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  • Local Leukocyte Invasion during Hyperacute Human Ischemic Stroke
    Ann. Neurol. (IF 9.496) Pub Date : 2020-01-16
    Alexander M. Kollikowski; Michael K. Schuhmann; Bernhard Nieswandt; Wolfgang Müllges; Guido Stoll; Mirko Pham

    Bridging the gap between experimental stroke and patients by ischemic blood probing during the hyperacute stage of vascular occlusion is crucial to assess the role of inflammation in human stroke and for the development of adjunct treatments beyond recanalization.

    更新日期:2020-01-16
  • Scn8a antisense oligonucleotide is protective in mouse models of SCN8A Encephalopathy and Dravet Syndrome
    Ann. Neurol. (IF 9.496) Pub Date : 2020-01-14
    Guy M. Lenk; Paymaan Jafar‐Nejad; Sophie F. Hill; Lucas D. Huffman; Corrine E. Smolen; Jacy L. Wagnon; Hayley Petit; Wenxi Yu; Julie Ziobro; Kritika Bhatia; Jack Parent; Roman J. Giger; Frank Rigo; Miriam H. Meisler

    SCN8A encephalopathy is a Developmental and Epileptic Encephalopathy (DEE) caused by de novo, gain‐of‐function mutations of sodium channel Nav1.6 that result in neuronal hyperactivity. Affected individuals exhibit early‐onset drug‐resistant seizures, developmental delay and cognitive impairment. This study was carried out to determine whether reducing the abundance of the Scn8a transcript with an anti‐sense oligonucleotide (ASO) would delay seizure onset and prolong survival in a mouse model of SCN8A encephalopathy.

    更新日期:2020-01-15
  • Neuroinflammatory markers associate with cognitive decline after major surgery: findings of an explorative study
    Ann. Neurol. (IF 9.496) Pub Date : 2020-01-12
    Mattias Danielson; Andreas Wiklund; Fredrik Granath; Kaj Blennow; Souren Mkrtchian; Bengt Nellgård; Jonatan Oras; Malin Jonsson Fagerlund; Anna Granström; Anna Schening; Lars S. Rasmussen; Helena Erlandsson Harris; Henrik Zetterberg; Sven‐Erik Ricksten; Lars I. Eriksson

    Long‐term cognitive decline is an adverse outcome after major surgery associated with increased risk for mortality and morbidity. We studied the cerebrospinal fluid (CSF) and serum biochemical inflammatory response to a standardized orthopedic surgical procedure and the possible association with long‐term changes in cognitive function. We hypothesized that the CSF inflammatory response pattern after surgery would differ in patients having long‐term cognitive decline defined as a composite cognitive z‐score ≥1.0 compared to patients without long‐term cognitive decline, at 3 months postsurgery.

    更新日期:2020-01-13
  • Antisense oligonucleotide reverses leukodystrophy in Canavan disease mice
    Ann. Neurol. (IF 9.496) Pub Date : 2020-01-10
    Vanessa Hull; Yan Wang; Travis Burns; Sheng Zhang; Sarah Sternbach; Jennifer McDonough; Fuzheng Guo; David Pleasure

    Marked elevation in the brain concentration of N‐acetyl‐L‐aspartate (NAA) is a characteristic feature of Canavan disease, a vacuolar leukodystrophy resulting from deficiency of the oligodendroglial NAA cleaving enzyme aspartoacylase. We now demonstrate that inhibiting NAA synthesis by intracisternal administration of a locked nucleic acid antisense oligonucleotide to young adult aspartoacylase‐deficient mice reverses their pre‐existing ataxia and diminishes cerebellar and thalamic vacuolation and Purkinje cell dendritic atrophy.

    更新日期:2020-01-13
  • Intravenous immunomodulatory nanoparticle treatment for traumatic brain injury
    Ann. Neurol. (IF 9.496) Pub Date : 2020-01-10
    Sripadh Sharma; Igal Ifergan; Jonathan E Kurz; Robert A. Linsenmeier; Dan Xu; John G. Cooper; Stephen D. Miller; John A. Kessler

    There are currently no definitive disease modifying therapies for traumatic brain injury (TBI). In this study, we present a strong therapeutic candidate for TBI, immunomodulatory nanoparticles (IMPs), which ablate a specific subset of hematogenous monocytes (hMos). We hypothesized that prevention of infiltration of these cells into brain acutely after TBI would attenuate secondary damage and preserve anatomic and neurologic function.

    更新日期:2020-01-13
  • Classification accuracy of TMS for the diagnosis of neurodegenerative dementias
    Ann. Neurol. (IF 9.496) Pub Date : 2020-01-10
    Alberto Benussi; Mario Grassi; Fernando Palluzzi; Giacomo Koch; Vincenzo Di Lazzaro; Raffaele Nardone; Valentina Cantoni; Valentina Dell'Era; Enrico Premi; Alessandro Martorana; Francesco di Lorenzo; Sonia Bonnì; Federico Ranieri; Fioravante Capone; Gabriella Musumeci; Maria Sofia Cotelli; Alessandro Padovani; Barbara Borroni

    Transcranial Magnetic Stimulation (TMS) has been suggested as a reliable, non‐invasive, and inexpensive tool for the diagnosis of neurodegenerative dementias. In this study we assessed the classification performance of TMS parameters in the differential diagnosis of common neurodegenerative disorders, including Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD).

