The standard of clinical care in many pediatric and neonatal neurocritical care units involves continuous monitoring of cerebral hemodynamics using hard-wired devices that physically adhere to the skin and connect to base stations that commonly mount on an adjacent wall or stand. Risks of iatrogenic skin injuries associated with adhesives that bond such systems to the skin and entanglements of the patients and/or the healthcare professionals with the wires can impede clinical procedures and natural movements that are critical to the care, development, and recovery of pediatric patients. This paper presents a wireless, miniaturized, and mechanically soft, flexible device that supports measurements quantitatively comparable to existing clinical standards. The system features a multiphotodiode array and pair of light-emitting diodes for simultaneous monitoring of systemic and cerebral hemodynamics, with ability to measure cerebral oxygenation, heart rate, peripheral oxygenation, and potentially cerebral pulse pressure and vascular tone, through the utilization of multiwavelength reflectance-mode photoplethysmography and functional near-infrared spectroscopy. Monte Carlo optical simulations define the tissue-probing depths for source–detector distances and operating wavelengths of these systems using magnetic resonance images of the head of a representative pediatric patient to define the relevant geometries. Clinical studies on pediatric subjects with and without congenital central hypoventilation syndrome validate the feasibility for using this system in operating hospitals and define its advantages relative to established technologies. This platform has the potential to substantially enhance the quality of pediatric care across a wide range of conditions and use scenarios, not only in advanced hospital settings but also in clinics of lower- and middle-income countries.

Congenital central hypoventilation syndrome (CCHS) is a neurodevelopmental disorder characterized by life-threatening hypoventilation, possibly resulting from disruption of central chemosensory integration. However, animal models suggest the possibility of residual chemosensory function in the human disease. Cardioventilatory function in a large cohort with CCHS and verified paired-like homeobox 2B (PHOX2B) mutations was assessed to determine the extent and genotype dependence of any residual chemosensory function in these patients. As part of inpatient clinical care and evaluation, 64 distinct studies from 32 infants, children, and young adults with the disorder were evaluated for physiological response to three different inspired steady-state gas exposures of 3 min each: hyperoxia [100% oxygen (O2)]; hyperoxic hypercapnia [95% O2 and 5% carbon dioxide (CO2)]; and hypoxic hypercapnia [14% O2 and 7% CO2 balanced with nitrogen (N2)]. These were followed by a hypoxia challenge consisting of five or seven breaths of N2 (100% N2). In addition, a control group of 15 young adults was exposed to all but the hypoxic challenge. Comprehensive monitoring was used to derive breath-to-breath and beat-to-beat measures of ventilatory, cardiovascular, and cerebrovascular function. On average, patients showed a residual awake ventilatory response to chemosensory challenge, independent of the specific patient PHOX2B genotype. Graded dysfunction in cardiovascular regulation was found to associate with genotype, suggesting differential effects on different autonomic subsystems. In addition, differences between cases and controls in the cerebrovascular response to chemosensory challenge may indicate alterations in cerebral autoregulation. Thus residual cardiorespiratory responses suggest partial preservation of central nervous system networks that could provide a fulcrum for potential pharmacological interventions.

INTRODUCTION: congenital central hypoventilation syndrome (cchs) is characterized by alveolar hypoventilation, autonomic nervous system (aNs) dysregulation (aNsD), and mutations in the paired-like homeobox 2B (PHOX2B) gene. aNsD in cchs affects multiple systems and includes ophthalmologic abnormalities. We hypothesized that quantitative pupil measures, obtained using pupillometry, would vary between cases with cchs and controls and within those with cchs by PHOX2B genotype. RESULTS: Measures known to be illustrative of sympathetic and parasympathetic response (prestimulus, maximum pupil diameter, percentage of pupil constriction after light stimulus, and average constriction and dilation velocities) were significantly reduced in those with cchs as compared with controls (all P < 0.05). DISCUSSION: These reductions are indicative of both sympathetic and parasympathetic deficits in cchs, which is in keeping with the role of PHOX2B in aNs development. an inverse linear relationship was apparent in pupil diameter and velocity measurements among the cases with cchs with the most common heterozygous PHOX2B polyalanine expansion repeat mutations, suggesting a graded phenotype/genotype dose response based on polyalanine repeat length. These results confirm our central hypotheses while offering the first objective measures of pupillary dysfunction and ophthalmologicspecific aNsD in cchs. METHODS: a total of 316 monocular measurements were taken under dark-adapted conditions with a fixed light stimulus from 22 PHOX2B mutation-confirmed cases with cchs and 68 healthy controls. C ongenital central hypoventilation syndrome (CCHS) ischaracterized by central alveolar hypoventilation with autonomic nervous system dysregulation (ANSD) and is diagnosed in the absence of primary pulmonary, cardiac, or neuromuscular disease or a brainstem lesion that can account for the full phenotype (1). Discovery of the CCHS disease-defining gene, pairedlike homeobox 2B (PHOX2B) (2-4), and appreciation of its role in both embryologic development and regulatory function of the autonomic nervous system (ANS) (5-7), has broadened the understanding of the CCHS phenotype. The majority of individuals with CCHS are heterozygous for PHOX2B polyalanine repeat expansion mutations (PARMs), with a range of 24-33 alanine bases on the affected allele (20 repeats is normal; normal genotype is 20/20). Missense, nonsense, frameshift, and stop codon mutations in the PHOX2B gene, referred to as nonpolyalanine repeat expansion mutations (NPARMs), account for the remaining mutations in CCHS. Quantitative assessment of the respiratory control and ANSD features of CCHS by PHOX2B genotype has identified a graded genotype-phenotype relationship between mutation repeat length and ventilatory requirements (3,4), Hirschsprung disease (8,9), neural crest tumors (8,9), and cardiac sinus pauses (10).Detailed understanding of the ANSD features in CCHS requires targeted investigation with objective measures of all organ systems served by the ANS. Ophthalmologic abnormalities th...

No abstract