Neonatal encephalopathy, MRI lesions, and later epilepsy: no harm, no foul?
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ABSTRACT:
SUBMITTER: Staley K
PROVIDER: S-EPMC3423207 | biostudies-literature | 2012 Jul
REPOSITORIES: biostudies-literature
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Neonatal encephalopathy, MRI lesions, and later epilepsy: no harm, no foul?
Epilepsy currents 20120701 4
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Project description:Background: Neonatal encephalopathy (NE) is associated with adverse neurodevelopmental outcome and is linked with systemic inflammation. Pro-inflammatory and anti-inflammatory cytokines are known to play a role in the pathology of NE by activating innate immune cells. Methods: Eighty-seven infants were enrolled including 53 infants with NE of whom 52 received therapeutic hypothermia (TH) and 34 term infant healthy controls (TC). Whole blood sampling was performed in the first 4 days of life, and a 14-spot ELISA Multiplex Cytokine Array was carried out on baseline samples or after stimulation with lipopolysaccharide (LPS) as an additional inflammatory stimulus. The cytokine medians were examined for differences between infants with NE and healthy TC; and then short-term outcomes of Sarnat stage, seizures, and MRI brain were examined within the NE group. The potential of LPS stimulation to predict abnormal MRI was explored using receiver operating characteristic (ROC) curves. Results: At baseline, infants with NE had significantly higher levels of erythropoietin (Epo), interleukin (IL)-6, and IL-1ra and significantly lower vascular endothelial growth factor (VEGF) than had controls. All cytokines were increased after LPS stimulation in infants with NE with an excessive Epo and IL-1ra response than in controls. Infants with NE had lower IL-8, IL-2, IL-6, tumor necrosis factor (TNF)-α, granulocyte-macrophage colony-stimulating factor (GM-CSF), VEGF, and interferon (IFN)-γ than controls had following LPS. GM-CSF and IFN-γ, IL-1β, IL-1ra, and VEGF were higher on days 1-2 in NE infants with abnormal neuroimaging. GM-CSF, IFN-γ, and TNF-α levels with LPS stimulation were different upon stimulation between normal and abnormal neuroimaging. TNF-α is the only strong cytokine predictor both pre- and post-LPS stimulation of abnormal brain imaging. Conclusions: Altered cytokine responses are found in infants with NE vs. controls, and more significant differences are unmasked by the additional stimulus of LPS, which potentially improves the predictive power of these cytokines for the detection of abnormal MRIs. Infants with NE undergoing TH demonstrate both trained immunity and tolerance, and understanding these responses will facilitate adjunctive immunomodulatory treatments.
| S-EPMC8547258 | biostudies-literature
Project description:BackgroundBrain magnetic resonance imaging (MRI) is a key tool for the prognostication of encephalic newborns in the context of hypoxic-ischemic events. The purpose of this study was to finely characterize brain injuries in this context.MethodsWe provided a complete, descriptive analysis of the brain MRIs of infants included in the French national, multicentric cohort LyTONEPAL.ResultsAmong 794 eligible infants, 520 (65.5%) with MRI before 12 days of life, grade II or III encephalopathy and gestational age ≥36 weeks were included. Half of the population had a brain injury (52.4%); MRIs were acquired before 6 days of life among 247 (47.5%) newborns. The basal ganglia (BGT), white matter (WM) and cortex were the three predominant sites of injuries, affecting 33.8% (n = 171), 33.5% (n = 166) and 25.6% (n = 128) of participants, respectively. The thalamus and the periventricular WM were the predominant sublocations. The BGT, posterior limb internal capsule, brainstem and cortical injuries appeared more frequently in the early MRI group than in the late MRI group.ConclusionThis study described an overview of brain injuries in hypoxic-ischemic neonatal encephalopathy. The basal ganglia with the thalamus and the WM with periventricular sublocation injuries were predominant. Comprehensive identification of brain injuries in the context of HIE may provide insight into the mechanism and time of occurrence.
