Fabry disease is an X-linked lysosomal deficiency of alpha-galactosidase A that results in cellular accumulation of galactoconjugates, mainly globotriaosylceramide, particularly in blood vessels. Neuroradiological findings include ischemic stroke, white matter lesions, vascular abnormalities (vertebrobasilar dolichoectasia and vessel tortuosity), and posterior thalamus involvement (the so called pulvinar sign). The purpose of our study was to investigate the presence of the increased pulvinar signal intensity on T1-weighted imaging - pulvinar sign and its relationship with other clinical findings, in a non-selected cohort of Fabry patients.
We performed a prospective analysis of two populations of patients (36 subjects) with Fabry disease. Patients were followed-up at the Department of Internal Medicine of the Bichat Hospital in Paris (France) and at the Neurological Clinic of the University Hospital of Padova (Italy). Brain MR studies of each patient included T1- and T2- weighted images, FLAIR sequences, and in some cases diffusion weighted images.
A total of 36 patients (16 males, 20 females) were investigated in 14 families. The pulvinar sign was found in 5 male patients, but not in female patients. Seven patients had had at least one stroke (territorial or lacunar). There was no correlation between stroke and the pulvinar sign. All patients with the pulvinar sign had hypertrophic cardiomyopathy. Four patients out of five with the pulvinar sign were on dialysis or had a kidney transplantation.
Our findings suggest that the pulvinar sign is a highly specific sign of Fabry disease, found in male patients with cardiac signs and severe kidney involvement.
"Hyperintensity in the pulvinar on T1-weighted images is a common finding in Fabry disease, likely reflecting the presence of calcification (Moore et al., 2003; Takahashi et al., 2003). The pulvinar sign is highly specific to Fabry disease and is found in male patients with cardiac signs and severe renal involvement (Burlina et al., 2008). Although progressive white matter lesions at early age, increased signal intensity in the pulvinar, and tortuosity and dilatation of the large vessels are well known on cranial MRI, increased basilar artery diameter has been shown to be superior for separating patients with Fabry disease from controls with an accuracy of 87% (Fellgiebel et al., 2009). "
[Show abstract][Hide abstract] ABSTRACT: This review discusses the literature on Fabry disease mainly in the domain of neurology with special attention to recent advancement.
Fabry neuropathy is known as a length-dependent peripheral neuropathy affecting mainly the small myelinated (Aδ) fibers and unmyelinated (C) fibers. Recently, concerning heterozygotes, it seems that they suffer from peripheral neuropathy at a higher rate than previously shown, significant multisystemic disease, and severely decreased quality of life. The existence of an atypical variant of Fabry disease with late-onset cerebrovascular disease (cerebrovascular variant) is now suggested, like the cardiac and renal variants of Fabry disease. Although enzyme replacement therapy (ERT) has been shown to have some positive effects on reduction of neuropathic pain, the improvement of detection threshold for thermal sensation and sweat function, the effect of ERT on the central nervous system has not been established. Gene replacement therapy, chemical chaperone therapy, and ERT using modified α-N-acetylgalactosaminidase are in progress, and induced pluripotent stem cells were generated from mouse models of Fabry disease.
Heterozygotes should be carefully monitored for precise estimation and adequate therapy. Early initiation of ERT before irreversible organ failure is most important, and alternative therapeutic approaches are currently being explored.
Current opinion in neurology 08/2011; 24(5):463-8. DOI:10.1097/WCO.0b013e32834a9433 · 5.31 Impact Factor
"This finding was later supported by Burlina et al.  who investigated the pulvinar sign and its relationship with other clinical findings in a total of 36 patients (16 males, 20 females) from 14 families. The pulvinar sign was found in 5 male patients but not in any of the investigated female patients. "
[Show abstract][Hide abstract] ABSTRACT: Fabry disease, an X-linked lysosomal storage disorder, results from deficient activity of the enzyme α-galactosidase A. Affected males with the classic phoenotype have acroparaesthesias, hypohidrosis, and corneal opacities in childhood and develop renal failure, cardiac hypertrophy or strokes in the third to fifth decade of life. Some female heterozygotes are asymptomatic, some as severely affected as males. The natural history of Fabry patients includes transitory cerebral ischaemia and strokes, even in very young persons of both genders. The mechanism is partly due to vascular endothelial accumulation of GL-3. White matter lesions on MRI occur. Both males and females can be safely treated with enzyme replacement; and thus screening for Fabry disease of young stroke populations should be considered. There are, however, no hard data of treatment effect on mortality and morbidity. The analyses of results from ongoing studirs will add to the decision on whether or not to screen young stroke patients for Fabry disease. Finally, stroke prophylactic therapy should be used liberally in patients of both genders with verified Fabry disease. This includes primary prevention such as lifestyle counseling, targeting blood pressure, managing atrial fibrillation, diabetes mellitus, hyperlipidaemia, and ASA.
Stroke Research and Treatment 06/2011; 2011:615218. DOI:10.4061/2011/615218
"Characteristic, but non specific, neuroradiological features of Fabry disease have been found almost exclusively in men. Indeed, bilateral T1 hyperintensity can be seen in the posterior region of thalamus (“pulvinar sign”) in male patients . Except for the “pulvinar sign” differential neuroradiological diagnosis of Fabry’s CNS lesions with other vascular pathologies or inflammatory disorders can be rather difficult. "
[Show abstract][Hide abstract] ABSTRACT: The X-linked genetic Fabry disease causes multiorgan lesions due to intracellular storage of the substrate globotriaosylceramide. Neurological involvement ranges from painful, small fiber neuropathy to cerebrovascular disorders to multifocal aggressive forms. Disease identification through proper differential diagnosis and timely assessment of organ damage should guide a careful treatment planning. Mainstay treatment, include enzyme replacement and support therapy. Neurologists have a pivotal role in early instrumental and clinical detection of organ damage. A panel of experts has developed a set of consensus recommendations to guide the approach of neurologists to Fabry disease.
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