scholarly journals Failure to clear developmental apoptosis contributes to the pathology of RNASET2-deficient leukoencephalopathy

2019 ◽  
Author(s):  
Noémie Hamilton ◽  
Holly A. Rutherford ◽  
Hannah M. Isles ◽  
Jessica J. Petts ◽  
Thomas Weber ◽  
...  
Keyword(s):  
Immune Response ◽  
White Matter ◽  
Neurological Disorders ◽  
Preclinical Model ◽  
First Year ◽  
Zebrafish Model ◽  
Brain Infection ◽  
White Matter Disorder ◽  
Embryonic Origin ◽  
First Year Of Life

SummaryThe contribution of microglia in neurological disorders is emerging as a leading driver rather than a consequence of pathology. RNAseT2-deficient leukoencephalopathy is a severe childhood white matter disorder affecting patients in their first year of life and mimics a cytomegalovirus brain infection. The early onset and resemblance of the symptoms to an immune response suggest an inflammatory and embryonic origin of the pathology. In this study, we identify deficient microglia as an early marker of pathology. Using the ex utero development and the optical transparency of an rnaset2-deficient zebrafish model, we found that dysfunctional microglia fail to clear apoptotic neurons during brain development. This was associated with increased number of apoptotic cells and behavioural defects lasting into adulthood. This zebrafish model recapitulates all aspect of the human disease to be used as a robust preclinical model. Using microglia-specific depletion and rescue experiments, we identified microglia as potential drivers of the pathology and highlight tissue-specific approaches as future therapeutic avenues.

scholarly journals White Matter Development from Birth to 6 Years of Age: A Longitudinal Study

2020 ◽  
Vol 30 (12) ◽  
pp. 6152-6168
Author(s):  
Rebecca L Stephens ◽  
Benjamin W Langworthy ◽  
Sarah J Short ◽  
Jessica B Girault ◽  
Martin A Styner ◽  
...  
Keyword(s):  
Individual Differences ◽  
White Matter ◽  
Diffusion Tensor ◽  
First Year ◽  
Imaging Data ◽  
White Matter Microstructure ◽  
White Matter Development ◽  
Psychiatric Outcomes ◽  
First Year Of Life ◽  
Diffusion Tensor Imaging Data

Abstract Human white matter development in the first years of life is rapid, setting the foundation for later development. Microstructural properties of white matter are linked to many behavioral and psychiatric outcomes; however, little is known about when in development individual differences in white matter microstructure are established. The aim of the current study is to characterize longitudinal development of white matter microstructure from birth through 6 years to determine when in development individual differences are established. Two hundred and twenty-four children underwent diffusion-weighted imaging after birth and at 1, 2, 4, and 6 years. Diffusion tensor imaging data were computed for 20 white matter tracts (9 left–right corresponding tracts and 2 commissural tracts), with tract-based measures of fractional anisotropy and axial and radial diffusivity. Microstructural maturation between birth and 1 year are much greater than subsequent changes. Further, by 1 year, individual differences in tract average values are consistently predictive of the respective 6-year values, explaining, on average, 40% of the variance in 6-year microstructure. Results provide further evidence of the importance of the first year of life with regard to white matter development, with potential implications for informing early intervention efforts that target specific sensitive periods.

scholarly journals Immune response to vaccine adjuvants during the first year of life

Vaccine ◽  
2013 ◽  
Vol 31 (21) ◽  
pp. 2500-2505 ◽  
Author(s):  
Ofer Levy ◽  
Stanislas Goriely ◽  
Tobias R. Kollmann
Keyword(s):  
Immune Response ◽  
First Year ◽  
Vaccine Adjuvants ◽  
First Year Of Life

scholarly journals Spatiotemporal dynamics of nonhuman primate white matter development during the first year of life

NeuroImage ◽  
2021 ◽  
Vol 231 ◽  
pp. 117825
Author(s):  
Nakul Aggarwal ◽  
Jason F. Moody ◽  
Douglas C. Dean ◽  
Do P.M. Tromp ◽  
Steve R. Kecskemeti ◽  
...  
Keyword(s):  
White Matter ◽  
Nonhuman Primate ◽  
Spatiotemporal Dynamics ◽  
First Year ◽  
White Matter Development ◽  
First Year Of Life

Variants in the ATP1A3 Gene Mutations within Severe Apnea Starting in Early Infancy: An Observational Study of Two Cases with a Possible Relation to Epileptic Activity

