Skip to main content

Advertisement

Log in

A narrative review of the mechanisms and consequences of intermittent hypoxia and the role of advanced analytic techniques in pediatric autonomic disorders

  • Review Article
  • Published:
Clinical Autonomic Research Aims and scope Submit manuscript

Abstract

Disorders of autonomic functions are typically characterized by disturbances in multiple organ systems. These disturbances are often comorbidities of common and rare diseases, such as epilepsy, sleep apnea, Rett syndrome, congenital heart disease or mitochondrial diseases. Characteristic of many autonomic disorders is the association with intermittent hypoxia and oxidative stress, which can cause or exaggerate a variety of other autonomic dysfunctions, making the treatment and management of these syndromes very complex. In this review we discuss the cellular mechanisms by which intermittent hypoxia can trigger a cascade of molecular, cellular and network events that result in the dysregulation of multiple organ systems. We also describe the importance of computational approaches, artificial intelligence and the analysis of big data to better characterize and recognize the interconnectedness of the various autonomic and non-autonomic symptoms. These techniques can lead to a better understanding of the progression of autonomic disorders, ultimately resulting in better care and management.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Adapted with permission from [30]

Fig. 3

Adapted with permission from [30]

Fig. 4

Adapted with permission from [26]

Similar content being viewed by others

References

  1. Abdala AP, Bissonnette JM, Newman-Tancredi A (2014) Pinpointing brainstem mechanisms responsible for autonomic dysfunction in Rett syndrome: therapeutic perspectives for 5-HT1A agonists. Front Physiol 5:205

    PubMed  PubMed Central  Google Scholar 

  2. Abdala AP, Dutschmann M, Bissonnette JM, Paton JF (2010) Correction of respiratory disorders in a mouse model of Rett syndrome. Proc Natl Acad Sci USA 107:18208–18213

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Abdala AP, Dutschmann M, Bissonnette JM, Paton JF (2010) Correction of respiratory disorders in a mouse model of Rett syndrome. Proc Natl Acad Sci USA 107:18208–18213

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Abdala AP, Lioy DT, Garg SK, Knopp SJ, Paton JF, Bissonnette JM (2014) Effect of Sarizotan, a 5-HT1a and D2-like receptor agonist, on respiration in three mouse models of Rett syndrome. Am J Respir Cell Mol Biol 50:1031–1039

    PubMed  PubMed Central  Google Scholar 

  5. AlMarabeh S, Abdulla MH, O’Halloran KD (2019) Is aberrant reno-renal reflex control of blood pressure a contributor to chronic intermittent hypoxia-induced hypertension? Front Physiol 10:465

    PubMed  PubMed Central  Google Scholar 

  6. Almendros I, Martinez-Garcia MA, Farre R, Gozal D (2020) Obesity, sleep apnea, and cancer. Int J Obes (Lond) 44:1653–1667

    PubMed  Google Scholar 

  7. Amaddeo A, De Sanctis L, Arroyo JO, Khirani S, Bahi-Buisson N, Fauroux B (2019) Polysomnographic findings in Rett syndrome. Eur J Paediatr Neurol 23:214–221

    PubMed  Google Scholar 

  8. Anand N, Leu RM, Simon D, Kasi AS (2021) Recurrent apnoea and respiratory failure in an infant: congenital central hypoventilation syndrome with a novel PHOX2B gene variant. BMJ Case Rep 14:e239633

    PubMed  PubMed Central  Google Scholar 

  9. Arques S (2020) Serum albumin and cardiovascular disease: State-of-the-art review. Ann Cardiol Angeiol (Paris) 69:192–200

    CAS  PubMed  Google Scholar 

  10. Athira SB, Pal P, Nair PP, Nanda N, Aghoram R (2023) Cardiovascular autonomic function and baroreflex sensitivity in drug-resistant temporal lobe epilepsy. Epilepsy Behav 138:109013

    CAS  PubMed  Google Scholar 

  11. BaHammam AS, Pirzada AR, Pandi-Perumal SR (2023) Neurocognitive, mood changes, and sleepiness in patients with REM-predominant obstructive sleep apnea. Sleep Breath 27:57–66

    PubMed  Google Scholar 

  12. Basoglu OK, Tasbakan MS, Kayikcioglu M (2023) Dyslipidemia prevalence in non-obese non-diabetic patients with obstructive sleep apnea: does sex matter? J Clin Sleep Med 19:889

    PubMed  Google Scholar 

  13. Bass JL, Corwin M, Gozal D, Moore C, Nishida H, Parker S, Schonwald A, Wilker RE, Stehle S, Kinane TB (2004) The effect of chronic or intermittent hypoxia on cognition in childhood: a review of the evidence. Pediatrics 114:805–816

    PubMed  Google Scholar 

  14. Bassett E, Heinle R, Johnston D (2016) Sleep apnea in patients with Rett syndrome: roles for polysomnography and adenotonsillectomy. J Child Neurol 31:1633–1634

    PubMed  Google Scholar 

  15. Bebensee DF, Can K, Müller M (2017) Increased mitochondrial mass and cytosolic redox imbalance in hippocampal astrocytes of a mouse model of Rett syndrome: subcellular changes revealed by ratiometric imaging of JC-1 and roGFP1 fluorescence. Oxid Med Cell Longev 2017:3064016

    PubMed  PubMed Central  Google Scholar 

  16. Bergmann F, Keller BU (2004) Impact of mitochondrial inhibition on excitability and cytosolic Ca2+ levels in brainstem motoneurones from mouse. J Physiol 555:45–59

    CAS  PubMed  Google Scholar 

  17. Bernardi L, Hilz M, Stemper B, Passino C, Welsch G, Axelrod FB (2003) Respiratory and cerebrovascular responses to hypoxia and hypercapnia in familial dysautonomia. Am J Respir Crit Care Med 167:141–149

    PubMed  Google Scholar 

  18. Besag FMC, Vasey MJ (2021) Neurocognitive effects of antiseizure medications in children and adolescents with epilepsy. Paediatr Drugs 23:253–286

    PubMed  Google Scholar 

  19. Bigagli E, Lodovici M, Vasarri M, Peruzzi M, Nassi N, Degl’Innocenti D (2022) Significance of serum oxidative and antioxidative status in congenital central hypoventilation syndrome (CCHS) patients. Antioxidants (Basel) 11:1497

    CAS  PubMed  Google Scholar 

  20. Bissonnette JM, Schaevitz LR, Knopp SJ, Zhou Z (2014) Respiratory phenotypes are distinctly affected in mice with common Rett syndrome mutations MeCP2 T158A and R168X. Neuroscience 267:166–176

    CAS  PubMed  Google Scholar 

  21. Bone M, Goodspeed K (2022) A case report of topiramate for severe breath holding spells in a teenage boy with pitt-hopkins syndrome. Child Neurol Open 9:2329048X221093172

    PubMed  PubMed Central  Google Scholar 

  22. Bonsignore MR (2022) Obesity and obstructive sleep apnea. Handb Exp Pharmacol 274:181–201

    CAS  PubMed  Google Scholar 

  23. Bradicich M, Sievi NA, Grewe FA, Gasperetti A, Kohler M, Schwarz EI (2020) Nocturnal heart rate variability in obstructive sleep apnoea: a cross-sectional analysis of the sleep heart health study. J Thorac Dis 12:S129–S138

