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Objectives: Amyotrophic lateral sclerosis (ALS) is a severe motor neuron disorder. Diagnosis is challenging due to its clinical heterogeneity and the absence of definitive diagnostic tools, leading to delays averaging between 9.1 and 27 months. In vivo corneal confocal microscopy, assessing the sub-basal nerve plexus of the cornea, has been proposed as a potential biomarker for ALS. We aimed to determine whether the assessment of corneal nerves using in vivo confocal microscopy can serve as an imaging biomarker for ALS. Methods: A single-centre prospective case–control study was conducted in France from September 2021 to March 2023 including patients with ALS according to the revised EI Escorial criteria. The corneal sub-basal nerve plexus was analysed using in vivo confocal microscopy. An automated algorithm (ACCMetrics) was used to evaluate corneal parameters: nerve fibre density, nerve branch density, nerve fibre length, nerve fibre area, nerve total branch density, nerve fibre width, and nerve fractal dimension. Results: Twenty-two patients with ALS and 30 controls were included. No significant differences were found between ALS and control groups for all corneal parameters (p > 0.05). Corneal sensitivity did not differ between groups, and no correlation was identified between corneal nerve parameters and ALS disease duration, severity and rate of progression (p > 0.05). Conclusions: The present study does not support the use of in vivo corneal confocal microscopy as an early diagnostic or prognostic tool for ALS. Further research, especially longitudinal investigations, is needed to understand any potential corneal innervation changes as ALS progresses. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the association between amyotrophic lateral sclerosis (ALS) and potential environmental risk factors, especially head traumas and pesticides, in two populations from Canada and France. Methods: A case–control study was performed in tertiary-care centers. Consecutive ALS cases were recruited along with a control group from the same age distribution and region. Participants answered a phone-administered questionnaire. Head trauma exposure was censored at age of symptom onset, and a sensitivity analysis considering old head traumas that occurred more than 3 years before onset was performed. Univariate and multivariate logistic regression were used to estimate odds ratios (ORs) and their 95% confidence intervals (CIs). Results: A total of 404 ALS cases and 381 controls completed the questionnaire. Previous head trauma was more frequently reported by cases (adjusted OR 1.50 (1.05–2.18)) with a dose-response relationship. This association was driven by a strong effect in men (adjusted OR 2.06 (1.22–3.55)) and was consistent for old traumas, but there was no association in women. For pesticides, a previous high-risk occupation was associated with ALS (adjusted OR 2.08 (1.36–3.24)), although reported occupational exposure to pesticides was not statistically significant in the multivariate model (adjusted OR 1.67 (0.97–2.97)). Past electrocution was associated with ALS (adjusted OR 1.79 (CI 1.13–2.87)), especially spinal-onset ALS. Residential exposure to pesticides, neck trauma, and welding were not associated with ALS. Conclusions: Head trauma is a risk factor for ALS in men only. Previous occupation at high risk for pesticides exposure and electrocution are also risk factors for ALS. [ABSTRACT FROM AUTHOR]

Objective: To assess spatial aggregates of amyotrophic lateral sclerosis (ALS) incident cases, using a solid geo-epidemiological statistical method, in France. Methods: This population-based study (2003–2011) investigated 47.1 million person-years of follow-up (PYFU). Case ascertainment of incident ALS cases was based on multiple sources (ALS referral centers, hospital centres and health insurance data). Neurologists confirmed all ALS diagnoses. Exhaustiveness was estimated through capture-recapture. Aggregates were investigated in four steps: (a) geographical modelling (standardized incidence ratio (SIR) calculation), (b) analysis of the spatial distribution of incidence (Phothoff-Winttinghill's test, Global Moran's Index, Kulldorf's spatial scan statistic, Local Moran's Index), (c) classification of the level of certainty of spatial aggregates (i.e. definite cluster; probable over-incidence area; possible over-incidence area) and (d) evaluation of the robustness of the results. Results: The standardized incidence of ALS was 2.46/100,000 PYFU (95% CI 2.31–2.63, European population as reference) based on 1199 incident cases. We identified 13 areas of spatial aggregates: one cluster (stable in robustness analysis), five probable over-incidence areas (2 stable in robustness analysis) and seven possible over-incidence areas (including 4 stable areas in robustness analysis). A cluster was identified in the Rhône-Alpes region: 100 observed vs 54.07 expected cases for 2,411,514 PYFU, SIR: 1.85 (95% CI 1.50–2.25). Conclusion: We report here one of the largest investigations of incidence and spatial aggregation of ALS ever performed in a western country. Using a solid methodology framework for case ascertainment and cluster analysis, we identified 13 areas that warrant further investigation. [ABSTRACT FROM AUTHOR]

This study retrospectively compared all‐cause and cause‐specific mortality in French male professional football players with data from France's national population. Altogether, 6114 individuals born in Metropolitan France or in one of its overseas territories who played at least one competitive match in France's professional football championships between January 1, 1968 and December 31, 2015, were identified and followed up for vital status obtained from a national reference database until December 31, 2015. Data on all‐cause and cause‐specific mortality were subsequently compared to the expected number of deaths for the national population after standardization for the year, age, and sex. Ratios between observed and expected deaths provided standardized mortality ratios (SMR) along with 95% confidence intervals (95% CI). Linear trends were investigated using the Poisson trend test. Altogether, 662 player deaths were observed. All‐cause mortality overall was lower than that of the national population (SMR: 0.69, 95% CI 0.64–0.75). An excess of deaths from dementia was observed in the players (SMR: 3.38, 95% CI: 2.49–4.50) whereas mortality from diseases of the nervous (SMR: 0.64, 95% CI: 0.35–1.08) and cardiovascular systems (SMR: 0.82, 95% CI: 0.70–0.96), and cancer (SMR: 0.67, 95% CI: 0.58–0.76) was lower. Lower overall mortality and that owing to common cardiovascular and cancer‐related diseases were reported in French professional football players compared to France's national population. In line with previous studies, however, excess mortality from dementia was observed in the players. Career length was not associated with all‐cause or cause‐specific mortality. Prospective matched‐cohort studies are necessary to identify the neurologic impact of participation in professional football. [ABSTRACT FROM AUTHOR]

