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Cover Image(Annals of Neurology: Volume 89, Number 1, January 2020)
doi : 10.1002/ana.25976
Volume89, Issue1 January 2021
A computer?generated image of the brain of a 26 week old fetus, segmented to show the cortical plate (red), subplate (ocean blue), intermediate zone (yellow), and deeper structures (for color designations, see Rollins et al. pp. 143–157). This segmentation map allows automated identification of regional loss of prenatal brain volumes of fetuses with congenital heart disease versus healthy controls.
What Are the Odds?
Clifford B. Saper MD, PhD
doi : 10.1002/ana.25960
Volume89, Issue1 January 2021 Pages 11-12
Role of B Cells in Multiple Sclerosis and Related Disorders
Giancarlo Comi MD Amit Bar?Or MD Hans Lassmann MD Antonio Uccelli MD Hans?Peter Hartung MD Xavier Montalban MD Per Solberg S?rensen MD Reinhard Hohlfeld MD Stephen L. Hauser MD Expert Panel of the 27th Annual Meeting of the European Charcot Foundation
doi : 10.1002/ana.25927
Volume89, Issue1 January 2021 Pages 13-23
The success of clinical trials of selective B?cell depletion in patients with relapsing multiple sclerosis (MS) and primary progressive MS has led to a conceptual shift in the understanding of MS pathogenesis, away from the classical model in which T cells were the sole central actors and toward a more complex paradigm with B cells having an essential role in both the inflammatory and neurodegenerative components of the disease process. The role of B cells in MS was selected as the topic of the 27th Annual Meeting of the European Charcot Foundation. Results of the meeting are presented in this concise review, which recaps current concepts underlying the biology and therapeutic rationale behind B?cell–directed therapeutics in MS, and proposes strategies to optimize the use of existing anti–B?cell treatments and provide future directions for research in this area. ANN NEUROL 2021;89:13–23
Yeo and Darras: Extraneuronal Phenotypes of Spinal Muscular Atrophy
Crystal Jing Jing Yeo MD, PhD, MRCP(UK) Basil T. Darras MD
doi : 10.1002/ana.25930
Volume89, Issue1 January 2021 Pages 24-26
Genetic Risk of Alzheimer's Disease – Sleepless with the Enemy
Alastair J. Noyce MRCP, PhD Christine Klein MD
doi : 10.1002/ana.25938
Volume89, Issue1 January 2021 Pages 27-29
Clinical Features and Risk of Relapse in Children and Adults with Myelin Oligodendrocyte Glycoprotein Antibody–Associated Disease
Alvaro Cobo?Calvo MD, PhD Anne Ruiz MSc Fabien Rollot MSc Georgina Arrambide MD, PhD Romain Deschamps MD, PhD Elisabeth Maillart MD Caroline Papeix MD, PhD Bertrand Audoin MD, PhD Anne Fabienne Lépine MD Hélène Maurey MD Helene Zephir MD, PhD Damien Biotti MD Jonathan Ciron MD Francoise Durand?Dubief MD, PhD Nicolas Collongues MD, PhD Xavier Ayrignac MD, PhD Pierre Labauge MD, PhD Pierre Meyer MD Eric Thouvenot MD, PhD Bertrand Bourre MD Alexis Montcuquet MD Mikael Cohen MD, PhD Philippe Horello PhD Mar Tintoré MD, PhD Jerome De Seze MD, PhD Sandra Vukusic MD, PhD Kumaran Deiva MD, PhD Romain Marignier MD, PhD the NOMADMUS, KidBioSEP, and OFSEP study groups
doi : 10.1002/ana.25909
Volume89, Issue1 January 2021 Pages 30-41
The main objective was to compare clinical features, disease course, and myelin oligodendrocyte glycoprotein (MOG) antibody (Ab) dynamics between children and adults with MOG?Ab–associated disease (MOGAD).
