17 recherche sur le mot-clé 'Severity of Illness Index'

Asymmetry of fusiform structure in autism spectrum disorder: trajectory and association with symptom severity / Chase C. DOUGHERTY in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 28p. Titre : Asymmetry of fusiform structure in autism spectrum disorder: trajectory and association with symptom severity Type de document : texte imprimé Auteurs : Chase C. DOUGHERTY, Auteur ; David W. EVANS, Auteur ; Gajendra J. KATUWAL, Auteur ; Andrew M. MICHAEL, Auteur Article en page(s) : 28p. Langues : Anglais (eng) Mots-clés : Adolescent  Adult  Algorithms  Autism Spectrum Disorder/diagnostic imaging/pathology  Child  Cross-Sectional Studies  Humans  Image Processing, Computer-Assisted  Magnetic Resonance Imaging  Male  Severity of Illness Index  Temporal Lobe/anatomy & histology  Young Adult  Asymmetry  Autism spectrum disorder  Development  Fusiform gyrus  Structural imaging Index. décimale : PER Périodiques Résumé : BACKGROUND: While asymmetry in the fusiform gyrus (FFG) has been reported in functional and structural studies in typically developing controls (TDC), few studies have examined FFG asymmetry in autism spectrum disorder (ASD) subjects and those studies are limited by small sample sizes, and confounded by cognitive ability or handedness. No previous work has examined FFG surface area or cortical thickness asymmetry in ASD; nor do we understand the trajectory of FFG asymmetry over time. Finally, it is not known how FFG structural asymmetry relates to ASD symptom severity. METHODS: In this study, we examined FFG volume, surface area, and cortical thickness asymmetry, as well as their cross-sectional trajectories in a large sample of right-handed males aged 7 to 25 years with 128 ASD and 127 TDC subjects using general linear models. In addition, we examined the relationship between FFG asymmetry and ASD severity using the Autism Diagnostic Observation Schedule (ADOS) and Gotham autism severity scores. RESULTS: Findings revealed that while group differences were evident with mean leftward asymmetry in ASD and mean near symmetry in TDC volume and surface area, asymmetry for both groups existed on a spectrum encompassing leftward and rightward asymmetry. In ASD subjects, volume asymmetry was negatively associated with ADOS and autism severity score symptom measures, with a subset of rightward asymmetric patients being most severely affected. We also observed differential trajectory of surface area asymmetry: ASD subjects exhibited a change from leftward asymmetry toward symmetry from age 7 to 25, whereas TDCs exhibited the reverse trend with a change from near symmetry toward leftward symmetry over the observed age range. CONCLUSIONS: Abnormalities in FFG structural asymmetry are related to symptom severity in ASD and show differential developmental trajectory compared to TDC. This study is the first to note these findings. These results may have important implications for understanding the role of FFG asymmetry in ASD. En ligne : http://dx.doi.org/10.1186/s13229-016-0089-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328 [article] Asymmetry of fusiform structure in autism spectrum disorder: trajectory and association with symptom severity [texte imprimé] / Chase C. DOUGHERTY, Auteur ; David W. EVANS, Auteur ; Gajendra J. KATUWAL, Auteur ; Andrew M. MICHAEL, Auteur . - 28p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 28p. Mots-clés : Adolescent  Adult  Algorithms  Autism Spectrum Disorder/diagnostic imaging/pathology  Child  Cross-Sectional Studies  Humans  Image Processing, Computer-Assisted  Magnetic Resonance Imaging  Male  Severity of Illness Index  Temporal Lobe/anatomy & histology  Young Adult  Asymmetry  Autism spectrum disorder  Development  Fusiform gyrus  Structural imaging Index. décimale : PER Périodiques Résumé : BACKGROUND: While asymmetry in the fusiform gyrus (FFG) has been reported in functional and structural studies in typically developing controls (TDC), few studies have examined FFG asymmetry in autism spectrum disorder (ASD) subjects and those studies are limited by small sample sizes, and confounded by cognitive ability or handedness. No previous work has examined FFG surface area or cortical thickness asymmetry in ASD; nor do we understand the trajectory of FFG asymmetry over time. Finally, it is not known how FFG structural asymmetry relates to ASD symptom severity. METHODS: In this study, we examined FFG volume, surface area, and cortical thickness asymmetry, as well as their cross-sectional trajectories in a large sample of