Cyclosporin neurotoxicity with Epstein-Barr virus-associated hemophagocytic syndrome

Hematology/Oncology Division, Department of Medicine, Hyogo Medical Center for Adults, 13-70, Kita-oji, Akashi, Hyogo 673-8558, Japan.

In September 2000, a 22-year-old female was admitted to our hospital due to high grade fever, liver enzymes elevation and pancytopenia. Bone marrow aspiration was performed, and hemophagocytosis was present. Epstein-Barr virus (EBV) DNA was positive in her peripheral blood, and we diagnosed the case as EBV-associated hemophagocytic syndrome (EB-VAHS) after excluding other malignancies. The initial therapy including etoposide and dexamethasone was started. As severe leukocytopenia developed, etoposide was stopped and cyclosporin A (CsA) was administered continuously. Four days after administration of CsA, she developed convulsive seizures with loss of consciousness. An MRI demonstrated decreased signal with T1-weighting and high signal with T2-weighting in the subcortical white matter including the posterior lobe. We stopped CsA infusion, and glycerol was administered. Soon the symptom disappeared. When patients developed an episode of convulsive seizure, other diagnostic possibilities were central nervous system (CNS) involvement of hemophagocytosis, EBV encephalitis and acute disseminated encephalomyelitis (ADEM). CsA neurotoxicity must be considered even in the case of EB-VAHS with administration of CsA. As previously reported, Fluid-attenuated Inversion Recovery (FLAIR) imaging improved diagnostic confidence and conspicuity of the T2 hyper intense lesions of CsA neurotoxicity, as well as tacrolimus encephalopathy, typically in the subcortical white matter.Key words; Cyclosporin neurotoxicity; Epstein-Barr virus associated-Hemophagocytic syndrome; Magnetic Resonance Image (MRI).