Editorial Material
Clinical Neurology
Laura Lazzarini Wo, Reem Itani, Thomas G. Keens, Araz Marachelian, Jianling Ji, Iris A. Perez
Summary: Congenital central hypoventilation syndrome (CCHS) is a rare condition caused by pathogenic variants of the PHOX2B gene. There have been case reports describing variable phenotypes and mutations of the PHOX2B gene, not commonly tested for, that may challenge the classic definition of CCHS. Our cases highlight the dilemmas in making a diagnosis of CCHS and emphasize the need for expanded genetic testing, including for PHOX2B gene deletion.
JOURNAL OF CLINICAL SLEEP MEDICINE
(2023)
Article
Clinical Neurology
Ajay S. Kasi, Hong Li, Taryn J. Jurgensen, Lokesh Guglani, Thomas G. Keens, Iris A. Perez
Summary: Patients with CCHS PHOX2B NPARM exhibit variable phenotypes, highlighting the importance of individualized care plans for each patient. The type of NPARM and their location on the PHOX2B gene may play a critical role in determining the severity of phenotypes displayed by each patient.
JOURNAL OF CLINICAL SLEEP MEDICINE
(2021)
Review
Neurosciences
Simona Di Lascio, Roberta Benfante, Silvia Cardani, Diego Fornasari
Summary: Congenital central hypoventilation syndrome (CCHS) is a rare genetic disorder caused by heterozygous mutations in the PHOX2B gene, leading to hypoventilation due to autonomic control failure. The underlying pathogenetic mechanism is still unclear, and there is currently no curative treatment for CCHS.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Reihaneh Khorasanian, Marzieh Mojbafan, Nastaran Khosravi
Summary: Congenital central hypoventilation syndrome (CCHS) is a rare genetic disorder caused by mutations in the PHOX2B gene. The genetic analysis of a one-month-old CCHS baby girl in Iran revealed a heterozygous duplication in exon 3, resulting in a polyalanine repeat expansion to 27 repeats. The mutation was found to be pathogenic and a denovo mutation in the family, with potential implications for prenatal or pre-implantation diagnosis.
MOLECULAR BIOLOGY REPORTS
(2021)
Article
Pediatrics
Federica Porcaro, Maria Giovanna Paglietti, Claudio Cherchi, Alessandra Schiavino, Maria Beatrice Chiarini Testa, Renato Cutrera
Summary: CCHS patients with more severe phenotypes are associated with a higher number of polyalanine repetitions or non-polyalanine repeat expansion mutations. Although invasive ventilation is often required, advancements in management skills and technology have improved therapeutic approaches for this population.
FRONTIERS IN PEDIATRICS
(2021)
Article
Clinical Neurology
Diego Alzate-Correa, Jillian Mei-ling Liu, Mikayla Jones, Talita M. Silva, Michele Joana Alves, Elizabeth Burke, Jessica Zuniga, Behiye Kaya, Giuliana Zaza, Mehmet Tahir Aslan, Jessica Blackburn, Marina Y. Shimada, Silvio A. Fernandes-Junior, Lisa A. Baer, Kristin Stanford, Amber Kempton, Sakima Smith, Caroline C. Szujewski, Abby Silbaugh, Jean-Charles Viemari, Ana C. Takakura, Alfredo J. Garcia, Thiago S. Moreira, Catherine M. Czeisler, Jose J. Otero
Summary: The mutated Phox2b protein expression in neurons is associated with apneic episodes in CCHS patients shortly after birth, possibly due to disruptions in visceral motor neuron development.
Article
Pediatrics
Irina N. Artamonova, Anna M. Zlotina, Olga R. Ismagilova, Tatyana A. Levko, Natalia Yu Kolbina, Aleksandr V. Bryzzhin, Andrey P. Smorodin, Alexandr V. Borodin, Ekaterina A. Mamaeva, Anna A. Sukhotskaya, Ilya M. Kagantsov, Daria A. Malysheva, Elena S. Vasichkina, Tatiana M. Pervunina, Natalia A. Petrova
Summary: This article describes a clinical case of a girl with a PHOX2B heterozygous genetic variant, causing congenital central hypoventilation syndrome (CCHS). The girl has a unique phenotype, requiring respiratory support and having several other associated conditions. This study is important for expanding the understanding of the molecular mechanisms and genotype-phenotype correlations of CCHS.
