Chronotype variability in epilepsy and clinical significance: scoping review.

PURPOSE: Chronotype, which captures a person's daily preferences for activity and sleep, is still a poorly researched area in epilepsy research. Finding common chronotype characteristics in people with epilepsy (PWE) and explaining possible effects on seizure management are the main goals. METHODS: Eleven large-scale investigations from 2010 to 2023 were examined in this scoping review. These studies included 1.167 PWE and 4.657 control subjects. RESULTS: PWE had intermediate chronotypes more often than not. Adult patients were more morning-oriented overall, while pediatric cohorts were variable. Relationships between chronotype and seizure control were limited since only two studies in adults reported this and those results conflicted. An evening-type chronotype was found to be more common in generalized epilepsy than focal. The relationship of chronotype and specific antiseizure medication (ASM) therapy was not investigated. CONCLUSIONS: The majority of PWE displayed an intermediate chronotype, but analyses based on age showed more nuanced trends, with children displaying variable patterns, adults generally tending toward morningness, and generalized epilepsy being associated with eveningness. This review underscores the importance of more research on the complex connections between epilepsy outcomes and chronotype. It emphasizes the need to study larger samples of PWE with carefully documented seizure control and ASM therapy, including dose and timing of administration to better understand the role of chronotype on epilepsy outcomes.

Impact of the sleep apnea management group clinic on positive airway pressure adherence.

BACKGROUND: Positive airway pressure (PAP) adherence is critical for managing obstructive sleep apnea (OSA). We postulate that group-based Sleep Apnea Management (SAM) clinic, which harnesses the benefits of providing mutual support as well as facilitates access to system-based resources and education, will confer improvements in PAP adherence. METHODS: Data from SAM clinic attendees from January 2017 to June 2018 were retrospectively analyzed. Adherence data at SAM baseline visit and 1-3 months follow-up were collected. Average PAP usage from all-days and days used were analyzed along with demographics, co-morbidities, and Epworth Sleepiness Scale. Adherence was defined as >4 hours a night for ≥70% of nights over a 30-day period. Key structural elements of the SAM group clinic model were co-presence of the OSA care team members and peer group support. Key efficiency elements were group education and the prompt-to-patient multidisciplinary troubleshooting adherence barriers. RESULTS: Of 110 SAM clinic attendees, average age was 60.9±12.7 years, 53% were men, and 46% Caucasian. At baseline, the mean for average-all-days usage was 4.2 hours, mean average-days-used usage was 5.2 hours, and mean percentage-of-days usage ≥4 hours was 57%. At follow-up, the mean average-all-days usage increased 1.2 hours (p<0.001), mean average-days-used usage increased 0.8 hours (p<0.001), and the mean percentage-of-days with usage ≥4 hours increased 16% (p<0.001). At baseline, 46% of patients met criteria for adherence, which increased to 66% at follow-up. CONCLUSION: In this study, after the SAM clinic, all PAP adherence parameters improved significantly. This observational study serves as a proof of concept study for future trials pertaining to group clinic in managing PAP adherence in OSA.

Bidirectional relationships of sleep and epilepsy in adults with epilepsy.

This targeted review addresses the best accepted and most intriguing recent observations on the complex relationships between sleep and epilepsy. Ten to 15% of all epilepsies are sleep-related. Included in these is sleep-related hypermotor epilepsy, renamed from nocturnal frontal lobe epilepsy by a 2016 consensus conference since 30% of cases are extra-frontal, seizures are related to sleep rather than clock time, and the predominant semiology is hypermotor. Stereo-EEG is providing crucial insights into network activation in sleep-related epilepsies and definition of the epileptogenic zone. Pathologic high-frequency oscillations, a promising biomarker for identifying the epileptogenic zone, are most frequent in NREM sleep, lowest in wakefulness and REM sleep, similar to interictal epileptiform discharges (IEDs). Most sleep-related seizures are followed by awakening or arousal and IEDs cause arousals and increase after arousals, likely contributing to sleep/wake complaints. Sleep/wake disorders are 2-3 times more common in adults with epilepsy than the general population; these comorbidities are associated with poorer quality of life and may impact seizure control. Treatment of sleep apnea reduces seizures in many cases. An emerging area of research is in circadian biology and epilepsy. Over 90% of people with epilepsy have seizures with circadian periodicity, in part related to sleep itself, and the majority of SUDEP cases occur in sleep. Recognizing these bidirectional relationships is important for patient and caregiver education and counseling and optimizing epilepsy outcomes.

