Weekly Publications

WashU weekly Neuroscience publications

“Clinical instrument to retrospectively capture levels of EDSS” (2020) Multiple Sclerosis and Related Disorders

Clinical instrument to retrospectively capture levels of EDSS
(2020) Multiple Sclerosis and Related Disorders, 39, art. no. 101884, . 

Ciotti, J.R.a , Sanders, N.b , Salter, A.c , Berger, J.R.d , Cross, A.H.a , Chahin, S.a

a Department of Neurology, Washington University in St. Louis, St. Louis, MO, United States
b University of Minnesota Medical School, Minneapolis, MN, United States
c Division of Biostatistics, Washington University in St. Louis, St. Louis, MO, United States
d Department of Neurology, University of Pennsylvania, Philadelphia, PA, United States

Abstract
Background: The Expanded Disability Status Scale (EDSS), a common outcome measure in Multiple Sclerosis (MS), is obtained prospectively through a direct standardized evaluation. The objective of this study is to develop and validate an algorithm to derive EDSS scores from previous neurological clinical documentation. Methods: The algorithm utilizes data from the history, review of systems, and physical exam. EDSS scores formally obtained from research patients were compared to captured EDSS (cEDSS) scores. To test interrater reliability, a second investigator captured scores from a subset of patients. Agreement between formal and c-EDSS scores was assessed using a weighted kappa. Clinical concordance was defined as a difference of one-step in EDSS (0.5) and functional system (1.0) scores. Results: Clinical documentation from 92 patients (EDSS range 0.0–8.5) was assessed. Substantial agreement between the cEDSS and formal EDSS (kappa 0.80; 95% CI 0.74–0.86) was observed. The mean difference between scores was 0.16. The clinical concordance was 78%. Near-perfect agreement was found between the two raters (kappa 0.89; 95% CI 0.84–0.95). The mean inter-rater difference in c-EDSS was 0.23. Conclusions: This algorithm reliably captures EDSS scores retrospectively with substantial correlation with formal EDSS and high interrater agreement. This algorithm may have practical implications in clinic, MS research and clinical trials. © 2019 Elsevier B.V.

Author Keywords
Algorithm;  Chart review;  Disability;  Examination;  Multiple sclerosis;  Outcome measure

Document Type: Article
Publication Stage: Final
Source: Scopus

“Ketamine sedation in mechanically ventilated patients: A systematic review and meta-analysis” (2020) Journal of Critical Care

Ketamine sedation in mechanically ventilated patients: A systematic review and meta-analysis
(2020) Journal of Critical Care, 56, pp. 80-88. 

Manasco, A.T.b , Stephens, R.J.c , Yaeger, L.H.d , Roberts, B.W.e , Fuller, B.M.a

a Departments of Anesthesiology and Emergency Medicine, Division of Critical Care, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, United States
b Department of Pulmonary and Critical Care, WakeMed Hospital, 3000 New Bern Ave, Raleigh, NC 27610, United States
c Department of Emergency Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, United States
d Medical Librarian, Bernard Becker Medical Library, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, United States
e Department of Emergency Medicine, Cooper University Hospital, Cooper Medical School of Rowan University, One Cooper Plaza, K152, Camden, NJ 08103, United States

Abstract
Purpose: Ketamine use as a sedative agent in mechanically ventilated patients is increasing. This systematic review and meta-analysis collates existing literature and quantifies the impact of ketamine in mechanically ventilated patients. Materials and methods: EMBASE, MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, conference proceedings, and reference lists were searched. Randomized and nonrandomized studies were included, and two reviewers independently screened abstracts of identified studies for eligibility. Results: Fifteen studies (n = 892 patients) were included. Random effects meta-analytic models revealed that ketamine was associated with a reduction in propofol infusion rate (mean difference in dose, −699 μg/min; 95% CI −1169 to −230, p = .003), but had no impact on fentanyl or midazolam. Ketamine was not associated with mortality, on-target sedation, vasopressor dependence, or hospital length of stay. Cardiovascular complications (e.g. tachycardia and hypertension) were most commonly reported, followed by neurocognitive events, such as agitation and delirium. Conclusions: The data regarding ketamine use in mechanically ventilated patients is limited in terms of quantity, methodological quality, and demonstrated clinical benefit. Ketamine may play a role as a sedative-sparing agent, but may be associated with harm. High-quality studies are needed before widespread adoption of ketamine earlier in the sedation pathway. © 2019 Elsevier Inc.

