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STUDY OBJECTIVES: This study examines the impact of cognitive behavioral therapy for insomnia (CBT-I) and positive airway pressure (PAP) therapy for comorbid insomnia and sleep apnea on nocturnal sleep and daytime functioning. METHODS: A partial factorial design was used to examine treatment pathways with CBT-I and PAP and the relative benefits of each treatment. One hundred eighteen individuals with comorbid insomnia and sleep apnea were randomized to receive CBT-I followed by PAP, self-monitoring followed by CBT-I concurrent with PAP, or self-monitoring followed by PAP only. Participants were assessed at baseline, PAP titration, and 30 and 90 days after PAP initiation. Outcome measures included sleep diary- and actigraphy-measured sleep, Flinders Fatigue Scale, Epworth Sleepiness Scale, Functional Outcome of Sleep Questionnaire, and cognitive emotional measures. RESULTS: A main effect of time was found on diary-measured sleep parameters (decreased sleep onset latency and wake after sleep onset; increased total sleep time and sleep efficiency) and actigraphy-measured sleep parameters (decreased wake after sleep onset; increased sleep efficiency) and daytime functioning (reduced Epworth Sleepiness Scale, Flinders Fatigue Scale; increased Functional Outcome of Sleep Questionnaire) across all arms (all P < .05). Significant interactions and planned contrast comparisons revealed that CBT-I was superior to PAP and self-monitoring on reducing diary-measured sleep onset latency and wake after sleep onset and increasing sleep efficiency, as well as improving Functional Outcome of Sleep Questionnaire and Flinders Fatigue Scale compared to self-monitoring. CONCLUSIONS: Improvements in sleep and daytime functioning were found with PAP alone or concomitant with CBT-I. However, more rapid effects were observed on self-reported sleep and daytime performance when receiving CBT-I regardless of when it was initiated. Therefore, concomitant treatment appears to be a favorable approach to accelerate treatment outcomes. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Multidisciplinary Approach to the Treatment of Insomnia and Comorbid Sleep Apnea (MATRICS); URL: https://clinicaltrials.gov/ct2/show/NCT01785303; Identifier: NCT01785303. CITATION: Tu AY, Crawford MR, Dawson SC, et al. A randomized controlled trial of cognitive behavioral therapy for insomnia and PAP for obstructive sleep apnea and comorbid insomnia: effects on nocturnal sleep and daytime performance. J Clin Sleep Med. 2022;18(3):789–800.

There is a small yet robust body of literature regarding autonomic dysfunction in idiopathic hypersomnia as well as sleep disturbances in postural orthostatic tachycardia syndrome. This review aims at summarizing the current literature and highlighting gaps in the current knowledge. This article additionally presents the personal experience of one of the authors at the sleep center. CITATION: Adra N, Reddy M, Attarian H, Sahni AS. Autonomic dysfunction in idiopathic hypersomnia: an overlooked association and potential management. J Clin Sleep Med. 2022;18(3):963–965.

Fibromyalgia (FM) is a chronic disorder characterised by chronic widespread pain, fatigue and sleep disturbances with higher prevalence in females. Psychological factors contribute largely to FM. Although women war refugees represent a fragile population that is prone to psychological distress, FM was not studied in this population.The current study had three objectives: (1) to screen FM and insomnia prevalence and severity, (2) to study the correlation between FM severity and insomnia and (3) to study FM treatment trends and their concordance with the guidelines among female Syrian refugees residing in Jordan.A cross-sectional study design was performed. Data from 384 Syrian female were analysed from four medical centres in Jordan. The Fibromyalgia Impact Questionnaire (FIQ) was used to study FM prevalence. Structured questions were designed to explore FM pharmacotherapeutic trend, and the Insomnia Severity Index (ISI) was used to screen insomnia.The prevalence of severe FM was about (30%), with a significant correlation with insomnia. Acetaminophen was used for FM relief in 60% of the study sample.Fibromyalgia prevalence is high among female refugees and is associated with insomnia. The treatment is suboptimal. The early screening and raising awareness of FM diagnosis and treatments are highly recommended. Key Points Fibromyalgia is an overlooked disorder especially among female war refugees The prevalence of severe fibromyalgia was about (30%), with a significant correlation with insomnia Fibromyalgia among the Syrian female refugees is mistreated perhaps due to lack of the proper diagnosis.

Traumatic brain injury (TBI) is a global health problem that affects millions of civilians, athletes, and military personnel yearly. Sleeping disorders are one of the underrecognized sequalae even though they affect 46% of individuals with TBI. After a mild TBI, 29% of patients have insomnia, 25% have sleep apnea, 28% have hypersomnia, and 4% have narcolepsy. The type of sleep disturbance may also vary according to the number of TBIs sustained. Diffuse axonal injury within the sleep regulation system, disruption of hormones involved in sleep, and insults to the hypothalamus, brain stem, and reticular activating system are some of the proposed theories for the pathophysiology of sleep disorders after TBI. Genetic and anatomical factors also come to play in the development and severity of these sleeping disorders. Untreated sleep disturbances following TBI can lead to serious consequences with respect to an individual's cognitive functioning. Initial management focuses on conservative measures with progression to more aggressive options if necessary. Future research should attempt to establish the effectiveness of the treatments currently used, as well as identify manageable co-existing factors that could be exacerbating sleep disorders.

