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Minimally invasive monitoring of brain activity is essential not only to gain understanding on the working principles of the brain, but also for the development of new diagnostic tools. In this perspective we describe how brain thermometry could be an alternative to conventional methods (e.g., magnetic resonance or nuclear medicine) for the acquisition of thermal images of the brain with enough spatial and temperature resolution to track brain activity in minimally perturbed animals. We focus on the latest advances in transcranial luminescence thermometry introducing a critical discussion on its advantages and shortcomings. We also anticipate the main challenges that the application of luminescent nanoparticles for brain thermometry will face in next years. With this work we aim to promote the development of near infrared luminescence for brain activity monitoring, which could also benefit other research areas dealing with the brain and its illnesses, This work was financed by the Spanish Ministerio de Innovación y Ciencias under project NANONERV PID 2019-106211RB-I00. BD acknowledges support from the Australian Research Council (DE200100985), RMIT University (Vice-Chancellor’s Fellowship Programme) and the Australian Academy of Sciences (JG Russell Award). PR-S is grateful for a Juan de la Cierva—Incorporación scholarship (IJC2019-041915-I). AB acknowledges funding from Comunidad de Madrid through TALENTO grant ref. 2019-T1/IND-14014. EX is grateful for a Juan de la Cierva - Incorporación scholarship (IJC2020-045229-I)

ZusammenfassungZiel dieser Studie ist es, ein kritisches postnatales Outcome als Prädiktor für die Entwicklung einer hypoxisch ischämischen Enzephalopathie (HIE) zu evaluieren. Methodik Auf Basis der Daten der hessischen Perinatalerhebung aus dem Jahr 2016 mit 52 122 Geburten (Lebendgeborene Einlinge, ≥ 37+0 Schwangerschaftswochen) wurden die Fälle mit kritischem Outcome identifiziert. Kriterien waren ein APGAR-Score 16,0 mmol/L. Diese Fälle wurden mit den HIE-Fällen aus der Neonatalerhebung zusammengeführt. Es wurden die Odds Ratio sowie Sensitivität/Spezifität und positiver (ppW)/negativer(npW) Vorhersagewert berechnet. Durch Evaluation des Geburtsverlaufes und des subpartalen CTG wurde die potentielle Vermeidbarkeit des Kritischen Outcomes/hypoxisch ischämischen Enzephalopathie überprüft. Ergebnisse Die Inzidenz der Fälle mit kritischem Outcome (n=11) und derer mit hypoxisch ischämischen Enzephalopathie (n=29) ist gering. Nach Zusammenführung der Daten aus der Perinatal- respektive Neonatalerhebung ergaben sich eine Sensitivität von 10,34%, eine Spezifität von 99,98%, ein positiver bzw. negativer prädiktiver Wert von 27,35, bzw. 99,95%. In nahezu einem Drittel der Fälle mit kritischem Outcome (4/11) oder hypoxisch ischämischen Enzephalopathie (9/29) fanden sich Hinweise auf eine potentielle Vermeidbarkeit. Schlussfolgerungen Ein postnataler Depressionszustand führt häufiger zur Diagnose einer HIE als eine schwere Azidose im Nabelschnurblut. Da ein Drittel der Fälle vermeidbar erscheinen, kann die fachübergreifende Einzelfallanalyse bei kritischem Neugeborenenstatus zur Optimierung der Geburtshilfe auch im Rahmen der externen Qualitätssicherung (QS) zielführend sein.

Hypoxic-ischemic encephalopathy (HIE) is a manifestation of perinatal asphyxial insult that continues to evolve over days to weeks following the initial injury. Therapeutic hypothermia has demonstrated that a proportion of this secondary brain injury may indeed be preventable. However, therapeutic hypothermia has also altered the prognostic utility of many bedside tools that are commonly used as predictors of long-term neurodevelopmental outcome in HIE. Clinicians are often confronted with uncertainty when assessing the prognosis of infants with HIE. Improved understanding of the implications and limitations of individual investigations may inform clinical decisions and allow for timely intervention. This review summarizes the predictive value of currently available prognostic markers in HIE infants in the therapeutic hypothermia era, including clinical, biochemical, neurophysiological, physiological, and neuroimaging predictors.