Prior Anticoagulation in Patients with Ischemic Stroke and Atrial Fibrillation
Thomas R. Meinel MD Mattia Branca PhD Gian Marco De Marchis MD, MSc Krassen Nedeltchev MD Timo Kahles MD Leo Bonati MD Marcel Arnold MD Mirjam R. Heldner MD, MS Simon Jung MD Emmanuel Carrera MD Elisabeth Dirren MD Patrik Michel MD Davide Strambo MD Carlo W. Cereda MD Giovanni Bianco MD Georg K?gi MD Jochen Vehoff MD Mira Katan MD Manuel Bolognese MD Roland Backhaus MD Stephan Salmen MD Sylvan Albert MD Friedrich Medlin MD Christian Berger MD Ludwig Schelosky MD Susanne Renaud MD Julien Niederhauser MD Christophe Bonvin MD, MSc Michael Schaerer MD Marie?Luise Mono MD Biljana Rodic MD Alexander A. Tarnutzer MD Pasquale Mordasini MD Jan Gralla MD Johannes Kaesmacher MD Stefan Engelter MD Urs Fischer MD, MSc David J. Seiffge MD the Investigators of the Swiss Stroke Registry
doi : 10.1002/ana.25917
Volume89, Issue1 January 2021 Pages 42-53
The aim was to evaluate, in patients with atrial fibrillation (AF) and acute ischemic stroke, the association of prior anticoagulation with vitamin?K antagonists (VKAs) or direct oral anticoagulants (DOACs) with stroke severity, utilization of intravenous thrombolysis (IVT), safety of IVT, and 3?month outcomes.
Causal Associations Between Modifiable Risk Factors and the Alzheimer's Phenome
Shea J. Andrews PhD Brian Fulton?Howard PhD Paul O'Reilly PhD Edoardo Marcora PhD Alison M. Goate PhD collaborators of the Alzheimer's Disease Genetics Consortium
doi : 10.1002/ana.25918
Volume89, Issue1 January 2021 Pages 54-65
The purpose of this study was to infer causal relationships between 22 previously reported risk factors for Alzheimer's disease (AD) and the “AD phenome”: AD, AD age of onset (AAOS), hippocampal volume, cortical surface area and thickness, cerebrospinal fluid (CSF) levels of amyloid?? (A?42), tau, and ptau181, and the neuropathological burden of neuritic plaques, neurofibrillary tangles (NFTs), and vascular brain injury (VBI).
CAG Repeat Size Influences the Progression Rate of Spinocerebellar Ataxia Type 3
Vanessa B. Leotti PhD Jeroen J. de Vries MD, PhD Camila M. Oliveira MD Eduardo P. de Mattos PhD Gerard J. Te Meerman PhD Ewout R. Brunt MD Harm H. Kampinga PhD Laura B. Jardim MD, PhD Dineke S. Verbeek PhD
doi : 10.1002/ana.25919
Volume89, Issue1 January 2021 Pages 66-73
In spinocerebellar ataxia type 3/Machado?Joseph disease (SCA3/MJD), the expanded cytosine adenine guanine (CAG) repeat in ATXN3 is the causal mutation, and its length is the main factor in determining the age at onset (AO) of clinical symptoms. However, the contribution of the expanded CAG repeat length to the rate of disease progression after onset has remained a matter of debate, even though an understanding of this factor is crucial for experimental data on disease modifiers and their translation to clinical trials and their design.
A Stearoyl–Coenzyme A Desaturase Inhibitor Prevents Multiple Parkinson Disease Phenotypes in ??Synuclein Mice
Silke Nuber PhD Alice Y. Nam BS Molly M. Rajsombath BS Haley Cirka Xiaoping Hronowski PhD Junmin Wang PhD Kevin Hodgetts PhD Liubov S. Kalinichenko PhD Christian P. Müller PhD Vera Lambrecht MS Jürgen Winkler MD Andreas Weihofen PhD Thibaut Imberdis PhD Ulf Dettmer PhD Saranna Fanning PhD Dennis J. Selkoe MD
doi : 10.1002/ana.25920
Volume89, Issue1 January 2021 Pages 74-90
Parkinson disease (PD) has useful symptomatic treatments that do not slow the neurodegenerative process, and no significant disease?modifying treatments are approved. A key therapeutic target in PD is ??synuclein (?S), which is both genetically implicated and accumulates in Lewy bodies rich in vesicles and other lipid membranes. Reestablishing ?S homeostasis is a central goal in PD. Based on previous lipidomic analyses, we conducted a mouse trial of a stearoyl–coenzyme A desaturase (SCD) inhibitor (“5b”) that prevented ?S?positive vesicular inclusions and cytotoxicity in cultured human neurons.
