Neonatal Seizures in Amplitude Integrated EEG Mohsen Javadzadeh Child Neurologist Fellow of Pediatric Clinical Neurophysiology

Basics: aEEG vs. cEEG Amplitude integrated electroencephalography is a limited channel electroencephalography that provides a noninvasive method for continuous observation of cerebral background activity at the bedside.

Basics: aEEG vs. cEEG (2) cEEG recording in the NICU presents some difficulty because the EEG signal is of very low amplitude, especially from the most physiologically fragile neonates. The electrically noisy NICU environment easily contaminates the signal with artifact. In addition, it is challenging for the neonatologists and EEG specialists to distinguish the emerging neurodevelopmental trends from an intermittent neonatal cEEG recording.

Basics: aEEG vs. cEEG (3) The cEEG is like a snapshot of the brain function and does not provide much information about how the infant is tolerating changes and activities over the course of care. The technical complexity, time demands, intermittent availability, interpretation specialty, and costs limit its use to diagnosis and treatment as necessary in the NICU.

Basics: aEEG vs. cEEG (4) Amplitude integrated EEG, in contrast to cEEG, is a simplified method of continuous brain function monitoring (CFM) that displays trended brain activity. Benefits of this new type of EEG include: limited number of electrodes; (readily applicable & easy to operate) relatively short training required for interpretation immediate interpretation available at the bedside lower cost continuous and long term recording; and condensed recording output.

How aEEG is constructed To produce aEEG, the cerebral electrical signal received from the electrodes is Amplified, Filtered, Rectified (Aligned), and Compressed

Filtering the signal to frequencies between 2-15 Hz

Time compression is standardized to one millimeter per minute and thus 6 cm per hour

Semi-logarithmic display of amplitude The amplitude of the signal is displayed semi-logarithmically, which means that the scale of amplitudes (measured in μV) initially runs from 1-10μV in a linear manner and from 10-100μV in a logarithmic manner. The reason for this is that the amplitudes of interest for the evaluation and differences in neonates are located roughly between 0-20μV. At the same time, however, it is not uncommon for very high amplitudes to occur due to bursts or artifacts, where it is not necessary to differentiate the absolute height with the same degree of fine detail. Thus a semi-logarithmic display provides the best overview.

Visual interpretation of pattern recognition Generally, aEEG tracing is visually interpreted by pattern recognition based on three basic variables: 1. Continuity: density of traces; (the difference between the lower and upper margins of the trace‘s narrowest part). wide trace indicates discontinuous trend with increased variability), 2. Amplitude (in microvolts) of the lower (minimum) and upper (maximum) border of the band. 3. Cycling (rhythmic periodic widening and narrowing of the trace),

The 5 things we get from aEEGs In general, the tracings present: Continuous and discontinuous brain background activity, Sleep and wake cycles, Amplitudes of the upper and lower margins of the tracing, Variability, and Seizure discharges.

aEEG classification The background pattern was originally classified (only according to voltage amplitude) as: Normal (upper band >10 mV and lower band >5 mV), Moderately abnormal (upper band >10 mV and lower band <5 mV), or Suppressed (Severely abnormal) (upper band <10 mV and lower band <5 mV). Interobserver agreement was excellent for voltage amplitude and the use of this scheme accurately predicted neurodevelopmental outcome at 18 to 24 months.

Pitfalls in Interpretation of Voltage Other than seizures, background voltage may be elevated in: ECG artifact, handling, muscle activity, high-frequency ventilation, status epilepticus, gasp artifact and movement artefacts associated with head bobbing due to breathing. Possible causes for depression of the background voltage are: severe scalp edema, sedation, and antiepileptics

aEEG classification (2) Others used pattern recognition as well as voltage criteria to describe aEEG patterns. This method uses cEEG terminology (for example, burst suppression, isoelectric tracing, trace alternant). The background pattern is continuous, discontinuous, burst suppression, continuous low voltage or flat/ isoelectric. and specific voltage criteria are used as well.

Continuous Normal Voltage (CNV) pattern (seen in full-term infants) Continuous activity with lower amplitude around 5 (7-10) μV, and maximum amplitudes 10-25(-50) μV

Discontinuous Pattern (DC) Minimum amplitude variable, but mainly below 5 μV, and maximum amplitudes over 10 μV

Flat Trace Pattern (Continuous low voltage) (CLV) continuous activity of very low amplitude (around or below 5 μV))

Burst suppression (BS) Minimum amplitude without variability at 0-1 (2) μV, and bursts with amplitude 25 μV. – BS+ denotes a BS background with dense burst ≥100 bursts/h – BS- defines a BS background with sparse bursts, 100 bursts/h

Normal aEEG features in Newborns at Different Postconceptional Ages Sleep-wake cycling: SWC (+)=imminent/immature; SWC +=developed SWC; QS=quiet/deep sleep; DC=discontinuous background pattern, (C)=continuous

Seizures in the cEEG Repetitive, stereotyped waveforms (spikes, sharp waves, spike-slow-wave complexes, rhythmic theta or delta activity without sharp components) with a definite onset, peak, and end (crescendo-decrescendo appearance).

