Relationship Between Early Functional and Structural Brain Developments and Brain Injury in Preterm Infants.

BACKGROUND: Recent studies explored the relationship between early brain function and brain morphology, based on the hypothesis that increased brain activity can positively affect structural brain development and that excitatory neuronal activity stimulates myelination. OBJECTIVE: To investigate the relationship between maturational features from early and serial aEEGs after premature birth and MRI metrics characterizing structural brain development and injury, measured around 30weeks postmenstrual age (PMA) and at term. Moreover, we aimed to verify whether previously developed maturational EEG features are related with PMA. DESIGN/METHODS: One hundred six extremely preterm infants received bedside aEEGs during the first 72h and weekly until week 5. 3T-MRIs were performed at 30weeks PMA and at term. Specific features were extracted to assess EEG maturation: (1) the spectral content, (2) the continuity [percentage of spontaneous activity transients (SAT%) and the interburst interval (IBI)], and (3) the complexity. Automatic MRI segmentation to assess volumes and MRI score was performed. The relationship between the maturational EEG features and MRI measures was investigated. RESULTS: Both SAT% and EEG complexity were correlated with PMA. IBI was inversely associated with PMA. Complexity features had a positive correlation with the cerebellar size at 30weeks, while event-based measures were related to the cerebellar size at term. Cerebellar width, cortical grey matter, and total brain volume at term were inversely correlated with the relative power in the higher frequency bands. CONCLUSIONS: The continuity and complexity of the EEG steadily increase with increasing postnatal age. Increasing complexity and event-based features are associated with cerebellar size, a structure with enormous development during preterm life. Brain activity is important for later structural brain development.

A brain-age model for preterm infants based on functional connectivity.

OBJECTIVE: In this study, the development of EEG functional connectivity during early development has been investigated in order to provide a predictive age model for premature infants. APPROACH: The functional connectivity has been assessed via the coherency function (its imaginary part (ImCoh) and its mean squared magnitude (MSC)), the phase locking value ([Formula: see text]) and the Hilbert-Schimdt dependence (HSD) in a dataset of 30 patients, partially described and employed in previous studies (Koolen et al 2016 Neuroscience 322 298-307; Lavanga et al 2017 Complexity 2017 1-13). Infants' post-menstrual age (PMA) ranges from 27 to 42 weeks. The topology of the EEG couplings has been investigated via graph-theory indices. MAIN RESULTS: Results show a sharp decrease in ImCoh indices in θ, (4-8) Hz and α, (8-16) Hz bands and MSC in ß, (16-32) Hz band with maturation, while a more modest positive correlation with PMA is found for HSD, [Formula: see text] and MSC in [Formula: see text], θ, α bands. The best performances for the PMA prediction were mean absolute error equal to 1.51 weeks and adjusted coefficient of determination [Formula: see text] equal to 0.8. SIGNIFICANCE: The reported findings suggest a segregation of the cortex connectivity, which favours a diffused tasks architecture on the brain scalp. In summary, the results indicate that the neonates' brain development can be described via lagged-interaction network features.

The Use of Hemodynamic and Cerebral Monitoring to Study Pharmacodynamics in Neonates.

BACKGROUND: Drugs acting on the cardiovascular and central nervous system often display relatively fast clinical responses, which may differ in neonates compared to children and adults. Introduction of bedside monitoring tools might be of additional value in the pharmacodynamic (PD) assessment of such drugs in neonates. METHODS: We aim to provide an overview of the frequently used monitoring tools to assess drug effects on the hemodynamic status as well as the cerebral circulation, oxygenation and cerebral metabolism in neonates. RESULTS: The use of blood pressure measurements, heart rate variability, functional echocardiography, nearinfrared spectroscopy and (amplitude-integrated) electroencephalography in neonates is discussed, as well as new parameters introduced by these tools. Based on the 'brain circulation model', the hemodynamic effects on the brain and their interplay are summarized. In this model, 3 processes (i.e. blood processes, vascular smooth muscle processes and tissue processes) and 3 mechanisms (i.e. autoregulation, blood flow metabolism coupling and cerebral oxygen balance) are distinguished, which all may be influenced by drug administration. Finally, propofol, sevoflurane, midazolam and inotropes are used as examples of which PD has been studied using the available hemodynamic and/or cerebral monitoring tools. CONCLUSION: The implementation of (non-)invasive monitoring tools to document hemodynamic and cerebral PD effects in neonates is of relevance both in a neonatal research and intensive clinical care setting. We highlight the need to integrate these tools in future PD research. Furthermore, besides short-term drug effects, long-term outcome of drug therapy in neonates also warrants further attention.