High prevalence of pathological alertness and wakefulness on maintenance of wakefulness test in adults with focal-onset epilepsy.

BACKGROUND: Excessive daytime sleepiness (EDS) is a common complaint in adults with epilepsy (AWE), but objective evaluation is lacking. We used the maintenance of wakefulness test (MWT) to objectively measure the ability of adults with focal-onset epilepsy to maintain wakefulness in soporific conditions. METHODS: Adults with epilepsy participating in a study investigating the effects of lacosamide on sleep and wakefulness underwent baseline ambulatory polysomnography (PSG)/EEG followed by MWT. Mean sleep latency (MSL) and mean percent sleep time (MST, mean percentage of non-wake EEG scored in 3-sec bins from lights out to sleep onset averaged over the 4 MWT trials) were quantified. Subjective sleepiness was assessed by the Epworth Sleepiness Scale (ESS). Spearman correlation and linear regression assessed relationships between MWT parameters, ESS and relevant sleep and epilepsy-related variables. RESULTS: Maintenance of wakefulness test MSL in 51 AWE (mean age 43.5 ±â€¯13 years, 69% female, mean BMI 24.6 ±â€¯11.2 kg/m2) was 21.7 ±â€¯11.9 min; 45.1% had an abnormally short MSL <19.4 min and 15.7% <8 min. MST was 9.3% [3.3, 19.1]. Mean ESS score was 8.8 ±â€¯5.7; 39% had elevated ESS (>10). No correlation between subjective ESS and objective MSL (p = 0.67) or MST (p = 0.61) was found. MSL was significantly shorter in subjects with focal to bilateral tonic-clonic seizures (FBTCS; 7.9 min [13.6, 22.3]) compared to those without (27.4 min [21.2, 33.6], p = 0.013). Younger subjects had shorter MSL; MSL increased 3.2 min for every 10-year increase in age. CONCLUSION: We found a high prevalence of objective sleepiness/difficulty maintaining wakefulness on the MWT and subjective sleepiness using the ESS in AWE without a correlation between the two. More severe objective sleepiness was found in subjects with a history of FBTCS and younger age. Further research is needed to determine mechanistic underpinnings and optimal measurements of pathological sleepiness in people with epilepsy given the burden of it on quality of life.

Prevalence of periodic limb movement in sleep in people with epilepsy: A semi-structured literature review.

OBJECTIVES: Epilepsy is a prevalent health problem worldwide in all ages, and it is essential to identify disease markers for diagnosis and treatment. Periodic limb movements in sleep (PLMS) are a common finding in polysomnography (PSG). Still, its clinical relevance in people with epilepsy (PWE) is unknown. The aim of this review was to compare PLMS frequency in PWE and controls. METHODS: A semi-structured literature review was conducted using PubMed in search of relevant studies in English on August 23, 2019, with the search terms "sleep," "epilepsy," or "seizure," and "polysomnography" in the title and/or abstract. The research was complemented with citation analysis and manual search using Google Scholar. Studies involved PWE and comparative controls using PSG with reported PLMS index (PLMI). RESULTS: Seven studies were identified. Only two showed a statistically significant difference in PLMI between cases and controls, and in another study, cases had uncontrolled seizures. In general, studies did not adjust for potential confounders including demographics, apnea-hypopnea index, or medication use. CONCLUSIONS: We found few studies exploring the prevalence of PLMS in PWE. In the majority, PLMI did not differ from controls. Further studies are warranted given the prevalence of sleep disturbances in epilepsy.

