{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T01:06:30Z","timestamp":1770339990269,"version":"3.49.0"},"reference-count":132,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T00:00:00Z","timestamp":1648512000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009888","name":"Regione Toscana","doi-asserted-by":"publisher","award":["142"],"award-info":[{"award-number":["142"]}],"id":[{"id":"10.13039\/501100009888","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Breathing abnormalities are common in Rett syndrome (RTT), a pervasive neurodevelopmental disorder almost exclusively affecting females. RTT is linked to mutations in the methyl-CpG-binding protein 2 (<jats:italic>MeCP2<\/jats:italic>) gene. Our aim was to assess the clinical relevance of apneas during sleep-wakefulness cycle in a population with RTT and the possible impact of apneas on circulating oxidative stress markers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Female patients with a clinical diagnosis of typical RTT (<jats:italic>n<\/jats:italic> = 66), <jats:italic>MECP2<\/jats:italic> gene mutation, and apneas were enrolled (mean age: 12.5 years). Baseline clinical severity, arterial blood gas analysis, and red blood cell count were assessed. Breathing was monitored during the wakefulness and sleep states (average recording time: 13 \u00b1 0.5 h) with a portable polygraphic screening device. According to prevalence of breath holdings, the population was categorized into the wakefulness apnea (WA) and sleep apnea (SA) groups, and apnea-hypopnea index (AHI) was calculated. The impact of respiratory events on oxidative stress was assessed by plasma and intra-erythrocyte non-protein-bound iron (P-NPBI and IE-NPBI, respectively), and plasma F<jats:sub>2<\/jats:sub>-isoprostane (F<jats:sub>2<\/jats:sub>-IsoP) assays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Significant prevalence of obstructive apneas with values of AHI &amp;gt; 15 was present in 69.7% of the population with RTT. The group with SA showed significantly increased AHI values &amp;gt; 15 (<jats:italic>p<\/jats:italic> = 0.0032), total breath holding episodes (<jats:italic>p<\/jats:italic> = 0.007), and average SpO<jats:sub>2<\/jats:sub> (<jats:italic>p<\/jats:italic> = 0.0001) as well as lower nadir SpO<jats:sub>2<\/jats:sub> (<jats:italic>p<\/jats:italic> = 0.0004) compared with the patients with WAs. The subgroups of patients with WA and SA showed no significant differences in arterial blood gas analysis variables (<jats:italic>p<\/jats:italic> &amp;gt; 0.089). Decreased mean cell hemoglobin (MCH) (<jats:italic>p<\/jats:italic> = 0.038) was observed in the group with WAs. P-NPBI levels were significantly higher in the group with WA than in that with SAs (<jats:italic>p<\/jats:italic> = 0.0001). Stepwise multiple linear regression models showed WA being related to nadir SpO<jats:sub>2<\/jats:sub>, average SpO<jats:sub>2<\/jats:sub>, and P-NPBI (adjusted <jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup> = 0.613, multiple correlation coefficient = 0.795 <jats:italic>p<\/jats:italic> &amp;lt; 0.0001), and P-NPBI being related to average SpO<jats:sub>2<\/jats:sub>, blood PaCO<jats:sub>2<\/jats:sub>, red blood cell mean corpuscular volume (MCV), age, and topiramate treatment (adjusted <jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup> = 0.551, multiple correlation coefficient = 0.765, <jats:italic>p<\/jats:italic> &amp;lt; 0.0001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings indicate that the impact of apneas in RTT is uneven according to the sleep-wakefulness cycle, and that plasma redox active iron represents a potential novel therapeutic target.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2022.833239","type":"journal-article","created":{"date-parts":[[2022,3,30]],"date-time":"2022-03-30T04:02:52Z","timestamp":1648612972000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Breathing Abnormalities During Sleep and Wakefulness in Rett Syndrome: Clinical Relevance and Paradoxical Relationship With Circulating Pro-oxidant Markers"],"prefix":"10.3389","volume":"13","author":[{"given":"Silvia","family":"Leoncini","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cinzia","family":"Signorini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lidia","family":"Boasiako","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valeria","family":"Scandurra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joussef","family":"Hayek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucia","family":"Ciccoli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcello","family":"Rossi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberto","family":"Canitano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudio","family":"De 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