Seizures in the cEEG (2) No specific criteria may be defined regarding as minimum duration of seizures. Although 10 s has been criterion in many studies, briefer runs of repetitive waveforms, often called epileptiform activity, are not uncommon in ill newborns. It is possible that shorter periods of repetitive activity, 5-10 s, should also be assessed as seizures since this type of activity has been associated with adverse neurologic sequalae.

Seizure pattern in the aEEG Epileptic seizure activity in the aEEG usually is seen as an abrupt rise in the minimum amplitude and a simultaneous rise in the maximum amplitude, often followed by a short period of decreased amplitude. Single seizure: A solitary seizure. Repetitive seizures: Single seizures appearing more frequently than at 30-minute intervals. Status epilepticus: Continuously ongoing seizure activity for >30 minutes.

Seizure pattern in the aEEG (2) Seizures may only be identified in aEEG if they are sufficiently prolonged, more than 2-3 minutes. Shorter lasting discharges may be missed since the aEEG is recorded in a very slow speed. It is important to inspect the underlying cEEG for to confirm the presence of seizures and distinguish artifacts from real signal.

Optimal number of electrodes The number of electrodes necessary for optimal identification and treatment of neonatal seizures is not known. Most seizures in newborn infants seem to start in the temporal and central areas. Consequently, when using EEG monitoring with a reduced number of electrodes, i.e. one or two channels, clinicians must be aware that not all electrographic seizure activity will be detected/shown.

Increase the positive yield Continuous EEG monitoring with a reduced number of electrodes detects around 80% of seizures, and at least 90% of infants with seizures. A full standard EEG should be recorded in all infants early during the monitoring, and repeated as required. Close collaboration between the NICU and departments of neurology and/or clinical neurophysiology increases the chances for optimal use of EEG monitoring.

Different types of aEEG seizure patterns

Two single seizures on a discontinuous background Two single seizures on a discontinuous background. The seizures appear with a 1-h interAval; each one can be seen as a transient rise of the lower margin. The original EEG shows slightly irregular 2–3 Hz spike-wave complexes.

Repetitive seizures on a CNV background pattern Repetitive seizures on a CNV background pattern. All seizures are seen as transient rises of both the lower and upper margins of the aEEG. The corresponding EEG below shows rhythmic spike-wave complexes of 3 Hz.

Repetitive seizures arising on an inactive (isoelectric) background The EEG during the seizures shows slow (0.7 Hz) polyspike-wave complexes.

Status epilepticus (‘saw-tooth pattern’) of at least 3 hours’ duration (i.e. the whole screen) on a potentially good electrocortical background.

This example also shows status epilepticus but on a very suppressed background. The status epilepticus could easily be mistaken for a BS pattern. The original EEG shows 0.7 Hz slow waves without clear spikes but with superimposed ECG artifacts.

Status epilepticus with continuously ongoing seizure activity for almost 2 h. During this time the baseline is continuously raised; before and after this a BS pattern is seen. If only the aEEG is evaluated during the status epilepticus it could easily be mistaken for CNV, but the EEG below reveals the true epileptic nature of this change in the aEEG background. The corresponding EEG shows slow rhythmical spike-wave complexes at around 1 Hz.

The next example shows a full-term infant with congenital heart disease. The seizure pattern in the discontinuous aEEG shows three seizures where a decrease in amplitude rather than a rise is seen. These episodes were seen as low voltage (<25 μV) spike-wave complexes at about 2 Hz, on the simultaneous original EEG. This seizure appearance is unusual, where the seizure is represented by desynchronization which is of lower voltage than the abnormal high-voltage background. This example in cardiac patient, shows the use in this group of infants, who usually have extensive monitoring of their cardiovascular system, but not routinely of their central nervous system.

The next two figures show how aEEG can be combined with other EEG trends, e.g. spectrogram/density spectral array (DSA), to enhance detection of neonatal seizures.

aEEG and DSA during a 6-h recording with four seizures (asterisks) and 25 s of EEG from the second seizure (blue vertical line through the trends). The seizures are seen as transient peaks of activity in both the aEEG and DSA.

Single-channel aEEG, DSA, and rhythmic event detection during a 2-h recording containing seven seizures

Sample of Normal trace

Missed seizure with sustained elevation in amplitude Samle of Nl trace

Recurrent seizures, some of which were nonclinical

Recurrent seizures, transient effect of phenobarbital

The effect of antiepileptic in decreasing the frequency and severity of seizures

The effect of speed on the appearance of the seizures

Severely abnormal tracings; with and without seizure With seizure