The first revision of the McDonald criteria in nearly a decade could improve diagnostic speed and accuracy in multiple sclerosis (MS), reducing the period of uncertainty and permitting earlier start of treatment, the authors of the criteria reported.

Developed by an international panel of more than 50 experts, the updated criteria incorporate an array of more recently identified or validated biomarkers and place an emphasis on neuroimaging to allow diagnostic criteria across a variety of presentations, including no outward manifestations of disease.

“These revisions represent an important step forward for the field. By integrating novel biomarkers and rigorous consensus methodology, the updated criteria strengthen diagnostic accuracy and become more globally applicable,” Bruno Stankoff, MD, PhD, president of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) said in a statement. 

ECTRIMS and the National Multiple Sclerosis Society in the US cosponsored the committee that developed the criteria, which were published in the October issue of The Lancet Neurology.

The criteria — developed by a committee cosponsored by ECTRIMS and the US National Multiple Sclerosis Society — are already shaping the conversation. At the Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2025, which is currently underway, several sessions will focus on their impact.

“This balance between sensitivity and specificity is essential — and now ensures that people with MS can be identified earlier, equally across all ages, and that misdiagnosis is reduced,” added Stankoff, who also is professor of neurology at Université Pierre-et-Marie-Curie, Paris.

‘Substantial Changes’ in New Criteria

Despite their release more than halfway through 2025, the new criteria are officially known as the 2024 revisions of the McDonald criteria. The deliberations began in late 2023 and were led by the International Advisory Committee on Clinical Trials in MS. 

As reported by Medscape Medical News, elements of the new criteria were previewed at the 2024 ECTRIMS conference, the 2025 Consortium of Multiple Sclerosis Centers meeting, and other major medical conferences. 

The latest version of the McDonald criteria — which were first published in 2001 and arrived shortly before the start of the 2025 ECTRIMS meeting — reflects “substantial” changes, Steven L. Galetta, MD, New York University School of Medicine, New York, and Jeffrey L. Bennett, MD, University of Colorado Anschutz Medical Campus, Aurora, wrote in an accompanying commentary. 

Among the highlights in the new version are the addition of the optic nerve as a fifth topographic sign of disease activity and the inclusion of central vein sign (CVS) and paramagnetic rim lesions (PRLs) as novel MRI biomarkers.

While they consider the addition of the optic nerve as the “most notable” change, they also consider the new criteria a reorientation.

Representative of a greater “global perspective on early diagnosis of multiple sclerosis,” the new criteria place “a strong emphasis on neuroimaging, CSF [cerebrospinal fluid] analysis and paraclinical tests,” the authors wrote.

The need for standardized criteria led the authors to include a pragmatic approach in places where access to imaging and laboratory tests is limited. However, the accelerated time to diagnosis that the new criteria make possible depend largely on paraclinical testing, including specialized neuroimaging techniques. This includes detection of not only lesions on the optic nerve but also CVS and PRLs. 

As the fifth topographic site of MS activity, lesions on the optic nerve join lesions on the spinal cord and in the periventricular, infratentorial, and the intracortical/juxtacortical regions for providing evidence of dissemination in space (DIS). For the optic nerve, strategies of detection include optical coherence tomography, MRI, and visual evoked potentials. 

By adding a fifth topographic site, the new criteria make an MS diagnosis easier to reach, according to the authors. This is noteworthy because the new criteria preserve the 2017 requirement of showing both DIS and dissemination in time. 

Easier Diagnosis of Atypical Features

Similarly, the CVS or the presence of PRLs are now confirmatory biomarkers. Neither is required for a diagnosis, but both can be used to make a probable diagnosis in the context of other signs and symptoms, a change that might be particularly helpful in patients presenting with atypical features, according to the authors of the new criteria.

This applies to asymptomatic patients. In patients with radiologically isolated syndrome, meaning incidental discovery of white matter T2-weighted hyperintensive foci, fulfillment of DIS criteria now allow those with “select 6” (at least six lesions that exhibit the central vein sign) or positive CSF to be diagnosed with MS. 

MS experts have endorsed the new criteria, noting potential to improve outcomes by speeding diagnosis.

“For people everywhere with MS, the revisions offer a clearer and faster path to diagnosis, giving them the chance to begin treatment sooner and move forward with greater certainty,” Lydia Makaroff, MD, PhD, chief executive at the MS International Federation, Cambridge, UK, said in a statement. 

The president and chief executive officer of the National Multiple Sclerosis Society in the US, Timothy Coetzee, PhD, also praised the new criteria for accelerating the diagnosis, which he expects will lead to earlier treatment and the potential for better outcomes.

“Decades ago, it could take years to diagnose MS. Now it’s down to months,” he said in a press release.

As previously reported by Medscape Medical News, a study testing the newly proposed criteria will have an impact. In this cross-sectional study of 166 patients with an atypical presentation and 25 with a radiologic-only presentation — none of whom would have met criteria for an MS diagnosis under previous guidance — 32% and 28% of these groups, respectively, received a probable diagnosis.

Even with additional and more sensitive biomarkers for making disease diagnosis, MS remains a diagnosis of exclusion, noted Xavier Montalban, MD, PhD, director of the Center for Multiple Sclerosis of Catalonia, Vall d’Hebron University Hospital, Barcelona, Spain, and leader of the committee that developed the criteria.

There is still no definitive sign, symptom, or finding that eliminates all alternative diagnoses. As a result, Montalban and his co-authors warned that risks for misdiagnosis and underdiagnosis cannot be ignored.

The signs and symptoms of MS “should be reassessed periodically” regardless which criteria were fulfilled, they suggested. Warning that other demyelinating syndromes might better still account for the symptoms over time, the suggested that it is prudent to remain sensitive to the potential for other underlying pathology. 

Galetta reported no potential conflicts of interest. Bennett reported financial relationships with AbbVie, Genentech-Roche, Genzyme, ImmPACT, and Novartis. Markoff reported no potential conflicts of interest. Stankoff reported financial relationships with Biogen, Janssen, Merck, Novartis, Roche, and Sanofi. Coetzee reported no potential conflicts of interest. Montalban reported that his institution has received compensation for travel expenses he has incurred and lectures he has delivered from AbbVie, Actelion, Alexion, Bial PD, Biogen, Bristol-Myers Squibb-Celgene, and other sources. Full disclosures are included in the original articles.