{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T12:41:27Z","timestamp":1793104887800,"version":"4.5.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T00:00:00Z","timestamp":1643673600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Congenital central hypoventilation syndrome (CCHS) is a rare autonomic disorder with altered regulation of breathing, heart rate (HR), and blood pressure (BP). Aberrant cerebral oxygenation in response to hypercapnia\/hypoxia in CCHS raises the concern that altered cerebral autoregulation may contribute to CCHS-related, variably impaired neurodevelopment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To evaluate cerebral autoregulation in response to orthostatic challenge in CCHS cases versus controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>CCHS and age- and sex-matched control subjects were studied with head-up tilt (HUT) testing to induce orthostatic stress. Fifty CCHS and 100 control HUT recordings were included. HR, BP, and cerebral oxygen saturation (regional oxygen saturation) were continuously monitored. The cerebral oximetry index (COx), a real-time measure of cerebral autoregulation based on these measures, was calculated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>HUT resulted in a greater mean BP decrease from baseline in CCHS versus controls (11% vs. 6%; P\u2009&amp;lt;\u20090.05) and a diminished increase in HR in CCHS versus controls (11% vs. 18%; P\u2009&amp;lt;\u20090.01) in the 5 minutes after tilt-up. Despite a similar COx at baseline, orthostatic provocation within 5 minutes of tilt-up caused a 50% greater increase in COx (P\u2009&amp;lt;\u20090.01) and a 29% increase in minutes of impaired autoregulation (P\u2009&amp;lt;\u20090.02) in CCHS versus controls (4.0 vs. 3.1 min).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Cerebral autoregulatory mechanisms appear to be intact in CCHS, but the greater hypotension observed in CCHS consequent to orthostatic provocation is associated with greater values of COx\/impaired autoregulation when BP is below the lower limits of autoregulation. Effects of repeated orthostatic challenges in everyday living in CCHS necessitate further study to determine their influence on neurodevelopmental disease burden.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.202103-0732oc","type":"journal-article","created":{"date-parts":[[2021,11,17]],"date-time":"2021-11-17T16:58:22Z","timestamp":1637168302000},"page":"340-349","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":15,"title":["Cerebral Autoregulation during Orthostatic Challenge in Congenital Central Hypoventilation Syndrome"],"prefix":"10.1093","volume":"205","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6329-1931","authenticated-orcid":false,"given":"Eric L.","family":"Vu","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Anesthesia, Department of Anesthesiology, and"},{"name":"Department of Anesthesia"},{"name":"Stanley Manne Children\u2019s Research Institute, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma C.","family":"Dunne","sequence":"additional","affiliation":[{"name":"Division of Autonomic Medicine, Department of Pediatrics, Ann & Robert H. Lurie Children\u2019s Hospital of Chicago, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison","family":"Bradley","sequence":"additional","affiliation":[{"name":"Division of Autonomic Medicine, Department of Pediatrics, Ann & Robert H. Lurie Children\u2019s Hospital of Chicago, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Zhou","sequence":"additional","affiliation":[{"name":"Division of Autonomic Medicine, Department of Pediatrics, Ann & Robert H. Lurie Children\u2019s Hospital of Chicago, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0526-7543","authenticated-orcid":false,"given":"Michael S.","family":"Carroll","sequence":"additional","affiliation":[{"name":"Division of Autonomic Medicine, Department of Pediatrics, Ann & Robert H. Lurie Children\u2019s Hospital of Chicago, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Casey M.","family":"Rand","sequence":"additional","affiliation":[{"name":"Stanley Manne Children\u2019s Research Institute, Chicago, Illinois"},{"name":"Division of Autonomic Medicine, Department of Pediatrics, Ann & Robert H. Lurie Children\u2019s Hospital of Chicago, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4699-8940","authenticated-orcid":false,"given":"Kenneth M.","family":"Brady","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Anesthesia, Department of Anesthesiology, and"},{"name":"Department of Anesthesia"},{"name":"Stanley Manne Children\u2019s Research Institute, Chicago, Illinois"},{"name":"Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracey M.","family":"Stewart","sequence":"additional","affiliation":[{"name":"Division of Autonomic Medicine, Department of Pediatrics, Ann & Robert H. Lurie Children\u2019s Hospital of Chicago, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6061-220X","authenticated-orcid":false,"given":"Debra E.","family":"Weese-Mayer","sequence":"additional","affiliation":[{"name":"Stanley Manne Children\u2019s Research Institute, Chicago, Illinois"},{"name":"Division of Autonomic Medicine, Department of Pediatrics, Ann & Robert H. Lurie Children\u2019s Hospital of Chicago, Chicago, Illinois"},{"name":"Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,2,1]]},"reference":[{"key":"2026022020534749700_bib1","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1164\/rccm.200807-1069ST","article-title":"An official ATS clinical policy statement: congenital central hypoventilation syndrome: genetic basis, diagnosis, and management","volume":"181","author":"Weese-Mayer","year":"2010","journal-title":"Am