Neurology Commons^™

Loss-Of-Function Variants In Tiam1 Are Associated With Developmental Delay, Intellectual Disability, And Seizures, Shenzhao Lu, Rebecca Hernan, Paul C Marcogliese, Yan Huang, Tracy S Gertler, Meltem Akcaboy, Shiyong Liu, Hyung-Lok Chung, Xueyang Pan, Xiaoqin Sun, Melahat Melek Oguz, Ulkühan Oztoprak, Jeroen H F De Baaij, Jelena Ivanisevic, Erin Mcginnis, Maria J Guillen Sacoto, Wendy K Chung, Hugo J Bellen

Duncan NRI Faculty and Staff Publications

TIAM Rac1-associated GEF 1 (TIAM1) regulates RAC1 signaling pathways that affect the control of neuronal morphogenesis and neurite outgrowth by modulating the actin cytoskeletal network. To date, TIAM1 has not been associated with a Mendelian disorder. Here, we describe five individuals with bi-allelic TIAM1 missense variants who have developmental delay, intellectual disability, speech delay, and seizures. Bioinformatic analyses demonstrate that these variants are rare and likely pathogenic. We found that the Drosophila ortholog of TIAM1, still life (sif), is expressed in larval and adult central nervous system (CNS) and is mainly expressed in a subset of neurons, but not in …

Barriers, Access And Management Of Paediatric Epilepsy With Telehealth., Kari Gali, Sucheta Joshi, Sarah Hueneke, Alexis Katzenbach, Linda Radecki, Trisha Calabrese, Linda Fletcher, Cristina Trandafir, Carey Wilson, Monisha Goyal, Courtney J. Wusthoff, Jean-Baptist Lepichon, Rhonda Corvalan, April Golson, Jessica Hardy, Michael Smith, Elizabeth Cook, Joshua L. Bonkowsky

Manuscripts, Articles, Book Chapters and Other Papers

Access to paediatric neurology care is complex, resulting in significant wait times and negative patient outcomes. The goal of the American Academy of Pediatrics National Coordinating Center for Epilepsy's project, Access Improvement and Management of Epilepsy with Telehealth (AIM-ET), was to identify access and management challenges in the deployment of telehealth technology. AIM-ET organised four paediatric neurology teams to partner with primary-care providers (PCP) and their multidisciplinary teams. Telehealth visits were conducted for paediatric epilepsy patients. A post-visit survey assessed access and satisfaction with the telehealth visit compared to an in-person visit. Pre/post surveys completed by PCPs and neurologists captured …

Post-Operative Seizure Control In Patients With Glioblastoma, Ummey Hani, Muhammad Ammar Haider, Saqib Kamran Bakhshi, Muhammad Shahzad Shamim

Section of Neurosurgery

While the median survival in patients with glioblastoma has not improved significantly over the past decade, aggressive attempts have been made on palliation and improving quality of life in these patients. A confluence of two debilitating pathologies which massively distorts the normal day-to-day functioning of the patients who experience it, seizures in glioblastoma patients portends a poor prognosis. There exists a paucity of reported seizure outcomes after glioblastoma treatment in neurosurgical literature. Herein we present a review examining post-operative seizure control in patients with glioblastoma.

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, …

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 …

Epilepsy Risk Prediction Model For Patients With Tuberous Sclerosis Complex, Laura S Farach, Melissa A Richard, Philip J Lupo, Mustafa Sahin, Darcy A Krueger, Joyce Y Wu, Elizabeth M Bebin, Kit Sing Au, Hope Northrup, Tacern Study Group

Faculty, Staff and Student Publications

BACKGROUND: Individuals with tuberous sclerosis complex are at increased risk of epilepsy. Early seizure control improves developmental outcomes, making identifying at-risk patients critically important. Despite several identified risk factors, it remains difficult to predict. The purpose of the study was to evaluate the combined risk prediction of previously identified risk factors for epilepsy in individuals with tuberous sclerosis complex.

