Does the supplementary motor area keep patients with Ondine's curse syndrome breathing while awake?

PLoS One. 2014 Jan 24;9(1):e84534. doi: 10.1371/journal.pone.0084534. eCollection 2014.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Carbon Dioxide
  • Case-Control Studies
  • Electroencephalography
  • Female
  • Humans
  • Hypoventilation / congenital*
  • Hypoventilation / physiopathology
  • Male
  • Motor Cortex / physiology*
  • Respiration*
  • Sleep Apnea, Central / physiopathology*
  • Wakefulness*
  • Young Adult

Substances

  • Carbon Dioxide

Supplementary concepts

  • Congenital central hypoventilation syndrome

Grants and funding

This research was funded in part by a “Legs Poix” grant from the “Chancellerie de l'Université de Paris,” France, the French national reference center for Congenital Central Alveolar Hypoventilation, and the program “Investissement d'Avenir ANR-10-A-IHU06” of the French government. It was also funded by two non-profit associations (“Association Française du Syndrome d'Ondine” -AFSO- and “Association pour le Développement et l'Organisation de la Recherche en Pneumologie et sur le Sommeil” -ADOREPS-). Anja Ranohavimparany was supported in part by an AFSO grant. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.