Author Keywords
Ketamine;  Mechanical ventilation;  Sedation

Document Type: Article
Publication Stage: Final
Source: Scopus

“Perceived safety of cannabis intoxication predicts frequency of driving while intoxicated” (2020) Preventive Medicine

Perceived safety of cannabis intoxication predicts frequency of driving while intoxicated
(2020) Preventive Medicine, 131, art. no. 105956, . 

Borodovsky, J.T.a , Marsch, L.A.b , Scherer, E.A.c , Grucza, R.A.a , Hasin, D.S.d , Budney, A.J.b

a Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
b Center for Technology and Behavioral Health, Dartmouth Geisel School of Medicine, Lebanon, NH, United States
c Department of Biomedical Data Science, Dartmouth Geisel School of Medicine, Lebanon, NH, United States
d Department of Psychiatry, Columbia University Medical Center, New York, NY, United States

Abstract
Driving under the influence of cannabis (DUIC) is a public health concern, and data are needed to develop screening and prevention tools. Measuring the level of intoxication that cannabis users perceive as safe for driving could help stratify DUIC risk. This study tested whether intoxication levels perceived as safe for driving predicted past-month DUIC frequency. Online survey data were collected in 2017 from a national sample of n = 3010 past-month cannabis users with lifetime DUIC (age 18+). Respondents indicated past-month DUIC frequency, typical cannabis intoxication level (1–10 scale), and cannabis intoxication level perceived as safe for driving (0–10 scale). Approximately 24%, 38%, 13%, and 24% of respondents engaged in DUIC on 0, 1–9, 10–19, and 20–30 days respectively in the past month. Among these four DUIC frequency groups, median typical intoxication varied little (5–6), but median intoxication perceived as safe for driving varied widely (3–8). Higher intoxication levels perceived as safe for driving corresponded to frequent DUIC (Spearman’s rho: 0.46). For each unit increase in intoxication level perceived as safe for driving, the odds of past-month DUIC increased 18% to 68% (multinomial logistic regression odds ratio – MOR1 – 9 days: 1.18, 95% CI: 1.13–1.23; MOR10 – 19 days: 1.40, 95% CI: 1.30–1.50; MOR20 – 30 days: 1.68, 95% CI: 1.57–1.80). In this targeted sample of past-month cannabis users, DUIC frequency varied widely, but daily/near-daily DUIC was common (24%). Measuring intoxication levels perceived as safe for driving permits delineation of past-month DUIC frequency. This metric has potential as a component of public health prevention tools. © 2019

Author Keywords
Cannabis;  Driving under the influence;  Intoxication;  Marijuana;  Risk perception

Document Type: Article
Publication Stage: Final
Source: Scopus

“Chronic Graft Versus Host Myopathies: Noninflammatory, Multi-Tissue Pathology With Glycosylation Disorders” (2020) Journal of Neuropathology and Experimental Neurology

Chronic Graft Versus Host Myopathies: Noninflammatory, Multi-Tissue Pathology With Glycosylation Disorders
(2020) Journal of Neuropathology and Experimental Neurology, 79 (1), pp. 102-112. 

Pestronk, A.

Departments of Neurology, Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri (AP), United States