OBJECTIVES: Electroencephalogram features predict neurologic recovery following cardiac arrest. Recent work has shown that prognostic implications of some key electroencephalogram features change over time. We explore whether time dependence exists for an expanded selection of quantitative electroencephalogram features and whether accounting for this time dependence enables better prognostic predictions. DESIGN: Retrospective. SETTING: ICUs at four academic medical centers in the United States. PATIENTS: Comatose patients with acute hypoxic-ischemic encephalopathy.None. MEASUREMENTS AND MAIN RESULTS: We analyzed 12,397 hours of electroencephalogram from 438 subjects. From the electroencephalogram, we extracted 52 features that quantify signal complexity, category, and connectivity. We modeled associations between dichotomized neurologic outcome (good vs poor) and quantitative electroencephalogram features in 12-hour intervals using sequential logistic regression with Elastic Net regularization. We compared a predictive model using time-varying features to a model using time-invariant features and to models based on two prior published approaches. Models were evaluated for their ability to predict binary outcomes using area under the receiver operator curve, model calibration (how closely the predicted probability of good outcomes matches the observed proportion of good outcomes), and sensitivity at several common specificity thresholds of interest. A model using time-dependent features outperformed (area under the receiver operator curve, 0.83 ± 0.08) one trained with time-invariant features (0.79 ± 0.07; p < 0.05) and a random forest approach (0.74 ± 0.13; p < 0.05). The time-sensitive model was also the best-calibrated. CONCLUSIONS: The statistical association between quantitative electroencephalogram features and neurologic outcome changed over time, and accounting for these changes improved prognostication performance., SCOPUS: ar.j, info:eu-repo/semantics/published

In light of recent works exploring automated pathological diagnosis, studies have also shown that medical text reports can be generated with varying levels of efficacy. Brain diffusion-weighted MRI (DWI) has been used for the diagnosis of ischaemia in which brain death can follow in immediate hours. It is therefore of the utmost importance to obtain ischaemic brain diagnosis as soon as possible in a clinical setting. Previous studies have shown that MRI acquisition can be accelerated using variable-density Cartesian undersampling methods. In this study, we propose an accelerated DWI acquisition pipeline for the purpose of generating text reports containing diagnostic information. We demonstrate that we can learn a semantic-preserving latent space for minor as well as extremely undersampled MR images capable of achieving promising results on a diagnostic report generation task.

Several methods of brain image registration have been proposed in order to overcome the requirement of clinicians. In this paper, we assess the performance of a hybrid method for brain image registration against the most used standard registration tools. Most traditional registration tools use different methods for mono- and multi-modal registration, whereas the hybrid registration method is providing both mono and multi-modal brain registration of PET, MRI and CT images. To determine the appropriate registration method, we used two challenging brain image datasets as well as two evaluation metrics. Results show that the hybrid method outperforms all other standard registration tools and has achieved promising accuracy for MRI/X brain image registration.

A review of the conundrum called mild hypoxic-ischemic encephalopathy (HIE) is provided. During the past decades, the definition of HIE has evolved to accommodate the short window of time required for the initiation of therapeutic hypothermia. Also, neurological evaluations have changed with the use of simpler staging systems that can be applied within the first 6 h of life. In this review, we discuss the challenges in the identification of newborns with “mild HIE” within 6 h after birth, the limitations in the existing early biomarkers of brain injury, and the current knowledge gaps in the long term neurodevelopmental outcomes of infants diagnosed with mild HIE. Progress in the understanding of mild HIE and its sequelae continues to be hindered by the lack of a standardized definition for mild HIE that will reliably identify at-risk infants who may benefit from neuroprotective strategies.

Therapeutic hypothermia has been shown to reduce brain damage due to postcardiac arrest syndrome. Actually, there is no agreement on which is the best device to perform therapeutic hypothermia. The 'ideal' device should not only 'cool' patient until 33-34°C as fast as possible, but also maintain the target temperature and reverse the therapeutic hypothermia. For out-of-hospital cardiac arrest, there are devices that allow starting of therapeutic hypothermia on the field (prehospital hypothermia). On hospital arrival, these prehospital devices can be quickly and easily replaced with other devices more suitable for the management of therapeutic hypothermia in ICUs (in-hospital hypothermia). Some studies have compared surface and endovascular devices and found no substantial differences in neurologic outcome or survival at hospital discharge. On a clinical ground, the knowledge of the technical aspects of therapeutic hypothermia (such as characteristics of devices) is mandatory for clinicians who have to perform therapeutic hypothermia in cardiac arrest patients because the timing of therapeutic hypothermia, the choice of the device for the single patients, and avoidance of temperature fluctuation have shown to affect outcome in these patients (also in terms of reducing the incidence of complications).