    更新日期:2020-01-13
  • Predicting upper limb motor impairment recovery after stroke: a mixture model
    Ann. Neurol. (IF 9.496) Pub Date : 2020-01-10
    Rick van der Vliet; Ruud W. Selles; Eleni‐Rosalina Andrinopoulou; Rinske Nijland; Gerard M. Ribbers; Maarten A. Frens; Carel Meskers; Gert Kwakkel

    Spontaneous recovery is an important determinant of upper extremity recovery after stroke, and has been described by the 70% proportional recovery rule for the Fugl‐Meyer motor upper extremity (FM‐UE) scale. However, this rule is criticized for overestimating the predictability of FM‐UE recovery. Our objectives were to (1) develop a longitudinal mixture model of FM‐UE recovery, (2) identify FM‐UE recovery subgroups, and (3) internally validate the model predictions.

    更新日期:2020-01-13
  • Optimizing Patient Selection for Endovascular Treatment in Acute Ischemic Stroke (SELECT): A Prospective Multicenter Cohort Study of Imaging Selection
    Ann. Neurol. (IF 9.496) Pub Date : 2020-01-09
    Amrou Sarraj; Ameer E. Hassan; James Grotta; Clark Sitton; Gary Cutter; Chunyan Cai; Peng R. Chen; Bita Imam; Deep Pujara; Ashish Arora; Sujan Reddy; Kaushik Parsha; Roy F Riascos; Nirav Vora; Michael Abraham; Randall Edgell; Frank Hellinger; Diogo C. Haussen; Spiros Blackburn; Haris Kamal; Andrew D. Barreto; Sheryl Martin‐Schild; Maarten Lansberg; Rishi Gupta; Sean Savitz; Gregory W. Albers

    The primary imaging modalities used to select patients for endovascular thrombectomy (EVT) are non‐contrast CT(CT) and CT‐perfusion(CTP). However, their relative utility is uncertain. We prospectively assessed CT and CTP concordance/discordance and correlated the imaging profiles on both with EVT treatment decisions and clinical outcomes.

    更新日期:2020-01-09
  • Impairment of glymphatic pathway and putative meningeal lymphatic vessels in aging human
    Ann. Neurol. (IF 9.496) Pub Date : 2020-01-09
    Ying Zhou; Jinsong Cai; Wenhua Zhang; Xiaoxian Gong; Shenqiang Yan; Kemeng Zhang; Zhongyu Luo; Jianzhong Sun; Quan Jiang; Min Lou

    Aging is a major risk factor for numerous neurological disorders and the mechanisms underlying brain aging remain elusive. Recent animal studies demonstrated tight relationship between impairment of glymphatic pathway, meningeal lymphatic vessels and aging. However, the relationship in human brain remains uncertain.

    更新日期:2020-01-09
  • Life course adiposity and amyotrophic lateral sclerosis: a Mendelian randomization study
    Ann. Neurol. (IF 9.496) Pub Date : 2020-01-09
    Linjing Zhang; Lu Tang; Tao Huang; Dongsheng Fan

    Observational studies have indicated that life course adiposity is associated with amyotrophic lateral sclerosis (ALS). However, whether such an association reflects causality remains unclear. We aimed to determine whether life course adiposity, such as birth weight (BW), childhood body mass index (BMI), adult BMI, body fat percentage (BF%), and waist‐to‐hip ratio (WHR), have causal effects on ALS.

    更新日期:2020-01-09
  • Restoration of Somatosensory Function by Pairing Vagus Nerve Stimulation with Tactile Rehabilitation
    Ann. Neurol. (IF 9.496) Pub Date : 2020-01-07
    Michael J. Darrow; Tabarak M. Mian; Miranda Torres; Zainab Haider; Tanya Danaphongse; Robert L. Rennaker; Michael P. Kilgard; Seth A. Hays

    Sensory dysfunction is a common consequence of many forms of neurological injury, including stroke and nerve damage. Rehabilitative paradigms that incorporate sensory retraining can provide modest benefits, but the majority of patients are left with lasting sensory loss. We have developed a novel strategy that uses closed‐loop vagus nerve stimulation (VNS) paired with tactile rehabilitation to enhance synaptic plasticity and facilitate recovery of sensory function.

    更新日期:2020-01-07
  • A Model to Study Myelinated Fiber Degeneration and Regeneration in Human Skin
    Ann. Neurol. (IF 9.496) Pub Date : 2020-01-06
    Vincenzo Provitera; Giuseppe Piscosquito; Fiore Manganelli; Stefania Mozzillo; Giuseppe Caporaso; Annamaria Stancanelli; Ilaria Borreca; Giovanni Di Caprio; Lucio Santoro; Maria Nolano

    To describe morphological changes associated with degeneration and regeneration of large fibers in the skin using a model of chronic compression of the median nerve.

    更新日期:2020-01-06
  • Effect of High‐Caloric Nutrition on Survival in Amyotrophic Lateral Sclerosis
    Ann. Neurol. (IF 9.496) Pub Date : 2020-01-06
    Albert C. Ludolph; Johannes Dorst; Jens Dreyhaupt; Jochen H. Weishaupt; Jan Kassubek; Ulrike Weiland; Thomas Meyer; Susanne Petri; Andreas Hermann; Alexander Emmer; Julian Grosskreutz; Torsten Grehl; Daniel Zeller; Matthias Boentert; Bertold Schrank; Johannes Prudlo; Andrea S. Winkler; Stanislav Gorbulev; Francesco Roselli; Joachim Schuster; Luc Dupuis;

    Weight loss has been identified as a negative prognostic factor in amyotrophic lateral sclerosis, but there is no evidence regarding whether a high‐caloric diet increases survival. Therefore, we sought to evaluate the efficacy of a high‐caloric fatty diet (HCFD) for increasing survival.

