Noah Andrews

Sleep apnea and epilepsy: Who's at risk?

Obstructive sleep apnea (OSA) is highly prevalent, affecting 25% of men and 10% of women. Treatment reduces seizures in some patients. Awareness of the comorbidity of sleep disturbances in epilepsy has been increasing. No study has explored OSA predictors in patients unselected for epilepsy severity and sleep disorder symptoms. We assessed cross-sectional OSA prevalence and predictors (apnea-hypopnea index [AHI] ≥10) in 130 consecutive adults using structured interview, subjective assessments, and polysomnography. Obstructive sleep apnea prevalence was 30%, 16% having moderate-severe disease, rates that markedly exceed general population estimates. Obstructive sleep apnea predictors in multivariate modeling included age, dental problems, and standardized AED dose. Male gender, older age, higher BMI, hypertension, and dental problems were associated with higher AHI. Adults with epilepsy appear at increased risk for OSA, increasing with age and AED load, regardless of gender, BMI, and seizure frequency. These findings support the implementation of routine OSA screening in adult epilepsy clinics.

Effect of positive airway pressure therapy on seizure control in patients with epilepsy and obstructive sleep apnea.

Previous studies suggest that treatment for obstructive sleep apnea (OSA) in patients with epilepsy can improve seizure control. We investigated the effect of positive airway pressure (PAP) therapy on seizures in adults with epilepsy referred to the Cleveland Clinic for polysomnography (PSG) from 1997 to 2010. Seizure outcome at baseline and 1 year later was compared in patients with no OSA (apnea-hypopnea index [AHI] <5), patients with PAP-treated OSA, and patients with untreated OSA. One hundred thirty-two subjects (age: 40.2±13 (18-76) years, 65.4% female) were included. Seventy-six (57.6%) subjects had OSA; of these, 43 (56.6%) were on PAP therapy, and 33 (43.4%) were not on PAP therapy (either PAP-intolerant or refused therapy). Of the group with PAP-treated OSA, 83.7% were adherent (use ≥4 h/night at least 5 nights/week). The percentage of subjects with ≥50% seizure reduction and the mean percentage of seizure reduction were significantly greater in the group with PAP-treated OSA (73.9%; 58.5%) than in subjects with untreated OSA (14.3%; 17.0%). There were significantly more subjects with successful outcomes (with ≥50% seizure reduction or seizure-free at both baseline and follow-up) in the group with PAP-treated OSA (83.7%) than in the groups with no OSA (53.6%) and untreated OSA (39.4%). After adjusting for age, gender, body mass index, AHI, and epilepsy duration, we found that the odds of successful outcomes in subjects in the group with PAP-treated OSA were 9.9 and 3.91 times those of the groups with untreated OSA and no OSA, respectively. The group with PAP-treated OSA had 32.3 times the odds of having a ≥50% seizure reduction compared with the group with untreated OSA and 6.13 times compared with the group with no OSA. Positive airway pressure therapy appears to produce beneficial effects on seizures in adult patients with epilepsy and OSA.

Continuous positive airway pressure therapy for obstructive sleep apnea reduces interictal epileptiform discharges in adults with epilepsy.

Obstructive sleep apnea (OSA) is highly prevalent, affecting 25% of men and 10% of women. We recently reported a prevalence of OSA of 30% among 130 adults with epilepsy unselected for sleep disorder complaints, including 16% with moderate-to-severe disease, rates that markedly exceed general population estimates. Treatment of OSA with continuous positive airway pressure (CPAP) therapy or upper airway surgery reduces seizures in many cases. A single study reported a reduction in interictal spike rate with CPAP in 6 patients with OSA. We explored the effect of CPAP therapy on spike rate in 9 adults with epilepsy and OSA. Interictal epileptiform discharges were quantified during a diagnostic polysomnogram (PSG) and a second PSG using therapeutic CPAP. Spike rates were calculated for each recording during wake and sleep stages. Continuous positive airway pressure therapy was associated with significant reductions in median (quartiles) spike rate overall (77.9 [59.7-90.7] %), in wakefulness (38.5 [0.3-55] %), and in sleep (77.7 [54.8-94.7] %) but not in REM sleep. Continuous positive airway pressure therapy also produced a significant improvement in oxygen saturation and arousals. Our work extends a single prior observation demonstrating beneficial effects of CPAP therapy on interictal EEG in patients with epilepsy with comorbid OSA and supports the hypothesis that sleep fragmentation due to OSA contributes to epileptogenicity.

