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Annals of Neurology: Volume 89, Number 6, June 2021
doi : 10.1002/ana.26099
Volume89, Issue6June 2021
A laser speckle contrast image showing blood flow in the face of a migraineur who had received an infusion of pramlinitide, an agonist for amylin receptors. Amylin is a peptide in the same family as CGRP, with which it shares agonist activity at the AMY1 receptor.
To Zoom or Not to Zoom: The Should I Travel Index Revisited during the Coronavirus Disease Pandemic
Seward B. Rutkove MD, Jeremy M. Shefner MD, PhD, Robert Bowser PhD, Martin R. Turner MA, MBBS, PhD, Michael Benatar MBChB, MS, Dphil
doi : 10.1002/ana.26038
Volume89, Issue6June 2021Pages 1057-1058
Approaches to Understanding COVID-19 and its Neurological Associations
Ettore Beghi MD, Benedict D. Michael PhD, MRCP, Tom Solomon PhD, MRCP, FRCP, Erica Westenberg MSc, Andrea S. Winkler MD, PhD, on behalf of the Global COVID-19 Neuro Research Coalition
doi : 10.1002/ana.26076
Volume89, Issue6June 2021Pages 1059-1067
There is an accumulating volume of research into neurological manifestations of coronavirus disease 2019 (COVID-19).
Superficial Siderosis: A Clinical Review
Neeraj Kumar MD
doi : 10.1002/ana.26083
Volume89, Issue6June 2021Pages 1068-1079
Superficial siderosis of the central nervous system results from subpial hemosiderin deposition due to chronic low-grade bleeding into the subarachnoid space. The confluent and marginal subpial hemosiderin is best appreciated on iron-sensitive magnetic resonance imaging sequences. With widespread use of magnetic resonance imaging, the disorder is increasingly being recognized, including in asymptomatic individuals. Gait ataxia, often with hearing impairment is a common clinical presentation. A clinical history of subarachnoid hemorrhage is generally not present.
To Reduce the Risk of Dementia, Focus on the Patient
Alvaro Pascual-Leone MD, PhD
doi : 10.1002/ana.26086
Volume89, Issue6June 2021Pages 1080-1083
Neuromyelitis Optica Spectrum Disorder: Therapeutic Innovations and Complex Decision-Making
Hans-Peter Hartung MD, FRCP, FANA, FAAN, FEAN
doi : 10.1002/ana.26087
Volume89, Issue6June 2021Pages 1084-1087
Long-Term Safety and Efficacy of Eculizumab in Aquaporin-4 IgG-Positive NMOSD
Dean M. Wingerchuk MD, Kazuo Fujihara MD, Jacqueline Palace DM, Achim Berthele MD, Michael Levy MD, PhD, Ho Jin Kim MD, PhD, Ichiro Nakashima MD, Celia Oreja-Guevara MD, PhD, Kai-Chen Wang MD, PhD, Larisa Miller PharmD, Shulian Shang PhD, Guido Sabatella MD, Marcus Yountz MD, FAAN, Sean J. Pittock MD, PREVENT Study Group
doi : 10.1002/ana.26049
Volume89, Issue6June 2021Pages 1088-1098
During PREVENT (NCT01892345), eculizumab significantly reduced relapse risk versus placebo in patients with aquaporin-4 immunoglobulin G-positive neuromyelitis optica spectrum disorder (AQP4-IgG+ NMOSD). We report an interim analysis of PREVENT's ongoing open-label extension (OLE; NCT02003144) evaluating eculizumab's long-term safety and efficacy.
How Can an Na+ Channel Inhibitor Ameliorate Seizures in Lennox–Gastaut Syndrome?
Yun-Chu Lin MS, Yi-Chen Lai MS, Ping Chou MS, Shu-Wei Hsueh MS, Tien-Hung Lin BS, Chen-Syuan Huang PhD, Ren-Wei Wang MS, Ya-Chin Yang PhD, Chung-Chin Kuo MD, PhD
doi : 10.1002/ana.26068
Volume89, Issue6June 2021Pages 1099-1113
Lennox–Gastaut syndrome (LGS) is an epileptic encephalopathy frequently associated with multiple types of seizures. The classical Na+ channel inhibitors are in general ineffective against the seizures in LGS. Rufinamide is a new Na+ channel inhibitor, but approved for the treatment of LGS. This is not consistent with a choice of antiseizure drugs (ASDs) according to simplistic categorical grouping.
