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Annals of Neurology: Volume 90, Number 3, September 2021
doi : 10.1002/ana.26203
Volume 90, Issue 3 p. C1-C1
A pair of photomicrographs showing the multiple sclerosis histological immunopathology pattern I. The image on the left is stained for myelin oligodendrocyte glycoprotein (MOG) and shows demyelination on the left side of the lesion. The image on the right shows an adjacent section through the same plaque, stained with the KiM1P antibody for macrophages and microglia, demonstrating the infiltration of macrophages into the demyelinated area. See paper by Metz and colleagues (pp. 440–454) in this issue.
Medicare Should Not Cover Aducanumab as a Treatment for Alzheimer's Disease
Nuriel Moghavem MD,Victor W. Henderson MD, MS,Michael D. Greicius MD, MPH,
doi : 10.1002/ana.26167
Volume 90, Issue 3 p. 331-333
Aducanumab: What about the Patient?
Ronald C. Petersen PhD, MD
doi : 10.1002/ana.26181
Volume 90, Issue 3 p. 334-335
Human Brain Resilience: A Call to Action
Alvaro Pascual-Leone MD, PhD,David Bartres-Faz PhD,
doi : 10.1002/ana.26157
Volume 90, Issue 3 p. 336-349
At present, resilience refers to a highly heterogeneous concept with ill-defined determinants, mechanisms, and outcomes. This call for action argues for the need to define resilience as a person-centered multidimensional metric, informed by a dynamic lifespan perspective and combining observational and interventional experimental studies to identify specific neural markers and correlated behavioral measures. The coronavirus disease 2019 (COVID-19) pandemic highlights the urgent need of such an effort with the ultimate goal of defining a new vital sign, an individual index of resilience, as a life-long metric with the capacity to predict an individual's risk for disability in the face of a stressor, insult, injury, or disease. ANN NEUROL 2021;90:336–349
Genetic Studies of Parkinson's and Alzheimer's Disease in Latinos/Hispanics: New Insights and Challenges
Eng-King Tan MD, FRCP(UK)
doi : 10.1002/ana.26179
Volume 90, Issue 3 p. 350-352
Characterizing the Genetic Architecture of Parkinson's Disease in Latinos
Douglas P. Loesch BA,Andrea R. V. R. Horimoto PhD,Karl Heilbron PhD,Elif I. Sarihan MD,Miguel Inca-Martinez BS,Emily Mason BS,Mario Cornejo-Olivas MD,Luis Torres MD,Pilar Mazzetti MD,Carlos Cosentino MD,Elison Sarapura-Castro MD,Andrea Rivera-Valdivia MD,Angel C. Medina PhD,Elena Dieguez MD,Victor Raggio MD,Andres Lescano MD,Vitor Tumas MD, PhD,Vanderci Borges MD, PhD,Henrique B. Ferraz MD, PhD,Carlos R. Rieder PhD,Artur Schumacher-Schuh MD, PhD,Bruno L. Santos-Lobato MD, PhD,Carlos Velez-Pardo PhD,Marlene Jimenez-Del-Rio PhD,Francisco Lopera MD,Sonia Moreno PhD,Pedro Chana-Cuevas MD,William Fernandez MD,Gonzalo Arboleda MD, PhD,Humberto Arboleda MD, MS,Carlos E. Arboleda-Bustos PhD,Dora Yearout BS,Cyrus P. Zabetian MD, MS,the 23andMe Research Team,Paul Cannon PhD,Timothy A. Thornton PhD,Timothy D. O'Connor PhD,Ignacio F. Mata PhD,and on behalf of the Latin American Research Consortium on the Genetics of Parkinson's Disease (LARGE-PD),
doi : 10.1002/ana.26153
Volume 90, Issue 3 p. 353-365
This work was undertaken in order to identify Parkinson's disease (PD) risk variants in a Latino cohort, to describe the overlap in the genetic architecture of PD in Latinos compared to European-ancestry subjects, and to increase the diversity in PD genome-wide association (GWAS) data.
Polygenic Risk Score for Alzheimer's Disease in Caribbean Hispanics
Sanjeev Sariya MSc,Daniel Felsky PhD,Dolly Reyes-Dumeyer BS,Ricky Lali PhD,Rafael A. Lantigua MD,Badri Vardarajan PhD,Ivonne Z. Jiménez-Vel?zquez MD,Jonathan L. Haines PhD,Gerard D. Shellenberg PhD,Margaret A Pericak-Vance MD,Guillaume Paré MD,Richard Mayeux MD,Giuseppe Tosto MD, PhD,
doi : 10.1002/ana.26131
Volume 90, Issue 3 p. 366-376
Polygenic risk scores (PRSs) assess the individual genetic propensity to a condition by combining sparse information scattered across genetic loci, often displaying small effect sizes. Most PRSs are constructed in European-ancestry populations, limiting their use in other ethnicities. Here we constructed and validated a PRS for late-onset Alzheimer's Disease (LOAD) in Caribbean Hispanics (CH).
