200 results on '"Hagebeuk E"'
Search Results
2. Failure to thrive: denk ook aan een hersentumor
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Hagebeuk, E. E. O., de Kraker, J., and Poll-The, B. T.
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- 2003
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3. Successful transfer to sulfonylurea therapy in an infant with developmental delay, epilepsy and neonatal diabetes (DEND) syndrome and a novel ABCC8 gene mutation
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Zwaveling-Soonawala, N., Hagebeuk, E. E., Slingerland, A. S., Ris-Stalpers, C., Vulsma, T., and van Trotsenburg, A. S.
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- 2011
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4. The landscape of epilepsy-related GATOR1 variants (vol 21, pg 398, 2019)
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Baldassari, S., Picard, F., Verbeek, N.E., Kempen, M. van, Brilstra, E.H., Lesca, G., Conti, V., Guerrini, R., Bisulli, F., Licchetta, L., Pippucci, T., Tinuper, P., Hirsch, E., Saint Martin, A. de, Chelly, J., Rudolf, G., Chipaux, M., Ferrand-Sorbets, S., Dorfmuller, G., Sisodiya, S., Balestrini, S., Schoeler, N., Hernandez-Hernandez, L., Krithika, S., Oegema, R., Hagebeuk, E., Gunning, B., Deckers, C., Berghuis, B., Wegner, I., Niks, E.H., Jansen, F.E., Braun, K., Jong, D. de, Rubboli, G., Talvik, I., Sander, V., Uldall, P., Jacquemont, M.L., Nava, C., Leguern, E., Julia, S., Gambardella, A., d'Orsi, G., Crichiutti, G., Faivre, L., Darmency, V., Benova, B., Krsek, P., Biraben, A., Lebre, A.S., Jennesson, M., Sattar, S., Marchal, C., Nordli, D.R., Lindstrom, K., Striano, P., Lomax, L.B., Kiss, C., Bartolomei, F., Lepine, A.F., Schoonjans, A.S., Stouffs, K., Jansen, A., Panagiotakaki, E., Ricard-Mousnier, B., Thevenon, J., Bellescize, J. de, Catenoix, H., Dorn, T., Zenker, M., Muller-Schluter, K., Brandt, C., Krey, I., Polster, T., Wolff, M., Balci, M., Rostasy, K., Achaz, G., Zacher, P., Becher, T., Cloppenborg, T., Yuskaitis, C.J., Weckhuysen, S., Poduri, A., Lemke, J.R., Moller, R.S., and Baulac, S.
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- 2019
5. Working memory in pediatric frontal lobe epilepsy.
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van den Berg L, de Weerd A, Reuvekamp M, Hagebeuk E, and van der Meere J
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- Child, Executive Function, Frontal Lobe, Humans, Memory Disorders, Memory, Short-Term, Neuropsychological Tests, Epilepsy, Frontal Lobe complications
- Abstract
Thirty-two children with frontal lobe epilepsy (FLE) were assessed using different working memory measures. In addition, parents and teachers completed the working memory scale of the Behavioral Rating Inventory of Executive Functioning (BRIEF) to assess the children's "daily life behavior." Results suggested minimal working memory deficits as assessed with performance-based measures. However, the BRIEF showed more working memory deficits suggesting that, on a daily life level, working memory problems seem to be associated with FLE. We discuss why the results of the performance-based measures are not consistent with results of the BRIEF.HighlightsParents as well as teachers report working memory dysfunction in daily life to the same extent.Performance based measures show minimal deficits of working memory.Correlation between working memory tasks and proxy measures are low.
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- 2021
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6. Epilepsy and Electroencephalographic Abnormalities in SATB2-Associated Syndrome.
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Lewis H, Samanta D, Örsell JL, Bosanko KA, Rowell A, Jones M, Dale RC, Taravath S, Hahn CD, Krishnakumar D, Chagnon S, Keller S, Hagebeuk E, Pathak S, Bebin EM, Arndt DH, Alexander JJ, Mainali G, Coppola G, Maclean J, Sparagana S, McNamara N, Smith DM, Raggio V, Cruz M, Fernández-Jaén A, Kava MP, Emrick L, Fish JL, Vanderver A, Helman G, Pierson TM, and Zarate YA
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- Adolescent, Adult, Age of Onset, Child, Child, Preschool, Electroencephalography, Female, Humans, Infant, Male, Retrospective Studies, Sleep Stages physiology, Syndrome, Young Adult, Epilepsy diagnosis, Epilepsy etiology, Epilepsy genetics, Epilepsy physiopathology, Genetic Diseases, Inborn complications, Genetic Diseases, Inborn diagnosis, Genetic Diseases, Inborn genetics, Genetic Diseases, Inborn physiopathology, Matrix Attachment Region Binding Proteins genetics, Nervous System Malformations diagnosis, Nervous System Malformations etiology, Nervous System Malformations genetics, Nervous System Malformations physiopathology, Sleep Wake Disorders diagnosis, Sleep Wake Disorders etiology, Sleep Wake Disorders genetics, Sleep Wake Disorders physiopathology, Transcription Factors genetics
- Abstract
Background: Seizures are an under-reported feature of the SATB2-associated syndrome phenotype. We describe the electroencephalographic findings and seizure semiology and treatment in a population of individuals with SATB2-associated syndrome., Methods: We performed a retrospective review of 101 individuals with SATB2-associated syndrome who were reported to have had a previous electroencephalographic study to identify those who had at least one reported abnormal result. For completeness, a supplemental survey was distributed to the caregivers and input from the treating neurologist was obtained whenever possible., Results: Forty-one subjects were identified as having at least one prior abnormal electroencephalography. Thirty-eight individuals (93%) had epileptiform discharges, 28 (74%) with central localization. Sleep stages were included as part of the electroencephalographies performed in 31 individuals (76%), and epileptiform activity was recorded during sleep in all instances (100%). Definite clinical seizures were diagnosed in 17 individuals (42%) with a mean age of onset of 3.2 years (four months to six years), and focal seizures were the most common type of seizure observed (42%). Six subjects with definite clinical seizures needed polytherapy (35%). Delayed myelination and/or abnormal white matter hyperintensities were seen on neuroimaging in 19 individuals (61%)., Conclusions: Epileptiform abnormalities are commonly seen in individuals with SATB2-associated syndrome. A baseline electroencephalography that preferably includes sleep stages is recommended during the initial evaluation of all individuals with SATB2-associated syndrome, regardless of clinical suspicion of epilepsy., (Copyright © 2020 Elsevier Inc. All rights reserved.)
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- 2020
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7. Correction: The landscape of epilepsy-related GATOR1 variants.
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Baldassari S, Picard F, Verbeek NE, van Kempen M, Brilstra EH, Lesca G, Conti V, Guerrini R, Bisulli F, Licchetta L, Pippucci T, Tinuper P, Hirsch E, de Saint Martin A, Chelly J, Rudolf G, Chipaux M, Ferrand-Sorbets S, Dorfmüller G, Sisodiya S, Balestrini S, Schoeler N, Hernandez-Hernandez L, Krithika S, Oegema R, Hagebeuk E, Gunning B, Deckers C, Berghuis B, Wegner I, Niks EH, Jansen FE, Braun K, de Jong D, Rubboli G, Talvik I, Sander V, Uldall P, Jacquemont ML, Nava C, Leguern E, Julia S, Gambardella A, d'Orsi G, Crichiutti G, Faivre L, Darmency V, Benova B, Krsek P, Biraben A, Lebre AS, Jennesson M, Sattar S, Marchal C, NordliJr DR, Lindstrom K, Striano P, Lomax LB, Kiss C, Bartolomei F, Lepine AF, Schoonjans AS, Stouffs K, Jansen A, Panagiotakaki E, Ricard-Mousnier B, Thevenon J, de Bellescize J, Catenoix H, Dorn T, Zenker M, Müller-Schlüter K, Brandt C, Krey I, Polster T, Wolff M, Balci M, Rostasy K, Achaz G, Zacher P, Becher T, Cloppenborg T, Yuskaitis CJ, Weckhuysen S, Poduri A, Lemke JR, Møller RS, and Baulac S
- Abstract
The original version of this article contained an error in the spelling of the author Erik H. Niks, which was incorrectly given as Erik Niks. This has now been corrected in both the PDF and HTML versions of the article.
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- 2019
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8. Correction: IQSEC2-related encephalopathy in males and females: a comparative study including 37 novel patients.
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Mignot C, McMahon AC, Bar C, Campeau PM, Davidson C, Buratti J, Nava C, Jacquemont ML, Tallot M, Milh M, Edery P, Marzin P, Barcia G, Barnerias C, Besmond C, Bienvenu T, Bruel AL, Brunga L, Ceulemans B, Coubes C, Cristancho AG, Cunningham F, Dehouck MB, Donner EJ, Duban-Bedu B, Dubourg C, Gardella E, Gauthier J, Geneviève D, Gobin-Limballe S, Goldberg EM, Hagebeuk E, Hamdan FF, Hančárová M, Hubert L, Ioos C, Ichikawa S, Janssens S, Journel H, Kaminska A, Keren B, Koopmans M, Lacoste C, Laššuthová P, Lederer D, Lehalle D, Marjanovic D, Métreau J, Michaud JL, Miller K, Minassian BA, Morales J, Moutard ML, Munnich A, Ortiz-Gonzalez XR, Pinard JM, Prchalová D, Putoux A, Quelin C, Rosen AR, Roume J, Rossignol E, Simon MEH, Smol T, Shur N, Shelihan I, Štěrbová K, Vyhnálková E, Vilain C, Soblet J, Smits G, Yang SP, van der Smagt JJ, van Hasselt PM, van Kempen M, Weckhuysen S, Helbig I, Villard L, Héron D, Koeleman B, Møller RS, Lesca G, Helbig KL, Nabbout R, Verbeek NE, and Depienne C
- Abstract
This Article was originally published under Nature Research's License to Publish, but has now been made available under a CC BY 4.0 license. The PDF and HTML versions of the Article have been modified accordingly.
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- 2019
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9. Correction to: The landscape of epilepsy-related GATOR1 variants.
- Author
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Baldassari S, Picard F, Verbeek NE, van Kempen M, Brilstra EH, Lesca G, Conti V, Guerrini R, Bisulli F, Licchetta L, Pippucci T, Tinuper P, Hirsch E, Martin AS, Chelly J, Rudolf G, Chipaux M, Ferrand-Sorbets S, Dorfmüller G, Sisodiya S, Balestrini S, Schoeler N, Hernandez-Hernandez L, Krithika S, Oegema R, Hagebeuk E, Gunning B, Deckers C, Berghuis B, Wegner I, Niks E, Jansen F, Braun K, Jong D, Rubboli G, Talvik I, Sander V, Uldall P, Jacquemont ML, Nava C, Leguern E, Julia S, Gambardella A, d'Orsi G, Crichiutti G, Faivre L, Darmency V, Benova B, Krsek P, Biraben A, Lebre AS, Jennesson M, Sattar S, Marchal C, NordliJr DR, Lindstrom K, Striano P, Lomax LB, Kiss C, Bartolomei F, Lepine AF, Schoonjans AS, Stouffs K, Jansen A, Panagiotakaki E, Ricard-Mousnier B, Thevenon J, Bellescize J, Catenoix H, Dorn T, Zenker M, Müller-Schlüter K, Brandt C, Krey I, Polster T, Wolff M, Balci M, Rostasy K, Achaz G, Zacher P, Becher T, Cloppenborg T, Yuskaitis CJ, Weckhuysen S, Poduri A, Lemke JR, Møller RS, and Baulac S
- Abstract
The original version of this Article contained an error in the author list where the corresponding author Stéphanie Baulac was repeated twice. This has now been corrected in the HTML, the PDF was correct at the time of publication.
