ACTRIMS 2025: Updated McDonald criteria could aid MS diagnosis
Analysis shows changes could diagnose people missed in earlier versions
Proposed revisions to the McDonald criteria, a set of diagnostic guidelines for multiple sclerosis (MS), may help diagnose people who could have been missed under earlier versions, according to a recent analysis.
That includes people with radiological-only onset, when there are signs of disease on MRI scans but no obvious neurological symptoms, as well as individuals with atypical clinical presentations not specific for MS.
The analysis showed that nearly one in five such individuals in a clinical study met the new criteria for an MS diagnosis.
Alexandra Scharf, a medical student at Case Western Reserve University School of Medicine in Cleveland, presented the findings at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2025, held Feb. 27-March 1 in Florida and virtually.
Scharf conducted the research at the Cleveland Clinic’s Mellen Center for Multiple Sclerosis Treatment and Research. Her talk was titled, “Application of 2024 McDonald Criteria to Individuals with Atypical and Radiological Only Presentations in a Multicenter Diagnostic Biomarker Study.”
Beyond clinical signs
The McDonald criteria, developed in 2001, take into account clinical, laboratory, and MRI findings to help hone in on an MS diagnosis. Across several revisions over time, the guidelines have indicated that a person must show classic clinical signs of disease to have their diagnosis confirmed.
“Previous revisions of the McDonald Criteria have not allowed a diagnosis of MS in the absence of a typical clinical attack or neurological progression,” Scharf said.
People who have lesions, areas of damage seen on an MRI scan consistent with MS, but no overt clinical symptoms would have been diagnosed with radiologically isolated syndrome (RIS). That could mean that patients with atypical clinical presentations not specific for MS would be missed.
Last year, a group of experts proposed revisions to the guidelines that would allow such individuals to be diagnosed with MS provided they met certain other criteria.
Under these revisions, an MS diagnosis can be made if there’s evidence of dissemination in space (DIS), meaning that neurological damage occurs in at least two different locations in the nervous system, and at least one of three other criteria are met.
These include dissemination in time (DIT), when neurological damage occurs at more than one point in time; evidence that antibodies related to MS are present in the spinal fluid (oligoclonal bands or kappa free light chains); or at least six lesions with the central vein sign (CVS), an MRI finding believed to be specific for MS in which a small vein appears running through a lesion.
Scharf applied the proposed 2024 McDonald criteria revisions to a subset of participants from the CAVS-MS study (NCT04495556).
CAVS-MS was designed to assess whether CVS could be used as a reliable MS biomarker. It recruited 420 people who were referred to MS centers in the U.S. for a diagnostic evaluation and underwent MRI scans at their first study visit (baseline) and over a two-year period.
Scharf’s analysis focused on data from the baseline visits of 191 participants who presented with atypical clinical onset (166 people) or who had radiological-only onset (25 people), whose diagnosis could be missed under previous versions of the criteria.
Overall, 36 participants (19%) met the 2024 McDonald Criteria, 32% with radiological-only onset and 17% with atypical clinical onset.
“Nearly one in five participants with atypical or radiological-only presentation met diagnostic criteria for MS under the 2024 revisions,” Scharf said.
Of these 36 people, seven met the criteria because they showed evidence of DIS and DIT. Of the remaining 29 people, who all met DIS criteria, 19 were CVS-positive, 15 had oligoclonal bands, and five had both.
Ultimately, 43% of people with DIS but not DIT could have their diagnosis confirmed based on the presence of CVS.
“Under the 2024 revisions, the central vein sign is among the most useful paraclinical tools” to establish a diagnosis in people with atypical or no clinical signs of disease, Scharf said.
Among people who met DIS, more than half (55%) had a diagnosis confirmed based on the presence of one other diagnostic criteria: CVS, oligoclonal bands, or DIT. It was much less common for patients to meet more than one additional criterion.
“Further study and long-term follow-up is required to validate diagnostic accuracy in this patient population,” Scharf said, noting that such analyses are planned through the CAVS-MS study.
The National Multiple Sclerosis Society and the National Institutes of Health were among funding sources for the study.
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