right-handed males aged 7 to 25 years with 128 ASD and 127 TDC subjects using general linear models. In addition, we examined the relationship between FFG asymmetry and ASD severity using the Autism Diagnostic Observation Schedule (ADOS) and Gotham autism severity scores. RESULTS: Findings revealed that while group differences were evident with mean leftward asymmetry in ASD and mean near symmetry in TDC volume and surface area, asymmetry for both groups existed on a spectrum encompassing leftward and rightward asymmetry. In ASD subjects, volume asymmetry was negatively associated with ADOS and autism severity score symptom measures, with a subset of rightward asymmetric patients being most severely affected. We also observed differential trajectory of surface area asymmetry: ASD subjects exhibited a change from leftward asymmetry toward symmetry from age 7 to 25, whereas TDCs exhibited the reverse trend with a change from near symmetry toward leftward symmetry over the observed age range. CONCLUSIONS: Abnormalities in FFG structural asymmetry are related to symptom severity in ASD and show differential developmental trajectory compared to TDC. This study is the first to note these findings. These results may have important implications for understanding the role of FFG asymmetry in ASD. En ligne : http://dx.doi.org/10.1186/s13229-016-0089-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328

Embryonic origin of two ASD subtypes of social symptom severity: the larger the brain cortical organoid size, the more severe the social symptoms / Eric COURCHESNE in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 22p. Titre : Embryonic origin of two ASD subtypes of social symptom severity: the larger the brain cortical organoid size, the more severe the social symptoms Type de document : texte imprimé Auteurs : Eric COURCHESNE, Auteur ; Vani TALUJA, Auteur ; Sanaz NAZARI, Auteur ; Caitlin M. AAMODT, Auteur ; Karen PIERCE, Auteur ; Kuaikuai DUAN, Auteur ; Sunny STOPHAEROS, Auteur ; Linda LOPEZ, Auteur ; Cynthia CARTER BARNES, Auteur ; Jaden TROXEL, Auteur ; Kathleen CAMPBELL, Auteur ; Tianyun WANG, Auteur ; Kendra HOEKZEMA, Auteur ; Evan E. EICHLER, Auteur ; Joao V. NANI, Auteur ; Wirla PONTES, Auteur ; Sandra S. SANCHEZ, Auteur ; Michael V. LOMBARDO, Auteur ; Janaina S. DE SOUZA, Auteur ; Mirian A.F. HAYASHI, Auteur ; Alysson R. MUOTRI, Auteur Article en page(s) : 22p. Langues : Anglais (eng) Mots-clés : Humans  Autism Spectrum Disorder/pathology/physiopathology  Organoids/pathology  Male  Female  Child, Preschool  Cerebral Cortex/pathology  Social Behavior  Organ Size  Infant  Severity of Illness Index  Brain/pathology Index. décimale : PER Périodiques Résumé : BACKGROUND: Social affective and communication symptoms are central to autism spectrum disorder (ASD), yet their severity differs across toddlers: Some toddlers with ASD display improving abilities across early ages and develop good social and language skills, while others with "profound" autism have persistently low social, language and cognitive skills and require lifelong care. The biological origins of these opposite ASD social severity subtypes and developmental trajectories are not known. METHODS: Because ASD involves early brain overgrowth and excess neurons, we measured size and growth in 4910 embryonic-stage brain cortical organoids (BCOs) from a total of 10 toddlers with ASD and 6 controls (averaging 196 individual BCOs measured/subject). In a 2021 batch, we measured BCOs from 10 ASD and 5 controls. In a 2022 batch, we  tested replicability of BCO size and growth effects by generating and measuring an independent batch of BCOs from 6 ASD and 4 control subjects. BCO size was analyzed within the context of our large, one-of-a-kind social symptom, social attention, social brain and social and language psychometric normative datasets ranging from N = 266 to N = 1902 toddlers. BCO growth rates were examined by measuring size changes between 1- and 2-months of organoid development. Neurogenesis markers at 2-months were examined at the cellular level. At the molecular level, we measured activity and expression of Ndel1; Ndel1 is a prime target for cell cycle-activated kinases; known to regulate cell cycle, proliferation, neurogenesis, and growth; and known to be involved in neuropsychiatric conditions. RESULTS: At the BCO level, analyses showed BCO size was significantly enlarged by 39% and 41% in ASD in the 2021 and 2022 batches. The larger the embryonic BCO size, the more severe the ASD social symptoms. Correlations between BCO size and social symptoms were r = 0.719 in the 2021 batch and r = 0. 