The Epworth Sleepiness Scale in epilepsy: Internal consistency and disease-related associations.

BACKGROUND: The Epworth Sleepiness Scale (ESS) is the most common instrument for measuring subjective sleep propensity in people with epilepsy but has not yet been validated in this population. STUDY OBJECTIVES: We aimed to systematically assess the validity, performance, and internal consistency of the ESS, as well as correlations between the ESS and disease-specific variables and patient-reported outcome measures in a cohort of adults with epilepsy (AWE). METHODS: Ninety-five AWE completed sleep and seizure diaries, in-laboratory polysomnography (PSG) and patient-reported outcome measures, including the ESS, Insomnia Severity Index (ISI), and the Beck Depression Inventory (BDI). Demographic information and data from 95 matched controls referred for PSG for suspected obstructive sleep apnea (OSA) was taken from the electronic medical record. Frequencies of high ESS item ratings (item score ≥2) were calculated for each group. Cronbach's α and factor analysis were performed to assess the internal consistency and validity of the ESS within cases and controls. Multivariable linear models were used to assess the association between ESS and predictors of interest, adjusting for demographic and disease-specific variables, including seizure type, frequency, and anti-seizure medication (ASM) therapy. RESULTS: While suspected OSA controls had significantly greater mean ESS total scores (9.9 vs 7.9, p = 0.004) and proportion with ESS >10 (42% vs 25%, p = 0.014), there were no significant differences in the severity of item responses, with the exception of "lying down to rest in the afternoon when circumstances permit," for which more controls rated as likely/very likely (79% vs 64%), p = 0.024). AWE with ESS >10 had higher mean standardized ASM dose (2.5 vs 1.7, p = 0.026). All ESS items were significantly correlated with the total score within each group. Cronbach's α was 0.75 for cases and 0.85 for controls, indicating good internal consistency of the ESS for both groups. After adjusting for demographic and sleep characteristics, higher ESS scores were associated with greater insomnia scores on the ISI (p = 0.024) and depressive symptoms on the BDI (p = 0.018). CONCLUSIONS: This study provides validity for the use of the ESS in adult populations with epilepsy.

Subjective and objective hypersomnia highly prevalent in adults with epilepsy.

INTRODUCTION: Sleepiness is among the most common complaints of people with epilepsy, but objective documentation is lacking. We systematically investigated subjective and objective sleepiness in an observational cross-sectional cohort of adults with epilepsy (AWE). METHODS: This is a prospective study of AWE consecutively recruited without foreknowledge of sleep/wake complaints. Polysomnography (PSG) with 18-channel electroencephalography (EEG) followed by multiple sleep latency testing (MSLT) was performed. Patients completed the Epworth Sleepiness Scale (ESS), a single-item question assessing excessive daytime sleepiness (EDS), and a 7-day sleep and seizure diary. Multivariable linear models were used to assess the association between MSLT mean sleep latency (MSL) and interests with adjustment of covariates of interest. Receiver operating characteristics (ROC) analysis was performed to evaluate the discrimination capability of ESS on MSL < 8 min and <5 min and investigate the optimal cutpoints. RESULTS: Among 127 AWE (mean age: 38.7 ±â€¯13.7 years), abnormal MSL (<8 min) was observed in 49.6% and MSL <5 min in 31.5%. While 78% reported feeling sleepy during the day on a single-item question, only 24% had elevated scores on the ESS (>10/24). The ESS score was associated with MSL even after adjusting for seizure frequency, antiseizure medication (ASM) standardized dose and number, age, gender, depression and insomnia symptom severity, and apnea-hypopnea index (HPI) and total sleep time on PSG (coefficients [95% confidence interval (CI)]: -0.26 [-0.48, -0.05], p = 0.018). The area under the curve (AUC) of the ESS ROC predicting MSL < 8 min and MSL < 5 min were similar: 0.62 (95%CI: 0.52-0.72) and 0.62 (95%CI: 0.51-0.74). CONCLUSIONS: This is the largest prospective cross-sectional observational study to date using MSLT in AWE. We found subjective and objective daytime sleepiness highly prevalent in AWE and not explained by seizure frequency, ASM burden, symptoms of insomnia/depression, or PSG findings although those with MSL < 5 min were more likely to have obstructive sleep apnea (OSA). Pathologic sleepiness with MSL < 8 min was present in half of AWE. Nearly one-third of AWE unselected for sleep/wake complaints had MSL < 5 min, a range typical of narcolepsy.

