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Multiple sclerosis is among the most common causes of disability in the young and its prevention is a feasible, albeit ambitious, goal. In this Perspective, Dobson et al. discuss the challenges in developing and testing preventive interventions in MS and propose strategies and solutions.

This article reviews the epidemiology and clinical characteristics of multiple sclerosis (MS) in Latin America and how they might be influenced by genetic, environmental and socioeconomic factors that are unique to this region. The authors also describe diagnostic criteria, differential diagnosis and current approaches to MS treatment and management in Latin American countries.

Racial and ethnic disparities in MS susceptibility and outcomes are often attributed to immutable factors such as genetic ancestry. In this Perspective, however, the authors argue that structural racism can lead to biological changes by shaping environmental exposures and lived experiences — a phenomenon termed ‘embodiment’.

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.

Epidemiological data indicate that genetic and environmental factors interact to determine an individual's risk of developing multiple sclerosis (MS). Handel et al. examine the key periods of life during which the environment might contribute to MS susceptibility, focusing on three putative MS risk factors: sun exposure (and its relationship with vitamin D levels), Epstein–Barr virus infection, and smoking.

A genome-wide association study including 22,389 cases of multiple sclerosis finds an association with disease progression at the DYSF–ZNF638 and DNM3–PIGC loci and identifies a potential of higher educational attainment in slowing disease progression.

Multiple sclerosis and type 1 diabetes mellitus are seemingly very different autoimmune diseases. However, this Review discusses recent studies in genetics, epidemiology and immunology that have uncovered many features common to both disorders. Overlaps between T1DM and MS might lead to similar strategies in preventing and treating these debilitating conditions.

Philip De Jager and colleagues report results of a large genome-wide association and replication study for multiple sclerosis. The work uncovers three new susceptibility loci for MS, including common and rare variants at TNFRSF1A and common variants at IRF8 and CD6.

Autologous haematopoietic stem cell transplantation (AHSCT) is a treatment option for some forms of multiple sclerosis (MS), but uncertainties remain about its implementation in clinical practice and treatment protocols need to be optimized. This Consensus Statement provides guidance and recommendations for the use of AHSCT in MS and neuromyelitis optica spectrum disorders.

Despite its relative rarity, pediatric multiple sclerosis (MS) is an important entity, as it provides unique insights into disease processes related to MS. Clinical, MRI and laboratory data suggest differences in the immune response and CNS environment between adults and children with MS. Yeh et al. provide a comprehensive overview of the pediatric MS field, including epidemiology, disease mechanisms, diagnosis and treatment.

Autoimmunity in multiple sclerosis (MS) is generally considered to be directed against components of myelin or oligodendrocytes. However, this Perspective argues that an immune attack on the ion and water homeostasis machinery in astrocytic endfeet is the primary event in MS and that myelin damage results from astrocyte dysfunction.

Myelin oligodendrocyte glycoprotein antibody-associated disease is an immune-mediated demyelinating disease that is distinct from multiple sclerosis but shares some of its characteristics. This Expert Recommendation, based on a Magnetic Resonance Imaging in MS workshop, proposes a diagnostic algorithm for the differential diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease and multiple sclerosis, using serological, imaging and clinical features.

Autologous haematopoietic stem cell transplantation has produced striking results in patients with aggressive multiple sclerosis in small trials. In this Review, Muraro et al. provide an overview of the procedure, detail evidence for its high efficacy in multiple sclerosis, and provide recommendations for its clinical use and future trials.

Increasing evidence supports a role for B cells and antibodies in the pathogenesis of multiple sclerosis (MS). Here, Meinl and colleagues discuss the proinflammatory contribution of B-cell signalling in MS, and consider potential targets of autoantibodies. The B-cell response to various MS therapies is also summarized.

Tumour-infiltrating lymphocytes from glioblastoma can recognize bacterial and gut microbial peptides.

Cerebrospinal fluid (CSF) investigation should be routinely performed in patients with a first clinical event that is suggestive of multiple sclerosis (MS). This Review highlights the value of existing CSF biomarkers in eliminating potential differential diagnoses for MS and understanding the underlying pathophysiology of this condition. The authors also discuss the potential for novel biomarkers that could be used in prognosis.

The higher incidence of multiple sclerosis (MS) in women than in men is widely acknowledged in the literature. The role of sex-related factors is, therefore, an important avenue for further investigation and for the development of novel therapeutic strategies for MS. In this Review, Voskuhl and Gold examine the effects of sex-related factors on MS susceptibility, activity and progression, and identify important areas for future research.

