Medicine and Health Sciences Commons^™

Severe Stiff-Person Syndrome After Covid: The First Video-Documented Covid Exacerbation And Viral Implications, Marinos C. Dalakas

Department of Neurology Faculty Papers

OBJECTIVES: To describe a patient with mild GAD-positive stiff-leg syndrome (SLS) who developed severely disabling stiff-person syndrome (SPS) 1 week after mild COVID-19 and discuss the impact of viral implications.

METHODS: Video-documented serial clinical observations at baseline, after acute COVID-19, and after IVIG treatments.

RESULTS: A 39-year-old man with left-SLS was stable during a 2-year follow-up with low-dose antispasmodics, working fully and functioning normally, even able to run. One week after mild COVID-19, he started to experience generalized SPS symptomatology that steadily worsened the following 2-3 weeks, becoming unable to walk, requiring a walker, with significant thoracolumbar and bilateral leg …

Nerve Transfer For Restoration Of Lower Motor Neuron-Lesioned Bladder, Urethral, And Anal Sphincter Function In A Dog Model. Part 3. Nicotinic Receptor Characterization, Nagat Frara, Mary F. Barbe, Dania Giaddui, Danielle S. Porreca, Alan S. Braverman, Ekta Tiwari, Attia Ahmad, Justin M. Brown, Benjamin R. Johnston, Stanley F. Bazarek, Michael R. Ruggieri

Department of Neurology Faculty Papers

Very little is known about the physiological role of nicotinic receptors in canine bladders, although functional nicotinic receptors have been reported in bladders of many species. Utilizing in vitro methods, we evaluated nicotinic receptors mediating bladder function in dogs: control (9 female and 11 male normal controls, 5 sham operated), Decentralized (9 females, decentralized 6–21 mo), and obturator-to-pelvic nerve transfer reinnervated (ObNT-Reinn; 9 females; decentralized 9–13 mo, then reinnervated with 8–12 mo recovery). Muscle strips were collected, mucosa-denuded, and mounted in muscle baths before incubation with neurotransmitter antagonists, and contractions to the nicotinic receptor agonist epibatidine were determined. Strip response …

A Learned Map For Places And Concepts In The Human Medial Temporal Lobe, Nora A. Herweg, Lukas Kunz, Daniel Schonhaut, Armin Brandt, Paul A. Wanda, Ashwini D. Sharan, Michael R. Sperling, Andreas Schulze-Bonhage, Michael J. Kahana

Department of Neurology Faculty Papers

Distinct lines of research in both humans and animals point to a specific role of the hippocampus in both spatial and episodic memory function. The discovery of concept cells in the hippocampus and surrounding medial temporal lobe (MTL) regions suggests that the MTL maps physical and semantic spaces with a similar neural architecture. Here, we studied the emergence of such maps using MTL microwire recordings from 20 patients (9 female, 11 male) navigating a virtual environment featuring salient landmarks with established semantic meaning. We present several key findings. The array of local field potentials in the MTL contains sufficient information …

Peripheral Neuropathy Evaluations Of Patients With Prolonged Long Covid., Anne Louise Oaklander, Alexander J Mills, Mary Kelley, Lisa S Toran, Bryan Smith, Marinos Dalakas, Avindra Nath

Department of Neurology Faculty Papers

Background and objectives: Recovery from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection appears exponential, leaving a tail of patients reporting various long COVID symptoms including unexplained fatigue/exertional intolerance and dysautonomic and sensory concerns. Indirect evidence links long COVID to incident polyneuropathy affecting the small-fiber (sensory/autonomic) axons.

Methods: We analyzed cross-sectional and longitudinal data from patients with World Health Organization (WHO)-defined long COVID without prior neuropathy history or risks who were referred for peripheral neuropathy evaluations. We captured standardized symptoms, examinations, objective neurodiagnostic test results, and outcomes, tracking participants for 1.4 years on average.

