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Objective: We use co-registration of foramen-ovale and scalp-EEG to investigate network alterations in temporal-lobe epilepsy during focal seizures without (aura) or with impairment of awareness (SIA)., Methods: One aura and one SIA were selected from six patients. Temporal dynamic among 4 epochs, as well as the differences between aura and SIA, were analyzed through partial directed coherence and graph theory-based indices of centrality., Results: Regarding the auras temporal evolution, fronto-parietal (FP) regions showed decreased connectivity with respect to the interictal period, in both epileptogenic (EH) and non-epileptogenic hemisphere (nEH). During SIAs, temporal dynamic showed more changes than auras: centrality of mesial temporal (mT) regions changes during all conditions, and nEH FP centrality showed the same dynamic trend of the aura (decreased centrality), until the last epoch, close to the impaired awareness, when showed increased centrality. Comparing SIA with aura, in proximity of impaired awareness, increased centrality was found in all the regions, except in nEH mT., Conclusions: Our findings suggested that the impairment of awareness is related to network alterations occurring first in neocortical regions and when awareness is still retained., Significance: The analysis of 'hub' alteration can represent a suitable biomarker for scalp EEG-based prediction of awareness impairment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Epilepsy surgery is recommended in selected patients with Tuberous Sclerosis Complex (TSC). However, reports on predictive factors of seizure outcome are variable. Here we report on seizure and cognitive outcome of 35 TSC patients who received surgery for refractory epilepsy in 7 Italian centers over a period of 22 years (1997-2019). The rate of seizure-free individuals at last follow-up (mean 7.5 years, range 1-21 years) was 51%. Patients with longer follow-up (≥10 years) had a lower rate of Engel I outcome (11.1%) than those who received surgery in the last 10 years (65.4%, p = 0.003). Factors associated with Engel II, III, IV outcome in our cohort included: high number of cortical tubers (≥5); presence of subependymal nodules (SENs); seizure onset before age 1 year; and multifocal interictal epileptic discharges (IEDs) on electroencephalogram (EEG). A subset of patients evaluated with Vineland Adaptive Behaviour Scales (VABS) showed developmental gains, in line with their developmental trajectories, but no improvement in standard scores after surgery was noted. Our study demonstrates that the rates of successful seizure outcome of epilepsy surgery in TSC have improved in the last 10 years. More than half of the patients achieved seizure freedom, and a high proportion of affected individuals experienced a reduction in seizure burden and in antiseizure medications. A comprehensive assessment after surgery should be performed in TSC patients to evaluate the overall neurodevelopmental outcome, as measures that are based only on seizure control do not adequately identify the benefits of surgery on global functioning in these patients., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: The importance of lung recruitment before surfactant administration has been shown in animal studies. Well designed trials in preterm infants are absent. We aimed to examine whether the application of a recruitment manoeuvre just before surfactant administration, followed by rapid extubation (intubate-recruit-surfactant-extubate [IN-REC-SUR-E]), decreased the need for mechanical ventilation during the first 72 h of life compared with no recruitment manoeuvre (ie, intubate-surfactant-extubate [IN-SUR-E])., Methods: We did a randomised, unblinded, controlled trial in 35 tertiary neonatal intensive care units in Italy. Spontaneously breathing extremely preterm neonates (24 + 0 to 27 + 6 weeks' gestation) reaching failure criteria for continuous positive airway pressure within the first 24 h of life were randomly assigned (1:1) with a minimisation algorithm to IN-REC-SUR-E or IN-SUR-E using an interactive web-based electronic system, stratified by clinical site and gestational age. The primary outcome was the need for mechanical ventilation in the first 72 h of life. Analyses were done in intention-to-treat and per-protocol populations, with a log-binomial regression model correcting for stratification factors to estimate adjusted relative risk (RR). This study is registered with ClinicalTrials.gov, NCT02482766., Findings: Of 556 infants assessed for eligibility, 218 infants were recruited from Nov 12, 2015, to Sept 23, 2018, and included in the intention-to-treat analysis. The requirement for mechanical ventilation during the first 72 h of life was reduced in the IN-REC-SUR-E group (43 [40%] of 107) compared with the IN-SUR-E group (60 [54%] of 111; adjusted RR 0·75, 95% CI 0·57-0·98; p=0·037), with a number needed to treat of 7·2 (95% CI 3·7-135·0). The addition of the recruitment manoeuvre did not adversely affect the safety outcomes of in-hospital mortality (19 [19%] of 101 in the IN-REC-SUR-E group vs 37 [33%] of 111 in the IN-SUR-E group), pneumothorax (four [4%] of 101 vs seven [6%] of 111), or grade 3 or worse intraventricular haemorrhage (12 [12%] of 101 vs 17 [15%] of 111)., Interpretation: A lung recruitment manoeuvre just before surfactant administration improved the efficacy of surfactant treatment in extremely preterm neonates compared with the standard IN-SUR-E technique, without increasing the risk of adverse neonatal outcomes. The reduced need for mechanical ventilation