Tacrolimus leukoencephalopathy: A neuropathologic confirmation

Abstract

Tacrolimus leukoencephalopathy has well documented clinical and neuroradiologic features.1 The latter suggest endothelial dysfunction as the underlying etiology.2 Confirmatory neuropathologic data have been lacking. A 40-year-old woman with biopsy-proven acute rejection was admitted 3 weeks after an orthotopic liver transplant for alcoholic cirrhosis. Alanine aminotransferase was elevated at 226 IU/L (<50 IU/L). She also had elevated cholesterol levels (237–411 IU/L) and was hypertensive (approximately 160/90). Erythrocytes showed anisocytosis and poikilocytosis (spiculated, fragmented, and targets). Tacrolimus 4 mg BID had been started the day after transplantation. The patient had 2 days of toxic tacrolimus levels of 25 ng/mL and 29 ng/mL (>20 ng/mL), followed 4 days later by new onset seizures and mental status changes (lethargy to agitation). BP just after the seizure was 172/104. The last reading prior to her seizure was 144/88. MRI revealed two large white matter lesions in the right frontal lobe without mass effect (figure 1A). There was minimal peripheral enhancement, as well as scattered white matter lesions in the frontal and parieto-occipital lobes bilaterally (figure 1B). Her condition continued to deteriorate over the next 2 days with increasing seizure activity culminating in unresponsiveness. Brain biopsy was performed to exclude a treatable infectious process. Her platelet count at this time was 329,000/μL (445,000/μL upon admission); her prothrombin time and partial thromboplastin time were normal. However, that same day bleeding at the biopsy site …