ObjectiveTo assess the predictive value of a novel magnetic resonance imaging (MRI) score, which includes diffusion-weighted imaging as well as assessment of the deep grey matter, white matter, and cerebellum, for neurodevelopmental outcome at 2 years and school age among term infants with hypoxic-ischemic encephalopathy treated with therapeutic hypothermia.Study designThis retrospective cohort study (cohort 1, The Netherlands 2008-2014; cohort 2, Sweden 2007-2012) including infants born at >36 weeks of gestational age treated with therapeutic hypothermia who had an MRI in the first weeks of life. The MRI score consisted of 3 subscores: deep grey matter, white matter/cortex, and cerebellum. Primary adverse outcome was defined as death, cerebral palsy, Bayley Scales of Infant and Toddler Development, third edition, motor or cognitive composite scores at 2 years of <85, or IQ at school age of <85.ResultsIn cohort 1 (n = 97) and cohort 2 (n = 76) the grey matter subscore was an independent predictor of adverse outcome at 2 years (cohort 1, OR, 1.6; 95% CI, 1.3-1.9; cohort 2, OR, 1.4; 95% CI, 1.2-1.6), and school age (cohort 1, OR, 1.3; 95% CI, 1.2-1.5; cohort 2, OR, 1.3; 95% CI, 1.1-1.6). The white matter and cerebellum subscore did not add to the predictive value. The positive predictive value, negative predictive value, and area under the curve for the grey matter subscore were all >0.83 in both cohorts, whereas the specificity was >0.91 with variable sensitivity.ConclusionA novel MRI score, which includes diffusion-weighted imaging and assesses all brain areas of importance in infants with therapeutic hypothermia after perinatal asphyxia, has predictive value for outcome at 2 years of age and at school age, for which the grey matter subscore can be used independently.

Background Despite the availability of continuous conventional electroencephalography (cEEG), accurate diagnosis of neonatal seizures is challenging in clinical practice. Algorithms for decision support in the recognition of neonatal seizures could improve detection. We aimed to assess the diagnostic accuracy of an automated seizure detection algorithm called Algorithm for Neonatal Seizure Recognition (ANSeR). Methods This multicentre, randomised, two-arm, parallel, controlled trial was done in eight neonatal centres across Ireland, the Netherlands, Sweden, and the UK. Neonates with a corrected gestational age between 36 and 44 weeks with, or at significant risk of, seizures requiring EEG monitoring, received cEEG plus ANSeR linked to the EEG monitor displaying a seizure probability trend in real time (algorithm group) or cEEG monitoring alone (nonalgorithm group). The primary outcome was diagnostic accuracy (sensitivity, specificity, and false detection rate) of health-care professionals to identify neonates with electrographic seizures and seizure hours with and without the support of the ANSeR algorithm. Neonates with data on the outcome of interest were included in the analysis. This study is registered with ClinicalTrials.gov, NCT02431780. Findings Between Feb 13, 2015, and Feb 7, 2017, 132 neonates were randomly assigned to the algorithm group and 132 to the non-algorithm group. Six neonates were excluded (four from the algorithm group and two from the non-algorithm group). Electrographic seizures were present in 32 (25•0%) of 128 neonates in the algorithm group and 38 (29•2%) of 130 neonates in the non-algorithm group. For recognition of neonates with electrographic seizures, sensitivity was 81•3% (95% CI 66•7-93•3) in the algorithm group and 89•5% (78•4-97•5) in the non-algorithm group; specificity was 84•4% (95% CI 76•9-91•0) in the algorithm group and 89•1% (82•5-94•7) in the non-algorithm group; and the false detection rate was 36•6% (95% CI 22•7-52•1) in the algorithm group and 22•7% (11•6-35•9) in the non-algorithm group. We identified 659 h in which seizures occurred (seizure hours): 268 h in the algorithm versus 391 h in the nonalgorithm group. The percentage of seizure hours correctly identified was higher in the algorithm group than in the non-algorithm group (177 [66•0%; 95% CI 53•8-77•3] of 268 h vs 177 [45•3%; 34•5-58•3] of 391 h; difference 20•8% [3•6-37•1]). No significant differences were seen in the percentage of neonates with seizures given at least one inappropriate antiseizure medication (37•5% [95% CI 25•0 to 56•3] vs 31•6% [21•1 to 47•4]; difference 5•9% [-14•0 to 26•3]). Interpretation ANSeR, a machine-learning algorithm, is safe and able to accurately detect neonatal seizures. Although the algorithm did not enhance identification of individual neonates with seizures beyond conventional EEG, recognition of seizure hours was improved with use of ANSeR. The benefit might be greater in less experienced centres, but further study is required.

