Progressive Changes in Cerebral Apparent Diffusion Values in Fabry Disease: A 5-Year Follow-up MRI Study.

Background and purpose: White matter lesions are commonly found in patients with Fabry disease. Existing studies have shown elevated diffusivity in healthy-appearing brain regions that are commonly associated with white matter lesions, suggesting that DWI could help detect white matter lesions at an earlier stage This study explores whether diffusivity changes precede white matter lesion formation in a cohort of patients with Fabry disease undergoing yearly MR imaging examinations during a 5-year period.

Materials and methods: T1-weighted anatomic, FLAIR, and DWI scans of 48 patients with Fabry disease (23 women; median age, 44 years; range, 15-69 years) were retrospectively included. White matter lesions and tissue probability maps were segmented and, together with ADC maps, were transformed into standard space. ADC values were determined within lesions before and after detection on FLAIR images and compared with normal-appearing white matter ADC. By means of linear mixed-effects modeling, changes in ADC and ΔADC (relative to normal-appearing white matter) across time were investigated.

Results: ADC was significantly higher within white matter lesions compared with normal-appearing white matter (P < .01), even before detection on FLAIR images. ADC and ΔADC were significantly affected by sex, showing higher values in men (60.1 [95% CI, 23.8-96.3] ×10^-6mm²/s and 35.1 [95% CI, 6.0-64.2] ×10^-6mm²/s), respectively. ΔADC increased faster in men compared with women (0.99 [95% CI, 0.27-1.71] ×10^-6mm²/s/month). ΔADC increased with time even when only considering data from before detection (0.57 [95% CI, 0.01-1.14] ×10^-6mm²/s/month).

Conclusions: Our results indicate that in Fabry disease, changes in diffusion precede the formation of white matter lesions and that microstructural changes progress faster in men compared with women. These findings suggest that DWI may be of predictive value for white matter lesion formation in Fabry disease.