Anti-transglutaminase 6 antibodies in children and young adults with cerebral palsy.
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ABSTRACT:
SUBMITTER: Stenberg R
PROVIDER: S-EPMC3996887 | biostudies-literature | 2014
REPOSITORIES: biostudies-literature
Publications
Anti-transglutaminase 6 antibodies in children and young adults with cerebral palsy.
Stenberg Reidun R Hadjivassiliou Marios M Aeschlimann Pascale P Hoggard Nigel N Aeschlimann Daniel D
Autoimmune diseases 20140402
Objectives. We have previously reported a high prevalence of gluten-related serological markers (GRSM) in children and young adults with cerebral palsy (CP). The majority had no enteropathy to suggest coeliac disease (CD). Antibodies against transglutaminase 6 (anti-TG6) represent a new marker associated with gluten-related neurological dysfunction. The aim of this study was to investigate the prevalence of anti-TG6 antibodies in this group of individuals with an early neurological injury result ...[more]
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Project description:ObjectiveTo develop an algorithm on the basis of data obtained with a reliable, standardized neurological examination and report the prevalence of cerebral palsy (CP) subtypes (diparesis, hemiparesis, and quadriparesis) in a cohort of 2-year-old children born before 28 weeks gestation.Study designWe compared children with CP subtypes on extent of handicap and frequency of microcephaly, cognitive impairment, and screening positive for autism.ResultsOf the 1056 children examined, 11.4% (120) were given an algorithm-based classification of CP. Of these children, 31% had diparesis, 17% had hemiparesis, and 52% had quadriparesis. Children with quadriparesis were 9 times more likely than children with diparesis (76% versus 8%) to be more highly impaired and 5 times more likely than children with diparesis to be microcephalic (43% versus 8%). They were more than twice as likely as children with diparesis to have a score <70 on the mental scale of the BSID-II (75% versus 34%) and had the highest rate of the Modified Checklist for Autism in Toddlers positivity (76%) compared with children with diparesis (30%) and children without CP (18%).ConclusionWe developed an algorithm that classifies CP subtypes, which should permit comparison among studies. Extent of gross motor dysfunction and rates of co-morbidities are highest in children with quadriparesis and lowest in children with diparesis.
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Project description:Background/Objectives: This study aimed to validate five published ActiGraph (AG) cut-off points for the measurements of physical activity (PA) and sedentary time (ST) in ambulatory children and young adults with cerebral palsy (CP). Additionally, four energy expenditure (EE) prediction equations based on AG counts and activPAL (AP) steps were examined in this population, using oxygen uptake (VO2) as the criterion.MethodsFour male and six female participants with CP (Gross Motor Function Classification System levels I-III, ages 9-21 years) completed seven activities while simultaneously wearing an AG, AP monitor and indirect calorimetry unit. VO2 was measured on a breath-by-breath basis using the indirect calorimetry and was converted into EE using metabolic equivalents. AG counts were classified as sedentary, light PA (LPA) or moderate-to-vigorous PA (MVPA) using five cut-off points: Puyau, Evenson, Romanzini, Clanchy and Baque. The predicted EE was computed using three AG-based equations (Freedson, Trost and Treuth) and an AP step-based equation.ResultsBased on 1920 available data points from the 10 participants, Baque (r = 0.896, κ = 0.773) and Clanchy (r = 0.935, κ = 0.721) AG cut-off points classified PA and ST most accurately. All the equations overestimated EE during sitting activities and underestimated EE during rapid walking. The Freedson, Treuth and AP equations exhibited systematic bias during rapid walking, as their differences from the criterion measure increased progressively with increasing activity intensity.ConclusionsThe AG accurately classified PA and ST when the Baque and Clanchy cut-off points were used. However, none of the available AG or AP equations accurately predicted the EE during PA and ST in children and young adults with CP. Further development is needed to ensure that both devices can estimate EE accurately in this population.
