McDonald criteria for diagnosis of multiple sclerosis (MS) - summary of changes between 2017 and 2024 guidance

Summary Comparison: 2017 vs. 2024 Criteria

• Anatomical Sites (Dissemination in Space - DIS)
  • 2017 McDonald Criteria:
    • restricted to 4 Regions (Periventricular, Cortical/Juxtacortical, Infratentorial, and Spinal Cord)
  • 2024 McDonald Criteria:
    • expanded to 5 Regions (The Optic Nerve has been officially added as a fifth diagnostic zone)
• Dissemination in Time (DIT) Requirement
  • 2017 McDonald Criteria:
    • always mandatory to prove a temporal split via separate clinical attacks, specific MRI features, or spinal fluid bands
  • 2024 McDonald Criteria:
    • can be bypassed entirely if a patient presents with typical, characteristic lesions in 4 or more of the 5 anatomical zones
• Advanced MRI Markers
  • 2017 McDonald Criteria:
    • not formally included in the core criteria.
  • 2024 McDonald Criteria:
    • central Vein Sign (CVS) and Paramagnetic Rim Lesions (PRLs) are now formally integrated to improve diagnostic specificity and rule out lookalikes
• Fluid Biomarkers
  • 2017 McDonald Criteria:
    • oligoclonal Bands (OCBs) from a lumbar puncture were the only recognized fluid biomarker.
  • 2024 McDonald Criteria:
    • Kappa Free Light Chain (kFLC) index is now officially recognized and fully interchangeable with OCBs
• Age Limits and Vascular Risks
  • 2017 McDonald Criteria:
    • offered only general, cautious advice for clinicians diagnosing older populations
  • 2024 McDonald Criteria:
    • implements strict biological thresholds and safeguards for patients aged 50 and older to prevent misdiagnosing normal, age-related white matter changes as MS

One clinical episode (Clinically Isolated Syndrome - CIS)

• 2017 criteria:
  • required proving that the disease was active across both space (DIS) and time (DIT) using follow-up MRIs or cerebrospinal fluid (CSF) oligoclonal bands.
• revised 2024 criteria:
  • if a patient presents with their very first clinical episode, but their baseline MRI shows typical MS lesions across 4 or 5 of the recognized anatomical zones, the requirement to prove Dissemination in Time (DIT) is completely bypassed and the patient can be be diagnosed immediately

More than one clinical episode (Relapsing-Remitting history)

• 2017 criteria:
  • if a patient had >=2 distinct attacks and objective clinical evidence of >=2 lesions, no further testing was strictly needed to diagnose MS (though MRI was always done to confirm).
• revised 2024 criteria:
  • remains unchanged
  • however, if they have the clinical episodes but only evidence of one lesion, the new 2024 rules make it much faster to prove "Dissemination in Space" by allowing the optic nerve to count as a location or by using advanced MRI markers like the Central Vein Sign (CVS) to confirm that the single lesion is definitively MS

Slowly progressive disorder (Primary Progressive MS - PPMS)

• 2017 criteria:
  • required 1 year of continuous clinical progression plus meeting two out of three specific structural/laboratory criteria.
• revised 2024 criteria:
  • requirement for 1 year of documented clinical progression remains the mandatory starting point
  • the 2024 criteria simplify the biological confirmation
  • the optic nerve is now a fifth anatomical zone and the Kappa Free Light Chain (kFLC) index is an approved fluid biomarker, it is now structurally easier and highly accurate to biologically confirm PPMS once that 1 year of progression has been established

Reference:

1. Montalban X et al. Diagnosis of multiple sclerosis: 2024 revisions of the McDonald criteria. Lancet Neurol. 2025 Oct;24(10):850-865. doi: 10.1016/S1474-4422(25)00270-4. Erratum in: Lancet Neurol. 2025 Nov;24(11):e13.