873 in the replication 2022 batch. ASD BCOs grew at an accelerated rate nearly 3 times faster than controls. At the cell level, the two largest ASD BCOs had accelerated neurogenesis. At the molecular level, Ndel1 activity was highly correlated with the growth rate and size of BCOs. Two BCO subtypes were found in ASD toddlers: Those in one subtype had very enlarged BCO size with accelerated rate of growth and neurogenesis; a profound autism clinical phenotype displaying severe social symptoms, reduced social attention, reduced cognitive, very low language and social IQ; and substantially altered growth in specific cortical social, language and sensory regions. Those in a second subtype had milder BCO enlargement and milder social, attention, cognitive, language and cortical differences. LIMITATIONS: Larger samples of ASD toddler-derived BCO and clinical phenotypes may reveal additional ASD embryonic subtypes. CONCLUSIONS: By embryogenesis, the biological bases of two subtypes of ASD social and brain development-profound autism and mild autism-are already present and measurable and involve dysregulated cell proliferation and accelerated neurogenesis and growth. The larger the embryonic BCO size in ASD, the more severe the toddler's social symptoms and the more reduced the social attention, language ability, and IQ, and the more atypical the growth of social and language brain regions. En ligne : https://dx.doi.org/10.1186/s13229-024-00602-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Embryonic origin of two ASD subtypes of social symptom severity: the larger the brain cortical organoid size, the more severe the social symptoms [texte imprimé] / Eric COURCHESNE, Auteur ; Vani TALUJA, Auteur ; Sanaz NAZARI, Auteur ; Caitlin M. AAMODT, Auteur ; Karen PIERCE, Auteur ; Kuaikuai DUAN, Auteur ; Sunny STOPHAEROS, Auteur ; Linda LOPEZ, Auteur ; Cynthia CARTER BARNES, Auteur ; Jaden TROXEL, Auteur ; Kathleen CAMPBELL, Auteur ; Tianyun WANG, Auteur ; Kendra HOEKZEMA, Auteur ; Evan E. EICHLER, Auteur ; Joao V. NANI, Auteur ; Wirla PONTES, Auteur ; Sandra S. SANCHEZ, Auteur ; Michael V. LOMBARDO, Auteur ; Janaina S. DE SOUZA, Auteur ; Mirian A.F. HAYASHI, Auteur ; Alysson R. MUOTRI, Auteur . - 22p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 22p. Mots-clés : Humans  Autism Spectrum Disorder/pathology/physiopathology  Organoids/pathology  Male  Female  Child, Preschool  Cerebral Cortex/pathology  Social Behavior  Organ Size  Infant  Severity of Illness Index  Brain/pathology Index. décimale : PER Périodiques Résumé : BACKGROUND: Social affective and communication symptoms are central to autism spectrum disorder (ASD), yet their severity differs across toddlers: Some toddlers with ASD display improving abilities across early ages and develop good social and language skills, while others with "profound" autism have persistently low social, language and cognitive skills and require lifelong care. The biological origins of these opposite ASD social severity subtypes and developmental trajectories are not known. METHODS: Because ASD involves early brain overgrowth and excess neurons, we measured size and growth in 4910 embryonic-stage brain cortical organoids (BCOs) from a total of 10 toddlers with ASD and 6 controls (averaging 196 individual BCOs measured/subject). In a 2021 batch, we measured BCOs from 10 ASD and 5 controls. In a 2022 batch, we  tested replicability of BCO size and growth effects by generating and measuring an independent batch of BCOs from 6 ASD and 4 control subjects. BCO size was analyzed within the context of our large, one-of-a-kind social symptom, social attention, social brain and social and language psychometric normative datasets ranging from N = 266 to N = 1902 toddlers. BCO growth rates were examined by measuring size changes between 1- and 2-months of organoid development. Neurogenesis markers at 2-months were examined at the cellular level. At the molecular level, we measured activity and expression of Ndel1; Ndel1 is a prime target for cell cycle-activated kinases; known to regulate cell cycle, proliferation, neurogenesis, and growth; and known to be involved in neuropsychiatric conditions. RESULTS: At the BCO level, analyses showed BCO size was significantly enlarged by 39% and 41% in ASD in the 2021 and 2022 batches. The larger the embryonic BCO size, the more severe the ASD social symptoms. Correlations between BCO size and social symptoms were r = 0.719 in the 2021 batch and r = 0. 