Reviews & Analysis

In this Perspective, Edwards and colleagues present their opinion that functional neurological disorder is categorically different from feigning and malingering. They discuss clinical, epidemiological and experimental evidence in support of this view.

This article reviews key pathogenic mechanisms underlying the development of CNS autoimmunity, focusing on the role of autoantibodies that target neuronal and/or glial cell-surface antigens. The authors consider novel therapeutic approaches based on knowledge of the immunopathogenesis of autoimmune CNS disorders.

In this Review, the authors provide an overview of the evidence indicating that multiple sclerosis is a rare complication of infection with the Epstein–Barr virus and discuss the mechanisms that could underlie this association.

Here, Sven Bölte and colleagues consider the effects of sex and gender on neurodevelopmental conditions. They discuss the available epidemiological, behavioural, neurobiological and endocrinological evidence and highlight the importance of further research in this area.

Here, Timothy Steiner and Lars Stovner discuss the progression of migraine epidemiology over the last seven decades and question the apparent increase in migraine prevalence over time.

In this Perspective article, Lipkin et al. consider the contribution of cohort studies to our understanding of autism spectrum disorders (ASDs) and debate the promise and potential challenges of such studies for dissecting the causes of ASDs and developing interventional strategies.

Findings from a worldwide cohort of cognitively unimpaired individuals demonstrate that the presence of two canonical Alzheimer disease biomarkers — amyloid and tau — can reliably predict progression to mild cognitive impairment in the short-term. The results support the use of these biomarkers to diagnose preclinical Alzheimer disease in a clinical setting.

Facioscapulohumeral muscular dystrophy is caused by aberrant expression of the transcription factor DUX4. Tihaya, Mul and colleagues describe advances in the development of targeted treatments for facioscapulohumeral muscular dystrophy and discuss potential clinical trial outcome measures as well as molecular and imaging biomarkers.

The phase III Clarity AD clinical trial of lecanemab, an amyloid-targeting antibody, showed a small clinical benefit in people with Alzheimer disease. However, several questions remain regarding the true clinical relevance, safety and accessibility of lecanemab in this patient population.

The results of the first randomized, placebo-controlled trial of dimethyl fumarate in a cohort of participants with radiologically isolated syndrome showed efficacy against the risk of a first clinical demyelinating event. The findings pave the way for preventive medicine in multiple sclerosis and highlight the need for more precise prognostication of risk.

Advances in neuroimaging research have enabled the development of predictive models that integrate information from multiple brain systems. Here, Perovnik, Rus and colleagues discuss the detection and validation of neurodegenerative disease-specific functional brain networks and consider their relationship to pathological processes and disease-related genotypes.

Technological advances over the past decade have made precision genetic diagnosis available to many patients. The findings of a new study demonstrate that genetic diagnosis in epilepsy can lead to changes in clinical management that manifest as positive outcomes for the patient. The results herald a new era in which precision diagnosis will lead to precision medicine.

Here, Spires-Jones and colleagues review our current understanding of the mechanisms underlying synaptic degeneration in Alzheimer disease and highlight key questions that still need to be answered. They also discuss novel therapeutic approaches that target the synapse.

Gene therapies show promise for treating epilepsy, but most strategies target cells across an entire brain region rather than selecting pathologically hyperexcited neurons. Researchers have now developed a conditional gene therapy strategy that downregulates firing activity only in neurons that are pathologically overactive and switches off when brain circuit activity has returned to baseline.

Amyotrophic lateral sclerosis (ALS) is a devastating, incurable disease characterized by progressive loss of upper and lower motor neurons. Here, the authors describe the current landscape of genetic therapies for ALS and discuss new opportunities for gene replacement therapy, focusing on loss-of-function mutations.

A new study provides evidence for an association between COVID-19 and long-term neurological syndromes. The findings highlight the need for further research into the long-term neurological consequences of SARS-CoV-2 infection and the development of strategies that lessen the effects of these consequences on patient quality of life and on healthcare systems.

Despite substantial research advances, treatment of neuropathic pain remains inadequate and responses to treatment are highly variable. In this Perspective, the authors argue that rational stratification of patients with neuropathic pain will aid identification of subgroups of patients who will benefit most from a given treatment.

In this Review, Savitz and Cox consider the evidence for a model of cell-based therapy referred to as the bioreactor hypothesis, in which exogenous cells migrate to peripheral organs and reprogramme host immune cells to generate an anti-inflammatory, regenerative environment.

In a study of 17,000 Medicare beneficiaries with mild cognitive impairment or dementia, non-Hispanic white older adults were more likely than Asian, Black or Hispanic older adults to have elevated cortical amyloid, as measured by PET. These findings have important implications for the use of amyloid-targeting therapies.

In this Review, the authors provide an overview of evidence that activity-regulated myelination is required for brain adaptation and learning, and discuss how dysregulation of activity-dependent myelination contributes to neurological disease and could be a new therapeutic target.