Results: Among 17 patients (mean age …

Language Tasks And The Network Control Role Of The Left Inferior Frontal Gyrus, John D Medaglia, Denise Y Harvey, Apoorva S Kelkar, Jared P Zimmerman, Joely A Mass, Danielle S Bassett, Roy H Hamilton

Department of Neurology Faculty Papers

Recent work has combined cognitive neuroscience and control theory to make predictions about cognitive control functions. Here, we test a link between whole-brain theories of semantics and the role of the left inferior frontal gyrus (LIFG) in controlled language performance using network control theory (NCT), a branch of systems engineering. Specifically, we examined whether two properties of node controllability, boundary and modal controllability, were linked to semantic selection and retrieval on sentence completion and verb generation tasks. We tested whether the controllability of the left IFG moderated language selection and retrieval costs and the effects of continuous θ burst stimulation …

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, …

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 …

Posterior Cortical Atrophy: Characteristics From A Clinical Data Registry., Jennifer J Olds, William L Hills, Judith Warner, Julie Falardeau, Lori Haase Alasantro, Mark L Moster, Robert A Egan, Wayne T Cornblath, Andrew G Lee, Benjamin M Frishberg, Roger E Turbin, David M Katz, John A Charley, Victoria S Pelak

Department of Neurology Faculty Papers

No abstract provided.

Nk Cell-Derived Gm-Csf Potentiates Inflammatory Arthritis And Is Negatively Regulated By Cis, Cynthia Louis, Fernando Souza-Fonseca-Guimaraes, Yuyan Yang, Damian D'Silva, Tobias Kratina, Laura Dagley, Soroor Hediyeh-Zadeh, Jai Rautela, Seth Lucian Masters, Melissa J Davis, Jeffrey J Babon, Bogoljub Ciric, Eric Vivier, Warren S Alexander, Nicholas D Huntington, Ian P Wicks

Department of Neurology Faculty Papers

Despite increasing recognition of the importance of GM-CSF in autoimmune disease, it remains unclear how GM-CSF is regulated at sites of tissue inflammation. Using GM-CSF fate reporter mice, we show that synovial NK cells produce GM-CSF in autoantibody-mediated inflammatory arthritis. Synovial NK cells promote a neutrophilic inflammatory cell infiltrate, and persistent arthritis, via GM-CSF production, as deletion of NK cells, or specific ablation of GM-CSF production in NK cells, abrogated disease. Synovial NK cell production of GM-CSF is IL-18–dependent. Furthermore, we show that cytokine-inducible SH2-containing protein (CIS) is crucial in limiting GM-CSF signaling not only during inflammatory arthritis but also …

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 …

Fremanezumab For The Preventive Treatment Of Chronic Migraine., Stephen D. Silberstein, David W. Dodick, Marcelo E. Bigal, Paul P. Yeung, Peter J. Goadsby, Tricia Blankenbiller, Melissa Grozinski-Wolff, Ronghua Yang, Yuju Ma, Ernesto Aycardi

Department of Neurology Faculty Papers

BACKGROUND: Fremanezumab, a humanized monoclonal antibody targeting calcitonin gene-related peptide (CGRP), is being investigated as a preventive treatment for migraine. We compared two fremanezumab dose regimens with placebo for the prevention of chronic migraine.

METHODS: In this phase 3 trial, we randomly assigned patients with chronic migraine (defined as headache of any duration or severity on ≥15 days per month and migraine on ≥8 days per month) in a 1:1:1 ratio to receive fremanezumab quarterly (a single dose of 675 mg at baseline and placebo at weeks 4 and 8), fremanezumab monthly (675 mg at baseline and 225 mg at …

Bimodal Coupling Of Ripples And Slower Oscillations During Sleep In Patients With Focal Epilepsy., Inkyung Song, Iren Orosz, Inna Chervoneva, Zachary J. Waldman, Itzhak Fried, Chengyuan Wu, Ashwini Sharan, Noriko Salamon, Richard Gorniak, Sandra Dewar, Anatol Bragin, Jerome Engel, Michael R. Sperling, Richard Staba, Shennan A. Weiss

Department of Neurology Faculty Papers

OBJECTIVE: Differentiating pathologic and physiologic high-frequency oscillations (HFOs) is challenging. In patients with focal epilepsy, HFOs occur during the transitional periods between the up and down state of slow waves. The preferred phase angles of this form of phase-event amplitude coupling are bimodally distributed, and the ripples (80-150 Hz) that occur during the up-down transition more often occur in the seizure-onset zone (SOZ). We investigated if bimodal ripple coupling was also evident for faster sleep oscillations, and could identify the SOZ.