873 in the replication 2022 batch. ASD BCOs grew at an accelerated rate nearly 3 times faster than controls. At the cell level, the two largest ASD BCOs had accelerated neurogenesis. At the molecular level, Ndel1 activity was highly correlated with the growth rate and size of BCOs. Two BCO subtypes were found in ASD toddlers: Those in one subtype had very enlarged BCO size with accelerated rate of growth and neurogenesis; a profound autism clinical phenotype displaying severe social symptoms, reduced social attention, reduced cognitive, very low language and social IQ; and substantially altered growth in specific cortical social, language and sensory regions. Those in a second subtype had milder BCO enlargement and milder social, attention, cognitive, language and cortical differences. LIMITATIONS: Larger samples of ASD toddler-derived BCO and clinical phenotypes may reveal additional ASD embryonic subtypes. CONCLUSIONS: By embryogenesis, the biological bases of two subtypes of ASD social and brain development-profound autism and mild autism-are already present and measurable and involve dysregulated cell proliferation and accelerated neurogenesis and growth. The larger the embryonic BCO size in ASD, the more severe the toddler's social symptoms and the more reduced the social attention, language ability, and IQ, and the more atypical the growth of social and language brain regions. En ligne : https://dx.doi.org/10.1186/s13229-024-00602-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

The effect of anxiety and autism symptom severity on restricted and repetitive behaviors over time in children with fragile X syndrome / Lauren J. MOSKOWITZ in Journal of Neurodevelopmental Disorders, 16 (2024)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 16 (2024) Titre : The effect of anxiety and autism symptom severity on restricted and repetitive behaviors over time in children with fragile X syndrome Type de document : texte imprimé Auteurs : Lauren J. MOSKOWITZ, Auteur ; Elizabeth A. WILL, Auteur ; Conner J. BLACK, Auteur ; Jane E. ROBERTS, Auteur Langues : Anglais (eng) Mots-clés : Humans  Fragile X Syndrome/complications/physiopathology  Male  Female  Child  Autism Spectrum Disorder/complications/physiopathology  Anxiety/etiology  Severity of Illness Index  Longitudinal Studies  Child, Preschool  Stereotyped Behavior/physiology  Adolescent  Comorbidity  Anxiety  Autism  Compulsive behavior  Fragile X syndrome  Restricted interests  Restricted repetitive behaviors  Ritualistic/sameness behavior  Self-injurious behaviors  Sensory-motor behaviors Index. décimale : PER Périodiques Résumé : BACKGROUND: Restricted and repetitive behaviors (RRBs) are highly prevalent and reduce function in individuals with fragile X syndrome (FXS). As transdiagnostic features of intellectual disability, elevated rates of RRBs in FXS could represent various underlying known co-occurring conditions in FXS such as anxiety or autism spectrum disorder (ASD), yet this distinction has not been investigated. Further, delineating whether RRBs are more indicative of anxiety or ASD in FXS may clarify phenotypic profiles within FXS and improve differential assessment. METHODS: We longitudinally examined the potentially independent or multiplicative effect of ASD and anxiety symptom severity on RRBs in 60 children with FXS. Anxiety was measured using the Child Behavior Checklist (CBCL), ASD severity was measured using the Childhood Autism Rating Scale (CARS), and RRBs were measured using the Repetitive Behavior Scale - Revised (RBS-R). We estimated a series of moderated regression models with anxiety and ASD symptoms at the initial assessment (Time 1) as predictors of RRBs at the outcome assessment two years later (Time 2), along with an anxiety-by-ASD interaction term to determine the potential multiplicative effect of these co-occurring conditions on RRBs. RESULTS: Results identified a significant interaction between ASD and anxiety symptom severity at the initial assessment that predicted elevated sensory-motor RRBs two years later. Increased sensory-motor RRBs were predicted by elevated ASD symptoms only when anxiety symptom severity was low. Likewise, increased sensory-motor RRBs were predicted by elevated anxiety symptoms only when ASD symptom severity was low. Interestingly, this relationship was isolated to Sensory-Motor RRBs, with evidence that it could also apply to total RRBs. CONCLUSIONS: Findings suggest that ASD and anxiety exert independent and differential effects on Sensory-Motor RRBs when at high severity levels and a multiplicative effect when at moderate levels, which has important implications for early and targeted