ROCKVILLE, MD. -- Magnetic resonance imaging can be used to diagnose suspected multiple sclerosis more quickly than current diagnostic standards, according to a new guideline issued by the American Academy of Neurology.

Studies have shown that MRI can detect occult disease activity in

50% to 80% of patients at the time of fast clinical presentation of a syndrome consistent with inflammatory demyelination. Such activity, which is a sensitive predictor of future conversion to clinically definite multiple sclerosis, provides sufficient evidence to support diagnosis and early treatment, Dr. Eliot M. Frohman and his colleagues said in a report by the AAN's subcommittee on therapeutics and technology assessment (Neurology 61[5]:602-11, 2003).

MS can be expected to develop within 7 to 10 years in more than 80% of young to middle-aged adults with a clinically isolated syndrome who meet these criteria: Alternative diagnoses have been ruled out and a T2-weighted MRI scan shows three or more white matter lesions, especially if one of the lesions is located in the periventricular region. The presence of two or more gadolinium (Gd)-enhancing lesions at baseline and the appearance of either new T2 lesions or new Gd enhancement on follow-up scans also is highly predictive of development of clinically definite multiple sclerosis in the near term, according to the report.

Early diagnosis and aggressive treatment of MS has been the subject of much debate in recent years. Under current standards, a diagnosis of clinically definite multiple sclerosis requires evidence of two or more distinct events separated in time and the involvement of at least two distinct areas of the central nervous system. Also, all alternative diagnoses need to have been excluded by appropriate laboratory and radiographic studies.

With growing evidence that early treatment can reduce the entire course of the disease, "we really needed to ask the question about how early the diagnosis can be made," said Dr. Frohman, director of the Multiple Sclerosis Program at the University of Texas Southwestern Medical School in Dallas.

The researchers evaluated 22 prospective studies of a minimum of 20 patients each. The studies assessed whether the presence of MRI lesions in the brain or spinal cord could predict the risk of clinically definite multiple sclerosis in patients with a clinically isolated syndrome. Overall, the presence of even one to three lesions at baseline was associated with a 98% chance of developing either probable or definite MS.

"A striking feature of the literature in patients with a clinically isolated syndrome with typical MRI lesions is the apparent low risk of any alternative diagnosis being made at follow-up, even when the MRI changes are minimal," Dr. Frohman and his colleagues said.

The results suggest that in patients with a clinically isolated syndrome, even a few characteristic MRI lesions are specific for demyelinating disease once appropriate alternative diagnoses have been excluded. "The principal diagnostic consideration is whether the patient has a nonrecurrent demyelinating disease or will ultimately prove to have the recurrent disease process we designate as MS," according to the AAN report.

"We now have multiple data sets [including two class 1 clinical trials] demonstrating the benefits of treating MS and those patients with a first attack of what appears to be MS," Dr. Frohman said in an interview. "We now know that early treatment can reduce attacks and brain lesions in these single-syndrome patients, so diagnosis at the time of the first event is now more than ever of great importance. MRI is vital in this approach, but careful consideration by an experienced clinician is still not expendable."

No systematic cost/benefit analyses have examined the effects of early versus delayed treatment, but the financial, physical, and emotional cost of MS-associated disability is much greater than the cost of the disease, modifying agents currently used, Dr. Frohman said.

If untreated in the early stages, MS can accelerate and may even become resistant to treatment. "'We now have evidence to suggest that with each new clinical event or new MRI lesions, the immune system appears to be expanding in its ability to recognize an ever-expanding number of "self" proteins--a process called epitope spreading. As such there appears to be both a bolstering of the immune response over time to previously recognized proteins as well as a diversification of the number and types of autoimmune responses within the brain and spinal cord," Dr. Frohman said.

Current drugs for MS have few downsides except for cost and minor side effects, so "there's not much sense" in waiting for additional disability and more attacks to confirm the diagnosis, Dr. Frohman said. "If the majority of these patients have MS and waiting could compromise how we can affect the course of the disease, then we need to go ahead and treat them."

The diagnostic criteria addressed by the subcommittee should not be applied to patients with progressive disease without attacks. "There have been no systematic longitudinal studies concerning the predictive validity of any MRI pattern in patients with progressive neurologic syndromes," the authors wrote.

In an editorial, Dr. Jack H. Simon of the University of Colorado Health Sciences Center, Denver, and Dr. Alan J. Thompson of the Institute of Neurology, London, noted that MRI studies and their interpretation vary in quality. "The Frohman report lacks recommendations regarding specific anatomic features of MRI lesions" and their distribution (Neurology 61[5]: 596-97, 2003).

"Common sense suggests that specific anatomic criteria may decrease the likelihood of false diagnoses, but definitive data are needed," the editorialists wrote. "'We need additional long-term follow-up studies and better standardization of MRI acquisition and interpretation to increase our confidence in MS diagnostic criteria."