Latest Reviews

  • Perspective |

    In the future, robotic devices that augment human care provision could transform dementia services and support. In this Perspectives article, Moyle discusses upcoming challenges in dementia care and suggests guidelines for the development and integration of smart assistive technologies.

    • Wendy Moyle
  • Review Article |

    Vaughn et al. review the challenges facing elderly patients with multiple sclerosis (MS). They describe the complex, evolving relationship between ageing and MS pathophysiology, highlight the lack of evidence for the safety and efficacy of disease-modifying therapies in elderly patients, and discuss treatment discontinuation and wellness strategies.

    • Caila B. Vaughn
    • , Dejan Jakimovski
    • , Katelyn S. Kavak
    • , Murali Ramanathan
    • , Ralph H. B. Benedict
    • , Robert Zivadinov
    •  & Bianca Weinstock-Guttman
  • Review Article |

    In this Review, the authors discuss findings that are transforming our understanding of neuropsychiatric diseases and the role of inflammation in these disorders. They suggest new diagnostic and therapeutic criteria for the emerging field of neuroimmunopsychiatry.

    • Katrin Pape
    • , Ryad Tamouza
    • , Marion Leboyer
    •  & Frauke Zipp
  • Review Article |

    Personalized multiple sclerosis therapy depends on evidence-based prognostication, an initial treatment choice and evaluation of early treatment responses to identify the need to switch therapy. In this Review, Rotstein and Montalban discuss the factors that need to be taken into account to make personalized treatment decisions.

    • Dalia Rotstein
    •  & Xavier Montalban
  • Perspective |

    Here, Bouthour et al. argue that the success of closed-loop deep brain stimulation based on electrophysiological biomarkers in patients with Parkinson disease could inspire novel treatments for other neuropsychiatric disorders in which symptoms are driven by pathological activity in motor, cognitive and limbic brain networks.

    • Walid Bouthour
    • , Pierre Mégevand
    • , John Donoghue
    • , Christian Lüscher
    • , Niels Birbaumer
    •  & Paul Krack
  • Review Article |

    Organic acidurias (OADs) are inherited neurometabolic diseases usually caused by deficiencies in enzymes involved in amino acid catabolism. Wajner reviews the main features of the OADs, focusing particularly on the cerebral manifestations, and highlights recent advances regarding pathophysiology and treatment.

    • Moacir Wajner
  • Review Article |

    In this Review, Nedelsky and Taylor review the evidence that disturbances in phase transition dynamics and the material properties of ribonucleoprotein granules underlie the pathogenesis of many neurodegenerative diseases, including forms of amyotrophic lateral sclerosis and frontotemporal dementia, among others.

    • Natalia B. Nedelsky
    •  & J. Paul Taylor
  • Review Article |

    Conventional therapies for Parkinson disease (PD) include dopamine replacement and therapies targeting symptomatic relief, but these approaches fail to modify the underlying disease. This Review explores the novel PD treatment strategies currently being investigated, including pharmaceuticals, cell therapies, immunotherapies, gene therapies and new technologies.

    • Ahmad Elkouzi
    • , Vinata Vedam-Mai
    • , Robert S. Eisinger
    •  & Michael S. Okun
  • Perspective |

    The opioid crisis constitutes a public health challenge at the intersection of two interrelated medical problems — opioid addiction and chronic pain. In this Perspectives article, Volkow and Koroschetz discuss how neurologists are uniquely positioned to help address the opioid crisis.

    • Nora D. Volkow
    •  & Walter J. Koroshetz
  • Review Article |

    In the past few years, substantial progress has been made towards effective treatment of Batten disease, a family of paediatric neurodegenerative lysosomal storage disorders. In this Review, the authors discuss new therapies for Batten disease, including cerliponase alfa, the first globally approved agent, and considers promising new therapeutic avenues for future treatments.

