Effectiveness of cognitive behavioral therapy for insomnia: influence of slight-to-moderate depressive symptom severity and worrying.

BACKGROUND: Cognitive behavioral therapy for insomnia (CBT-I) is a well-known, effective treatment for primary insomnia. However, the majority of sleeping problems occur in the presence of another medical or psychiatric disorder. Depression and general anxiety disorder (with a main feature of excessive generalized worrying) are disorders that frequently co-occur with insomnia. The purpose of this study is to evaluate whether depressive symptom severity or worrying influences the subjective effectiveness of CBT-I. METHODS: Patients with a complaint of insomnia received CBT-I. At the beginning of the therapy, patients completed a sleep evaluation list, the Beck Depression Inventory (BDI-II-NL, N = 92), and the Penn State Worry Questionnaire (PSWQ, N = 119). Based on the BDI and the PSWQ, the sample was divided into different groups: patients with low versus high depression scores, low worriers versus high worriers, and patients without depressive symptoms who were also classified as low worriers and patients with depressive symptoms who were also classified as high worriers. The sleep evaluation list was completed directly after the treatment and 6 months later. RESULTS: Sleep evaluation scores, subjective total sleep time, subjective sleep onset latency, and subjective wake after sleep onset all changed in a positive way after CBT-I and remained that way over the next 6 months for all patients. These positive effects of CBT-I did not differ between the subgroups. CONCLUSIONS: Results suggest that CBT-I improves subjective sleep experiences, regardless of depressive symptom severity or worrying.

Respiratory and sleep disorders in female children with atypical Rett syndrome caused by mutations in the CDKL5 gene.

AIM: In female children with drug-resistant seizures and developmental delay from birth, atypical Rett syndrome caused by mutations in the CDKL5 gene should be considered. Several clinical features resemble classic Rett syndrome. Respiratory and sleep abnormalities are frequently present in Rett syndrome, whereas little is known in patients with CDKL5 mutations. METHOD: In four genetically confirmed female patients with CDKL5 mutations (age range 2-15 y), the presence of breathing and sleep abnormalities was evaluated using the validated Sleep Disturbance Scale for Children and polysomnography (PSG). RESULTS: The Sleep Disturbance Scale for Children indicated disorders of initiating and maintaining sleep, daytime somnolence, and sleep breathing disorders. In one patient, PSG showed central apnoeas during sleep: her total apnoea-hypopnoea index (AHI) was 4.9, of which the central AHI was 3.4/h. When awake, central apnoeas were present in two of the four female children (central AHI 28/h and 41/h respectively), all preceded by hyperventilation. PSG showed low rapid eye movement (REM) sleep (9.7-18.3%), frequent awakenings, and low sleep efficiency (range 59-78%). INTERPRETATION: Episodic hyperventilation followed by central apnoeas was present while awake in two of four patients. This may indicate failure of brainstem respiratory centres. In addition, low REM sleep, frequent arousals (not caused by apnoeas/seizures), and low sleep efficiency were present. Similar to Rett syndrome, in patients with CDKL5 mutations PSG seems warranted to evaluate breathing and sleep disturbances.

Effects of daytime secondarily generalized epileptic seizures on sleep during the following night.

Nocturnal seizures may disturb sleep, but the effect of an epileptic seizure during daytime on sleep during the next night has been under investigated. In this proof-of-principle study, the sleep of 425 patients with epilepsy, who underwent long-term video-electroencephalography recordings, was analyzed. The sleep recordings were retrospectively divided into two groups: Seizure Free, no seizure occurred at least 24 h before the start of the night sleep recording, and Daytime Seizure, at least one (secondarily) generalized seizure occurred during the day before. In Daytime Seizure, longer time in bed and latency to first REM and more NREM II were seen as well as a decrease of deep sleep and REM sleep compared to Seizure Free. As many participants underwent long-term recordings over a period longer than 48 h, we had the opportunity to compare in individual patients the sleep architecture during nights with and without seizures on the day before the recording. Time in bed and WASO were longer, and sleep efficiency was less in the nights after a seizure on the day before the recording. These differences were statistically significant, but their clinical relevance is doubtful.

Morningness and eveningness: when do patients take their antiepileptic drugs?

Almost one-third of epilepsy patients continue to have seizures despite adequate drug treatment. Chronotherapy (based on dynamic changes in drug pharmacology and disease-related processes) could be a promising treatment option. We aimed to explore whether different circadian types adjust administration times of anti-epileptic drugs (AEDs) as a step in exploring chronotherapeutic possibilities. We performed a questionnaire-based study to compare behavior of different circadian types in relation to times of taking drugs. Circadian type was determined by the Morningness-Eveningness Questionnaire. Results clearly show that morning types are taking their AEDs significantly earlier than do evening types on free days. Times of taking AEDs in the morning on work days also differ significantly between morning and evening types. Regardless of circadian type, drugs on free days are taken later than on working days. In conclusion, our study shows that patients adapt times of taking medication to their circadian type.

