Cyclosporine Central Neurotoxicity Following Renal Transplantation

Scheinman, Steven J.; Reinitz, Emanuel R.; Petro, George R.; Schwartz, Robert A.; Szmalc, Frank S.

doi:10.1097/00007890-199001000-00048

Cited by 27 publications

(7 citation statements)

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“…Retrospective reviews of the neuroimaging studies of transplant recipients have suggested that the majority of these findings were related to cyclosporine toxicity. 2,16,17 We could not identify any pre-or posttransplant risk factors that predicted CNS events. Nutritional status, which may reflect the severity of malabsorption in CF patients, did not differ between groups.…”

Section: Discussionmentioning

confidence: 95%

Cystic fibrosis patients with and without central nervous system complications following lung transplantation

Goldstein

Perl

et al. 2000

Pediatr. Pulmonol.

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Central nervous system (CNS) complications occur more frequently in cystic fibrosis (CF) patients than other lung transplant recipients. The purpose of this study was to compare CF patients with and without CNS complications following lung transplantation, to identify risk factors for CNS events. Records of 21 patients with CF who underwent lung transplant between 1991–1996 were reviewed. Data were collected on multiple variables, including: age at transplant; gender; cytomegalovirus (CMV) status; cholesterol and triglyceride levels; sinusitis; percent ideal body weight (IBW); body mass index (BMI); augmented immunosuppression, acute lung rejection episodes (ALR); cyclosporine doses; electrolytes; magnesium, blood urea nitrogen (BUN), and creatinine levels; and 6‐month survival. CNS complications identified were seizures, severe headaches (HA), strokes, or confusional episodes. Eleven of 21 patients (52%) with CF had CNS events: eight had seizures, five HA, three strokes, and one confusional episode. There was no difference in age at transplant, pretransplant percent IBW or BMI, cholesterol and triglyceride levels, or number of ALR. CMV mismatch and clinical sinusitis had no effect. Cyclosporine doses did not differ between groups at 30 days, or 3 or 6 months posttransplant. Both BUN and creatinine concentrations showed a rise over time that did not differ between groups. Potassium levels were within normal limits for both groups. While sodium levels did not differ between groups pretransplant, or at 30 days or 6 months posttransplant, a decrease in sodium values was seen at the time of CNS events. There was no difference in 6‐month survival. We could not identify any pre‐ or posttransplant risk factors that predicted CNS events. It is likely that cyclosporine toxicity is the major cause of CNS complications. Despite the high rate of CNS events, the overall prognosis was good, and 6‐month survival was not affected. Pediatr Pulmonol. 2000; 30:203–206. © 2000 Wiley‐Liss, Inc.

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Section: Discussionmentioning

confidence: 95%

Cystic fibrosis patients with and without central nervous system complications following lung transplantation

Goldstein

Perl

et al. 2000

Pediatr. Pulmonol.

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“…Cyclosporine can produce white matter changes leading to cortical blindness and seizures in different transplant populations including kidney, heart, liver, and bone marrow. [2][3][4][5][6][7] There is less known about FK506 neurotoxicity. Cortical blindness and white matter lesions have been previously reported in a liver transplant recipient receiving FK506.…”

Section: Discussionmentioning

confidence: 99%

“…Azathioprine was chosen instead of cyclosporine because cyclosporine has also been associated with cortical blindness. [2][3][4][5][6][7] It is unknown if a reduction in the FK506 dosage would have resulted in a similar outcome. In the three bone marrow transplant recipients reported by Devine and colleagues 9 who developed cortical blindness while receiving FK506, two subsequently received cyclosporine without sequelae.…”

Section: Discussionmentioning

confidence: 99%

Cortical blindness and seizures in a patient receiving FK506 after bone marrow transplantation

