We conducted an evaluation of changes in cognition in progressive multiple sclerosis (MS) patients receiving monthly intravenously pulse of cyclophosphamide (700 mg/m2) with methylprednisolone (1g). Twenty-eight consecutive progressive MS patients (10 primary progressive, 18 secondary progressive MS) were evaluated before and after six and 12 months of treatment. The WAIS-R score, memory and executive functions were evaluated. Under treatment we found a significant improvement in global cognitive efficiency, encoding abilities, planning abilities and inhibition after six and 12 months. However, mechanisms of action of the positive effect of these anti-inflammatory and immunosuppressive treatments on cognition remain unclear.