Automatic quiet sleep detection based on multifractality in preterm neonates: Effects of maturation.

This study investigates the multifractal formalism framework for quiet sleep detection in preterm babies. EEG recordings from 25 healthy preterm infants were used in order to evaluate the performance of multifractal measures for the detection of quiet sleep. Results indicate that multifractal analysis based on wavelet leaders is able to identify quiet sleep epochs, but the classifier performances seem to be highly affected by the infant's age. In particular, from the developed classifiers, the lowest area under the curve (AUC) has been obtained for EEG recordings at very young age (≤ 31 weeks post-menstrual age), and the maximum at full-term age (≥ 37 weeks post-menstrual age). The improvement in classification performances can be due to a change in the multifractality properties of neonatal EEG during the maturation of the infant, which makes the EEG sleep stages more distinguishable.

The suppression curve as a quantitative approach for measuring brain maturation in preterm infants.

OBJECTIVES: We apply the suppression curve (SC) as an automated approach to describe the maturational change in EEG discontinuity in preterm infants. This method allows to define normative values of interburst intervals (IBIs) at different postmenstrual ages (PMA). METHODS: Ninety-two multichannel EEG recordings from 25 preterm infants (born ⩽32weeks) with normal developmental outcome at 9months, were first analysed using the Line Length method, an established method for burst detection. Subsequently, the SC was defined as the 'level of EEG discontinuity'. The mean and the standard deviation of the SC, as well as the IBIs from each recording were calculated and correlated with PMA. RESULTS: Over the course of development, there is a decrease in EEG discontinuity with a strong linear correlation between the mean SC and PMA till 34weeks. From 30weeks PMA, differences between discontinuous and continuous EEG become smaller, which is reflected by the decrease of the standard deviation of the SC. IBIs are found to have a significant correlation with PMA. CONCLUSIONS: Automated detection of individual maturational changes in EEG discontinuity is possible with the SC. These changes include more continuous tracing, less amplitude differences and shorter suppression periods, reflecting development of the vigilance states. SIGNIFICANCE: The suppression curve facilitates automated assessment of EEG maturation. Clinical applicability is straight forward since values for IBIs according to PMA are generated automatically.

Early development of synchrony in cortical activations in the human.

Early intermittent cortical activity is thought to play a crucial role in the growth of neuronal network development, and large scale brain networks are known to provide the basis for higher brain functions. Yet, the early development of the large scale synchrony in cortical activations is unknown. Here, we tested the hypothesis that the early intermittent cortical activations seen in the human scalp EEG show a clear developmental course during the last trimester of pregnancy, the period of intensive growth of cortico-cortical connections. We recorded scalp EEG from altogether 22 premature infants at post-menstrual age between 30 and 44 weeks, and the early cortical synchrony was quantified using recently introduced activation synchrony index (ASI). The developmental correlations of ASI were computed for individual EEG signals as well as anatomically and mathematically defined spatial subgroups. We report two main findings. First, we observed a robust and statistically significant increase in ASI in all cortical areas. Second, there were significant spatial gradients in the synchrony in fronto-occipital and left-to-right directions. These findings provide evidence that early cortical activity is increasingly synchronized across the neocortex. The ASI-based metrics introduced in our work allow direct translational comparison to in vivo animal models, as well as hold promise for implementation as a functional developmental biomarker in future research on human neonates.

Improved multi-stage neonatal seizure detection using a heuristic classifier and a data-driven post-processor.

OBJECTIVE: After identifying the most seizure-relevant characteristics by a previously developed heuristic classifier, a data-driven post-processor using a novel set of features is applied to improve the performance. METHODS: The main characteristics of the outputs of the heuristic algorithm are extracted by five sets of features including synchronization, evolution, retention, segment, and signal features. Then, a support vector machine and a decision making layer remove the falsely detected segments. RESULTS: Four datasets including 71 neonates (1023h, 3493 seizures) recorded in two different university hospitals, are used to train and test the algorithm without removing the dubious seizures. The heuristic method resulted in a false alarm rate of 3.81 per hour and good detection rate of 88% on the entire test databases. The post-processor, effectively reduces the false alarm rate by 34% while the good detection rate decreases by 2%. CONCLUSION: This post-processing technique improves the performance of the heuristic algorithm. The structure of this post-processor is generic, improves our understanding of the core visually determined EEG features of neonatal seizures and is applicable for other neonatal seizure detectors. SIGNIFICANCE: The post-processor significantly decreases the false alarm rate at the expense of a small reduction of the good detection rate.

Mental retardation, deafness, skeletal abnormalities, and coarse face with full lips: confirmation of the Fountain syndrome.

