Monday, 1 February 2016

New MRI criteria for the diagnosis of MS - MAGNI(MS)FICENT?

MRI criteria for the diagnosis of multiple sclerosis: MAGNIMS consensus guidelines Lancet Neurology 2016

Massimo Filippi, Maria A Rocca, Olga Ciccarelli, Nicola De Stefano, Nikos Evangelou, Ludwig Kappos, Alex Rovira, Jaume Sastre-Garriga, Mar Tintorè, Jette L Frederiksen, Claudio Gasperini, Jacqueline Palace, Daniel S Reich, Brenda Banwell, Xavier Montalban, Frederik Barkhof, on behalf of the MAGNIMS Study Group*

In patients presenting with a clinically isolated syndrome, MRI can support and substitute clinical information in the diagnosis of multiple sclerosis by showing disease dissemination in space and time and by helping to exclude disorders that can mimic multiple sclerosis. MRI criteria were first included in the diagnostic work-up for multiple sclerosis in 2001, and since then several modifications to the criteria have been proposed in an attempt to simplify lesion-count models for showing disease dissemination in space, change the timing of MRI scanning to show dissemination in time, and increase the value of spinal cord imaging. Since the last update of these criteria, new data on the use of MRI to establish dissemination in space and time have become available, and MRI technology has improved. State-of-the-art MRI findings in these patients were discussed in a MAGNIMS workshop, the goal of which was to provide an evidence based and expert-opinion consensus on proposed modifications to MRI criteria for the diagnosis of multiple sclerosis.

The list of "proposed modifications to the 2010 McDonald criteria for MRI in the diagnosis of multiple sclerosis" is rather extensive, which no doubt improves their accuracy.  Given their complexity it remains to be seen whether these new criteria will make much difference in clinical practise for neurologists and people who (are suspected to) have MS:

• Three or more lesions are needed to define the involvement of the periventricular region to establish disease dissemination in space (expert consensus)

• The presence of a lesion in the optic nerve should be added to the criteria for dissemination in space as an additional CNS area (expert consensus)

• The combined term cortical/juxtacortical is recommended to expand the concept of juxtacortical lesion in the criteria for dissemination in space, by including all multiple
sclerosis cortical lesion types, involvement of the white matter next to the cortex, or both; when available, advanced imaging sequences should be applied to visualise
cortical lesions (expert consensus)

• No distinction needs to be made between symptomatic and asymptomatic MRI lesions for dissemination in time or space (evidence based)

• Imaging of the whole spinal cord is recommended to define dissemination in space (especially in patients who do not fulfil brain MRI criteria for dissemination in space); spinal cord imaging has a limited role for identification of dissemination in time (evidence based)

• Identical criteria for dissemination in space should be used for primary progressive multiple sclerosis and relapse-onset multiple sclerosis (expert consensus); CSF results should be considered for clinically uncertain cases of primary progressive multiple sclerosis (evidence based)

• In children aged older than 11 years with presentation that does not resemble acute disseminated encephalomyelitis (ADEM), MRI criteria used to establish dissemination in time and space in adults should be applied (evidence based)

• Caution is recommended when applying the 2010 criteria solely at baseline in patients younger than age 11 years, even in those with a non-ADEM presentation

• MRI criteria can be applied equally well to patients with multiple sclerosis in Asia or Latin America as to patients from Europe and North America, once alternative neurological disorders (eg, neuromyelitis optica spectrum disorder) have been carefully excluded (evidence based)

• MRI criteria used to establish dissemination in time and space in multiple sclerosis should be applied for assessment of radiologically isolated syndromes; when a clinical attack occurs in patients with radiologically isolated syndromes with evidence of dissemination in time (who, by definition, have dissemination in space), a diagnosis of multiple sclerosis can be made (expert consensus)

Additional clarifications and summary statements

• MRI criteria for disease dissemination in time can remain unchanged

• Presence of non-enhancing black holes is not useful as a potential alternative criterion for dissemination in time in adults; the contribution of non-enhancing black holes seems to be more robust in distinguishing children with multiple sclerosis from children with monophasic demyelination (especially ADEM)