    PubMed  PubMed Central  Google Scholar 

  24. Brito LC, Queiroga T, Franco RR, Passone CGB, Lopes MC, Shea SA, Bueno C, Soster L (2021) Cardiac autonomic control during non-REM and REM sleep stages in paediatric patients with Prader-Willi syndrome. J Sleep Res 30:e13165

    PubMed  Google Scholar 

  25. Bruno E, Maira G, Biondi A, Richardson MP, Consortium R-C (2018) Ictal hypoxemia: a systematic review and meta-analysis. Seizure 63:7–13

    PubMed  Google Scholar 

  26. Carroll MS, Kenny AS, Patwari PP, Ramirez JM, Weese-Mayer DE (2012) Respiratory and cardiovascular indicators of autonomic nervous system dysregulation in familial dysautonomia. Pediatr Pulmonol 47:682–691

    PubMed  Google Scholar 

  27. Carroll MS, Patwari PP, Kenny AS, Brogadir CD, Stewart TM, Weese-Mayer DE (2015) Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD): response to ventilatory challenges. Pediatr Pulmonol 50:1336–1345

    PubMed  Google Scholar 

  28. Carroll MS, Patwari PP, Kenny AS, Brogadir CD, Stewart TM, Weese-Mayer DE (1985) Residual chemosensitivity to ventilatory challenges in genotyped congenital central hypoventilation syndrome. J Appl Physiol 116(439–450):2014

    Google Scholar 

  29. Carroll MS, Ramirez J-M, Weese-Mayer DE (2020) Diurnal variation in autonomic regulation among patients with genotyped Rett syndrome. J Med Genet 57(11):786-793. https://doi.org/10.1136/jmedgenet-2019-106601

  30. Carroll MS, Ramirez JM, Weese-Mayer DE (2020) Diurnal variation in autonomic regulation among patients with genotyped Rett syndrome. J Med Genet 57:786–793

    CAS  PubMed  Google Scholar 

  31. Castner DM, Clark SJ, Judelson DA, Rubin DA (2016) Obesity and prader-willi syndrome affect heart rate recovery from dynamic resistance exercise in youth. Diseases 4:4

    PubMed  PubMed Central  Google Scholar 

  32. Ceccherini I, Kurek KC, Weese-Mayer DE (2022) Developmental disorders affecting the respiratory system: CCHS and ROHHAD. Handb Clin Neurol 189:53–91

    PubMed  Google Scholar 

  33. Ciccoli L, De Felice C, Leoncini S, Signorini C, Cortelazzo A, Zollo G, Pecorelli A, Rossi M, Hayek J (2015) Red blood cells in Rett syndrome: oxidative stress, morphological changes and altered membrane organization. Biol Chem 396:1233–1240

    CAS  PubMed  Google Scholar 

  34. Cleary CM, James S, Maher BJ, Mulkey DK (2021) Disordered breathing in a Pitt-Hopkins syndrome model involves Phox2b-expressing parafacial neurons and aberrant Nav1.8 expression. Nat Commun 12:5962

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Cortelazzo A, De Felice C, Guy J, Timperio AM, Zolla L, Guerranti R, Leoncini S, Signorini C, Durand T, Hayek J (2020) Brain protein changes in Mecp2 mouse mutant models: effects on disease progression of Mecp2 brain specific gene reactivation. J Proteomics 210:103537–103537

    CAS  PubMed  Google Scholar 

  36. Costa RA, Ferreira IR, Cintra HA, Gomes LHF, Guida LDC (2019) Genotype-phenotype relationships and endocrine findings in Prader-Willi syndrome. Front Endocrinol (Lausanne) 10:864

    PubMed  Google Scholar 

  37. Dahan T, Nassar S, Yajuk O, Steinberg E, Benny O, Abudi N, Plaschkes I, Benyamini H, Gozal D, Abramovitch R, Gileles-Hillel A (2022) Chronic intermittent hypoxia during sleep causes browning of interscapular adipose tissue accompanied by local insulin resistance in mice. Int J Mol Sci 23:15462

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Dampney RA, Michelini LC, Li DP, Pan HL (2018) Regulation of sympathetic vasomotor activity by the hypothalamic paraventricular nucleus in normotensive and hypertensive states. Am J Physiol Heart Circ Physiol 315:H1200–H1214

    CAS  PubMed  PubMed Central  Google Scholar 

  39. De Felice C, Ciccoli L, Leoncini S, Signorini C, Rossi M, Vannuccini L, Guazzi G, Latini G, Comporti M, Valacchi G, Hayek J (2009) Systemic oxidative stress in classic Rett syndrome. Free Radic Biol Med 47:440–448

    PubMed  Google Scholar 

  40. De Felice C, Della Ragione F, Signorini C, Leoncini S, Pecorelli A, Ciccoli L, Scalabrì F, Marracino F, Madonna M, Belmonte G, Ricceri L, De Filippis B, Laviola G, Valacchi G, Durand T, Galano J-M, Oger C, Guy A, Bultel-Poncé V, Guy J, Filosa S, Hayek J, D’Esposito M (2014) Oxidative brain damage in Mecp2-mutant murine models of Rett syndrome. Neurobiol Dis 68:66–77

    PubMed  PubMed Central  Google Scholar 

  41. De Felice C, Della Ragione F, Signorini C, Leoncini S, Pecorelli A, Ciccoli L, Scalabri F, Marracino F, Madonna M, Belmonte G, Ricceri L, De Filippis B, Laviola G, Valacchi G, Durand T, Galano JM, Oger C, Guy A, Bultel-Ponce V, Guy J, Filosa S, Hayek J, D’Esposito M (2014) Oxidative brain damage in Mecp2-mutant murine models of Rett syndrome. Neurobiol Dis 68:66–77

    PubMed  PubMed Central  Google Scholar 

  42. De Felice C, Signorini C, Durand T, Ciccoli L, Leoncini S, D’Esposito M, Filosa S, Oger C, Guy A, Bultel-Ponce V, Galano JM, Pecorelli A, De Felice L, Valacchi G, Hayek J (2012) Partial rescue of Rett syndrome by omega-3 polyunsaturated fatty acids (PUFAs) oil. Genes Nutr 7:447–458

    PubMed  PubMed Central  Google Scholar 

  43. De Felice C, Signorini C, Leoncini S, Pecorelli A, Durand T, Valacchi G, Ciccoli L, Hayek J (2012) The role of oxidative stress in Rett syndrome: an overview. Ann NY Acad Sci 1259:121–135

    PubMed  Google Scholar 

  44. Del Rio R, Moya EA, Iturriaga R (2014) Carotid body potentiation during chronic intermittent hypoxia: implication for hypertension. Front Physiol 5:434

    PubMed  PubMed Central  Google Scholar 

  45. Dempsey JA, Veasey SC, Morgan BJ, O’Donnell CP (2010) Pathophysiology of sleep apnea. Physiol Rev 90:47–112

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Dergacheva O, Griffioen KJ, Neff RA, Mendelowitz D (2010) Respiratory modulation of premotor cardiac vagal neurons in the brainstem. Respir Physiol Neurobiol 174:102–110

