McDonald Criteria Update: Further Distinction Between Relapsing-Remitting, Primary-Progressive MS

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The McDonald Criteria function as the standard clinical measure for diagnosis of multiple sclerosis.
The McDonald Criteria function as the standard clinical measure for diagnosis of multiple sclerosis.

The diagnosis of multiple sclerosis (MS) has rested primarily on the use of the McDonald Criteria, first introduced in 2001, the utility of which has only become stronger over successive revisions in 2005 and 2010.1-3 At the recent 7th Joint European Committee for Treatment and Research in Multiple Sclerosis-Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) conference in Paris, Jeffrey Cohen, MD, cochair of the 30-member International Panel on Diagnosis of MS presented the 2017 updated recommendations based on the most recent data.4

The 2017 updates reflect changes in 4 main areas, including differentiating MS phenotypes, the addition of new categories by disease activity status, renewed interest in the use of cerebrospinal fluid (CSF) testing, and an expanded role for magnetic resonance imaging (MRI) in diagnosis.4

Identifying Different MS Phenotypes

Dr Cohen, director of Cleveland Clinic's Mellen Center for Multiple Sclerosis Treatment and Research in Ohio, reported that a primary feature of the 2017 revision was the retention of the Lublin-Reingold classifications of disease course delineating relapsing-remitting MS (RRMS) and primary-progressive MS as distinct forms of the disease.3 The new criteria clarify these distinctions by separating progressive presentations at disease onset from those that initiate as RRMS and later convert to progressive disease.

"Relapsing and progressive courses represent different phenotypes of the same disease," Dr Cohen told Neurology Advisor, explaining that the aim of the revised criteria was to better distinguish between these phenotypes in earlier stages of the disease.

Categorizing Disease Activity

In the current revision, 2 additional categories were proposed, designed to provide information on status and patterns of disease activity: Active vs nonactive disease, based on the presence of recent clinical relapses or MRI lesion activity, and progression vs nonprogression, based on whether they had worsened gradually during the preceding period.

CSF Testing

After de-emphasis in 2010, whereby CSF testing only played a supportive role, the 2017 criteria suggest a significant utility of CSF in creating a new path for diagnosing MS. "Recognition that CSF examination is useful in general in situations where additional supporting data are needed to increase diagnostic certainty led to increased emphasis overall. New data led to the specific revision in the 2017 criteria to allow demonstration of CSF oligoclonal bands to substitute for demonstration of dissemination in time in patients with a typical clinically isolated syndrome and clinical or MRI demonstration of dissemination in space," Dr Cohen said.

Modifications to MRI Criteria

The 2017 revisions also recommend expansion of 2010 MRI criteria to include the presence of cortical lesions, as well as juxtacortical lesions to meet previous requirements for dissemination in space that involved at least 1 lesion in at least 2 locations. At the same time, it is no longer useful for diagnosis to distinguish between symptomatic and asymptomatic lesions.

Benefits for Early Treatment of MS

The 2017 criteria target early diagnosis for early treatment, Dr Cohen explained, such that "they allow for early diagnosis of MS in patients with a high likelihood of having MS, while preserving the specificity of the criteria to lessen the risk of misdiagnosis."

The committee determined that asymptomatic MS is destructive, based on research indicating that patients with clinically isolated syndrome and an abnormal MRI scan were found to be at high risk of developing MS, particularly in the first 6 months after the initial clinically isolated syndrome episode.5

Inflammatory activity clinically predates the first relapse in RRMS and is generally predictive of the onset of progressive disease, marked by Expanded Disability Status Scale scores of 3 to 4 and brain atrophy on MRI. In progressive stages of disease, both MRI and inflammatory signs are less predictive of outcomes, which, Carlo Comi, MD, reported in a 2013 ECTRIMS abstract, was "probably the major reason why treatments targeting inflammation have a decreased efficacy during the advanced relapsing and progressive phases of MS."5

Little progress has been made in treatments for advanced disease since then, Dr Cohen said in his ECTRIMS-ACTRIMS presentation. As the main clinical and pathological features of primary and secondary progressive MS are yet to be identified, he noted, the 2017 criteria aim to set research targets that take a broad approach on progressive disease, including:

  • Biologic targets and opportunities for repurposing existing medicinal compounds need to be found;
  • Proof-of-concept clinical trial outcomes should be designed to develop accurate surrogate measures to gadolinium-enhancing lesions in RRMS;
  • Development of precise, reproducible, and broad-based clinical outcome measures that are sensitive to change and are predictive over time; and
  • New symptom-management and rehabilitation strategies are needed to help lessen the effect of disability and enhance quality of life for patients with RRMS and primary-progressive MS.

When asked whether application of the new criteria will change therapeutic goals and strategies for individual patients, Dr Cohen told Neurology Advisor that, "The McDonald Criteria are not treatment guidelines per se. They affect treatment indirectly by facilitating early and accurate diagnosis, thus allowing initiation of treatment."

He also pointed out that, as the original criteria were based on MS presenting in adults older than 50 years, the new criteria expand patient subsets to include very young and very old adults in clinical studies. The primary clinical goal of the new criteria is that individual patients would be more appropriately categorized and assigned to treatment, with the opportunity for periodic reassessment as their disease status changes or new data emerge.

References

  1. McDonald WI, Compston A, Edan G, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001;50:121-127.
  2. Polman CH, Reingold SC, Edan G, et al. Diagnostic criteria for multiple sclerosis: 2005 revisions to the "McDonald Criteria". Ann Neurol. 2005;58:840-846.
  3. Polman CH, Reingold SC, Banwell B, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011;69:292-302.
  4. Cohen JA. Proposed Revisions to the McDonald diagnostic criteria. Presented at: 2017 Joint ECTRIMS-ACTRIMS Congress. October 25-28, 2017; Paris, France. Abstract 93.
  5. Comi G. Early treatment of multiple sclerosis. Presented at: 2013 ECTRIMS Congress. October 2-5, 2013; Copenhagen, Denmark.

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