| S-EPMC9032533 | biostudies-literature
Project description:ObjectiveThe objective of this work was to determine the impact of therapeutic hypothermia (TH) on the magnitude and time course of mean diffusivity (MD) changes following hypoxic-ischemic encephalopathy (HIE) in newborns.MethodsCerebral MRI scans of infants undergoing whole body TH for HIE from 2007 to 2010 were retrospectively reviewed. The data were analyzed identically to a control group of newborns with HIE previously published, prior to the development of TH. Anatomic injury was defined on T1- and T2-weighted ("late") MRI obtained after the fifth day of life. Since MD values vary regionally, the ratios of MD values for injured and normal tissue were calculated for areas of injury. Normal values were obtained from corresponding brain regions of 12 infants undergoing TH who had no injury on MRI studies.ResultsTwenty-three of 59 infants who underwent TH and MRI displayed cerebral injury on late MRI and were included in the study. MD ratios were decreased in all injured infants within the first 7 days of life. The return of MD to normal (pseudonormalization) occurred after the tenth day as compared to 6-8 days in the control group. Infants with severest injury demonstrated greater reduction in MD, but no difference in time to pseudonormalization.ConclusionTH slows the evolution of diffusion abnormalities on MRI following HIE in term infants.
| S-EPMC3345786 | biostudies-literature
Project description:ObjectivesTo determine the incidence of later epilepsy in full-term infants with neonatal encephalopathy (NE) who undergo continuous electroencephalography (cEEG) monitoring in the neonatal period and to identify potential predictors of later epilepsy both in infants with and without electrographic neonatal seizures (ENS).MethodsThis was a retrospective observational study performed at Cork University Maternity Hospital, Cork, Ireland, between 2003 and 2019. All term infants with NE had a minimum of 2 h of cEEG monitoring in the neonatal period. ENS were identified via cEEG monitoring. Pediatric medical charts were reviewed to determine if epilepsy developed after the neonatal period and to determine potential predictors of epilepsy in infants both with and without ENS.ResultsTwo hundred and eighty infants were included. The overall incidence rate of epilepsy was 17.55 per 1000 person-years (95% CI: 10.91 to 28.23). In infants with ENS (n = 82), the incidence rate was 39.27 per 1000 person-years (95% CI: 22.30 to 69.16). In infants without ENS (n = 198), the incidence rate was 7.54 per 1000 person-years (95% CI: 3.14 to 18.12). The incidence rate was significantly higher in the ENS group compared to the non-ENS group (p-value = 0.002). Several potential predictors for the development of later epilepsy were identified including infants delivered vaginally, low Apgar scores at 1 and 5 min, severe HIE diagnosis, presence of ENS, a severely abnormal EEG background and an abnormal brain MRI.SignificanceFollowing NE, term infants are at risk of epilepsy with a significantly higher incidence rate in infants who experience ENS compared to those who did not. Close follow-up is required in both groups well into the childhood period.Plain language summaryThis study aimed to determine the occurrence of epilepsy in children who were monitored for seizures in the newborn period. The occurrence of epilepsy was higher in infants who experienced seizures in the newborn period compared to those who did not. Several potential predictors of later epilepsy were identified in both groups of infants (those with and without seizures in the newborn period). Both groups of infants require close follow-up in childhood.
| S-EPMC11803292 | biostudies-literature
Project description:BackgroundDeep nuclear gray matter injury in neonatal hypoxic-ischemic encephalopathy (HIE) is associated with worse neurodevelopmental outcomes. We previously published a qualitative MRI injury scoring system utilizing serial T1-weighted, T2-weighted and diffusion-weighted imaging (DWI), weighted for deep nuclear gray matter injury.ObjectivesTo establish the validity of the MRI scoring system with neurodevelopmental outcome at 18-24 months.Materials and methodsMRI scans from neonates with moderate to severe HIE treated with therapeutic hypothermia were evaluated. Signal abnormality was scored on T1-weighted, T2-weighted and DWI sequences and assessed using an established system in five regions: (a) subcortical: caudate nucleus, globus pallidus and putamen, thalamus and the posterior limb of the internal capsule; (b) white matter; (c) cortex, (d) cerebellum and (e) brainstem. MRI injury was graded as none, mild, moderate or severe. Inter-rater reliability was tested on a subset of scans by two independent and blinded neuroradiologists. Surviving infants underwent the Bayley Scales of Infant and Toddler Development-III (Bayley-III) at 18-24 months. Data were analyzed using univariate and multivariate linear and logistic regression.ResultsFifty-seven eligible neonates underwent at least one MRI scan in the first 2 weeks of life. Mean postnatal age at scan 1 was 4±2 days in 50/57 (88%) neonates and 48/54 (89%) surviving infants underwent scan 2 at 10±2 days. In 54/57 (95%) survivors, higher MRI injury grades were significantly associated with worse outcomes in the cognitive, motor and language domains of the Bayley-III.ConclusionA qualitative MRI injury scoring system weighted for deep nuclear gray matter injury is a significant predictor of neurodevelopmental outcome at 18-24 months in neonates with HIE.
