Aberrant Neural Responses to Cold Pressor Challenges in Congenital Central Hypoventilation Syndrome

In summary, we found a reduced cardiac baroreflex and a blunted sympathetic mediated response in the individual with adult-onset CCHS, possibly due to dysfunction in the afferent pathway. Our results confirm that PHOX2B affects the development of the autonomic nervous system, possibly causing absence of normal maturation of carotid body and visceral sensory ganglia and leading to autonomic dysfunction in adult-onset CCHS.

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“…Aberrant neural responses to forehead cold pressor stimuli in children with CCHS support our findings [7].…”

Section: Discussionsupporting

confidence: 89%

Vagal and sympathetic heart rate and blood pressure control in adult onset PHOX2B mutation–confirmed congenital central hypoventilation syndrome

et al. 2007

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“…Reduced chemoreceptor function, such as observed in CCHS, produces frequent and severe sleep related hypoventilation which has adverse consequences throughout the brain including within regions whose development is not directly influenced by Phox2b mutations (225, 257). However, the neural control of the circulation is also dysfunctional in CCHS patients (256,346,451). Furthermore, CCHS is a degenerative disease in which RTN neurons are presumably absent (144).…”

Section: Interplay Between Peripheral and Central Chemoreceptorsmentioning

confidence: 99%

Regulation of Breathing and Autonomic Outflows by Chemoreceptors

Guyenet

2014

Comprehensive Physiology

269

293

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Lung ventilation fluctuates widely with behavior but arterial PCO2 remains stable. Under normal conditions, the chemoreflexes contribute to PaCO2 stability by producing small corrective cardiorespiratory adjustments mediated by lower brainstem circuits. Carotid body (CB) information reaches the respiratory pattern generator (RPG) via nucleus solitarius (NTS) glutamatergic neurons which also target rostral ventrolateral medulla (RVLM) presympathetic neurons thereby raising sympathetic nerve activity (SNA). Chemoreceptors also regulate presympathetic neurons and cardiovagal preganglionic neurons indirectly via inputs from the RPG. Secondary effects of chemoreceptors on the autonomic outflows result from changes in lung stretch afferent and baroreceptor activity. Central respiratory chemosensitivity is caused by direct effects of acid on neurons and indirect effects of CO2 via astrocytes. Central respiratory chemoreceptors are not definitively identified but the retrotrapezoid nucleus (RTN) is a particularly strong candidate. The absence of RTN likely causes severe central apneas in congenital central hypoventilation syndrome. Like other stressors, intense chemosensory stimuli produce arousal and activate circuits that are wake- or attention-promoting. Such pathways (e.g., locus coeruleus, raphe, and orexin system) modulate the chemoreflexes in a state-dependent manner and their activation by strong chemosensory stimuli intensifies these reflexes. In essential hypertension, obstructive sleep apnea and congestive heart failure, chronically elevated CB afferent activity contributes to raising SNA but breathing is unchanged or becomes periodic (severe CHF). Extreme CNS hypoxia produces a stereotyped cardiorespiratory response (gasping, increased SNA). The effects of these various pathologies on brainstem cardiorespiratory networks are discussed, special consideration being given to the interactions between central and peripheral chemoreflexes.

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“…Deficiencies also include loss of dyspnea (13) and reduced anxiety (14). This complex phenotype of CCHS suggests widespread functional brain deficits, although these had not been investigated until the present studies by Woo et al (1) and Macey et al (2).…”

mentioning

confidence: 78%

“…Woo et al (1) used cold pressure challenge and Macey et al (2) hyperoxia to induce these deficits. The results constitute the first evidence of functional brain abnormalities in specific locations, thereby providing information on the brain sites that generate some of the clinical characteristics of CCHS (3,4).…”

mentioning

confidence: 99%

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Functional Brain Deficits in Congenital Central Hypoventilation Syndrome: Commentary on the articles by Woo et al. on page 510 and Macey et al. on page 500.

Gaultier

2005

Pediatr Res

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Aberrant Neural Responses to Cold Pressor Challenges in Congenital Central Hypoventilation Syndrome

Cited by 32 publications

References 55 publications

Vagal and sympathetic heart rate and blood pressure control in adult onset PHOX2B mutation–confirmed congenital central hypoventilation syndrome

Vagal and sympathetic heart rate and blood pressure control in adult onset PHOX2B mutation–confirmed congenital central hypoventilation syndrome

Regulation of Breathing and Autonomic Outflows by Chemoreceptors

Functional Brain Deficits in Congenital Central Hypoventilation Syndrome: Commentary on the articles by Woo et al. on page 510 and Macey et al. on page 500.

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