Background: ALS exclusively involves motor neurons, however, accumulating evidence suggests involvement of sympathetic neurons, as in other diseases including Parkinson's disease and multiple system atrophy. In these diseases increased risk of sudden cardiac arrest is established, while that in ALS remains uncertain.
Methods: The authors retrospectively studied 12 pathologically confirmed sporadic ALS patients who received no assisted ventilation. Among them, two patients died of sudden cardiac arrest. Changes in QTc interval and dispersion, indices of sympathetic activities obtainable by routine electrocardiograms, were evaluated at the early stage and the terminal stage. Pathologically, intermediolateral nucleus (IML) sympathetic neurons in the upper thoracic cord were examined.
Results: The QTc intervals and dispersion were significantly increased at the terminal stage compared with that at the early stage (p<0.01). The numbers of IML neurons were significantly lower in ALS patients than in controls (p=0.017), and had linear inverse correlation with the rate of increases in maximum QTc interval and QTc dispersion (p=0.01, r=-0.915 and p=0.02, r=-0.884). Notably, two patients with sudden cardiac arrest showed longer QTc interval, larger QTc dispersion, and lower number of IML neurons than most of others.
Conclusions: Patients with ALS had reduced sympathetic activities at the terminal stage of disease, presumably due to neuronal loss in IML, which may increase risk of sudden cardiac arrest. Thus, prolonged QTc intervals and increased QTc dispersion may suggest an increased risk of sudden death in ALS, as in other neurodegenerative diseases.