Determinants of cerebral radiological progression in Fabry disease.

Abstract

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.

• Authors: Simon Körver, Maria G F Longo, Marjana R Lima, Carla E M Hollak, Mohamed El Sayed, Ivo N van Schaik, Leonardo Vedolin, Marcel G W Dijkgraaf, Mirjam Langeveld
• Journal: Journal of neurology, neurosurgery, and psychiatry (J Neurol Neurosurg Psychiatry) Vol. 91 Issue 7 Pg. 756-763 (07 2020) ISSN: 1468-330X [Electronic] England
• PMID: 32317398 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

Topics

• Adolescent
• Adult
• Aged
• Brain (diagnostic imaging)
• Child
• Disease Progression
• Fabry Disease (diagnostic imaging)
• Female
• Follow-Up Studies
• Humans
• Magnetic Resonance Imaging
• Male
• Middle Aged
• White Matter (diagnostic imaging)
• Young Adult