    更新日期:2020-01-06
  • Human CSF monoclonal LGI1 autoantibodies increase neuronal excitability
    Ann. Neurol. (IF 9.496) Pub Date : 2020-01-03
    Hans‐Christian Kornau; Jakob Kreye; Alexander Stumpf; Yuko Fukata; Daniel Parthier; Rosanna P. Sammons; Barbara Imbrosci; Sarah Kurpjuweit; Alexander B. Kowski; Masaki Fukata; Harald Prüss; Dietmar Schmitz

    Leucine‐rich glioma‐inactivated 1 (LGI1) encephalitis is the second most common autoimmune encephalopathy, but insight into the intrathecal B cell autoimmune response including clonal relationships, isotype distribution, frequency and pathogenic effects of single LGI1 antibodies has remain limited.

    更新日期:2020-01-04
  • ASC‐1 Is a Cell Cycle Regulator Associated with Severe and Mild Forms of Myopathy
    Ann. Neurol. (IF 9.496) Pub Date : 2019-12-27
    Rocío N. Villar‐Quiles; Fabio Catervi; Eva Cabet; Raul Juntas‐Morales; Casie A. Genetti; Teresa Gidaro; Asuman Koparir; Adnan Yüksel; Sandra Coppens; Nicolas Deconinck; Emma Pierce‐Hoffman; Xavière Lornage; Julien Durigneux; Jocelyn Laporte; John Rendu; Norma B. Romero; Alan H. Beggs; Laurent Servais; Mireille Cossée; Montse Olivé; Johann Böhm; Isabelle Duband‐Goulet; Ana Ferreiro

    Recently, the ASC‐1 complex has been identified as a mechanistic link between amyotrophic lateral sclerosis and spinal muscular atrophy (SMA), and 3 mutations of the ASC‐1 gene TRIP4 have been associated with SMA or congenital myopathy. Our goal was to define ASC‐1 neuromuscular function and the phenotypical spectrum associated with TRIP4 mutations.

    更新日期:2019-12-27
  • Identification of Restless Legs Syndrome Genes by Mutational Load Analysis
    Ann. Neurol. (IF 9.496) Pub Date : 2019-12-19
    Erik Tilch; Barbara Schormair; Chen Zhao; Aaro V. Salminen; Ana Antic Nikolic; Evi Holzknecht; Birgit Högl; Werner Poewe; Cornelius G. Bachmann; Walter Paulus; Claudia Trenkwalder; Wolfgang H. Oertel; Magdolna Hornyak; Ingo Fietze; Klaus Berger; Peter Lichtner; Christian Gieger; Annette Peters; Bertram Müller‐Myhsok; Alexander Hoischen; Juliane Winkelmann; Konrad Oexle

    Restless legs syndrome is a frequent neurological disorder with substantial burden on individual well‐being and public health. Genetic risk loci have been identified, but the causatives genes at these loci are largely unknown, so that functional investigation and clinical translation of molecular research data are still inhibited. To identify putatively causative genes, we searched for highly significant mutational burden in candidate genes.

    更新日期:2019-12-19
  • Randomized Placebo‐Controlled Trial of Intravenous Immunoglobulin in Autoimmune LGI1/CASPR2 Epilepsy
    Ann. Neurol. (IF 9.496) Pub Date : 2019-12-14
    Divyanshu Dubey; Jeffrey Britton; Andrew McKeon; Avi Gadoth; Anastasia Zekeridou; Sebastian A. Lopez Chiriboga; Michelle Devine; Jane H. Cerhan; Katie Dunlay; Jessica Sagen; Melanie Ramberger; Patrick Waters; Sarosh R. Irani; Sean J. Pittock

    Drug‐resistant seizures are common in patients with leucine‐rich, glioma‐inactivated 1 (LGI1)‐IgG associated and contactin‐associated protein‐like 2 (CASPR2)‐IgG associated encephalitis. We performed the first randomized double‐blind placebo‐controlled trial to evaluate efficacy of intravenous immunoglobulin (IVIG) in reducing seizure frequency.

    更新日期:2019-12-17
  • How the Human Brain Sleeps: Direct Cortical Recordings of Normal Brain Activity
    Ann. Neurol. (IF 9.496) Pub Date : 2019-12-13
    Nicolás von Ellenrieder; Jean Gotman; Rina Zelmann; Christine Rogers; Dang Khoa Nguyen; Philippe Kahane; François Dubeau; Birgit Frauscher

    Regional variations in oscillatory activity during human sleep remain unknown. Using the unique ability of intracranial electroencephalography to study in situ brain physiology, this study assesses regional variations of electroencephalographic sleep activity and creates the first atlas of human sleep using recordings from the first sleep cycle.

    更新日期:2019-12-13
  • SCN1A Variants in vaccine‐related febrile seizures: A prospective study
    Ann. Neurol. (IF 9.496) Pub Date : 2019-12-12
    John A. Damiano; Lucy Deng; Wenhui Li; Rosemary Burgess; Amy L. Schneider; Nigel W. Crawford; Jim Buttery; Michael Gold; Peter Richmond; Kristine K. Macartney; Michael S. Hildebrand; Ingrid E. Scheffer; Nicholas Wood; Samuel F. Berkovic

    Febrile seizures may follow vaccination. Common variants in the sodium channel gene, SCN1A, are associated with febrile seizures, and rare pathogenic variants in SCN1A cause the severe developmental and epileptic encephalopathy Dravet syndrome. Following vaccination, febrile seizures may raise the specter of poor outcome and inappropriately implicate vaccination as the cause. We aimed to determine the prevalence of SCN1A variants in children having their first febrile seizure either proximal to vaccination or unrelated to vaccination compared to controls.