• In the case of atypical imaging presentation, other acquired and inherited white matter diseases should always be considered in the differential diagnosis

• At present, insufficient evidence exists to support earlier diagnosis of multiple sclerosis when using high-field or ultra-high-field scanners

CoI: none


  1. What about a diagnosis of asymptomatic MS?

    1. Here's what MAGNIMS says: "We propose that the MRI criteria used to establish dissemination in time and space in multiple sclerosis should be applied for assessment of radiologically isolated syndromes, and that when a clinical attack occurs in patients with radiologically isolated syndromes with evidence of dissemination in time (who by definition have dissemination in space), a diagnosis of multiple sclerosis can be made. Thus, we agreed that people should not be diagnosed with multiple sclerosis on the basis of MRI findings alone, and at least one clinical event consistent with acute demyelination remains a cornerstone for multiple sclerosis diagnosis."
      This may appear conservative given 2/3 of people with RIS develop new lesions on follow-up MRI scans and 1/3 develop neurological symptoms within 5 years (i.e. they had MS from the moment MRI detectable lesions were spotted, or even well before that), especially those with gadolinium-enhancing or spinal cord lesions. Evidence suggests the presence of oligo-clonal bands, younger age (≤37 years), male sex, and abnormal visual evoked potentials are predictors of development of a first clinical attack (i.e. the confirmation of MS).
      Essentially MAGNIMS suggests applying a “reverse McDonald”: Whilst the actual McDonald criteria require at least one clinical attack and MRI evidence of dissemination in time and space, for people with RIS they recommend making a diagnosis based on their MRI presentation only once clinical symptoms/signs occur.
      Obviously, there is a difference between RIS and CIS: It is unpredictable when pwCIS develop symptoms (and which) that make them seek help; as a result we are left with the damage done by that time. Conversely, picking out pwRIS provides an opportunity to develop and apply more sensitive tools, be they biomarkers or clinical tests, to identify the clinical relevance of the damage done, ideally avoiding any delays making a diagnosis. On a number of occasions I have seen pwMS with an EDSS of 0, yet review of their occupational or school/study performance and detailed psychometry showed evidence of what you call the “brain shredder” at work. These people surely have MS, and almost invariably develop more classical symptoms/signs as the disease evolves, but unless they attend a neurologist or centre that reviews many pwMS, delays in effective treatment are likely.

  2. Is too much emphasis placed on MRI findings for a diagnosis? Especially when you consider some centres are still using sub-optimal scanning protocols, without contrast, etc.

    1. Well, it's MAGNIMS, so they deal mainly with the MRI aspects of MS. Availability of MRI capacity certainly cannot be assumed in many places.

  3. I think there is too much emphasis on MRI findings alone as well. I had one CIS, confirmed on the MRI and a second attack without findings on the MRI. But that doesn't mean there is no damage. Even with the 7T MRIs half of the real pathological damage is missed. So what happends with the attacks without clear MRI findings?

    1. Clinical experience and judgement continue to play a role. This paper focusses on MRI, but the diagnosis of MS can, of course, be made in many situations on the basis of clinical symptoms/signs alone, and/or supported by MRI. Diagnosing MS can be anything between straightforward and quite complex.

  4. Curious as to why none enhancing black holes cannot be used? What role do black holes play in diagnosis of MS? Can SPMS be diagnosed at the initial presentation?

    1. Evidence suggests non-enhancing black holes don't add any useful information over and above T2-hyperintense and Gd-enhancing lesions in the *diagnostic* situation. Non-enhancing black holes are commonly seen with established MS. Not sure I understood correctly, but if you are asking whether SPMS can be detected at onset of MS, the answer is no. If asking for the diagnosis of "SP" in somebody with MS, this is usually diagnosed retrospectively as the transition from relapsing to SPMS is sometimes difficult to clarify.


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