Your diagnosis of multiple sclerosis may have been made using the McDonald criteria. This is a tool for neurologists to ensure that they provide an accurate diagnosis of MS as early as possible, and guide them to the tests they should arrange for you in order to be sure.
The first set of criteria were published in 2001 by a team led by Prof Ian McDonald. They have been extensively revised several times. The revisions are made by a panel of MS experts who look at the most up-to-date research on how MS appears and progresses in patients.
The McDonald criteria were last revised in 2017, and these are the criteria currently in use. In 2024, a new revision process began, to take into account recent advances in imaging and research. The team announced their findings at a major MS conference, the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Over the coming months, the 2024 revisions are likely to be published and used more widely.
Diagnosing MS can be difficult, as the initial symptoms are varied and can be hard to distinguish from other conditions. Over the years, researchers have been looking for ways to confidently identify MS as early as possible. Early diagnosis and treatment has been shown to lead to better outcomes for people with MS, such as slower progression and less severe disability.
To give a diagnosis of MS, the neurologist is looking for evidence of damage to the central nervous system that is disseminated (spread out) in time and space. This means showing that damage has occurred at different dates (dissemination in time, or DIT) and to different parts (dissemination in space, or DIS) of the brain and/or spinal cord. This generally distinguishes MS from other similar neurological conditions.
Neurologists can use a range of evidence sources, including a neurological examination, MRI scans, samples from a lumbar puncture or measures of nerve conductance (evoked potentials tests). Your personal history of symptoms is an important part of the evidence too.
A diagnosis of MS is most secure if there is more than one kind of evidence. Misdiagnosing MS could put patients at risk from unnecessary side-effects of MS drugs.
Dissemination in Time (DIT)
To find evidence of DIT, the neurologist is looking for signs that you have had more than one episode of inflammation around your central nervous system. This could be a relapse, an MRI scan that shows new lesions compared to an older scan, or a lumbar puncture sample that shows you have had inflammation in the past (oligoclonal bands).
Dissemination in Space (DIS)
To find evidence of DIS, the neurologist is looking for signs that inflammation has happened in more than one place in your central nervous system. This could be shown if you have had symptoms that affect different parts of your body, or you have an MRI scan that shows lesions in different places in your central nervous system. Neurologists define areas in your central nervous system in a way that means closely linked areas (topologies) count as one place.
The four areas where neurologists focus are the spinal cord, around the lateral ventricles or spaces in the centre of the brain (periventricular), in or touching the outermost brain layer or cortex (cortico-juxtacortical) and around the brainstem or base of your brain (infratentorial).
When you visit your neurologist for the first time, they will listen to your account of your symptoms including how and when you experienced them. Using the McDonald criteria, the neurologist can assess what additional evidence they need to collect to make a robust diagnosis of MS.
So, if you have a neurological symptom that suggests a potential first MS event (CIS), your neurologist may ask you to have an MRI scan and lumbar puncture. If these tests show lesions in the central nervous system and oligoclonal bands in your spinal fluid, a diagnosis of MS could be made immediately. You would not need to wait for another attack or relapse before starting treatment.
The table below shows the 2017 McDonald criteria. In the left column is the information that the neurologist already has, and in the right column is the additional evidence they need to collect.
The proposed 2024 revisions to the McDonald criteria include new guidance on diagnostic markers that have been shown to be accurate at identifying MS. These new markers include the central vein sign (CVS), paramagnetic rim lesions and kappa free light chains.
MS lesions are different to other brain lesions in that they often have a blood vessel through the middle of them that can be seen on MRI scans. This is the central vein sign. A feature of active MS lesions can be a ring of iron that shows up around the edge. This is the paramagnetic rim and can also be detected by MRI.
Kappa free light chains are molecules that are produced by white blood cells, as part of the immune response. They can be detected in cerebrospinal fluid taken from a lumbar puncture, and indicate inflammation. Researchers have compared them to oligoclonal bands and shown that they are just as accurate in identifying MS.
The 2024 revisions also include the optic nerve as a fifth separate topology or affected area. This means that a lesion in the optic nerve could be used as evidence that indicates MS. The research team have also shown that dissemination in time is not necessary to prove if you have lesions in four or five different topologies. This means that an MS diagnosis could be made right away, without having to wait for more disease activity.
Eventually, neurologists may be able to diagnose MS in people with no symptoms, who have an MRI or lumbar puncture done for other reasons. Previously, where this happened, people were given a diagnosis of radiologically isolated syndrome (RIS) and had to wait for symptoms to appear before a confirmed diagnosis. Theoretically, once MS is diagnosed, the person could begin treatment right away.
The 2024 McDonald criteria revisions also include guidance on diagnosing MS in children and people over 50.
New research papers will come out over the next few months to explain the 2024 revisions and make recommendations on how to put them into practice. In the short term, the revisions may increase inequity in the NHS as not all hospitals will have the technology and staff to look for these new markers. Eventually the hope is that they will lead to faster diagnosis and treatment and better long-term outcomes for people with MS.