    更新日期:2019-12-13
  • Amyotrophic Lateral Sclerosis with Pallidonigroluysian Degeneration: A Clinicopathological Study
    Ann. Neurol. (IF 9.496) Pub Date : 2019-12-10
    Junko Ito, Hiroshi Shimizu, Kentaro Ohta, Jiro Idezuka, Hajime Tanaka, Hiroshi Kondo, Takashi Nakajima, Hitoshi Takahashi, Kohei Akazawa, Osamu Onodera, Akiyoshi Kakita

    The pallidonigroluysian (PNL) system, the primary component of corticosubcortical circuits, is generally spared in amyotrophic lateral sclerosis (ALS). We evaluated the clinicopathological features of an unusual form of ALS with PNL degeneration (PNLD) and assessed whether ALS with PNLD represents a distinct ALS subtype.

    更新日期:2019-12-11
  • Evolution of anosognosia in alzheimer disease and its relationship to amyloid
    Ann. Neurol. (IF 9.496) Pub Date : 2019-12-05
    Bernard J. Hanseeuw, Matthew R. Scott, Sietske A. M. Sikkes, Michael Properzi, Jennifer R. Gatchel, Eric Salmon, Gad A. Marshall, Patrizia Vannini,

    Unawareness, or anosognosia, of memory deficits is a challenging manifestation of Alzheimer disease (AD) that adversely affects a patient's safety and decision‐making. However, there is a lack of consensus regarding the presence, as well as the evolution, of altered awareness of memory function across the preclinical and prodromal stages of AD. Here, we aimed to characterize change in awareness of memory abilities and its relationship to beta‐amyloid (Aβ) burden in a large cohort (N = 1,070) of individuals across the disease spectrum.

    更新日期:2019-12-05
  • Self‐Reported Head Trauma Predicts Poor Dual Task Gait in Retired National Football League Players
    Ann. Neurol. (IF 9.496) Pub Date : 2019-11-29
    Brad Manor, Junhong Zhou, On‐Yee Lo, Hao Zhu, Natalia A. Gouskova, Wanting Yu, Ross Zafonte, Lewis A. Lipsitz, Thomas G. Travison, Alvaro Pascual‐Leone

    Symptomatic head trauma associated with American‐style football (ASF) has been linked to brain pathology, along with physical and mental distress in later life. However, the longer‐term effects of such trauma on objective metrics of cognitive–motor function remain poorly understood. We hypothesized that ASF‐related symptomatic head trauma would predict worse gait performance, particularly during dual task conditions (ie, walking while performing an additional cognitive task), in later life.

    更新日期:2019-11-30
  • Safety and Efficacy of Otaplimastat in Patients with Acute Ischemic Stroke Requiring tPA (SAFE‐TPA): A Multicenter, Randomized, Double‐Blind, Placebo‐Controlled Phase 2 Study
    Ann. Neurol. (IF 9.496) Pub Date : 2019-11-29
    Jong S. Kim, Kyung Bok Lee, Jong‐Ho Park, Sang Min Sung, Kyungmi Oh, Eung‐Gyu Kim, Dae‐il Chang, Yang Ha Hwang, Eun‐Jae Lee, Won‐Ki Kim, Chung Ju, Byung Su Kim, Jei‐Man Ryu,

    Otaplimastat is a neuroprotectant that inhibits matrix metalloprotease pathway, and reduces edema and intracerebral hemorrhage induced by recombinant tissue plasminogen activator (rtPA) in animal stroke models. We aimed to assess the safety and efficacy of otaplimastat in patients receiving rtPA.

    更新日期:2019-11-30
  • Central Role of Subthreshold Currents in Myotonia
    Ann. Neurol. (IF 9.496) Pub Date : 2019-11-27
    Sabrina Metzger, Chris Dupont, Andrew A. Voss, Mark M. Rich

    It is generally thought that muscle excitability is almost exclusively controlled by currents responsible for generation of action potentials. We propose that smaller ion channel currents that contribute to setting the resting potential and to subthreshold fluctuations in membrane potential can also modulate excitability in important ways. These channels open at voltages more negative than the action potential threshold and are thus termed subthreshold currents. As subthreshold currents are orders of magnitude smaller than the currents responsible for the action potential, they are hard to identify and easily overlooked. Discovery of their importance in regulation of excitability opens new avenues for improved therapy for muscle channelopathies and diseases of the neuromuscular junction. ANN NEUROL 2019

    更新日期:2019-11-28
  • Early Intrathecal T Helper 17.1 Cell Activity in Huntington Disease
    Ann. Neurol. (IF 9.496) Pub Date : 2019-11-27
    Marina R. von Essen, Marie N. N. Hellem, Tua Vinther‐Jensen, Cecilie Ammitzbøll, Rikke H. Hansen, Lena E. Hjermind, Troels T. Nielsen, Jørgen E. Nielsen, Finn Sellebjerg

    Huntington disease (HD) is an autosomal dominantly inherited neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin (HTT) gene. No disease‐modifying therapy exists for the treatment of patients with HD. The purpose of this study was therefore to investigate early disease mechanisms that potentially could be used as a target therapeutically.

