Literature search from ms 29/4/2010

Liess, B. D., J. S. Dost, et al. (2008). "Congenital central alveolar hypoventilation syndrome (Ondine's curse) with survival into adulthood." CLINICAL PEDIATRICS 47(9): 941-6.

Ondine's curse or central alveolar hypoventilation (CCAH) syndrome is a disorder of the autonomic nervous system resulting in respiratory dysregulation. The clinical outcome is typically poor, with few individuals living into adulthood and even fewer surviving to adulthood with normal neurological function. Our patient initially presented following an uncomplicated delivery with hypotonia, poor respiratory effort, and hypoxemia that required ventilatory support. Laboratory workup, radiographic evaluation, and ancillary testing ruled out brain stem lesions, neuromuscular diseases, cardiovascular and pulmonary disease, and metabolic disorders, resulting in a diagnosis of CCAH syndrome. The patient underwent tracheotomy and chronic ventilatory support. Close long-term management and appropriate treatment modifications have provided for an excellent outcome and good quality of life. The patient is currently 22 years old and is earning her teaching degree for K-12 art education. A combination of early recognition and a multidisciplinary approach may lead to a successful outcome in patients with CCAH syndrome.

Lim, K.-L., P. Jacobs, et al. (2006). "A population-based analysis of healthcare utilization of persons with back disorders: results from the Canadian Community Health Survey 2000-2001." SPINE 31(2): 212-8.

STUDY DESIGN: A retrospective, population-based analysis. OBJECTIVES: To analyze the utilization of a variety of healthcare services for persons with and without a chronic back disorder, and to identify factors associated with specific patterns of healthcare resource use. SUMMARY OF BACKGROUND DATA: Although there have been studies of how chronic back disorders influence the use of specific healthcare services, we do not currently have a broad, population-based overview of how this condition influences healthcare service utilization. METHODS: Person-level data were taken from the 2000-2001 Canadian Community Health Survey (CCHS), a nationwide cross-sectional survey of health determinants, health status, and health system utilization of Canadians. A series of binary logistic regressions examining healthcare resource utilization were performed on a full study sample (n = 113,229), as well as a restricted sample (n = 36,713) with attention focused on subjects with a single diagnosis of a chronic back disorder. RESULTS: Persons with chronic back disorders were more likely to use physician resources (multivariate odds ratio [OR] = 1.2; 95% confidence interval, 1.1-1.2), and nonphysician resources (OR range, 2.1-3.6) compared with persons without the condition, with chiropractic care having an odds ratio of 3.6 (95% confidence interval, 3.5-3.8). Higher socioeconomic status, the presence of activity-limiting pain, and depressive symptoms were associated with a significant increase in utilization of almost all healthcare services. CONCLUSIONS: With increasing disability as indicated by the presence of pain and functional limitations, and the presence of depressive symptoms, the higher the utilization of physician and nonphysician resources, with the exception of chiropractic care, which appears to be used by those with less severe symptoms. Lower socioeconomic status was associated with significantly lower receipt of services for almost all healthcare providers.

Limeres, J., P. Diz, et al. (2004). "Individualized nasal mask fabrication for positive pressure ventilation using dental methods." International Journal of Prosthodontics 17(2): 247-50.

PURPOSE: The aim of this study was to develop a simple technique to manufacture individualized ventilatory nasal masks for pediatric patients using materials and procedures commonly applied in dentistry. MATERIALS AND METHODS: Three cases of pediatric patients who met with severe difficulties in their adaptation to commercially available nasal masks are described: one premature infant, one child diagnosed with achondroplasia, and one child with congenital central hypoventilation syndrome. RESULTS: In each case, a light nasal mask was designed with two independent parts that become perfectly adapted to the patient's nose: one soft for the skin contact, and another rigid for dimensional stability. In all patients, adequate levels of ventilation were reached. CONCLUSION: This easy, inexpensive nasal mask fabrication technique can be used in a great number of patients, increasing the efficacy of individualized masks.

Lin, Z., M. L. Chen, et al. (2004). "Noninvasive assessment of cardiovascular autonomic control in congenital central hypoventilation syndrome." Conference Proceedings: ... Annual International Conference of the IEEE Engineering in Medicine & Biology Society 5: 3870-3.

