Latest Reviews

  • Review Article |

    Drug repositioning and repurposing can enhance traditional drug development efforts and could accelerate the identification of new treatments. In this Review, Ballard and colleagues highlight priority compounds for repurposing for the treatment of Alzheimer disease.

    • Clive Ballard
    • , Dag Aarsland
    • , Jeffrey Cummings
    • , John O’Brien
    • , Roger Mills
    • , Jose Luis Molinuevo
    • , Tormod Fladby
    • , Gareth Williams
    • , Pat Doherty
    • , Anne Corbett
    •  & Janet Sultana
  • Consensus Statement |

    Malformations of cortical development (MCDs) are neurodevelopmental disorders that result from abnormal development of the cerebral cortex in utero. In this Consensus Statement, the international MCD network Neuro-MIG provides recommendations to aid both expert and non-expert clinicians in the diagnostic work-up of MCDs.

    • Renske Oegema
    • , Tahsin Stefan Barakat
    • , Martina Wilke
    • , Katrien Stouffs
    • , Dina Amrom
    • , Eleonora Aronica
    • , Nadia Bahi-Buisson
    • , Valerio Conti
    • , Andrew E. Fry
    • , Tobias Geis
    • , David Gomez Andres
    • , Elena Parrini
    • , Ivana Pogledic
    • , Edith Said
    • , Doriette Soler
    • , Luis M. Valor
    • , Maha S. Zaki
    • , Ghayda Mirzaa
    • , William B. Dobyns
    • , Orly Reiner
    • , Renzo Guerrini
    • , Daniela T. Pilz
    • , Ute Hehr
    • , Richard J. Leventer
    • , Anna C. Jansen
    • , Grazia M. S. Mancini
    •  & Nataliya Di Donato
  • Review Article |

    This Review outlines the advances of molecular treatment of brain metastases from non-small-cell lung cancer, breast cancer and melanoma. Substantial improvements in survival have been achieved in patients with molecular subgroups whose alterations can be targeted with specific molecular compounds.

    • Riccardo Soffietti
    • , Manmeet Ahluwalia
    • , Nancy Lin
    •  & Roberta Rudà
  • Perspective |

    Acute respiratory distress syndrome is a common occurrence in COVID-19, an infectious disease caused by the coronavirus SARS-CoV-2. In this article, the authors consider how lung innervation might crosstalk with the immune system to modulate lung function and influence outcomes in COVID-19.

    • Francesco De Virgiliis
    •  & Simone Di Giovanni
  • Perspective |

    In this Perspective, Pezzini and Padovani critique the evidence for neurological manifestations of COVID-19, including epidemiological, neuropathological and neuroimaging data, and highlight the need for further work to establish whether SARS-CoV-2 is responsible for these symptoms.

    • Alessandro Pezzini
    •  & Alessandro Padovani
  • Review Article |

    Imaging-based assessment is becoming increasingly important in the management of acute stroke, but processing and interpretation of images in clinical practice is challenging. In this Review, Parsons and colleagues explore the potential of artificial intelligence to provide treatment decision support.

    • Andrew Bivard
    • , Leonid Churilov
    •  & Mark Parsons
  • Review Article |

    A distinct set of CNS diseases are caused by autoantibodies to neuroglial surface proteins, and immunotherapy has limited ability to control these conditions in the long term. In this Review, the authors discuss in detail the B cell biology that underlies these diseases and consider the therapeutic implications.

    • Bo Sun
    • , Melanie Ramberger
    • , Kevin C. O’Connor
    • , Rachael J. M. Bashford-Rogers
    •  & Sarosh R. Irani
  • Review Article |

    In this Review, the authors describe the latest developments in the use of machine learning to interrogate neurodegenerative disease-related datasets. They discuss applications of machine learning to diagnosis, prognosis and therapeutic development, and the challenges involved in analysing health-care data.

    • Monika A. Myszczynska
    • , Poojitha N. Ojamies
    • , Alix M. B. Lacoste
    • , Daniel Neil
    • , Amir Saffari
    • , Richard Mead
    • , Guillaume M. Hautbergue
    • , Joanna D. Holbrook
    •  & Laura Ferraiuolo
  • Review Article |

    This Review discusses the advantages and pitfalls of metagenomic next-generation sequencing (mNGS) in patients with encephalitis, meningitis and myelitis. The authors outline data on mNGS test performance, cost and turnaround time and highlight future directions for mNGS technology.