    更新日期:2019-11-28
  • Comparison of the Response to Rituximab between Myelin Oligodendrocyte Glycoprotein and Aquaporin‐4 Antibody Diseases
    Ann. Neurol. (IF 9.496) Pub Date : 2019-11-27
    Pierre Durozard, Audrey Rico, Clémence Boutiere, Adil Maarouf, Romaric Lacroix, Sylvie Cointe, Shirley Fritz, Corinne Brunet, Jean Pelletier, Romain Marignier, Bertrand Audoin

    To compare response to rituximab (RTX) between adult patients positive for myelin oligodendrocyte glycoprotein (MOG) and aquaporin‐4 (AQP4) antibodies.

    更新日期:2019-11-28
  • Midlife Atherosclerosis and Development of Alzheimer or Vascular Dementia
    Ann. Neurol. (IF 9.496) Pub Date : 2019-11-27
    Anna‐Märta Gustavsson, Danielle van Westen, Erik Stomrud, Gunnar Engström, Katarina Nägga, Oskar Hansson

    To investigate whether midlife atherosclerosis is associated with different dementia subtypes and related underlying pathologies.

    更新日期:2019-11-28
  • Duration of American Football Play and Chronic Traumatic Encephalopathy
    Ann. Neurol. (IF 9.496) Pub Date : 2019-11-23
    Jesse Mez, Daniel H. Daneshvar, Bobak Abdolmohammadi, Alicia S. Chua, Michael L. Alosco, Patrick T. Kiernan, Laney Evers, Laura Marshall, Brett M. Martin, Joseph N. Palmisano, Christopher J. Nowinski, Ian Mahar, Jonathan D. Cherry, Victor E. Alvarez, Brigid Dwyer, Bertrand R. Huber, Thor D. Stein, Lee E. Goldstein, Douglas I. Katz, Robert C. Cantu, Rhoda Au, Neil W. Kowall, Robert A. Stern, Michael D. McClean, Jennifer Weuve, Yorghos Tripodis, Ann C. McKee

    Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to contact and collision sports, including American football. We hypothesized a dose–response relationship between duration of football played and CTE risk and severity.

    更新日期:2019-11-28
  • Therapeutic Drug Monitoring of Newer Antiepileptic Drugs: A Randomized Trial for Dosage Adjustment
    Ann. Neurol. (IF 9.496) Pub Date : 2019-11-26
    Irene Aícua‐Rapún, Pascal André, Andrea O. Rossetti, Philippe Ryvlin, Andreas F. Hottinger, Laurent A. Decosterd, Thierry Buclin, Jan Novy

    Therapeutic drug monitoring (TDM) of antiepileptic drugs (AEDs) is widely established for older generation AEDs, whereas there is limited evidence about newer AEDs. Our aim is to assess the benefit of TDM of newer generation AEDs in epilepsy.

    更新日期:2019-11-27
  • Why Most Acute Stroke Studies Are Positive in Animals but Not in Patients: A Systematic Comparison of Preclinical, Early Phase, and Phase 3 Clinical Trials of Neuroprotective Agents
    Ann. Neurol. (IF 9.496) Pub Date : 2019-11-26
    Antje Schmidt‐Pogoda, Nadine Bonberg, Mailin Hannah Marie Koecke, Jan‐Kolja Strecker, Jürgen Wellmann, Nils‐Martin Bruckmann, Carolin Beuker, Wolf‐Rüdiger Schäbitz, Sven G. Meuth, Heinz Wiendl, Heike Minnerup, Jens Minnerup

    To analyze why numerous acute stroke treatments were successful in the laboratory but failed in large clinical trials.

    更新日期:2019-11-27
  • Layer‐ and Cell‐Specific Recruitment Dynamics during Epileptic Seizures In Vivo
    Ann. Neurol. (IF 9.496) Pub Date : 2019-11-22
    Fadi Aeed, Tal Shnitzer, Ronen Talmon, Yitzhak Schiller

    To investigate the network dynamics mechanisms underlying differential initiation of epileptic interictal spikes and seizures.

    更新日期:2019-11-22
  • A 30‐Year Clinical and Magnetic Resonance Imaging Observational Study of Multiple Sclerosis and Clinically Isolated Syndromes
    Ann. Neurol. (IF 9.496) Pub Date : 2019-11-22
    Karen K. Chung, Daniel Altmann, Frederik Barkhof, Katherine Miszkiel, Peter A. Brex, Jonathan O'Riordan, Michael Ebner, Ferran Prados, M. Jorge Cardoso, Tom Vercauteren, Sebastien Ourselin, Alan Thompson, Olga Ciccarelli, Declan T. Chard

    Clinical outcomes in multiple sclerosis (MS) are highly variable. We aim to determine the long‐term clinical outcomes in MS, and to identify early prognostic features of these outcomes.

