Inefficient skeletal muscle oxidative function flanks impaired motor neuron recruitment in Amyotrophic Lateral Sclerosis during exercise.

This study aimed to evaluate muscle oxidative function during exercise in amyotrophic lateral sclerosis patients (pALS) with non-invasive methods in order to assess if determinants of reduced exercise tolerance might match ALS clinical heterogeneity. 17 pALS, who were followed for 4 months, were compared with 13 healthy controls (CTRL). Exercise tolerance was assessed by an incremental exercise test on cycle ergometer measuring peak O uptake ([Formula: see text]O), vastus lateralis oxidative function by near infrared spectroscopy (NIRS) and breathing pattern ([Formula: see text]E ).

Blood trace metals in a sporadic amyotrophic lateral sclerosis geographical cluster.

Amyotrophic lateral sclerosis (ALS) is a fatal disorder with unknown etiology, in which genetic and environmental factors interplay to determine the onset and the course of the disease. Exposure to toxic metals has been proposed to be involved in the etiology of the disease either through a direct damage or by promoting oxidative stress. In this study we evaluated the concentration of a panel of metals in serum and whole blood of a small group of sporadic patients, all living in a defined geographical area, for which acid mine drainage has been reported.

Diagnosis of Duchenne Muscular Dystrophy in Italy in the last decade: Critical issues and areas for improvements.

Despite all the advances in diagnosis and management of Duchenne muscular dystrophy over the past 50 years, the average age at diagnosis in most countries in the world around is still around 4-5 years. This retrospective study investigates the age at diagnosis in Italy in the past 10 years. We report findings from 384 boys who were diagnosed with DMD from 2005 to 2014.

Meditation training for people with amyotrophic lateral sclerosis: a randomized clinical trial.

Background And Purpose: Studies investigating psychological interventions for the promotion of well-being in people with amyotrophic lateral sclerosis (ALS) are lacking. The purpose of the current study was to examine the use of an ALS-specific mindfulness-based intervention for improving quality of life in this population.

Methods: A randomized, open-label and controlled clinical trial was conducted on the efficacy of an ALS-specific meditation programme in promoting quality of life.

Unraveling gene expression profiles in peripheral motor nerve from amyotrophic lateral sclerosis patients: insights into pathogenesis.

The aim of the present study is to investigate the molecular pathways underlying amyotrophic lateral sclerosis (ALS) pathogenesis within the peripheral nervous system. We analyzed gene expression changes in human motor nerve diagnostic biopsies obtained from eight ALS patients and seven patients affected by motor neuropathy as controls. An integrated transcriptomics and system biology approach was employed.

Factors predicting survival in ALS: a multicenter Italian study.

The aim of this multicenter, retrospective study is to investigate the role of clinical characteristics and therapeutic intervention on ALS prognosis. The study included patients diagnosed from January 1, 2009 to December 31, 2013 in 13 Italian referral centers for ALS located in 10 Italian regions. Caring neurologists collected a detailed phenotypic profile and follow-up data until death into an electronic database.

Clinical exome sequencing in early-onset generalized dystonia and large-scale resequencing follow-up.

Background: Dystonia is clinically and genetically heterogeneous. Despite being a first-line testing tool for heterogeneous inherited disorders, whole-exome sequencing has not yet been evaluated in dystonia diagnostics. We set up a pilot study to address the yield of whole-exome sequencing for early-onset generalized dystonia, a disease subtype enriched for monogenic causation.

Osteopathic Manual Treatment for Amyotrophic Lateral Sclerosis: A Feasibility Pilot Study.

Background: Current interventions in amyotrophic lateral sclerosis (ALS) are focused on supporting quality of life (QoL) and easing pain with a multidisciplinary approach.

Objective: Primary aim of this pilot work assessed feasibility, safety, tolerability and satisfaction of osteopathic manual treatment (OMT) in 14 ALS outpatients.

Methods: Patients were randomized according to an initial single-blind design (12 weeks, T0-T1), in order to receive OMT (weekly for 4 weeks, and fortnightly for the following 8 weeks) versus usual-care (n=7 each group), followed by an OMT open period (T1-T2, once a week for 8 weeks, n=10).

Recent advances in amyotrophic lateral sclerosis.

ALS is a relentlessly progressive and fatal disease, with no curative therapies available to date. Symptomatic and palliative care, provided in a multidisciplinary context, still remains the cornerstone of ALS management. However, our understanding of the molecular mechanisms underlying the disease has advanced greatly over the past years, giving new hope for the development of novel diagnostic and therapeutic approaches.

