Prevalence and etiology of false normal aEEG recordings in neonatal hypoxic-ischaemic encephalopathy.

BACKGROUND: Amplitude-integrated electroencephalography (aEEG) is a useful tool to determine the severity of neonatal hypoxic-ischemic encephalopathy (HIE). Our aim was to assess the prevalence and study the origin of false normal aEEG recordings based on 85 aEEG recordings registered before six hours of age. METHODS: Raw EEG recordings were reevaluated retrospectively with Fourier analysis to identify and describe the frequency patterns of the raw EEG signal, in cases with inconsistent aEEG recordings and clinical symptoms. Power spectral density curves, power (P) and median frequency (MF) were determined using the raw EEG. In 7 patients non-depolarizing muscle relaxant (NDMR) exposure was found. The EEG sections were analyzed and compared before and after NDMR administration. RESULTS: The reevaluation found that the aEEG was truly normal in 4 neonates. In 3 neonates, high voltage electrocardiographic (ECG) artifacts were found with flat trace on raw EEG. High frequency component (HFC) was found as a cause of normal appearing aEEG in 10 neonates. HFC disappeared while P and MF decreased significantly upon NDMR administration in each observed case. CONCLUSION: Occurrence of false normal aEEG background pattern is relatively high in neonates with HIE and hypothermia. High frequency EEG artifacts suggestive of shivering were found to be the most common cause of false normal aEEG in hypothermic neonates while high voltage ECG artifacts are less common

Role of EEG background activity, seizure burden and MRI in predicting neurodevelopmental outcome in full-term infants with hypoxic-ischaemic encephalopathy in the era of therapeutic hypothermia

OBJECTIVE: To investigate the role of EEG background activity, electrographic seizure burden, and MRI in predicting neurodevelopmental outcome in infants with hypoxic-ischaemic encephalopathy (HIE) in the era of therapeutic hypothermia. METHODS: Twenty-six full-term infants with HIE (September 2011-September 2012), who had video-EEG monitoring during the first 72 h, an MRI performed within the first two weeks and neurodevelopmental assessment at two years were evaluated. EEG background activity at age 24, 36 and 48 h, seizure burden, and severity of brain injury on MRI, were compared and related to neurodevelopmental outcome. RESULTS: EEG background activity was significantly associated with neurodevelopmental outcome at 36 h (p = 0.009) and 48 h after birth (p = 0.029) and with severity of brain injury on MRI at 36 h (p = 0.002) and 48 h (p = 0.018). All infants with a high seizure burden and moderate-severe injury on MRI had an abnormal outcome. The positive predictive value (PPV) of EEG for abnormal outcome was 100% at 36 h and 48 h and the negative predictive value (NPV) was 75% at 36 h and 69% at 48 h. The PPV of MRI was 100% and the NPV 85%. The PPV of seizure burden was 78% and the NPV 71%. CONCLUSION: Severely abnormal EEG background activity at 36 h and 48 h after birth was associated with severe injury on MRI and abnormal neurodevelopmental outcome. High seizure burden was only associated with abnormal outcome in combination with moderate-severe injury on MRI

Characterisation of neonatal seizures and their treatment using continuous EEG monitoring: a multicentre experience.

OBJECTIVE: The aim of this multicentre study was to describe detailed characteristics of electrographic seizures in a cohort of neonates monitored with multichannel continuous electroencephalography (cEEG) in 6 European centres. METHODS: Neonates of at least 36 weeks of gestation who required cEEG monitoring for clinical concerns were eligible, and were enrolled prospectively over 2 years from June 2013. Additional retrospective data were available from two centres for January 2011 to February 2014. Clinical data and EEGs were reviewed by expert neurophysiologists through a central server. RESULTS: Of 214 neonates who had recordings suitable for analysis, EEG seizures were confirmed in 75 (35%). The most common cause was hypoxic-ischaemic encephalopathy (44/75, 59%), followed by metabolic/genetic disorders (16/75, 21%) and stroke (10/75, 13%). The median number of seizures was 24 (IQR 9-51), and the median maximum hourly seizure burden in minutes per hour (MSB) was 21 min (IQR 11-32), with 21 (28%) having status epilepticus defined as MSB>30 min/hour. MSB developed later in neonates with a metabolic/genetic disorder. Over half (112/214, 52%) of the neonates were given at least one antiepileptic drug (AED) and both overtreatment and undertreatment was evident. When EEG monitoring was ongoing, 27 neonates (19%) with no electrographic seizures received AEDs. Fourteen neonates (19%) who did have electrographic seizures during cEEG monitoring did not receive an AED. CONCLUSIONS: Our results show that even with access to cEEG monitoring, neonatal seizures are frequent, difficult to recognise and difficult to treat. OBERSERVATION STUDY NUMBER: NCT02160171

Near-infrared spectroscopy as a predictor of clinical deterioration: a case report of two infants with duct-dependent congenital heart disease