    更新日期:2019-11-22
  • Strategic Considerations for Applying the Flipped Classroom to Neurology Education
    Ann. Neurol. (IF 9.496) Pub Date : 2019-11-21
    Stefano Sandrone, Jimmy V. Berthaud, Chad Carlson, Jacquelyne Cios, Neel Dixit, Amtul Farheen, Jessica Kraker, James W. M. Owens, Gustavo Patino, Harini Sarva, Daniel Weber, Logan D. Schneider

    Nowadays, the “flipped classroom” approach is taking the center stage within medical education. However, very few reports on the implementation of the flipped classroom in neurology have been published to date, and this educational model still represents a challenge for students and educators alike. In this article, neurology educators from the American Academy of Neurology's A. B. Baker Section on Neurological Education analyze reports of flipped classroom in other medical/surgical subspecialties, review the current implementation in neurology, and discuss future strategies to flip the neurology curriculum through contextualization of the benefits and the consequences. ANN NEUROL 2019

    更新日期:2019-11-21
  • α‐Amino‐3‐Hydroxy‐5‐Methyl‐4‐Isoxazolepropionic Acid Receptor Plasticity Sustains Severe, Fatal Status Epilepticus
    Ann. Neurol. (IF 9.496) Pub Date : 2019-11-20
    Nadia Adotevi, Ewa Lewczuk, Huayu Sun, Suchitra Joshi, Natalia Dabrowska, Sarah Shan, John Williamson, Jaideep Kapur

    Generalized convulsive status epilepticus is associated with high mortality. We tested whether α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptor plasticity plays a role in sustaining seizures, seizure generalization, and mortality observed during focal onset status epilepticus. We also determined whether modified AMPA receptors generated during status epilepticus could be targeted with a drug.

    更新日期:2019-11-20
  • Genetic, Structural, and Functional Evidence Link TMEM175 to Synucleinopathies
    Ann. Neurol. (IF 9.496) Pub Date : 2019-11-18
    Lynne Krohn, Tuğba Nur Öztürk, Benoît Vanderperre, Bouchra Ouled Amar Bencheikh, Jennifer A. Ruskey, Sandra B. Laurent, Dan Spiegelman, Ronald B. Postuma, Isabelle Arnulf, Michele T. M. Hu, Yves Dauvilliers, Birgit Högl, Ambra Stefani, Christelle Charley Monaca, Giuseppe Plazzi, Elena Antelmi, Luigi Ferini‐Strambi, Anna Heidbreder, Uladzislau Rudakou, Valérie Cochen De Cock, Peter Young, Pavlina Wolf, Petra Oliva, Xiaokui Kate Zhang, Lior Greenbaum, Christopher Liong, Jean‐François Gagnon, Alex Desautels, Sharon Hassin‐Baer, Jacques Y. Montplaisir, Nicolas Dupré, Guy A. Rouleau, Edward A. Fon, Jean‐François Trempe, Guillaume Lamoureux, Roy N. Alcalay, Ziv Gan‐Or

    The TMEM175/GAK/DGKQ locus is the 3rd strongest risk locus in genome‐wide association studies of Parkinson disease (PD). We aimed to identify the specific disease‐associated variants in this locus, and their potential implications.

    更新日期:2019-11-18
  • The “maternal effect” on epilepsy risk: Analysis of familial epilepsies and reassessment of prior evidence
    Ann. Neurol. (IF 9.496) Pub Date : 2019-11-18
    Colin A. Ellis, Samuel F. Berkovic, Michael P. Epstein, Ruth Ottman,

    Previous studies have observed that epilepsy risk is higher among offspring of affected women than offspring of affected men. We tested whether this “maternal effect” was present in familial epilepsies, which are enriched for genetic factors that contribute to epilepsy risk.

    更新日期:2019-11-18
  • Lipid lowering and Alzheimer's disease risk: a Mendelian randomization study
    Ann. Neurol. (IF 9.496) Pub Date : 2019-11-12
    Dylan M. Williams, Chris Finan, Amand F. Schmidt, Stephen Burgess, Aroon D. Hingorani

    To examine whether genetic variation affecting the expression or function of lipid‐lowering drug targets is associated with Alzheimer's disease (AD) risk, to evaluate the potential impact of long‐term exposure to corresponding therapeutics.

    更新日期:2019-11-13
  • T lymphocytes and cytotoxic astrocyte blebs correlate across autism brains
    Ann. Neurol. (IF 9.496) Pub Date : 2019-11-04
    Marcello M. DiStasio, Ikue Nagakura, Monica J. Nadler, Matthew P. Anderson

    Autism spectrum disorder (ASD) affects 1 in 59 children, yet except for rare genetic causes, the etiology in most ASD remains unknown. In the ASD brain, inflammatory cytokine and transcript profiling shows increased expression of genes encoding mediators of the innate immune response. We evaluated postmortem brain tissue for adaptive immune cells and immune cell–mediated cytotoxic damage that could drive this innate immune response in the ASD brain.

    更新日期:2019-11-04
  • Antiepileptic Drugs and Suicide: Role of Prior Suicidal Behavior and Parental Psychiatric Disorder
    Ann. Neurol. (IF 9.496) Pub Date : 2019-10-31
    Julie W. Dreier, Carsten B. Pedersen, Christiane Gasse, Jakob Christensen

    To examine whether prior suicidal behavior and familial predisposition to psychiatric disorders modify the association between antiepileptic drug use and completed suicide.

    更新日期:2019-11-01
  • Low‐Frequency Brain Oscillations Track Motor Recovery in Human Stroke
    Ann. Neurol. (IF 9.496) Pub Date : 2019-10-30
    Marlene Bönstrup, Lutz Krawinkel, Robert Schulz, Bastian Cheng, Jan Feldheim, Götz Thomalla, Leonardo G. Cohen, Christian Gerloff

    The majority of patients with stroke survive the acute episode and live with enduring disability. Effective therapies to support recovery of motor function after stroke are yet to be developed. Key to this development is the identification of neurophysiologic signals that mark recovery and are suitable and susceptible to interventional therapies. Movement preparatory low‐frequency oscillations (LFOs) play a key role in cortical control of movement. Recent animal data point to a mechanistic role of motor cortical LFOs in stroke motor deficits and demonstrate neuromodulation intervention with therapeutic benefit. Their relevance in human stroke pathophysiology is unknown.