The authors investigated feasibility of undilated handheld spectral domain optical coherence tomography (SDOCT) retinal imaging in preterm infants and children with neurologic abnormalities.Under an institutional review board-approved protocol, the authors attempted handheld SDOCT imaging of the retina, choroid, and optic nerve in infants and young children without pupil dilation. Scans were analyzed for quality and successful capture of foveal, optic nerve, and retinal structural parameters and abnormalities.The authors obtained images through an undilated pupil of 11 infants/children over 28 eye imaging sessions, 27 at the bedside without sedation, and one under anesthesia. Infants had retinopathy of prematurity (n = 8), hypoxic ischemic encephalopathy (n = 2), or obstructive hydrocephalus (n = 1 child). Pupil sizes ranged from 1.0 mm to 3.5 mm. The authors captured fovea and optic nerve scans in 25/28 eye imaging sessions, with scans of adequate quality to discern prespecified foveal and optic nerve morphology, and of the 25 sessions, the choroidal-scleral junction was visible in all but 6 sessions.Undilated, handheld SDOCT imaging is a potential alternative method to evaluate the retina and optic nerve in patients with relative contraindication to pharmacological pupil dilation. This approach will enable the study of the eye-brain connection and ocular manifestations of neurologic diseases.

There has been a significant increase in the utilization of NIRS in neonatal care over the last few years, with some centers now routinely utilizing this monitoring technique for direct intervention at the bedside. In this review, we provide a summary of the most up-to-date evidence on near infrared spectroscopy utilization, with particular emphasis on measurement of cerebral oxygenation in preterm infants.There have been significant advances in the technology, leading to an increase in the number of available devices and in the use of this monitoring tool to reduce cerebral injury in preterm infants. The role of NIRS in assessing cerebral autoregulation in preterm and term infants, in evaluating somatic oxygenation, and in the management of newborns with hypoxic ischaemic encephalopathy is discussed.Two recent pilot randomized controlled trials highlight the potential of cerebral oxygenation monitoring to direct management in the delivery room and the neonatal intensive care unit. However, we urge caution against routine use and await the results of further studies in this area before considering this type of monitoring as standard of care.

Fe2O3 nanoparticles (NPs) have been synthesized and functionalized with SiO2 and -NH2 group, respectively. Conjugation to fluorescently-labeled poly-caspase inhibitor (SR-FLIVO) has been carried out for better cellular uptake studies of apoptosis arising from brain focal cerebral ischemia. Highest conjugation affinity to SR-FLIVO was found to be ca. 80% for Fe2O3-SiO-NH2 functionalized nanoparticles (FNPs). Tracking of SR-FLIVO conjugated functionalized nanoparticles (SR-FLIVO-FNPs) in vivo and in vitro has been carried out and detected using microscopic techniques after histochemical staining methods. Experimental results revealed that SR-FLIVO-FNPs probe could passively cross the blood brain barrier (BBB) and accumulated within the apoptotic cell. Optimization of SR-FLIVO-FNPs probe can effectively promise to open a new era for intracellular drug delivery and brain diagnosis.

Objective Amplitude-integrated electroencephalography (aEEG) is a simplified method for continuous monitoring of brain activity in the neonatal intensive care unit (NICU). Our objective was to describe current aEEG use in the United States. Study Design An online survey was distributed to the American Academy of Pediatrics Section on Perinatal Pediatrics' list serve. Result A total of 654 surveys were received; 55% of respondents reported using aEEG. aEEG was utilized more often in academic and levels III and IV NICUs; hypoxic-ischemic encephalopathy and suspected seizures were the most common indications for use. aEEG was primarily interpreted by neonatologists (87%), with approximately half reporting either self-teaching or hospital-based training for interpretation. For those not using aEEG, uncertain clinical benefit (40%) and cost (17%) were reported as barriers to use. Conclusion More than half of neonatologists utilize aEEG, with practice variation by NICU setting. Barriers to wider adoption include education regarding potential benefit, training, and cost.

