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Time-to-event clinical trial designs: Existing evidence and remaining concerns
Wesley T. Kerr, Stéphane Auvin, Serge Van der Geyten, Christopher Kenney, Gerald Novak, Nathan B. Fountain, Caitlin Grzeskowiak, Jacqueline A. French
doi : 10.1111/epi.17621
Well-designed placebo-controlled clinical trials are critical to the development of novel treatments for epilepsy, but their design has not changed for decades. Patients, clinicians, regulators, and innovators all have concerns that recruiting for trials is challenging, in part, due to the static design of maintaining participants for long periods on add-on placebo when there are an increasing number of options for therapy.
Impact of epilepsy surgery on quality of life: Systematic review and meta-analysis
Lubna Shakhatreh, Emma Foster, Pakeeran Siriratnam, Andrew Neal, Patrick W. Carney, Graeme D. Jackson, Terence J. O'Brien, Patrick Kwan, Zhibin Chen, Zanfina Ademi
doi : 10.1111/epi.17644
Improved quality of life (QoL) is an important outcome goal following epilepsy surgery. This study aims to quantify change in QoL for adults with drug-resistant epilepsy (DRE) who undergo epilepsy surgery, and to explore clinicodemographic factors associated with these changes. We conducted a systematic review and meta-analysis using Medline, Embase, and Cochrane Central Register of Controlled Trials.
A meta-analytic review of the effectiveness of psychological treatment of functional/dissociative seizures on non-seizure outcomes in adults
Chris Gaskell, Niall Power, Barbora Novakova, Melanie Simmonds-Buckley, Markus Reuber, Stephen Kellett, Gregg H. Rawlings
doi : 10.1111/epi.17626
Psychological therapies are considered the treatment of choice for functional/dissociative seizures (FDSs). Although most previous studies have focused on seizure persistence or frequency, it has been argued that well-being or health-related quality of life outcomes may actually be more meaningful.
Twenty-four hour pattern of childhood febrile seizures substantiated by time series meta-analysis: Circadian medicine perspectives
Michael H. Smolensky, Ami P. Shah, José R. Fernández, Linda Sackett-Lundeen, Ramon C. Hermida
doi : 10.1111/epi.17639
Major objectives of this work were to: (1) substantiate the 24-hour pattern in the occurrence of childhood febrile seizures (CFSs) by a novel time series meta-analysis of past reported time-of-day data and (2) discuss its potential circadian rhythm-dependencies.
Intracerebroventricular administration for delivery of antiseizure therapeutics: Challenges and opportunities
Firas Fahoum, Sara Eyal
doi : 10.1111/epi.17625
Intracerebroventricular (ICV) administration is increasingly being explored as a means for delivering antiseizure and antiepileptic therapies to epileptic brain tissue. This route bypasses the blood–brain barrier, thus enabling the delivery of therapeutics that are restricted from the brain, while reducing the risk of systemic adverse reactions.
Integrated psychological care services within seizure settings: Key components and implementation factors among example services in four ILAE regions: A report by the ILAE Psychiatry Commission
Milena Gandy, Rosa Michaelis, Jayne Acraman, Kirsten A. Donald, Michael Fitzpatrick, W. Curt LaFrance Jr., Seth A. Margolis, Avani C. Modi, Markus Reuber, Venus Tang, Zoe Thayer, Kirsten Verity, Janelle L. Wagner, Jo Wilmshurst, Sarah Whittaker, Heidi M. Munger Clary
doi : 10.1111/epi.17647
Mental health comorbidities are prevalent and problematic in patients with seizures but often suboptimally managed. To address common gaps in care, the Integrated Mental Health Care Pathways Task Force of the International League Against Epilepsy (ILAE) Psychiatry Commission was tasked with providing education and guidance on the integration of mental health management (e.g., screening, referral, treatment) into routine seizure care.
Life following epilepsy surgery: Building a holistic framework for enhancing postsurgical recovery and rehabilitation
Lorryn Delle Baite, Evelyn E. Harvey, Michael W. K. Fong, Aileen McGonigal, Sarah J. Wilson
doi : 10.1111/epi.17646
Automated, machine learning–based alerts increase epilepsy surgery referrals: A randomized controlled trial
Benjamin D. Wissel, Hansel M. Greiner, Tracy A. Glauser, Francesco T. Mangano, Katherine D. Holland-Bouley, Nanhua Zhang, Rhonda D. Szczesniak, Daniel Santel, John P. Pestian, Judith W. Dexheimer
doi : 10.1111/epi.17629
To determine whether automated, electronic alerts increased referrals for epilepsy surgery.
Hemispherotomy in children: A retrospective analysis of 152 surgeries at a single center and predictors for long-term seizure outcome
Thilo Kalbhenn, Thomas Cloppenborg, Friedrich G. Woermann, Anne Hagemann, Tilman Polster, Roland Coras, Ingmar Blümcke, Christian G. Bien, Matthias Simon
doi : 10.1111/epi.17632
Completeness as a predictor of seizure freedom is broadly accepted in epilepsy surgery. We focused on the requirements for a complete hemispherotomy and hypothesized that the disconnection of the insula contributes to a favorable postoperative seizure outcome. We analyzed surgical and nonsurgical predictors influencing long-term seizure outcome before and after a modification of our hemispherotomy technique.
