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

Abstract

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.

Cyclosporin A-related cerebral vasculopathy

“…It mainly manifests as white matter brain lesions. 10 The neurologic deterioration of case 1 fits the known cerebral effects of Aspergillus infection, including hemorrhagic infarctions and enhancing cortical lesions. An autopsy was not obtained.…”

Tacrolimus‐associated posterior reversible encephalopathy syndrome in hematopoietic allogeneic stem cell transplantation

“…The available literature comments on the basics of managing PRES including withdrawal or dose reduction of the offending agent, blood pressure control, and anticonvulsants in those with seizures [2][3][4]. More specifically, in terms of tacrolimus management, case reports and retrospective reviews report their experience and collectively, these hardly define a trend to a successful management strategy [1][2][3]7,8,10,13]. In our study, there did not seem to be a trend in favor of one strategy over another since the survival percentages to discharge were similar.…”

Factors affecting the pharmacokinetics of tacrolimus (FK506) in hematopoietic cell transplant (HCT) patients

“…14 Neurotoxicity ranging from mild tremors and paresthesia to severe manifestations such as cortical blindness and seizures are also well described following HCT. 3,13,[17][18][19][20][21] These toxicities underscore the need for vigilant monitoring of tacrolimus blood concentrations and accurate dose modifications.The objective of this study was to determine the population pharmacokinetic parameters of intravenous and oral tacrolimus in the first 4 months post transplant, and to evaluate relevant clinical covariates for their effects on tacrolimus clearance and bioavailability. …”

“…14 Neurotoxicity ranging from mild tremors and paresthesia to severe manifestations such as cortical blindness and seizures are also well described following HCT. 3,13,[17][18][19][20][21] These toxicities underscore the need for vigilant monitoring of tacrolimus blood concentrations and accurate dose modifications.…”