Disorders Of Excessive Daytime Sleepiness Research Articles

Medications for daytime sleepiness in individuals with idiopathic hypersomnia.

Idiopathic hypersomnia is a disorder of excessive daytime sleepiness, often accompanied by long sleep times or pronounced difficulty in awakening, in the absence of a known cause. The optimal treatment strategy for idiopathic hypersomnia is currently unknown. To assess the effects of medications for daytime sleepiness and related symptoms in individuals with idiopathic hypersomnia and, in particular, whether medications may: 1. reduce subjective measures of sleepiness; 2. reduce objective measures of sleepiness; 3. reduce symptoms of cognitive dysfunction; 4. improve quality of life; and 5. be associated with adverse events. We searched the following databases on 4 February 2021: Cochrane Register of Studies (CRS Web), MEDLINE (Ovid, 1946 to 1 February 2021), and reference lists of articles. CRS Web includes randomized or quasi-randomized controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the specialized registers of Cochrane Review Groups, including the Cochrane Epilepsy Group. We previously searched the WHO ICTRP separately when loading of ICTRP records into CRS Web was temporarily suspended. Randomized studies comparing any medication to placebo, another medication, or a behavioral intervention. Two review authors independently extracted data and assessed trial quality. We contacted study authors for additional data. We collected data on adverse events from the included trials. We included three trials, with a total of 112 participants. Risk of bias was low for the included studies. Two pharmaceutical company-sponsored trials compared modafinil with placebo, involving 102 participants, nearly all of whom had idiopathic hypersomnia without long sleep time. Modafinil significantly improved self-reported sleepiness on the Epworth Sleepiness Scale by 5.08 points more than placebo (95% confidence interval (CI) 3.01 to 7.16; 2 studies, 101 participants; high-certainty evidence). Modafinil also significantly improved disease severity on the Clinical Global Impression of Severity scale by 1.02 points (95% CI 0.11 to 1.93; 1 study, 30 participants; moderate-certainty evidence) and resulted in a greater proportion of participants who were "much improved" or "very much improved" on the Clinical Global Impression of Change (odds ratio (OR) for improvement 5.14, 95% CI 1.76 to 15.00; 1 study, 70 participants; moderate-certainty evidence). Ability to remain awake on the Maintenance of Wakefulness Test was significantly improved with modafinil, by 4.74 minutes more than with placebo (95% CI 2.46 to 7.01; 2 studies, 99 participants; high-certainty evidence).Ratings of exhaustion and effectiveness/performance were improved with modafinil compared to placebo in one study.Number of naps per week was no different between modafinil and placebo across two studies. Participants receiving modafinilexperienced more side effects, although the difference did not reach statistical significance (OR 1.68, 95% CI 0.28 to 9.94; 2 studies, 102 participants; low-certainty evidence). One trial studying 20 participants with different disorders of sleepiness included 10 participants with idiopathic hypersomnia, with or without long sleep time, and compared clarithromycin to placebo. We only included the subset of trial data for those participants with idiopathic hypersomnia, per our protocol. There were no significant differences between clarithromycin and placebo for the Epworth Sleepiness Scale, psychomotor vigilance testing, sleep inertia, other subjective ratings, or side effects. Modafinil is effective for the treatment of several aspects of idiopathic hypersomnia symptomatology, based on studies predominantly including participants with idiopathic hypersomnia without long sleep times, with low risk of bias, and evidence certainty ranging from high to low.There is insufficient evidence to conclude whether clarithromycin is effective for the treatment of idiopathic hypersomnia. There is a clear need for additional studies testing interventions for the treatment of idiopathic hypersomnia.

Regional brain metabolism differs between narcolepsy type 1 and idiopathic hypersomnia.

