ALS: disease or syndrome?
- Correspondence to Leonard H van den Berg, Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht, PO Box 85500, Utrecht 3508 GA, The Netherlands;
- Received 13 March 2011
- Accepted 15 March 2011
- Published Online First 2 April 2011
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 …