Findings of neonatal encephalopathy (NE) and specifically those of hypoxic-ischemic injury are frequently evident on magnetic resonance imaging (MRI). Although MRI has become more widely used and has gained widespread acceptance as the study of choice for the evaluation of NE in recent years, its costs are high and access to MRI is sometimes limited for extremely sick neonates. Therefore, head sonography (US) continues to be the first-line imaging modality for the evaluation of the brain in neonates with NE; furthermore, in many of these infants, the diagnosis of NE may have first been made or suggested using head US. US is noninvasive, inexpensive, and portable, allowing examinations to be performed without moving the infant. However, many of the telltale signs of NE on US are subtle and may be easily overlooked, contributing to diagnostic delay or misdiagnosis. We aim to illustrate the spectrum of US findings in NE, with emphasis on those findings that may be easily overlooked on US. Recognition of these findings could potentially improve detection rates, reduce errors, and improve patient management.

Background: The health risks associated with dichloromethane (DCM) for the general population living near industrial activities have not yet been quantified, primarily due to lack of epidemiological datasets. In the absence of such human data, we undertook a cancer cluster investigation in Cyprus around a historically using DCM plant producing shoe soles that were globally exported. We designed the methodology to investigate the possible existence of a cancer cluster in the area around the factory (point zero) and within a radius of 500 meters. Methods: A retrospective comparative population study was designed using a group of cancer patients living or working in the chosen geographical area around the factory. Results: Mean stack emissions of DCM of 88 mg/Nm(3) and flow rates of 850 g/h exceeded the permissible DCM limits established for industrial zones. Brain and central nervous system (CNS) cancer incidence rates showed significant (P < 0.001) increase in the study area around the plant when compared with those observed in other areas of Cyprus. Calculated standardized incidence ratios for brain/CNS after adjusting for the age at diagnosis ranged from 11.3-25.7 [mean 6.5 (3.02 : 12.3)] for the study area. Conclusions: We showed the association between chronic, unintentional DCM exposures and brain/CNS cancer cases for the general population located in a residential area being in close proximity with a plant historically emitting DCM.

Purpose The reliability of somatosensory evoked potentials (SSEPs) in predicting outcome in comatose survivors of cardiac arrest treated with therapeutic hypothermia (TH) has been questioned. We investigated whether the absence of cortical (N20) responses was a reliable predictor of a nonawakening in the setting of TH. Methods A retrospective review was conducted in cardiac arrest survivors treated with TH admitted to a single tertiary care hospital from April, 2010 to March, 2013 who underwent SSEP testing at various time points after cardiac arrest. N20 responses were categorized as normal, present but abnormal, bilaterally absent, or inadequate for interpretation. Neurologic outcome was assessed at discharge by the Cerebral Performance Category Scale (CPC). Results Ninety-three SSEP studies were performed in 73 patients. Fourteen patients had absent N20 responses; all had poor outcome (CPC 4-5). Eleven patients had absent N20 s during hypothermia, three of whom had follow-up SSEPs after rewarming and cortical responses remained absent. Fifty-seven patients had N20 peaks identified and had variable outcomes. Evaluation of 1 or more N20 peaks was limited or inadequate in 11.4% of SSEPs performed during the cooling because of artifact. Conclusions Somatosensory evoked potentials remain a reliable prognostic indicator in patients undergoing TH. The limited sample size of patients who had SSEP performed during TH and repeated after normothermia added to the effect of self-fulfilling prophecy limit the interpretation of the reliability of this testing when performed during cooling. Further prospective, multicenter, large scale studies correlating cortical responses in SSEPs during and after TH are warranted. Technical challenges are commonplace during TH and caution is advised in the interpretation of suboptimal recordings.