J Respir Crit Care Med"},{"key":"2026022020534749700_bib2","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1038\/pr.2016.196","article-title":"Congenital central hypoventilation syndrome: a bedside-to-bench success story for advancing early diagnosis and treatment and improved survival and quality of life","volume":"81","author":"Weese-Mayer","year":"2017","journal-title":"Pediatr Res"},{"key":"2026022020534749700_bib3","doi-asserted-by":"crossref","first-page":"99","DOI":"10.2147\/PHMT.S95054","article-title":"Congenital central hypoventilation syndrome: diagnostic and management challenges","volume":"7","author":"Kasi","year":"2016","journal-title":"Pediatric Health Med Ther"},{"key":"2026022020534749700_bib4","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1152\/japplphysiol.01310.2013","article-title":"Residual chemosensitivity to ventilatory challenges in genotyped congenital central hypoventilation syndrome","volume":"116","author":"Carroll","year":"2014","journal-title":"J Appl Physiol (1985)"},{"key":"2026022020534749700_bib5","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1002\/ppul.21170","article-title":"Congenital central hypoventilation syndrome: neurocognitive functioning in school age children","volume":"45","author":"Zelko","year":"2010","journal-title":"Pediatr Pulmonol"},{"key":"2026022020534749700_bib6","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1378\/chest.15-0402","article-title":"Congenital central hypoventilation syndrome: neurocognition already reduced in preschool-aged children","volume":"149","author":"Charnay","year":"2016","journal-title":"Chest"},{"key":"2026022020534749700_bib7","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1152\/physrev.1959.39.2.183","article-title":"Cerebral blood flow and oxygen consumption in man","volume":"39","author":"Lassen","year":"1959","journal-title":"Physiol Rev"},{"key":"2026022020534749700_bib8","doi-asserted-by":"crossref","first-page":"2818","DOI":"10.1161\/STROKEAHA.107.485706","article-title":"Continuous time-domain analysis of cerebrovascular autoregulation using near-infrared spectroscopy","volume":"38","author":"Brady","year":"2007","journal-title":"Stroke"},{"key":"2026022020534749700_bib9","doi-asserted-by":"crossref","first-page":"1957","DOI":"10.1161\/STROKEAHA.109.575167","article-title":"Monitoring cerebral blood flow pressure autoregulation in pediatric patients during cardiac surgery","volume":"41","author":"Brady","year":"2010","journal-title":"Stroke"},{"key":"2026022020534749700_bib10","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.12688\/f1000research.11351.1","article-title":"Recent advances in cerebral oximetry: assessment of cerebral autoregulation with near-infrared spectroscopy: myth or reality?","volume":"6","author":"Moerman","year":"2017","journal-title":"F1000 Res"},{"key":"2026022020534749700_bib11","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1093\/bja\/aes148","article-title":"Risks for impaired cerebral autoregulation during cardiopulmonary bypass and postoperative stroke","volume":"109","author":"Ono","year":"2012","journal-title":"Br J Anaesth"},{"key":"2026022020534749700_bib12","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1097\/CCM.0b013e31826ab3a1","article-title":"Blood pressure excursions below the cerebral autoregulation threshold during cardiac surgery are associated with acute kidney injury","volume":"41","author":"Ono","year":"2013","journal-title":"Crit Care Med"},{"key":"2026022020534749700_bib13","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1161\/STROKEAHA.109.575159","article-title":"Real-time continuous monitoring of cerebral blood flow autoregulation using near-infrared spectroscopy in patients undergoing cardiopulmonary bypass","volume":"41","author":"Brady","year":"2010","journal-title":"Stroke"},{"key":"2026022020534749700_bib14","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.jtcvs.2013.07.069","article-title":"Duration and magnitude of blood pressure below cerebral autoregulation threshold during cardiopulmonary bypass is associated with major morbidity and operative mortality","volume":"147","author":"Ono","year":"2014","journal-title":"J Thorac Cardiovasc Surg"},{"key":"2026022020534749700_bib15","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1007\/s12028-008-9140-5","article-title":"Near-infrared spectroscopy can monitor dynamic cerebral autoregulation in adults","volume":"10","author":"Steiner","year":"2009","journal-title":"Neurocrit Care"},{"key":"2026022020534749700_bib16","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/s12028-012-9721-1","article-title":"Continuous cerebral blood flow autoregulation monitoring in patients undergoing liver transplantation","volume":"17","author":"Zheng","year":"2012","journal-title":"Neurocrit Care"},{"key":"2026022020534749700_bib17","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1186\/s13054-018-2258-8","article-title":"Impaired cerebral autoregulation is associated with brain dysfunction in patients with sepsis","volume":"22","author":"Crippa","year":"2018","journal-title":"Crit Care"},{"key":"2026022020534749700_bib18","doi-asserted-by":"crossref","first-page":"H1","DOI":"10.1152\/ajpheart.00581.2016","article-title":"Functional vascular contributions to cognitive impairment and dementia: mechanisms and consequences of cerebral autoregulatory dysfunction, endothelial impairment, and neurovascular uncoupling in aging","volume":"312","author":"Toth","year":"2017","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"2026022020534749700_bib19","doi-asserted-by":"crossref","first-page":"765","DOI":"10.3233\/JAD-132018","article-title":"Dynamic