Depression score changes in response to sleep disordered breathing treatment with positive airway pressure in a large clinic-based cohort.

OBJECTIVE: The clinical-population impact of positive airway pressure (PAP) on depressive symptoms in sleep disordered breathing (SDB) awaits clear documentation. We hypothesized that depressive symptoms improve in response to PAP treatment in a large clinical setting, and that lower socio-economic status poses barriers to full therapeutic response. METHOD: We performed a retrospective cohort study of SDB patients attending a tertiary ambulatory sleep center between January 1, 2010 and December 31, 2015. Data extracted from electronic health records included Patient Health Questionnaire-9 (PHQ-9) scores, demographic characteristics, PAP adherence, and medical history. Paired- and two-sample t tests were utilized to assess changes in PHQ-9 score according to PAP adherence. Linear regression models were constructed to evaluate the association of socioeconomic status (SES) and other clinical variables on PHQ-9 scores. RESULTS: The cohort consisted of 1981 SDB patients (56.4 ± 13.3 years; 45.7% female; 76.2% Caucasian). Regardless of adherence, PAP therapy improved PHQ-9 scores (- 2.4 ± 4.6, p < 0.0001), with more robust responses in patients with baseline PHQ-9 scores > 10 (- 4.8 ± 5.7; p < 0.0001). Adherent patients had significantly greater improvement (- 2.8 ± 4.4 vs. 1.6 + 4.2, p < 0.0001), and even greater benefit if baseline PHQ-9 was > 10 (-6.0 ± 5.3 vs. - 3.8 ± 4.9, p < 0.001). Patients from lower socioeconomic status and greater depressive symptom had worse post-PAP PHQ-9 scores. CONCLUSIONS: PAP therapy and adherence were associated with improvement in depressive symptom severity in this clinical cohort. Patients with lower socioeconomic status derived less therapeutic benefit, suggesting that they faced additional barriers to treatment effectiveness.

Longitudinal assessment of excessive daytime sleepiness in early Parkinson's disease.

BACKGROUND: Excessive daytime sleepiness (EDS) is common and disabling in Parkinson's disease (PD). Predictors of EDS are unclear, and data on biological correlates of EDS in PD are limited. We investigated clinical, imaging and biological variables associated with longitudinal changes in sleepiness in early PD. METHODS: The Parkinson's Progression Markers Initiative is a prospective cohort study evaluating progression markers in participants with PD who are unmedicated at baseline (n=423) and healthy controls (HC; n=196). EDS was measured with the Epworth Sleepiness Scale (ESS). Clinical, biological and imaging variables were assessed for associations with EDS for up to 3 years. A machine learning approach (random survival forests) was used to investigate baseline predictors of incident EDS. RESULTS: ESS increased in PD from baseline to year 3 (mean±SD 5.8±3.5 to 7.55±4.6, p<0.0001), with no change in HC. Longitudinally, EDS in PD was associated with non-tremor dominant phenotype, autonomic dysfunction, depression, anxiety and probable behaviour disorder, but not cognitive dysfunction or motor severity. Dopaminergic therapy was associated with EDS at years 2 and 3, as dose increased. EDS was also associated with presynaptic dopaminergic dysfunction, whereas biofluid markers at year 1 showed no significant associations with EDS. A predictive index for EDS was generated, which included seven baseline characteristics, including non-motor symptoms and cerebrospinal fluid phosphorylated-tau/total-tau ratio. CONCLUSIONS: In early PD, EDS increases significantly over time and is associated with several clinical variables. The influence of dopaminergic therapy on EDS is dose dependent. Further longitudinal analyses will better characterise associations with imaging and biomarkers.

