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1.
Brain ; 146(8): 3444-3454, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37143309

RESUMO

Brain oedema is a life-threatening complication of various neurological conditions. Understanding molecular mechanisms of brain volume regulation is critical for therapy development. Unique insight comes from monogenic diseases characterized by chronic brain oedema, of which megalencephalic leukoencephalopathy with subcortical cysts (MLC) is the prototype. Variants in MLC1 or GLIALCAM, encoding proteins involved in astrocyte volume regulation, are the main causes of MLC. In some patients, the genetic cause remains unknown. We performed genetic studies to identify novel gene variants in MLC patients, diagnosed by clinical and MRI features, without MLC1 or GLIALCAM variants. We determined subcellular localization of the related novel proteins in cells and in human brain tissue. We investigated functional consequences of the newly identified variants on volume regulation pathways using cell volume measurements, biochemical analysis and electrophysiology. We identified a novel homozygous variant in AQP4, encoding the water channel aquaporin-4, in two siblings, and two de novo heterozygous variants in GPRC5B, encoding the orphan G protein-coupled receptor GPRC5B, in three unrelated patients. The AQP4 variant disrupts membrane localization and thereby channel function. GPRC5B, like MLC1, GlialCAM and aquaporin-4, is expressed in astrocyte endfeet in human brain. Cell volume regulation is disrupted in GPRC5B patient-derived lymphoblasts. GPRC5B functionally interacts with ion channels involved in astrocyte volume regulation. In conclusion, we identify aquaporin-4 and GPRC5B as old and new players in genetic brain oedema. Our findings shed light on the protein complex involved in astrocyte volume regulation and identify GPRC5B as novel potentially druggable target for treating brain oedema.


Assuntos
Edema Encefálico , Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central , Humanos , Proteínas de Membrana/genética , Edema Encefálico/genética , Edema Encefálico/metabolismo , Mutação/genética , Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central/genética , Encéfalo/metabolismo , Astrócitos/metabolismo , Aquaporina 4/genética , Aquaporina 4/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo
2.
Pediatr Res ; 91(4): 879-887, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-33790412

RESUMO

BACKGROUND: Evidence suggests that fronto-limbic brain regions and connecting white matter fibre tracts in the left hemisphere are more sensitive to glucocorticoids than in the right hemisphere. It is unknown whether treatment with glucocorticoids in childhood is associated with microstructural differences of the uncinate fasciculus and cingulum bundle, which connect fronto-limbic brain regions. Here, we tested the hypothesis that prior glucocorticoid treatment would be associated with differences in fractional anisotropy (FA) of the left relative to right uncinate fasciculus and cingulum bundle. METHODS: We performed diffusion-weighted imaging in 28 children and adolescents aged 7-16 years previously treated with glucocorticoids for nephrotic syndrome or rheumatic disease and 28 healthy controls. RESULTS: Patients displayed significantly different asymmetry in the microstructure of uncinate fasciculus with higher left but similar right uncinate fasciculus FA and axial diffusivity compared to controls. No apparent differences were observed for the cingulum. Notably, higher cumulative glucocorticoid doses were significantly associated with higher uncinate fasciculus FA and axial diffusivity bilaterally. CONCLUSIONS: Our findings indicate that previous glucocorticoid treatment for non-cerebral diseases in children and adolescents is associated with long-term changes in the microstructure of the uncinate fasciculi, and that higher cumulative glucocorticoid doses have a proportional impact on the microstructure. IMPACT: It is unknown if treatment with glucocorticoids in childhood have long-term effects on fronto-limbic white matter microstructure. The study examined if children and adolescents previously treated with glucocorticoids for nephrotic syndrome or rheumatic disorder differed in fronto-limbic white matter microstructure compared to healthy controls. The nephrotic and rheumatic patients had higher left but similar right uncinate fasciculus FA and axial diffusivity. Higher bilateral uncinate fasciculus FA and axial diffusivity was associated with higher cumulative glucocorticoid doses. We revealed new evidence suggesting that previous glucocorticoid treatment for non-cerebral diseases in children and adolescents is associated with long-term changes in uncinate fasciculi microstructure.


