Abstract
BackgroundCongenital 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.MethodsWe 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.ResultsIn 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.ConclusionsThis 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.
Highlights
Congenital central hypoventilation syndrome (CCHS) is a rare neuro-respiratory disorder associated with several possible mutations of the PHOX2B gene [1]
pre-inspiratory potentials’’ (PIPs) were inconsistent during spontaneous breathing (‘‘Control 1’’, ‘‘Control 2’’, ‘‘Control 3’’) and during ‘‘Chemostimulation’’, as one subject exhibited a PIP during ‘‘Control 1’’, 3 during ‘‘Control 2’’, 1 during ‘‘Control 3’’
PIPs were clearly visible in the Cz derivation and none of the other ones
Summary
Congenital central hypoventilation syndrome (CCHS) is a rare neuro-respiratory disorder associated with several possible mutations of the PHOX2B gene [1]. Animal models have shown that these mutations result in major alterations in the development of the parafacial region of the brainstem that is instrumental to respiratory chemosensitivity [2] Patients with these mutations experience hypoventilation when sleeping, resulting in sleeprelated ventilator-dependency [1]. 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 ventilator-dependent. They breathe almost normally while awake, indicating the existence of cortical mechanisms compensating for the deficient brainstem generation of automatic breathing. We hypothesized that the wake-related maintenance of spontaneous breathing in patients with CCHS could involve supplementary motor area
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