app

McDonald Criteria for MS May Incorporate CSF Testing

— Revision committee finds OCB testing may be useful in specific cases

Last Updated May 26, 2017
MedpageToday

NEW ORLEANS -- An upcoming revised version of the McDonald diagnostic criteria for multiple sclerosis (MS) will likely expand the role of cerebrospinal fluid (CSF) testing in diagnosing the disease, a researcher said here.

Last , the diagnostic algorithm holds that when a patient has clinically isolated syndrome (CIS) plus magnetic resonance imaging (MRI) evidence showing dissemination in space (DIS), but not dissemination in time (DIT), that patient must have a second clinical event or new MRI evidence to show DIT before they can be diagnosed with MS, said Jeffrey Cohen, MD, of the Cleveland Clinic.

With the revised criteria, however, physicians won't have to wait for that second event; instead, they can test CSF for the presence of oligoclonal bands (OCBs) to diagnose MS, Cohen said during a lecture at the here.

"On the one hand, this is somewhat of a return to the past, as this was in fact one of the categories in Poser criteria. On the other hand, this may be a somewhat controversial proposal in that it could be viewed as no longer requiring a demonstration of dissemination in time."

Other revisions, he noted, will focus on avoiding misdiagnosis and updating diagnostic criteria for specific populations, including children, Asians, and Latin Americans.

Cohen, who along with Alan Thompson, MD, of University College London Hospitals in England, co-chaired the revision committee, said the group met for the first time in Philadelphia in November, and just completed a second and final meeting in Berlin last weekend. He said he expects the recommendations to be written and submitted for publication by the end of the summer.

Cerebrospinal Fluid Testing

Cohen noted that while CSF testing has been de-emphasized in previous versions of the criteria, "perhaps we need an increased emphasis now."

OCBs in CSF have become a more reliable test of intrathecal antibody production than the IgG index, he said, but testing for them must be done by a laboratory that "knows what it's doing and has the appropriate test. It's not obligatory in all patients, but there should be a low threshold for using it to increase diagnostic confidence if the clinical and MRI evidence is equivocal."

In that case, doctors should be "hesitant to make the diagnosis of MS if OCBs aren't demonstrated," although there are some caveats, such as very early in the disease when patients may turn up negative for OCBs, Cohen continued. These patients should be followed longer. In addition, OCBs may be present in other conditions, but in that case they are usually transient.

Avoiding Misdiagnosis

Given the push to diagnose MS as early as possible to maximize treatment benefit, clinicians need to be careful about misdiagnosis, Cohen said. One recent study found that MS has been mistaken for migraine, fibromyalgia, and neuromyelitis optica spectrum disorder -- and that about a third of these patients are taking disease-modifying therapies that will have little effect and come at steep costs.

"Our conclusion was that although some misdiagnosis might be created by the criteria, it's mostly a problem of misapplying the criteria," Cohen said. "We have to apply the criteria with rigor."

He emphasized that the criteria were developed and validated to identify MS in patients with a high likelihood of the disease following CIS, and the criteria were not designed to differentiate MS from other potential mimics.

"In the absence of classic CIS, the diagnosis needs to be made with caution," Cohen said. "The farther one gets from CIS, the more caution one needs to have. There needs to be a low threshold for obtaining additional testing, including CSF or MRI when needed, and in some cases the clinician needs to postpone making a diagnosis, or postpone disease-modifying therapy, if there's some diagnostic uncertainty. Longer follow-up may be needed."

He added that physicians need to take care in accepting historical events that sound like CIS but where there is not current evidence of the expected consequences of that event: "If you are basing your diagnosis of MS on what you think is the prior history of optic neuritis, it needs to be a good story for optic neuritis. There needs to be evidence now of persistent optic neuropathy."

Other Populations

Cohen said there have been a number of studies that support the applicability of the McDonald criteria in children -- noting, however, that physicians should be careful in diagnosing MS in children under age 11. Their initial event cannot be acute disseminated encephalomyelitis; instead, it should be more typical of CIS. Also, other considerations must be ruled out, particularly neuromyelitis optica spectrum disorders (NMOSDs).

There are more modest data that the criteria can also be effectively applied to Asian and Latin American patients, but physicians need to carefully address alternative diagnoses like NMOSD, and for Latin American patients, infectious diseases. Cohen noted that the group will recommend further studies in these populations.

The evidence base is far less extensive for diagnosing MS in older patients, but the criteria could apply here, he said.

Finally, substantial amounts of new data have become available about NMOSDs: "Although manifestations of NMOSD and MS can overlap, they are now recognized to be different diseases," Cohen said, adding that in most cases, MS and NMOSD diagnostic criteria largely differentiate these disorders.

Still Under Consideration

Other aspects still under consideration by the revision panel include how to incorporate the revised phenotype characterizations into diagnosis, whether new MRI in MS criteria should be accepted in aggregate or in part, how optic nerve involvement is best incorporated into making a diagnosis of MS, and how best to diagnose patients with non-classical presentations.

Disclosures

Cohen disclosed financial relationships with Adamas, Celgene, Merck, Mallinckrodt, Novartis, Synthron, and Teva.