METHODS: Using an automated ripple detector, we identified ripple events in 40-60 min intracranial electroencephalography (iEEG) recordings from 23 …

Erenumab (Amg 334) In Episodic Migraine: Interim Analysis Of An Ongoing Open-Label Study., Messoud Ashina, David Dodick, Peter J. Goadsby, Uwe Reuter, Stephen Silberstein, Feng Zhang, Julia R. Gage, Sunfa Cheng, Daniel D. Mikol, Robert A. Lenz

Department of Neurology Faculty Papers

OBJECTIVE: To assess long-term safety and efficacy of anti-calcitonin gene-related peptide receptor erenumab in patients with episodic migraine (EM).

METHODS: Patients enrolled in a 12-week, double-blind, placebo-controlled clinical trial (NCT01952574) who continued in an open-label extension (OLE) study will receive erenumab 70 mg every 4 weeks for up to 5 years. This preplanned interim analysis, conducted after all participants had completed the 1-year open-label follow-up, evaluated changes in monthly migraine days (MMD), achievement of ≥50%, ≥75%, and 100% reductions, Headache Impact Test (HIT-6) score, Migraine-Specific Quality of Life (MSQ), Migraine Disability Assessment (MIDAS), and safety. Data reported as observed without …

Ibrutinib Unmasks Critical Role Of Bruton Tyrosine Kinase In Primary Cns Lymphoma., Christian Grommes, Alessandro Pastore, Nicolaos Palaskas, Sarah S. Tang, Carl Campos, Derrek Schartz, Paolo Codega, Donna Nichol, Owen Clark, Wan-Ying Hsieh, Dan Rohle, Marc Rosenblum, Agnes Viale, Viviane S. Tabar, Cameron W. Brennan, Igor T. Gavrilovic, Thomas J. Kaley, Craig P. Nolan, Antonio Omuro, Elena Pentsova, Alissa A. Thomas, Elina Tsyvkin, Ariela Noy, M. Lia Palomba, Paul Hamlin, Craig S. Sauter, Craig H. Moskowitz, Julia Wolfe, Ahmet Dogan, Minhee Won, Jon Glass, Scott Peak, Enrico C. Lallana, Vaios Hatzoglou, Anne S. Reiner, Philip H. Gutin, Jason T. Huse, Katherine S. Panageas, Thomas G. Graeber, Nikolaus Schultz, Lisa M. Deangelis, Ingo K. Mellinghoff

Department of Neurology Faculty Papers

Bruton tyrosine kinase (BTK) links the B-cell antigen receptor (BCR) and Toll-like receptors with NF-κB. The role of BTK in primary central nervous system (CNS) lymphoma (PCNSL) is unknown. We performed a phase I clinical trial with ibrutinib, the first-in-class BTK inhibitor, for patients with relapsed or refractory CNS lymphoma. Clinical responses to ibrutinib occurred in 10 of 13 (77%) patients with PCNSL, including five complete responses. The only PCNSL with complete ibrutinib resistance harbored a mutation within the coiled-coil domain of CARD11, a known ibrutinib resistance mechanism. Incomplete tumor responses were associated with mutations in the B-cell antigen receptor-associated …

Tia1 Mutations In Amyotrophic Lateral Sclerosis And Frontotemporal Dementia Promote Phase Separation And Alter Stress Granule Dynamics., Ian R. Mackenzie, Alexandra M. Nicholson, Mohona Sarkar, James Messing, Maria D. Purice, Cyril Pottier, Kavya Annu, Matt Baker, Ralph B. Perkerson, Aishe Kurti, Billie J. Matchett, Tanja Mittag, Jamshid Temirov, Ging-Yuek R. Hsiung, Charles Krieger, Melissa E. Murray, Masato Kato, John D. Fryer, Leonard Petrucelli, Lorne Zinman, Sandra Weintraub, Marsel Mesulam, Julia Keith, Sasha A. Zivkovic, Veronica Hirsch-Reinshagen, Raymond P. Roos, Stephan Züchner, Neill R. Graff-Radford, Ronald C. Petersen, Richard J. Caselli, Zbigniew K. Wszolek, Elizabeth Finger, Carol Lippa, David Lacomis, Heather Stewart, Dennis W. Dickson, Hong Joo Kim, Ekaterina Rogaeva, Eileen Bigio, Kevin B. Boylan, J. Paul Taylor, Rosa Rademakers

