Amyotrophic lateral sclerosis: new ideas from cancer

In the past 20 years, findings of epidemiological studies have substantially changed ideas about the incidence and phenotype of amyotrophic lateral sclerosis that were previously based on data from tertiary centres. In 2010, Logroscino and colleagues 1 Logroscino G Traynor BJ Hardiman O et al. Incidence of amyotrophic lateral sclerosis in Europe. J Neurol Neurosurg Psychiatry. 2010; 81: 385-390 Crossref PubMed Scopus (506) Google Scholar reported that like the two other major neurodegenerative diseases, Alzheimer's disease and Parkinson's disease, amyotrophic lateral sclerosis is age dependent, with peak incidence in people aged 70–80 years, and a flattening age-adjusted incidence curve thereafter. Phukan and colleagues 2 Phukan J Elamin M Bede P et al. The syndrome of cognitive impairment in amyotrophic lateral sclerosis: a population-based study. J Neurol Neurosurg Psychiatry. 2012; 83: 102-108 Crossref PubMed Scopus (466) Google Scholar reported a much broader disease phenotype than previously described and non-motor features (cognitive and behavioural) that affect prognosis. Uenal and colleagues 3 Uenal H Rosenbohm A Kufeldt J et al. Incidence and geographical variation of amyotrophic lateral sclerosis (ALS) in Southern Germany-completeness of the ALS registry Swabia. PLoS One. 2014; 9: e93932 Crossref PubMed Scopus (38) Google Scholar showed that incidence of amyotrophic lateral sclerosis is much higher than previously believed and was almost three per 100 000 people in Swabia, Germany. Logroscino and colleagues 4 Logroscino G Traynor BJ Hardiman O et al. Descriptive epidemiology of amyotrophic lateral sclerosis: new evidence and unsolved issues. J Neurol Neurosurg Psychiatry. 2008; 79: 6-11 Crossref PubMed Scopus (338) Google Scholar noted that incidence is expected to increase with the ageing of the general population, especially in women. However, even the most robust data have about 20% of cases missing, 3 Uenal H Rosenbohm A Kufeldt J et al. Incidence and geographical variation of amyotrophic lateral sclerosis (ALS) in Southern Germany-completeness of the ALS registry Swabia. PLoS One. 2014; 9: e93932 Crossref PubMed Scopus (38) Google Scholar and so far the contribution of observational studies to the understanding of the causes of amyotrophic lateral sclerosis has been limited. Genetics has identified several determinants, but the effect at the population level is small, even for mutations with high prevalence like C9orf72. 5 Al-Chalabi A Hardiman O The epidemiology of ALS: a conspiracy of genes, environment and time. Nat Rev Neurol. 2013; 9: 617-628 Crossref PubMed Scopus (462) Google Scholar Analysis of amyotrophic lateral sclerosis as a multistep process: a population-based modelling studyA linear relationship between the log incidence and log age of onset of amyotrophic lateral sclerosis is consistent with a multistage model of disease. The slope estimate suggests that amyotrophic lateral sclerosis is a six-step process. Identification of these steps could lead to preventive and therapeutic avenues. Full-Text PDF