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Cyclosporine-associated Neurotoxicity. The Need For A Better Guide For Immunosuppressive Therapy.
Published 1996 · Medicine
Heart transplantation has become the most effective treatment of end-stage heart failure in selected patients. More than 30 000 heart transplantations have been performed worldwide since its introduction in 1967, with a current 1-year survival rate of ≈85% and 5-year survival rate of 70%.1 Besides the enormous survival advantage associated with heart transplantation compared with all other therapies, it also usually is associated with the restoration of a nearly normal age-predicted functional capacity. In this issue of Circulation , Grimm and colleagues2 document with the use of P300-evoked potentials that patients with end-stage heart failure awaiting transplantations also have impaired cortical function, a finding that reaffirms that of previous reports using psychometric tests.3 These abnormalities also were totally normalized within 4 months of transplantation, which is consistent with the hypothesis of decreased cerebral perfusion as the cause of the impairment. These patients underwent repeated testing 12 months after transplantation. The results showed that the mean evoked potentials had declined to levels similar to those before transplantation, although none of the patients were thought to have any clinically detectable neurological symptoms. This suggests that evoked potentials are more sensitive than more traditional psychometric tests, which also were abnormal before transplantation, improved 4 months after transplantation, but did not change 12 months after transplantation. Using multiple regression analysis, Grimm et al found that the cumulative dose of cyclosporine was the only significant variable associated with the changes in cortical function. Cyclosporine has been used as the primary immunosuppressive agent in heart transplantation for 15 years. Its introduction was associated with a significant improvement in survival, which led to a significant increase in the number of patients undergoing heart transplantation. Its use also has been associated with a decrease in the incidence and severity of rejection. However, the dosage of cyclosporine …