Does the supplementary motor area keep patients with Ondine's curse syndrome breathing while awake?
BACKGROUND
Congenital central hypoventilation syndrome (CCHS) is a rare neuro-respiratory disorder associated with mutations of the PHOX2B gene. Patients with this disease experience severe hypoventilation during sleep and are consequently ventilator-dependent. However, they breathe almost normally while awake, indicating the existence of cortical mechanisms compensating for the deficient brainstem generation of automatic breathing. Current evidence indicates that the supplementary motor area plays an important role in modulating ventilation in awake normal humans. We hypothesized that the wake-related maintenance of spontaneous breathing in patients with CCHS could involve supplementary motor area.


METHODS
We studied 7 CCHS patients (5 women; age: 20-30; BMI: 22.1 ± 4 kg.m(-2)) during resting breathing and during exposure to carbon dioxide and inspiratory mechanical constraints. They were compared with 8 healthy individuals. Segments of electroencephalographic tracings were selected according to ventilatory flow signal, from 2.5 seconds to 1.5 seconds after the onset of inspiration. After artefact rejection, 80 or more such segments were ensemble averaged. A slow upward shift of the EEG signal starting between 2 and 0.5 s before inspiration (pre-inspiratory potential) was considered suggestive of supplementary motor area activation.


RESULTS
In the control group, pre-inspiratory potentials were generally absent during resting breathing and carbon dioxide stimulation, and consistently identified in the presence of inspiratory constraints (expected). In CCHS patients, pre-inspiratory potentials were systematically identified in all study conditions, including resting breathing. They were therefore significantly more frequent than in controls.


CONCLUSIONS
This study provides a neurophysiological substrate to the wakefulness drive to breathe that is characteristic of CCHS and suggests that the supplementary motor area contributes to this phenomenon. Whether or not this "cortical breathing" can be taken advantage of therapeutically, or has clinical consequences (like competition with attentional resources) remains to be determined.
UMR_S1158, Inserm-Université Paris 6, Paris, France.
Lysandre
L
Tremoureux
UMR_S1158, Inserm-Université Paris 6, Paris, France ; Département d'Anesthésie Réanimation-Groupe Hospitalier Pitié-Salpêtrière Charles Foix, Assistance Publique-Hôpitaux de Paris, Paris, France.
Mathieu
M
Raux
UMR_S1158, Inserm-Université Paris 6, Paris, France ; Neuroscience Research Australia and University of New South Wales, Sydney, Australia.
Anna L
AL
Hudson
UMR_S1158, Inserm-Université Paris 6, Paris, France.
Anja
A
Ranohavimparany
UMR_S1158, Inserm-Université Paris 6, Paris, France ; Service Central des Explorations Fonctionelles Respiratoires de l'Exercice et de la Dyspnée-Groupe Hospitalier Pitié-Salpêtrière Charles Foix, Assistance Publique-Hôpitaux de Paris, Paris, France ; Centre National de Référence Maladies Rares pour le syndrome d'Ondine (adultes)-Groupe Hospitalier Pitié-Salpêtrière Charles Foix, Assistance Publique-Hôpitaux de Paris, Paris, France.
Christian
C
Straus
UMR_S1158, Inserm-Université Paris 6, Paris, France ; Centre National de Référence Maladies Rares pour le syndrome d'Ondine (adultes)-Groupe Hospitalier Pitié-Salpêtrière Charles Foix, Assistance Publique-Hôpitaux de Paris, Paris, France ; Service de Pneumologie et Réanimation Médicale-Groupe Hospitalier Pitié-Salpêtrière Charles Foix, Assistance Publique-Hôpitaux de Paris, Paris, France.
Thomas
T
Similowski
D000328:Adult; D002245:Carbon Dioxide; D016022:Case-Control Studies; D004569:Electroencephalography; D005260:Female; D006801:Humans; D007040:Hypoventilation / Q000151:congenital* / Q000503:physiopathology; D008297:Male; D009044:Motor Cortex / Q000502:physiology*; D012119:Respiration; D020182:Sleep Apnea, Central / Q000503:physiopathology*; D014851:Wakefulness; D055815:Young Adult
D002245:Carbon Dioxide