interventions. En ligne : https://dx.doi.org/10.1186/s11689-024-09569-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576 [article] The effect of anxiety and autism symptom severity on restricted and repetitive behaviors over time in children with fragile X syndrome [texte imprimé] / Lauren J. MOSKOWITZ, Auteur ; Elizabeth A. WILL, Auteur ; Conner J. BLACK, Auteur ; Jane E. ROBERTS, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 16 (2024) Mots-clés : Humans  Fragile X Syndrome/complications/physiopathology  Male  Female  Child  Autism Spectrum Disorder/complications/physiopathology  Anxiety/etiology  Severity of Illness Index  Longitudinal Studies  Child, Preschool  Stereotyped Behavior/physiology  Adolescent  Comorbidity  Anxiety  Autism  Compulsive behavior  Fragile X syndrome  Restricted interests  Restricted repetitive behaviors  Ritualistic/sameness behavior  Self-injurious behaviors  Sensory-motor behaviors Index. décimale : PER Périodiques Résumé : BACKGROUND: Restricted and repetitive behaviors (RRBs) are highly prevalent and reduce function in individuals with fragile X syndrome (FXS). As transdiagnostic features of intellectual disability, elevated rates of RRBs in FXS could represent various underlying known co-occurring conditions in FXS such as anxiety or autism spectrum disorder (ASD), yet this distinction has not been investigated. Further, delineating whether RRBs are more indicative of anxiety or ASD in FXS may clarify phenotypic profiles within FXS and improve differential assessment. METHODS: We longitudinally examined the potentially independent or multiplicative effect of ASD and anxiety symptom severity on RRBs in 60 children with FXS. Anxiety was measured using the Child Behavior Checklist (CBCL), ASD severity was measured using the Childhood Autism Rating Scale (CARS), and RRBs were measured using the Repetitive Behavior Scale - Revised (RBS-R). We estimated a series of moderated regression models with anxiety and ASD symptoms at the initial assessment (Time 1) as predictors of RRBs at the outcome assessment two years later (Time 2), along with an anxiety-by-ASD interaction term to determine the potential multiplicative effect of these co-occurring conditions on RRBs. RESULTS: Results identified a significant interaction between ASD and anxiety symptom severity at the initial assessment that predicted elevated sensory-motor RRBs two years later. Increased sensory-motor RRBs were predicted by elevated ASD symptoms only when anxiety symptom severity was low. Likewise, increased sensory-motor RRBs were predicted by elevated anxiety symptoms only when ASD symptom severity was low. Interestingly, this relationship was isolated to Sensory-Motor RRBs, with evidence that it could also apply to total RRBs. CONCLUSIONS: Findings suggest that ASD and anxiety exert independent and differential effects on Sensory-Motor RRBs when at high severity levels and a multiplicative effect when at moderate levels, which has important implications for early and targeted interventions. En ligne : https://dx.doi.org/10.1186/s11689-024-09569-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576

Characterizing the journey of Rett syndrome among females in the United States: a real-world evidence study using the Rett syndrome natural history study database / Damian MAY in Journal of Neurodevelopmental Disorders, 16 (2024)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 16 (2024) Titre : Characterizing the journey of Rett syndrome among females in the United States: a real-world evidence study using the Rett syndrome natural history study database Type de document : texte imprimé Auteurs : Damian MAY, Auteur ; Kalé KPONEE-SHOVEIN, Auteur ; Jeffrey L. NEUL, Auteur ; Alan K. PERCY, Auteur ; Malena MAHENDRAN, Auteur ; Nathaniel DOWNES, Auteur ; Grace CHEN, Auteur ; Talissa WATSON, Auteur ; Dominique C. PICHARD, Auteur ; Melissa KENNEDY, Auteur ; Patrick LEFEBVRE, Auteur Langues : Anglais (eng) Mots-clés : Humans  Rett Syndrome/physiopathology/therapy/complications  Female  United States/epidemiology  Adult  Child  Adolescent  Retrospective Studies  Young Adult  Child, Preschool  Severity of Illness Index  Registries  Infant  Databases, Factual  Clinical manifestations  Disease progression  Natural history  Registry  Rett syndrome  Treatment patterns  International Rett Syndrome Foundation. KKS, MM, ND, GC, TW, and PL are employees  of Analysis Group, Inc., a consultancy that received funding from Acadia  Pharmaceuticals, Inc. to conduct this study. AKP is co-editor of Translational  Science of Rare