Cyclosporine Neurotoxicity

A comprehensive search of the published literature was undertaken to identify reports providing patient‐specific data relating to adverse neurologic events with cyclosporine. References cited in the articles identified 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 cyclosporine neurotoxicity, including epidemiology, clinical manifestations, postulated mechanisms, and management implications, was evaluated. Estimates from case series suggest a 0.5–35% frequency of the disorder. Risk factors include supratherapeutic blood concentrations of cyclosporine, and pharmacokinetic and pharmacodynamic drug interactions, hypocholesterolemia, 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. Reported adverse events involved all levels of the neuraxis. Associated abnormalities include elevated cerebrospinal fluid protein and pleocytosis, various electroencephalogram abnormalities, and characteristic neuroimaging findings. In most patients these events were reversible with dosage reduction or withdrawal of therapy. Many reports described positive rechallenge, and in rare instances the events regressed despite continuing or reintroducing the drug.