Methylene Blue in Management of Acute Ifosfamide-Induced Encephalopathy-Case Report and Literature Review

Administration of several chemotherapeutic agents is associated with a significant risk of neurotoxicity. Neurologic adverse reactions are frequently observed after ifosfamide, which metabolites may cause acute ifosfamide-induced encephalopathy (IIE). There is no standard management in this clinical setting. Herein we report a case of 28 year old male with a B-cell lymphoma unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma. The patient developed a severe IIE with catatonia, as well as fecal and urinary incontinence during combined systemic ifosfamide-based chemotherapy. The infusion was interrupted; hydration and forced diuresis were implemented. Drugs with known sedative effect on the central nervous system were eliminated. Nevertheless, no improvement was observed. At this point a decision was made to administer methylene blue (MB). Two doses were infused at intervals of 6 hours with fast improvement and elimination of IIE symptoms on the second day after MB infusion. Noteworthy, no toxicity attributable to MB was observed. Described treatment was based on previous case reports and small retrospective series and obtained results fully confirmed the conclusions of these publications.