METHODS: The study group (n = 333) consisted of individuals with tuberous sclerosis complex who were enrolled in the Tuberous Sclerosis Complex Autism Center of Excellence Research Network and UT TSC Biobank. The outcome was defined as having an epilepsy diagnosis. …

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 …

Thalamus And Focal To Bilateral Seizures: A Multiscale Cognitive Imaging Study., Lorenzo Caciagli, Luke A Allen, Xiaosong He, Karin Trimmel, Sjoerd B Vos, Maria Centeno, Marian Galovic, Meneka K Sidhu, Pamela J Thompson, Danielle S Bassett, Gavin P Winston, John S Duncan, Matthias J Koepp, Michael R Sperling

Department of Neurology Faculty Papers

OBJECTIVE: To investigate the functional correlates of recurrent secondarily generalized seizures in temporal lobe epilepsy (TLE) using task-based fMRI as a framework to test for epilepsy-specific network rearrangements. Because the thalamus modulates propagation of temporal lobe onset seizures and promotes cortical synchronization during cognition, we hypothesized that occurrence of secondarily generalized seizures, i.e., focal to bilateral tonic-clonic seizures (FBTCS), would relate to thalamic dysfunction, altered connectivity, and whole-brain network centrality.

METHODS: FBTCS occur in a third of patients with TLE and are a major determinant of disease severity. In this cross-sectional study, we analyzed 113 patients with drug-resistant TLE (55 …

Unexpected Brain Imaging Findings In Patients With Seizures, Boulenouar Mesraoua, Matthias Koepp, Bernhard Schuknecht, Dirk Deleu, Hassan J Al Hail, Gayane Melikyan, Lubna Elsheikh, A A Asadi-Pooya

Department of Neurology Faculty Papers

New imaging technologies have advanced our ability to localize the epileptogenic zone in patients with epilepsy. As a result of the constant improvement of the image quality, magnetic resonance imaging (MRI) has become the most important ancillary tool in the management of patients with epilepsy. Magnetic resonance imaging for the evaluation of patients with epilepsy should be done using a special temporal lobe protocol and read by physicians experienced with the findings in patients with epilepsy. On the other hand, in the healthy populations, incidental structural brain abnormalities have been reported in 18% of people. Incidental, subtle, or unexpected structural …

Dramatic Outcomes In Epilepsy: Depression, Suicide, Injuries, And Mortality, Boulenouar Mesraoua, Dirk Deleu, Al Hail Hassan, Melykian Gayane, Alsheikh Lubna, Musab Abdalhalim Ali, Torbjorn Tomson, Bassel Abou Khalil, J Helen Cross, Ali A Asadi-Pooya

Department of Neurology Faculty Papers

In this narrative review, we will discuss some of the significant risks and dramatic consequences that are associated with epilepsy: depression, suicide, seizure-related injuries, and mortality, both in adults and in children. Considering the high prevalence of depression among people with epilepsy (PWE), routine and periodic screening of all PWE for early detection and appropriate management of depression is recommended. PWE should be screened for suicidal ideation regularly and when needed, patients should be referred for a psychiatric evaluation and treatment. When starting an antiepileptic drug (AED) or switching from one to another AED, patients should be advised to report …

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 …

Neurological Manifestations Of Covid-19, Dureshahwar Kanwar, Abdul Mannan Baig, Mohammad Wasay

Section of Neurology

Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) has turned out to be a formidable pandemic. Upcoming evidence from confirmed cases of COVID-19 suggests an anticipated incursion of patients with neurological manifestations in the weeks to come. An expression of the angiotensin-converting enzyme 2 (ACE 2), the cellular receptor for SARS-CoV-2 over the glial cells and neurons have made the brain a potential target. Neurotoxicity may occur as a result of direct, indirect and post-infectious complications. Attention to neurological deficits in COVID-19 is fundamental to ensure appropriate, timely, beneficial management of the affected patients. Most …

Using Simple Ct Perfusion To Help Identify Ictal Vs. Interictal Lateralized Periodic Discharges (Lpds): A Case Report, Michelle Nunes, Aqsa Ullah, Amna Imran, Enrique Serrano

Neurology

No abstract provided.

Editorial: Sudden Unexpected Death In Epilepsy: Bio-Markers, Mechanisms, Risk Identification And Prevention., Rainer Surges, Michael R. Sperling, Christopher M. Degiorgio

Department of Neurology Faculty Papers

No abstract provided.

