The prognostic value of neonatal conventional-EEG monitoring in hypoxic-ischemic encephalopathy during therapeutic hypothermia.

AIM: To determine the prognostic value of conventional electroencephalography (EEG) monitoring in neonatal hypoxic-ischemic encephalopathy (HIE). METHOD: In this multicentre retrospective study, 95 full-term neonates (mean of 39.3wks gestational age [SD  1.4], 36 [38%] females, 59 [62%] males) with HIE (2013-2016) undergoing therapeutic hypothermia were divided between favourable or adverse outcomes. Background EEG activity (French classification scale: 0-1-2-3-4-5) and epileptic seizure burden (epileptic seizure scale: 0-1-2) were graded for seven 6-hour periods. Conventional EEG monitoring was investigated by principal component analysis (PCA), with clustering methods to extract prognostic biomarkers of development at 2 years and infant death. RESULTS: Eighty-one per cent of infants with an adverse outcome had a French classification scale equal to or greater than 3 after H48 (100% at H6-12). The H6-12 epileptic seizure scale was equal to or greater than 1 for 39%, increased to 52% at H30-36 and then remained equal to or greater than 1 for 39% after H48. Forty-five per cent of infants with a favourable outcome had a H6-12 French classification scale equal to or greater than 3, which dropped to 5% after H48; 13% had a H6-12 epileptic seizure scale equal to or greater than 1 but no seizures after H48. Clustering methods based on PCA showed the high efficiency (96%) of conventional EEG monitoring for outcome prediction and allowed the definition of three prognostic EEG biomarkers: H6-78 French classification scale mean, H6-78 French classification scale slope, and H30-78 epileptic seizure scale mean. INTERPRETATION: Early lability and recovery of physiological features is prognostic of a favourable outcome. Seizure onset from the second day should also be considered to accurately predict neurodevelopment in HIE and support the importance of conventional EEG monitoring in HIE in infants cooled with therapeutic hypothermia. WHAT THIS PAPER ADDS: Comprehensive analysis showed the high prognostic efficiency (96%) of conventional electroencephalography (EEG) monitoring. Prognostic EEG biomarkers consist of the grade of background EEG activity, its evolution, and the mean seizure burden. Persistent seizures (H48) without an improvement in background EEG activity were consistently associated with an adverse outcome.

Distinct attentional and executive profiles in neurofibromatosis type 1: Is there difference with primary attention deficit-hyperactivity disorder?

PURPOSE: Attentional and executive dysfunctions are the most frequent cognitive disorders in neurofibromatosis type 1 (NF1), with a high prevalence of attention deficit-hyperactivity disorder (ADHD). We (i) compared attentional profiles between NF1 children with and without ADHD and children with primary ADHD criteria and (ii) investigated the possible relationship between attentional disorders and "unidentified bright objects" (UBOs) in NF1. METHODS: This retrospective study included 47 NF1 children, 25 with ADHD criteria (NF1+adhd group), matched for age, sex, and cognitive level with 47 children with primary ADHD (ADHD group). We collected computer task (sustained-attention, visuomotor-decision, inhibition, and cognitive-flexibility tasks) scores normalized for age and sex, and brain magnetic resonance imaging data. RESULTS: (i) Working memory was impaired in all groups. (ii) Omissions (p < 0.002) and response-time variability (p < 0.05) in sustained-attention and visuomotor-decision tasks and errors (p < 0.02) in the cognitive-flexibility task were lower for the NFI+adhd and ADHD groups than for the NF1-no-adhd group. (iii) The NF1+adhd group had slower response times (p ≤ 0.02) for inhibition and visuomotor-decision tasks than the other groups. (iv) We found no relevant association between cognitive performance and UBOs. CONCLUSIONS: NF1 children with ADHD have an attentional and executive functions deficit profile similar to that of children with primary ADHD, but with a slower response-time, increasing learning difficulties. The atypical connectivity of fronto-striatal pathways, poorer dopamine homeostasis, and increased GABA inhibition observed in NF1 renders vulnerable the development of the widely distributed neural networks that support attentional, working-memory, and executive functions.

Negative central activity in extremely preterm newborns: EEG characterization and relationship with brain injuries and neurodevelopmental outcome.

OBJECTIVE: To characterize Negative Central Activity (NCA), an overlooked electroencephalographic activity of preterm newborns and investigate its relationship with brain injuries, dysfunction, and neurodevelopmental outcome. METHODS: 109 preterm infants (23-28 weeks) were retrospectively included. NCA were selected at the negative peak on EEG. Individual averaged NCA were automatically characterized. Brain structural data were collected from cranial ultrasounds (cUS). The neurodevelopmental outcome at two years of age was assessed by the Denver Developmental Screening Test-II. RESULTS: Thirty-six (33%) children showed NCA: 6,721 NCA were selected, a median of 75 (interquartile range, 25/157.3) per EEG. NCA showed a triphasic morphology, with a mean amplitude and duration of the negative component of 24.6-40.0 µV and 222.7-257.3 ms. The presence of NCA on EEG was associated with higher intraventricular haemorrhage (IVH) grade on the first (P = 0.016) and worst neonatal cUS (P < 0.001) and poorer neurodevelopmental outcome (P < 0.001). CONCLUSIONS: NCA is an abnormal EEG feature of extremely preterm newborns that may correspond to the functional neural impact of a vascular pathology. SIGNIFICANCE: The NCA relationships with an adverse outcome and the presence/severity of IVH argue for considering NCA in the assessment of pathological processes in the developing brain network and for early outcome prediction.

