MR imaging with quantitative diffusion mapping of tacrolimus-induced neurotoxicity in organ transplant patients

Abstract. Our objective was to investigate brain MR imaging findings and the utility of diffusion-weighted (DW) imaging in organ transplant patients who developed neurologic symptoms during tacrolimus therapy. Brain MR studies, including DW imaging, were prospectively performed in 14 organ transplant patients receiving tacrolimus who developed neurologic complications. In each patient who had abnormalities on the initial MR study, a follow-up MR study was performed 1 month later. Apparent diffusion coefficient (ADC) values on the initial MR study were correlated with reversibility of the lesions. Of the 14 patients, 5 (35.7%) had white matter abnormalities, 1 (7.1%) had putaminal hemorrhage, and 8 (57.1%) had normal findings on initial MR images. Among the 5 patients with white matter abnormalities, 4 patients (80.0%) showed higher than normal ADC values on initial MR images, and all showed complete resolution on follow-up images. The remaining 1 patient (20.0%) showed lower than normal ADC value and showed incomplete resolution with cortical laminar necrosis. Diffusion-weighted imaging may be useful in predicting the outcomes of the lesions of tacrolimus-induced neurotoxicity.

[1]  R. Fenstermaker,et al.  Severe cerebellar swelling and thrombotic thrombocytopenic purpura associated with FK506 , 1998, Bone Marrow Transplantation.

[2]  D. V. van Thiel,et al.  Adverse effects associated with the use of FK 506. , 1991, Transplantation proceedings.

[3]  Linda Sher,et al.  A comparison of tacrolimus (FK 506) and cyclosporine for immunosuppression in liver transplantation. , 1994, The New England journal of medicine.

[4]  J. Sageshima,et al.  Clinical and radiological features of two cases of tacrolimus-related posterior leukoencephalopathy in living related liver transplantation. , 1998, Transplantation proceedings.

[5]  J. E. Tanner,et al.  Spin diffusion measurements : spin echoes in the presence of a time-dependent field gradient , 1965 .

[6]  M. Okuhara,et al.  FK 506: historical perspectives. , 1991, Transplantation proceedings.

[7]  B. Siewert,et al.  Acute human stroke studied by whole brain echo planar diffusion‐weighted magnetic resonance imaging , 1995, Annals of neurology.

[8]  S. Small,et al.  Immunosuppression‐induced leukoencephalopathy from tacrolimus (FK506) , 1996, Annals of neurology.

[9]  F. Buonanno,et al.  Posterior leukoencephalopathy without severe hypertension , 1998, Neurology.

[10]  S. Blacklow,et al.  Neuroimaging findings in patients on immunosuppressive therapy: experience with tacrolimus toxicity. , 1996, AJR. American journal of roentgenology.

[11]  Nina Singh,et al.  Immunosuppressive-associated leukoencephalopathy in organ transplant recipients. , 1999, Transplantation.

[12]  J. Post,et al.  FK506-induced leukoencephalopathy in children with organ transplants , 1999, Neurology.

[13]  C. Tornatore,et al.  Reversible tacrolimus-induced neurotoxicity isolated to the brain stem. , 2000, AJNR. American journal of neuroradiology.

[14]  G. Pizzolato,et al.  Cerebral vasculitis during FK 506 treatment in a liver transplant patient , 1998, Neurology.

[15]  A. Çobanoğlu,et al.  FK506-induced fulminant leukoencephalopathy after single-lung transplantation. , 1997, The Annals of thoracic surgery.

[16]  D. V. van Thiel,et al.  Neurologic complications of FK 506. , 1991, Transplantation proceedings.

[17]  N. Tomura,et al.  Transient neurotoxicity associated with FK506: MR findings. , 1998, Journal of computer assisted tomography.

[18]  J. Roberts,et al.  Similar clinical presentation of neurotoxicity following FK 506 and cyclosporine in a liver transplant recipient. , 1991, Transplantation proceedings.

[19]  R V Mulkern,et al.  Diffusion-weighted MR imaging in hypertensive encephalopathy: clues to pathogenesis. , 1998, AJNR. American journal of neuroradiology.

[20]  T. Starzl,et al.  FK 506 FOR LIVER, KIDNEY, AND PANCREAS TRANSPLANTATION , 1989, The Lancet.

[21]  D. V. van Thiel,et al.  Adverse effects of FK 506 overdosage after liver transplantation. , 1993, Transplantation proceedings.

[22]  J. Petrella,et al.  Quantitative assessment of diffusion abnormalities in posterior reversible encephalopathy syndrome. , 2001, AJNR. American journal of neuroradiology.

[23]  L R Caplan,et al.  A reversible posterior leukoencephalopathy syndrome. , 1996, The New England journal of medicine.

[24]  W. Bechstein,et al.  Neurotoxicity after orthotopic liver transplantation. A comparison between cyclosporine and FK506. , 1994, Transplantation.

[25]  D. Andrews,et al.  Watershed imaging features and clinical vascular injury in cyclosporin A neurotoxicity. , 1997, Journal of computer assisted tomography.

[26]  N. Bargalló,et al.  Cortical laminar necrosis caused by immunosuppressive therapy and chemotherapy. , 2000, AJNR. American journal of neuroradiology.

[27]  P. Grenier,et al.  MR imaging of intravoxel incoherent motions: application to diffusion and perfusion in neurologic disorders. , 1986, Radiology.

[28]  P. Barnes,et al.  Cyclosporine neurotoxicity and its relationship to hypertensive encephalopathy: CT and MR findings in 16 cases. , 1995, AJR. American journal of roentgenology.

[29]  R. Wiesner,et al.  FK506‐induced neurotoxicity in liver transplantation , 1994, Annals of neurology.

[30]  J. Tsuruda,et al.  Cytotoxic brain edema: assessment with diffusion-weighted MR imaging. , 1992, Radiology.

[31]  A. Elster,et al.  Calculation of apparent diffusion coefficients (ADCs) in brain using two-point and six-point methods. , 1998, Journal of computer assisted tomography.

[32]  S. Terae,et al.  MRI in seven cases of tacrolimus (FK-506) encephalopathy: utility of FLAIR and diffusion-weighted imaging , 2001, Neuroradiology.