Staufen1 in Human Neurodegeneration
Sharan Paul PhD, Warunee Dansithong PhD, Karla P. Figueroa MS, Mandi Gandelman PhD, Daniel R. Scoles PhD, Stefan M. Pulst MD
doi : 10.1002/ana.26069
Volume89, Issue6June 2021Pages 1114-1128
Mutations in the ATXN2 gene (CAG expansions ?32 repeats) can be a rare cause of Parkinson's disease and amyotrophic lateral sclerosis (ALS). We recently reported that the stress granule (SG) protein Staufen1 (STAU1) was overabundant in neurodegenerative disorder spinocerebellar ataxia type 2 (SCA2) patient cells, animal models, and ALS-TDP-43 fibroblasts, and provided a link between SG formation and autophagy. We aimed to test if STAU1 overabundance has a role in the pathogenesis of other neurodegenerative diseases.
Meningeal CGRP-Prolactin Interaction Evokes Female-Specific Migraine Behavior
Amanda Avona MS, Bianca N. Mason PhD, Carolina Burgos-Vega PhD, Anahit H. Hovhannisyan MS, Sergei N. Belugin MD, PhD, Jennifer Mecklenburg MS, Vincent Goffin PhD, Naureen Wajahat MS, Theodore J. Price PhD, Armen N. Akopian PhD, Gregory Dussor PhD
doi : 10.1002/ana.26070
Volume89, Issue6June 2021Pages 1129-1144
Migraine is three times more common in women. CGRP plays a critical role in migraine pathology and causes female-specific behavioral responses upon meningeal application. These effects are likely mediated through interactions of CGRP with signaling systems specific to females. Prolactin (PRL) levels have been correlated with migraine attacks. Here, we explore a potential interaction between CGRP and PRL in the meninges.
NIA-AA Alzheimer's Disease Framework: Clinical Characterization of Stages
Ronald C. Petersen MD, PhD, Heather J. Wiste BA, Stephen D. Weigand MS, Julie A. Fields PhD, Yonas E. Geda MD, Jonathan Graff-Radford MD, David S. Knopman MD, Walter K. Kremers PhD, Val Lowe MD, Mary M. Machulda PhD, Michelle M. Mielke PhD, Nikki H. Stricker PhD, Terry M. Therneau PhD, Prashanthi Vemuri PhD, Clifford R. Jack Jr MD
doi : 10.1002/ana.26071
Volume89, Issue6June 2021Pages 1145-1156
To operationalize the National Institute on Aging – Alzheimer's Association (NIA-AA) Research Framework for Alzheimer's Disease 6-stage continuum of clinical progression for persons with abnormal amyloid.
Amylin Analog Pramlintide Induces Migraine-like Attacks in Patients
Hashmat Ghanizada MD, PhD, Mohammad Al-Mahdi Al-Karagholi MD, Christopher S. Walker PhD, Nanna Arngrim MD, PhD, Tayla Rees MSc, Jakeb Petersen MSc, Andrew Siow MSc, Mette M?rch-Rasmussen MD, Sheryl Tan PhD, Simon J. O'Carroll PhD, Paul Harris PhD, Lene Theil Skovgaard MSc, Niklas Rye J?rgensen MD, PhD, DMSc, Margaret Brimble PhD, Jayme S. Waite BSE, Brandon J. Rea BS, Levi P. Sowers PhD, Andrew F. Russo PhD, Debbie L. Hay PhD, Messoud Ashina MD, PhD, DMSc
doi : 10.1002/ana.26072
Volume89, Issue6June 2021Pages 1157-1171
Migraine is a prevalent and disabling neurological disease. Its genesis is poorly understood, and there remains unmet clinical need. We aimed to identify mechanisms and thus novel therapeutic targets for migraine using human models of migraine and translational models in animals, with emphasis on amylin, a close relative of calcitonin gene-related peptide (CGRP).