Associating executive dysfunction with behavioral and socioemotional problems in children with epilepsy. A systematic review.

As children with epilepsy may have a number of learning and behavioral problems, it is important that insight into the underlying neurocognitive differences in these children, which may underlie these areas of challenge is gained. Executive function (EF) problems particularly are associated with specific learning abilities as well as behavioral problems. We aim to review systematically the current status of empirical studies on the association between EF problems and behavior and socioemotional problems in children with epilepsy. After search, 26 empirical studies were identified, most of them of moderate quality. Overall, attention problems were the most reported cognitive deficit in test assessment and the most reported problem by parents. In 54% of the studies, children with epilepsy scored below average compared to controls/normative samples on different aspects of EF. Most studies reported behavior problems, which ranged from mild to severe. Forty-two percent of the studies specifically reported relationships between EF deficits and behavioral problems. In the remaining studies, below average neuropsychological functioning seemed to be accompanied by above average reported behavioral problems. The association was most pronounced for cognitive control and attention in relation to externalizing behavior problems. This cognitive control is also associated with social functioning. Relevant epilepsy variables in this relationship were early age at onset and high seizure frequency.Future research should distinguish specific aspects of EF and take age into account, as this provides more insight on the association between EF and behavior in pediatric epilepsy, which makes it possible to develop appropriate and early intervention.

Temporal distribution of clinical seizures over the 24-h day: a retrospective observational study in a tertiary epilepsy clinic.

PURPOSE: Very few studies have evaluated seizure occurrence in humans over the 24-h day; data from children are particularly scarce. Circadian patterns in seizure occurrence may be of importance in epilepsy research and may have important implications in diagnosis and therapy. METHODS: We have analyzed clinical seizures of 176 consecutive patients (76 children, 100 adults) who had continuous electroencephalography (EEG) and video monitoring lasting more than 22 h. Several aspects of seizures were noted, including classification, time of day, origin, and sleep stage. RESULTS: More than 800 seizures were recorded. Significantly more seizures were observed from 11:00 to 17:00 h, and from 23:00 to 05:00 h significantly fewer seizures were seen. The daytime peak incidences were observed in seizures overall, complex partial seizures (in children and adults), seizures of extratemporal origin (in children), and seizures of temporal origin (in adults). Incidences significantly lower than expected were seen in the period 23:00 to 05:00 h in seizures overall, complex partial seizures (in children and adults), and in tonic seizures (in children). In addition, significantly fewer seizures of temporal (in children and adults) and extratemporal origin (in children) were observed in this period. DISCUSSION: The results suggest that certain types of seizures have a strong tendency to occur in true diurnal patterns. These patterns are characterized by a peak during midday and a low in the early night.

Diurnal rhythms in seizures detected by intracranial electrocorticographic monitoring: an observational study.

Few studies have evaluated human seizure occurrence over the 24-hour day, and only one group has employed intracranial electrocorticography monitoring to record seizures. Circadian patterns in seizures may have important implications in diagnosis and therapy and provide opportunities in research. We have analyzed spontaneous seizures in 33 consecutive patients with long-term intracranial EEG and video monitoring. Several aspects of seizures were noted, including time of day, origin, type, and behavioral state (sleeping/awake). We recorded 450 seizures that showed an uneven distribution over the day, depending on lobe of origin: temporal lobe seizures occurred preferentially between 1100 and 1700 hours, frontal seizures between 2300 and 0500 hours, and parietal seizures between 1700 and 2300 hours. In the awake state, larger proportions of clinical seizures were seen from 0500 to 1100 hours and from 1700 to 2300 hours. During sleep, larger proportions occurred from 1100 to 1700 hours and from 2300 to 0500 hours. Our results suggest that seizures from different brain regions have a strong tendency to occur in different diurnal patterns.

Prevalence of sleep disturbances in people with epilepsy and the impact on quality of life: a survey in secondary care.

PURPOSE: Studies in adults with epilepsy, mainly in specialized epilepsy clinics, have shown that sleep disturbances were twice as prevalent in people with epilepsy as in healthy controls. Our aim was to determine the prevalence of sleep disturbances in people with epilepsy treated in district hospitals, as well as the impact of it on Quality of Life. METHOD: Adults with epilepsy, attending outpatient clinics in three district hospitals were invited to participate. Those who accepted (N = 122) provided their own controls matched for age and sex. Both groups completed four questionnaires (Groningen Sleep Quality Scale (GSQ), Medical Outcomes Study-Sleep scale (MOSS), Sleep Diagnosis List (SDL) and Epworth Sleepiness Scale) to measure their sleep over different periods and the 36-Item Short Form Health Survey (SF-36) to measure Quality of Life (QoL). The prevalence of sleep disturbances and scores on QoL were compared between both groups. RESULTS: Sleep quality, measured by the SDL, was in the pathological range 50% more often in the epilepsy group than in controls. This was confirmed by the MOSSINDEX and GSQ. People with epilepsy experienced excessive daytime sleepiness more often than controls. The lowest scores on nearly all domains of the SF-36 were seen in people with epilepsy and associated sleep disturbances. CONCLUSION: We confirmed the higher prevalence of sleep disturbances in people with epilepsy compared to controls as previously reported from specialized settings. The (co-morbid) sleep disturbances result in lower QoL scores, in both people with epilepsy and in controls, but more in people with epilepsy.

