Muromonab-CD3-induced neurotoxicity: Report of two siblings, one of whom had subsequent cyclosporin-induced neurotoxicity

Muromonab-CD3 is widely used for immunosuppression in patients undergoing s olid organ transplant. We report two siblings with oligomeganephronia and e nd-stage renal disease who developed encephalopathy and seizures from murom onab-CD3 following renal transplant. The first case is a 13-year-old girl w ho developed encephalopathy, seizure, and triparesis following renal transp lant while muromonab-CD3 was used for immunosuppression. The second case wa s the 6-year-old sister of the first case, who also developed recurrent foc al seizures while she was on muromonab-CD3 for renal transplant immunosuppr ession. In both cases, a sequential brain magnetic resonance image (MRI) sh owed progression of abnormalities from the cerebral cortex to the white mat ter. In the first case, the MRI normalized after muromonab-CD3 was disconti nued. In the second case, the patient developed a leukoencephalopathy follo wing cyclosporin administration. The pathophysiology of muromonab-CD3 encep halopathy is believed to be a disturbance to the blood-brain barrier mediat ed by cytokine release from lymphocyte stimulation by muromonab-CD3. Becaus e the major histocompatibility complex genes are known to regulate cytokine responses, it is possible that the excessive production of cytokines that causes encephalopathy may occur in patients who share close major histocomp atibility complex genes. Muromonab-CD3 in a patient whose sibling has devel oped cerebral complications from its use should be administered with cautio n. The second case suggests that muromonab-CD3 encephalopathy predisposes p atients to develop cyclosporin neurotoxicity Because the pathogenesis of mu romonab-CD3 encephalopathy and cyclosporin-related cerebral complications a re both potentially mediated through a disturbance of the blood-brain barri er, it is possible that one agent may predispose a patient to the complicat ion of the other.