cerebral autoregulation and tissue oxygenation in amnestic mild cognitive impairment","volume":"41","author":"Tarumi","year":"2014","journal-title":"J Alzheimers Dis"},{"key":"2026022020534749700_bib20","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/j.sleep.2010.03.008","article-title":"Images in sleep medicine: altered cerebral blood flow in a patient with congenital central hypoventilation syndrome","volume":"11","author":"Macey","year":"2010","journal-title":"Sleep Med"},{"key":"2026022020534749700_bib21","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1002\/9781444345186.ch7","volume-title":"Gregory\u2019s pediatric anesthesia","author":"Brady","year":"2012"},{"key":"2026022020534749700_bib22","author":"Vu"},{"key":"2026022020534749700_bib23","author":"Dunne","year":"2018"},{"key":"2026022020534749700_bib24","first-page":"334","article-title":"Cerebral regional oxygen saturation during head-up tilt testing (HUT) in children and adolescents with postural orthostatic tachycardia syndrome (POTS) and matched controls","volume":"26","author":"Panicker","year":"2016","journal-title":"Clin Auton Res"},{"key":"2026022020534749700_bib25","first-page":"243","article-title":"Cerebral regional blood flow\/oxygenation, heart rate, and blood pressure responses in Congenital Central Hypoventilation Syndrome (CCHS) during head up tilt as compared to children referred with dizziness","volume":"23","author":"Carroll","year":"2013","journal-title":"Clin Auton Res"},{"key":"2026022020534749700_bib26","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1152\/japplphysiol.00068.2013","article-title":"The frequency response of cerebral autoregulation","volume":"115","author":"Fraser","year":"2013","journal-title":"J Appl Physiol (1985)"},{"key":"2026022020534749700_bib27","doi-asserted-by":"crossref","first-page":"121","DOI":"10.2307\/2531248","article-title":"Longitudinal data analysis for discrete and continuous outcomes","volume":"42","author":"Zeger","year":"1986","journal-title":"Biometrics"},{"key":"2026022020534749700_bib28","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1042\/CS20040282","article-title":"Short-term blood pressure and heart rate variability in congenital central hypoventilation syndrome (Ondine\u2019s curse)","volume":"108","author":"Trang","year":"2005","journal-title":"Clin Sci (Lond)"},{"key":"2026022020534749700_bib29","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1016\/j.neuroscience.2010.02.078","article-title":"Central autonomic regulation in congenital central hypoventilation syndrome","volume":"167","author":"Ogren","year":"2010","journal-title":"Neuroscience"},{"key":"2026022020534749700_bib30","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1161\/01.STR.26.6.1014","article-title":"Comparison of static and dynamic cerebral autoregulation measurements","volume":"26","author":"Tiecks","year":"1995","journal-title":"Stroke"},{"key":"2026022020534749700_bib31","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1161\/hc3301.094908","article-title":"Cerebral autoregulatory responses to head-up tilt in normal subjects and patients with recurrent vasovagal syncope","volume":"104","author":"Carey","year":"2001","journal-title":"Circulation"},{"key":"2026022020534749700_bib32","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1177\/0300060516635383","article-title":"Comparison of the non-invasive Nexfin\u00ae monitor with conventional methods for the measurement of arterial blood pressure in moderate risk orthopaedic surgery patients","volume":"44","author":"Balzer","year":"2016","journal-title":"J Int Med Res"},{"key":"2026022020534749700_bib33","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1093\/oxfordjournals.eurheartj.a060791","article-title":"A comparison of non-invasive continuous finger blood pressure measurement (Finapres) with intra-arterial pressure during prolonged head-up tilt","volume":"16","author":"Petersen","year":"1995","journal-title":"Eur Heart J"},{"key":"2026022020534749700_bib34","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1179\/1743132815Y.0000000094","article-title":"Acute hypercarbia increases the lower limit of cerebral blood flow autoregulation in a porcine model","volume":"38","author":"Nusbaum","year":"2016","journal-title":"Neurol Res"},{"key":"2026022020534749700_bib35","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1093\/oxfordjournals.aje.a009786","article-title":"Factors influencing the optimal control-to-case ratio in matched case-control studies","volume":"149","author":"Hennessy","year":"1999","journal-title":"Am J Epidemiol"}],"container-title":["American Journal of Respiratory and Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/205\/3\/340\/67008922\/ajrccm_205_3_340.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/205\/3\/340\/67008922\/ajrccm_205_3_340.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T01:53:57Z","timestamp":1771638837000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrccm\/article\/205\/3\/340\/8491916"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,1]]},"references-count":35,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,2,1]]},"published-print":{"date-parts":[[2022,2,1]]}},"URL":"https:\/\/doi.org\/10.1164\/rccm.202103-0732oc","relation":{},"ISSN":["1073-449X","1535-4970"],"issn-type":[{"value":"1073-449X","type":"print"},{"value":"1535-4970","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,2]]},"published":{"date-parts":[[2022,2,1]]},"assertion":[{"value":"2021-03-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-11-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-02-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}