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive diaphragm weakness and deteriorating lung function. Bulbar involvement and cough weakness contribute to respiratory morbidity and mortality. ALS-related respiratory failure significantly affects quality of life and is the leading cause of death. Non-invasive ventilation (NIV), which is the main recognized treatment for alleviating the symptoms of respiratory failure, prolongs survival and improves quality of life. However, the optimal timing for the initiation of NIV is still a matter of debate. NIV is a complex intervention. Multiple factors influence the efficacy of NIV and patient adherence. The aim of this work was to develop practical evidence-based advices to standardize the respiratory care of ALS patients in French tertiary care centres., Methods: For each proposal, a French expert panel systematically searched an indexed bibliography and prepared a written literature review that was then shared and discussed. A combined draft was prepared by the chairman for further discussion. All of the proposals were unanimously approved by the expert panel., Results: The French expert panel updated the criteria for initiating NIV in ALS patients. The most recent criteria were established in 2005. Practical advice for NIV initiation were included and the value of each tool available for NIV monitoring was reviewed. A strategy to optimize NIV parameters was suggested. Revisions were also suggested for the use of mechanically assisted cough devices in ALS patients., Conclusion: Our French expert panel proposes an evidence-based review to update the respiratory care recommendations for ALS patients in daily practice., (Copyright © 2024. Published by Elsevier Masson SAS.)

Objectives: Mortality data have been used as a proxy for amyotrophic lateral sclerosis (ALS) incidence. However, the accuracy of death certificates (DCs) needs to be validated. This study aims to assess the accuracy of DCs in the identification of ALS cases. Methods: This is a retrospective population-based validation study. DC information, provided by the "Centre d'épidémiologie sur les causes médicales de décès", including ICD10 codes for specific cause of death for patients recorded in the French register of ALS cases in the Limousin region (FRALim) and deceased between 2000 and 2011, was assessed. The FRALim register was used as gold standard. Results: In the study period, DCs were available for 197 patients diagnosed with ALS, of whom 185 (93.9%) were correctly identified with an ICD10 code (G12.2) corresponding to ALS. The overall sensitivity was 93.9% (95% CI 89.6–96.8) and the positive predictive value (PPV) was 64.9 (59.1–70.4), with higher values in the period 2004–2011 (75.0–78.9). Stratification for sex, age, and year at death did not show difference in accuracy, except a lower PPV during the first years of observation. Conclusions: DCs identifying subjects with a diagnosis of ALS in the Limousin region, France showed an overall good sensitivity and moderate PPV. The absence of ALS diagnosis as the main and underlying cause of death on DCs highlights the need to use DC in combination with other administrative data to create algorithms with higher accuracy performances. [ABSTRACT FROM AUTHOR]

Covid-19-related lockdown (LD) in France precluded in-person follow-up in referral ALS centers. ALS patients' evolution and worsening before and during LD were studied to analyze its impact. A total of 84 patients were identified. The monthly rate of ALSFRS-R decline during LD was 1.06 ± 1.42 and was significantly increased compared to the pre-LD period, 0.58 ± 0.73, corresponding to an 83% increase (p = 0.007). Weight loss was unchanged between pre-LD and LD, gender and site of onset did not influence the rates of change of ALSFRS-R score. Several factors may be implicated in this increased severity of ALS during LD, such as psychological consequences of LD, interruptions of physiotherapy and speech therapy, or in-patient visits both to the tertiary center and the GP. Physicians and health authorities should be aware of that, in order to prevent the consequences of future sanitary restrictions. [ABSTRACT FROM AUTHOR]

People with amyotrophic lateral sclerosis (pALS) require complex, multi-disciplinary care, resulting in extensive healthcare resource utilization (HCRU). To investigate the relationship between HCRU and ALS progression, the study objectives were (i) to characterize HCRU in pALS and (ii) to establish whether this varied according to disease stage, as defined using three different methodologies: neurologist-defined early/mid/late stage, the King's clinical staging system for ALS, and the Milan Torino Staging system for ALS (MiToS). Real-world data were drawn from the Adelphi ALS Disease-Specific Programme™, a point-in-time survey of neurologists in France, Germany, Italy, Spain, the UK, and the USA conducted July 2020-March 2021. The analysis included survey responses from 142 physicians with respect to 880 pALS. With advancing ALS stage, significant differences were observed in the number of healthcare professional consultations and X-rays per person (both p < 0.05 for all staging systems), and the proportion of pALS with emergency room admissions, intensive care unit admissions, and assisted ventilation (all p < 0.05 for all staging systems). Across stages, >55% of pALS received care from a general neurologist and a general/primary care practitioner. With increasing stage, there was a significant difference in the proportion receiving care from a physical therapist, pulmonologist/respiratory care practitioner, respiratory therapist, speech/language therapist, and palliative care team, and in the proportion receiving care only from professional caregivers (all p < 0.05 for all staging systems). This study confirmed the substantial HCRU required to support pALS through all stages of ALS and highlighted an increasing need for healthcare resources as the disease progresses., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: There are no estimates of the nationwide incidence of motor neuron disease (MND) in France. We used the French health insurance information system to identify incident MND cases (2012–2014), and compared incidence figures to those from three external sources.Methods: We identified incident MND cases (2012–2014) based on three data sources (riluzole claims, hospitalisation records, long-term chronic disease benefits), and computed MND incidence by age, gender, and geographic region. We used French mortality statistics, Limousin ALS registry data, and previous European studies based on administrative databases to perform external comparisons.Results: We identified 6553 MND incident cases. After standardisation to the United States 2010 population, the age/gender-standardised incidence was 2.72/100,000 person-years (males, 3.37; females, 2.17; male:female ratio = 1.53, 95% CI1.46–1.61). There was no major spatial difference in MND distribution. Our data were in agreement with the French death database (standardised mortality ratio = 1.01, 95% CI = 0.96–1.06) and Limousin ALS registry (standardised incidence ratio = 0.92, 95% CI = 0.72–1.15). Incidence estimates were in the same range as those from previous studies.Conclusions: We report French nationwide incidence estimates of MND. Administrative databases including hospital discharge data and riluzole claims offer an interesting approach to identify large population-based samples of patients with MND for epidemiologic studies and surveillance. [ABSTRACT FROM PUBLISHER]