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- 2019
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10. IQSEC2-related encephalopathy in males and females: a comparative study including 37 novel patients.
- Author
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Mignot C, McMahon AC, Bar C, Campeau PM, Davidson C, Buratti J, Nava C, Jacquemont ML, Tallot M, Milh M, Edery P, Marzin P, Barcia G, Barnerias C, Besmond C, Bienvenu T, Bruel AL, Brunga L, Ceulemans B, Coubes C, Cristancho AG, Cunningham F, Dehouck MB, Donner EJ, Duban-Bedu B, Dubourg C, Gardella E, Gauthier J, Geneviève D, Gobin-Limballe S, Goldberg EM, Hagebeuk E, Hamdan FF, Hančárová M, Hubert L, Ioos C, Ichikawa S, Janssens S, Journel H, Kaminska A, Keren B, Koopmans M, Lacoste C, Laššuthová P, Lederer D, Lehalle D, Marjanovic D, Métreau J, Michaud JL, Miller K, Minassian BA, Morales J, Moutard ML, Munnich A, Ortiz-Gonzalez XR, Pinard JM, Prchalová D, Putoux A, Quelin C, Rosen AR, Roume J, Rossignol E, Simon MEH, Smol T, Shur N, Shelihan I, Štěrbová K, Vyhnálková E, Vilain C, Soblet J, Smits G, Yang SP, van der Smagt JJ, van Hasselt PM, van Kempen M, Weckhuysen S, Helbig I, Villard L, Héron D, Koeleman B, Møller RS, Lesca G, Helbig KL, Nabbout R, Verbeek NE, and Depienne C
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- Brain growth & development, Brain metabolism, Brain Diseases epidemiology, Brain Diseases physiopathology, Female, Humans, Infant, Infant, Newborn, Intellectual Disability epidemiology, Intellectual Disability physiopathology, Male, Mutation, Pedigree, Phenotype, Protein Isoforms genetics, Seizures epidemiology, Seizures physiopathology, Sex Characteristics, Brain Diseases genetics, Guanine Nucleotide Exchange Factors genetics, Intellectual Disability genetics, Seizures genetics
- Abstract
Purpose: Variants in IQSEC2, escaping X inactivation, cause X-linked intellectual disability with frequent epilepsy in males and females. We aimed to investigate sex-specific differences., Methods: We collected the data of 37 unpublished patients (18 males and 19 females) with IQSEC2 pathogenic variants and 5 individuals with variants of unknown significance and reviewed published variants. We compared variant types and phenotypes in males and females and performed an analysis of IQSEC2 isoforms., Results: IQSEC2 pathogenic variants mainly led to premature truncation and were scattered throughout the longest brain-specific isoform, encoding the synaptic IQSEC2/BRAG1 protein. Variants occurred de novo in females but were either de novo (2/3) or inherited (1/3) in males, with missense variants being predominantly inherited. Developmental delay and intellectual disability were overall more severe in males than in females. Likewise, seizures were more frequently observed and intractable, and started earlier in males than in females. No correlation was observed between the age at seizure onset and severity of intellectual disability or resistance to antiepileptic treatments., Conclusion: This study provides a comprehensive overview of IQSEC2-related encephalopathy in males and females, and suggests that an accurate dosage of IQSEC2 at the synapse is crucial during normal brain development.
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- 2019
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11. The landscape of epilepsy-related GATOR1 variants.
- Author
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Baldassari S, Picard F, Verbeek NE, van Kempen M, Brilstra EH, Lesca G, Conti V, Guerrini R, Bisulli F, Licchetta L, Pippucci T, Tinuper P, Hirsch E, de Saint Martin A, Chelly J, Rudolf G, Chipaux M, Ferrand-Sorbets S, Dorfmüller G, Sisodiya S, Balestrini S, Schoeler N, Hernandez-Hernandez L, Krithika S, Oegema R, Hagebeuk E, Gunning B, Deckers C, Berghuis B, Wegner I, Niks E, Jansen FE, Braun K, de Jong D, Rubboli G, Talvik I, Sander V, Uldall P, Jacquemont ML, Nava C, Leguern E, Julia S, Gambardella A, d'Orsi G, Crichiutti G, Faivre L, Darmency V, Benova B, Krsek P, Biraben A, Lebre AS, Jennesson M, Sattar S, Marchal C, Nordli DR Jr, Lindstrom K, Striano P, Lomax LB, Kiss C, Bartolomei F, Lepine AF, Schoonjans AS, Stouffs K, Jansen A, Panagiotakaki E, Ricard-Mousnier B, Thevenon J, de Bellescize J, Catenoix H, Dorn T, Zenker M, Müller-Schlüter K, Brandt C, Krey I, Polster T, Wolff M, Balci M, Rostasy K, Achaz G, Zacher P, Becher T, Cloppenborg T, Yuskaitis CJ, Weckhuysen S, Poduri A, Lemke JR, Møller RS, and Baulac S
- Subjects
- Adolescent, Brugada Syndrome genetics, Brugada Syndrome mortality, Brugada Syndrome physiopathology, Child, Child, Preschool, DNA Copy Number Variations genetics, Epilepsy complications, Epilepsy epidemiology, Epilepsy physiopathology, Female, Genetic Predisposition to Disease, Humans, INDEL Mutation genetics, Infant, Infant, Newborn, Loss of Function Mutation genetics, Male, Mechanistic Target of Rapamycin Complex 1 genetics, Multiprotein Complexes genetics, Pedigree, Seizures complications, Seizures epidemiology, Seizures genetics, Seizures physiopathology, Signal Transduction genetics, Epilepsy genetics, GTPase-Activating Proteins genetics, Repressor Proteins genetics, Tumor Suppressor Proteins genetics
- Abstract
Purpose: To define the phenotypic and mutational spectrum of epilepsies related to DEPDC5, NPRL2 and NPRL3 genes encoding the GATOR1 complex, a negative regulator of the mTORC1 pathway METHODS: We analyzed clinical and genetic data of 73 novel probands (familial and sporadic) with epilepsy-related variants in GATOR1-encoding genes and proposed new guidelines for clinical interpretation of GATOR1 variants., Results: The GATOR1 seizure phenotype consisted mostly in focal seizures (e.g., hypermotor or frontal lobe seizures in 50%), with a mean age at onset of 4.4 years, often sleep-related and drug-resistant (54%), and associated with focal cortical dysplasia (20%). Infantile spasms were reported in 10% of the probands. Sudden unexpected death in epilepsy (SUDEP) occurred in 10% of the families. Novel classification framework of all 140 epilepsy-related GATOR1 variants (including the variants of this study) revealed that 68% are loss-of-function pathogenic, 14% are likely pathogenic, 15% are variants of uncertain significance and 3% are likely benign., Conclusion: Our data emphasize the increasingly important role of GATOR1 genes in the pathogenesis of focal epilepsies (>180 probands to date). The GATOR1 phenotypic spectrum ranges from sporadic early-onset epilepsies with cognitive impairment comorbidities to familial focal epilepsies, and SUDEP.
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- 2019
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12. Characterisation of sleep apneas and respiratory circuitry in mice lacking CDKL5.
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Matteoli G, Alvente S, Bastianini S, Berteotti C, Ciani E, Cinelli E, Lo Martire V, Medici G, Mello T, Miglioranza E, Silvani A, Mutolo D, and Zoccoli G
- Abstract
CDKL5 deficiency disorder is a rare genetic disease caused by mutations in the CDKL5 gene. Central apneas during wakefulness have been reported in patients with CDKL5 deficiency disorder. Studies on CDKL5-knockout mice, a CDKL5 deficiency disorder model, reported sleep apneas, but it is still unclear whether these events are central (central sleep apnea) or obstructive (obstructive sleep apnea) and may be related to alterations of brain circuits that modulate breathing rhythm. This study aimed to discriminate central sleep apnea and obstructive sleep apnea in CDKL5-knockout mice, and explore changes in the somatostatin neurons expressing high levels of neurokinin-1 receptors within the preBötzinger complex. Ten adult male wild-type and 12 CDKL5-knockout mice underwent electrode implantation for sleep stage discrimination and diaphragmatic activity recording, and were studied using whole-body plethysmography for 7 hr during the light (resting) period. Sleep apneas were categorised as central sleep apnea or obstructive sleep apnea based on the recorded signals. The number of somatostatin neurons in the preBötzinger complex and their neurokinin-1 receptors expression were assessed through immunohistochemistry in a sub-group of animals. CDKL5-knockout mice exhibited a higher apnea occurrence rate and a greater prevalence of obstructive sleep apnea during rapid eye movement sleep, compared with wild-type, whereas no significant difference was observed for central sleep apnea. Moreover, CDKL5-knockout mice showed a reduced number of somatostatin neurons in the preBötzinger complex, and these neurons expressed a lower level of neurokinin-1 receptors compared with wild-type controls. These findings underscore the pivotal role of CDKL5 in regulating normal breathing, suggesting its potential involvement in shaping preBötzinger complex neural circuitry and controlling respiratory muscles during sleep., (© 2024 The Author(s). Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)
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- 2024
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13. Executive and behavioral functioning in pediatric frontal lobe epilepsy.
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van den Berg L, de Weerd A, Reuvekamp M, Hagebeuk E, and van der Meere J
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- Child, Child Behavior Disorders diagnosis, Epilepsy, Frontal Lobe diagnosis, Female, Humans, Male, Mental Disorders diagnosis, Mental Disorders epidemiology, Mental Disorders psychology, Child Behavior Disorders epidemiology, Child Behavior Disorders psychology, Epilepsy, Frontal Lobe epidemiology, Epilepsy, Frontal Lobe psychology, Executive Function physiology
- Abstract
Objective: Epilepsy, as a chronic and neurological disease, is generally associated with an increased risk for social and emotional behavior problems in children. These findings are mostly derived from studies on children with different epilepsy types. However, there is limited information about the associations between frontal lobe epilepsy (FLE) and cognitive and behavioral problems. The aim of this study was to examine relationships between FLE and executive and behavioral functioning reported by parents and teachers., Material and Methods: Teachers and parents of 32 children (18 boys, 14 girls, mean age 9; 2 years ±1;6) with a confirmed diagnosis of FLE completed the Behavioral Rating Inventory of Executive Function (BRIEF), the Child Behavior Checklist (CBCL), and Teacher Report Form (TRF)., Results: About 25 to 35% of the parents and teachers rated children in the abnormal range of the main scales of the BRIEF, CBCL, and TRF. Teachers tend to report more metacognition problems, whereas parents tend to report more behavior regulation problems. Children with left-sided FLE showed more problems than children with bilateral or right-sided FLE. The whole range of executive dysfunctioning is linked to behavioral dysfunctioning in FLE, but ratings vary across settings and informants. The epilepsy variables age of onset, lateralization, drug load, and duration of epilepsy had only a small and scattered contribution., Conclusion: Ratings on the BRIEF, CBCL, and TRF are moderately to highly correlated, suggesting a (strong) link between executive and behavioral functioning. Subtle differences between parents and teachers ratings suggest different executive function demands in various settings., (Copyright © 2018 Elsevier Inc. All rights reserved.)