The neuropeptide secretoneurin (SN) shows widespread distribution in the brain. We evaluated whether SN is elevated after cardiopulmonary resuscitation (CPR) and could serve as a potential new biomarker for hypoxic brain injury after CPR.This was a prospective observational clinical study. All patients admitted to a tertiary medical intensive care unit after successful CPR with expected survival of at least 24 h were consecutively enrolled from September 2008 to April 2013. Serum SN and neuron-specific enolase were determined in 24 h intervals starting with the day of CPR for 7 days. Neurological outcome was assessed with the Cerebral Performance Categories Scale (CPC) at hospital discharge.A total of 134 patients were included with 49 % surviving to good neurological outcome (CPC 1-2). SN serum levels peaked within the first 24 h showing on average a sixfold increase above normal. SN levels were significantly higher in patients with poor (CPC 3-5) than in patients with good neurological outcome [0-24 h: 75 (43-111) vs. 38 (23-68) fmol/ml, p0.001; 24-48 h: 45 (24-77) vs. 23 (16-39) fmol/ml, p0.001]. SN determined within the first 48 h showed a receiver operating characteristic (ROC) area under the curve (AUC) of 0.753 (0.665-0.841). NSE in the first 72 h had a ROC-AUC of 0.881 (0.815-0.946). When combining the two biomarkers an AUC of 0.925 (0.878-0.972) for outcome prediction could be reached.SN is a promising early biomarker for hypoxic brain injury. Further studies will be required for confirmation of these results.

Resume Objectifs Determiner l’apport de l’examen clinique, de l’electroencephalogramme (EEG) et de l’imagerie par resonance magnetique (IRM) cerebrale pour evaluer le pronostic des encephalopathies neonatales precoces (ENNP). Patients et methodes Etude retrospective ayant concerne 30 nouveau-nes a terme atteints d’ENNP classee selon les criteres d’Amiel-Tison et hospitalises entre janvier 2006 et decembre 2008 avant la mise en place de l’hypothermie. Les donnees de l’examen clinique ont ete recueillies durant la premiere semaine de vie, une IRM cerebrale a ete realisee avant cinq jours de vie et apres sept jours de vie, au moins un EEG a ete realise durant les deux premiers jours. Le suivi a permis d’evaluer l’evolution des enfants. Resultats Notre etude a confirme le lien entre le stade d’Amiel-Tison, le trace EEG et l’evolution a l’âge scolaire. Dans les ENNP moderees, les traces EEG etaient de gravite variable et l’IRM cerebrale affinait le pronostic. Les lesions des noyaux gris centraux et la diminution ou la disparition de l’hypersignal physiologique du bras posterieur de la capsule interne etaient des facteurs de mauvais pronostic. Les troubles cognitifs touchaient 40 % des enfants survivants dans notre serie, justifiant un suivi pediatrique prolonge. Conclusion Notre travail confirme l’interet de l’IRM cerebrale associee aux donnees de l’examen clinique et de l’EEG pour l’evaluation pronostique des ENNP.

To evaluate cooling practices and neonatal outcomes in the state of California during 2010 using the California Perinatal Quality Care Collaborative and California Perinatal Transport System databases.Database analysis to determine the perinatal and neonatal demographics and outcomes of neonates cooled in transport or after admission to a cooling center.Of the 223 infants receiving therapeutic hypothermia for hypoxic ischemic encephalopathy (HIE) in California during 2010, 69% were cooled during transport. Despite the frequent use of cooling in transport, cooling center admission temperature was in the target range (33-34 °C) in only 62 (44%). Among cooled infants, gestational age was35 weeks in 10 (4.5%). For outborn and transported infants, chronologic age at the time of cooling initiation was6 h in 20 (11%). When initiated at the birth hospital, cooling was initiated at6 h of age in 131 (92.9%).More than half of the infants cooled in transport do not achieve target temperature by the time of arrival at the cooling center. The use of cooling devices may improve temperature regulation on transport.

The growth processes involved early in gestation and further into the intricate signaling networks in the brain form the basis for rapid cortical electrical bursting patterns. This leads to the quantification of cortical activity from the electroencephalogram (EEG) in full-term hypoxic infants and preterm infants. The associated neurological sequelae in both populations are foregrounded by a summary into current epidemiology and common clinical practices. The present review article highlights recent advances in physics and neuroscience, which will help in development of reliable predictors of outcome for full-term and preterm neonates after birth.