    • Tyler B. Johnson
    • , Jacob T. Cain
    • , Katherine A. White
    • , Denia Ramirez-Montealegre
    • , David A. Pearce
    •  & Jill M. Weimer
  • Review Article |

    In this Review, Limousin and Foltynie discuss the current evidence on the long-term outcomes of deep brain stimulation in Parkinson disease and consider the clinical implications of these findings for future use of this therapeutic approach.

    • Patricia Limousin
    •  & Tom Foltynie
  • Review Article |

    Alzheimer disease (AD) pathology is found in almost all adults with Down syndrome (DS), primarily owing to overexpression of APP, present on chromosome 21. Here, Lott and Head examine the commonalities and disparities between DS and AD and highlight findings in DS that can inform research into AD in the general population.

    • Ira T. Lott
    •  & Elizabeth Head
  • Review Article |

    Abnormalities in sensory functions, including tactile, proprioceptive and nociceptive processing, are increasingly recognized in patients with focal dystonias. The authors explore the link between sensory system abnormalities and dystonic motor activity in the context of the 'network model' of dystonia.

    • Antonella Conte
    • , Giovanni Defazio
    • , Mark Hallett
    • , Giovanni Fabbrini
    •  & Alfredo Berardelli
  • Review Article |

    Over the past 20 years, deep brain stimulation (DBS) has transformed the treatment of movement disorders. Now, new therapeutic possibilities for DBS are emerging for other neurological and psychiatric disorders. This Review considers the clinical and scientific advances facilitated by DBS and the crucial questions, challenges and opportunities that face this technology.

    • Andres M. Lozano
    • , Nir Lipsman
    • , Hagai Bergman
    • , Peter Brown
    • , Stephan Chabardes
    • , Jin Woo Chang
    • , Keith Matthews
    • , Cameron C. McIntyre
    • , Thomas E. Schlaepfer
    • , Michael Schulder
    • , Yasin Temel
    • , Jens Volkmann
    •  & Joachim K. Krauss
  • Perspective |

    In this Perspectives article, Smith et al. address the misconceptions about the clinical and pathological features of chronic traumatic encephalopathy that cause confusion and controversy not only in the public but also among health-care professionals.

    • Douglas H. Smith
    • , Victoria E. Johnson
    • , John Q. Trojanowski
    •  & William Stewart
  • Review Article |

    Potential disease-modifying therapies for Alzheimer disease have mostly targeted brain accumulation of amyloid-β, but this approach has yet to provide substantial clinical benefits. The authors consider the reasons for this failure and suggest alternative strategies, including modification of risk factors.

    • Francesco Panza
    • , Madia Lozupone
    • , Giancarlo Logroscino
    •  & Bruno P. Imbimbo
  • Review Article |

    Biologics are emerging as important therapeutic tools in myasthenia gravis. In this Review, Marinos Dalakas considers the promise of these drugs and how they could overcome the limitations of current standard treatments.

    • Marinos C. Dalakas
  • Review Article |

    In this Review, Reindl and Waters provide an overview of what we currently know about anti-myelin oligodendrocyte glycoprotein antibodies and their association with demyelinating diseases, including the value of detection assays and evidence for antibody pathogenicity and its mechanism.

    • Markus Reindl
    •  & Patrick Waters
  • Review Article |

    Dementia with Lewy bodies (DLB) causes about one-tenth of all instances of dementia. This Review considers the substantial progress made in the basic and clinical research in DLB within the past few years, with discussion of the definition, pathology, genetics, prognosis, clinical features and current and future treatment of DLB.

    • Nikitas A. Arnaoutoglou
    • , John T. O’Brien
    •  & Benjamin R. Underwood
  • Review Article |

    Impairment of cerebral autoregulation after traumatic brain injury (TBI) is associated with poor outcomes, but the reasons underlying this association are poorly understood. This Review highlights genetic polymorphisms that might be linked to cerebrovascular function after TBI that might promote improved understanding of the pathogenic mechanisms underlying impaired vascular reactivity and offer potential targets for new therapies.

