Newborn babies less than four weeks of age are termed neonates, and their EEGs reflect the rapid development of their brain in that time. The normal neonatal EEG exhibits many characteristics that would be grossly abnormal in an adult, including diffuse slowing, discontinuity, asynchrony, and minimal reactivity, but all of these unique characteristics should evolve, in normalized increments of time, into the familiar tracings of infants, children and adults (it seems that babies like to keep both their parents and neurophysiologists on their toes). Below is a summary of the changes across the first weeks of life for a neonate that will be further discussed in the sections below:
After the first month of life, a baby is no longer a neonate, and becomes an infant. With this there are further expected changes that slowly lead into the tracing of an adult.
Given the small and sometime alien appearing head size of neonates, a full 10-20 montage puts the electrodes too close together and risks forming salt bridges (discussed in the artifact section) between them. So, the neonatal montage is a pared down version of the 10-20 system that focuses on the central areas, which tend to be more active in neonates, and includes a transverse chain going across from T3 to T4. This version is used until the baby is full term, or at most 46 weeks postmenstrual age (see below for PMA definition).
In the neonate, in addition to the brain and ECG electrodes, there are also extraocular electrodes (electro-oculogram, EOG) placed lateral to the eyes, electromyography electrodes (EMG) on the chin, and leads to assess chest movements for breathing (pneumograph). Neonatal studies are read at a faster page speed of 15mm/sec, with a low frequency filter of 0.01 - 0.5Hz.
As stated above, neonatal EEGs are starkly different than adults, showing diffuse slowing, discontinuity, asynchrony, and minimal reactivity. Sleep is also different in a neonate, being broken down into quiet and active sleep as opposed to the four stages in adults. These differences, marked as they are, progress into a more classic childhood and then adult EEG, and knowing the timeframe of such changes is critical because what is normal one week for a neonate may be abnormal by the next week.
The timeframe for changes is measured by the postmenstrual age (PMA; also called conceptual or conceptional age), rather than chronological age, to take into account prematurity or delayed delivery. The PMA is calculated by adding the gestational age (the time from the mother’s last menstruation, aka the length of the pregnancy) to the chronological age (the time since the baby’s birth). So, a 4 week old baby who was born at 34 weeks would have a PMA of 34 + 4 = 38 weeks.
A baby is born prematurely at 28 weeks and is cared for in the neonatal ICU. Three weeks after birth, what is the baby's postmenstrual age?
The postmenstrual age (PMA) is a calculated age that combines the gestational age (essentially, the length of the pregnancy) and the chronological age (time since birth). The PMA should be used when assessing age-based findings on neonatal studies, which change rapidly in the first weeks of life.
The background of a neonatal EEG is grossly broken down into awake, quiet sleep, and active sleep states. Awake is marked simply by the presence of the eyes being open, and asleep by the eyes being closed. However, for up to 29 weeks of postmenstrual age the neonatal EEG looks essentially the same across the awake, active sleep and quiet sleep states. After that, things start to change rapidly.
Before we delve into neonatal development, lets review some key terms regarding the background. Continuity refers to continuous waves across the page, without flat periods. Synchrony describes bursts of activity happening at the time in both sides of the brain (note that this is different than symmetry, in which the activity is the same in frequency and amplitude on both sides). Reactivity refers to a response or change in the tracing due to external stimuli. Amplitude refers to the height of a given waveform, while frequency (in hertz, Hz) is the number of times a set of waves happens per second. Morphology describes the shape of a given waveform. In reviewing neonatal studies, you should assess all of these components just as you do with adult studies, so let's get started.
The most striking component of a neonatal background is discontinuity, or periods of essentially flat activity in between bursts of activity. In an adult, such a pattern is highly abnormal, but in neonates as long as the periods of flat activity—termed interburst intervals (IBI)—remain within expected durations (discussed below), it is normal.
The acceptable IBI shortens over time, being up to 60 seconds at 24 weeks PMA, 40 seconds at 26 weeks, 20 seconds at 28 weeks, 10 seconds from 34-36 weeks, and 6 seconds from 37-40 weeks; note that these values are generally on the upper limit of normal. After 40 weeks, you can still see some discontinuity in sleep but by 46 weeks at the most, the tracing should be completely continuous during both sleep and awake states. In the example below, the IBI is about 6 seconds for this 39 week PMA neonate, approximately as expected.