Background: Dyspnoea is a threatening sensation of respiratory discomfort that presents many similarities with pain. Experimental dyspnoea in healthy subjects induces analgesia. This 'dyspnoea-pain counter-irritation' could, in reverse, imply that relieving dyspnoea in patients with chronic respiratory diseases would lower their pain thresholds.Methods: We first determined pressure pain thresholds in 25 healthy volunteers (22-31 years; 13 men; handheld algometer), during unloaded breathing (BASELINE) and during inspiratory threshold loading (ITL). Two levels of loading were used, adjusted to induce dyspnoea self-rated at 60% or 80% of a 10 cm visual analogue scale (ITL6 and ITL8). 18 patients with chronic respiratory failure due to amyotrophic lateral sclerosis (ALS) were then studied during unassisted breathing and after 30 and 60 min of non-invasive ventilation-NIV30 and NIV60-(same dyspnoea evaluation).Results: In healthy volunteers, pressure pain thresholds increased significantly in the deltoid during ITL6 (p<0.05) and ITL8 (p<0.05) and in the trapezius during ITL8 (p<0.05), validating the use of pressure pain thresholds to study dyspnoea-pain counter-irritation. In patients with ALS, the pressure pain thresholds measured in the deltoid during unassisted breathing decreased by a median of 24.5%-33.0% of baseline during NIV30 and NIV60 (p<0.05).Conclusion: Relieving dyspnoea by NIV in patients with ALS having respiratory failure is associated with decreased pressure pain thresholds. Clinical implications have yet to be determined, but this observation suggests that patients with ALS could become more susceptible to pain after the institution of NIV, hence the need for reinforced attention towards potentially painful diagnostic and therapeutic interventions. [ABSTRACT FROM AUTHOR]

The accuracy of French medico-administrative data concerning amyotrophic lateral sclerosis (ALS) is to date unknown. We aimed to assess the validity of hospital discharge data (HDD) and health insurance data (HID) related to ALS. A retrospective population-based study was performed. The French register of ALS in Limousin (FRALim) was used as gold standard (2000–2013 period). All patients discharged from the regional hospitals with a ‘G12.2’ code in their HDD (according to the International Classification of Disease-10th version) or having a G12 HID code were considered. In the study period, the register included a total of 322 incident ALS patients. Among 451 subjects identified through HDD, 290 were true incident ALS cases, corresponding to 90.1% (95% CI 86.3–93.1) sensitivity and 64.3% (95% CI 59.7–68.7) positive predictive value (PPV). A total of 184 subjects were identified through HID, 142 of which were true ALS cases. This corresponded to 44.1% (95% CI 38.6–49.7) sensitivity and 75.5% (95% CI 68.7–81.5) PPV. The combination of both HDD and HID led to 93.8% (95% CI 90.6–96.2) sensitivity and 60.8% (95% CI 56.3–65.1) PPV. This study shows that French HDD and HID, even if combined, are not per se suitable for accurate and exhaustive direct identification of ALS cases. [ABSTRACT FROM AUTHOR]

Although the global benefits of gastrostomy have been proven in amyotrophic lateral sclerosis (ALS), the impact on biological parameters has not been explored yet. The aim of this preliminary work was to evaluate the modification of biological parameters in patients with ALS undergoing gastrostomy. We retrospectively collected clinical and biological data from 44 patients having undergone gastrostomy at three time points (T0, T1 and T2: before, at the time of and after gastrostomy). We examined the relationship between the biological parameters and disease progression. Variations of the concentrations of total cholesterol significantly differed before (T1-T0) vs those after gastrostomy (T2-T1; P=0.0044). The variations of total cholesterol and low-density lipoprotein cholesterol concentrations after gastrostomy were negatively associated with survival (P=0.0002). This study showed for the first time that patients with ALS fed quite exclusively by gastrostomy had decreased blood cholesterol after gastrostomy. We suggest that a restoration of normal lipid metabolism should be planned in patients with ALS. [ABSTRACT FROM AUTHOR]

The article presents abstracts on epidemiology which include estimation of amyotrophic lateral sclerosis (ALS) from the U.S. national databases, determination of the course and phenotypic variety of ALS in Rhineland, Palatinate and identification of the presence of clusters of ALS in France.

There is an unmet need for validated tools to measure sialorrhea in amyotrophic lateral sclerosis, especially to evaluate treatments. We assessed the inter-/intra-rate reviewer reliability of two scales: the Oral Secretion Scale (OSS), specifically developed for ALS patients, and the Sialorrhea Scoring Scale (SSS), initially developed for Parkinson's disease patients. Sialorrhea was rated in 69 ALS consecutive patients by four evaluators: two neurologists, one nurse and one speech therapist. Inter-rater reliability was evaluated by the light kappa coefficient and intra-rater reliability by the weighted kappa coefficient. We also compared patients' and caregivers' answers. Results demonstrated that the two scales present a high inter-/intra-rater reliability: weighted kappas were 0.85 for both scales and light kappas 0.89 for the OSS and 0.88 for the SSS. Both scales also showed a good intra-profession reliability (OSS kappa = 0.84; SSS kappa = 0.79) and agreement between patients' and caregivers' answers. The SSS showed a higher responsiveness compared to OSS. In conclusion, both Oral Secretion Scale and Sialorrhea Scoring Scale are reliable tools to measure sialorrhea in ALS patients. Because of the wide range of salivation degrees, SSS may be more sensitive as a tool to evaluate treatments in patients with severe hypersialorrhea. [ABSTRACT FROM AUTHOR]

Background and Objectives: Amyotrophic lateral sclerosis (ALS) is a fatal, neurological disease, which can potentially impact mental health as well as the adaptation process of people who are affected. Most of the results available are cross-sectional. The aim of this study was to study the evolution of coping strategies, Quality of Life (QoL), and mental health in a sample of ALS patients. Methods: Forty-nine patients with ALS were interviewed in order to obtain their demographic and medical data. Then, each one was asked to complete a questionnaire of coping strategies (Brief COPE), mental health (GHQ-28), and QoL (SF-36) at two different moments of the disease evolution. As many patients died in the interim, only 30 completed questionnaires at T2. The Wilcoxon test was used in order to compare mean scores between T1 and T2. Results: On the GHQ-28, the differences concerned two dimensions: somatic disorders (Z=−2.15, p=0.03) and anxiety sleep disorders (Z=−2.07, p=0.04). We noted that mean scores increased between T1 and T2. Regarding coping strategies, only one tendency was found on the COPE. It concerned behavioral disengagement (Z=1.84, p=0.06), which was used more at T2 than at T1. Concerning QoL, one significant difference and one tendency between T1 and T2 were found. They involved pain (Z=2.52, p=0.01) and a tendency toward emotional role functioning (Z=−1.86, p=0.06). Discussion: This study, the first to evaluate psychosocial aspects of ALS over time, underlines the importance of global, multidisciplinary, and adapted care. [ABSTRACT FROM AUTHOR]

