Pattern of microstructural brain tissue alterations in Fabry disease

Abstract

Fabry disease (FD) is a lysosomal storage disorder that is associated with marked cerebrovascular disease. Conventional MRI shows a progressive load of white matter lesions (WMLs) due to cerebral vasculopathy in the course of FD. To quantify brain structural changes in clinically affected male and female patients with FD we performed a prospective Diffusion-Tensor Imaging (DTI) study in 27 adult Fabry patients (13m, 14f) and 21 age-matched controls (12 m, 9f). Global Mean Diffusivity (MD) was increased in FD (P = 0.003) whereas global Fractional Anisotropy (FA) did not differ significantly between FD and controls. Even FD patients without significant WMLs (9m, 9f) showed increased global MD (P = 0.004). Regions of interest with significant MD elevations were located in the frontal, parietal and temporal white matter. No differences of thalamic and hippocampal DTI measurements could be detected between FD and controls. DTI parameters did not differ between male and female patients. The data provide the first evidence of a pattern of marked structural brain tissue alterations in adult FD male and female patients even without WMLs. DTI seems to be an appropriate diagnostic tool to quantify brain tissue integrity in FD. Moreover, this method could be favorable for longitudinal assessment of brain structure alterations in FD, and for monitoring the cerebral effects of enzyme replacement therapy.

The pulvinar sign: frequency and clinical correlations in Fabry disease

“…In these two papers a total number of 104 patients were analysed, 103 were male, and the pulvinar sign was present in 29 male patients. More recently, Fellgiebel et al reported 27 Fabry patients, 13 male and 14 female, and no one showed the pulvinar sign on T1 images [15]. In another article, Gavazzi and co-workers studied 16 Fabry patients, 8 male and 8 female, and they demonstrated the presence of a T1-hyperintense lesion on the right pulvinar only in a 36-year-old man [16].…”

“…Several studies found significant cerebral hyperperfusion in patients with Fabry disease compared with controls, predominantly in the posterior cerebral circulation [23,24]. Moore et al could show calcification on CT scans in a few Fabry patients; however the only CT scan performed in one of the patients described by Takanashi et al revealed no evidence of calcifications [14,15].…”

Brain white matter abnormalities in paediatric Gaucher Type I and Type III using diffusion tensor imaging

“…In adults with Fabry disease MD was increased whereas FA did not differ significantly compared to controls (Fellgiebel et al 2006). In paediatric LSD patients, a loss of diffusion anisotropy was noted in Krabbe (Guo et al 2001) with bilaterally decreased FA and increased MD reported children with Cystinosis (Bava et al 2010).…”

Neurological Complications of Anderson-Fabry Disease

“…Another study has been conducted [32] to quantify brain structural changes in clinically affected male and female patients with FD. Authors performed a prospective Diffusion-Tensor Imaging (DTI) study in 27 adult Fabry patients (13m, 14f) and 21 age-matched controls (12 m, 9f).…”

“…Conventional MRI shows a progressive load of white matter lesions (WMLs) due to cerebral vasculopathy in the course of AFD. To quantify brain structural changes in clinically affected male and female patients with AFD, Fellgiebel A. et al [71] performed a prospectiveDiffusion-Tensor Imaging (DTI) study in 27 adult Fabry patients (13m, 14f) and 21 age-matched controls (12 m, 9f). Global Mean Diffusivity (MD) was increased in FD (P = 0.003) whereas global Fractional Anisotropy (FA) did not differ significantly between FD and controls.…”