Abstract
Fabry disease (FD) is a rare X-linked disorder characterised by abnormal progressive lysosomal deposition of globotriaosylceramide in a large variety of cell types. The central nervous system (CNS) is often involved in FD, with a wide spectrum of manifestations ranging from mild symptoms to more severe courses related to acute cerebrovascular events. In this review we present the current knowledge on brain imaging for this condition, with a comprehensive and critical description of its most common neuroradiological imaging findings. Moreover, we report results from studies that investigated brain physiopathology underlying this disorder by using advanced imaging techniques, suggesting possible future directions to further explore CNS involvement in FD patients.Teaching Points• Conventional neuroradiological findings in FD are aspecific.• White matter hyperintensities represent the more consistent brain imaging feature of FD• Abnormalities of the vasculature wall of posterior circulation are also consistent features.• The pulvinar sign is not reliable as a finding pathognomonic for FD.• Advanced imaging techniques have increased our knowledge about brain involvement in FD.
Highlights
Fabry disease (FD) is a multiorgan X-linked lysosomal storage disorder caused by mutation in the GLA gene, which encodes for the α-galactosidase A (α-GalA) enzyme [1–4]
Cardiomyopathy, and central nervous system (CNS) alterations are the main causes of morbidity and reduced life expectancy in these patients, enzyme replacement therapy (ERT) in addition to supportive treatments have had a positive impact on FD clinical management [6]
A large microstructural white matter (WM) involvement was recently confirmed by a combined tract-based spatial statistics (TBSS)-functional Magnetic resonance imaging (MRI) study, in which extensive areas of reduced fractional anisotropy were found in FD patients, despite the low incidence and load of WM hyperintensities (WMH) [63]
Summary
Fabry disease (FD) is a multiorgan X-linked lysosomal storage disorder caused by mutation in the GLA gene, which encodes for the α-galactosidase A (α-GalA) enzyme [1–4]. A large microstructural WM involvement was recently confirmed by a combined TBSS-functional MRI (fMRI) study, in which extensive areas of reduced fractional anisotropy were found in FD patients, despite the low incidence and load of WMH [63] These areas included different supratentorial and infratentorial WM regions, with a relative sparing of only few brain regions [63], and were correlated to functional cortical changes, denoting the complexity of physiopathological mechanisms of cerebral involvement in FD [63] (Fig. 4). This study showed the presence in FD patients of a diffuse reduction of the NAA/Cr ratio in different brain areas, affecting both cortical and subcortical structures [70] This alteration extended beyond the presence of visible WMH, and was attributed to a possible direct metabolic dysfunction secondary to neuronal Gb3 accumulation rather than a vascular disturbance [70]. Still under-exploited or limited to anecdotal reports [92], other nuclear medicine techniques such as single photon emission computed tomography (SPECT) could further contribute to improve present knowledge on CNS impairment in FD, with particular reference to recent evidences suggesting a possible link between FD and other neurodegenerative disorders such as Parkinson’s disease [93–95]
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