    PubMed  PubMed Central  Google Scholar 

  47. Di Pierro D, Ciaccio C, Sbardella D, Tundo GR, Bernardini R, Curatolo P, Galasso C, Pironi V, Coletta M, Marini S (2020) Effects of oral administration of common antioxidant supplements on the energy metabolism of red blood cells. Attenuation of oxidative stress-induced changes in Rett syndrome erythrocytes by CoQ10. Mol Cell Biochem 463:101–113

    PubMed  Google Scholar 

  48. Diaz-Morales N, Baranda-Alonso EM, Martinez-Salgado C, Lopez-Hernandez FJ (2022) Renal sympathetic activity: a key modulator of pressure natriuresis in hypertension. Biochem Pharmacol 208:115386

    PubMed  Google Scholar 

  49. Dienel GA, Gillinder L, McGonigal A, Borges K (2022) Potential new roles for glycogen in epilepsy. Epilepsia 64:29

    PubMed  Google Scholar 

  50. Donnelly DF, Jiang C, Haddad GG (1992) Comparative responses of brain stem and hippocampal neurons to O2 deprivation: in vitro intracellular studies. Am J Physiol 262:L549-554

    CAS  PubMed  Google Scholar 

  51. Donze SH, Damen L, Mahabier EF, Hokken-Koelega ACS (2020) Cognitive functioning in children with Prader-Willi syndrome during 8 years of growth hormone treatment. Eur J Endocrinol 182:405–411

    CAS  PubMed  Google Scholar 

  52. Ehrler M, Brugger P, Greutmann M, Schlosser L, Wehrle FM, Liamlahi R, Naef N, Kretschmar O, O’Gorman RT, Latal B (2022) White matter microstructure and executive functions in congenital heart disease from childhood to adulthood: a pooled case-control study. Child Neuropsychol Nov 14: 1-24. https://doi.org/10.1080/09297049.2022.2144633

  53. Esmaeili B, Kaffashi F, Theeranaew W, Dabir A, Lhatoo SD, Loparo KA (2018) Post-ictal modulation of baroreflex sensitivity in patients with intractable epilepsy. Front Neurol 9:793

    PubMed  PubMed Central  Google Scholar 

  54. Fabbri M, Vetrugno R, Provini F, Bosi M, Santucci M (2012) Breathing instability in Joubert syndrome. Mov Disord 27:64

    PubMed  Google Scholar 

  55. Fabisiak T, Patel M (2022) Crosstalk between neuroinflammation and oxidative stress in epilepsy. Front Cell Dev Biol 10:976953

    PubMed  PubMed Central  Google Scholar 

  56. Farias JG, Molina VM, Carrasco RA, Zepeda AB, Figueroa E, Letelier P, Castillo RL (2017) Antioxidant therapeutic strategies for cardiovascular conditions associated with oxidative stress. Nutrients 9:966

    PubMed  PubMed Central  Google Scholar 

  57. Ferreira CB, Silva TM, Silva PE, Castro CL, Czeisler C, Otero JJ, Takakura AC, Moreira TS (2022) Phox2b mutation mediated by Atoh1 expression impaired respiratory rhythm and ventilatory responses to hypoxia and hypercapnia. Elife 11:e73130. https://doi.org/10.7554/eLife.73130

  58. Ferretti G, Bacchetti T, Masciangelo S, Grugni G, Bicchiega V (2012) Altered inflammation, paraoxonase-1 activity and HDL physicochemical properties in obese humans with and without Prader-Willi syndrome. Dis Model Mech 5:698–705

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Fletcher EC, Bao G, Miller CC 3rd (1985) Effect of recurrent episodic hypocapnic, eucapnic, and hypercapnic hypoxia on systemic blood pressure. J Appl Physiol 78:1516–1521

    Google Scholar 

  60. Formichi P, Battisti C, Dotti MT, Hayek G, Zappella M, Federico A (1998) Vitamin E serum levels in Rett syndrome. J Neurol Sci 156:227–230

    CAS  PubMed  Google Scholar 

  61. Frank JG, Jameson HS, Gorini C, Mendelowitz D (2009) Mapping and identification of GABAergic neurons in transgenic mice projecting to cardiac vagal neurons in the nucleus ambiguus using photo-uncaging. J Neurophysiol 101:1755–1760

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Garcia AJ 3rd, Dashevskiy T, Khuu MA, Ramirez J-M (2017) Chronic intermittent hypoxia differentially impacts different states of inspiratory activity at the level of the preBötzinger complex. Front Physiol 8:571–571

    PubMed  PubMed Central  Google Scholar 

  63. Garcia AJ 3rd, Zanella S, Dashevskiy T, Khan SA, Khuu MA, Prabhakar NR, Ramirez J-M (2016) Chronic intermittent hypoxia alters local respiratory circuit function at the level of the preBötzinger complex. Front Neurosci 10:4–4

    PubMed  PubMed Central  Google Scholar 

  64. Glaze DG, Percy AK, Skinner S, Motil KJ, Neul JL, Barrish JO, Lane JB, Geerts SP, Annese F, Graham J, McNair L, Lee HS (2010) Epilepsy and the natural history of Rett syndrome. Neurology 74:909–912

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Gracia CM, Bittencourt PC, Mazer S, Bittencourt PR (1986) Neurofibromatosis and extensive intracranial arterial occlusive disease (Moyamoya disease). Report of a case. Arq Neuropsiquiatr 44:395–400 (article in Portuguese)

  66. Grange RMH, Sharma R, Shah H, Reinstadler B, Goldberger O, Cooper MK, Nakagawa A, Miyazaki Y, Hindle AG, Batten AJ, Wojtkiewicz GR, Schleifer G, Bagchi A, Marutani E, Malhotra R, Bloch DB, Ichinose F, Mootha VK, Zapol WM (2021) Hypoxia ameliorates brain hyperoxia and NAD(+) deficiency in a murine model of Leigh syndrome. Mol Genet Metab 133:83–93

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Hayashi G, Cortopassi G (2015) Oxidative stress in inherited mitochondrial diseases. Free Radic Biol Med 88:10–17

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Heymans JF, Heymans C (1927) Sur les modifications directes et sur la régulation réflexe de l’activité du centre respiratoire de la tête isolée du chien. Arch Int Pharmacodyn Ther 33:273–372

    Google Scholar 

  69. Hosseini H, Homayouni-Tabrizi M, Amiri H, Safari-Faramani R, Moradi MT, Fadaei R, Khazaie H (2022) The effect of continuous positive airway pressure on total antioxidant capacity in obstructive sleep apnea: a systematic review and meta-analysis. Sleep Breath. https://doi.org/10.1007/s11325-022-02733-9

    Article  PubMed  Google Scholar 

  70. Ingram DG, Arganbright JM, Paprocki E, Halpin KL (2022) Sleep disorders in children with Prader Willi syndrome: current perspectives. Nat Sci Sleep 14:2065–2074

    PubMed  PubMed Central  Google Scholar 

  71. Iturriaga R, Alcayaga J, Chapleau MW, Somers VK (2021) Carotid body chemoreceptors: physiology, pathology, and implications for health and disease. Physiol Rev 101:1177–1235