Abstract
Myopathies during chronic graft-versus-host disease (cGvHD) are syndromes for which tissue targets and mechanisms of muscle damage remain incompletely defined. This study reviewed, and pathologically analyzed, 14 cGvHD myopathies, comparing myopathology to other immune myopathies. Clinical features in cGvHD myopathy included symmetric, proximal weakness, associated skin, gastrointestinal and lung disorders, a high serum aldolase (77%), and a 38% 2-year survival. Muscle showed noninflammatory pathology involving all 3 tissue components. Perimysial connective tissue had damaged structure and histiocytic cells. Vessel pathology included capillary loss, and reduced α-l-fucosyl and chondroitin sulfate moieties on endothelial cells. Muscle fibers often had surface pathology. Posttranslational glycosylation moieties on α-dystroglycan had reduced staining and abnormal distribution in 86%. Chondroitin-SO4 was reduced in 50%, a subgroup with 3-fold longer times from transplant to myopathy, and more distal weakness. cGvHD myopathies have noninflammatory pathology involving all 3 tissue components in muscle, connective tissue, small vessels, and myofibers. Abnormal cell surface glycosylation moieties are common in cGvHD myopathies, distinguishing them from other immune myopathies. This is the first report of molecular classes that may be immune targets in cGvHD. Disordered cell surface glycosylation moieties could produce disease-related tissue and cell damage, and be biomarkers for cGvHD features and activity. © 2019 American Association of Neuropathologists, Inc. All rights reserved.

Author Keywords
Chronic graft-versus-host;  Glycosylation;  Immune;  Myopathy;  Myositis

Document Type: Article
Publication Stage: Final
Source: Scopus

“Adaptation of the Clinical Dementia Rating Scale for adults with Down syndrome” (2019) Journal of Neurodevelopmental Disorders

Adaptation of the Clinical Dementia Rating Scale for adults with Down syndrome
(2019) Journal of Neurodevelopmental Disorders, 11 (1), p. 39. 

Lessov-Schlaggar, C.N.a b , Del Rosario, O.L.a b , Morris, J.C.c d , Ances, B.M.c d e f , Schlaggar, B.L.g h i , Constantino, J.N.a b

a Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA
b Intellectual and Developmental Disabilities Research Center, Washington University School of Medicine, St. Louis, MO, USA
c Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA
d Knight Alzheimer Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA
e Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA
f Department of Neuroscience, Washington University School of Medicine, St. Louis, MO, USA
g Kennedy Krieger Institute, MD, Baltimore, United States
h Department of Neurology, Johns Hopkins University School of Medicine, MD, Baltimore, United States
i Department of Pediatrics, Johns Hopkins University School of Medicine, MD, Baltimore, United States

Abstract
BACKGROUND: Adults with Down syndrome (DS) are at increased risk for Alzheimer disease dementia, and there is a pressing need for the development of assessment instruments that differentiate chronic cognitive impairment, acute neuropsychiatric symptomatology, and dementia in this population of patients. METHODS: We adapted a widely used instrument, the Clinical Dementia Rating (CDR) Scale, which is a component of the Uniform Data Set used by all federally funded Alzheimer Disease Centers for use in adults with DS, and tested the instrument among 34 DS patients recruited from the community. The participants were assessed using two versions of the modified CDR-a caregiver questionnaire and an in-person interview involving both the caregiver and the DS adult. Assessment also included the Dementia Scale for Down Syndrome (DSDS) and the Raven’s Progressive Matrices to estimate IQ. RESULTS: Both modified questionnaire and interview instruments captured a range of cognitive impairments, a majority of which were found to be chronic when accounting for premorbid function. Two individuals in the sample were strongly suspected to have early dementia, both of whom had elevated scores on the modified CDR instruments. Among individuals rated as having no dementia based on the DSDS, about half showed subthreshold impairments on the modified CDR instruments; there was substantial agreement between caregiver questionnaire screening and in-person interview of caregivers and DS adults. CONCLUSIONS: The modified questionnaire and interview instruments capture a range of impairment in DS adults, including subthreshold symptomatology, and the instruments provide complementary information relevant to the ascertainment of dementia in DS. Decline was seen across all cognitive domains and was generally positively related to age and negatively related to IQ. Most importantly, adjusting instrument scores for chronic, premorbid impairment drastically shifted the distribution toward lower (no impairment) scores.

Author Keywords
Cognitive decline;  Cognitive impairment;  Dementia;  Down syndrome;  Premorbid ability

Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access

“The role of glia in epilepsy, intellectual disability, and other neurodevelopmental disorders in tuberous sclerosis complex” (2019) Journal of Neurodevelopmental Disorders

The role of glia in epilepsy, intellectual disability, and other neurodevelopmental disorders in tuberous sclerosis complex
(2019) Journal of Neurodevelopmental Disorders, 11 (1), art. no. 30, . Cited 1 time.

