The intrathecal synthesis of IgM in patients presenting with acute monosymptomatic syndromes may be relevant in predicting eventual progression to multiple sclerosis but has not been previously evaluated. We undertook a prospective 18-month combined clinical, cerebrospinal fluid, and magnetic resonance imaging study of 45 patients who had presented with acute isolated lesions of brainstem and spinal cord to evaluate the predictive value of intrathecal synthesis of IgM and IgG (through the detection of cerebrospinal fluid oligoclonal bands) and magnetic resonance imaging brain lesions at presentation, for the subsequent progression to multiple sclerosis. Results indicate that the highest risk of developing multiple sclerosis is seen in patients who are positive for oligoclonal IgM and IgG bands and who have disseminated cerebral white matter magnetic resonance imaging lesions at the initial presentation. Oligoclonal IgM bands predict progression to multiple sclerosis more frequently than oligoclonal IgG or magnetic resonance imaging alone. Our results confirm and further extend previous reports, and indicate that detection of cerebrospinal fluid oligoclonal IgM bands at presentation is a valuable prognostic indicator in patients presenting with acute isolated brainstem or spinal cord syndromes.