FRONTIERS IN PEDIATRICS
(2023)
Article
Clinical Neurology
Jacob McCoy, Natalya Karp, Jagraj Brar, Reshma Amin, Aaron St-Laurent
Summary: With the increasing prevalence of obesity in children, the number of severe complications associated with it is also on the rise. Obesity hypoventilation syndrome is a rare disorder characterized by altered respiratory mechanics, sleep-disordered breathing, and impaired ventilatory responses leading to persistent hypercapnia in children. There is growing knowledge about the potential genetic contributors to this syndrome, including the paired-like homeobox 2B gene and the brain-derived neurotrophic factor gene. We report a case of obesity hypoventilation syndrome in pediatrics, possibly related to a congenital predisposition for central hypoventilation caused by a deletion in the brain-derived neurotrophic factor gene.
JOURNAL OF CLINICAL SLEEP MEDICINE
(2022)
Article
Pediatrics
Prakarn Tovichien, Krittin Rattananont, Narathorn Kulthamrongsri, Mongkol Chanvanichtrakool, Buranee Yangthara
Summary: This report presents a case of neonatal CCHS and describes the diagnostic work up in a resource-limited setting. The diagnosis of CCHS was confirmed through genetic testing, and respiratory care training was provided to the patient's caregivers.
Article
Medicine, General & Internal
Emily R. Ribeiro, Floyd Livingston, Madelyn Kahana, Robert Smith
Summary: CCHS, caused by a genetic mutation in the PHOX2B gene, results in profound hypoventilation most prominent during sleep. LO-CCHS, a late-onset form of the syndrome, presents in a dramatic fashion, with unclear reasons for its late onset.
CUREUS JOURNAL OF MEDICAL SCIENCE
(2021)
Review
Pediatrics
Mei Mei, Lin Yang, Yulan Lu, Laishuan Wang, Guoqiang Cheng, Yun Cao, Chao Chen, Liling Qian, Wenhao Zhou
Summary: This study retrospectively analyzed 60 cases of neonatal-onset CCHS, providing data on clinical and genetic features. Severe hypoventilation and HSCR were frequently observed in this group, with NPARMs accounting for half of the cohort and showing tendencies towards mild phenotypes. Molecular testing and genetic counseling for CCHS families are highly recommended based on the results.
TRANSLATIONAL PEDIATRICS
(2021)
Review
Clinical Neurology
Susan M. Slattery, Iris A. Perez, Isabella Ceccherini, Maida L. Chen, Kyle C. Kurek, Kai Lee Yap, Thomas G. Keens, Ilya Khaytin, Heather A. Ballard, Elizabeth A. Sokol, Angeli Mittal, Casey M. Rand, Debra E. Weese-Mayer
Summary: This review summarizes key clinical and management considerations for patients with CCHS and LO-CCHS and provides guidance for transitional care areas. The lack of experience and evidence in the care of adults with CCHS and LO-CCHS is addressed through a review of the relevant literature and expert consensus.
CLINICAL AUTONOMIC RESEARCH
(2023)
Article
Pediatrics
Kanokkarn Sunkonkit, Jackie Chiang, Theo J. Moraes, William To, Jane E. Schneiderman, Barbara Cifra, Reshma Amin
Summary: This study described longitudinal CPET findings in children with CCHS and found that none of the children experienced oxygen desaturation below 90%, while hypercapnia was the most common abnormality. End-tidal CO2 (PetCO2) at rest and at peak exercise in CPETs were significantly correlated with PSG TcCO2.
PEDIATRIC PULMONOLOGY
(2021)
Review
Clinical Neurology
Antoon Meylemans, Pieter Depuydt, Elfride De Baere, Katrien Hertegonne, Eric Derom, Bart Dermaut, Dimitri Hemelsoet
Summary: Central hypoventilation in adult patients is a rare and life-threatening condition that can be caused by brainstem lesions or primary diseases. CCHS is a rare genetic cause of central hypoventilation and requires genetic analysis for confirmation.
ACTA NEUROLOGICA BELGICA
(2021)
Article
Clinical Neurology
Ashley Kwon, Madison Lodge, J. Gordon McComb, Susan Durham, Cathy E. Shin, Thomas G. Keens, Iris A. Perez
Summary: This case report describes a 38-year-old female with congenital central hypoventilation syndrome who experienced diaphragm pacing (DP) failure due to calcification of the right pacer. Surgical replacement of the receivers closer to the skin surface resulted in improved diaphragm contractions bilaterally.