    更新日期:2019-11-01
  • Reply to "Grading the severity of autoimmune encephalitis: Advances and pitfalls".
    Ann. Neurol. (IF 9.496) Pub Date : 2019-05-03
    Jung-Ah Lim,Soon-Tae Lee,Kon Chu,Sang Kun Lee

    更新日期:2019-11-01
  • 更新日期:2019-11-01
  • Reply to "Pregnancy, NMDA receptor antibodies, and neuropsychiatric diseases".
    Ann. Neurol. (IF 9.496) Pub Date : null
    Betty Jurek,Mariya Chayka,Jakob Kreye,Michael Koelch,Harald Prüss

    更新日期:2019-11-01
  • TMEM106B Effect on cognition in Parkinson disease and frontotemporal dementia.
    Ann. Neurol. (IF 9.496) Pub Date : 2019-04-12
    Thomas F Tropea,Jordan Mak,Michael H Guo,Sharon X Xie,Eunran Suh,Jacqueline Rick,Andrew Siderowf,Daniel Weintraub,Murray Grossman,David Irwin,David A Wolk,John Q Trojanowski,Vivianna Van Deerlin,Alice S Chen-Plotkin

    OBJECTIVE Common variants near TMEM106B associate with risk of developing frontotemporal dementia (FTD). Emerging evidence suggests a role for TMEM106B in neurodegenerative processes beyond FTD. We evaluate the effect of TMEM106B genotype on cognitive decline across multiple neurogenerative diseases. METHODS We longitudinally followed 870 subjects with diagnoses of Parkinson disease (PD; n = 179), FTD (n = 179), Alzheimer disease (AD; n = 300), memory-predominant mild cognitive impairment (MCI; n = 75), or neurologically normal control subjects (NC; n = 137) at the University of Pennsylvania (UPenn). All participants had annual Mini-Mental State Examination (MMSE; median follow-up duration = 3.0 years) and were genotyped at TMEM106B index single nucleotide polymorphism rs1990622. Genotype effects on cognition were confirmed by extending analyses to additional cognitive instruments (Mattis Dementia Rating Scale-2 [DRS-2] and Montreal Cognitive Assessment [MoCA]) and to an international validation cohort (Parkinson's Progression Markers Initiative [PPMI], N = 371). RESULTS The TMEM106B rs1990622T allele, linked to increased risk of FTD, associated with greater MMSE decline over time in PD subjects but not in AD or MCI subjects. For FTD subjects, rs1990622T associated with more rapid decrease in MMSE only under the minor-allele, rs1990622C , dominant model. Among PD patients, rs1990622T carriers from the UPenn cohort demonstrated more rapid longitudinal decline in DRS-2 scores. Finally, in the PPMI cohort, TMEM106B risk allele carriers demonstrated more rapid longitudinal decline in MoCA scores. INTERPRETATION Irrespective of cognitive instrument or cohort assessed, TMEM106B acts as a genetic modifier for cognitive trajectory in PD. Our results implicate lysosomal dysfunction in the pathogenesis of cognitive decline in 2 different proteinopathies. ANN NEUROL 2019;85:801-811.

    更新日期:2019-11-01
  • 更新日期:2019-11-01
  • Passages 2019.
    Ann. Neurol. (IF 9.496) Pub Date : 2018-12-20
    Clifford B Saper

    更新日期:2019-11-01
  • Heat opens axon initial segment sodium channels: a febrile seizure mechanism?
    Ann. Neurol. (IF 9.496) Pub Date : 2009-09-11
    Evan A Thomas,Roger J Hawkins,Kay L Richards,Ruwei Xu,Elena V Gazina,Steven Petrou

    OBJECTIVE A number of hypotheses have been put forward as to why humans respond to fever by seizing. The current leading hypotheses are that respiratory alkalosis produces an as yet unidentified change in neural excitability or that inflammatory mediators potentiate excitatory synaptic transmission. However, it is well known that ion channel gating rates increase with increased temperature. Furthermore, skeletal and cardiac sodium channel activation can be temperature sensitive in some situations. We measured the temperature sensitivity of the brain sodium channel, Na(V)1.2, to determine whether febrile temperatures might produce a direct increase in neuronal excitability. METHODS The effect of temperature on Na(V)1.2 electrophysiological properties was measured in a transfected mammalian cell line. The subcellular location of Na(V)1.2 in the mouse brain was ascertained using antibodies against Na(V)1.2 and ankyrin-G. Computer simulation of a hippocampal granule cell model was used to predict the effect of temperature on action potential firing. RESULTS As well as the expected increase in gating rates, the voltage dependence of activation became 7.6 mV more negative when the temperature was increased from 37 degrees C to 41 degrees C. Na(V)1.2 was localized to the axon initial segment in hippocampal and cortical neurons. Computer simulation showed that increased gating rates and the more negative activation dramatically increase neuronal excitability. INTERPRETATION The direct effect of heat on ion channels localized to the site of action potential initiation potentially causes a profound increase in neuronal excitability. This is likely to contribute to febrile seizure genesis.