| S-EPMC6219383 | biostudies-literature
Project description:Background: The use of magnetic resonance imaging (MRI) in diagnosis of neonatal acute bilirubin encephalopathy (ABE) in newborns has been limited by its difficulty in differentiating confounding image contrast changes associated with normal myelination. This study aims to demonstrate the feasibility of building a machine learning prediction model based on radiomics features derived from MRI to better characterize and distinguish ABE from normal myelination. Methods: In this retrospective study, we included 32 neonates with clinically confirmed ABE and 29 age-matched controls with normal myelination. Radiomics features were extracted from the manually segmented region of interest (ROI) on T1-weighted spin echo images, followed by the feature selection using two-sample independent t-test, least absolute shrinkage and selection operator (Lasso) regression, and Pearson's correlation matrix. Additional feature quantifying the relative mean intensity of ROI was defined and calculated. A prediction model based on the selected features was built to classify ABE and normal myelination using multiple machine learning classifiers and a leave-one-out cross-validation scheme. Receiver operating characteristics (ROC) analysis was used to evaluate the prediction performance with the area under the curve (AUC) and feature importance ranked based on the Fisher score. Results: Among 1319 radiomics features, one radiologist-defined intensity-based feature and 12 texture features were selected as the most discriminative features. Based on these features, decision trees had the best classification performance with the largest AUC of 0.946, followed by support vector machine (SVM), tree-bagger, logistic regression, Naïve Bayes, discriminant analysis, and k-nearest neighborhood (KNN), which have an AUC of 0.931, 0.925, 0.905, 0.891, 0.883, and 0.817, respectively. The relative mean intensity outperformed other 12 texture features in differentiating ABE from controls. Conclusions: The results from this study demonstrated a new strategy of characterizing ABE-induced intensity and morphological changes in MRI, which are difficult to be recognized, interpreted, or quantified by the routine experience and visual-based reading strategy. With more quantitative and objective measurements, the reported machine learning assisted radiomics features-based approach can improve the diagnosis and support clinical decision-making.
| S-EPMC6779823 | biostudies-literature
Project description:ObjectivePathogenic variants of KCNQ2, which encode a potassium channel subunit, cause either benign (familial) neonatal epilepsy-B(F)NE)-or KCNQ2 encephalopathy (KCNQ2 DEE). We examined the characteristics of KCNQ2 variants.MethodsKCNQ2 pathogenic variants were collected from in-house data and two large disease databases with their clinical phenotypes. Nonpathogenic KCNQ2 variants were collected from the Genome Aggregation Database (gnomAD). Pathogenicity of all variants was reevaluated with clinical information to exclude irrelevant variants. The cumulative distribution plots of B(F)NE, KCNQ2 DEE, and gnomAD KCNQ2 variants were compared. Several algorithms predicting genetic variant pathogenicity were evaluated.ResultsA total of 259 individuals or pedigrees with 216 different pathogenic KCNQ2 variants and 2967 individuals with 247 different nonpathogenic variants were deemed eligible for the study. Compared to the distribution of nonpathogenic variants, B(F)NE and KCNQ2 DEE missense variants occurred in five and three specific KCNQ2 regions, respectively. Comparison between B(F)NE and KCNQ2 DEE sets showed that B(F)NE missense variants frequently localized to the intracellular domain between S2 and S3, whereas those of KCNQ2 DEE were more frequent in S6, and its adjacent pore domain, as well as in the intracellular domain between S6 and helix A. The scores of Protein Variation Effect Analyzer (PROVEAN) and Percent Accepted Mutation (PAM) 30 prediction algorithms were associated with phenotypes of the variant loci.SignificanceMissense variants in the intracellular domain between S2 and S3 are likely to cause B(F)NE, whereas those in S6 and its adjacent regions are more likely to cause KCNQ2 DEE. With such regional specificities of variants, PAM30 is a helpful tool to examine the possibility that a novel KCNQ2 variant is a B(F)NE or KCNQ2 DEE variant in genetic analysis.
