Determinants of cerebral radiological progression in Fabry disease
Open Access
- 21 April 2020
- journal article
- research article
- Published by BMJ in Journal of Neurology, Neurosurgery & Psychiatry
- Vol. 91 (7), 756-763
- https://doi.org/10.1136/jnnp-2019-322268
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.Funding Information
- Academisch Medisch Centrum (Innovation grant 2014)
This publication has 37 references indexed in Scilit:
- Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegenerationThe Lancet Neurology, 2013
- Targets, trends, excesses, and deficiencies: refocusing clinical investigation to improve patient outcomesKidney International, 2013
- Low glomerular filtration rate and risk of stroke: meta-analysisBMJ, 2010
- The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: systematic review and meta-analysisBMJ, 2010
- Reliability and Sensitivity of Visual Scales versus Volumetry for Evaluating White Matter Hyperintensity ProgressionCerebrovascular Diseases, 2008
- Enzyme therapy for Fabry disease: Neutralizing antibodies toward agalsidase alpha and betaKidney International, 2004
- Measuring progression of cerebral white matter lesions on MRINeurology, 2004
- A semiquantative rating scale for the assessment of signal hyperintensities on magnetic resonance imagingJournal of the Neurological Sciences, 1993
- MR angiography by multiple thin slab 3D acquisitionMagnetic Resonance in Medicine, 1991
- MR signal abnormalities at 1.5 T in Alzheimer's dementia and normal agingAmerican Journal of Roentgenology, 1987