الفهرس 
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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
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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
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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
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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.
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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.
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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.