Neurology Commons^™

Multifocal Myoclonus As A Presentation Of Levetiracetam Toxicity., Mei Bou Nasif, Shweta Varade, Mohamad Z. Koubeissi

Neurology Faculty Publications

No abstract provided.

Hypothalamic Hamartomas: Evolving Understanding And Management., Nathan T. Cohen, J Helen Cross, Alexis Arzimanoglou, Samuel F Berkovic, John F Kerrigan, Ilene Penn Miller, Erica Webster, Lisa Soeby, Arthur Cukiert, Dale K Hesdorffer, Barbara L Kroner, Clifford B Saper, Andreas Schulze-Bonhage, William D. Gaillard

Neurology Faculty Publications

No abstract provided.

Treatment Of Thoracolumbar Type A3 Fractures Using A Percutaneous Intravertebral Expandable Titanium Implant: Long-Term Follow-Up Results Of A Pilot Single Center Study., David C Noriega, Jesus Crespo-Sanjuan, Wayne J. Olan, Ruben Hernandez-Ramajo, Douglas P Bell, J Javier Castrodeza Sanz, Gregorio De Jesus Labrador Hernandez, Israel Sanchez-Lite, Francisco Ardura

Neurological Surgery Faculty Publications

BACKGROUND: There are controversies about the optimal management of AO subtype A3 burst fractures. The most common surgical treatment consists of posterior fixation with pedicle screw and rod augmentation. Nevertheless, a loss of correction in height restoration and kyphotic reduction has been observed.

OBJECTIVES: The aim of this study was to assess long-term outcomes of a minimally invasive technique using a percutaneous intravertebral expandable titanium implant (PIETI).

STUDY DESIGN: This prospective, single center, pilot study was carried out on a consecutive case series of 44 patients with acute (< 2 weeks) traumatic thoracolumbar fractures AO type A3. The average follow-up was 5.6 years.

SETTING: A single center in Castilla y Leon, SpainMETHODS: Clinical outcomes …

Neurotransmitter, Fall 2019, George Washington Institute For Neuroscience Neurological Institute, George Washington University Hospital

Neurotransmitter

No abstract provided.

Emerging Cellular And Molecular Strategies For Enhancing Central Nervous System (Cns) Remyelination., Mohammad Abu-Rub, Robert H Miller

Anatomy and Regenerative Biology Faculty Publications

Myelination is critical for the normal functioning of the central nervous system (CNS) in vertebrates. Conditions in which the development of myelin is perturbed result in severely compromised individuals often with shorter lifespans, while loss of myelin in the adult results in a variety of functional deficits. Although some form of spontaneous remyelination often takes place, the repair process as a whole often fails. Several lines of evidence suggest it is feasible to develop strategies that enhance the capacity of the CNS to undergo remyelination and potentially reverse functional deficits. Such strategies include cellular therapies using either neural or mesenchymal …

Amygdala Corticofugal Input Shapes Mitral Cell Responses In The Accessory Olfactory Bulb, Livio Oboti, Eleonora Russo, Tuyen Tran, Daniel Durstewitz, Joshua G. Corbin

Pediatrics Faculty Publications

Interconnections between the olfactory bulb and the amygdala are a major pathway for triggering strong behavioral responses to a variety of odorants. However, while this broad mapping has been established, the patterns of amygdala feedback connectivity and the influence on olfactory circuitry remain unknown. Here, using a combination of neuronal tracing approaches, we dissect the connectivity of a cortical amygdala [posteromedial cortical nucleus (PmCo)] feedback circuit innervating the mouse accessory olfactory bulb. Optogenetic activation of PmCo feedback mainly results in feedforward mitral cell (MC) inhibition through direct excitation of GABAergic granule cells. In addition, LED-driven activity of corticofugal afferents increases …

Electromyographic And Joint Kinematic Patterns In Runner's Dystonia., Omar F Ahmad, Pritha Ghosh, Christopher Stanley, Barbara Karp, Mark Hallett, Codrin Lungu, Katharine Alter

