A prospective study in patients with a clinical acute isolated brainstem or spinal cord disorder was undertaken. The aim was to evaluate the predictive value of IgG intrathecal synthesis (through the detection of oligoclonal bands in CSF) and MRI lesions at presentation, for the subsequent progression to multiple sclerosis. Forty four patients took part in this study: 22 had a brainstem disorder and 22 a spinal cord disorder. After a mean period of 26 (SD 22) months, 30 patients (68.2%) developed clinically definite multiple sclerosis. The remaining 14 patients were followed up for more than seven years. Twenty six (59.1%) patients had oligoclonal bands in CSF, with a sensitivity of 80.0%, specificity of 85.7%, and a predictive value of 92.2%. Magnetic resonance imaging showed disseminated white matter lesions in 22 patients (50.0%), with a sensitivity of 60.0%, a specificity of 71.4%, and a predictive value of 81.7%. The difference between patients with multiple sclerosis and patients without the disease was statistically significant for the findings of an IgG intrathecal synthesis (P < 0.001). It was only borderline for the MRI findings (P = 0.052). Thus the detection of an intrathecal synthesis at presentation seemed to be a better prognostic indicator of the progression to multiple sclerosis in patients affected by acute isolated brainstem or spinal cord syndromes.