2018 ◽  
Vol 49 (05) ◽  
pp. 342-346 ◽  
Author(s):  
Niklas Holze ◽  
Andreas Baalen ◽  
Ulrich Stephani ◽  
Ingo Helbig ◽  
Hiltrud Muhle
Keyword(s):  
Neurological Disorders ◽  
Gene Mutations ◽  
Epileptic Seizures ◽  
Rapid Onset ◽  
Epileptic Activity ◽  
First Year ◽  
Pathogenic Variants ◽  
Alternating Hemiplegia Of Childhood ◽  
First Year Of Life ◽  
Atp1a3 Gene

AbstractMutations in the ATP1A3 gene are known to cause alternating hemiplegia of childhood (AHC) and rapid-onset dystonia parkinsonism (RDP). Both conditions are childhood-onset neurological disorders with distinct symptoms and different times of onset. ATP1A3 has also been associated with CAPOS syndrome (cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss). Within the various ATP1A3-related neurological syndromes, a specific genotype–phenotype correlation is starting to emerge. Several mutations such as the relatively common p.E815K pathogenic variant have been shown to strongly correlate with AHC, while others may cause both AHC and RDP. A significant subset of patients with AHC and RDP are reported to have epileptic seizures. Even though detailed clinical descriptions of seizures in childhood are rare, seizures involving apneic events seem to be frequent in ATP1A3-related neurological disorders. Here, we describe two children with unexplained severe apnea beginning around the first year of life and pathogenic variants in ATP1A3. We hypothesize that the symptoms are early-onset autonomic seizures related to the underlying pathogenic ATP1A3 variants.

La sindrome di Aicardi-Goutières

2003 ◽  
Vol 16 (3) ◽  
pp. 511-514
Author(s):  
C. Uggetti ◽  
E. Fazzi ◽  
S. D'Arrigo ◽  
F. Zappoli ◽  
G. Lanzi
Keyword(s):  
White Matter ◽  
Autosomal Recessive ◽  
Progressive Increase ◽  
Specific Pattern ◽  
First Year ◽  
White Matter Changes ◽  
Basal Nuclei ◽  
Progressive Encephalopathy ◽  
Neuroradiological Diagnosis ◽  
First Year Of Life

We describe the clinical and neuroradiological features of eleven patients with Aicardi-Goutières syndrome, a rare and severe progressive encephalopathy with onset in the first year of life. The syndrome is autosomal recessive with varying clinical presentation and course. Our patients were studied by CT and MR imaging and findings were in agreement with literature reports. Calcification of the basal nuclei was found in 100% of cases and six patients presented a progressive increase in the number and size of the calcifications which were bilateral and largely symmetrical. White matter changes were seen in 76% of cases without a specific pattern of distribution. Early neuroradiological diagnosis of suspect Aicardi-Goutières syndrome is established by ruling out other pathological processes and the site and features of the calcifications rather than the white matter changes is important to then search for typical CSF changes.

Higher exhaled nitric oxide at 6 weeks of age is associated with less bronchiolitis and wheeze in the first 12 months of age

Thorax ◽  
2021 ◽  
pp. thoraxjnl-2021-217299
Author(s):  
Carla Rebeca Da Silva Sena ◽  
Ediane de Queiroz Andrade ◽  
Patricia de Gouveia Belinelo ◽  
Elizabeth Percival ◽  
Benjamin Prangemeier ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Immune Response ◽  
Respiratory Symptoms ◽  
Beta Agonist ◽  
First Year ◽  
Type 2 Immune Response ◽  
Unit Increase ◽  
Altered Immune Response ◽  
First Year Of Life ◽  
Robust Poisson Regression

