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Multicenter Study
. 2025 Mar;97(3):571-582.
doi: 10.1002/ana.27145. Epub 2024 Nov 28.

Towards a Unified Set of Diagnostic Criteria for Multiple Sclerosis

Wallace J Brownlee  1   2 , Angela Vidal-Jordana  3 , Madiha Shatila  1 , Eva Strijbis  4 , Lisa Schoof  4 , Joep Killestein  4 , Frederik Barkhof  1   4   5 , Luca Bollo  3 , Alex Rovira  6 , Jaume Sastre-Garriga  3 , Mar Tintore  3   7 , Maria A Rocca  8   9   10 , Federica Esposito  9 , Matteo Azzimonti  8   9   10 , Massimo Filippi  8   9   10 , Benedetta Bodini  11   12 , Andrea Lazzarotto  11   12 , Bruno Stankoff  11   12 , Xavier Montalban  3   7 , Ahmed T Toosy  1   2 , Alan J Thompson  1 , Olga Ciccarelli  1   2 ; MAGNIMS Study Group
Affiliations
Multicenter Study

Towards a Unified Set of Diagnostic Criteria for Multiple Sclerosis

Wallace J Brownlee et al. Ann Neurol. 2025 Mar.

Abstract

Objective: The 2017 McDonald criteria continued the separation of diagnostic criteria for relapsing-remitting multiple sclerosis (RRMS) and primary progressive MS (PPMS) for historical, rather than biological, reasons. We aimed to explore the feasibility of a single, unified set of diagnostic criteria when applied to patients with suspected PPMS.

Methods: We retrospectively identified patients evaluated for suspected PPMS at 5 European centers. The 2017 McDonald PPMS criteria was the gold standard against which the 2017 McDonald RRMS dissemination in space (DIS) and dissemination in time criteria were evaluated. We also investigated modified RRMS DIS criteria, including: (i) optic nerve lesions; (ii) ≥2 spinal cord lesions; and (iii) higher fulfilment of DIS criteria alone (lesions in ≥3 regions) without dissemination in time/positive cerebrospinal fluid, for a diagnosis of PPMS.

Results: A total of 282 patients were diagnosed with PPMS using the 2017 McDonald criteria, and 40 with alternate disorders. The 2017 McDonald RRMS DIS criteria and the modified DIS criteria including the optic nerve or ≥2 spinal cord lesions performed well in PPMS diagnosis when combined with dissemination in time/positive cerebrospinal fluid (sensitivity 92.9-95.4%, specificity 95%, accuracy 93.2-95.3%). A diagnosis of PPMS based on high fulfillment of modified RRMS DIS criteria had high specificity, but low sensitivity. A diagnostic algorithm applicable to patients evaluated for suspected MS is proposed.

Interpretation: The 2017 McDonald RRMS criteria and modifications to DIS criteria, currently under consideration, performed well in PPMS diagnosis. Forthcoming revisions to the McDonald criteria should consider a single, unified set of diagnostic criteria for MS. ANN NEUROL 2025;97:571-582.

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Conflict of interest statement

J.K., F.B., A.R., J.S.G., M.T., M.A.R., M.F., BS, XM, AJT, and OC participated in the 2023 McDonald Diagnostic Criteria Review Meeting in November/December 2023, where data presented in this manuscript were presented and discussed. The conception, design, and analysis of this study, and the preparation of this manuscript are independent of the 2023 McDonald Diagnostic Criteria Review Meeting. The authors have nothing to report.

Figures

FIGURE 1
FIGURE 1
Flow chart showing patient disposition. CSF = cerebrospinal fluid; PPMS = primary progressive multiple sclerosis.
FIGURE 2
FIGURE 2
Percentage of primary progressive multiple sclerosis patients fulfilling the 2017 McDonald relapsing–remitting multiple sclerosis (RRMS) diagnostic criteria (dissemination in time [DIS] and dissemination in time [DIT] presented separately), and the modified DIS criteria. MRI = magnetic resonance imaging. [Color figure can be viewed at www.annalsofneurology.org]
FIGURE 3
FIGURE 3
Diagnostic algorithm for suspected primary progressive multiple sclerosis. CSF = cerebrospinal fluid; DIT = dissemination in time; MRI = magnetic resonance imaging; OCBs = oligoclonal bands; PPMS = primary progressive multiple sclerosis. [Color figure can be viewed at www.annalsofneurology.org]
See this image and copyright information in PMC

References

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