SAN FRANCISCO—“Predicting the outcome of clinically isolated syndromes has become more important in light of current discussions of disease-modifying treatments,” according to Magnhild Sandberg-Wollheim, MD. “The objective of this study was to evaluate the risk for multiple sclerosis [MS] in a prospective, population-based cohort of previously healthy individuals with acute optic neuritis after an observation period of 30 years and to reexamine previously suggested risk factors.” Dr. Sandberg-Wollheim, of the Department of Neurology at the University of Lund in Sweden, reported the results of the study at the 56th Annual Meeting of the American Academy of Neurology.

LONG-TERM FOLLOW-UP

The cohort of 86 patients with optic neuritis was collected between 1969 and 1981 and patients were followed prospectively for up to 31 years or until diagnosis of MS could be established, Dr. Sandberg-Wollheim reported. The age of MS onset was similar to that among patients in the general MS population, she said; “75 of them were between 20 and 50 and there were a few teenagers. One third of the individuals were male. This cohort was collected when MRI was not yet a general clinical practice—therefore we have no MRI data at onset,” she noted.

Lumbar puncture was performed at onset of the optic neuritis attack. Abnormal cerebrospinal fluid was obtained in 63% of the patients, gliocytosis in 54%, and oligoclonal bands were present in slightly less than half of the patients, said Dr. Sandberg-Wollheim. All patients were also typed for human leukocyte antigen (HLA); 52% were DR2 positive, “which is similar to the frequency in MS cases in our area compared to the healthy controls, which is 29%, so this is a very significant difference,” she noted.

PREDICTION PATTERN

Of the 86 patients, 34 (40%) developed MS: 10 within one year, 20 within two to three years, and all of them within 14 years, according to Dr. Sandberg-Wollheim. “The risk of developing MS is highest in the first three to five years,” she said. Additionally, patients who had abnormal inflammatory changes in the cerebrospinal fluid at onset of optic neuritis had a higher risk of developing MS than those with normal cerebrospinal fluid (49% versus 23%, respectively). A second attack of optic neuritis, especially if it occurred early, also increased the risk significantly, Dr. Sandberg-Wollheim noted.

Neither sex, nor age at onset, nor HLA DR2 conferred greater risk, she said. “Females had a greater risk than males, but not significantly, and younger patients had a greater risk than older patients, but also not significantly.”

IMAGING DATA

“As I mentioned, we were not able to do MRI at onset, but we were able to do MRI at two occasions during follow-up,” Dr. Sandberg-Wollheim said. Thirty of 42 patients with optic neuritis consented to MRI scans of their brains. The investigators found that 20 of these patients had two or more lesions suggestive of demyelinating disease.

“I should add that we compared these MRI findings with the published MRI criteria for MS and with the more permissive Paty and Fazekas criteria; most of the patients actually fulfilled those, whereas no patient fulfilled the Barkhof criteria,” noted Dr. Sandberg-Wollheim.

SUMMING UP THE FUTURE

“In summary, the risk of MS after optic neuritis was approximately 40%. The risk was greater if cerebrospinal fluid was not normal at onset, and the risk increased after a new attack of optic neuritis,” Dr. Sandberg-Wollheim reviewed. “MRI lesions were seen in two of three patients with optic neuritis, and I think this should perhaps be taken into account when people discuss how to treat patients with clinically isolated syndromes,” she concluded.

NR

—C. Justin Romano

Suggested Reading
Fazekas F, Offenbacher H, Fuchs S, et al. Criteria for an increased specificity of MRI interpretation in elderly subjects with suspected multiple sclerosis. Neurology. 1988;38:1822-1825.
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.
Miller DH, Albert PS, Barkhof F, et al. Guidelines for the use of magnetic resonance techniques in monitoring the treatment of multiple sclerosis: US National MS Society Task Force. Ann Neurol. 1996;39:6-16.

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