    • Prashanth S. Ramachandran
    •  & Michael R. Wilson
  • Review Article |

    Nodes of Ranvier are unmyelinated domains that enable fast saltatory propagation of action potentials along myelinated axons. This Review describes the organization and function of CNS nodes of Ranvier and considers how these nodes change in demyelinating and remyelinating disorders.

    • Catherine Lubetzki
    • , Nathalie Sol-Foulon
    •  & Anne Desmazières
  • Review Article |

    In this Review, the authors synthesize recommendations on the management of neuroimmunological disease in the context of the COVID-19 pandemic. They consider these recommendations alongside the first available data from patients, and provide an overview of management approaches in the COVID-19 era.

    • Catharina Korsukewitz
    • , Stephen W. Reddel
    • , Amit Bar-Or
    •  & Heinz Wiendl
  • Review Article |

    The search for effective therapies for neurological disease has been impeded by our limited understanding of the causative molecular and cellular mechanisms. Kampmann describes how new CRISPR-based functional genomics approaches can uncover disease mechanisms and therapeutic targets in neurological diseases.

    • Martin Kampmann
  • Review Article |

    This Review examines the rationale for the use of virtual reality in research and rehabilitation of people with Parkinson disease. The authors provide a critical appraisal of the current state of the art, make recommendations for future research and outline clinical implications.

    • Colleen G. Canning
    • , Natalie E. Allen
    • , Evelien Nackaerts
    • , Serene S. Paul
    • , Alice Nieuwboer
    •  & Moran Gilat
  • Review Article |

    In this Review, Brennan and Henshall discuss how microRNAs determine and control neuronal and glial functions, how this process is altered in states associated with hyperexcitability, and the prospects for microRNA targeting for the treatment of epilepsy.

    • Gary P. Brennan
    •  & David C. Henshall
  • Consensus Statement
    | Open Access

    In 2018, the Discovery and Validation of Biomarkers to Develop Non-Addictive Therapeutics for Pain workshop convened to discuss strategies to facilitate the development of biomarkers and end points for pain. The outcomes of this workshop are outlined in this Consensus Statement.

    • Karen D. Davis
    • , Nima Aghaeepour
    • , Andrew H. Ahn
    • , Martin S. Angst
    • , David Borsook
    • , Ashley Brenton
    • , Michael E. Burczynski
    • , Christopher Crean
    • , Robert Edwards
    • , Brice Gaudilliere
    • , Georgene W. Hergenroeder
    • , Michael J. Iadarola
    • , Smriti Iyengar
    • , Yunyun Jiang
    • , Jiang-Ti Kong
    • , Sean Mackey
    • , Carl Y. Saab
    • , Christine N. Sang
    • , Joachim Scholz
    • , Marta Segerdahl
    • , Irene Tracey
    • , Christin Veasley
    • , Jing Wang
    • , Tor D. Wager
    • , Ajay D. Wasan
    •  & Mary Ann Pelleymounter
  • Review Article |

    Smeland and colleagues examine the evidence for a polygenic architecture of schizophrenia. This new knowledge of schizophrenia pathobiology has important implications for understanding its genetic overlap with other traits and disorders, which could influence future disease classifications and mechanistic research.

    • Olav B. Smeland
    • , Oleksandr Frei
    • , Anders M. Dale
    •  & Ole A. Andreassen
  • Review Article |

    Antibodies to glutamic acid decarboxylase (GAD) are associated with several neurological syndromes but their importance and role are controversial. In this Review, Graus et al. propose criteria for assessing the association between GAD antibodies and neurological syndromes and discuss the pathogenicity of GAD antibodies.

    • Francesc Graus
    • , Albert Saiz
    •  & Josep Dalmau
  • Review Article |

    Zoonotic and vector-borne parasites are important preventable risk factors for epilepsy. The authors explore the pathophysiological basis of the link between parasitic infections and epilepsy and consider preventive and therapeutic approaches to reduce the epilepsy burden associated with parasitic disorders.

    • Gagandeep Singh
    • , Samuel A. Angwafor
    • , Alfred K. Njamnshi
    • , Henry Fraimow
    •  & Josemir W. Sander
  • Review Article |

    In this Review, the authors discuss the treatment and management of cognitive impairment in people with multiple sclerosis. They describe the theoretical rationales, challenges and advances in cognitive rehabilitation and exercise training for treating multiple sclerosis-related cognitive impairment, and discuss future directions for research in this field.

