The predictive value of MRI scores for neurodevelopmental outcome in infants with neonatal encephalopathy.

BACKGROUND: MRI 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. METHODS: Data 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). RESULTS: Weeke 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. CONCLUSION: A 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 STATEMENTS: A 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.

Predictive performance and metabolite dynamics of proton MR spectroscopy in neonatal hypoxic-ischemic encephalopathy.

BACKGROUND: Prognostic value of proton MR spectroscopy (H-MRS) in hypoxic-ischemic encephalopathy (HIE) is acknowledged; however, effects of gestational age (GA) and postnatal age (PA) on prediction and metabolite levels are unknown. METHODS: One hundred and sixty-nine newborns with moderate-to-severe HIE were studied, having ≥1 H-MRS scan during postnatal days 0-14 and known neurodevelopmental outcome (Bayley-II score/cerebral palsy/death). Initial scans were categorized by PA (day 1-3/4-6/≥7), and metabolite ratios were compared by predictive value. Metabolite dynamics were assessed in a total of 214 scans performed in the study population, using regression modeling, with predictors GA, PA, and outcome. RESULTS: N-acetyl-aspartate (NAA)/creatine (Cr) and myo-inositol (mI)/NAA height ratios were consistently associated with outcome throughout the first 14 days, with the highest predictive value in the late (≥7 days) period (AUC = 0.963 and 0.816, respectively). Neither GA nor PA had an overall effect on these metabolite ratios, which showed strongest association with outcome (p < 0.001). Assessed separately in patients with good outcome, GA became a significant covariate for metabolite ratios (p = 0.0058 and 0.0002, respectively). However, this association disappeared in the poor outcome group. CONCLUSIONS: In HIE, NAA/Cr and mI/NAA give most accurate outcome prediction throughout postnatal days 0-14. GA only affected metabolite levels in the good outcome group. IMPACT: Proton MR spectroscopy metabolite ratios N-acetyl-aspartate/creatine and myo-inositol/N-acetyl-aspartate have persistently high predictive value throughout postnatal days 0-14 in newborns with hypoxic-ischemic encephalopathy, with the highest predictive power between postnatal days 7 and 14. Overall, neither metabolite ratio was affected by gestational age nor by postnatal age, while they showed the strongest association with neurological outcome. However, in newborns facing good outcome, metabolite ratios were associated with gestational age, whereas in cases facing poor outcome, this association disappeared. Proton MR spectroscopy provides valuable prognostic information in neonatal hypoxic-ischemic encephalopathy throughout the first 2 weeks of life, irrespective of the timing of MR scan.

Prevalence of cerebral palsy and data quality assessment of patient documentation at the Clinics of Semmelweis University / A cerebralis paresis elofordulása és a betegdokumentáció minoségi vizsgálata a Semmelweis Egyetem klinikáin

Introduction, aim: Quality control of patient documentation for cerebral palsy (CP) at Semmelweis University. METHOD: In our retrospective audit, we revised patient records for all children born between 2005 and 2015, with suspected CP, registering 673 cases with confirmed CP. Based on the available patient data, we assessed clinical and etiological classification of CP and data availability. RESULTS: Patient records of 86% of children were suitable for clinical classification. Among them, 90.5% were spastic, 7.8% hypotonic, 1.2% dyskinetic and 0.5% ataxic. Among the classifiable spastic cases (98% of all spastic cases), 51% presented with tetraparetic/tetraplegic, 26% diparetic/diplegic and 23% hemiparetic/hemiplegic localization; in the remaining 2%, sufficient data for topological classification was unavailable. Severity assessed on Gross Motor Function Classification System was definable in 82% of cases, 43% showing grade I-II, 28% grade III and 29% grade IV-V impairment. Patient history was specified in 91% of cases. Prematurity was documented in 55%, perinatal asphyxia/hypoxic-ischemic encephalopathy in 31%, intraventricular/intracranial haemorrhage in 27%, multiple births in 19%, intrauterine growth restriction in 18%, intrauterine/perinatal/infancy infection in 15%, congenital malformation in 12%, in vitro fertilisation in 5%, stroke in 3% and CP-associated genetic mutation in 3% of cases. Negative patient history was determined in 16% of children. CONCLUSIONS: Our audit established that clinical documentation of CP is performed based on uniform criteria, detecting missing data primarily in clinical classification and patient history. We propose a patient documentation standard in the clinical care of affected children, which is a prerequisite for unified data recording and a future national CP registry. Orv Hetil. 2020; 161(21): 873-880.