Functional Outcomes in Patients with REM-Related Obstructive Sleep Apnea Treated with Positive Airway Pressure Therapy

STUDY OBJECTIVES To evaluate functional outcomes in adults with REM-related obstructive sleep apnea (OSA) treated with positive airway pressure (PAP) therapy. DESIGN Retrospective observational study. SETTING Outpatient sleep clinic. PATIENTS 330 adults (171 males) with OSA receiving PAP therapy, including 130 with REM OSA and 200 with OSA not restricted to REM. MEASUREMENTS AND RESULTS REM OSA was defined as a REM apnea-hypopnea index (AHI) / NREM AHI > 2 and NREM AHI < 15. Patients had baseline and post-PAP functional outcomes, including Epworth Sleepiness Scale (ESS), Fatigue Severity Scale (FSS), Patient Health Questionnaire-9 (PHQ-9), and Functional Outcomes Sleep Questionnaire (FOSQ) scores. We compared functional outcomes, demographic, clinical and polysomnographic features, and PAP adherence in patients with REM OSA and OSA not restricted to REM. Female gender was significantly more common in REM OSA. Age, BMI, neck girth, and baseline ESS, FSS, PHQ-9, and FOSQ were similar between groups. Smoking history and comorbid disorders were also similar except for a higher prevalence of depression and cardiovascular disease in OSA not restricted to REM. All functional outcomes improved significantly after PAP therapy in both groups. Change from baseline to post treatment was similar for all functional outcomes between groups. CONCLUSIONS The study is the first addressing clinical outcomes in REM OSA using validated measures. Functional outcomes in patients with REM OSA improve after treatment with PAP therapy comparable to that observed in patients with OSA not restricted to REM. COMMENTARY A commentary on this article appears in this issue on page 249.

Use of the Sleep Apnea Scale of the Sleep Disorders Questionnaire (SA-SDQ) in adults with epilepsy

OBJECTIVE A growing body of literature supports the importance of sleep comorbidities in epilepsy. The prevalence of obstructive sleep apnea (OSA) in adults with epilepsy exceeds that of the general population, and its presence adversely impacts seizure control in some cases. The Sleep Apnea Scale of the Sleep Disorders Questionnaire (SA-SDQ) is a 12-item screening instrument generally used in clinical research. One prior study suggested modified cutoffs for the prediction of OSA in adults with epilepsy using this instrument. Our purpose was to further investigate the validity of the SA-SDQ in adults with epilepsy. METHODS Ninety adults with epilepsy who underwent polysomnography (PSG) completed the SA-SDQ. Receiver operating characteristics were constructed to assess optimal sensitivity and specificity for predicting OSA (apnea-hypopnea index [AHI]≥5). RESULTS Obstructive sleep apnea was diagnosed in 40 (44.4%) subjects. The overall area under the curve for the diagnosis of OSA was 0.771 (0.926 for males, 0.687 for females). For all subjects, a SA-SDQ cutoff score of 25 provided good sensitivity (73%) and specificity (72%) for OSA diagnosis. The same cutoff score provided optimal sensitivity (94%) and specificity (83%) for males, whereas for females, it provided lower sensitivity (55%) and specificity (68%). In females, a cutoff of 24 improved sensitivity (68%) but not specificity (58%). For all subjects with moderate-to-severe OSA (AHI≥15), the area under the curve was 0.766, and the optimal cutoff was 28. SIGNIFICANCE Our work confirms the validity of the SA-SDQ as a screening instrument for OSA in clinical research involving adults with epilepsy. Further, our findings support the use of cutoffs lower than those applied to the general population and a single cutoff score (25) for predicting any severity of OSA in adults with epilepsy.