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- 2018
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14. PP4.6 – 1784 S-adenosylmethionine and S-adenosylhomocysteine in plasma and cerebrospinal fluid in Rett syndrome and the effect of folinic acid supplementation
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Hagebeuk, E, primary, Duran, M, additional, Abeling, NG, additional, Vyth, A, additional, and Poll-The, BT, additional
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- 2013
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15. Successful transfer to sulfonylurea therapy in an infant with developmental delay, epilepsy and neonatal diabetes (DEND) syndrome and a novel ABCC8 gene mutation
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Zwaveling-Soonawala, N., primary, Hagebeuk, E. E., additional, Slingerland, A. S., additional, Ris-Stalpers, C., additional, Vulsma, T., additional, and van Trotsenburg, A. S., additional
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- 2010
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16. NNO03 Vein of Galen malformation with neonatal presentation: incidence and outcome in relation to MRI appearance in the Netherlands and Flanders (1990-2006)
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Vermeulen, J.R., primary, van den Berg, D., additional, Hagebeuk, E., additional, Laroche, S., additional, Zecic, A., additional, van Wezel-Meijler, G., additional, Swarte, R., additional, Naulaers, G., additional, van den Berg, R., additional, and de Vries, L.S., additional
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- 2007
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17. Effect of vaccinations on seizure risk and disease course in Dravet syndrome.
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Verbeek NE, van der Maas NA, Sonsma AC, Ippel E, Vermeer-de Bondt PE, Hagebeuk E, Jansen FE, Geesink HH, Braun KP, de Louw A, Augustijn PB, Neuteboom RF, Schieving JH, Stroink H, Vermeulen RJ, Nicolai J, Brouwer OF, van Kempen M, de Kovel CG, Kemmeren JM, Koeleman BP, Knoers NV, Lindhout D, Gunning WB, and Brilstra EH
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- Adolescent, Adult, Age of Onset, Child, Child, Preschool, Epilepsies, Myoclonic complications, Epilepsies, Myoclonic genetics, Female, Humans, Incidence, Infant, Male, NAV1.1 Voltage-Gated Sodium Channel genetics, Retrospective Studies, Risk, Young Adult, Diphtheria-Tetanus-Pertussis Vaccine adverse effects, Diphtheria-Tetanus-acellular Pertussis Vaccines adverse effects, Disease Progression, Epilepsies, Myoclonic physiopathology, Measles-Mumps-Rubella Vaccine adverse effects, Seizures etiology, Vaccination adverse effects
- Abstract
Objective: To study the effect of vaccination-associated seizure onset on disease course and estimate the risk of subsequent seizures after infant pertussis combination and measles, mumps, and rubella (MMR) vaccinations in Dravet syndrome (DS)., Methods: We retrospectively analyzed data from hospital medical files, child health clinics, and the vaccination register for children with DS and pathogenic SCN1A mutations. Seizures within 24 hours after infant whole-cell, acellular, or nonpertussis combination vaccination or within 5 to 12 days after MMR vaccination were defined as "vaccination-associated." Risks of vaccination-associated seizures for the different vaccines were analyzed in univariable and in multivariable logistic regression for pertussis combination vaccines and by a self-controlled case series analysis using parental seizure registries for MMR vaccines. Disease courses of children with and without vaccination-associated seizure onset were compared., Results: Children who had DS (n = 77) with and without vaccination-associated seizure onset (21% and 79%, respectively) differed in age at first seizure (median 3.7 vs 6.1 months, p < 0.001) but not in age at first nonvaccination-associated seizure, age at first report of developmental delay, or cognitive outcome. The risk of subsequent vaccination-associated seizures was significantly lower for acellular pertussis (9%; odds ratio 0.18, 95% confidence interval [CI] 0.05-0.71) and nonpertussis (8%; odds ratio 0.11, 95% CI 0.02-0.59) than whole-cell pertussis (37%; reference) vaccines. Self-controlled case series analysis showed an increased incidence rate ratio of seizures of 2.3 (95% CI 1.5-3.4) within the risk period of 5 to 12 days following MMR vaccination., Conclusions: Our results suggest that vaccination-associated earlier seizure onset does not alter disease course in DS, while the risk of subsequent vaccination-associated seizures is probably vaccine-specific., (© 2015 American Academy of Neurology.)
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- 2015
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18. Candesartan restores blood–brain barrier dysfunction, mitigates aberrant gene expression, and extends lifespan in a knockin mouse model of epileptogenesis.
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Hammer, Michael F., Bahramnejad, Erfan, Watkins, Joseph C., and Ronaldson, Patrick T.
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ANGIOTENSIN-receptor blockers ,CHILDREN with epilepsy ,GENE expression profiling ,CHILDHOOD epilepsy ,ANGIOTENSIN I - Abstract
Blockade of Angiotensin type 1 receptor (AT1R) has potential therapeutic utility in the treatment of numerous detrimental consequences of epileptogenesis, including oxidative stress, neuroinflammation, and blood–brain barrier (BBB) dysfunction. We have recently shown that many of these pathological processes play a critical role in seizure onset and propagation in the Scn8a-N1768D mouse model. Here we investigate the efficacy and potential mechanism(s) of action of candesartan (CND), an FDA-approved angiotensin receptor blocker (ARB) indicated for hypertension, in improving outcomes in this model of pediatric epilepsy. We compared length of lifespan, seizure frequency, and BBB permeability in juvenile (D/D) and adult (D/+) mice treated with CND at times after seizure onset. We performed RNAseq on hippocampal tissue to quantify differences in genome-wide patterns of transcript abundance and inferred beneficial and detrimental effects of canonical pathways identified by enrichment methods in untreated and treated mice. Our results demonstrate that treatment with CND gives rise to increased survival, longer periods of seizure freedom, and diminished BBB permeability. CND treatment also partially reversed or ‘normalized’ disease-induced genome-wide gene expression profiles associated with inhibition of NF-κB, TNFα, IL-6, and TGF-β signaling in juvenile and adult mice. Pathway analyses reveal that efficacy of CND is due to its known dual mechanism of action as both an AT1R antagonist and a PPARγ agonist. The robust effectiveness of CND across ages, sexes and mouse strains is a positive indication for its translation to humans and its suitability of use for clinical trials in children with SCN8A epilepsy [ABSTRACT FROM AUTHOR]
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- 2024
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19. Analysis of genetic characteristics in four children with atypical Rett syndrome and developmental epileptic encephalopathy caused by IQSEC2 gene variation.
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LIN Li, CUI Zhen-zhen, HE Fan, ZHAO Xiao-ling, JIN Dan-qun, and YANG Bin
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RETT syndrome ,ACADEMIC medical centers ,RESEARCH funding ,BRAIN diseases ,CHILD development deviations ,GENETIC mutation ,CASE studies ,GENOMES ,SEQUENCE analysis ,SYMPTOMS ,CHILDREN - Abstract
Objective Summarize the clinical and genetic characteristics of atypical Rett syndrome and developmental epileptic encephalopathy caused by IQSEC2 gene variation. Methods and Results From May 2020 to April 2022, Anhui Provincial Children's Hospital diagnosed and treated 4 children with atypical Rett syndrome and developmental epileptic encephalopathy caused by IQSEC2 gene variation, including 2 males and 2 females were a pair of identical twins. They all had comprehensive developmental delay before onset. At the age of 2 years, all cases gradually exhibited clinical manifestations of atypical Rett syndrome, such as frequent clapping, biting, sleep disorders (increased sleep or difficulty falling asleep), and grinding teeth, followed by developmental regression and seizures. The initial age of epilepsy was from 2 years and 2 months to 2 years and 10 months. All cases started with generalized tonic-clonic seizure, with epileptic spasm occurring between 2 and 11 months of course. Case 2, Case 3 and Case 4 were also accompanied by focal seizures. Four cases with VEEG background of 4-6 Hz θ wave, the VEEG during the interictal phase was a broad multifocal sharp slow complex wave. In Case 2, Case 3 and Case 4, MRI was abnormal, mainly with increased depth of cerebral hemispheric sulcus and gyrus. The whole exome sequencing suggested pathogenicity and possible pathogenic variations in the IQSEC2 gene, Case 1 and Case 2 were frameshift mutations of c. 608dup (p. Gln204Profs*35), while Case 3 and Case 4 were nonsense mutations of c.2231C>A (p.Ser744Ter) and c.2521C>T (p. Gln841Ter), respectively. The four mutation sites have not been reported domestically or internationally. All cases received treatment with multiple antiepileptic seizure medicine. The last follow-up age was from 4 years and 3 months to 6 years and 3 months. All cases were unable to walk alone and had no active language. There were no seizures in Case 1 for 3 years, occasional seizures in Case 2 and Case 4, and frequent seizures in Case 3. Conclusions IQSEC2 gene variation can manifest as atypical Rett syndrome, which can be accompanied by refractory epileptic spasms. Both males and females have severe phenotypes, and the severity of clinical phenotypes at the same mutation site varies. Our report enriches the variation spectrum and clinical phenotype spectrum of the IQSEC2 gene, expands the genetic spectrum of Rett syndrome and developmental epileptic encephalopathy, and provides value for the clinical diagnosis, treatment and subsequent research of this disease. [ABSTRACT FROM AUTHOR]
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- 2024
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20. Circadian Rest-Activity Rhythm Disturbances in Alzheimer's Disease
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Someren, E. J. W. Van, Hagebeuk, E. E. O., Lijzenga, C., Scheltens, P., Rooij, S. E. J. A. De, Jonker, C., Pot, A.-M., Mirmiran, M., and Swaab, D. F.
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- 1996
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21. Seasonality in regional brain glucose metabolism.
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Zhang, Rui, Tomasi, Dardo, Shokri-Kojori, Ehsan, Manza, Peter, Demiral, Sukru Baris, Wang, Gene-Jack, and Volkow, Nora D.
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BRAIN metabolism ,CROSS-sectional method ,SEASONS ,RESEARCH funding ,POSITRON emission tomography ,ACTIGRAPHY ,GLUCOSE metabolism disorders ,WHITE matter (Nerve tissue) ,COMPUTER-aided diagnosis ,DIAGNOSIS of brain abnormalities - Abstract
Background: Daylength and the rates of changes in daylength have been associated with seasonal fluctuations in psychiatric symptoms and in cognition and mood in healthy adults. However, variations in human brain glucose metabolism in concordance with seasonal changes remain under explored. Methods: In this cross-sectional study, we examined seasonal effects on brain glucose metabolism, which we measured using 18F-fluorodeoxyglucose-PET in 97 healthy participants. To maximize the sensitivity of regional effects, we computed relative metabolic measures by normalizing the regional measures to white matter metabolism. Additionally, we explored the role of rest–activity rhythms/sleep–wake activity measured with actigraphy in the seasonal variations of regional brain metabolic activity. Results: We found that seasonal variations of cerebral glucose metabolism differed across brain regions. Glucose metabolism in prefrontal regions increased with longer daylength and with greater day-to-day increases in daylength. The cuneus and olfactory bulb had the maximum and minimum metabolic values around the summer and winter solstice respectively (positively associated with daylength), whereas the temporal lobe, brainstem, and postcentral cortex showed maximum and minimum metabolic values around the spring and autumn equinoxes, respectively (positively associated with faster daylength gain). Longer daylength was associated with greater amplitude and robustness of diurnal activity rhythms suggesting circadian involvement. Conclusions: The current findings advance our knowledge of seasonal patterns in a key indicator of brain function relevant for mood and cognition. These data could inform treatment interventions for psychiatric symptoms that peak at specific times of the year. [ABSTRACT FROM AUTHOR]
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- 2024
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22. Virus-Induced Epilepsy vs. Epilepsy Patients Acquiring Viral Infection: Unravelling the Complex Relationship for Precision Treatment.
