Fatal outcome due to cyclosporine neurotoxicity with associated pathological findings

We present a case of death likely to be directly due to cyclosporine (CsA) neurotoxicity. To date, there have been no reports of deaths directly due t o CsA neurotoxicity, nor has an associated histological lesion been describ ed independent of confounding processes. A 54-year-old male received an BLA -matched-unrelated BMT for CML, He developed progressive encephalopathy and on day +79 had a generalized seizure. All CSF studies were negative for in fectious causes. MRI revealed diffuse, symmetrical white matter abnormaliti es located in the occipital sub-cortex, thalamus, mid brain, pens, and cere bellum which were typical of CsA toxicity. The patient died of central resp iratory failure within 72 h of discontinuing CsA. Autopsy revealed diffuse patchy white matter edema and astrocytic injury without evidence of axonopa thy, demyelination, microvascular injury, or infectious/inflammatory proces s. This case demonstrates previously undescribed lethal CsA neurotoxicity a nd may reveal an associated primary pathological lesion.