Reviews & Analysis

In this Review, the authors summarize the interactions of the neurovascular unit with systemic biology after ischaemic stroke, consider how these interactions influence stroke outcome, and discuss how these interactions could be targeted to improve outcomes.

In this Perspective article, the authors outline how studying multiple sclerosis (MS) genetics in ancestrally diverse populations is likely to yield insights that could benefit individuals with MS from all ancestral groups.

In this Perspective, Fiorio et al. discuss the relationship between functional neurological disorder and placebo and nocebo effects, with the aim of providing insights into the pathogenesis of the disorder and identifying potential therapeutic targets.

In this Review, Fong and Inouye explore mechanisms that might be common to both delirium and dementia. They present delirium as a possible modifiable risk factor for dementia and discuss the importance of delirium prevention strategies in reducing this risk.

Numerous studies have attempted to identify pathogenic autoantibodies in people with multiple sclerosis (MS), but their results are conflicting. In this Perspective, the authors explore the available evidence and provide their own opinions on a possible role for autoantibodies in MS.

A phase II trial of the tau antibody semorinemab indicates that it has no clinical benefit in the earliest stages of Alzheimer disease. The repeated finding that antibody-mediated reductions in protein pathology have limited or no clinical benefit indicates that we need to consider more specific or combined therapeutic targets.

In this Review, the authors provide detailed insight into how the gut microbiota influences the immune system, with implications for neuroinflammation, and discuss the accumulating evidence that the gut microbiota is an important factor in multiple sclerosis pathogenesis and a potential therapeutic target.

Cognitive rehabilitation is a promising approach to limit the effect of cognitive impairment on patients with multiple sclerosis, although results so far are conflicting. A new study indicates that structural and functional MRI techniques could provide reliable measures to predict treatment responses and tailor the rehabilitative approach to each patient.

This Review considers how variants in genes encoding proteins that regulate epigenetic mechanisms might contribute to epilepsy. The discussion is structured around five categories of epigenetic mechanisms: DNA methylation, histone modifications, histone–DNA crosstalk, non-coding RNAs and chromatin remodelling.

In this Roadmap, Marrie and colleagues set out the steps needed to improve our understanding of the multiple sclerosis (MS) prodrome and develop standardized criteria for identifying individuals with prodromal MS, thereby facilitating trials of interventions that could slow progression to classical MS.

A new longitudinal study involving carriers of amyotrophic lateral sclerosis (ALS)-associated mutations has identified a prodromal phase of ALS characterized by mild motor impairment. The findings could help us to define a time window during which neuroprotective interventions might be effective in patients with genetic forms of ALS.

The prominence of gastrointestinal dysfunction among the non-motor features of Parkinson disease (PD) indicates a close bidirectional link between the brain and the gut. This Review discusses the proposed roles of gut-related factors in PD development, progression and treatment responses, and as therapeutic targets.

The fifth edition of the WHO classification of CNS tumours was published in 2021. Here, Horbinski and colleagues summarize the main changes in this new edition and discuss how each change will affect post-surgical treatment, clinical trial enrolment and cooperative studies.

In this Review, Oh and Bar-Or provide an overview of selected emerging therapies for multiple sclerosis with the potential to limit non-relapsing, progressive disease injury and to promote tissue repair, thereby addressing crucial unmet therapeutic needs.

In this Perspective, the authors present their vision for a closed-loop system for automatic symptom monitoring and levodopa administration in individuals with Parkinson disease. The system would capitalize on the ongoing advances in wearable sensor technology, drug delivery systems and machine learning.

A new genome-wide association study has identified 41 previously unknown loci associated with Alzheimer disease. However, these data provide limited insight into disease mechanisms or benefits for clinical prediction of Alzheimer disease.

A new paper published in Neuron presents an analysis of mRNA expression in human and mouse trigeminal ganglia at single-nucleus resolution. The resulting resource is thought-provoking and suggests new targets for pain therapies; however, the findings should be interpreted in the context of the available protein data and warrant functional verification.

Recent technological advances have enabled the detection of specific forms of phosphorylated tau in blood. Here, the authors summarize the performance of blood phosphorylated tau biomarkers in the context of Alzheimer disease and highlight related ethical, analytical and clinical challenges.

Many episodes of status epilepticus do not respond to first-line treatment with benzodiazepines. In this Perspective, Richard Burman and colleagues discuss seizure-induced alterations to the sensitivity of the GABA receptor to benzodiazepines, presenting these changes as a possible mechanism of treatment resistance.

In this Review, Diener et al. discuss the concept of embolic stroke of undetermined source, proposing updates to the criteria and diagnostic algorithm in light of evidence gathered since the concept was first introduced.