WHAT IS KNOWN ON THE SUBJECT?: Fibromyalgia (FM) is a syndrome of chronic widespread pain, typically associated with fatigue, sleep, cognitive dysfunction and disordered mood. FM may limit an individual's ability to participate in everyday work and social activities, thereby making it difficult to maintain normal relationships with other individuals. While it has been studied in different populations and settings, the impact of FM and associated psychological factors has not been previously studied among female war refugees. WHAT DOES THE PAPER ADD TO EXISTING KNOWLEDGE?: The study showed the high impact of FM on female refugees in Jordan; approximately three quarters of the participants had a moderate to severe FM impact. Refugees settled in Irbid city, Iraq, showed increased age, anxiety and post-traumatic stress disorder correlated with a higher FM impact. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: The study recommends evaluation of the impact of FM among all female refugees living in Jordan, along with its neighbouring countries hosting refugees. Healthcare providers, including mental health nurses, should be aware of the role of PTSD and anxiety on the impact of FM. Accordingly, healthcare workers should design appropriate mental health treatment plans to help to decrease the impact of FM. Mental health nurses should evaluate FM impact among all refugees worldwide. Nurses in Jordan are recommended to share their experience with nurses outside of Jordan as this may help with funds being obtained and the implementation of advanced psychological interventions. Abstract INTRODUCTION: Fibromyalgia (FM) is a syndrome of chronic widespread pain. While it has been studied in different populations and settings, the impact of FM and its associated psychological factors has not been previously studied among female war refugees. Aim To assess the impact of FM and its associated factors in female refugees. Methods A cross-sectional study was conducted. The impact of FM, anxiety, post-traumatic stress (PTSD) and insomnia was investigated. Results 288 refugees previously diagnosed with FM were recruited. The results showed that 73.62% of the participants had a moderate to severe FM impact. Refugees settled in Irbid city were six times more likely to have a higher FM impact than refugees settled in Zarqa, and Iraqi refugees were more likely to have a higher impact than Syrian. Increased age, anxiety and PTSD were correlated with a greater impact. Conclusion Mental health nursing services should be directed towards female refugees, particularly those with increased age, anxiety and PTSD. Implications for practice Mental health nurses should evaluate the FM impact among all refugees worldwide. Furthermore, nurses in Jordan are recommended to share their experiences with nurses outside of Jordan, as this may help to raise funds and implement advanced psychological interventions.

Study Objectives To investigate treatment models using cognitive behavioral therapy for insomnia (CBT-I) and positive airway pressure (PAP) for people with obstructive sleep apnea (OSA) and comorbid insomnia. Methods 121 adults with OSA and comorbid insomnia were randomized to receive CBT-I followed by PAP, CBT-I concurrent with PAP, or PAP only. PAP was delivered following standard clinical procedures for in-lab titration and home setup and CBT-I was delivered in four individual sessions. The primary outcome measure was PAP adherence across the first 90 days, with regular PAP use (≥4 h on ≥70% of nights during a 30-day period) serving as the clinical endpoint. The secondary outcome measures were the Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI) with good sleeper (PSQI 7) serving as the clinical endpoints. Results No significant differences were found between the concomitant treatment arms and PAP only on PAP adherence measures, including the percentage of participants who met the clinical endpoint. Compared to PAP alone, the concomitant treatment arms reported a significantly greater reduction from baseline on the ISI (p = .0009) and had a greater percentage of participants who were good sleepers (p = .044) and remitters (p = .008). No significant differences were found between the sequential and concurrent treatment models on any outcome measure. Conclusions The findings from this study indicate that combining CBT-I with PAP is superior to PAP alone on insomnia outcomes but does not significantly improve adherence to PAP.

The differential diagnosis of primary hypersomnias in women includes narcolepsy (type 1/with cataplexy and type 2/without cataplexy), idiopathic hypersomnia, recurrent hypersomnia (Klein-Levin Syndrome, menstrual-related hypersomnia), idiopathic hypersomnia, behaviorally induced insufficient sleep syndrome, hypersomnia due to a medical disorder, hypersomnia due to a medication or substance, and hypersomnia associated with a psychiatric disorder. The hallmark symptom of hypersomnia is excessive daytime sleepiness (EDS). There is evidence suggesting higher prevalence of EDS in women, possibly due to work and family responsibilities, increased prevalence of mood disorders, hormonal changes, and/or the underdiagnoses of sleep disorders in women. In the realm of recurrent hypersomnias, menstrual-related hypersomnia is especially of importance in the evaluation of women. Similarly, given the increased prevalence of depression in women, the relationship between hypersomnia and depression is important to be aware of in evaluating these patients as well. There are several different options for treatment of primary hypersomnias. Special consideration should be given when prescribing modafinil or armodafinil to women given the interaction of these medications with exogenous hormones and oral contraceptives, leading to reduced efficacy and increased clearance of these hormonal treatments. Not enough pregnancy safety data exists with any of the pharmacological treatments for hypersomnia.

Background Sleep disorders play a significant role in the care of those with Traumatic Brain Injury (TBI). Objective To provide a literature review on the interaction of sleep and circadian processes on those with TBI. Methods A literature review was conducted on PubMed using the following key words and their combination: "Sleep Apnea", "Traumatic Brain Injury", "Circadian", "Parasomnia", "Insomnia", "Hypersomnia", "Narcolepsy", and "Restless Legs". We review the spectrum of traumatic brain injury associated sleep disorders and discuss clinical approaches to diagnosis and treatment. Results Disordered sleep and wakefulness after TBI is common. Sleep disruption contributes to morbidity, such as the development of neurocognitive and neurobehavioral deficits, and prolongs the recovery phase after injury. Early recognition and correction of these problems may limit the secondary effects of traumatic brain injury and improve neuro recovery/patient outcomes. Conclusions A more focused approach to sleep health is appropriate when caring for those with TBI.