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2012-11-21 | E-GEOD-31243 | biostudies-arrayexpress
Project description:BackgroundCeliac disease (CD) is an autoimmune gastrointestinal disorder characterized by the presence of anti-transglutaminase 2 (TG2) and anti-gliadin antibodies. Amongst the neurological dysfunctions associated with CD, ataxia represents the most common one.MethodsWe analyzed by immunohistochemistry, the anti-neural reactivity of the serum from 20 CD patients. To determine the role of anti-TG2 antibodies in ataxia, two anti-TG2 single chain variable fragments (scFv), isolated from a phage-display IgA antibody library, were characterized by immunohistochemistry and ELISA, and injected in mice to study their effects on motor coordination. We found that 75% of the CD patient population without evidence of neurological involvement, has circulating anti-neural IgA and/or IgG antibodies. Two anti-TG2 scFvs, cloned from one CD patient, stained blood vessels but only one reacted with neurons. This anti-TG2 antibody showed cross reactivity with the transglutaminase isozymes TG3 and TG6. Intraventricular injection of the anti-TG2 or the anti-TG2/3/6 cross-reactive scFv provoked transient, equally intensive ataxia in mice.ConclusionThe serum from CD patients contains anti-TG2, TG3 and TG6 antibodies that may potentially cause ataxia.
| S-EPMC2837746 | biostudies-literature
Project description:Cerebral palsy is primarily an upper motor neuron disease that results in a spectrum of progressive movement disorders. Secondary to the neurological lesion, muscles from patients with cerebral palsy are often spastic and form debilitating contractures that limit range of motion and joint function. With no genetic component, the pathology of skeletal muscle in cerebral palsy is a response to aberrant neurological input in ways that are not fully understood. This study was designed to gain further understanding of the skeletal muscle response to cerebral palsy using microarrays and correlating the transcriptional data with functional measures. Hamstring biopsies from gracilis and semitendinosus muscles were obtained from a cohort of patients with cerebral palsy (n=10) and typically developing patients (n=10) undergoing surgery. Affymetrix HG-U133A 2.0 chips (n=40) were used and expression data was verified for 6 transcripts using quantitative real-time PCR, as well as for two genes not on the microarray. Chips were clustered based on their expression and those from patients with cerebral palsy clustered separately. Significant genes were determined conservatively based on the overlap of three summarization algorithms (n=1,398). Significantly altered genes were analyzed for over-representation among gene ontologies, transcription factors, pathways, microRNA and muscle specific networks. These results centered on an increase in extracellular matrix expression in cerebral palsy as well as a decrease in metabolism and ubiquitin ligase activity. The increase in extracellular matrix products was correlated with mechanical measures demonstrating the importance in disability. These data lay a framework for further studies and novel therapies.
2012-11-21 | GSE31243 | GEO
Project description:BACKGROUND:Cerebral Palsy (CP) is a group of disorders that affect the development of movement and posture. CP results from injuries to the immature brain during the prenatal, perinatal, or postnatal stage of development. Neuroimaging research in CP has focused on the structural changes of the brain during early development, but little is known about brain's structural and functional changes during late adolescence and early adulthood, a period in time when individuals experience major changes as they transition into adulthood. The work reported here served as a feasibility study within a larger program of research (MyStory Study). We aimed to determine whether it would be feasible to scan and obtain good quality data without the use of sedation during a resting state condition for functional connectivity (FC) analyses in young adults with CP. Second, we aimed to identify the FC pattern(s) that are associated with depressive mood ratings, indices of pain and fatigue, and quality of life in this group. METHODS:Resting state functional images were collected from 9 young people with CP (18-29?years). We applied a stringent head motion correction and quality control methods following preprocessing. RESULTS:We were able to scan and obtain good quality data without the use of sedation from this group of young individuals with CP who demonstrated a range of gross motor ability. The functional connectivity networks of interest were identified in the data using standard seed regions. Our analyses further revealed that higher well-being scores were associated with higher levels of FC between the Medial Pre-Frontal Cortex and the right Lateral Parietal regions, which are implicated in prosocial and emotion regulations skills. The implications of this association are discussed. CONCLUSION:The findings of the present study demonstrate that it is feasible to conduct resting state functional connectivity in young adults with CP with different gross motor abilities without the use of sedation. Our results also highlight a neural circuitry that is associated with the self-report of quality of life and emotion regulation. These findings identify these regions/circuitries as important seeds for further investigations into mental health and wellbeing in CP.
