Toward a personalized real-time diagnosis in neonatal seizure detection

The problem of creating a personalized seizure detection algorithm for newborns is tackled in this paper. A probabilistic framework for semi-supervised adaptation of a generic patient-independent neonatal seizure detector is proposed. A system that is based on a combination of patient-adaptive (generative) and patient-independent (discriminative) classifiers is designed and evaluated on a large database of unedited continuous multichannel neonatal EEG recordings of over 800 h in duration. It is shown that an improvement in the detection of neonatal seizures over the course of long EEG recordings is achievable with on-the-fly incorporation of patient-specific EEG characteristics. In the clinical setting, the employment of the developed system will maintain a seizure detection rate at 70% while halving the number of false detections per hour, from 0.4 to 0.2 FD/h. This is the first study to propose the use of online adaptation without clinical labels, to build a personalized diagnostic system for the detection of neonatal seizures

Neonatal EEG graded for severity of background abnormalities in hypoxic-ischaemic encephalopathy

This report describes a set of neonatal electroencephalogram (EEG) recordings graded according to the severity of abnormalities in the background pattern. The dataset consists of 169 hours of multichannel EEG from 53 neonates recorded in a neonatal intensive care unit. All neonates received a diagnosis of hypoxic-ischaemic encephalopathy (HIE), the most common cause of brain injury in full term infants. For each neonate, multiple 1-hour epochs of good quality EEG were selected and then graded for background abnormalities. The grading system assesses EEG attributes such as amplitude and frequency, continuity, sleep--wake cycling, symmetry and synchrony, and abnormal waveforms. Background severity was then categorised into 4 grades: normal or mildly abnormal EEG, moderately abnormal EEG, severely abnormal EEG, and inactive EEG. The data can be used as a reference set of multi-channel EEG for neonates with HIE, for EEG training purposes, or for developing and evaluating automated grading algorithms

Early postnatal EEG features of perinatal arterial ischaemic stroke with seizures

Background: Stroke is the second most common cause of seizures in term neonates and is associated with abnormal long-term neurodevelopmental outcome in some cases. Objective: To aid diagnosis earlier in the postnatal period, our aim was to describe the characteristic EEG patterns in term neonates with perinatal arterial ischaemic stroke (PAIS) seizures. Design: Retrospective observational study. Patients: Neonates >37 weeks born between 2003 and 2011 in two hospitals. Method: Continuous multichannel video-EEG was used to analyze the background patterns and characteristics of seizures. Each EEG was assessed for continuity, symmetry, characteristic features and sleep cycling; morphology of electrographic seizures was also examined. Each seizure was categorized as electrographic-only or electroclinical; the percentage of seizure events for each seizure type was also summarized. Results: Nine neonates with PAIS seizures and EEG monitoring were identified. While EEG continuity was present in all cases, the background pattern showed suppression over the infarcted side; this was quite marked (>50% amplitude reduction) when the lesion was large. Characteristic unilateral bursts of theta activity with sharp or spike waves intermixed were seen in all cases. Sleep cycling was generally present but was more disturbed over the infarcted side. Seizures demonstrated a characteristic pattern; focal sharp waves/spike-polyspikes were seen at frequency of 1-2 Hz and phase reversal over the central region was common. Electrographic-only seizure events were more frequent compared to electroclinical seizure events (78 vs 22%). Conclusions: Focal electrographic and electroclinical seizures with ipsilateral suppression of the background activity and focal sharp waves are strong indicators of PAIS. Approximately 80% of seizure events were the result of clinically unsuspected seizures in neonates with PAIS. Prolonged and continuous multichannel video-EEG monitoring is advocated for adequate seizure surveillance

Parent-led massage and sleep EEG for term-born infants: A randomized controlled parallel-group study