Wong, M.

Department of Neurology and the Hope Center for Neurological Disorders, Washington University School of Medicine Box 8111, 660 South Euclid Avenue, St. Louis, MO 63110, United States

Abstract
Background: Tuberous sclerosis complex (TSC) is a genetic disorder characterized by severe neurological manifestations, including epilepsy, intellectual disability, autism, and a range of other behavioral and psychiatric symptoms, collectively referred to as TSC-Associated neuropsychiatric disorders (TAND). Various tumors and hamartomas affecting different organs are the pathological hallmarks of the disease, especially cortical tubers of the brain, but specific cellular and molecular abnormalities, such as involving the mechanistic target of rapamycin (mTOR) pathway, have been identified that also cause or contribute to neurological manifestations of TSC independent of gross structural lesions. In particular, while neurons are immediate mediators of neurological symptoms, different types of glial cells have been increasingly recognized to play important roles in the phenotypes of TSC. Main body: This review summarizes the literature supporting glial dysfunction from both mouse models and clinical studies of TSC. In particular, evidence for the role of astrocytes, microglia, and oligodendrocytes in the pathophysiology of epilepsy and TAND in TSC is analyzed. Therapeutic implications of targeting glia cells in developing novel treatments for the neurological manifestations of TSC are also considered. Conclusions: Different types of glial cells have both cell autonomous effects and interactions with neurons and other cells that are involved in the pathophysiology of the neurological phenotype of TSC. Targeting glial-mediated mechanisms may represent a novel therapeutic approach for epilepsy and TAND in TSC patients. © 2019 The Author(s).

Author Keywords
Astrocyte;  Autism spectrum disorder;  Epilepsy;  Glia;  Intellectual disability;  Microglia;  Oligodendrocyte;  TAND;  Tuberous sclerosis;  White matter

Document Type: Review
Publication Stage: Final
Source: Scopus
Access Type: Open Access

“Dynamics and sources of response variability and its coordination in visual cortex” (2019) Visual Neuroscience

Dynamics and sources of response variability and its coordination in visual cortex
(2019) Visual Neuroscience, art. no. E012, . 

Hoseini, M.S.a d , Wright, N.C.a , Xia, J.a , Clawson, W.b , Shew, W.c , Wessel, R.a

Dynamics and sources of response variability and its coordination in visual cortex
(2019) Visual Neuroscience

a Department of Physics, Washington University, St. Louis, MO, United States
b Department of Electrical Engineering, University of Arkansas, Fayetteville, AK, United States
c Department of Physics, University of Arkansas, Fayetteville, AK, United States
d Center for Integrative Neuroscience, Department of Physiology, University of California, 675 Nelson Rising Lane, San Francisco, CA, United States

Abstract
The trial-to-trial response variability in sensory cortices and the extent to which this variability can be coordinated among cortical units have strong implications for cortical signal processing. Yet, little is known about the relative contributions and dynamics of defined sources to the cortical response variability and their correlations across cortical units. To fill this knowledge gap, here we obtained and analyzed multisite local field potential (LFP) recordings from visual cortex of turtles in response to repeated naturalistic movie clips and decomposed cortical across-trial LFP response variability into three defined sources, namely, input, network, and local fluctuations. We found that input fluctuations dominate cortical response variability immediately following stimulus onset, whereas network fluctuations dominate the response variability in the steady state during continued visual stimulation. Concurrently, we found that the network fluctuations dominate the correlations of the variability during the ongoing and steady-state epochs, but not immediately following stimulus onset. Furthermore, simulations of various model networks indicated that (i) synaptic time constants, leading to oscillatory activity, and (ii) synaptic clustering and synaptic depression, leading to spatially constrained pockets of coherent activity, are both essential features of cortical circuits to mediate the observed relative contributions and dynamics of input, network, and local fluctuations to the cortical LFP response variability and their correlations across recording sites. In conclusion, these results show how a mélange of multiscale thalamocortical circuit features mediate a complex stimulus-modulated cortical activity that, when naively related to the visual stimulus alone, appears disguised as high and coordinated across-trial response variability. Copyright © 2019 Cambridge University Press.

