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Annals of Neurology: Volume 89, Number 3, March 2021
doi : 10.1002/ana.26036
Annals of NeurologyPages: C1, i-viii, 423-635
A flortaucipir PET image of the brain of a patient with logopenic progressive aphasia associated with Alzheimer disease. There is extensive deposition of phospho?tau and atrophy, including in the perisylvian area and the anterior part of the temporal lobe. See Buciuc et al., pp. 520–533 for details.
Beware of Optimism Bias in the Context of the COVID?19 Pandemic
Alvaro Pascual?Leone MD, PhD Gabriele Cattaneo PhD D?dac Macià PhD Javier Solana PhD José M. Tormos MD, PhD David Bartrés?Faz PhD
doi : 10.1002/ana.26001
Annals of NeurologyVolume 89, Issue 3 p. 423-425
Probabilistic Mapping of Deep Brain Stimulation: Insights from 15?Years of Therapy
Gavin J. B. Elias BA Alexandre Boutet MD, PhD Suresh E. Joel PhD Jürgen Germann PhD Dave Gwun Clemens Neudorfer MD Robert M. Gramer MD, MEng Musleh Algarni MD Vijayashankar Paramanandam MD Sreeram Prasad MBBS Michelle E. Beyn BSc Andreas Horn MD, PhD Radhika Madhavan PhD Manish Ranjan MBBS, MCh Christopher S. Lozano BSc Andrea A. Kühn MD, PhD Jeff Ashe MSc Walter Kucharczyk MD Renato P. Munhoz MD, PhD Peter Giacobbe MD, MSc Sidney H. Kennedy MD D. Blake Woodside MD, MSc Suneil K. Kalia MD, PhD Alfonso Fasano MD, PhD Mojgan Hodaie MD, MSc Andres M. Lozano MD, PhD
doi : 10.1002/ana.25975
Annals of NeurologyVolume 89, Issue 3 p. 426-443
Deep brain stimulation (DBS) depends on precise delivery of electrical current to target tissues. However, the specific brain structures responsible for best outcome are still debated. We applied probabilistic stimulation mapping to a retrospective, multidisorder DBS dataset assembled over 15?years at our institution (ntotal = 482 patients; nParkinson disease = 303; ndystonia = 64; ntremor = 39; ntreatment?resistant depression/anorexia nervosa = 76) to identify the neuroanatomical substrates of optimal clinical response. Using high?resolution structural magnetic resonance imaging and activation volume modeling, probabilistic stimulation maps (PSMs) that delineated areas of above?mean and below?mean response for each patient cohort were generated and defined in terms of their relationships with surrounding anatomical structures. Our results show that overlap between PSMs and individual patients' activation volumes can serve as a guide to predict clinical outcomes, but that this is not the sole determinant of response. In the future, individualized models that incorporate advancements in mapping techniques with patient?specific clinical variables will likely contribute to the optimization of DBS target selection and improved outcomes for patients. ANN NEUROL 2021;89:426–443
Short?Term Cessation of Dabigatran Causes a Paradoxical Prothrombotic State
Jiwon Kim MS Hee Jeong Jang MS Dawid Schellingerhout MBChB Su?Kyoung Lee BS Ha Kim MS Young Dae Kim MD, PhD Kyung?Yul Lee MD, PhD Hye?Yeon Choi MD, PhD Han?Jin Cho MD, PhD Seong?Soo Jang MD Sangmin Jeon PhD Ick Chan Kwon PhD Kwangmeyung Kim PhD Wi?Sun Ryu MD, PhD Matthias Nahrendorf MD, PhD Seungbum Choi PhD Dong?Eog Kim MD, PhD
doi : 10.1002/ana.25964
Annals of NeurologyVolume 89, Issue 3 p. 444-458
It is unclear if stopping treatment with dabigatran, a new oral anticoagulant (NOAC), induces a paradoxical rebound prothrombotic state. We investigated if short?term (1–3?days) dabigatran cessation is associated with a higher thrombus volume than expected from a simple reversal of the anticoagulant effect.
