CYCLOSPORINE NEUROTOXICITY

A comprehensive search of the published literature was undertaken to i dentify reports providing patient-specific data relating to adverse ne urologic events with cyclosporine. References cited in the articles id entified by the search were manually reviewed to ensure that articles were pertinent. Studies and case reports on cyclosporine neurotoxicity in which individualized patient data were provided were included for review and analysis. Information pertaining to all aspects of cyclospo rine neurotoxicity, including epidemiology, clinical manifestations, p ostulated mechanisms, and management implications, was evaluated. Esti mates from case series suggest a 0.5-35% frequency of the disorder. Ri sk factors include supratherapeutic blood concentrations of cyclospori ne, and pharmacokinetic and pharmacodynamic drug interactions, hypocho lesterolemia, and other metabolic abnormalities. Postulated mechanisms include a vasculopathy based on cyclosporine's effect on endothelial cell synthesis of prostaglandin, and release and uptake of endothelin as well as inhibition of mitochondrial steroid 26-hydroxylase. Reporte d adverse events involved all levels of the neuraxis. Associated abnor malities include elevated cerebrospinal fluid protein and pleocytosis, various electroencephalogram abnormalities, and characteristic neuroi maging findings. In most patients these events were reversible with do sage reduction or withdrawal of therapy. Many reports described positi ve rechallenge, and in rare instances the events regressed despite con tinuing or reintroducing the drug.