Redefining the Pulvinar Sign in Fabry Disease.

BACKGROUND AND PURPOSE: The pulvinar sign refers to exclusive T1WI hyperintensity of the lateral pulvinar. Long considered a common sign of Fabry disease, the pulvinar sign has been reported in many pathologic conditions. The exact incidence of the pulvinar sign has never been tested in representative cohorts of patients with Fabry disease. The aim of this study was to assess the prevalence of the pulvinar sign in Fabry disease by analyzing T1WI in a large Fabry disease cohort, determining whether relaxometry changes could be detected in this region independent of the pulvinar sign positivity. MATERIALS AND METHODS: We retrospectively analyzed brain MR imaging of 133 patients with Fabry disease recruited through specialized care clinics. A subgroup of 26 patients underwent a scan including 2 FLASH sequences for relaxometry that were compared with MRI scans of 34 healthy controls. RESULTS: The pulvinar sign was detected in 4 of 133 patients with Fabry disease (3.0%). These 4 subjects were all adult men (4 of 53, 7.5% of the entire male population) with renal failure and under enzyme replacement therapy. When we tested for discrepancies between Fabry disease and healthy controls in quantitative susceptibility mapping and relaxometry maps, no significant difference emerged for any of the tested variables. CONCLUSIONS: The pulvinar sign has a significantly lower incidence in Fabry disease than previously described. This finding, coupled with a lack of significant differences in quantitative MR imaging, allows hypothesizing that selective involvement of the pulvinar is a rare neuroradiologic sign of Fabry disease.

Early markers of Fabry disease revealed by proteomics.

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by a deficiency of the lysosomal hydrolase α-galactosidase A (α-GalA) that leads to the intra-lysosomal accumulation of globotriaosylceramide (Gb3) in various organ systems. As a consequence, a multisystems disorder develops, culminating in stroke, progressive renal and cardiac dysfunction. Enzyme replacement therapy (ERT) offers a specific treatment for patients affected by FD, though the monitoring of treatment is hindered by a lack of surrogate markers of response. Remarkably, due to the high heterogeneity of the Fabry phenotype, both diagnostic testing and treatment decisions are more challenging in females than in males; thus, reliable biomarkers for Fabry disease are needed, particularly for female patients. Here, we use a proteomic approach for the identification of disease-associated markers that can be used for the early diagnosis of FD as well as for monitoring the effectiveness of ERT. Our data show that the urinary proteome of Fabry naïve patients is different from that of normal subjects. In addition, biological pathways mainly affected by FD are related to immune response, inflammation, and energetic metabolism. In particular, the up-regulation of uromodulin, prostaglandin H2 d-isomerase and prosaposin in the urine of FD patients was demonstrated; these proteins might be involved in kidney damage at the tubular level, inflammation and immune response. Furthermore, comparing the expression of these proteins in Fabry patients before and after ERT treatment, a decrease of their concentration was observed, thus demonstrating the correlation between the identified markers and the effectiveness of the pharmacological treatment.

[Renal involvement in Fabry's disease: diagnosis, follow-up and enzyme replacement therapy]. / La nefropatia in corso di malattia di Fabry: diagnosi, follow-up e terapia enzimatica sostitutiva.

Renal involvement in Fabry's disease in males starts at an early age with microalbuminuria and proteinuria and progresses rapidly towards end-stage renal disease requiring dialysis or renal transplantation. Renal involvement, together with cardiac and cerebral damage, is responsible for the severe morbidity and mortality in patients with Fabry's disease. In heterozygous female patients renal involvement has also been documented, but the onset of renal damage occurs later and the progression to end-stage renal disease is slower. Considering the relevance of renal damage in the prognosis of Fabry's disease, it is mandatory to point out the diagnostic criteria of Fabry's nephropathy and the modalities of follow-up of patients with renal involvement. The aim of this study is also to provide recommendations regarding the diagnosis, follow-up and indication for enzyme replacement therapy in patients with Fabry's disease.