Predicting the Neurodevelopmental Outcome in Extremely Preterm Newborns Using a Multimodal Prognostic Model Including Brain Function Information.

Importance: Early assessment of the prognosis of preterm newborns is crucial for accurately informing parents and making treatment decisions. The currently available prognostic models rarely incorporate functional brain information from conventional electroencephalography (cEEG). Objective: To examine the performance of a multimodal model combining (1) brain function information with (2) brain structure information (cranial ultrasonography), and (3) perinatal and (4) postnatal risk factors for the prediction of death or neurodevelopmental impairment (NDI) in extremely preterm infants. Design, Setting, and Participants: Preterm newborns (23-28 weeks' gestational age) admitted to the neonatal intensive care unit at Amiens-Picardie University Hospital were retrospectively included (January 1, 2013, to January 1, 2018). Risk factors from the 4 categories were collected during the first 2 weeks post delivery. Neurodevelopmental impairment was assessed at age 2 years with the Denver Developmental Screening Test II. No or moderate NDI was considered a favorable outcome. Death or severe NDI was considered an adverse outcome. Data analysis was performed from August 26, 2021, to March 31, 2022. Main Outcomes and Measures: After the selection of variables significantly associated with outcome, 4 unimodal prognostic models (considering each category of variable independently) and 1 multimodal model (considering all variables simultaneously) were developed. After a multivariate analysis for models built with several variables, decision-tree algorithms were run on each model. The areas under the curve for decision-tree classifications of adverse vs favorable outcomes were determined for each model, compared using bootstrap tests, and corrected for type I errors. Results: A total of 109 newborns (58 [53.2% male]) born at a mean (SD) gestational age of 26.3 (1.1) weeks were included. Among them, 52 (47.7%) had a favorable outcome at age 2 years. The multimodal model area under the curve (91.7%; 95% CI, 86.4%-97.0%) was significantly higher than those of the unimodal models (P < .003): perinatal model (80.6%; 95% CI, 72.5%-88.7%), postnatal model (81.0%; 95% CI, 72.6%-89.4%), brain structure model (cranial ultrasonography) (76.6%; 95% CI, 67.8%-85.3%), and brain function model (cEEG) (78.8%; 95% CI, 69.9%-87.7%). Conclusions and Relevance: In this prognostic study of preterm newborns, the inclusion of brain information in a multimodal model was associated with significant improvement in the outcome prediction, which may have resulted from the complementarity of the risk factors and reflected the complexity of the mechanisms that interfered with brain maturation and led to death or NDI.

Distinct response time distributions in attention deficit hyperactivity disorder subtypes.

OBJECTIVE: To address the issue of response time (RT) profiles in hyperactive-impulsive (ADHD-HI), inattentive (ADHD-IA), and combined (ADHD-C) subtypes of ADHD. We hypothesized that children with ADHD-HI should respond more rapidly than children without ADHD and children with ADHD-IA and ADHD-C should respond more slowly than children without ADHD. METHOD: Four groups (3 ADHD groups and 1 non-ADHD group) each composed of 16 children (7-13 years old) performed a visuospatial choice task. RESULTS: ANOVA indicated very variable RTs for each ADHD subtype when controlling for individual RT. ANOVA performed on RT distribution showed significant differences between the ADHD and non-ADHD groups: biased to fast responses in ADHD-HI and biased to slow responses in ADHD-IA and ADHD-C. CONCLUSION: The results suggest that response time profiles were abnormal in all ADHD subtypes and were markedly different between children meeting criteria for ADHD-HI and those meeting criteria for ADHD-IA or ADHD-C.

Deficit of endogenous spatial orienting of attention in children with benign epilepsy with centrotemporal spikes (BECTS).

Attention difficulties have been reported in children with benign epilepsy with centrotemporal spikes (BECTS) but have not yet been fully specified. The aim of this study was to evaluate the functions of exogenous and endogenous spatial orienting of attention and alerting in these children. Two versions of the spatial cueing paradigm and an alerting task, including trials with and without warning signal, were performed by 25 children with BECTS aged 6-12 years and 25 controls matched for age, gender and IQ. In these three tasks, patients were slower and made more omissions than controls. The alert effect amplitude was comparable in both groups at the longer SOAs (450 ms and 800 ms) while, at the shortest SOA (100 ms), it was greater in controls than in the BECTS group. In the first version of the spatial cueing task (peripheral cues and no probability information), the validity effect amplitude, measured by longer response times (RTs) in invalid trials compared to valid trials, was comparable in both groups. In the second version (central cues and a 75% probability that the target would appear at the cued location), the validity effect was larger in the BECTS group compared to controls because of a higher cost of invalid trials compared to neutral trials. These results suggest the existence of impairments in the endogenous orienting of attention in children with BECTS, in particular an attention disengagement deficit, while exogenous orienting of attention appears to be preserved.