Recommendations For The Design Of Therapeutic Trials For Neonatal Seizures., Janet S. Soul, Ronit Pressler, Marilee Allen, Geraldine Boylan, Heike Rabe, Ron Portman, Pollyanna Hardy, Sarah Zohar, Klaus Romero, Brian Tseng, Varsha Bhatt-Mehta, Cecil Hahn, Scott Denne, Stephane Auvin, Alexander Vinks, John Lantos, Neil Marlow, Jonathan M. Davis, International Neonatal Consortium

Manuscripts, Articles, Book Chapters and Other Papers

Although seizures have a higher incidence in neonates than any other age group and are associated with significant mortality and neurodevelopmental disability, treatment is largely guided by physician preference and tradition, due to a lack of data from well-designed clinical trials. There is increasing interest in conducting trials of novel drugs to treat neonatal seizures, but the unique characteristics of this disorder and patient population require special consideration with regard to trial design. The Critical Path Institute formed a global working group of experts and key stakeholders from academia, the pharmaceutical industry, regulatory agencies, neonatal nurse associations, and patient advocacy …

Choice Of Therapeutic Anti-Seizure Medication In Patients With Brain Tumour, Altaf Ali Laghari, Syed Ijlal Ahmed, Namra Qadeer, Muhammad Shahzad Shamim

Section of Neurosurgery

Seizures are common in patients with brain tumours, even though prophylactic anti-seizure treatment for all patients with brain tumours is not recommended. Newer anti-epileptic drugs have shown benefits that outweigh the side effects of treatment and can also be given in combination with traditional anti-epileptic drugs. The authors have reviewed the literature on the various combinations of anti-epileptics in patients with seizures and brain tumours.

The Risk Of New-Onset Epilepsy And Refractory Epilepsy In Older Adult Stroke Survivors, Jorge G. Burneo, Tresah C. Antaya, Britney N. Allen, Andrea Belisle, Salimah Z. Shariff, Gustavo Saposnik

Neuroepidemiology Research Unit Project Summaries

Research Summary: Key Findings

• Stroke is a common cause of epilepsy in older adults, but little is known about stroke-related epilepsy or its outcomes in this population.
• 1.1% of older adult stroke survivors developed epilepsy in this study, of whom 12.9% developed refractory epilepsy, indicating that this population is particularly responsive to treatment.
• Over 85% of deaths in this population are not due to stroke or epilepsy.

Does Transcutaneous Vagal Nerve Stimulation (T-Vns) Reduce Seizure Frequency In Adult Patients With Pharmacoresistent Epilepsy?, Scott Poirier

PCOM Physician Assistant Studies Student Scholarship

Objective The objective of this selective EBM review is to determine whether or not transcutaneous vagal nerve stimulation is an effective measure in reducing seizure frequency in adult patients with pharmacoresistant epilepsy.

Study Design This systematic review comprises a randomized controlled trial and an observational pilot study, both published in 2014, as well as a double-blind randomized control trial published in 2016.

Data Sources All articles were published and displayed in English. The articles were obtained via the PubMed database.

Outcomes Measured Reductions in average seizure frequency were analyzed based on data from patient seizure diaries. Secondary outcomes, including quality …

Effects Of Adjunctive Eslicarbazepine Acetate On Serum Lipids In Patients With Partial-Onset Seizures: Impact Of Concomitant Statins And Enzyme-Inducing Antiepileptic Drugs., Scott Mintzer, Robert T. Wechsler, Joanne B. Rogin, Barry E. Gidal, Matthias Schwab, Elinor Ben-Menachem, Mar Carreño, Patrício Soares Da Silva, Joana Moreira, Yan Li, David Blum, Todd Grinnell

Department of Neurology Faculty Papers

PURPOSE: To evaluate the effects of eslicarbazepine acetate (ESL) on lipid metabolism and to determine whether reduced statin exposure during ESL therapy has clinical consequences.