Diseases, received research funding from the National Institutes  of Health, and is a consultant for Acadia Pharmaceuticals Inc., Anavex Life  Sciences Corp., AveXis, and GW Pharmaceuticals, as well as advisor to the  International Rett Syndrome Foundation. JLN has received research funding from  the International Rett Syndrome Foundation, the National Institutes of Health,  and Rett Syndrome Research Trust and personal consultancy fees from Acadia  Pharmaceuticals Inc., Analysis Group, AveXis, GW Pharmaceuticals, Hoffmann-La  Roche, Myrtelle, Neurogene, Newron Pharmaceuticals, Signant Health, and Taysha  Gene Therapies, and for the preparation of CME activities for Medscape and Peer  Review Institute  serves on the scientific advisory board of Alcyone  Lifesciences  is a scientific cofounder of LizarBio Therapeutics  and was a  member of a data safety monitoring board for clinical trials conducted by Ovid  Therapeutics. Index. décimale : PER Périodiques Résumé : BACKGROUND: With the advent of the first targeted therapy for Rett Syndrome (RTT), a comprehensive assessment of the journey of RTT is needed to elucidate on present unmet needs in this population. This study characterized females with RTT in the United States and their disease journey with respect to longitudinal treatment patterns, RTT-related outcomes, and changes in disease severity. METHODS: This retrospective cohort study used registry data of females with RTT from the 5211 RTT Natural History Study (RNHS) (November 2015-July 2021). Pharmacological and supportive therapy use, RTT-related outcomes, and RTT severity, as measured by the Clinical Severity Scale and Motor Behavioral Assessment scale, were evaluated following the first RNHS visit. Analyses were conducted overall and in subgroups by RTT type (classic and atypical RTT) and age at first visit (pediatric and adult). RESULTS: A total of 455 females with RTT were included in the study, of whom 90.5% had classic RTT and 79.8% were pediatric individuals. Over a median follow-up of 4 years, use of pharmacological therapies, including prokinetic agents (42.7% vs. 28.3%), and supportive therapies, including physical therapy (87.3% vs. 40.2%) and speech-language therapy (86.8% vs. 23.9%), were more common in pediatric than adult individuals (all p < 0.05). Nearly half (44.6%) of all individuals had a hospital or emergency room visit, with a higher proportion of visits in individuals with classic RTT than atypical RTT and pediatric than adult individuals (both p = 0.001). An increasing trend in clinical severity was observed in pediatric individuals (mean change per year: 0.24; 95% confidence interval [CI]: 0.03, 0.44), while an increasing trend in motor-behavioral dysfunction was observed in pediatric individuals (mean change per year: 1.12; 95% CI: 0.63, 1.60) and those with classic RTT (mean change per year: 0.97; 95% CI: 0.53, 1.41). CONCLUSIONS: Findings from this study highlight the considerable burden of RTT across disease subtype and age. Despite reliance on supportive therapies and healthcare encounters, individuals with RTT experience increasing disease severity and motor-behavioral dysfunction in childhood and adolescence, underscoring the unmet needs of this population and the value of early intervention to manage RTT in the long-term. En ligne : https://dx.doi.org/10.1186/s11689-024-09557-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=575 [article] Characterizing the journey of Rett syndrome among females in the United States: a real-world evidence study using the Rett syndrome natural history study database [texte imprimé] / Damian MAY, Auteur ; Kalé KPONEE-SHOVEIN, Auteur ; Jeffrey L. NEUL, Auteur ; Alan K. PERCY, Auteur ; Malena MAHENDRAN, Auteur ; Nathaniel DOWNES, Auteur ; Grace CHEN, Auteur ; Talissa WATSON, Auteur ; Dominique C. PICHARD, Auteur ; Melissa KENNEDY, Auteur ; Patrick LEFEBVRE, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 16 (2024) Mots-clés : Humans  Rett Syndrome/physiopathology/therapy/complications  Female  United States/epidemiology  Adult  Child  Adolescent  Retrospective Studies  Young Adult  Child, Preschool  Severity of Illness Index  Registries  Infant  Databases, Factual  Clinical manifestations  Disease progression  Natural history  Registry  Rett syndrome  Treatment patterns  International Rett Syndrome Foundation. KKS, MM, ND, GC, TW, and PL are employees  of Analysis Group, Inc., a consultancy that received funding from Acadia  Pharmaceuticals, Inc. to conduct this study. AKP is co-editor of Translational  Science of Rare Diseases, received research funding