We carried out a prospective study with continuous EEG in 82 children with acute non-traumatic coma. Initial medium amplitude was associated with better outcome. We detected seizures in 34% of the children during monitoring and 20% had electrographic seizures only. Clinical observations alone did not detect 66% of the seizures apparent on EEG.
Previous studies have documented electrographic seizures in 7–65% of comatose children.18–22
Most of these studies have included children of different age groups, varied aetiology including epilepsy, and conditions that are not primarily neurological. Further, in developed countries where most of these studies have been performed, children are often paralysed and ventilated, thus suppressing clinical manifestations of seizures. In one study of non-ventilated Kenyan children with CM, EEG monitoring, albeit with intermittent (6 h) recordings, revealed clinically subtle and electrographic seizures in 23% of the patients.23
This is similar to the findings in our study, where electrographic seizures were observed in 27% of children with CM and 24% of children with unknown encephalopathies. Thus, the occurrence of electrographic seizures does not appear to be modified by aetiology and it could be that there are genetic or environmental factors that influence predisposition to seizures in childhood encephalopathies irrespective of aetiology. As only four of our children had ABM and one had sepsis, it was inappropriate to calculate the prevalence of electrographic seizures in these groups.
In our study, most of the electroclinical seizures had focal clinical manifestations. However, on EEG they appeared mostly as generalised, bilateral multifocal or focal with secondary generalisation. Overall, the majority of the seizures, electroclinical or electrographic, were generalised. Focal seizures, as apparent on EEG, were mostly either hemispheric or frontal in origin even when considering CM patients only. This differs from the findings in the earlier study on children with CM from this centre in which most of the seizures on EEG appeared to originate from the posterior temporo-parietal region.23
This is a watershed region lying between the areas supplied by the middle and posterior cerebral arteries, which is vulnerable to hypoxia. In contrast, we found that most seizures were generalised in origin and the few that were focal were hemispheric, frontal or occipital in origin. Studies with concurrent MRI and cerebral blood flow measurements may help clarify the relationship between pathology and the origin of seizures.
Occurrence of any type of seizure was associated with poor outcome. Status epilepticus was associated with an even greater risk of poor outcome. Electrographic seizures alone were not independently associated with poor outcome. Experimental evidence indicates that prolonged electrographic seizures may result in memory and behavioural problems.24
It is possible that cognitive tests and prolonged follow-up in larger studies may reveal neuro-cognitive deficits in patients with electrographic seizures. Whether seizures are a cause or consequence of brain damage in acute encephalopathies can be clarified by a trial of prophylactic AEDs.
Our study has a number of limitations. We initially intended to obtain concurrent video and EEG data to clearly demonstrate discrepancies between clinical and EEG seizure detection. Unfortunately, this was not consistently possible because of technical difficulties, likely due to the high humidity and temperatures in our setting. To determine the presence or lack of a clinical correlate to an EEG seizure event, we partly relied on observations by the nurses. It is possible that some of the seizures classified as electrographic may have had subtle clinical correlates or may have been classified as such due to a lapse in observation.
Considering the study design, we were often not able to include children who were not clinically stable at admission and who were therefore more likely to die shortly after admission. Thus, a greater proportion of eligible children who were not monitored died compared to those who were monitored (). These children were more likely to have a diagnosis of ABM and unknown encephalopathy (), conditions which were associated with greater mortality compared to CM (see online supplementary ). In our study, we assessed for motor neurological sequelae at discharge. Previous studies have documented significant occurrence of neuro-cognitive sequelae many years after hospital admission for acute non-traumatic encephalopathies.25–27
Other studies have also documented resolution of neurological deficits observed at discharge.28
Thus, it would have been optimal to assess for neurological deficits over a longer period after discharge. Further, cognitive assessments may have revealed more deficits, perhaps helping to clarify their association with electrographic seizures.
All the observers involved in EEG analysis were trained in clinical neurophysiology by SW, a consultant clinical neurophysiologist, but only GO and EC were formally certified EEG technologists. SW examined all EEGs in which there was lack of agreement between two raters.
In spite of these limitations, our study highlights the significant burden of seizures missed by clinical observations alone in sub-Saharan African children with acute coma. Although continuous EEG monitoring with more leads is more sensitive for detecting seizures in comatose patients, devices with one to four EEG channels which are cheaper and can be more easily interpreted by less experienced clinicians and nurses, have potential utility in resource-poor settings. However, such use will have to be guided by appropriate training and experience to promote accuracy of analysis and reporting. Prophylactic AEDs on admission should be investigated for improving outcomes in this group of children.