Author Keywords
Correlation;  Local field potential;  Response variability;  Turtle;  Visual cortex

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

“Targeting Muscles in the Brain to Enhance Cerebral Perfusion” (2019) JACC: Basic to Translational Science

Targeting Muscles in the Brain to Enhance Cerebral Perfusion
(2019) JACC: Basic to Translational Science, 4 (8), pp. 959-961. 

Lee, J.-M.a , Diwan, A.b , Zipfel, G.J.c

a Department of Neurology and the Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, United States
b Division of Cardiology, Department of Internal Medicine, Washington University School of Medicine and John Cochran Veterans Affairs Medical Center, St. Louis, MO, United States
c Department of Neurosurgery and the Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, United States

 Author Keywords
cerebral autoregulation;  chronic heart failure;  cystic fibrosis transmembrane regulator;  subarachnoid hemorrhage

Document Type: Editorial
Publication Stage: Final
Source: Scopus
Access Type: Open Access

“Optimizing Lectures From a Cognitive Load Perspective” (2019) AEM Education and Training

Optimizing Lectures From a Cognitive Load Perspective
(2019) AEM Education and Training, . 

Jordan, J.a , Wagner, J.b , Manthey, D.E.c , Wolff, M.d , Santen, S.e , Cico, S.J.f

a Department of Emergency Medicine, Ronald Reagan UCLA Medical Center, and Acute Care College, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States
b Department of Emergency Medicine, Washington University in St. Louis School of Medicine, St. Louis, MO, United States
c Department of Emergency Medicine, Wake Forest School of Medicine, Winston-Salem, NC, United States
d Department of Emergency Medicine and Pediatrics, University of Michigan Medical School, Ann Arbor, MI, United States
e Virginia Commonwealth University School of Medicine, Richmond, VA, United States
f Indiana University School of Medicine, Indianapolis, IN, United States

Abstract
Lectures are a common instructional method in medical education. Understanding the cognitive processes and theories involved in learning is essential for lecturers to be effective. Cognitive load theory is one theory that is becoming increasingly recognized in medical education and addresses the appropriate use of one’s working memory. Memory is essential to knowledge acquisition. Two types of memory can be considered, working memory (processing of information) and long-term memory (storage of information). Working memory has a limited capacity. Cognitive load refers to the amount of information processing activity imposed on working memory and can be divided into three domains: intrinsic, extraneous, and germane. By attending to cognitive load, educators can promote learning. This paper highlights various ways of improving cognitive load for learners during lecture-based instruction by minimizing extraneous load, optimizing intrinsic load, and promoting germane load. © 2019 by the Society for Academic Emergency Medicine

Document Type: Note
Publication Stage: Article in Press
Source: Scopus

“Publisher Correction: Common brain disorders are associated with heritable patterns of apparent aging of the brain (Nature Neuroscience, (2019), 22, 10, (1617-1623), 10.1038/s41593-019-0471-7)” (2019) Nature Neuroscience

Publisher Correction: Common brain disorders are associated with heritable patterns of apparent aging of the brain (Nature Neuroscience, (2019), 22, 10, (1617-1623), 10.1038/s41593-019-0471-7)
(2019) Nature Neuroscience, . 

