Medicine and Health Sciences Commons^™

Genetic Variation In Padi6-Padi4 On 1p36.13 Is Associated With Common Forms Of Human Generalized Epilepsy, Russell J. Buono, Jonathan P. Bradfield, Zhi Wei, Michael R. Sperling, Dennis J. Dlugos, Michael D. Privitera, Jacqueline A. French, Warren Lo, Patrick Cossette, Steven C. Schachter, Heather Basehore, Falk W. Lohoff, Struan F.A. Grant, Thomas N. Ferraro, Hakon Hakonarson

Department of Neurology Faculty Papers

We performed a genome-wide association study (GWAS) to identify genetic variation associated with common forms of idiopathic generalized epilepsy (GE) and focal epilepsy (FE). Using a cohort of 2220 patients and 14,448 controls, we searched for single nucleotide polymorphisms (SNPs) associated with GE, FE and both forms combined. We did not find any SNPs that reached genome-wide statistical significance (p ≤ 5 × 10⁻⁸) when comparing all cases to all controls, and few SNPs of interest comparing FE cases to controls. However, we document multiple linked SNPs in the PADI6-PADI4 genes that reach genome-wide significance and are associated …

Analysis Of Deep Brain Stimulation Lead Targeting In The Stimulation Of Anterior Nucleus Of The Thalamus For Epilepsy Clinical Trial., Robert E. Gross, Robert S. Fisher, Michael R. Sperling, Jonathon E. Giftakis, Paul H. Stypulkowski

Department of Neurology Faculty Papers

BACKGROUND: Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is an effective therapy for patients with drug-resistant focal epilepsy. Best practices for surgical targeting of the ANT can be refined as new information becomes available regarding effective stimulation sites.

OBJECTIVE: To conduct a retrospective analysis of the relationship between outcomes (seizure reduction during year 1) and DBS lead locations in subjects from the SANTÉ pivotal trial (Stimulation of ANT for Epilepsy) based upon recent clinical findings.

METHODS: Postoperative images from SANTÉ subjects (n = 101) were evaluated with respect to lead trajectory relative to defined anatomic …

Psychological Problems Among Patients With Chronic Medical Disorders During The Covid-19 Pandemic, Ali Akbar Asadi-Pooya, Seyed Ali Nabavizadeh, Saeid Sadeghian, Mina Shahisavandi, Zohreh Barzegar, Abdullah Nezafat, Nahid Ashjazadeh, Hamed Bazrafshan Drissi, Ali Sahraian

Department of Neurology Faculty Papers

The aim of the current study was to investigate the rates of stress, anxiety, and depression among people in south Iran (a group from the general population without a history of any chronic medical problems, and cohorts of patients were recruited from epilepsy, diabetes, and cardiac disease clinics). We surveyed a sample of people during September 2020: a group of the general population without a history of any chronic medical problems, people with epilepsy, people with diabetes mellitus (DM), and people with cardiac problems. The survey included four general questions and two COVID-19 specific questions [contracting COVID-19, relatives with COVID-19]. …

Distinct Cortical Systems Reinstate The Content And Context Of Episodic Memories., James E. Kragel, Youssef Ezzyat, Bradley C. Lega, Michael R. Sperling, Gregory A. Worrell, Robert E. Gross, Barbara C. Jobst, Sameer A. Sheth, Kareem A. Zaghloul, Joel M. Stein, Michael J. Kahana

Department of Neurology Faculty Papers

Episodic recall depends upon the reinstatement of cortical activity present during the formation of a memory. Evidence from functional neuroimaging and invasive recordings in humans suggest that reinstatement organizes our memories by time or content, yet the neural systems involved in reinstating these unique types of information remain unclear. Here, combining computational modeling and intracranial recordings from 69 epilepsy patients, we show that two cortical systems uniquely reinstate the semantic content and temporal context of previously studied items during free recall. Examining either the posterior medial or anterior temporal networks, we find that forward encoding models trained on the brain's …

Long-Term Efficacy And Tolerability Of Adjunctive Brivaracetam In Adults With Focal To Bilateral Tonic-Clonic (Secondary Generalized) Seizures: Post Hoc Pooled Analysis, Brian D Moseley, Svetlana Dimova, Sami Elmoufti, Cédric Laloyaux, Aliakbar Asadi-Pooya