| S-EPMC11812603 | biostudies-literature
Project description:ObjectiveTo investigate if an association exists between motion artefacts on brain MRI and comprehension, co-ordination, or hyperactivity scores in children aged 6-8 years, cooled for neonatal encephalopathy (cases) and controls.MethodsCase children (n = 50) without cerebral palsy were matched with 43 controls for age, sex, and socioeconomic status. Children underwent T1-weighted (T1w), diffusion-weighted image (DWI) brain MRI and cognitive, behavioural, and motor skills assessment. Stepwise multivariable logistic regression assessed associations between unsuccessful MRI and comprehension (including Weschler Intelligence Scale for Children (WISC-IV) verbal comprehension, working memory, processing speed and full-scale IQ), co-ordination (including Movement Assessment Battery for Children (MABC-2) balance, manual dexterity, aiming and catching, and total scores) and hyperactivity (including Strengths and Difficulties Questionnaire (SDQ) hyperactivity and total difficulties scores).ResultsCases had lower odds of completing both T1w and DWIs (OR: 0.31, 95% CI 0.11-0.89). After adjusting for case-status and sex, lower MABC-2 balance score predicted unsuccessful T1w MRI (OR: 0.81, 95% CI 0.67-0.97, p = 0.022). Processing speed was negatively correlated with relative motion on DWI (r = -0.25, p = 0.026) and SDQ total difficulties score was lower for children with successful MRIs (p = 0.049).ConclusionsMotion artefacts on brain MRI in early school-age children are related to the developmental profile.ImpactChildren who had moderate/severe neonatal encephalopathy are less likely to have successful MRI scans than matched controls. Motion artefact on MRI is associated with lower MABC-2 balance scores in both children who received therapeutic hypothermia for neonatal encephalopathy and matched controls, after controlling for case-status and sex. Exclusion of children with motion artefacts on brain MRI can introduce sampling bias, which impacts the utility of neuroimaging to understand the brain-behaviour relationship in children with functional impairments.
| S-EPMC10033414 | biostudies-literature
Project description:This series represents samples of multiple myeloma patients with and without bone lytic lesion by MRI. Keywords = multiple myeloma Keywords = osteolytic lesions Keywords = MRI Keywords = osteoblast Keywords = mesenchymal stem cell Keywords = Wnt signaling Keywords = DKK1 Keywords: other
2004-01-01 | GSE755 | GEO
Project description:BackgroundMRI scoring systems are utilized to quantify brain injury and predict outcome in infants with neonatal encephalopathy (NE). Our aim was to evaluate the predictive accuracy of total scores, white matter (WM) and grey matter (GM) subscores of Barkovich and Weeke scoring systems for neurodevelopmental outcome at 2 years of age in infants receiving therapeutic hypothermia for NE.MethodsData of 162 infants were analyzed in this retrospective cohort study. DeLong tests were used to compare areas under the curve of corresponding items of the two scoring systems. LASSO logistic regression was carried out to evaluate the association between MRI scores and adverse composite (death or severe disabilities), motor and cognitive outcomes (Bayley developmental index <70).ResultsWeeke scores predicted each outcome measure with greater accuracy than the corresponding items of Barkovich system (DeLong tests p < 0.03). Total scores, GM and cerebellum involvement were associated with increased odds for adverse outcomes, in contrast to WM injury, after adjustment to 5' Apgar score, first postnatal lactate and aEEG normalization within 48 h.ConclusionA more detailed scoring system had better predictive value for adverse outcome. GM injury graded on both scoring systems was an independent predictor of each outcome measure.Impact statementsA more detailed MRI scoring system had a better predictive value for motor, cognitive and composite outcomes. While hypoxic-ischemic brain injuries in the deep grey matter and cerebellum were predictive of adverse outcome, white matter injury including cortical involvement was not associated with any of the outcome measures at 2 years of age. Structured MRI evaluation based on validated scores may aid future clinical research, as well as inform parents and caregivers to optimize care beyond the neonatal period.
| S-EPMC11798823 | biostudies-literature