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Costa, Bárbara and Vale, Nuno
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PEOPLE with epilepsy ,VIRUS diseases ,EPILEPSY ,ANTICONVULSANTS ,BRAIN physiology ,DRUG target - Abstract
The intricate relationship between viruses and epilepsy involves a bidirectional interaction. Certain viruses can induce epilepsy by infecting the brain, leading to inflammation, damage, or abnormal electrical activity. Conversely, epilepsy patients may be more susceptible to viral infections due to factors, such as compromised immune systems, anticonvulsant drugs, or surgical interventions. Neuroinflammation, a common factor in both scenarios, exhibits onset, duration, intensity, and consequence variations. It can modulate epileptogenesis, increase seizure susceptibility, and impact anticonvulsant drug pharmacokinetics, immune system function, and brain physiology. Viral infections significantly impact the clinical management of epilepsy patients, necessitating a multidisciplinary approach encompassing diagnosis, prevention, and treatment of both conditions. We delved into the dual dynamics of viruses inducing epilepsy and epilepsy patients acquiring viruses, examining the unique features of each case. For virus-induced epilepsy, we specify virus types, elucidate mechanisms of epilepsy induction, emphasize neuroinflammation's impact, and analyze its effects on anticonvulsant drug pharmacokinetics. Conversely, in epilepsy patients acquiring viruses, we detail the acquired virus, its interaction with existing epilepsy, neuroinflammation effects, and changes in anticonvulsant drug pharmacokinetics. Understanding this interplay advances precision therapies for epilepsy during viral infections, providing mechanistic insights, identifying biomarkers and therapeutic targets, and supporting optimized dosing regimens. However, further studies are crucial to validate tools, discover new biomarkers and therapeutic targets, and evaluate targeted therapy safety and efficacy in diverse epilepsy and viral infection scenarios. [ABSTRACT FROM AUTHOR]
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- 2024
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23. How many days are enough? Sleep-wake timing regularity and fragmentation scores change with the number of days included.
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Lok R, Suh S, Rue S, Weed L, and Zeitzer JM
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The duration of sleep data collection from actigraphy is often influenced by practical factors (e.g. workdays versus non-workdays), but the impact of the variation of duration on outcome measures of interest has not been well explored. This study investigates the effect of the duration of actigraphy measurement on non-parametric measures of 24-hr sleep-wake rhythms. We examined regularity inter-daily stability and fragmentation intra-daily variation over 14 days or the first 7 days in participants (n = 41) undergoing evaluation for sleep disorders. Bland-Altman plots assessed the impact of fewer than 14 or 7 days, respectively, on inter-daily stability and intra-daily variation scores. Intra-daily variation values were also calculated for each day and compared with the 14-day intra-daily variation. Compared with the entire 14-day period, using shorter durations (< 7 days) led to a higher estimated bias and increased variance in the limits of agreement for inter-daily stability. Intra-daily variation values showed increased variation in the limits of agreement with fewer days. Similar trends were observed when comparing shorter actigraphy periods 3 or 5 days-7 days. Daily intra-daily variation calculations indicate that individuals with higher daily fragmentation experienced more pronounced day-to-day fragmentation and greater variability in the degree of fragmentation, in a linear association between daily intra-daily variation standard deviation and 14-day intra-daily variation values. Our data indicate that a minimum of 7 full days of actigraphy is recommended to reduce measurement errors, and intra-daily variation and inter-daily stability derived from less than 7 days cannot be compared with those from more than 7 days without significant error., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA.)
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- 2024
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24. An exploratory pilot study on social rhythm regularity, and its associations with sleep, circadian, affective, and alcohol use outcomes in late adolescents.
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Tracy EL, Xie Y, Buysse DJ, Smagula SF, Soehner AM, and Hasler BP
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The current exploratory pilot study examined whether social rhythm regularity, as measured by a social rhythm metric, was associated with: (1) the regularity of circadian rhythms and/or sleep regularity metrics; and (2) sleep quality, affective function and alcohol use. Late adolescents (18-22 years old) who drink alcohol (n = 36; 61.1% female, M
age = 21.26 years) completed a 14-day ecological momentary assessment protocol, wore a wrist actigraph for 14 days, and completed two overnight visits (Thursday and Sunday) to assess dim light melatonin onset. Sleep regularity metrics included standard deviation, composite phase deviation, social jet lag and inter-daily stability. We used dim light melatonin onset data to calculate the stability of the circadian phase (Sunday minus Thursday). Participants completed surveys and ecological momentary assessments that assessed global and daily sleep quality, affective function, and alcohol use. Correlational analysis and robust regression modelling were used. More regular social rhythms were associated with higher regularities of mid-sleep timing based on standard deviations, but were not associated with other sleep regularity metrics or stability of the circadian phase. More regular social rhythms were associated with better sleep quality, but were not associated with affective function or alcohol use. Social rhythm regularity is a unique construct compared with existing sleep quality metrics. In contrast with the social zeitgeber hypothesis, social rhythm regularity was not associated with circadian rhythm regularity measured by dim light melatonin onset. However, social rhythm regularity may be an under-recognized contributor to better sleep quality., (© 2024 European Sleep Research Society.)- Published
- 2024
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25. Circadian rhythm alterations affecting the pathology of neurodegenerative diseases.
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Canever JB, Queiroz LY, Soares ES, de Avelar NCP, and Cimarosti HI
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- Humans, Animals, Neurodegenerative Diseases physiopathology, Neurodegenerative Diseases pathology, Neurodegenerative Diseases metabolism, Circadian Rhythm physiology
- Abstract
The circadian rhythm is a nearly 24-h oscillation found in various physiological processes in the human brain and body that is regulated by environmental and genetic factors. It is responsible for maintaining body homeostasis and it is critical for essential functions, such as metabolic regulation and memory consolidation. Dysregulation in the circadian rhythm can negatively impact human health, resulting in cardiovascular and metabolic diseases, psychiatric disorders, and premature death. Emerging evidence points to a relationship between the dysregulation circadian rhythm and neurodegenerative diseases, suggesting that the alterations in circadian function might play crucial roles in the pathogenesis and progression of neurodegenerative diseases. Better understanding this association is of paramount importance to expand the knowledge on the pathophysiology of neurodegenerative diseases, as well as, to provide potential targets for the development of new interventions based on the dysregulation of circadian rhythm. Here we review the latest findings on dysregulation of circadian rhythm alterations in Parkinson's disease, Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, spinocerebellar ataxia and multiple-system atrophy, focusing on research published in the last 3 years., (© 2023 International Society for Neurochemistry.)
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- 2024
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26. Frontal lobe epilepsy: an eye tracking study of memory and attention.
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Qiong Zhang, Weifeng Sun, Kailing Huang, Li Qin, Shirui Wen, Xiaoyan Long, Quan Wang, and Li Feng
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EYE tracking ,FRONTAL lobe ,SHORT-term memory ,MEMORY disorders ,MEMORY - Abstract
Objective: To explore the characteristics and mechanisms of working memory impairment in patients with frontal lobe epilepsy (FLE) through a memory game paradigm combined with eye tracking technology. Method: We included 44 patients with FLE and 50 healthy controls (HC). All participants completed a series of neuropsychological scale assessments and a short-term memory game on an automated computer-based memory evaluation platform with an eye tracker. Results: Memory scale scores of FLE patients including digit span (U = 747.50, p = 0.007), visual recognition (U = 766.50, p = 0.010), and logical memory (U = 544.00, p < 0.001) were significantly lower than HC. The patients with FLE took longer to complete the four levels of difficulty of the short-term memory game than healthy controls (level 1: U = 2974.50, p = 0.000; level 2: U = 3060.50, p = 0.000; level 3: U = 2465.00, p = 0.000; level 4: U = 2199.00, p = 0.000). During the memory decoding period, first fixation on the targets took significantly longer for FLE patients for all difficulty levels compared to controls (level 1: U = 3407.00, p = 0.008; level 2: U = 3618.00, p = 0.036; level 3: U = 3345.00, p = 0.006; level 4: U = 2781.00, p = 0.000). The average fixation duration per target among patients with FLE was found to be significantly longer compared to HC (level 1: U = 2994.50, p = 0.000; level 2: U = 3101.00, p = 0.000; level 3: U = 2559.50, p = 0.000; level 4: U = 2184.50, p = 0.000). The total fixation duration on AOI/ total completion time of FLE patients was significantly lower than those of HC for levels 1 to 3 (level 1: U = 1557.00, p = 0.000; level 2: U = 2333.00, p = 0.000; level 3: U = 2757.00, p = 0.000). Furthermore, the eye tracking data during the memory decoding phase were correlated with neuropsychological scale scores (p < 0.05). Conclusion: Patients with FLE exhibited short-term memory impairment probably due to deficits in attentional maintenance, especially during the memory decoding phase. Eye tracking technology provided the possibility to help separate and quantify visual attention from memory processing, contributing to exploring underlying mechanisms of memory impairment in FLE. [ABSTRACT FROM AUTHOR]
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- 2023
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27. Evaluatie van slaap- en ademhaling bij kinderen met CDKL5-deficiëntiestoornis: lange termijn beloop.
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Hagebeuk, Eveline and Al de Weerd, Annelies Smits en
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- 2023
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28. Fetal and infant growth patterns, sleep, and 24‐h activity rhythms: a population‐based prospective cohort study in school‐age children.
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Beunders, Victoria A. A., Koopman‐Verhoeff, M. Elisabeth, Vermeulen, Marijn J., Silva, Carolina C. V., Jansen, Pauline W., Luik, Annemarie I., Reiss, Irwin K. M., Joosten, Koen F. M., and Jaddoe, Vincent W. V.
