Дисертації з теми "Developmental and epileptic encephalopathy"
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Sprissler, Ryan S., Jacy L. Wagnon, Rosie K. Bunton-Stasyshyn, Miriam H. Meisler, and Michael F. Hammer. "Altered gene expression profile in a mouse model of SCN8A encephalopathy." ACADEMIC PRESS INC ELSEVIER SCIENCE, 2017. http://hdl.handle.net/10150/622816.
Повний текст джерелаSCN8A encephalopathy is a severe, early-onset epilepsy disorder resulting from de novo gain-of-function mutations in the voltage-gated sodium channel Na(v)1.6. To identify the effects of this disorder on mRNA expression, RNA-seq was performed on brain tissue from a knock-in mouse expressing the patient mutation p.Asn1768Asp (N1768D). RNA was isolated from forebrain, cerebellum, and brainstem both before and after seizure onset, and from age-matched wildtype littermates. Altered transcript profiles were observed only in forebrain and only after seizures. The abundance of 50 transcripts increased more than 3-fold and 15 transcripts decreased more than 3 fold after seizures. The elevated transcripts included two anti-convulsant neuropeptides and more than a dozen genes involved in reactive astrocytosis and response to neuronal damage. There was no change in the level of transcripts encoding other voltage-gated sodium, potassium or calcium channels. Reactive astrocytosis was observed in the hippocampus of mutant mice after seizures. There is considerable overlap between the genes affected in this genetic model of epilepsy and those altered by chemically induced seizures, traumatic brain injury, ischemia, and inflammation. The data support the view that gain-of-function mutations of SCN8A lead to pathogenic alterations in brain function contributing to encephalopathy.
Tona, Risa. "The Phenotypic Landscape of a Tbc1d24 Mutant Mouse Includes Convulsive Seizures Resembling Human Early Infantile Epileptic Encephalopathy." Kyoto University, 2019. http://hdl.handle.net/2433/242396.
Повний текст джерелаTRIVISANO, MARINA. "Characterization of a new epileptic syndrome due to PCDH19 gene mutation." Doctoral thesis, Università di Foggia, 2017. http://hdl.handle.net/11369/363290.
Повний текст джерелаObjective: PCDH19-related epilepsy is an epileptic syndrome, arising within the first three years of life and characterized by clustered and fever-induced seizures. In most of cases it is associated with Intellectual Disability (ID) and autistic features. Aim of this study is to analyze a large Italian population with PCDH19-related epilepsy in order to better define the epileptic phenotype, identify genotype-phenotype correlation, predicting factors for outcome, and markers for differential diagnosis with Dravet Syndrome (DS). The unusual, gender reversed X-chromosome inheritance of PCDH19-FE led also to speculate that genes with different expression between the two sexes may play a role in the pathogenesis and that AKR1C1-3 genes, could be dysregulated, thus resulting in allopegnanolone reduced blood levels. Methods: We retrospectively collected genetic, clinical and EEG data of 61 patients affected by PCDH19-related Epilepsy, coming from 15 Italian hospitals. We stratified patients into two groups according the outcome. We analysed the following variables: mutation type, age at onset, age at study, seizure type, occurrence of status epilepticus, EEG abnormalities, cognitive and behavioural disorders. ROC curve analysis was performed in order to discriminate the age at which seizures could decrease in frequency. A group of 15 patients with PCDH19-related epilepsy were compared with 19 patients with DS. Comparisons were performed with Fisher's exact test or Student's t-test. In order to ascertain allopregnanolone deficiency, we performed a prospective case-control study. We enrolled 12 patients affected by PCDH19-related epilepsy and 15 controls, age-and sex-matched. Controls were recruited among subjects evaluated for praecox puberty or hyperandrogenism. In both groups blood samples were taken at basal (T0) and 60 min after (ACTH) administration (T1). Quantitative analysis of neuroactive steroids in serum was performed by liquid chromatography-electrospray tandem mass spectrometry. Results: At last follow-up (median 12 years; range 1.9-42.1), 13 patients (21.3%) had monthlyweekly seizures, 78.7% annual seizures/clusters or less frequent. Twelve patients (19.7%) were seizure-free since > 2 years. ROC analysis showed a significant decreasing of seizure frequency after the age of 10.5 years (sensitivity 81.0%; specificity 70.0%). Thirty-six patients (59.0%) had ID and behavioral disturbances. ID was moderate-severe in almost half of them. Autistic spectrum disorder was present in 31 patients. An earlier age at epilepsy onset resulted the only predictor factor for ID (p=0.05) and autistic spectrum disorder (p<0.014). Conversely, age at onset was not a predictor factor for seizure outcome (p<0.214). Epilepsy onset was earlier in DS (5.0+2.1 vs 11.2+7.0 months; p<0.05). The second seizure/cluster occurred after a longer latency in PCDH19- related epilepsy rather than in DS (10.1+13.6 vs 2.2+2.1 months; p<0.05). All neuroactive steroids resulted down produced in patients with PCDH19-related epilepsy rather than controls and this data was confirmed after ACTH stimulus. Conclusions: We found that an earlier age at epilepsy onset is linked with a significant risk for ID and autistic spectrum disorder. The decreasing of seizure frequency after the age of 10.5 years supports the hypothesis of a down-regulation of neurosteroid-metabolizing enzymes and allopregnanolone deficiency in PCDH19-related epilepsy. We also documented a down regulation of all steroidogenesis in PCDH19-related epilepsy. Particularly we found allopregnanolone and pregnenolone sulfate deficiency. Allopregnanolone is a GABA-A receptor modulator influencing the neuronal excitability, thus representing a realistic therapeutic target for PCDH19-related epilepsy. We failed to identify any genotype-phenotype correlation considering the site and type of PCDH19 mutations. We were able to find out some distinctive features, which could address the diagnosis towards DS or PCDH19-related epilepsy, since first manifestation. These considerations suggest to definitively considering PCDH19 gene as cause of a proper epileptic phenotype.
Komulainen-Ebrahim, J. (Jonna). "Genetic aetiologies and phenotypic variations of childhood-onset epileptic encephalopathies and movement disorders." Doctoral thesis, Oulun yliopisto, 2019. http://urn.fi/urn:isbn:9789526222356.
Повний текст джерелаTiivistelmä Uusien sekvensointimenetelmien käyttöönotto on mahdollistanut epileptisten enkefalopatioiden ja liikehäiriöiden uusien geneettisten syiden löytymisen. Näissä sairausryhmissä geenien ja ilmiasujen vaihtelevuus on suurta. Tutkimuksen tarkoituksena oli löytää uusia geneettisiä syitä ja ilmiasuja lapsuusiällä alkavissa vaikeahoitoisissa epilepsioissa ja epileptisissä tai kehityksellisissä joko itsenäisesti tai yhdessä liikehäiriön kanssa esiintyvissä enkefalopatioissa sekä perheittäin esiintyvissä liikehäiriöissä. Lisäksi selvitettiin eksomisekvensoinnin käyttökelpoisuutta kliinisessä diagnostiikassa näiden potilasryhmien kohdalla. Tutkimukseen osallistui yhteensä 12 sisäänottokriteerit täyttävää lasta, joiden sairauden syy oli jäänyt tuntemattomaksi. GABRG2-geenin mutaatiot aiheuttivat epileptisiä enkefalopatioita, joiden uutena ilmiasuna oli etenevä taudinkuva, johon liittyivät aivojen rappeutuminen, migroiva imeväisiän paikallisalkuinen epilepsia sekä autismikirjon häiriö. Tutkimuksessa löydettiin uusia GABRG2-mutaatioita: p.P282T ja p.S306F. NACC1-geenin mutaatio aiheutti epilepsian, kehitysvammaisuuden, molemminpuolisen kaihin ja autonomisen hermoston toiminnan häiriön. Hyperkineettinen liikehäiriö oli uusi NACC1 p.R298W -mutaatioon liittyvä ilmiasu. SAMD9L-geenin mutaatio aiheutti perheessä esiintyvän liikehäiriön. Neurologinen ja hematologinen ilmiasu olivat hyvin vaihtelevia. Aivojen kuvantamislöydöksiin sisältyi pikkuaivojen rappeutumista ja valkoisen aivoaineen muutoksia aivokammioiden ympärillä. Näiden tutkimustulosten julkaisemisen jälkeen SAMD9L-geenin mutaatioiden on todettu olevan yksi yleisimmistä perinnöllisistä luuytimen vajaatoiminnan ja myelodysplasian syistä. Homotsygoottinen MTR-geenin mutaatio aiheutti varhain alkaneen epileptisen enkefalopatian, liikehäiriön ja hematologisen häiriön. Kofaktori- ja vitamiini hoidot vähensivät epileptisiä kohtauksia, joihin tavanomainen lääkitys ei tehonnut. Geneettiset syyt ja ilmiasut ovat epileptisissä enkefalopatioissa ja liikehäiriöissä hyvin vaihtelevia, ja osaan on olemassa spesifi hoito. Eksomisekvensointi on käyttökelpoinen diagnostiikan ja uusien geneettisten syiden etsimisen apuna. Tässä tutkimuksessa eksomisekvensoinnin avulla kymmenestä potilaasta kahdelle (20%) saatiin varmistettua geneettinen diagnoosi
Stipa, Carlotta <1983>. "Epileptic and developmental encephalopathies: clinical and genetic study of adult patients attending a tertiary Epilepsy Centre." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2019. http://amsdottorato.unibo.it/9133/1/Stipa_Carlotta_tesi.pdf.
