The 2024 McDonald Criteria: How Multiple Sclerosis Is Diagnosed Now

The short answer

Multiple sclerosis is now diagnosed using the 2024 revisions of the McDonald criteria, published in September 2025 in The Lancet Neurology by an international committee led by Xavier Montalban, Christine Lebrun-Frénay, Jiwon Oh, and colleagues. The revision does two things at once. It lets clinicians confirm MS earlier, including in some people who have not yet had a classic attack, by adding the optic nerve as a site of disease and by admitting newer biomarkers such as the central vein sign and kappa free light chains. At the same time, it tightens the rules for the people most often misdiagnosed, so that speed does not come at the cost of accuracy.

This article is educational and not medical advice.

What the McDonald criteria are trying to do

MS is an inflammatory disease of the brain, spinal cord, and optic nerves. There is no single test that proves it. Instead, since 2001 the McDonald criteria have combined the clinical picture with MRI and spinal fluid findings to show that damage is spread across the central nervous system (dissemination in space) and has occurred at more than one point in time (dissemination in time). The 2024 revision, developed by the International Advisory Committee on Clinical Trials in MS with 56 experts from 16 countries and a consensus threshold of at least 80 percent agreement, is the first full update since 2017.

The tension the committee had to manage is real. Diagnose too slowly and a treatable disease progresses while the patient waits. Diagnose too loosely and people are labeled with a lifelong condition, and sometimes given immune-modulating drugs, for something else entirely. Studies over the past decade have repeatedly shown that a meaningful share of people carrying an MS label do not actually have it, often because ordinary changes on brain MRI were over-read.

The optic nerve joins the map

The most intuitive change is anatomical. Earlier criteria recognized four regions where MS lesions accumulate: periventricular, cortical or juxtacortical, infratentorial, and spinal cord. The 2024 revision adds the optic nerve as a fifth region.

This matters because optic neuritis, an inflamed optic nerve causing painful vision loss, is one of the most common ways MS first announces itself. Under older rules, that event did not formally count toward showing disease spread. Now it can, documented through the clinical history plus supporting tests such as optical coherence tomography, visual evoked potentials, or MRI of the nerve. Dissemination in space is generally shown by involvement of at least two of the five regions.

New biomarkers enter the criteria

Two imaging findings and one spinal-fluid test are the headline additions.

The central vein sign

MS lesions tend to form around a small central vein, a pattern visible on specialized MRI sequences. Ordinary age-related or vascular white-matter spots usually do not have this signature. The 2024 criteria let the central vein sign help confirm MS, which is especially useful for separating true demyelination from the vascular changes that accumulate with age and blood-pressure problems. Paramagnetic rim lesions, which mark chronically active inflammation, are recognized as a further supportive marker.

Kappa free light chains

Historically, the spinal-fluid evidence for MS came from oligoclonal bands, a labor-intensive test showing that the immune system is producing antibodies inside the central nervous system. The 2024 criteria accept the kappa free light chain index as an interchangeable alternative. It is measured on an automated platform, is less dependent on the individual reading it, and reported diagnostic performance is comparable to oligoclonal bands. Positive spinal fluid, by either method, can now substitute for waiting to see a second attack over time.

A shift toward a biological diagnosis

Because these markers can stand in for the passage of time, dissemination in time is no longer mandatory in every scenario. The committee has described this as a move toward diagnosing MS biologically, the way fields such as Alzheimer's and Parkinson's disease increasingly define disease by underlying pathology rather than by waiting for symptoms to recur. In practice this can allow diagnosis at the first clinical event, and in carefully defined cases of radiologically isolated syndrome, where MS-like lesions are found incidentally, before any symptom at all.

The guardrails against misdiagnosis

Earlier diagnosis raises the stakes on getting it right, so the revision builds in safeguards rather than leaving them implicit.

The clearest example concerns people over 50 and those with vascular risk factors such as high blood pressure, diabetes, high cholesterol, or smoking, as well as people whose main complaint is headache. In these groups, small white-matter spots on MRI are common and are frequently not MS at all. The 2024 criteria ask for stronger evidence in these situations, for example a spinal cord lesion, positive spinal fluid, or the central vein sign, before MS is diagnosed. Similar caution is applied in children, whose differential diagnosis differs from adults.

The underlying logic is that a biomarker's value depends on who is being tested. In a young person with typical optic neuritis, a supportive MRI finding is highly meaningful. In a 60-year-old with vascular risk and nonspecific spots, the same finding needs corroboration. Requiring the more specific markers exactly where false positives cluster is how the committee tried to buy earlier diagnosis without inflating error.

What this means in practice

For someone being evaluated, the 2024 framework can mean fewer months of uncertainty and, potentially, a diagnosis from a single well-characterized episode supported by MRI and spinal-fluid or vein-based markers. It also means the workup may look different from a relative's experience a decade ago, with newer MRI sequences and the kappa free light chain test appearing alongside familiar ones. As a physician-scientist, my aim in describing these changes is to help readers understand what their care team is weighing, not to substitute for that team's judgment. Diagnostic criteria are tools for specialists, and applying them still depends on the full clinical picture.