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SLEEP duration ,FETAL development ,INFANT growth ,THIRD trimester of pregnancy ,FETAL growth retardation ,SECOND trimester of pregnancy ,LOW birth weight ,PREMATURE labor - Abstract
Summary: The study objective was to explore associations of fetal and infant weight patterns and preterm birth with sleep and 24‐h activity rhythm parameters at school‐age. In our prospective population‐based study, 1327 children were followed from birth to age 10–15 years. Fetal weight was estimated using ultrasound in the second and third trimester of pregnancy. Birth weight and gestational age were available from midwife registries. Infant weight was measured at 6, 12 and 24 months. Fetal and infant weight acceleration or deceleration were defined as a change of >0.67 standard deviation between the corresponding age intervals. At school‐age, sleep duration, sleep efficiency, wake after sleep onset, social jetlag, inter‐daily stability, and intra‐daily variability were assessed using tri‐axial wrist actigraphy for 9 consecutive nights. We observed that low birth weight (<2500 g) was associated with 0.24 standard deviation (95% confidence interval [CI] 0.04; 0.43) longer sleep duration compared to normal weight. Compared to normal growth, growth deceleration in fetal life and infancy was associated with 0.40 standard deviation (95% CI 0.07; 0.73) longer sleep duration, 0.44 standard deviation (95% CI 0.14; 0.73) higher sleep efficiency, and −0.41 standard deviation (95% CI −0.76; ‐0.07) shorter wake after sleep onset. A pattern of normal fetal growth followed by infant growth acceleration was associated with −0.40 standard deviation (95% CI −0.61; −0.19) lower inter‐daily stability. Preterm birth was not associated with any sleep or 24‐h rhythm parameters. Our findings showed that children with fetal and infant growth restriction had longer and more efficient sleep at school‐age, which may be indicative of an increased need for sleep for maturational processes and development after a difficult start in life. [ABSTRACT FROM AUTHOR]
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- 2023
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29. Clinical and genetic features of GATOR1 complex-associated epilepsy.
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Kaili Yin, Xingxing Lei, Zhaofen Yan, Yujiao Yang, Qinqin Deng, Qiang Lu, Xue Zhang, Mengyang Wang, and Qing Liu
- Abstract
Objectives To analyse the prevalence of pathogenic variants in DEPDC5, NPRL2 and NPRL3 that encode the GATOR1 (GTPase-activating protein towards the Rags 1) complex, a modulator in the mammalian target of rapamycin (mTOR) pathway, and to define the characteristics of GATOR1-associated epilepsy. Methods Clinical details and whole-exome sequencing data of 170 novel probands with lesional or non-lesional epilepsy were retrieved. Candidate variants in GATOR1 genes were verified by Sanger sequencing, and cosegregate analysis was performed. The pathogenicity of variants and their effect on mTOR signalling were investigated. Results Two novel frameshift variants and one recurrent nonsense variant were detected in DEPDC5, with a prevalence of 1.8% (3 out of 170) in the whole cohort and 3.1% (3 out of 97) in focal epilepsies. These variants cosegregated in pedigrees with epilepsy, respectively. Rare missense variants in NPRL2 and NPRL3 did not segregate with epilepsy in families, respectively. Epileptic phenotypes of 21 patients with DEPDC5 variants showed focal seizures with non-lesional variable foci that were predominantly sleep-related, with a median onset age of 10 years (range 1-30). Seizure outcome was variable. About 24% of patients were drug-resistant, and seizure attacks were absent in 33% of variant carriers. Of 13 patients who experienced seizures, 54% tended to resolve spontaneously. Functional assessments showed that the three variants affected DEPDC5 expression. These loss-of-function (LoF) variants affected the DEPDC5-dependent inhibition of mTOR. Conclusions Patients carrying DEPDC5-LoF variants might show a high prevalence of focal seizures with a dynamic phenotype, indicating reduced penetrance and self-resolving features. The associated epilepsy was caused by loss of inhibition of the mTOR pathway. The pathogenicity of missense variants in GATOR1 genes should be cautiously evaluated. [ABSTRACT FROM AUTHOR]
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- 2023
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30. Abnormalities of regional brain activity and executive function in patients with temporal lobe epilepsy: A cross-sectional and longitudinal resting-state functional MRI study.
- Author
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Huang H, Huang D, Luo C, Qiu Z, and Zheng J
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- Humans, Male, Female, Cross-Sectional Studies, Adult, Longitudinal Studies, Case-Control Studies, Brain Mapping methods, Middle Aged, Epilepsy, Temporal Lobe diagnostic imaging, Epilepsy, Temporal Lobe physiopathology, Magnetic Resonance Imaging methods, Executive Function physiology
- Abstract
Purpose: We decided to track changes in regional brain activity and executive function in temporal lobe epilepsy (TLE) patients based on cross-sectional and longitudinal designs and sought potential imaging features for follow-up observation., Methods: Thirty-two TLE patients and thirty-three healthy controls (HCs) were recruited to detect changes in fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo) and to evaluate executive function both at baseline and at two-year (23.3 ± 8.3 months) follow-up. Moreover, multivariate pattern analysis (MVPA) was used for follow-up observation., Results: TLE patients displayed lower fALFF values in the right superior frontal gyrus (SFG) and higher ReHo values in the left putamen (PUT) relative to the HCs. Longitudinal analysis revealed that TLE patients at follow-up exhibited higher fALFF values in the left postcentral gyrus (PoCG), higher ReHo values in the left PoCG and the right middle frontal gyrus (MFG), lower ReHo values in the bilateral PUT and the right fusiform gyrus (FFG) compared with these patients at baseline. The executive function was impaired in TLE patients but didn't deteriorate over time. No correlations were discovered between regional brain activity and executive function. The MVPA based on ReHo performed well in differentiating the follow-up group from the baseline group., Conclusion: We revealed the abnormalities in regional brain activity and executive function as well as their longitudinal trends in TLE patients. The ReHo might be a good imaging feature for follow-up observation., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2024
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31. The contribution of Na V 1.6 to the efficacy of voltage-gated sodium channel inhibitors in wild type and Na V 1.6 gain-of-function (GOF) mouse seizure control.
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Johnson JP Jr, Focken T, Karimi Tari P, Dube C, Goodchild SJ, Andrez JC, Bankar G, Burford K, Chang E, Chowdhury S, Christabel J, Dean R, de Boer G, Dehnhardt C, Gong W, Grimwood M, Hussainkhel A, Jia Q, Khakh K, Lee S, Li J, Lin S, Lindgren A, Lofstrand V, Mezeyova J, Nelkenbrecher K, Shuart NG, Sojo L, Sun S, Waldbrook M, Wesolowski S, Wilson M, Xie Z, Zenova A, Zhang W, Scott FL, Cutts AJ, Sherrington RP, Winquist R, Cohen CJ, and Empfield JR
- Abstract
Background and Purpose: Inhibitors of voltage-gated sodium channels (Na
V s) are important anti-epileptic drugs, but the contribution of specific channel isoforms is unknown since available inhibitors are non-selective. We aimed to create novel, isoform selective inhibitors of Nav channels as a means of informing the development of improved antiseizure drugs., Experimental Approach: We created a series of compounds with diverse selectivity profiles enabling block of NaV 1.6 alone or together with NaV 1.2. These novel NaV inhibitors were evaluated for their ability to inhibit electrically evoked seizures in mice with a heterozygous gain-of-function mutation (N1768D/+) in Scn8a (encoding NaV 1.6) and in wild-type mice., Key Results: Pharmacologic inhibition of NaV 1.6 in Scn8aN1768D/+ mice prevented seizures evoked by a 6-Hz shock. Inhibitors were also effective in a direct current maximal electroshock seizure assay in wild-type mice. NaV 1.6 inhibition correlated with efficacy in both models, even without inhibition of other CNS NaV isoforms., Conclusions and Implications: Our data suggest NaV 1.6 inhibition is a driver of efficacy for NaV inhibitor anti-seizure medicines. Sparing the NaV 1.1 channels of inhibitory interneurons did not compromise efficacy. Selective NaV 1.6 inhibitors may provide targeted therapies for human Scn8a developmental and epileptic encephalopathies and improved treatments for idiopathic epilepsies., (© 2024 The Author(s). British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)- Published
- 2024
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32. The landscape of epilepsy-related GATOR1 variants
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Johannes R. Lemke, Pia Zacher, Thomas Dorn, Laura Hernandez-Hernandez, Natasha E. Schoeler, Stéphanie Baulac, Sara Baldassari, Anne de Saint Martin, Eleni Panagiotakaki, Anne Fabienne Lepine, Markus Wolff, Arnaud Biraben, Renske Oegema, Edouard Hirsch, Anna Jansen, Charles Deckers, Nienke E. Verbeek, Fabienne Picard, Georg Dorfmüller, Sarah Ferrand-Sorbets, Barbora Benova, Francesca Bisulli, Inga Talvik, Kristin Lindstrom, Tilman Polster, Douglas R. Nordli, Tommaso Pippucci, Eva H. Brilstra, Shifteh Sattar, Erik H. Niks, Marie Line Jacquemont, Kees P.J. Braun, Karen Müller-Schlüter, Sanjay M. Sisodiya, Sarah Weckhuysen, Lysa Boissé Lomax, Sophie Julia, Brigitte Ricard-Mousnier, Mathilde Chipaux, Laura Licchetta, Gaetan Lesca, Bianca Berghuis, S. Krithika, Jamel Chelly, Renzo Guerrini, Hélène Catenoix, Annapurna Poduri, Melanie Jennesson, Pasquale Striano, Rikke S. Møller, Antonio Gambardella, Guillaume Achaz, Peter Uldall, Fabrice Bartolomei, Giuseppe d'Orsi, Laurence Faivre, Floor E. Jansen, An Sofie Schoonjans, Kevin Rostasy, Thomas Becher, Pavel Krsek, Julien Thevenon, Marjan J. A. van Kempen, Guido Rubboli, Cécile Marchal, Meral Balci, Boudewijn Gunning, Ilona Krey, Julitta de Bellescize, Veronique Darmency, Christopher J. Yuskaitis, Daniëlle de Jong, Giovanni Crichiutti, Paolo Tinuper, Katrien Stouffs, Valentin Sander, Anne-Sophie Lebre, Thomas Cloppenborg, Valerio Conti, Gabrielle Rudolf, Courtney Kiss, Eveline Hagebeuk, Caroline Nava, Eric LeGuern, Ilse Wegner, Christian Brandt, Martin Zenker, Simona Balestrini, Picard, Fabienne, Baldassari S., Picard F., Verbeek N.E., van Kempen M., Brilstra E.H., Lesca G., Conti V., Guerrini R., Bisulli F., Licchetta L., Pippucci T., Tinuper P., Hirsch E., de Saint Martin A., Chelly J., Rudolf G., Chipaux M., Ferrand-Sorbets S., Dorfmuller G., Sisodiya S., Balestrini S., Schoeler N., Hernandez-Hernandez L., Krithika S., Oegema R., Hagebeuk E., Gunning B., Deckers C., Berghuis B., Wegner I., Niks E., Jansen F.E., Braun K., de Jong D., Rubboli G., Talvik I., Sander V., Uldall P., Jacquemont M.-L., Nava C., Leguern E., Julia S., Gambardella A., d'Orsi G., Crichiutti G., Faivre L., Darmency V., Benova B., Krsek P., Biraben A., Lebre A.-S., Jennesson M., Sattar S., Marchal C., Nordli D.R., Lindstrom K., Striano P., Lomax L.B., Kiss C., Bartolomei F., Lepine A.F., Schoonjans A.