Kaufmann, T.a , van der Meer, D.a b , Doan, N.T.a , Schwarz, E.c , Lund, M.J.a , Agartz, I.a d e , Alnæs, D.a , Barch, D.M.f g h , Baur-Streubel, R.i , Bertolino, A.j k , Bettella, F.a , Beyer, M.K.l m , Bøen, E.d n , Borgwardt, S.o p q , Brandt, C.L.a , Buitelaar, J.r s , Celius, E.G.l t , Cervenka, S.e , Conzelmann, A.u , Córdova-Palomera, A.a , Dale, A.M.v w x y , de Quervain, D.J.F.z aa , Di Carlo, P.k , Djurovic, S.ab ac , Dørum, E.S.a ad ae , Eisenacher, S.c , Elvsåshagen, T.a l t , Espeseth, T.ad , Fatouros-Bergman, H.e , Flyckt, L.e , Franke, B.af , Frei, O.a , Haatveit, B.a ad , Håberg, A.K.ag ah , Harbo, H.F.l t , Hartman, C.A.ai , Heslenfeld, D.aj ak , Hoekstra, P.J.al , Høgestøl, E.A.l t , Jernigan, T.L.am an ao , Jonassen, R.ap , Jönsson, E.G.a e , Farde, L.e , Flyckt, L.e , Engberg, G.br , Erhardt, S.br , Fatouros-Bergman, H.e , Cervenka, S.e , Schwieler, L.br , Piehl, F.bs , Agartz, I.a d e , Collste, K.e , Victorsson, P.e , Malmqvist, A.br , Hedberg, M.br , Orhan, F.br , Kirsch, P.aq ar , Kłoszewska, I.as , Kolskår, K.K.a ad ae , Landrø, N.I.d ad , Le Hellard, S.ac , Lesch, K.-P.at au av , Lovestone, S.aw , Lundervold, A.ax ay , Lundervold, A.J.az , Maglanoc, L.A.a ad , Malt, U.F.l ba , Mecocci, P.bb , Melle, I.a , Meyer-Lindenberg, A.c , Moberget, T.a , Norbom, L.B.a ad , Nordvik, J.E.bc , Nyberg, L.bd , Oosterlaan, J.aj be , Papalino, M.k , Papassotiropoulos, A.z bf bg , Pauli, P.i , Pergola, G.k , Persson, K.bh bi , Richard, G.a ad ae , Rokicki, J.a ad , Sanders, A.-M.a ad ae , Selbæk, G.l bh bi , Shadrin, A.A.a , Smeland, O.B.a , Soininen, H.bj bk , Sowa, P.m , Steen, V.M.ac bl , Tsolaki, M.bm , Ulrichsen, K.M.a ad ae , Vellas, B.bn , Wang, L.bo , Westman, E.p bp , Ziegler, G.C.at , Zink, M.c bq , Andreassen, O.A.a , Westlye, L.T.a ad , Karolinska Schizophrenia Project (KaSP)bt