Повний текст джерелаBrough, Jenna Louise. "Using Multiple Sequential Functional Analysis (MSFA) to identify potential developmental pathways of Non-Epileptic Attack Disorder (NEAD)." Thesis, University of Lincoln, 2016. http://eprints.lincoln.ac.uk/23756/.
Повний текст джерелаLindström, Katarina. "Long-term neurodevelopmental outcome after moderate neonatal encephalopathy and after post-term birth : two population-based studies /." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-702-2/.
Повний текст джерелаKuramoto, Takashi. "Tremor and zitter, cauative mutant genes for epilepsy with spongiform encephalopathy in spontaneously epileptic rat (SER), are tightly linked to synaptobrevin-2 and prion protein genes, respectively." Kyoto University, 1998. http://hdl.handle.net/2433/156989.
Повний текст джерелаKyoto University (京都大学)
0048
新制・課程博士
博士(医学)
甲第7060号
医博第1956号
新制||医||681(附属図書館)
UT51-98-C173
京都大学大学院医学研究科病理系専攻
(主査)教授 川口 三郎, 教授 柴崎 浩, 教授 芹川 忠夫
学位規則第4条第1項該当
Kuchenbuch, Mathieu. "Modélisation computationelle de l'épilepsie avec crises focales migrantes du nourrisson." Thesis, Rennes 1, 2019. http://www.theses.fr/2019REN1B062.
Повний текст джерелаEpilepsy in infancy with migrating focal seizures is characterized by focal seizures beginning before 6 months that intensify to a stormy phase where so-called migrating focal seizures appear. The gain-of-function mutations of the KCNT1 gene are the main causes of this epilepsy. We focused on a cohort of patients with a KCNT1 mutations and this epilepsy to better understand this syndrome in order to model it. First, we specified the clinic for these patients, including long-term poor outcomes, high mortality, microcephaly and the presence of extra-neurological symptoms. Then, we determined, through the study of ictal EEGs, that migrating seizures were not chaotic but rather corresponded to a type of propagation and we have identified specific markers of this epilepsy. Then, we showed that the majority of KCNT1 mutations appeared to cluster in "hot spots" and that there was no strict genotypephenotype correlation. Finally, we modelled this epilepsy at microscopic and mesoscopic levels. Preliminary results showed a decrease in excitation, a fall in inhibition and involvement of depolarizing GABA. We then discuss the different aspects of our work in the light of the literature and describe the perspectives opened by this thesis from a fundamental, clinical and physiological point of views
Huynh, Minh Tuan. "Apport de l'analyse chromosomique sur différents microréseaux d'ADN dans l'identification de nouvelles mutations et la caractérisation de gènes candidats impliqués dans la déficience intellectuelle." Thesis, Université de Lorraine, 2013. http://www.theses.fr/2013LORR0129/document.