Circulating microRNAs Associated With Reversible Cerebral Vasoconstriction Syndrome
Shih?Pin Chen MD, PhD Yi?An Chang PhD Chih?Hung Chou PhD Chi?Chang Juan PhD Hsin?Chen Lee PhD Luen?Kui Chen PhD Pei?Chun Wu PhD Yen?Feng Wang MD, PhD Jong?Ling Fuh MD Jiing?Feng Lirng MD Anne Ducros MD, PhD Hsien?Da Huang PhD Shuu?Jiun Wang MD
doi : 10.1002/ana.25965
Annals of NeurologyVolume 89, Issue 3 p. 459-473
The purpose of this study was to investigate the significance of circulating micro RNAs (miRNAs) in the pathogenesis of reversible cerebral vasoconstriction syndrome (RCVS).
Multicenter Validation of the max?ICH Score in Intracerebral Hemorrhage
Jochen A. Sembill MD Juan P. Castello MD Maximilian I. Sprügel MD Stefan T. Gerner MD Philip Hoelter MD Hannes Lücking MD Arnd Doerfler MD Stefan Schwab MD Hagen B. Huttner MD, PhD Alessandro Biffi MD Joji B. Kuramatsu MD … See fewer authors
doi : 10.1002/ana.25969
Annals of NeurologyVolume 89, Issue 3 p. 474-484
Outcome prognostication unbiased by early care limitations (ECL) is essential for guiding treatment in patients presenting with intracerebral hemorrhage (ICH). The aim of this study was to determine whether the max?ICH (maximally treated ICH) Score provides improved and clinically useful prognostic estimation of functional long?term outcomes after ICH.
EIF2AK2 Missense Variants Associated with Early Onset Generalized Dystonia
Demy J. S. Kuipers BSc Wim Mandemakers PhD Chin?Song Lu MD Simone Olgiati PhD Guido J. Breedveld BSc Christina Fevga MD, MSc Vera Tadic MD Miryam Carecchio MD, PhD Bradley Osterman MD Lena Sagi?Dain MD Yah?Huei Wu?Chou PhD Chiung C. Chen MD, PhD Hsiu?Chen Chang MSc Shey?Lin Wu MD, PhD Tu?Hsueh Yeh MD, PhD Yi?Hsin Weng MD, PhD Antonio E. Elia MD Celeste Panteghini PhD Nicolas Marotta BSc Martje G. Pauly MD Andrea A. Kühn MD Jens Volkmann MD, PhD Baiba Lace MD, PhD Inge A. Meijer MD, PhD Krishna Kandaswamy PhD Marialuisa Quadri PhD Barbara Garavaglia MD Katja Lohmann PhD Peter Bauer MD Niccol? E. Mencacci MD, PhD Steven J. Lubbe PhD Christine Klein MD, Aida M. Bertoli?Avella MD, PhD Vincenzo Bonifati MD, PhD
doi : 10.1002/ana.25973
Annals of NeurologyVolume 89, Issue 3 p. 485-497
The study was undertaken to identify a monogenic cause of early onset, generalized dystonia.
Iron Heterogeneity in Early Active Multiple Sclerosis Lesions
Mylyne Tham MSc Josa M. Frischer MD, PhD Stephen D. Weigand MSc Patrick D. Fitz?Gibbon MSc Samuel M. Webb PhD Yong Guo MD, PhD Reginald C. Adiele PhD Christopher A. Robinson MD Wolfgang Brück MD Hans Lassmann PhD Kendra L. Furber PhD M. Jake Pushie PhD Joseph E. Parisi MD Claudia F. Lucchinetti MD Bogdan F. Popescu MD, PhD
doi : 10.1002/ana.25974
Annals of NeurologyVolume 89, Issue 3 p. 498-510
Multiple sclerosis (MS) is a heterogeneous inflammatory demyelinating disease. Iron distribution is altered in MS patients' brains, suggesting iron liberation within active lesions amplifies demyelination and neurodegeneration. Whether the amount and distribution of iron are similar or different among different MS immunopatterns is currently unknown.