Prediction of prognosis in comatose patients surviving a cardiac arrest is still one of the intractable problems in critical care neurology because of lack of fool-proof ways to assess the outcome. Of all these measures, somatosensory-evoked potential (SSEP) has been perhaps the most evaluated and heavily relied-upon tool over the past several decades for assessing coma. Recent studies have given rise to concerns regarding the "absoluteness" of SSEP signals for the prognostic evaluation of coma. In this critical review, we searched the literature to focus on studies conducted so far on the prognostic evaluation of postanoxic coma using SSEPs. All those studies published on the use of SSEP as a prognostication tool in postanoxic coma were reviewed. A narrative review was created that included the strengths as well as limitations of the use of SSEP in postanoxic coma. The use of SSEP in coma has been universal for the purpose of prognostication. However, it has its own advantages as well as limitations. The limitations include challenges in performing and getting SSEP signals during coma as well as the challenges involved in reading and interpreting the signals. The recent usage of therapeutic hypothermia has become another factor that often interferes with the SSEP recording. Finally, based on these study results, some recommendations are generated for the effective use of SSEPs in comatose patients for further prognostication. We advocate that SSEP should be an integral component for the assessment of postanoxic comatose patients due to its several advantages over other assessment tools. However, SSEP recordings should follow certain standards. One should be aware that its interpretation may be biased by several factors. The bias created by the concept of "self-fulfilling hypothesis" should always be borne in mind before discontinuation of life support systems in terminal patients.

Literature regarding callosal injury after hypoxic-ischemic injury (HII) is scant.To present the MRI and US findings of callosal injury after HII.MRI and US studies of 76 neonates were evaluated for HII and 53 were considered positive.Of the 53 neonates with HII, 40 demonstrated restricted diffusion on DWI; of these, 30 revealed callosal involvement. Nine of the 13 neonates with normal DWI, whose routine MRI images were compatible with HII, were imaged after 1 week of age. Five out of ten neonates imaged during the 1st week of life who did not show callosal restriction on DWI had predominantly basal ganglia injury. Callosal US images were regarded as abnormal in 16 out of the 53 neonates with HII, 15 of which revealed concomitant restricted diffusion on DWI.Callosal injuries are common after HII. DWI is effective in confirming these injuries and easily demonstrates injury if performed prior to 1 week of age. The restricted diffusion demonstrated after this time could be attributed to continued injury. US is not a sensitive modality for callosal injury detection; however, abnormally increased callosal echogenicity might be a specific marker of injury in this setting.

Objective To determine the agreement among conventional electroencephalography (CEEG) terminology background classification and a simple and an advanced amplitude-integrated EEG (aEEG) system, and to evaluate whether aEEG interpreter experience or electrographic seizures affect this agreement. Study design CEEG background was classified by traditional interpretive criteria for 144 neonatal recordings, from which a single channel was converted to aEEGs. These aEEGs were independently interpreted by neonatologists according to the simple and advanced classification systems. Results Interreader agreement was better with the simple aEEG system compared with the advanced aEEG system (multirater κ, 0.66 vs 0.44). Fair-to-moderate agreement was found between both of the aEEG classification systems and CEEG (simple: κ, 0.34 to 0.45; advanced: κ, 0.36 to 0.45). Agreement did not vary significantly based on the aEEG interpreter experience or the presence of seizures. Conclusions Neonatologists found better agreement using the simple aEEG system regardless of their expertise or the presence of seizures. This finding has implications for patient selection in future multicenter neonatal neuroprotection studies.

Hypoxic ischemic encephalopathy (HIE) is common in children, and providing accurate and timely prognostic information is important in determining the appropriate level of care. While practice parameters are available for prognostication in adults, similar reviews are not available for children. This article reviews the current evidence in domains used to provide prognostic information in children with coma due to HIE. These include historical features of the event; physical exam signs; neurophysiologic studies, such as electroencephalogram and evoked potentials; and neuroimaging.A literature search of MEDLINE was performed using the search terms HIE and prognosis cross-referenced in series with specific domains used to provide prognostic information, including physical examination, electroencephalogram, evoked potentials, neuroimaging, and magnetic resonance imaging. The results of these searches were scanned by the authors to identify articles pertaining to children (nonneonates). Further literature was identified from the reference lists of the literature identified by MEDLINE search. Clinical, preclinical, and review articles were identified that were related to the current understanding of prognosis in pediatric HIE. Only literature in English was reviewed.When performed at least 24 hrs after the inciting event, abnormal exam signs (pupil reactivity and motor response), absent N20 waves bilaterally on somatosensory evoked potentials, electrocerebral silence or burst suppression patterns on electroencephalogram (not due to metabolic or medication etiology), and abnormal magnetic resonance imaging with diffusion restriction in the cortex and basal ganglia are each highly predictive of poor outcome. Combining these modalities improves the overall predictive value.All testing provides the best prognostic information several days after hypoxic-ischemic injury, and often multiple tests are required to improve prognostic ability and rule out potentially confounding conditions. Thus, when decisions can be postponed several days, neurologic consultation and testing can provide the best prognostic information to families.