Department of Neurology Faculty Papers

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are age-related neurodegenerative disorders with shared genetic etiologies and overlapping clinical and pathological features. Here we studied a novel ALS/FTD family and identified the P362L mutation in the low-complexity domain (LCD) of T cell-restricted intracellular antigen-1 (TIA1). Subsequent genetic association analyses showed an increased burden of TIA1 LCD mutations in ALS patients compared to controls (p = 8.7 × 10

Presurgical Thalamic "Hubness" Predicts Surgical Outcome In Temporal Lobe Epilepsy., Xiaosong He, Gaelle E. Doucet, Dorian Pustina, Michael R. Sperling, Ashwini D. Sharan, Joseph I. Tracy

Department of Neurology Faculty Papers

OBJECTIVE: To characterize the presurgical brain functional architecture presented in patients with temporal lobe epilepsy (TLE) using graph theoretical measures of resting-state fMRI data and to test its association with surgical outcome.

METHODS: Fifty-six unilateral patients with TLE, who subsequently underwent anterior temporal lobectomy and were classified as obtaining a seizure-free (Engel class I, n = 35) vs not seizure-free (Engel classes II-IV, n = 21) outcome at 1 year after surgery, and 28 matched healthy controls were enrolled. On the basis of their presurgical resting-state functional connectivity, network properties, including nodal hubness (importance of a node to the network; …

The Evolution Of Epilepsy Surgery Between 1991 And 2011 In Nine Major Epilepsy Centers Across The United States, Germany, And Australia., Lara Jehi, Daniel Friedman, Chad Carlson, Gregory Cascino, Sandra Dewar, Christian Elger, Jerome Engel, Robert Knowlton, Ruben Kuzniecky, Anne Mcintosh, Terence J O'Brien, Dennis Spencer, Michael R. Sperling, Gregory Worrell, Bill Bingaman, Jorge Gonzalez-Martinez, Werner Doyle, Jacqueline French

Department of Neurology Faculty Papers

OBJECTIVE: Epilepsy surgery is the most effective treatment for select patients with drug-resistant epilepsy. In this article, we aim to provide an accurate understanding of the current epidemiologic characteristics of this intervention, as this knowledge is critical for guiding educational, academic, and resource priorities.

METHODS: We profile the practice of epilepsy surgery between 1991 and 2011 in nine major epilepsy surgery centers in the United States, Germany, and Australia. Clinical, imaging, surgical, and histopathologic data were derived from the surgical databases at various centers.

RESULTS: Although five of the centers performed their highest number of surgeries for mesial temporal sclerosis …

Type Of Preoperative Aura May Predict Postsurgical Outcome In Patients With Temporal Lobe Epilepsy And Mesial Temporal Sclerosis., Ali Akbar Asadi-Pooya, Maromi Nei, Ashwini Sharan, Michael R. Sperling

Department of Neurology Faculty Papers

PURPOSE: As the initial symptoms of epileptic seizures, many types of auras have significant localizing or lateralizing value. In this study, we hypothesized that the type of aura may predict postsurgical outcome in patients with medically refractory temporal lobe epilepsy (TLE) and mesial temporal sclerosis (MTS).

METHODS: In this retrospective study, all patients with a clinical diagnosis of medically refractory TLE due to unilateral mesial temporal sclerosis who underwent epilepsy surgery at the Jefferson Comprehensive Epilepsy Center were recruited. Patients were prospectively registered in a database from 1986 through 2014. Postsurgical outcome was classified into two groups: seizure freedom or …

Age At Onset In Patients With Medically Refractory Temporal Lobe Epilepsy And Mesial Temporal Sclerosis: Impact On Clinical Manifestations And Postsurgical Outcome., Ali Akbar Asadi-Pooya, Michael R. Sperling

Department of Neurology Faculty Papers

PURPOSE: To evaluate the demographic and clinical manifestations and postsurgical outcome of childhood-onset mesial temporal sclerosis and temporal lobe epilepsy (MTS-TLE) and establishing the potential differences as compared to the patients with adult-onset MTS-TLE.