    • John DeLuca
    • , Nancy D. Chiaravalloti
    •  & Brian M. Sandroff
  • Review Article |

    In this Review, Tan et al. provide an overview of the clinical and preclinical evidence that immune system dysfunction is involved in Parkinson disease, and discuss how increasing knowledge of the underlying mechanisms is driving development of immune-based therapeutic approaches.

    • Eng-King Tan
    • , Yin-Xia Chao
    • , Andrew West
    • , Ling-Ling Chan
    • , Werner Poewe
    •  & Joseph Jankovic
  • Review Article |

    In this Review, Montaner and colleagues summarize how proteomics, genomics, transcriptomics and metabolomics are contributing to the discovery and development of biomarkers in stroke, and how bringing them together with integromics could provide new biomarkers and therapeutic opportunities.

    • Joan Montaner
    • , Laura Ramiro
    • , Alba Simats
    • , Steffen Tiedt
    • , Konstantinos Makris
    • , Glen C. Jickling
    • , Stephanie Debette
    • , Jean-Charles Sanchez
    •  & Alejandro Bustamante
  • Review Article |

    Most research into blood-based biomarkers for neurodegenerative disorders has so far focused on Alzheimer disease. In this Review, Aarsland and colleagues give an overview of the current status of blood-based biomarkers for the non-Alzheimer disease neurodegenerative disorders.

    • Nicholas J. Ashton
    • , Abdul Hye
    • , Anto P. Rajkumar
    • , Antoine Leuzy
    • , Stuart Snowden
    • , Marc Suárez-Calvet
    • , Thomas K. Karikari
    • , Michael Schöll
    • , Renaud La Joie
    • , Gil D. Rabinovici
    • , Kina Höglund
    • , Clive Ballard
    • , Tibor Hortobágyi
    • , Per Svenningsson
    • , Kaj Blennow
    • , Henrik Zetterberg
    •  & Dag Aarsland
  • Review Article |

    In this Review, Panza and colleagues provide an overview of the current understanding of pathogenic mechanisms of frontotemporal dementia spectrum disorders and discuss how this knowledge is driving the development of potential disease-modifying drugs.

    • Francesco Panza
    • , Madia Lozupone
    • , Davide Seripa
    • , Antonio Daniele
    • , Mark Watling
    • , Gianluigi Giannelli
    •  & Bruno P. Imbimbo
  • Review Article |

    In this Review, Peng et al. summarize the evidence for cell-to-cell transmission of pathological proteins in neurodegenerative diseases such as Alzheimer disease and Parkinson disease, and identify key questions for future investigation.

    • Chao Peng
    • , John Q. Trojanowski
    •  & Virginia M.-Y. Lee
  • Viewpoint |

    In 2019, the Alzheimer’s Association International Conference featured a debate on the role of infections in AD pathogenesis. Here, participants from that debate discuss the evidence regarding the infectious theory of AD and suggest avenues for future investigation.

    • Ruth F. Itzhaki
    • , Todd E. Golde
    • , Michael T. Heneka
    •  & Ben Readhead
  • Review Article |

    In this Review, Karimy et al. discuss the mechanisms by which inflammation can contribute to the pathogenesis of acquired hydrocephalus and highlight targets for therapeutic intervention.

    • Jason K. Karimy
    • , Benjamin C. Reeves
    • , Eyiyemisi Damisah
    • , Phan Q. Duy
    • , Prince Antwi
    • , Wyatt David
    • , Kevin Wang
    • , Steven J. Schiff
    • , David D. Limbrick Jr.
    • , Seth L. Alper
    • , Benjamin C. Warf 
    • , Maiken Nedergaard
    • , J. Marc Simard
    •  & Kristopher T. Kahle
  • Review Article |

    Few therapies for spinal cord injury (SCI) have successfully reached the clinic, owing to the complex nature of the injury. This Review highlights two potential new multi-target therapeutic strategies for SCI: olfactory mucosa-derived mesenchymal stromal cells and heparan sulfate mimetics.

    • Susan L. Lindsay
    • , George A. McCanney
    • , Alice G. Willison
    •  & Susan C. Barnett
  • Consensus Statement
    | Open Access

    In this Consensus statement, the Magnetic Resonance Imaging in MS (MAGNIMS) study group reviews the application of brain and spinal cord atrophy in clinical practice in the management of MS and makes consensus statements and recommendations for future research.