BackgroundNitric oxide in exhaled air (eNO) is used as a marker of type 2 immune response-induced airway inflammation. We aimed to investigate the association between eNO and bronchiolitis incidence and respiratory symptoms in infancy, and its correlation with eosinophil protein X (EPX).MethodsWe followed up infants at 6 weeks of age born to mothers with asthma in pregnancy and measured eNO during natural sleep using a rapid response chemiluminescense analyser (CLD88; EcoMedics), collecting at least 100 breaths, interpolated for an expiratory flow of 50 mL/s. EPX normalised to creatinine was measured in urine samples (uEPX/c). A standardised questionnaire was used to measure symptoms in first year of life. Associations were investigated using multiple linear regression and robust Poisson regression models.ResultseNO levels were obtained in 184 infants, of whom 125/184 (68%) had 12 months questionnaire data available and 51/184 (28%) had uEPX/c measured. Higher eNO was associated with less respiratory symptoms during the first 6 weeks of life (n=184, ß-coefficient: –0.49, 95% CI –0.95 to –0.04, p=0.035). eNO was negatively associated with uEPX/c (ß-coefficient: –0.004, 95% CI –0.008 to –0.001, p=0.021). Risk incidence of bronchiolitis, wheeze, cold or influenza illness and short-acting beta-agonist use significantly decreased by 18%–24% for every unit increase in eNO ppb.ConclusionHigher eNO levels at 6 weeks of age may be a surrogate for an altered immune response that is associated with less respiratory symptoms in the first year of life.

scholarly journals НЕДОНОШЕННЫЕ ДЕТИ: ФАКТОРЫ РИСКА, ОТДАЛЕННЫЕ ПОСЛЕДСТВИЯ

2018 ◽  
pp. 15-19
Author(s):  
L. V. Krivitskaya
Keyword(s):  
Risk Factors ◽  
Premature Infants ◽  
Neurological Disorders ◽  
Perinatal Period ◽  
Physical Development ◽  
Psychomotor Development ◽  
First Year ◽  
Premature Births ◽  
First Year Of Life ◽  
Modern Technologies

In recent years there is an increasing topicality of the problem of prematurity because of the growing incidence of premature births in spite of the treatment of pregnant women and application of modern technologies of pregnancy prolongation. According to the WHO report (2015), 15 million children are born prematurely every year and this number is increasing. The article analyzes the risk factors for miscarriage depending on the degree of prematurity and also studies the pathology of the perinatal period, physical and psychomotor development in the first year of life of premature infants. Some distant outcomes of prematurity related to disturbances of physical development, motor and neurological disorders, and premature infant`s intellectual malfunction have been analyzed.

scholarly journals Natural history of Krabbe disease – a nationwide study in Germany using clinical and MRI data

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Sarah Isabel Krieg ◽  
Ingeborg Krägeloh-Mann ◽  
Samuel Groeschel ◽  
Stefanie Beck-Wödl ◽  
Ralf A. Husain ◽  
...  
Keyword(s):  
White Matter ◽  
Natural History ◽  
Neurodegenerative Disorder ◽  
Tube Feeding ◽  
Krabbe Disease ◽  
First Year ◽  
Rapid Progression ◽  
Disease Course ◽  
History Of ◽  
First Year Of Life

Abstract Background Krabbe disease or globoid cell leukodystrophy is a severe neurodegenerative disorder caused by a defect in the GALC gene leading to a deficiency of the enzyme ß-galactocerebrosidase. The aim of this work was to describe the natural disease course covering the whole spectrum of the disease. Methods Natural history data were collected with a standardized questionnaire, supplemented by medical record data. We defined different forms of the disease according to Abdelhalim et al. (2014). Developmental and disease trajectories were described based on the acquisition and loss of milestones as well as the time of first clearly identifiable symptoms and needs such as spasticity, seizures and tube feeding. MRI was assessed using the scoring system by Loes et al. (1999) and in addition a pattern recognition approach, based on Abdelhalim et al. (2014). Results Thirty-eight patients were identified, from 27 of these patients 40 MRIs were available; 30 (79%) had an infantile onset, showing first symptoms in their first year of life, almost all (27 out of 30) starting in the first six months. A later onset after the first year of life was observed in 8 patients (21%, range 18 months to 60 years). Irritability, abnormalities in movement pattern as well as general developmental regression were the first symptoms in the infantile group; disease course was severe with rapid progression, e.g. loss of visual fixation, need for tube feeding and then an early death. Gait disorders were the first symptoms in all patients of the later onset groups; progression was variable. The different forms of the disease were characterized by different MRI patterns (infantile: diffuse white matter involvement and cerebellar structures specifically affected, later onset: parieto-occipital white matter and splenium affected, adult: motor tracts specifically affected). Conclusion This is the first description of the natural history of Krabbe disease in a larger European cohort using developmental, clinical and MRI data. We would like to highlight the very different clinical and MRI characteristics of the later onset forms. These data are important for counselling affected patients and families and may serve as a basis for future treatment trials.

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