The goal of this study was to quantify autonomic system dysfunction, as manifested by cardiovascular and respiratory response abnormalities, in patients with congenital central hypoventilation syndrome (CCHS). During wakefulness, we continuously measured the ECG, arterial blood pressure (ABP), airflow, end-tidal CO2 partial pressure (PETCO2), and arterial oxygen saturation (SatO2) in each subject. These measurements were made during spontaneous breathing in supine, sitting and standing postures, and also when each subject tracked his/her prior spontaneous breathing pattern while supine. We also performed the cold face test, hyperoxic hypercapnic rebreathing and the isocapnic hypoxic rebreathing challenges. Using spectral analysis and modeling techniques, we sought to computationally delineate the physiological mechanisms that mediate these abnormalities, as well as to determine the extent to which these abnormalities are related to peripheral or central chemoreflex dysfunction. Our preliminary results support the notion that sympathetic tone is markedly elevated in CCHS, and that differences in autonomic control from normal controls can be delineated by observing the responses to different stressors.

Litscher, G., G. Schwarz, et al. (1996). "Abnormal brain stem auditory evoked potentials in a girl with the central alveolar hypoventilation syndrome." INTERNATIONAL JOURNAL OF NEUROSCIENCE 87(3-4): 113-7.

Brainstem auditory evoked potentials were recorded in a 3-year-old girl with the central alveolar hypoventilation syndrome (Ondine's syndrome). Abnormal findings were seen at the level of the mid to upper brain stem (wave III), which was not reproducibly recordable on the left side. This electrophysiologic abnormality is consistent with a previous finding in a patient with sleep apnea.

Little, R. (2008). "A 2-year old with no ventilator requirement but who cannot be extubated." SEMINARS IN PEDIATRIC NEUROLOGY 15(4): 157-9; discussion 159.

A 2-year-old boy was intubated during treatment for pneumonia. After resolution of the infection, he had no pulmonary requirement for ventilation and could function without it while awake. When he slept, however, he would have decreasing respiratory effort, increasing hypercapnia, and episodic apnea. This report provides an example of late-onset congenital central hypoventilation syndrome.

Liu, C.-P., X.-G. Li, et al. (2009). "Association analysis of the PHOX2B gene with Hirschsprung disease in the Han Chinese population of Southeastern China." JOURNAL OF PEDIATRIC SURGERY 44(9): 1805-11.

BACKGROUND: Hirschsprung disease (HSCR, OMIM 142623) is a complex congenital disorder characterized by intestinal obstructions caused by the absence of the intestinal ganglion cells of the nerve plexuses in variable lengths of the digestive tract. The PHOX2B gene is involved in neurogenesis and disruption of Phox2b in mice results in a HSCR-like phenotype. The first association study of the PHOX2B gene with HSCR derived from Chinese population in Hong Kong; here, we address the question of whether PHOX2B acts as a predisposing factor in HSCR pathogenesis in Chinese population in mainland. METHODS: To investigate the contribution of PHOX2B to the HSCR phenotype, polymerase chain reaction amplification and direct sequencing were used to screen PHOX2B coding regions and intron/exon boundaries for mutations and polymorphisms in 102 patients with HSCR and 96 ethnically matched controls, in Han Chinese populations of Southeastern China. RESULTS: In this study, we genotyped 4 single nucleotide polymorphisms (SNPs) (including 1 novel SNP) located within the PHOX2B gene. Statistically significant differences were found for c.701 A > G and IVS2 + 100 A > G, and the log-additive model was accepted as the best inheritance model (odds ratio [OR], 1.79; 95% confidence interval [CI], 1.11-2.87) for IVS2 + 100 A > G. We also showed that the haplotype-A G A N composed of 4 SNPs exhibited significant association with the disease (P = .03); this haplotype was more frequently observed in cases than in controls (OR, 2.31; 95% CI, 1.11-4.82). CONCLUSIONS: Our study provided further evidence that the PHOX2B gene is involved in the susceptibility to HSCR in the Han Chinese population. Our findings are in accordance with the involvement of PHOX2B in the signaling pathways governing the development of enteric neurons.

Liu, H. M., J. M. Loew, et al. (1978). "Congenital central hypoventilation syndrome: a pathologic study of the neuromuscular system." NEUROLOGY 28(10): 1013-19.

An infant with congenital central hypoventilation was managed by bilateral phrenic nerve pacing for 3 months. He died at 8 months of age, following 19 days of continuous bilateral pacing necessitated by the eventual loss of voluntary as well as autonomic ventilatory control. The phrenic nerves showed axonal dystrophy at the site of electrode implantation and more severe distal degeneration. Focal neurogenic atrophy was seen in the diaphragmatic muscle. These changes were attributed to electrical injury resulting from the period of continuous pacing. The most significant neuropathologic finding was a mild generalized decrease in the density of neurons and myelinated nerve fibers in the respiratory centers of the medulla. These morphologic abnormalities were attributed to a sublethal intrauterine lesion that would be the first example of a morphologic correlation with the functional abnormality in congenital central hypoventilation.