Characterization of the Insular Role in Cardiac Function through Intracranial Electrical Stimulation of the Human Insula
Alvaro Sanchez-Larsen MD,, Alessandro Principe MD, PhD,, Miguel Ley MD,, Javier Navarro-Cuartero MD,, Rodrigo Rocamora MD, PhD
doi : 10.1002/ana.26074
Volume89, Issue6June 2021Pages 1172-1180
The link between brain function and cardiovascular dynamics is an important issue yet to be elucidated completely. The insula is a neocortical brain area that is thought to have a cardiac chronotropic regulatory function, but its role in cardiac contractility is unknown. We aimed to analyze the variability in heart rate and cardiac contractility after functional activation of different insular regions through direct electrical stimulation (E-stim) in humans.
Unravelling the Neural Basis of Spatial Delusions After Stroke
Pedro N. Alves MD, Ana C. Fonseca MD, MPH, PhD, Daniela P. Silva MD, Matilde R. Andrade MSc, Teresa Pinho-e-Melo MD, Michel Thiebaut de Schotten PhD, Isabel P. Martins MD, PhD
doi : 10.1002/ana.26079
Volume89, Issue6June 2021Pages 1181-1194
Knowing explicitly where we are is an interpretation of our spatial representations. Reduplicative paramnesia is a disrupting syndrome in which patients present a firm belief of spatial mislocation. Here, we studied the largest sample of patients with delusional misidentifications of space (ie, reduplicative paramnesia) after stroke to shed light on their neurobiology.
Gut Microbiome in Progressive Multiple Sclerosis
Laura M. Cox PhD, Amir Hadi Maghzi MD, Shirong Liu MD, PhD, Stephanie K. Tankou MD, PhD, Fyonn H. Dhang BS, Valerie Willocq BS, Anya Song BS, Caroline Wasén PhD, Shahamat Tauhid MD, Renxin Chu PhD, Mark C. Anderson MD, Philip L. De Jager MD, PhD, Mariann Polgar-Turcsanyi MBA, Brian C. Healy PhD, Bonnie I. Glanz PhD, Rohit Bakshi MD, Tanuja Chitnis MD, Howard L. Weiner MD
doi : 10.1002/ana.26084
Volume89, Issue6June 2021Pages 1195-1211
This study was undertaken to investigate the gut microbiome in progressive multiple sclerosis (MS) and how it relates to clinical disease.
Alpha-Synuclein Oligomers and Neurofilament Light Chain Predict Phenoconversion of Pure Autonomic Failure
Wolfgang Singer MD, Ann M. Schmeichel, Mohammad Shahnawaz PhD, James D. Schmelzer, David M. Sletten, Tonette L. Gehrking, Jade A. Gehrking, Anita D. Olson, Mariana D. Suarez, Pinaki P. Misra PhD, Claudio Soto PhD, Phillip A. Low MD
doi : 10.1002/ana.26089
Volume89, Issue6June 2021Pages 1212-1220
To explore the role of alpha-synuclein (?Syn) oligomers and neurofilament light chain (NfL) in cerebrospinal fluid (CSF) of patients with pure autonomic failure (PAF) as markers of future phenoconversion to multiple system atrophy (MSA).
Frailty and Risk of Dementia in Mild Cognitive Impairment Subtypes
David D. Ward PhD, Lindsay M. K. Wallace PhD, Kenneth Rockwood MD
doi : 10.1002/ana.26064
Volume89, Issue6June 2021Pages 1221-1225
Risk factors for developing dementia from mild cognitive impairment (MCI) probably differ between MCI subtypes. We investigated how frailty relates to dementia risk in amnestic MCI (a-MCI; n = 2,799) and non-amnestic MCI (na-MCI; n = 629) in the National Alzheimer's Coordinating Center database.
Prediction Model of Amyotrophic Lateral Sclerosis by Deep Learning with Patient Induced Pluripotent Stem Cells
Keiko Imamura MD, PhD, Yuichiro Yada PhD, Yuishin Izumi MD, PhD, Mitsuya Morita MD, PhD, Akihiro Kawata MD, Takayo Arisato MD, PhD, Ayako Nagahashi MS, Takako Enami BS, Kayoko Tsukita BA, Hideshi Kawakami MD, PhD, Masanori Nakagawa MD, PhD, Ryosuke Takahashi MD, PhD, Haruhisa Inoue MD, PhD
doi : 10.1002/ana.26047
Volume89, Issue6June 2021Pages 1226-1233
In amyotrophic lateral sclerosis (ALS), early diagnosis is essential for both current and potential treatments. To find a supportive approach for the diagnosis, we constructed an artificial intelligence-based prediction model of ALS using induced pluripotent stem cells (iPSCs). Images of spinal motor neurons derived from healthy control subject and ALS patient iPSCs were analyzed by a convolutional neural network, and the algorithm achieved an area under the curve of 0.97 for classifying healthy control and ALS.
