Medical Sciences Commons^™

The Effect Of Polyunsaturated And Saturated Fatty Acids On Seizure Presence And Severity In A Cohort Of Subjects In An Epilepsy Monitoring Unit, Jana K. Wells

Theses & Dissertations

Ketogenic diet therapies (KDTs) have been used to treat epilepsy for nearly 100 years. Although effective, restrictive diet patterns and unknown impacts on long-term health outcomes often prevent their use as first-line therapy. To date, a distinct mechanism of action for KDTs has not been determined and evidence suggests fatty acids (FAs) may play a role in eliciting anti-seizure effects. This dissertation aimed to provide insights into the effect of polyunsaturated fatty acids (PUFAs) and saturated fatty acids (SFAs) on seizure presence and severity through the analysis of dietary intake in a cohort of patients admitted to an epilepsy monitoring …

Perampanel-Induced Cataplexy In A Young Male With Generalized Epilepsy, Kelsey Kenaan, Mohsin Zafar, Ronnie Bond, Barbara L. Gracious

HCA Healthcare Journal of Medicine

Perampanel (Fycompa) is a newer anti-epileptic drug believed to exert its effects in the central nervous system by inhibiting post-synaptic glutamate receptors. However, the precise therapeutic mechanism is unknown. The most common neuropsychiatric side effect is affective dysregulation; there are also reports of psychosis. We describe a 32 year old African American male with recurring generalized tonic-clonic (GTC) seizures, who presented to our hospital with onset of mood lability for several months, after Perampanel was added to his antiepileptic medications. Perampanel administration was temporarily withheld, and subsequently on restarting, noted to be coincident with neuropsychiatric symptomatology, including motor weakness in …

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 …

Epilepsy Risk Among Survivors Of Intensive Care Unit Hospitalization For Sepsis, Tresah C. Antaya, Britney N. Allen, Lucie Richard, Salimah Z. Shariff, Gustavo Saposnik, Jorge Burneo

Neuroepidemiology Research Unit Project Summaries

Research Summary: Key Findings

• 407 (0.28%) patients developed epilepsy within 2 years of their ICU discharge, 103 (25.3%) of whom were exposed to sepsis.
• Sepsis survivors were significantly more likely to develop epilepsy, relative to non-septic ICU survivors.
• Among sepsis survivors, epilepsy risk increased with age and was higher among those with chronic kidney disease.

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

Operational 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, …

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

Gaelle Eve Doucet

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 …

Pediatric Super-Refractory Status Epilepticus Treated With Allopregnanolone, Eileen Broomall, Joanne Natale, Michele Grimason, Joshua Goldstein, Craig Smith, Celia Chang, Stephen Kanes, Michael Rogawski, Mark Wainwright

Michael A. Rogawski

Super-refractory status epilepticus is a life-threatening condition. Resistance to benzodiazepine and barbiturate treatment for this disorder is thought to be due to internalization of synaptic GABA-A receptors, and withdrawal of benzodiazepines and barbiturates during treatment often triggers seizure recurrence. The neurosteroid allopregnanolone acts as a positive allosteric modulator of synaptic and extrasynaptic GABA-A receptors. Here we describe the use of allopregnanolone in two pediatric patients with super-refractory status epilepticus. This treatment allowed the general anesthetic infusions to be weaned with resolution of status epilepticus. This is the first report of allopregnanolone use to treat status epilepticus in children.

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 …