Background: Some infants with congenital heart disease are at risk of in-hospital cardiac arrest. To better foresee cardiac arrest in infants with congenital heart disease, it might be useful to continuously assess end-organ perfusion. Near-infrared spectroscopy is a non-invasive method to continuously assess multisite regional tissue oxygen saturation. Case presentation: We report on two infants with duct-dependent congenital heart disease who demonstrated a gradual change in cerebral and/or renal tissue oxygen saturation before cardiopulmonary resuscitation was required. In both cases, other clinical parameters such as heart rate, arterial oxygen saturation and blood pressure did not indicate that deterioration was imminent. Conclusions: These two cases demonstrate that near-infrared spectroscopy might contribute to detecting a deteriorating clinical condition and might therefore be helpful in averting cardiopulmonary collapse and need for resuscitation in infants with congenital heart disease

Neonatal seizures in a rural Kenyan District Hospital: aetiology, Incidence and outcome of hospitalization

<p>Abstract</p> <p>Background</p> <p>Acute seizures are common among children admitted to hospitals in resource poor countries. However, there is little data on the burden, causes and outcome of neonatal seizures in sub-Saharan Africa. We determined the minimum incidence, aetiology and immediate outcome of seizures among neonates admitted to a rural district hospital in Kenya.</p> <p>Methods</p> <p>From 1^stJanuary 2003 to 31^stDecember 2007, we assessed for seizures all neonates (age 0-28 days) admitted to the Kilifi District Hospital, who were resident in a defined, regularly enumerated study area. The population denominator, the number of live births in the community on 1 July 2005 (the study midpoint) was modelled from the census data.</p> <p>Results</p> <p>Seizures were reported in 142/1572 (9.0%) of neonatal admissions. The incidence was 39.5 [95% confidence interval (CI) 26.4-56.7] per 1000 live-births and incidence increased with birth weight. The main diagnoses in neonates with seizures were sepsis in 85 (60%), neonatal encephalopathy in 30 (21%) and meningitis in 21 (15%), but only neonatal encephalopathy and bacterial meningitis were independently associated with seizures. Neonates with seizures had a longer hospitalization [median period 7 days - interquartile range (IQR) 4 to10] -compared to 5 days [IQR 3 to 8] for those without seizures, <it>P </it>= 0.02). Overall, there was no difference in inpatient case fatality between neonates with and without seizures but, when this outcome was stratified by birth weight, it was significantly higher in neonates ≥ 2.5 kg compared to low birth weight neonates [odds ratio 1.59 (95%CI 1.02 to 2.46), <it>P </it>= 0.037]. Up to 13% of the surviving newborn with seizures had neurological abnormalities at discharge.</p> <p>Conclusion</p> <p>There is a high incidence of neonatal seizures in this area of Kenya and the most important causes are neonatal encephalopathy and meningitis. The high incidence of neonatal seizures may be a reflection of the quality of the perinatal and postnatal care available to the neonates.</p

Seizures in 204 comatose children: incidence and outcome

Purpose: Seizures are common in comatose children, but may be clinically subtle or only manifest on continuous electroencephalographic monitoring (cEEG); any association with outcome remains uncertain. Methods: cEEG (one to three channels) was performed for a median 42 h (range 2–630 h) in 204 unventilated and ventilated children aged $\leq$ 15 years (18 neonates, 61 infants) in coma with different aetiologies. Outcome at 1 month was independently determined and dichotomized for survivors into favourable (normal or moderate neurological handicap) and unfavourable (severe handicap or vegetative state). Results: Of the 204 patients, 110 had clinical seizures (CS) before cEEG commenced. During cEEG, 74 patients (36 %, 95 % confidence interval, 95 % CI, 32–41 %) had electroencephalographic seizures (ES), the majority without clinical accompaniment (non-convulsive seizures, NCS). CS occurred before NCS in 69 of the 204 patients; 5 ventilated with NCS had no CS observed. Death (93/204; 46 %) was independently predicted by admission Paediatric Index of Mortality (PIM; adjusted odds ratio, aOR, 1.027, 95 % CI 1.012–1.042; p 3 % fast, aOR 5.43, 95 % CI 1.90–15.6; excess slow with <3 % fast, aOR 8.71, 95 % CI 2.58–29.4; low amplitude, 10th centile <9 $\mu$V, aOR 3.78, 95 % CI 1.23–11.7; and burst suppression, aOR 10.68, 95 % CI 2.31–49.4) compared with normal cEEG, as well as absence of CS at any time (aOR 2.38, 95 % CI 1.18–4.81). Unfavourable outcome (29/111 survivors; 26 %) was independently predicted by the presence of ES (aOR 15.4, 95 % CI 4.7–49.7) and PIM (aOR 1.036, 95 % CI 1.013–1.059). Conclusion: Seizures are common in comatose children, and are associated with an unfavourable outcome in survivors. cEEG allows the detection of subtle CS and NCS and is a prognostic tool

Phosphorylation of GFAP is associated with injury in the neonatal pig hypoxic-ischemic brain

