Global, regional, and national burden of Parkinson's disease, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016.

BACKGROUND: Neurological disorders are now the leading source of disability globally, and ageing is increasing the burden of neurodegenerative disorders, including Parkinson's disease. We aimed to determine the global burden of Parkinson's disease between 1990 and 2016 to identify trends and to enable appropriate public health, medical, and scientific responses. METHODS: Through a systematic analysis of epidemiological studies, we estimated global, regional, and country-specific prevalence and years of life lived with disability for Parkinson's disease from 1990 to 2016. We estimated the proportion of mild, moderate, and severe Parkinson's disease on the basis of studies that used the Hoehn…

Parkin gene analysis in late onset Parkinson's disease families

Clinical characteristics of patients with familial amyotrophic lateral sclerosis carrying the pathogenic GGGGCC hexanucleotide repeat expansion of C9ORF72

A large hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72, a gene located on chromosome 9p21, has been recently reported to be responsible for 40% of familial amyotrophic lateral sclerosis cases of European ancestry. The aim of the current article was to describe the phenotype of amyotrophic lateral sclerosis cases carrying the expansion by providing a detailed clinical description of affected cases from representative multi-generational kindreds, and by analysing the age of onset, gender ratio and survival in a large cohort of patients with familial amyotrophic lateral sclerosis. We collected DNA and analysed phenotype data for 141 index Italian familial amyotrophic l…

The MITOS system predicts long-term survival in amyotrophic lateral sclerosis

ObjectiveThe choice of adequate proxy for long-term survival, the ultimate outcome in randomised clinical trials (RCT) assessing disease-modifying treatments for amyotrophic lateral sclerosis (ALS), is a key issue. The intrinsic limitations of the ALS Functional Rating Scale-Revised (ALSFRS-R), including non-linearity, multidimensionality and floor-effect, have emerged and its usefulness argued. The ALS Milano-Torino staging (ALS-MITOS) system was proposed as a novel tool to measure the progression of ALS and overcome these limitations. This study was performed to validate the ALS-MITOS as a 6-month proxy of survival in 200 ALS patients followed up to 18 months.MethodsAnalyses were performe…

ATNX2 is not a regulatory gene in Italian amyotrophic lateral sclerosis patients with C9ORF72 GGGGCC expansion

Abstract There are indications that both familial amyotrophic lateral sclerosis (ALS) and sporadic ALS phenotype and prognosis are partly regulated by genetic and environmental factors, supporting the theory that ALS is a multifactorial disease. The aim of this article was to assess the role of ATXN2 intermediate length repeats in a large series of Italian and Sardinian ALS patients and controls carrying a pathogenetic C9ORF72 GGGGCC hexanucleotide repeat. A total of 1972 ALS cases were identified through the database of the Italian ALS Genetic consortium, a collaborative effort including 18 ALS centers throughout Italy. The study population included: (1) 276 Italian and 57 Sardinian ALS ca…

Randomized double-blind placebo-controlled trial of acetyl-L-carnitine for ALS.

Our objective was to assess the effects of acetyl-L-carnitine (ALC) with riluzole on disability and mortality of amyotrophic lateral sclerosis (ALS). Definite/probable ALS patients, 40-70 years of age, duration 6-24 months, self-sufficient (i.e. able to swallow, cut food/handle utensils, and walk), and with forced vital capacity (FVC) > 80% entered a pilot double-blind, placebo-controlled, parallel group trial and were followed for 48 weeks. ALC or placebo 3 g/day was added to riluzole 100 mg/day. Primary endpoint: number of patients no longer self-sufficient. Secondary endpoints: changes in ALSFRS-R, MRC, FVC and McGill Quality of Life (QoL) scores. Analysis was made in the intention-to-tr…

DJ-1 gene in late-onset recessive Parkinson's Disease

Association of Variants in the SPTLC1 Gene with Juvenile Amyotrophic Lateral Sclerosis

Key Points Question What genetic variants are associated with juvenile amyotrophic lateral sclerosis (ALS)? Findings In this family-based genetic study, exome sequencing was performed in 3 patients diagnosed with juvenile ALS and failure to thrive; this identified de novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient). Variants in SPTLC1 are a known cause of hereditary sensory and autonomic neuropathy, type 1A, and these data extend the phenotype associated with this gene. Meaning De novo variants in the SPTLC1 gene are associated with juvenile ALS, a fatal neurological disorder.

Parkin gene analysis in late onset autosomal recessive Parkinson's Disease

CHCH10 mutations in an Italian cohort of familial and sporadic amyotrophic lateral sclerosis patients

Mutations in CHCHD10 have recently been described as a cause of frontotemporal dementia (FTD) comorbid with amyotrophic lateral sclerosis (ALS). The aim of this study was to assess the frequency and clinical characteristics of CHCHD10 mutations in Italian patients diagnosed with familial (n= 64) and apparently sporadic ALS (n= 224). Three apparently sporadic patients were found to carry c.100C>T (p.Pro34Ser) heterozygous variant in the exon 2 of CHCHD10. This mutation had been previously described in 2 unrelated French patients with FTD-ALS. However, our patients had a typical ALS, without evidence of FTD, cerebellar or extrapyramidal signs, or sensorineural deficits. We confirm that CHC…

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

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 centres and randomly assigned (1:1) to receive intravenous rhEPO 40 000 IU or placebo fortnightly as add-on treatment to riluzole 100 mg daily for 12 months. The primary composite outcome was survival, tracheotomy or >23 h non-invasive ventilation (NIV). Secondary outcomes were ALSFRS-R, slow vital capacity (sVC) and quality of life (ALSAQ-40) decline. Tolerability was evaluated analysing adverse events (AEs) causing withdrawal. The randomisation sequence was computer-…

Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013

Summary Background Up-to-date evidence about levels and trends in disease and injury incidence, prevalence, and years lived with disability (YLDs) is an essential input into global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013), we estimated these quantities for acute and chronic diseases and injuries for 188 countries between 1990 and 2013. Methods Estimates were calculated for disease and injury incidence, prevalence, and YLDs using GBD 2010 methods with some important refinements. Results for incidence of acute disorders and prevalence of chronic disorders are new additions to the analysis. Key improvements include expansion to the cause an…