New Recommendations on MRI Diagnosis of Multiple Sclerosis

February 09, 2016

New revisions to the MRI criteria for the diagnosis of multiple sclerosis (MS) have been proposed.

The revisions, published online in The Lancet Neurology on January 25, have been put forward by the European collaborative research network that studies MRI in MS (MAGNIMS).

MAGNIMS member and coauthor of the paper, Maria A. Rocca, MD, San Raffaele Scientific Institute, Milan, Italy, explained to Medscape Medical News that diagnosis of MS relies on proof of disease "dissemination in space and time" — meaning symptoms or lesions need to be seen in different locations and at different times.

The new recommendations for MRI diagnosis mainly relate to the "dissemination in space" criteria, which Dr Rocca says currently lead to MS being overdiagnosed. "We have proposed slightly stricter conditions for some of these criteria, which we believe will lead to more accurate diagnosis," she said.

The recommendations are the product of discussions at a MAGNIMS workshop that had the goal of providing an "evidence-based and expert-opinion consensus on proposed modifications to MRI criteria for the diagnosis of multiple sclerosis." Travel expenses for the workshop were paid by Novartis through a provider.

The author of an accompanying editorial, Dr Robert J. Fox, Cleveland Clinic, Ohio, who is not part of the MAGNIMS group, told Medscape Medical News that the new recommendations were a "helpful step forward" in diagnosing MS.

He explained that MRI has become an invaluable tool for MS diagnosis and following the evolution of the disease over time. "But how MRI is used to confirm or exclude MS and the specific criteria needed for an MS diagnosis change over time as new studies are reported."

He noted that if there is more than one clinical episode in different locations in the body, an MRI is not needed to diagnose MS. "But it is helpful to confirm the diagnosis and to stage the disease. But if there has been only one clinical symptom, then an MRI is often conducted to look for characteristic lesions to confirm the diagnosis."

There has always been the requirement that lesions should be found in at least two different locations, Dr Fox added. "The new recommendations still specify this requirement but instead of four different possible locations to consider they have added in another one — the optic nerve. This will widen the diagnosis a little. But they have also raised the requirements when considering lesions in the periventricular space, which will narrow the diagnosis. The net result is that an MS diagnosis should now be more precise."

The new document recommends that to fulfil the "dissemination in space," at least two of the following are required:

  • Three or more periventricular lesions;

  • One or more infratentorial lesion;

  • One or more spinal cord lesion;

  • One or more optic nerve lesion; and

  • One or more cortical or juxtacortical lesion.

Some of the most important changes in the new recommendations are summarized below:

Three periventricular lesions: Dr Rocca explained that one of the reasons for the overdiagnosis of MS with the previous criteria was that a single lesion in the periventricular space was allowed as one of the two diagnostic factors. But she notes that a single periventricular lesion is unspecific and can be found in several other neurologic conditions. "We are therefore now recommending that we go back to the original criteria that there should be at least three periventricular lesions as one of the two diagnostic criteria."

Dr Fox said this was a sensible change. "Periventricular lesions can occur in other conditions as well as MS. We often perform MRI scans on patients for other reasons — we are not looking for an MS diagnosis, but if we find just one periventricular lesion then this has raised the possibility of MS. Now three periventricular lesions are required for one of the two MRI criteria in terms of location, so this will improve specificity."

Optic nerve included: The new recommendations include the optic nerve as another possible site to look for lesions. "There used to be four different sites which could be considered when looking for lesions and now we are including the optic nerve, so there are there now five possible locations," Dr Rocca said.

Dr Fox said he was not sure about this recommendation, saying: "We don't often see lesions in the optic nerve even in patients with optic neuritis."

But Dr Rocca stressed that the optic nerve does not have to be the subject of a separate MRI scan. "An optic nerve lesion could be detected by other means: clinical exam, other imaging or neurophysiological exam," she said. "We just wanted optic nerve involvement to be included as one of the possible diagnostic factors. If optic neuritis is present, then the patient just has to have lesions in one of the other four sites to have an MS diagnosis rather than previously, when they had to have lesions in two other sites."

Symptomatic lesions included: In the previous recommendations, a symptomatic lesion did not count toward the two lesions in separate locations necessary for an MS diagnosis, Dr Rocca said. "But now we have several studies which show that these lesions are important, and it can be difficult to differentiate between symptomatic and asymptomatic lesions. So we have included the recommendation that a symptomatic lesion counts similarly to an asymptomatic lesion for the purpose of MS diagnosis.

Dr Fox welcomed this change. "Including symptomatic lesions is a sensible idea. The concern has been that including the symptomatic lesion may reduce the specificity of an MS diagnosis, but actually studies have suggested that this is not the case. It is also more straightforward to include the symptomatic lesion, so this will simplify the process," he said.

Cortical and juxta-cortical lesions combined: Dr Rocca explained that a single cortical lesion signifies a high risk for MS. "If there are cortical lesions, then this is quite specific for MS. At present there isn't a unique technique for identifying cortical lesions, so we felt it was reasonable to include them with juxta-cortical lesions."

Dr Fox said he was unsure about this recommendation. "It is difficult to see cortical lesions on standard imaging, so I'm not sure they should be included in diagnostic criteria. There may be artifacts that may be interpreted as cortical lesions."

But Dr Rocca countered, "It is possible to see cortical lesions with more sophisticated imaging, and it is often possible to discern them with a trained eye on 3DPI weighted scans which are widely available now. We need to make clear the importance of cortical lesions if they are found. If there is just one visible this is important for MS diagnosis."

Identical criteria for primary progressive and relapsing-remitting MS: Dr Rocca explained that previously these have had different criteria for MRI diagnosis, but latest studies suggest that the criteria for relapsing-remitting disease applies equally well to primary progressive. Previously it was thought that primary progressive MS had more involvement of the spinal cord, but the latest studies suggest that the spinal cord and brain are similarly important in both forms of the disease. "The way we differentiate between the two forms is from clinical symptoms, not by imaging."

Dr Fox agrees with this. In his editorial he writes: "Substantial work is needed to better understand progressive multiple sclerosis, and conventional MRI does not seem promising in this regard."

Nonwhite populations: The new populations recommend that the same imaging criteria can be used in nonwhite populations as is used in white population. Dr Rocca commented: "Previously the studies have only involved European and North American patients, so we didn't know if the criteria for MS diagnosis also applied to other populations, but new studies from other parts of the world suggest that these criteria apply equally well to other populations."

In his editorial, Dr Fox concludes that: "Multiple sclerosis remains a clinical diagnosis, relying on assimilation of clinical history, neurological examination, and supporting diagnostic testing such as MRI." But he adds that "MRI continues to be an immensely powerful method for understanding multiple sclerosis."

Travel expenses for the MAGNIMS workshop were paid by Novartis through a provider. The speakers did not receive direct reimbursement. Dr Rocca reports she has received speaker's honoraria from Biogen Idec, Novartis, Genzyme, Sanofi-Aventis, and Excemed. Disclosures for coauthors appear in the paper. Dr Fox reports he has received personal consulting fees from Actelion, Biogen, Genentech, Mallinckrodt, MedDay, Novartis, Teva, and XenoPort; served on advisory committees for Biogen Idec and Novartis; and received research grant funding from Novartis.

Lancet Neurol. Published online January 25, 2016. Abstract Editorial

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