Subicular Caspase-1 Contributes to Pharmacoresistance in Temporal Lobe Epilepsy
Cenglin Xu PhD,Shuo Zhang MS,Yiwei Gong MS,Jiazhen Nao MS,Yujia Shen MS,Bei Tan MS,Shuheng Xu PhD,Sunliang Cui PhD,Yeping Ruan PhD,Shuang Wang MD,Yi Wang PhD,Zhong Chen PhD
doi : 10.1002/ana.26173
Volume 90, Issue 3 p. 377-390
Unidentified mechanisms largely restrict the viability of effective therapies in pharmacoresistant epilepsy. Our previous study revealed that hyperactivity of the subiculum is crucial for the genesis of pharmacoresistance in temporal lobe epilepsy (TLE), but the underlying molecular mechanism is not clear.
Longitudinal Changes in Hippocampal Network Connectivity in Alzheimer's Disease
Sophie Dautricourt MSc, MD,Robin de Flores PhD,Brigitte Landeau MSc,Géraldine Poisnel PhD,Matthieu Vanhoutte PhD,Nicolas Delcroix PhD,Francis Eustache PhD,Denis Vivien PhD,Vincent de la Sayette MD,Gaël Chételat PhD
doi : 10.1002/ana.26168
Volume 90, Issue 3 p. 391-406
The hippocampus is connected to 2 distinct cortical brain networks, the posterior–medial and the anterior–temporal networks, involving different medial temporal lobe (MTL) subregions. The aim of this study was to assess the functional alterations of these 2 networks, their changes over time, and links to cognition in Alzheimer's disease.
Metabolite Signature of Alzheimer's Disease in Adults with Down Syndrome
Victor Montal MSc,Isabel Barroeta MD, PhD,Alexandre Bejanin PhD,Jordi Pegueroles MSc,Mar?a Carmona-Iragui MD, PhD,Miren Altuna MD, PhD,Bessy Benejam MSc,Laura Videla MSc,Susana Fern?ndez MD,Concepcion Padilla PhD,Mateus Rozalem Aranha MD,Maria Florencia Iulita PhD,Didac Vidal-Pi?eiro PhD,Daniel Alcolea MD, PhD,Rafael Blesa MD, PhD,Alberto Lle? MD, PhD,Juan Fortea MD, PhD,and Down Alzheimer Barcelona Neuroimaging Initiative,
doi : 10.1002/ana.26178
Volume 90, Issue 3 p. 407-416
The purpose of this study was to examine the Alzheimer's disease metabolite signature through magnetic resonance spectroscopy in adults with Down syndrome and its relation with Alzheimer's disease biomarkers and cortical thickness.
Perfusion Imaging and Clinical Outcome in Acute Ischemic Stroke with Large Core
Pierre Seners MD, PhD,Catherine Oppenheim MD, PhD,Guillaume Turc MD, PhD,Jean-François Albucher MD,Adrien Guenego MD,Nicolas Raposo MD, PhD,Soren Christensen PhD,Lionel Calvière MD,Alain Viguier MD,Jean Darcourt MD,Anne-Christine Januel MD,Michael Mlynash MD,Agnes Sommet MD, PhD,Claire Thalamas MD,Igor Sibon MD, PhD,Vanessa Rousseau PhD,Thomas Tourdias MD, PhD,Patrice Menegon MD,Fabrice Bonneville MD, PhD,Mikael Mazighi MD, PhD,Sylvain Charron PhD,Laurence Legrand MD, MSc,Christophe Cognard MD, PhD,Gregory W. Albers MD,Jean-Claude Baron MD, ScD,Jean-Marc Olivot MD, PhD,and on behalf of the FRAME investigators
doi : 10.1002/ana.26152
Volume 90, Issue 3 p. 417-427
Mechanical thrombectomy (MT) is not recommended for acute stroke with large vessel occlusion (LVO) and a large volume of irreversibly injured tissue (“core”). Perfusion imaging may identify a subset of patients with large core who benefit from MT.
Targeted tDCS Mitigates Dual-Task Costs to Gait and Balance in Older Adults
Junhong Zhou PhD,Brad Manor PhD,Wanting Yu ME,On-Yee Lo PhD,Natalia Gouskova PhD,Ricardo Salvador PhD,Racheli Katz MScPT,Pablo Cornejo Thumm MS,Marina Brozgol PhD,Giulio Ruffini PhD,Alvaro Pascual-Leone MD, PhD,Lewis A. Lipsitz MD,Jeffrey M. Hausdorff PhD
doi : 10.1002/ana.26156
Volume 90, Issue 3 p. 428-439
Among older adults, the ability to stand or walk while performing cognitive tasks (ie, dual-tasking) requires coordinated activation of several brain networks. In this multicenter, double-blinded, randomized, and sham-controlled study, we examined the effects of modulating the excitability of the left dorsolateral prefrontal cortex (L-DLPFC) and the primary sensorimotor cortex (SM1) on dual-task performance “costs” to standing and walking.