Glial fibrillary acidic protein (GFAP) is an intermediate filament protein expressed in the astrocyte cytoskeleton that plays an important role in the structure and function of the cell. GFAP can be phosphorylated at six serine (Ser) or threonine (Thr) residues but little is known about the role of GFAP phosphorylation in physiological and pathophysiological states. We have generated antibodies against two phosphorylated GFAP (pGFAP) proteins: p8GFAP, where GFAP is phosphorylated at Ser-8 and p13GFAP, where GFAP is phosphorylated at Ser-13. We examined p8GFAP and p13GFAP expression in the control neonatal pig brain and at 24 and 72 h after an hypoxic-ischemic (HI) insult. Immunohistochemistry demonstrated pGFAP expression in astrocytes with an atypical cytoskeletal morphology, even in control brains. Semi-quantitative western blotting revealed that p8GFAP expression was significantly increased at 24 h post-insult in HI animals with seizures in frontal, parietal, temporal and occipital cortices. At 72 h post-insult, p8GFAP and p13GFAP expression were significantly increased in HI animals with seizures in brain regions that are vulnerable to cellular damage (cortex and basal ganglia), but no changes were observed in brain regions that are relatively spared following an HI insult (brain stem and cerebellum). Increased pGFAP expression was associated with poor neurological outcomes such as abnormal encephalography and neurobehaviour, and increased histological brain damage. Phosphorylation of GFAP may play an important role in astrocyte remodelling during development and disease and could potentially contribute to the plasticity of the central nervous system

Reducing Crowding by Weakening Inhibitory Lateral Interactions in the Periphery with Perceptual Learning

We investigated whether lateral masking in the near-periphery, due to inhibitory lateral interactions at an early level of central visual processing, could be weakened by perceptual learning and whether learning transferred to an untrained, higher-level lateral masking known as crowding. The trained task was contrast detection of a Gabor target presented in the near periphery (4°) in the presence of co-oriented and co-aligned high contrast Gabor flankers, which featured different target-to-flankers separations along the vertical axis that varied from 2λ to 8λ. We found both suppressive and facilitatory lateral interactions at target-to-flankers distances (2λ - 4λ and 8λ, respectively) that were larger than those found in the fovea. Training reduces suppression but does not increase facilitation. Most importantly, we found that learning reduces crowding and improves contrast sensitivity, but has no effect on visual acuity (VA). These results suggest a different pattern of connectivity in the periphery with respect to the fovea as well as a different modulation of this connectivity via perceptual learning that not only reduces low-level lateral masking but also reduces crowding. These results have important implications for the rehabilitation of low-vision patients who must use peripheral vision to perform tasks, such as reading and refined figure-ground segmentation, which normal sighted subjects perform in the fovea

The TOBY Study. Whole body hypothermia for the treatment of perinatal asphyxial encephalopathy: A randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>A hypoxic-ischaemic insult occurring around the time of birth may result in an encephalopathic state characterised by the need for resuscitation at birth, neurological depression, seizures and electroencephalographic abnormalities. There is an increasing risk of death or neurodevelopmental abnormalities with more severe encephalopathy. Current management consists of maintaining physiological parameters within the normal range and treating seizures with anticonvulsants.</p> <p>Studies in adult and newborn animals have shown that a reduction of body temperature of 3–4°C after cerebral insults is associated with improved histological and behavioural outcome. Pilot studies in infants with encephalopathy of head cooling combined with mild whole body hypothermia and of moderate whole body cooling to 33.5°C have been reported. No complications were noted but the group sizes were too small to evaluate benefit.</p> <p>Methods/Design</p> <p>TOBY is a multi-centre, prospective, randomised study of term infants after perinatal asphyxia comparing those allocated to "intensive care plus total body cooling for 72 hours" with those allocated to "intensive care without cooling".</p> <p>Full-term infants will be randomised within 6 hours of birth to either a control group with the rectal temperature kept at 37 +/- 0.2°C or to whole body cooling, with rectal temperature kept at 33–34°C for 72 hours. Term infants showing signs of moderate or severe encephalopathy +/- seizures have their eligibility confirmed by cerebral function monitoring. Outcomes will be assessed at 18 months of age using neurological and neurodevelopmental testing methods.</p> <p>Sample size</p> <p>At least 236 infants would be needed to demonstrate a 30% reduction in the relative risk of mortality or serious disability at 18 months.</p> <p>Recruitment was ahead of target by seven months and approvals were obtained allowing recruitment to continue to the end of the planned recruitment phase. 325 infants were recruited.</p> <p>Primary outcome</p> <p>Combined rate of mortality and severe neurodevelopmental impairment in survivors at 18 months of age. Neurodevelopmental impairment will be defined as any of:</p> <p>• Bayley mental developmental scale score less than 70</p> <p>• Gross Motor Function Classification System Levels III – V</p> <p>• Bilateral cortical visual impairments</p> <p>Trial Registration</p> <p>Current Controlled Trials ISRCTN89547571</p