Navigating the 2024 McDonald Criteria

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Multiple sclerosis (MS) is a complex, chronic inflammatory disease of the central nervous system that affects over 2.8 million people worldwide. For over two decades, the McDonald criteria have served as the diagnostic gold standard, integrating clinical, imaging, and laboratory findings to identify the disease.

 However, as our understanding of MS pathophysiology and imaging technology evolves, so too must our diagnostic frameworks.

Following major revisions in 2005, 2010, and 2017, the newly published 2024 update to the McDonald criteria introduces critical modifications designed to enhance diagnostic precision, enable earlier detection, and prevent misdiagnosis.

Here is a breakdown of the most significant changes every clinician, radiologist, and patient advocate should know.

Historically, Dissemination in Space (DIS)—the principle that MS affects multiple parts of the central nervous system—was established by identifying lesions in four distinct topographic areas: periventricular, juxtacortical/cortical, infratentorial, and the spinal cord.

The 2024 criteria officially recognize the optic nerve as the fifth topographic site for DIS. Given the high prevalence of optic nerve involvement in MS, this is a major step forward. To fulfill DIS criteria, optic nerve involvement can be confirmed not only through MRI, but also via alternative clinical modalities like visual evoked potentials (VEP) and optical coherence tomography (OCT).

Previously, demonstrating Dissemination in Time (DIT)—evidence that MS attacks are occurring at different points in time—required serial MRI scans or a second clinical attack. The 2017 criteria allowed the presence of cerebrospinal fluid (CSF) oligoclonal bands (OCBs) to substitute for DIT.

Now, kappa-free light chains (kFLCs) have been added as a second, validated CSF biomarker. Similar to OCBs, kFLCs represent chronic intrathecal inflammation and can substitute for DIT, allowing for faster diagnoses without waiting for a second clinical or radiological event.

One of the most exciting additions is the integration of highly specific imaging markers visualized on susceptibility-sensitive MRI sequences. These optional diagnostic tools include:

• The Central Vein Sign (CVS): A small vein located centrally within a demyelinating lesion. Under the newly validated "rule of six," identifying CVS-positive lesions can substitute for DIT.
• Paramagnetic Rim Lesion (PRL): A lesion surrounded by a dark rim of iron-laden macrophages, signifying chronic inflammation. The presence of at least one nonenhancing PRL can also substitute for DIT in specific diagnostic scenarios.

Radiologically Isolated Syndrome (RIS) occurs when an asymptomatic patient receives an MRI for an unrelated reason, but the scan reveals incidental findings typical of MS. In previous iterations of the criteria, RIS was considered a risk factor but could not be formally diagnosed as MS.

The 2024 update changes this: patients with RIS can now receive an official MS diagnosis if they demonstrate DIS alongside DIT, positive CSF biomarkers (OCBs or kFLCs), or $\ge$6 CVS-positive lesions. This opens the door for closer monitoring and potentially earlier treatment for high-risk individuals.

While the new criteria aim to speed up diagnosis, they also introduce vital safeguards to prevent misdiagnosis in atypical populations. The criteria now strongly recommend stricter diagnostic thresholds for patients over age 50, those with vascular risk factors (like diabetes or hypertension), and individuals with headache disorders. Because these groups naturally have a higher prevalence of non-MS white matter spots, a secure MS diagnosis now requires the additional presence of a spinal cord lesion, positive CSF biomarkers, or $\ge$6 CVS-positive lesions.

Additionally, pediatric patients presenting with acute disseminated encephalomyelitis (ADEM) must now experience a second clinical attack or the appearance of new lesions over 90 days after their initial onset before adult criteria can be applied.

Finally, the 2024 update simplifies the pathway for some of the most clear-cut cases. A patient can now be diagnosed with MS without demonstrating DIT at all, provided they have typical lesions in at least four of the five defined topographies. Furthermore, for Primary Progressive MS (PPMS)—which is characterized by a steady decline rather than distinct relapses—DIS can now be satisfied simply by the presence of at least two spinal cord lesions, as long as the patient has experienced progressive symptoms for at least 12 months.

The 2024 update to the McDonald criteria represents a massive leap forward in the neurological and radiological fields. By validating new biomarkers like kFLCs, embracing advanced MRI markers like CVS and PRL, and refining the rules for vulnerable demographics, the medical community is better equipped than ever to provide earlier, safer, and more accurate MS diagnoses.