    • Frederick A. Zeiler
    • , Eric P. Thelin
    • , Joseph Donnelly
    • , Andrew R. Stevens
    • , Peter Smielewski
    • , Marek Czosnyka
    • , Peter J. Hutchinson
    •  & David K. Menon
  • Review Article |

    Early diagnosis of Alzheimer disease (AD) is crucial for efficient selection of clinical trial participants for drug development and ultimately for timely treatment of individuals with AD. Here, Claire Murphy examines the potential for olfactory and other sensory impairments as very early indicators of AD and considers the important questions that remain to be answered.

    • Claire Murphy
  • Review Article |

    In this Review, Handel and colleagues examine the contribution of thymic T cell selection to CNS autoimmune conditions and consider how a better understanding of this contribution could lead to novel therapeutic strategies for these conditions.

    • Adam E. Handel
    • , Sarosh R. Irani
    •  & Georg A. Holländer
  • Review Article |

    Pathogenic variants in POLG, which encodes the catalytic subunit of DNA polymerase γ, cause a spectrum of overlapping disease phenotypes. This Review describes the clinical features, pathophysiology, natural history and treatment of POLG-related disorders, focusing particularly on the neurological manifestations.

    • Shamima Rahman
    •  & William C. Copeland
  • Review Article |

    Premonitory symptoms of migraine can start hours to days before the onset of headache. In this Review, Karsan and Goadsby discuss the phenotypes of these premonitory symptoms and the insights that they provide into the neurobiology of migraine.

    • Nazia Karsan
    •  & Peter J. Goadsby
  • Review Article |

    New technological advances in genomics have enabled the rapid discovery of hundreds of gene mutations linked to epilepsy. This Review considers the prospects for precision medicine in genetic epilepsies, the use of conventional and novel experimental models to unpick the complex pathogenic mechanisms of these diseases and the opportunities and challenges that face basic and clinical researchers.

    • Scott T. Demarest
    •  & Amy Brooks-Kayal
  • Author Correction |

    • Elizabeth Wells
    • , Yael Hacohen
    • , Amy Waldman
    • , Jan M. Tillema
    • , Ariane Soldatos
    • , Beau Ances
    • , Susanne Benseler
    • , Bibi Bielekova
    • , Russel C. Dale
    • , Josep Dalmau
    • , William Gaillard
    • , Mark Gorman
    • , Benjamin Greenberg
    • , Ann Hyslop
    • , Carlos A. Pardo
    • , Robert C. Tasker
    • , E. Ann Yeh
    • , Amit Bar-Or
    • , Sean Pittock
    • , Adeline Vanderver
    • , Brenda Banwell
    • , Jessica Carpenter
    • , Irene Cortese
    • , Nathan Dean
    • , Racquel Farias-Moeller
    • , William Gallentine
    • , Carol Glaser
    • , Raphaela Goldbach-Mansky
    • , Ilana Kahn
    • , Bennett Lavenstein
    • , William McClintock
    • , William McDow
    • , Jennifer Murphy
    • , Avindra Nath
    • , Roger Packer
    • , Tova Ronis
    • , David Schleyer
    • , Stephanie Schleyer
    • , Peter Shibuya
    • , Ursula Utz
    • , Gilbert Vezina
    •  & David Wessel
  • Review Article |

    Traumatic brain injury (TBI) susceptibility and outcomes are influenced by numerous factors, many relating to sex and gender. The authors review recent research exploring the influence of sex and gender in the TBI context, focusing particularly on marginalized populations.

    • Tatyana Mollayeva
    • , Shirin Mollayeva
    •  & Angela Colantonio
  • Perspective |

    The development of treatment for multiple sclerosis over the past 25 years is a success of translational medicine. In this Timeline article, Tintore et al. chart major developments and discuss the implications for current and future patient management.