Neurology Faculty Publications

Runner’s dystonia (RD) is a task-specific focal dystonia of the lower limbs that occurs when running. In this retrospective case series, we present surface electromyography (EMG) and joint kinematic data from thirteen patients with RD who underwent instrumented gait analysis (IGA) at the Functional and Biomechanics Laboratory at the National Institutes of Health. Four cases of RD are described in greater detail to demonstrate the potential utility of EMG with kinematic studies to identify dystonic muscle groups in RD. In these cases, the methodology for muscle selection for botulinum toxin therapy and the therapeutic response is discussed. Lateral heel whip, …

Neurotransmitter, Spring 2018, George Washington Institute For Neuroscience Neurological Institute, George Washington University Hospital

Neurotransmitter

No abstract provided.

Why West? Comparisons Of Clinical, Genetic And Molecular Features Of Infants With And Without Spasms., Anne T Berg, Samya Chakravorty, Sookyong Koh, Zachary M Grinspan, Renée A Shellhaas, William D Gaillard, +Several Additional Authors

Neurology Faculty Publications

Infantile spasms are the defining seizures of West syndrome, a severe form of early life epilepsy with poorly-understood pathophysiology. We present a novel comparative analysis of infants with spasms versus other seizure-types and identify clinical, etiological, and molecular-genetic factors preferentially predisposing to spasms. We compared ages, clinical etiologies, and associated-genes between spasms and non-spasms groups in a multicenter cohort of 509 infants (

Absolute Lymphocyte And Neutrophil Counts In Neonatal Ischemic Brain Injury., Jessica M Povroznik, Elizabeth B Engler-Chiurazzi, Tania Nanavati, Paola Pergami

Neurology Faculty Publications

Objectives: This study aimed to identify differences in absolute neutrophils, lymphocytes, and neutrophil-to-lymphocyte ratio between neonates with two forms of ischemic brain injury, hypoxic-ischemic encephalopathy, and acute ischemic stroke, compared to controls. We also aimed to determine whether this neutrophil/lymphocyte response pattern is associated with disease severity or is a consequence of the effects of total-body cooling, an approved treatment for moderate-to-severe hypoxic-ischemic encephalopathy.

Methods: A retrospective chart review of 101 neonates with hypoxic-ischemic encephalopathy + total-body cooling (n = 26), hypoxic-ischemic encephalopathy (n = 12), acute ischemic stroke (n = 15), and transient tachypnea of the newborn (n = …

A Checklist For Clinical Trials In Rare Disease: Obstacles And Anticipatory Actions-Lessons Learned From The For-Dmd Trial, R Crow, K Hart, M Mcdermott, R Tawil, W Martens, Mathula Thangarajh, +Several Additional Authors

Neurology Faculty Publications

Background: Trials in rare diseases have many challenges, among which are the need to set up multiple sites in different countries to achieve recruitment targets and the divergent landscape of clinical trial regulations in those countries. Over the past years, there have been initiatives to facilitate the process of international study set-up, but the fruits of these deliberations require time to be operationally in place. FOR-DMD (Finding the Optimum Steroid Regimen for Duchenne Muscular Dystrophy) is an academic-led clinical trial which aims to find the optimum steroid regimen for Duchenne muscular dystrophy, funded by the National Institutes of Health (NIH) …

Regional Microstructural Organization Of The Cerebral Cortex Is Affected By Preterm Birth., Marine Bouyssi-Kobar, Marie Brossard-Racine, Marni Jacobs, Jonathan Murnick, Taeun Chang, Catherine Limperopoulos

Pediatrics Faculty Publications

Objectives: To compare regional cerebral cortical microstructural organization between preterm infants at term-equivalent age (TEA) and healthy full-term newborns, and to examine the impact of clinical risk factors on cerebral cortical micro-organization in the preterm cohort.

