Paul B. Colditz

A computer-aided detection of EEG seizures in infants: a singular-spectrum approach and performance comparison

Presents a scalp electroencephalogram (EEG) seizure detection scheme based on singular spectrum analysis (SSA) and Rissanen minimum description length (MDL) model-order selection (SSA-MDL). Preprocessing of the signals allows for the drastic reduction of the number of false alarms. Statistical performance comparison with seizure detection schemes of Gotman et al. (1997) and Liu et al. (1992) is performed on both synthetic data and real EEG seizures. Monte Carlo simulations based on synthetic infant EEG seizure data reveals some detection drawbacks on a large variety of seizure waveforms. Detection using both Monte Carlo and four real infant scalp EEG signals shows the superiority of the SSA-MDL method with an average good detection rate of >93% and false detection rate <4%.

Seizure detection algorithm for neonates based on wave-sequence analysis

OBJECTIVE The description and evaluation of the performance of a new real-time seizure detection algorithm in the newborn infant. METHODS The algorithm includes parallel fragmentation of EEG signal into waves; wave-feature extraction and averaging; elementary, preliminary and final detection. The algorithm detects EEG waves with heightened regularity, using wave intervals, amplitudes and shapes. The performance of the algorithm was assessed with the use of event-based and liberal and conservative time-based approaches and compared with the performance of Gotmans and Lius algorithms. RESULTS The algorithm was assessed on multi-channel EEG records of 55 neonates including 17 with seizures. The algorithm showed sensitivities ranging 83-95% with positive predictive values (PPV) 48-77%. There were 2.0 false positive detections per hour. In comparison, Gotmans algorithm (with 30s gap-closing procedure) displayed sensitivities of 45-88% and PPV 29-56%; with 7.4 false positives per hour and Lius algorithm displayed sensitivities of 96-99%, and PPV 10-25%; with 15.7 false positives per hour. CONCLUSIONS The wave-sequence analysis based algorithm displayed higher sensitivity, higher PPV and a substantially lower level of false positives than two previously published algorithms. SIGNIFICANCE The proposed algorithm provides a basis for major improvements in neonatal seizure detection and monitoring.

Folic Acid Supplementation and Spontaneous Preterm Birth: Adding Grist to the Mill?

Nicholas Fisk and colleagues discuss a new study reporting that additional voluntary folic acid supplementation was associated with a major reduction in very preterm births.

Glial glutamate transporter expression patterns in brains from multiple mammalian species

It is generally assumed that rodent brains can be used as representative models of neurochemical function in other species, such as humans. We have compared the distributions of the predominant glial glutamate transporters in rodents, rabbits, cats, pigs, monkeys, and humans. We identify similarities but also significant differences between species. GLT‐1v, which is abundantly expressed by rodent astrocytes, is expressed only in a rare subset of astrocytes of cats and humans, and appears to be absent from brains of rabbits and monkeys. Conversely, in the pig brain GLT‐1v is expressed only by oligodendrocytes. GLAST and GLT‐1α expression differed significantly between species; while rodents and rabbits exhibited uniform expression patterns in cortex, higher species, including cats, pigs, monkeys, and humans, exhibited heterogeneities in cortical and hippocampal expression. Patches devoid of labeling intermingling with patches of strong labeling were evident in areas such as temporal cortex and frontal cortex. In addition, we noted that in human motor cortex, there were inconsistencies in labeling for the C‐terminal of GLT‐1α and common domains of GLT‐1, suggesting that the C‐terminal region may be missing or that an unidentified splicing is present in many human astrocytes. Collectively our data suggest that assumptions as to the roles of glutamate transporters in any species may need to be tested empirically.