during the first 72 h of life might facilitate implementation of a non-invasive respiratory support strategy., Funding: None., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Focal Cortical Dysplasia (FCD) represents a broad spectrum of histopathological entities that cause drug-resistant epilepsy. Surgery has been shown to be the treatment of choice, but incomplete resection represents the leading cause of seizure persistence. Preliminary experiences with intraoperative ultrasound (ioUS) have proven its potential in defining and characterizing the lesion. In this study we analyzed the feasibility of advanced ultrasound techniques such as sono-elastography (SE) and contrast enhancement ultrasound (CEUS) in a small cohort of patients with FCD., Material and Methods: We retrospectively reviewed all clinical records and images of patients with drug resistant epilepsy who underwent at least one advanced sonographic technique (SE and/or CEUS) during ioUS guided surgery between November 2014 and October 2017. We excluded from our analysis all patients with lesions other than FCD or those who had FCD associated with other pathological entities., Results: Four patients with type IIb FCD in the right frontal lobe were evaluated. All of them underwent SE, which highlighted heterogeneous stiffness in the dysplastic foci, also multiple areas of higher consistency were detected in all patients. Three patients evaluated with CEUS had visible enhancement in the FCD. Neither SE nor CEUS were better than ioUS in the identification of lesion boundaries. In the three patients who underwent both SE and CEUS we found no correspondence between stiffer areas and enhancement in the dysplastic areas., Conclusion: Ourpreliminary report confirms the feasibility of SE and CEUS in FCD surgery and describes the imaging findings in this category of patients. Studies on larger cohorts of patients are warranted to better clarify the role of these advanced intraoperative ultrasound techniques in patients with FCD., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: To define Stereo-EEG (SEEG) ictal and interictal patterns associated with different pathologies in a cohort of patients with drug-resistant focal epilepsy., Methods: We retrospectively analyzed findings from 102 patient with epilepsy due to Polymicrogyria (PMG), Periventricular Nodular Heterotopia (PNH), Focal Cortical Dysplasia (FCD) type I, IIa, IIb and Hippocampal Sclerosis (HS). Ictal and interictal SEEG recordings were reviewed to describe Seizure Onset Zone (SEEG-SOZ) patterns and to define the Lesional and Irritative Zones., Results: Five SEEG-SOZ patterns were identified: significant associations were found between low-voltage fast activity and PMG and between repetitive fast spikes bursts and FCD type IIa. A trend was found between fast activity and PNH, rhythmic sharp activity and FCD type I, repetitive fast spikes bursts and FCD type IIb, slow burst and HS. In 62 of the 102 patients, a complete surgical resection of the SEEG-SOZ was performed, and in 12 patients a partial resection was carried out to preserve eloquent areas. In 18 patients (15 with PNH) the SEEG-SOZ was thermo-coagulated. Seizure freedom was achieved in 58% of surgically treated patients and in 72% of those treated with thermocoagulation (mean ± SD follow-up 5.9 ± 2.3 years). Seizure freedom after surgery was achieved in 84% of the patients with PMG, FCD I, IIa and IIb presenting with characteristic SEEG-SOZ patterns. With the exception of FCD type II, interictal activity was not sufficient to identify SEEG-SOZ boundaries., Conclusion: The study demonstrates that specific histopathologies correlate with particular neurophysiological patterns, reflecting lesion-specific seizure patterns in focal epilepsies., (Copyright © 2019 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Background: Premature birth is often associated with neurodevelopmental difficulties throughout childhood. In the first three years of life, the Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III) constitute one of the most used tools for assessing child development. Since Bayley-III original norms are based on United States (US) population, it remains uncertain whether their use in other countries (e.g., European) is appropriate., Aims: This research aimed to examine neurodevelopment of preterm infants and full-term infants, using Bayley-III US norms in comparison to Italian (IT) norms. Patterns of developmental outcomes for both infant groups were also explored., Methods: 104 preterm and 58 full-term infants were included in the study. Bayley-III was used for neurodevelopmental assessment at 1year of corrected age, considering both IT and US norms for scores computation., Results: Comparing scores obtained with IT vs US norms, differences in means were all significant across five subscales (p<0.05 at least) for preterm infants, whereas for full-term peers significant differences were found only for Receptive Language and Fine Motor subscales (p<0.001). Effect size (η 2 ) ranged from 0.22 to 0.94. Within each group, significant discrepancies across subscales were found. Moreover, Italian preterm infants had significantly lower performances than full-term peers, excepting for Expressive Language and Gross Motor subscales., Conclusions: As regards to Italian 1-year children, our study seems to provide evidence for the tendency of Bayley-III US norms to overestimate development compared to IT norms. These findings emphasize the need to early detect children at risk for developmental delay and to plan early intervention., (Copyright © 2017 Elsevier B.V. All rights reserved.)

