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In multiple sclerosis (MS), a clinicoradiological paradox exists whereby clinical and MRI measures show poor correlation. New findings suggest that quantitative imaging to assess microstructural changes in the spinal cords of patient with MS could overcome this paradox, and provide novel markers to monitor disease progression.

Patients with relapsing–remitting multiple sclerosis have been shown to benefit from disease-modifying treatments over prolonged periods. More focus should now be placed on monitoring the long-term evolution of this disease (making use of tools such as MRI), alongside the patients' response and adherence to such treatments.

In the second part of the MAGNIMS network's evidence-based guidelines, Wattjes and colleagues discuss the use of MRI in prognostication and follow-up in patients with multiple sclerosis. The group recommend several techniques that are useful for monitoring disease activity and treatment efficacy, and identify those techniques that require further study.

2010 represented a milestone in the history of multiple sclerosis monitoring and treatment. MRI and immunological biomarkers were identified to track disease evolution and, ultimately, to guide treatment decisions. Moreover, oral disease-modifying therapies emerged that should increase treatment regimen adherence and improve patient outcomes.

The use of MRI in patients with multiple sclerosis (MS) is commonplace in clinical settings. However, the precise implementation of MRI in the diagnosis of MS is highly variable, which is problematic in the context of the substantial technical advances of the past decade. In these Evidence-based Guidelines, members of the MAGNIMS study group present a standardized approach to the use of MRI in the diagnosis of MS.

Genome-wide association analyses of intracranial and nine subcortical brain volumes in 74,898 participants of European ancestry identify 254 independent loci and yield polygenic scores accounting for brain variation across ancestries.

Data collected from 138,015 hospital-based singleton births in four sub-Saharan African countries revealed an association between heat exposure in the week leading up to the birth and perinatal mortality.

This study identifies distinct genetic-epigenetictranscriptional interplay at the 1q21.1 locus in relation to neuronal deficits in primary progressive multiple sclerosis (PPMS).

Lesion activity detected on MRI scans has become an accepted surrogate for disease activity in relapsing–remitting multiple sclerosis (MS). Barkhof and colleagues provide key recommendations for efficient use of MRI in clinical trials for relapse-onset MS, including practical issues related to acquisition, analysis and reporting of MRI data, approaches to optimization of trial design, and safety considerations.

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.

A new study suggests that patients with relapsing–remitting multiple sclerosis can experience long-term increases in disability in the absence of disease relapses. Monitoring this ‘silent progression’ will require a paradigm shift in the way disease progression is evaluated.

MRI provides a very sensitive reflection of the histopathological changes in multiple sclerosis. Many short-term studies fail to appreciate the relationship between MRI and clinical findings, although such shortcomings might be argued to reflect a weakness of clinical measures, rather than of MRI.

In this Consensus statement, the Magnetic Resonance Imaging in MS (MAGNIMS) study group reviews the application of brain and spinal cord atrophy in clinical practice in the management of MS and makes consensus statements and recommendations for future research.

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.

The extent to which white matter lesions affect brain function in elderly individuals has important implications for the development of drugs to treat cognitive impairment and dementia. In this article, Frisoni et al. argue that white matter lesions can contribute to cognitive impairment in elderly individuals, although their effects are minor when compared with those of other causes of cognitive deterioration, such as Alzheimer's disease.

Here, the authors report that exhausted HCV-specific CD8+ T cells are marked by upregulation of p53 signaling already detectable in an early phase of chronic HCV infection and by a later development of a repressive chromatin state, and show that chemical targeting of these pathways improves CD8+ T cell metabolism and antiviral function.

In a GWAS study of 32,438 adults, the authors discovered five novel loci for intracranial volume and confirmed two known signals. Variants for intracranial volume were also related to childhood and adult cognitive function and to Parkinson's disease, and enriched near genes involved in growth pathways, including PI3K-AKT signaling.

The occurrence of cortical lesions in multiple sclerosis (MS) is an early phenomenon. Furthermore, immunohistochemical data indicate that demyelination of cortical gray matter is extensive in MS. In this Review, Calabrese and colleagues provide a summary of the main histopathological and MRI findings with regard to cortical lesions in MS, and discuss the evidence indicating that cortical lesion burden positively correlates with the severity of physical and cognitive impairments.

The study performed on a large, heterogeneous and multisite sample of youth with anxiety disorders reveals that only modest classification performances can be realistically achieved with machine learning using neuroanatomical data.

Multiple sclerosis is characterized by the formation of demyelination lesions throughout the central nervous system, leading to neurological dysfunction. This Primer provides an overview of the immunopathology, diagnosis and management of multiple sclerosis.

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.

In 2018, the distinguishing pathological features of white matter lesions in patients with progressive multiple sclerosis (MS) were refined, and serological and MRI biomarkers of clinical worsening and evolution to progressive MS were identified. We also saw therapeutic advances in progressive MS with the emergence of new neuroprotective strategies and putative markers of neurodegeneration.

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.

In our third and final installment from the MAGNIMS study group, Enzinger et al. consider how dramatic progress in MRI has enabled nonconventional structural imaging techniques to shed new light on the pathophysiology of multiple sclerosis. The authors discuss the present use of these techniques in the disease, and consider their future application to clinical research and practice.

In this Review, MAGNIMS provides an update on the imaging features that differentiate multiple sclerosis (MS) from its most common imaging mimics and a summary of the red-flag MRI features that indicate a diagnosis other than MS.