A cross-reactive antibody and T cell response is identified in a large portion of patients with multisystem inflammatory syndrome in children.

By leveraging paired microbiome and human gene expression data from pediatric patients who underwent hematopoietic cell transplantation, distinct lung–immune system–microorganism interactions were identified as important drivers of fatal lung injury.

The end of 2015 saw the passing of John F. Kurtzke and Richard T. Johnson, two legends in neurology, and founding fathers of neuroepidemiology, neurovirology and neuroimmunology. Here, we pay tribute to these two giants by discussing their impact on the genesis of these profoundly important disciplines.

2013 witnessed advances in many aspects of multiple sclerosis (MS) research. Two studies highlighted a potential role for salt as an MS trigger, and one immunomodulatory drug performed well in clinical trials. Moreover, treatment effects of MS drugs were shown to correlate inversely with brain atrophy and disease progression.

The growing literature on comorbidity in multiple sclerosis (MS)—in particular, the association of MS with other autoimmune diseases—provides interesting clues to the complex pathogenesis of this disease, but also raises awareness of the important issues that need to be considered in its management.

In this Review, Reindl et al. discuss a range of CNS disorders that are known to be associated with autoantibodies against myelin oligodendrocyte glycoprotein (MOG). They examine the experimental evidence for a role for MOG autoantibodies in the pathogenesis of demyelinating CNS disorders such as multiple sclerosis and acute disseminated encephalomyelitis, and explore the potential of MOG to function as a biomarker in these diseases.

Most patients who present with longitudinal extensive transverse myelitis (LETM) are diagnosed with neuromyelitis optica (NMO). Trebst et al. use case studies of patients without NMO who presented with spinal lesions to show the variety of different etiologies that can underlie LETM. The authors highlight the diagnostic indicators and difficulties encountered in making differential diagnoses in these patients.

Genome-wide analysis identifies variants associated with the volume of seven different subcortical brain regions defined by magnetic resonance imaging. Implicated genes are involved in neurodevelopmental and synaptic signaling pathways.

In this Review, the authors discuss all aspects of immune-mediated disorders of the CNS in children, from the clinical features and treatment to pathological mechanisms and biomarkers, and outline priorities for collaborative research to develop precision medicine for these disorders.

Studies suggest almost the same amount of biomass is present in subterranean settings as on Earth’s surface. Here, the authors propose that a large intraterrestrial microbial system was responsible for mineralization in southern Spain, and that microbes may play a major role in sub-surface ore-forming processes.

Exome-wide analysis identifies rare and low-frequency coding variants associated with body mass index. Gene-based meta-analysis and functional studies implicate 13 genes, eight of which are novel, and neuronal pathways as factors in human obesity.

This overview of the ENCODE project outlines the data accumulated so far, revealing that 80% of the human genome now has at least one biochemical function assigned to it; the newly identified functional elements should aid the interpretation of results of genome-wide association studies, as many correspond to sites of association with human disease.

Tumor–normal paired DNA samples from a breast cancer cell line and a matched lymphoblastoid cell line enable calibration of clinical sequencing pipelines and benchmarking ‘tumor-only’ or ‘matched tumor–normal’ analyses.

Paediatric systemic lupus erythematosus (SLE) has higher morbidity and mortality than adult-onset SLE. Interestingly, a new paper reinforces these differences between adult and childhood disease, but reasons for the more severe phenotype in children are varied and poorly understood.

In this Review, the authors describe how immune responses are initiated and propagated against antigens found in the central nervous system (CNS). They explain how the unique anatomy of the CNS affects immune surveillance of its tissues, and discuss the implications for autoimmune responses in the CNS.

Epidemiologic, genetic and immunophenotypic evidence suggests that oligoarticular and polyarticular subtypes of juvenile idiopathic arthritis are distinct etiopathologic conditions with some overlapping pathogenic pathways. As discussed in this Review, further research is needed before we can generate a full molecular picture of these chronic childhood arthropathies.

The selection of patients with prostate cancer who are suitable for focal therapy remains a controversial topic. In this Review, Mouraviev and colleagues discuss pathological insights into the biology of early-stage disease, and highlight the critical role of three-dimensional prostate mapping protocols in the localization of disease.

African Americans, Hispanics and Native Americans are significantly underrepresented in chemistry and related sciences. An innovative approach based on course revision, peer support, precollege training and strong mentoring offers promise for engaging and retaining more underrepresented minority students and more members of the majority population in these fields.