What Do the 2024 McDonald Criteria Mean for an MS Diagnosis?

The current guidelines for diagnosing multiple sclerosis are known as the McDonald criteria, most recently updated in 2024 ^[1]. While this guide focuses on relapsing-remitting MS (RRMS), the criteria themselves are used to diagnose the presence of MS; the specific course of the disease (such as relapsing-remitting) is determined based on your symptom history during or after this diagnostic process. The 2024 updates provide more ways to confirm a diagnosis, which can help some people get answers earlier, but navigating these tests can still feel uncertain ^[1][2].

To diagnose MS, a doctor generally must find evidence of myelin damage (demyelination) spread across different parts of the central nervous system (dissemination in space) and occurring at different times (dissemination in time) ^[1]. Crucially, these rules apply only when there is no better explanation for your symptoms ^[3]. MS is never diagnosed by MRI or lab tests alone—conditions that mimic MS, like Neuromyelitis Optica Spectrum Disorder (NMOSD) or MOG Antibody Disease (MOGAD), must be considered and reasonably excluded based on your specific clinical picture ^[1][4].

Dissemination in Space (DIS) and the Optic Nerve

Dissemination in space means finding typical MS lesions (areas of damage or scarring) in multiple specific regions of the central nervous system ^[1]. The 2024 update requires evidence of typical lesions in at least two of these five areas:

• Periventricular (around the fluid-filled spaces in the center of the brain)
• Cortical/juxtacortical (in or near the outer layer of the brain)
• Infratentorial (the lower part of the brain, including the brainstem and cerebellum)
• Spinal cord
• Optic nerve (the nerve connecting the eye to the brain) ^[1][5]

The addition of the optic nerve as a formal fifth location is a major update ^[1]. Optic nerve damage can be identified on an MRI, or supported by eye tests like Optical Coherence Tomography (OCT) (which measures retinal layers to indirectly show nerve injury) or Visual Evoked Potentials (VEP) (which measure how fast electrical signals travel to the brain) ^[5][6]. Abnormal OCT or VEP results can be caused by non-MS eye conditions, so they must be interpreted carefully alongside your medical history ^[5].

The “Four-of-Five” Exception: If a person with a typical MS attack has characteristic lesions in at least four of these five regions, and there is no better explanation for them, a diagnosis might be made based on dissemination in space alone—without needing separate proof of dissemination in time ^[7][8].

Dissemination in Time (DIT) and Spinal Fluid Tests

Dissemination in time shows that the immune system’s attacks are ongoing rather than a one-time event. On an MRI, this is traditionally shown by seeing both “enhancing” lesions (which take up contrast dye, indicating active inflammation) and “non-enhancing” lesions on the same scan, suggesting damage from different times ^[9]. Finding a new lesion on a comparable follow-up MRI also proves dissemination in time ^[9].

If an MRI doesn’t show dissemination in time, spinal fluid analysis from a lumbar puncture (spinal tap) can sometimes provide the needed evidence ^[10]. Doctors look for signs of intrathecal immunoglobulin production (immune system activity inside the central nervous system), specifically:

• Oligoclonal bands (OCBs): Specific immune proteins in the spinal fluid that are not found in the blood ^[11].
• Kappa free light-chain (kFLC) index: A newer quantitative test now accepted in the 2024 criteria as an alternative to OCBs ^[12][13].

A qualifying OCB or kFLC result shows ongoing immune activity, which can satisfy the dissemination in time requirement in the appropriate clinical context ^[14][13]. However, these markers are not unique to MS—they can appear in other infections or neurological disorders, so they cannot diagnose MS on their own ^[13]. Furthermore, kFLC cutoffs and test availability can vary by laboratory ^[13][15].

New MRI Markers: CVS and PRL

The 2024 criteria introduced two optional MRI markers to help doctors be more certain when a case is unusual or when conventional MRI evidence is insufficient ^[16][7]:

• Central Vein Sign (CVS): MS lesions often form around small veins. Specialized scans can detect a vein running through the center of a lesion ^[17].
• Paramagnetic Rim Lesions (PRL): A dark rim around a lesion indicating trapped iron and chronic active inflammation ^[17].

These signs are strictly “supportive.” They increase a doctor’s confidence that a lesion is due to MS, but a lone central vein sign or dark rim doesn’t prove MS, and these features aren’t mandatory for a diagnosis ^[16][18]. Additionally, detecting CVS or PRL requires specialized susceptibility-sensitive MRI scans that may not be available or routinely read at every imaging center ^[17].

What If You Don’t Meet the Criteria Yet?

Sometimes, a person experiences a single neurological attack (Clinically Isolated Syndrome, or CIS) but does not yet meet the full criteria ^[19]. In other cases, a person might have incidental MRI findings without any MS symptoms (Radiologically Isolated Syndrome, or RIS) ^[20]. The 2024 criteria provide specific pathways to evaluate RIS using the new biomarkers, but often, the most appropriate next step in both situations is careful monitoring with repeat MRIs and clinical exams ^[1]. The McDonald criteria are meant to empower your care team, but they never replace your doctor’s clinical expertise and judgment ^[21][1].