Epilepsy and OSA are two common disorders that can coexist and profoundly exacerbate each other [11]. Studies showed that patients with epilepsy are at higher risk for apnea than the general population, due to sedentary lifestyle or the effects of AEDs on OSA [1]. Moreover, OSA is underdiagnosed particularly in epileptic patients [12]. Prevalence of sleep apnea in epileptics varies in literature, ranging from 20% up to nearly 60% [13].
Sleep fragmentation in OSA which causes increased sleep stage transitions, sleep deprivation, cerebral hypoxemia, decreased cardiac output, and cardiac arrhythmias can facilitate interictal epileptiform spikes and precipitate epileptic seizures, whereas the latter can induce apneas [14,15,16].
There have been several studies showing improvement of epileptic seizures with treatment of OSA, where more than half of these patients showed improvement in seizure frequencies independent from AED changes [17,18,19]. Positive airway pressure, positional therapy, or upper airway surgery reduces obesity and blood pressure and improves cognition, mood, and daytime sleepiness, which in turn reduced seizures in 40–86% of people with epilepsy and OSA [20, 21]. There is report of direct effect of CPAP on reducing the interictal spikes and therefore potentially reducing epileptogenicity [22].
Our findings support previous studies that show a higher percentage of OSA in epilepsy patients compared to the general population [23,24,25]. Increased sleep apnea in the refractory group is agreeing with previous studies. In a study by Malow and colleagues, the prevalence of OSA was 30% in intractable epilepsy group and 10% of unselected adult epilepsy group [1]. Another study by Zanzmera and colleagues showed that the prevalence of OSA was 20% in refractory epilepsy versus none in medically controlled group [26]. However, we did not find a statistically significant higher OSA rate in refractory versus controlled epilepsy patients, which is in accordance with a study by Li and colleagues [25].
The reason for low prevalence in our study can be attributed to difference in patients’ selection as other studies included only the patients who complained of sleep disorders where higher prevalence of OSA is suspected, whereas in our study, we aimed to investigate OSA in epileptic patients regardless the presence of sleep complaints. However, more reasons need to be explored in the future [21].
Our study is the first Egyptian study, to our knowledge, to compare sleep-related clinical data associated with OSA, between controlled and refractory epilepsy groups. In refractory epilepsy patients with OSA, we found significantly frequent sleep disturbance symptoms and younger age of seizure onset compared with patients with medically controlled epilepsy and OSA, which is in accordance with other studies [25, 26].
About 40% of our refractory epilepsy patients with OSA showed O2 desaturation to critical levels (below 70%), which may question the causes of Sudden Unexplained Death in Epileptic Patients (SUDEP) especially in refractory epilepsy patients. SUDEP represents the main cause of death in patients with refractory epilepsy [27]. Cardiac arrhythmias, respiratory dysfunctions, and dysregulation of systemic or cerebral circulation have been suggested as potential pathophysiological mechanisms. Moreover, clinical data suggest that SUDEP occur preferentially during sleep [28]. In our study, we hypothesize that these apneic events, with this severe desaturation may help to unravel the epileptogenesis of SUDEP, and this is in accordance to a previous study by Dominici and colleagues [29]. Thus, better understanding the role of apnea and epilepsy in the spectrum of SUDEP may help to clarify the epileptogenesis of this syndrome.
Few previous studies have assessed the risk factors for OSA in an epilepsy population. They showed that patients with epilepsy and OSA tend to be older, with higher BMI, more frequently males, and sleepier than epileptic patients without OSA [30]. Foldvary-Schaefer and colleagues in 2012 found that traditional OSA risk factors of older age, higher BMI, and male gender were predictive of OSA in epilepsy patients [24]. Abad-Alegria and colleagues in 1997 found that those with OSA were more likely to be males, with higher BMI and a history of snoring, witnessed apnea, and nocturnal seizures [13]. Li and colleagues reported higher BMI, snoring, sleep disturbance symptoms, and younger age of seizure onset in refractory epilepsy patients with OSA versus patients with controlled epilepsy with OSA [25].
In addition to these factors, we found also that subjects with OSA and medically controlled epilepsy have experienced the first seizure at a later age, which was shown before in different studies [25, 30, 31]. Those with refractory epilepsy and co-existing OSA were older, with older age of onset of epilepsy, and longer duration of epilepsy as compared to those without OSA. However, they were not with higher BMI compared to the non-apneic patients, indicating that the occurrence of apnea in medically refractory epilepsy patients is independent on the weight of the patients, and thus, other factors should be considered: as the age of the patient, the duration of the illness, and the age of onset of the epilepsy, which may play role in the pathogenesis of the disease.
In our study, we found that age is an independent risk factor of having OSA in the controlled epilepsy group. Thus, older patients tend to have higher AHI. On the other hand, it was found that age of patients, age of onset of epilepsy, and duration of epilepsy are all independent factors in determining patients with OSA in the refractory epilepsy group. We found that younger subjects, with early onset of epilepsy, and longer duration of the illness tend to have higher AHI. Thus, other factors should be considered in patients with refractory epilepsy and not only the traditional risk factors of the OSA, which may play role in the pathogenesis of the disease.
Excessive daytime somnolence and snoring are the most common complaints of OSA patients; however, we found that self-reported EDS were not helpful in predicting OSA in medically controlled patients, and this is in accordance with the study of Foldvary-Schaefer and colleagues in 2012 [24], possibly related to a ceiling effect of general sleepiness among epilepsy patients from diverse causes.
We studied patients referred to the adult epilepsy clinic regardless of their sleep problems. The included patients were not biased toward any sleep-related complaints.
Finally, our findings should be viewed more as hypothesis-generating and will require larger studies. Nevertheless, we hope that our results will prompt an increased routine screening of epileptic patients for sleep-related disorders.