Related Experiment Video
Updated: Mar 21, 2026
Diffusion Tensor Magnetic Resonance Imaging in the Analysis of Neurodegenerative Diseases
Published on: July 28, 2013
Determinants of white matter hyperintensity burden in patients with Fabry disease
Natalia S Rost1, Lisa Cloonan2, Allison S Kanakis2
1From the J. Philip Kistler Stroke Research Center, Department of Neurology (N.S.R., L.C., A.S.K., K.M.F.), and the Center for Human Genetic Research, Department of Neurology (N.S.R., D.R.A., V.C., K.B.S.), Massachusetts General Hospital, Boston; Neurogenetics Unit (C.M.L.), School of Medicine of Riberirao Preto, University of São Paulo, Brazil; Division of Medical Genetics (D.P.G.), University of Versailles-St Quentin en Yvelines Paris-Saclay University, France; Fundación para el Estudio de las Enfermedades Neurometabólicas (FESEN) (J.M.P.), Buenos Aires, Argentina; and Departments of Neuroradiology (G.A.H.) and Neurology (C.S., N.Ü.), Fabry Center for Interdisciplinary Therapy (FAZIT) (C.S., N.Ü.), University of Würzburg, Germany. nrost@partners.org.
Objective:
Using a semiautomated volumetric MRI assessment method, we aimed to identify determinants of white matter hyperintensity (WMH) burden in patients with Fabry disease (FD).
Methods:
Patients with confirmed FD and brain MRI available for this analysis were eligible for this protocol after written consent. Clinical characteristics were abstracted from medical records. T2 fluid-attenuated inversion recovery MRI were transferred in electronic format and analyzed for WMH volume (WMHV) using a validated, computer-assisted method. WMHV was normalized for head size (nWMHV) and natural log-transformed (lnWMHV) for univariate and multivariate linear regression analyses. Level of significance was set at p < 0.05 for all analyses.
Results:
Of 223 patients with FD and WMHV analyzed, 132 (59%) were female. Mean age at MRI was 39.2 ± 14.9 (range 9.6-72.7) years, and 136 (61%) patients received enzyme replacement therapy prior to enrollment. Median nWMHV was 2.7 cm(3) (interquartile range 1.8-4.0). Age (β 0.02, p = 0.008) and history of stroke (β 1.13, p = 0.02) were independently associated with lnWMHV. However, WMH burden-as well as WMHV predictors-varied by decade of life in this cohort of patients with FD (p < 0.0001).
Conclusions:
In this largest-to-date cohort of patients with FD who had volumetric analysis of MRI, age and prior stroke independently predicted the burden of WMH. The 4th decade of life appears to be critical in progression of WMH burden, as novel predictors of WMHV emerged in patients aged 31-40 years. Future studies to elucidate the biology of WMH in FD and its role as potential MRI marker of disease progression are needed.
Insights
Age and prior stroke independently predict white matter hyperintensity (WMH) burden in Fabry disease (FD). The fourth decade is critical for WMH progression, with new predictors emerging in patients aged 31-40.
Area of Science:
- Neurology
- Radiology
- Genetics
Background:
- Fabry disease (FD) is a rare genetic disorder affecting multiple organs.
- White matter hyperintensities (WMH) are common in FD and may indicate disease progression.
- Volumetric MRI assessment offers a quantitative method to evaluate WMH burden.
Purpose of the Study:
- To identify determinants of white matter hyperintensity (WMH) burden in patients with Fabry disease (FD).
- To utilize a semiautomated volumetric MRI assessment method for WMH quantification.
Main Methods:
- Retrospective analysis of brain MRI from 223 patients with confirmed FD.
- Volumetric assessment of WMH using a validated, computer-assisted method (T2-FLAIR MRI).
- Statistical analysis including univariate and multivariate linear regression (lnWMHV).
Main Results:
- Age and history of stroke were independently associated with WMH burden (lnWMHV).
- WMH burden and its predictors varied significantly by decade of life (p < 0.0001).
- The cohort included 132 females (59%), with a mean age of 39.2 years.
Conclusions:
- Age and prior stroke are key independent predictors of WMH burden in FD.
- The fourth decade of life (ages 31-40) is a critical period for WMH progression in FD.
- Further research is needed to understand WMH biology and its role as an MRI marker in FD progression.
More Related Videos
11:50A Standardized Pipeline for Examining Human Cerebellar Grey Matter Morphometry using Structural Magnetic Resonance Imaging
Published on: February 4, 2022
13:26Measuring Connectivity in the Primary Visual Pathway in Human Albinism Using Diffusion Tensor Imaging and Tractography
Published on: August 11, 2016
