Nonconvulsive status epilepticus (NCSE) is a medical emergency, which is diagnosed most frequently with the routine use of EEG in the pediatric emergency and intensive care units.

Data from eight patients, ranging from 2.8-15 years old (median 8.7 years), treated with the diagnosis of NCSE were evaluated on clinical basis. The patients attended the hospital with acute confusional state ranging from sudden onset of verbal cooperation insufficiency to aimless-meaningless behavior and confusion without any motor component of seizure. While five of the cases were diagnosed and followed up with epilepsy, the other three had no history of epilepsy. No reason was detected that could cause acute encephalopathy. EEG examinations during acute confusional state showed partial or generalized continuous electrographic seizure activity lasting at least 30 minutes without clinical seizure activity. After administration of intravenous antiepileptic medication, the confusional states of the patients recovered, and the EEG examinations showed normal baseline activity with significantly diminished discharges or complete normal waveform.

Nonconvulsive status epilepticus should be considered in all children admitted to the hospital with acute unexplained encephalopathy, whether they have a history of epilepsy or not. Emergent EEG examination should be a routine part of evaluation in these children for the diagnosis and treatment of NCSE.

The EEG recordings were performed during and after an intravenous anticonvulsant medication with a 14-channel electroencephalogram (Nihon Cohden) using the International 10-20 system of electrode placement and clinical follow-up was done. NCSE was described as “acute confusional state at the time of EEG discharges consistent with electrophysiological status lasting more than 30 minutes, which were abated with intravenous antiepileptic medication”. Standard dose intravenous anticonvulsant drugs including diazepam, midazolam, phenobarbital (PB) and diphenylhydantoin (DPH) were selected based on the clinical and EEG findings. The clinical features and electrophysiological findings of the patients were evaluated.

There is a clear overlap of encephalopathies with different etiologies; patients with metabolic, infectious, toxic encephalopathies and acute cerebral injury also show the same or a very similar clinical picture considering consciousness and EEG findings, including partial or generalized continuous epileptiform discharges[12-14]. However, as Kaplan[1] indicated, NCSE should be considered as an epileptic state. The patients with metabolic, toxic or infectious encephalopathies and acute intracranial pathologies were not included in this series. The mainstay of our study was to consider NCSE as a differential diagnosis in patients with encephalopathy that is not caused by any metabolic or infectious or another identifiable etiology. Although these etiologies readily show a similar clinical picture and EEG patterns, the underlying cause of change in consciousness is difficult to claim, whether a result of the underlying cause or a result of the electrophysiological discharges. The diagnosis of NCSE is difficult in some cases because there are no specific clinical features or laboratory test other than EEG examination. For the accurate diagnosis, the presence of seizure activity on EEG in addition to variable clinical findings without convulsive movements should be demonstrated[1,2].

The real incidence of NCSE is unknown and it is accepted that NCSE is an underestimated clinical entity due to failure to diagnose[1,3,4,15]. Another problem in determining the incidence is the confusion regarding its definition. It is postulated that 25% of patients who experience SE have NCSE, either absence or complex partial SE[3,16]. In the study of Towne et al.[15], which was conducted in unselected comatose patients, NCSE was found as an under-recognized cause of coma, occurring in 8% of all comatose patients without signs of seizure activity. Alehan et al.[4] investigated the role of EEG in the pediatric emergency unit, and reported that seven patients of a total of 56 children with new-onset seizures or known epilepsy presenting with worsening seizures and altered mentation or with acute confusional states were diagnosed as NCSE. Saengpattrachai et al.[17] reported that the diagnosis of NCSE was made in 23 of 141 children with an unexplained decrease in level of consciousness and no overt clinical seizures.