Severity of self-reported insomnia in adults with epilepsy is related to comorbid medical disorders and depressive symptoms

BACKGROUND Few studies have systematically investigated insomnia in adults with epilepsy. METHODS We performed a prospective cross-sectional investigation of the prevalence, severity, and comorbidities of insomnia in 90 adults with epilepsy using a battery of self-reported instruments and polysomnography. We quantified insomnia severity using the Insomnia Severity Index (ISI). RESULTS Fifty-nine of 90 (65.5%) adults with epilepsy reported insomnia (ISI≥8), moderate or severe (ISI≥15) in 28.9%. Good agreement between standard clinical diagnostic criteria and ISI was found for patients with ISI scores <8 and ≥15. Scores on the modified Beck Depression Inventory (mBDI) (r=0.25, p=0.021), the original BDI (r=0.32, p=0.002), and self-reported total sleep duration (TSD) (r=-0.3, p=0.006) were significantly related to ISI score. A multiple regression model found that decreased TSD (ß=-0.93, p=0.007), head trauma (ß=4.37, p=0.003), sedative-hypnotic use (ß=4.86, p=0.002), AED polytherapy (ß=3.52, p=0.005), and asthma/COPD (ß=3.75, p=0.014) were predictors of a higher ISI score. For 63 patients with focal epilepsy, an increased mBDI (ß=0.24, p=0.015), decreased TSD (ß=-1.11, p=0.008), asthma/COPD (ß=4.19, p=0.02), and epilepsy surgery (ß=5.33, p=0.006) were significant predictors of an increased ISI score. Patients with temporal lobe epilepsy (TLE) showed a trend for greater severity compared with those with extra-TLE (ß=-2.92, p=0.054). CONCLUSIONS Our findings indicate that severity of insomnia in adults with epilepsy is more likely to be associated with comorbid medical and depressive symptoms and less likely to be directly related to epilepsy. Good agreement between standard clinical diagnostic criteria for insomnia and the ISI for subjects without insomnia symptoms and for those with moderate-to-severe symptoms supports the use of this instrument in epilepsy research.

Prevalence of Undetected Sleep Apnea in Patients Undergoing Cardiovascular Surgery and Impact on Postoperative Outcomes.

STUDY OBJECTIVE We examined the prevalence of obstructive sleep apnea (OSA) among patients undergoing cardiac surgery and its impact on postoperative outcomes. METHODS Subjects were recruited from inpatient cardiovascular surgery units at two tertiary care centers. Crystal Monitor 20-H recorded polysomnograms preoperatively. Regression analyses were performed to explore associations between OSA using different apnea-hypopnea index (AHI) cutoffs and postoperative outcomes adjusting for key covariates. Prevalence of postoperative outcomes was compared among groups defined by AHI and left ventricle ejection fraction (LVEF) median cutoffs. RESULTS Of 107 participants, the AHI was ≥ 5 in 79 (73.8%), ≥ 10 in 63 (58.9%), ≥ 15 in 51(47.7%), and ≥ 30 in 29 (27.1%). Patients with AHI ≥ 15 had significantly lower LVEF (p < 0.001). Logistic regression analyses with OSA cutoffs as above adjusting for age, gender, race, BMI, and LVEF found no significant increase in odds for any postoperative outcomes. No significant differences were found in %Total sleep time (TST) with SpO2 < 90% between AHI or LVEF groups, or by presence/absence of complications. Patients with any amount of TST with SpO2 < 90% had greater BMI, longer OR tube time, and greater prevalence of prolonged intubation (p = 0.007, 0.035, 0.038, respectively). CONCLUSIONS OSA is highly prevalent in patients undergoing cardiovascular surgery. It could not be shown that OSA was significantly associated with adverse postoperative outcomes, but this may have been due to an insufficient number of subjects. AHI ≥ 15 was associated with lower LVEF. Larger samples are required to explore the impact of OSA on key postoperative outcomes that have clinical and economic importance in the care of cardiovascular surgery populations. COMMENTARY A commentary on this article appears in this issue on page 1081.