    • Mar Tintore
    • , Angela Vidal-Jordana
    •  & Jaume Sastre-Garriga
  • Review Article |

    Advances in biomarker research are aiding the development of targeted therapies and prevention strategies for Alzheimer disease (AD). In this Review, an international working group assesses the current status of blood-based AD biomarkers and outlines a roadmap for future research.

    • Harald Hampel
    • , Sid E. O’Bryant
    • , José L. Molinuevo
    • , Henrik Zetterberg
    • , Colin L. Masters
    • , Simone Lista
    • , Steven J. Kiddle
    • , Richard Batrla
    •  & Kaj Blennow
  • Review Article |

    Prevention of dementia through moderation of risk factors presents a promising strategy to counter the rising dementia epidemic. In this Review, Kivipelto and colleagues discuss lifestyle-related risk factors for dementia, results from clinical trials of lifestyle interventions and new multinational initiatives that aim to identify and test effective dementia prevention strategies.

    • Miia Kivipelto
    • , Francesca Mangialasche
    •  & Tiia Ngandu
  • Perspective |

    Many disorders of brain and behaviour affect human and veterinary patients. In this Perspectives, Orrin Devinsky and colleagues outline a cross-species approach to understanding neurological and psychiatric conditions, including pain, cognitive decline, epilepsy, anxiety and CNS infections, and propose that collaborations between physicians and veterinarians will generate new insights for therapy development.

    • Orrin Devinsky
    • , Jordyn M. Boesch
    • , Sofia Cerda-Gonzalez
    • , Barbara Coffey
    • , Kathryn Davis
    • , Daniel Friedman
    • , Brian Hainline
    • , Katherine Houpt
    • , Daniel Lieberman
    • , Pamela Perry
    • , Harald Prüss
    • , Martin A. Samuels
    • , Gary W. Small
    • , Holger Volk
    • , Artur Summerfield
    • , Charles Vite
    • , Thomas Wisniewski
    •  & Barbara Natterson-Horowitz
  • Review Article |

    In this Review, the authors describe the current data detailing the role of triggering receptor expressed on myeloid cells (TREM2) in microglial biology and Alzheimer disease (AD), and discuss the possibility of targeting TREM2 as a treatment for AD.

    • Tyler K. Ulland
    •  & Marco Colonna
  • Review Article |

    In this Review, Khalil et al. consider how technological advances have enabled the detection of neurofilament proteins in the blood, and discuss how these proteins consequently have the potential to be easily measured biomarkers of neuroaxonal injury in various neurological conditions.

    • Michael Khalil
    • , Charlotte E. Teunissen
    • , Markus Otto
    • , Fredrik Piehl
    • , Maria Pia Sormani
    • , Thomas Gattringer
    • , Christian Barro
    • , Ludwig Kappos
    • , Manuel Comabella
    • , Franz Fazekas
    • , Axel Petzold
    • , Kaj Blennow
    • , Henrik Zetterberg
    •  & Jens Kuhle
  • Review Article |

    Lafora disease is an autosomal recessive, progressive myoclonus epilepsy caused by loss of function of laforin or malin, leading to impaired glycogen metabolism. The authors review the clinical and molecular features of Lafora disease and discuss current and emerging treatment options.

    • Felix Nitschke
    • , Saija J. Ahonen
    • , Silvia Nitschke
    • , Sharmistha Mitra
    •  & Berge A. Minassian
  • Review Article |

    Advances in our understanding of the pathogenic mechanisms of spinocerebellar ataxias (SCAs) have resulted in the development of promising therapeutic strategies for these inherited neurodegenerative disorders. Here, Ashizawa and colleagues review the current progress and future challenges facing clinical trials of new therapies for the SCAs.

    • Tetsuo Ashizawa
    • , Gülin Öz
    •  & Henry L. Paulson
  • Review Article |

    In this Review, the authors consider advances over the past decade that have set the stage for a resurgence in attempts to predict seizures in epilepsy, and they propose new avenues of investigation that combine mechanisms, models, data, devices and algorithms.

