Milena Pavlova

Sleep Restriction for 1 Week Reduces Insulin Sensitivity in Healthy Men

OBJECTIVE Short sleep duration is associated with impaired glucose tolerance and an increased risk of diabetes. The effects of sleep restriction on insulin sensitivity have not been established. This study tests the hypothesis that decreasing nighttime sleep duration reduces insulin sensitivity and assesses the effects of a drug, modafinil, that increases alertness during wakefulness. RESEARCH DESIGN AND METHODS This 12-day inpatient General Clinical Research Center study included 20 healthy men (age 20–35 years and BMI 20–30 kg/m2). Subjects spent 10 h/night in bed for ≥8 nights including three inpatient nights (sleep-replete condition), followed by 5 h/night in bed for 7 nights (sleep-restricted condition). Subjects received 300 mg/day modafinil or placebo during sleep restriction. Diet and activity were controlled. On the last 2 days of each condition, we assessed glucose metabolism by intravenous glucose tolerance test (IVGTT) and euglycemic-hyperinsulinemic clamp. Salivary cortisol, 24-h urinary catecholamines, and neurobehavioral performance were measured. RESULTS IVGTT-derived insulin sensitivity was reduced by (means ± SD) 20 ± 24% after sleep restriction (P = 0.001), without significant alterations in the insulin secretory response. Similarly, insulin sensitivity assessed by clamp was reduced by 11 ± 5.5% (P < 0.04) after sleep restriction. Glucose tolerance and the disposition index were reduced by sleep restriction. These outcomes were not affected by modafinil treatment. Changes in insulin sensitivity did not correlate with changes in salivary cortisol (increase of 51 ± 8% with sleep restriction, P < 0.02), urinary catecholamines, or slow wave sleep. CONCLUSIONS Sleep restriction (5 h/night) for 1 week significantly reduces insulin sensitivity, raising concerns about effects of chronic insufficient sleep on disease processes associated with insulin resistance.

Sleep debt and depression in female college students.

The objective of the study was to evaluate relationships between sleep habits and depressive symptoms. Pilot study data were collected about sleep schedules, related factors and depression in female college students to find whether their sleep schedules correlate with affective symptoms. In the subsequent main study, similar information was collected under more controlled conditions. Depression was measured using the CES-D (Center for Epidemiologic Studies Depression Scale) and HAM-D-3 (modified Hamilton Depression Rating Scale). Response rates were 31.3% of eligible students for the pilot survey and 71.6% for the main study. Both studies showed that about 20% of students reported weekday sleep debts of greater than 2 h and about 28% reported significantly greater sleep debt and had significantly higher depression scores (P<0.0001) than other students. Melancholic symptoms indicated by high CES-D scores (>24), were observed in 24% of students. Sleep problems explained 13% of the variance for both the CESD scale and the HAM-D-3 scale. Among female college students, those who report a sleep debt of at least 2 h or significant daytime sleepiness have a higher risk of reporting melancholic symptoms than others.

Self-reported hyperarousal traits among insomnia patients

Hyperarousal Scale scores for certain self-reported behaviors reportedly correlate with EEG arousal measures. We tested whether an insomnia subject group had different Hyperarousal Scale scores compared with hypersomnia, delayed sleep phase syndrome, procrastinator or normal subject groups. Compared with 139 normal subjects, mean scores for a group of 256 insomnia subjects was significantly 1.2 S.D. higher on Hyperarousal total scale score, 0.82 S.D. higher on React subscale score and 0.85 S.D. higher on Introspectiveness subscale score. The insomnia group median Extreme score was 2.25 times that of the normal group. These self-report findings suggest that insomnia subjects may be more responsive generally. All sleep disorder groups had increased total Hyperarousal scores, although these increases were accounted for by different scale items. The procrastinator group had Hyperarousal score patterns that generally differed from those of the other groups.