More than a decade has passed since multi-channel magnetoencepharography (MEG) systems based on superconducting quantum interference devices (SQUIDs) became commercially available. In collaboration with medical doctors, neuroscientists and engineers, MEG systems have been improved and progress continues to be made as one of the cutting-edge instruments useful for brain diagnosis and research. On the other hand, SQUID technology is also promising for new biomagnetic applications. MEG and other nerve measurement systems using SQUIDs are introduced and challenges from a technical point of view are described.

When a new technology is introduced it is important to empower the bedside practitioner with a resource tool that outlines the purpose, placement procedure, technology application guidelines, and interventions associated with that new technology. This promotes product and patient safety and successful implementation of the new technology. Continued evaluation of bedside clinical practice and the technology used in the care and treatment of the severe brain injured patient can lead to improvements in management and in technology design. Future clinical research initiatives exploring the impact of new technology will enable us to discover cost-effective treatments and interventions that will improve the outcome for a person with traumatic brain injury, a condition that devastates hundreds of thousands of Americans each year.

Resume Objectif. – Demontrer la valeur diagnostique et la faisabilite du dosage des lactates au scalp pendant le travail de l'accouchement dans l'appreciation de l'acidose fœtale en cas d'anomalie du rythme cardiaque fœtal. Patientes et methode. – Une etude prospective observationnelle a ete conduite sur 129 prelevements de sang capillaire au scalp fœtal. Le dosage des lactates au scalp a ete compare au pH au scalp (technique de reference), a la gazometrie neonatale au cordon (pH et lactates) et au score d'Apgar. Les valeurs seuils pathologiques retenues ont ete pour les lactates au scalp superieure a 5 mmol/l, pour le pH au scalp inferieure a 7,20, pour le pH arteriel au cordon inferieure a 7,10, pour les lactates a l'artere ombilicale superieure a 6,35 mmol/l, et pour le score d'Apgar inferieur a 7 a une et cinq minutes. Les mesures ont ete obtenues par microdosage avec l'analyseur Rapid Lab ™ 860 de Bayer, disponible en salle de naissance. Resultats. – Les lactates au scalp etaient correles significativement au pH au scalp ( r = –0,54, p = 0,001), au pH de l'artere ombilicale ( r = –0,46, p = 0,01), aux lactates de l'artere ombilicale ( r = 0,49, p = 0,01). La valeur predictive negative et la specificite des lactates au scalp etaient bonnes (92 %) et comparables a celles du pH au scalp pour le diagnostic d'acidose a la naissance objectivee par un pH a l'artere ombilicale inferieur a 7,10 et/ou des lactates a l'artere ombilicale superieures a 6,35 mmol/l. La faisabilite du dosage des lactates au scalp etait meilleure que le mesure de pH (moins de 1 % d'echec contre 18 %). Discussion et conclusion. – La mesure des lactates au scalp fœtal par microdosage a une valeur diagnostique comparable a celle du pH au scalp ; sa valeur predictive negative est aussi bonne dans l'appreciation de l'acidose fœtale. En outre cette technique est plus facilement realisable que celle du pH. Le dosage des lactates au scalp apparait comme un complement diagnostique important en presence d'anomalies du RCF. Bien que des etudes prospectives soient encore necessaires, l'existence de materiel portable necessitant un volume sanguin encore plus faible rend possible la mesure des lactates fœtaux dans toutes les maternites.

