Phenobarbital reduces EEG amplitude and propagation of neonatal seizures but does not alter performance of automated seizure detection.

OBJECTIVE: Phenobarbital increases electroclinical uncoupling and our preliminary observations suggest it may also affect electrographic seizure morphology. This may alter the performance of a novel seizure detection algorithm (SDA) developed by our group. The objectives of this study were to compare the morphology of seizures before and after phenobarbital administration in neonates and to determine the effect of any changes on automated seizure detection rates. METHODS: The EEGs of 18 term neonates with seizures both pre- and post-phenobarbital (524 seizures) administration were studied. Ten features of seizures were manually quantified and summary measures for each neonate were statistically compared between pre- and post-phenobarbital seizures. SDA seizure detection rates were also compared. RESULTS: Post-phenobarbital seizures showed significantly lower amplitude (p<0.001) and involved fewer EEG channels at the peak of seizure (p<0.05). No other features or SDA detection rates showed a statistical difference. CONCLUSION: These findings show that phenobarbital reduces both the amplitude and propagation of seizures which may help to explain electroclinical uncoupling of seizures. The seizure detection rate of the algorithm was unaffected by these changes. SIGNIFICANCE: The results suggest that users should not need to adjust the SDA sensitivity threshold after phenobarbital administration.

Short-Term Effects of Phenobarbitone on Electrographic Seizures in Neonates.

BACKGROUND: Phenobarbitone is the most common first-line anti-seizure drug and is effective in approximately 50% of all neonatal seizures. OBJECTIVE: To describe the response of electrographic seizures to the administration of intravenous phenobarbitone in neonates using seizure burden analysis techniques. METHODS: Multi-channel conventional EEG, reviewed by experts, was used to determine the electrographic seizure burden in hourly epochs. The maximum seizure burden evaluated 1 h before each phenobarbitone dose (T-1) was compared to seizure burden in periods of increasing duration after each phenobarbitone dose had been administered (T+1, T+2 to seizure offset). Differences were analysed using linear mixed models and summarized as means and 95% CI. RESULTS: Nineteen neonates had electrographic seizures and met the inclusion criteria for the study. Thirty-one doses were studied. The maximum seizure burden was significantly reduced 1 h after the administration of phenobarbitone (T+1) [-14.0 min/h (95% CI: -19.6, -8.5); p < 0.001]. The percentage reduction was 74% (IQR: 36-100). This reduction was temporary and not significant within 4 h of administrating phenobarbitone. Subgroup analysis showed that only phenobarbitone doses at 20 mg/kg resulted in a significant reduction in the maximum seizure burden from T-1 to T+1 (p = 0.002). CONCLUSIONS: Phenobarbitone significantly reduced seizures within 1 h of administration as assessed with continuous multi-channel EEG monitoring in neonates. The reduction was not permanent and seizures were likely to return within 4 h of treatment.

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 0.04-0.36FD/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.

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.

EEG suppression associated with apneic episodes in a neonate.

We describe the EEG findings from an ex-preterm neonate at term equivalent age who presented with intermittent but prolonged apneic episodes which were presumed to be seizures. A total of 8 apneic episodes were captured (duration 23-376 seconds) during EEG monitoring. The baseline EEG activity was appropriate for corrected gestational age and no electrographic seizure activity was recorded. The average baseline heart rate was 168 beats per minute (bpm) and the baseline oxygen saturation level was in the mid-nineties. Periods of complete EEG suppression lasting 68 and 179 seconds, respectively, were recorded during 2 of these 8 apneic episodes. Both episodes were accompanied by bradycardia less than 70 bpm and oxygen saturation levels of less than 20%. Short but severe episodes of apnea can cause complete EEG suppression in the neonate.

Cooling and seizure burden in term neonates: an observational study.

OBJECTIVE: To investigate any possible effect of cooling on seizure burden, the authors quantified the recorded electrographic seizure burden based on multichannel video-EEG recordings in term neonates with hypoxic-ischaemic encephalopathy (HIE) who received cooling and in those who did not. STUDY DESIGN: Retrospective observational study. PATIENTS: Neonates >37 weeks gestation born between 2003 and 2010 in two hospitals. METHODS: Off-line analysis of prolonged continuous multichannel video-EEG recordings was performed independently by two experienced encephalographers. Comparison between the recorded electrographic seizure burden in non-cooled and cooled neonates was assessed. Data were treated as non-parametric and expressed as medians with interquartile ranges (IQR). RESULTS: One hundred and seven neonates with HIE underwent prolonged continuous multichannel EEG monitoring. Thirty-seven neonates had electrographic seizures, of whom 31 had EEG recordings that were suitable for the analysis (16 non-cooled and 15 cooled). Compared with non-cooled neonates, multichannel EEG monitoring commenced at an earlier postnatal age in cooled neonates (6 (3-9) vs 15 (5-20) h)and continued for longer (88 (75-101) vs 55 (41-60) h). Despite this increased opportunity to capture seizures in cooled neonates, the recorded electrographic seizure burden in the cooled group was significantly lower than in the non-cooled group (60 (39-224) vs 203 (141-406) min). Further exploratory analysis showed that the recorded electrographic seizure burden was only significantly reduced in cooled neonates with moderate HIE (49 (26-89) vs 162 (97-262) min). CONCLUSIONS: A decreased seizure burden was seen in neonates with moderate HIE who received cooling. This finding may explain some of the therapeutic benefits of cooling seen in term neonates with moderate HIE.

Early continuous video electroencephalography in neonatal stroke.

Perinatal stroke is the second most common cause of neonatal seizures, and can result in long-term neurological impairment. Diagnosis is often delayed until after seizure onset, owing to the subtle nature of associated signs. We report the early electroencephalographic (EEG) findings in a female infant with a perinatal infarction, born at 41 weeks 2 days and weighing 3.42 kg. Before the onset of seizures, the EEG from 3 hours after delivery demonstrated occasional focal sharp waves over the affected region. After electroclinical seizures, focal sharp waves became more frequent, complex, and of higher amplitude, particularly in 'quiet sleep'. In 'active sleep', sharp waves often disappeared. Diffusion-weighted imaging confirmed the infarct, demonstrating left frontal and parietal diffusion restriction. At 9 months, the infant has had no further seizures, and neurological examination is normal. To our knowledge, this report is the first to describe the EEG findings in perinatal stroke before seizures, and highlights the evolution of characteristic background EEG features.

Reversible multiorgan system involvement in a neonate with complex IV deficiency.

Mitochondrial respiratory chain deficiencies can present as fulminant liver failure or disease, and the prognosis when associated with severe neonatal lactic acidosis is frequently guarded. We report the case of a neonate who presented with acute liver failure and fulminant lactic acidosis with profound complex IV deficiency documented in muscle and liver biopsies. The neonate subsequently experienced clinical resolution by 3 months of age, and was observed to have reversibility of the biochemical deficiency noted in muscle. This case illustrates that resolution of this severe neonatal phenotype does occur, of importance for accurate prognostic and genetic counseling for such affected neonates.