Performance of the 2024 McDonald Criteria in Patients Under Evaluation for Suspected Multiple Sclerosis

Background and Objectives – The 2024 McDonald criteria provide new recommendations for multiple sclerosis (MS) diagnosis, but validation of the criteria is lacking. We wanted to investigate the application and performance of the 2024 McDonald criteria in patients with suspected MS seen in routine clinical practice.Methods – We retrospectively identified patients referred with clinical and/or radiologic suspicion for MS between January and December 2024. All patients had a minimum diagnostic evaluation with brain and spinal cord MRI. The 2017 McDonald criteria were applied prospectively, and the 2024 McDonald criteria were applied retrospectively after the initial diagnostic workup and at last follow-up. We investigated (1) the number of patients diagnosed with MS using the 2017 McDonald criteria or the 2024 McDonald criteria, and (2) the diagnostic performance of the 2024 McDonald criteria when applied during the initial diagnostic workup, with an MS diagnosis using the 2017 McDonald criteria as the reference-standard.Results – In 347 patients (mean age 39.4 years, 66% female) with suspected MS followed up for mean 15.3 (range 8–20) months, 73 (21%) had alternative disorders and were excluded. After applying the 2024 McDonald criteria in the remaining 274 patients, more patients were diagnosed with MS after the initial diagnostic workup (220 vs 172, p < 0.01), and at follow-up (237 vs 204, p < 0.01), compared with the 2017 McDonald criteria, and fewer patients were diagnosed with clinically or radiologically isolated syndrome. The median time to diagnosis was 40 vs 84 days (p < 0.01), respectively. After initial diagnostic workup, the 2024 McDonald criteria demonstrated high sensitivity (92.6%, 95% CI 88.1%–95.8%) and accuracy (83.6%, 95% CI 78.7%–87.8%), for an MS diagnosis using 2017 McDonald criteria at last follow-up, but moderate specificity (57.8%, 95% CI 45.4%–69.4%). The increased rate of MS diagnosis and the diagnostic performance of the revised criteria was similar in children (<18 years) and older adults (>50 years).Discussion – Use of the 2024 McDonald allows for earlier MS diagnosis, but also more frequent diagnosis including in patients with radiologically isolated syndrome. The revised criteria have similar performance across the lifespan. Limitations include the lack of data on central vein sign and kappa free light chains, and missing optic nerve assessment in some patients.