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Iturriaga R, Andrade DC, Del Rio R (2015) Crucial role of the carotid body chemoreceptors on the development of high arterial blood pressure during chronic intermittent hypoxia. Adv Exp Med Biol 860:255–260

    CAS  PubMed  Google Scholar 

  73. Iturriaga R, Castillo-Galan S (2019) Potential contribution of carotid body-induced sympathetic and renin-angiotensin system overflow to pulmonary hypertension in intermittent hypoxia. Curr Hypertens Rep 21:89

    PubMed  Google Scholar 

  74. Iturriaga R, Del Rio R, Alcayaga J (2022) Carotid body inflammation: role in hypoxia and in the anti-inflammatory reflex. Physiology (Bethesda) 37:128–140

    CAS  PubMed  Google Scholar 

  75. Iturriaga R, Del Rio R, Idiaquez J, Somers VK (2016) Carotid body chemoreceptors, sympathetic neural activation, and cardiometabolic disease. Biol Res 49:13

    PubMed  PubMed Central  Google Scholar 

  76. Iturriaga R, Moya EA, Del Rio R (2010) Cardiorespiratory alterations induced by intermittent hypoxia in a rat model of sleep apnea. Adv Exp Med Biol 669:271–274

    PubMed  Google Scholar 

  77. Iturriaga R, Moya EA, Del Rio R (2015) Inflammation and oxidative stress during intermittent hypoxia: the impact on chemoreception. Exp Physiol 100:149–155

    CAS  PubMed  Google Scholar 

  78. Jackson ML, Howard ME, Barnes M (2011) Cognition and daytime functioning in sleep-related breathing disorders. Prog Brain Res 190:53–68

    PubMed  Google Scholar 

  79. Jameson H, Bateman R, Byrne P, Dyavanapalli J, Wang X, Jain V, Mendelowitz D (2016) Oxytocin neuron activation prevents hypertension that occurs with chronic intermittent hypoxia/hypercapnia in rats. Am J Physiol Heart Circ Physiol 310:H1549-1557

    PubMed  PubMed Central  Google Scholar 

  80. Janc OA, Huser MA, Dietrich K, Kempkes B, Menzfeld C, Hulsmann S, Muller M (2016) Systemic radical scavenger treatment of a mouse model of Rett syndrome: merits and limitations of the vitamin E derivative trolox. Front Cell Neurosci 10:266

    PubMed  PubMed Central  Google Scholar 

  81. John AS, Jackson JL, Moons P, Uzark K, Mackie AS, Timmins S, Lopez KN, Kovacs AH, Gurvitz M, American Heart Association Adults With Congenital Heart Disease Committee of the Council on Lifelong Congenital Heart Disease and Heart Health in the Young and the Council on Clinical Cardiology, Council on Cardiovascular and Stroke Nursing, Council on Arteriosclerosis, Thrombosis and Vascular Biology, Stroke Council (2022) Advances in managing transition to adulthood for adolescents with congenital heart disease: a practical approach to transition program design: a scientific statement from the American Heart Association. J Am Heart Assoc 11:e025278

  82. Ju Wang JD, Chen M, Zhang C, Parker J, Saneto R, Ramirez JM (2022) Sleep and breathing disturbances in children with Leigh syndrome: a comparative study. Pediatr Neurol 136:56–63

    PubMed  Google Scholar 

  83. Kalume F, Westenbroek RE, Cheah CS, Yu FH, Oakley JC, Scheuer T, Catterall WA (2013) Sudden unexpected death in a mouse model of Dravet syndrome. J Clin Invest 123:1798–1808

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Kamdar BB, Nandkumar P, Krishnan V, Gamaldo CE, Collop NA (2011) Self-reported sleep and breathing disturbances in Joubert syndrome. Pediatr Neurol 45:395–399

    PubMed  Google Scholar 

  85. Kanth K, Park K, Seyal M (2020) Severity of peri-ictal respiratory dysfunction with epilepsy duration and patient age at epilepsy onset. Front Neurol 11:618841

    PubMed  PubMed Central  Google Scholar 

  86. Katz DM, Dutschmann M, Ramirez JM, Hilaire G (2009) Breathing disorders in Rett syndrome: progressive neurochemical dysfunction in the respiratory network after birth. Respir Physiol Neurobiol 168:101–108

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Khaytin I, Stewart TM, Zelko FA, Kee MAL, Osipoff JN, Slattery SM, Weese-Mayer DE (2022) Evolution of physiologic and autonomic phenotype in rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation over a decade from age at diagnosis. J Clin Sleep Med 18:937–944

    PubMed  PubMed Central  Google Scholar 

  88. Khuu MA, Pagan CM, Nallamothu T, Hevner RF, Hodge RD, Ramirez J-M, Garcia AJ 3rd (2019) Intermittent hypoxia disrupts adult neurogenesis and synaptic plasticity in the dentate gyrus. J Neurosci 39:1320–1331

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Kim HY, Jo JH, Chung JW, Park JW (2022) The multisystemic effects of oral appliance therapy for obstructive sleep apnea: a narrative review. Medicine (Baltimore) 101:e29400

    PubMed  Google Scholar 

  90. Kim SJ, Cho SY, Jin DK (2021) Prader-Willi syndrome: an update on obesity and endocrine problems. Ann Pediatr Endocrinol Metab 26:227–236

    PubMed  PubMed Central  Google Scholar 

  91. Kline DD, Ogier M, Kunze DL, Katz DM (2010) Exogenous brain-derived neurotrophic factor rescues synaptic dysfunction in Mecp2-null mice. J Neurosci 30:5303–5310

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Koike S, Sudo H, Turudome S, Ueyama M, Tanaka Y, Kimura H, Ishida YI, Ogasawara Y (2022) Hyperoxidized peroxiredoxin 2 is a possible biomarker for the diagnosis of obstructive sleep apnea. Antioxidants (Basel) 11:2486

    CAS  PubMed  Google Scholar 

  93. Kron M, Howell CJ, Adams IT, Ransbottom M, Christian D, Ogier M, Katz DM (2012) Brain activity mapping in Mecp2 mutant mice reveals functional deficits in forebrain circuits, including key nodes in the default mode network, that are reversed with ketamine treatment. J Neurosci 32:13860–13872

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Kumagai H, Oshima N, Matsuura T, Iigaya K, Imai M, Onimaru H, Sakata K, Osaka M, Onami T, Takimoto C, Kamayachi T, Itoh H, Saruta T (2012) Importance of rostral ventrolateral medulla neurons in determining efferent sympathetic nerve activity and blood pressure. Hypertens Res 35:132–141

    CAS  PubMed  Google Scholar 

  95. Lacuey N, Martins R, Vilella L, Hampson JP, Rani MRS, Strohl K, Zaremba A, Hampson JS, Sainju RK, Friedman D, Nei M, Scott C, Gehlbach BK, Hupp NJ, Schuele S, Ogren J, Harper RM, Allen L, Diehl B, Bateman LM, Devinsky O, Richerson GB, Lhatoo S (2019) The association of serotonin reuptake inhibitors and benzodiazepines with ictal central apnea. Epilepsy Behav 98:73–79