Liu, M. T., Y. H. Kuan, et al. (2009). "5-HT4 receptor-mediated neuroprotection and neurogenesis in the enteric nervous system of adult mice." JOURNAL OF NEUROSCIENCE 29(31): 9683-9699.

Although the mature enteric nervous system (ENS) has been shown to retain stem cells, enteric neurogenesis has not previously been demonstrated in adults. The relative number of enteric neurons in wild-type (WT) mice and those lacking 5-HT4 receptors [knock-out (KO)] was found to be similar at birth; however, the abundance of ENS neurons increased during the first 4 months after birth in WT but not KO littermates. Enteric neurons subsequently decreased in both WT and KO but at 12 months were significantly more numerous in WT. We tested the hypothesis that stimulation of the 5-HT4 receptor promotes enteric neuron survival and/or neurogenesis. In vitro, 5-HT4 agonists increased enteric neuronal development/survival, decreased apoptosis, and activated CREB (cAMP response element-binding protein). In vivo, in WT but not KO mice, 5-HT4 agonists induced bromodeoxyuridine incorporation into cells that expressed markers of neurons (HuC/D, doublecortin), neural precursors (Sox10, nestin, Phox2b), or stem cells (Musashi-1). This is the first demonstration of adult enteric neurogenesis; our results suggest that 5-HT 4 receptors are required postnatally for ENS growth and maintenance. Copyright copyright 2009 Society for Neuroscience.

Lo, L., X. Morin, et al. (1999). "Specification of neurotransmitter identity by Phox2 proteins in neural crest stem cells." NEURON 22(4): 693-705.

We have investigated the specification of noradrenergic neurotransmitter identity in neural crest stem cells (NCSCs). Retroviral expression of both wild-type and dominant-negative forms of the paired homeodomain transcription factor Phox2a indicates a crucial and direct role for this protein (and/or the closely related Phox2b) in the regulation of endogenous tyrosine hydroxylase (TH) and dopamine-beta hydroxylase (DBH) gene expression in these cells. In collaboration with cAMP, Phox2a can induce expression of TH but not of DBH or of panneuronal genes. Phox2 proteins are, moreover, necessary for the induction of both TH and DBH by bone morphogenetic protein 2 (BMP2) (which induces Phox2a/b) and forskolin. They are also necessary for neuronal differentiation. These data suggest that Phox2a/b coordinates the specification of neurotransmitter identity and neuronal fate by cooperating environmental signals in sympathetic neuroblasts.

Lokke, A., P. G. Fabricius, et al. (2007). "[Prevalence of chronic obstructive pulmonary disease in Copenhagen. Results from The Copenhagen City Heart Study]." UGESKRIFT FOR LAEGER 169(46): 3956-60.

INTRODUCTION: COPD is one of the leading causes of death worldwide. No recent prevalence study has been carried out in Denmark, but it is estimated that approximately 200,000 Danes have COPD. The aim of this study was to determine the prevalence of COPD in Copenhagen using data from the 4th examination of The Copenhagen City Heart Study (CCHS from 2001-2004) and to estimate the total number of COPD patients in Denmark. MATERIALS AND METHODS: 6,238 people participated in the 4th examination of CCHS. We selected all participants aged 35 years or older with adequate information regarding smoking habits and lung function for the final prevalence analyses (n = 4,908). COPD staging was done according to the GOLD and ERS/ATS criteria. We received information regarding the Danish population from The National Bureau of Statistics Denmark. RESULTS: The prevalence of COPD in the 4th CCHS increased with age and was higher among males than females. The total number of Danes with COPD is estimated to 430,000, 270,000 of whom have clinically important COPD (GOLD 2-4) and 40,000 have severe COPD (GOLD 3-4). CONCLUSION: The prevalence of COPD in Denmark is higher than previously anticipated. The 40,000 patients with severe COPD are in immediate need of relevant medical treatment and rehabilitation. Danish society also needs to exert a substantial effort comprising early detection, prophylaxis and relevant treatment for the 230,000 persons with moderate COPD in order to prevent disease progression.

Long, K. J. (1992). "Ondine's curse and sudden infant death syndrome." PEDIATRIC EMERGENCY CARE 8(1): 61-2.