Daytime sleepiness is a manifestation of multiple sleep and neurologic disorders. Few studies have assessed patterns of regional brain metabolism across different disorders of excessive daytime sleepiness. One such disorder, idiopathic hypersomnia (IH), is particularly understudied. People with IH, narcolepsy (NT1), and non-sleepy controls underwent [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) with electroencephalography (EEG). Participants were instructed to resist sleep and were awoken if sleep occurred. Voxel-wise parametric analysis identified clusters that significantly differed between each pair of groups, with a minimum cluster size of 100 voxels at a cluster detection threshold of p < 0.005. Correlations between glucose metabolism and sleep characteristics were evaluated. Participants (77% women) had IH (n = 16), NT1 (n = 14), or were non-sleepy controls (n = 9), whose average age was 33.8 (±10.7) years. Compared to controls, NT1 participants demonstrated hypermetabolism in fusiform gyrus, middle occipital gyrus, superior and middle temporal gyri, insula, cuneus, precuneus, pre- and post-central gyri, and culmen. Compared to controls, IH participants also demonstrated hypermetabolism in precuneus, inferior parietal lobule, superior and middle temporal gyri, and culmen. Additionally, IH participants demonstrated altered metabolism of the posterior cingulate. Most participants fell asleep. Minutes of N1 during uptake was significantly negatively correlated with metabolism of the middle temporal gyrus. NT1 and IH demonstrate somewhat overlapping, but distinct, patterns of regional metabolism.

1231 Slurred Speech- Unusual Presentation of Cataplexy in Childhood Narcolepsy

Abstract Introduction Narcolepsy, a chronic neurological disorder of excessive daytime sleepiness, cataplexy, sleep paralysis, and hypnagogic/hypnopompic hallucinations, frequently presents in late childhood/early adolescence. Cataplexy, the most specific symptom, presents as transient loss of muscle tone causing weakness. Approximately 80% of children with narcolepsy present with cataplexy1. Report of Case Eight year old African American boy presented to sleep clinic with concerns for excessive daytime sleepiness and slurred speech. Teachers initially referred to speech therapy because of slurred speech. There, speech got noticeably worse with frustration. Subsequently, sleepiness developed, and his pediatrician referred him for polysomnogram (PSG) and Mean Sleep Latency test (MSLT). After unremarkable PSG, MSLT demonstrated mean sleep latency of 10 minutes with no SOREM sleep. Patient came for evaluation in Sleep Medicine clinic where family reported worsening speech with extreme emotions and profound sleepiness, Epworth of 20. Because of the presentation and lack of REM sleep on MSLT, brain MRI was ordered and was normal. HLA typing for narcolepsy positively showed HLA haplotype associated with narcolepsy. Patient was diagnosed with narcolepsy with cataplexy and started on Modafinil 50 mg. Modafinil was progressively increased to 200 mg in a.m. and 100 mg at noon. To address cataplexy symptoms, he started Venlafaxine 12.5 mg and increased to 25 mg. Epworth score improved on Modafinil, his cataplexy symptoms, including speech difficulties, subsided on Venlafaxine. Patient’s communication improved, as did school performance and social life, and patient is currently thriving in 10th grade. Current Epworth is 5 and current medications include Modafinil 200 mg in the morning, 100 mg at noon and Venlaflaxine 25 mg at night. Conclusion This case report highlights the importance of recognizing unusual presentations of cataplexy and the impact of treatment. These symptoms can be easily missed and erroneously attributed to developmental delay or behavioral issues.