A quantitative method was developed to map cortical areas responsive to cognitive tasks during intracerebral stereo-EEG recording sessions in drug-resistant patients candidate for epilepsy surgery. Frequency power changes were evaluated with a computer-assisted analysis in 7 patients during phonemic fluency tasks. All patients were right-handed and were explored with depth electrodes in the dominant frontal lobe. We demonstrate that fluency tasks enhance beta-gamma frequencies and reduce background activities in language network regions of the dominant hemisphere. Non-reproducible changes were observed in other explored brain areas during cognitive tests execution., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Zinc plays a pivotal role in the pathogenesis of many diseases and in body growth. Preterm neonates have high zinc requirements., Objective: The objective of the study was to investigate the efficacy of zinc supplementation in reducing morbidity and mortality in preterm neonates and to promote growth., Design: This was a prospective, double-blind, randomized controlled study of very-low-birth-weight preterm neonates randomly allocated on the seventh day of life to receive (zinc group) or not receive (control group) oral zinc supplementation. Total prescribed zinc intake ranged from 9.7 to 10.7 mg/d in the zinc group and from 1.3 to 1.4 mg/d in the placebo control group. The main endpoint was the rate of neonates with ≥ 1 of the following morbidities: late-onset sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, periventricular leucomalacia, and retinopathy of prematurity. Secondary outcomes were mortality and body growth., Results: We enrolled 97 neonates in the zinc group and 96 in the control group. Morbidities were significantly lower in the zinc group (26.8% compared with 41.7%; P = 0.030). The occurrence of necrotizing enterocolitis was significantly higher in the control group (6.3% compared with 0%; P = 0.014). Mortality risk was higher in the placebo control group (RR: 2.37; 95% CI: 1.08, 5.18; P = 0.006). Daily weight gain was similar in the zinc (18.2 ± 5.6 g · kg⁻¹ · d⁻¹) and control (17.0 ± 8.7 g · kg⁻¹ · d⁻¹) groups (P = 0.478)., Conclusion: Oral zinc supplementation given at high doses reduces morbidities and mortality in preterm neonates. This trial was registered in the Australian New Zealand Clinical Trial Register as ACTRN12612000823875.

Although great efforts have been made to improve neonatal nutrition in very low birthweight (VLBW) infants, many do not receive adequate nutrient intake and thus develop extrauterine growth restriction. In order to minimize the interruption of nutrients that occurs at birth, an "aggressive" nutritional approach has been proposed. Parenteral nutrition, which allows the infant's requirements for growth and development to be met, is indicated in infants for whom feeding via the enteral route is impossible, inadequate, or hazardous. In the last few years, great attention has been given to high amino acid supply in VLBW infants from the first day of life in order to avoid catabolism, establish anabolism, achieve in utero protein accretion rates, and promote linear growth. Whenever possible, enteral feeding should commence with human milk, which is the preferred feeding method for all infants, including those born preterm. In order to meet the unique nutritional requirements of VLBW infants and preserve the singular benefit of breastfeeding, human milk should be fortified to allow adequate growth and bone mineralization. When feeding of preterm infants with human milk is impossible or extremely limited, cow-milk-based formulas for preterm infants must be used., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Transcutaneous bilirubin (TcB) measurement is widely used as screening for neonatal hyperbilirubinaemia., Aims: To prospectively validate TcB measurement using hour-specific nomogram in identifying newborn infants not at risk for severe hyperbilirubinaemia., Study Design: prospective, observational, multicenter., Subjects: 2167 term and late preterm infants born in 5 neonatal units in the Lazio region of Italy., Methods: All neonates had simultaneous TcB and total serum bilirubin (TSB) measurements, when jaundice appeared and/or before hospital discharge. TcB and TSB values were plotted on a percentile-based hour-specific transcutaneous nomogram previously developed, to identify the safe percentile able to