Background Little is known about the impact of sleep disturbances (SD) or sleep-related impairment (SRI) in adults with AD or their relationship with severity of AD and itch and other predictors. Objective The aim of this study was to determine the relationship between AD severity, SD, and SRI. Methods We conducted a prospective online questionnaire-based study of 287 adults with AD, including assessment of AD severity by Patient-Oriented Eczema Measure, self-reported global AD severity, Self-Assessed Eczema Area and Severity Index and visual analog scale-itch, Patient-Reported Outcome Measurement Information System SD and SRI individual items, and T scores. Results Adults with AD commonly endorsed all SD and SRI symptoms examined; only 58 (21.8%) reported having good or very good sleep quality in the past week. However, only a minority of adults with AD endorsed a more profound impact from these individual aspects of SD and SRI in the past week or Patient-Reported Outcome Measurement Information System T scores greater than 55. In particular, SD and SRI were associated with severe or very severe AD (Patient-Oriented Eczema Measure, self-reported severity, visual analog scale-itch, and/or Self-Assessed Eczema Area and Severity Index). Sleep-related impairment was also associated with comorbid hay fever and/or anxiety. Conclusions This study suggests that SD and SRI are common in adults with AD, particularly those with severe diseases. Sleep disturbances and SRI should be considered when assessing burden of AD and therapeutic decisions.

Background: Refugees and war survivors are at higher risk of developing mental health disorders. Anxiety and stress are caused by many factors, including a stressful environment that could cause fatigue and low quality of life. Despite the existence of many synthetic anxiolytic and antidepressant drugs, symptom management has still not been successful. Ginkgo biloba extract has been used as one of the potential herbal remedies to enhance cognitive functions. Psycho-education plays a significant role in alleviating psychological distress. However, the role of G. biloba in alleviating anxiety, stress and fatigue among refugees was not well studied previously. Objectives: In this study, we aimed to compare the effect of G. biloba and psycho-education with only psycho-education on refugees’ anxiety, stress and fatigue. Methods: A randomized controlled, pre-test–post-test design was used. Data were measured at baseline and 6 weeks later. Results: Providing psycho-education for the control group showed a non-significant improvement in outcome variables. However, adding G. biloba to psycho-education for the experimental group showed a significant reduction in mental, physical, activity fatigue and anxiety. Conclusion: The addition of G. biloba to the psycho-education proved superior to psycho-education alone. Therefore, combining the two approaches is beneficial in alleviating anxiety and fatigue.

Sleep disturbances and disorders are common during pregnancy, and they can be risk factors for a number of serious pregnancy-related sleep disorders. These include postpartum depression, pregnancy-induced hypertension, gestational diabetes, and intrauterine growth retardation. In addition, certain chronic sleep disorders, such as narcolepsy, are quite challenging to manage in the context of pregnancy and during lactation, particularly with medications that can be teratogenic. This review discusses 4 common sleep disorders and their impacts on pregnancy, and suggests ways to deal with these disorders that improves maternal and fetal outcomes safely. The review discusses diagnosis and treatment of obstructive sleep apnea, restless legs syndrome, insomnia, and narcolepsy in pregnancy.

Citation:Khachatryan SG, Attarian, HP. Excessive daytime sleepiness could be multifactorial in adults with epilepsy. J Clin Sleep Med. 2020;16(8):1395–1396.

Atopic dermatitis, or eczema, is chronic inflammatory pruritic skin disorder, affecting both children and adults. Patients with atopic dermatitis often experience sleep disturbance, especially during flares of their skin disease. Sleep disturbances in atopic dermatitis range from difficulty falling asleep, shorter sleep duration, nighttime awakenings, and daytime sleepiness and fatigue. In addition, atopic dermatitis has also been associated with parasomnias and sleep-related breathing disorders. In children with atopic dermatitis, sleep disturbance may extend from the child to adult caregiver. The effects of sleep disruption in this setting are widespread including increased risk of mood disorders, impaired ability to perform activities of daily living, and decreased quality of life.

Introduction This study examines the effects of treatment sequences using cognitive-behavioral therapy for insomnia (CBT-I) and continuous positive airway pressure (CPAP) therapy on daytime functioning in people with comorbid insomnia and sleep apnea (COMISA). Methods 118 participants with COMISA (Age=49.99±13.12; 53.4% female) were randomized to one of the three study arms: Arm A- CBT-I followed by CPAP, Arm B- CBT-I concurrent with CPAP, and Arm C- CPAP only. Participants were assessed at four time points [baseline/ start of phase 1 (A1), CPAP titration/ start of phase 2 (A2), 30 days (A3) and 90 days (A4) after CPAP initiation]. This study examined secondary outcome measures of daytime functioning, including the Functional Outcomes of Sleep Questionnaire (FOSQ), Epworth Sleepiness Scale, and Flinders Fatigue Scale (FFS). Results Linear mixed model analyses showed a main effect of time on improving functional outcomes in all measurements, with all p< 0.001. There were also arm by time interactions on FOSQ [F(6, 105.36)=4.21, p=0.001] and FFS scores [F(6, 106.95)=3.10, p=0.008]. Pairwise comparisons with Bonferroni adjustment showed improved FOSQ scores in Arm A from A1 to A2 (p=0.011) and A2 to A3 (p=0.005), Arm B from A2 to A3 (p< 0.001), and Arm C from A2 to A3 (p=0.006). For FFS scores, improvements were shown in Arm A from A1 to A2 (p=0.003), and Arm B from A2 to A3 (p < 0.001). Conclusion The results show daytime functioning improvements in patients with COMISA following CPAP and CBT-I. In addition, CBT-I appears to facilitate improvement in sleepiness-related functional status and daytime fatigue. The findings suggest that the combination of CBT-I and CPAP may have a beneficial effect on daytime functioning in patients with COMISA. Support This study was supported by the National Institutes of Health (R01HL114529).