Assuntos
Síndrome Nefrótica , Substância Branca , Adolescente , Anisotropia , Encéfalo , Criança , Imagem de Tensor de Difusão/métodos , Feminino , Glucocorticoides/uso terapêutico , Humanos , Masculino , Síndrome Nefrótica/diagnóstico por imagem , Síndrome Nefrótica/tratamento farmacológico , Fascículo Uncinado , Substância Branca/diagnóstico por imagem
3.
Acta Paediatr ; 111(2): 323-335, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34655503

RESUMO

AIM: Children with dyskinetic cerebral palsy (CP) are often severely affected and effective treatment is difficult, due to different underlying disease mechanisms. Comprehensive systematic movement disorder evaluations were carried out on patients with this disorder. METHODS: Patients born from 1995 to 2007 were identified from the Danish Cerebral Palsy Register and referrals to the neuropaediatric centre, Rigshospitalet, Copenhagen. They were classified by gross motor function, manual functional ability, communication ability, dystonia and spasticity. Electromyography was carried out on the upper and lower limbs. Magnetic resonance imaging scans were revised, and aetiological searches for underlying genetic disorders were performed. RESULTS: We investigated 25 patients with dyskinetic CP at a mean age of 11.7 years. Dystonia, spasticity and rigidity were found in the upper limbs of 21, four and six children, respectively, and in the lower limbs of 18, 18 and three children. The mean total Burke-Fahn-Marsden score for dystonia was 45.02, and the mean Disability Impairment Scale level was 38% for dystonia and 13% for choreoathetosis. Sustained electromyography activity was observed in 20/25 children. Stretching increased electromyography activity more in children with spasticity. There were 10 re-classifications. CONCLUSION: The children had heterogenic characteristics, and 40% were reclassified after systematic movement disorder evaluation.


Assuntos
Paralisia Cerebral , Distonia , Transtornos dos Movimentos , Paralisia Cerebral/complicações , Paralisia Cerebral/diagnóstico , Criança , Eletromiografia , Humanos , Transtornos dos Movimentos/diagnóstico , Transtornos dos Movimentos/etiologia , Índice de Gravidade de Doença
4.
Neuropediatrics ; 52(6): 462-468, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33706403

RESUMO

AIM: The diagnostic workup in patients with delayed motor milestones suspected of having either myopathy or a congenital myasthenic syndrome is complex. Our hypothesis was that performance of a muscle biopsy and neurophysiology including stimulated single-fiber electromyography during an anesthetic procedure, combined with genetic testing has a high diagnostic quality. MATERIALS AND METHODS: Clinical and paraclinical data were retrospectively collected from 24 patients aged from 1 month to 10 years (median: 5.2 years). RESULTS: Neurophysiology examination was performed in all patients and was abnormal in 11 of 24. No patients had findings suggestive of a myasthenic syndrome. Muscle biopsy was performed in 21 of 24 and was normal in 16. Diagnostic findings included nemaline rods, inclusion bodies, fiber size variability, and type-II fiber atrophy. Genetic testing with either a gene panel or exome sequencing was performed in 18 of 24 patients, with pathogenic variants detected in ACTA1, NEB, SELENON, GRIN2B, SCN8A, and COMP genes. CONCLUSION: Results supporting a neuromuscular abnormality were found in 15 of 24. In six patients (25%), we confirmed a genetic diagnosis and 12 had a clinical neuromuscular diagnosis. The study suggests that combined use of neurophysiology and muscle biopsy in cases where genetic testing does not provide a diagnosis can be useful in children with delayed motor milestones and clinical evidence of a neuromuscular disease.


Assuntos
Doenças Neuromusculares , Anestesia Geral , Biópsia , Criança , Eletrofisiologia , Humanos , Músculo Esquelético/patologia , Músculos , Mutação , Doenças Neuromusculares/diagnóstico , Doenças Neuromusculares/genética , Doenças Neuromusculares/patologia , Estudos Retrospectivos
5.
Dev Med Child Neurol ; 63(12): 1374-1381, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34247401

