Several studies have reported a higher prevalence of unipolar depression and bipolar disorder among patients with multiple sclerosis (MS). However, only a few studies have reported manic episodes concomitant with new lesions enhanced by gadolinium on brain magnetic resonance imaging (MRI). Here we report the case of a 47-year-old woman suffering from MS admitted for a manic episode with psychotic features. Brain MRI revealed three new T2 lesions enhanced by gadolinium located in the corpus callosum and in ventromedial prefrontal regions. She rapidly recovered with intravenous methylprednisolone in combination with risperidone. In conclusion, in this patient, the fact that gadolinium-enhancing lesion coincided with new symptoms which responded quickly to corticosteroids suggests that the manic episode was an acute manifestation of MS.