Clinical question — What is the chance of developing multiple sclerosis following the first episode of optic neuritis in a 19-year-old male?
This question was asked of us at the Centre for General Practice, University of Queensland, Australia, where we were providing a literature-search service in collaboration with the Department of Primary Health Care at the University of Newcastle, funded through the NHS Northern and Yorkshire Regional Library Advisory Service, for local GPs. The service was based on an Australian model.1
We present our response to one of the questions asked, updating the original search July 2005.
SEARCH QUESTION
First, the clinical question was reformatted into a ‘searchable question’.2
What is the risk of developing clinically apparent multiple sclerosis following a first episode of optic neuritis in a young male?
The ideal study to answer this question would be an inception cohort study of adults experiencing a first episode of optic neuritis over several years, with minimal loss to follow-up, and the development of clinically apparent multiple sclerosis as the outcome.
RAPID SEARCH
We searched Medline (on SilverPlatter via WebSpirs) for articles published in English using the following terms ‘optic neuritis’ (MeSH and text) AND ‘multiple sclerosis’ (MeSH and text) combined with a sensitive search filter for detecting clinically sound prognostic studies.3
SUMMARY OF FINDINGS
There were many studies evaluating the risk of developing multiple sclerosis after a single episode of optic neuritis.4–13 Their quality was good, although there may have been differential measurement causing bias (people with positive brain MRIs may have been less likely to have been lost to follow up, for example).
The risk of developing multiple sclerosis after an episode of optic neuritis ranged from 13 to 58%. Even with brain lesions identified at baseline, only slightly more than half of patients later developed clinical multiple sclerosis, although their absence did not eliminate the risk (0–22%).
Abnormal brain MRI were a strong predictor of multiple sclerosis in the largest study (optic neuritis trial), with 87% complete follow-up, the presence of one or more white matter lesions on baseline MRI brain scan more than doubled the 10-year risk of multiple sclerosis.4
COMMENT
The variation in results may be attributable to differences in study design, variation in criteria for the diagnosis of multiple sclerosis and optic neuritis, and length of follow-up. The studies give a reasonably robust indication of the prognosis.
The prognosis seems to be better than expected, and raises questions about whether optic neuritis may have other causes than the demyelination of multiple sclerosis, or that multiple sclerosis has a wide spectrum of expression, often little or never interfering with patients' lives.14
APPLYING THE RESULTS TO THE PATIENT
Apart from offering an overall prognosis, the literature suggests that this can be improved on by testing with MRI for other lesions on diagnosis of optic neuritis.
It also raises the question of treatment. The CHAMPS trial compared interferon β–1a and placebo on developing multiple sclerosis after a single demyelinating event among 192 patients.15 After 3 years, the adjusted rate ratios of clinically definite multiple sclerosis between the two trial arms was 0.58, (95% CI = 0.34 to 1.00). Similarly, in a second randomised placebo controlled trial of interferon ≤β–1a among 309 patients with a first neurologic episode consistent with multiple sclerosis (although in only 35% was this from optic neuritis), clinically apparent multiple sclerosis developed in 34% intervention patients compared with 45% controls.16 But this is a different question …
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