    PubMed  PubMed Central  Google Scholar 

  96. Leoncini S, De Felice C, Signorini C, Pecorelli A, Durand T, Valacchi G, Ciccoli L, Hayek J (2011) Oxidative stress in Rett syndrome: natural history, genotype, and variants. Redox Rep 16:145–153

    CAS  PubMed  Google Scholar 

  97. Leoncini S, Signorini C, Boasiako L, Scandurra V, Hayek J, Ciccoli L, Rossi M, Canitano R, De Felice C (2022) Breathing abnormalities during sleep and wakefulness in rett syndrome: clinical relevance and paradoxical relationship with circulating pro-oxidant markers. Front Neurol 13:833239

    PubMed  PubMed Central  Google Scholar 

  98. Levitt ES, Hunnicutt BJ, Knopp SJ, Williams JT, Bissonnette JM (1985) A selective 5-HT1a receptor agonist improves respiration in a mouse model of Rett syndrome. J Appl Physiol 115(1626–1633):2013

    Google Scholar 

  99. Lin CH, Perger E, Lyons OD (2018) Obstructive sleep apnea and chronic kidney disease. Curr Opin Pulm Med 24:549–554

    PubMed  Google Scholar 

  100. Lira AB, de Sousa Rodrigues CF (2016) Evaluation of oxidative stress markers in obstructive sleep apnea syndrome and additional antioxidant therapy: a review article. Sleep Breath 20:1155–1160

    PubMed  Google Scholar 

  101. Liu P, Zhang HM, Hu K, Zhou XF, Tang S (2019) Sensory plasticity of carotid body is correlated with oxidative stress in paraventricular nucleus during chronic intermittent hypoxia. J Cell Physiol 234:13534–13543

    CAS  PubMed  Google Scholar 

  102. Lorincz K, Bone B, Karadi K, Kis-Jakab G, Toth N, Halasz L, Eross L, Balas I, Faludi B, Jordan Z, Chadaide Z, Gyimesi C, Fabo D, Janszky J (2023) Effects of anterior thalamic nucleus DBS on interictal heart rate variability in patients with refractory epilepsy. Clin Neurophysiol 147:17–30

    PubMed  Google Scholar 

  103. Lukoshe A, Hokken-Koelega AC, van der Lugt A, White T (2014) Reduced cortical complexity in children with Prader-Willi syndrome and its association with cognitive impairment and developmental delay. PLoS One 9:e107320

    PubMed  PubMed Central  Google Scholar 

  104. Machado BH, Zoccal DB, Moraes DJA (2017) Neurogenic hypertension and the secrets of respiration. Am J Physiol Regul Integr Comp Physiol 312:R864–R872

    PubMed  PubMed Central  Google Scholar 

  105. Marcus CL, Jansen MT, Poulsen MK, Keens SE, Nield TA, Lipsker LE, Keens TG (1991) Medical and psychosocial outcome of children with congenital central hypoventilation syndrome. J Pediatr 119:888–895

    CAS  PubMed  Google Scholar 

  106. Mauracher AA, Pagliarulo F, Faes L, Vavassori S, Gungor T, Bachmann LM, Pachlopnik SJ (2017) Causes of low neonatal T-cell receptor excision circles: a systematic review. J Allerg Clin Immunol Pract 5(1457–1460):e1422

    Google Scholar 

  107. Medical Advisory Secretariat (2005) Endovascular repair of descending thoracic aortic aneurysm: an evidence-based analysis. Ont Health Technol Assess Ser 5:1–59

  108. Medrihan L, Tantalaki E, Aramuni G, Sargsyan V, Dudanova I, Missler M, Zhang W (2008) Early defects of GABAergic synapses in the brain stem of a MeCP2 mouse model of Rett syndrome. J Neurophysiol 99:112–121

    CAS  PubMed  Google Scholar 

  109. Melo E, Fiel J, Milhomens R, Ribeiro T, Navegantes R, Gomes F, Duarte Gomes B, Pereira A (2022) Dynamic coupling between the central and autonomic cardiac nervous systems in patients with refractory epilepsy: a pilot study. Front Neurol 13:904052

    PubMed  PubMed Central  Google Scholar 

  110. Menzies B, Teng A, Burns M, Lah S (2022) Neurocognitive outcomes of children with sleep disordered breathing: a systematic review with meta-analysis. Sleep Med Rev 63:101629

    PubMed  Google Scholar 

  111. Meszaros M, Bikov A (2022) Obstructive sleep apnoea and lipid metabolism: the summary of evidence and future perspectives in the pathophysiology of OSA-associated dyslipidaemia. Biomedicines 10:2754

    CAS  PubMed  PubMed Central  Google Scholar 

  112. Moraes DJA, Bonagamba LGH, da Silva MP, Paton JFR, Machado BH (2017) Role of ventral medullary catecholaminergic neurons for respiratory modulation of sympathetic outflow in rats. Sci Rep 7:16883

    PubMed  PubMed Central  Google Scholar 

  113. Moya EA, Arias P, Varela C, Oyarce MP, Del Rio R, Iturriaga R (2016) Intermittent hypoxia-induced carotid body chemosensory potentiation and hypertension are critically dependent on peroxynitrite formation. Oxid Med Cell Longev 2016:9802136

    PubMed  Google Scholar 

  114. Muller M (2019) Disturbed redox homeostasis and oxidative stress: Potential players in the developmental regression in Rett syndrome. Neurosci Biobehav Rev 98:154–163

    PubMed  Google Scholar 

  115. Müller M (2019) Disturbed redox homeostasis and oxidative stress: Potential players in the developmental regression in Rett syndrome. Neurosci Biobehav Rev 98:154–163

    PubMed  Google Scholar 

  116. Nanduri J, Peng Y-J, Wang N, Prabhakar NR (2019) Neural activation of molecular circuitry in intermittent hypoxia. Curr Opin Physiol 7:9–14

    PubMed  Google Scholar 

  117. Nanduri J, Wang N, Yuan G, Khan SA, Souvannakitti D, Peng YJ, Kumar GK, Garcia JA, Prabhakar NR (2009) Intermittent hypoxia degrades HIF-2alpha via calpains resulting in oxidative stress: implications for recurrent apnea-induced morbidities. Proc Natl Acad Sci USA 106:1199–1204

    CAS  PubMed  PubMed Central  Google Scholar 

  118. Ortinau CM, Smyser CD, Arthur L, Gordon EE, Heydarian HC, Wolovits J, Nedrelow J, Marino BS, Levy VY (2022) Optimizing neurodevelopmental outcomes in neonates with congenital heart disease. Pediatrics 50(Suppl 2):e2022056415L. https://doi.org/10.1542/peds.2022-056415L

  119. Parsons ALM, Bucknor EMV, Castroflorio E, Soares TR, Oliver PL, Rial D (2022) The interconnected mechanisms of oxidative stress and neuroinflammation in epilepsy. Antioxidants (Basel) 11:157

    CAS  PubMed  Google Scholar 

  120. Pecorelli A, Cervellati C, Cordone V, Hayek J, Valacchi G (2020) Compromised immune/inflammatory responses in Rett syndrome. Free Radic Biol Med 152:100-106. https://doi.org/10.1016/j.freeradbiomed.2020.02.023

