Proposal for New Diagnostic Critera for Clinically Isolated Syndrome (CIS)

Weren't we just recently talking about diagnostic criteria and the impact of "earlier diagnosis"? That and the Will Rogers Phenomenon....

New Diagnostic Criteria for Multiple Sclerosis Published
(by Allison Gandey, Medscape Medical News)

February 12, 2010 — Investigators are proposing new diagnostic standards for multiple sclerosis in clinically isolated syndromes. Their criteria are less stringent than other proposals and are designed to improve sensitivity to promote early diagnosis.

The authors report they wanted to simplify existing diagnostic criteria for multiple sclerosis. The group, led by Xavier Montalban, MD, from the Hospital Universitari Vall d'Hebron, in Barcelona, Spain, suggests current recommendations are complex and that "a good working knowledge of them is not always evident even among neurologists and neuroradiologists."

They point out that multiple magnetic resonance imaging (MRI) examinations are often needed to achieve an accurate diagnosis.

"This provides an incentive for continued efforts to refine the incorporation of MRI-derived information into the diagnostic workup of patients presenting with a clinically isolated syndrome," they note.

The new criteria appear in the February 2 issue of Neurology.

Recommendations

• Clinically definite multiple sclerosis can be confirmed if a MRI is performed at any time demonstrating dissemination in space and showing at least 1 or more asymptomatic gadolinium-enhancing and nonenhancing lesions.
• Patients without any enhancing or with all enhancing lesions would require a new MRI to demonstrate new T2 or gadolinium-enhancing lesions.
• Patients with an abnormal MRI performed at any time, but not showing dissemination in space or time, would require follow-up imaging.

"We recommend 1 dissemination in space criterion," the authors note. This would represent 1 or more asymptomatic T2 lesions in 2 or more of 4 locations considered characteristic for multiple sclerosis in previous MRI criteria — juxtacortical, periventricular, infratentorial, and spinal cord.

"We recommend 2 dissemination in time criteria," they add, and call for the presence of at least 1 or more asymptomatic gadolinium-enhancing and nonenhancing lesions irrespective of the time of the scan and the presence of a new T2 or gadolinium-enhancing lesion compared with a previous scan.

Asked by Medscape Neurology to comment on the new criteria, Gary Birnbaum, MD, from the Minneapolis Clinic of Neurology in Golden Valley, Minnesota, raised some concerns about the effect these recommendations could have.

"The proposed criteria are less stringent than other criteria, possibly increasing the sensitivity of detecting conversion to clinically definite multiple sclerosis, but possibly decreasing the specificity of the changes," he said. "This will need to be monitored carefully."

Increasing the Risk for Misdiagnosis

Dr. Birnbaum says the data supporting early treatment of multiple sclerosis are good; however, he suggests that not all patients with clinically isolated syndrome need, or necessarily benefit from, treatment with disease-modifying therapies.

This will need to be monitored carefully.

"Indeed, recent long-term data show that more than 30% of persons with 'high-risk' MRI changes do not have significant disease after 20 years of follow-up," he said. "There may not be a great urgency for establishing a diagnosis of clinically definite multiple sclerosis in a significant proportion of individuals with clinically isolated syndrome, especially if the specificity of criteria are less stringent — increasing the risk of misdiagnosis."

Dr. Birnbaum points out there are many disease-modifying therapies already approved for the treatment of patients with clinically isolated syndrome. "If a physician feels there is a need to begin treatment early, conversion to clinically definite multiple sclerosis is not necessary to prescribe such agents," he said.

More Study Needed

Dr. Birnbaum emphasizes that having less stringent MRI criteria for establishing disease progression may not be necessary and could increase the risk of treating people with diseases other than multiple sclerosis.

Ben Thrower, MD, a neurologist and senior medical advisor for the Multiple Sclerosis Foundation, said he agrees there are risks involved in early diagnosis. This could lead to inaccurate diagnosis or patients starting therapy with expensive and inconvenient medications, he suggests.

However, Dr. Thrower also acknowledges the benefits of early diagnosis, including peace of mind for patients and families dealing with unexplained symptoms. He points to data suggesting fewer relapses and new MRI lesions in those who start therapy sooner.

"These new proposed guidelines offer the possibility of using a single MRI to fulfil diagnostic criteria," Dr. Thrower said. "If the brain MRI shows lesions with and without active inflammation, this would demonstrate dissemination in time and space."

Dr. Thrower says the new criteria will need to be studied further and compared with existing McDonald criteria to determine whether they are sufficient.

Dr. Montalban and his team acknowledge that testing these criteria in new, prospectively followed clinically isolated syndrome cohorts is needed.

They also point out that scans in most studies have been performed on 1.5-Tesla or lower field-strength scanners using conventional T2-weighted spin echo or fluid-attenuated inversion recovery sequences.

They note, "The impact of 3 Tesla or higher field MRI findings or other MRI sequences on diagnosis will have to be considered in the future."

Dr. Xavier Montalban has received support from Novartis, Teva, Merck, Biogen Idec, Bayer, Schering Pharma, Sanofi-Aventis, Almirall, Eli Lilly, Genentech, Genzyme, Wyeth, and Fundació Esclerosi Multiple.

Neurology. 2010;74:427-434. Abstract

Medscape Medical News © 2010 Medscape, LLC