Sleep-Related Breathing Disorders in Young Adults With Prader-Willi Syndrome: A Placebo-Controlled, Crossover GH Trial.

CONTEXT: Sleep-related breathing disorders (SRBD) are common in people with Prader-Willi syndrome (PWS). Young adults with PWS benefit from GH continuation after attaining adult height by maintaining the improved body composition obtained during childhood. There are, no studies about the effects of GH on SRBD in young adults with PWS who were treated with GH during childhood. OBJECTIVE: Investigate the effects of GH vs placebo on SRBD in young adults with PWS who were treated with GH during childhood and had attained adult height. DESIGN: Two-year, randomized, double-blind, placebo-controlled, crossover study in 27 young adults with PWS, stratified for sex and body mass index. SETTING: Dutch PWS Reference Center. INTERVENTION: Crossover intervention with GH (0.67 mg/m2/d) and placebo, both over one year. MAIN OUTCOME MEASURES: Apnea hypopnea index (AHI), obstructive apnea index (OAI), central apnea index (CAI), measured by polysomnography. RESULTS: Compared with placebo, GH did not increase AHI, CAI, or OAI (P > 0.35). The effect of GH vs placebo was neither different between men and women, nor between patients with a deletion or maternal uniparental disomy/imprinting center defect. After two years, there was no difference in AHI, CAI, or OAI compared with baseline (P > 0.18). Two patients (7%) fulfilled the criteria of obstructive sleep apnea regardless of GH or placebo. CONCLUSIONS: GH compared with placebo does not cause a substantial increase in AHI, CAI, or OAI in adults with PWS who were treated with GH during childhood and have attained adult height. Our findings are reassuring and prove that GH can be administered safely.

Efficacy of rotigotine for treatment of moderate-to-severe restless legs syndrome: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Continuous administration of a dopamine agonist could be used to treat patients with restless legs syndrome. Our aim was to investigate the efficacy of transdermal rotigotine in the treatment of idiopathic restless legs syndrome. METHODS: In this randomised, double-blind, placebo-controlled trial, 458 patients with moderate-to-severe idiopathic restless legs syndrome (average baseline International Restless Legs Syndrome Study Group severity rating scale [IRLS] sum score of 28.1) were randomly assigned to receive transdermal rotigotine 1 mg over 24 h (n=115), 2 mg over 24 h (n=112), or 3 mg over 24 h (n=114), or to receive placebo (n=117). Study medication was delivered via patches, applied once a day for 6 months. Randomisation was done with a computer-generated randomisation list, stratified by centre. Primary efficacy outcomes were absolute change from baseline to end of maintenance in IRLS sum score and in the clinical global impressions (CGI) item 1 score, assessed by analysis of covariance in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00136045. FINDINGS: Efficacy analyses were done on 112 patients in the 1 mg group, 109 in the 2 mg group, 112 in the 3 mg group, and 114 in the placebo group. Mean change in IRLS sum score from baseline at the end of the maintenance phase was -13.7 (SE 0.9) in the 1 mg group, -16.2 (0.9) in the 2 mg group, -16.8 (0.9) in the 3 mg group, and -8.6 (0.9) in the placebo group (p<0.0001 for treatment difference vs placebo with each dose). Mean change in CGI item 1 score from baseline at the end of the maintenance phase was -2.09 (0.14) in the 1 mg group, -2.41 (0.14) in the 2 mg group, -2.55 (0.14) in the 3 mg group, and -1.34 (0.14) in the placebo group (p<0.0001 for treatment difference vs placebo with each dose). Skin reactions, mostly mild or moderate, were seen in 145 (43%) of 341 patients who received rotigotine and in two (2%) of 117 who received placebo. Ten patients had serious adverse event that were deemed to be related to rotigotine: elevation of liver enzymes (one patient), worsening of tinnitus (one patient), non-response to anticoagulation (one patient), electrocardiogram changes (one patient), and application-site reactions (six patients). No admissions to hospital were needed for the application-site reactions, and they all resolved within a short time of patch removal without any other therapeutic intervention. The rate of typical dopaminergic side-effects in patients who received rotigotine was low; no signs of augmentation were noted. INTERPRETATION: 24 h transdermal delivery of low-dose rotigotine could be used to relieve the night-time and daytime symptoms of restless legs syndrome. FUNDING: Schwarz Biosciences.