Magnetic Resonance Imaging Correlates of Multiple Sclerosis Immunopathological Patterns
Imke Metz MD,Ralitza H. Gavrilova MD,Stephen D. Weigand,Josa M. Frischer MD,Bogdan F. Popescu MD,Yong Guo MD,Mareike Gloth MD,William Oliver Tobin PhD,Nicholas L. Zalewski MD,Hans Lassmann MD,Jan M. Tillema MD,Bradley J. Erickson MD,Joseph E. Parisi MD,Stephanie Becker MD,Fatima B. K?nig MD,Wolfgang Brück MD,Claudia F. Lucchinetti MD,
doi : 10.1002/ana.26163
Volume 90, Issue 3 p. 440-454
Histology reveals that early active multiple sclerosis lesions can be classified into 3 main interindividually heterogeneous but intraindividually stable immunopathological patterns of active demyelination (patterns I–III). In patterns I and II, a T-cell- and macrophage-associated demyelination is suggested, with pattern II only showing signs of a humoral immune response. Pattern III is characterized by inflammatory lesions with an oligodendrocyte degeneration. Patterns suggest pathogenic heterogeneity, and we postulated that they have distinct magnetic resonance imaging (MRI) correlates that may serve as biomarkers.
Genomic Insights into Myasthenia Gravis Identify Distinct Immunological Mechanisms in Early and Late Onset Disease
Lahiru Handunnetthi MD, PhD,Bogdan Knezevic PhD,Silva Kasela PhD,Katie L. Burnham PhD,Lili Milani PhD,Sarosh R. Irani MD, PhD,Hai Fang PhD,Julian C. Knight MD, PhD
doi : 10.1002/ana.26169
Volume 90, Issue 3 p. 455-463
The purpose of this study was to identify disease relevant genes and explore underlying immunological mechanisms that contribute to early and late onset forms of myasthenia gravis.
Postictal Psychosis in Epilepsy: A Clinicogenetic Study
Vera Braatz MD,Helena Martins Custodio PhD,Costin Leu PhD,Luigi Agr? MD,Baihan Wang MSc,Stella Calafato PhD,Genevieve Rayner PhD,Michael G. Doyle MRCPI,Christian Hengsbach MD,Francesca Bisulli PhD,Yvonne G. Weber MD,Antonio Gambardella MD,Norman Delanty FRCPI,Gianpiero Cavalleri PhD,Jacqueline Foong FRCPsych,Ingrid E. Scheffer FRS,Samuel F. Berkovic FRS,Elvira Bramon PhD,Simona Balestrini PhD,Sanjay M. Sisodiya FRCP
doi : 10.1002/ana.26174
Volume 90, Issue 3 p. 464-476
Psychoses affecting people with epilepsy increase disease burden and diminish quality of life. We characterized postictal psychosis, which comprises about one quarter of epilepsy-related psychoses, and has unknown causation.
Intrathecal Immunoglobulin M Synthesis is an Independent Biomarker for Higher Disease Activity and Severity in Multiple Sclerosis
Johanna Oechtering MD,Sabine Schaedelin MSc,Pascal Benkert PhD,Stefanie Müller MD,Lutz Achtnichts MD,Jochen Vehoff MD,Giulio Disanto MD, PhD,Oliver Findling MD,Bettina Fischer-Barnicol MD,Annette Orleth PhD,Andrew Chan MD,Caroline Pot MD,Muhamed Barakovic PhD,Reza Rahmanzadeh MD,Riccardo Galbusera MD,Ingmar Heijnen PhD,Patrice H. Lalive MD,Jens Wuerfel MD,Suvitha Subramaniam MSc,Stefanie Aeschbacher PhD,David Conen MD,Yvonne Naegelin MD,Aleksandra Maceski MSc,Stephanie Meier MSc,Klaus Berger PhD,Heinz Wiendl MD,Therese Lincke MD,Johanna Lieb MD,?zgür Yaldizli MD,Tim Sinnecker MD,Tobias Derfuss MD,Axel Regeniter MD,Chiara Zecca MD,Claudio Gobbi MD,Ludwig Kappos MD,Cristina Granziera MD, PhD,David Leppert MD,Jens Kuhle MD, PhD,and for the Swiss Multiple Sclerosis Cohort Study,
doi : 10.1002/ana.26137
Volume 90, Issue 3 p. 477-489
We aimed to determine in relapsing multiple sclerosis (MS) whether intrathecal synthesis of immunoglobulin (Ig) M and IgG is associated with outcomes reflecting inflammatory activity and chronic worsening.