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.

"Go! to Sleep": A Web-Based Therapy for Insomnia.

BACKGROUND: Insomnia is a common complaint of individuals presenting to healthcare providers and is associated with decreased quality of life and higher healthcare utilization. In-person cognitive behavioral therapy (CBT) is an effective treatment for insomnia but is hindered by cost and limited access to treatment. Initial research suggests that Web-based CBT may mitigate these obstacles. INTRODUCTION: This study tests the effectiveness of a Web-based program for insomnia based on principles of CBT and stress management. MATERIALS AND METHODS: We conducted a randomized trial with wait-list controls among adults with primary insomnia (n = 88). Two hundred sixty-three adults with comorbid insomnia were also included and analyzed separately. The intervention was a 6-week online program, and effectiveness was measured via the Insomnia Severity Index (ISI). RESULTS: Baseline ISI score for the intervention group (n = 43) was 17.0; 16.6 for the control group (n = 45). At first follow-up, the intervention group (n = 25) had a mean change from baseline of -7.3 (95% CI: -9.0, -5.6), sustained through second follow-up, while the control group (n = 35) had a change of -1.3 (-2.7, 0.1). The between-group difference was statistically significant (p < 0.001). Participants in the comorbid insomnia group had a baseline ISI score of 16.7 with improvement similar to the primary insomnia group (-6.9; -7.6, -6.2). DISCUSSION: We observed clinically meaningful improvements in insomnia severity in adults with primary or comorbid insomnia. Sustained improvement over 4 months underscores the effectiveness of a well-constructed online CBT for insomnia program. CONCLUSIONS: Go! to Sleep

Frequency of Restless Legs Syndrome in adults with epilepsy in Turkey.

BACKGROUND: Restless Legs Syndrome (RLS) is a common disorder characterized by an irresistible urge to move the legs particularly during rest in the evenings often leading to insomnia and daytime impairment. No prior studies estimate the prevalence of RLS in a diverse sample of adults with epilepsy using standard diagnostic criteria. MATERIAL AND METHOD: A total of 225 patients with epilepsy (61.8% female; mean age 33.3 ± 12.3 years) seen in the epilepsy clinic of Çukurova University Neurology Department were included. Restless Legs Syndrome diagnosis was based on structured interviews using internationally accepted criteria. Demographic and epilepsy-related variables were obtained through medical record review. RESULTS: The prevalence of RLS was 5.8% (n=13). Mean score on the International RLS Study Group rating scale for these subjects was 9.3 ± 3.6 (6-18). Ten (76.9%) patients with RLS scored in the mild range and the remainder in the moderate range of severity. Patients with RLS were not significantly different from others in terms of demographics, epilepsy classification or duration, treatment regimen (polytherapy vs. monotherapy), patient-reported sleep assessment, or relevant laboratory data. CONCLUSION: The prevalence of RLS in adults with epilepsy was similar to that observed in the adult general Turkish population (3.18-5.2%), although we excluded subjects with conditions associated with RLS, rendering ours a conservative estimate. While preliminary, these findings support the need for future studies exploring RLS in epilepsy given the potential impact of untreated sleep disorders and sleep deprivation on seizures and quality of life in people with epilepsy.

Lacosamide tolerability in adult patients with partial-onset seizures: Impact of planned reduction and mechanism of action of concomitant antiepileptic drugs.