  121. Pena E, Brito J, El Alam S, Siques P (2020) Oxidative stress, kinase activity and inflammatory implications in right ventricular hypertrophy and heart failure under hypobaric hypoxia. Int J Mol Sci 21:6421

    CAS  PubMed  PubMed Central  Google Scholar 

  122. Peng YJ, Makarenko VV, Nanduri J, Vasavda C, Raghuraman G, Yuan G, Gadalla MM, Kumar GK, Snyder SH, Prabhakar NR (2014) Inherent variations in CO-H2S-mediated carotid body O2 sensing mediate hypertension and pulmonary edema. Proc Natl Acad Sci USA 111:1174–1179

    CAS  PubMed  PubMed Central  Google Scholar 

  123. Peng YJ, Yuan G, Ramakrishnan D, Sharma SD, Bosch-Marce M, Kumar GK, Semenza GL, Prabhakar NR (2006) Heterozygous HIF-1alpha deficiency impairs carotid body-mediated systemic responses and reactive oxygen species generation in mice exposed to intermittent hypoxia. J Physiol 577:705–716

    CAS  PubMed  PubMed Central  Google Scholar 

  124. Peng YJ, Zhang X, Gridina A, Chupikova I, McCormick DL, Thomas RJ, Scammell TE, Kim G, Vasavda C, Nanduri J, Kumar GK, Semenza GL, Snyder SH, Prabhakar NR (2017) Complementary roles of gasotransmitters CO and H2S in sleep apnea. Proc Natl Acad Sci USA 114:1413–1418

    CAS  PubMed  PubMed Central  Google Scholar 

  125. Pereira Kda R, Firpo C, Gasparin M, Teixeira AR, Dornelles S, Bacaltchuk T, Levy DS (2015) Evaluation of swallowing in infants with congenital heart defect. Int Arch Otorhinolaryngol 19:55–60

    PubMed  Google Scholar 

  126. Perinelli MG, Riva A, Amadori E, Follo R, Striano P (2023) Learnings in developmental and epileptic encephalopathies: what do we know? Expert Rev Neurother 23:45–57

    CAS  PubMed  Google Scholar 

  127. Peruzzi M, Ramazzotti M, Damiano R, Vasarri M, la Marca G, Arzilli C, Piumelli R, Nassi N, Degl’Innocenti D (2022) Urinary biomarkers as a proxy for congenital central hypoventilation syndrome patient follow-up. Antioxidants (Basel) 11:929

    CAS  PubMed  Google Scholar 

  128. Pham LV, Jun J, Polotsky VY (2022) Obstructive sleep apnea. Handb Clin Neurol 189:105–136

    PubMed  Google Scholar 

  129. Pintaudi M, Veneselli E, Voci A, Vignoli A, Castiglione D, Calevo MG, Grasselli E, Ragazzoni M, Cogliati F, Calzari L, Scornavacca GF, Russo S, Vergani L (2016) Blood oxidative stress and metallothionein expression in Rett syndrome: probing for markers. World J Biol Psychiatry 17:198–209

    PubMed  Google Scholar 

  130. Portelli SS, Hambly BD, Jeremy RW, Robertson EN (2021) Oxidative stress in genetically triggered thoracic aortic aneurysm: role in pathogenesis and therapeutic opportunities. Redox Rep 26:45–52

    CAS  PubMed  PubMed Central  Google Scholar 

  131. Poulsen JP, Rognum TO, Hauge S, Oyasaeter S, Saugstad OD (1993) Post-mortem concentrations of hypoxanthine in the vitreous humor–a comparison between babies with severe respiratory failure, congenital abnormalities of the heart, and victims of sudden infant death syndrome. J Perinat Med 21:153–163

    CAS  PubMed  Google Scholar 

  132. Prabhakar NR, Peng Y-J, Yuan G, Nanduri J (2018) Reactive oxygen radicals and gaseous transmitters in carotid body activation by intermittent hypoxia. Cell Tissue Res 372:427–431

    CAS  PubMed  PubMed Central  Google Scholar 

  133. Prabhakar NR, Peng YJ, Nanduri J (2020) Hypoxia-inducible factors and obstructive sleep apnea. J Clin Invest 130:5042–5051

    CAS  PubMed  PubMed Central  Google Scholar 

  134. Quintana A, Zanella S, Koch H, Kruse SE, Lee D, Ramirez JM, Palmiter RD (2012) Fatal breathing dysfunction in a mouse model of Leigh syndrome. J Clin Invest 122:2359–2368

    CAS  PubMed  PubMed Central  Google Scholar 

  135. Ramirez JM, Baertsch N (2018) Defining the rhythmogenic elements of mammalian breathing. Physiology (Bethesda) 33:302–316

    PubMed  Google Scholar 

  136. Ramirez JM, Garcia AJ 3rd, Anderson TM, Koschnitzky JE, Peng YJ, Kumar GK, Prabhakar NR (2013) Central and peripheral factors contributing to obstructive sleep apneas. Respir Physiol Neurobiol 189:344–353

    PubMed  PubMed Central  Google Scholar 

  137. Ramirez JM, Karlen-Amarante M, Wang JJ, Bush NE, Carroll MS, Weese-Mayer DE, Huff A (2020) The pathophysiology of Rett syndrome with a focus on breathing dysfunctions. Physiology (Bethesda) 35:375–390

    CAS  PubMed  Google Scholar 

  138. Ramirez JM, Karlen-Amarante M, Wang JJ, Huff A, Burgraff N (2022) Breathing disturbances in Rett syndrome. Handb Clin Neurol 189:139–151

    PubMed  PubMed Central  Google Scholar 

  139. Ramirez JM, Ward CS, Neul JL (2013) Breathing challenges in Rett syndrome: lessons learned from humans and animal models. Respir Physiol Neurobiol 189:280–287

    PubMed  Google Scholar 

  140. Rana M, Mohanty M (2018) The spectrum of sleep disordered breathing in Joubert syndrome. Sleep Med 52:177–179

    PubMed  Google Scholar 

  141. Richerson GB (2004) Serotonergic neurons as carbon dioxide sensors that maintain ph homeostasis. Nat Rev Neurosci 5:449–461

    CAS  PubMed  Google Scholar 

  142. Rodriguez-Quintana J, Bueno-Florez S, Mora-Munoz L, Orrego-Gonzalez E, Barragan AM, Suarez-Burgos F, Velez-Van-Meerbeke A, Cendes F (2023) Dysautonomia in people with epilepsy: a scoping review. Seizure 105:43–51

    PubMed  Google Scholar 

  143. Romanowski EF, McNamara N (2021) Surgery for Intractable epilepsy in pediatrics, a systematic review of outcomes other than seizure freedom. Semin Pediatr Neurol 39:100928

    PubMed  Google Scholar 

  144. Roux JC, Brismar H, Aperia A, Lagercrantz H (2005) Developmental changes in HIF transcription factor in carotid body: relevance for O2 sensing by chemoreceptors. Pediatr Res 58:53–57

