Neurobiological and Immunological Mechanisms of Dyspnea in ALS
Neurobiological and Immunological Mechanisms of Dyspnea in ALS
Dyspnea; subjective experience of respiratory discomfort; which produces negative emotional
 experience, is the most common symptom of patients afflicted with chronic respiratory failure
 and its treatments are limited. Amyotrophic Lateral Sclerosis (ALS) related - dyspnea, due to
 diaphragmatic dysfunction, is similar to dyspnea during mechanical inspiratory load
 (activation of the supplementary motor area, SMA). The perception of pain and dyspnea is
 processed in similar brain areas (insula, dorsal anterior cingulate cortex, amygdala and
 medial thalamus) and in ALS; relieving dyspnea by noninvasive ventilation (NIV) is associated
 with decreased pain thresholds. Otherwise, it is reported systemic elevations of
 pro-inflammatory cytokines in chronic pain patients, correlating with intensity of pain, and
 during respiratory load in healthy volunteers.

 The objectives are to evaluate the cytokines and endorphins rates variations after initiation
 of NIV in ALS patients, and to correlate cytokines and endorphins rates with the intensity of
 the affective component and the intensity of the sensory component of dyspnea.

 The investigators will perform a prospective, experimental study, including 30 ALS patients.
 Dyspnea, ventilatory and cardiac settings, electromyographic recording of the scalene muscle
 and biological assays (ACTH, endorphin, Neuropeptide P, BDNF, IL1, IL6, IL8, IL10, TNF), will
 be measured during spontaneous breathing and during NIV at different times after initiation.

 The investigators expect a reduction of immunological and neurobiological markers after
 relieving dyspnea by NIV. This work could lead to the development of new treatments for
 dyspnea.
Inclusion Criteria:

 - Patients with chronic respiratory failure with diaphragmatic dysfunction linked to
 amyotrophic lateral sclerosis and requiring long-term NIV

 Exclusion Criteria:

 -  Other respiratory disease (COPD, asthma, obstructive sleep apnea)

 -  Alcohol or psychotropic drug the lasts 24 hours

 -  Cognitive impairment

 -  Smoking > 10 PA

 -  Exacerbation or infection 6 weeks earlier

 -  Endstage of illness

 -  Chronic or acute pain (VAS > 3)