a NORMENT, Division of Mental Health and Addiction Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
b School of Mental Health and Neuroscience Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, Netherlands
c Department of Psychiatry and Psychotherapy Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
d Department of Psychiatry Diakonhjemmet Hospital, Oslo, Norway
e Centre for Psychiatry Research, Department of Clinical Neuroscience Karolinska Institutet & Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden
f Department of Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, United States
g Department of Psychiatry Washington, University in St. Louis, St. Louis, United States
h Department of Radiology Washington, University in St. Louis, St. Louis, United States
i Department of Psychology I, University of Würzburg, Würzburg, Germany
j Institute of Psychiatry Bari University Hospital, Bari, Italy
k Department of Basic Medical Science, Neuroscience and Sense Organs University of Bari, Bari, Italy
l Institute of Clinical Medicine, University of Oslo, Oslo, Norway
m Division of Radiology and Nuclear Medicine, Section of Neuroradiology Oslo University Hospital, Oslo, Norway
n Psychosomatic and CL Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
o Department of Psychiatry (UPK), University of Basel, Basel, Switzerland
p Department of Psychiatry, Psychosomatics and Psychotherapy University of Lübeck, Lübeck, Germany
q Institute of Psychiatry King’s College, London, United Kingdom
r Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour Radboud University Medical Center, Nijmegen, Netherlands
s Karakter Child and Adolescent Psychiatry University Centre, Nijmegen, Netherlands
t Department of Neurology, Oslo University Hospital, Oslo, Norway
u Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy University of Tübingen, Tübingen, Germany
v Center for Multimodal Imaging and Genetics, University of California at San Diego, La Jolla, CA, United States
w Department of Radiology, University of California, San Diego, La Jolla, CA, United States
x Department of Neurosciences, University of California, San Diego, La Jolla, CA, United States
y Department of Psychiatry, University of California, San Diego, La Jolla, CA, United States
z Division of Cognitive Neuroscience, University of Basel, Basel, Switzerland
aa Transfaculty Research Platform Molecular and Cognitive Neurosciences University of Basel, Basel, Switzerland
ab Department of Medical Genetics, Oslo University Hospital, Oslo, Norway
ac NORMENT, Department of Clinical Science, University of Bergen, Bergen, Norway
ad Department of Psychology, University of Oslo, Oslo, Norway
ae Sunnaas Rehabilitation Hospital HT, Nesodden, Norway
af Departments of Human Genetics and Psychiatry, Donders Institute for Brain, Cognition and Behaviour Radboud University Medical Center, Nijmegen, Netherlands
ag Department of Neuromedicine and Movement Science Norwegian, University of Science and Technology, Trondheim, Norway
ah Department of Radiology and Nuclear Medicine St. Olavs Hospital, Trondheim, Norway
ai Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
aj Clinical Neuropsychology section Vrije Universiteit Amsterdam, Amsterdam, Netherlands
ak Department of Cognitive Psychology, Vrije Universiteit Amsterdam, Amsterdam, Netherlands
al Department of Child and Adolescent Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
am Center for Human Development, University of California, San Diego, United States
an Department of Cognitive Science, University of California, San Diego, United States
ao Departments of Psychiatry and Radiology, University of California, San Diego, United States
ap Faculty of Health Sciences, Oslo Metropolitan University, Oslo, Norway
aq Department of Clinical Psychology Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
ar Bernstein Center for Computational Neuroscience Heidelberg/Mannheim, Mannheim, Germany
as Department of Old Age Psychiatry and Psychotic Disorders Medical University of Lodz, Lodz, Poland
at Division of Molecular Psychiatry, Center of Mental Health, University of Würzburg, Würzburg, Germany
au Laboratory of Psychiatric Neurobiology, Institute of Molecular Medicine Sechenov First Moscow State Medical University, Moscow, Russian Federation
av Department of Neuroscience, School for Mental Health and Neuroscience (MHeNS) Maastricht University, Maastricht, Netherlands
aw Department of Psychiatry, Warneford Hospital University of Oxford, Oxford, United Kingdom
ax Department of Biomedicine, University of Bergen, Bergen, Norway
ay Mohn Medical Imaging and Visualization Centre, Department of Radiology, Haukeland University Hospital, Bergen, Norway
az Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway
ba Department of Research and Education, Oslo University Hospital, Oslo, Norway
bb Institute of Gerontology and Geriatrics, University of Perugia, Perugia, Italy
bc CatoSenteret Rehabilitation Center Son, Oslo, Norway
bd Departments of Radiation Sciences and Integrative Medical Biology, Umeå Center for Functional Brain Imaging Umeå University, Umeå, Sweden
be Emma Children’s Hospital, Amsterdam UMC University of Amsterdam and Vrije Universiteit Amsterdam, Emma Neuroscience Group, Department of Pediatrics, Amsterdam Reproduction & Development, Amsterdam, Netherlands
bf Division of Molecular Neuroscience University of Basel, Basel, Switzerland
bg Life Sciences Training Facility, Department Biozentrum University of Basel, Basel, Switzerland
bh Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway
bi Norwegian National Advisory Unit on Ageing and Health, Vestfold Hospital Trust, Tønsberg, Norway
bj Department of Neurology, Institute of Clinical Medicine University of Eastern Finland, Kuopio, Finland
bk Neurocenter, Neurology Kuopio University Hospital, Kuopio, Finland
bl Dr. E. Martens Research Group for Biological Psychiatry, Department of Medical Genetics Haukeland University Hospital, Bergen, Norway
bm 1st Department of Neurology Aristotle University of Thessaloniki, Thessaloniki, Greece
bn UMR Inserm 1027, CHU Toulouse, UPS, Toulouse, France
bo Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
bp Department of Neurobiology Care Sciences and Society, Karolinska Institute, Stockholm, Sweden
bq District hospital Ansbach, Ansbach, Germany
br Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
bs Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden

Abstract
In the version of this article initially published, spaces were missing in the names of Stephanie Le Hellard and Pasquale Di Carlo. The errors have been corrected in the HTML and PDF versions of the article. © 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.

