Neurotoxicity of calcineurin inhibitors: impact and clinical management.
Between 10%-28% of patients who receive the immunosuppressant cyclosporine (CsA) experience some form of neurotoxic adverse event. Both sensorial motoric functions may be adversely affected, and thus patients present with a wide range of neurological and psychiatrical disorders. Mild symptoms are common and include tremor, neuralgia, and peripheral neuropathy. Severe symptoms affect up to 5 % of patients and include psychoses, hallucinations, blindness, seizures, cerebellar ataxia, motoric weakness, or leukoencephalopathy. Tacrolimus is associated with similar neurotoxic adverse events. Neurotoxicity may result in serious complications for some patients, particularly recipients of orthotopic liver transplants. Factors that may promote the development of serious complications include advanced liver failure, hypertension, hypocholesterolemia, elevated CsA or tacrolimus blood levels, hypomagnesemia, and methylprednisolone. Occipital white matter appears to be uniquely susceptible to the neurotoxic effects of CsA; injury to both the major and minor vasculature may cause hypoperfusion or ischemia and local secondary toxicity in the white matter. Calcineurin inhibition by CsA and tacrolimus alters sympathetic outflow, which may play a role in the mediation of neurotoxic and hypertensive adverse events. The symptoms of CsA- and tacrolimus-associated neurotoxicity may be reversed in most patients by substantially reducing the dosage of immunosuppressant or discontinuing these drugs. However, some patients have experienced permanent or even fatal neurological damage even after dose reduction or discontinuation. CsA-sparing and tacroli-mus-sparing drug regimens that use the immunosuppressant mycophenolate mofetil, which has no neurotoxic effects, may reduce the incidence and severity of neurotoxic adverse events while maintaining an adequate level of immunoisuppression.
Bechstein
W O
WO
Department of Surgery, Ruhr-University Bochum, Knappschaftskrankenhaus Bochum-Langendreer, Germany.
D065095:Calcineurin Inhibitors; D016572:Cyclosporine / Q000009:adverse effects* / Q000633:toxicity; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000633:toxicity; D001523:Mental Disorders / Q000139:chemically induced* / Q000628:therapy; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000628:therapy; D009498:Neurotoxins; D011183:Postoperative Complications; D016559:Tacrolimus / Q000009:adverse effects* / Q000633:toxicity; D014181:Transplantation Immunology
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D009498:Neurotoxins; D016572:Cyclosporine; D016559:Tacrolimus