Rivastigmine in Parkinson's Disease Dementia with Orthostatic Hypotension
Alberto J. Espay MD, MSc Luca Marsili MD, PhD Abhimanyu Mahajan MD, MHS Andrea Sturchio MD Rashidkhan Pathan MSc Andrea Pilotto MD Damodaran S. Elango MD Nicole Pezous MSc Mario Masellis MD, MSc, PhD Baltazar Gomez?Mancilla MD, PhD
doi : 10.1002/ana.25923
Volume89, Issue1 January 2021 Pages 91-98
The purpose of this study was to evaluate if the cognitive benefit of rivastigmine is affected by the presence of orthostatic hypotension (OH) in patients with Parkinson's disease dementia (PDD).
Optogenetic Spreading Depression Elicits Trigeminal Pain and Anxiety Behavior
Andrea M. Harriott MD, PhD David Y. Chung MD, PhD Aylin Uner Refik O. Bozdayi Andreia Morais MS Tsubasa Takizawa MD, PhD Tao Qin Cenk Ayata MD, PhD
doi : 10.1002/ana.25926
Volume89, Issue1 January 2021 Pages 99-110
Cortical spreading depression (SD) is an intense depolarization underlying migraine aura. Despite the weight of evidence linking SD to the pain phase of migraine, controversy remains over a causal role of SD in cephalgia because of the invasive nature of previous SD induction methods. To overcome this problem, we used a novel minimally invasive optogenetic SD induction method and examined the effect of SD on behavior.
Noninvasive Characterization of Human Glymphatics and Meningeal Lymphatics in an in vivo Model of Blood–Brain Barrier Leakage
Chia?Hung Wu MD Jiing?Feng Lirng MD Yu?Hsiang Ling MD Yen?Feng Wang MD, PhD Hsiu?Mei Wu MD Jong?Ling Fuh MD Po?Chen Lin MD Shuu?Jiun Wang MD Shih?Pin Chen MD, PhD
doi : 10.1002/ana.25928
Volume89, Issue1 January 2021 Pages 111-124
To evaluate human glymphatics and meningeal lymphatics noninvasively.
Blood Metal Levels and Amyotrophic Lateral Sclerosis Risk: A Prospective Cohort
Susan Peters PhD Karin Broberg PhD Valentina Gallo MD, PhD Michael Levi PhD Maria Kippler PhD Paolo Vineis MD, MPH, FFPH Jan Veldink MD, PhD Leonard van den Berg MD, PhD Lefkos Middleton MD, FRCP Ruth C. Travis PhD Manuela M. Bergmann PhD Domenico Palli MD Sara Grioni MSc Rosario Tumino MD Alexis Elbaz MD, PhD Tim Vlaar MSc Francesca Mancini PhD Tilman Kühn PhD Verena Katzke PhD Antonio Agudo MD, PhD Fernando Go?i PhD Jes?s?Humberto G?mez MD Miguel Rodr?guez?Barranco PhD Susana Merino RN Aurelio Barricarte MD, PhD Antonia Trichopoulou PhD Mazda Jenab PhD Elisabete Weiderpass MD, PhD Roel Vermeulen PhD
doi : 10.1002/ana.25932
Volume89, Issue1 January 2021 Pages 125-133
Metals have been suggested as a risk factor for amyotrophic lateral sclerosis (ALS), but only retrospective studies are available to date. We compared metal levels in prospectively collected blood samples from ALS patients and controls, to explore whether metals are associated with ALS mortality.
Scalp Ripples Can Predict Development of Epilepsy After First Unprovoked Seizure in Childhood
Kerstin A. Klotz MD Yusuf Sag Jan Sch?nberger MD Julia Jacobs MD
doi : 10.1002/ana.25939
Volume89, Issue1 January 2021 Pages 134-142
Identification of children at risk of developing epilepsy after a first unprovoked seizure can be challenging. Interictal epileptiform discharges are associated with higher risk but have limited sensitivity and specificity. High frequency oscillations (HFOs) are newer biomarkers for epileptogenesis. We prospectively evaluated the predictive value of HFOs for developing epilepsy in scalp electroencephalogram (EEG) of children after a first unprovoked seizure.
