Implementing the 2024 McDonald criteria in the NHS: opportunities and challenges for MS teams

The updated McDonald criteria shift emphasis away from clinical presentation and toward paraclinical tests, especially MRI, to demonstrate lesions in different parts of the nervous system.

It makes diagnosis more consistent, regardless of whether patients have relapses, insidious progression, atypical symptoms, or even no symptoms at all, said Dr Wallace Brownlee, consultant neurologist and clinical lead for the multiple sclerosis service at the National Hospital for Neurology and Neurosurgery.

Speaking at a recent MS Academt webinar, he explain that the optic nerve is newly recognised as a site for dissemination in space (DIS). MS can now be diagnosed based on DIS alone, involving four typical regions including the optic nerve. New biomarkers have also been introduced, most notably the central vein sign (CVS), which may allow diagnosis without follow-up MRI or lumbar puncture in some patients, and Kappa-free light chains (KFLC).

Implementation of CVS

CVS is small vein visible within the centre of a white matter legion in two perpendicular planes on susceptibility-based (SWI) MRI sequences. An emerging biomarker, it has been included in the updated McDonald criteria as it improves diagnostic specificity by helping to distinguish between MS and vascular or migraine-related lesions.

Dr Andrew Martin, consultant neuroradiologist at Sheffield Teaching Hospitals NHS Foundation Trust, said there were “significant hurdles” to implementing the technique.

While 3T is the best method for identifying the vein, the NHS has a limited number of 3T scanners, he explained, adding that the increasing demand for MRI across the health service “cannot be ignored”.

At Sheffield, for example, Andrew’s team has developed separate brain MRI protocols for MS query, MS follow-up, and MS follow-up post-contrast, as well as a MS whole cord protocol. Each takes a fixed amount of time. Adding additional, updated McDonald criteria parameters, such as orbit and SWI, to these protocols increases the time they take by between 17% and 31%, he explained. “This is still going to be a significant increase in time needed on the scanner.”

Andrew advocated for the rationalisation of MRI requesting, both for MS and other indications. “We need to think about the frequency and the need for contrast; all these things increase scanner demand and time on the scanner – and we only have a certain number of scanners and a certain amount of time.” He recommended engaging with radiology management to emphasise the role of additional MRI parameters, and only adding CVS to the initial imaging request.

Optical nerve evaluation

Dr Sara Collorone, consultant neurologist at Luton and Dunstable University Hospital and locum consultant neurologist at Queen Square MS Centre, explained that the optic nerve can now be used as the fifth topography to demonstrate DIS.

As well as MRI, the optic nerve can be evaluated using optical coherence tomography (OCT) or visual evoked potential (VEP), which conserves MRI scanner time. However, it presents challenges as well as opportunities, Sara went on. “For OCT, you must be sure the protocol is of good, rigorous quality, and for VEP you must be aware that there are no cut off values in the paper: these are dependent on your own lab.” The challenge relating to MRI is understanding the clinical context and red flags, as “many things may mimic optic nerve involvement”, she added.

In patients presenting with symptoms or signs of optic nerve involvement, Sara said an MRI scan would still be the best option in most cases. This is because it enables the demonstration of gadolinium enhancement and aids with differential diagnosis by helping to distinguish between similar conditions such as NMOSD or MOGAD.

VEP may be appropriate in this scenario if a brain and spinal cord MRI is already available and suggestive of MS. However, Sara highlighted that VEP normative values can vary by laboratory, and recommended including centre-specific cut off values on VEP reports to help with interpretation.

When evaluating optic nerve involvement to demonstrate DIS in a patient with or without a history of optic neuritis, “OCT can be very helpful in the subacute and chronic phase”. However, the assessment is not disease specific, meaning the results need to be put into clinical context, said Sara. She also recommended reviewing the scan, to ensure it is robust.

Oligoclonal bands and KFLC

The 2024 McDonald criteria state that KFLC, a form of serum-free light chain (SFLC) can be used instead of oligoclonal bands in the diagnosis of MS. Together, Kappa and Lambda SFLC are a well established biomarker in the diagnosis and monitoring of conditions including multiple myeloma, lymphocytic neoplasms, and light chain amyloidosis, but it is a “tricky assay”, said Dr Melanie Hart, consultant clinical scientist and laboratory director at NGS Neuroimmunology ad CSF Laboratory at the Queen Square Institute of Neurology.

Oligoclonal bands (OCB) are still part of the updated McDonald criteria – and for good reason, she added. The long-established gold standard method of isoelectric focussing plus immunoblotting for IgG in cerebrospinal fluid (CSF) has a sensitivity of >90% for MS. It also aids in differential diagnosis.

Melanie explained that there were are advantages and disadvantages to the KFLC testing. On one hand it is a quick, quantitative test that could be useful in resource-poor settings with little access to the specialists needed to carry out the four-hour, skilled OCB assay. However, unlike OCB, there is no international reference standard, no external quality control scheme, and, as it is new, the local evidence base is lacking. Melanie highlighted that few, if any, UK laboratories were currently providing the assay.

Any new test, she went on, must be extensively validated and verified locally, in house, to ensure it is clinically and scientifically fit for purpose, and that staff are trained to a high level of expertise.

This can be difficult to achieve with new biomarkers. Decisions around calculation of indices, biological reference range, test frequency and prognostic implications, for example, all need to be validated, at cost. “But laboratory resources are not unlimited,” said Melanie, “Research grants and studies with the MS community will greatly help us build on knowledge, especially in expert centres.”