Etiology of Cortical and White Matter Lesions in Cyclosporin-A and FK-506 Neurotoxicity

Abstract

BACKGROUND AND PURPOSE: The etiology of the neurotoxicity associated with cyclosporin-A (CsA) and FK-506 treatment is not fully understood. At our institution, we noticed a distinct, abrupt change in the imaging characteristics of CsA and FK-506 neurotoxicity, which consisted of a shift in lesion morphology from a white matter abnormality to a mixed cortical and white matter pattern. The purpose of this study was to assess clinical parameters that might explain this change.

METHODS: Twenty-two patients had a neurotoxic reaction and brain imaging changes while receiving CsA or FK-506. Nineteen patients received allogeneic bone marrow transplants, and three had aplastic marrow disorders. Fifty-one imaging studies (CT or MR imaging) were obtained, and lesion characteristics, locations, and time courses were evaluated along with relevant clinical data.

RESULTS: Nine patients who had been conditioned for transplantation with cyclophosphamide and chemotherapy (busulfan or thiotepa) had a mixed pattern of cortical and white matter involvement (57 lesions). Isolated white matter involvement (62 lesions) developed in three nontransplant patients and 10 transplant patients conditioned with cyclophosphamide and total-body irradiation. All lesions occurred at typical brain watershed zones. Lesion enhancement was noted in two patients conditioned with chemotherapy. Initial images demonstrated characteristic lesions in 15 patients (68%). Initial images were normal in four patients (18%) and nonspecific in three patients (14%).

CONCLUSION: Lesion location in CsA and FK-506 neurotoxicity may depend on the presence or type of conditioning used before bone marrow transplantation. Nontransplant patients or those conditioned with total-body irradiation develop white matter lesions, whereas those conditioned with chemotherapy develop mixed cortical and white matter lesions.