predict subsequent significant hyperbilirubinaemia defined as serum bilirubin >17 mg/dL or need for phototherapy., Results: Fifty-five babies (2.5%) developed significant hyperbilirubinaemia. The 50th percentile of our nomogram was able to identify all babies who were at risk of significant hyperbilirubinaemia, but with a high false positive rate. Using the 75th percentile, two false negatives reduced sensitivity in the first 48 hours but we were able to detect all babies at risk after the 48th hour of age., Conclusions: This study demonstrates that the 75th percentile of our TcB nomogram is able to exclude any subsequent severe hyperbilirubinaemia from 48 h of life ahead., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: There is still no study evaluating the influence of gestational age (GA) per se on C reactive protein (CRP) and procalcitonin (PCT) reference intervals. We therefore investigated how length of gestation, age (hours), and prenatal and perinatal variables might influence the levels of CRP and PCT. We also determined 95% age-specific reference intervals for CRP and PCT in healthy preterm and term babies during the early neonatal period., Methods: One blood sample (one observation per neonate) was taken for CRP and PCT from each newborn between birth and the first 4 (for term), or 5 days (for preterm newborns) of life by using a high-sensitive CRP and PCT assays., Results: Independently of gender and sampling time, GA had a significantly positive effect on CRP, and a significantly negative effect on PCT. Compared with healthy term babies, healthy preterm babies had a lower and shorter CRP response, and, conversely, an earlier, higher, and longer PCT response. CRP reference intervals were affected by a number of pro-inflammatory risk factors., Conclusions: Age- and GA-specific reference ranges for both CRP and PCT should be taken into account to optimize their use in the diagnosis of early-onset neonatal sepsis., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: Docosahexaenoic acid (DHA) and arachidonic acid (AA) are long-chain polyunsaturated fatty acids (LCPs) that play pivotal roles in growth and neurodevelopment., Objective: We aimed to quantify the synthesis of LCPs in preterm infants fed infant formula containing LCPs., Design: Twenty-two preterm infants were randomly assigned to either the no-LCP group (fed formula without LCPs; n = 11) or the LCP group (fed formula with LCPs; n = 11). Dietary LCPs had higher (13)C content than did the endogenously synthesized LCPs, which were derived from linoleic and alpha-linolenic acids. The (13)C content of major selected plasma fatty acids was measured by using gas chromatography-isotope ratio mass spectrometry at birth and at age 1, 3, and 7 mo. Absolute LCP synthesis and the percentage of LCP synthesis relative to dietary intake were calculated., Results: Percentage AA synthesis was 67.2 +/- 7.8%, 35.9 +/- 9.8%, and 29.0 +/- 10.3%, and that of DHA was 41.7 +/- 14.9%, 10.5 +/- 8.1%, and 7.4 +/- 6.2% at 1, 3, and 7 mo old, respectively. Absolute AA synthesis was 26.7 +/- 4.2, 14.4 +/- 3.9, and 11.6 +/- 4.1 mg x kg(-1) x d(-1) and that of DHA was 12.6 +/- 4.5, 3.2 +/- 2.5, and 2.3 +/- 1.9 mg x kg(-1) . d(-1) at 1, 3, and 7 mo old, respectively. AA and DHA synthesis decreased significantly (P < 0.01) with time, and AA synthesis was significantly (P < 0.01) greater than DHA synthesis., Conclusions: By this novel approach, we measured endogenous LCP synthesis in infants receiving dietary LCPs over long periods. By age 7 mo, LCP synthesis was dramatically lower in preterm infants fed LCPs.

In recent years, improvements in care have significantly improved survival in preterm and, particularily, the very low birth weight infant (VLBW). While immediate survival can be directly related to pulmonary maturity, several studies stress the importance of timely and adequate nutrition in these high-risk infants on a short- and long-term [1]. Yet, nutritional support remains a very controversial issue in these high-risk infants. Early provision of adequate intakes may be limited by clinical instability and immaturity. At the same time, nutritional requirements and methods of nutritional assessment are not well defined. The aim of this paper is to outline some of the methods used during nutritional assessment in preterm infants with special reference to the measurement of body composition., (Copyright 2002 Elsevier Science Ltd.)