Malnutrition is associated with poor survival among patients with amyotrophic lateral sclerosis (ALS). This study aimed to evaluate nutritional assessment by a network during first consultations in patients' homes. Patients identified by the regional ALS centre gave their informed consent. Assessment included functional, nutritional issues, evaluation of the need for help, whether personal or the use of aids, and noted any dietary supplementation and modification of the texture of food. Forty patients were seen a mean of 7.4 months after diagnosis; 52.5% had bulbar disease, 7.5% were malnourished; 29.4 ± 10.1 kcal/kg/day were consumed and protein intake was 1.3 ± 0.5 g/kg/day. Thirty-five percent of patients were anorexic, 43.8% reported taste disorders, and 70% had dysphagia, significantly associated with salivary stasis. Only 30% of dysphagic patients ate texture-modified food, and 90% of patients with problems drinking liquids did not use a thickener. In conclusion, assessment at home by a nutritional network can be conducted promptly. Malnutrition is rare in early disease, despite the fact that patients' diets are often low in energy and dysphagia is common. Unexpected taste disorders are detected. Dysphagia is very common but inadequately addressed. Consequently, home assessment by the network led several beneficial interventions. [ABSTRACT FROM AUTHOR]

Mutations in the superoxide dismutase-1 (SOD1) gene have been found in 12-23% of patients with a diagnosis of ALS. Here we describe a large ALS Polish family with a branch in France, carrying a G41S mutation in the SOD1, and characterized by an early onset of the disease and extremely short survival time. The mutation has been initially detected in Italian ALS families with common founder effect. However, in the Polish population the G41S mutation most probably originated from an independent mutation event, as indicated by haplotype analysis. Collected data support the hypothesis that a SOD1 mutation is not the sole factor determining the clinical ALS phenotype. [ABSTRACT FROM AUTHOR]

Abstract: This article aimed to detect clusters of amyotrophic lateral sclerosis (ALS) and their relationships with exposure of the population to various environmental factors in the Limousin region of France. Methods used were extensively described. We adopted a geographical approach that revealed variations in the incidence of ALS and permitted us to identify three regional clusters and their spatial spread. We considered environmental factors and the potent locations or source of substances or activities hypothesized to be associated with ALS. Notably, we determined which industrial activities seem to affect the incidence of ALS in Limousin. The results were interpreted at a regional level. Among the 50 factors this article considered, paper paste and water treatment plants were particularly geostatistically significant and deserve special attention in the ongoing investigations into high resolution spatial clusters (geographical and epidemiological studies). [Copyright &y& Elsevier]

The incidence and mortality of motor neuron disease (MND) increase with age and appear to have increased with time. The examination of period and cohort effects using age-period-cohort (APC) models can help characterize temporal trends. Our objective was to describe mortality from MND in France (1968-2007), and to examine the role of age, period of death, and birth-cohort on changes in mortality. The number of people who died from MND and population statistics (1968-2007) were extracted from French national records. Annual standardized (age/sex) mortality ratios (SMRs) were computed. Using Poisson regression, APC models examined the relationship between mortality rates and age, period of death, and birth-cohort in subjects aged 40-89 years. Deviance/degrees-of-freedom ratios evaluated model fit; ratios close to one indicated adequate fit. Between 1968 and 2007, 38,863 individuals died from MND (mortality rate = 1.74/100,000); 37,624 were aged 40-89 years. SMRs increased from 54 (95% CI = 49-59) in 1968 to 126 (120-132) in 2007. Male-to-female ratios declined from 1.80 in 1968 to 1.45 in 2007. Changing mortality rates were best explained by cohort effects (deviance/degrees-of-freedom = 1.09). The relative risk of dying from MND increased markedly for persons born between 1880 and 1920, and more slowly after 1920. In conclusion, mortality rates for MND increased between 1968 and 2007, and more rapidly in women than men. This increase was better explained by the birth-cohort of individuals than by period effects. Changing environmental exposures may be a possible explanation and these findings warrant the continued search for environmental risk factors for MND. [ABSTRACT FROM AUTHOR]

Chromogranins interact with mutant forms of superoxide dismutase 1 (SOD1) responsible for a portion of familial amyotrophic lateral sclerosis (ALS). A particular variation (P413L) in the chromogranin B gene, CHGB, has been recently associated with an earlier age at onset in both familial and sporadic ALS. The aim of our study was to evaluate the P413L chromogranin variation in French patients with sporadic amyotrophic lateral sclerosis. We developed a High Resolution DNA Melting (HRM) protocol to analyse the P413L variation in the CHGB gene in 540 French patients with sporadic ALS and 504 controls. The clinical characteristics of patients were analysed in relation to their genotype. Results showed that our study on a large cohort of French-Caucasian patients with SALS and controls failed to confirm an increased frequency of the 413L variant in SALS patients. This frequency was 5.3% in the SALS population and 5.5% in the control group. Moreover, we did not observe a previous observation of a difference of age at onset between T-allele carriers and non-carriers (median age of onset 60.4 vs. 62.0 years of age, respectively). Thus, our findings do not support the 413L variant of rs742710 as a risk factor for sporadic ALS in the French population. [ABSTRACT FROM AUTHOR]

We carried out a retrospective multicentre study to assess the safety of home parenteral nutrition (HPN) in patients with ALS. We reviewed the case records of patients from French ALS centres treated with HPN by central venous catheter (CVC) using an implantable port between January 2005 and October 2009. Seventy-three patients received HPN for a total of 11,908 catheter days. Twenty-seven patients experienced a total of 37 CVC related complications resulting in an incidence rate of 3.11 CVC complications/1000 catheter days, including 1.93 septic complications and 1.09 mechanical complications/1000 catheter days. Metabolic complications were frequent but without serious consequences on mortality. The use of the catheter for intravenous therapies in addition to HPN was identified as a septicaemia's risk factor (relative risk (RR) == 2.54, confidence interval (CI) 1.56--4.14, p == 0.04). In conclusion, HPN is an alternative procedure to PEG in advanced ALS patients. The incidence of complications appears to be comparable to data from the literature on HPN in other diseases. A prospective study comparing HPN and radiologic inserted gastrostomy (RIG) would allow comparison of the relative risk-benefit and survival of these procedures. The relation of CVC and RIG placement timing and the complications'' occurrence should also be investigated. [ABSTRACT FROM AUTHOR]