MEF2D and MEF2C pathways disruption in sporadic and familial ALS patients.

Amyotrophic lateral sclerosis (ALS) is a progressive neuro-muscular disease characterized by motor neuron loss. MEF2D and MEF2C are members of the myocyte enhancer factor 2 family (MEF2), a group of transcription factors playing crucial roles both in muscle and in neural development and maintenance; for this reason, a possible involvement of MEF2 in ALS context has been investigated. Since the transcriptional activity of each tissue specific MEF2 isoform is conserved in different cell types, we chose to assess our parameters in an easily accessible and widely used experimental tool such as peripheral blood mononuclear cells (PBMCs) obtained from 30 sporadic ALS patients (sALS), 9 ALS patients with mutations in SOD1 gene (SOD1+) and 30 healthy controls.

Genetic Modifiers of Duchenne Muscular Dystrophy and Dilated Cardiomyopathy.

Objective: Dilated cardiomyopathy (DCM) is a major complication and leading cause of death in Duchenne muscular dystrophy (DMD). DCM onset is variable, suggesting modifier effects of genetic or environmental factors. We aimed to determine if polymorphisms previously associated with age at loss of independent ambulation (LoA) in DMD (rs28357094 in the SPP1 promoter, rs10880 and the VTTT/IAAM haplotype in LTBP4) also modify DCM onset.

Amyotrophic Lateral Sclerosis Survival Score (ALS-SS): A simple scoring system for early prediction of patient survival.

Our objectives were: (1) to identify independent prognostic factors to determine a survival score for amyotrophic lateral sclerosis (ALS) in a cohort of patients followed in the NEMO Centre (NEuroMuscular Omnicentre); (2) to replicate results in an independent cohort obtained from the Pooled Resource Open Access ALS Clinical Trial Consortium (PRO-ACT) database. Samples were collected from 428 ALS patients from the NEMO database and 2481 patients from the PRO-ACT database. Study design was a retrospective analysis with clinical and biochemical variables, using univariable and multivariable Cox models of analysis.

Novel FUS mutations identified through molecular screening in a large cohort of familial and sporadic amyotrophic lateral sclerosis.

Background And Purpose: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Approximately 5%-10% of cases are familial (FALS) and the remaining are sporadic (SALS). To date FUS mutations are responsible for 4%-6% of familial cases as well as 0.

Gonadal failure is associated with visceral adiposity in myotonic dystrophies.

Background: Hypogonadism occurs in myotonic dystrophies type 1 (MD1) and type 2 (MD2). Sertoli and Leydig cell secretions, including insulin-like peptide-3 (INSL3), anti-Müllerian hormone (AMH) and inhibin B, were evaluated in male patients with MD.

Design: Academic settings.

Peptidylprolyl isomerase A governs TARDBP function and assembly in heterogeneous nuclear ribonucleoprotein complexes.

Peptidylprolyl isomerase A (PPIA), also known as cyclophilin A, is a multifunctional protein with peptidyl-prolyl cis-trans isomerase activity. PPIA is also a translational biomarker for amyotrophic lateral sclerosis, and is enriched in aggregates isolated from amyotrophic lateral sclerosis and frontotemporal lobar degeneration patients. Its normal function in the central nervous system is unknown.

Valproate Treatment in an ALS Patient Carrying a c.194G>A Spastin Mutation and SMN2 Homozygous Deletion.

Here we report the case of an ALS patient found to carry both a novel heterozygous change (c.194G>A) within the spastin gene and a homozygous deletion of the SMN2 gene. The patient was started on valproic acid (VPA, 600 mg/die per os) considering the capacity of this drug of increasing survival motor neuron through an epigenetic mechanism.

Asymptomatic myotonia congenita unmasked by severe hypothyroidism.

Myotonia congenita is an inherited muscle disorder sustained by mutations in the skeletal muscle chloride channel gene CLCN1. Symptoms vary from mild to severe and generalized myotonia and worsen with cold, stressful events and hormonal fluctuations. Here we report the case of a young woman who sought medical attention because of subacute onset of diffuse and severe limb myotonia.

[Towards a multi-step informed consent: considerations and proposals for a good practice].

Any therapeutic intervention needs consent from the patient, after have received information from the physician. This is often seen as a bureaucratic accomplishment but it could enhance therapeutic alliance. We propose to divide consent from information, offering a place in which doubts and emotions can be explored, with the assistance of a psychological interview.