Study design: We prospectively enrolled very preterm infants (gestational age (GA) at birth<32 >weeks; birthweight<1500 >g) and healthy full-term controls. Using non-invasive 3T diffusion tensor imaging (DTI) metrics, we quantified regional micro-organization in ten cerebral cortical areas: medial/dorsolateral prefrontal cortex, anterior/posterior cingulate cortex, insula, posterior parietal cortex, motor/somatosensory/auditory/visual cortex. ANCOVA analyses were performed controlling for sex and postmenstrual age at MRI.

Results: We studied …

X-Linked Hypomyelination With Spondylometaphyseal Dysplasia (H-Smd) Associated With Mutations In Aifm1., Noriko Miyake, Nicole I Wolf, Ferdy K Cayami, Joanna Crawford, Annette Bley, Dorothy Bulas, Ryan J Taft, Adeline Vanderver, +Several Additional Authors

Neurology Faculty Publications

An X-linked condition characterized by the combination of hypomyelinating leukodystrophy and spondylometaphyseal dysplasia (H-SMD) has been observed in only four families, with linkage to Xq25-27, and recent genetic characterization in two families with a common AIFM1 mutation. In our study, 12 patients (6 families) with H-SMD were identified and underwent comprehensive assessment accompanied by whole-exome sequencing (WES). Pedigree analysis in all families was consistent with X-linked recessive inheritance. Presentation typically occurred between 12 and 36 months. In addition to the two disease-defining features of spondylometaphyseal dysplasia and hypomyelination on MRI, common clinical signs and symptoms included motor deterioration, spasticity, tremor, …

Ufm1 Founder Mutation In The Roma Population Causes Recessive Variant Of H-Abc., Eline M C Hamilton, Enrico Bertini, Luba Kalaydjieva, Bharti Morar, Dana Dojčáková, Adeline Vanderver, Recessive H-Abc Research Group.

Neurology Faculty Publications

OBJECTIVE: To identify the gene defect in patients with hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) who are negative for TUBB4A mutations.

METHODS: We performed homozygosity mapping and whole exome sequencing (WES) to detect the disease-causing variant. We used a Taqman assay for population screening. We developed a luciferase reporter construct to investigate the effect of the promoter mutation on expression.

RESULTS: Sixteen patients from 14 families from different countries fulfilling the MRI criteria for H-ABC exhibited a similar, severe clinical phenotype, including lack of development and a severe epileptic encephalopathy. The majority of patients had a …

Application Of Rns In Refractory Epilepsy: Targeting Insula., Hai Chen, Patricia Dugan, Derek J Chong, Anli Liu, Werner Doyle, Daniel Friedman

Neurology Faculty Publications

Although responsive neurostimulation (RNS) is approved for treatment of resistant focal epilepsy in adults, little is known about response to treatment of specific cortical targets. We describe the experience of RNS targeting the insular lobe. We identified patients who had RNS implantation with at least one electrode within the insula between April 2014 and October 2015. We performed a retrospective review of preoperative clinical features, imaging, electrocardiogram (EEG), intraoperative electrocorticography (ECoG), and postoperative seizure outcome. Eight patients with at least 6 months of postimplant follow-up were identified. Ictal localization was inconclusive with MRI or scalp EEG findings. Intracranial EEG monitoring …

Functionally Pathogenic Ears2 Variants In Vitro May Not Manifest A Phenotype In Vivo, Nathan Mcneill, Alessia Nasca, Aurelio Reyes, Benjamin Lemoine, Brandi Cantarel, Adeline Vanderver, Raphael Schiffmann, Daniele Ghezzi

Neurology Faculty Publications

Objective: To investigate the genetic etiology of a patient diagnosed with leukoencephalopathy, brain calcifications, and cysts (LCC).

Methods: Whole-exome sequencing was performed on a patient with LCC and his unaffected family members. The variants were subject to in silico and in vitro functional testing to determine pathogenicity.

