Muromonab-CD3 is widely used for immunosuppression in patients undergoing solid organ transplant. We report two siblings with oligomeganephronia and
end-stage renal disease who developed
encephalopathy and
seizures from
muromonab-CD3 following renal transplant. The first case is a 13-year-old girl who developed
encephalopathy, seizure, and triparesis following renal transplant while
muromonab-CD3 was used for immunosuppression. The second case was the 6-year-old sister of the first case, who also developed recurrent
focal seizures while she was on
muromonab-CD3 for renal transplant immunosuppression. In both cases, a sequential brain magnetic resonance image (MRI) showed progression of abnormalities from the cerebral cortex to the white matter. In the first case, the MRI normalized after
muromonab-CD3 was discontinued. In the second case, the patient developed a
leukoencephalopathy following
cyclosporin administration. The pathophysiology of
muromonab-CD3 encephalopathy is believed to be a disturbance to the blood-brain barrier mediated by
cytokine release from lymphocyte stimulation by
muromonab-CD3. Because 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 histocompatibility complex genes.
Muromonab-CD3 in a patient whose sibling has developed cerebral complications from its use should be administered with caution. The second case suggests that
muromonab-CD3 encephalopathy predisposes patients to develop
cyclosporin neurotoxicity. Because the pathogenesis of
muromonab-CD3 encephalopathy and
cyclosporin-related cerebral complications are both potentially mediated through a disturbance of the blood-brain barrier, it is possible that one agent may predispose a patient to the complication of the other.