JOURNAL OF CLINICAL SLEEP MEDICINE
(2022)
Article
Multidisciplinary Sciences
Luis Rodrigo Hernandez-Miranda, Daniel M. Ibrahim, Pierre-Louis Ruffault, Madeleine Larrosa, Kira Balueva, Thomas Mueller, Willemien de Weerd, Irene Stolte-Dijkstra, Robert M. W. Hostra, Jean-Francois Brunet, Gilles Fortin, Stefan Mundlos, Carmen Birchmeier
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2018)
Article
Anesthesiology
Thomas Bourgeois, Maud Ringot, Nelina Ramanantsoa, Boris Matrot, Stephan Dauger, Christophe Delclaux, Jorge Gallego
Article
Multidisciplinary Sciences
Ruslan Soldatov, Marketa Kaucka, Maria Eleni Kastriti, Julian Petersen, Tatiana Chontorotzea, Lukas Englmaier, Natalia Akkuratova, Yunshi Yang, Martin Haring, Viacheslav Dyachuk, Christoph Bock, Matthias Farlik, Michael L. Piacentino, Franck Boismoreau, Markus M. Hilscher, Chika Yokota, Xiaoyan Qian, Mats Nilsson, Marianne E. Bronner, Laura Croci, Wen-Yu Hsiao, David A. Guertin, Jean-Francois Brunet, Gian Giacomo Consalez, Patrik Ernfors, Kaj Fried, Peter V. Kharchenko, Igor Adameyko
Article
Developmental Biology
Charlotte Chaimowicz, Pierre-Louis Ruffault, Cyril Cheret, Andrew Woehler, Niccolo Zampieri, Gilles Fortin, Alistair N. Garratt, Carmen Birchmeier
Review
Neurosciences
Agathe Duchateau, Aurelie de Thonel, Rachid El Fatimy, Veronique Dubreuil, Valerie Mezger
NEUROSCIENCE LETTERS
(2020)
Article
Biochemistry & Molecular Biology
Ichrak Drissi, Chloe Deschamps, Rachel Alary, Alexandre Robert, Veronique Dubreuil, Anne Le Mouel, Myriame Mohammed, Delara Saberan-Djoneidi, Valerie Mezger, Mickael Naassila, Olivier Pierrefiche
Summary: Ethanol consumption impairs learning and memory by disrupting NMDA receptor-dependent synaptic plasticity in the hippocampus. This study demonstrates that the stress-responsive transcription factor HSF2 plays a key role in regulating glutamatergic neurotransmission and LTD plasticity. Furthermore, HSF2 is also involved in mediating ethanol-induced neuroadaptations in the hippocampus network after chronic ethanol intake.
Article
Biology
Coralie Herent, Severine Diem, Gilles Fortin, Julien Bouvier
Article
Critical Care Medicine
Amelia Madani, Gabriel Pitollat, Eleonore Sizun, Laura Cardoit, Maud Ringot, Thomas Bourgeois, Nelina Ramanantsoa, Christophe Delclaux, Stephane Dauger, Marie-Pia D'ortho, Muriel Thoby-Brisson, Jorge Gallego, Boris Matrot
Summary: Phox2b(27Ala/+) mutation in mice predisposes them to not only hypoventilation and central apneas, but also obstructive and mixed apneas, likely due to hypoglossal dysgenesis. These findings highlight the importance of paying attention to obstructive events in infants with CCHS.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2021)
Article
Neurosciences
Xin Paul Wei, Matthew Collie, Bowen Dempsey, Gilles Fortin, Kevin Yackle
Summary: Human speech and the vocalizations of other species are rhythmic. The cellular and molecular mechanisms that regulate the tempo of mammalian vocalizations are still unknown. A brainstem node called the intermediate reticular oscillator (iRO) has been identified to play a crucial role in structuring neonatal vocalizations by autonomously controlling key muscles and the respiratory rhythm generator.