The aim of the study is to determine the shape of the progression curve in ALS, assess the impact of clinical variables on the rate of progression, and evaluate the association between functional decline and survival. Data were prospectively collected and entered into a clinical database from all patients seen in 2002-2008 at the Centre SLA, Hôpital de la Salpêtrière, Paris. Variables analyzed were demographic and baseline information, the ALS functional rating scale (ALSFRS-R), strength testing (MMT), and survival. Generalized additive mixed models characterized changes in ALSFRS-R and MMT scores over time. Linear mixed effects assessed the impact of demographic and clinical measures on rate of progression and Cox models examined their effect on survival. Of 2,452 patients with ALS identified, 1,884 had adequate data for analysis. The ALSFRS-R and MMT declined in a curvilinear way; a quadratic fit described the trends but a linear fit did not. The total ALSFRS-R score was negatively associated with age-of-onset ( p < 0.001), and positively associated with baseline ALSFRS-R ( p < 0.001) as well as more severe bulbar features ( p < 0.001). Higher rate of decline in ALSFRS-R and MMT, older age-at-onset and bulbar-onset predicted shorter survival. Deterioration in ALS is non-linear. The early and late phases of the illness show the most rapid rates of decline. Older age and bulbar signs are associated with a steeper decline, and along with more rapid initial rate of decline, but not current functional status, also predict survival. [ABSTRACT FROM AUTHOR]

Our objective was to compare clinical features and survival in two groups of ALS patients from countries in opposite hemispheres. The study took place at an ALS referral centre in the Limousin region of France (LIM) and in Uruguay (UY). All consecutive patients diagnosed with ALS between 1 January 2002 and 31 December 2004 were enrolled. Data from a total of 187 ALS patients were analysed: 84 from LIM and 103 from UY. Mean ages at onset and diagnosis were significantly higher in LIM (66 vs. 61 years). UY patients demonstrated more advanced disease at the time of diagnosis. The proportions of definite forms were 82% in UY versus 10% in LIM ( p<0.001), and median manual muscle testing (MMT) and ALSFRS scores were significantly lower in LIM. This observed difference was not directly explained by a longer diagnostic delay in UY (10 vs. 9 months). Median survival from time of diagnosis was significantly shorter in UY patients (19 vs. 28 months; log-rank test, p=0.030). In conclusion, survival of ALS patients in UY is nine months shorter than in LIM, probably due to the heterogeneity of medical care and the absence of an ALS referral centre. [ABSTRACT FROM AUTHOR]

Our objective was to assess the incidence of amyotrophic lateral sclerosis (ALS), and its temporal variations, between 1997 and 2007. The study was based on data prospectively gathered by the referral ALS 'expert centre' of the Regional University Hospital of Limousin (710,792 inhabitants). Patients were included if they were diagnosed with ALS according to the revised El Escorial criteria either at the time of diagnosis or at subsequent follow-up, and if they resided in Limousin when diagnosed. We identified a high crude incidence (2.5/100,000). When age-standardized for the 1999 French population, the mean annual incidence was 2.0/100,000 inhabitants (95% CI 1.8-2.3) overall and 4.4 (95% CI 3.6-5.2) in the 45-74 years age group. Crude incidence by age groups showed a progressive increase up to 85 years, followed by a sharp decrease thereafter. Age at diagnosis was particularly high in our population (median, 69.4 years). Incidence of ALS in Limousin was consistent with previous work published by European population-based registries. The atypical epidemiology was explained in part by Limousin's older aged population. It is proposed that our referral centre will become a population-based registry. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: In France, a recent law emphasizes patient rights and prohibits unwanted therapies in end-of-life care. As end-of-life home care is increasing, we aimed to assess French district nurses'' attitudes toward terminally ill patients'' autonomy. Materials and Methods: We used data from a nationwide telephone survey conducted in 2005 among a random sample of French district nurses (n = 602). Nurses'' attitudes were assessed with a clinical case describing a patient (randomly defined as a male or a female aged 50 years) having amyotrophic lateral sclerosis (ALS) who urgently needs mechanical ventilation. Nurses were asked whether patient consent was necessary before performing intubation/tracheotomy, and the analysis took into account various covariates, including nurses'' religiosity, nurses'' attitudes toward living wills, and patient sex. Results: Overall, 44% of nurses considered that an ALS patient with respiratory failure should always be intubated (53% for a female patient, 40% for a male patient, P < .01), and after intubation, 27% upheld tracheotomy without considering patient consent as a necessary prerequisite (39% among male nurses, 30% among female nurses, P < .05). Poor communication with terminal patients and hostility toward living will were also predictive of willingness to perform both mechanical ventilation and tracheotomy without patient consent. Conclusions: A significant part of French district nurses may have a disturbing propensity to support intubation and tracheotomy with insufficient attention paid to the patient''s will. Further research should investigate potential causal factors (such as increased workload) as well as sex-related attitudes in nurse-patient relationship. [Copyright &y& Elsevier]

