McDonald Criteria 2024: what changed in multiple sclerosis (MS) diagnosis — and why it matters to patients

In brief: the 2024 McDonald criteria update refines how clinicians confirm dissemination in space (DIS) and dissemination in time (DIT), recognizes the optic nerve as a distinct region, and discusses supportive markers (CVS, PRL, κ free light chains) — aiming for earlier and more accurate diagnosis while reducing misdiagnosis.

The McDonald criteria are international diagnostic rules used by neurologists to confirm MS based on the clinical picture, MRI findings, and additional tests — while minimizing the risk of a wrong diagnosis. The 2024 revision is designed to support earlier and more precise diagnosis in patients where this is justified.

Why the criteria were updated in 2024

Since 2017, diagnostic tools have improved substantially: MRI markers became more informative, knowledge about inflammatory biology expanded, and CSF biomarkers became more widely discussed. The goal of the 2024 revision is to support earlier correct diagnosis where appropriate, while maintaining (or strengthening) specificity — protection against mistakenly labeling someone with MS.

Core logic: “dissemination in space and time”

MS diagnosis relies on evidence that inflammatory lesions occur:

• in different CNS regions (dissemination in space, DIS);
• at different points in time (dissemination in time, DIT).

MRI and supportive tests can demonstrate these principles earlier than waiting for multiple clinical attacks.

How DIS and DIT are assessed in 2025 when MS is suspected

Across different McDonald versions, the foundation remains the same: proving that lesions arise in different anatomical regions and at different times. The 2024 revision keeps the core principles but adds supportive tools that may help confirm them earlier and more precisely, especially in borderline cases.

Dissemination in space (DIS): where lesions should be

DIS means lesions involve different typical CNS regions. Current practice considers:

• periventricular (around the lateral ventricles);
• cortical and juxtacortical (cortex and adjacent white matter);
• infratentorial (brainstem and cerebellum);
• spinal cord;
• optic nerve (added as a separate region in the 2024 revision).

To meet DIS, lesions are typically required in at least two different regions. A key safety principle is that the MRI pattern must have no more likely alternative explanation (vascular, metabolic, infectious, etc.).

Dissemination in time (DIT): how activity at different times is shown

DIT means inflammation in the CNS is not a single-time event. In 2025, DIT may be supported by:

• simultaneous enhancing and non-enhancing lesions on the same MRI;
• new lesions on follow-up MRI compared with a prior scan;
• supportive markers of chronic activity (e.g., PRL) in selected situations;
• supportive CSF markers of intrathecal inflammation (e.g., κ-FLC) when available and clinically appropriate.

This means DIT can sometimes be supported without waiting for another clinical relapse, provided objective evidence is strong and alternatives have been excluded.

Key 2024 additions

Optic nerve as a distinct region

Traditionally, DIS focused on four typical regions: periventricular, cortical/juxtacortical, infratentorial, and spinal cord. In the 2024 revision, the optic nerve can be treated as a separate region.

This is particularly relevant when visual symptoms are the leading or earliest manifestation. The core safety rule remains: clinicians must exclude a more likely alternative cause of optic nerve pathology.

What CVS, PRL and κ-FLC add — and why it matters

These features do not “make the diagnosis” on their own. They can increase diagnostic confidence in challenging cases and help distinguish MS from mimics.

Central Vein Sign (CVS)

CVS refers to a small vein visible in the center of a demyelinating lesion on dedicated MRI sequences. It improves specificity, especially when standard MRI findings are borderline.

Paramagnetic Rim Lesions (PRL)

PRL are lesions with a paramagnetic rim reflecting chronic active inflammation. They may support the interpretation of disease chronicity and, in selected situations, DIT.

κ free light chains (κ-FLC)

κ-FLC are a quantitative CSF marker of intrathecal immune activity. They are considered supportive when available and clinically appropriate.

Radiologically isolated syndrome (RIS) and “atypical” situations

RIS describes MRI findings suggestive of MS in a person without typical clinical episodes. In selected situations, diagnostic frameworks may be discussed, but only with strict adherence to criteria and careful exclusion of alternatives.

Reducing the risk of misdiagnosis

MS misdiagnosis can occur with migraine, small-vessel disease, and other conditions. That is why clinical context, MRI quality, evolution over time, and ruling out NMOSD/MOGAD in uncertain cases are critical.

What this changes for patients

• Earlier confirmation in some cases, enabling faster discussion of monitoring and treatment choices.
• Greater emphasis on accuracy: supportive tools help reduce the risk of a wrong diagnosis.
• Clearer boundaries vs NMOSD and MOGAD, which is essential for safe therapy selection.

FAQ

Sources

1. Montalban X, et al. Diagnosis of multiple sclerosis: 2024 revisions of the McDonald criteria. Lancet Neurology. 2025;24:850–865. DOI: 10.1016/S1474-4422(25)00270-4 (PubMed: 40975101)
2. ECTRIMS / International Advisory Committee on Clinical Trials in MS. 2024 McDonald Criteria – Slide Deck. PDF
3. Cohen JA. 2024 revision of the McDonald diagnostic criteria for MS: Substantial and substantive changes. Multiple Sclerosis Journal. 2025;31(11):1269–1275. DOI: 10.1177/13524585251351860 (PubMed: 40652383)