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Front. Neurol.
Sec. Sleep Disorders
Volume 15 - 2024 | doi: 10.3389/fneur.2024.1388506
This article is part of the Research Topic Sleep in Children with Rare Disorders Volume II View all 3 articles

24-hours continuous noninvasive multiparameter home monitoring of vitals in patients with Rett syndrome by an innovative wearable technology: Evidence of an overlooked chronic fatigue status

Provisionally accepted
Silvia Leoncini Silvia Leoncini 1,2,3*Lidia Boasiako Lidia Boasiako 2,4Sofia Di Lucia Sofia Di Lucia 4Amir Beker Amir Beker 5Valeria Scandurra Valeria Scandurra 6Aglaia Vignoli Aglaia Vignoli 7Maria Paola Canevini Maria Paola Canevini 8Giulia Prato Giulia Prato 9Lino Nobili Lino Nobili 10,11Antonio G. Nicotera Antonio G. Nicotera 12Gabriella Di Rosa Gabriella Di Rosa 12,13Maria Beatrice C. Testa Maria Beatrice C. Testa 14Renato Cutrera Renato Cutrera 14Salvatore Grosso Salvatore Grosso 15,16Giacomo Lazzeri Giacomo Lazzeri 15,3Enrico Tongiorgi Enrico Tongiorgi 17Pasquale Morano Pasquale Morano 18Matteo Botteghi Matteo Botteghi 19,20Alessandro Barducci Alessandro Barducci 21Claudio De Felice Claudio De Felice 16,2,4*
  • 1 U.O.C. Terapia Intensiva Neonatale, Azienda Ospedaliera Universitaria Senese, Siena, Italy
  • 2 Rett Syndrome Trial Center, University Hospital Azienda Ospedaliera Universitaria Senese, Siena, Italy
  • 3 Siena University Hospital, Siena, Italy
  • 4 U.O.C. Terapia Intensiva Neonatale, Azienda Ospedaliera Universitaria Senese, Siena, Italy, Siena, Tuscany, Italy
  • 5 AccYouRate Group S.p.A., L'Aquila, Italy
  • 6 Child Neuropsychiatry Unit, University Hospital Azienda Ospedaliera Universitaria Senese, Siena, Italy
  • 7 Childhood and Adolescence Neurology and Psychiatry Unit, ASST GOM Niguarda, Milan, Italy
  • 8 Epilepsy Center - Sleep Medicine Center, Childhood and Adolescence Neuropsychiatry Unit, ASST Santi Paolo e Carlo, San Paolo Hospital, Milan, Italy
  • 9 Child Neuropsychiatry Unit, IRCCS Istituto Giannina Gaslini, Genova, Italy
  • 10 Child Neuropsychiatry Unit, IRCCS Istituto Giannina Gaslini,, Genova, Italy
  • 11 Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health (DINOGMI), University of Genova, Genova, Italy
  • 12 Unità di Neurologia e Psichiatria Infantile, Azienda Ospedaliera Universitaria Policlinico G.Martino, Messina, Italy
  • 13 Dipartimento di Scienze Biomediche, Odontoiatriche, Morfologiche e Funzionali per Immagini, Università degli Studi di Messina, Messina, Sicily, Italy
  • 14 Pneumology and Cystic Fibrosis Unit, Academic Department of Pediatrics, Bambino Gesù Children’s Hospital, Rome, Sicily, Italy
  • 15 Department of Molecular and Developmental Medicine, University of Siena, Siena, Tuscany, Italy
  • 16 Pediatrics Unit, University Hospital Azienda Ospedaliera Universitaria Senese, Siena, Italy
  • 17 Department of Life Sciences, University of Trieste, Trieste, Italy
  • 18 Croce Rossa Italiana, Roma, Italy
  • 19 Dipartimento di Scienze Cliniche e Molecolari, Facoltà di Medicina e Chirurgia, Università Politecnica delle Marche, Ancona, Marche, Italy
  • 20 Medical Physics Activities Coordination Centre, University of Bologna, Bologna, Emilia-Romagna, Italy
  • 21 Italian Color Solutions I.C.S. S.r.l.,, Pistoia, Italy

The final, formatted version of the article will be published soon.

    Background: Sleep is disturbed in Rett syndrome (RTT), a rare and progressive neurodevelopmental disorder primarily affecting females (prevalence 7.1/100,000 females) linked to pathogenic variations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene. Autonomic nervous system dysfunction, with a predominance of the sympathetic nervous system (SNS) over the parasympathetic nervous system (PSNS) is reported in RTT, along with exercise fatigue, and increased sudden death risk. Aim of the present study was to test the feasibility of a continuous 24h noninvasive home monitoring of the biological vitals (biovitals) by an innovative wearable sensor device in pediatric and adolescent/adult RTT patients. Methods: A total of 10 female patients (mean age 18.3±9.4 years, range 4.7–35.5 years) with typical RTT and MECP2 pathogenic variations were enrolled. Clinical severity was assessed by validated scales. Heart rate (HR), respiratory rate (RR), and skin temperature (SkT) were monitored by the YOUCARE Wearable Medical Device (Accyourate Group SpA, L’Aquila, Italy). The average percentage of maximum HR (HRmax%) was calculated. Heart Rate Variability (HRV) was expressed by consolidated time-domain and frequency-domain parameters. The HR/LF (low frequency) ratio, indicating SNS activation under dynamic exercise, was calculated. Simultaneous continuous measurement of indoor air quality variables was performed, and the patients’ contributions to the surrounding water vapor partial pressure [PH2O (pt)] and carbon dioxide [PCO2 (pt)] were indirectly estimated. Results: Of 6,559.79 hours of biovital recordings, 5051.03 hours (77%) were valid for data interpretation. Sleep and wake hours were 9.0±1.1 hours and 14.9±1.1 hours, respectively. HRmax % [median: 71.86% (interquartile range 61.03-82%)] and HR/LF [median: 3.75 (interquartile range 3.19-5.05)] were elevated, independent from the wake-sleep cycle. The majority of HRV time- and frequency-domain parameters were significantly higher in the pediatric patients (p≤0.031). The HRV HR/LF ratio was associated with phenotype severity, disease progression, clinical sleep disorder, subclinical hypoxia, and electroencephalographic observations of multifocal epileptic activity and general background slowing. Conclusion: Our findings indicate the feasibility of a continuous 24-hour noninvasive home monitoring of biovital parameters in RTT. Moreover, for the first time, HRmax% and the HR/LF ratio were identified as potential objective markers of fatigue, illness severity and disease progression.

    Keywords: Rett Syndrome, Cardiorespiratory monitoring, wearable devices, sleep-wake cycle, Exercise fatigue

    Received: 19 Feb 2024; Accepted: 13 May 2024.

    Copyright: © 2024 Leoncini, Boasiako, Di Lucia, Beker, Scandurra, Vignoli, Canevini, Prato, Nobili, Nicotera, Di Rosa, Testa, Cutrera, Grosso, Lazzeri, Tongiorgi, Morano, Botteghi, Barducci and De Felice. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Silvia Leoncini, U.O.C. Terapia Intensiva Neonatale, Azienda Ospedaliera Universitaria Senese, Siena, Italy
    Claudio De Felice, U.O.C. Terapia Intensiva Neonatale, Azienda Ospedaliera Universitaria Senese, Siena, Italy, Siena, Tuscany, Italy

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