Повний текст джерелаChromosomal structural abnormalities and Intellectual Disability : In search of intellectual disability candidate genes by using pangenomic comparative genomic hybridization 180 K and high resolution comparative genomic hybridization 1M targeting intellectual disability candidate gene.High resolution microarray-based comparative genomic hybridization (a-CGH) has been a powerful technical innovation in order to detect submicroscopic chromosomal aberrations related to copy number variations. By using a-CGH 180K, 1M high resolution a-CGH and quantitative PCR, we have identified 5 pathogenic intragenic copy number variations (CNVs) de novo : RUNX1T1, KIAA1468, FABP7, ZEB2 (Mowat-Wilson syndrome) and ANKRD11 (KBG syndrome). All five patients had intellectual disability (ID) and facial dysmorphism. Interestingly, a-CGH 180K has revealed a 92 kb deletion of a candidate gene KIAA1468 for West syndrome in a 3 year-old boy with severe ID and early infantile epileptic encephalopathy. Mutational screening for candidate gene KIAA1468 was performed in 35 patients with West syndrome. An intronic variant c.2761-7 T>C and a non synonymous maternally inherited variant c.3547 G>A with unknown clinical significance were identified. By using 1M high-resolution a-CGH approach in 45 patients presenting moderate to severe idiopathic ID, only one causal CNV was identified, a 28.37 kb intragenic ZEB2 deletion. Our study has confirmed the low frequency of intragenic deletion/duplication with the detection of only one chromosomal aberration (1/45). In conclusion, providing that the high frequency of intragenic point mutation, we also stressed the application of next-generation sequencing technology with 45-55% diagnostic yield in patients with idiopathic severe ID in case of no apparent CNV(s) on high-resolution a-CGH
Abidi, Affef. "Contribution à l'étude des encéphalopathies épileptiques précoces : recherche de nouvelles causes génétiques & caractérisation fonctionnelle des mutations du gène KCNQ2." Thesis, Aix-Marseille, 2016. http://www.theses.fr/2016AIXM5009/document.
Повний текст джерелаEarly onset epileptic encephalopathies are rare and severe disorders, characterized by frequent motor seizures occurring before three months of age associated with an altered interictal EEG pattern. The prognosis is poor. During the course of the genetic characterization of a cohort of 402 EOEE patients, we identified a de novo deletion located at Xp11.23 in a male patient and 34 KCNQ2 de novo mutations. The first part of my project consisted in the study of the pathogenicity of the Xp11.23 deletion that encompasses three genes including WDR45. Mutations in the WDR45 gene been have recently identified in patients suffering from neurodegeneration with brain iron accumulation. WDR45 mutations have been almost exclusively found in females. Our patient with the Xp11.23 deletion presented a normal MRI and the EOEE phenotype was predominant. Iron accumulation began only at 5 years. My work reveals that deletions of WDR45 are viable in males and can be diagnosed as EOEE. The second part of my project was aimed at the functional study of two KCNQ2 gene mutations. During this work, my results showed that those mutations were involved in new pathological mechanisms, namely a mislocalization or gain of function. Those results provide new perspectives in term of disease knowledge and therapy. The last part of my project consisted in the development of two new in vitro models for the study of KCNQ2 mutations: stable cell lines expressing the Kv7.2 channel for high-throughput screening of drugs and the production of neurons from induced pluripotent stem cells arising from reprogrammed patient fibroblasts
Dugger, Sarah Anne. "Evaluation of a precision medicine approach for hnRNP U-related developmental epileptic encephalopathy using a mouse model of disease." Thesis, 2020. https://doi.org/10.7916/d8-qevc-mw16.
Повний текст джерелаBeňová, Barbora. "Vliv časné léčby na psychomotorický vývoj u dětí s epileptickou encefalopatií." Doctoral thesis, 2019. http://www.nusl.cz/ntk/nusl-394111.
Повний текст джерелаKolc, Kristy Louise. "Variable Clinical and Molecular Expressivity of PCDH19 Variants and Girls Clustering Epilepsy A disorder of cellular "mosaics"." Thesis, 2020. http://hdl.handle.net/2440/126965.
Повний текст джерелаThesis (Ph.D.) -- University of Adelaide, Adelaide Medical School, 2020
Bitton, Jonathan Y. "Implications des spasmes infantiles sur le neurodéveloppement des enfants." Thèse, 2016. http://hdl.handle.net/1866/18576.
