McDonald Criteria Update Aims to Simplify, Speed MS Diagnosis

COPENHAGEN, Denmark — Multiple sclerosis (MS) experts are recommending updates to the 2017 McDonald diagnostic criteria in order to make diagnosis easier, faster, and more accurate.
Among its recommendations, the expert panel advises incorporating optic nerve imaging for diagnosis and applying stricter criteria for older patients. In addition, it proposes that radiologically isolated syndrome (RIS) may be diagnosed as MS in certain cases and that disease dissemination in time (DIT) should no longer be required. 
The proposed criteria changes were presented September 18 at the Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2024.
Committee member Xavier Montalban, MD, PhD, from the Department of Neurology and the MS Centre of Catalonia at Vall d’Hebron University Hospital in Barcelona, Spain, told conference attendees that MS is a diagnosis of exclusion.
Brain and spinal cord MRI remains the most useful paraclinical test to diagnose the disease, he said, and an abnormal MRI showing typical lesions is required.
Montalban noted that optic neuritis is the first manifestation of MS in 25%-35% of cases with clinically isolated syndrome (CIS) — one of the four MS disease courses.
Therefore, he said, the panel is recommending that the optic nerve serve as the “fifth topography” or a fifth anatomical location to demonstrate dissemination in space (DIS) if there’s no better explanation for optic nerve pathology, he said. 
Considerable evidence supports the minimal threshold of at least one lesion in at least 2 of the 5 topographies after including the optic nerve, he added.
DIS Alone Sufficient?
The panel also concluded that demonstrating DIS alone, without the need for DIT or positive cerebrospinal fluid (CSF), may be sufficient for an MS diagnosis. Currently, both DIS and DIT are required.
The committee broached the topic of RIS, which is identified by the incidental discovery of central nervous system (CNS) white matter T2-weighted hyperintense foci on MRI. These hyperintense foci demonstrate morphological and spatial characteristics highly typical of MS but without clinical symptomatology related to inflammatory demyelination.
Montalban noted that most patients with RIS will develop MS within 10 years. For these individuals, the panel concluded that the following criteria are sufficient for an MS diagnosis: fulfilling both DIS and DIT; fulfilling DIS and the presence of oligoclonal bands (OCBs) in the cerebrospinal fluid; or fulfilling DIS along with six or more central vein signs (CVS).
The panel proposes the addition of CVS and paramagnetic rim lesions, which are MRI markers of chronic active lesions, as optional tools for MS diagnosis in certain situations. Demonstration of CVS by MRI can increase specificity, said Montalban.
Evidence also suggests that kappa free light chains (KFLCs) could serve as a valid, simpler, and rater-independent alternative to detecting OCBs, he added. Because KFLCs are interchangeable with OCBs, they can be used in place of OCBs for diagnosing MS through CSF analysis.
Stricter Criteria
The panel is also calling for stricter criteria for confirming an MS diagnosis in those over age 50 or individuals with headache or vascular disorders. In such patients, they strongly recommend additional features such as a spinal cord lesion, positive CSF, and CVS select 6 (six positive lesions).
The panel is also recommending laboratory tests (MOG-IgG Ab) to confirm a diagnosis in children and adolescents. Montalban noted the presence of CVS in about 50% of T2 lesions strongly suggests MS in this population.
Primary progressive MS (PPMS) requires evidence of clinical progression over at least 12 months. The committee determined that the same criteria for relapsing-remitting MS could be used for PPMS. 
Having a single, unified framework of diagnostic criteria will be “very useful,” said Montalban.
During the same meeting session, Marcello Moccia, MD, PhD, University College London (UCL) Queen Square Institute of Neurology, Faculty of Brain Sciences, London, England, presented examples of patients for whom the revised criteria could be beneficial. 
These examples help illustrate how using the new criteria, for example optic nerve imaging, could lead to earlier diagnoses, and, in some cases, easier diagnoses, possibly with less CSF, he said. It could also lead to fewer misdiagnoses, he added, thanks to high-specificity tools.
Implementing the new criteria could offer greater flexibility and reduce complexity, Moccia concluded, adding that not every patient with suspected MS requires exhaustive testing.
The committee’s next steps will include consulting with the wider MS community and preparing the information for publication, said Montalban.
Commenting on the proposals, Bruce Bebo, executive vice president of research, National MS Society, agreed the proposed changes to the McDonald Criteria will make diagnosing MS “faster and easier.”
“Importantly, we are providing guidance that is inclusive — how to confirm diagnoses in children, or in people over the age of 50,” said Bebo. “We’re bringing the latest research and imaging technology to the forefront, to help people with MS get treatment faster, so they can live their best lives.”
Montalban’s institution has received compensation for lecture honoraria and travel expenses, participation in scientific meetings, clinical trial steering committee membership, or clinical advisory board participation in recent years from AbbVie, Actelion, Alexion, Bial PD, Biogen, Bristol Myers Squibb/Celgene, EMD Serona, Genzyme, Hoffmann-La Roche, Immunic Therapeutics, Janssen Pharmaceuticals, MedDay, Merck, Mylan, Nervgen, Neuraxpharm, Novartis, PeerVoice, Samsung-Biosys Sandoz Sanofi-Genzyme, Teva Pharmaceuticals, TG Therapeutics, EXCEMED, ECTRIMS, MSIF, and NMSS or any of their affiliates. Moccia reports receiving a salary from University of Naples, Policlinico University Hospital (Naples) and Neurology (US); research grants from MUR PNRR Extended Partnership, ECTRIMS-MAGNIMS, UK MS Society, and Merck; honoraria from AbbVie, Biogen, BMS Celgene, Ipsen, Jansen, Merck, Novartis, Roche, and Sanofi-Genzyme. 
 
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