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Updated: Aug 10, 2026
Diffusion Tensor Magnetic Resonance Imaging in the Analysis of Neurodegenerative Diseases
Published on: July 28, 2013
Determinants of cerebral radiological progression in Fabry disease
Simon Körver1, Maria G F Longo2, Marjana R Lima3
1Endocrinology and Metabolism, Amsterdam UMC-Locatie AMC, Amsterdam, The Netherlands.
Background And Aim:
It is unclear which patients with Fabry disease (FD) are at risk for progression of white matter lesions (WMLs) and brain infarctions and whether enzyme replacement therapy (ERT) changes this risk. The aim of this study was to determine the effect of ERT and clinical characteristics on progression of WMLs and infarctions on MRI in patients with FD.
Methods:
MRIs were assessed for WMLs (Fazekas scale), infarctions and basilar artery diameter (BAD). The effect of clinical characteristics (renal and cardiac involvement, cardiovascular risk factors, cardiac complications, BAD) and ERT on WML and infarction progression was evaluated using mixed models.
Results:
One hundred forty-nine patients were included (median age: 39 years, 38% men, 79% classical phenotype). Median follow-up time was 7 years (range: 0-13 years) with a median number of MRIs per patient of 5 (range: 1-14), resulting in a total of 852 scans. Variables independently associated with WML and infarction progression were age, male sex and a classical phenotype. Progression of WMLs and infarctions was not affected by adding ERT to the model, neither for the whole group, nor for early treated patients. Progression was highly variable among patients which could not be explained by other known variables such as hypertension, cholesterol, atrial fibrillation and changes in kidney function, left ventricular mass or BAD.
Conclusion:
Progression of WMLs and cerebral infarctions in FD is mainly related to age, sex and phenotype. Additional effects of established cardiovascular risk factors, organ involvement and treatment with ERT are probably small to negligible.
Insights
Progression of white matter lesions and brain infarctions in Fabry disease (FD) is primarily linked to age, sex, and phenotype. Enzyme replacement therapy (ERT) showed minimal impact on these progressions.
Area of Science:
- Neurology
- Medical Imaging
- Genetics
Background:
- Fabry disease (FD) is a rare genetic disorder.
- Risk factors for white matter lesion (WML) and brain infarction progression in FD are not well understood.
- The impact of enzyme replacement therapy (ERT) on FD progression remains unclear.
Purpose of the Study:
- To determine the effect of ERT and clinical characteristics on the progression of WMLs and brain infarctions in FD patients.
- To identify patient subgroups at higher risk for FD-related neurological complications.
Main Methods:
- Retrospective analysis of MRI scans from 149 FD patients over a median of 7 years.
- Assessment of WMLs (Fazekas scale), infarctions, and basilar artery diameter (BAD).
- Mixed-effects models used to evaluate the influence of clinical factors and ERT on WML and infarction progression.
Main Results:
- Age, male sex, and classical phenotype were independently associated with WML and infarction progression.
- ERT did not significantly affect the progression of WMLs or infarctions in the overall group or in early-treated patients.
- Progression variability could not be explained by factors like hypertension, cholesterol, atrial fibrillation, or changes in kidney function, cardiac structure, or BAD.
Conclusions:
- Neurological progression in FD is mainly driven by intrinsic patient factors: age, sex, and phenotype.
- The influence of cardiovascular risk factors, organ damage, and ERT on WML and infarction progression appears minimal.
- Further research may be needed to identify other factors contributing to FD progression variability.
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