Background Multiple sclerosis (MS) is a common disease with considerable risk for disability. Optic neuritis (ON) is a common first symptom of MS but it can also remain an isolated episode. Therefore, predicting the outcome of ON has gained in importance, particularly in light of current discussions of early disease modifying treatments in individuals at risk of developing MS. We reported previously on our cohort of 86 patients with acute monosymptomatic unilateral ON of whom 33 had progressed to MS after up to 18 years. Three patients had died. The present study extends the observation period to 31 years. Methods Patients were followed for up to 31 years or until a diagnosis of MS was made. Cerebrospinal fluid (CSF) was examined at onset. HLA class I and II antigens were determined. Magnetic Resonance Imaging (MRI) was performed during follow up. Findings Only one of 50 patients at risk developed clinical manifestations of MS during the extended follow up period. The estimated 15-year-risk of MS was 40%(confidence interval [CI]-31%-52%). Most cases, 20 of 34 or 60%, occurred within three years. Among factors present at onset, CSF with mononuclear pleocytosis and/or oligoclonal Ig increased the risk for subsequent MS significantly, 49%(CI 38%-65%) compared with 23%(CI 12%-44%) for those with normal CSF, p=0.02. Younger patients and those with winter onset also had greater risk. Recurrence ofONsimilarly elevated the risk significantly, p < 0.001. After 19-31 years MRI lesions suggestive of demyelinating disease were detected in 20 of 30 individuals although no clinical manifestations of MS had occurred. Conclusion The risk of MS in this large population-based prospective ON patient series was 40%and significantly higher in those with inflammatory CSF abnormalities at onset. Clinically silent MRI lesions suggestive of MS were detected in a majority of those with “ON-only”. This finding should be taken into account when discussing prognosis and early intervention in patients with clinically isolated ON.
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