A clinical tool for predicting survival in ALS

Abstract

BackgroundAmyotrophic lateral sclerosis (ALS) is a progressive and usually fatal neurodegenerative disease. Survival from diagnosis varies considerably. Several prognostic factors are known, including site of onset (bulbar or limb), age at symptom onset, delay from onset to diagnosis and the use of riluzole and non-invasive ventilation (NIV). Clinicians and patients would benefit from a practical way of using these factors to provide an individualised prognosis.Methods575 consecutive patients with incident ALS from a population-based registry in South-East England register for ALS (SEALS) were studied. Their survival was modelled as a two-step process: the time from diagnosis to respiratory muscle involvement, followed by the time from respiratory involvement to death. The effects of predictor variables were assessed separately for each time interval.FindingsYounger age at symptom onset, longer delay from onset to diagnosis and riluzole use were associated with slower progression to respiratory involvement, and NIV use was associated with lower mortality after respiratory involvement, each with a clinically significant effect size. Riluzole may have a greater effect in younger patients and those with longer delay to diagnosis. A patient's survival time has a roughly 50% chance of falling between half and twice the predicted median.InterpretationA simple and clinically applicable graphical method of predicting an individual patient's survival from diagnosis is presented. The model should be validated in an independent cohort, and extended to include other important prognostic factors.

Amyotrophic lateral sclerosis: Clinical heterogeneity and approaches to classification

“…Индивидуальное течение болезни может быть крайне вариабельным и трудно прогнозируемым, несмотря на разработку в последние годы ряда относительно точных предиктивных моде-лей [44]. После постановки диагноза >1 года живут 76 % пациентов, >5 лет -24 %, >10 лет -11 % [45].…”

The benefit of evolving multidisciplinary care in ALS: a diagnostic cohort survival comparison

“…It has been proposed that improved survival is a result of the accurate timing of interventions by specialist teams (7). The importance of timing of interventions has also been shown by prognostic modelling (11).…”

Energy metabolism in amyotrophic lateral sclerosis: assessment of body composition and energy expenditure

“…Given the expanding phenotype of ALS, its clinical heterogeneity (del Aguila et al, 2003) and the absence of specific diagnostic markers, there is often delay in its diagnosis (Talman et al, 2016, Knibb et al, 2016. Therefore to aid in the diagnosis of ALS, clinical (Brooks et al, 2000 and electrodiagnostic criteria (de Carvalho et al, 2008) are widely employed in research and clinical settings.…”

“…There are currently no curative treatments for ALS and the median survival is only 18 months from diagnosis (Knibb et al, 2016). Neuromuscular respiratory failure is the commonest cause of death; therefore, non-invasive ventilation (NIV) is used in some patients to prolong survival and improve quality of life (Radunovic et al, 2013).…”

“…Therefore there has been a search for factors that influence the progression of disease (Chiò et al, 2009). In addition to interventions such as riluzole therapy (Miller et al, 1996) and NIV (Radunovic et al, 2013), a number of patient and disease factors have been found to affect prognosis (Knibb et al, 2016).…”