    • Jaume Sastre-Garriga
    • , Deborah Pareto
    • , Marco Battaglini
    • , Maria A. Rocca
    • , Olga Ciccarelli
    • , Christian Enzinger
    • , Jens Wuerfel
    • , Maria P. Sormani
    • , Frederik Barkhof
    • , Tarek A. Yousry
    • , Nicola De Stefano
    • , Mar Tintoré
    • , Massimo Filippi
    • , Claudio Gasperini
    • , Ludwig Kappos
    • , Jordi Río
    • , Jette Frederiksen
    • , Jackie Palace
    • , Hugo Vrenken
    • , Xavier Montalban
    •  & Àlex Rovira
  • Review Article |

    In this Review, Wardlaw et al. discuss the anatomy, physiology and pathology of perivascular spaces, particularly as seen with MRI in humans, and consider translation from models to humans to highlight knowns, unknowns, controversies and clinical relevance.

    • Joanna M. Wardlaw
    • , Helene Benveniste
    • , Maiken Nedergaard
    • , Berislav V. Zlokovic
    • , Humberto Mestre
    • , Hedok Lee
    • , Fergus N. Doubal
    • , Rosalind Brown
    • , Joel Ramirez
    • , Bradley J. MacIntosh
    • , Allen Tannenbaum
    • , Lucia Ballerini
    • , Ravi L. Rungta
    • , Davide Boido
    • , Melanie Sweeney
    • , Axel Montagne
    • , Serge Charpak
    • , Anne Joutel
    • , Kenneth J. Smith
    •  & Sandra E. Black
  • Review Article |

    Neuromyelitis optica spectrum disorders (NMOSD) are a type of neurological autoimmune disease characterized by attacks of CNS inflammation. In this Review, the authors discuss the relationship between pregnancy outcomes and NMOSD disease activity, and outline potential treatment approaches.

    • Yang Mao-Draayer
    • , Sandra Thiel
    • , Elizabeth A. Mills
    • , Tanuja Chitnis
    • , Michelle Fabian
    • , Ilana Katz Sand
    • , M. Isabel Leite
    • , Sven Jarius
    •  & Kerstin Hellwig
  • Review Article |

    In this Review, Tolosa et al. discuss the strategies in development for disease-modifying treatments in Parkinson disease cause by mutations in the LRRK2 gene, and consider the challenges in designing and implementing clinical trials in this condition.

    • Eduardo Tolosa
    • , Miquel Vila
    • , Christine Klein
    •  & Olivier Rascol
  • Review Article |

    Degenerative cervical myelopathy is the leading cause of spinal cord dysfunction in adults worldwide. In this Review, the authors provide a comprehensive pathophysiological and clinical overview of the condition to equip physicians across broad disciplines with the knowledge needed for its diagnosis and management.

    • Jetan H. Badhiwala
    • , Christopher S. Ahuja
    • , Muhammad A. Akbar
    • , Christopher D. Witiw
    • , Farshad Nassiri
    • , Julio C. Furlan
    • , Armin Curt
    • , Jefferson R. Wilson
    •  & Michael G. Fehlings
  • Review Article |

    Sex-based differences in demographics, clinical features and therapeutic response are emerging in a range of neurological diseases, including movement disorders. The authors review current knowledge of sex-related differences in Parkinson disease, essential tremor, dystonia, Huntington disease and chronic tic disorders.

    • Sara Meoni
    • , Antonella Macerollo
    •  & Elena Moro
  • Review Article |

    In this Review, Cristino, Bisogno and Di Marzo outline the biology of cannabinoids, the endocannabinoid system and the expanded endocannabinoid system and discuss the involvement of these systems and the therapeutic potential of cannabinoids across the spectrum of neurological disease.

    • Luigia Cristino
    • , Tiziana Bisogno
    •  & Vincenzo Di Marzo
  • Review Article |

    Amyloid-β deposition underlies the pathogenesis of cerebral amyloid angiopathy (CAA) and Alzheimer disease (AD), but the disease pathways differ. Here, Greenberg et al. consider the interactions between CAA and AD, the factors that determine which disease pathway transpires, and the implications for therapeutic development.

