Fatal chemotherapy-induced encephalopathy following high-dose therapy for metastatic breast cancer: a case report and review of the literature

Abstract

Summary:Chemotherapy-induced encephalopathies occur in a variety of clinical settings and the most detailed accounts have been described following combination methotrexate and radiation therapy. The case described herein developed severe encephalopathy following a high-dose chemotherapy protocol used in the treatment of metastatic carcinoma of the breast. Visual symptoms developed 3 weeks after completing high-dose chemotherapy and peripheral blood hematopoietic stem cell transplantation. Over the next several weeks, additional neurologic deficits developed and continued to progress despite various treatment interventions. Diffuse deep gray matter damage was identified on MR imaging and a brain biopsy revealed pathological findings similar in many respects to those described for methotrexate/radiation, cisplatin, BCNU and/or 5 FU/levamisole-related leukoencephalopathy. The patient succumbed to complications resulting from the CNS disorder, 8 weeks after the onset of symptoms. This case is unusual for two reasons. First, the patient developed severe encephalopathy following a high-dose chemotherapy protocol commonly used in the treatment of metastatic breast carcinoma and second, the encephalopathy involved primarily deep gray matter structures rather than white matter.

The Confused Cancer Patient: A Case of 5-Fluorouracil—Induced Encephalopathy

“…However, the optimal “antidote” and appropriate steps in the subsequent management of this condition remain unclear. Proposed treatment modalities have varied considerably in the literature, ranging from purely supportive measures to the use of corticosteroids or thiamine (or both), which, alone or in combination, have shown no consistent efficacy 8,11. In our case, the elevated ammonia level prompted a trial of lactulose administered in a manner similar to that used in hepatic encephalopathy.…”

Potential Mechanisms for Chemotherapy-Induced Impairments in Cognitive Function

“…Leukoencephalopathy has been reported with many chemotherapy drugs, including asparaginase, cisplatin, cyclophosphamide, cytarabine, 5-FU, ifosfamide, methotrexate (Cohen, Lossos, & Polliack, 2002), nitrosureas, paclitaxel, and vincristine (Choi et al, 2001;Cohen et al;Cossaart, SantaCruz, Preston, Johnson, & Skikne, 2003;Keime-Guibert et al, 1998;Lee, Nauert, & Glass, 1986;Mizutani, Morimatsu, & Hayakawa, 1984;Moore, 2003;Verstappen et al, 2003). Severe leukoencephalopathy has occurred following the administration of highdose methotrexate (Tuxen & Hansen, 1994), cisplatin (Troy et al, 2000), and paclitaxel (Nieto et al, 1999).…”

Methotrexate‐related leukoencephalopathy without radiation therapy: Distribution of brain lesions and pathological heterogeneity on two autopsy cases

“…They originally described the disease in children with CNS involvement of acute lymphoblastic leukemia treated with intrathecal chemotherapy of MTX and whole brain irradiation 2 . Similar cases have been reported both in adult patients with other tumor types, including primary CNS and systemic lymphomas, and a variety of metastatic carcinomas and sarcomas 7–16 . DNL is macroscopically characterized by small discrete gray‐to‐brown foci of the friable white matter lesion with edema.…”

“…The mechanisms of chemotherapy‐induced leukoencephalopathy are also enigmatic. Leukoencephalopathy is particularly common in regimens that include MTX, although other drugs, such as carmustine, melphalan, fludarabine, 5‐FU, and cisplatin have also been implicated 3,6,11,12,14 . In some cases, the pathology appears to be partially or entirely reversible, whereas others show permanent deficits or fatal progression.…”