The article provides information on the European ALS Consortium's second annual research workshop, held in Nice, France, on May 14-16, 2005. The programme comprised 66 papers and posters. Twenty concerned the pathogenesis of human ALS and 16 dealt with the SOD1 transgenic mouse. Twenty papers were clinical and 10 dealt with animal models, cultured cells or slices, or drug discovery. Jaine Kirby and Christine Teitsma described the use of microarrays for mRNA in fibroblasts to study gene expression in SOD1 mice as an introduction to their use in humans. As described by Christopher Miller, protein transport is slowed in the motor nerves of SOD1 mutant mice and also in neurofilament mutants. Abnormalities of mitochondrial structure and function are found in animal models of ALS, including SOD1 mutants as well as VEGF deficiency and the wobbler mouse.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease. No treatment is currently able to stop the disease process. In the absence of new active compounds there is an urgent need to develop new strategies based on the neuroprotective activity of available drugs. ALS is a heterogeneous disease. To build up these therapeutic trials, we need to have a better understanding of the prognostic factors in this disease. During the Phase IV Rilutek Trial in France, we developed in a large population of patients a prognostic score based on clinical parameters available at the bedside. The most significant variables are vital capacity, spasticity, fasciculations, swallowing, cough and creatininemia. This score proved to be very useful in daily use in the clinic and for planning disease management in ALS as in the design of therapeutic trials. In ALS clinical trials, efficacy can be evaluated using survival or functional parameters. In phase II trials, function remains the most commonly used. In phase III trials, the gold standard endpoint remains the survival rate at month 18. We analyzed the most recent ALS trials published in the literature. This review suggests that in these trials there is a discrepancy between drug effects on survival versus function. These results suggest that a reappraisal of strategies to identify therapeutic targets for ALS is required. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The objective of this study was to identify prognostic factors for survival in amyotrophic lateral sclerosis from a large prospective observational study performed in France. The study included a cohort of 2069 patients fulfilling broad entry criteria treated with riluzole. Over 100 demographic, biological, clinical and quality-of-life variables were monitored and assessed for their effect on survival. Patients were randomized post hoc into two groups: one group (two-thirds of the patients) to generate the prognostic models and one group (one-third of the patients) to validate the resulting models. Thirteen variables were found to affect survival independently and were used to construct a survival prediction score, RL401. These included age, disease duration, slow vital capacity, intensity of tiredness (visual analogue scale), number of body levels with spasticity, atrophy and/or fasciculations, cough, distal muscle strength, household income, depression and two biological parameters, plasma creatinine levels and neutrophil counts. A simplified score, RL401S, was constructed, designed to be easy to use and interpret. The predictive powers of the two scores were similar. [ABSTRACT FROM AUTHOR]

Background: The origin of amyotrophic lateral sclerosis (ALS) remains largely unknown but seems to be multifactorial. We believe that ALS clusters may help clinicians understand or analyze the role of environmental factors in ALS pathogenesis. Objective: To describe a cluster of conjugal ALS in southeastern France. Patients: We describe 9 couples in which both spouses were affected by ALS. Eight of the 9 had lived in southeastern France. In all cases, the spouses were married for more than 10 years. Three couples lived in the same département and 2 of them in the same city. Results: To our knowledge, such a large cluster of conjugal ALS cases has not been previously reported. No precise environmental factors could be identified at the origin of these conjugal cases. Conclusions: We suggest that genetic and environmental factors, or both, may explain the occurrence of this cluster of ALS. [ABSTRACT FROM AUTHOR]

Louis-Stanislas Duménil (1823-1890) was a surgeon from Normandy who was a contemporary of Jean-Martin Charcot (1825-1893). Throughout his career, Duménil published annotated observations of neurological pathologies. One year before Guillaume Duchenne de Boulogne (1806-1875), he reported a case of "progressive muscular paralysis of the tongue, soft palate, and lips". He added five other cases of progressive muscular atrophy in 1867, together with histological examinations which showed atrophy in the anterior horns of the spinal cord. Charcot, who described amyotrophic lateral sclerosis, did not fail to pay homage to Duménil for his contribution. In 1862, Duménil added clinical observations of progressive locomotor ataxia, one of the first to do so. This included anatomopathological examinations, thus significantly completing the clinical picture presented by Duchenne in 1858. He confirmed the damage to the roots and posterior tracts of the spinal cord. Finally, by providing multiple observations of the syndrome described by Octave Landry (1826-1865) in 1859, he contributed to the clinical picture of "acute ascending paralysis" which has come down to us as Guillain-Barré syndrome, with no mention of the perspicacious physicians of the previous century who had already perfectly recognised this disease. Finally, Augusta Dejerine-Klumpke (1859-1927) paid a warm tribute to Duménil in her 1889 thesis, calling him one of the pioneers in understanding "the individuality and autonomy of the peripheral nervous system." He was indeed a pioneer, although he has been often overlooked., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

DPP6 and FGGY genes have been recently associated with an increased susceptibility for sporadic amyotrophic lateral sclerosis. Here, we evaluated the role of these genes in ALS pathogenesis by undertaking a sequence analysis of a cohort of 190 ALS patients from France and Quebec. We did not observe any evidence that mutations in DPP6 and FGGY genes are involved in ALS. Our data indicate that mutations in these genes are unlikely to be a common cause of ALS in the French and French Canadian populations. [ABSTRACT FROM AUTHOR]

The 2nd Consensus Conference (Versailles) recommended that an ALS knowledge-base for initial healthcare providers, diagnosing neurologists and confirming neurologists should be defined to include a simplified version of diagnostic criteria less formal than the World Federation of Neurology El Escorial Revisted Criteria (‘ALS diagnosis – An algorithm’), a set of rules concerning red flags which should increase the suspicion of ALS as the diagnosis and minimize the time between suspicion and referral for confirmation of diagnosis (‘ALS axioms of referral’), as well as a site of symptom onset-specific checklist of minimal clinical examination, neuroimaging, electrodiagnostic, pulmonary function and laboratory test information required to confirm the diagnosis of ALS (‘Versailles minimal dataset’). Although introductory discussions addressed the advantages and disadvantages of earlier diagnosis, false-positive or false-negative diagnosis, the frequency of follow-up and what potential biological markers to be followed, these issues will have to be further evaluated at future consensus conferences. (ALS 2000; 1 (suppl 1): S79–S81). [ABSTRACT FROM AUTHOR]