Long, K. J. and N. Allen (1984). "Abnormal brain-stem auditory evoked potentials following Ondine's curse." ARCHIVES OF NEUROLOGY 41(10): 1109-10.

Longman, K., J. Wileman, et al. (2004). "Central hypoventilation: A complex presentation in an 83 year old." CME Journal Geriatric Medicine 6(3): 132-134.

Central hyperventilation resulting from a congenital neurological defect has been well described in children and young adults and is often referred to as "Ondine's Curse". However, acquired central neurological causes of reduced ventilation are rare, even in those with extensive cerebrovascular disease. Hypoventilation secondary to brainstem stroke resulting in chronic respiratory failure is extremely uncommon.¹ We present an elderly patient with central hypoventilation and discuss the diagnosis and management of suspected cases.

Longo, L., S. Borghini, et al. (2008). "PHOX2A and PHOX2B genes are highly co-expressed in human neuroblastoma." International Journal of Oncology 33(5): 985-91.

The detection of PHOX2B mutations in a small proportion of patients affected with either familial or sporadic neuroblastoma (NB), has arisen interest on the possible pathogenic role of this gene in the disease determination. In this light, we have carried out a quantitative expression analysis of PHOX2B and its paralogue PHOX2A on a panel of NB cell lines and NB tumour samples to identify a possible differential expression between NB cells and their normal counterpart (adrenal medulla cells). Our results revealed that both PHOX2A and PHOX2B are over-expressed in tumour samples and NB cell lines. Particularly, the expression levels of the two genes in NB cell lines show a highly significant correlation, suggesting their possible synergistic role or a coordinated expression regulation. Furthermore, PHOX2 gene over-expression in NB tumours and cell lines suggests these genes may be widely involved in NB development through either a direct mechanism of up-regulation or a failure in maintaining proper transcript levels after embryonic development.

Longo, L., G. P. Tonini, et al. (2005). "Oligogenic inheritance in neuroblastoma." CANCER LETTERS 228(1-2): 65-9.

Neuroblastoma (NB), a childhood malignancy affecting neural crest deriving cell lineages, is characterized by great clinical variability and histological heterogeneity. As NB usually occurs as sporadic form, molecular studies were mainly carried out on tumor samples and derived cell lines, leading to the identification of several somatic alterations. Although familial NB is rare, linkage data obtained from different families have provided evidence of linkage to markers mapping to different chromosomal regions, indicating a remarkable genetic heterogeneity of NB. The first evidence of germline mutations in NB pedigrees has been recently reported in the paired-like homeobox 2B (PHOX2B) gene, involved in the development of neural crest deriving cells. Nevertheless, as only a few NB families but not others have been shown to carry PHOX2B mutations, the role of this gene in NB predisposition has still to be clarified. On the basis of the current data, familial NB cannot be modeled as a Mendelian monogenic trait. Instead, an oligogenic mode of inheritance might explain the existence of different NB loci genetically interacting to cause and/or modify the disease-phenotype.

Longobucco, D. B. and E. P. Siddell (1993). "Daniel's story: congenital central hypoventilation syndrome." Neonatal Network - Journal of Neonatal Nursing 12(8): 17-22.

Central hypoventilation syndrome (CHS) is a disorder characterized by little or no ventilatory or arousal sensitivity to hypercapnia and variable reactivity to hypoxemia, with little or no hypoxic arousal responsiveness. CHS may be congenital or acquired and can be idiopathic or secondary to a known central nervous system abnormality. Infants often present with life-threatening apnea during quiet sleep and develop severe respiratory acidosis because of the inadequate response to hypercapnia and hypoxia. Long-term treatment usually involves use of mechanical ventilation during sleep.

Lopez-Herce Cid, J., M. Moreno de Guerra Giron, et al. (2000). "Non-invasive mechanical ventilation for congenital central alveolar hypoventilation syndrome. [Spanish]." ANALES ESPANOLES DE PEDIATRIA 52(2): 198-199.

Lovell, B. L., R. E. Bullock, et al. (2010). "An unusual presentation of congenital central hypoventilation syndrome (Ondine's Curse)." Emergency Medicine Journal 27(3): 237-8.