RESUMO

AIM: To examine nutritional screening methods for children and adolescents with cerebral palsy. METHOD: A scoping review was performed using established methodologies. In June 2020 we searched PubMed, Embase, CINAHL Complete, and the Cochrane Central Register of Controlled Trials to identify articles on tools/methods for nutritional screening of our target groups. RESULTS: Thirty studies were included, containing various tools/methods used to identify under- and/or overnutrition by weight/height, circumferences, skinfolds, questionnaires, and/or technically advanced or invasive methods. Questionnaires, weight/height, circumferences, and skinfolds were considered feasible based on clinical utility, whereas bioelectrical impedance analysis and blood samples were not. INTERPRETATION: We identified two screening tools for undernutrition that include no physical measurements, but did not find any screening tools for overweight and obesity. Most of the studies recommended one or more methods, indicating that determining nutritional status most likely includes a combination of methods, not all of which may be feasible in clinical practice. What this paper adds No nutritional screening tool using anthropometry or body composition was discovered. Heterogenous methods to identify under- and/or overnutrition are recommended. Preferable methods for nutritional screening include assessment of body composition. A validated nutritional screening tool for identification of overweight is warranted.


Assuntos
Peso Corporal/fisiologia , Paralisia Cerebral/complicações , Desnutrição/diagnóstico , Sobrepeso/diagnóstico , Adolescente , Paralisia Cerebral/fisiopatologia , Criança , Humanos , Desnutrição/complicações , Avaliação Nutricional , Estado Nutricional , Sobrepeso/complicações , Dobras Cutâneas , Inquéritos e Questionários
6.
Acta Paediatr ; 110(12): 3367-3375, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34407566

RESUMO

AIM: This study explored hypoglycaemia and metabolic crises, including hyperketosis, in patients with spinal muscular atrophy (SMA). METHODS: The study comprised four adolescents aged 15-17 and six adults aged 19-37 with SMA type II and eight adult controls aged 21-41, who were recruited by the Rigshospitalet, Denmark, from May 1st to October 30th 2017. We used stable isotope technique and indirect calorimetry to investigate fat and glucose metabolism during a 24-h fast or until hypoglycaemia occurred. RESULTS: All patients with SMA II developed moderate to severe hyperketosis and 60% had symptoms of hypoglycaemia or blood glucose levels below 3 mmol/L. None of the controls developed hyperketosis or hypoglycaemia. Plasma bicarbonate decreased, in line with increased ketone bodies, indicating the start of metabolic acidosis in patients with SMA II. Increased fat production and utilisation were seen in healthy controls during the fasting period, but were absent in patients with SMA II, indicating blunted fat oxidation. CONCLUSION: Low skeletal muscle mass was the best explanation for why patients with SMA II had an increased risk of hypoglycaemia, hyperketosis, metabolic acidosis and disturbed fat and glucose metabolism during fasting. These risks have implications for children facing surgery and those with severe illnesses.


Assuntos
Hipoglicemia , Atrofia Muscular Espinal , Atrofias Musculares Espinais da Infância , Adolescente , Adulto , Criança , Jejum , Humanos , Hipoglicemia/etiologia
7.
Pediatr Res ; 83(4): 804-812, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29252981

RESUMO

BackgroundPerinatal exposure to glucocorticoids and elevated endogenous glucocorticoid levels during childhood can have detrimental effects on the developing brain. Here, we examined the impact of glucocorticoid treatment during childhood on brain volumes.MethodsA total of 30 children and adolescents with rheumatic or nephrotic disease previously treated with glucocorticoids and 30 controls matched on age, sex, and parent education underwent magnetic resonance imaging (MRI) of the brain. Total cortical gray and white matter, brain, intracranial volume, and total cortical thickness and surface area were derived from MRI scans.ResultsPatients had significantly smaller gray and white matter and total brain volumes relative to healthy controls. Brain volume differences disappeared when accounting for intracranial volume, as patients had relatively smaller intracranial volumes. Group differences were mainly driven by the children with rheumatic disease. Total cortical thickness and cortical surface area did not significantly differ between groups. We found no significant associations between glucocorticoid-treatment variables and volumetric measures.ConclusionObserved smaller total brain, cortical gray, and white matter volumes in children and adolescents previously treated with glucocorticoids compared with that in healthy controls may reflect both developmental and degenerative processes. Prospective longitudinal studies are warranted to clarify whether findings are related to treatment or disease.


