ORLANDO—Although the diagnostic criteria for multiple sclerosis (MS) have evolved over the years, the emphasis has always been on accuracy. “We have new tools and are better at diagnosing MS today than we were five years ago. In an effort to identify those cases of MS that are likely to advance quickly and require early therapy, we need to utilize those tools and all the information we have,” said Anthony Traboulsee, MD.

He cited the McDonald criteria, which were propsed as a revision to the Poser criteria and developed by an international panel of MS experts, the focus of which was to “bring into the 21st century additional, objective tools” such as MRI that were not available when the previous criteria were developed. The McDonald criteria, which incorporate the common MRI abnormalitites found in MS patients, allow for an earlier diagnosis of MS in patients with a clinically isolated syndrome and who do not fulfill clinical criteria for MS. He made his comments at the 19th Annual Conference of the Consortium of Multiple Sclerosis Centers.

MAXIMIZING SENSITIVITY AND SPECIFICITY

When applying MRI to the diagnosis of MS, the purpose is not only to identify potential cases of MS but ideally also to identify those patients who are likely to have more aggressive forms of the disease, Dr. Traboulsee believes. “We really do want to show that these potential cases do have the disease, and this is the focus of specificity, and that is the underlying theme that we’re driving for with diagnostic criteria.” He is Assistant Professor in the Division of Neurology, Department of Medicine, at the University of British Columbia, Vancouver.

As for sensitivity, Dr. Traboulsee said, “We need to pick up on all the patients who have the disease, but we want to be sure those patients actually have the disease. Specificity and sensitivity need to be maximal in order to be accurate.” He did caution that no diagnostic tool can be 100% accurate, however. Indeed, the inverse relationship that exists between sensitivity and specificity dictates that increased sensitivity will cause more false-positive results.

Dr. Traboulsee referred to the McDonald criteria that state that two distinguishing lesions on clinical examination in conjunction with two or more clinical attacks is sufficient for a diagnosis of MS. Although additional testing may not be required under those criteria, he emphasized that most patients would also have an MRI performed. In early MS, it was possible to have negative MRI and spinal fluid results. With such reports, he acknowledged, “I’d be very hesitant to make a diagnosis of MS, as I’m always thinking about what else it can be.”

THE CLINICALLY ISOLATED SYNDROME CRITERIA

If a patient history includes two clear demyelinating events and only one evident lesion on clinical examination, MRI can be used to provide the needed evidence of additional lesions “separated in space.” But what about the patient with a single episode? With a clinically isolated syndrome, “clearly, you are not able to make a diagnosis of MS and you need to have evidence that there is dissemination not only in space—which the MRI can tell us—but in time as well,” Dr. Traboulsee noted. Until evidence from the second clinical event is available, the presence of lesion activity on MRI can serve as a criterion, he suggested. The McDonald guidelines “allow us to use MRI evidence for new lesion activity—dissemination in time—for patients with clinically isolated syndrome to fulfill diagnostic criteria for MS,” he said.

A number of studies have been published that have attempted to validate the McDonald criteria in the setting of clinically isolated syndromes. A study by Dalton et al found that more than 60% of patients initially presenting with a clinically isolated syndrome, most commonly optic neuritis, had lesions on MRI. In this study patients underwent regular MRI studies and were followed for three years to determine whether they progressed to clinically definite MS. According to the McDonald criteria, these patients with clinically isolated syndrome were diagnosed with MS quite early in the disease process, with a sensitivity of 83%. Additionally, Dr. Traboulsee said, the specificity was also very high, at 83%, “which means that accuracy was reasonably good.”

He cited a second study by Tintore et al that followed 139 patients for three years, with MRI at three and 12 months. The researchers compared the updated McDonald criteria, which incorporate MRI, with the Poser diagnostic criteria. They found that “one year after symptom onset, more than three times as many patients with clinically isolated syndrome were diagnosed with MS using new diagnostic criteria incorporating MRI results” compared with older criteria. The newer McDonald criteria demonstrated sensitivity of 74%, specificity of 86%, and accuracy of 80% in predicting conversion to clinically definite MS. Although the sensitivity was somewhat lower, “the benefit is increased specificity, and that is really the goal of the criteria—to make sure we’re making the right diagnosis and an 80% accuracy rate is not bad.”

As Dr. Traboulsee summarized, “We need to make an early diagnosis … but we need to make an accurate diagnosis.” The concern is that precise criteria may imply that MS can be diagnosed by MRI; however, a negative MRI at the time of a clinically isolated syndrome does not rule out MS. Until recently, the validations of the McDonald criteria have focused on specificity, and as for their application to patients with a clinically isolated syndrome. He believes that “It is inevitable that the diagnostic criteria will be applied to patients with symptoms that are not classic for clinically isolated syndrome but suspicious for MS. Unfortunately, the MRI diagnostic criteria have not been validated for this more challenging group of patients.”

NR

—Heidi W. Moore

Suggested Reading
Dalton CM, Brex PA, Miszkiel KA, et al. Application of the new McDonald criteria to patients with clinically isolated syndromes suggestive of multiple sclerosis. Ann Neurol. 2002;52:47-53.
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.
Poser CM, Paty DW, Scheinberg L, et al. New Diagnostic Criteria for Multiple Sclerosis: Guidelines for Research Protocols. Ann Neurol. 1983;13:227-231.
Swanton JK, Fernando KT, Dalton CM, et al. Modification of MRI criteria for MS in patients with clinically isolated syndromes. J Neurol Neurosurg Psychiatry. July 25, 2005. E-pub ahead of print.
Tintore M, Rovira A, Rio J, et al. New diagnostic criteria for multiple sclerosis: application in first demyelinating episode. Neurology. 2003;60:27-30.

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