    • Levin Kuhlmann
    • , Klaus Lehnertz
    • , Mark P. Richardson
    • , Björn Schelter
    •  & Hitten P. Zaveri
  • Review Article |

    Repeat expansions in the C9orf72 gene are a frequent cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Balendra and Isaacs review the pathological and mechanistic features of C9orf72-associated ALS and FTD, highlighting loss-of-function, gain-of-function and downstream mechanisms.

    • Rubika Balendra
    •  & Adrian M. Isaacs
  • Review Article |

    In this Review, the authors consider the evidence for the contribution of various factors to the pathogenesis of cerebral palsy, highlighting the complexities in its aetiology to inform translational research for the prevention of cerebral palsy.

    • Steven J. Korzeniewski
    • , Jaime Slaughter
    • , Madeleine Lenski
    • , Peterson Haak
    •  & Nigel Paneth
  • Review Article |

    Migraine is prevalent in the paediatric population and represents a major cause of disability. This Review outlines the epidemiology and natural history of paediatric migraine, discusses the recent landmark clinical trials of treatments for paediatric migraine and examines the best evidence-based interventions for this population in light of these new findings.

    • Serena L. Orr
    • , Marielle A. Kabbouche
    • , Hope L. O’Brien
    • , Joanne Kacperski
    • , Scott W. Powers
    •  & Andrew D. Hershey
  • Review Article |

    In this Review, Ferretti et al. discuss the evidence for sex-related differences in Alzheimer disease symptoms, progression, risk factors and treatment, and consider how understanding sex differences is crucial in developing precision medicine.

    • Maria Teresa Ferretti
    • , Maria Florencia Iulita
    • , Enrica Cavedo
    • , Patrizia Andrea Chiesa
    • , Annemarie Schumacher Dimech
    • , Antonella Santuccione Chadha
    • , Francesca Baracchi
    • , Hélène Girouard
    • , Sabina Misoch
    • , Ezio Giacobini
    • , Herman Depypere
    •  & Harald Hampel
  • Review Article |

    Glioblastomas remain one of the most aggressive and lethal tumours, with no effective treatments available. Here, Xandra Breakefield and colleagues examine the ways in which glioblastomas manipulate brain cells and immune cells in their environment to support tumour growth and the opportunities available for new therapies that disrupt these interactions.

    • Marike L. Broekman
    • , Sybren L. N. Maas
    • , Erik R. Abels
    • , Thorsten R. Mempel
    • , Anna M. Krichevsky
    •  & Xandra O. Breakefield
  • Review Article |

    This Review appraises the available evidence for spatial navigation and/or orientation deficits in preclinical, prodromal and confirmed Alzheimer disease with a focus on using spatial navigation as a diagnostic tool. Research gaps and future research priorities are also identified.

    • Gillian Coughlan
    • , Jan Laczó
    • , Jakub Hort
    • , Anne-Marie Minihane
    •  & Michael Hornberger
  • Review Article |

    Non-rapid eye movement (NREM) sleep parasomnias are thought to derive from incomplete arousal from NREM sleep. Here, the authors present evidence for coexistence of sleep-like and wake-like brain activity in disorders of arousal, including confusional arousals, sleep terrors and sleepwalking.

    • Anna Castelnovo
    • , Régis Lopez
    • , Paola Proserpio
    • , Lino Nobili
    •  & Yves Dauvilliers
  • Perspective |

    New research is increasingly challenging old notions of an immunologically isolated CNS. In this Perspectives article, Jun Chen and colleagues highlight discoveries on the beneficial roles of regulatory immune cells in brain repair and regeneration, and discuss their promise as therapies for neurological disorders.

    • Xiaoming Hu
    • , Rehana K. Leak
    • , Angus W. Thomson
    • , Fang Yu
    • , Yuguo Xia
    • , Lawrence R. Wechsler
    •  & Jun Chen