Amyotrophic Lateral Sclerosis and Multiple Sclerosis Overlap: A Case Report

The concurrence of amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) is extremely rare. We reported the case of a 33-year-old woman with a past history of paresthesias at the right hand, who developed progressive quadriparesis with muscular atrophy of limbs and, finally, bulbar signs and dyspnea. Clinical and neurophysiologic investigations revealed upper and lower motor neuron signs in the bulbar region and extremities, suggesting the diagnosis of ALS. Moreover, magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) analysis demonstrated 3 periventricular and juxtacortical lesions, hyperintense in T2 and FLAIR sequences, and 3 liquoral immunoglobulin G (IgG) oligoclonal bands, consistent with diagnosis of primary progressive MS (PPMS). This unusual overlap of ALS and MS leads to the discussion of a hypothetical common pathological process of immunological dysfunction in these two disorders, although the role of immune response in ALS remains ambivalent and unclear

A Large Family with p.Arg554His Mutation in ABCD1: Clinical Features and Genotype/Phenotype Correlation in Female Carriers

X-linked adrenoleukodystrophy (X-ALD, OMIM #300100) is the most common peroxisomal disorder clinically characterized by two main phenotypes: adrenomyeloneuropathy (AMN) and the cerebral demyelinating form of X-ALD (cerebral ALD). The disease is caused by defects in the gene for the adenosine triphosphate (ATP)-binding cassette protein, subfamily D (ABCD1) that encodes the peroxisomal transporter of very-long-chain fatty acids (VLCFAs). The defective function of ABCD1 protein prevents β-oxidation of VLCFAs, which thus accumulate in tissues and plasma, to represent the hallmark of the disease. As in many X-linked diseases, it has been routinely expected that female carriers are asymptomatic. Nonetheless, recent findings indicate that most ABCD1 female carriers become symptomatic, with a motor disability that typically appears between the fourth and fifth decade. In this paper, we report a large family in which affected males died during the first decade, while affected females develop, during the fourth decade, progressive lower limb weakness with spastic or ataxic-spastic gait, tetra-hyperreflexia with sensory alterations. Clinical and genetic evaluations were performed in nine subjects, eight females (five affected and three healthy) and one healthy male. All affected females were carriers of the c.1661G>A (p.Arg554His, rs201568579) mutation. This study strengthens the relevance of clinical symptoms in female carriers of ABCD1 mutations, which leads to a better understanding of the role of the genetic background and the genotype-phenotype correlation. This indicates the relevance to include ABCD1 genes in genetic panels for gait disturbance in women

Efficacy and safety of growth hormone treatment in children with short stature: the Italian cohort of the GeNeSIS clinical study

Purpose: We examined auxological changes in growth hormone (GH)-treated children in Italy using data from the Italian cohort of the multinational observational Genetics and Neuroendocrinology of Short Stature International Study (GeNeSIS) of pediatric patients requiring GH treatment. Methods: We studied 711 children (median baseline age 9.6 years). Diagnosis associated with short stature was as determined by the investigator. Height standard deviation score (SDS) was evaluated yearly until final or near-final height (n = 78). Adverse events were assessed in all GH-treated patients. Results: The diagnosis resulting in GH treatment was GH deficiency (GHD) in 85.5 % of patients, followed by Turner syndrome (TS 6.6 %). Median starting GH dose was higher in patients with TS (0.30 mg/kg/week) than patients with GHD (0.23 mg/kg/week). Median (interquartile range) GH treatment duration was 2.6 (0.6\u20133.7) years. Mean (95 % confidence interval) final height SDS gain was 2.00 (1.27\u20132.73) for patients with organic GHD (n = 18) and 1.19 (0.97\u20131.40) for patients with idiopathic GHD (n = 41), but lower for patients with TS, 0.37 ( 120.03 to 0.77, n = 13). Final height SDS was > 122 for 94 % of organic GHD, 88 % of idiopathic GHD and 62 % of TS patients. Mean age at GH start was lower for organic GHD patients, and treatment duration was longer than for other groups, resulting in greater mean final height gain. GH-related adverse events occurred mainly in patients diagnosed with idiopathic GHD. Conclusions: Data from the Italian cohort of GeNeSIS showed auxological changes and safety of GH therapy consistent with results from international surveillance databases

Health tourism: an opportunity for sustainable development

In February 2017, the “Programma Mattone Internazionale Salute” (ProMis), that is the Italian Program for Internationalization of Regional Health Systems of the Ministry of Health (MoH), presented the first version of its Position Paper on Health Tourism, which embeds a first shared approach to the recommendations expressed by the European Committee of Regions (CoR) on "AgeFriendly" tourism. The CoR stresses the importance of local and regional authorities in the coordination of multi-sectoral policies such as healthcare, social assistance, transport, urban planning and rural development in relation to the promotion of mobility, security, accessibility of services, including health care and social services. "Age-friendly" tourism is an example of an innovative tourist offer that strives to meet the health needs of the entire "traveling" population, with an integrated and cross-sector approach that involves various organizations operating in sectors such as healthcare, accessibility and transport. The aim of the workshop was to explore the interest of the stakeholders to participate in a systemic action in the field of "health" tourism, and to identify priority implementation areas that offer opportunities to take advantage of validated, innovative experiences that strengthen the accessibility to health and social services in regional, national and international contexts. This effort provides the opportunity to take advantage of aligning the European Structural and Investment Funds (ESIF) to the development of tourism, coherently with the needs and resources of local and regional health authorities

