Encephalopathy after cyclophosphamide with response to methylene blue

We present two cases of encephalopathy occurring after chemotherapy containing cyclophosphamide. Patient 1 was receiving vincristine, cisplatin and cyclophosphamide for recurrent medulloblastoma, whilst patient 2 received cyclophosphamide‐containing chemotherapy as adjuvant treatment for early breast cancer. After cumulative doses of 2.8 and 6 g/m 2 of cyclophosphamide both patients developed a gradual onset of fluctuating attention, slowed mentation and decreased consciousness. Extensive investigations excluded other causes of this altered conscious state. Given the similarity of presentation to ifosfamide encephalopathy, methylene blue (50 mg i.v.) was administered. Patient 1 experienced an immediate improvement that was not sustained, with a subsequent deterioration over several weeks and became unresponsive before death. Patient 2 experienced a dramatic improvement within 3 h and received a second dose of methylene blue with further improvement. To our knowledge, cyclophosphamide has not previously been implicated as a cause of encephalopathy. A review of the literature is presented. We hypothesize that cyclophosphamide may rarely cause encephalopathy and may also contribute to the cognitive dysfunction reported in association with chemotherapy for breast cancer and non‐Hodgkin’s lymphoma.