AIM: To examine the impact of parent-led massage on the sleep electroencephalogram (EEG) features of typically developing term-born infants at 4 months. METHOD: Infants recruited at birth were randomized to intervention (routine parent-led massage) and control groups. Infants had a daytime sleep EEG at 4 months and were assessed using the Griffiths Scales of Child Development, Third Edition at 4 and 18 months. Comparative analysis between groups and subgroup analysis between regularly massaged and never-massaged infants were performed. Groups were compared for sleep stage, sleep spindles, quantitative EEG (primary analysis), and Griffiths using the Mann-Whitney U test. RESULTS: In total, 179 out of 182 infants (intervention: 83 out of 84; control: 96 out of 98) had a normal sleep EEG. Median (interquartile range) sleep duration was 49.8 minutes (39.1-71.4) (n = 156). A complete first sleep cycle was seen in 67 out of 83 (81%) and 72 out of 96 (75%) in the intervention and control groups respectively. Groups did not differ in sleep stage durations, latencies to sleep and to rapid eye movement sleep. Sleep spindle spectral power was greater in the intervention group in main and subgroup analyses. The intervention group showed greater EEG magnitudes, and lower interhemispherical coherence on subgroup analyses. Griffiths assessments at 4 months (n = 179) and 18 months (n = 173) showed no group differences in the main and subgroup analyses. INTERPRETATION: Routine massage is associated with distinct functional brain changes at 4 months

In-depth performance analysis of an EEG based neonatal seizure detection algorithm

Objective: To describe a novel neurophysiology based performance analysis of automated seizure detection algorithms for neonatal EEG to characterize features of detected and non-detected seizures and causes of false detections to identify areas for algorithmic improvement. Methods: EEGs of 20 term neonates were recorded (10 seizure, 10 non-seizure). Seizures were annotated by an expert and characterized using a novel set of 10 criteria. ANSeR seizure detection algorithm (SDA) seizure annotations were compared to the expert to derive detected and non-detected seizures at three SDA sensitivity thresholds. Differences in seizure characteristics between groups were compared using univariate and multivariate analysis. False detections were characterized. Results: The expert detected 421 seizures. The SDA at thresholds 0.4, 0.5, 0.6 detected 60%, 54% and 45% of seizures. At all thresholds, multivariate analyses demonstrated that the odds of detecting seizure increased with 4 criteria: seizure amplitude, duration, rhythmicity and number of EEG channels involved at seizure peak. Major causes of false detections included respiration and sweat artefacts or a highly rhythmic background, often during intermediate sleep. Conclusion: This rigorous analysis allows estimation of how key seizure features are exploited by SDAs. Significance: This study resulted in a beta version of ANSeR with significantly improved performance

Neurodevelopmental outcome of low-risk moderate to late preterm infants at 18 months

BackgroundOf the 15 million preterm births that occur worldwide each year, approximately 80% occur between 32 and 36 + 6 weeks gestational age (GA) and are defined as moderate to late preterm (MLP) infants. This percentage substantiates a need for a better understanding of the neurodevelopmental outcome of this groupAimTo describe neurodevelopmental outcome at 18 months in a cohort of healthy low-risk MLP infants admitted to the neonatal unit at birth and to compare the neurodevelopmental outcome to that of a healthy term-born infant group.Study design and methodThis single-centre observational study compared the neurodevelopmental outcome of healthy MLP infants to a group of healthy term control (TC) infants recruited during the same period using the Griffith's III assessment at 18 months.ResultsSeventy-five MLP infants and 92 TC infants were included. MLP infants scored significantly lower in the subscales: Eye-hand coordination (C), Personal, Social and Emotional Development (D), Gross Motor Development (E) and General Developmental (GD) (p < 0.001 for each) and Foundations of Learning (A), (p = 0.004) in comparison to the TC infant group with Cohen's d effect sizes ranging from 0.460 to 0.665. There was no statistically significant difference in mean scores achieved in subscale B: Language and Communication between groups (p = 0.107).ConclusionMLP infants are at risk of suboptimal neurodevelopmental outcomes. Greater surveillance of the neurodevelopmental trajectory of this group of at-risk preterm infants is required