While the IBI decreases across development, synchrony and reactivity increase. Up to 28 weeks PMA a normal tracing may show no reactivity, but starting at 30 weeks you should start to see reactivity to external stimuli; most babies are fully reactive starting between 32 and 40 weeks PMA. Synchrony is acheived somewhat faster, with about 80% of the record becoming synchronous by 30 weeks, and the entire tracing should be synchronous by 38 weeks. This is roughly summarized below:
Recall that the max acceptable interburst interval (IBI) decreases across the span of neonatal development, as follows:
24 weeks | 60 seconds
26 weeks | 30 seconds
28 weeks | 20 seconds
30-34 weeks | 10-20 seconds
34-38 weeks | 10 seconds
38-40 weeks | 6 seconds
This baby at 33 weeks PMA would be expected to have closer to a 10 seconds IBI, but we see a nearly 20 second attenuated period across this tracing. So, there is excessive attenuation.
While adults have awake and asleep states, and the asleep state goes through several cycles, up to 29 weeks PMA the neonatal EEG looks essentially the same all the time, and is always discontinuous, unreactive and asynchronous. However, after about 28 weeks PMA neonates have three states of consciousness: awake, active sleep and quiet sleep.
Awake is simply marked by the presence of the eyes being open. The hallmark awake feature from 30-32 weeks PMA is a mostly continuous but rather low voltage background; reactivity and synchrony can vary by age as discussed above. Starting around 35 weeks PMA, the awake background becomes higher amplitude and with a greater mixture of frequencies. Below is a good example of a normal full term neonatal study in the awake state; note the irregular respiratory pattern and movement artifact toward the end of the page that help to confirm the baby is awake.
Active sleep is similar to REM in adults, and is marked by the eyes being closed but with other activity such as eye movements, irregular respirations / apneic episodes, and sometimes body movements. From 30 to 36 weeks PMA activity sleep is mostly filled by continuous theta to delta activity, and starting at 38 weeks a greater mixture of faster frequencies is also seen. You'll note that this is somewhat similar to the awake state. Below is a good example of active sleep; note the lack of movement artifact, lateral eye movements seen best in the LOC and ROC leads, and the continuity of the tracing with mixed frequencies.
Quiet sleep is characterized by the eyes being closed with minimal eye movements and regular respirations. Generally, neonates move from awake into active sleep, then into quiet sleep (they spend about 50/50 in each type of sleep). From 30-32 weeks PMA quiet sleep is predominated by a trace discontinu pattern, which can appear similar to an interburst interval pattern, but the IBI must be less than 15 seconds (usually much less so) and the bursts of activity have an amplitude less than 25 microvolts. Starting at 34 weeks PMA, trace discontinu evolves into trace alternans, in which the bursts of activity are higher amplitude (above 25 microvolts) and the IBI continues to shorten. From 38 weeks PMA onward trace alternans continues to evolve into slow wave sleep. To summarize, discontinu and alternans differ primarily in their amplitude (discontinu is <25 microvolts), and alternans is a more mature pattern; take a look at the examples below (both captured at the same sensitivity) to get a better sense of the difference.
Between awake and quiet sleep, there are often periods of transition that can be unclear, but as development continues the states should become more clearly defined; such periods of indeterminate sleep may be seen more often in neonates with brain injury, such as hypoxic ischemic injury (HIE). No matter what, though, being able to recognize the state of a baby is just as important as it is for adults, albeit often less clear cut. Take a minute to review the expected timeline for state changes, remembering that prior to 28-30 weeks there really aren't any different states:
Recall that by 40 weeks the background for an awake neonate should be most always continuous, but periods of discontinuity can remain during quiet sleep. On this tracing we see periods of attenuation between higher amplitude activity, and while we don't have a measurement of the actual voltage, the attenuated periods are not too flat, likely most consistent with a trace alternans pattern. As such, this baby is in quiet sleep. Note also the lack of eye movements seen in the LOC and ROC leads, and the presence of mostly just ECG artifact in the EMG chin lead; both of these also support quiet sleep. There are a few sharp transients here too, which are discussed more below.
Transients (also termed graphoelements) describe particular waveforms that are seen only in neonatal studies, many of which could be mistaken for abnormalities to the inexperienced eye. Of course, with your ever-increasing EEG expertise, you won't have that problem. As with all elements of the neonatal study, normal transients vary by age. Below is a summary of the more commonly seen neonatal transients and their expected timelines:
The earliest transients seen are premature temporal theta and monomorphic occipital delta. Both start around 24 weeks PMA and last until around 30-32 weeks PMA. They both also have very descriptive names; with temporal theta, look for sharply contoured, moderate to high amplitude bursts of theta activity in the bitemporal regions, while monomorphic occipital delta is appears as its name suggests. Both of these patterns are really only seen in very premature babies, as they fade away before delivery for most neonates.
