021 Fludarabine-induced subacute, often fatal leukoencephalopathy: a case series. Issue 12 (14th November 2019)

• Record Type: Journal Article
• Authors: Awad, Amine; Solis, Jamie; Albjerg, Lydia; Albert, Julie; Bartrum, Elizabeth; Childs, Richard; Nath, Avindra; Khan, Omar I
• Is Part Of: Journal of neurology, neurosurgery and psychiatry. Volume 90:Issue 12(2019)
• Page Start: A16
• Page End: A16
• Publication Date: 2019-11-14
• Subjects: Neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; Psychiatry -- Periodicals; 616.8
• DOI: 10.1136/jnnp-2019-ABN-2.50
• Languages: English
• ISSNs: 0022-3050

Abstract

Abstract : Fludarabine, a purine agonist, is associated with a rare dose-dependent risk of severe and often fatal neurotoxicity. Referencing the clinical course of seven such patients, we report the clinical, radiological, and pathological findings in one patient who developed a fatal leukoencephalopathy to highlight potential mechanisms of fludarabine-induced neurotoxicity. Of the seven cases, one presented with paraparesis, two with cognitive impairment, and four with blurred vision; five cases were fatal, with a variable time course of symptom onset and progression. All patients had unexplained progressive, symmetric leukoencephalopathy on serial brain MRIs. One patient underwent post-mortem neuropathological examination; she was a 49-year-old female with severe aplastic anaemia and myelodysplastic syndrome who had received fludarabine at 25 mg/m2 for five days prior to stem cell transplantation. Thirteen days later, she developed rapidly-progressive cognitive deterioration and motor weakness. Serial brain MRIs showed extensive leukoencephalopathy extending into the midbrain and pons bilaterally. She passed away at day 39 post-transplant. Histopathology revealed diffuse, gross softening of the white matter and microscopic evidence of a demyelinating process with diffuse myelin loss, axonal injury, and spheroid formation. Electron microscopy revealed abnormally proliferative, reticulated, densely packed endoplasmic reticulum, suggesting a toxic, progressive demyelinating process.