Article
Multidisciplinary Sciences
Bowen Dempsey, Selvee Sungeelee, Phillip Bokiniec, Zoubida Chettouh, Severine Diem, Sandra Autran, Evan R. Harrell, James F. A. Poulet, Carmen Birchmeier, Harry Carey, Auguste Genovesio, Simon McMullan, Christo Goridis, Gilles Fortin, Jean-Francois Brunet
Summary: The study uncovers two nuclei, IRt(Phox2b) and Peri5(Atoh1), in the brainstem of mice that can organize the movements for ingesting fluids. These neuronal groups pre-motor all jaw-opening and tongue muscles, revealing one of the subcortical nuclei underpinning a stereotyped feeding behavior.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Dounia Ben Amar, Karine Thoinet, Benjamin Villalard, Olivier Imbaud, Clelia Costechareyre, Loraine Jarrosson, Florie Reynaud, Julia Novion Ducassou, Yohann Coute, Jean-Francois Brunet, Valerie Combaret, Nadege Corradini, Celine Delloye-Bourgeois, Valerie Castellani
Summary: Using experimental models mimicking the embryonic context and proteomic/transcriptomic analyses, this study demonstrates that signals released by embryonic sympathetic ganglia can induce the transformation of neuroblastoma cells and activate gene programs promoting metastasis.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Maria Eleni Kastriti, Louis Faure, Dorothea Von Ahsen, Thibault Gerald Bouderlique, Johan Bostroem, Tatiana Solovieva, Cameron Jackson, Marianne Bronner, Dies Meijer, Saida Hadjab, Francois Lallemend, Alek Erickson, Marketa Kaucka, Viacheslav Dyachuk, Thomas Perlmann, Laura Lahti, Jan Krivanek, Jean-Francois Brunet, Kaj Fried, Igor Adameyko
Summary: The study reveals the similarities between Schwann cell precursors (SCPs) and neural crest cells in terms of transcriptional profiles and cell fate. SCPs diverge from neural crest cells during lineage differentiation. Defects in SCPs may affect neural crest cells along peripheral nerves and are associated with certain tumor development.
Article
Multidisciplinary Sciences
Laure Lecoin, Bowen Dempsey, Alexandra Garancher, Steeve Bourane, Pierre-Louis Ruffault, Marie-Pierre Morin-Surun, Nathalie Rocques, Martyn Goulding, Alain Eychene, Celio Pouponnot, Gilles Fortin, Jean Champagnat
Summary: Apneas are associated with various pathological and fatal conditions. This study shows that a mutation in the transcription factor Mafa leads to an abnormally high incidence of breath holding apneas and death in newborn mice. The mutation affects GABAergic inhibitory neurons, causing decreased motor drive to muscles controlling the airways.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Aurelie de Thonel, Johanna K. Ahlskog, Kevin Daupin, Veronique Dubreuil, Jeremy Berthelet, Carole Chaput, Geoffrey Pires, Camille Leonetti, Ryma Abane, Lluis Cordon Barris, Isabelle Leray, Anna L. Aalto, Sarah Naceri, Marine Cordonnier, Carene Benasolo, Matthieu Sanial, Agathe Duchateau, Anniina Vihervaara, Mikael C. Puustinen, Federico Miozzo, Patricia Fergelot, Elise Lebigot, Alain Verloes, Pierre Gressens, Didier Lacombe, Jessica Gobbo, Carmen Garrido, Sandy D. Westerheide, Laurent David, Michel Petitjean, Olivier Taboureau, Fernando Rodrigues-Lima, Sandrine Passemard, Delara Saberan-Djoneidi, Laurent Nguyen, Madeline Lancaster, Lea Sistonen, Valerie Mezger
Summary: This study reveals the contribution of a stress-responsive pathway to Rubinstein-Taybi syndrome (RSTS), indicating that impaired HSF2 acetylation due to RSTS-associated CBP/EP300 mutations alters the expression of neurodevelopmental players, leading to cell-cell adhesion defects.
NATURE COMMUNICATIONS
(2022)
Article
Physiology
Alyssa R. Mickle, Jesus D. Penaloza-Aponte, Richard Coffey, Natale A. Hall, David Baekey, Erica A. Dale
Summary: Closed-loop epidural stimulation (CL-ES) can improve respiratory deficits caused by cervical spinal cord injury, restoring diaphragm activity and enhancing contralateral activity. This treatment has the potential to lead to lasting recovery and device independence.
RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY
(2024)
Article
Physiology
Shawn Miller Jr, Edgar Juarez Lopez, Jessica M. L. Grittner, Brendan J. Dougherty
Summary: This study tested the impact of CO2 supplementation at different concentrations on ventilatory long-term facilitation (vLTF) in rats and found that 2% CO2 supplementation during and after acute, intermittent hypoxia (AIH) was sufficient to maintain isocapnia and induce significant vLTF.
RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY
(2024)
Article
Physiology
Behnam Vafadari, Yoshitaka Oku, Charlotte Tacke, Ali Harb, Swen Huelsmann
Summary: The preBo·tzinger Complex (preBo·tC) in the brainstem plays a critical role in generating respiratory rhythm. This study aimed to investigate the activity of inhibitory glycinergic neurons in the preBo·tC of anesthetized mice. Using juxtacellular recordings and optogenetic activation, the researchers were able to identify and characterize the activity pattern of these inhibitory neurons in relation to the breathing rhythm.
RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY
(2024)
Article
Physiology
Stephen M. Johnson, Maia G. Gumnit, Sarah M. Johnson, Tracy L. Baker, Jyoti J. Watters
Summary: Low-level activation of mu-opioid receptors can increase the amplitude of inspiratory bursts in neonatal rat brainstem-spinal cord preparations. Endomorphin-2, an endogenous ligand for these receptors, was found to have similar effects. Disinhibition of inhibitory synaptic transmission may not be involved in the changes induced by endomorphin-2, and different mechanisms may underlie the increase in burst amplitude and decrease in burst frequency.
RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY
(2024)
Article
Physiology
Raphael Martins de Abreu, Beatrice Cairo, Patricia Rehder-Santos, Claudio Donisete da Silva, Etore De Favari Signini, Juliana Cristina Milan-Mattos, Camila Akemi Sakaguchi, Aparecida Maria Catai, Alberto Porta
Summary: The purpose of this study was to determine the association between exercise capacity based on peak oxygen uptake (VO2peak) and resting cardiorespiratory coupling (CRC) levels. The results showed that resting CRC values were associated with exercise capacity in athletes but not in non-athletes.
RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY
(2024)
Article
Physiology
Sarah M. Russel, Raluca E. Gosman, Katherine Gonzalez, Joshua Wright, Dennis O. Frank-Ito
Summary: This study aimed to characterize the response of different nasal morphologies to airflow-related variables during rapid/deep inspiration. The results showed that notched nasal vestibules had higher resistance values and airflow velocities, while standard nasal vestibules had higher mucosal heat flux. Different nasal phenotypes may predispose individuals to exercise-induced rhinitis.
RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY
(2024)
Article
Physiology
Ivan Poliacek, Lukas Martvon, Michal Simera, Marcel Veternik, Jakub Misek, Lucia Cibulkova, Kimberly E. Iceman, Donald C. Bolser, Teresa Pitts
Summary: An animal model study evaluated the effects of an abdominal incision on cough and swallow, revealing that abdominal wall manipulations can increase pharyngeal muscle activity during swallow without affecting the cough reflex. Swallowing tended to occur more during the inspiratory phase. The results highlight the important role of abdominal wall sensory feedback in regulating swallow motor patterns.
RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY
(2024)
Article
Physiology
Rui Yu, Tatsuma Okazaki, Yuzhuo Ren, Junko Okuyama, Satoru Ebihara, Shin-Ichi Izumi
Summary: Body postures significantly influence respiratory muscle force, cough pressure, subjective ease of coughing, and pulmonary function. The 60-degree semi-recumbent posture and sitting posture show better results compared to the supine posture.
RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY
(2024)
Article
Physiology
Suzuna Sato, Koji Ishida, Noriko I. Tanaka, Keisho Katayama
Summary: Respiratory muscle endurance training has beneficial effects on whole-body endurance performance. A novel high-intensity interval (HII) protocol is found to enhance the efficacy of respiratory muscle training programs.
RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY
(2024)
Letter
Physiology
R. Arieli
RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY
(2024)
Correction
Physiology
Ivan Poliacek, Michal Simera, Marcel Veternik, Zuzana Kotmanova, Teresa Pitts, Jan Hanacek, Jana Plevkova, Peter Machac, Nadezda Visnovcova, Jakub Misek, Jan Jakus
RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY
(2024)
Article
Physiology
Dimitrios I. Bourdas, Nickos D. Geladas
Summary: This study examined the effects of breath-hold training on the performance of novice and elite breath-hold divers. The results showed that breath-hold training significantly improved red blood cell concentration, hemoglobin oxygen saturation steady state duration, and breath-hold time in novice divers. Elite divers had better breath-hold performance and higher peak mean arterial pressure compared to novices. The study suggests that breath-hold training can enhance the performance of divers.
RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY
(2024)