Objectives/hypothesis To assess if there is a significant difference in the prevalence and severity of chronic cough symptoms in obstructive sleep apnea (OSA) patients versus non-OSA patients and examine this relationship in regard to laryngopharyngeal reflux (LPR) symptoms. Study design Prospective cohort study. Methods Patients referred to Northwestern Medicine Sleep Lab for home sleep testing were enrolled. Patients filled out the Leicester Cough Questionnaire (LCQ) and Reflux Symptom Index (RSI) before completing sleep testing. Home sleep testing results were reviewed, and patients were separated into non-OSA and OSA groups by standard Apnea-Hypopnea Index (AHI) criteria. Demographic characteristics and questionnaire scores of the two groups were compared. The relationship between OSA severity, as determined by AHI, and LCQ and RSI scores was assessed. Results Of the 52 patients enrolled, 33 patients met criteria for OSA and 19 patients did not. Comparing patients without OSA versus those with OSA, there was a significant difference in mean LCQ score (129.9 vs. 120.0, respectively; P = .02), implying worse cough symptoms among OSA patients, and mean RSI score (3.2 vs. 11.2, respectively; P = .0013), implying worse upper-airway reflux symptoms among OSA patients. There was a significant correlation between LCQ score and AHI (r = -0.39, P = .0061) and between RSI score and AHI (r = 0.37, P = .0078). Conclusions OSA patients demonstrate worse chronic cough and LPR-related quality of life versus non-OSA patients. Furthermore, the severity of these quality-of-life measures was correlated with the severity of the AHI. Chronic cough and particularly the pharyngeal LPR symptoms may be associated with the presence and severity of OSA. Level of evidence 2 . Laryngoscope, 129:1244-1249, 2019.

Circadian misalignment is hypothesized to contribute to increased diabetes and obesity among shift workers and individuals with late sleep timing. Accordingly, the goal of our study was to identify-among normal and overweight/obese adults-associations between circadian timing (dim light melatonin onset; DLMO) and circadian misalignment (the interval between DLMO and sleep onset) with metabolic disease risk. This was a secondary analysis of data from a larger study. Participants ages 18 to 50 years without depression, diabetes, or shift work, with sleep duration 6.5 h or more, completed the following evaluations: 7 days of wrist actigraphy, circadian timing assessment (DLMO), and a fasting blood draw to measure glucose and insulin and calculate the Homeostatic Model of Assessment-Insulin Resistance (HOMA-IR). Data were analyzed using correlation and regression analyses controlling for age, sex, DLMO, and sleep duration. Analyses were conducted for the entire sample ( n = 54) and stratified by normal weight ( n = 36) and overweight/obese groups ( n = 18). Mean age was 26.4 years (SD = 7.1 years). Average sleep duration was 436.2 min (SD = 55.1 min), DLMO was 2250h (SD = 01:31), and interval between DLMO and sleep onset was 2 h 18 min (SD = 53 min). Average BMI was 24.3 kg/m2 (SD = 4.5 kg/m2). Circadian timing and interval between DLMO and sleep onset were not associated with glucose, insulin, or HOMA-IR in the main analyses. Among overweight/obese participants, a shorter interval between DLMO and sleep onset was associated with higher insulin ( B[SE] = -5.12 [2.24], p = 0.04) and HOMA-IR ( B[SE] = -1.32 [0.57], p = 0.04). Results of our multivariable model indicated that among overweight/obese participants, insulin was 5.1 pmol/L higher and HOMA was 1.3 µU/mL higher for every hour closer that sleep onset was to DLMO. The strengths of this study include the use of objective measures of circadian timing, but results should be considered hypothesis generating due to the small sample size and use of subgroup analyses.

Objective Insomnia both as a symptom and as part of chronic insomnia disorder is quite common in menopause. Comorbid conditions, such as restless legs syndrome and obstructive sleep apnea, occur with high prevalence among perimenopausal women with insomnia. Insomnia in this population group is associated with adverse health outcomes, and there are no clear standards on how to treat it. Methods Based on extensive literature search, 76 articles were identified. Two authors independently graded evidence according to the Oxford Centre for Evidence-Based Medicine Levels of Evidence. Results Evaluation and treatment of other comorbid sleep disorders are recommended, as is cognitive-behavioral therapy for insomnia. Hormone therapy, eszopiclone, escitalopram, gabapentin, isoflavones, valerian, exercise, and hypnosis are suggested. Zolpidem, quiteiapine XL, citalopram, mirtazapine followed by long-acting melatonin, ramelteon, Pycnogenol, Phyto-Female Complex, yoga, and massage may be considered. Kampo formulas are not recommended. Acupuncture may not be suggested, and cognitive-behavioral therapy that is not tailored for insomnia probably should not be considered. Conclusions Although a variety of interventions are shown to be helpful in improving sleep in menopause, there is a need for well-designed head-to-head trials with uniform outcome measures.

Sleep disturbances are common in neurodegenerative disease and impair quality of life. People with Alzheimer’s disease (AD) develop daytime hypersomnia and nighttime insomnia. These symptoms likely result from circadian rhythm disruption due to reduced zeitgeber input, suprachiasmatic nucleus dysfunction, and melatonin alterations. In Parkinson’s disease (PD), various sleep disorders, such as insomnia, hypersomnia, and REM sleep behavior disorder (RBD) are often seen. These problems are related to neurodegeneration of brain structures influencing sleep and wake states, circadian rhythm dysfunction, and motor and non-motor symptoms. RBD can precede PD motor symptoms by several years, and it represents a window of opportunity to treat the disease process when a disease-modifying therapy for PD becomes available in the future. Effective treatments for sleep disturbances in AD and PD are limited. Deeper understanding of sleep and circadian dysfunction is necessary to develop treatments that improve quality of life and potentially alter the degenerative course.