Document Type: Erratum
Publication Stage: Article in Press
Source: Scopus
Access Type: Open Access

“Mood Disorders and Dementia: Time for Action” (2019) American Journal of Geriatric Psychiatry

Mood Disorders and Dementia: Time for Action
(2019) American Journal of Geriatric Psychiatry, . 

Diniz, B.S.a , Lavretsky, H.b , Karp, J.F.c , Rutherford, B.d , Mulsant, B.a , Lenze, E.e

a Department of Psychiatry, Faculty of Medicine, University of Toronto & Adult Neurodevelopment and Geriatric Psychiatry Division, Centre for Addiction and Mental Health, Toronto, ON, Canada
b Department of Psychiatry, Semel Institute for Neuroscience and Human Behavior, UCLA, Los Angeles, CA, United States
c Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States
d Department of Psychiatry, Columbia University, New York, NY, United States
e Deprtment of Psychiatry, Washington University School of Medicine, St Louis, MO, United States

Document Type: Editorial
Publication Stage: Article in Press
Source: Scopus

“Intrathecal enzyme replacement for cognitive decline in mucopolysaccharidosis type I, a randomized, open-label, controlled pilot study” (2019) Molecular Genetics and Metabolism

Intrathecal enzyme replacement for cognitive decline in mucopolysaccharidosis type I, a randomized, open-label, controlled pilot study
(2019) Molecular Genetics and Metabolism, . 

Chen, A.H.a , Harmatz, P.b , Nestrasil, I.c , Eisengart, J.B.c , King, K.E.c , Rudser, K.c , Kaizer, A.M.e , Svatkova, A.c , Wakumoto, A.c , Le, S.Q.f , Madden, J.b , Young, S.d , Zhang, H.d , Polgreen, L.E.a , Dickson, P.I.f

a Department of Pediatrics, Los Angeles Biomedical Institute at Harbor-UCLA, Torrance, CA, United States
b Children’s Hospital Oakland Research Institute, Oakland, CA, United States
c Department of Pediatrics, University of Minnesota, Minneapolis, MN, United States
d Duke University, Durham, NC, United States
e Department of Biostatistics and Informatics, University of Colorado-Anschutz Medical Campus, Aurora, CO, United States
f Department of Pediatrics, Washington University in St. Louis School of Medicine, St. Louis, MO, United States

Abstract
Central nervous system manifestations of mucopolysaccharidosis type I (MPS I) such as cognitive impairment, hydrocephalus, and spinal cord compression are inadequately treated by intravenously-administered enzyme replacement therapy with laronidase (recombinant human alpha-L-iduronidase). While hematopoietic stem cell transplantation treats neurological symptoms, this therapy is not generally offered to attenuated MPS I patients. This study is a randomized, open-label, controlled pilot study of intrathecal laronidase in eight attenuated MPS I patients with cognitive impairment. Subjects ranged between 12 years and 50 years old with a median age of 18 years. All subjects had received intravenous laronidase prior to the study over a range of 4 to 10 years, with a mean of 7.75 years. Weekly intravenous laronidase was continued throughout the duration of the study. The randomization period was one year, during which control subjects attended all study visits and assessments, but did not receive any intrathecal laronidase. After the first year, all eight subjects received treatment for one additional year. There was no significant difference in neuropsychological assessment scores between control or treatment groups, either over the one-year randomized period or at 18 or 24 months. However, there was no significant decline in scores in the control group either. Adverse events included pain (injection site, back, groin), headache, neck spasm, and transient blurry vision. There were seven serious adverse events, one judged as possibly related (headache requiring hospitalization). There was no significant effect of intrathecal laronidase on cognitive impairment in older, attenuated MPS I patients over a two-year treatment period. A five-year open-label extension study is underway. © 2019 Elsevier Inc.

Author Keywords
Cognitive decline;  Glycosaminoglycan;  Hurler;  Intrathecal enzyme replacement therapy;  Lysosomal disease;  Mucopolysaccharidosis

Document Type: Article
Publication Stage: Article in Press
Source: Scopus