Congenital central hypoventilation syndrome is a rare illness, which classically presents in the neonatal period; newborns present with shallow breathing and cyanosis, without a physiological rise in breathing rate. Incidence has been estimated from 1 in 10,000 to 1 in 200,000 live births. This case report describes the case of a young man who was asymptomatic until his presentation in acute respiratory failure at the age of 36 years. This case is reported to highlight the importance of considering this treatable illness as a potential cause of collapse and respiratory failure in adults presenting to emergency departments.
Lowitzsch, K., R. Thuemler, et al. (1980). "Neurogenic breathing disorders. [German]." Atemwegs- und Lungenkrankheiten 6(3): 170-171.

Periodic apnea is the main symptom of breathing disorders in some diseases of the central nervous system, such as 1. the Sudden infant death syndrome (SIDS) with prolonged sleep apneas and hypoventilation, 2. the Pickwickian syndrome with adipositas, cyanosis, hypersomnia and secondary airway obstruction, 3. the Ondine's curse which is similar to the Pickwickian syndrome except obesitas, and 4. the Kleine-Levin syndrome with megaphagia, hypersomnia, hypoventilation, sleep apneas and bradycardia. The clinical symptomatology is described, the suggestion of an involvement of the lower brainstem as the joint underlying lesion is discussed.

Lucas, M. E., F. Muller, et al. (2006). "The bHLH transcription factor hand2 is essential for noradrenergic differentiation of sympathetic neurons." DEVELOPMENT 133(20): 4015-4024.

The basic helix-loop-helix transcription factor Hand2, together with Ascl1, Phox2a, Phox2b and Gata2/Gata3, is induced by bone morphogenetic proteins in neural crest-derived precursor cells during sympathetic neuron generation. Hand2 overexpression experiments and the analysis of its function at the Dbh promotor implicated Hand2 in the control of noradrenergic gene expression. Using the zebrafish hand2 deletion mutant hands off, we have now investigated the physiological role of hand2 in the development of sympathetic ganglia. In hands off mutant embryos, sympathetic precursor cells aggregate to form normal sympathetic ganglion primordia characterized by the expression of phox2b, phox2a and the achaete-scute family member zash1a/ascl1. The expression of the noradrenergic marker genes th and dbh is strongly reduced, as well as the transcription factors gata2 and tfap2a (Ap-2alpha). By contrast, generic neuronal differentiation seems to be unaffected, as the expression of elavl3 (HuC) is not reduced in hands off sympathetic ganglia. These results demonstrate in vivo an essential and selective function of hand2 for the noradrenergic differentiation of sympathetic neurons, and implicates tfap2a and gata2 as downstream effectors.

Lugaresi, E., F. Cirignotta, et al. (1982). "Sleep related respiratory impairment." Clinical Respiratory Physiology 18(Suppl. 4): 187-198.

Snoring and obstructive sleep apneas represent the end-points of sleep induced stenosis of the upper airways. Between them there exists a continuum of intermediate forms. Epidemiological data seem to indicate that habitual snoring, even without leading to a true disease state, may constitute a risk factor for the cardio-circulatory system. Tranquillizers such as benzodiazepines aggravate snoring and increase the number of obstructive apneas, thus worsening alveolar ventilation during sleep. Stimulant drugs such as mazindol show the opposite effect. Ondine's curse is a rare clinical condition, which should be kept distinct from the obstructive sleep apnea syndrome. Central apneas, present during normal sleep, may become especially numerous and prolonged in both obstructive sleep apnea syndrome and in Ondine's curse. They represent only a concomitant phenomenon and are not the cause of the syndrome. In all respiratory disturbances arising at the periphery (bronchopulmonary, neuromuscular, skeletal), sleep, REM sleep in particular, represents an unfavourable situation, during which alveolar hypoventilation is apt to worsen.

Lugaresi, E., F. Cirignotta, et al. (1985). "Sleep-related respiratory disorders." ITALIAN JOURNAL OF NEUROLOGICAL SCIENCES 6(4): 389-99.

Neurologists are becoming increasingly aware of the frequency and clinical importance of sleep-related respiratory impairment. Sleep-induced narrowing of the upper airways underlies the widespread and supposedly trivial complaint of snoring, which may not only constitute a risk factor for the cardiocirculatory system, but in predisposed individuals, may lead to a sleep apnea syndrome, with its array of serious disturbances, including hypersomnia, systemic and pulmonary hypertension and ultimately heart failure. Idiopathic chronic alveolar hypoventilation, or Ondine's curse, is a fairly stereotyped clinical syndrome: sleep-related respiratory insufficiency in the absence of airways stenosis. Finally, sleep, and REM sleep in particular, significantly aggravates hypoventilation in patients with chronic obstructive pulmonary disease (COPD), kyphoscoliosis or chest musculoskeletal disorders.