The impact of upper motor neuron degeneration on respiration in wakefulness and sleep in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of upper (UMN) and lower motor neurons (LMN), which eventually leads to respiratory insufficiency. The individual differences between patients in the presentation of respiratory insufficiency signs in wakefulness and sleep are marked and poorly understood. We hypothesized that they are related to the extent of UMN and respiratory LMN degeneration and aimed to describe this relationship. We assessed the severity of UMN and respiratory LMN degeneration in 15 ALS patients who presented with at least one sign or symptom of respiratory insufficiency. Further, we correlated the degeneration pattern with several respiratory variables. For comparison we tested 14 healthy age, and sex matched participants. We found that the patients with concomitant severe UMN and respiratory LMN degeneration were more likely to have normal pCO2 and HCO3 upon awakening, and a normal proportion of REM sleep as opposed to patients with severe LMN degeneration. In addition, these patients were also breathing faster than healthy participants (p = 0.017), and activated their accessory respiratory muscles in NREM sleep the most. We conclude that the concomitant degeneration of UMN and respiratory LMN, but not an isolated degeneration of respiratory LMN, allows the development of a respiratory adaptation, similar to acclimatization to high altitudes. This adaptation leads to increased respiratory drive in sleep, and protects the patients from morning hypercapnia and loss of REM sleep. This compensation is initially protective, but can mask the respiratory vulnerability of these patients.