METHOD: In this retrospective study all patients with a clinical diagnosis of medically refractory TLE due to mesial temporal sclerosis, who underwent epilepsy surgery at Jefferson comprehensive epilepsy center, were recruited. Patients were prospectively registered in a database from 1986 through 2014. Postsurgical outcome was classified into two groups; seizure-free or relapsed. Clinical manifestations and outcome were compared between patients with childhood-onset MTS-TLE (i.e., age at …

Theta And High-Frequency Activity Mark Spontaneous Recall Of Episodic Memories., John F Burke, Ashwini D Sharan, Michael R Sperling, Ashwin G Ramayya, James J. Evans, M Karl Healey, Erin N Beck, Kathryn A Davis, Timothy H Lucas, Michael J Kahana

Department of Neurology Faculty Papers

Humans possess the remarkable ability to search their memory, allowing specific past episodes to be re-experienced spontaneously. Here, we administered a free recall test to 114 neurosurgical patients and used intracranial theta and high-frequency activity (HFA) to identify the spatiotemporal pattern of neural activity underlying spontaneous episodic retrieval. We found that retrieval evolved in three electrophysiological stages composed of: (1) early theta oscillations in the right temporal cortex, (2) increased HFA in the left hemisphere including the medial temporal lobe (MTL), left inferior frontal gyrus, as well as the ventrolateral temporal cortex, and (3) motor/language activation during vocalization of the …

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 …

B-Vitamin Deficiency In Patients Treated With Antiepileptic Drugs., Scott Mintzer, Christopher T Skidmore, Michael R Sperling

Department of Neurology Faculty Papers

Enzyme-inducing antiepileptic drugs (AEDs) produce many alterations in metabolism, including vitamin levels. Whether they produce clinically relevant deficiency of B vitamins has rarely been assessed. We obtained B-vitamin levels in patients who were being converted from an inducing AED (phenytoin or carbamazepine) to a non-inducing AED (levetiracetam, lamotrigine, or topiramate), with measurements both before and ≥ 6 weeks after the switch. A group of normal subjects underwent the same studies. Neither folate nor B12 deficiency was seen in any patient. Vitamin B6 deficiency was found in 16/33 patients (48%) taking inducers, compared to 1/11 controls (9%; p=0.031). After switch to …

Rituximab Induces Sustained Reduction Of Pathogenic B Cells In Patients With Peripheral Nervous System Autoimmunity., Michael A Maurer, Goran Rakocevic, Carol S Leung, Isaak Quast, Martin Lukačišin, Norbert Goebels, Christian Münz, Hedda Wardemann, Marinos Dalakas, Jan D Lünemann

Department of Neurology Faculty Papers

The B cell-depleting IgG1 monoclonal antibody rituximab can persistently suppress disease progression in some patients with autoimmune diseases. However, the mechanism underlying these long-term beneficial effects has remained unclear. Here, we evaluated Ig gene usage in patients with anti-myelin-associated glycoprotein (anti-MAG) neuropathy, an autoimmune disease of the peripheral nervous system that is mediated by IgM autoantibodies binding to MAG antigen. Patients with anti-MAG neuropathy showed substantial clonal expansions of blood IgM memory B cells that recognized MAG antigen. The group of patients showing no clinical improvement after rituximab therapy were distinguished from clinical responders by a higher load of clonal …

Hormonal Consequences Of Epilepsy And Its Treatment In Men., Kartik Sivaraaman, Scott Mintzer

Department of Neurology Faculty Papers

PURPOSE OF REVIEW: Epilepsy and anticonvulsant medications may substantially alter endocrine homeostasis, including the male reproductive hormonal system.

RECENT FINDINGS: Seizures in medial temporal lobe structures, through their connectivity to the hypothalamus, alter the secretion of gonadotropins. Levels of circulating bioavailable testosterone are affected by changes in the level of binding proteins, which in turn may be affected by seizure medications. The use of older generation medications that induce the cytochrome P450 system is associated with an increase in sex hormone-binding globulin and lower bioactive testosterone. Sexual dysfunction, including decreased libido and decreased potency, and infertility, is seen commonly in …

A Test Of The Role Of The Medial Temporal Lobe In Single-Word Decoding., Karol Osipowicz, Tyler Rickards, Atif Shah, Ashwini Sharan, Michael Sperling, Waseem Kahn, Joseph Tracy

Department of Neurology Faculty Papers

The degree to which the MTL system contributes to effective language skills is not well delineated. We sought to determine if the MTL plays a role in single-word decoding in healthy, normal skilled readers. The experiment follows from the implications of the dual-process model of single-word decoding, which provides distinct predictions about the nature of MTL involvement. The paradigm utilized word (regular and irregularly spelled words) and pseudoword (phonetically regular) stimuli that differed in their demand for non-lexical as opposed lexical decoding. The data clearly showed that the MTL system was not involved in single word decoding in skilled, native …

Acetate Causes Alcohol Hangover Headache In Rats., Christina R Maxwell, Rebecca Jay Spangenberg, Jan B Hoek, Stephen D Silberstein, Michael L Oshinsky

Department of Neurology Faculty Papers

BACKGROUND: The mechanism of veisalgia cephalgia or hangover headache is unknown. Despite a lack of mechanistic studies, there are a number of theories positing congeners, dehydration, or the ethanol metabolite acetaldehyde as causes of hangover headache.

