Multiple Sclerosis: Putting the Revised McDonald Criteria Into Practice

Since 1868 when Jean Martin Charcot first described multiple sclerosis (MS) as a neurologic disease, the way in which MS is diagnosed has evolved from pathologic identification to recognition of classical phenotypes and disease courses, and now in the 21st century, to a clinicoradiologic construct of dissemination in space and time.  With recent advances in our knowledge of underlying pathophysiologic mechanisms, the recently revised 2024 McDonald diagnostic criteria, published in The Lancet Neurology in September 2025, again redefines MS now as a biologic disease.  Each iteration of the McDonald diagnostic criteria has endeavored to gradually broaden its sensitivity while maintaining accuracy, thereby allowing for earlier diagnosis and intervention.  With the advent of highly efficacious–and riskier–disease-modifying therapies and the paradigm shift in treatment sequencing towards an induction rather than an escalation approach, this balance between early and accurate diagnosis against the risk of misdiagnosis has never been more important.

Revisions to the diagnostic criteria have not always simplified the pathway to MS diagnosis, and this iteration is no different.  In this issue of Practical Neurology, Stefan et al provide a high-level review explaining the rationale behind the recent updates of the McDonald diagnostic criteria, including definitions of new concepts and terminology.  This newest iteration promises to be the most substantial change to the diagnostic criteria since the incorporation of MRI findings in 2001; for the first time, not only are typical MRI findings included in support of an MS diagnosis, they are now required for the diagnosis of MS, and even some asymptomatic individuals with typical MRI lesions can now be diagnosed with MS in certain settings.  

Acknowledging this emphasis on classical imaging findings, Stefan et al also present a reconfigured and unified algorithm which follows the 2024 McDonald diagnostic criteria, but considers these MRI findings before other clinical and paraclinical testing.  Such an algorithm may be more easily applicable to scenarios commonly seen in clinical practice in which a radiology report with incidental MRI findings prompts further (and sometimes retrospective) clinical consideration of an MS diagnosis.

Subsequent articles in this issue take a deeper dive into newer concepts included in the 2024 McDonald diagnostic criteria which are important for practicing clinicians to understand.  Elfasi and Fagundo showcase emerging radiologic features, including the central vein sign and paramagnetic rim lesions, which can now clinch an MS diagnosis in certain scenarios.  The optic nerve has now been included as a fifth anatomic location for consideration in dissemination in space; Van Stavern highlights uses and pitfalls of paraclinical optic nerve tests including optical coherence tomography, visual evoked potentials, and orbital MRI to demonstrate optic nerve involvement for diagnosis of MS.  Newer biomarkers beyond oligoclonal bands are also now included in the diagnostic criteria; Dunn reviews kappa free light chains and how their quantifiability in cerebrospinal fluid may serve as an improved surrogate marker of immunologic activity in the central nervous system.

Each iteration of the diagnostic criteria has preserved the important caveat of exclusion of better explanations for a patient’s presentation; it is therefore vital to recognize atypical factors more suggestive of common MS mimics.  Robertson et al review clinical features more suggestive of neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD), in addition to the important implications this diagnostic clarification has for long-term treatment.  In keeping with the renewed emphasis on MRI in MS diagnosis, Goodman et al review typical radiologic features of these mimics; the tables in this article will serve as an excellent reference for the clinical setting.

My sincere thanks to all the authors for their outstanding contributions.  I hope that you find this issue helpful in navigating the complexities of the revised McDonald diagnostic criteria.