from the National Institutes  of Health, and is a consultant for Acadia Pharmaceuticals Inc., Anavex Life  Sciences Corp., AveXis, and GW Pharmaceuticals, as well as advisor to the  International Rett Syndrome Foundation. JLN has received research funding from  the International Rett Syndrome Foundation, the National Institutes of Health,  and Rett Syndrome Research Trust and personal consultancy fees from Acadia  Pharmaceuticals Inc., Analysis Group, AveXis, GW Pharmaceuticals, Hoffmann-La  Roche, Myrtelle, Neurogene, Newron Pharmaceuticals, Signant Health, and Taysha  Gene Therapies, and for the preparation of CME activities for Medscape and Peer  Review Institute  serves on the scientific advisory board of Alcyone  Lifesciences  is a scientific cofounder of LizarBio Therapeutics  and was a  member of a data safety monitoring board for clinical trials conducted by Ovid  Therapeutics. Index. décimale : PER Périodiques Résumé : BACKGROUND: With the advent of the first targeted therapy for Rett Syndrome (RTT), a comprehensive assessment of the journey of RTT is needed to elucidate on present unmet needs in this population. This study characterized females with RTT in the United States and their disease journey with respect to longitudinal treatment patterns, RTT-related outcomes, and changes in disease severity. METHODS: This retrospective cohort study used registry data of females with RTT from the 5211 RTT Natural History Study (RNHS) (November 2015-July 2021). Pharmacological and supportive therapy use, RTT-related outcomes, and RTT severity, as measured by the Clinical Severity Scale and Motor Behavioral Assessment scale, were evaluated following the first RNHS visit. Analyses were conducted overall and in subgroups by RTT type (classic and atypical RTT) and age at first visit (pediatric and adult). RESULTS: A total of 455 females with RTT were included in the study, of whom 90.5% had classic RTT and 79.8% were pediatric individuals. Over a median follow-up of 4 years, use of pharmacological therapies, including prokinetic agents (42.7% vs. 28.3%), and supportive therapies, including physical therapy (87.3% vs. 40.2%) and speech-language therapy (86.8% vs. 23.9%), were more common in pediatric than adult individuals (all p < 0.05). Nearly half (44.6%) of all individuals had a hospital or emergency room visit, with a higher proportion of visits in individuals with classic RTT than atypical RTT and pediatric than adult individuals (both p = 0.001). An increasing trend in clinical severity was observed in pediatric individuals (mean change per year: 0.24; 95% confidence interval [CI]: 0.03, 0.44), while an increasing trend in motor-behavioral dysfunction was observed in pediatric individuals (mean change per year: 1.12; 95% CI: 0.63, 1.60) and those with classic RTT (mean change per year: 0.97; 95% CI: 0.53, 1.41). CONCLUSIONS: Findings from this study highlight the considerable burden of RTT across disease subtype and age. Despite reliance on supportive therapies and healthcare encounters, individuals with RTT experience increasing disease severity and motor-behavioral dysfunction in childhood and adolescence, underscoring the unmet needs of this population and the value of early intervention to manage RTT in the long-term. En ligne : https://dx.doi.org/10.1186/s11689-024-09557-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=575

Cortisol profiles and clinical severity in MECP2 duplication syndrome / Sarika U. PETERS in Journal of Neurodevelopmental Disorders, 12 (2020)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 12 (2020) Titre : Cortisol profiles and clinical severity in MECP2 duplication syndrome Type de document : texte imprimé Auteurs : Sarika U. PETERS, Auteur ; Cary FU, Auteur ; Jeffrey L. NEUL, Auteur ; Douglas A. GRANGER, Auteur Langues : Anglais (eng) Mots-clés : Adolescent  Biomarkers  Child  Child, Preschool  Chromosome Duplication  Female  Humans  Hydrocortisone/metabolism  Male  X-Linked Intellectual Disability/metabolism  Saliva  Severity of Illness Index  Young Adult Index. décimale : PER Périodiques Résumé : BACKGROUND: MECP2 duplication syndrome (MDS) is a rare X-linked genomic disorder primarily affecting males which is caused by interstitial chromosomal duplications at Xq28 encompassing the MECP2 gene. Core clinical features of MDS include choreiform movements, progressive spasticity, recurrent respiratory infections, developmental delays in the first 6 months of life, hypotonia, vasomotor disturbances, constipation, drooling, and bruxism. Prior studies suggest that HPA axis activity may