Seizure-free days as a novel outcome in patients with Lennox–Gastaut syndrome: Post hoc analysis of patients receiving cannabidiol in two randomized controlled trials
Stéphane Auvin, Charlotte Nortvedt, Douglas S. Fuller, Farhad Sahebkar
doi : 10.1111/epi.17618
In this post hoc analysis, we aimed to assess seizure-free days as a potential new outcome measure to use in randomized placebo-controlled trials (RCTs) of patients with Lennox–Gastaut syndrome (LGS).
Epileptic spasms in CDKL5 deficiency disorder: Delayed treatment and poor response to first-line therapies
Heather E. Olson, Scott Demarest, Elia Pestana-Knight, Ahsan N. Moosa, Xiaoming Zhang, José R. Pérez-Pérez, Judy Weisenberg, Erin O’Connor Prange, Eric D. Marsh, Rajsekar R. Rajaraman, Bernhard Suter, Akshat Katyayan, Isabel Haviland, Carolyn Daniels, Bo Zhang, Caitlin Greene, Michelle DeLeo, Lindsay Swanson, Jamie Love-Nichols, Timothy Benke, Chellamani Harini, Annapurna Poduri
doi : 10.1111/epi.17630
We aimed to assess the treatment response of infantile-onset epileptic spasms (ES) in CDKL5 deficiency disorder (CDD) vs other etiologies.
Recognition and epileptology of protracted CLN3 disease
Jillian M. Cameron, John A. Damiano, Bronwyn Grinton, Patrick W. Carney, Penny McKelvie, Peter Silbert, Nicholas Lawn, Ingrid E. Scheffer, Karen L. Oliver, Michael S. Hildebrand, Samuel F. Berkovic
doi : 10.1111/epi.17616
This study was undertaken to analyze phenotypic features of a cohort of patients with protracted CLN3 disease to improve recognition of the disorder.
Predicting posttraumatic epilepsy using admission electroencephalography after severe traumatic brain injury
Matthew Pease, Jonathan Elmer, Ameneh Zare Shahabadi, Arka N. Mallela, Juan F. Ruiz-Rodriguez, Daniel Sexton, Niravkumar Barot, Jorge A. Gonzalez-Martinez, Lori Shutter, David O. Okonkwo, James F. Castellano
doi : 10.1111/epi.17622
Posttraumatic epilepsy (PTE) develops in as many as one third of severe traumatic brain injury (TBI) patients, often years after injury. Analysis of early electroencephalographic (EEG) features, by both standardized visual interpretation (viEEG) and quantitative EEG (qEEG) analysis, may aid early identification of patients at high risk for PTE.
Time-dependent risk factors for epileptic seizures in glioblastoma patients: A retrospective analysis of 520 cases
Jenny Stritzelberger, Anna Gesmann, Imke Fuhrmann, Sebastian Brandner, Tamara M. Welte, Stefanie Balk, Felix Eisenhut, Arnd Dörfler, Roland Coras, Werner Adler, Stefan Schwab, Florian Putz, Rainer Fietkau, Luitpold Distel, Hajo Hamer
doi : 10.1111/epi.17658
Epilepsy is a common comorbidity of glioblastoma. Seizures may occur in various phases of the disease. We aimed to assess potential risk factors for seizures in accordance with the point in time at which they occurred.
Characterizing the treatment gap in the United States among adult patients with a new diagnosis of epilepsy
Barbara M. Decker, Colin A. Ellis, Emily Schriver, Kelly Fischbein, Debbie Smith, Jason T. Moyer, Catherine V. Kulick-Soper, Danielle Mowery, Brian Litt, Chloe E. Hill
doi : 10.1111/epi.17641
Epilepsy is largely a treatable condition with antiseizure medication (ASM). Recent national administrative claims data suggest one third of newly diagnosed adult epilepsy patients remain untreated 3 years after diagnosis. We aimed to quantify and characterize this treatment gap within a large US academic health system leveraging the electronic health record for enriched clinical detail.
The “make or break� impact of family dynamics on psychological outcomes in focal epilepsy
Genevieve Rayner, Jessamae Pieters, Grace Broomfield, Jacquie Eyres, Jasmine Schipp, Sarah J. Wilson
doi : 10.1111/epi.17619
Living with epilepsy can shape the dynamics of the whole family unit. The first objective of this study was to establish the reliability and validity of our purpose-built online family mapping tool: “Living with Epilepsy.
Domain-specific relationships of subjective and objective cognition in epilepsy
Louisa Hohmann, Justus Berger, Shirley-Uloma Kastell, Martin Holtkamp
doi : 10.1111/epi.17624
Many people with epilepsy report subjective cognitive impairment (SCI), i.e., problems with memory, attention, or executive functions, reducing quality of life. Nevertheless, overlap with objective cognitive impairment (OCI) is often weak.
