Background: Although previously considered rare, nowadays there are a growing number of reports describing association of psychotic impairment and multiple sclerosis (MS). Still, this connection remains unclear. The etiology of psychosis in MS has also not been explained adequately. Material and methods: The authors report a case of multiple sclerosis evolution with psychotic impairment in a 62-year old male. The patient, who had previously been diagnosed with acute disseminated encephalomyelitis, complained of acute delusional disorder during his rehabilitation course. Magnetic resonance tomography was carried out and revealed progression of the focci of demyelination in fronto-basal lobes, paraventricular and perviventricular regions. Mental condition of the patient improved after steroid therapy. The patient was followed up after a period of 2 weeks wherein, improvement in psychotic symptoms was reported. Results: On the grounds of the clinical symptoms and magnetic resonance tomography findings a diagnosis of multiple sclerosis by Revised McDonald Criteria (2010) was made. Conclusions: The present case report describes a psychotic impairment as an isolated clinical manifestation of the second onset of multiple sclerosis. The case demonstrates the importance in considering multiple sclerosis as a cause of acute or progressive severe cognitive impairment even with relative sparing of other neurological deficits. We suggest that the acute psychosis that has been described in the case is associated with the lesions in frontobasal and periventricular area of temporoparietal region and pericallosal area.