Steg

Kessinger

Wszołek

1999

Bone Marrow Transplant

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Summary:A 54-year-old woman with a myelodysplastic syndrome treated with high-dose chemotherapy and an allogenic bone marrow transplant developed acute cortical blindness while receiving tacrolimus (FK506). MRI showed white matter abnormalities. After discontinuation of FK506, the patient's vision returned within 8 days. FK506 neurotoxicity is similar to cyclosporine neurotoxicity and can occur in allogenic bone marrow transplant patients treated with FK506. Keywords: cortical blindness and seizures; FK506 neurotoxicity; bone marrow transplantation FK506 (tacrolimus), a fungal metabolite produced by Streptomyces tsukubaenis, is an effective immunosuppressive agent used for bone marrow and organ transplantation patients. A case of FK506 neurotoxicity is discussed. Case reportA 54-year-old woman had been diagnosed 11 years earlier with extensive low-grade non-Hodgkin's lymphoma. She was treated with chemotherapy and achieved a complete remission. However, 2 years later her disease recurred and she received salvage chemotherapy. One year later, she had high-dose therapy and an autologous peripheral blood stem cell transplant. Her post-transplant course was essentially uneventful until 6 years later when she developed a myelodysplastic syndrome and underwent a matched, unrelated bone marrow transplant (BMT). Cyclophosphamide and total body irradiation were used as conditioning. She had never received intrathecal chemotherapy or brain irradiation prior to this conditioning. Three days prior to her allogenic transplant, cyclosporine was first given as prophylaxis for graft-versus-host disease. During intravenous infusion of this drug she developed chest tightness and wheezing Correspondence: Dr RE Steg, Department of Neurology, Creighton University School of Medicine, Suite 5300, 601 North 30th Street, Omaha, NE 68131-2197, USA Received 5 May 1998; accepted 3 December 1998 accompanied by acute dyspnea, thready pulse, low oxygen saturation and hypotension. These symptoms reversed with corticosteroid administration. The suspected but unconfirmed allergen was polyoxyethylated castor oil, a vehicle, in addition to alcohol, in the commercial cyclosporine product for injection. Tacrolimus (FK506) was substituted.Eleven days after the allogenic transplant, she developed acute renal failure following a period of sepsis and hypotension from which she gradually recovered without requiring dialysis. However, on day 22, she developed a slight worsening of her recovering renal function and FK506 toxicity was suspected. On day 23, the blood level of FK506 was 50 ng/ml, exceeding the target level of 10-20 ng/ml, and FK506 dosage was reduced to one attenuated dose on day 28 and then was discontinued. Renal function slowly improved over the next few days but on day 27, when the FK506 level was 20 ng/ml, she complained of confusion and spatial disorientation. Her blood pressure was 156/82 mm Hg. Clinical examination revealed cortical blindness with visual defects and a visual acuity of light perception only.

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“…MRI is more sensitive and more specific [10,11] than CT for investigating the white matter. The T2-weighted sequences show high signal in the areas that are abnormal by CT.…”

Section: Discussionmentioning

confidence: 99%

Central neurotoxicity of cyclosporine in two children with nephrotic syndrome

Taque

Peudenier

Gié

et al. 2004

Pediatric Nephrology

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The central neurotoxicity of cyclosporin A (CsA) has been abundantly documented in pediatric and adult recipients of bone marrow or organ transplants, with variations in the rate of occurrence from 0.5% to 35%. We report two cases of central neurotoxicity ascribable to CsA in children with nephrotic syndrome due to lipoid nephrosis. The manifestations of CsA-related central neurotoxicity include confusion, aphasia, dystonias, akinetic mutism, parkinsonism, palsies, seizures, catatonia, coma, brain hemorrhage, and cortical blindness. Decreased density of the cerebral white matter is visible by computed tomography (CT) in 50% of cases, with the most commonly involved sites being the occipital cortex, the cerebellum, the periventricular substance, and the brainstem. Magnetic resonance imaging is more sensitive and more specific than CT for investigating the white matter. High-signal lesions are seen on T2-weighted sequences in the areas that are abnormal by CT. Many risk factors have been reported, including hypomagnesemia, hypocholesterolemia, high-dose glucocorticoid therapy, arterial hypertension, and infections. We present two patients with central neurotoxicity both of whom have elevated cholesterol levels.

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Cyclosporine Central Neurotoxicity Following Renal Transplantation

Cited by 27 publications

References 0 publications

Cystic fibrosis patients with and without central nervous system complications following lung transplantation

Cystic fibrosis patients with and without central nervous system complications following lung transplantation

Cortical blindness and seizures in a patient receiving FK506 after bone marrow transplantation

Central neurotoxicity of cyclosporine in two children with nephrotic syndrome

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