Toxic leukoencephalopathy with axonal spheroids caused by chemotherapeutic drugs other than methotrexate

Abstract

Background The objective of this report is to share the clinicopathological features of chemotherapy-induced toxic leukoencephalopathy, which is a rare and under-recognized disease, clinically characterized by rapidly progressive cognitive loss that often leads to sudden death. Case presentation A 64-year-old woman and a 63-year-old man, who had both suffered from a rapid deterioration of consciousness, were autopsied under the clinical impressions of either the central nervous system graft versus host disease (CNS-GVHD), infectious encephalitis, or autoimmune encephalitis. Both patients had been treated with multiple chemotherapy regimens, including adriamycin, cytarabine arabinoside, daunorubicin, fludarabine, azacitidine, and allogeneic peripheral blood stem cell transplantation to treat hematological malignancies (acute myelogenous leukemia and myelodysplastic syndrome). Neuropathological findings at autopsy revealed rarefaction and vacuolar changes of the white matter with axonal spheroids, reactive gliosis, and foamy macrophage infiltration, predominantly in the visual pathways of the occipital and temporal lobes. Damaged axons exhibited immunoreactivity to beta-amyloid, consistent with axonopathy. However, there was no lymphocyte infiltration that suggested CNS-GVHD or any type of encephalitis. Conclusion The neuropathology found in the presented cases had the characteristic features of toxic leukoencephalopathy (chemobrain). Our cases showed that toxic leukoencephalopathy can also be caused by chemotherapy drugs other than methotrexate.

An Acute Presentation of Marchiafava–Bignami Disease

“…Where periventricular lesions dominate, MBD can be difficult to radiographically separate from lymphoma. Toxic leukoencephalopathy following administration of chemotherapy, including methotrexate, often involves the cortical white matter, which is relatively unaffected in MBD 4 …”

“…Toxic leukoencephalopathy following administration of chemotherapy, including methotrexate, often involves the cortical white matter, which is relatively unaffected in MBD. 4…”

FOLFIRI-bevacizumab-induced acute toxic leukoencephalopathy

“…Acute toxic leukoencephalopathy (ATL) is a rare complication of cancer treatment, such as chemotherapeutics, biologic agents, or tyrosine kinase inhibitors, which is progressive structural damage to white matter mainly due to myelin damage. 1 Patients might have a wide range of symptoms including minor cognitive impairment and coma. Symptoms might be reversible.…”