Medical Sciences Commons^™

De Novo Variants Of Nr4a2 Are Associated With Neurodevelopmental Disorder And Epilepsy., Sakshi Singh, Aditi Gupta, Michael Zech, Ashley N. Sigafoos, Karl J. Clark, Yasemin Dincer, Matias Wagner, Jennifer B. Humberson, Sarah Green, Koen Van Gassen, Tracy Brandt, Rhonda E. Schnur, Francisca Millan, Yue Si, Volker Mall, Juliane Winkelmann, Ralitza H. Gavrilova, Eric W. Klee, Kendra Engleman, Nicole P. Safina, Rachel Slaugh, Emily M. Bryant, Wen-Hann Tan, Jorge Granadillo, Sunita N. Misra, G Bradley Schaefer, Shelley Towner, Eva H. Brilstra, Bobby P C Koeleman

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: This study characterizes the clinical and genetic features of nine unrelated patients with de novo variants in the NR4A2 gene.

METHODS: Variants were identified and de novo origins were confirmed through trio exome sequencing in all but one patient. Targeted RNA sequencing was performed for one variant to confirm its splicing effect. Independent discoveries were shared through GeneMatcher.

RESULTS: Missense and loss-of-function variants in NR4A2 were identified in patients from eight unrelated families. One patient carried a larger deletion including adjacent genes. The cases presented with developmental delay, hypotonia (six cases), and epilepsy (six cases). De novo status was …

Coordination Of Inpatient And Outpatient Care For Neurology Patients Undergoing Epilepsy Monitoring, Sara Schrock, Michelle Beane, Kathryn Cope, Mark Parker, Suneela Nayak, Ruth Hanselman, Stephen Tyzik, Amy Sparks, Brendan Lilley

Operations Transformation

ORGANIZING A SYSTEM TO CONSOLIDATE EPILEPSY REFERRALS TO AN OUTPATIENT NEUROLOGY PRACTICE

An outpatient neurology practice was experiencing delayed or lost referrals for epilepsy monitoring. This delay was leading many patients to suffer unnecessary and unmanaged seizures and, in some cases, frequent trips to the emergency department.

As a result, a team consisting of the neurology practice and neuro-navigators used baseline metrics to demonstrate the current state of the problem and conducted a root cause analysis that outlined several causes. A number of countermeasures were initiated with the goal of decreasing referral misses.

Post the initiation of two KPIs, a …

Functional Neuroplasticity In The Nucleus Tractus Solitarius And Increased Risk Of Sudden Death In Mice With Acquired Temporal Lobe Epilepsy, Isabel D. Derera, Brian P. Delisle, Bret N. Smith

Physiology Faculty Publications

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in individuals with refractory acquired epilepsy. Cardiorespiratory failure is the most likely cause in most cases, and central autonomic dysfunction has been implicated as a contributing factor to SUDEP. Neurons of the nucleus tractus solitarius (NTS) in the brainstem vagal complex receive and integrate vagally mediated information regarding cardiorespiratory and other autonomic functions, and GABAergic inhibitory NTS neurons play an essential role in modulating autonomic output. We assessed the activity of GABAergic NTS neurons as a function of epilepsy development in the pilocarpine-induced status epilepticus (SE) model of …

Metabolic Dysfunction Underlying Autism Spectrum Disorder And Potential Treatment Approaches, Ning Cheng, Jong M. Rho, Susan A. Masino

Faculty Scholarship

Autism spectrum disorder (ASD) is characterized by deficits in sociability and communication, and increased repetitive and/or restrictive behaviors. While the etio-pathogenesis of ASD is unknown, clinical manifestations are diverse and many possible genetic and environmental factors have been implicated. As such, it has been a great challenge to identify key neurobiological mechanisms and to develop effective treatments. Current therapies focus on co-morbid conditions (such as epileptic seizures and sleep disturbances) and there is no cure for the core symptoms. Recent studies have increasingly implicated mitochondrial dysfunction in ASD. The fact that mitochondria are an integral part of diverse cellular functions …

Ketogenic Diet Decreases Emergency Room Visits And Hospitalizations Related To Epilepsy., Husam R. Kayyali, Anastasia Luniova, Ahmed Abdelmoity

Manuscripts, Articles, Book Chapters and Other Papers

Background. Approximately, one-third of patients with epilepsy are refractory to pharmacological treatment which mandates extensive medical care and imposes significant economic burden on patients and their societies. This study intends to assess the impact of the treatment with ketogenic diet (KD) on reducing seizure-related emergency room visits and hospitalizations in children with refractory epilepsy. Methods. This is a retrospective review of children treated with the KD in one tertiary center. We compared a 12 months' period prior to KD with 12 months after the diet was started in regard to the number of emergency department (ED) visits, hospitalizations, …

Prolonged Febrile Seizures Cause Reversible Reductions In White Matter Integrity☆, M. Yoong, K. Seunarine, M. Martinos, R. F. Chin, C. A. Clark, R. C. Scott

Dartmouth Scholarship

Prolonged febrile seizures (PFS) are the commonest cause of childhood status epilepticus and are believed to carry a risk of neuronal damage, in particular to the mesial temporal lobe. This study was designed to determine: i) the effect of prolonged febrile seizures on white matter and ii) the temporal evolution of any changes seen.

33 children were recruited 1 month following PFS and underwent diffusion tensor imaging (DTI) with repeat imaging at 6 and 12 months after the original episode of PFS. 18 age-matched healthy control subjects underwent similar investigations at a single time point. Tract-based spatial statistics (TBSS) was …

Hippocampal Functional Connectivity Patterns During Spatial Working Memory Differ In Right Versus Left Temporal Lobe Epilepsy., Gaelle Eve Doucet, Karol Osipowicz, Ashwini Sharan Md, Michael R Sperling, Joseph I Tracy

Department of Neurology Faculty Papers

Temporal lobe epilepsy (TLE), affecting the medial temporal lobe, is a disorder that affects not just episodic memory but also working memory (WM). However, the exact nature of hippocampal-related network activity in visuospatial WM remains unclear. To clarify this, we utilized a functional connectivity (FC) methodology to investigate hippocampal network involvement during the encoding phase of a functional magnetic resonance imaging (fMRI) visuospatial WM task in right and left TLE patients. Specifically, we assessed the relation between FC within right and left hippocampus-seeded networks, and patient performance (rate of correct responses) during the encoding phase of a block span WM …