Assuntos
Encéfalo/efeitos dos fármacos , Glucocorticoides/efeitos adversos , Glucocorticoides/uso terapêutico , Nefropatias/tratamento farmacológico , Doenças Reumáticas/tratamento farmacológico , Substância Branca/patologia , Adolescente , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Estudos de Casos e Controles , Criança , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Modelos Lineares , Masculino , Síndrome Nefrótica/tratamento farmacológico , Reconhecimento Automatizado de Padrão
8.
Dev Med Child Neurol ; 60(11): 1123-1131, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29744874

RESUMO

AIM: The International Paediatric Multiple Sclerosis Study Group (IPMSSG) has proposed criteria for acute disseminated encephalomyelitis (ADEM) not evaluated in clinical practice. Our objective was to assess epidemiological implications of the IPMSSG criteria for ADEM in a cohort study using prospectively collected data. METHOD: We identified all diagnosed cases of ADEM in Denmark between 2008 and 2015 from the Danish National Patient Register by International Classification of Diseases 10 codes assigned to acute demyelinating episodes, and we reviewed all medical records to validate ADEM. RESULTS: We found 52 children up to the age of 18 years with a verified clinical diagnosis of ADEM (incidence rate 0.54/100 000 person-years; all had abnormal brain magnetic resonance imaging). Only 18 (35%) fulfilled the IPMSSG criteria regarding encephalopathy and polyfocal neurological deficits. Among all 52 children with ADEM, 33 per cent had clinical sequelae after a median follow-up of 4 years 6 months (range: 10mo-8y 3mo). Surprisingly, none progressed to multiphasic ADEM or multiple sclerosis, but median age at end of follow-up was only 10 years 9 months (range: 2y-24y 3mo). INTERPRETATION: Among 52 children with ADEM, none converted to multiphasic ADEM or multiple sclerosis (median follow-up: 4y 6mo; range: 10mo-8y 3mo). Applying the IPMSSG criteria to all children with a diagnosis of ADEM leaves 65 per cent of the cases without a diagnosis and lowers the incidence rate of paediatric ADEM. WHAT THIS PAPER ADDS: The incidence of paediatric acute disseminated encephalomyelitis (ADEM) was 0.54 per 100 000 person-years in children younger than 18 years. Only 35 per cent of children with ADEM fulfilled the International Paediatric Study Group consensus criteria. ADEM in clinical practice was primarily based on magnetic resonance imaging findings. Paediatric neurologists diagnosed ADEM in the absence of encephalopathy. None of the children with ADEM progressed to multiple sclerosis/multiphasic ADEM during follow-up.


Assuntos
Encefalomielite Aguda Disseminada/diagnóstico , Encefalomielite Aguda Disseminada/epidemiologia , Adolescente , Biomarcadores/líquido cefalorraquidiano , Encéfalo/diagnóstico por imagem , Criança , Pré-Escolar , Consenso , Dinamarca , Feminino , Seguimentos , Humanos , Incidência , Lactente , Imageamento por Ressonância Magnética , Masculino , Esclerose Múltipla , Sistema de Registros , Adulto Jovem
11.
J Biol Chem ; 288(47): 33745-33759, 2013 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-24108130

RESUMO

Hyperekplexia is a syndrome of readily provoked startle responses, alongside episodic and generalized hypertonia, that presents within the first month of life. Inhibitory glycine receptors are pentameric ligand-gated ion channels with a definitive and clinically well stratified linkage to hyperekplexia. Most hyperekplexia cases are caused by mutations in the α1 subunit of the human glycine receptor (hGlyR) gene (GLRA1). Here we analyzed 68 new unrelated hyperekplexia probands for GLRA1 mutations and identified 19 mutations, of which 9 were novel. Electrophysiological analysis demonstrated that the dominant mutations p.Q226E, p.V280M, and p.R414H induced spontaneous channel activity, indicating that this is a recurring mechanism in hGlyR pathophysiology. p.Q226E, at the top of TM1, most likely induced tonic activation via an enhanced electrostatic attraction to p.R271 at the top of TM2, suggesting a structural mechanism for channel activation. Receptors incorporating p.P230S (which is heterozygous with p.R65W) desensitized much faster than wild type receptors and represent a new TM1 site capable of modulating desensitization. The recessive mutations p.R72C, p.R218W, p.L291P, p.D388A, and p.E375X precluded cell surface expression unless co-expressed with α1 wild type subunits. The recessive p.E375X mutation resulted in subunit truncation upstream of the TM4 domain. Surprisingly, on the basis of three independent assays, we were able to infer that p.E375X truncated subunits are incorporated into functional hGlyRs together with unmutated α1 or α1 plus ß subunits. These aberrant receptors exhibit significantly reduced glycine sensitivity. To our knowledge, this is the first suggestion that subunits lacking TM4 domains might be incorporated into functional pentameric ligand-gated ion channel receptors.