Post-insult minocycline treatment attenuates hypoxia-ischemia-induced neuroinflammation and white matter injury in the neonatal rat: a comparison of two different dose regimens

An increase in the number of activated microglia in the brain is a key feature of neuroinflammation after a hypoxic–ischemic insult to the preterm neonate and can contribute to white matter injury in the brain. Minocycline is a potent inhibitor of microglia and may have a role as a neuroprotective agent that ameliorates brain injury after hypoxia–ischemia in neonatal animal models. However to date large doses, pre‐insult administration and short periods of treatment after hypoxia–ischemia have mostly been investigated in animal models making it difficult to translate minocyclines potential applicability to protect the human preterm neonatal brain exposed to hypoxia–ischemia. We investigated whether repeated doses of minocycline can minimize white matter injury and neuroinflammation one week after hypoxia–ischemia (right carotid artery ligation and 30 min 6% O2) in the post‐natal day 3 rat pup. Two dosage regimens of minocycline were administered for one week; a high dose of 45 mg/kg 2 h after hypoxia–ischemia then 22.5 mg/kg daily or a low dose 22.5 mg/kg 2 h after hypoxia–ischemia then 10 mg/kg. Post‐natal day 3 hypoxia–ischemia significantly reduced myelin content, numbers of O1‐ and O4‐positive oligodendrocyte progenitor cells and increased activated microglia one week later on post‐natal day 10. The low dose minocycline regimen was as effective as the high dose in ameliorating neuroinflammation after post‐natal day 3 hypoxia–ischemia. However only the high dose regimen significantly attenuated reductions in O1‐ and O4‐positive oligodendrocyte progenitor cells and myelin content. The low dose only significantly attenuated the reduction in O1‐positive oligodendrocyte cell counts. Repeated, daily, post‐insult treatment with minocycline abolished neuroinflammation and may provide neuroprotection to white matter for up to one week after hypoxia–ischemia in a rodent preterm model. The present findings suggest the potential clinical relevance of a repeated, daily minocycline treatment strategy, administered after a hypoxia–ischemia insult, as a therapeutic intervention for hypoxia–ischemia‐affected preterm neonates.

Cytoskeletal Anchoring of GLAST Determines Susceptibility to Brain Damage AN IDENTIFIED ROLE FOR GFAP

Glial fibrillary acidic protein (GFAP) is an enigmatic protein; it currently has no unambiguously defined role. It is expressed in the cytoskeleton of astrocytes in the mammalian brain. We have used co-immunoprecipitation to identify in vivo binding partners for GFAP in the rat and pig brain. We demonstrate interactions between GFAP, the glutamate transporter GLAST, the PDZ-binding protein NHERF1, and ezrin. These interactions are physiologically relevant; we demonstrate in vitro that transport of d-aspartate (a glutamate analogue) is significantly increased in the presence of GFAP and NHERF1. Moreover, we demonstrate in vivo that expression of GFAP is essential in retaining GLAST in the plasma membranes of astrocytes after an hypoxic insult. These data indicate that the cytoskeleton of the astrocyte plays an important role in protecting the brain against glutamate-mediated excitotoxicity.

Seizures are associated with brain injury severity in a neonatal model of hypoxia-ischemia.

Hypoxia-ischemia is a significant cause of brain damage in the human newborn and can result in long-term neurodevelopmental disability. The loss of oxygen and glucose supply to the developing brain leads to excitotoxic neuronal cell damage and death; such over-excitation of nerve cells can also manifest as seizures. The newborn brain is highly susceptible to seizures although it is unclear what role they have in hypoxic-ischemic (H/I) injury. The aim of this study was to determine an association between seizures and severity of brain injury in a piglet model of perinatal H/I and, whether injury severity was related to type of seizure, i.e. sub-clinical (electrographic seizures only) or clinical (electrographic seizures+physical signs). Hypoxia (4% O(2)) was induced in anaesthetised newborn piglets for 30 min with a final 10 min period of hypotension; animals were recovered and survived to 72 h. Animals were monitored daily for seizures both visually and with electroencephalogram (EEG) recordings. Brain injury was assessed with magnetic resonance imaging (MRI), (1)H-MR spectroscopy ((1)H-MRS), EEG and by histology (haematoxylin and eosin). EEG seizures were observed in 75% of all H/I animals, 46% displayed clinical seizures and 29% sub-clinical seizures. Seizure animals showed significantly lower background amplitude EEG across all post-insult days. Presence of seizures was associated with lower cortical apparent diffusion coefficient (ADC) scores and changes in (1)H-MRS metabolite ratios at both 24 and 72 h post-insult. On post-mortem examination animals with seizures showed the greatest degree of neuropathological injury compared to animals without seizures. Furthermore, clinical seizure animals had significantly greater histological injury compared with sub-clinical seizure animals; this difference was not apparent on MRI or (1)H-MRS measures. In conclusion we report that both sub-clinical and clinical seizures are associated with increased severity of H/I injury in a term model of neonatal H/I.