Повний текст джерелаWest syndrome (WS), commonly referred to as infantile spasms (IS), is an epileptic disorder usually characterized by the triad of infantile spasms, a pathognomonic electroencephalogram (EEG) pattern called hypsarrhythmia, and developmental regression. While previous treatment studies were able to achieve relatively adequate spasm control and hypsarrhythmia resolution in this population of patients, they have failed to provide conclusive and definite therapeutic options aimed at improving the poor cognitive outcome often associated to IS. Our study, on which this thesis is based, was the first to use an add-on treatment to conventional antiepileptic drugs, with the intent to improve long-term cognitive outcome in this population. Patients recruited in our original randomized clinical trial (RCT) followed a standardized treatment protocol consisting of vigabatrin (VGB) as first-line treatment for two weeks, followed by adrenocorticotropic hormone (ACTH) in non-responders for another two-week period, and topiramate in refractory cases. In addition, patients were randomized to either receive placebo or flunarizine adjunct therapy for six months. Our multi-centric RCT recruited and evaluated 68 patients, most of which were followed at 8 different time points over a five-year period, to precisely evaluate their neurodevelopmental progress. Our clinical trial generated three main studies which comprise the core of this thesis. In a first study, clinical and cognitive data from the first two years were analyzed. Spasm arrest and hypsarrhythmia resolution were the short-term clinical endpoint measures, while the Vineland Adaptive Behavior Scale (VABS) and Bayley Scales of Infant Development (BSID) were used as cognitive outcome measures at 2 years. This first study most importantly reports on the superior short-term clinical response rate achieved in our study population. Preliminary cognitive results were also presented in this work. Our second study essentially presented long-term cognitive data 5 years after the start of the study. Cognitive outcome measures were similar to those used at two years with the addition of the Stanford-Binet Intelligence Scale, Fifth Edition (SB5) for higher functioning patients. Most IS patients, particularly those with no known etiology, displayed a significant and progressive improvement of cognitive functions, irrespective of adjunctive therapy. Risk factors of long term poor cognitive outcome were also revealed in this study. Our last study tried to understand the relationship between IS and autism spectrum disorders (ASD). Autism was initially screened by means of the Checklist for Autism in Toddlers (CHAT) at 24 months, and formally assessed at the 30-and 60-month follow-up visits using the Autism Diagnostic Observation Schedule (ADOS). ADOS was performed in 44 patients, 10 of which were diagnosed with ASD. A description of risk factors associated with an ASD outcome in the IS population were presented in this article. Finally, based on our study results and in conjunction with literature information on the topic, we attempted to elucidate the pathophysiological characteristics of the disorder. A conceivable description of the underlying biological mechanisms implicated in West syndrome and associated target treatments were presented. Although our complementary treatment, flunarizine, did not prove to be beneficial in our cohort, our treatment protocol was nonetheless able to demonstrate superior clinical and cognitive outcomes in patients with unknown etiologies. These findings, as well as the identification of new potential neurodevelopmental risk factors, could be used clinically to improve the diagnosis and medical follow-up of patients with West syndrome.
Ruzzo, Elizabeth Kathryn. "Identification and Characterization of Pathogenic Mutations in Neurodevelopmental Disorders Discovered by Next-Generation Sequencing." Diss., 2014. http://hdl.handle.net/10161/8784.
Повний текст джерелаNeurodevelopmental disorders develop over time and are characterized by a wide variety of mental, behavioral, and physical phenotypes. The categorization of neurodevelopmental disorders encompasses a broad range of conditions including intellectual disability, autism spectrum disorder, attention deficit hyperactivity disorder, cerebral palsy, schizophrenia, bipolar disorder, and epilepsy, among others. Diagnostic classifications of neurodevelopmental disorders are complicated by comorbidities among these neurodevelopmental disorders, unidentified causal genes, and growing evidence of shared genetic risk factors.