OBJECTIVE: We evaluated the impact of planned dose reduction and mechanism of action of concomitant AEDs on tolerability in adults with partial-onset seizures undergoing lacosamide (LCM) titration. METHODS: Data were collected at baseline and 3-6 and 12-24 months post-LCM initiation. Subjects were categorized as having planned reduction of concomitant AEDs or not; AEDs were categorized as traditional sodium channel blockers (TSCB) or non-TSCB (NTSCB). Groups with/without planned reduction were compared on the presence and number of treatment-emergent adverse events (TEAEs) using chi-square tests or logistic regression and on time to LCM discontinuation with time-to-event methods controlling for standardized (STD) AED dose, a measure of concomitant AED load. Similar analyses were performed comparing subjects taking TSCB and NTSCB agents and used to identify relationships with ≥50% decreases in seizure frequency. RESULTS: One hundred six adults (mean age 41.4 ± 13.4; 50% male) underwent LCM titration from June 2009-2011 with complete data. Reduction of concomitant AEDs was planned at the time of LCM initiation in 59 (55.7%) subjects. Fewer subjects with planned reduction had TEAEs (49.2% vs. 68.1%; p=0.05), and these subjects had a lower risk of TEAEs (OR 0.36; p=0.019) after adjusting for STD AED dose. The hazard ratio (95% CI) for LCM discontinuation was 0.46 (0.23, 0.94) in subjects with planned reduction of concomitant AEDs vs. others (p=0.033) and 3.29 (1.01, 10.70) in subjects taking TSCB vs. NTSCB agents (p=0.048). Among all cases, those who ever had TEAEs had significantly higher STD dose at both follow-up visits (p=0.033 and p=0.023, respectively). Seizure outcomes were not significantly different between groups at the last follow-up assessment. SIGNIFICANCE: Planned reduction of concomitant AEDs during LCM initiation and the use of NTSCB agents only are associated with a reduced risk of TEAEs and LCM discontinuation in adults with partial-onset seizures. This study extends prior observations by considering total AED load in the assessment of tolerability and supports the benefits of early reduction of concomitant AEDs during LCM initiation.

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.

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.

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.

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.

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.

Validation of the Patient Health Questionnaire-9 (PHQ-9) for depression screening in adults with epilepsy.

OBJECTIVE: This study aimed to assess the accuracy and operating characteristics of the Patient Health Questionnaire-9 (PHQ-9) for depression screening in adults with epilepsy. METHODS: Tertiary epilepsy center patients served as the study population, with 237 agreeing to structured interview using the Mini-International Neuropsychiatric Interview (MINI), a "gold standard" instrument developed for rapid diagnosis of neuropsychiatric disorders, including major depressive disorder (MDD); 172 also completed the PHQ-9, and 127 completed both the PHQ-9 and the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) within two days of the MINI. Sensitivity, specificity, positive and negative predictive values, and areas under the ROC curves for each instrument were determined. Cut-points of 10 for the PHQ-9 and 15 for the NDDI-E were used, and ratings at or above the cut-points were considered screen-positive. The PHQ-9 was divided into cognitive/affective (PHQ-9/CA) and somatic (PHQ-9/S) subscales to determine comparative depression screening accuracy. RESULTS: The calculated areas under the ROC curves for the PHQ-9 (n=172) and the PHQ-9/CA and PHQ-9/S subscales were 0.914, 0.924, and 0.846, respectively, with the PHQ-9 more accurate than the PHQ-9/S (p=0.002) but not different from the PHQ-9/CA (p=0.378). At cut-points of 10 and 15, respectively, the PHQ-9 had higher sensitivity (0.92 vs 0.87) but lower specificity (0.74 vs 0.89) compared with the NDDI-E. The areas under the ROC curves of the PHQ-9 and the NDDI-E showed similar accuracy (n=127; 0.930 vs 0.934; p=0.864). SIGNIFICANCE: The PHQ-9 is an efficient and nonproprietary depression screening instrument with excellent accuracy validated for use in adult patients with epilepsy as well as multiple other medical populations.