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Abstract Summary Epilepsy and obstructive sleep apnea (OSA) are two common disorders that can coexist and profoundly exacerbate each other’s. OSA is one of the most common sleep-breathing disorders which may exacerbate epilepsy by causing sleep disruption and deprivation, hypoxemia, and decreased cerebral blood flow. Studies have shown 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. To make matters worse, obstructive sleep apnea is notoriously underdiagnosed particularly in patients with epilepsy. In the present study we sought to investigate the possible relationship between Obstructive Sleep Apnea Syndrome (OSA) and refractory epilepsy. To fulfill our aim, we recruited sixty adult epileptic patients from Ain Shams University hospitals. Patients` age ranged from 18 to 57 yrs old. All subjects had normal neurological and general examination. Subjects included were divided into 2 groups; group (I); included thirty patients with controlled epilepsy and group (II); included thirty patients with refractory epilepsy. Patients with following criteria were excluded; Patients with seizures secondary to drugs, infection, neoplasia, demyelination, degenerative diseases, or metabolic disease, Patients with medical illnesses affecting their sleep pattern (as chronic liver disease, hypothyroidism), patients with history of drug intake that could affect sleep such as hypnotics or sedatives, patients with recent medication discontinuation, Narcolepsy or another primary sleep disorder requiring intervention with medication and potentially affecting results of the study, history of OSA prior to the diagnosis of epilepsy, subjects who underwent epilepsy surgery. All subjects completed Summary 92 sleep questionnaire and Sleep Apnea scale of the sleep disorders questionnaire (SA-SDQ), with Cutoffs of 26 or higher for women and 29 or higher for men. Sleep EEG and an overnight PSG were done. Patients having an AHI > 5 were identified as having OSA. Comparison between the 2 groups: Patients with medically refractory seizures tended to have younger age of seizure onset with longer duration of epilepsy. They tended also to have focal epilepsies, mainly temporal lobe epilepsy, as compared to those with medically controlled epilepsy. Sleep symptoms were reported in both groups. Patients with medically controlled epilepsy reported frequent insomnia, whereas, snoring and EDS were reported more frequently in patients with refractory epilepsy. There was no significant difference in number of patients having OSA between the refractory epilepsy and the medically controlled epilepsy group. The frequency of OSA was found to be 10% (3 out of 30) in patient with controlled epilepsy, while its frequency in patients with refractory epilepsy was found to be 16.7% (5 out of 30). Interestingly, O2 desaturation nadir was significantly higher in group II, compared to group I. As regards sleep architecture, patients in group I (medically controlled epilepsy) showed marked decreased in sleep latency and increased REM sleep percentage, as compared to those in group II (medically refractory epilepsy). While light sleep was prolonged in both groups, it is still being higher in group II (medically refractory epilepsy). Comparison between characteristics of OSA in both groups: Number of patients with OSA having BMI> 30 Kg/m2 was found to be higher among medically controlled epilepsy (group I) patients with OSA. Compared with medically controlled patient with OSA, patients with refractory epilepsy and OSA had their first seizure at a younger age, with longer duration of epilepsy, with the Summary 93 majority had focal epilepsy (mainly temporal lobe epilepsy). Our study showed that patients with OSA in refractory epilepsy group were taking higher number of AEDs than those in controlled epilepsy group. Patients with medically refractory epilepsy and OSA reported more frequent sleep complaints, specifically, EDS. Classification of OSA: We found that 3 out of 5 refractory epilepsy patients (60%) had mild OSA, vs. 2 out of 3 patients in the controlled epilepsy group (66.7%). Regarding moderate OSA, we got 2 out of 5 refractory epilepsy patients (40%) vs. 1 patient (33.3%) of the medically controlled epilepsy group. Thus, refractory epilepsy patients tended to get more higher degrees of apnea, compared to the medically controlled epilepsy patients, which tended to show milder forms (yet, this was not significant statistically, P>0.05). Patients with OSA and medically refractory epilepsy showed also more decreased in the O2 level during sleep, compared to the controlled epilepsy group with OSA. Moreover, 2 out of 5 patients of the refractory group showed DROP of oxygen >70%, which signifies severe degrees of desaturation among those with refractory epilepsy and OSA. Yet, this was not statistically significant. Characteristics of patients with OSA in the controlled epilepsy group: Compared to well controlled epileptic patients without OSA, those with OSA were found to be older and heavier with delayed age of onset of epilepsy. Patients with OSA in group I reported more frequent sleep symptoms. Snoring was the most common symptom reported among those patients. Characteristics of patients with OSA in the refractory epilepsy group: Patients with OSA in the refractory epilepsy group were older, with delayed age