The Space Infrared Interferometric Telescope (SPIRIT): High-resolution imaging and spectroscopy in the far-infrared

We report results of a recently-completed pre-Formulation Phase study of SPIRIT, a candidate NASA Origins Probe mission. SPIRIT is a spatial and spectral interferometer with an operating wavelength range 25 - 400 microns. SPIRIT will provide sub-arcsecond resolution images and spectra with resolution R = 3000 in a 1 arcmin field of view to accomplish three primary scientific objectives: (1) Learn how planetary systems form from protostellar disks, and how they acquire their inhomogeneous composition; (2) characterize the family of extrasolar planetary systems by imaging the structure in debris disks to understand how and where planets of different types form; and (3) learn how high-redshift galaxies formed and merged to form the present-day population of galaxies. Observations with SPIRIT will be complementary to those of the James Webb Space Telescope and the ground-based Atacama Large Millimeter Array. All three observatories could be operational contemporaneously.Comment: 20 pages, 12 figures, accepted for publication in J. Adv. Space Res. on 26 May 200

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

Noncarious Cervical Lesions: Correlation between Abfraction and Wear Facets in Permanent Dentition

Non-carious cervical lesions (NCCLs) are defined as the loss of dental hard tissue at the cement- enamel junction. Erosion, abrasion, and attrition have been associated with this disorder. Objective: Recently, occlusal stress causing of cervical enamel cracks (abfraction) has been considered as an additional etiology for NCCLs to facilitate the erosion and abrasion mechanisms in tooth wear. Study Design: The prevalence of NNCLs and wear facets in a population with permanent dentition in absence of any clear etiological factors related to erosion and abrasion causes is evaluated. A total 295 subjects are enrolled for this study and divided into four age groups (subjects aged 15 - 27 years, 28 - 42 years, 43 - 57 years and 58 - 75 years respectively). An overall of 6629 teeth are investigated to find NCCLs and wear facets. The occlusion is analyzed in each patient. Results: An overall of 801 teeth (12%) show NCCLs and 623 of them (78%) highlight also wear facets. The higher number of teeth with NCCLs and of these with simultaneous presence also of wear facets are found on teeth of patients of group-3 (11% of all teeth examined for group and 81% respectively) and to group-4 (24.4% of all teeth examined for group and 86.5% respectively) of remaining teeth without NCCLs (5828) only 138 (2.4%) shown wear facets. Conclusion: The results of this study held the occlusal forces as the main cause of NCCLs on teeth in presence of wear facets

An Italian kindred with FALS due to c.149T>C mutation in the SOD1 gene: case report of an affected family member

We report the first Italian kindred with Familial Amyotrophic Lateral Sclerosis (FALS) due to c.149T>C mutation in the exon 5 of superoxide dismutase-1 (SOD1) gene. The proband was a 49-year-old woman who came to our observation because of an history of progressive limbs weakness and gait impairment. She belonged to a family of 24 affected members. The prevalent phenotype of the affected members was characterized by slowly progressive spinal impairment with proximal distribution of weakness, and bulbar involvement in advanced stages. We briefly reviewed the few previous reports about the same SOD1 mutation and discussed the hypothesis that structural instability of the mutant codon 149 protein may underlie some toxic effects significantly involved in FALS pathogenesis

A comparison of salivary substitutes versus a natural sialogogue (citric acid) in patients complaining of dry mouth as an adverse drug reaction: A clinical, randomized controlled study

Objective: We aimed to compare the efficacy of saliva substitutes and citric acid long-term therapy for oral dryness relief and unstimulated salivary flow in patients reporting drug-induced xerostomia. Study design: Fifty-four patients reporting drug-induced xerostomia were randomly subdivided into 3 groups and respectively administered artificial saliva, 3% citric acid, or distilled water in mouthwash 4 times a day for 30 days. Patients underwent measurement of unstimulated whole saliva before and after they finished therapy and were asked to note in a daily diary any symptomatologic changes 15 minutes and 1 hour after each daily intake of test solution. Results: Fifteen minutes after solution intake, 12 patients (67%) belonging to the artificial saliva group, 9 (50%) from the citric acid group, and 2 (11%) from the water group reported significant symptomatologic improvement. One hour after solution intake, 7 patients (39%) from the artificial saliva group, 10 (56%) from the citric acid group, and 0 from the water group noted significant symptomatologic improvement. None of the drugs tested affected unstimulated whole saliva flow. Conclusions: Both artificial saliva and citric acid provided immediate relief from oral dryness. Citric acid also provided a longer-lasting feeling of oral moistness at 1 hour after use owing to its protracted activity on salivary gland function. © 2011 Mosby, Inc. All rights reserved