The International Advisory Committee on Clinical Trials led a multinational panel updating the McDonald criteria, adding the optic nerve as a fifth anatomical location and allowing specific magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) markers to support diagnosis without mandatory dissemination in time in defined scenarios.
Multiple sclerosis diagnosis has long required proof that lesions occur in different places and at different times, with MRI and CSF biomarkers gradually shortening time to treatment.
Previous revisions improved sensitivity and specificity across ages and regions, yet misdiagnosis risk still persists, especially with overlapping conditions and when access to specialized tests is limited.
In the study, “Diagnosis of multiple sclerosis: 2024 revisions of the McDonald criteria,” published in The Lancet Neurology, researchers convened an international consensus process to revise diagnostic rules in light of advances in imaging and biomarkers.
Fifty-six contributors met in Barcelona, including 32 members of the International Advisory Committee on Clinical Trials. Voting used a comprehensive list of statements with predefined thresholds, and four items were voted on again after discussion.
Experts applied a modified nominal group technique with anonymous electronic voting on a five-point scale. Consensus required at least 90% participation and 80% agreement. Evidence covered optic nerve assessment by optical coherence tomography (OCT), visual evoked potentials (VEP), and MRI, central vein sign methods, paramagnetic rim lesions on susceptibility imaging, and kappa free-light chain assays, along with algorithms for relapsing, progressive, pediatric, and radiologically isolated presentations.
Findings set the optic nerve as a fifth site for dissemination in space when no better explanation exists.
Dissemination in space is fulfilled when two of five regions show typical lesions, symptomatic or not, with a provision that lesions in four or five regions can suffice for diagnosis in typical presentations.
Dissemination in time (DIT) is no longer mandatory in defined scenarios, yet was retained in the criteria because new or simultaneous enhancing and non-enhancing lesions increase diagnostic specificity.
Central vein sign using the select-6 method is sufficient to diagnose multiple sclerosis in clinically or radiologically isolated syndrome when lesions involve at least two anatomical locations. In patients with typical clinical presentations with lesions in only one location, select-6 positivity together with either positive CSF or DIT on MRI is also sufficient for diagnosis.
Paramagnetic rim lesions can similarly increase specificity and, in defined scenarios, contribute to diagnosis with CSF positivity or dissemination in time. Kappa free light chain index is interchangeable with oligoclonal bands for identifying positive CSF.
Radiologically isolated syndrome and other non-specific presentations can meet criteria when dissemination in space is present with additional features such as positive CSF, central vein sign, or dissemination in time.
A single framework now applies to pediatric-onset and adult-onset disease and to relapsing and progressive courses, with recognition that two or more spinal cord lesions can demonstrate dissemination in space in progressive presentations.
Additional tests are strongly recommended for individuals aged 50 years or older or with vascular risk factors, including spinal cord lesions, positive CSF, or central vein sign positivity, to reduce misdiagnosis.
Authors conclude that updated criteria should expedite diagnosis while maintaining specificity across diverse settings. The updated guidance addresses older age and comorbidities, incorporates accessible paraclinical tools, and moves toward a unified biological framework that can improve pathways to timely care.