Delta brush, on the other hand, is a finding you may see only mildly premature newborns, and describes 8-20 Hz fast activity overriding delta waves, like the bristles on a brush. It arises around 28 weeks rather diffusely, should become mostly posterior by 36 weeks, and usually goes away completely by 40 or, at most, 42 weeks. While delta brush is a normal part of neonatal EEG, you may also find it present in the abnormal tracings of adult patients with NMDA receptor encephalitis.
Starting around 34 weeks PMA, frontal sharp transients, or encoches frontales, arise. These are bifrontal and synchronous frontal discharges that are normal from 34 weeks to up to 46 weeks. Note that they should always be synchronous, as lack of synchronicity for them suggests it to instead be an abnormal epileptiform discharge.
Aside from frontal sharp transients, centrotemporal sharp transients are also commonly seen normally, and more widespread multifocal sharp transients are most often normal within the first month of life, but should fade away by 49 weeks PMA. On the example below from a healthy 39 week PMA baby, note the numerous sharp transients in various locations--as long a particular location doesn't become excessive in sharps, this is most likely normal.
This tracing has a lot of movement and other artifact on it, but you can see right near the middle a clear spike at O2 and, about 1/5 of a second later, a smaller spike at O1. Both of these are consistent with sharp transients although the O2 discharge has a slightly spike wave morphology. It is possible that with a bit more brain maturation, these would become a synchronous, symmetric bioccipital discharge. With such a finding you'd want to continue looking for more to ensure that these don't become very frequent, persistent, or strongly lateralized, which would be more concerning for epileptiform activity. Note that this tracing has an improper reading speed for neonatal studies--they should be read at 15mm/sec, and this page is at the adult speed of 30mmsec.
Epileptiform activity in neonates follows the same rules as it does for adults--it tends to be negative in polarity, the classic spike and slow wave morphology is often present, and it should disturb the background with a field. The difficulty with differentiating neonatal epileptiform activity comes mostly from the fact that it exists among the many other normal neonatal transients we discussed above, and you need to pick out one group from the other.
As mentioned already, the location of sharp waves in neonates can be helpful in determining if they are epileptiform or not: frontal and centrotemporal sharps are probably benign, while midline and occipital sharps are probably epileptiform. Rare multifocal spikes (a few per hours) are also most often normal. As with any rule of thumb, though, there are exceptions; for example, an excess of frontal or other localized sharps, persistently focal sharps, or asymmetric discharges in any location should raise alarm for true epileptiform activity rather than just normal transients. Furthermore, spikes in the awake or active sleep state after about 42 weeks PMA are more likely to be abnormal.
Similar to adults, persistent rhythmic activity can also be concerning as epileptiform activity in neonates. Normally, you can see centrotemporal bursts of rhythmic activity, or randomly localized rhythmic activity. If you start to see a particular region with consistent rhythmicity, though, be suspicious of abnormality.
Aside from interictal activity, neonatal seizures are particularly important to see on EEG because many neonatal seizures are clinically silent; EEG is the only way you'll know they're having them. Fortunately, seizures in neonates follow the same rules as those for adults: they must evolve in time and space.
Generally, focal or multifocal seizures are much more common than generalized seizures in neonates. They can, however, be easy to pass by on screening because they can be relatively low amplitude with longer sharps; their rhythmicity or periodicity, however, should still be apparent. For neonates, particularly, seizures can come with desaturation events or other very subtle clinical findings. Below is an example of a right hemispheric onset neonatal seizure:
While neonatal transients can sometimes occur in the occipital regions, the marked waveforms are a rhythmic run of spike wave discharges lasting four seconds, which is not consistent with normal transients. Note that we do see some normal transients here via encoches frontales--synchronous bifrontal discharges--in the first few seconds of the page. There is also some hypoglossal artifact picked up on the EMG lead, which could cause rhythmic artifact on the EEG but in this case the hypoglossal activity 1) doesn't match up timewise to the occipital discharges and 2) the occipital discharges have a spike wave morphology that makes them less likely to be just artifact.
Neonates can have many sharp transients, which are "epileptiform" discharges that are actually normal as long as they aren't too frequent or persistent in one particular area. They should all fade away by 49 weeks PMA. This example also shows a normal awake background for a full term baby.
Trace discontinu is seen during quiet sleep from 30-34 weeks PMA, and is marked by periods of attenuation less than 25 microvolts in between periods of higher amplitude activity.