Results: Whole-exome sequencing uncovered compound heterozygous mutations in EARS2, c.328G>A (p.G110S), and c.1045G>A (p.E349K). This gene has previously been implicated in the autosomal recessive leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL). The p.G110S mutation has been found in multiple patients with LTBL. In silico analysis supported pathogenicity …

A Defect In Myoblast Fusion Underlies Carey-Fineman-Ziter Syndrome, S Digioia, S Connors, N. Matsunami, J Cannavino, M Rose, N Gillette, Andrea Gropman, +Several Additional Authors

Neurology Faculty Publications

Multinucleate cellular syncytial formation is a hallmark of skeletal muscle differentiation. Myomaker, encoded by Mymk (Tmem8c), is a well-conserved plasma membrane protein required for myoblast fusion to form multinucleated myotubes in mouse, chick, and zebrafish. Here, we report that autosomal recessive mutations in MYMK (OMIM 615345) cause Carey-Fineman-Ziter syndrome in humans (CFZS; OMIM 254940) by reducing but not eliminating MYMK function. We characterize MYMK-CFZS as a congenital myopathy with marked facial weakness and additional clinical and pathologic features that distinguish it from other congenital neuromuscular syndromes. We show that a heterologous cell fusion assay in vitro and allelic …

Neurotransmitter, Summer 2017, George Washington Institute For Neuroscience Neurological Institute, George Washington University Hospital

Neurotransmitter

No abstract provided.

The Specific Vulnerabilities Of Cancer Cells To The Cold Atmospheric Plasma-Stimulated Solutions., Dayun Yan, Haitao Cui, Wei Zhu, Niki Nourmohammadi, Julian Milberg, Lijie G Zhang, Jonathan H Sherman, Michael Keidar

Neurological Surgery Faculty Publications

Cold atmospheric plasma (CAP), a novel promising anti-cancer modality, has shown its selective anti-cancer capacity on dozens of cancer cell lines in vitro and on subcutaneous xenograft tumors in mice. Over the past five years, the CAP-stimulated solutions (PSS) have also shown their selective anti-cancer effect over different cancers in vitro and in vivo. The solutions used to make PSS include several bio-adaptable solutions, mainly cell culture medium and simple buffered solutions. Both the CAP-stimulated medium (PSM) and the CAP-stimulated buffered solution (PSB) are able to significantly kill cancer cells in vitro. In this study, we systematically compared the anti-cancer …

Universal Connection Through Art: Role Of Mirror Neurons In Art Production And Reception., Bartlomiej Piechowski-Jozwiak, François Boller, Julien Bogousslavsky

Neurology Faculty Publications

Art is defined as expression or application of human creative skill and imagination producing works to be appreciated primarily for their aesthetic value or emotional power. This definition encompasses two very important elements—the creation and reception of art—and by doing so it establishes a link, a dialogue between the artist and spectator. From the evolutionary biological perspective, activities need to have an immediate or remote effect on the population through improving survival, gene selection, and environmental adjustment, and this includes art. It may serve as a universal means of communication bypassing time, cultural, ethnic, and social differences. The neurological mechanisms …

Pediatric Intrafalcine Empyema From A Sinogenic Origin: A Case Report., Kyle Mueller, John Myseros

Neurological Surgery Faculty Publications

Sinusitis and otitis are common within the pediatric population. If left untreated, these can extend intracranially and lead to the development of infections in the various intracranial compartments resulting in a high rate of morbidity and mortality. We report the first case of an intrafalcine empyema, absent subdural purulence, in a patient with the likely spread from a sinogenic origin. This case illustrates the novelty of this as a pathological entity as well as the surgical considerations for intrafalcine purulence in the absence of expected subdural collections.