Objectives: The most relevant results of studies on the anatomo-physiological substrate of the thalamic rhythmogenic mechanisms responsible for sleep spindles and spike-wave discharges are reviewed., Methods: The reviewed experiments have been carried out in cats, rodents and other mammals with either in vivo or in vitro electrophysiological recording., Results: The rhythmic bilateral and synchronous EEG activities underlying sleep spindles and spike-wave discharges have been found to be correlated with oscillatory patterns involving mutually interconnected cortical and thalamic neurons. These rhythmic patterns are generated in thalamic neurons when the membrane potential, which is modulated by aminergic and cholinergic systems, is set to a level where the low threshold calcium current is de-inactivated. The pacemaker structure responsible for the initiation of the thalamo-cortical oscillatory activities has been identified as the reticular thalamic nucleus, a GABAergic structure projecting exclusively to the other thalamic nuclei. Experiments carried out in GAERS (genetic absence epilepsy rat from Strasbourg) demonstrated in this rat model of inherited absence epilepsy an enhancement of the pacemaker properties of the thalamic nucleus, due to a genetically determined increase in the low threshold calcium current, which is responsible for the pathological synchronization underlying spike-wave discharges., Conclusions: Recent experiments confirm the longstanding hypothesis that spindles and spike-wave discharges share common mechanisms involving thalamo-cortical circuitry. Due to its unusual anatomic and functional organization the nucleus reticularis thalami plays a crucial role as pacemaker of these rhythmic EEG activities.

In very low birth weight (VLBW) infants careful growth and nutritional supervision are necessary in order to reduce the incidence of persistent growth retardation after 2 to 3 years of age. Recently, post-discharge formulas with higher protein, energy and mineral content has been developed with the aim to promote catch up growth and mineral accretion during the first months of life. Based upon the most recent nutritional and growth data, the authors propose guidelines for the nutrition and growth follow-up of VLBW infants after discharge from the neonatal unit.

This study was performed in order to evaluate possible changes in behavior in jaundiced infants without perinatal complications other than hyperbilirubinemia treated with phototherapy. Thirty jaundiced infants (mean bilirubinemia 13.3 mg/100 ml, range 8.4-17.5) born spontaneously at term and undergoing phototherapy for 6 h or more, and 30 comparison subjects similar for sex, birthweight, gestational age, Apgar score, obstetrical history and father's profession were examined during the 3rd day of life according to Brazelton Neonatal Behavior Assessment Scale (BNBAS). For 6 of 26 items we found higher values for comparison group (Wilcoxon's Test): inanimate visual median (m.) 5 vs. 3 (P less than 0.05); animate visual m. 5 vs. 3.5 (P less than 0.01); visual and auditory 5.5 vs. 4 (P less than 0.005); pull-to-sit m. 6 vs. 5 (P less than 0.01); cuddliness m. 5 vs. 4 (P less than 0.01); alertness m. 5 vs. 4 (P less than 0.005). Visual orientation responses were the most compromised. On the 4th day of life, 14 infants who had terminated phototherapy at least 2 h before (mean 9.9 h) were compared with their matched comparison group subjects and the same significantly poorer performances, mainly in visual orientation, were found. At one month of age, 12 of these infants treated with phototherapy still showed a significantly poorer performance in 2 items of orientation: inanimate visual m. 6 vs. 4.5 (P less than 0.05); visual and auditory m. 6.5 vs. 4 (P less than 0.05). Whether these results depend on the jaundice or on the phototherapy remain to be established.

We studied the behaviour of 20 preterm infants (average gestational age 33 weeks) brought to term, without any serious disorder. These infants were compared with a group of 21 healthy term infants. To evaluate behaviour we used the 26 items of the Brazelton Neonatal Behavioural Assessment Scale (BNBAS). Our preterm infants had on the whole better scores than those reported in the literature for preterm infants with various disorders. Apart from lower ability to bring hand to mouth and in getting used to visual stimuli (these differences are statistically significant) they had, in the items of orientation a lower score only in ability to follow a voice and a face (not statistically significant). These results show that preterm infants reaching term without any serious disorder do on the whole as well as full-term infants. This correlates with the observations of Dubowitz on behaviour and particularly on visual function of preterm infants and confirms the preliminary report of Daum regarding the influence of the type of neonatal pathology on the ability of orientation at the moment of term.

The prolonged and total separation of a premature infant from its parents in a Neonatal Intensive Care Unit is an additional element of anxiety in a family already upset by the premature birth itself. However, while encouraging parents to participate in the care of their child lessens some problems, it also tends to create others. The environment of intensive care and continuous contact with the nursing of the infant may give rise to distress, and parental reactions may interfere with the running of the department. We report some results from 60 semistructured interviews between a clinical psychologist and 30 couples whose preterm infants had spent at least 10 days in the Neonatal Intensive Care Unit (NICU) of the 2nd School of Medicine of Naples. For more than 4 years we have encouraged parents to take care of their infants, to touch them, change them and feed them. The results of our study appear to suggest that allowing parents unrestricted access to the Unit stimulates paternal interest in the child.