ECTRIMS 2024: McDonald criteria changes could speed diagnoses
Revised criteria may allow diagnoses before patients show symptoms
A revised version of the McDonald criteria, a set of guidelines used to diagnose multiple sclerosis (MS), is expected to include additional features that will help doctors make an accurate diagnosis at an earlier stage of the disease, even if patients have yet to manifest clinical symptoms.
The 2024 revised criteria will allow diagnosing MS in some patients who would be classified as having radiologically isolated syndrome (RIS), which is defined as the presence of MRI brain lesions similar to those of MS but no overt clinical symptoms related of the disease.
Dissemination in time — or damage that occurs in the brain and spinal cord at more than one point in time — should in turn no longer be required to diagnose MS, based on the proposed revisions from the International Advisory Committee on Clinical Trials in MS, a group of 55 MS experts from 16 countries who met late last year in Barcelona to discuss potential updates to the guidelines. This represents the first time the criteria will be updated since 2017.
Xavier Montalban, MD, PhD, who chairs the advisory committee, presented these and other new criteria at this year’s European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) annual meeting, held Sept. 18-20 in Copenhagen and online.
“We are moving toward a biological diagnosis,” said Montalban, chair of neurology at the Vall d’Hebron University Hospital in Barcelona. “This is happening as well in other neurodegenerative conditions such as Alzheimer’s or Parkinson’s disease.”
Limitations on criteria
The McDonald criteria are widely used in MS research and clinical practice, where they help in the dialogue between patients and their doctors, inform treatment decisions, and provide a reference to predict the disease prognosis.
But “there are limitations in its ability to render an accurate and timely diagnosis,” Daniel Ontaneda, MD, PhD, a neurologist at the Cleveland Clinic who contributed to the criteria, said in an emailed statement to Multiple Sclerosis News Today. “We know that on average, it takes two years from the onset of symptoms to receive a diagnosis, and of those diagnosed, 20% do not actually have MS.”
MS is a diagnosis of exclusion, made after ruling out all other possible causes of a patient’s symptoms through several laboratory and clinical tests. Brain and spinal cord MRI remains the most sensitive imaging tool to help diagnose the disease.
To fulfill a diagnosis of MS, the newly revised McDonald criteria now state that a patient must show evidence of typical damage to the brain or spinal cord in the form of lesions on MRI scans. “A diagnosis by clinical means alone is no longer permitted,” Montalban said.
More than half of patients with RIS develop MS within 10 years. In these patients, a diagnosis of MS can be made if they fulfill the criteria for both dissemination in time and dissemination in space — damage is occurring in at least two of five locations in the nervous system.
The 2017 McDonald criteria stated that patients would met the criteria for dissemination in space if they showed lesions in at least two of four nervous system locations, including three in the brain (periventricular, juxtacortical or cortical, and infratentorial) as well as the spinal cord. The revised criteria recommend adding the optic nerve, which connects the eyes to the brain, as a fifth location to demonstrate dissemination in space.
“The optic nerve may serve as a fifth anatomical location to demonstrate [dissemination in space] if no better explanation exists for optic nerve [damage],” Montalban wrote in the slides for his oral presentation.
Changing approach to treatment
While a person with RIS can be diagnosed with MS if they show dissemination in space and time, the proposed criteria also enable an MS diagnosis in someone with dissemination in space plus the presence of either oligoclonal bands, a type of antibody in the cerebrospinal fluid (CSF) that surrounds the brain and spinal cord, or at least six lesions with a central vein sign, a feature of MS seen on MRI scans where a lesion forms around a small vein.
This means that “dissemination in time [is] no longer needed,” Montalban said. The proposed revision is in line with the 2017 McDonald criteria, which allowed oligoclonal bands in the CSF to be used instead of dissemination in time as a criterion for MS in patients who had experienced a single episode of MS-like symptoms.
“The broadening of the criteria will change how we approach treatment of the disease,” Ontaneda said. “Previously, asymptomatic individuals were diagnosed with radiologically-isolated syndrome, thought to be an early form of the disease, but typically did not start treatment. Now, because we can rely on additional features in the new criteria, we can diagnose MS and begin treatment right away.”
In patients with typical symptoms of MS, the presence of lesions in at least four locations should be enough to diagnose MS. In primary progressive MS, in which disease progresses gradually from its onset, two lesions in the spinal cord should be enough to indicate dissemination in space.
If patients manifest symptoms but have lesions in a single location, the presence of at least six lesions with a central vein sign or paramagnetic rim lesions, which are areas of damage with chronically active inflammation, plus dissemination in time or the presence of oligoclonal bands should be enough.
While finding lesions with a central vein sign or paramagnetic rim lesions on MRI scans “is not required for the diagnosis of MS,” their presence could be “very helpful in a number of situations,” Montalban said.
“Essentially, the new criteria says that if certain conditions are present, we no longer have to wait for new clinical symptoms or new MRI lesions to occur to confirm it is MS, effectively moving up the timeline for diagnosis,” Ontaneda said. “For example, having lesions in 4 typical locations, having [lesions in] fewer typical locations with positive oligoclonal bands or having 6 central vein lesions is now also MS,” he said.
The new guidelines also now allow oligoclonal bands to be replaced by kappa free light chains, which “can be measured rapidly and in a quantitative way,” Montalban said. Kappa free light chains build up in the CSF upon inflammation, and appear to work just as well as oligoclonal bands as a biomarker for MS.
In addition to the newly proposed criteria, additional features may be required to diagnose MS in certain patients, such as children and adolescents, adults older than 50, and those who have a blood vessel disease, migraine, or risk factors like high blood pressure, diabetes, or abnormal levels of blood fats.
“There are a number of open questions for future revisions,” Montalban said. In addition to publishing the 2024 McDonald criteria in a scientific journal, the advisory committee plans to consult with a wider MS community and set up a global education campaign.
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