Long-term epilepsy outcome dynamics revealed by natural language processing of clinic notes
Kevin Xie, Ryan S. Gallagher, Russell T. Shinohara, Sharon X. Xie, Chloe E. Hill, Erin C. Conrad, Kathryn A. Davis, Dan Roth, Brian Litt, Colin A. Ellis
doi : 10.1111/epi.17633
Electronic medical records allow for retrospective clinical research with large patient cohorts. However, epilepsy outcomes are often contained in free text notes that are difficult to mine. We recently developed and validated novel natural language processing (NLP) algorithms to automatically extract key epilepsy outcome measures from clinic notes. In this study, we assessed the feasibility of extracting these measures to study the natural history of epilepsy at our center.
Flexible, high-resolution cortical arrays with large coverage capture microscale high-frequency oscillations in patients with epilepsy
Katrina J. Barth, James Sun, Chia-Han Chiang, Shaoyu Qiao, Charles Wang, Shervin Rahimpour, Michael Trumpis, Suseendrakumar Duraivel, Agrita Dubey, Katie E. Wingel, Alex E. Voinas, Breonna Ferrentino, Werner Doyle, Derek G. Southwell, Michael M. Haglund, Matthew Vestal, Stephen C. Harward, Florian Solzbacher, Sasha Devore, Orrin Devinsky, Daniel Friedman, Bijan Pesaran, Saurabh R. Sinha, Gregory B. Cogan, Justin Blanco, Jonathan Viventi
doi : 10.1111/epi.17642
Effective surgical treatment of drug-resistant epilepsy depends on accurate localization of the epileptogenic zone (EZ). High-frequency oscillations (HFOs) are potential biomarkers of the EZ.
Stimulation-induced respiratory enhancement in corticothalamic regions
Blanca Talavera, Ganne Chaitanya, Norma Hupp, Sandipan Pati, Johnson P. Hampson, Xi Luo, Jaison Hampson, Yash S. Vakilna, M. R. Sandhya Rani, Rabeha Noor, John C. Mosher, Nitin Tandon, Samden D. Lhatoo, Nuria Lacuey
doi : 10.1111/epi.17635
We aimed to identify corticothalamic areas and electrical stimulation paradigms that optimally enhance breathing.
Excitatory–inhibitory mismatch shapes node recruitment in an epileptic network
Peijuan Luo, Fan Yang, Jing Li, James E. Niemeyer, Fengrui Zhan, Joshua Estin, Mingrui Zhao, Dan Li, Weihong Lin, Jyun-You Liou, Hongtao Ma, Theodore H. Schwartz
doi : 10.1111/epi.17638
Focal epilepsy is thought to be a network disease, in which epileptiform activity can spread noncontiguously through the brain via highly interconnected nodes, or hubs, within existing networks. Animal models confirming this hypothesis are scarce, and our understanding of how distant nodes are recruited is also lacking. Whether interictal spikes (IISs) also create and reverberate through a network is not well understood.
Antiseizure medications in the World Health Organization list of “essential medicines�
Ali A. Asadi-Pooya, Alla Guekht
doi : 10.1111/epi.17649
Correction to “Heterozygous GABAA receptor β3 subunit N110D knock-in mice have epileptic spasms�
doi : 10.1111/epi.17667
Chronic intracranial recordings after resection for epilepsy reveal a "running down" of epileptiform activity
Bornali Kundu, Chantel M. Charlebois, Daria Nesterovich Anderson, Angela Peters, John D. Rolston
doi : 10.1111/epi.17645
We describe an electrical "running down" phenomenon and also a consistent spectral change (in the aperiodic component of the power spectrum) derived from chronic interictal electrocorticography (ECoG) after surgery in a patient with drug-resistant epilepsy. These data were recorded using a closed-loop neurostimulation system that was implanted after resection.
Ezogabine impacts seizures and development in patients with KCNQ2 developmental and epileptic encephalopathy
Devon Knight, Sonal Mahida, Mckenna Kelly, Annapurna Poduri, Heather E. Olson
doi : 10.1111/epi.17627
Genetic variants in KCNQ2 are associated with a range of epilepsies, from self- limited (familial) neonatal-infantile epilepsy to developmental and epileptic encephalopathy (DEE). We retrospectively reviewed clinical data from eight patients with KCNQ2-related DEE who were treated with ezogabine.
A novel KCNC1 gain-of-function variant causing developmental and epileptic encephalopathy: “Precision medicine� approach with fluoxetine
Paolo Ambrosino, Francesca Ragona, Ilaria Mosca, Chiara Vannicola, Laura Canafoglia, Roberta Solazzi, Ilaria Rivolta, Elena Freri, Tiziana Granata, Giuliana Messina, Barbara Castellotti, Cinzia Gellera, Maria Virginia Soldovieri, Jacopo Cosimo DiFrancesco, Maurizio Taglialatela
doi : 10.1111/epi.17656
Variable phenotypes, including developmental encephalopathy with (DEE) or without seizures and myoclonic epilepsy and ataxia due to potassium channel mutation, are caused by pathogenetic variants in KCNC1, encoding for Kv3.1 channel subunits.