This study aimed to investigate the prevalence of insomnia and associated sociodemographic factors among refugees in Jordan. A cross-sectional survey was undertaken with a representative sample of 373 refugees. The majority of refugees had moderate to severe insomnia (

Background Many sedatives and anxiolytics are used in single dose or chronically to aid sleep. Clinically important sedatives include valerian-hops and antihistamines as they are used over the counter and are highly accessible and safe agents. Objectives To evaluate and compare a single dose of chlorpheniramine versus valerian-hops combination in modulating subjective sleep measures in insomniac war refugees. Methods Insomnia among refugees was screened using the Insomnia Severity Index (ISI). Insomniac subjects were randomized to received a single dose valerian-hops (320/80 mg) (n = 65), or chlorpheneramine (4 mg) (n = 50) or placebo (n = 76) two hours prior sleeping. Participants were instructed to complete Leeds Sleep Evaluation Questionnaire (LSEQ), visual analogue scales of anxiety and sedation. Also sleep latency, total hours slept and self-rated improvement were obtained. Results Almost 75% of screened refugees had insomnia. Chlorpheneramine reduced sleep latency and anxiety significantly, however it resulted in poor sleep quality. Valerian-hops group showed marked anxiolysis one hour after dosing, a sleep quality similar to placebo and better than chlorpheneramine, and better alertness compared to placebo. Participants satisfaction was higher with chlorpheneramine and there was no difference in the total hours slept. Discussion Valerian-hops combination may provide better sleep quality than antihistamines.

Both normal sleep physiology and sleep disorders have gender-specific features. Gender bias in medicine has resulted in women not being diagnosed in a timely manner with such serious disorders as obstructive sleep apnea and has led to misdiagnosis of primary sleep disorders as depression. Below we highlight the specific diagnostic, therapeutic, and epidemiologic aspects of sleep disorders in women. The first section is about the unique presentation of insomnia throughout a woman’s life span with specific pharmacological considerations when dealing with sedative hypnotics. The second section is on the symptomatology of sleep apnea in women and the impact it has on their health, particularly during pregnancy as well as that of other sleep related breathing disorders. The third section is on Restless Legs Syndrome and its relationship with pregnancy and lastly we discuss the impact of shift work on women’s health particularly in relation with gynecological cancers.

Insufficient sleep is common in the general population, and can result from environmental and psychosocial factors, medical and psychiatric disorders, and sleep disorders, such as insomnia, circadian rhythm disorders, sleep apnoea and restless legs. Women are particularly at risk for sleep disorders, and complaints of sleep disturbance are more prevalent among women than men across the life span. During the perinatal period, many common sleep disorders, such as obstructive sleep apnoea or restless legs may be exacerbated, or in the case of insomnia or narcolepsy, treatment options may change. In addition, the role of circadian rhythms in fertility and perinatal health is just beginning to be appreciated. In this chapter, we provide an overview of the current knowledge of the unique aspects of diagnosis and treatment of sleep disorders during the perinatal period.

Chronic insomnia is a common condition that affects people worldwide and has negative effects on patients' health and wellbeing. The treatment of insomnia can be complex and time consuming for patients and providers. Although behavioral interventions are the first line therapy, there are barriers to access for these treatments. However, in recent years, alternative ways of providing these behavioral therapies that make them more widely available have been investigated. Drugs also play an important role in the treatment of insomnia and new drugs have been introduced as options for treating patients with sleep initiation and sleep maintenance insomnia. In this review, we will discuss advances in the past six years in both non-pharmacologic and pharmacologic treatments for patients with chronic insomnia. We will also review the controversies surrounding some of the current drug treatments, as well as the role that technology and personal activity monitoring devices may play in treating insomnia.

Introduction Disruption of circadian rhythms is one of the proposed mechanisms linking late sleep timing to obesity risk but few studies have evaluated biological markers outside of the laboratory. The goal of this study was to determine the relationship between the timing and alignment of melatonin and sleep onset (phase angle) with BMI, body fat and obesity related behaviors. We hypothesized that circadian alignment (relationship of melatonin to sleep timing) rather than circadian (melatonin) timing would be associated with higher BMI, body fat, dietary intake and lower physical activity. Subjects/Methods Adults with sleep duration ≥6.5 hours completed 7 days of wrist actigraphy, food diaries and SenseWear arm band monitoring. Circadian timing, measured by dim light melatonin onset (DLMO) was measured in the clinical research unit. Circadian alignment was calculated as the duration between dim light melatonin onset and average sleep onset time in the prior week (phase angle). Body fat was evaluated using dual-energy absorptiometry (DXA). Data were analyzed using bivariate correlations and multivariable regression analyses controlling for age, sex, sleep duration and evening light exposure. Results Participants included 97 adults (61 F, age 26.8 ± 7.3 years) with average sleep duration 443.7 (SD= 50.4) minutes. Average phase angle was 2.2 hours (SD= 1.5). Circadian alignment was associated with circadian timing (p

Although the basic function of sleep remains a mystery, insufficient sleep is associated with mood disturbance, fatigue and daytime lethargy, cognitive impairments, daytime behavior problems, academic problems, use of stimulants, work absenteeism, lost work production and an increase in healthcare utilization. The International Classification of Sleep Disorders distinguishes 90 different disorders, many of which can be effectively treated, but when left untreated can be costly in terms of quality of life, health and healthcare cost. Over the past 50 years we have become more effective in measuring sleep and have honed our treatments to better address the sleep disorders that most impact us. This article will focus on the three sleep disorders for which patients most frequently seek care, including insomnia, obstructive sleep apnea syndrome and restless leg syndrome.

Parasomnias are undesirable physical or experiential events that occur in and around sleep. Treatments include reassurance in some cases, various forms of cognitive-behavioral therapy (CBT), and pharmacologic agents. Cognitive restructuring, imagery rehearsal, relaxation, hypnosis, desensitization, and anticipatory awakenings are some of the common CBT and nonpharmacologic interventions. Medications that are used belong to a wide variety of pharmacologic classes, such as alpha-blockers (prazosin), tricyclic antidepressants (imipramine and clomipramine), selective serotonin reuptake inhibitors, benzodiazepines (diazepam and clonazepam), anticonvulsants (topiramate and gabapentin), desmopressin acetate, and anticholinergic agents (oxybutynin and tolterodine). Data on efficacy are only available from randomized trials on CBT and prazosin for nightmares and on pharmacologic and alarm therapy for enuresis. No large-scale randomized trials are available to assess the efficacy of the other treatments, and most data come from anecdotal case reports, case series, or small open-label trials.