Time from I.V. Thrombolysis to Thrombectomy and Outcome in Acute Ischemic Stroke
François Zhu MD, MSc Maxime Gauberti MD, PhD Gaultier Marnat MD Romain Bourcier MD, PhD Maéva Kyheng BST Julien Labreuche BST Igor Sibon MD, PhD Cyril Dargazanli MD, MSc Caroline Arquizan MD René Anxionnat MD, PhD Gérard Audibert MD, PhD Mikaël Mazighi MD, PhD Raphaël Blanc MD, MSc Bertrand Lapergue MD, PhD Arturo Consoli MD, MSc Sébastien Richard MD, PhD Benjamin Gory MD, PhD ETIS Registry Investigators
doi : 10.1002/ana.25978
Annals of NeurologyVolume 89, Issue 3 p. 511-519
Whether the time from intravenous thrombolysis (IVT) to endovascular treatment (EVT) in patients with acute ischemic stroke has an effect on the functional outcome is unknown.
Lewy Body Disease is a Contributor to Logopenic Progressive Aphasia Phenotype
Marina Buciuc MD Jennifer L. Whitwell PhD Koji Kasanuki MD Jonathan Graff?Radford MD Mary M. Machulda PhD Joseph R. Duffy PhD Edythe A. Strand PhD Val J. Lowe MD Neill R. Graff?Radford MD Beth K. Rush PhD Malgorzata B. Franczak MD Margaret E. Flanagan MB, BCh Matthew C. Baker BS Rosa Rademakers PhD Owen A. Ross PhD Bernardino F. Ghetti MD Joseph E. Parisi MD Aditya Raghunathan MD R. Ross Reichard MD Eileen H. Bigio MD Dennis W. Dickson MD Keith A. Josephs MD
doi : 10.1002/ana.25979
Annals of NeurologyVolume 89, Issue 3 p. 520-533
The objective of this study was to describe clinical features, [18F]?fluorodeoxyglucose (FDG)?positron emission tomography (PET) metabolism and digital pathology in patients with logopenic progressive aphasia (LPA) and pathologic diagnosis of diffuse Lewy body disease (DLBD) and compare to patients with LPA with other pathologies, as well as patients with classical features of probable dementia with Lewy bodies (pDLB).
Childhood Neurotoxicity and Brain Resilience to Adverse Events during Adulthood
AnnaLynn M. Williams PhD Yin Ting Cheung PhD Geehong Hyun PhD Wei Liu PhD Kirsten K. Ness PhD Matthew J. Ehrhardt MD Daniel A. Mulrooney MD Nickhill Bhakta MD Pia Banerjee PhD Tara M. Brinkman PhD Daniel M. Green MD Wassim Chemaitilly MD I?Chan Huang PhD Deokumar Srivastava PhD Melissa M. Hudson MD Leslie L. Robison PhD Kevin R. Krull PhD
doi : 10.1002/ana.25981
Annals of NeurologyVolume 89, Issue 3 p. 534-545
This study used childhood cancer survivors as a novel model to study whether children who experience central nervous system (CNS) injury are at higher risk for neurocognitive impairment associated with subsequent late onset chronic health conditions (CHCs).
Gut Microbial Ecosystem in Parkinson Disease: New Clinicobiological Insights from Multi?Omics
Ai Huey Tan MD, FRCP Chun Wie Chong PhD Shen?Yang Lim MD, FRACP Ivan Kok Seng Yap PhD Cindy Shuan Ju Teh PhD Mun Fai Loke PhD Sze?Looi Song PhD Jiun Yan Tan MBBS Ban Hong Ang MBBS Yong Qi Tan BPharm Mee Teck Kho MSc Jeff Bowman PhD Sanjiv Mahadeva MD Hoi Sen Yong PhD Anthony E. Lang MD, FRCPC
doi : 10.1002/ana.25982
Annals of NeurologyVolume 89, Issue 3 p. 546-559
Gut microbiome alterations in Parkinson disease (PD) have been reported repeatedly, but their functional relevance remains unclear. Fecal metabolomics, which provide a functional readout of microbial activity, have scarcely been investigated. We investigated fecal microbiome and metabolome alterations in PD, and their clinical relevance.
