Cortical drive to breathe in amyotrophic lateral sclerosis: a dyspnoea-worsening defence?

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease causing diaphragm weakness that can be partially compensated by inspiratory neck muscle recruitment. This disappears during sleep, which is compatible with a cortical contribution to the drive to breathe. We hypothesised that ALS patients with respiratory failure exhibit respiratory-related cortical activity, relieved by noninvasive ventilation (NIV) and related to dyspnoea.We studied 14 ALS patients with respiratory failure. Electroencephalographic recordings (EEGs) and electromyographic recordings of inspiratory neck muscles were performed during spontaneous breathing and NIV. Dyspnoea was evaluated using the Multidimensional Dyspnea Profile.Eight patients exhibited slow EEG negativities preceding inspiration (pre-inspiratory potentials) during spontaneous breathing. Pre-inspiratory potentials were attenuated during NIV (p=0.04). Patients without pre-inspiratory potentials presented more advanced forms of ALS and more severe respiratory impairment, but less severe dyspnoea. Patients with pre-inspiratory potentials had stronger inspiratory neck muscle activation and more severe dyspnoea during spontaneous breathing.ALS-related diaphragm weakness can engage cortical resources to augment the neural drive to breathe. This might reflect a compensatory mechanism, with the intensity of dyspnoea a negative consequence. Disease progression and the corresponding neural loss could abolish this phenomenon. A putative cognitive cost should be investigated.

Reduced survival in patients with ALS with upper airway obstructive events on non-invasive ventilation

“…First, NIV may reduce PaCO 2 , which would decrease the global ventilatory drive and could promote glottal closure phenomena in the same way as induction of hypocapnia in healthy participants 35. Second, NIV could induce mechanical inhibition of the ventilatory drive, independent of any variations in CO 2 , and related to changes in thoracic afferents36 and their cortical processing,37 as NIV abolishes the cortical activity related to breathing that characterises some patients with ALS, which has been interpreted to be a compensatory mechanism 38. Finally, a third mechanism could be related to sleep induction, as described in OSAS 39…”

The Pathophysiology of Respiratory Failure: Control of Breathing, Respiratory Load, and Muscle Capacity

“…Cortical activation to augment the drive to breathe is also observed in weak amyotrophic lateral sclerosis (ALS) patients with dyspnea. Georges et al [23] hypothesized that cortical activation to maintain ventilation may not only accentuate dyspnea, but may also interfere with cognitive and even motor performance. Of note, premotor potentials were attenuated with noninvasive ventilation (NIV) treatment in their study.…”

Pathophysiologie der Ateminsuffizienz: Atmungsregulation, Atemlast und Muskelkapazität

“…Eine kortikale Aktivierung zur Steigerung des Atemantriebs ist auch bei Patienten mit amyotropher Lateralsklerose (ALS) und damit verbundener Muskelschwäche und Dyspnoe zu beobachten. Georges et al [23] stellten die Hypothese auf, dass die kortikale Aktivierung zur Aufrechterhaltung der Atmung nicht nur eine Dyspnoe verstärken, sondern auch die kognitive und sogar die motorische Leistung beeinträchtigen kann. In ihrer Studie waren die Bereitschaftspotenziale bei NIV abgeschwächt.…”