Assuntos
Regulação da Expressão Gênica , Rigidez Muscular/metabolismo , Mutação de Sentido Incorreto , Receptores de Glicina/metabolismo , Substituição de Aminoácidos , Feminino , Humanos , Masculino , Rigidez Muscular/genética , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Receptores de Glicina/genética
12.
Nutr Clin Pract ; 37(4): 783-796, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35403308

RESUMO

BACKGROUND: The use of homemade tube feeding formula has become increasingly popular for children requiring enteral nutrition. This project aimed to investigate nutrition and preparation of blenderized tube feeding in the field of children and adolescents with neurological impairment. METHODS: A scoping review was performed using established methodologies. In January 2021, we searched PubMed, Embase, CINAHL Complete, the Cochrane Central Register of Controlled Trials, and gray literature to identify relevant articles. MAJOR FINDINGS: Twenty-two papers were included describing the composition of food items, preparation procedures, and food safety. No randomized controlled trials and only a few prospective studies were included. A broad variety of food items from all food groups and many examples of recipes were presented. Most recipes provided 1.0 kcal/ml but tended to contain less energy and nutrients than expected, which could be due to preparation issues, such as sieving and the high viscosity of the blend. Preparation requires a commercial-grade household blender and diligence to ensure thorough household hygiene for adequate food safety. CONCLUSIONS: This review revealed practical experience in the nutrition and preparation aspects of blenderized tube feeding but minimal empirical evidence. Multiple examples of the composition of food items and preparation procedures for blenderized tube feeding were found, but uncertainty regarding the ideal composition or preparation was also exposed. The future of blenderized tube feeding would benefit from clinically tested recipes that include an evaluation of nutrients, viscosity, and microbial contamination, as well as the effect of the food's appearance and scent on the target group.


Assuntos
Nutrição Enteral , Alimentos Formulados , Adolescente , Criança , Nutrição Enteral/métodos , Inocuidade dos Alimentos , Humanos , Estado Nutricional , Estudos Prospectivos
13.
Mult Scler Relat Disord ; 33: 162-167, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31276927

RESUMO

BACKGROUND: The incidence of pediatric neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease have not been reported previously. Our aim was to estimate the incidence of pediatric NMOSD and the occurrence of anti-MOG antibody-associated disease in Denmark during 2008-18, and to evaluate the diagnostic usefulness of antibodies against MOG and aquaporin-4 (AQP4) in children <18 years. METHODS: We undertook a nationwide, population-based, multicenter cohort study using data from the Danish National Patient Register, the Danish Multiple Sclerosis Registry, and laboratories providing anti-AQP4 and anti-MOG antibody analyses. Diagnoses were confirmed by review of the medical records, including blinded MRI review in most children with acute disseminated encephalomyelitis (ADEM). RESULTS: In children with acquired demyelinating syndromes, anti-AQP4 antibodies were detected in 4% and anti-MOG antibodies in 18%, including in the two children with ADEM who relapsed. We identified four children with NMOSD, equivalent to an incidence of 0.031/100,000 (95% confidence interval = 0.011‒0.082). In anti-MOG antibody-positive children, 32% relapsed during follow-up. CONCLUSIONS: Pediatric NMOSD and MOG antibody-associated disease are rare, but one-third of anti-MOG-positive children relapsed. In pediatric ADEM, only anti-MOG antibody-positive children relapsed, but the overall risk of relapse after pediatric ADEM was low.