Spontaneous retroperitoneal hemorrhage due to massive rupture of renal angiomyolipoma treated with nephrectomy: an unusual onset of tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is a genetic and systemic disorder characterized by benign hamartomatous tumors that involve multiple organ systems. The classical clinical triad of TSC consists of seizure, adenoma sebaceum (facial angiofibromata) and mental retardation. Renal angiomyolipomas are documented in approximately 40 - 80% of tuberous sclerosis patients and usually are small and asymptomatic. Less frequently nodules are large and lead to retroperitoneal hemorrhage. In these cases diagnosis can be difficult but definitive only after the histological examination or the systemic investigation of other possible tissue involvements. We describe the case of a 28 year old woman who came to the emergency department with acute postprandial abdominal pain and severe anemia due to hemorrhagic renal angiomyolipoma treated by nephrectomy in whom the following examination led to the diagnosis of TSC.

Nail-patella syndrome and renal involvement. Description of three cases and literature review.

Nail-patella syndrome (NPS) is a rare, autosomal dominant disorder reported in approximatively 1/50,000 individuals. It is characterized by hypoplastic or absent patellae, dystrophic nails, dysplasia of the elbows and iliac horns. Less frequently renal and ocular damages occur. The abnormal gene in NPS is located at the distal end of the long arm of Chromosome 9. Mutations in the human LMX1B gene have been demonstrated to be responsible for NPS. It encodes a LIM-homeodomain transcription factor which plays an important role in limb development in vertebrates. Extensive mutation analysis of different NPS families by different groups failed to demonstrate any genotype-phenotype correlation. Renal involvement occurs in 30-60% of patients and presents with proteinuria and/or microscopic hematuria, edema, hypertension. Progression to nephrotic syndrome occurs in less than 20% of patients, and renal failure in about 10% of NPS patients requiring dialysis and/or transplantation. We report three cases of NPS with different degrees of renal involvement and present a review of the literature on this rare hereditary condition.

Central nervous system involvement in Anderson-Fabry disease: a clinical and MRI retrospective study.

BACKGROUND: Anderson-Fabry disease (AFD) is an X-linked lysosomal storage disorder caused by deficiency of alpha-galactosidase A. Central nervous system (CNS) manifestations consist mainly of cerebrovascular events. Brain MRI results are often abnormal. PURPOSE: The aim of the study was to describe CNS involvement in a group of Italian patients with AFD. METHODS: Clinical and brain MRI data of 43 patients with AFD (25 men, 41.94+/-10.83 years old and 18 women, 52.48+/-17.50 years old) were analysed retrospectively. 17 male patients and 7 female patients were under treatment with enzyme replacement therapy (ERT). RESULTS: All 43 patients had signs or symptoms of AFD. 16 men (64%) and 13 women (72%) demonstrated CNS involvement, although with varying severity. Overall, 6 men and 5 women had suffered from cerebrovascular accidents with an age at onset of 33.64+/-13.65 years and 53.68+/-11.71 years, respectively. Brain MR images were abnormal in 16/25 men and in 13/16 women. During CNS monitoring, some patients receiving ERT (5/17 men and 2/6 women) demonstrated neurological deterioration, especially those who had presented with cerebrovascular disease already before starting ERT. CONCLUSIONS: The study demonstrated a high frequency of CNS involvement in homozygous and heterozygous AFD patients, often characterised by early age at onset and abnormal brain MRIs. At present, ERT is widely used; however, potential beneficent effects may be disguised by the progression of irreversible pathology in short-term follow-up. Therefore, primary and secondary prophylaxes of cerebrovascular disease are extremely important.

Geminga's tails: a pulsar bow shock probing the interstellar medium.

We report the X-ray Multimirror Mission-Newton European Photon Imaging Camera observation of two elongated parallel x-ray tails trailing the pulsar Geminga. They are aligned with the object's supersonic motion, extend for approximately 2', and have a nonthermal spectrum produced by electron-synchrotron emission in the bow shock between the pulsar wind and the surrounding medium. Electron lifetime against synchrotron cooling matches the source transit time over the x-ray features' length. Such an x-ray detection of a pulsar bow shock (with no Halpha emission) allows us to gauge the pulsar electron injection energy and the shock magnetic field while constraining the angle of Geminga's motion and the local matter density.

