Stroke and Fabry disease

Abstract

Fabry disease (FD) is a rare inherited disorder of the metabolism, associated with renal, cardiac, and cerebrovascular complications. Ischemic and hemorrhagic stroke in FD present with a similar proportion to that observed in the general population, but usually at an early age. Ischemic stroke may result from cardiac embolism, large and small vessel disease, while hemorrhagic stroke is usually attributed to hypertension. Deposition of glycosphingolipids in endothelial cells results in a specific FD vasculopathy that contributes to the different vascular phenotypes. Neuroimaging features of cerebrovascular involvement in FD include white matter lesions, dolichoectasia, and the "pulvinar sign", a T1 MRI hyperintensity of the posterior thalamus. The role of enzymatic replacement therapy in the prevention of stroke remains to be established, but its utilization should be considered in FD stroke patients, for prevention of renal and cardiac complications, together with general prevention measures. Enzymatic replacement therapy increased our awareness of FD, underlining the importance of incomplete phenotypes in specific settings such as stroke. An overview of studies on the prevalence of FD in stroke patients is presented. Available data suggest that prevalence of FD is similar to some of the rare causes of stroke usually considered, and that classic features of the disease may be absent or more subtle. Moreover, FD should be considered in both cryptogenic and all-cause stroke. The role of FD in stroke on a multifactorial basis and the identification of a putative "stroke variant" are questions that need to be further elucidated in future studies.

Pulvinar

“…Deposition of glycosphingolipids in endothelial cells results in a specific vasculopathy that may result in different vascular phenotypes. 82 Pulvinar hyperintensity on T1-weighted images is a common finding in FD 83,84 and has been attributed to dystrophic calcification related to cerebral hyperperfusion in the posterior circulation and selective vulnerability of the pulvinar. 85 A review of neuroradiologic records of 104 hemizygous patients with FD showed that approximately 23% had pulvinar hyperintensity on T1-weighted images; the frequency increased with age to over 30% by age 50 years.…”

Monogenic causes of stroke: now and the future

“…These strokes may be due to small vessel or large vessel disease, or secondary to cardioembolism from Fabry related cardiac disease [37]. Large vessel ischaemic events tend to occur in the posterior circulation territory where dolichoectasia of the vertebral arteries can be a feature [37].…”

Spontaneous intracerebral hemorrhage in CADASIL

“…To the best of our knowledge, only 3 patients with ICH were reported among MELAS syndrome [21]. Fabry disease is a rare X-linked inherited disorder of glycosphingolipid metabolism because of deficient or absent lysosomal α-galactosidase A activity [22]. Its classical manifestations include neuropathic pain, skin lesion and gastrointestinal symptoms, progressive renal and cardiac insufficiency and stroke [22].…”