Department of Neurology Faculty Papers

This post hoc analysis was conducted to evaluate the efficacy, tolerability, and health-related quality of life during long-term adjunctive brivaracetam (BRV) treatment in adult patients with focal to bilateral tonic-clonic seizures (FBTCS). Patients (≥ 16 years) were included in this post hoc analysis if they were randomized to BRV or placebo in double-blind, placebo-controlled (N01252 [NCT00490035], N01253 [NCT00464269], N01358 [NCT01261325]; core) trials, and received adjunctive BRV in the corresponding long-term follow-up (N01125 [NCT00175916], N01199 [NCT00150800], N01379 [NCT01339559]) trials, and reported FBTCS during the 8-week prospective baseline (core trial). Efficacy (concomitant levetiracetam excluded) and tolerability (concomitant levetiracetam included) were assessed from …

Evaluation Of Diazepam Nasal Spray In Patients With Epilepsy Concomitantly Using Maintenance Benzodiazepines: An Interim Subgroup Analysis From A Phase 3, Long-Term, Open-Label Safety Study., Eric B Segal, Daniel Tarquinio, Ian Miller, James W Wheless, Dennis Dlugos, Victor Biton, Gregory D Cascino, Jay Desai, R Edward Hogan, Kore Liow, Michael R Sperling, Blanca Vazquez, David F Cook, Adrian L Rabinowicz, Enrique Carrazana

Department of Neurology Faculty Papers

OBJECTIVE: Diazepam nasal spray (Valtoco), indicated for acute treatment of frequent seizure activity (seizure clusters) in patients with epilepsy ≥6 years of age, is designed to be a rapid, noninvasive, socially acceptable route of administration. This interim analysis evaluated the safety profile of diazepam nasal spray in patients with and without concomitant use of benzodiazepines, with use of a second dose for a seizure cluster as a proxy for effectiveness.

METHODS: A long-term, phase 3, open-label safety study enrolled patients with epilepsy who had seizures despite a stable antiseizure medication regimen.

RESULTS: Among 175 patients enrolled by October 31, 2019, …

Automated Analysis Of Risk Factors For Postictal Generalized Eeg Suppression, Xiuhe Zhao, Laura Vilella, Liang Zhu, M R Sandhya Rani, Johnson P Hampson, Jaison Hampson, Norma J Hupp, Rup K Sainju, Daniel Friedman, Maromi Nei, Catherine Scott, Luke Allen, Brian K Gehlbach, Stephan Schuele, Ronald M Harper, Beate Diehl, Lisa M Bateman, Orrin Devinsky, George B Richerson, Guo-Qiang Zhang, Samden D Lhatoo, Nuria Lacuey

Department of Neurology Faculty Papers

Rationale: Currently, there is some ambiguity over the role of postictal generalized electro-encephalographic suppression (PGES) as a biomarker in sudden unexpected death in epilepsy (SUDEP). Visual analysis of PGES, known to be subjective, may account for this. In this study, we set out to perform an analysis of PGES presence and duration using a validated signal processing tool, specifically to examine the association between PGES and seizure features previously reported to be associated with visually analyzed PGES. Methods: This is a prospective, multicenter epilepsy monitoring study of autonomic and breathing biomarkers of SUDEP in adult patients with intractable epilepsy. We …

Cardiovascular Disease Risk, Awareness, And Treatment In People With Epilepsy, Samuel W Terman, Carole E Aubert, Chloe E Hill, Jeremy Skvarce, James F Burke, Scott Mintzer

Department of Neurology Faculty Papers

OBJECTIVE: To evaluate whether cardiovascular risk, risk awareness, and guideline concordant treatment differ in individuals with versus without epilepsy.

METHODS: This was a retrospective cross-sectional study using the National Health and Nutrition Examination Survey. We included participants ≥18 years for 2013-2018. We classified participants as having epilepsy if reporting ≥1 medication treating seizures. We calculated 10-year atherosclerotic cardiovascular disease (ASCVD) risk using the revised pooled cohort equation. We compared unadjusted and adjusted risk for participants with versus without epilepsy. We then assessed hypertension and diabetes disease awareness and control, plus statin guideline-concordance. We assessed mediators for both ASCVD risk and …

Characterizing The Timeline Of Drug Resistant Epilepsy Surgery., Nicole Belliard Martuscelli, Caio Matias, Ashwini Sharan

Phase 1

Introduction: Although early detection and surgery are crucial for positive outcomes in individuals with drug-resistant epilepsy (DRE), a minority of qualifying patients receive it in the US. This retrospective study investigates why some DRE patients who undergo complete pre-surgical assessment end up not receiving surgery.

Methods: We analyzed 211 EPIC charts from all of Jefferson Comprehensive Epilepsy Center's patients who underwent DRE surgical evaluation from 2017 through 2019. To that end, we characterized the DRE surgery timeline and collected data on age, onset of seizures and drug resistance, surgery dates, surgical modalities, and notes that elucidated the reasoning behind …