Risk factors in the early diagnosis of ALS: European epidemiological studies

Significant changes in the epidemiology of amyotrophic lateral sclerosis (ALS) have been observed over the last few years. Based on reports of studies from the 1970s and early 1980s, the incidence of ALS in Europe has been considered to be constant, with only slight differences in the incidence of ALS between different countries. However, flaws in the methodologies of these studies, such as case definition, case ascertainment, selection bias, study design and difficulties in the early diagnosis of cases, have been identified. More recent studies reveal a trend towards an increase in the ALS mortality rate over the past two decades, but the significance of this trend remains unclear. Recent ALS incidence studies, particularly those based on the 'register model', have given new insight into ALS epidemiology. ALS seems to be a uniform problem across Europe, with age-specific incidence rates showing a progressive increase up to the 70-79 age group. False-negative cases are frequent, ranging from 26-42% of cases. The rate of false-positive cases is approximately 10%. In approximately half of the false-positive cases, the possible diagnosis of ALS was withdrawn because the initial symptoms did not progress. No consistent epidemiological clues concerning the cause of ALS have been found in epidemiological studies. The only possible associations that perhaps warrant further investigation include farming, mechanical and electrical traumas, heavy labour and toxins or chemicals.