-S., Stouffs K., Jansen A., Panagiotakaki E., Ricard-Mousnier B., Thevenon J., de Bellescize J., Catenoix H., Dorn T., Zenker M., Muller-Schluter K., Brandt C., Krey I., Polster T., Wolff M., Balci M., Rostasy K., Achaz G., Zacher P., Becher T., Cloppenborg T., Yuskaitis C.J., Weckhuysen S., Poduri A., Lemke J.R., Moller R.S., Baulac S., Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Department of Genetics [Utrecht, the Netherlands], University Medical Center [Utrecht], Service de Génétique [HCL Groupement Hospitalier Est], Groupement Hospitalier Lyon-Est (GHE), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Children's Hospital A. Meyer, Service de Neurologie [Strasbourg], CHU Strasbourg-Hopital Civil, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Clinical and Experimental Epilepsy, University College of London [London] (UCL), Academic Center for Epileptology Kempenhaeghe & Maastricht UMC+ [Heeze], Danish Epilepsy Centre, Denmark and Aarhus University, Aarhus, Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de génétique médicale [Toulouse], CHU Toulouse [Toulouse], Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), FHU TRANSLAD (CHU de Dijon), Université de Bourgogne (UB), Service de Neurophysiologie Clinique (CHU Dijon), CHU Pontchaillou [Rennes], Service de pédiatrie spécialisée et médecine infantile (neurologie, pneumologie, maladies héréditaires du métabolisme) [Hôpital de la Timone - APHM], Hôpital de la Timone [CHU - APHM] (TIMONE), Epilepsie, sommeil et explorations fonctionnelles neuropédiatriques, Hospices Civils de Lyon (HCL)-Hôpital Femme Mère Enfant, Equipe GAD (LNC - U1231), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Université Bourgogne Franche-Comté [COMUE] (UBFC), Département d'Epilepsie, Sommeil et Neurophysiologie Pédiatrique [HCL, Lyon], Hospices Civils de Lyon (HCL), Institute of Human Genetics, University Hospital Magdeburg, Institut de Systématique, Evolution, Biodiversité (ISYEB ), Muséum national d'Histoire naturelle (MNHN)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles (UA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Groupement hospitalier Lyon-Est, Centre de recherche en neurosciences de Lyon (CRNL), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse]
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Male ,0301 basic medicine ,Proband ,DEPDC5 ,SUDEP ,030105 genetics & heredity ,Bioinformatics ,Loss of Function Mutation/genetics ,Epilepsy ,INDEL Mutation ,Loss of Function Mutation ,mTORC1 pathway ,Genetics(clinical) ,Child ,Genetics (clinical) ,Multiprotein Complexes/genetics ,Brugada Syndrome ,DNA Copy Number Variation ,Brugada syndrome ,INDEL Mutation/genetics ,GTPase-Activating Proteins ,NPRL3 ,Seizure ,Phenotype ,Pedigree ,3. Good health ,Brugada Syndrome/genetics ,Child, Preschool ,Female ,Human ,Signal Transduction ,DNA Copy Number Variations ,Adolescent ,Seizures/complications ,Mechanistic Target of Rapamycin Complex 1/genetics ,DNA Copy Number Variations/genetics ,Mechanistic Target of Rapamycin Complex 1 ,Tumor Suppressor Proteins/genetics ,Article ,Focal cortical dysplasia ,03 medical and health sciences ,Seizures ,GTPase-Activating Proteins/genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,Genetic focal epilepsy ,Epilepsy/complications ,Repressor Proteins/genetics ,business.industry ,GTPase-Activating Protein ,Tumor Suppressor Proteins ,Infant, Newborn ,Correction ,Infant ,Repressor Protein ,Cortical dysplasia ,medicine.disease ,ddc:616.8 ,Repressor Proteins ,030104 developmental biology ,Frontal lobe seizures ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,Multiprotein Complexes ,Multiprotein Complexe ,Signal Transduction/genetics ,Human medicine ,business - Abstract
Purpose:\ud \ud To define the phenotypic and mutational spectrum of epilepsies related to DEPDC5, NPRL2 and NPRL3 genes encoding the GATOR1 complex, a negative regulator of the mTORC1 pathway.\ud \ud Methods:\ud \ud We analyzed clinical and genetic data of 73 novel probands (familial and sporadic) with epilepsy-related variants in GATOR1-encoding genes and proposed new guidelines for clinical interpretation of GATOR1 variants.\ud \ud Results:\ud \ud The GATOR1 seizure phenotype consisted mostly in focal seizures (e.g., hypermotor or frontal lobe seizures in 50%), with a mean age at onset of 4.4 years, often sleep-related and drug-resistant (54%), and associated with focal cortical dysplasia (20%). Infantile spasms were reported in 10% of the probands. Sudden unexpected death in epilepsy (SUDEP) occurred in 10% of the families. Novel classification framework of all 140 epilepsy-related GATOR1 variants (including the variants of this study) revealed that 68% are loss-of-function pathogenic, 14% are likely pathogenic, 15% are variants of uncertain significance and 3% are likely benign.\ud \ud Conclusion:\ud \ud Our data emphasize the increasingly important role of GATOR1 genes in the pathogenesis of focal epilepsies (>180 probands to date). The GATOR1 phenotypic spectrum ranges from sporadic early-onset epilepsies with cognitive impairment comorbidities to familial focal epilepsies, and SUDEP.
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- 2018
33. Sleep problems in Rett syndrome animal models: A systematic review.
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Zhang X, Lin JS, and Spruyt K
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- Animals, Brain physiopathology, CRISPR-Cas Systems, Drosophila melanogaster genetics, Epileptic Syndromes genetics, Epileptic Syndromes physiopathology, Female, Gene Editing, Gene Knock-In Techniques, Humans, Macaca fascicularis genetics, Male, Methyl-CpG-Binding Protein 2 genetics, Mice, Mice, Mutant Strains genetics, Mutation, Rett Syndrome genetics, Rett Syndrome physiopathology, Sleep Stages, Sleep Wake Disorders physiopathology, Spasms, Infantile genetics, Spasms, Infantile physiopathology, Species Specificity, Disease Models, Animal, Rett Syndrome complications, Sleep Wake Disorders etiology
- Abstract
Due to the discovery of Rett Syndrome (RTT) genetic mutations, animal models have been developed. Sleep research in RTT animal models may unravel novel neural mechanisms for this severe neurodevelopmental heritable rare disease. In this systematic literature review we summarize the findings on sleep research of 13 studies in animal models of RTT. We found disturbed efficacy and continuity of sleep in all genetically mutated models of mice, cynomolgus monkeys, and Drosophila. Models presented highly fragmented sleep with distinct differences in 24-hr sleep/wake cyclicity and circadian arrhythmicity. Overall, animal models mimic sleep complaints reported in individuals with RTT. However, contrary to human studies, in mutant mice, attenuated sleep delta waves, and sleep apneas in non-rapid eye movement sleep were reported. Future studies may focus on sleep structure and EEG alterations, potential central mechanisms involved in sleep fragmentation and the occurrence of sleep apnea across different sleep stages. Given that locomotor dysfunction is characteristic of individuals with RTT, studies may consider to integrate its potential impact on the behavioral analysis of sleep., (© 2020 Wiley Periodicals LLC.)
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- 2021
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34. Genetic basis of sleep phenotypes and rare neurodevelopmental syndromes reveal shared molecular pathways.
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Moysés‐Oliveira, Mariana, Paschalidis, Mayara, Souza‐Cunha, Lais A., Esteves‐Guerreiro, Pedro A., Adami, Luana Nayara Gallego, Kloster, Anna K., Mosini, Amanda C., Moreira, Gustavo A., Doria, Sandra, Tempaku, Priscila F., Pires, Gabriel N., Andersen, Monica L., and Tufik, Sergio
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- 2023
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35. Transcarpal Motor Conduction Velocity: Repeatability and Application in Carpal Tunnel Syndrome.
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Das, Pinaki, Ghosh, Parasar, Halder, Subhankar, and Kumar, Subhankar
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CARPAL tunnel syndrome ,STATISTICAL reliability ,MEASUREMENT errors ,MEDIAN nerve ,VELOCITY - Abstract
Background: Conduction velocity of the short segment of the median motor nerve, across wrist (transcarpal motor conduction velocity (TCMCV)), has been used to increase diagnostic yield in carpal tunnel syndrome (CTS). However, repeatability of this parameter has not been studied till date. It has not been used as an indicator of response to treatment. Using surface stimulation techniques, it is difficult to localize the sites of stimulation of transcarpal segment of median nerve in palm. As a result, small errors in measurements of TCMCV can be magnified and variability of TCMCV may occur on successive measurements. Despite this possible variation, TCMCV can be a useful tool for assessing response to therapy, if its repeatability is assessed and a cut-off value determined for a significant change in nerve conduction velocity. Purpose: In this study, it was determined whether TCMCV is repeatable. If found to be repeatable, we show a method to determine the cut-off value of the change in this parameter for it to be considered significant. Methods: Difference between values of TCMCV on successive measurements was obtained in hands of 26 controls. Repeatability of this parameter was determined in this control population following criteria of British Standards Institution. In 19 patients of CTS, treated with intracarpal steroid injection, pre-treatment and post-treatment values of TCMCV, and of symptom severity scale (SSS) and functional status scale (FSS), were obtained at 1, 2, and 3 months after treatment. Results: Repeat measurements of TCMCV were made in each hand of all controls. After applying criteria of British Standards Institution, to such recordings, TCMCV was found to be repeatable and the cut-off value for significant change determined. According to this cut-off value, 4 patients of CTS showed improvement in TCMCV, with consistent improvement in SSS and FSS. Change in TCMCV corroborated qualitatively with changes in SSS and FSS. Conclusion: Repeatability of TCMCV can be assessed by criteria of British Standards Institution and a cut-off value determined to use it as an indicator of response to treatment in CTS. [ABSTRACT FROM AUTHOR]
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- 2023
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36. Circadian regulation of pulmonary disease: the importance of timing.
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Cunningham, Peter S., Jackson, Callum, Chakraborty, Amlan, Cain, Jafar, Durrington, Hannah J., and Blaikley, John F.
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LUNG diseases ,CHRONIC obstructive pulmonary disease ,RESPIRATORY infections ,RESPIRATORY diseases ,ANIMAL models in research - Abstract
Circadian regulation causes the activity of biological processes to vary over a 24-h cycle. The pathological effects of this variation are predominantly studied using two different approaches: pre-clinical models or observational clinical studies. Both these approaches have provided useful insights into how underlying circadian mechanisms operate and specifically which are regulated by the molecular oscillator, a key time-keeping mechanism in the body. This review compares and contrasts findings from these two approaches in the context of four common respiratory diseases (asthma, chronic obstructive pulmonary disease, pulmonary fibrosis, and respiratory infection). Potential methods used to identify and measure human circadian oscillations are also discussed as these will be useful outcome measures in future interventional human trials that target circadian mechanisms. [ABSTRACT FROM AUTHOR]
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- 2023
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37. 教师教育者的角色、专业素质与专业发展: 对话荷兰教师教育学者鲁能伯格教授.
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祝 刚, 史可媛, and 吴天一
- Abstract
Copyright of Teacher Development Research is the property of Teacher Development Research and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2023
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38. The clinical and sleep manifestations in children with FOXG1 syndrome.
