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Introduction: Extrapyramidal deficits are poorly characterised in amyotrophic lateral sclerosis (ALS) despite their contribution to functional disability, increased fall risk and their quality-of-life implications. Given the concomitant pyramidal and cerebellar degeneration in ALS, the clinical assessment of extrapyramidal features is particularly challenging.Objective: The comprehensive characterisation of postural instability in ALS using standardised clinical assessments, gait analyses and computational neuroimaging tools in a prospective study design.Methods: Parameters of gait initiation in the anticipatory postural adjustment phase (APA) and execution phase (EP) were evaluated in ALS patients with and without postural instability and healthy controls. Clinical and gait analysis parameters were interpreted in the context of brain imaging findings.Results: ALS patients with postural instability exhibit impaired gait initiation with an altered APA phase, poor dynamic postural control and significantly decreased braking index. Consistent with their clinical profile, “unsteady” ALS patients have reduced caudate and brain stem volumes compared to “steady” ALS patients.Interpretation: Our findings highlight that the ALS functional rating scale (ALSFRS-r) does not account for extrapyramidal deficits, which are major contributors to gait impairment in a subset of ALS patients. Basal ganglia degeneration in ALS does not only contribute to cognitive and behavioural deficits, but also adds to the heterogeneity of motor disability. [ABSTRACT FROM AUTHOR]

The aim of this work was to determine whether survival changed during 2002-2009 at a French amyotrophic lateral sclerosis (ALS) center. We included all patients with ALS who were seen consecutively at the center from January 2002-May 2009. Participants were followed from date of first visit through death, date of censoring, or December 31, 2009, whichever occurred first. Cox proportional hazard models computed hazard ratios (HR; 95% confidence interval CI) of death, and flexible modeling of continuous predictors (splines) assessed trends in survival. We analyzed a total of 2,037 ALS patients, of whom 1,471 died before the end of follow-up. Median survival was 2.83 years from onset and 1.65 years from first visit. Compared to patients first seen before 2004, the HR of death was 0.97 (95% CI = 0.85-1.11, p = 0.6721) for patients first seen in 2004-2005, 0.96 (95% CI = 0.83-1.10, p = 0.5125) for 2006-2007, and 0.56 (95% CI = 0.46-0.69, p < 0.0001) after 2007, while adjusting for other survival predictors. Spline analysis confirmed that survival remained stable during 2002-2006, then markedly improved. The proportion of patients receiving non-invasive ventilation (NIV) increased from 16 (2004) to 51% (2008). At this large ALS center, survival improved after 2006. Because more aggressive use of NIV was the principal therapeutic adaptation, our data suggest that better survival resulted from improved respiratory care. [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]