Subtype Diagnosis of Sporadic Creutzfeldt–Jakob Disease with Diffusion Magnetic Resonance Imaging
Alberto Bizzi MD Riccardo Pascuzzo PhD Janis Blevins BSc Marco E. M. Moscatelli MD Marina Grisoli MD Raffaele Lodi MD Fabio M. Doniselli MD Gianmarco Castelli MSc Mark L. Cohen MD Aymeric Stamm PhD Lawrence B. Schonberger MD Brian S. Appleby MD Pierluigi Gambetti MD
doi : 10.1002/ana.25983
Annals of NeurologyVolume 89, Issue 3 p. 560-572
Sporadic Creutzfeldt–Jakob disease (sCJD) comprises several subtypes as defined by genetic and prion protein characteristics, which are associated with distinct clinical and pathological phenotypes. To date, no clinical test can reliably diagnose the subtype. We established two procedures for the antemortem diagnosis of sCJD subtype using diffusion magnetic resonance imaging (MRI).
Characterization of the GABRB2?Associated Neurodevelopmental Disorders
Christelle M. el Achkar MD Merle Harrer MSc Lacey Smith MS, CGC McKenna Kelly BA Sumaiya Iqbal PhD Snezana Maljevic PhD Cristina E. Niturad PhD Lisenka E. L. M. Vissers PhD Annapurna Poduri MD, MPH Edward Yang MD, PhD Dennis Lal PhD Holger Lerche MD Rikke S. M?ller PhD Heather E. Olson MD, MS for the GABRB2 Working Group
doi : 10.1002/ana.25985
Annals of NeurologyVolume 89, Issue 3 p. 573-586
We aimed to characterize the phenotypic spectrum and functional consequences associated with variants in the gene GABRB2, coding for the ??aminobutyric acid type A (GABAA) receptor subunit ?2.
Predictors of Long?Term Outcome of Subthalamic Stimulation in Parkinson Disease
Francesco Cavallieri MD Valérie Fraix MD, PhD Francesco Bove MD Delia Mulas MD Manuela Tondelli MD, PhD Anna Castrioto MD, PhD Paul Krack MD, PhD Sara Meoni MD, PhD Emmanuelle Schmitt MA Eugénie Lhommée MA Amélie Bichon MA Pierre Pélissier CRA Eric Chevrier BPT Andrea Kistner PhD Eric Seigneuret MD Stephan Chabardès MD, PhD Elena Moro MD, PhD
doi : 10.1002/ana.25994
Annals of NeurologyVolume 89, Issue 3 p. 587-597
This study was undertaken to identify preoperative predictive factors of long?term motor outcome in a large cohort of consecutive Parkinson disease (PD) patients with bilateral subthalamic nucleus deep brain stimulation (STN?DBS).
Incidence, clinical, risk factors and outcomes of Guillain?Barré in Covid?19
Marcos Fragiel MD ?scar Mir? PhD, MD Pere Llorens PhD, MD S?nia Jiménez PhD, MD Pascual Pi?era MD Guillermo Burillo PhD, MD Alfonso Mart?n PhD, MD Francisco J. Mart?n?S?nchez PhD, MD Eric J. Garc?a?Lamberechts PhD, MD Javier Jacob PhD, MD Aitor Alquézar?Arbé PhD, MD Ricardo Ju?rez MD Blas Jiménez MD Rigoberto Del Rio MD Miriam Mateo Roca MD Arturo H. Garc?a MD Nieves L?pez Laguna MD Mar?a P. Lopez Diez MD Jorge Pedraza Garc?a MD Amparo Fern?ndez de Sim?n Almela MD Juan J. Lopez Diaz MD Patricia Eiroa Hern?ndez MD Noem? Ruiz de Lobera MD Jes?s Porta?Etessam PhD, MD Cristina Fern?ndez Pérez PhD, MD Elpidio Calvo PhD, MD Juan Gonz?lez del Castillo PhD, MD SIESTA (Spanish Investigators in Emergency Situations Team) network
doi : 10.1002/ana.25987
Annals of NeurologyVolume 89, Issue 3 p. 598-603