We sought to identify the genetic underpinnings of a variety of neurodevelopmental disorders, with a particular emphasis on the epilepsies, by employing next–generation sequencing to thoroughly interrogate genetic variation in the human genome/exome. First, we investigated four families presenting with a seemingly identical and previously undescribed neurodevelopmental disorder characterized by congenital microcephaly, intellectual disability, progressive cerebral atrophy, and intractable seizures. These families all exhibited an apparent autosomal recessive pattern of inheritance. Second, we investigated a heterogeneous cohort of ∼60 undiagnosed patients, the majority of whom suffered from severe neurodevelopmental disorders with a suspected genetic etiology. Third, we investigated 264 patients with epileptic encephalopathies — severe childhood epilepsy disorders — looking specifically at infantile spasms and Lennox–Gastaut syndrome. Finally, we investigated ∼40 large multiplex epilepsy families with complex phenotypic constellations and unclear modes of inheritance. The studied neurodevelopmental disorders exhibited a range of genetic complexity, from clear Mendelian disorders to common complex disorders, resulting in varying degrees of success in the identification of clearly causal genetic variants.
In the first project, we successfully identified the disease–causing gene. We show that recessive mutations in
In the second project, we exome sequenced 62 undiagnosed patients and their unaffected biological parents (trios). By analyzing all identified variants that were annotated as putatively functional and observed as a novel genotype in the probands (not observed in the unaffected parents or controls), we obtained a genetic diagnosis for 32% (20/62) of these patients. Additionally, we identify strong candidate variants in 31% (13/42) of the undiagnosed cases. We also present additional analysis methods for moving beyond traditional screens, e.g., considering only securely implicated genes, or subjecting qualifying variants from any gene to two unique analysis approaches. This work adds to the growing evidence for the utility of diagnostic exome sequencing, increases patient sizes for rare neurodevelopmental disorders (enabling more detailed analyses of the phenotypic spectrum), and proposes novel analysis approaches which will likely become beneficial as the number of sequenced undiagnosed patients grows.
In the third project, we again employ a trio–based exome sequencing design to investigate the role of
Finally, we investigated multiplex epilepsy families to uncover novel epilepsy susceptibility factors. Candidate variants emerging from sequencing within discovery families were further assessed by cosegregation testing, variant association testing in a case–control cohort, and gene–based resequencing in a cohort of additional multiplex epilepsy families. Despite employing multiple approaches, we did not identify any clear genetic associations with epilepsy. This work has, however, identified a set of candidates that may include real risk factors for epilepsy; the most promising of these is the
Collectively, this body of work has securely implicated three novel neurodevelopmental disease genes that inform the underlying pathology of these disorders. Furthermore, in the final three studies, this work has highlighted additional candidate variants and genes that may ultimately be validated as disease–causing as sample sizes increase.
Dissertation
Novák, Vilém. "Identifikace prediktorů kognitivní dysfunkce u dětí s farmakorezistentní epilepsií." Doctoral thesis, 2020. http://www.nusl.cz/ntk/nusl-435165.
Повний текст джерелаBARILE, ANNA. "Characterisation of the key enzymes involved in vitamin B6 salvage pathway in Escherichia coli and humans." Doctoral thesis, 2019. http://hdl.handle.net/11573/1379435.
Повний текст джерелаPereira, Bianca Chantelle. "Developmental outcomes for infants with hypoxic ischaemic encephalopathy (HIE) who have and have not undergone whole-body hypothermia." Thesis, 2016. http://hdl.handle.net/10539/21307.
Повний текст джерелаThis study aimed to determine the developmental outcomes for infants between the ages of five and 16 months who had and had not received induced hypothermia at Chris Hani Baragwanath Academic Hospital (CHBAH). Forty-three infants diagnosed with HIE II and HIE III were assessed using the Bayley Scales of Infant and Toddler Development – III (Bayley-III) at baseline and were reassessed three to nine months later having received intervention from the transdisciplinary rehabilitation team at CHBAH. The majority of infants (78.3%) who had and had not received induced hypothermia both presented with typical developmental outcomes at baseline with 21.7% having moderate to severe dysfunction. On reassessment (31 infants), the developmental outcomes deteriorated for both groups; with more infants in the group which had received hypothermia falling into the at risk category. In spite of this, the majority of infants (in both groups) that were reassessed were overall developmentally on par. This study highlights the importance of on-going monitoring of infants with HIE, receiving home programmes and the need for therapeutic intervention after the age of one year with a focus on specific developmental issues. Standardized assessments are essential to facilitate more precise and effective intervention programmes.