Neurodevelopmental effect of intracranial hemorrhage observed in hypoxic ischemic brain injury in hypothermia-treated asphyxiated neonates - an MRI study.

BACKGROUND: Identification of early signs of hypoxic ischemic encephalopathy (HIE) with magnetic resonance imaging (MRI) has proven of prognostic significance. Yet, the importance of intracranial hemorrhage (ICH), being present concomitantly had not been investigated yet, despite the known influence of hypothermia on hemostasis. We aimed to determine whether presence of ICH on MRI alongside the signs of HIE have an impact on prognosis in neonates with the clinical diagnosis of HIE. METHODS: A retrospective study of consecutively sampled 108 asphyxiated term infants admitted to a tertiary neonatal intensive care unit (between 2007 and 2016), treated with whole body hypothermia and having brain MRI within 1 week of life was conducted. Presence or absence of HIE signs on MRI (basal ganglia-thalamus, watershed pattern and total brain injury) and on MR spectroscopy (lactate peak with decreased normal metabolites measured by Lac/NAA ratio) and/or of the five major types of ICH were recorded. Neurodevelopmental outcome was measured with Bayley Scales of Infant Development-II (BSID-II) test. Death or abnormal neurodevelopment (BSID-II score < 85) was defined as poor outcome in Chi-square test. Multivariate logistic regression analysis was performed on survivors. RESULTS: MRI and MR-spectroscopy (MRS) signs of HIE were present in 72% (n = 78). 36% (n = 39) of neonates had ICH, being mainly small in size. Chi-square test showed a relationship between neurodevelopmental outcome and initial MRI. Unadjusted logistic regression showed that neonates presenting MRI and MRS signs of HIE have 6.23 times higher odds for delayed mental development (OR = 6.2292; CI95% = [1.2642; 30.6934], p = 0.0246), than infants without imaging alterations; with no ICH effect on outcome. Adjustment for clinical and imaging parameters did not change the pattern of results, i.e. HIE remained an independent risk factor for delayed neurodevelopment (OR = 6.2496; CI95% = [1.2018; 32.4983], p = 0.0294), while ICH remained to have no significant effect. CONCLUSION: HIE related MRI abnormalities proved to be important prognostic factors of poor outcome in cooled asphyxiated infants when present, suggesting that early MRI with MRS is beneficial for prognostication. Interestingly, ICHs present in about one third of all cases had no significant effect on neurodevelopmental outcome, despite the known hemostasis altering effects of hypothermia.

Prognostic value of early, conventional proton magnetic resonance spectroscopy in cooled asphyxiated infants.