Regional Brain Growth Trajectories in Fetuses with Congenital Heart Disease
Caitlin K. Rollins MD, SM Cynthia M. Ortinau MD Christian Stopp MS Kevin G. Friedman MD Wayne Tworetzky MD Borjan Gagoski PhD Clemente Velasco?Annis BS Onur Afacan PhD Lana Vasung MD, PhD Jeanette I. Beaute BS Valerie Rofeberg MS Judy A. Estroff MD P. Ellen Grant MD Janet S. Soul MDCM Edward Yang MD David Wypij PhD Ali Gholipour PhD Simon K. Warfield PhD Jane W. Newburger MD, MPH
doi : 10.1002/ana.25940
Volume89, Issue1 January 2021 Pages 143-157
Congenital heart disease (CHD) is associated with abnormal brain development in utero. We applied innovative fetal magnetic resonance imaging (MRI) techniques to determine whether reduced fetal cerebral substrate delivery impacts the brain globally, or in a region?specific pattern. Our novel design included two control groups, one with and the other without a family history of CHD, to explore the contribution of shared genes and/or fetal environment to brain development.
Discordant Monozygotic Parkinson Disease Twins: Role of Mitochondrial Integrity
Marija Dulovic?Mahlow MD, PhD Inke R. K?nig PhD Joanne Trinh PhD Sokhna Haissatou Diaw MSc Peter P. Urban MD Evelyn Knappe MSc Neele Kuhnke BSc Lena?Christin Ingwersen MSc Frauke Hinrichs Joachim Weber BSc Patrycja Kupnicka MSc Alexander Balck MD Sylvie Delcambre PhD Tillman Vollbrandt PhD Anne Grünewald PhD Christine Klein MD Philip Seibler PhD Katja Lohmann PhD
doi : 10.1002/ana.25942
Volume89, Issue1 January 2021 Pages 158-164
Even though genetic predisposition has proven to be an important element in Parkinson's disease (PD) etiology, monozygotic (MZ) twins with PD displayed a concordance rate of only about 20% despite their shared identical genetic background.
Retinal Thickness Predicts the Risk of Cognitive Decline in Parkinson Disease
Ane Murueta?Goyena PhD Roc?o Del Pino PhD Marta Gald?s PhD Bego?a Arana PhD Marian Acera MSc Mar Carmona?Abell?n MD, PhD Tamara Fern?ndez?Valle MD Beatriz Tijero MD, PhD Olaia Lucas?Jiménez PhD Natalia Ojeda PhD Naroa Ibarretxe?Bilbao PhD Javier Pe?a PhD Jesus Cortes PhD Unai Ayala PhD Maitane Barrenechea PhD Juan Carlos G?mez?Esteban MD, PhD I?igo Gabilondo MD, PhD
doi : 10.1002/ana.25944
Volume89, Issue1 January 2021 Pages 165-176
This study was undertaken to analyze longitudinal changes of retinal thickness and their predictive value as biomarkers of disease progression in idiopathic Parkinson's disease (iPD).
Genetic Risk of Alzheimer's Disease and Sleep Duration in Non?Demented Elders
Yue Leng MD, PhD Sarah F. Ackley PhD Maria M. Glymour ScD Kristine Yaffe MD Willa D. Brenowitz PhD, MPH
doi : 10.1002/ana.25910
Volume89, Issue1 January 2021 Pages 177-181
Growing evidence has suggested an association between sleep duration and Alzheimer's disease (AD), but it is unclear if sleep duration is a manifestation of the AD disease process. We studied whether genetic liability for AD predicts sleep duration using a genetic risk score (GRS) for AD (AD?GRS), in 406,536 UK Biobank participants with European ancestry and without dementia at enrollment. Higher AD?GRS score was associated with shorter sleep (b = ?0.014, 95% confidence interval [CI] = ?0.022 to ?0.006), especially in those aged 55+. Using AD?GRS as an instrumental variable for AD diagnosis, incipient AD reduced sleep duration by 1.87 hours (95% CI = 0.96, 2.78). Short sleep duration might be an early marker of AD. ANN NEUROL 2021;89:177–181