MT2016
Nicolson, Tasha. "Developmental motor outcomes of children aged nine to twenty-four months with hypoxic ischaemic encephalopathy based on the Thompson score." Thesis, 2019. https://hdl.handle.net/10539/29807.
Повний текст джерелаHypoxic ischaemic encephalopathy (HIE) is the occurrence of impaired neurological function in a new-born, associated with asphyxia at birth. It may be considered mild, moderate or severe depending on the presence or absence of various clinical signs. The incidence of HIE in South Africa ranges from 0.4 – 3.7 per 1000 live births. In the moderate and severe form, HIE is known to cause functional motor deficits, cognitive deficits, intellectual impairment, language, learning and executive skills limitations and/or social impairments. This study was a quantitative cross-sectional study investigating the motor outcomes, as measured by the Peabody Developmental Motor Scales: second edition (PDMS-2), of 28 children with various severities of HIE. The severity of the HIE was measured by the Thompson HIE score. Participants were between the ages of nine and twenty-four months and attended the Mowbray Maternity Hospital Neurodevelopmental High-Risk Clinic. There were thirteen participants with mild HIE, seven participants with moderate HIE and eight participants with severe HIE. Demographic and perinatal factors were comparable across groups. Results of the study showed that all participants functioned within the normal range for all subtests of the PDMS-2. The mild and moderate HIE groups were comparable in all areas and therefore were combined and compared to the severe group. This comparison showed that the severe HIE group performed worse in all subtests with small to large effect sizes. It is therefore important for occupational therapists to ensure that children with severe HIE, according to the Thompson HIE score receive comprehensive assessment and follow up treatment. This assessment and treatment should focus on fine motor development, particularly VMI.
MT 2020
Tomé, Fernanda Manuela da Silva. "West Syndrome: from etiology to prognosis." Master's thesis, 2020. http://hdl.handle.net/10316/97741.
Повний текст джерелаThe West syndrome is an epileptic encephalopathy in the child's first year of life, corresponding to 1.4% of the epileptic syndromes in pediatric age. It is characterized by the triad: 1) epileptic spasms, 2) hypsarrhythmic tracing on the electroencephalogram (EEG) and 3) neurodevelopment regression. It affects both sexes, with a higher incidence in males. The syndrome's etiology is diverse, including genetic, structural, metabolic, infectious, immunological and still unknown causes, which is why its diagnostic complexity is not negligible. Neonatal hypoxic-ischemic encephalopathy is one of the most frequent etiologies, but extensive genetic, structural and metabolic investigation is often necessary for a correct etiological diagnosis. The epileptic spasms accompanying this pathology are sometimes brief and subtle and are often confused with abdominal cramps or episodes of gastroesophageal reflux, which delays the recognition of this syndrome. At diagnosis, it is possible to document ictal and interictal epileptic activity on the EEG that occurs in an early period of brain maturation, which is why it is the cause of significant cognitive impairment. The prognosis is variable, according to the etiology, the age of onset, the age of diagnosis, the therapy instituted and the response to therapy.In about two thirds of cases, the prognosis of West Syndrome is reserved, with progression to Lennox Gastaut syndrome and/or association with Autism Spectrum Disorder. The identification of the etiology can play a crucial role, since it provides information that should be considered in the selection of the most effective antiepileptic therapy. Some etiologies respond better to specific medications and may show a worse response with others. The unfavorable prognostic impact of this encephalopathy will depend, among other factors, fundamentally on the etiology, on an early diagnosis of the encephalopathy and will certainly benefit from a therapeutic approach as directed as possible.