METHODS: We used a chronic headache model to examine how pure ethanol produces increased sensitivity for nociceptive behaviors in normally hydrated rats.

RESULTS: Ethanol initially decreased sensitivity to mechanical stimuli on the face (analgesia), followed 4 to 6 hours later by inflammatory pain. Inhibiting alcohol dehydrogenase extended the analgesia whereas inhibiting aldehyde dehydrogenase decreased analgesia. Neither treatment had nociceptive effects. Direct administration of acetate …

Ms4a4b, A Cd20 Homologue In T Cells, Inhibits T Cell Propagation By Modulation Of Cell Cycle., Hui Xu, Yaping Yan, Mark S Williams, Gregory B Carey, Jingxian Yang, Hongmei Li, Guang-Xian Zhang, Abdolmohamad Rostami

Department of Neurology Faculty Papers

MS4a4B, a CD20 homologue in T cells, is a novel member of the MS4A gene family in mice. The MS4A family includes CD20, FcεRIβ, HTm4 and at least 26 novel members that are characterized by their structural features: with four membrane-spanning domains, two extracellular domains and two cytoplasmic regions. CD20, FcεRIβ and HTm4 have been found to function in B cells, mast cells and hematopoietic cells respectively. However, little is known about the function of MS4a4B in T cell regulation. We demonstrate here that MS4a4B negatively regulates mouse T cell proliferation. MS4a4B is highly expressed in primary T cells, natural …

Functional Interleukin-17 Receptor A Is Expressed In Central Nervous System Glia And Upregulated In Experimental Autoimmune Encephalomyelitis., Jayasri Das Sarma, Bogoljub Ciric, Ryan Marek, Sanjoy Sadhukhan, Michael L. Caruso, Jasmine Shafagh, Denise C. Fitzgerald, Kenneth S. Shindler, Am Rostami

Department of Neurology Faculty Papers

BACKGROUND: Interleukin-17A (IL-17A) is the founding member of a novel family of inflammatory cytokines that plays a critical role in the pathogenesis of many autoimmune diseases, including multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). IL-17A signals through its receptor, IL-17RA, which is expressed in many peripheral tissues; however, expression of IL-17RA in the central nervous system (CNS) and its role in CNS inflammation are not well understood.

METHODS: EAE was induced in C57Bl/6 mice by immunization with myelin oligodendroglial glycoprotein. IL-17RA expression in the CNS was compared between control and EAE mice using RT-PCR, in situ …

Short-Wavelength Light Sensitivity Of Circadian, Pupillary, And Visual Awareness In Humans Lacking An Outer Retina, Farhan H. Zaidi, Joseph T. Hull, Stuart N. Peirson, Katharina Wulff, Daniel Aeschbach, Joshua J. Gooley, George C. Brainard, Kevin Gregory-Evans, Joseph F. Rizzo Iii, Charles A. Czeisler, Russell G. Foster, Merrick J. Moseley, Steven W. Lockley

Department of Neurology Faculty Papers

As the ear has dual functions for audition and balance, the eye has a dual role in detecting light for a wide range of behavioral and physiological functions separate from sight. These responses are driven primarily by stimulation of photosensitive retinal ganglion cells (pRGCs) that are most sensitive to short-wavelength ( approximately 480 nm) blue light and remain functional in the absence of rods and cones. We examined the spectral sensitivity of non-image-forming responses in two profoundly blind subjects lacking functional rods and cones (one male, 56 yr old; one female, 87 yr old). In the male subject, we found …

Teaching Case: Headache Stigmata, Michael Marmura, Seymour Solomon

Department of Neurology Faculty Papers

A 38-year-old man with past medical history of hypertension and obesity presented to our clinic for evaluation of severe headaches and multiple episodes of discoloration of the forehead on the same side as the headache.