Background

Multiple Sclerosis (MS) is a chronic autoimmune demyelinating disease characterized by the immune system attacking the central nervous system. Given that irreversible damage to the brain and spinal cord is concentrated early in the disease course, early diagnosis and initiation of treatment are critical factors in determining patient prognosis. Clinicians have used the McDonald Criteria, which are based on clinical symptoms and magnetic resonance imaging (MRI) findings, to demonstrate spatial dissemination (DIS) and temporal dissemination (DIT) of lesions in the central nervous system.

The 2017 revision aimed to accelerate the diagnostic process but had limitations. Many patients experience optic neuritis as their initial symptom, yet the optic nerve was excluded as a DIS area. The cerebrospinal fluid (CSF) oligoclonal band (OCB) test also suffered from subjectivity and standardization issues. Therefore, a revised set of criteria incorporating the latest scientific findings was needed to reduce misdiagnosis and facilitate early diagnosis. The recently published 2024 McDonald Criteria revision is the result of addressing these unmet needs.

Key Findings

Inclusion of Optic Neuritis and Relaxed DIS Criteria

This revision officially incorporates the optic nerve as the fifth anatomical area for DIS determination. In addition to the existing areas (periventricular, cortical and juxtacortical, infratentorial, and spinal cord), the optic nerve is now included, and DIS is met if two or more of these five areas show typical lesions. This allows for earlier confirmation of diagnosis in patients with optic neuritis but few brain lesions on MRI.

Introduction of CSF kFLC Index

Advances in molecular biological diagnostic markers are also noteworthy. The revision recognizes the CSF kappa free light chain (kFLC) index as an equivalent alternative to the OCB test. The OCB test has the drawbacks of requiring subjective interpretation by the analyst and laborious manual processing. In contrast, the kFLC test allows for quantitative analysis, ensuring objectivity and reproducibility, and also reduces the interpretation time. This marker can be used to more rapidly confirm the diagnosis.

Adoption of New MRI Markers

To aid in precise diagnosis, the central vein sign (CVS) and paramagnetic rim lesion (PRL) have been approved as auxiliary markers. The CVS distinguishes between lesions with and without the presence of the central vein, helping to differentiate from migraine or microvascular disease. The PRL indicates chronic active lesions with iron deposition in the rim, which can be used as a marker to predict the risk of long-term disease progression.

Significance and Prospects

This revision provides an opportunity to further shift the paradigm of multiple sclerosis treatment toward earlier intervention. By enabling early diagnosis, disease-modifying therapy (DMT) can be initiated before irreversible nerve damage accumulates, minimizing long-term disability. The new criteria will also facilitate faster patient recruitment, which is expected to activate the clinical trial environment for subsequent therapeutic agent development.

However, the challenge of standardization remains. As the diagnostic range expands, the risk of increased misdiagnosis cannot be ruled out. Multi-center collaborative research and standardization efforts are needed to establish the diagnostic cutoff value for the kFLC index. Guidelines are also needed to reduce variability among clinicians in interpreting the latest MRI markers, such as CVS and PRL, in clinical practice. When these detailed guidelines are supplemented, the clinical benefits of the diagnostic revision will be fully realized.