Medications for daytime sleepiness in individuals with idiopathic hypersomnia

Background Idiopathic hypersomnia is a disorder of excessive daytime sleepiness, often accompanied by long sleep times or pronounced difficulty in awakening, in the absence of a known cause. The optimal treatment strategy for idiopathic hypersomnia is currently unknown. Objectives To assess the effects of medications for daytime sleepiness and related symptoms in individuals with idiopathic hypersomnia and, in particular, whether medications may: 1. reduce subjective measures of sleepiness; 2. reduce objective measures of sleepiness; 3. reduce symptoms of cognitive dysfunction; 4. improve quality of life; and 5. be associated with adverse events. Search methods We searched the following databases on 4 February 2021: Cochrane Register of Studies (CRS Web), MEDLINE (Ovid, 1946 to 1 February 2021), and reference lists of articles. CRS Web includes randomized or quasi-randomized controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the specialized registers of Cochrane Review Groups, including the Cochrane Epilepsy Group. We previously searched the WHO ICTRP separately when loading of ICTRP records into CRS Web was temporarily suspended. Selection criteria Randomized studies comparing any medication to placebo, another medication, or a behavioral intervention. Data collection and analysis Two review authors independently extracted data and assessed trial quality. We contacted study authors for additional data. We collected data on adverse events from the included trials. Main results We included three trials, with a total of 112 participants. Risk of bias was low for the included studies. Two pharmaceutical company-sponsored trials compared modafinil with placebo, involving 102 participants, nearly all of whom had idiopathic hypersomnia without long sleep time. Modafinil significantly improved self-reported sleepiness on the Epworth Sleepiness Scale by 5.08 points more than placebo (95% confidence interval (CI) 3.01 to 7.16; 2 studies, 101 participants; high-certainty evidence). Modafinil also significantly improved disease severity on the Clinical Global Impression of Severity scale by 1.02 points (95% CI 0.11 to 1.93; 1 study, 30 participants; moderate-certainty evidence) and resulted in a greater proportion of participants who were "much improved" or "very much improved" on the Clinical Global Impression of Change (odds ratio (OR) for improvement 5.14, 95% CI 1.76 to 15.00; 1 study, 70 participants; moderate-certainty evidence). Ability to remain awake on the Maintenance of Wakefulness Test was significantly improved with modafinil, by 4.74 minutes more than with placebo (95% CI 2.46 to 7.01; 2 studies, 99 participants; high-certainty evidence). Ratings of exhaustion and effectiveness/performance were improved with modafinil compared to placebo in one study. Number of naps per week was no different between modafinil and placebo across two studies. Participants receiving modafinil experienced more side effects, although the difference did not reach statistical significance (OR 1.68, 95% CI 0.28 to 9.94; 2 studies, 102 participants; low-certainty evidence). One trial studying 20 participants with different disorders of sleepiness included 10 participants with idiopathic hypersomnia, with or without long sleep time, and compared clarithromycin to placebo. We only included the subset of trial data for those participants with idiopathic hypersomnia, per our protocol. There were no significant differences between clarithromycin and placebo for the Epworth Sleepiness Scale, psychomotor vigilance testing, sleep inertia, other subjective ratings, or side effects. Authors' conclusions Modafinil is effective for the treatment of several aspects of idiopathic hypersomnia symptomatology, based on studies predominantly including participants with idiopathic hypersomnia without long sleep times, with low risk of bias, and evidence certainty ranging from high to low. There is insufficient evidence to conclude whether clarithromycin is effective for the treatment of idiopathic hypersomnia. There is a clear need for additional studies testing interventions for the treatment of idiopathic hypersomnia.

Sleepiness in Narcolepsy.

Narcolepsy represents the best understood disorder of excessive daytime sleepiness (EDS). EDS presents in 100% of patients with narcolepsy; it is usually the first and the most disabling symptom, which varies in aspects, such as onset age, severity, and clinical characteristics. Early recognition of this symptom leads to early diagnosis and intervention. A diagnosis of narcolepsy is based on clarifying EDS through history, subjective evaluation using questionnaires, and objective measurement, including nocturnal polysomnography followed by a daytime multiple sleep latency test. The therapeutic goal is to optimize control of EDS through wake-promoting medications and nonpharmacologic treatments.

Disorders of Excessive Daytime Sleepiness Including Narcolepsy and Idiopathic Hypersomnia.

Central disorders of hypersomnolence are rare conditions with a poorly understood pathophysiology, making the identification and management challenging for sleep clinicians. Clinical history is essential for ruling out secondary causes of hypersomnolence and distinguishing among diagnoses. Current diagnostic criteria rely heavily on the polysomnogram and multiple sleep latency test. The current focus of treatment of hypersomnolence is on drugs that promote alertness. Additionally, in the case of narcolepsy type 1, medication management addresses control of cataplexy, the hallmark symptom of this disorder. Elucidation of pathophysiology of these disorders in the future will be essential to better categorization and management.