Nonconvulsive status epilepticus may be the first seizure in healthy children without a history of epilepsy; on the other hand, epileptic children may present NCSE with or without any preceding factor[2,3,9,18]. Three of our eight patients had no previous history of seizure, whereas five of them had been treated with the diagnosis of epilepsy; three of these five patients had symptomatic epilepsy (Sturge- Weber syndrome, operated brain tumor and focal cortical dysplasia), whereas the etiology of epilepsy was unknown in the other two patients. NCSE may occur as both generalized and partial epilepsies, similarly both in symptomatic and non-symptomatic epilepsies.

Clinical findings of NCSE are quite variable during childhood; children with NCSE may be admitted to the emergency units because of strange behavior, acute confusional state, or coma[3,9]. One of our patients (patient number 6) presented with only bizarre behaviors, meaningless talking and laughing, but she could obey simple commands and limited verbal communication was possible. The other seven patients were non-cooperative, ranging from mild-moderate confusional state to coma. Current pediatric emergency practice for a confused child includes investigations to detect any metabolic, toxic or infectious etiology, as well as intracranial pathologies. Children admitted to the hospital with acute, unexplained consciousness or behavior change, with or without a history or diagnosis of epilepsy, should be evaluated by EEG for the diagnosis and treatment of NCSE. Emergent EEG was defined as any EEG examination requested for immediate performance during non-business hours or any EEG done to exclude NCSE with 24-hours-a-day, 7-days-a-week availability and after approval by the neurology or neurosurgery services[19-21]. The role of emergent EEG has been studied both for adults and children[4,19,22]. EEG monitoring has been an inevitable part of pediatric intensive units[23]. We believe that emergent EEG examination should be a part of diagnostic studies in the pediatric emergency units.

The EEG findings of NCSE are heterogeneous; generalized or focal (temporal, temporo-frontal) spike-and-slow wave complexes, polyspike discharges, irregular sharp or slow waves may be seen[2,3]. Classification of NCSE is not yet clear[3,5,6]. Previously, NCSE has been generally divided into two types: absence SE and complex partial SE[3]. With the advent of electrophysiological and neuroradiological methods, new classification schemes have been proposed. According to Kaplan[7], NCSE may be classified as

1) localization-related NCSE,
2) generalized NCSE, and
3) indeterminate or intermediate NCSE.

Moreover, partial (localization-related) NCSE has been classified based on the localization of epileptic discharges as NCSE of temporal origin and NCSE of extratemporal origin, and electroclinical varieties of NCSE subtypes have been reported[23]. The accurate subclassification of NCSE can be difficult, not only in children without previous diagnosis of epilepsy but also in patients with localization-related epilepsy[18]. Emergent EEG examinations of seven of our eight patients revealed epileptic discharges with focal dominance, whereas only one patient had bilateral synchronous discharges. Based on the emergent EEG findings, we could not make thorough sub-classification of NCSE free of any doubt. Clinical data including types of new seizures obtained during a long-term follow-up period, as well as ictal and interictal video EEG monitoring may be helpful for the classification.

The therapy regimens of NCSE are controversial; benzodiazepines, DPH and PB are believed to be effective[3,12,25-27]. Midazolam, propofol, and topiramate have been found as effective in patients with refractory status epilepticus[25,28,29]. In our series, diazepam was selected as the drug of first choice in six patients, but clinical and EEG findings disappeared only in one patient. In four patients unresponsive to diazepam, PB or DPH had to be administered as second drug, and in four patients, midazolam was used as third anticonvulsant. Our experiences do not allow us to propose the drug of first choice; however, it should be taken into consideration that diazepam might not be effective as the first choice in the treatment of NCSE.

The prognosis of NCSE is still inconclusive[30-34]. A few basic scientific studies demons-trated that NCSE may produce long-term behavioral deficits and functional changes in neurons that alter electrical excitability in neuronal circuits despite the absence of neuronal damage[35,36]. Recently, persistent abnormality on magnetic resonance imaging after NCSE was reported[37]. The outcome from de novo NCSE in ambulatory patients has not been studied in detail. All children with NCSE should be followed carefully, since the data collected to the present is not satisfactory.