Presurgical Language Fmri: Mapping Of Six Critical Regions, Christopher Benjamin, Patricia Walshaw, Kayleigh Hale, William D. Gaillard, +Several Additional Authors

Neurology Faculty Publications

Language mapping is a key goal in neurosurgical planning. fMRI mapping typically proceeds with a focus on Broca's and Wernicke's areas, although multiple other language-critical areas are now well-known. We evaluated whether clinicians could use a novel approach, including clinician-driven individualized thresholding, to reliably identify six language regions, including Broca's Area, Wernicke's Area (inferior, superior), Exner's Area, Supplementary Speech Area, Angular Gyrus, and Basal Temporal Language Area. We studied 22 epilepsy and tumor patients who received Wada and fMRI (age 36.4[12.5]; Wada language left/right/mixed in 18/3/1). fMRI tasks (two × three tasks) were analyzed by two clinical neuropsychologists who flexibly …

Choriocarcinoma With Brain, Lung And Vaginal Metastases Successfully Treated Without Brain Radiation Or Intrathecal Chemotherapy: A Case Report, Anja Frost, Jonathan Sherman, M. Katayoon Rezaei, Alivia Aron, Micael Lopez-Acevedo

Neurological Surgery Faculty Publications

Highlights:

• • There is no consensus on optimal treatment for GTN and brain metastases.
• • Brain metastasis treated with craniotomy and intravenous, EMA-CO chemotherapy
• • Intravenous high-dose methotrexate may be adequate to treat brain metastases.

Medical Resource Utilization Of Outpatient Care For Children With Neurofibromatosis Type 1, Rabia Idrees, Michael Fisher, Rachel Hachen, Brian Callaghan, Robert A. Avery

GW Research Days 2016 - 2020

Background:

Neurofibromatosis Type 1 (NF1) is an autosomal dominant syndrome with manifestations affecting the central nervous system, musculoskeletal system, peripheral nervous system, and cognitive/behavioral functions. Many of these manifestations persist throughout life and require medical/surgical interventions.

The resource utilization and economic burden of caring for children with NF1 is unknown. Prior research has inherent selection bias and does not accurately reflect the incidence/resource utilization of morbidities. In order to identify which disease manifestations are in the most need of improved clinical algorithms and novel therapeutics, the frequency/type of resources utilized (i.e., diagnostic imaging and specialty visits) must be determined.

The …

Differential Mrna Expression In Ectopic Germinal Centers Of Myasthenia Gravis Thymus, Manjistha Sengupta, Bi-Dar Wang, Norman H. Lee, Gary Cutter, Linda L. Kusner, Henry J. Kaminski

GW Research Days 2016 - 2020

Myasthenia gravis (MG) is an autoimmune neuromuscular disorder resulting in weakness of voluntary muscles. It is caused by antibodies directed against proteins present at the post-synaptic surface of neuromuscular junction (NMJ). A characteristic pathology of patients with early onset MG is thymic hyperplasia with ectopic germinal centers (GC). However, mechanisms that trigger and maintain thymic hyperplasia are poorly characterized.

In order to determine the central mechanisms involved in the pathology, thymus samples from MG patients were assessed by histology and grouped based on appearance of GC compared to samples without them. We assessed the differential mRNA expression profiles between the …

A Normative Spatiotemporal Mri Atlas Of The Fetal Brain For Automatic Segmentation And Analysis Of Early Brain Growth., Ali Gholipour, Caitlin K Rollins, Clemente Velasco-Annis, Abdelhakim Ouaalam, Alireza Akhondi-Asl, Onur Afacan, Cynthia M Ortinau, Sean Clancy, Catherine Limperopoulos, Edward Yang, Judy A Estroff, Simon K Warfield

Pediatrics Faculty Publications

Longitudinal characterization of early brain growth in-utero has been limited by a number of challenges in fetal imaging, the rapid change in size, shape and volume of the developing brain, and the consequent lack of suitable algorithms for fetal brain image analysis. There is a need for an improved digital brain atlas of the spatiotemporal maturation of the fetal brain extending over the key developmental periods. We have developed an algorithm for construction of an unbiased four-dimensional atlas of the developing fetal brain by integrating symmetric diffeomorphic deformable registration in space with kernel regression in age. We applied this new …