Circadian rhythms govern all biological functions. Circadian misalignment has a major impact on health. Late chronotype is a risk factor for circadian misalignment which in turn can affect the control of seizures in epilepsy patients. We compared a group of 87 confirmed epilepsy patients regardless of subtypes with age- and sex-matched healthy controls. We compared generalized epilepsy patients with localization related epilepsy patients and with healthy controls. We found that primary generalized epilepsy patients were 5 times more likely to have a late chronotype than healthy controls. We did not find any significant differences between localization related epilepsy patients and healthy controls or between the overall epilepsy cohort and healthy controls. Generalized epilepsy patients are more likely to be evening types as compared to those with focal epilepsy or subjects without epilepsy. Epilepsy patients do not experience the same age related increase in morningness as do age-matched healthy controls. This is important in regard to timing of AED, identifying and preventing sleep deprivation, and integrating chronotype evaluations and chronotherapy in comprehensive epilepsy care. Further studies, using objective phase markers or the impact of chronotherapy on seizure control, are necessary.

OSAS is a serious, prevalent condition that has significant mortality and morbidity when untreated. It is easy to diagnose and treat. Treatment improves quality of life and prevents associated morbidity or death. Response to treatment is high. The goal is to keep the airway open during sleep, leading to improved sleep, better oxygenation, and enhanced day-time alertness. The treatment of choice is CPAP, although bilevel positive airway pressure devices may be used in patients unable to tolerate CPAP. Many surgical treatments have proved effective. Drug therapy may be useful. Weight loss and training to avoid the supine sleeping position are helpful for some patients.

In the absence of sleep deprivation (either because of behavioral or medical causes) or pharmacologically induced sleepiness, hypersomnia is a manifestation of one of the central disorders of hypersomnolence, such as narcolepsy types 1 and 2, idiopathic hypersomnia, and recurrent hypersomnias such as Kleine-Levin syndrome. Narcolepsy and most primary hypersomnias are chronic conditions, thus, before committing an individual to chronic, possibly, life-long treatments, an accurate diagnosis is important. The key to effective management of hypersomnia, thus, lies in a thorough history, detailed physical examination, and appropriate diagnostic tests. Secondary causes of hypersomnia are expected to resolve once these disorders are treated. The treatment of central hypersomnias, on the other hand, is guided by a level of diagnostic certainty as to the etiology of the hypersomnia. Narcolepsy, for example, has well defined pathophysiologic and diagnostic criteria, including low levels of hypocretin in cerebrospinal fluid (CSF) and specific findings on a polysomnography/multiple sleep latency test (PSG/MSLT). For these patients, life-long therapy is the norm and involves initiating treatment usually with modafinil, armodafinil, or sodium oxybate, with methylphenidate, amphetamine-like stimulants, atomoxetine, or antidepressants used as second-line therapy. Pharmacologic therapy is usually done in concert with behavioral modifications such as scheduled napping for the best response. On the other hand, the etiology and pathophysiology of non-hypocretin-related hypersomnias (eg, idiopathic hypersomnia, Kleine-Levine syndrome) are unknown. For these reasons, treatment of these disorders is more challenging and less well defined. A trial of modafinil or armodafinil may be considered as first line therapy along with behavioral modifications. Methylphenidate, amphetamine-based stimulants, and even clarithromycin have also been used. There is no effective cure for hypersomnia, and the current therapy is purely symptomatic. Thus, initial patient education, addressing treatment expectations, as well as continued regular follow-up to monitor treatment response are vital to effective management of hypersomnia. The focus of this article is limited to a discussion of treatment of central disorders of hypersomnolence.

Obstructive sleep apnea syndrome (OSAS) is a common disorder characterized by repetitive episodes of breathing cessation due to complete or partial collapse of the upper airway therefore affecting ventilation. It is quite common, with a prevalence of about 2-4%, has a strong genetic component, and creates a proinflammatory state with elevated TNFα and other cytokines. If untreated, OSA can lead to significant neurological problems that include stroke, cognitive decline, depression, headaches, peripheral neuropathy, and nonarteritic ischemic optic neuropathy (NAION). Treatment reverses some of these neurological problems. Treatment includes continuous positive airway pressure and its variants, oral appliances, weight loss, upper airway surgery, and rarely maxillofacial procedures. Other sleep breathing disorders such as hypoventilation, central sleep apnea, complex sleep apnea, and Cheyne-Stokes respiration are less common and are sometimes associated with neuromuscular disorders causing diaphragmatic paralysis, but can also be seen in opiate exposure and severe obesity.

Article history: Received 8 December 2008 Received in revised form 12 January 2009 Accepted 2 February 2009

In this article we discuss the impact of various neurological disorders on insomnia. We cover such disorders as migraine and headaches, cerebrovascular disease and stroke, epilepsy, neurodegenerative diseases such as Alzheimer's disease and Parkinson disease, and multiple sclerosis. We also discuss the potential pathophysiology of this association and various treatment options.

The objective of this study was to determine prevalence and predictive risk factors of suicidality in a large sample of epilepsy outpatients. We prospectively examined 193 consecutive adult epilepsy outpatients for depression, including suicidal ideation. Demographic and epilepsy factors, medication toxicity and health-related quality of life were also evaluated. The prevalence of suicidal ideation within the past two weeks was 11.9%. Although medication toxicity, health-related quality of life and BDI scores were each associated with suicidal ideation in the bivariate analyses, only the BDI remained significant in the logistic regression analysis. About one-fourth of the subjects with suicidal ideation had no significant symptoms of depression. Recent thoughts of suicide are a common occurrence in the outpatient epilepsy clinic setting, but these are not predicted by gender, age, seizure factors, medication toxicity or self-perceived quality of life. Although depression is associated with suicidal ideation, about one-fourth of the suicidal subjects were euthymic or only mildly depressed.

