Showing papers by "Fabrizio Salvi published in 2015"

Cardiac amyloidosis: the great pretender

Abstract: Cardiac amyloidosis (CA) is often misdiagnosed because of both physician-related and disease-related reasons including: fragmented knowledge among different specialties and subspecialties, shortage of centres and specialists dedicated to disease management, erroneous belief it is an incurable disease, rarity of the condition, intrinsic phenotypic heterogeneity, genotypic heterogeneity in transthyretin-related forms and the necessity of target organ tissue histological diagnosis in the vast majority of cases. Pitfalls, incorrect beliefs and deceits challenge not only the path to the diagnosis of CA but also the precise identification of aetiological subtype. The awareness of this condition is the most important prerequisite for the management of the risk of underdiagnoses and misdiagnosis. Almost all clinical, imaging and laboratory tests can be misinterpreted, but fortunately each of these diagnostic steps can also offer diagnostic “red flags” (i.e. highly suggestive findings that can foster the correct diagnostic suspicion and facilitate early, timely diagnosis). This is especially important because outcomes in CA are largely driven by the severity of cardiac dysfunction and emerging therapies are aimed at preventing further amyloid deposition.

Heterogeneity in ALSFRS-R decline and survival: a population-based study in Italy

Abstract: Very few studies examined trend over time of the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) and factors influencing it; previous studies, then, included only patients attending tertiary ALS Centres. We studied ALSFRS-R decline, factors influencing this trend and survival in a population-based setting. From 2009 onwards, a prospective registry records all incident ALS cases among residents in Emilia Romagna (population: 4.4 million). For each patient, demographic and clinical details (including ALSFRS-R) are collected by caring physicians at each follow-up. Analysis was performed on 402 incident cases (1279 ALSFRS-R assessments). The average decline of the ALSFRS-R was 0.60 points/month during the first year after diagnosis and 0.34 points/month in the second year. ALSFRS-R decline was heterogeneous among subgroups. Repeated measures mixed model showed that ALSFRS-R score decline was influenced by age at onset (p < 0.01), phenotype (p = 0.01), body mass index (BMI) (p < 0.01), progression rate at diagnosis (ΔFS) (p < 0.01), El Escorial Criteria-Revised (p < 0.01), and FVC% at diagnosis (p < 0.01). Among these factors, at multivariate analysis, only age, site of onset and ΔFS independently influenced survival. In this first population-based study on ALSFRS-R trend, we confirm that ALSFRS-R decline is not homogeneous among ALS patients and during the disease. Factors influencing ALSFRS-R decline may not match with those affecting survival. These disease modifiers should be taken into consideration for trials design and in clinical practice during discussions with patients on prognosis.

Calcium micro-depositions in jugular truncular venous malformations revealed by Synchrotron-based XRF imaging.

Abstract: It has been recently demonstrated that the internal jugular vein may exhibit abnormalities classified as truncular venous malformations (TVMs). The investigation of possible morphological and biochemical anomalies at jugular tissue level could help to better understand the link between brain venous drainage and neurodegenerative disorders, recently found associated with jugular TVMs. To this end we performed sequential X-ray Fluorescence (XRF) analyses on jugular tissue samples from two TVM patients and two control subjects, using complementary energies at three different synchrotrons. This investigation, coupled with conventional histological analyses, revealed anomalous micro-formations in the pathological tissues and allowed the determination of their elemental composition. Rapid XRF analyses on large tissue areas at 12.74 keV showed an increased Ca presence in the pathological samples, mainly localized in tunica adventitia microvessels. Investigations at lower energy demonstrated that the high Ca level corresponded to micro-calcifications, also containing P and Mg. We suggest that advanced synchrotron XRF micro-spectroscopy is an important analytical tool in revealing biochemical changes, which cannot be accessed by conventional investigations. Further research on a larger number of samples is needed to understand the pathogenic significance of Ca micro-depositions detected on the intramural vessels of vein walls affected by TVMs.

Erythropoietin in amyotrophic lateral sclerosis: a multicentre, randomised, double blind, placebo controlled, phase III study

Abstract: Objective To assess the efficacy of recombinant human erythropoietin (rhEPO) in amyotrophic lateral sclerosis (ALS). Methods Patients with probable laboratory-supported, probable or definite ALS were enrolled by 25 Italian

Stereotactic Radiotherapy in the Treatment of Lung Metastases from Bone and Soft-tissue Sarcomas.

