Prevalence, Risk Factors, and Impact of Preoperative Seizures in Neonates With Congenital Heart Disease.

PURPOSE: The purpose of this study was to assess the prevalence, risk factors, and impact of electrographic seizures in neonates with complex congenital heart disease before cardiac surgery. METHODS: A cohort of 31 neonates with congenital heart disease monitored preoperatively with continuous video-EEG (cEEG) was first reviewed for electrographic seizure burden and EEG background abnormalities. Second, cEEG findings were correlated with brain MRI and 18-month outcomes. RESULTS: Continuous video-EEG was recorded preoperatively for a median duration of 20.5 hours (range, 2.5-93.5 hours). The five neonates (16%; 95% confidence interval, 5.5% to 34%) with seizures detected on cEEG in the preoperative period had a diagnosis of transposition of the great arteries or similar physiology, detected in four of five postnatally. None of the 157 recorded electrographic seizures had a clinical correlate. The median time to first seizure was 65 minutes (range, 6-300 minutes) after cEEG hookup. The median maximum hourly seizure burden was 12.4 minutes (range, 7-23 minutes). Before the first electrographic seizure, a prolonged interburst interval (>10 seconds) was not associated with seizures (coefficient 1.2; 95% confidence interval, -1.1 to 3.6). MRI brain lesions were three times more common in neonates with seizures. Sharp wave transients on cEEG were associated with delayed opercular development. CONCLUSIONS: In this cohort, preoperative electrographic seizures were common, were all subclinical, and were associated with MRI brain injury and postnatal diagnosis of transposition of the great arteries. The findings motivate further study of the mechanisms of preoperative brain injury, particularly among neonates with a postnatal diagnosis of transposition of the great arteries.

Neural Correlates of Voice Perception in Newborns and the Influence of Preterm Birth.

Maternal voice is a highly relevant stimulus for newborns. Adult voice processing occurs in specific brain regions. Voice-specific brain areas in newborns and the relevance of an early vocal exposure on these networks have not been defined. This study investigates voice perception in newborns and the impact of prematurity on the cerebral processes. Functional magnetic resonance imaging (fMRI) and high-density electroencephalography (EEG) were used to explore the brain responses to maternal and stranger female voices in full-term newborns and preterm infants at term-equivalent age (TEA). fMRI results and the EEG oddball paradigm showed enhanced processing for voices in preterms at TEA than in full-term infants. Preterm infants showed additional cortical regions involved in voice processing in fMRI and a late mismatch response for maternal voice, considered as a first trace of a recognition process based on memory representation. Full-term newborns showed increased cerebral activity to the stranger voice. Results from fMRI, oddball, and standard auditory EEG paradigms highlighted important change detection responses to novelty after birth. These findings suggest that the main components of the adult voice-processing networks emerge early in development. Moreover, an early postnatal exposure to voices in premature infants might enhance their capacity to process voices.

Newborns and preterm infants at term equivalent age: A semi-quantitative assessment of cerebral maturity.

BACKGROUND AND PURPOSE: Currently available MRI scoring systems of cerebral maturation in term and preterm infant at term equivalent age do not include the changes of transient fetal compartments that persist to term age. We studied the visibility and the pattern of these structures in healthy term newborns compared to preterm infants at term equivalent age in order to investigate if they can be included in a new MRI score system. We hypothesized that transient fetal compartments are different in both groups, and that these differences can be characterized using the clinical T2-weighted MRIs. MATERIALS AND METHODS: Using 3T MRI T2-weighted brain sequences of 21 full-term and 41 preterm infants (< 32 weeks), scanned at term equivalent age, 3 raters independently scored the maturation level of 3 transient fetal compartments: the periventricular crossroads, von Monakow segments of the white matter, and the subplate compartment. These 3 new items were included in a scoring system along with validated parameters of brain maturation (germinal matrix, bands of migration, subarachnoid space and quality of gyrification). A cumulative maturity score was calculated separately for both groups of newborns by adding together each item. More mature were the brain structures, higher was the cumulative maturity score. RESULTS: Cumulative maturity score distinguished full-term from preterm infants (mean score 41/60 ± 1.4 versus 37/60 ± 2.5 points, p < 0.001), with an increase of 0.5 points for each supplemental gestational week at birth (r = 0.5, 95% CI 0.5 - 0.85). While a majority of transient fetal compartments were less mature in preterm group at term equivalent age, von Monakow segments of the white matter and subplate compartment presented a more advanced maturational stage in the preterm group compared to the term group. No subject had all scored items in the most mature state. Except a slight intra-rater agreement for von Monakow segment II, inter- and intra-rater agreements were moderate to excellent indicating the potential of the developed scoring system in routine clinical practice. CONCLUSION: Brain transient fetal structures can be assessed on regular T2-weighted MRI in newborns. Their appearance differs between term and preterm babies. However our results suggest a more complex situation, with both delayed and accelerated maturation pattern in preterm infants. It remains to be determined if these differences could be biomarkers of the future neurodevelopment of preterm infants.

Music in premature infants enhances high-level cognitive brain networks.