Understanding Automatic Behavior in Narcolepsy: New Insights Using a Phenomenological Approach

Automatic behaviors are stereotyped, repetitive behaviors performed without awareness and are a common auxiliary symptom of narcolepsy (a disorder of excessive daytime sleepiness). The goal of the study was to expand our knowledge of this complex but poorly understood phenomenon. Here we present new insights based on an analysis of the experiences of ten individuals with narcolepsy. Proceduresincluded two interviews, a family member interview, a one week journal and a one day journal when participants agreed to take minimal or no stimulant medication. Three different types of automatic behavior were identified; sleepiness with low cognitive load, sleepiness with high cognitive load and high cognitive load withoutsleepiness. Original contributionsinclude: notion of cognitive load, possible progression of automatic behaviorto sleep, a new classification of errors, importance of adequatemedication, as well as a theoretical discussion.

Sleep and Behavioral Problems in Rolandic Epilepsy

Although patients with benign childhood epilepsy with centrotemporal spikes exhibit a benign course of the disease, some of them display sleep and behavioral problems. Sixty-one patients with rolandic epilepsy, aged 6-11 years, were included in this study. The patients were divided into two subgroups according to the presence of seizures over the preceding 6 months. The control group comprised 25 patients without epilepsy and with similar characteristics in terms of age and sex. All patients underwent evaluation of sleep (Sleep Disturbance Scale for Children) and behavior (Lithuanian version of the Child Behaviour Checklist). Only patients who had had seizures over the preceding 6 months displayed significantly higher scores for sleep problems (disorders of excessive daytime sleepiness, disorders of sleep-wake transition, and scores for total sleep problems), worse sleep quality (longer sleep-onset latency), and behavioral problems (anxiety/depression, social problems, thought problems, attention problems, and aggressive behavior) than the patients of the control group. Our data add to evidence that active epilepsy has an impact on sleep and behavior. Clinically significant sleep problems were related to the higher risk of behavioral problems. Parents' ratings for existing sleep problems were sensitive to Sleep Disturbance Scale for Children scores above normal values.

Sustained attention to response task (SART) shows impaired vigilance in a spectrum of disorders of excessive daytime sleepiness

The sustained attention to response task comprises withholding key presses to one in nine of 225 target stimuli; it proved to be a sensitive measure of vigilance in a small group of narcoleptics. We studied sustained attention to response task results in 96 patients from a tertiary narcolepsy referral centre. Diagnoses according to ICSD-2 criteria were narcolepsy with (n=42) and without cataplexy (n=5), idiopathic hypersomnia without long sleep time (n=37), and obstructive sleep apnoea syndrome (n=12). The sustained attention to response task was administered prior to each of five multiple sleep latency test sessions. Analysis concerned error rates, mean reaction time, reaction time variability and post-error slowing, as well as the correlation of sustained attention to response task results with mean latency of the multiple sleep latency test and possible time of day influences. Median sustained attention to response task error scores ranged from 8.4 to 11.1, and mean reaction times from 332 to 366ms. Sustained attention to response task error score and mean reaction time did not differ significantly between patient groups. Sustained attention to response task error score did not correlate with multiple sleep latency test sleep latency. Reaction time was more variable as the error score was higher. Sustained attention to response task error score was highest for the first session. We conclude that a high sustained attention to response task error rate reflects vigilance impairment in excessive daytime sleepiness irrespective of its cause. The sustained attention to response task and the multiple sleep latency test reflect different aspects of sleep/wakefulness and are complementary.

Mit Narkolepsie aufwachsen

Narcolepsy, a disorder of excessive daytime sleepiness, often has its major onset in adolescence. The aim of the present study was to focus on the scope and psychosocial impact of narcolepsy symptoms in adolescence. Semistructured interviews with 9 adolescents and young adults with narcolepsy provided detailed descriptions of the topic as perceived by the participants. Narcolepsy symptoms in adolescence varied and often worsened at puberty onset. Sleep may be experienced as unrefreshing. The widespread and often severe psychosocial effects partially arose from a delay in diagnosis. Severe educational failure was a common consequence. Symptoms affected work and life goals. Increased social withdrawal and lower self esteem were often evident. Sleepiness was a problem both for public transportation and driving, substantially affecting independent mobility. Increased awareness of the disease and the provision of psychoeducational support, in conjunction with early diagnosis and medical treatment, are strongly warranted to prevent the most common educational and psychosocial problems, including risk of depression.

