The use of amplitude-integrated electroencephalography (aEEG) to assess brain function and detect seizures has been increasing worldwide. Results from previous studies have demonstrated that seizure patterns can be recognized as transient rises on aEEG traces. We report here a case of an infant with neonatal seizures that showed paradoxical transient drops on aEEG traces. The ictal EEG showed initial low-amplitude fast rhythmic activity followed by epileptic recruiting rhythms and high-voltage slow waves. Therefore, downward patterns on aEEG traces should be recognized as suspected seizure patterns.
Amplitude-integrated electroencephalography (aEEG) is useful for monitoring cerebral function in the neonatal intensive care unit due to its ease of use and interpretation.1, 2, 3 The severity of brain injury and presence or absence of neonatal seizures can be assessed using aEEG. Neonatal seizures are often subtle or subclinical and can be missed easily without EEG monitoring.4 Therefore, the diagnosis of neonatal seizures using aEEG is increasingly important.Typically, an ictal seizure pattern is characterized by a rapid rise in the lower and upper margins of an aEEG trace, often accompanied by narrowing of the bandwidth. Repetitive seizures are observed as a ‘saw-tooth’ pattern on aEEG.
Conversely, some seizure activity corresponds to a transient downward ictal pattern on an aEEG trace. This paper reports the case of a neonate with holoprosencephaly (HPE) and repetitive seizures displaying a unique downward seizure pattern on aEEG. The significance of recognizing this seizure pattern on aEEG is also discussed.
The female infant was the second child in the family and her family history was unremarkable. At 27 weeks of gestation, fetal screening with ultrasound suggested a brain anomaly which was diagnosed as HPE with fetal magnetic resonance imaging at 34 weeks of gestation. She was born at 41 weeks and 1 day of gestation by vaginal delivery and her birth weight was 2814 g. At birth, the infant presented cranio-facial anomalies of microcephaly, orbital hypotelorism, a flat nose and nasal bridge without nostrils, absence of the philtrum, and median cleft lip and alveolus. No other physical anomalies were observed. Her karyotype test was normal. Brain magnetic resonance imaging confirmed a diagnosis of HPE with characteristic findings (Figure 1).
Because infants with HPE often have neonatal seizures, cerebral function monitoring with an aEEG device (Nicolet One, Cardinal Health, Dublin, OH, USA) was performed after birth. Frequent seizures were observed in this infant from 12 h after birth and aEEG traces showed higher voltage bands of more than 50 to 100 μV with recurring transient drops in the upper and lower borders (Figure 2a). The simultaneous raw EEGs at higher voltage band parts showed periodic high-voltage activities with intervening periods of low-amplitude activity lasting 0.5 s (Figure 2b and b'). In accordance with general recognition of seizure patterns on aEEG traces, the higher voltage bands were suspected as seizures, although the infant appeared to be asleep and did not show any identifiable motor phenomena or other clinical symptoms. In contrast, the transient drops on aEEG traces showed low-voltage fast rhythms (Figure 2c-1) followed by slow waves of increasing amplitude and decreasing frequency (Figure 2c-2). During these phases, she seemed to manifest subtle symptoms consisting of opening of the eyes, deviation of the eyeballs, nystagmus, twitching of the eyelids, tonic or clonic activities of the limbs or apnea, suggesting ictal phenomena. Video-conventional EEG on the third day of age confirmed that the former high-voltage portions of the aEEG traces were inter-ictal background activities and that the latter transient drops were ictal (Figure 3).
Because the seizure frequency was not reduced by initial treatment with phenobarbital, topiramate was added after the ninth day of age. The seizures remained intractable to these anticonvulsants and valproate was added after 1 month of age. She was discharged at day 47 of age on these drugs with diazepam as needed.
Based on the results of several studies, the seizure patterns on aEEG traces are characterized by a transient rise of the lower margin or both the lower and upper margins, often accompanied by bandwidth narrowing.1,2,5 In this report, however, seizures showed a paradoxical transient drop on the aEEG traces.
The contrast in amplitude between ictal and inter-ictal activities determines whether the seizure pattern on aEEG shows a rise or drop. The most common neonatal seizures are focal, regardless of the clinical manifestations. On EEG, ictal activity is seen as repetitive, rhythmic, stereotyped patterns that evolve in amplitude, frequency and morphology, leading to a transient increase in the lower margin or both the lower and upper margins of the aEEG trace. In contrast, the ictal EEG traces from the infant described here showed attenuation or low-amplitude fast rhythmic activities followed by epileptic recruiting rhythms progressively slowing to 1 to 2 Hz high-amplitude slow waves (Figure 3). The characteristic ictal pattern resulted in transient drops on the aEEG traces. Interestingly, such ictal patterns are common in neonates with HPE.6, 7, 8
The background EEG in a neonate with HPE also differs from that in healthy neonates. HPE is a congenital brain malformation characterized by partial or complete failure of the prosencephalon to separate into the two cerebral hemispheres between the 18th and 28th days of gestation.9 Most children with HPE have intractable epileptic seizures.10,11 During the neonatal period, EEG in HPS shows characteristic rhythmic high-voltage activities, with no physiological EEG background. These findings have been recognized by several authors. Previously, we reported that EEG in HPS showed generalized high-amplitude rhythmic alpha/beta activity during wakefulness, which became discontinuous during sleep as inter-ictal activity.6 Similarly, Demyer et al.7 and Shah et al.8 reported that the background EEG record in HPE showed sharp waves, spike and wave, or polyspike and wave complexes rhythmically. Such characteristic inter-ictal EEG activity might be misunderstood as a seizure. Indeed, looking at the one-channel raw EEG displayed on an aEEG device (Figure 2b and b'), one might suspect seizure activity. However, ictal EEG generally shows not only repetitive, rhythmic, stereotyped EEG activities but also evolutional changes in amplitude, frequency and morphology. Therefore, we should perform full-channel standard EEG to assess brain function and the presence or absence of seizure activity in infants with brain anomalies.
Although desynchronized or attenuated seizure activity is rare in neonatal seizures, it can be observed in tonic seizures, epileptic startles or epileptic spasms in children. One study reported a 2-month-old infant with infantile spasms and a transient amplitude decrease during seizures on aEEG traces, although it was difficult to detect each spasm with the commonly used compression rate of 6 cm h–1 due to their short duration.12
In conclusion, a transient drop in amplitude from the baseline activity on aEEG, in addition to a transient rise, should be suspected as a seizure pattern. Video-conventional EEG is also essential for correctly assessing both the ictal and inter-ictal activity in infants with such downward seizure patterns on aEEG traces.
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We thank Drs T Negoro and H Yamamoto for critical comments on the interpretation of EEG results.
The authors declare no conflict of interest.
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Ito, M., Kidokoro, H., Sugiyama, Y. et al. Paradoxical downward seizure pattern on amplitude-integrated electroencephalogram. J Perinatol 34, 642–644 (2014). https://doi.org/10.1038/jp.2013.84
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