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Why am I still stuck on the new McDonald criteria?

Posted on November 11, 2025 by
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The new 2024 revisions to the McDonald criteria for the diagnosis of MS have significantly changed the way we view the condition. Beyond the general confusion caused by not everyone remembering all the points of the criteria, one area I still find difficult to form a clear decision on is Radiologically Isolated Syndrome (RIS). Below is the published excerpt from the criteria:

Radiologically isolated syndrome (RIS)

• RIS is identified by the incidental discovery of CNS white matter T2-weighted hyperintense foci on MRI, which are highly typical of multiple sclerosis in the absence of typical clinical symptoms related to inflammatory demyelination or findings on clinical examination

• In patients with RIS, fulfilling dissemination in space (DIS) and dissemination in time is sufficient for diagnosing multiple sclerosis

• In patients with RIS, fulfilling DIS and positive CSF is sufficient for diagnosing multiple sclerosis

• In patients with RIS fulfilling DIS, the presence of the select 6 central vein sign (CVS) is sufficient for diagnosing multiple sclerosis

• These recommendations can also apply to patients with other non-specific presentations

RIS is an incidental MRI finding of lesions characteristic of multiple sclerosis (MS), occurring in individuals without clinical symptoms of demyelination. This definition aligns with contemporary diagnostic awareness of RIS as a potential preclinical phase of MS. However, the subsequent statements in the RIS criteria appear to blur the diagnostic boundaries between RIS and MS. According to the current McDonald criteria, the diagnosis of MS requires both clinical evidence and radiological findings, RIS alone does not meet these criteria, even if dissemination in space (DIS) or time is demonstrated radiologically.

The assertion that fulfilling DIS and dissemination in time, or DIS with positive cerebrospinal fluid (CSF) oligoclonal bands, is “sufficient” for diagnosing MS is problematic and premature. While such features increase the risk of future clinical conversion to MS, they do not justify a definitive MS diagnosis in the absence of clinical symptoms. Similarly, suggesting that the presence of the central vein sign (CVS) can alone confirm MS is unsupported by current consensus; although CVS improves diagnostic specificity, it is not yet a formal diagnostic criterion.

Applying these recommendations to “patients with other non-specific presentations” risks overdiagnosis and unnecessary anxiety or treatment, emphasizing the importance of clinical-radiological correlation and cautious longitudinal monitoring.

In clinical practice, overstating diagnostic certainty raises several questions, including what treatments are available for these individuals. Equally, since many of our current clinical trials enrolled PwMS under the older criteria, do we have the necessary legislation to use these DMTs in RIS?

Source: multiple-sclerosis-research.org

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