Fatigue or Daytime Sleepiness?

Daytime sleepiness is one of the criteria for daytime impairment (section-C of ICSD-2) for the diagnosis of insomnia as stipulated by International Classification of Sleep Disorders, 2nd edition.1 Similarly, in the proposed DSM-V criteria2 for primary insomnia, daytime sleepiness has been included as one of the criteria to indicate associated impairment. At our Sleep Research and Treatment Center, Penn State University College of Medicine, we have seen hundreds of patients with chronic insomnia. Most of these patients were referred by other providers for their chronic sleep complaints. Patients with chronic insomnia present with complaints of sleep difficulty for several months and often for more than a year.3 Along with nocturnal sleep disturbances, most of them report several daytime symptoms. Notable among the daytime symptoms are excessive fatigue and exhaustion during the day. However, most of the patients with chronic insomnia deny daytime sleepiness. In our clinical practice to differentiate daytime fatigue/tiredness from sleepiness we use a clarifying question; “Since you feel tired/fatigued, if given a chance would you be able to sleep during the day” and almost all of the patients with chronic insomnia report inability to sleep during the day despite having an opportunity and feeling excessively tired or fatigued. When a patient answers “yes” to the above mentioned question, i.e., ability to sleep during the day, we found that such patients often will have an underlying other primary sleep disorder of excessive daytime sleepiness or chronic sleep deprivation. The differentiation of daytime sleepiness and fatigue as clinical criterion has been suggested earlier by us4,5 and has been adopted by 25 leading investigators in the field of insomnia research convened in Pittsburgh, Pennsylvania on March 10-11, 2005.6 Our clinical experiences are further supported by the data from objective measures of daytime sleepiness using MSLT (multiple sleep latency tests) in insomnia. Mean sleep latency during MSLT have been consistently found to be increased in insomniacs compared to normal controls.7–10 The mean sleep latency on MSLT in insomniacs were longer despite significantly decreased nocturnal sleep efficiency.7 Recent data by Randall and colleagues10 found that more than 70% of the patients with primary insomnia had mean sleep latency on MSLTs of more than 10 minutes in comparison to only 47% in general population controls. Considering the subjective reports of inability to sleep during the day and the supporting MSLT data indicating decreased propensity to fall asleep during the day in insomniacs, it is prudent to consider deleting the “daytime sleepiness” criteria from the impairment section of proposed DSM-V criteria for primary insomnia. In fact, insomniacs endorsing daytime sleepiness may actually be suffering from other primary sleep disorders or sleep deprivation and may lead to misdiagnosis of insomnia.

Current Evaluation and Management of Excessive Daytime Sleepiness

Excessive daytime sleepiness has significant impact on neurological function, and has societal implications. Sleepiness is a common feature of many neurological conditions. A careful history will often reveal one of many common causes of excessive daytime sleepiness and suggest appropriate treatment. Neurophysiological testing can provide objective assessment. Behavioural management is an important first step in management. Treatment of common concurrent sleep disorders is also essential. Currently available medications can further symptomatically improve function in many individuals. The strongest evidence base is for the treatment of narcolepsy--a prototype disorder of excessive daytime sleepiness. Currently used medications include modafinil, stimulants, and sodium oxybate amongst others. This review discusses important features in the diagnosis of daytime sleepiness in adults, and outlines a treatment approach. Further evidence-based information about the management of this common problem is essential.

Narcolepsy and Disruption to Social Functioning

This study sought to create an in depth understanding of the impact of living with narcolepsy (a disorder of excessive daytime sleepiness) through qualitative research. The study used an essentially phenomenological methodology. Twenty- seven participants (18 females, 9 males, Mean age = 54.30, range = 26-90 years) were recruited from medical files in Canada and the narcolepsy support group in Australia. Data were collected via an open-ended narrative inviting the informant to focus on the impact of the disorder and analysed thematically. The issue of social context emerged as a key theme in understanding perceptions of the impact of living with narcolepsy. A secondary theme was that narcolepsy was experienced as an invisible illness. Thus the impact of living with narcolepsy is embedded in the need to maintain acceptable social functioning (within family, friendship and work relationships) and, related to this, cognitive functioning. This is complicated by the often indistinguishable nature of the symptoms from behaviors that people without narcolepsy experience. Health professionals need to understand that narcolepsy differs from other illnesses in that its key impact is a disruption to normal social functioning.