Background: Gastrostomy is recommended in patients with Amyotrophic Lateral Sclerosis (ALS) in the presence of weight loss over 10% as compared to usual weight, repeated aspirations or meal time duration longer than 45 min. Currently, the impact of gastrostomy on survival of ALS patients is not clear., Aims: i) to describe diagnosis factors associated with the indication for gastrostomy ii) to evaluate survival of ALS patients with gastrostomy indication according to their acceptance of feeding tube placement., Methods: Patients with ALS were included and followed in the ALS referral centre of Limoges's teaching hospital between 2006 and 2017. Neurological, nutritional and respiratory status was assessed prospectively from diagnosis to death. Statistical analysis was performed using Mann-Whitney test, Chi 2 tests, Cox model and multivariate logistic regression., Results: Two hundred and eighty-five patients were included. Among the 182 for whom gastrostomy was indicated, 63.7% accepted the placement. The median time was 7.3 months [IQR: 3.2-15.0] and 2.7 months [IQR: 0.9-5.8] respectively from diagnosis to indication and from indication to placement. Weight loss >5% significantly increased the risk of death by 17% (p < 0.0001). At time of diagnosis, bulbar onset, a loss of one point in the body mass index or on the bulbar functional scale were all positively associated with indication for gastrostomy (aOR = 10.0 [95%CI: 1.96-25.0]; p = 0.002, aOR = 1.17 [95%CI: 1.02-1.36]; p = 0.025 and aOR = 1.19 [95%CI: 1.06-1.32]; p = 0.002, respectively). However, gastrostomy placement did not have any impact on survival (aHR = 1.25 [95%CI: 0.88-1.79]; p = 0.22)., Conclusion: Both neurological and nutritional criteria were associated with an indication for gastrostomy at diagnosis. Gastrostomy placement had no impact on survival. The study of earlier gastrostomy placement might be of interest in further prospective studies., Competing Interests: Conflict of interest No conflicts are declared., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Amyotrophic 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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

To understand the home-based difficulties encountered in the health care pathways of patients with Amyotrophic Lateral Sclerosis (ALS), we must annotate a large amount of textual data, from a database created by the ALS Île de France coordination network. For this purpose, we have developed a modular ontology, consisting of four modules, and a semantic annotation tool integrating the created ontology. The specificity of our approach is the creation of equivalent classes at different levels of the ontology. These equivalent classes represent variables of interest allowing a statistical approach and a clinical analysis of comprehension of care pathways ruptures causing.

In the 19th century, neurologists discovered a series of diseases characterized by limb weakness and muscle atrophy, but it was not certain whether they were variants of the same disease or completely different diseases. In 1869, Jean-Martin Charcot first diagnosed the disease, and began to use the term "amyotrophic lateral sclerosis" in 1874. The disease is also known as "Lou Gehrig's disease" in the United States, "Charcot's disease" in France, and "Motor Neuron Disease (MND)" in UK. In China, it is commonly known as "Jian-Dong Ren disease" .

Objectives: To assess the association between amyotrophic lateral sclerosis (ALS) and previous traumatic events, age of trauma, and site of injury., Methods: A population-based case-control study was performed in five European countries (Italy, Ireland, France, United Kingdom, Serbia). Newly diagnosed ALS patients and matched controls were interviewed to collect relevant demographic factors and exposures. Key clinical features at diagnosis were collected in ALS patients. Trauma was any accidental event causing an injury. Injuries were dated and classified according to cause, severity, type, site, and complications. All exposures were censored five years before symptoms onset. Risks were computed as odds ratios (OR) with 95% confidence intervals (CI) using univariate and multivariate conditional logistic regression models., Results: Five hundred and seventy-five ALS patients and 1150 controls were interviewed. Disabling traumatic events predominated in the cases (OR 1.54 (95% CI 1.24-1.92)) and maintained significance after adjustment, with a significant gradient. A history of 2 + head injuries was associated with an almost three-fold increased risk of ALS. The risk was almost two-fold when trauma occurred at age 35-54 years. Site of injury was uneventful., Conclusions: Traumatic events leading to functional disability or confined to the head are risk factors for ALS. Traumatic events experienced at age 35-54 years carry the highest risk.

A biography of neurologist Albert Gombault is presented. Gombault was born in 1844 in Orleans, France and received his medical training in Paris, France. He produced his medical thesis on amyotrophic lateral sclerosis (ALS) in August 1877. As a scientist, Gombault was an astute clinician as well as an experimentalist. Gombault published reviews on a variety of neurological topics including cerebral localization and aphasia. He died on September 23, 1904.

Mutations in CHCHD10 have been reported as the cause of a large panel of neurologic disorders. To confirm the contribution of this gene to amyotrophic lateral sclerosis (ALS) disease, we analyzed the 4 coding exons of CHCHD10 by Sanger sequencing in a cohort of 118 French familial ALS already excluded for all known ALS-related genes. We did not find any pathogenic mutation suggesting that CHCHD10 is not a major genetic cause of familial ALS, in France. [ABSTRACT FROM AUTHOR]

Focuses on the Amyotrophic Lateral Sclerosis Center of Montpellier, France. Aims of the center; Source of funding; Patients managed; Types of research conducted in the center; Areas of special expertise; Achievements; Publications.

Background and Purpose: Our objective was to evaluate the extent to which the 2005 recommendations of the European Federation of Neurological Sciences (EFNS) on the multidisciplinary management of amyotrophic lateral sclerosis (ALS) are followed in clinical practice., Methods: This was a multicentre observational study involving six French ALS referral centres receiving prevalent and incident cases. Recommendations were translated into ad hoc questions referring to key aspects of management, and their application was evaluated by a clinical research assistant who independently examined the medical charts (MCs). When necessary, an independent board-certified neurologist answered the questions based on examination of the MC and interview of the caring neurologist. Questions regarding diagnosis and communication were put to patients in a self-administered questionnaire., Results: In all, 376 patients [176 incident, 200 prevalent cases; median age at diagnosis 62.8 years (interquartile range 55.7-72.3); sex ratio 1.37; 27.3% bulbar onset] were included. All the topics covered in the recommendations were evaluated: diagnostic delay (e.g. mean 13.6 months, associated with age and onset); breaking the news (e.g. criteria for communication quality were satisfactory in more than 90%); multidisciplinary and sustained support (e.g. clinic visits were scheduled every 2-3 months in 90%). Also considered were whether riluzole had been offered, symptom management, genetic testing, ventilation, communication defects, enteral nutrition, palliative and end-of-life care. Characteristics associated with poor compliance with some guidelines (schedule of visits, delayed riluzole initiation) were also identified., Conclusion: This is the first evaluation of the application of the EFNS recommendations for the management of ALS in a nationwide sample. The results allow us to highlight areas for improvement., (© 2016 EAN.)