SUBJECTS AND METHODS: We conducted a post-hoc analysis of pooled data for serum lipids (laboratory values) from three phase III, multicenter, randomized, double-blind, placebo-controlled trials of adjunctive ESL therapy (400, 800, or 1200 mg once daily) in patients with treatment-refractory partial-onset seizures. Changes from baseline in serum lipid levels were analyzed according to use of statins and/or enzyme-inducing antiepileptic drugs (EIAEDs) during the baseline period.

KEY FINDINGS: In total, 426 and 1021 placebo- and ESL-treated …

Burden Of Arrhythmias In Epilepsy Patients: A Nationwide Inpatient Analysis Of 1.4 Million Hospitalizations In The United States, Rupak Desai, Chintan Rupareliya, Upenkumar Patel, Syeda Naqvi, Smit Patel, Abhishek Lunagariya, Zabeen Mahuwala

Neurology Faculty Publications

Arrhythmias have been one of the common complications in epilepsy patients and have also been the reason for death. However, limited data exist about the burden and outcomes of arrhythmias by subtypes in epilepsy. Our study aims at evaluating the burden and differences in outcomes of various subtypes of arrhythmias in epilepsy patient population. The Nationwide Inpatient Sample (NIS) database from 2014 was examined for epilepsy and arrhythmias related discharges using appropriate International Classification of Disease, Ninth Revision Clinical Modification (ICD-9-CM) codes. The frequency of arrhythmias, gender differences in arrhythmia by subtypes, in-hospital outcomes and mortality predictors was analyzed. A …

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, …

Prevalence Of And Risk Factors For Intracranial Abnormalities In Unprovoked Seizures., Peter S. Dayan, Kathleen Lillis, Jonathan Bennett, Gregory P. Conners, Pam Bailey, James Callahan, Cigdem Akman, Neil Feldstein, Joshua Kriger, W Allen Hauser, Nathan Kuppermann

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND AND OBJECTIVES: Prospective data are lacking to determine which children might benefit from prompt neuroimaging after unprovoked seizures. We aimed to determine the prevalence of, and risk factors for, relevant intracranial abnormalities in children with first, unprovoked seizures.

METHODS: We conducted a 6-center prospective study in children aged >28 days to 18 years with seemingly unprovoked seizures. Emergency department (ED) clinicians documented clinical findings on a standardized form. Our main outcome was the presence of a clinically relevant intracranial abnormality on computed tomography (CT) or MRI, defined as those that might change management, either emergently, urgently, or nonurgently.

RESULTS: …

The Piriform, Perirhinal, And Entorhinal Cortex In Seizure Generation., Marta S Vismer, Patrick A Forcelli, Mark D Skopin, Karen Gale, Mohamad Z. Koubeissi

Neurology Faculty Publications

Understanding neural network behavior is essential to shed light on epileptogenesis and seizure propagation. The interconnectivity and plasticity of mammalian limbic and neocortical brain regions provide the substrate for the hypersynchrony and hyperexcitability associated with seizure activity. Recurrent unprovoked seizures are the hallmark of epilepsy, and limbic epilepsy is the most common type of medically-intractable focal epilepsy in adolescents and adults that necessitates surgical evaluation. In this review, we describe the role and relationships among the piriform (PIRC), perirhinal (PRC), and entorhinal cortex (ERC) in seizure-generation and epilepsy. The inherent function, anatomy, and histological composition of these cortical regions are …

Phenytoin Versus Leviteracetam For Seizure Prophylaxis After Brain Injury - A Meta Analysis, Syed Nabeel Zafar, Abdul Ahad Khan, Asfar Ayaz Gauri, Muhammad Shahzad Shamim

Section of Neurosurgery

Background: Current standard therapy for seizure prophylaxis in Neuro-surgical patients involves the use of Phenytoin (PHY). However, a new drug Levetiracetam (LEV) is emerging as an alternate treatment choice. We aimed to conduct a meta-analysis to compare these two drugs in patients with brain injury.
Methods: An electronic search was performed in using Pubmed, Embase, and CENTRAL. We included studies that compared the use of LEV vs. PHY for seizure prophylaxis for brain injured patients (Traumatic brain injury, intracranial hemorrhage, intracranial neoplasms, and craniotomy). Data of all eligible studies was extracted on to a standardized abstraction sheet. Data about baseline …