of onset of epilepsy and longer duration of the illness, compared Summary 94 to those without OSA. Patients with OSA reported more sleep symptoms in the form of EDS and snoring. Predictors of AHI: It was found that age is independent risk factor of having OSA in the controlled epilepsy group. That, older patients tend to have higher AHI. On the other hand, it was found that age of patients, age of onset of epilepsy, duration of epilepsy are all independent factors in determining patients with OSA. We found that older subjects, with early onset of epilepsy, and shorter duration of the illness tend to have higher AHI. Case presentation: In our study, one patient diagnosed with OSA and refractory epilepsy was offered CPAP treatment for 3 months, along with his AEDs. Treatment of OSA with CPAP markedly reduced seizures frequency. In our study, both groups of patients reported sleep symptoms. Medically refractory epilepsy (group II) patients reported frequent snoring and EDS, which could be attributed to the presence of OSA in 5 patients in this group, and could also to the related to the use of polytherapy, including first generation AEDs, namely CBZ and VPA, which could suppress limb movement during sleep. Thus, self-reported EDS were not helpful in predicting OSA in medically controlled patients, possibly related to a ceiling effect of general sleepiness among epilepsy patients from diverse causes. On the other hand, medically controlled group (group I) reported frequent insomnia, which could be related to coexisting depression. Worth mentioning, that this group of patients showed on PSG, frequent limb movement and awakening and arousals, which may contribute to the occurrence of this insomnia. The increase in REM percentage among medically controlled epilepsy patients may be interpreted cautiously as a consequence of this insomnia. Summary 95 Whether medication are related or not to the insomnia encountered in this group of patients, is uncertain because of the variable effect of AEDs on REM sleep. In our study, the architecture of sleep of medically refractory epilepsy patients was markedly disturbed on seizure-free nights compared with medically controlled subjects with poorer efficiency of sleep and increased light sleep percentage among the patients with medically refractory epilepsy. We noted significant decrease in sleep latencies among our patients in both groups, which could be attributed to the effect of AEDs, especially CBZ and VPA. Our findings support previous studies that show a higher percentage of OSA in epilepsy patients (10% in medically controlled epilepsy patients and 16.6% in refractory epilepsy patients) compared to the general. Also, study revealed a higher prevalence of OSA in a group of adults with refractory epilepsy than those with medically controlled epilepsy, however, we did not find statistically significant higher OSA rate in refractory vs. well-controlled epilepsy patients. Nevertheless, this study suggests that OSA may be a contributing factor to worsening seizure control or new onset seizures in older adults. In our study we compared the characteristics of OSA between well-controlled and refractory epilepsy groups. In refractory epilepsy patients with OSA, we found significantly frequent sleep disturbance symptoms and younger age of seizure onset and frequent sleep symptoms compared with patients with coexisting medically controlled epilepsy and OSA. Also, we noted decreased O2 saturation to critical levels among patients with refractory epilepsy and OSA as compared to those in the medically controlled epilepsy group, which put this category of patients at risk. Summary 96 We hypothesize that the traditional risk factors of OSA do not apply to patients with refractory epilepsy, as we showed in our study, only 1 patient out of 5 patients with refractory epilepsy and OSA was obese (had BMI exceeding 30 kg/m2), while others indicating that BMI is not predictor of OSA, and not only obese patients with refractory epilepsy are at higher risk for OSA. On assessing predicting factors of OSA and increase AHI, we found that age is independent risk factor in both medically controlled and refractory epilepsy. Beside this, other factors are considered as predicting factors in our sample of refractory epilepsy patients, as the early age of onset of epilepsy, shorter duration of epilepsy, which is interpreted cautiously and needed to be confirmed in other studies We cannot ignore the role of first generation AEDs medications in the pathogenesis of OSA, particularly VA. Several factors could explain the observed increased prevalence of OSA in people with first generation AEDs, which may be related to the weight gain caused by VPA. This study is unique in that it compared sleep abnormalities in medically controlled epileptic patients, and refractory patients. Our study demonstrates that medical refractoriness in patients with epilepsy has a deleterious effect on sleep quality in general. Hence, treatment strategies specifically targeting refractory patients may bear the potential to improve sleep quality and contribute to overall improvement in quality of life. The use of CPAP in our refractory epilepsy patient with OSA significantly improved his seizure control. We suggest that in refractory epilepsy patients with diabetes specific attention should be focused on further sleep study tests. |