Abstract: Background The purpose of this study was to evaluate local control and toxicity in a group of patients treated with stereotactic body radiotherapy (SBRT) for lung metastases (LM) from bone and soft tissue sarcomas. Patients and methods From October 2010 to July 2014, patients with LM from sarcomas not suitable for surgery were treated with daily cone-beam computed tomography-guided SBRT. The dose administered ranged from 30 to 60 Gy in 3-8 fractions. Acute and late toxicity were scored according to Common Terminology Criteria for Adverse Events version 4.0. Results A total of 24 patients with 68 LM from sarcomas were treated with SBRT. The median follow-up after SBRT was 17 months (range=11-51 months). Two-year actuarial lesion local control and overall survival were 85.9% and 66.4%, respectively. No G3 or greater acute and late toxicities were observed. Conclusion SBRT is a safe and effective treatment for LM from sarcoma and might be used as an alternative option in patients unfit for surgery.

Ultrastructure of internal jugular vein defective valves

Abstract: ObjectivesTo study the ultrastructure of intraluminal defects found in the internal jugular vein by using a scanning electron microscopy.MethodsUsing a scanning electron microscopy, intraluminal septa and/or defective valves blocking the flow in the distal internal jugular vein of seven patients were studied together with the adjacent wall and compared with control specimen.ResultsThe internal jugular veins’ wall showed a significant derangement of the endothelial layer as compared to controls. Surprisingly, no endothelial cells were found in the defective cusps, and the surface of the structure is covered by a fibro-reticular lamina.ConclusionsAlthough the lack of endothelial cells in the internal jugular vein intraluminal obstacles is a further abnormality found in course of chronic cerebrospinal venous insufficiency, our investigation cannot clarify whether this finding is primary or caused by progressive loss of endothelium in relation to altered haemodynamic forces and/or to a past post-thrombotic/in...

Brain Microbleeds 12 Years after Orthotopic Liver Transplantation in Val30Met Amyloidosis

Abstract: Unexplained focal neurologic episodes (FNEs) can occur in patients with transthyretin-related familial amyloidotic polyneuropathy (TTR-FAP) after orthotopic liver transplantation (OLT). A patient with Val30Met FAP underwent OLT at age 34 years. Twelve years after transplantation, she presented with recurrent FNEs lasting from 10 minutes to 8 hours each, with nonuniform deficitary clinical features and variably associated with headache. Magnetic resonance imaging showed multiple brain microbleeds and diffuse contrast enhancement of the craniospinal leptomeninges consistent with amyloid deposits. Our observation suggests that microbleeds associated with meningovascular amyloidosis can underlie FNEs in TTR-FAP. Moreover, it confirms that OLT does not halt progression of leptomeningeal and vascular amyloid deposition due to TTR production in the choroid plexuses. Such a progression might compromise the good long-term prognosis of patients with TTR-FAP due to increased risk of intracranial hemorrhages. Pharmacologic therapies targeting brain TTR production may modify this scenario.

P037. Headache in multiple sclerosis: prevalence and clinical features in a case control-study.

Abstract: Methods One hundred and fifty adults (F/M = 98/52; mean age 40 years) with a diagnosis of MS and 150 sex and agematched controls (F/M = 101/49; mean age 40 years) from the general population were evaluated by means of an ad hoc semi-structured interview according to the International Classification Headache Disorders (ICHD-3-beta) criteria. All subjects filled out validated questionnaires about fatigue, Fatigue Severity Scale (FSS) and Modified Fatigue Impact Scale (MFIS). The c2 and Kruskal-Wallis tests were used when appropriate. Results The two groups differed significantly for education level and employment. Among the 150 patients with MS, 1 (0.7%) presented a radiologically isolated syndrome (RIS), 17 (11.3%) a clinically isolated syndrome (CIS), 20 (13.3%) a primary progressive form (PPMS), 96 (64%) a relapsing remitting form (RR), and 16 (10.7%) a secondary progressive form (SPMS). Headache was reported by 80 (53.3%) MS cases and 71 controls (47.3%), (p = 0.356); migraine was reported by 47 (31.33%) cases and 51 (34%) controls, tension-type headache was present in 21 (14%) MS affected vs 14 (9.33%) controls (p = 0.245). The simultaneous presence of migraine and tension-type headache was statistically higher (p = 0.002) in MS (28.8%) compared to controls (8.5%). Women with MS presented a low correlation between migraine and menstruation compared to controls while migraine normally improves during pregnancy as much as in controls (p = 0.65). The preliminary analysis of FSS and MFIS scores showed that fatigue resulted overall higher in MS patients with or without headache. Conclusions

Prevalence, risk factors and correlation with cardiac involvement of carpal tunnel syndrome in amyloidosis

Abstract: Background Carpal tunnel syndrome (CTS) is one of the most common clinical manifestations of TTR-related amyloidosis, both hereditary (ATTR), and wild type (senile systemic amyloidosis, SSA) and often precedes cardiac symptoms. The exact prevalence of CTS in light-chain amyloidosis (AL), ATTR and SSA is not known. We therefore aimed to establish prevalence, risk factors and possible association with cardiac involvement in patients with TTRrelated and AL amyloidosis.