Electroencephalographic sleep macrostructure and sleep spindles in early infancy

Study Objectives: Sleep features in infancy are potential biomarkers for brain maturation but poorly characterized. We describe normative values for sleep macrostructure and sleep spindles at 4–5 months of age. Methods: Healthy term infants were recruited at birth and had daytime sleep electroencephalograms (EEGs) at 4–5 months. Sleep staging was performed and five features were analyzed. Sleep spindles were annotated and seven quantitative features were extracted. Features were analyzed across sex, recording time (am/pm), infant age, and from first to second sleep cycles. Results: We analyzed sleep recordings from 91 infants, 41% females. Median (interquartile range [IQR]) macrostructure results: sleep duration 49.0 (37.8–72.0) min (n = 77); first sleep cycle duration 42.8 (37.0–51.4) min; rapid eye movement (REM) percentage 17.4 (9.5–27.7)% (n = 68); latency to REM 36.0 (30.5–41.1) min (n = 66). First cycle median (IQR) values for spindle features: number 241.0 (193.0–286.5), density 6.6 (5.7–8.0) spindles/min (n = 77); mean frequency 13.0 (12.8–13.3) Hz, mean duration 2.9 (2.6–3.6) s, spectral power 7.8 (4.7–11.4) µV2, brain symmetry index 0.20 (0.16–0.29), synchrony 59.5 (53.2–63.8)% (n = 91). In males, spindle spectral power (µV2) was 24.5% lower (p = .032) and brain symmetry index 24.2% higher than females (p = .011) when controlling for gestational and postnatal age and timing of the nap. We found no other significant associations between studied sleep features and sex, recording time (am/pm), or age. Spectral power decreased (p < .001) on the second cycle. Conclusion: This normative data may be useful for comparison with future studies of sleep dysfunction and atypical neurodevelopment in infancy. Clinical Trial Registration: BABY SMART (Study of Massage Therapy, Sleep And neurodevelopMenT) (BabySMART). URL: https://clinicaltrials.gov/ct2/show/results/NCT03381027?view=results. ClinicalTrials.gov Identifier: NCT0338102

Validation of an automated seizure detection algorithm for term neonates

Objective: The objective of this study was to validate the performance of a seizure detection algorithm (SDA) developed by our group, on previously unseen, prolonged, unedited EEG recordings from 70 babies from 2 centres. Methods: EEGs of 70 babies (35 seizure, 35 non-seizure) were annotated for seizures by experts as the gold standard. The SDA was tested on the EEGs at a range of sensitivity settings. Annotations from the expert and SDA were compared using event and epoch based metrics. The effect of seizure duration on SDA performance was also analysed. Results: Between sensitivity settings of 0.5 and 0.3, the algorithm achieved seizure detection rates of 52.6–75.0%, with false detection (FD) rates of 0.04–0.36 FD/h for event based analysis, which was deemed to be acceptable in a clinical environment. Time based comparison of expert and SDA annotations using Cohen’s Kappa Index revealed a best performing SDA threshold of 0.4 (Kappa 0.630). The SDA showed improved detection performance with longer seizures. Conclusion: The SDA achieved promising performance and warrants further testing in a live clinical evaluation. Significance: The SDA has the potential to improve seizure detection and provide a robust tool for comparing treatment regimens

Neonatal Seizure Management - Is the Timing of Treatment Critical?

Objective: To assess the impact of the time to treatment of the first electrographic seizure on subsequent seizure burden and describe overall seizure management in a large neonatal cohort. Study design: Newborns (36-44 weeks of gestation) requiring electroencephalographic (EEG) monitoring recruited to 2 multicenter European studies were included. Infants who received antiseizure medication exclusively after electrographic seizure onset were grouped based on the time to treatment of the first seizure: antiseizure medication within 1 hour, between 1 and 2 hours, and after 2 hours. Outcomes measured were seizure burden, maximum seizure burden, status epilepticus, number of seizures, and antiseizure medication dose over the first 24 hours after seizure onset. Results: Out of 472 newborns recruited, 154 (32.6%) had confirmed electrographic seizures. Sixty-nine infants received antiseizure medication exclusively after the onset of electrographic seizure, including 21 infants within 1 hour of seizure onset, 15 between 1 and 2 hours after seizure onset, and 33 at >2 hours after seizure onset. Significantly lower seizure burden and fewer seizures were noted in the infants treated with antiseizure medication within 1 hour of seizure onset (P =.029 and.035, respectively). Overall, 258 of 472 infants (54.7%) received antiseizure medication during the study period, of whom 40 without electrographic seizures received treatment exclusively during EEG monitoring and 11 with electrographic seizures received no treatment. Conclusions: Treatment of neonatal seizures may be time-critical, but more research is needed to confirm this. Improvements in neonatal seizure diagnosis and treatment are also needed

A machine-learning algorithm for neonatal seizure recognition: a multicentre, randomised, controlled trial

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 (non algorithm 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 non algorithm 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