The cooccurrence of interictal discharges and seizures in pediatric sleep-disordered breathing

Highlights

• About 16% of children with obstructive sleep apnea have interictal epileptiform discharges.

• Interictal epileptiform discharges may disappear with the resolution of obstructive sleep apnea.

• Persistence of pediatric obstructive sleep apnea may be a risk to develop epilepsy.

Abstract

Studies in the literature data have shown that the prevalence of obstructive sleep apnea (OSA) in children with epilepsy is high and that treatment for OSA leads to a reduction in the number of seizures; by contrast, few studies have demonstrated an increased prevalence of interictal epileptiform discharges (IEDs) or epilepsy in children with sleep-disordered breathing (SDB). The aim of the present study was to confirm the high prevalence of IEDs or epilepsy in a large sample of children with SDB and to collect follow-up data.

Children were recruited prospectively and underwent their first video-polysomnography (video-PSG) for SDB in a teaching hospital sleep center.

Of the 298 children who fulfilled the diagnostic criteria for sleep-disordered breathing, 48 (16.1%) children were found to have IEDs, three of these 48 children were also found to have nocturnal seizures (two females diagnosed with rolandic epilepsy and a male diagnosed with frontal lobe epilepsy). Only 11 subjects underwent a second video-PSG after 6 months; at the second video-PSG, the IEDs had disappeared in six subjects, who also displayed a reduced AHI and an increased mean overnight saturation. Thirty-eight of the 250 children without IEDs underwent a second video-PSG after 6 months. Of these 250 children, four, who did not display any improvement in the respiratory parameters and were found to experience numerous stereotyped movements during sleep, were diagnosed with nocturnal frontal lobe epilepsy.

Our study confirms the high prevalence of IEDs in children with SDB. Follow-up data indicate that they may recede over time, accompanied by an improvement of sleep respiratory parameters.

Introduction

Sleep activates both focal and generalized spikes in about one-third of all individuals with epilepsy. Some types of epilepsy are closely related to sleep, with the clinical onset occurring exclusively or mainly during sleep (e.g., rolandic epilepsy and nocturnal frontal lobe epilepsy) [1]. However, few data are available on the comorbidity of epilepsy and specific sleep disorders, such as obstructive sleep apnea (OSA), restless leg syndrome, and periodic limb movements. Sleep-related breathing disorders may trigger paroxysmal events during sleep, such as parasomnias, and may exacerbate preexisting seizures. Moreover, it has been suggested that sleepiness, a common complaint of patients with epilepsy that is frequently attributed to antiepileptic drugs, may be linked to undiagnosed sleep disorders such as restless leg syndrome or OSA [2], [3], [4]. Some authors have reported that melatonin may, by improving sleep efficiency and reducing sleep disruption, help control seizures in children and adolescents with epilepsy [5], while others have reported that the treatment of OSA may improve seizure control and reduce daytime somnolence [6], [7], [8], [9]. Numerous studies have explored the relationship between sleep-disordered breathing and epilepsy in adults with epilepsy [8], [10]. Interestingly, it has been demonstrated that the use of continuous positive airway pressure in adults with drug-refractory epilepsy and OSA improves seizure control [11]. A high prevalence (approximately 30%) of OSA was recently reported in a relatively large population of children with epilepsy, with a higher incidence being observed in children with refractory epilepsy or on multiple antiepileptic drugs; OSA in that study was, however, investigated solely by means of questionnaires [12]. Another study demonstrated that treatment of OSA in children with epilepsy may reduce seizure frequency, particularly in children with high body mass index scores and younger age at the time of adenotonsillectomy [13]. In addition, a few studies have demonstrated an increased prevalence of interictal epileptiform discharges (IEDs) or of nocturnal seizures in children with sleep-disordered breathing without a previous history of epilepsy [14], [15]. We previously reported a high prevalence (14.3%) of IEDs in a population of children with OSA. Children with IEDs were older and had a longer duration of disease, a lower incidence of adenotonsillar hypertrophy, and a higher occurrence of perinatal injuries than controls. Epileptiform discharges prevalently occurred over the centrotemporal regions, thus being comparable with the IEDs that occur in benign epilepsy with centrotemporal spikes (BECTS). Interictal epileptiform discharges have been hypothesized to disrupt cognitive abilities, such as learning and memory, with a significant improvement in cognitive performances following remission [16]. Many studies have provided data on the relationship between epileptiform discharges during sleep and, in particular, centrotemporal or rolandic spikes and neuropsychological dysfunction in children with language disorders, autism, and ADHD [17], [18], [19]. The fact that the EEG patterns changed following treatment and were abnormal only during sleep suggests that they are a physiological phenomenon and not merely a structural deficit [17].

The high prevalence of IEDs in children with OSA possibly reflects a prefrontal cortical dysfunction. Indeed, IEDs may be due to a shift in brain activity during sleep (particularly NREM sleep), with a predominance of thalamocortical activity over prefrontal activity. Some authors have recently postulated that cognitive impairment in subjects with IEDs may be caused by a disruption in sleep architecture [14], [20], [21]. In this regard, our previous findings may partly explain neurocognitive impairment in children with OSA [14]. The aim of the present study was to replicate our previous study on a larger sample of children with sleep-disordered breathing in order to verify whether there is indeed a high prevalence of IEDs in this pediatric population. We also investigated whether children with IEDs and sleep-disordered breathing are at risk of developing epilepsy, and we collected follow-up data.