The technology of transcranial near-infrared spectroscopy (NIRS) for the measurement of cerebral oxygen balance was introduced 25 years ago. Until very recently, there has been only occasional interest in its use during surgical monitoring. Now, however, substantial technologic advances and numerous clinical studies have, at least partly, succeeded in overcoming long-standing and widespread misunderstanding and skepticism regarding its value. Our goals are to clarify common misconceptions about near-infrared spectroscopy and acquaint the reader with the substantial literature that now supports cerebral oximetric monitoring in cardiac and major vascular surgery.

The terms "cerebral palsy," "neonatal encephalopathy," and "intrapartum asphyxia" are frequently used in pediatric neurology. This article presents concise, verifiable definitions for each of these entities based on our current understanding and formulates the nature of the interrelationships between them. The aim is to provide a level of clarity that will enhance diagnostic and pathogenetic precision and minimize conceptual misunderstanding. This should aid future therapeutic and research efforts in this important area.

Melatonin has been shown to be neuroprotective in animal models. The objective of this study is to examine the effect of melatonin on clinical, biochemical, neurophysiological and radiological outcomes of neonates with hypoxic-ischemic encephalopathy (HIE).We conducted a prospective trial on 45 newborns, 30 with HIE and 15 healthy controls. HIE infants were randomized into: hypothermia group (N=15; received 72-h whole-body cooling) and melatonin/hypothermia group (N=15; received hypothermia and five daily enteral doses of melatonin 10 mg kg(-1)). Serum melatonin, plasma superoxide dismutase (SOD) and serum nitric oxide (NO) were measured at enrollment for all infants (N=45) and at 5 days for the HIE groups (N=30). In addition to electroencephalography (EEG) at enrollment, all surviving HIE infants were studied with brain magnetic resonance imaging (MRI) and repeated EEG at 2 weeks of life. Neurologic evaluations and Denver Developmental Screening Test II were performed at 6 months.Compared with healthy neonates, the two HIE groups had increased melatonin, SOD and NO. At enrollment, the two HIE groups did not differ in clinical, laboratory or EEG findings. At 5 days, the melatonin/hypothermia group had greater increase in melatonin (P0.001) and decline in NO (P0.001), but less decline in SOD (P=0.004). The melatonin/hypothermia group had fewer seizures on follow-up EEG and less white matter abnormalities on MRI. At 6 months, the melatonin/hypothermia group had improved survival without neurological or developmental abnormalities (P0.001).Early administration of melatonin to asphyxiated term neonates is feasible and may ameliorate brain injury.

Neonatal EEG can be useful for predicting outcome soon after acute hypoxia-ischemia. There are techniques that can optimize the prognostic accuracy of EEG. Seizure medications and the time interval between hypoxia-ischemia and the EEG must be taken into account. Serial EEGs also improve the predictive ability of EEG.

Thyroid storm most often occurs in patients with known thyrotoxicosis. This report discusses a severe case of thyroid storm developing as a direct result of strangulation in a patient without a preexisting history of thyroid disease. Classification and treatment of this entity are discussed.

Background: Initial aEEG background pattern has been used as a predictor of neurological outcome after asphyxia and has been used as inclusion criterion for trials evaluating efficacy of therapeutic hypothermia in encephalopathic newborns. The utility of continuous aEEG monitoring during hypothermia has not been well described. Objectives: (1) To describe the evolution of aEEG during therapeutic hypothermia in newborns with encephalopathy, and (2) to evaluate the utility of continuous aEEG monitoring during therapeutic hypothermia. Methods: This is a retrospective review of continuous aEEG data from encephalopathic newborns treated with whole-body hypothermia. aEEG segments were scored for background and sleep-wake cycling (SWC). Sensitivity and specificity calculations and logistic regression analyses were performed to evaluate the ability of aEEG to predict death or severe MRI abnormality/significant neurological deficit at discharge. Results: aEEG data from 75 encephalopathic newborns were reviewed. Abnormal aEEG background was predictive of adverse outcome with increasing positive predictive value over the course of hypothermia. Few patients (5%) had early SWC, but 58% developed SWC by rewarming and all had favorable outcome. Conclusions: Persisting aEEG background abnormality beyond 48 h of life and lack of SWC over the course of hypothermia is predictive of adverse NICU outcome in encephalopathic newborns.