ObjectiveThe 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.MethodsNeonates 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.ResultsOf 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.ConclusionsOur results show that even with access to cEEG monitoring, neonatal seizures are frequent, difficult to recognise and difficult to treat.Oberservation study numberNCT02160171

During and after therapeutic hypothermia, low ADC values and high Lac/NAA ratios of the basal ganglia and thalamus are associated with an adverse outcome in infants with perinatal asphyxia.

Background: Recurrent and prolonged seizures are harmful for the developing brain, emphasizing the importance of early seizure recognition and effective therapy. Amplitude-integrated electroencephalography (aEEG) has become a valuable tool to diagnose epileptic seizures, and, in parallel, genetic etiologies are increasingly being recognized, changing the paradigmof the workup and management of neonatal seizures. Objective: To report the ictal aEEG pattern in neonates with KCNQ2-related epilepsy. Subjects and Methods: In this multicenter descriptive study, clinical data and aEEG findings of 9 newborns with KCNQ2 mutations are reported. Results: Refractory seizures occurred in the early neonatal period with similar seizure type, including tonic features, apnea, and desaturation. A distinct aEEG seizure pattern, consisting of a sudden rise of the lower and upper margin of the aEEG, followed by a marked depression of the aEEG amplitude, was found in 8 of the 9 patients. Prompt recognition of this pattern led to early treatment with carbamazepine in the 2 most recent cases. Conclusion: Early recognition of the electroclinical phenotype by using aEEG may direct genetic testing and a precision medicine approach with sodium channel blockers in neonates with KCNQ2 mutations.

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.

No abstract

SUMMARYObjective: To investigate the seizure response rate to lidocaine in a large cohort of infants who received lidocaine as second-or third-line antiepileptic drug (AED) for neonatal seizures. Methods: Full-term (n = 319) and preterm (n = 94) infants, who received lidocaine for neonatal seizures confirmed on amplitude-integrated EEG (aEEG), were studied retrospectively (January 1992-December 2012). Based on aEEG findings, the response was defined as good (>4 h no seizures, no need for rescue medication); intermediate (0-2 h no seizures, but rescue medication needed after 2-4 h); or no clear response (rescue medication needed <2 h). Results: Lidocaine had a good or intermediate effect in 71.4%. The response rate was significantly lower in preterm (55.3%) than in full-term infants (76.1%, p < 0.001). In full-term infants the response to lidocaine was significantly better than midazolam as second-line AED (21.4% vs. 12.7%, p = 0.049), and there was a trend for a higher response rate as third-line AED (67.6% vs. 57%, p = 0.086). Both lidocaine and midazolam had a higher response rate as third-line AED than as second-line AED (p < 0.001). Factors associated with a good response to lidocaine were the following: higher gestational age, longer time between start of first seizure and administration of lidocaine, lidocaine as third-line AED, use of new lidocaine regimens, diagnosis of stroke, use of digital aEEG, and hypothermia. Multivariable analysis of seizure response to lidocaine included lidocaine as second-or third-line AED and seizure etiology. Significance: Seizure response to lidocaine was seen in~70%. The response rate was influenced by gestational age, underlying etiology, and timing of administration. Lidocaine had a significantly higher response rate than midazolam as second-line AED, and there was a trend for a higher response rate as third-line AED. Both lidocaine and midazolam had a higher response rate as third-line compared to second-line AED, which could be due to a pharmacologic synergistic mechanism between the two drugs.