A Murine Model To Study Epilepsy And Sudep Induced By Malaria Infection., Paddy Ssentongo, Anna E Robuccio, Godfrey Thuku, Derek G Sim, Ali Nabi, Fatemeh Bahari, Balaji Shanmugasundaram, Myles W Billard, Andrew Geronimo, Kurt W Short, Patrick J Drew, Jennifer Baccon, Steven L Weinstein, Frank G Gilliam, José A Stoute, Vernon M Chinchilli, Andrew F Read, Bruce J Gluckman, Steven J Schiff

Neurology Faculty Publications

One of the largest single sources of epilepsy in the world is produced as a neurological sequela in survivors of cerebral malaria. Nevertheless, the pathophysiological mechanisms of such epileptogenesis remain unknown and no adjunctive therapy during cerebral malaria has been shown to reduce the rate of subsequent epilepsy. There is no existing animal model of postmalarial epilepsy. In this technical report we demonstrate the first such animal models. These models were created from multiple mouse and parasite strain combinations, so that the epilepsy observed retained universality with respect to genetic background. We also discovered spontaneous sudden unexpected death in epilepsy …

Embryonic Transcription Factor Expression In Mice Predicts Medial Amygdala Neuronal Identity And Sex-Specific Responses To Innate Behavioral Cues., Julieta E Lischinsky, Katie Sokolowski, Li Peijun, Shigeyuki Esumi, Yasmin Kamal, Meredith Goodrich, Livio Oboti, Timothy R Hammond, Meera Krishnamoorthy, Daniel Feldman, Molly Huntsman, Judy Liu, Joshua G Corbin

Pediatrics Faculty Publications

The medial subnucleus of the amygdala (MeA) plays a central role in processing sensory cues required for innate behaviors. However, whether there is a link between developmental programs and the emergence of inborn behaviors remains unknown. Our previous studies revealed that the telencephalic preoptic area (POA) embryonic niche is a novel source of MeA destined progenitors. Here, we show that the POA is comprised of distinct progenitor pools complementarily marked by the transcription factors Dbx1 and Foxp2. As determined by molecular and electrophysiological criteria this embryonic parcellation predicts postnatal MeA inhibitory neuronal subtype identity. We further find that Dbx1-derived and …

Pediatric High-Grade Glioma: Biologically And Clinically In Need Of New Thinking., Chris Jones, Matthias A Karajannis, David T W Jones, Mark W Kieran, Michelle Monje, Suzanne J Baker, Roger J Packer, +Several Additional Authors

Neurology Faculty Publications

High-grade gliomas in children are different from those that arise in adults. Recent collaborative molecular analyses of these rare cancers have revealed previously unappreciated connections among chromatin regulation, developmental signaling, and tumorigenesis. As we begin to unravel the unique developmental origins and distinct biological drivers of this heterogeneous group of tumors, clinical trials need to keep pace. It is important to avoid therapeutic strategies developed purely using data obtained from studies on adult glioblastoma. This approach has resulted in repetitive trials and ineffective treatments being applied to these children, with limited improvement in clinical outcome. The authors of this perspective, …

Unmasking Of Myoclonus By Lacosamide In Generalized Epilepsy, Daniel Birnbaum, Mohamad Z. Koubeissi

Neurology Faculty Publications

Lacosamide is a new-generation antiseizure medication that is approved for use as an adjunctive treatment and monotherapy in focal epilepsy. Its use in generalized epilepsy, however, has not been adequately evaluated in controlled trials. We report a 67-year-old woman who experienced new-onset myoclonic seizures after initiation of lacosamide. We presume that she had an undiagnosed generalized epilepsy syndrome, likely juvenile myoclonic epilepsy. Myoclonic seizures were not reported before introducing lacosamide and completely resolved after lacosamide was discontinued. This suggests that lacosamide may have the potential to worsen myoclonus, similar to what has been reported with another sodium channel agent, lamotrigine, …