Objective: To investigate the course of diffusion changes in Wilson disease (WD) and to evaluate their clinical and radiologic correlates. Methods: MRI with fluid- attenuated inversion recovery (FLAIR) and diffusion weighted images (DWI) were performed in 13 symptomatic patients with WD who had typical neurologic manifestations of the disease (sWD patients) and in 5 presymptomatic patients (psWD patients). Follow- up clinical and MRI data were obtained in 12/13 patients with sWD. Ten subjects without neurologic disease and with normal cerebral MRI were used as controls. Apparent diffusion coefficient (ADC) was measured in areas where hyperintense lesions were detected on FLAIR images and in the normal- appearing white matter. Results: Hyperintense lesions were detected in all symptomatic patients on FLAIR MR images but only in 11 of 13 patients with sWD on DWI. These lesions were absent in patients with psWD. The mean ADC was found increased in the putamen, pallidum, internal capsule, mesencephalon, and within the white matter in the symptomatic group in comparison to controls. This was not observed in patients with psWD, who even had a decreased ADC in the putamen. A significant correlation was found between the increase in diffusion and the modified Rankin Scale in presence of symptoms. Moreover, the variation of the clinical scale was significantly correlated with the variation of diffusion in the putamen of symptomatic patients. Conclusion: A decrease in diffusion in the putamen can be detected before the occurrence of neurologic manifestations in WD. In contrast, a large increase in diffusion is detected after the occurrence of symptoms within the putamen, pallidum, internal capsule, and subcortical white matter parallel to the signal changes as seen on fluid- attenuated inversion recovery and diffusion weighted images. Methods: MRI with fluid-attenuated inversion recovery (FLAIR) and diffusion weighted images (DWI) were performed in 13 symptomatic patients with WD who had typical neurologic manifestations of the disease (sWD patients) and in 5 presymptomatic patients (psWD patients). Follow-up clinical and MRI data were obtained in 12/13 patients with sWD. Ten subjects without neurologic disease and with normal cerebral MRI were used as controls. Apparent diffusion coefficient (ADC) was measured in areas where hyperintense lesions were detected on FLAIR images and in the normal-appearing white matter. Results: Hyperintense lesions were detected in all symptomatic patients on FLAIR MR images but only in 11 of 13 patients with sWD on DWI. These lesions were absent in patients with psWD. The mean ADC was found to increase in the putamen, pallidum, internal capsule, mesencephalon, and within the white matter in the symptomatic group in comparison to controls. This was not observed in patients with psWD, who even had a decreased ADC in the putamen. A significant correlation found between the increase in diffusion and the modified Rankin Scale in presence of symptoms. Moreover, the variation of the clinical scale was significantly correlated with the variation of diffusion in the putamen of symptomatic patients. Conclusion: A decrease in diffusion in the putamen can be detected before the occurrence of neurologic manifestations in WD. In contrast, a large increase in diffusion is detected after the occurrence of symptoms within the putamen, pallidum, internal capsule, and subcortical white matter parallel to the signal changes as seen on fluid- attenuated inversion recovery and diffusion weighted images.