The evolution of multiple sclerosis (MS) diagnostic criteria over the past 4 decades has shortened the time to diagnosis of MS, enabling earlier institution of immunomodulatory therapy and therefore improved clinical outcomes. In response to a recent expansion of knowledge related to approaches and paraclinical tools that may aid diagnosis of MS and identify causes of MS misdiagnosis, the 2024 McDonald criteria reflect substantive changes and introduce new pathways to MS diagnosis. These revisions carry potential for both earlier and more accurate diagnosis of MS, yet require expertise for their appropriate application in clinical practice and introduce new challenges for global implementation. These changes include expansion of anatomical locations that represent dissemination in space, new paraclinical findings that can substitute for dissemination in time, inclusion of patients with asymptomatic or nonspecific clinical presentations, and recommendations for diagnostic approaches in specific patient populations. These changes also incorporate new paraclinical tools for the first time, including MRI central vein sign and paramagnetic rim lesions, CSF kappa free light chains, and optical coherence tomography. The revised criteria have now unified the diagnostic pathway for clinical presentations typical of MS with attack or progressive onset, and established a new pathway for patients without symptoms or with nonspecific clinical presentations accompanied by MRI findings typical of MS. The 2024 revisions continue to rely on recognition of typical clinical and MRI findings of MS, and additionally recommend specific approaches to pediatric patients, patients with vascular comorbidities, and older patients to further reduce the risk of misdiagnosis. Previous data suggest barriers to implementation, and misunderstanding and misapplication of prior revisions to MS diagnostic criteria that may be associated with misdiagnosis. Implementation of the revised 2024 McDonald criteria globally, particularly in low and low-middle income countries, will require educational outreach, leveraging and maximizing existing resources, and engagement of health care systems to improve access to new technology. This review contextualizes the implications of key revisions in the 2024 criteria for routine clinical care, while providing accessible guidance for its appropriate application with a lens toward nonspecialist clinicians and trainees globally, to ensure early and accurate MS diagnosis.
A. J. Solomon, W. Brownlee, Shanthi Viswanathan et al.· Neurology· 0 citations
BACKGROUND AND OBJECTIVES
Serum neurofilament light chain (sNfL) reflects inflammatory axonal damage in relapsing multiple sclerosis (RMS). Longitudinal sNfL dynamics may aid treatment response assessment, although data on expected changes under disease-modifying treatments remain limited, particularly in real-world practice. This study evaluated whether on-treatment changes in sNfL were associated with subsequent evidence of disease activity (EDA) and whether they provided complementary information to established treatment response scoring systems (TRSS).
METHODS
This prospective, real-world cohort study was conducted at the Multiple Sclerosis Center of Catalonia (Cemcat). Adult RMS patients initiating disease-modifying treatments (DMTs) with serum samples at treatment initiation (baseline) and after 1 year (Y1) were included. The primary exposure was change in sNfL z-scores (ΔzNfL = zNfLY1 - zNfL-baseline) analyzed using data-derived thresholds (ΔzNfL ≥0 and <0.5-point reduction). At Y1, Expanded Disability Status Scale progression, clinical/radiologic activity, and TRSS (Rio [RS], modified Rio [mRS], and MAGNIMS) were assessed. The primary outcome was EDA between years 1 and 2 (EDA-Y2). Multivariable logistic regression models evaluated associations between ΔzNfL and EDA-Y2, as well as the added value of ΔzNfL across TRSS strata.
RESULTS
A total of 329 patients (66.3% female; median age 39 years) initiated 352 DMTs; 342 remained on treatment for ≥1 year and 182 had complete EDA-Y2 data. Mean (SD) ΔzNfL at Y1 was -0.62 (1.2), with greater reductions in monoclonal antibody-treated and treatment-naïve patients. Lack of zNfL reduction over the first year (ΔzNfL ≥0) was associated with higher odds of EDA-Y2 in the overall cohort (OR [95% CI], p: 3.07 [1.47-6.39], 0.003), in treatment-naïve cases (14.04 [2.47-79.93], 0.003), and in those achieving No Evidence of Disease Activity (NEDA-3) at Y1 (4.54 [1.26-16.30], 0.02). Similar associations were observed for <0.5-point reductions. Adding ΔzNfL to TRSS showed persistent associations with EDA-Y2 despite otherwise favorable scores [e.g., RS: 2.26 (1.12-4.59), 0.024].
DISCUSSION
Failure to reduce zNfL levels after 1 year of treatment was associated with subsequent disease activity, even in patients otherwise considered stable, providing complementary information to clinical and MRI-based monitoring. Limitations include incomplete follow-up and the modest discriminative performance of ΔzNfL, supporting a complementary rather than stand-alone role for zNfL dynamics.
Victoria Fernández, Agustín Pappolla, Pere Carbonell-Mirabent et al.· Neurology· 0 citations
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