Normal variants, also known as benign epileptiform variants (BEVs), are uncommonly occurring waveforms that may appear epileptogenic to the untrained eye. Five BEVs have been described. This chapter shows samples of three BEVs that often occur in sleep and that a sleep specialist may therefore encounter on a polysomnography (PSG). We also show samples of four other electroencephalographic (EEG) phenomena that occur frequently yet may cause confusion in certain situations.

The purpose of this study is to assess excessive daytime sleepiness (EDS) among attending physicians. Emails with an embedded link to an IRB approved questionnaire were sent to attending physicians of two closely affiliated academic institutions. An online hospital directory was used to compile a list of active attending physicians who practiced clinical medicine. Two additional reminder emails, about 2 weeks apart, were also sent. Data were collected anonymously and participation was voluntary. Three hundred fifteen responses out of 506 emails were returned (responder rate of 62.2%). The average age was 47 years and the majority was married with children. The mean Epworth Sleepiness Scale score was six and only 50 (15.9%) physicians were sleepy with a score of >10. Only working longer hours (p = 0.014), habitual napping (p = 0.01) and the feeling of not getting enough sleep (p = 0.01) significantly correlated with daytime sleepiness. Hours at work, however, did not correlate with hours of sleep, and the latter surprisingly did not correlate with sleepiness. Physicians in our sample were slightly more sleep deprived than the general population but not as sleep deprived as resident physicians.

Over the past quarter century, multiple studies have firmly established an association between obstructive sleep apnea syndrome (OSAS) and stroke. Case reports, case series, and case-control studies have demonstrated an 70% prevalence of OSAS in stroke survivors. Furthermore, the severity of OSAS (Apnea Hypopnea Index [AHI] of .30/hour) is much higher in stroke patients than in controls. In many cases, the symptoms of OSAS precede the occurrence of stroke, suggesting a cause-andeffect relationship. Early large-scale risk ratio studies showed a strong association between snoring and cerebral infarction, with a risk ratio of 10.3; the more habitual the snoring, the greater the risk of stroke. Specifically, persistent snoring is an independent risk factor for cerebrovascular events, with a risk ratio of 3.16, especially for events occurring during sleep or shortly after awakening. Adding obesity and daytime sleepiness to habitual snoring more than doubles the risk. With apnea added, the risk is 7-fold greater. Subjects diagnosed with OSAS (AHI $ 5) have a 1.58 relative odds of prevalent stroke, with a hazard ratio of 2.89. After stratifying for severity, mild OSAS ($ 5 AHI , 15) carries a 2.44-fold greater risk of cerebrovascular events, whereas moderate ($ 15 AHI , 30) or severe OSAS (AHI $ 30) carries a 3.56-fold greater risk. One of the seminal articles on this subject was published by Arzt et al in 2005. The authors followed a population of 1475 subjects aged 30-60 years for 12

Narcolepsy is generally considered an illness of youth because its incidence peaks around the second to third decade of life. Despite this it should still be on the differential of an older adult presenting with excessive daytime sleepiness. A small percentage of patients with narcolepsy have onset beyond age 35 with case reports of patients developing narcolepsy as late as the ninth decade. In addition to late onset of narcolepsy, cases of narcolepsy diagnosed after age 35 are sometimes due to delayed diagnosis despite symptom onset at a more typical age. Late-onset narcolepsy can also be due to symptomatic narcolepsy or narcolepsy-like symptoms that are due to another medical condition such as sarcoidosis, demyelinating disease, paraneoplastic disorders, or stroke.

This chapter discusses excessive daytime sleepiness (EDS) related to primary sleep disorders other than obstructive sleep apnea syndrome (OSAS) and restless legs syndrome (RLS) and EDS secondary to other medical problems-the secondary hypersomnias.

Sleep medicine as a field was not established until the early 1970s after the discovery of obstructive sleep apnea syndrome (OSAS) in Europe in 1965 (1,2) and the establishment of the first sleep laboratory at Stanford in 1972. The term polysomnography was coined by Dr. Jerome Holland at Stanford, in 1974, to describe the studies that were done during all-night sleep.

Background Fatigue is experienced by most patients with multiple sclerosis (MS) and often is profoundly debilitating. No large-scale studies to our knowledge have examined circadian rhythm abnormalities in MS patients or the relationship of fatigue to circadian rhythms. Objective To determine if patients with MS and fatigue have sleep disturbances or circadian rhythm abnormalities associated with fatigue. Design Case-control study. Setting Washington University School of Medicine, St Louis, Mo. Patients Fifteen patients with MS and fatigue were compared with 15 patients with MS without fatigue and 15 age- and sex-matched, healthy controls. Main Outcome Measures Sleep disturbances and circadian rhythm abnormalities were quantitated by actigraphy, fatigue by the Fatigue Descriptive Scale, and excessive sleepiness by the Epworth Sleepiness scale (ESS). Results Of the 15 fatigued patients with MS, 2 had delayed sleep phase, 10 had disrupted sleep, and 3 had normal sleep. One of the 15 nonfatigued MS patients had irregular sleep cycles, 2 others had disrupted sleep, and 12 had normal sleep. All 15 of the healthy controls had normal sleep. Nine patients with MS and fatigue scored 10 or higher on the ESS, suggesting excessive daytime sleepiness. Only 2 patients with MS without fatigue scored higher than 10 on the ESS. None of the healthy controls were fatigued, and 14 were not excessively sleepy. A relationship was found between fatigue and abnormal sleep cycles or disrupted sleep (Fisher exact test, P = .003). There was also a relationship between subjective excessive daytime sleepiness and fatigue in MS patients ( P = .02). Conclusion There is a significant correlation between fatigue in MS patients and disrupted sleep or abnormal sleep cycles.

