming Zhu, Meiping Ding, Zhong Chen, Shuang Wang
doi : 10.1111/epi.17518
Sleep strongly activates interictal epileptic activity through an unclear mechanism. We investigated how scalp sleep slow waves (SSWs), whose positive and negative half-waves reflect the fluctuation of neuronal excitability between the up and down states, respectively, modulate interictal epileptic events in focal epilepsy.
Clinical utility of exome sequencing in a pediatric epilepsy cohort
Jordana L. Graifman, Natalie C. Lippa, Maureen S. Mulhern, Amanda L. Bergner, Tristan T. Sands
doi : 10.1111/epi.17534
Exome sequencing (ES) has played an important role in the identification of causative variants for individuals with epilepsy and has proven to be a valuable diagnostic tool. Less is known about its clinical utility once a diagnosis is received. This study systematically reviewed the impact of ES results on clinical decision-making and patient care in a pediatric epilepsy cohort at a tertiary care medical center.
Atypical intrinsic neural timescales in temporal lobe epilepsy
Ke Xie, Jessica Royer, Sara Lariviere, Raul Rodriguez-Cruces, Reinder Vos de Wael, Bo-yong Park, Hans Auer, Shahin Tavakol, Jordan DeKraker, Chifaou Abdallah, Lorenzo Caciagli, Dani S. Bassett, Andrea Bernasconi, Neda Bernasconi, Birgit Frauscher, Luis Concha, Boris C. Bernhardt
doi : 10.1111/epi.17541
Temporal lobe epilepsy (TLE) is the most common pharmacoresistant epilepsy in adults. Here we profiled local neural function in TLE in vivo, building on prior evidence that has identified widespread structural alterations
Comorbidities and predictors of health-related quality of life in Dravet syndrome: A 10-year, prospective follow-up study
Phoebe Makiello, Tony Feng, Benjamin Dunwoody, Felix Steckler, Joseph Symonds, Sameer M. Zuberi, Liam Dorris, Andreas Brunklaus
doi : 10.1111/epi.17531
Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy, leading to reduced health-related quality of life (HRQOL). Prospective outcome data on HRQOL are sparse, and this study investigated long-term predictors of HRQOL in DS.
Quantifying trial-by-trial variability during cortico-cortical evoked potential mapping of epileptogenic tissue
Measuring cortico-cortical evoked potentials (CCEPs) is a promising tool for mapping epileptic networks, but it is not known how variability in brain state and stimulation technique might impact the use of CCEPs for epilepsy localization. We test the hypotheses that (1) CCEPs demonstrate systematic variability across trials and (2) CCEP amplitudes depend on the timing of stimulation with respect to endogenous, low-frequency oscillations.
doi : 10.1111/epi.17528
We studied 11 patients who underwent CCEP mapping after stereo-electroencephalography electrode implantation for surgical evaluation of drug-resistant epilepsy. Evoked potentials were measured from all electrodes after each pulse of a 30 s, 1 Hz bipolar stimulation train. We quantified monotonic trends, phase dependence, and standard deviation (SD) of N1 (15–50 ms post-stimulation) and N2 (50–300 ms post-stimulation) amplitudes across the 30 stimulation trials for each patient. We used linear regression to quantify the relationship between measures of CCEP variability and the clinical seizure-onset zone (SOZ) or interictal spike rates.
Influence of comorbidity on mortality in patients with epilepsy and psychogenic nonepileptic seizures
Michael Tan, Neil Pearce, Aurelio Tobias, Mark J. Cook, Wendyl J. D'Souza
doi : 10.1111/epi.17532
This study aims to determine the contribution of comorbidities to excess psychogenic nonepileptic seizures (PNES) mortality.
Metabolomic, proteomic, and transcriptomic changes in adults with epilepsy on modified Atkins diet
Dominique F. Leitner, Yik Siu, Aryeh Korman, Ziyan Lin, Evgeny Kanshin, Daniel Friedman, Sasha Devore, Beatrix Ueberheide, Aristotelis Tsirigos, Drew R. Jones, Thomas Wisniewski, Orrin Devinsky
doi : 10.1111/epi.17540
High-fat and low-carbohydrate diets can reduce seizure frequency in some treatment-resistant epilepsy patients, including the more flexible modified Atkins diet (MAD), which is more palatable, mimicking fasting and inducing high ketone body levels. Low-carbohydrate diets may shift brain energy production, particularly impacting neuron- and astrocyte-linked metabolism.
Heterozygous GABAA receptor β3 subunit N110D knock-in mice have epileptic spasms
Shimian Qu, Laurel G. Jackson, Chengwen Zhou, DingDing Shen, Wangzhen Shen, Gerald Nwosu, Rachel Howe, Mackenzie A. Catron, Carson Flamm, Marshall Biven, Jing-Qiong Kang, Robert L. Macdonald
doi : 10.1111/epi.17470
Infantile spasms is an epileptic encephalopathy of childhood, and its pathophysiology is largely unknown. We generated a heterozygous knock-in mouse with the human infantile spasms-associated de novo mutation GABRB3 (c.A328G, p.N110D) to investigate its molecular mechanisms and to establish the Gabrb3+/N110D knock-in mouse as a model of infantile spasms syndrome.
A library of quantitative markers of seizure severity
Sarah J. Gascoigne, Leonard Waldmann, Gabrielle M. Schroeder, Mariella Panagiotopoulou, Jess Blickwedel, Fahmida Chowdhury, Alison Cronie, Beate Diehl, John S. Duncan, Jennifer Falconer, Ryan Faulder, Yu Guan, Veronica Leach, Shona Livingstone, Christoforos Papasavvas, Rhys H. Thomas, Kevin Wilson, Peter N. Taylor, Yujiang Wang
doi : 10.1111/epi.17525
Understanding fluctuations in seizure severity within individuals is important for determining treatment outcomes and responses to therapy, as well as assessing novel treatments for epilepsy.
Corrigendum to “systematic analysis and comparison of commercial seizure detection software�
doi : 10.1111/epi.17527
A retrospective non-interventional study evaluating the pharmacokinetic interactions between cenobamate and clobazam
Sally Elakkary, Anne Hagemann, Dennis Klimpel, Christian G. Bien, Christian Brandt
doi : 10.1111/epi.17515
18F-SynVesT-1 positron emission tomography in a hypothalamic hamartoma with abnormal uptake
Ling Xiao, Ming Zhou, Yongxiang Tang, Shuo Hu
doi : 10.1111/epi.17533
Hypothalamic hamartomas (HHs) are uncommon benign lesions of neuronal and glial cells in the inferior hypothalamus. They have been linked to epilepsy, premature puberty, and cognitive and behavioral impairment.