Altered white matter diffusion anisotropy in normal and preterm infants at term equivalent age

To investigate white matter (WM) development, voxelwise analyses of diffusion tensor MRI (DTMRI) data, acquired from 12 very preterm and 11 preterm infants with gestational ages (GA) ranging from 25 to 29 and 29 to 32 weeks, respectively, and 10 newborn normal term infants were performed. T2 relaxation measures were also generated to assess brain water content. Compared with newborn term infants, very preterm infants were found to possess reduced fractional anisotropy (FA) within the frontal lobe, and a number of anterior and posterior commissural pathways. Preterm infants possessed reduced FA mainly within the posterior regions of the corpus callosum. Unexpectedly, we observed significantly reduced FA and increased T2 within a number of corticospinal projections in the newborn term infants compared to the preterm groups. This finding may reflect increased water concentration and/or a lowering of FA due to the presence of crossing interhemispheric WM projections. These findings indicate that care should be taken when interpreting FA indices without knowledge of the possible effects of water concentration in the newborn infant brain. Magn Reson Med 60:761–767, 2008.

Body Composition From Birth to 4.5 Months in Infants Born to Non-Obese Women

Infant body composition is affected by maternal obesity, which results in increased % body fat in the infant. With the rapidly increasing incidence of obesity, it is important that normative data are available for infant body composition that is not affected by this trend in maternal obesity. This study assessed body composition in infants born at term to women with a BMI between 18.5 and 25. Infant % body fat, fat mass (FM), and fat free mass (FFM) were assessed at birth, 6 wk, 3 mo, and 4.5 mo of age by air displacement plethysmography, using the PEA POD body composition system. The effects of age, gender, GA, and feeding mode on these parameters were assessed. The % body fat doubled between birth and 6 wk of age and then increased at a slower rate. FFM was higher in male infants at all ages, whereas % body fat was higher in female infants at 4.5 mo. There was a trend to increased % fat and decreased FFM in breastfed (BF) infants. The study provides unique data regarding changes in infant body composition and growth in infants born to women in the healthy weight range.

Preprocessing and time-frequency analysis of newborn EEG seizures

Neurological disease or dysfunction in newborn infants is often first manifested by seizures. Prolonged seizures can result in impaired neurodevelopment or even death. In adults, the clinical signs of seizures are well defined and easily recognized. In newborns, however, the clinical signs are subtle and may be absent or easily missed without constant close observation. This article describes the use of adaptive signal processing techniques for removing artifacts from newborn electroencephalogram (EEG) signals. Three adaptive algorithms have been designed in the context of EEG signals. This preprocessing is necessary before attempting a fine time-frequency analysis of EEG rhythmical activities, such as electrical seizures, corrupted by high amplitude signals. After an overview of newborn EEG signals, the authors describe the data acquisition set-up. They then introduce the basic physiological concepts related to normal and abnormal newborn EEGs and discuss the three adaptive algorithms for artifact removal. They also present time-frequency representations (TFRs) of seizure signals and discuss the estimation and modeling of the instantaneous frequency related to the main ridge of the TFR.