We describe 3 moderately to severely mentally retarded males (2 brothers and 1 isolated patient) with congenital deafness due to an anatomical inner ear anomaly, the same manifestations that were present in the 4 sibs reported by Fountain [1974]: skeletal abnormalities with broad, stubby hands and feet and hyperkyphosis, and a peculiar "coarse" face with swelling of the subcutaneous tissue, particularly of cheeks and lips. According to the present observations early-onset, generalized seizures can be added to the symptom complex of this autosomal recessive trait.

Partial fra(X) phenotype with megalotestes in fra (X)-negative patients with acquired lesions of the central nervous system.

We describe 3 men with acquired lesions of the central nervous system (one male with tumor of the third ventricle, two males with peri- or postnatal accidents). In all three patients macroorchidism was associated with facial characteristics similar to those found in fra(X) males, but they were fra(X)-negative. The finding of megalotestes associated with a partial fra(X) phenotype in the present patients and, more particularly, the documentation of a hypothalamic tumor in the first patient, suggests that a specific hypothalamic lesion in fra(X) males is responsible for some of their manifestations.

[Long-term results of interbody fusion in neck pathology]. / Résultats à très long terme de la fusion intercorporéale dans la pathologie cervicale.

For a long-term period (25-30 years) the author sums up the results obtained by cervical discectomy through a ventral route followed by interbody arthrodisis. In the disc diseases, the radicular syndromes gave excellent results, the medullar syndromes good results. In the cervical injuries, the results were always good. The discussion analyses the different physio-pathologic elements of this intervention. In lateral amyotrophic sclerosis the results were always bad.

Hypomelanosis of Ito and severe sensorineural deafness.

In this report we describe an 8-year-old boy of Algerian origin with profound sensorineural deafness and skin pigmentation anomalies consistent with the diagnosis of hypomelanosis of Ito. On the basis of this observation the etiologic heterogeneity of this condition is discussed.

On the nosology of moderate mental retardation with special attention to X-linked mental retardation. A diagnostic genetic survey of 274 institutionalized moderately mentally retarded men.

In this paper we report the results of a genetic-diagnostic survey of 274 institutionalized moderately mentally retarded adult males and compare these data with those from our previous studies in the severely mentally retarded and from a comparable population of 262 institutionalized moderately mentally retarded males and females (The Borgenstein experience). Special attention is paid to the nosology of X-linked mental retardation and familial mental retardation in general.

[Surgeons responsibility in infectious complications (author's transl)]. / Responsabilité du chirurgien dans les complications infectieuses.

Law suits of surgeons are increasing in number. Although the surgeon has no obligation concerning results, but only concerning means, the causes of postoperative infections are numerous: inadequate preoperative work-up (chronic focal infection), operative infection by means of an assistant or a visitor, inadequate air conditioning, lengthy operation, prolonged intravenous catheter and viral hepatitis after transfusion are some examples. Liability of the anaesthetist is a difficult problem. In many institutes one anaesthetist simultaneously monitors more than one anaesthesia. The cause-effect relation between the infection and the surgical malpractice must be proven by the patient; this creates an athmosphere of suspicion in the surgical team. More recently the courts have admitted that an infection can render the patient less resistant to another complication, of which he may die.

An experimental permeabilization of the blood-brain barrier by electric field application.

This work investigates the method of 'transcerebral electrolysis' in rabbits previously used by other authors (e.g. G. Bourguignon). The observation of the animal, with EEG record, and the macroscopic and microscopic studies, have allowed to precise the physical parameters which do not damage the brain functions: current intensity of not more than 5 mA, applied on large electrodes. In this manner, without traumatization of the brain, the blood-brain barrier allows passage of many substances (dyes, tracers, drugs) and this permeability remains for several days.

Frontal dynamic thermometry. Improvement in diagnosis of carotid stenosis.

This new method of frontal thermometry is based on a recording of the spontaneous reheating curve of the skin after cooling it to 25 degrees C. In cases of carotid stenosis, a thermal asymmetry of one of the three following kinds can be observed: thermal asymmetry from the start; asymmetry only during the reheating, or asymmetry during reheating and remaining afterwards. The reduction of the blood flow and a vaso-motor factor explain this asymmetry. This method allows better detection of clinical latent carotid stenosis.

Mental retardation and Y/8 translocation [karyotype: 46,XY, t(Y;8)(q12;q24)] in father and son.

In the present report we describe a 98/12-year-old male with Noonan phenotype, moderate mental retardation and 46,XY, der(8), t(Y;8)(q12;q24) karyotype. Further examination of the family revealed that the boy inherited the Noonan features from his mother and the Y/8 translocation from his moderately mentally handicapped father.