Lewy Body–like Inclusions in Human Midbrain Organoids Carrying Glucocerebrosidase and ?-Synuclein Mutations
Junghyun Jo PhD,Lin Yang PhD,Hoang-Dai Tran PhD,Weonjin Yu PhD,Alfred Xuyang Sun PhD,Ya Yin Chang BSc,Byung Chul Jung PhD,Seung-Jae Lee PhD,Tzuen Yih Saw MSc,Bin Xiao MD, PhD,Audrey Tze Ting Khoo PhD,Lai-Ping Yaw MSc,Jessica Jiaxin Xie MSc,Hidayat Lokman BSc,Wei-Yi Ong PhD,Grace Gui Yin Lim PhD,Kah-Leong Lim PhD,Eng-King Tan MD,Huck-Hui Ng PhD,Hyunsoo Shawn Je PhD,
doi : 10.1002/ana.26166
Volume 90, Issue 3 p. 490-505
We utilized human midbrain-like organoids (hMLOs) generated from human pluripotent stem cells carrying glucocerebrosidase gene (GBA1) and ?-synuclein (?-syn; SNCA) perturbations to investigate genotype-to-phenotype relationships in Parkinson disease, with the particular aim of recapitulating ?-syn– and Lewy body–related pathologies and the process of neurodegeneration in the hMLO model.
Postvaccinal Encephalitis after ChAdOx1 nCov-19
Frédéric Zuhorn MD,Tilmann Graf MD,Randolf Klingebiel MD,Wolf-Rüdiger Sch?bitz MD,Andreas Rogalewski MD,
doi : 10.1002/ana.26182
Volume 90, Issue 3 p. 506-511
The global SARS-CoV-2 pandemic has contributed to more than 163 million confirmed infections and 3.3 million deaths worldwide. The severity of the pandemic has led to an unprecedented effort to develop multiple effective vaccines. Due to excellent safety and efficacy data from clinical trials, several vaccines were approved. We report a case series of postvaccinal encephalitis in temporal correlation to vaccination with ChAdOx1 nCov-19. The diagnostic criteria for possible autoimmune encephalitis were fulfilled. Our patients responded well to immunosuppressive therapy with corticosteroids. The incidence has been estimated to be approximately 8 per 10 million vaccine doses. Complication of postvaccinal encephalitis after ChAdOx1 nCoV-19 vaccination still appear to be very rare, but need to be diagnosed and treated adequately. Large pooled data from observational epidemiologic studies are necessary to verify causality. ANN NEUROL 2021;90:506–511
Dural Arteriovenous Fistula Presenting with Reversible Dementia
Joseph Y. Yoon MD, MSc, MAEd,Robert W. Regenhardt MD, PhD,Thabele M. Leslie-Mazwi MD,
doi : 10.1002/ana.26138
Volume 90, Issue 3 p. 512-513
Spontaneous Intracranial Hypotension Due to Skull-Base Cerebrospinal Fluid Leak
Wouter I. Schievink MD,L. Madison Michael II MD,Marcel Maya MD,Paul Klimo Jr MD,Lucas Elijovich MD,
doi : 10.1002/ana.26175
Volume 90, Issue 3 p. 514-516
Prior anticoagulation in patients with ischemic stroke and atrial fibrillation
Tomoyuki Kawada
doi : 10.1002/ana.26183
Volume 90, Issue 3 p. 517-517
Reply to “Prior Anticoagulation in Patients with Ischemic Stroke and Atrial Fibrillation”
Thomas R. Meinel,David Seiffge,
doi : 10.1002/ana.26184
Volume 90, Issue 3 p. 517-518
Impact of Time of Day and Season on Outcome in Acute Ischemic Stroke
Yelson Alejandro Pic?n-Jaimes MD, MSc,Ivan David Lozada-Mart?nez MS,Tariq Janjua MD,Luis Rafael Moscote-Salazar MD,
doi : 10.1002/ana.26162
Volume 90, Issue 3 p. 518-519
Gut Microbiome Signatures of Risk and Prodromal Markers of Parkinson Disease
Sebastian Heinzel PhD,Velma T. E. Aho PhD,Ulrike Suenkel MD,Anna-Katharina von Thaler PhD,Claudia Schulte MSc,Christian Deuschle,Lars Paulin MSc,Sari Hantunen PhD,Kathrin Brockmann MD,Gerhard W. Eschweiler MD,Walter Maetzler MD,Daniela Berg MD,Petri Auvinen PhD,Filip Scheperjans MD,
doi : 10.1002/ana.26128
Volume 90, Issue 3 p. E1-E12