    • Steven M. Greenberg
    • , Brian J. Bacskai
    • , Mar Hernandez-Guillamon
    • , Jeremy Pruzin
    • , Reisa Sperling
    •  & Susanne J. van Veluw
  • Review Article |

    Some individuals with post-stroke language impairment, or aphasia, will spontaneously recover partial language function. In this Review, the authors propose that existing hypotheses about this recovery from aphasia can be considered as examples of two principles: degeneracy and variable neuro-displacement.

    • James D. Stefaniak
    • , Ajay D. Halai
    •  & Matthew A. Lambon Ralph
  • Review Article |

    Spinal cord injury leads to disruption of neural circuitry and connectivity, resulting in permanent neurological disability. Hutson and Di Giovanni assess the clinical potential of emerging strategies that are designed to augment neuroplasticity and promote sensorimotor recovery after spinal cord injury.

    • Thomas H. Hutson
    •  & Simone Di Giovanni
  • Review Article |

    In this Review, David et al. discuss the ability of advanced quantitative MRI techniques to identify secondary degenerative changes induced by spinal cord injury and assess the suitability of these techniques for predicting patient outcome.

    • Gergely David
    • , Siawoosh Mohammadi
    • , Allan R. Martin
    • , Julien Cohen-Adad
    • , Nikolaus Weiskopf
    • , Alan Thompson
    •  & Patrick Freund
  • Perspective |

    In this Perspectives article, Jan Lünemann and colleagues discuss the potential of immune reconstitution therapies to induce remission in individuals with multiple sclerosis. They highlight our limited understanding of the mechanisms underlying this remission and suggest future areas of research.

    • Jan D. Lünemann
    • , Tobias Ruck
    • , Paolo A. Muraro
    • , Amit Bar-Or
    •  & Heinz Wiendl
  • Review Article |

    In this Review, the authors describe the evidence for abnormalities in energy metabolism and mitochondrial function in migraine, consider the potential mechanisms and highlight treatments that affect metabolism. They conclude that migraine is a conserved adaptive response that helps to restore brain energy homeostasis.

    • Elena C. Gross
    • , Marco Lisicki
    • , Dirk Fischer
    • , Peter S. Sándor
    •  & Jean Schoenen
  • Review Article |

    Charcot–Marie–Tooth disease (CMT) encompasses a group of inherited neuropathies that exhibit phenotypic and genetic heterogeneity. The authors discuss the application of next-generation sequencing (NGS) to the diagnosis of CMT and present a method for incorporating NGS into CMT clinical practice.

    • Menelaos Pipis
    • , Alexander M. Rossor
    • , Matilde Laura
    •  & Mary M. Reilly
  • Review Article |

    Axonal transport is the process whereby motor proteins navigate microtubules to deliver diverse cargoes from one end of the axon to the other. In this Review, Schiavo and colleagues explore the link between perturbations in axonal transport and neurological disease.

    • James N. Sleigh
    • , Alexander M. Rossor
    • , Alexander D. Fellows
    • , Andrew P. Tosolini
    •  & Giampietro Schiavo
  • Consensus Statement
    | Open Access

    In this Consensus Statement, Leonhard et al. provide a globally applicable guideline for the diagnosis and management of Guillain–Barré syndrome, including information on early recognition of the disease, prediction of clinical course and outcome, and management of complications and sequelae.

    • Sonja E. Leonhard
    • , Melissa R. Mandarakas
    • , Francisco A. A. Gondim
    • , Kathleen Bateman
    • , Maria L. B. Ferreira
    • , David R. Cornblath
    • , Pieter A. van Doorn
    • , Mario E. Dourado
    • , Richard A. C. Hughes
    • , Badrul Islam
    • , Susumu Kusunoki
    • , Carlos A. Pardo
    • , Ricardo Reisin
    • , James J. Sejvar
    • , Nortina Shahrizaila
    • , Cristiane Soares
    • , Thirugnanam Umapathi
    • , Yuzhong Wang
    • , Eppie M. Yiu
    • , Hugh J. Willison
    •  & Bart C. Jacobs
  • Review Article |

    This Review discusses the contribution of adverse early-life experiences to aberrant brain maturation, which might underlie vulnerability to cognitive brain disorders. The authors suggest that fragmented and unpredictable environmental and parental signals comprise a novel and potent type of adversity.

    • Annabel K. Short
    •  & Tallie Z. Baram