Low-dose weekly methotrexate for progressive neuropsychiatric manifestations in Behcet's disease

The most serious central nervous system (CNS) manifestation in Behcet's disease is a slowly progressive dementia (progressive NB), which may ultimately lead to the deterioration of the personality of patients. An open trial was designed to investigate the efficacy of low dose weekly methotrexate (MTX) therapy for progressive NB. Six patients with Behcet's disease, whose neuropsychiatric manifestations were judged to be progressive (4 females and 2 males, aged 55.0+/-8.2 years), were given oral MTX (7.5-12.5 mg/week) until the end of the 12-month trial. The clinical responses of the patients to MTX were judged by neuropsychiatric findings, intelligence test, brain MRI scans and cerebrospinal fluid (CSF) IL-6 levels. After the 12-month trial, CSF IL-6 levels were found to be significantly decreased. Accordingly, the neuropsychological manifestations as well as the findings on MRI scans and intelligence quotients were not significantly worsened after the trial. Three patients presented with mild liver dysfunction, which returned to normal by decreasing the dose of MTX. However, 6 months after discontinuation of MTX, all the six patients showed significant exacerbation of the manifestations as evidenced by a decrease in verbal intelligence quotients along with the marked elevation of CSF IL-6. These results suggest that low dose weekly MTX therapy might have a beneficial effect in the treatment of progressive NB, although a trial for a longer period would be necessary.