Treatment of delayed sleep phase syndrome

Delayed sleep phase syndrome (DSPS) is a common but little reported cause of severe insomnia. Affected individuals complain of difficulty falling asleep and difficulty awaking at socially acceptable hours. It results from a dysregulation of the circadian sleep-wake cycle. DSPS presents in clinically heterogenous ways as modulated by motivation, psychopathology, drug status, and treatment compliance factors. Patients respond variably to the range of possible treatments. Bright light treatment potentially corrects the circadian abnormality of DSPS. Other treatments reported to relieve some DSPS patients include schedule shifts, drugs, and vitamin and hormone treatments. The safety and efficacy of light treatment have not been conventionally defined, but available information suggests that it is ophthalmologically safe. At present, DSPS must be managed empirically by various methods.

IS THERE A CIRCADIAN VARIATION OF EPILEPTIFORM ABNORMALITIES IN IDIOPATHIC GENERALIZED EPILEPSY

Epileptiform abnormalities often occur at specific times of day or night, possibly attributable to state of consciousness (sleep vs. wake) and/or influences from the endogenous circadian pacemaker. In this pilot study we tested for the existence of circadian variation of interictal epileptiform discharges (IEDs), independent of changes in state, environment, or behavior. Five patients with generalized epilepsy underwent a protocol whereby their sleep/wake schedule was evenly distributed across the circadian cycle while undergoing full-montage electroencephalography and hourly plasma melatonin measurements. Light was <8 lux to prevent circadian entrainment. All patients completed the protocol, testifying to its feasibility. All patients had normal circadian rhythmicity of plasma melatonin relative to their habitual sleep times. In the three patients with sufficient IEDs to assess variability, most IEDs occurred during non-rapid eye movement (NREM) sleep (ratio NREM:wake=14:1, P<0.001). In both patients who had NREM at all circadian phases, there was apparent circadian variation in IEDs but with different phases relative to peak melatonin.

Diurnal pattern of seizures outside the hospital Is there a time of circadian vulnerability

Objective: To evaluate whether the distribution of seizures throughout the day is the same in ambulatory outpatient conditions as observed in inpatient conditions. Methods: We analyzed records from consecutive patients who had ambulatory EEG monitoring for 24 to 72 hours using Digitrace™ EEG recording system. The participants maintained a log of symptoms and signaled the time when symptoms occurred by pushing an event button. Additionally, automatic seizure and spike detection was performed on each record using Persyst detection software. Results: Of 831 reports analyzed, 44 unique patients had definite ictal events. There were a total of 129 electrographic seizures (34 subclinical) with timing as follows: frontal (31), temporal (71), and generalized, posterior, or central (27). Frontal lobe seizures occurred more frequently between 12 am and 12 pm as compared to temporal lobe seizures, which occurred more frequently between 12 pm and 12 am (p = 0.017). Analysis of frontal lobe seizures revealed a cluster of 10 seizures centered at 6:33 am (range 5:15–7:30 am) with p = 0.0064. Temporal lobe seizures had a cluster of 24 seizures centered at 8:49 pm (range 6:45–11:56 pm) with p = 0.0437. Conclusion: In ambulatory outpatient conditions, electrographic seizures follow day/night patterns similar to those observed in hospital conditions. Frontal seizures occur preferentially in the early morning hours and temporal lobe seizures occur in the early evening hours.

Why Are Seizures Rare in Rapid Eye Movement Sleep? Review of the Frequency of Seizures in Different Sleep Stages

Since the formal characterization of sleep stages, there have been reports that seizures may preferentially occur in certain phases of sleep. Through ascending cholinergic connections from the brainstem, rapid eye movement (REM) sleep is physiologically characterized by low voltage fast activity on the electroencephalogram, REMs, and muscle atonia. Multiple independent studies confirm that, in REM sleep, there is a strikingly low proportion of seizures (~1% or less). We review a total of 42 distinct conventional and intracranial studies in the literature which comprised a net of 1458 patients. Indexed to duration, we found that REM sleep was the most protective stage of sleep against focal seizures, generalized seizures, focal interictal discharges, and two particular epilepsy syndromes. REM sleep had an additional protective effect compared to wakefulness with an average 7.83 times fewer focal seizures, 3.25 times fewer generalized seizures, and 1.11 times fewer focal interictal discharges. In further studies REM sleep has also demonstrated utility in localizing epileptogenic foci with potential translation into postsurgical seizure freedom. Based on emerging connectivity data in sleep, we hypothesize that the influence of REM sleep on seizures is due to a desynchronized EEG pattern which reflects important connectivity differences unique to this sleep stage.