Assuntos
Autoanticorpos/imunologia , Glicoproteína Mielina-Oligodendrócito/imunologia , Neuromielite Óptica/epidemiologia , Neuromielite Óptica/imunologia , Adolescente , Autoantígenos/imunologia , Criança , Pré-Escolar , Estudos de Coortes , Dinamarca/epidemiologia , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino
14.
Mol Syndromol ; 7(4): 210-219, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27781031

RESUMO

In recent years, several genes have been causally associated with epilepsy. However, making a genetic diagnosis in a patient can still be difficult, since extensive phenotypic and genetic heterogeneity has been observed in many monogenic epilepsies. This study aimed to analyze the genetic basis of a wide spectrum of epilepsies with age of onset spanning from the neonatal period to adulthood. A gene panel targeting 46 epilepsy genes was used on a cohort of 216 patients consecutively referred for panel testing. The patients had a range of different epilepsies from benign neonatal seizures to epileptic encephalopathies (EEs). Potentially causative variants were evaluated by literature and database searches, submitted to bioinformatic prediction algorithms, and validated by Sanger sequencing. If possible, parents were included for segregation analysis. We identified a presumed disease-causing variant in 49 (23%) of the 216 patients. The variants were found in 19 different genes including SCN1A, STXBP1, CDKL5, SCN2A, SCN8A, GABRA1, KCNA2, and STX1B. Patients with neonatal-onset epilepsies had the highest rate of positive findings (57%). The overall yield for patients with EEs was 32%, compared to 17% among patients with generalized epilepsies and 16% in patients with focal or multifocal epilepsies. By the use of a gene panel consisting of 46 epilepsy genes, we were able to find a disease-causing genetic variation in 23% of the analyzed patients. The highest yield was found among patients with neonatal-onset epilepsies and EEs.

15.
Eur J Paediatr Neurol ; 17(6): 531-6, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23751291

RESUMO

INTRODUCTION: Refractory status epilepticus (RSE) in children is associated with a significant risk of death or neurological morbidity. Recently attention has been drawn to the ketogenic diet (KD) as an acute treatment, as it has shown promise in controlling seizures in otherwise refractory status epilepticus in several cases. We have listed these and reviewed all cases of KD used in RSE at our centre. KD was given as 4:1 fat:carbohydrate-protein solution. RESULTS: A 3-year-old girl with RSE due to Hemiconvulsion-Hemiplegia Epilepsy syndrome. KD was instigated on day 6. Seizures stopped with ketosis on day 7. A 10-year-old boy rapidly developing RSE. After months a mitochondrial disorder was discovered. KD was tried twice with severe side-effects but no seizure control. 11-year-old healthy boy with RSE as FIRES. On KD seizures stopped for 24 h one day after reaching ketosis. He improved over 3-4 weeks. DISCUSSION: KD was efficient in two of three cases of RSE. The non-responder had severe side-effects and proved to have a mitochondrial disorder which is arguably a contraindication for KD. More studies are needed to prove efficacy of KD in RSE, to define optimal timing of KD and possible contraindications for KD in RSE.


Assuntos
Dieta Cetogênica/normas , Estado Epiléptico/dietoterapia , Criança , Pré-Escolar , Feminino , Humanos , Masculino
16.
Neuroimage ; 28(4): 947-55, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16095921

RESUMO

Acute normobaric hypoxia as well as longstanding hypobaric hypoxia induce pronounced physiological changes and may eventually lead to impairment of cerebral function. The aim of the present study is to investigate the effect of hypoxia on the cerebral activation response as well as to explore possible structural changes as measured by diffusion weighted imaging. Eleven healthy sea-level residents were studied after 5 weeks of adaptation to high altitude conditions at Chacaltaya, Bolivia (5260 m). The subjects were studied immediately after return to sea-level in hypoxic and normoxic conditions, and the examinations repeated 6 months later after re-adaptation to sea-level conditions. The BOLD response, measured at 1.5 T, was severely reduced during acute hypoxia both in the altitude and sea-level adapted states (50% reduction during an average S(a)O(2) of 75%). On average, the BOLD response magnitude was 23% lower in altitude than sea-level adaptation in the normoxic condition, but in the hypoxic condition, no significant differences were found. A small but statistically significant decrease in the apparent diffusion coefficient (ADC) was seen in some brain regions during acute hypoxia, whereas ADC was slightly elevated in high altitude as compared to sea-level adaptation. It is concluded that hypoxia significantly diminishes the BOLD response, and the mechanisms underlying this finding are discussed. Furthermore, altitude adaptation may influence both the magnitude of the activation-related response, as well as micro-structural features.


Assuntos
Aclimatação/fisiologia , Altitude , Hipóxia/metabolismo , Oxigênio/sangue , Adulto , Química Encefálica/fisiologia , Interpretação Estatística de Dados , Difusão , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Estimulação Luminosa
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