Effects of Methylphenidate on Default-Mode Network/Task-Positive Network Synchronization in Children With ADHD.

OBJECTIVE: A failure of the anti-phase synchronization between default-mode (DMN) and task-positive networks (TPN) may be involved in a main manifestation of ADHD: moment-to-moment variability. The study investigated whereby methylphenidate may improve TPN/DMN synchronization in ADHD. METHOD: Eleven drug-naive ADHD children and 11 typically developing (TD) children performed a flanker task during functional magnetic resonance imaging. The ADHD group was scanned without and 1 month later with methylphenidate. The signal was analyzed by independent component analysis. RESULTS: The TD group showed anti-phase DMN/TPN synchronization. The unmedicated ADHD group showed synchronous activity in the posterior DMN only, which was positively correlated with response time variability for the flanker task. Methylphenidate initiated a partial anti-phase TPN/DMN synchronization, reduced variability, and abolished the variability/DMN correlation. CONCLUSION: Although results should be interpreted cautiously because the sample size is small, they suggest that a failure of the TPN/DMN synchronization could be involved in the moment-to-moment variability in ADHD. Methylphenidate initiated TPN/DMN synchronization, which in turn appeared to reduce variability.

Vagus nerve stimulation in the treatment of drug-resistant epilepsy in 29 children.

BACKGROUND/PURPOSE: Vagus nerve stimulation (VNS) has been demonstrated to be safe and effective for adults and children with drug-resistant epilepsy and is able to improve most types of epilepsy. The aim of this study, in a paediatric population, was to assess the overall efficacy of vagus nerve stimulation on seizures, to assess tolerability and quality of life. METHODS: This single-centre, retrospective study reviewed the files of 29 children in whom a vagus nerve stimulator was implanted between 1995 and 2012. The response rate (greater than 50% reduction of the seizure frequency), antiepileptic efficacy according to the type of epilepsy or age at implantation or age at onset of epilepsy, the time-course of seizures, adverse effects, overall quality of life and number of hospitalisations were studied. RESULTS: In our population, vagus nerve stimulation achieved a significant reduction in the seizure frequency throughout follow-up (p = 0.015). Response rates were 59% at 3 months, and 66% at 6 months, and the response rate then remained stable at about 70%. Stimulation tended to be more effective in patients with non-idiopathic partial epilepsy than in patients with non-idiopathic and idiopathic generalised epilepsy (0.01 < p < 0.11). No other predictive factors of efficacy were identified. Patients, parents, caregivers reported improvement in overall quality of life in 38% of patients during clinical interviews. A significant reduction in the number of hospitalisations due to a reduction of seizure frequency was observed after implantation (p = 0.03). VNS was stopped because of complications or insufficient efficacy in 9 cases. CONCLUSION: Vagus nerve stimulation is a safe and effective treatment option in children with drug-resistant epilepsy who are not candidates for surgery.

Individual differences in subcortical microstructure organization reflect reaction time performances during a flanker task: a diffusion tensor imaging study in children with and without ADHD.

The results of several previous magnetic resonance imaging studies suggest that the fronto-striato-thalamic circuitry is involved in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). However, few studies have investigated the putative association between quantitative diffusion tensor imaging measurements of subcortical gray matter and subject task performances in children with ADHD. Here, we examined whether reaction time (RT) parameters during a flanker task were correlated with mean diffusivity (MD) measurements in the basal ganglia and thalamus in children with ADHD and in controls. For the study group as a whole, both the mean RT and the intra-individual variability in RTs were found to be significantly correlated with MD measurements in the right and left caudate, putamen and thalamus. In contrast, the correlation between the interference effect and MD failed to reach statistical significance. The present results may advance our understanding of the anatomical substrates of ADHD.

Dysfunction of the attentional brain network in children with Developmental Coordination Disorder: a fMRI study.

Children with Developmental Coordination Disorder (DCD) present impaired motor skills, frequently associated with impaired attentional and executive functions. The objective of this study was to assess the impact of DCD on effective connectivity applied to a putative model of inhibition. fMRI was performed in 9 children with DCD and 10 control children (8-13 years old) performing a go-nogo task. As previously reported, children with DCD obtained a similar score for correct inhibitions as controls, but responses were slower and more variable than in controls. Compared to controls, Structural Equation Modeling indicated that: (1) path coefficients from both middle frontal cortex (MFC) and anterior cingulate cortex (ACC) to inferior parietal cortex (IPC) increased in children with DCD particularly in the left hemisphere; (2) path coefficients between striatum and parietal cortex decreased in children with DCD in the right hemisphere. Results suggest that DCD could be characterized by abnormal brain hemispheric specialization during development. Furthermore, connectivity in the MFC-ACC-IPC network could indicate that children with DCD are less able than healthy children to easily and/or promptly switch between go and nogo motor responses. However, children with DCD seem to compensate for this poor efficiency by more actively engaging the ACC to prevent commissions allowing maintenance of a good level of inhibition.