A high-velocity black hole on a Galactic-halo orbit in the solar neighbourhood.

Only a few of the dozen or so known stellar-mass black holes have been observed away from the plane of the Galaxy. Those few could have been ejected from the plane as a result of a 'kick' received during a supernova explosion, or they could be remnants of the population of massive stars formed in the early stages of evolution of the Galaxy. Determining their orbital motion should help to distinguish between these options. Here we report the transverse motion (in the plane of the sky) for the black-hole X-ray nova XTE J1118+480 (refs 2, 3, 4, 5), from which we derive a large space velocity. This X-ray binary system has an eccentric orbit around the Galactic Centre, like most objects in the halo of the Galaxy, such as ancient stars and globular clusters. The properties of the system suggest that its age is comparable to or greater than the age of the Galactic disk. Only an extraordinary 'kick' from a supernova could have launched the black hole into an orbit like this from a birthplace in the disk of the Galaxy.

Ethylene-oxide and steam-sterilised polysulfone membrane in dialysis patients with eosinophilia.

Eosinophilia and some acute dialysis side-effects, such as itching, flushing and bronchospasm, are often associated with the presence of ethylene oxide (ETO) as dialyzer sterilizing agent. This study evaluated the effects of two different polysulfone (PS) hollow-fiber dialysers sterilized with ETO and steam in 31 chronic dialysis patients with eosinophilia. Clinical symptoms, metabolic and biochemical parameters, complement (C3a and C5a) activation and production were evaluated in each patient dialysed for two months at a time with Cuprophan dialyser, ETO-PS dialyser and steam-PS dialyser. The steam-sterilizer agent does not alter the purifying capacity of the PS membrane which maintains its superiority over Cuprophan in terms of biocompatibility. Using steam-PS, intradialytic eosinophil kinetics seems to improve. In some patients with high serum levels of ETO-specific IgE these levels tend to diminish. Generic intradialytic symptoms do not differ between the two sterilization methods, although some hypersensitivity symptoms during the first dialysis hour are considerably lower in some patients when steam-sterilized PS is used.

[Destructive cervical amyloidotic spondyloarthropathy in patients undergoing periodic dialysis. Personal experience]. / La spondiloartropatia cervicale destruente amiloidotica nei pazienti in dialisi periodica. Esperienza personale.

The accumulation of amyloid (beta 2-microglobulin) in several organs and tissues of patients in chronic dialysis is a recent pathologic condition. A wide range of cases, supported by specific tests for amyloid on bioptic and autoptic samples, showed a radiographic semiology of osteostructural alterations in various areas which allows amyloidotic condition of bone to be diagnosed with high reliability. In 11 of 62 patients (17.74%) we observed destructive cervical amyloidotic spondyloarthropathy (DCAS). The radiological patterns common to all patients were subchondral sclerosis, erosions of vertebral body plates, widening/narrowing of intervertebral spaces, no/poor osteophytosis. Over-hanging was present in 54.5% of cases, and deformation of vertebral bodies in 45.4%. CT was useful in improving the definition of the various alterations, and in locating others, such as cavitations in vertebral bodies and involvement of apophyseal joints. Constant factors were the association with extravertebral osseous amyloidosis, dyalitic age over 60 months, and the use of Cuprophan membranes for dialysis. The frequent (72.72%) association with alterations involving the lumbar rachis (subchondral sclerosis, erosions and geodes) was suggestive of amyloidotic condition.

Normalization of renal function and blood pressure after dissolution with intra-arterial fibrinolytics of a massive renal artery embolism to a solitary functioning kidney.

The intra-arterial administration of fibrinolytics in a massive embolism to the renal artery of a solitary functioning kidney determined quick normalization of the severe renal failure and hypertension.

Percutaneous transluminal dilatation of posttransplant renal artery stenosis: beneficial effects in two cases at high surgical risk.

Two clinical cases are described in which percutaneous transluminal dilatation (PTD) determined the correction of hypertension and renal hypoperfusion due to renal artery stenosis of the transplanted kidney.