{"doi":"10.3389/fneur.2022.833239","title":"Breathing Abnormalities During Sleep and Wakefulness in Rett Syndrome: Clinical Relevance and Paradoxical Relationship With Circulating Pro-oxidant Markers","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 ± 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>","journal":"Frontiers in Neurology","year":2022,"id":648515,"datarank":0.5501508429209673,"base_score":2.70805020110221,"endowment":2.70805020110221,"self_citation_contribution":0.40620753016533157,"citation_network_contribution":0.1439433127556357,"self_endowment_contribution":0.40620753016533157,"citer_contribution":0.1439433127556357,"corpus_percentile":null,"corpus_rank":null,"citation_count":14,"citer_count":12,"citers_with_citation_signal":8,"citers_with_endowment":8,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1650319,"name":"Cinzia Signorini","orcid":"0000-0003-0006-9414","position":1,"is_corresponding":false},{"id":1690126,"name":"Lidia Boasiako","orcid":null,"position":2,"is_corresponding":false},{"id":1690127,"name":"Valeria Scandurra","orcid":null,"position":3,"is_corresponding":false},{"id":1690128,"name":"Joussef Hayek","orcid":null,"position":4,"is_corresponding":false},{"id":1690129,"name":"Lucia Ciccoli","orcid":null,"position":5,"is_corresponding":false},{"id":227548,"name":"Marcello Rossi","orcid":"0000-0002-8125-6571","position":6,"is_corresponding":false},{"id":1083944,"name":"Roberto Canitano","orcid":"0000-0002-6584-658X","position":7,"is_corresponding":false},{"id":1690130,"name":"Claudio De Felice","orcid":null,"position":8,"is_corresponding":false},{"id":1690125,"name":"Silvia Leoncini","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":false,"title":null,"abstract":null,"is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":null,"pmcid":null,"openalex_id":null,"authors":[],"funders":[],"total_grants":0,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":null,"license":null,"oa_locations":[],"fields_of_study":[],"mesh_terms":[],"keywords":[],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-10T02:41:19.679977Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}