be altered in MDS and measures of HPA axis activity may offer insight into disease severity. METHODS: To ascertain whether cortisol profiles are a potential biomarker of clinical severity, diurnal profiles of cortisol and the cortisol awakening response were examined from saliva samples in 31 participants with MDS (ages 2-24 years), and 27 of these samples were usable. Documentation of a positive diagnostic test for MECP2 duplication was required for entry into the study. Samples were collected on each of two consecutive weekdays at four time points during the day: immediately after waking, 30 min after waking, between 3 and 4 PM, and in the evening before bedtime. Correlations with duplication size, clinical severity, sleep problems, and behavior were also examined. RESULTS: Results revealed that a majority of participants with MDS exhibit a declining cortisol awakening response (n = 17). A declining CAR was significantly associated with increased clinical severity scores (r = - .508; p = .03), larger duplication size, waking later, and an increased number of hospitalizations for infections. CONCLUSIONS: Future mechanistic studies will have to determine whether the declining CAR in MDS is attributable to problems with "flip-flop switching" of regional brain activation (involving the suprachiasmatic nucleus and the hippocampus, and the HPA axis) that is responsible for the switch from reduced to increased adrenal sensitivity. Taken together, results suggest the possibility that cortisol profiles could potentially be a biomarker of clinical severity and utilized for the purposes of patient stratification for future clinical trials in MDS. En ligne : https://dx.doi.org/10.1186/s11689-020-09322-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Cortisol profiles and clinical severity in MECP2 duplication syndrome [texte imprimé] / Sarika U. PETERS, Auteur ; Cary FU, Auteur ; Jeffrey L. NEUL, Auteur ; Douglas A. GRANGER, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 12 (2020) Mots-clés : Adolescent  Biomarkers  Child  Child, Preschool  Chromosome Duplication  Female  Humans  Hydrocortisone/metabolism  Male  X-Linked Intellectual Disability/metabolism  Saliva  Severity of Illness Index  Young Adult Index. décimale : PER Périodiques Résumé : BACKGROUND: MECP2 duplication syndrome (MDS) is a rare X-linked genomic disorder primarily affecting males which is caused by interstitial chromosomal duplications at Xq28 encompassing the MECP2 gene. Core clinical features of MDS include choreiform movements, progressive spasticity, recurrent respiratory infections, developmental delays in the first 6 months of life, hypotonia, vasomotor disturbances, constipation, drooling, and bruxism. Prior studies suggest that HPA axis activity may be altered in MDS and measures of HPA axis activity may offer insight into disease severity. METHODS: To ascertain whether cortisol profiles are a potential biomarker of clinical severity, diurnal profiles of cortisol and the cortisol awakening response were examined from saliva samples in 31 participants with MDS (ages 2-24 years), and 27 of these samples were usable. Documentation of a positive diagnostic test for MECP2 duplication was required for entry into the study. Samples were collected on each of two consecutive weekdays at four time points during the day: immediately after waking, 30 min after waking, between 3 and 4 PM, and in the evening before bedtime. Correlations with duplication size, clinical severity, sleep problems, and behavior were also examined. RESULTS: Results revealed that a majority of participants with MDS exhibit a declining cortisol awakening response (n = 17). A declining CAR was significantly associated with increased clinical severity scores (r = - .508; p = .03), larger duplication size, waking later, and an increased number of hospitalizations for infections. CONCLUSIONS: Future mechanistic studies will have to determine whether the declining CAR in MDS is attributable to problems with "flip-flop switching" of regional brain activation (involving the suprachiasmatic nucleus and the hippocampus, and the HPA axis) that is responsible for the switch from reduced to increased adrenal sensitivity. Taken together, results suggest the possibility that cortisol profiles could potentially be a biomarker of clinical severity and utilized for the purposes of patient stratification for future clinical trials in MDS. En ligne : https://dx.doi.org/10.1186/s11689-020-09322-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

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