Impact of sleep duration on seizure frequency in adults with epilepsy: A sleep diary study

BACKGROUND Prolonged sleep deprivation activates epileptiform EEG abnormalities and seizures in people with epilepsy. Few studies have addressed the effect of chronic partial sleep deprivation on seizure occurrence in populations with epilepsy. We tested the primary hypothesis that partial sleep deprivation over 24- and 72-hour periods increases seizure occurrence in adults with epilepsy. METHODS Forty-four subjects completed a series of self-reported instruments, as well as 1-month sleep and seizure diaries, to characterize their sleep and quality of life. Diaries were used to determine the relationship between seizure occurrence and total sleep time 24 and 72h before seizure occurrence using random effects models and a logistic regression model fit by generalized estimating equations. RESULTS A total of 237 seizures were recorded during 1295 diary days, representing 5.5±7.0 (mean±SD) seizures per month. Random effects models for 24- and 72-hour total sleep times showed no clinically or statistically significant differences in the total sleep time between preseizure periods and seizure-free periods. The average 24-hour total sleep time during preseizure 24-hour periods was 8min shorter than that during seizure-free periods (p=0.51). The average 72-hour total sleep time during preseizure periods was 20min longer than that during seizure-free periods (p=0.86). The presence of triggers was a significant predictor of seizure occurrence, with stress/anxiety noted most often as a trigger. Mean total sleep time was 9h, and subjects took an average of 12±10 naps per month, having a mean duration of 1.9±1.2h. Daytime sleepiness, fatigue, and insomnia symptoms were commonly reported. CONCLUSIONS Small degrees of sleep loss were not associated with seizure occurrence in our sample of adults with epilepsy. Our results also include valuable observations of the altered sleep times and frequent napping habits of adults with refractory epilepsy and the potential contribution of these habits to quality of life and seizure control.

Wake up to sleep: The effects of lacosamide on daytime sleepiness in adults with epilepsy.

OBJECTIVE The objective of the study was to investigate the effects of lacosamide (LCM) on daytime sleepiness ascertained by the Epworth Sleepiness Scale (ESS) in adults with focal epilepsy in a randomized, controlled design. METHODS Subjects taking ≤2 AEDs for ≥4weeks underwent polysomnography with EEG followed by the maintenance of wakefulness test (MWT) and completed the ESS and other patient-reported outcomes (PROs) at baseline, LCM 200mg/day, and LCM 400mg/day (Visit 4; V4). Primary endpoint was ESS change (V4 to baseline) between LCM and placebo. Noninferiority test on ESS used a one-sided t-test based on a hypothesized difference of 4-point change between groups. Superiority test used a two-sided t-test to investigate the difference in change in PROs and MWT mean sleep latency (MSL) between groups. Fifty-five subjects provided 80% power to show noninferiority of LCM assuming 10% dropout. RESULTS Fifty-two subjects (mean age: 43.5±13.2years, 69% female, median monthly seizure frequency: 1 [0, 4.0]) participated. Baseline group characteristics including age, sex, ethnicity, standardized AED dose, seizure frequency, and ESS were similar. Abnormal baseline ESS scores were found in 35% of subjects. Noninferiority test found a ≤4-point increase in ESS (mean [95% CI]) in LCM subjects vs. placebo (-1.2 [-2.9, 0.53] vs. -1.1 [-5.2, 3.0], p=0.027) at V4. No significant difference in change in PROs, MSL, seizure frequency, or AED standardized dose was observed between groups. SIGNIFICANCE Our interventional trial found that LCM is not a major contributor to daytime sleepiness based on subjective and objective measures. Inclusion of sleepiness measures in AED trials is warranted given the high prevalence of sleep-wake complaints in people with epilepsy.