Multiple Sclerosis Is Rare in Epstein–Barr Virus–Seronegative Children with Central Nervous System Inflammatory Demyelination
Bardia Nourbakhsh MD, MAS, Christian Cordano MD, PhD, Carlo Asteggiano MD, Klemens Ruprecht MD, Carolin Otto MD, Alice Rutatangwa DO, Allysa Lui BS, Janace Hart BS, Eoin P. Flanagan MBBCh, Judith A. James MD, PhD, Emmanuelle Waubant MD, PhD
doi : 10.1002/ana.26062
Volume89, Issue6June 2021Pages 1234-1239
Although Epstein–Barr virus (EBV) is hypothesized to be a prerequisite for multiple sclerosis (MS), up to 15% of children with a diagnosis of MS were reported to be EBV-seronegative.
Mitochondrial DNA Analysis from Exome Sequencing Data Improves Diagnostic Yield in Neurological Diseases
Olivia V. Poole MD, Chiara Pizzamiglio MD, David Murphy MSc, Micol Falabella PhD, William L. Macken MD, Enrico Bugiardini MD, PhD, Cathy E. Woodward BSc, Robyn Labrum PhD, Stephanie Efthymiou PhD, Vincenzo Salpietro MD, PhD, Viorica Chelban MD, PhD, Rauan Kaiyrzhanov MD, Reza Maroofian PhD, the SYNaPS Study Group , Anthony A. Amato MD, Allison Gregory MS, Susan J. Hayflick MD, Queen Square Genomics , Hallgeir Jonvik MSc, Nicholas Wood MD, PhD, Henry Houlden MD, PhD, Jana Vandrovcova PhD, Michael G. Hanna MD, Alan Pittman PhD, Robert D.S. Pitceathly MD, PhD
doi : 10.1002/ana.26063
Volume89, Issue6June 2021Pages 1240-1247
A rapidly expanding catalog of neurogenetic disorders has encouraged a diagnostic shift towards early clinical whole exome sequencing (WES). Adult primary mitochondrial diseases (PMDs) frequently exhibit neurological manifestations that overlap with other nervous system disorders.
Detection of Brain Somatic Mutations in Cerebrospinal Fluid from Refractory Epilepsy Patients
Seyeon Kim BS, Sara Baldassari PhD, Nam Suk Sim MD, PhD, Mathilde Chipaux MD, PhD, Georg Dorfmüller MD, Dong Seok Kim MD, PhD, Won Seok Chang MD, PhD, Valérie Taly PhD, Jeong Ho Lee MD, PhD, Stéphanie Baulac PhD
doi : 10.1002/ana.26080
Volume89, Issue6June 2021Pages 1248-1252
Brain mosaic mutations are a major cause of refractory focal epilepsies with cortical malformations such as focal cortical dysplasia, hemimegalencephaly, malformation of cortical development with oligodendroglial hyperplasia in epilepsy, and ganglioglioma.
Cocaine and Levamisole Cerebral Toxicity
Julien Allard MD, Claire Ancelet MD, Christian Denier MD, PhD
doi : 10.1002/ana.26035
Volume89Issue6Pages1253 - 1254
Pembrolizumab-Induced Migrating Cortico-Subcortical Brain Lesions
Nicolas Lambert MD, Maximilien Steinmetz MD, Anne Sibille MD, Bernard Sadzot MD, PhD
doi : 10.1002/ana.26054
Volume89Issue6Pages1255 - 1256
A Recurrent EIF2AK2 Missense Variant Causes Autosomal-Dominant Isolated Dystonia
Thomas Musacchio MD, Michael Zech MD, Martin M. Reich MD, Juliane Winkelmann MD, Jens Volkmann MD
doi : 10.1002/ana.26081
Volume89, Issue6June 2021Pages 1257-1258