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Wong, Lee‐Chin, Huang, Cheng‐Hsien, Chou, Wan‐Yun, Hsu, Chia‐Jui, Tsai, Wen‐Che, and Lee, Wang‐Tso
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FOXG1 syndrome is a rare neurodevelopmental disorder associated with severe cognitive dysfunction, autistic behavior, and early‐onset hyperkinetic movement disorders. Patients have also been reported to experience sleep disturbances. However, these findings are mainly based on subjective caregivers' reports, and limited by small case numbers. Moreover, no studies using objective evaluation tools, such as actigraphy, have been reported. We analyzed the clinical and sleep manifestations of children with FOXG1 syndrome registered in the FOXG1 Research Foundation Patient Registry database. A total of 258 individuals with FOXG1 syndrome were included in this research. 132 (51.16%) had sleep disturbances. The more impaired of language acquisitions (absence of speech, OR: 3.99, 95%CI = 1.69–9.42, p = 0.002), hyperkinetic movement disorders (OR: 2.64, 95%CI = 1.34‐5.20 p = 0.005) and feeding difficulties (OR: 2.81, 95% CI = 1.52–5.19, p = 0.001) were significantly associated with an increase in odds of sleep disturbance after adjusting for age, sex, and antiepileptic drugs. We also performed sleep studies on six individuals with FOXG1 syndrome using The Children's Sleep Habits Questionnaire (CSHQ), the Sleep Disturbance Scale for Children (SDSC), and 7‐day data from Actiwatch. The Pittsburgh Sleep Quality Index (PSQI) and 7‐day data from Actiwatch were also used to evaluate the sleep condition of their parents. The CSHQ scores revealed bedtime resistance, sleep onset delay, sleep duration, sleep anxiety, night‐waking, and parasomnia. Sleep–wake transition disorders and disorders of initiating and maintaining sleep were also suggested by the SDSC scores. The children's actigraphy revealed short sleep durations, impaired sleep efficiency, longer wake after sleep onset, and frequent night‐waking. All caregivers reported significantly higher PSQI scores, mildly declined sleep efficiency, and shorter total sleep duration. Sleep disturbances, especially in initiating and maintaining sleep, are common in individuals with FOXG1 syndrome and their caregivers. Sleep disorders in patients with FOXG1 syndrome and their caregivers should be investigated. Lay Summary: FOXG1 syndrome is a rare disorder with several comorbidities, including sleep disorders. However, studies focusing on sleep conditions in FOXG1 syndrome are scarce. Our studies showed that sleep disturbances occur across different genders, ages, and genotypes in FOXG1 syndrome. Hyperkinetic movements, feeding difficulties, and absence of language acquisition significantly increased the probability of sleep disturbance. Our results also demonstrated greater difficulty in initiating and maintaining sleep, as identified in actigraphy studies, and sleep‐disordered breathing symptoms, as revealed by the report questionnaires submitted by the parents of six children with FOXG1 syndrome. Caregivers of children with this condition also tended to have shorter total sleep durations. [ABSTRACT FROM AUTHOR]
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- 2023
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39. Quantitative Phenotype Morbidity Description of SATB2-Associated Syndrome.
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Zarate, Yuri A., Bosanko, Katherine, Kannan, Amrit, Thomason, Ashlen, Nutt, Beth, Kumar, Nihit, Simmons, Kirt, Hiegert, Aaron, Hartzell, Larry, Johnson, Adam, Prater, Tabitha, Pérez-Palma, Eduardo, Brünger, Tobias, Stefanski, Arthur, Lal, Dennis, and Caffrey, Aisling R.
- Abstract
Characterized by developmental delay with severe speech delay, dental anomalies, cleft palate, skeletal abnormalities, and behavioral difficulties, SATB2-associated syndrome (SAS) is caused by pathogenic variants in SATB2. The SAS phenotype range of severity has been documented previously in large series. Using data from the SAS registry, we present the SAS severity score, a comprehensive scoring rubric that encompasses 15 different individual neurodevelopmental and systemic features. Higher (more severe) systemic and total (sum of neurodevelopmental and systemic scores) scores were seen for null variants located after amino acid 350 (the start of the CUT1 domain), the recurrent missense Arg389Cys variant (n = 10), intragenic deletions, and larger chromosomal deletions. The Arg389Cys variant had the highest cognitive, verbal, and sialorrhea severity scores, while large chromosomal deletions had the highest expressive, ambulation, palate, feeding and growth, neurodevelopmental, and total scores. Missense variants not located in the CUT1 or CUT2 domain scored lower in several subcategories. We conclude that the SAS severity score allows quantitative phenotype morbidity description that can be used in routine clinical counseling. Further refinement and validation of the SAS severity score are expected over time. All data from this project can be interactively explored in a new portal. [ABSTRACT FROM AUTHOR]
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- 2023
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40. In vitro effects of eslicarbazepine (S‐licarbazepine) as a potential precision therapy on SCN8A variants causing neuropsychiatric disorders.
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Bayraktar, Erva, Liu, Yuanyuan, Sonnenberg, Lukas, Hedrich, Ulrike B. S., Sara, Yildirim, Eltokhi, Ahmed, Lyu, Hang, Lerche, Holger, Wuttke, Thomas V., and Lauxmann, Stephan
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SODIUM channels ,NEUROBEHAVIORAL disorders ,EPILEPSY ,CHANNEL coding ,BRAIN diseases ,GENETIC code - Abstract
Background and Purpose: Variants in SCN8A, the NaV1.6 channel's coding gene, are characterized by a variety of symptoms, including intractable epileptic seizures, psychomotor delay, progressive cognitive decline, autistic features, ataxia or dystonia. Standard anticonvulsant treatment has a limited impact on the course of disease. Experimental Approach: We investigated the therapeutic potential of eslicarbazepine (S‐licarbazepine; S‐lic), an enhancer of slow inactivation of voltage gated sodium channels, on two variants with biophysical and neuronal gain‐of‐function (G1475R and M1760I) and one variant with biophysical gain‐of‐function but neuronal loss‐of‐function (A1622D) in neuroblastoma cells and in murine primary hippocampal neuron cultures. These three variants cover the broad spectrum of NaV1.6‐associated disease and are linked to representative phenotypes of mild to moderate epilepsy (G1475R), developmental and epileptic encephalopathy (M1760I) and intellectual disability without epilepsy (A1622D). Key Results: Similar to known effects on NaV1.6 wildtype channels, S‐lic predominantly enhances slow inactivation on all tested variants, irrespective of their particular biophysical mechanisms. Beyond that, S‐lic exhibits variant‐specific effects including a partial reversal of pathologically slowed fast inactivation dynamics (A1622D and M1760I) and a trend to reduce enhanced persistent Na+ current by A1622D variant channels. Furthermore, our data in primary transfected neurons reveal that not only variant‐associated hyperexcitability (M1760I and G1475R) but also hypoexcitability (A1622D) can be modulated by S‐lic. Conclusions and Implications: S‐lic has not only substance‐specific effects but also variant‐specific effects. Personalized treatment regimens optimized to achieve such variant‐specific pharmacological modulation may help to reduce adverse side effects and improve the overall therapeutic outcome of SCN8A‐related disease. [ABSTRACT FROM AUTHOR]
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- 2023
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41. Effects of coronavirus disease 2019 vaccination on seizures in patients with epilepsy.
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Fang, Xiqin, Qiao, Shan, Zhang, Ranran, Yang, Tingting, Wang, Zhihao, Kong, Qingxia, Sun, Meihua, Geng, Jianhong, Fang, Chunyan, Chen, Yanxiu, Sun, Yanping, Zhang, Dongmei, Qu, Lixing, Shang, Wei, Wang, Jianguo, and Liu, Xuewu
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- 2023
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42. Research progress on common pathological types of somatic mutation in epilepsy surgery.
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LI Zi-lin, HU Wen-han, and ZHANG Kai
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EPILEPSY surgery ,GENETIC mutation ,HIPPOCAMPUS (Brain) ,HAMARTOMA ,ATTENTION ,GENES ,MEDICAL research - Abstract
Epilepsy is a common neurological disease in clinic. Epilepsy caused by structural causes can be cured by surgery, which has been the focus of attention in the field of epilepsy surgery. With the development of gene sequencing technology, more and more studies have found that structural etiology may be caused by somatic mutations of genes. In this paper, somatic mutation-related pathogenic genes of four common pathological types of epilepsy surgery, including malformation of cortical development (MCD), long-term epilepsy associated tumor (LEAT), hippocampal sclerosis (HS) and hypothalamic hamartoma (HH), were reviewed, and their effects on surgical protocol formulation and prognosis were reviewed, in order to provide a new idea for the treatment of epilepsy. [ABSTRACT FROM AUTHOR]
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- 2023
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43. Do vaccines cause epilepsy? Review of cases in the National Vaccine Injury Compensation Program.
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Scott RC, Moshé SL, and Holmes GL
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- Humans, Child, Compensation and Redress, Vaccination adverse effects, Spasms, Infantile, Vaccines adverse effects
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Objective: The National Childhood Vaccine Injury Act of 1986 created the National Vaccine Injury Compensation Program (VICP), a no-fault alternative to the traditional tort system. Since 1988, the total compensation paid exceeds $5 billion. Although epilepsy is one of the leading reasons for filing a claim, there has been no review of the process and validity of the legal outcomes given current medical information. The objectives were to review the evolution of the VICP program in regard to vaccine-related epilepsy and assess the rationale behind decisions made by the court., Methods: Publicly available cases involving epilepsy claims in the VICP were searched through Westlaw and the US Court of Federal Claims websites. All published reports were reviewed for petitioner's theories supporting vaccine-induced epilepsy, respondent's counterarguments, the final decision regarding compensation, and the rationale underlying these decisions. The primary goal was to determine which factors went into decisions regarding whether vaccines caused epilepsy., Results: Since the first epilepsy case in 1989, there have been many changes in the program, including the removal of residual seizure disorder as a vaccine-related injury, publication of the Althen prongs, release of the acellular form of pertussis, and recognition that in genetic conditions the underlying genetic abnormality rather than the immunization causes epilepsy. We identified 532 unique cases with epilepsy: 105 with infantile spasms and 427 with epilepsy without infantile spasms. The petitioners' experts often espoused outdated, erroneous causation theories that lacked an acceptable medical or scientific foundation and were frequently criticized by the court., Significance: Despite the lack of epidemiological or mechanistic evidence indicating that childhood vaccines covered by the VICP result in or aggravate epilepsy, these cases continue to be adjudicated. After 35 years of intense litigation, it is time to reconsider whether epilepsy should continue to be a compensable vaccine-induced injury., (© 2023 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)
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- 2024
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44. SLC6A1 variant pathogenicity, molecular function and phenotype:a genetic and clinical analysis
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Stefanski, Arthur, Pérez-Palma, Eduardo, Brünger, Tobias, Montanucci, Ludovica, Gati, Cornelius, Klöckner, Chiara, Johannesen, Katrine M., Goodspeed, Kimberly, Macnee, Marie, Deng, Alexander T., Aledo-Serrano, Ángel, Borovikov, Artem, Kava, Maina, Bouman, Arjan M., Hajianpour, M. J., Pal, Deb K., Engelen, Marc, Hagebeuk, Eveline E.O., Shinawi, Marwan, Heidlebaugh, Alexis R., Oetjens, Kathryn, Hoffman, Trevor L., Striano, Pasquale, Freed, Amanda S., Futtrup, Line, Balslev, Thomas, Abulí, Anna, Danvoye, Leslie, Lederer, Damien, Balci, Tugce, Nouri, Maryam Nabavi, Butler, Elizabeth, Drewes, Sarah, van Engelen, Kalene, Howell, Katherine B., Khoury, Jean, May, Patrick, Trinidad, Marena, Froelich, Steven, Lemke, Johannes R., Tiller, Jacob, Freed, Amber N., Kang, Jing Qiong, Wuster, Arthur, Møller, Rikke S., Lal, Dennis, Stefanski, Arthur, Pérez-Palma, Eduardo, Brünger, Tobias, Montanucci, Ludovica, Gati, Cornelius, Klöckner, Chiara, Johannesen, Katrine M., Goodspeed, Kimberly, Macnee, Marie, Deng, Alexander T., Aledo-Serrano, Ángel, Borovikov, Artem, Kava, Maina, Bouman, Arjan M., Hajianpour, M. J., Pal, Deb K., Engelen, Marc, Hagebeuk, Eveline E.O., Shinawi, Marwan, Heidlebaugh, Alexis R., Oetjens, Kathryn, Hoffman, Trevor L., Striano, Pasquale, Freed, Amanda S., Futtrup, Line, Balslev, Thomas, Abulí, Anna, Danvoye, Leslie, Lederer, Damien, Balci, Tugce, Nouri, Maryam Nabavi, Butler, Elizabeth, Drewes, Sarah, van Engelen, Kalene, Howell, Katherine B., Khoury, Jean, May, Patrick, Trinidad, Marena, Froelich, Steven, Lemke, Johannes R., Tiller, Jacob, Freed, Amber N., Kang, Jing Qiong, Wuster, Arthur, Møller, Rikke S., and Lal, Dennis
- Abstract
Genetic variants in the SLC6A1 gene can cause a broad phenotypic disease spectrum by altering the protein function. Thus, systematically curated clinically relevant genotype-phenotype associations are needed to understand the disease mechanism and improve therapeutic decision-making. We aggregated genetic and clinical data from 172 individuals with likely pathogenic/pathogenic (lp/p) SLC6A1 variants and functional data for 184 variants (14.1% lp/p). Clinical and functional data were available for a subset of 126 individuals. We explored the potential associations of variant positions on the GAT1 3D structure with variant pathogenicity, altered molecular function and phenotype severity using bioinformatic approaches. The GAT1 transmembrane domains 1, 6 and extracellular loop 4 (EL4) were enriched for patient over population variants. Across functionally tested missense variants (n = 156), the spatial proximity from the ligand was associated with loss-of-function in the GAT1 transporter activity. For variants with complete loss of in vitro GABA uptake, we found a 4.6-fold enrichment in patients having severe disease versus non-severe disease (P = 2.9 × 10-3, 95% confidence interval: 1.5-15.3). In summary, we delineated associations between the 3D structure and variant pathogenicity, variant function and phenotype in SLC6A1-related disorders. This knowledge supports biology-informed variant interpretation and research on GAT1 function. All our data can be interactively explored in the SLC6A1 portal (https://slc6a1-portal.broadinstitute.org/).
