Reviews & Analysis

Ageing is a risk factor for many neurodegenerative diseases, including Alzheimer disease and Parkinson disease. This Review synthesizes current knowledge about the biological processes that underlie normal brain ageing and neurodegeneration, and discusses promising therapeutic strategies based on these mechanisms.

The benefits of targeting calcitonin gene-related peptide (CGRP) could go beyond migraine prevention, and three new studies report success with a new small-molecule CGRP receptor antagonist in acute migraine and with a monoclonal antibody in cluster headache.

In this Review, Matthews considers how advanced imaging techniques are enabling in vivo visualization of chronic CNS inflammation in multiple sclerosis that has previously been identified in histopathological studies.

Polymorphism in the apolipoprotein E (APOE) gene influences the risk of Alzheimer disease (AD). The authors describe recent research into the role of APOE in AD pathogenesis and discuss how new AD therapies could be tailored to APOE genotype.

Guillain–Barré syndrome (GBS) outbreaks associated with endemic and epidemic infections have increased in recent decades, and the need for standard treatment guidelines is compelling. A new study presents data from a worldwide prospective observational registry, providing insights into current treatment practices and laying the foundations for future clinical trials.

In patients with drug-resistant focal epilepsy, the success of surgery depends on predicting which resection or disconnection strategy will yield full seizure control. This Review highlights recent advances in presurgical assessment and discusses how concepts of focal epilepsy are changing.

An altered microglial landscape and ageing-related inflammatory changes contribute to the neurodegeneration associated with frontotemporal dementia (FTD). Here, Bright and colleagues discuss the evidence for a pathogenetic role of neuroinflammatory mechanisms in FTD, including links with autoimmunity and gene mutations associated with neuroinflammation.

In the past 20 years, understanding of the clinical manifestations, aetiopathophysiology, diagnosis and treatment of narcolepsy has greatly advanced. In this Review, Bassetti et al. present these advances, discuss unmet needs and offer future perspectives for the field of narcolepsy.

A new report presents post-mortem neuropathological follow-up of patients 4 months to 15 years after they received active amyloid-β (Aβ) immunization during its first trial in Alzheimer disease. The study documents effects on plaque clearance, tau pathology, plasma anti-Aβ antibody titres and final cognitive status; variability was seen between patients.

Migraine is one of the world’s most prevalent diseases, and approximately 2% of the general population experiences chronic migraine. Edvinsson and colleagues argue that inflammation could have an important role in migraine chronification, through a mechanism termed neurogenic neuroinflammation.

Ischaemic stroke causes a neuroinflammatory response, but the functional consequences of this response have been unclear. In this Review, Stoll and Nieswandt consider the roles of T cells, platelets and their interactions in this neuroinflammatory response and how these roles could be exploited therapeutically.

In this Review, Vezzani and colleagues discuss inflammatory pathways that are activated in pharmacoresistant epilepsy and can be modulated to therapeutic effect in animal models. They consider how targeting these pathways could overcome limitations of existing anti-epileptic treatments.

In this Review, Lloyd and Miron consider how regulation of microglial activation influences the ability of microglia to promote remyelination in the CNS. They also discuss the potential to exploit the pre-remyelination properties of microglia to treat multiple sclerosis and other demyelinating diseases.

A new study has found that levels of primary fatty amides in plasma correlate with amyloid-β pathology and other Alzheimer disease (AD)-related phenomena. In addition to identifying potential plasma biomarkers for AD, the findings suggest new avenues for investigation into the early stages of AD.

A new trial has demonstrated the benefits of intravenous thrombolysis, guided by perfusion imaging, 4.5–9.0 h after stroke onset and in individuals with wake-up stroke. In addition to extending the time window for thrombolysis after acute ischaemic stroke, these findings could aid the refinement of imaging and thrombolytic protocols.

In this Review of adult diffuse gliomas, Molinaro et al. discuss the latest epidemiological data and highlight advances from the past decade, including the identification of genetic and other risk factors for glioma included in the 2016 WHO integrated classification system.

Paterson and colleagues describe how stable isotope labelling kinetics (SILK) can be used to determine protein production and clearance rates. They highlight the promise of SILK studies for elucidating the role of pathogenic proteins in neurodegenerative diseases, including Alzheimer disease.

In this Review, Adams et al. discuss the latest insights into various aspects of hereditary transthyretin amyloidosis and its management, including its epidemiology, pathogenesis and the latest success with RNA interference and antisense oligonucleotide therapies.

The Global Burden of Disease, Injuries and Risk Factors 2016 study has shown that neurological diseases have the highest burden and that this burden is increasing. Stroke is the biggest contributor, highlighting a need to improve resources globally for stroke prevention, management and rehabilitation.

Patients present to general practitioners with a variety of symptoms that eventually turn out to be caused by early Parkinson disease. Now, methods to calculate Parkinson disease risk in general practitioner settings are becoming available.