Cardiopulmonary complications during pediatric seizures: A prelude to understanding SUDEP

Sudden unexpected death in epilepsy (SUDEP) is an important, unexplained cause of death in epilepsy. Role of cardiopulmonary abnormalities in the pathophysiology of SUDEP is unclear in the pediatric population. Our objective was to assess cardiopulmonary abnormalities during epileptic seizures in children, with the long‐term goal of identifying potential mechanisms of SUDEP.

Risk factors for probable REM sleep behavior disorder: A community-based study.

Objective: To examine risk factors for REM sleep behavior disorder (RBD) in a large-scale community-based study. Methods: This community-based study included 12,784 Chinese adults (10,556 men and 2,228 women, aged 24 years or older) who were free of Parkinson disease and dementia in 2012. Probable RBD (pRBD) status was determined by a validated questionnaire (Chinese RBD questionnaire–Hong Kong) in 2012. Potential risk factors—including age, sex, smoking, socioeconomic status, physical activity, obesity, consumption of tea (surrogate for caffeine intake) and alcohol, serum concentrations of lipids and glucose, and chronic disease status—were assessed in 2006. Logistic regression was used to calculate odds ratios and 95% confidence intervals and to test differences in prevalence of pRBD across exposures. Results: Prevalence of pRBD was 5.9% in men and 4.1% in women. In the fully adjusted model, risk factors that were significantly associated with a higher risk of having pRBD included lower education level, coal mining and other blue collar occupation, lower physical activity level, diabetes or prediabetes, lower body mass index, head injury, higher low-density lipoprotein level, and chronic olfactory and taste dysfunction. In sensitivity analyses, restricting to pRBD cases with symptom onset within 1 year or excluding coal miners or those with history of head injury generated similar results. Conclusion: We found several potential risk factors for pRBD, including socioeconomic status, head injury, olfactory and taste dysfunction, and various cardiovascular risk factors. Future prospective studies to establish the temporal relationship between these potential risk factors and RBD are warranted.

Comparison of cardiorespiratory and EEG abnormalities with seizures in adults and children.

Cardiopulmonary dysfunction and postictal generalized EEG suppression (PGES) are proposed as possible risk factors for the occurrence of SUDEP. The evolution of cardiorespiratory abnormalities with seizures has not been systematically studied for any age-related findings. Additionally, not many studies have looked into the possible effect of age-related brain maturation on PGES. The purpose of this study was to compare these SUDEP risk factors in adults versus children. We prospectively recorded cardiopulmonary abnormalities during seizures using pulse oximetry, EKG, and respiratory inductance plethysmography. Linear and logistic regression models adjusting for multiple seizures in a single patient were used to compare the cardiorespiratory and EEG findings between adults and children. We recorded 101 seizures in 26 children and 55 seizures in 22 adults. Ictal central apnea and bradycardia occurred more often in children than in adults (p=0.02 and p=0.008, respectively), while ictal tachycardia occurred more often in adults (p=0.001) than in children. Postictal generalized EEG suppression of longer duration occurred more often in adults (p=0.003) than in children. Minimum O2 saturation and seizure duration/generalization/lateralization did not significantly differ between adults and children (p>0.1). Children had more frontal lobe seizures, and adults had more temporal lobe seizures recorded (p=0.01). There may be an age-related effect on cardiorespiratory and EEG abnormalities associated with seizures, with higher rates of apnea and bradycardia in children and a much higher prevalence of PGES of longer duration in adults. This may indicate why, despite lower rates of cardiopulmonary dysfunction, adults die more frequently from SUDEP than children.