    CAS  PubMed  Google Scholar 

  145. Sahai N, Bard AM, Devinsky O, Kalume F (2021) Disordered autonomic function during exposure to moderate heat or exercise in a mouse model of Dravet syndrome. Neurobiol Dis 147:105154

    CAS  PubMed  Google Scholar 

  146. Sarber KM, Howard JJM, Dye TJ, Pascoe JE, Simakajornboon N (2019) Sleep-disordered breathing in pediatric patients with Rett syndrome. J Clin Sleep Med 15:1451–1457

    PubMed  PubMed Central  Google Scholar 

  147. Schwartz DL, Mitchell AD, Lahna DL, Luber HS, Huckans MS, Mitchell SH, Hoffman WF (2010) Global and local morphometric differences in recently abstinent methamphetamine-dependent individuals. Neuroimage 50:1392–1401

    PubMed  Google Scholar 

  148. Semenza GL, Prabhakar NR (2018) The role of hypoxia-inducible factors in carotid body (patho) physiology. J Physiol 596:2977–2983

    CAS  PubMed  PubMed Central  Google Scholar 

  149. Shobatake R, Ota H, Takahashi N, Ueno S, Sugie K, Takasawa S (2020) The impact of intermittent hypoxia on metabolism and cognition. Int J Mol Sci 23:12957

    Google Scholar 

  150. Shulyakova N, Andreazza AC, Mills LR, Eubanks JH (2017) Mitochondrial dysfunction in the pathogenesis of Rett syndrome: implications for mitochondria-targeted therapies. Front Cell Neurosci 11:58–58

    PubMed  PubMed Central  Google Scholar 

  151. Signorini C, De Felice C, Leoncini S, Møller RS, Zollo G, Buoni S, Cortelazzo A, Guerranti R, Durand T, Ciccoli L, D’Esposito M, Ravn K, Hayek J (2016) MECP2 duplication syndrome: evidence of enhanced oxidative stress. A comparison with Rett syndrome. PloS One 11:e0150101

    PubMed  PubMed Central  Google Scholar 

  152. Smith JC, Ellenberger HH, Ballanyi K, Richter DW, Feldman JL (1991) Pre-Botzinger complex: a brainstem region that may generate respiratory rhythm in mammals. Science 254:726–729

    CAS  PubMed  PubMed Central  Google Scholar 

  153. Stettner GM, Huppke P, Brendel C, Richter DW, Gärtner J, Dutschmann M (2007) Breathing dysfunctions associated with impaired control of postinspiratory activity in Mecp2−/y knockout mice. J Physiol 579:863–876

    CAS  PubMed  PubMed Central  Google Scholar 

  154. Stokes JC, Bornstein RL, James K, Park KY, Spencer KA, Vo K, Snell JC, Johnson BM, Morgan PG, Sedensky MM, Baertsch NA, Johnson SC (2022) Leukocytes mediate disease pathogenesis in the Ndufs4(KO) mouse model of Leigh syndrome. JCI Insight 7(5):e156522. https://doi.org/10.1172/jci.insight.156522

  155. Sun X, Lv Y, Lin J (2023) The mechanism of sudden unexpected death in epilepsy: a mini review. Front Neurol 14:1137182

    PubMed  PubMed Central  Google Scholar 

  156. Suzuki YJ, Jain V, Park AM, Day RM (2006) Oxidative stress and oxidant signaling in obstructive sleep apnea and associated cardiovascular diseases. Free Radic Biol Med 40:1683–1692

    CAS  PubMed  PubMed Central  Google Scholar 

  157. Taneja P, Ogier M, Brooks-Harris G, Schmid DA, Katz DM, Nelson SB (2009) Pathophysiology of locus ceruleus neurons in a mouse model of Rett syndrome. J Neurosci 29:12187

    CAS  PubMed  PubMed Central  Google Scholar 

  158. Tarquinio DC, Hou W, Neul JL, Berkmen GK, Drummond J, Aronoff E, Harris J, Lane JB, Kaufmann WE, Motil KJ, Glaze DG, Skinner SA, Percy AK (2018) The course of awake breathing disturbances across the lifespan in Rett syndrome. Brain Dev 40:515–529

    PubMed  PubMed Central  Google Scholar 

  159. Tarquinio DC, Motil KJ, Hou W, Lee HS, Glaze DG, Skinner SA, Neul JL, Annese F, McNair L, Barrish JO, Geerts SP, Lane JB, Percy AK (2012) Growth failure and outcome in Rett syndrome: specific growth references. Neurology 79:1653–1661

    PubMed  PubMed Central  Google Scholar 

  160. Tillotson R, Bird A (2019) The molecular basis of MeCP2 function in the brain. J Mol Biol S0022–2836(0019):30595–30599

    Google Scholar 

  161. Toledo C, Andrade DC, Diaz-Jara E, Ortolani D, Bernal-Santander I, Schwarz KG, Ortiz FC, Marcus NJ, Oliveira LM, Takakura AC, Moreira TS, Del Rio R (2022) Cardiorespiratory alterations following intermittent photostimulation of RVLM C1 neurons: Implications for long-term blood pressure, breathing and sleep regulation in freely moving rats. Acta Physiol (Oxf) 236:e13864

    CAS  PubMed  Google Scholar 

  162. Toward MA, Abdala AP, Knopp SJ, Paton JF, Bissonnette JM (2013) Increasing brain serotonin corrects CO2 chemosensitivity in methyl-CpG-binding protein 2 (Mecp2)-deficient mice. Exp Physiol 98:842–849

    CAS  PubMed  Google Scholar 

  163. Umeda A, Miyagawa K, Mochida A, Takeda H, Takeda K, Okada Y, Gozal D (2020) Effects of normoxic recovery on intima-media thickness of aorta and pulmonary artery following intermittent hypoxia in mice. Front Physiol 11:583735

    PubMed  PubMed Central  Google Scholar 

  164. Vacca M, Della Ragione F, Scalabri F, D’Esposito M (2016) X inactivation and reactivation in X-linked diseases. Semin Cell Dev Biol 56:78–87

    PubMed  Google Scholar 

  165. Valacchi G, Sticozzi C, Belmonte G, Cervellati F, Pecorelli A, Signorini C, Leoncini S, Ciccoli L, De Felice C, Della Ragione F, Scalabri F, Marracino F, Madonna M, D’Esposito M, Joussef H, Cervellati F, Stefania F (2014) Scavenger receptor B1 oxidative post-translational modifications are responsible for its loss in Rett syndrome. Free Radic Biol Med 75(Suppl 1):S10–S11

    PubMed  Google Scholar 

  166. Valenti D, de Bari L, Vigli D, Lacivita E, Leopoldo M, Laviola G, Vacca RA, De Filippis B (2017) Stimulation of the brain serotonin receptor 7 rescues mitochondrial dysfunction in female mice from two models of Rett syndrome. Neuropharmacology 121:79–88

    CAS  PubMed  Google Scholar 

  167. van den Berg L, de Weerd AW, Reuvekamp MHF, van der Meere JJ (2021) Associating executive dysfunction with behavioral and socioemotional problems in children with epilepsy. A systematic review. Child Neuropsychol 27:661–708