We diagnosed 11 Guillain–Barré syndrome (GBS) cases among 71,904 COVID patients attended at 61 Spanish emergency departments (EDs) during the 2?month pandemic peak. The relative frequency of GBS among ED patients was higher in COVID (0.15‰) than non?COVID (0.02‰) patients (odds ratio [OR] = 6.30, 95% confidence interval [CI] = 3.18–12.5), as was the standardized incidence (9.44 and 0.69 cases/100,000 inhabitant?years, respectively, OR = 13.5, 95% CI = 9.87–18.4). Regarding clinical characteristics, olfactory–gustatory disorders were more frequent in COVID?GBS than non?COVID–GBS (OR = 27.59, 95% CI = 1.296–587) and COVID–non?GBS (OR = 7.875, 95% CI = 1.587–39.09) patients. Although COVID?GBS patients were more frequently admitted to intensive care, mortality was not increased versus control groups. Our results suggest SARS?CoV?2 could be another viral infection causing GBS. ANN NEUROL 2021;89:598–603
Statewide Emergency Medical Services Protocols for Status Epilepticus Management
Ethan J. Han BS Carlin C. Chuck BS Thomas J. Martin BA Tracy E. Madsen MD, ScM Jan Claassen MD, PhD Michael E. Reznik MD
doi : 10.1002/ana.25989
Annals of NeurologyVolume 89, Issue 3 p. 604-609
Although seizures are common in prehospital settings, standardized emergency medical services (EMS) treatment algorithms do not exist nationally. We examined nationwide variability in status epilepticus treatment by analyzing 33 publicly available statewide EMS protocols. All adult protocols recommend intravenous benzodiazepines (midazolam, n = 33; lorazepam, n = 23; diazepam, n = 24), 30 recommend intramuscular benzodiazepines (midazolam, n = 30; lorazepam, n = 8; diazepam, n = 3), and 27 recommend intranasal benzodiazepines (midazolam, n = 27; lorazepam, n?=?3); pediatric protocols also frequently recommend rectal diazepam (n = 14). Recommended dosages vary widely, and first? and second?line agents are designated in only 18 and 2 states, respectively. Given this degree of variability, standardized national EMS guidelines are needed. ANN NEUROL 2021;89:604–609
Serum Neurofilament Light Chain Levels in the Intensive Care Unit: Comparison between Severely Ill Patients with and without Coronavirus Disease 2019
Raoul Sutter MD Lisa Hert MD Gian Marco De Marchis MD, MSc Raphael Twerenbold MD Ludwig Kappos MD Yvonne Naegelin MD Gabriela M. Kuster MD Pascal Benkert PhD Jasmine Jost MS Aleksandra Maleska Maceski MSc Stephan Rüegg MD Martin Siegemund MD David Leppert MD Sarah Tschudin?Sutter MD, MSc Jens Kuhle MD, PhD
doi : 10.1002/ana.26004
Annals of NeurologyVolume 89, Issue 3 p. 610-616
There is emerging evidence for multifarious neurological manifestations of coronavirus disease 2019 (COVID?19), but little is known regarding whether they reflect structural damage to the nervous system. Serum neurofilament light chain (sNfL) is a specific biomarker of neuronal injury. We measured sNfL concentrations of 29 critically ill COVID?19 patients, 10 critically ill non–COVID?19 patients, and 259 healthy controls. After adjusting for neurological comorbidities and age, sNfL concentrations were higher in patients with COVID?19 versus both comparator groups. Higher sNfL levels were associated with unfavorable short?term outcome, indicating that neuronal injury is common and pronounced in critically ill patients. ANN NEUROL 2021;89:610–616
Vessel Wall Imaging of Basilar Artery Perforator Disease
Jae W. Song MD, MS Sahily Reyes?Esteves MD, PhD Brett L. Cucchiara MD
doi : 10.1002/ana.25980
Annals of NeurologyVolume 89, Issue 3 p. 617-618
Giant Sphenoidal Mucocele Revealed by Orbital Pain
Maxime Fieux MD Sandra Zaouche MD Jean?Baptiste Pialat MD, PhD Stephane Tringali MD, PhD
doi : 10.1002/ana.25984