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- 2023
45. Rest-Activity Rhythm Fragmentation and Weaker Circadian Strength Are Associated With Cognitive Impairment in Survivors of Acute Respiratory Failure.
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Yang, Pei-Lin, Chaytor, Naomi S., Burr, Robert L., Kapur, Vishesh K., McCurry, Susan M., Vitiello, Michael V., Hough, Catherine L., and Parsons, Elizabeth C.
- Subjects
COGNITION disorders ,PATIENT aftercare ,RESPIRATORY insufficiency ,CHRONOBIOLOGY disorders ,SCIENTIFIC observation ,AGE distribution ,CIRCADIAN rhythms ,ACTIGRAPHY ,TERTIARY care ,PSYCHOLOGY of movement ,NEUROPSYCHOLOGICAL tests ,ARTIFICIAL respiration ,SLEEP disorders ,FACTOR analysis ,RESEARCH funding ,DESCRIPTIVE statistics ,DATA analysis software ,EDUCATIONAL attainment ,LONGITUDINAL method - Abstract
Background : Survivors of acute respiratory failure (ARF) experience long-term cognitive impairment and circadian rhythm disturbance after hospital discharge. Although prior studies in aging and neurodegenerative diseases indicate actigraphy-estimated rest-activity circadian rhythm disturbances are risk factors for cognitive impairment, it is unclear if this applies to ARF survivors. This study explored the relationships of actigraphy-estimated rest-activity circadian rhythms with cognitive functioning in ARF survivors at 3 months after discharge. Methods : 13 ARF survivors (mean age 51 years and 69% males) completed actigraphy and sleep diaries for 9 days, followed by at-home neuropsychological assessment. Principal component factor analysis created global cognition and circadian rhythm variables, and these first components were used to examine the global relationships between circadian rhythm and cognitive measure scores. Results : Global circadian function was associated with global cognition function in ARF survivors (r =.70, p =.024) after adjusting for age, education, and premorbid cognition. Also, greater fragmented rest-activity circadian rhythm (estimated by intradaily variability, r =.85, p =.002), and weaker circadian strength (estimated by amplitude, r =.66, p =.039; relative strength, r =.70, p =.024; 24-h lag serial autocorrelation, r =.67, p =.035), were associated with global cognition and individual cognitive tests. Conclusions : These results suggest circadian rhythm disturbance is associated with poorer global cognition in ARF survivors. Future prospective research with larger samples is needed to confirm these results and increase understanding of the relationship between disrupted circadian rhythms and cognitive impairment among ARF survivors. [ABSTRACT FROM AUTHOR]
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- 2023
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46. Negative impact of insomnia and daytime sleepiness on quality of life in individuals with the cyclin‐dependent kinase‐like 5 deficiency disorder.
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Downs, Jenny, Jacoby, Peter, Saldaris, Jacinta, Leonard, Helen, Benke, Tim, Marsh, Eric, and Demarest, Scott
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DROWSINESS ,CHILDREN with intellectual disabilities ,SLEEP interruptions ,QUALITY of life ,SLEEP quality ,INSOMNIA - Abstract
Summary: Cyclin‐dependent kinase‐like 5 (CDKL5) gene pathogenic variants result in CDKL5 deficiency disorder (CDD). Early onset intractable epilepsy and severe developmental delays are prominent symptoms of CDD. Comorbid sleep disturbances are a major concerning symptom for families. We aimed to explore the relationship between insomnia, daytime sleepiness, sleep medications and quality of life in children with CDD. Caregivers of 129 children with CDD in the International CDKL5 Disorder Database completed the Quality‐of‐Life Inventory‐Disability (QI‐Disability) questionnaire and "Disorders of Maintaining Sleep" (DIMS) and the "Disorders of Excessive Somnolence" (DOES) items of the Sleep Disturbance Scale for Children. Adjusting for covariates, a unit increase in DOES score was associated with reduced quality of life total (coefficient −3.06, 95% confidence interval [CI] 1.35–7.80), physical health (coefficient −7.20, 95% CI −10.64, −3.76) and negative emotions (coefficient −3.90, 95% CI −7.38, −0.42) scores. Adjusting for covariates, a unit increase in DIMS score was associated with reduced negative emotions (coefficient −6.02, 95% CI −10.18, −2.86). Use of sleep medications had small influences on the effect sizes. This study highlights the importance of sleep problems as a determinant of quality of life in children with CDD, consistent with effects observed for other groups of children with intellectual disability. Excessive daytime sleepiness was particularly associated with detrimental effects on quality of life. Further research in optimal behavioural and pharmaceutical management of sleep problems for this population is required. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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47. Learning and Living Self-Study Research: Guidelines to the Self-Study Journey.
- Author
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Diacopoulos, Mark M., Gregory, Kristen H., Branyon, Angela, and Butler, Brandon M.
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LEARNING ,DOCTORAL students ,TEACHER education - Abstract
The teaching and learning of self-study research have received increased attention in recent years, although there is still limited research about the learning of self-study. In this article, we share results from a self-study community of practice that describes how one group of novice teacher-educator-researchers learned self-study in a doctoral seminar on teacher education. The doctoral seminar served as a space through which the students simultaneously learned about and enacted self-study research methods. Data for the study included educational autobiographies and journals between students and the instructor, transcribed audio-recordings of course meetings and coding sessions, and course assignments. Through data analysis, we identified six steps in our particular journey of learning self-study: (1) advancing a willingness to improve; (2) acknowledging the power of reflection, (3) examining practice through collaboration, (4) identifying changes in practice, (5) developing new identities, and (6) sharing with others. We offer our experience of learning self-study to provide readers with one set of signposts, support, encouragement, and direction for the teaching and learning of self-study methods. Findings from this research may provide insights to new self-study researchers, scholars who teach self-study research, and experienced self-study researchers who provide on-going support for self-study colleagues. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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48. Structures and Functions of the Human GATOR1 Complex.
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Ivanova I and Shen K
- Subjects
- Humans, Animals, Mechanistic Target of Rapamycin Complex 1 metabolism, Signal Transduction
- Abstract
Eukaryotic cells coordinate available nutrients with their growth through the mechanistic target of rapamycin complex 1 (mTORC1) pathway, in which numerous evolutionarily conserved protein complexes survey and transmit nutrient inputs toward mTORC1. mTORC1 integrates these inputs and activates downstream anabolic or catabolic programs that are in tune with cellular needs, effectively maintaining metabolic homeostasis. The GAP activity toward Rags-1 (GATOR1) protein complex is a critical negative regulator of the mTORC1 pathway and, in the absence of amino acid inputs, is activated to turn off mTORC1 signaling. GATOR1-mediated inhibition of mTORC1 signaling is tightly regulated by an ensemble of protein complexes that antagonize or promote its activity in response to the cellular nutrient environment. Structural, biochemical, and biophysical studies of the GATOR1 complex and its interactors have advanced our understanding of how it regulates cellular metabolism when amino acids are limited. Here, we review the current research with a focus on GATOR1 structure, its enzymatic mechanism, and the growing group of proteins that regulate its activity. Finally, we discuss the implication of GATOR1 dysregulation in physiology and human diseases., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)
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- 2024
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49. De waarde van aanvalsdetectie in de kinderkamer.
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Thijs, Roland
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- 2024
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50. Novel finding of lissencephaly and severe osteopenia in a Chinese patient with SATB2‐associated syndrome and a brief review of literature.
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Lo, Hui‐Yin, Ng, Wai‐Fu, Fong, Nai‐Chung, Lui, Choi‐Yu Dilys, and Lam, Ching‐Wan
- Abstract
SATB2‐associated syndrome (SAS) is a rare disorder characterized by developmental delay, behavioral problems, and craniofacial anomalies in particular dental and palatal abnormalities. We describe the clinical course, genetic and autopsy findings in a Chinese boy with global developmental delay, hypotonia, epilepsy, recurrent fractures and osteopenia. Brain magnetic resonance imaging showed pachygyria, white matter hypoplasia and hypogenesis of the corpus callosum. Whole‐exome sequencing identified a novel heterozygous missense variant c.1555G>A p.(Glu519Lys) in the SATB2 gene. Unfortunately, he died at 26 months of bronchiolitis and pneumonia. Autopsy revealed pachygyria which was more severe anteriorly, dilated lateral and third ventricles and partial agenesis of the corpus callosum. Histology showed features compatible with two‐layered lissencephaly. The bone showed disordered lamination and bone matrix. Although SATB2 has been shown to be involved in the regulation of neuronal migration in the developing brain, lissencephaly has not been reported so far. This could represent a more severe phenotype of SAS. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
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