BACKGROUND: Neonatal hypoxic-ischemic encephalopathy (HIE) commonly leads to neurodevelopmental impairment, raising the need for prognostic tools which may guide future therapies in time. Prognostic value of proton MR spectroscopy (H-MRS) between 1 and 46 days of age has been extensively studied; however, the reproducibility and generalizability of these methods are controversial in a general clinical setting. Therefore, we investigated the prognostic performance of conventional H-MRS during first 96 postnatal hours in hypothermia-treated asphyxiated neonates. METHODS: Fifty-one consecutive hypothermia-treated HIE neonates were examined by H-MRS at three echo-times (TE = 35, 144, 288 ms) between 6 and 96 h of age, depending on clinical stability. Patients were divided into favorable (n = 35) and unfavorable (n = 16) outcome groups based on psychomotor and mental developmental index (PDI and MDI, Bayley Scales of Infant Development II) scores (≥ 70 versus < 70 or death, respectively), assessed at 18-26 months of age. Associations between 36 routinely measured metabolite ratios and outcome were studied. Age-dependency of metabolite ratios in whole patient population was assessed. Prognostic performance of metabolite ratios was evaluated by Receiver Operating Characteristics (ROC) analysis. RESULTS: Three metabolite ratios showed significant difference between outcome groups after correction for multiple testing (p < 0.0014): myo-inositol (mIns)/N-acetyl-aspartate (NAA) height, mIns/creatine (Cr) height, both at TE = 35 ms, and NAA/Cr height at TE = 144 ms. Assessment of age-dependency showed that all 3 metabolite ratios (mIns/NAA, NAA/Cr and mIns/Cr) stayed constant during first 96 postnatal hours, rendering them optimal for prediction. ROC analysis revealed that mIns/NAA gives better prediction for outcome than NAA/Cr and mIns/Cr with cut-off values 0.6798 0.6274 and 0.7798, respectively, (AUC 0.9084, 0.8396 and 0.8462, respectively, p < 0.00001); mIns/NAA had the highest specificity (95.24%) and sensitivity (84.62%) for predicting outcome of neonates with HIE any time during the first 96 postnatal hours. CONCLUSIONS: Our findings suggest that during first 96 h of age even conventional H-MRS could be a useful prognostic tool in predicting the outcome of asphyxiated neonates; mIns/NAA was found to be the best and age-independent predictor.

Distinct cytokine patterns may regulate the severity of neonatal asphyxia-an observational study.

BACKGROUND: Neuroinflammation and a systemic inflammatory reaction are important features of perinatal asphyxia. Neuroinflammation may have dual aspects being a hindrance, but also a significant help in the recovery of the CNS. We aimed to assess intracellular cytokine levels of T-lymphocytes and plasma cytokine levels in moderate and severe asphyxia in order to identify players of the inflammatory response that may influence patient outcome. METHODS: We analyzed the data of 28 term neonates requiring moderate systemic hypothermia in a single-center observational study. Blood samples were collected between 3 and 6 h of life, at 24 h, 72 h, 1 week, and 1 month of life. Neonates were divided into a moderate (n = 17) and a severe (n = 11) group based on neuroradiological and amplitude-integrated EEG characteristics. Peripheral blood mononuclear cells were assessed with flow cytometry. Cytokine plasma levels were measured using Bioplex immunoassays. Components of the kynurenine pathway were assessed by high-performance liquid chromatography. RESULTS: The prevalence and extravasation of IL-1b + CD4 cells were higher in severe than in moderate asphyxia at 6 h. Based on Receiver operator curve analysis, the assessment of the prevalence of CD4+ IL-1ß+ and CD4+ IL-1ß+ CD49d+ cells at 6 h appears to be able to predict the severity of the insult at an early stage in asphyxia. Intracellular levels of TNF-α in CD4 cells were increased at all time points compared to 6 h in both groups. At 1 month, intracellular levels of TNF-α were higher in the severe group. Plasma IL-6 levels were higher at 1 week in the severe group and decreased by 1 month in the moderate group. Intracellular levels of IL-6 peaked at 24 h in both groups. Intracellular TGF-ß levels were increased from 24 h onwards in the moderate group. CONCLUSIONS: IL-1ß and IL-6 appear to play a key role in the early events of the inflammatory response, while TNF-α seems to be responsible for prolonged neuroinflammation, potentially contributing to a worse outcome. The assessment of the prevalence of CD4+ IL-1ß+ and CD4+ IL-1ß+ CD49d+ cells at 6 h appears to be able to predict the severity of the insult at an early stage in asphyxia.