A 71-year-old woman with a 3-year history of excessive daytime sleepiness and an increased need for sleep did not feel restored upon awakening and had daytime fatigue despite a full night's sleep. She was evaluated with polysomnography (PSG). She significantly underestimated her sleep latency and awake time after sleep onset. The following morning, she stated that she had slept all night, when in fact she had extremely poor sleep efficiency and prolonged sleep latency. Another PSG and a two-week long actigraphy confirmed her misperception. Therefore, she perceived physiologic wakefulness, by PSG and actiraphy criteria, as subjective sleep, in direct contrast to ‘conventional’ sleep state misperception, in which patients usually present with a complaint of insomnia but have normal sleep quality and duration by PSG criteria. This patient may have a previously undescribed variation of sleep state misperception that the authors have tentatively named ‘reverse’ sleep state misperception.

REM sleep behavior disorder (RBD) is an injurious parasomnia occasionally associated with narcolepsy. RBD usually occurs within REM sleep. We report a case of RBD in a narcoleptic patient arising from cataplexy and wakeful dreaming. The problem of state boundary control inherent in narcolepsy together with the pharmacological effects of tricyclic antidepressants used to treat cataplexy are usually the reason of RBD in narcoleptics. By similar mechanism our patient has presumed RBD out of REM intrusions into wakefulness.

In the International Classification of Sleep Disorders 2nd Edition (ICSD −2), sleep related rhythmic movement disorder (RMD) is classified as a disorder characterized by rhythmic movements of large muscle groups in different parts of the body. These are repetitive, stereotyped, rhythmic motor behaviors that occur predominantly during drowsiness or sleep,and are typically seen in infants and children. Episodes often occur at sleep onset, at any time during the night, and during quiet wakeful activities at a frequency of 0.5–2 sec), lasting < 15 min. The prevalence is high in infants (59%), dropping to 5% at the age of 5 years. When persisting to older childhood or beyond, association with mental retardation, autism, or other significant pathology is reported.1 Few cases in adults of normal intelligence have been reported in the literature.2–5 There is a strong association with attention deficit hyperactivity disorder, suggesting a similar pathogenetic mechanism.5 There is also one adult case report occurring during strictly REM sleep.6 Mayer et al reported 24 subjects with RMD that persisted into adolescence and adulthood. Twenty of the subjects were adults, and 16 of them had the condition since childhood. Of these 20, 16 had no other sleep disorders (but 2 had a family history of RMD), and 4 had obstructive sleep apnea.7 This was the first ever report of familial RMD.

Allergies to antiseizure medications present with a variety of manifestations. Most common are simple, uncomplicated exanthematous rashes. Anticonvulsant hypersensitivity syndrome (AHS) is a delayed reaction to an antiseizure medication characterized by fever, skin rash ranging from mild morbilliform eruptions to toxic epidermal necrosis, lymphadenopathy, and other organ involvement.1 Certain medications, particularly phenytoin, have been associated with a positive antinuclear antibody (ANA) and symptoms of connective tissue disease, a condition termed drug-induced lupus (DIL).2 Patients who develop DIL as a reaction to one antiseizure medication are at a higher risk of developing DIL as a reaction to other, chemically unrelated, antiseizure medications.3 We retrospectively reviewed the records of 1,830 consecutive patients evaluated in the Strong Epilepsy Center between 1990 and 1997. Twenty-three patients were identified with documented allergies (rashes) to more than one antiseizure medication. The charts of these 23 patients were reviewed for medications, type of reaction, and evidence of a connective tissue disease. Many …

lasting 3–5 s and occurring every minute for up to 40 min. A videotape of one such spell showed frequent myoclonic jerks affecting her lower extremities more than her upper extremities. She had them occasionally while standing up, but they never caused her to fall. She did not report loss of consciousness and had no history of seizures. There was no oral trauma or urinary incontinence with these episodes. She did have a 10-year history of restless leg syndrome and was being treated with clonazepam and trazodone. When these myoclonic jerks developed, she was also started on ropinirole with modest, if any, improvement in her symptoms. The patient denied head trauma, stating that 20 years ago she had had a mild whip lash injury. She denied any family history of similar problems. An EEG with added surface EMG electrodes applied to the tibialis anterior muscle revealed multiple jerks with no associated epileptiform abnormalities. An SSEP revealed normal latencies and no giant potentials. A previously performed CT scan of the brain was normal, and MRI of the cervical and thoracic spine was ordered. It did not show any neurological abnormalities, but did find an incidental solid enhancing lesion within the right lobe of the thyroid measuring approximately 2 cm in diameter. This appeared to be a solitary nodule and further evaluation with ultrasound and biopsy revealed papillary carcinoma. She underwent complete thyroidecDear Sir, Myoclonus consists of sudden, involuntary muscular contractions [1] . The feature that distinguishes spinal, or segmental myoclonus from other forms of more generalized myoclonia is its restriction to one somatic region secondary to spinal cord pathology at the involved level [2] . Propriospinal myoclonus is characterized by generalized and symmetric jerks that arise from axial muscles and spread to other myotomes by means of propriospinal pathways [3] . Neurologic paraneoplastic disorders are syndromes that are neither due to direct metastases nor to toxicity of cancer therapy, coagulopathy, infection, or toxic/ metabolic causes. They are far less common than metastases and other nonmetastatic neurologic complications of cancer, but they are important because of the severe and permanent neurologic morbidity. Also, because often they are the presenting feature of an otherwise undiagnosed tumor, early diagnosis maximizes the likelihood of successful tumor treatment and favorable neurologic outcome [4] .