    更新日期:2019-11-01
  • In Memoriam: Frederick Andermann, MD.
    Ann. Neurol. (IF 9.496) Pub Date : null
    Donald L Schomer,Joseph B Martin,Christopher A Walsh,Mark L Andermann

    更新日期:2019-11-01
  • 更新日期:2019-11-01
  • Reply to "Quantitative Motor Functioning in Prodromal Parkinson Disease".
    Ann. Neurol. (IF 9.496) Pub Date : 2019-10-01
    Walter Maetzler,Silvia Del Din,Morad Elshehabi,Brook Galna,Daniela Berg,Lynn Rochester

    更新日期:2019-11-01
  • Quantitative Motor Functioning in Prodromal Parkinson Disease.
    Ann. Neurol. (IF 9.496) Pub Date : 2019-10-01
    Lisanne J Dommershuijsen,M Kamran Ikram,Sirwan K L Darweesh

    更新日期:2019-11-01
  • Clinicopathology conference: 41-year-old woman with chronic relapsing meningitis.
    Ann. Neurol. (IF 9.496) Pub Date : 2018-12-20
    Erin S Beck,Prashanth S Ramachandran,Lillian M Khan,Hannah A Sample,Kelsey C Zorn,Elise M O'Connell,Theodore Nash,Daniel S Reich,Arun Venkatesan,Joseph L DeRisi,Avindra Nath,Michael R Wilson

    更新日期:2019-11-01
  • Low stability of Huntington muscle mitochondria against Ca2+ in R6/2 mice.
    Ann. Neurol. (IF 9.496) Pub Date : 2006-01-27
    Zemfira Z Gizatullina,Katrin S Lindenberg,Phoebe Harjes,Ying Chen,Christoph M Kosinski,Bernhard G Landwehrmeyer,Albert C Ludolph,Frank Striggow,Stephan Zierz,Frank N Gellerich

    OBJECTIVE The aim of the present work was the detection of Mitochondrial dysfunction of Huntington's disease (HD). METHODS We investigated muscle and muscle mitochondria of 14- to 16-week-old R6/2 mice in comparison with wild-type mice. RESULTS Atrophic fibers, increased fuchsinophilic aggregates, and reduced cytochrome c oxidase (15%) were found in HD muscle. With swelling measurements and Ca2+ accumulation experiments, a decreased stability of HD mitochondria against Ca2+-induced permeability transition was detected. Complex I-dependent respiration of HD mitochondria was more sensitive to inhibition by adding 10 microm Ca2+ than wild-type mitochondria. INTERPRETATION Data suggest that the decreased stability of HD mitochondria against Ca2+ contributes to energetic depression and cell atrophy.

    更新日期:2019-11-01
  • Paroxetine retards disease onset and progression in Huntingtin mutant mice.
    Ann. Neurol. (IF 9.496) Pub Date : 2004-03-30
    Wenzhen Duan,Zhihong Guo,Haiyang Jiang,Bruce Ladenheim,Xiangru Xu,Jean Lud Cadet,Mark P Mattson

    We report that administration of paroxetine, a widely prescribed antidepressant drug that acts by inhibiting reuptake of the neurotransmitter serotonin, suppresses the neurodegenerative process and increases the survival of huntingtin mutant mice, an animal model of Huntington's disease (HD). Paroxetine attenuated motor dysfunction and body weight loss and improved glucose metabolism in the HD mice. Paroxetine was beneficial when treatment was initiated before or after the onset of motor dysfunction, suggesting a potential for such antidepressant drugs in the treatment of presymptomatic and symptomatic HD patients.

    更新日期:2019-11-01
  • Minocycline and doxycycline are not beneficial in a model of Huntington's disease.
    Ann. Neurol. (IF 9.496) Pub Date : 2003-08-02
    Donna L Smith,Benjamin Woodman,Amarbirpal Mahal,Kirupa Sathasivam,Shabnam Ghazi-Noori,Philip A S Lowden,Gillian P Bates,Emma Hockly

    Huntington's Disease (HD) is an inherited neurological disorder causing movement impairment, personality changes, dementia, and premature death, for which there is currently no effective therapy. The modified tetracycline antibiotic, minocycline, has been reported to ameliorate the disease phenotype in the R6/2 mouse model of HD. Because the tetracyclines have also been reported to inhibit aggregation in other amyloid disorders, we have investigated their ability to inhibit huntingtin aggregation and further explored their efficacy in preclinical mouse trials. We show that tetracyclines are potent inhibitors of huntingtin aggregation in a hippocampal slice culture model of HD at an effective concentration of 30 microM. However, despite achieving tissue levels approaching this concentration by oral treatment of R6/2 mice with minocycline, we observed no clear difference in their behavioral abnormalities, or in aggregate load postmortem. In the light of these new data, we would advise that caution be exercised in proceeding into human clinical trials of minocycline.

    更新日期:2019-11-01
  • 更新日期:2019-11-01
  • Reply to "Usefulness of Plasma Amyloid as Prescreener of the Earliest Alzheimer Pathological Changes Depends on the Study Population".
    Ann. Neurol. (IF 9.496) Pub Date : 2019-11-02
    Inge M W Verberk,Charlotte E Teunissen,Wiesje M Van der Flier

    更新日期:2019-11-01
  • 更新日期:2019-11-01
  • Developing a successful global neurology program.
    Ann. Neurol. (IF 9.496) Pub Date : 2016-12-27
    Omar K Siddiqi,Merritt Brown,Christine Cooper,Masharip Atadzhanov,Shabir Lakhi,Igor J Koralnik

    更新日期:2019-11-01
  • Early electroencephalogram for neurologic prognostication: A self-fulfilling prophecy?
    Ann. Neurol. (IF 9.496) Pub Date : 2019-06-30
    Sung-Min Cho,Maximilian Mulder,Romergryko G Geocadin

    更新日期:2019-11-01
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