ALS: disease or syndrome?

In scientific papers on genetics, pathogenesis, animal models, new therapy or biomarkers in amyotrophic lateral sclerosis (ALS), the disease is usually described as a progressive disorder of upper- and lower motor neurons leading to muscle weakness and death owing to respiratory failure on average 3 years after the onset of symptoms.1 In clinical practice, however, we experience a large variability in the clinical expression (site of onset, survival, involvement of lower- or upper motor neuron) of the disease. In addition, there is evidence that several distinct molecular mechanisms or pathogenic pathways (glutamate excitotoxicity, mitochondrial dysfunction, apoptosis, oxidative stress, protein aggregation, defective energy metabolism, aberrant axonal transport or RNA processing) play a role in progressive motor …