NOTCH2NLC Intermediate?Length Repeat Expansions Are Associated with Parkinson Disease
Chang?he Shi MD, PhD Yu Fan MD Jing Yang MD, PhD Yan?peng Yuan MD, PhD Si Shen MD Fen Liu MD Cheng?yuan Mao MD, PhD Han Liu MD, PhD Shuo Zhang MD Zheng?wei Hu MD Li?yuan Fan MD Meng?jie Li MD Shi?heng Fan MD Xiao?jing Liu MD Yu?ming Xu MD, PhD
doi : 10.1002/ana.25925
Volume89, Issue1 January 2021 Pages 182-187
NOTCH2NLC GGC repeat expansions were recently identified in neuronal intranuclear inclusion disease (NIID); however, it remains unclear whether they occur in other neurodegenerative disorders. This study aimed to investigate the role of intermediate?length NOTCH2NLC GGC repeat expansions in Parkinson disease (PD). We screened for GGC repeat expansions in a cohort of 1,011 PD patients and identified 11 patients with intermediate?length repeat expansions ranging from 41 to 52 repeats, with no repeat expansions in 1,134 controls. Skin biopsy revealed phospho?alpha?synuclein deposition, confirming the PD diagnosis in 2 patients harboring intermediate?length repeat expansions instead of NIID or essential tremor. Fibroblasts from PD patients harboring intermediate?length repeat expansions revealed NOTCH2NLC upregulation and autophagic dysfunction. Our results suggest that intermediate?length repeat expansions in NOTCH2NLC are potentially associated with PD. ANN NEUROL 2021;89:182–187
Lentiform Fork Sign in Metabolic Acidosis
Niraj Kumar MD, DM Deepak Kumar MD
doi : 10.1002/ana.25896
Volume89, Issue1 January 2021 Pages 188-189
Ictal Pulvinar Hyperperfusion Sign
Dimitri Renard MD Anne Le Floch MD Camille Heitz MD
doi : 10.1002/ana.25898
Volume89, Issue1 January 2021 Pages 190-191
Retinal INL Thickness in Multiple Sclerosis: A Mere Marker of Neurodegeneration?
Christian Cordano MD, PhD Hao H. Yiu BS Frederike C. Oertel MD University of California, San Francisco MS?EPIC Team Jeffrey M. Gelfand MD, MAS Stephen L. Hauser MD Bruce A. C. Cree MD, PhD, MAS Ari J. Green MD, MCR
doi : 10.1002/ana.25933
Volume89, Issue1 January 2021 Pages 192-193
Reply to “Retinal INL Thickness in Multiple Sclerosis: A Mere Marker of Neurodegeneration?”
Elias S. Sotirchos MD Peter A. Calabresi MD Shiv Saidha MBBCh, MRCPI
doi : 10.1002/ana.25936
Volume89, Issue1 January 2021 Pages 193-194
PPP2R5D Genetic Mutations and Early?Onset Parkinsonism
Ian M. Walker MD Giulietta M. Riboldi MD Patrick Drummond MD Sandra Saade?Lemus MD Juan Sebastian Martin?Saavedra MD Steven Frucht MD Tanya M. Bardakjian MS, CGC Pedro Gonzalez?Alegre MD, PhD Andres Deik MD
doi : 10.1002/ana.25943
Volume89, Issue1 January 2021 Pages 194-195
Reply to “PPP2R5D Genetic Mutations and Early Onset Parkinsonism”
Christine Y. Kim MD Thomas Wirth MD, MS Cécile Hubsch MD, PhD Andrea H. Németh MBBS, DPhil Volkan Okur MD Mathieu Anheim MD, PhD Nathalie Drouot MS Christine Tranchant MD, PhD Gabrielle Rudolf PhD Jamel Chelly MD, PhD Katrina Tatton?Brown MD Cornelis Blauwendraat PhD Jean Paul G. Vonsattel MD Etty Cortes MD Roy N. Alcalay MD, MS Wendy K. Chung MD, PhD
doi : 10.1002/ana.25945
Volume89, Issue1 January 2021 Pages 195-196
Cardiovascular Safety of Nilotinib in Alzheimer Disease
Sean Tan MBBS Diva Baggio MBBS Jake Shortt BMedSc, MBChB, PhD Brian Ko BSc, MBBS, MD, PhD
doi : 10.1002/ana.25947
Volume89, Issue1 January 2021 Pages 196-196
Reply to “Cardiovascular Safety of Nilotinib in Alzheimer's Disease”
Charbel Moussa MBBS, PhD
doi : 10.1002/ana.25946
Volume89, Issue1 January 2021 Pages 196-197
