Cyclosporine neurotoxicity: a review

Abstract

Cyclosporin A (CsA) induces neurological side effects in up to 40% of patients. A reversible posterior leukoencephalopathy syndrome is the most serious complication. Symptoms include headache, altered mental functioning, seizures, cortical blindness, and other visual disturbances, with hypertension. Neuroimaging studies show white matter changes in the posterior regions of the brain. Other neurological side effects of CsA include tremor, diffuse encephalopathy, cerebellar syndrome, extrapyramidal syndrome, pyramidal weakness, and peripheral neuropathy. Hypertension, hypomagnesemia, hypocholesteremia, and the vasoactive agent endothelin may all play a role in the pathogenesis of CsA neurotoxicty. Neurotoxicity is more frequent with high CsA blood levels, but levels may be within the therapeutic range. Dose reduction or withdrawal of CsA usually results in resolution of clinical symptoms and of neuroimaging abnormalities.

Cyclosporin A-induced encephalopathy after allogeneic bone marrow transplantation with prevention of graft-versus-host disease by tacrolimus

“…Why there was no evidence of tacrolimus-induced neurotoxicity might relate to the differences in pharmacological actions of CsA and tacrolimus. 8 Also, the high concentration of CsA might have been one of the causes of encephalopathy, although it has been reported that neurotoxicity does not always occur in the presence of a high concentration of CsA. 1,2 We conclude that accurate diagnosis, and prompt substitution of tacrolimus for CsA and careful monitoring of serum drug concentrations in this case prompted the good clinical outcome.…”

Movement disorders secondary to long-term treatment with cyclosporine A

“…Possible risk factors for neurological complications of CsA include intensive pre-transplantation c h e m o t h e r a p y, radiation, drug interactions, metabolic disturbances, tissue rejection, fluid re t e n t i o n and hypertension related to cort i c o s t e roids, hyperc h o l e s t e rolemia, hypomagnesemia and aluminum overload in RT 4 . Other drugs that interf e re with CsA metabolism may increase blood levels to potentially toxic levels 4 .…”

“…The most commonly described complications inclu-de confusion, disorientation, a wide variety of changes in behavioral and in the level of conscience, seizures, cortical blindness, aphasia, pyramidal signs and movement disorders (MD) 3 . Among this p a rticular group, tremor is the best re c o g n i z e d 4 , but case re p o rts of other forms of MD exist in the l i t e r a t u reincluding ataxia 5 , parkinsonism 6 , 7 , myoclonus 8 and chorea 9 . The objectives of our study were to analyze the p revalence of MD among individuals using CsA c h ronically after bone marrow transplantation (BMT) and to assess the severity and functional interference of the possible findings.…”

FK506-associated limbic injury following umbilical cord blood transplantation

“…Hypertension has been noted in patients with CsA and FK506, but also can be seen with high doses of PSL. [1][2][3] The leukoencephalopathy seen with CsA and FK506 is observed predominantly in the occipital areas, as in hypertensive encephalopathy with vasogenic edema, 4 but it may or may not be accompanied by hypertension. The proposed mechanism of such leukoencephalopathy is endothelial injury of blood vessels from CsA and FK506.…”

“…She achieved complete hematological remission following continuous intravenous infusion of Ara-C at 20 mg/m 2 /day for 3 weeks. Following pretreatment with Ara-C of 24 g/m 2 and total body irradiation of 12 Gy, she underwent umbilical cord blood transplantation from a 5/6 major HLA-antigen matched unrelated donor, 2 months after achieving remission. She received CsA (3 mg/kg/day in two divided doses) and short-term methotrexate (15 mg/m 2 Â 1, 10 mg/ m 2 Â 3) for prophylaxis against graft-versus-host disease (GVHD).…”