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Project description:Data describing the unmet health needs of young adults with cerebral palsy (CP) may support the development of appropriate health services. This study aimed to describe unmet health needs among young adults with CP in Ireland and examine if these differed between young adults who were and were not yet discharged from children's services. In this cross-sectional study, young adults with CP aged 16-22 years completed a questionnaire assessing unmet health needs. Logistic regression was used to examine the association between discharge status and unmet health needs. Seventy-five young adults (mean age 18.4 yr; 41% female; 60% in GMFCS levels I-III) were included in the study. Forty (53%) had been discharged from children's services. Unmet health need, as a proportion of those with needs, was highest for speech (0.64), followed by epilepsy (0.50) and equipment, mobility, control of movement and bone or joint problems (0.39 or 0.38). After adjusting for ambulatory status, unmet health needs did not differ according to discharge status. The proportion of young adults with unmet health needs highlights the importance of taking a life-course approach to CP and providing appropriate services to people with CP regardless of age.
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Project description:Cerebral palsy (CP) is a disorder characterized by abnormal tone, posture and movement and clinically classified based on the predominant motor syndrome-spastic hemiplegia, spastic diplegia, spastic quadriplegia, and extrapyramidal or dyskinetic. The incidence of CP is 2-3 per 1,000 live births. Prematurity and low birthweight are important risk factors for CP; however, multiple other factors have been associated with an increased risk for CP, including maternal infections, and multiple gestation. In most cases of CP the initial injury to the brain occurs during early fetal brain development; intracerebral hemorrhage and periventricular leukomalacia are the main pathologic findings found in preterm infants who develop CP. The diagnosis of CP is primarily based on clinical findings. Early diagnosis is possible based on a combination of clinical history, use of standardized neuromotor assessment and findings on magnetic resonance imaging (MRI); however, in most clinical settings CP is more reliably recognized by 2 years of age. MRI scan is indicated to delineate the extent of brain lesions and to identify congenital brain malformations. Genetic tests and tests for inborn errors of metabolism are indicated based on clinical findings to identify specific disorders. Because CP is associated with multiple associated and secondary medical conditions, its management requires a multidisciplinary team approach. Most children with CP grow up to be productive adults.
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Project description:Introduction: While most people with cerebral palsy (CP) will have a life expectancy similar to that of the general population, international research has primarily focused on childhood and adolescence; and knowledge about the quality of life (QoL) of young adults with CP, its trajectories, and associated factors remains scarce. Methods: This longitudinal study included young adults with CP living in five European regions and who had previously participated in the SPARCLE cohort as children and/or adolescents. Their QoL in the psychological well-being and social relationships domains was estimated using age-appropriate validated instruments (KIDSCREEN-52 in childhood/adolescence and WHOQOL-Bref in young adulthood). We used generalized linear mixed-effect models with random intercept to estimate long-term trajectories of QoL in both domains and to investigate whether severity of impairment, pain, and seizure influenced these trajectories. We sought to identify potentially different trajectories of QoL from childhood to adulthood using a shape-based clustering method. Results: In total, 164 young adults with CP aged 22-27 years participated in the study. Psychological well-being linearly decreased by 0.78 points (scale 0-100) per year (95% confidence interval (CI) -0.99 to -0.56) from childhood to young adulthood, whereas QoL in the social relationships domain increased (β coefficient 1.24, 95% CI 0.92-1.55). Severity of impairment was associated with reduced QoL in all life periods of the study (childhood, adolescence, and young adulthood): motor impairment with social relationships, and more nuancedly intellectual disability with psychological well-being and social relationships. At all periods, frequent pain significantly reduced psychological well-being, and seizures were associated with lower QoL in the social relationships domain. In both domains, we identified a group of individuals with CP who presented a reverse trajectory compared with the general QoL trajectory. Conclusion: Identification of QoL trajectories and their associated factors yields improved knowledge about the experience of individuals with CP until young adulthood. Further studies are needed to better understand the determinants that have the greatest influence on the different shapes of long-term trajectories of QoL.
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