Annals of NeurologyVolume 89, Issue 3 p. 619-620
Open Repair of Hemangioma?Associated Cerebrospinal Fluid?Venous Fistula
Julie L. Chan MD, PhD Marcel M. Maya MD Wouter I. Schievink MD
doi : 10.1002/ana.25986
Annals of NeurologyVolume 89, Issue 3 p. 621-622
Ekbom Syndrome: Ataxia, Myoclonus, and Cervical Lipomas
Karthik Muthusamy MD John P. Fasolino MD Erika D. Driver?Dunckley MD Radhika Dhamija MD
doi : 10.1002/ana.25992
Annals of NeurologyVolume 89, Issue 3 p. 623-624
Truncating VPS16 Mutations Are Rare in Early Onset Dystonia
Hendrik Pott MD Norbert Brüggemann MD Rene Reese MD Kirsten E. Zeuner MD Florin Gandor MD Doreen Gruber MD DysTract Study Group Christine Klein MD Jens Volkmann MD Katja Lohmann PhD
doi : 10.1002/ana.25990
Annals of NeurologyVolume 89, Issue 3 p. 625-626
Reply to “Truncating VPS16 Mutations are Rare in Early?Onset Dystonia”
Michael Zech MD Dora Steel BMBCh Manju A. Kurian PhD Juliane Winkelmann MD
doi : 10.1002/ana.25988
Annals of NeurologyVolume 89, Issue 3 p. 626-626
Migraine and Cryptogenic Ischemic Stroke
Valentina Mazzoleni MD Mario Grassi PhD Corrado Lodigiani MD, PhD Maurizia Rasura MD Marialuisa Zedde MD Carlo Gandolfo MD Andrea Zini MD Maria Luisa DeLodovici MD Maurizio Paciaroni MD Massimo Del Sette MD Antonella Toriello MD Rossella Musolino MD Rocco Salvatore Calabr? MD Paolo Bovi MD Alessia Giossi MD Alessandro Adami MD Giorgio Silvestrelli MD Anna Cavallini MD Simona Marcheselli MD Domenico Marco Bonifati MD Nicoletta Checcarelli MD Lucia Tancredi MD Alberto Chiti MD Elisa Giorli MD Debora Pezzini MD Martina Locatelli MD Sonia Bonacina MD Giacomo Giacalone MD Giorgio Dalla Volta MD Mauro Magoni MD Paolo Cerrato MD Valeria Bignamini MD Giuseppe Micieli MD Maurizio Melis MD Sandro Sanguigni MD Massimiliano Braga MD Alessandro Padovani MD, PhD Alessandro Pezzini MD Italian Project on Stroke in Young Adults Investigators
doi : 10.1002/ana.25996
Annals of NeurologyVolume 89, Issue 3 p. 627-629
Reply to “Migraine and Cryptogenic Ischemic Stroke”
Jukka Putaala MD, PhD Ville Artto MD, PhD Nicolas Martinez?Majander MD
doi : 10.1002/ana.25997
Annals of NeurologyVolume 89, Issue 3 p. 629-629
Pediatric Leigh Syndrome: Neuroimaging Features and Genetic Correlations
Sarah L. Stenton Ying Zou Hua Cheng Holger Prokisch Fang Fang
doi : 10.1002/ana.25998
Annals of NeurologyVolume 89, Issue 3 p. 629-631
Reply to “Pediatric Leigh Syndrome: Neuroimaging Features and Genetic Correlations”
Cesar Augusto Pinheiro Ferreira Alves MD Sara Reis Teixeira MD, PhD Juan Sebastian Martin?Saavedra MD Fabr?cio Guimar?es Gonçalves MD Francesco Lo Russo MD Colleen Muraresku MS, L?CGC Elizabeth M. McCormick MS, L?CGC Zarazuela Zolkipli?Cunningham MBCHB, MRCP Rebecca Ganetzky MD Marni J. Falk MD Arastoo Vossough MD, PhD Amy Goldstein MD Giulio Zuccoli MD
doi : 10.1002/ana.25999
Annals of NeurologyVolume 89, Issue 3 p. 631-633
NOTCH2NLC Intermediate?Length Repeat Expansion and Parkinson's Disease in Patients of European Descent
Wai Yan Yau FRACP Roisin Sullivan MSc Clarissa Rocca MSc Elisa Cali MD Jana Vandrovcova PhD Nicholas W. Wood FRCP, PhD Henry Houlden FRCP, PhD
doi : 10.1002/ana.26003
Annals of NeurologyVolume 89, Issue 3 p. 633-635
Reply to “NOTCH2NLC Intermediate?Length Repeat Expansions Are Associated with Parkinson Disease”
Chang?he Shi MD, PhD Yu Fan MD Yu?ming Xu MD, PhD
doi : 10.1002/ana.26005
Annals of NeurologyVolume 89, Issue 3 p. 635-635