O Síndrome de West é uma encefalopatia epilética do primeiro ano de vida da criança, correspondendo a 1,4% dos síndromes epiléticos, em idade pediátrica. Caracteriza-se pela tríada de espasmos epiléticos, traçado hipsarrítmico no eletroencefalograma (EEG) e paragem/regressão do neurodesenvolvimento. Atinge ambos os sexos, com maior incidência no sexo masculino. A etiologia do síndrome é diversa, incluindo causas genéticas, estruturais, metabólicas, infeciosas, imunológicas ou ainda desconhecida, pelo que lhe está associado uma complexidade diagnóstica não negligenciável. A encefalopatia hipóxico-isquémica neonatal é uma das etiologias mais frequentes, mas é muitas vezes necessária extensa investigação genética, estrutural e metabólica para um correto diagnóstico etiológico. Os espasmos infantis que acompanham esta patologia apresentam-se por vezes breves e subtis, sendo frequentemente confundidos com cólicas abdominais ou episódios de refluxo gastroesofágico, o que leva a algum atraso na identificação deste síndrome. Ao diagnóstico, é possível documentar atividade epilética ictal e interictal no EEG que ocorre num período precoce de maturação cerebral, sendo, por isso, causa de importante atraso no neurodesenvolvimento. O prognóstico é variável, de acordo com a etiologia, a idade de início e de diagnóstico, a terapêutica instituída e sua resposta. Em cerca de dois terços dos casos, o prognóstico do Síndrome de West é reservado, com evolução para síndrome Lennox Gastaut e/ou associação a perturbação do espectro do autismo. A identificação da etiologia pode desempenhar um papel crucial, uma vez que fornece informação que pode e deve ser considerada na seleção da terapêutica antiepilética mais eficaz. Algumas etiologias respondem melhor a medicações específicas e poderão mostrar pior resposta com outras. O impacto prognóstico desfavorável desta encefalopatia dependerá, entre outros factores, fundamentalmente da etiologia, do diagnóstico precoce da encefalopatia, beneficiando certamente de uma abordagem terapêutica o mais dirigida possível.
Sukha, Neelam. "The developmental motor outcomes of infants with hypoxic ischaemic encephalopathy II and III between the ages of 12-14 months at Chris Hani Baragwanath academic hospital." Thesis, 2013.
Знайти повний текст джерелаThis study determined outcomes for motor developmental delay in infants, 12-14 months, diagnosed with HIE II and III, at Chris Hani Baragwanath Academic Hospital. Twenty nine infants diagnosed with HIE II and nine infants diagnosed with HIE III were assessed using the Peabody Development Motor Scale- 2, at their corrected age. Demographic, antenatal and perinatal factors similar to those in other studies were found for this sample. Infants with HIE III had significantly more developmental delay (p=0.01) than infants with HIE II. Fifty two percent of infants with HIE II had no delay while a 100% of infants with HIE III presented with disability. A greater percentage of infants had delay in fine motor skills. Infants with severe and moderate disabilities were receiving intervention whereas those mild disabilities were often missed in screening clinics. It is vital to ensure these infants are assessed and followed up to remediate difficulties as soon as they arise.
Cloutier, Véronique. "Criblage génétique et caractérisation fonctionnelle des mutations dans le gène CHD2 associé à l’épilepsie dans un modèle de poisson zèbre." Thèse, 2018. http://hdl.handle.net/1866/21388.
Повний текст джерелаMarcoux, Lydia. "Investigation du rôle de Myo9b dans la migration des interneurones GABAergiques corticaux." Thèse, 2015. http://hdl.handle.net/1866/13860.
Повний текст джерелаEpileptic encephalopathies are early-onset diseases characterized by refractory epilepsy with developmental delay. To identify the underlying genetic cause of these disorders, Dr Rossignol’s laboratory has performed whole-exome sequencing in children with sporadic epileptic encephalopathies. They have identified a novel de novo mutation in the MYO9B gene in one patient. Myo9b is known to regulate cell migration in the immune system and in cancer cells. It is expressed in the developing rodent brain, but its roles during brain development are largely unknown. Recent evidence suggests that epilepsy can be caused by an imbalance between inhibition and excitation in cortical circuits. Indeed, defects in the development or the functions of cortical GABAergic interneurons (INs) have been associated with epilepsy in human and in mouse models. Therefore, we postulated that Myo9b might play a role in the development of INs. In this thesis, I show that Myo9b is expressed in INs from early embryonic ages to post-natal ages. Furthermore, I demonstrate that the ex vivo downregulation of Myo9b in INs in cortical embryonic organotypic cultures causes morphological defects in migrating INs, including aberrant polarization of these cells. These morphological changes might result in aberrant IN migration, which would be expected to perturb the cortical inhibitory-excitatory ratio.
Mendizabal, Sandrine. "La mémoire de travail visuelle chez l'enfant avec une épilepsie bénigne à pointes centro-temporales et chez l'enfant sain." Thèse, 2016. http://hdl.handle.net/1866/18496.
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