    PubMed  Google Scholar 

  168. Vardanian M, Ravdin L (2022) Cognitive complaints and comorbidities in obstructive sleep apnea. Sleep Med Clin 17:647–656

    PubMed  Google Scholar 

  169. Veatch OJ, Malow BA, Lee HS, Knight A, Barrish JO, Neul JL, Lane JB, Skinner SA, Kaufmann WE, Miller JL, Driscoll DJ, Bird LM, Butler MG, Dykens EM, Gold JA, Kimonis V, Bacino CA, Tan WH, Kothare SV, Peters SU, Percy AK, Glaze DG (2021) Evaluating sleep disturbances in children with rare genetic neurodevelopmental syndromes. Pediatr Neurol 123:30–37

    PubMed  PubMed Central  Google Scholar 

  170. Viemari JC, Roux JC, Tryba AK, Saywell V, Burnet H, Pena F, Zanella S, Bevengut M, Barthelemy-Requin M, Herzing LB, Moncla A, Mancini J, Ramirez JM, Villard L, Hilaire G (2005) Mecp2 deficiency disrupts norepinephrine and respiratory systems in mice. J Neurosci 25:11521–11530

    CAS  PubMed  PubMed Central  Google Scholar 

  171. Vinod S, Ghaly E, Cruz Soriano P, Sampath H, February M, Gupta A (2020) A variable presentation of Joubert syndrome: case report and a brief review. J Neonatal Perinatal Med 13:587–591

    CAS  PubMed  Google Scholar 

  172. Vu EL, Dunne EC, Bradley A, Zhou A, Carroll MS, Rand CM, Brady KM, Stewart TM, Weese-Mayer DE (2022) Cerebral autoregulation during orthostatic challenge in congenital central hypoventilation syndrome. Am J Respir Crit Care Med 205:340–349

    CAS  PubMed  Google Scholar 

  173. Ward CS, Huang TW, Herrera JA, Samaco RC, McGraw CM, Parra DE, Arvide EM, Ito-Ishida A, Meng X, Ure K, Zoghbi HY, Neul JL (2020) Loss of MeCP2 function across several neuronal populations impairs breathing response to acute hypoxia. Front Neurol 11:593554

    PubMed  PubMed Central  Google Scholar 

  174. Weese-Mayer DE, Kenny AS, Bennett HL, Ramirez JM, Leurgans SE (2008) Familial dysautonomia: frequent, prolonged and severe hypoxemia during wakefulness and sleep. Pediatr Pulmonol 43:251–260

    PubMed  Google Scholar 

  175. Weese-Mayer DE, Lieske SP, Boothby CM, Kenny AS, Bennett HL, Ramirez JM (2008) Autonomic dysregulation in young girls with Rett syndrome during nighttime in-home recordings. Pediatr Pulmonol 43:1045–1060

    PubMed  Google Scholar 

  176. Weese-Mayer DE, Lieske SP, Boothby CM, Kenny AS, Bennett HL, Silvestri JM, Ramirez JM (2006) Autonomic nervous system dysregulation: breathing and heart rate perturbation during wakefulness in young girls with Rett syndrome. Pediatr Res 60:443–449

    PubMed  Google Scholar 

  177. Welbel RZ, Rand CM, Zhou A, Fadl-Alla A, Chen ML, Weese-Mayer DE, Zelko FA (2022) Neurocognitive monitoring in congenital central hypoventilation syndrome with the NIH Toolbox(R). Pediatr Pulmonol 57:2040–2047

    PubMed  PubMed Central  Google Scholar 

  178. Wittman S, Abdala AP, Rubin JE (2019) Reduced computational modelling of Kölliker-Fuse contributions to breathing patterns in Rett syndrome. J Physiol 597:2651–2672

    CAS  PubMed  PubMed Central  Google Scholar 

  179. Wolff MD, Farrell JS, Scantlebury MH, Teskey GC (2020) Dynamic oxygen changes during status epilepticus and subsequent endogenous kindling. Epilepsia 61:1515–1527

    CAS  PubMed  PubMed Central  Google Scholar 

  180. Wong SB, Yang MC, Tzeng IS, Tsai WH, Lan CC, Tsai LP (2022) Progression of obstructive sleep apnea syndrome in pediatric patients with Prader-Willi syndrome. Children (Basel) 9:912

    PubMed  Google Scholar 

  181. Yamada H, Tamasaki A, Oguri M, Hori I, Saitoh S, Maegaki Y (2020) Frequent epileptic apnoea in a patient with Pitt-Hopkins syndrome. Epileptic Disord 22:673–677

    PubMed  Google Scholar 

  182. Yang CF, Kim EJ, Callaway EM, Feldman JL (2020) Monosynaptic projections to excitatory and inhibitory preBotzinger complex neurons. Front Neuroanat 14:58

    CAS  PubMed  PubMed Central  Google Scholar 

  183. Yuan G, Peng YJ, Khan SA, Nanduri J, Singh A, Vasavda C, Semenza GL, Kumar GK, Snyder SH, Prabhakar NR (2016) H2S production by reactive oxygen species in the carotid body triggers hypertension in a rodent model of sleep apnea. Sci Signal 9:ra80

    PubMed  PubMed Central  Google Scholar 

  184. Zelko FA, Welbel RZ, Rand CM, Stewart T, Fadl-Alla A, Khaytin I, Slattery SM, Weese-Mayer DE (2022) Neurocognition as a biomarker in the rare autonomic disorders of CCHS and ROHHAD. Clin Auton Res. https://doi.org/10.1007/s10286-022-00901-1

    Article  PubMed  Google Scholar 

  185. Zhang X, Su J, Cui N, Gai H, Wu Z, Jiang C (2011) The disruption of central CO2 chemosensitivity in a mouse model of Rett syndrome. Am J Physiol Cell Physiol 301:C729–C738

    CAS  PubMed  PubMed Central  Google Scholar 

  186. Zilberter Y, Popova I, Zilberter M (2022) Unifying mechanism behind the onset of acquired epilepsy. Trends Pharmacol Sci 43:87–96

    CAS  PubMed  Google Scholar 

  187. Zock AZRW, Boccalandro F (2021) Rare presentation of atrial myxoma: chest pain, dysphagia and left upper extremity weakness. BMJ Case Rep 14:e225460

    Google Scholar 

  188. Zong D, Liu X, Shen C, Liu T, Ouyang R (2022) Involvement of Galectin-3 in neurocognitive impairment in obstructive sleep apnea via regulating inflammation and oxidative stress through NLRP3. Sleep Med 101:1–10

    PubMed  Google Scholar 

Download references

Funding

Funding was provided by NIH grants R01 HL151389, R01 HL126523, R01 HL144801, P01 HL144454 (Jan-Marino Ramirez), F32HL154558 (Nicholas Burgraff), and R03TR003869 (Debra E. Weese-Mayer).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jan-Marino Ramirez.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ramirez, JM., Carroll, M.S., Burgraff, N. et al. A narrative review of the mechanisms and consequences of intermittent hypoxia and the role of advanced analytic techniques in pediatric autonomic disorders. Clin Auton Res 33, 287–300 (2023). https://doi.org/10.1007/s10286-023-00958-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10286-023-00958-6

Keywords

Navigation