Abstract: We did not include any new trials in this update. One randomised controlled trial of 32 patients is included. Concerning risk of bias, generation of the allocation sequence was at low risk; however, allocation concealment, blinding and selective reporting were at high risk. Treatment response, defined as 20% improvement from basal conditions by clinical, serological and specific neurological measures, was found in 94.7% (18/19) of patients using cyclophosphamide compared with 46.2% (6/13) in the methylprednisolone group at 24 months (RR 2.05, 95% CI 1.13 to 3.73). This was statistically significant and the number needed to treat for an additional beneficial outcome (NNTB) of treatment response is three. We found no statistically significant differences between the groups in damage index measurements (Systemic Lupus International Collaborating Clinics (SLICC)). The median SLE Disease Activity Index (SLEDAI) rating favoured the cyclophosphamide group. Cyclophosphamide use was associated with a reduction in prednisone requirements. All the patients in the cyclophosphamide group had electroencephalographic improvement but there was no statistically significant difference in decrease between groups in the number of monthly seizures. No statistically significant differences in adverse effects, including mortality, were reported between the groups. This systematic review found one randomised controlled trial with a small number of patients in the different clinical subgroups of neurological manifestation. There is very low-quality evidence that cyclophosphamide is more effective in reducing symptoms of neuropsychiatric involvement in SLE compared with methylprednisolone. However, properly designed randomised controlled trials that involve large numbers of individuals, with explicit clinical and laboratory diagnostic criteria, sufficient duration of follow-up and description of all relevant outcome measures, are necessary to guide practice. As we did not find any new trials to include in this review at update, the conclusions of the review did not change.

Plain-language summary: In people with central nervous system lupus: - We are uncertain whether cyclophosphamide improves signs and symptoms or disease activity compared to methylprednisolone. - No differences between the two groups were found in tissue or organ damage, or in the number of monthly seizures, but this may have happened by chance. - After six months of treatment, people who took cyclophosphamide took fewer prednisone pills than people who took methylprednisolone. - And at the end of two years, more people who took cyclophosphamide stayed on their treatment than people who took methylprednisolone. We often do not have precise information about side effects and complications. This is particularly true for rare but serious side effects. Side effects, such as infections, high blood sugar and high blood pressure, pancreas problems and death occurred about the same amount in people who took cyclophosphamide or methylprednisolone. Systemic lupus erythematosus (SLE) is a disease in which the body's immune system attacks the body. In CNS lupus (central nervous system lupus) the body may have attacked and damaged the cells in the brain and spine. This damage may cause a person to have convulsions/seizures, chronic headaches, confusion and psychosis. Drugs such as corticosteroids (prednisone or methylprednisolone) are usually used for lupus to decrease inflammation and control the immune system. Immunosuppressive agents or cytotoxics such as cyclophosphamide (CTX or Cytoxan) may also be used. - 49 more people who took cyclophosphamide improved than people who took methylprednisolone. - 95 out of 100 people had at least a 20% improvement in symptoms with cyclophosphamide. - 46 out of 100 people had at least a 20% improvement in symptoms with methylprednisolone.