Abstract: Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are 2 adult onset neurological disorders with overlapping symptoms and clinical characteristics. It is well established that they share a common pathologic and genetic background. Recently, mutations in profilin 1 gene (PFN1) have been identified in patients with familial ALS, suggesting a role for this gene in the pathogenesis of the disease. Based on this, we hypothesized that mutations in PFN1 might also contribute to FTLD disease. We studied a French cohort of 165 ALS/FTLD patients, without finding any variant. We conclude that mutations in PFN1 are not a common cause for ALS/FTLD in France. [Copyright &y& Elsevier]

The cyanobacteria-derived neurotoxin β-methylamino-L-alanine (BMAA) represents a plausible environmental trigger for amyotrophic lateral sclerosis (ALS), a debilitating and fatal neuromuscular disease. With the eutrophication of water bodies, cyanobacterial blooms and their toxins are becoming increasingly prevalent in France, especially in the Brittany region. Cyanobacteria are monitored at only a few recreational sites, preventing an estimation of exposure of the human population. By contrast, phosphorus, a limiting nutrient for cyanobacterial growth and thus considered a good proxy for cyanobacteria exposure, is monitored in many but not all surface water bodies. Our goal was to develop a geographic exposure indicator that could be used in epidemiological research. We considered the total phosphorus (TP) concentration (mg/L) of samples collected between October 2007 and September 2012 at 179 monitoring stations distributed throughout the Brittany region. Using readily available spatial data, we computed environmental descriptors at the watershed level with a Geographic Information System. Then, these descriptors were introduced into a backward stepwise linear regression model to predict the median TP concentration in unmonitored surface water bodies. TP concentrations in surface water follow an increasing gradient from West to East and inland to coast. The empirical concentration model included five predictor variables with a fair coefficient of determination (R(2) = 0.51). The specific total runoff and the watershed slope correlated negatively with the TP concentrations (p = 0.01 and p< 10(-9), respectively), whereas positive associations were found for the proportion of built-up area, the upstream presence of sewage treatment plants, and the algae volume as indicated by the Landsat red/green reflectance ratio (p < 0.01, p < 10(-6) and p < 0.01, respectively). Complementing the monitoring networks, this geographical modeling can help estimate TP concentrations at the watershed level, delivering a proxy for cyanobacteria exposure that can be used along with other risk factors in further ALS epidemiologic case-control studies., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are adult-onset neurodegenerative diseases with overlapping clinical characteristics. They share common genetic causes and pathologic hallmarks such as TDP-43 neuronal accumulations. Recently, exome analysis identified mutations in matrin 3 (MATR3) gene in patients with familial ALS, suggesting a role for this gene in the pathogenesis of the disease. MATR3 is a nuclear matrix protein with DNA and RNA binding domains that interacts with TDP-43. To confirm the contribution of MATR3 to ALS, we studied a French cohort of 153 familial ALS or ALS/FTLD patients, without finding any variant. We conclude that mutations in MATR3 are rare in French familial ALS and ALS with FTLD patients., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background Mutations in SOD1, ANG, VAPB, TARDBP and FUS genes have been identified in amyotrophic lateral sclerosis (ALS). Methods The relative contributions of the different mutations to ALS were estimated by systematically screening a cohort of 162 families enrolled in France and 500 controls (1000 chromosomes) using molecular analysis techniques and performing phenotype-genotype correlations. Results 31 pathogenic missense mutations were found in 36 patients (20 SOD1, 1 ANG, 1 VAPB, 7 TARDBP and 7 FUS). Surprisingly two FUS mutation carriers also harboured ANG variants. One family of Japanese origin with the P56S VAPB mutation was identified. Seven novel mutations (three in SOD1, two in TARDBP, two in FUS) were found. None of them was detected in controls. Segregation of detected mutations with the disease was confirmed in 11 families including five pedigrees carrying the novel mutations. Clinical comparison of SOD1, TARDBP, FUS and other familial ALS patients (with no mutation in the screened genes) revealed differences in site of onset (predominantly lower limbs for SOD1 and upper limbs for TARDBP mutations), age of onset (younger with FUS mutations), and in lifespan (shorter for FUS carriers). One third of SOD1 patients survived more than 7 years: these patients had earlier disease onset than those presenting with a more typical course. Differences were also observed among FUS mutations, with the R521H FUS mutation being associated with longer disease duration. Conclusions This study identifies new genetic associations with ALS and provides phenotype-genotype correlations with both previously reported and novel mutations. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron disease including about 15% of genetically determined forms. A de novo mutation in the SS18L1 (also known as CREST or KIAA0693) gene encoding the calcium-responsive transactivator and/or neuronal chromatin remodeling complex subunit has recently been identified by exome sequencing of 47 sporadic ALS trios. This Q388stop mutation deleting the last 9 amino acids was shown to impair activity-dependent dendritic outgrowth. A missense mutation (c.369T>G, p.Ileu123Met) was also found in 1 of 62 ALS families previously screened for other ALS-related genes and not carrying any mutation. To confirm the contribution of SS18L1 to ALS, we sequenced the 11 coding exons and exon-intron boundaries in 87 familial ALS (FALS). We identified 2 variants: the c.660&#95;668del, p.Gln222&#95;Ser224del in a patient devoid of mutation in any ALS related genes and the c.790G>A, p.Ala264Thr in a patient carrying a p.Arg96Leu variant in the OPTN gene. As these variants were not found in Single Nucleotide Polymorphism databases and were absent from 180 controls they could be new SS18L1 mutations causing ALS., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: To compare survival, to describe the progression of anthropometry, pulmonary capacity and functioning in ALS (Amyotrophic Lateral Sclerosis) and to identify the most relevant variables to adapt ALS management for patients., Methods: A cohort study was performed in French ALS centres between January 2003 and July 2005. Eligible patients were treated by Riluzole and had a slow vital capacity (SVC) or a forced vital capacity (FVC) at least equal to 60%. Demographic, medical and ALS characteristics were registered. Manual Muscular Testing (MMT) and ALS Functional Rating Scale (ALSFRS) were performed. Kaplan Meier method was used to analyse survival. ALS progression was measured by the percentage weight, FVC, SVC, MMT and ALSFRS loss and was analysed as longitudinal data using mixed model., Results: Three hundred and eighty three patients were included. The median survival since ALS diagnosis was 2.34 years (95%CI 2.10-2.65). Mixed model analyses revealed a more significant worsening progression of weight and FVC loss for bulbar onset. The drop of ALSFRS and SVC is similar whatever the ALS forms., Conclusions: Rates of progression of weight and FVC should be regularly watched over to support neurologists to adapt ALS management for patients., (Copyright © 2013 Elsevier B.V. All rights reserved.)