Characteristics and Prognosis of Oldest Old Subjects with Amyotrophic Lateral Sclerosis.

International audienceAmyotrophic Lateral Sclerosis (ALS) is an age-related neurodegenerative disease with unclear characteristics and prognosis in the oldest old (80 years and over). The aim of this study was to compare the oldest old and younger ALS patients in terms of clinical and socio-demographic characteristics, and prognosis.ALS incident cases from the register of ALS in Limousin (FRALim), diagnosed between January 2000 and July 2013, were included. Descriptive and comparative analyses by age group were carried out. For time to event univariate analysis, Kaplan-Meier estimator and log rank test were used. Univariate and multivariate survival analyses were carried out with Cox's proportional hazard model.Out of 322 patients, 50 (15.5%) were aged 80 or over ("oldest old" ALS) at the time of diagnosis. Among them, the male:female gender-ratio was 1.27, and 32.6% had a bulbar onset (not different from subjects aged less than 80 years). With increasing age, there was a worsening of the clinical state of the patients at time of diagnosis in terms of weight loss, forced vital capacity, ALSFRS-R and manual muscular testing. Access to ALS referral centres decreased with age, and the use of riluzole tended to be lower in the oldest old group. The median survival of oldest old patients appeared to be 10 months shorter than that of subjects aged less than 80 years (7.4 vs. 17.4 months).The survival of oldest old ALS patients is particularly short. It relates to prognostic features at baseline and to an independent effect of advanced age

Stratification of ALS patients' survival: a population-based study

The natural history of amyotrophic lateral sclerosis (ALS) and patient risk stratification are areas of considerable research interest. We aimed (1) to describe the survival of a representative cohort of French ALS patients, and (2) to identify covariates associated with various patterns of survival using a risk classification analysis. ALS patients recruited in the FRALim register (2000â2013) were included. Time-to-death analyses were performed using KaplanâMeier method and Cox model. A recursive partitioning and amalgamation (RECPAM) algorithm analysis identified subgroups of patients with different patterns of survival. Among 322 patients, median survival times were 26.2 and 15.6 months from time of onset and of diagnosis, respectively. Four groups of patients were identified, depending on their baseline characteristics and survival (1) ALSFRS-R slope >0.46/month and definite or probable ALS (median survival time (MST) 10.6 months); (2) ALSFRS-R slope >0.46/month and possible or probable laboratory-supported ALS (MST: 18.1 months); (3) ALSFRS-R slope â¤0.46/month and definite or probable ALS (MST: 22.5 months), and (4) ALSFRS-R slope â¤0.46/month and possible or probable laboratory-supported ALS (MST: 37.6 months). Median survival time is among the shortest ever reported by a worldwide population-based study. This is probably related to the age structure of the patients (the oldest identified to date), driven by the underlying population (30 % of subjects older than 60 years). Further research in the field of risk stratification could help physicians better anticipate prognosis of ALS patients, and help improve the design of randomized controlled trials

Results from the first French ALS register: the Limousin ALS register.

International audienceBackground: In France, until recently, there was no register of ALS cases. Hence description of the disease in France was only hospital based and then exposed to bias.Objective: To assess the incidence of ALS in the Limousin region of France using multiple sources of cases ascertainment, and to describe the sociodemographical and clinical profile of new ALS cases.Methods: A register has been settled in the Limousin region of France, 743,000 inhabitants (1). Multiple sources of information were used to ensure complete case ascertainment of individuals diagnosed with ALS according to Airlie House criteria, within the Limousin since 2000. Multiple sources of case were (i) Limousin ALS expert center and other ALS centers of France; (ii) private hospitals and clinics; (iii) health insurance structures (reimbursement of Rilutek® and long duration affection notification); and (iv) private neurologists. Data were collected in a secured database. Crude incidence per 100,000 inhabitants was assessed using estimates of population from the Insee (2). Direct standardized incidence based on 2010 US population was also calculated (3). Ninety-five percent confidence intervals (95% CI) were calculated assuming a poisson distribution.Results: Between 1 January 2000 and 31 December 2011 (12 years), 279 patients were diagnosed as having possible, probable, probable laboratory supported, or definite ALS. The median number of sources by patient was 2 (Interquartile range: 2–3). The average annual crude incidence rate was 3.18 per 100,000 person-years (95% CI 2.81–3.56). Standardized incidence on US population was 2.18 (95% CI 1.92–2.45). Mean age at diagnosis was 69.1 ± 11.2 years and the male/female sex-ratio was 1.45. First symptoms were mostly spinal (65.5%) and 6.45% of cases had familial ALS.Discussion and conclusion: We report here the results of the first ALS register settled in France. The epidemiological profile of ALS incidence in Limousin, France is consistent with those published by other European registers (2). The register will be the base of analytic and geoepidemioloical studies (clustering). We are now extending the register in other region of France: Languedoc Roussillon and some departments of Rhône Alpes.Acknowledgments: Sources of cases: French National coordination of ALS centers; Health insurance structures: Régime Général, Mutuelle Sociale Agricole, Régime Social des Indépendants, Caisse Nationale Militaire de Sécurité Sociale; Private Neurologists; Hospital and Clinics

Residential exposure to ultra high frequency electromagnetic fields emitted by Global System for Mobile (GSM) antennas and amyotrophic lateral sclerosis incidence: A geo-epidemiological population-based study

International audienceAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of unknown etiology. Mobile communication antennas have increased over the last few decades. Consequently, there has been a steady increase in environmental exposure to ultra high frequency electromagnetic fields (UHF-EMFs) emitted by Global System for Mobile (GSM) communication antennas, which raises concerns about possible health risks in the general population. We aimed to evaluate the relationship between residential exposure to UHF-EMFs generated by GSM antennas and the risk of ALS in general population. A geo-epidemiological population-based study was performed in Limousin (France). ALS incident cases were identified through a register (FRALim, 2000-2012 period). A model to estimate UHF-EMF exposure was developed based on the distance and the power of GSM antennas. Exposure to multiple emissions from multiple directions was considered. A non-cumulative and a cumulative model were established. A geographic information system integrated the raster model of exposure, and the residential distribution of observed and expected cases. A generalized linear model was performed to test the association. Overall, 312 ALS cases were included. We estimated exposures below 1.72 V/m in urban areas and below 1.23 V/m in rural areas for 90% of the population. A gradient effect between UHF-EMF exposure and ALS incidence was apparent with a statistically significant trend. A significant increased risk of ALS was observed between the non-exposure category and the highest exposure category, with a relative risk of 1.78 (95% CI: 1.28-2.48) in the non-cumulative model and 1.83 (95% CI: 1.32-2.54) in the cumulative model. Our results suggest a possible association between residential UHF-EMF exposure and ALS. Ecological studies are a means of generating hypotheses. Further studies are needed to clarify the potential role of EMFs on neurodegeneration

Weight Loss at Time of Diagnosis and Survival in ALS a Population-Based Study

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Incidence de la Sclérose Latérale Amyotrophique (SLA) en Limousin (2000-2011) : résultats du premier registre français des cas de SLA (Registre Fralim)

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Population-Based Evidence that Survival in Amyotrophic Lateral Sclerosis Is Related to Weight Loss at Diagnosis

International audienceBACKGROUND/AIMS:In a population-based setting, we aimed to (i) describe weight loss (WL) of amyotrophic lateral sclerosis (ALS) patients at the time of diagnosis and (ii) evaluate the association between WL and survival.METHODS:All patients recruited in the FRALim register (2000-2013) were considered to be included in this study. Time-to-death analyses were performed using a multivariable Cox model. Model discrimination and calibration were assessed.RESULTS:Among 322 patients in the register, 261 (81%) were included. At the time of diagnosis, 50.6% of patients reported a WL of more than 5%: 14.6% with WL between 5 and 10% and 36.0% with a WL of more than 10%. WL was independently associated with survival (p = 0.002). Patients with a WL of 10% or more experienced a 45% increase in the risk of death (95% CI 6-99) with respect to patients with a WL lower than 5% or no WL. The introduction of WL significantly improved the model's discrimination achieving a survival C statistic of 79.5% (95% CI 75.6-83.5, p = 0.006) at 12 months.CONCLUSION:More than 50% of ALS patients experience a WL of more than 5% at the time of diagnosis. This finding highlights the need for randomized trials to evaluate the effect of nutritional interventions to improve ALS survival

Quelle est la relation entre la perte de poids au moment du diagnostic et la survie au cours de la SLA ? Une étude du registre FRALIM.

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Clinical features and prognosis of amyotrophic lateral sclerosis in Africa: the TROPALS study

International audienceOBJECTIVE:We describe and compare the sociodemographic and clinical features, treatments, and prognoses and survival times of patients with amyotrophic lateral sclerosis (ALS) in Africa.METHODOLOGY:We conducted a multicentre, hospital-based cohort study in Africa. Patients with ALS diagnosed in the neurology departments of participating hospitals from 2005 to 2017 were included. Subgroup analysis was performed by subcontinent. Survival analyses were conducted using the Cox proportional hazards model.RESULTS:Nine centres from eight African countries participated. A total of 185 patients with ALS were included: 114 from Northern Africa, 41 from Western Africa and 30 from Southern Africa. A male predominance (male to female ratio 2.9) was evident. The median age at onset was 53.0 years (IQR 44.5-64.0 years). The onset was bulbar in 22.7%. Only 47 patients (26.3%) received riluzole, mainly in Northern and Western Africa. The median survival from the time of diagnosis was 14.0 months (95% CI 10.7 to 17.2 months). The median survival was longer in Northern Africa (19.0 months, 95% CI 10.8 to 27.2 months) than in Western (4.0 months, 95% CI 0.8 to 7.1 months) and Southern (11.0 months, 95% CI 5.6 to 16.4 months) Africa (Breslow test, p<0.0001). Both subcontinental location and riluzole treatment independently affected survival.CONCLUSION:More African patients with ALS were male and younger and exhibited a lower proportion of bulbar onset compared with patients with ALS from Western nations. Survival was consistent with that in Western registers but far shorter than what would be expected for young patients with ALS. The research improves our understanding of the disease in Africa

Infected erythrocytes and plasma proteomics reveal a specific protein signature of severe malaria

International audienceAbstract Cerebral malaria (CM), the most lethal complication of Plasmodium falciparum severe malaria (SM), remains fatal for 15–25% of affected children despite the availability of treatment. P. falciparum infects and multiplies in erythrocytes, contributing to anemia, parasite sequestration, and inflammation. An unbiased proteomic assessment of infected erythrocytes and plasma samples from 24 Beninese children was performed to study the complex mechanisms underlying CM. A significant down-regulation of proteins from the ubiquitin–proteasome pathway and an up-regulation of the erythroid precursor marker transferrin receptor protein 1 ( TFRC ) were associated with infected erythrocytes from CM patients. At the plasma level, the samples clustered according to clinical presentation. Significantly, increased levels of the 20S proteasome components were associated with SM. Targeted quantification assays confirmed these findings on a larger cohort ( n = 340). These findings suggest that parasites causing CM preferentially infect reticulocytes or erythroblasts and alter their maturation. Importantly, the host plasma proteome serves as a specific signature of SM and presents a remarkable opportunity for developing innovative diagnostic and prognostic biomarkers