“The field now relies on a unified toolkit,” says Professor Bruno Stankoff, President of ECTRIMS, summarising the essence of the 2024 revisions to the McDonald Criteria [1].
These updates mark a defining moment in multiple sclerosis (MS) diagnosis – a move toward a single, universally applicable framework. The result is a more specific and timely approach to diagnosis, adaptable across all disease forms, ages, and clinical contexts.
But what are the major innovations underpinning the 2024 revisions? Professor Stankoff walks us through the three most crucial ones.
First change – Broader Coverage
“The latest revisions serve as a one-stop toolkit for diagnosing every form of the disease – relapsing and progressive. Unlike in the past, they now cover all age ranges, from children to older adults over 50. Most importantly, this unified framework is applicable across regions and in patients with comorbidities.”
Second change – Biological Breakthrough
“We finally have a biological definition of the condition, which makes it possible to include very early forms — such as the radiologically isolated syndrome (RIS) — that could not previously be integrated. In the past, diagnosis required waiting for a characteristic clinical episode. Today, paraclinical findings are sufficient for a diagnosis, reflecting the integration of the earliest forms of the disease within a biological and radiological framework.”
Third Change – Diagnostic Integration
“We now have a unified and enlarged diagnostic toolkit that can be applied broadly, while allowing for greater specificity and accuracy. This should enable clinicians to be more precise and make fewer diagnostic errors. Among the tools retained from previous revisions are dissemination in space, dissemination in time (which is however no longer mandatory), and the presence of oligoclonal bands. In addition, several new tools have been introduced: the optic nerve has been included as a fifth topographical area (see also Redefining Diagnostic Boundaries: Optic Nerve Assessment in MS | ECTRIMS); new radiological markers such as the central vein sign (CVS) and paramagnetic rim lesions (PRLs) have been incorporated; and kappa free light chains (kFLCs), a more quantitative and standardised alternative to oligoclonal bands, can now be used.”
Overall Impact: A More Comprehensive and Flexible Diagnostic Process
These major changes make the diagnostic process more comprehensive, specific, and adaptable to different clinical situations.
Professor Stankoff continues, “If I were to summarise their overall significance, that is how I would put it. We now have multiple possible entry points for applying the criteria. As before, they can be used in patients with a typical clinical presentation and radiological evidence of dissemination in space, which remains broadly consistent with earlier versions of the McDonald criteria. We can now also establish the diagnosis a bit earlier, and in those cases the criteria become slightly more stringent — always requiring dissemination in space, but also either dissemination in time, the presence of oligoclonal bands/positive kFLCs, or the presence of CVS. These supporting signs further increase diagnostic specificity.”
Special Cases: Tailoring the Criteria to Specific Patient Groups
Having many diagnostic tools does not mean that all must be used in every situation. The value of the toolkit lies in the assurance that, whatever the circumstances, the right tools will be available when needed.
The revised criteria offer a single reference framework with multiple diagnostic options, to be selected according to the specific clinical context.
Another possible entry point, for instance, concerns patients who have experienced a typical clinical event and do not show dissemination in space on the MRI — those with only a single lesion location, whereas dissemination in space requires at least two. Professor Stankoff says, “For these patients, more specific criteria are applied to support the diagnosis. In such cases, we rely on positive oligoclonal bands/positive kFLCs or dissemination in time, with the addition of specific MRI markers such as the CVS or PRLs. Notably, PRLs are mentioned exclusively in this context — in the current form they apply only to patients who do not yet show dissemination in space. Additionally, for children, older adults, or patients with comorbidities, greater diagnostic specificity is also required. In these situations, the presence of CVS, a spinal cord lesion, or positive kFLCs is recommended to support the diagnosis. It is important to notice that the full toolkit is not applied to every patient; it is reserved only for the more complex cases in which additional tools are needed.”
Together, these refinements illustrate not only the flexibility of the new framework but also its clear break with traditional approaches.
A Historical Turning Point
A rupture with the past defines the 2024 revisions to the McDonald Criteria, marking a major shift in how MS is diagnosed. The updates establish globally consistent standards and highlight the essential role of paraclinical tests in enabling earlier and more accurate diagnoses [1].
Which elements represent a clear break from previous diagnostic criteria, allowing clinicians to establish the diagnosis earlier and with greater confidence?
“These diagnostic criteria have been established based on evidence from previous studies, rather than simply on expert opinion.” Professor Stankoff tells us, “It is as if there has been a kind of pre-validation of the tools we have now introduced — something that was not the case in the past. The priority is now given to specificity, but also to speed of diagnosis. For this reason, compared to earlier versions, the criterion of dissemination in time has become less central — it is no longer mandatory, whereas it was in the past. The key objective today is to diagnose patients early, preventing the condition from evolving over time. Of course, when dissemination in time is present, it remains useful, but it is no longer required. We must still exclude red flags and alternative diagnoses, as before — it remains a diagnosis that must be weighed against other possibilities. However, what stands out in these new criteria is precisely this rupture with previous approaches and the emphasis on greater specificity, which should help reduce the risk of misdiagnosis.”
***
Written by Stefania de Vito
Special thanks to Professor Bruno Stankoff (President of ECTRIMS, Université Sorbonne, Hôpital Universitaire Pitié-Salpêtrière) for his insights.
References
[1] Montalban X et al. Lancet Neurol. 2025; 24.10: 850-865.