Neonatal intensive care units are willing to apply environmental enrichment via music for preterm newborns. However, no evidence of an effect of music on preterm brain development has been reported to date. Using resting-state fMRI, we characterized a circuitry of interest consisting of three network modules interconnected by the salience network that displays reduced network coupling in preterm compared with full-term newborns. Interestingly, preterm infants exposed to music in the neonatal intensive care units have significantly increased coupling between brain networks previously shown to be decreased in premature infants: the salience network with the superior frontal, auditory, and sensorimotor networks, and the salience network with the thalamus and precuneus networks. Therefore, music exposure leads to functional brain architectures that are more similar to those of full-term newborns, providing evidence for a beneficial effect of music on the preterm brain.

Effects of an Early Postnatal Music Intervention on Cognitive and Emotional Development in Preterm Children at 12 and 24 Months: Preliminary Findings.

Preterm birth is associated with a higher prevalence of neurodevelopmental deficits. Indeed, preterm children are at increased risk for cognitive, behavioral, and socio-emotional difficulties. There is currently an increasing interest in introducing music intervention in neonatal intensive care unit (NICU) care. Several studies have shown short-term beneficial effects. A recent study has shown that listening to a familiar music (heard daily during the NICU stay) enhanced preterm infants' functional connectivity between auditory cortices and subcortical brain regions at term-equivalent age. However, the long-term effects of music listening in the NICUs have never been explored. The aim of this study was to evaluate at 12 and 24 months the effects of music listening in the NICU on cognitive and emotional development in preterm children by comparing them to a preterm control group with no previous music exposure and to a full-term group. Participants were 44 children (17 full-term and 27 preterm). Preterm children were randomized to either music intervention or control condition (without music). The preterm-music group regularly listened to music from 33 weeks postconceptional age until hospital discharge or term-equivalent age. At 12 months, children were evaluated on the Bayley Scales of Infant and Toddler Development, Third Edition, then with 4 episodes of the Laboratory Temperament Assessment Battery (assessing expressions of joy, anger, and fear, and sustained attention). At 24 months, the children were evaluated with the same tests, and with 3 additional episodes of the Effortful Control Battery (assessing inhibition). Results showed that the scores of preterm children, music and control, differed from those of full-term children for fear reactivity at 12 months of age and for anger reactivity at 24 months of age. Interestingly, these significant differences were less important between the preterm-music and the full-term groups than between the preterm-control and the full-term groups. The present study provides preliminary, but promising, scientific findings on the beneficial long-term effects of music listening in the NICU on neurodevelopmental outcomes in preterm children, and more specifically on emotion mechanisms at 12 and 24 months of age. Our findings bring new insights for supporting early music intervention in the NICU.

Acute cortical deafness in a child with MELAS syndrome.

Auditory impairment in mitochondrial disorders are usually due to peripheral sensorineural dysfunction. Central deafness is only rarely reported. We report here an 11-year-old boy with MELAS syndrome who presented with subacute deafness after waking up from sleep. Peripheral hearing loss was rapidly excluded. A brain MRI documented bilateral stroke-like lesions predominantly affecting the superior temporal lobe, including the primary auditory cortex, confirming the central nature of deafness. Slow recovery was observed in the following weeks. This case serves to illustrate the numerous challenges caused by MELAS and the unusual occurrence of acute cortical deafness, that to our knowledge has not be described so far in a child in this setting.

Dying neurons in thalamus of asphyxiated term newborns and rats are autophagic.

OBJECTIVE: Neonatal hypoxic-ischemic encephalopathy (HIE) still carries a high burden by its mortality and long-term neurological morbidity in survivors. Apart from hypothermia, there is no acknowledged therapy for HIE, reflecting the lack of mechanistic understanding of its pathophysiology. (Macro)autophagy, a physiological intracellular process of lysosomal degradation, has been proposed to be excessively activated in excitotoxic conditions such as HIE. The present study examines whether neuronal autophagy in the thalamus of asphyxiated human newborns or P7 rats is enhanced and related to neuronal death processes. METHODS: Neuronal autophagy and cell death were evaluated in the thalamus (frequently injured in severe HIE) of both human newborns who died after severe HIE (n = 5) and P7 hypoxic-ischemic rats (Rice-Vannuci model). Autophagic (LC3, p62), lysosomal (LAMP1, cathepsins), and cell death (TUNEL, caspase-3) markers were studied by immunohistochemistry in human and rat brain sections, and by additional methods in rats (immunoblotting, histochemistry, and electron microscopy). RESULTS: Following severe perinatal asphyxia in both humans and rats, thalamic neurons displayed up to 10-fold (p < 0.001) higher numbers of autophagosomes and lysosomes, implying an enhanced autophagic flux. The highly autophagic neurons presented strong features of apoptosis. These findings were confirmed and elucidated in more detail in rats. INTERPRETATION: These results show for the first time that autophagy is enhanced in severe HIE in dying thalamic neurons of human newborns, as in rats. Experimental neuroprotective strategies targeting autophagy could thus be a promising lead to follow for the development of future therapeutic approaches.