Sleep apnea is a manifestation of the metabolic syndrome

Obstructive sleep apnea (OSA) is a prevalent disorder particularly among middle-aged, obese men, although its existence in women as well as in lean individuals is increasingly recognized. Despite the early recognition of the strong association between OSA and obesity, and OSA and cardiovascular problems, sleep apnea has been treated as a 'local abnormality' of the respiratory track rather than as a 'systemic illness.' In 1997, we first reported that the pro-inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNFalpha) were elevated in patients with disorders of excessive daytime sleepiness (EDS) and proposed that these cytokines were mediators of daytime sleepiness. Also, we reported a positive correlation between IL-6 or TNFalpha plasma levels and the body-mass-index (BMI). In subsequent studies, we showed that IL-6, TNFalpha, and insulin levels were elevated in sleep apnea independently of obesity and that visceral fat, was the primary parameter linked with sleep apnea. Furthermore, our findings that women with the polycystic ovary syndrome (PCOS) (a condition associated with hyperandrogenism and insulin resistance) were much more likely than controls to have sleep disordered breathing (SDB) and daytime sleepiness, suggests a pathogenetic role of insulin resistance in OSA. Other findings that support the view that sleep apnea and sleepiness in obese patients may be manifestations of the Metabolic Syndrome, include: obesity without sleep apnea is associated with daytime sleepiness; PCOS and diabetes type 2 are independently associated with EDS after controlling for SDB, obesity, and age; increased prevalence of sleep apnea in post-menopausal women, with hormonal replacement therapy associated with a significantly reduced risk for OSA; lack of effect of continuous positive airway pressure (CPAP) in obese patients with apnea on hypercytokinemia and insulin resistance indices; and that the prevalence of the metabolic syndrome in the US population from the Third National Health and Nutrition Examination Survey (1988-1994) parallels the prevalence of symptomatic sleep apnea in general random samples. Finally, the beneficial effect of a cytokine antagonist on EDS in obese, male apneics and that of exercise on SDB in a general random sample, supports the hypothesis that cytokines and insulin resistance are mediators of EDS and sleep apnea in humans. In conclusion, accumulating evidence provides support to our model of the bi-directional, feed forward, pernicious association between sleep apnea, sleepiness, inflammation, and insulin resistance, all promoting atherosclerosis and cardiovascular disease.

Upper airway resistance syndrome-one decade later

The term upper airway resistance syndrome (UARS) was coined to describe a group of patients who did not meet the criteria for diagnosis of obstructive apnea-hypopnea syndrome and thus were left untreated. Today, most of the patients with UARS remain undiagnosed and are left untreated. Today, the clinical picture of UARS is better defined. We have learned that patients usually seek treatment with a somatic functional syndrome rather than sleep-disordered breathing or even a disorder of excessive daytime sleepiness. Therefore, most of these patients are seen by psychiatrists. In addition, recent technologic advances have allowed a better recognition of the problem. We have learned that obstructive apnea-hypopnea syndrome is associated with a local neurologic impairment that is responsible for the occurrence of the hypopnea and apneas. In contrast, patients with UARS have an intact local neurologic system and have the ability to respond to minor changes in upper airway dimension and resistance to airflow. New treatment options including internal jaw distraction osteogenesis are used and are promising for treatment of patients with UARS. The clinical presentation of patients with UARS is similar to the presentation of subjects with functional somatic syndrome. To diagnose UARS, nocturnal polysomnography should include additional measurement channels.

Metabolic disturbances in obesity versus sleep apnoea: the importance of visceral obesity and insulin resistance.

Obstructive sleep apnoea (OSA) is a very prevalent disorder particularly amongst middle-aged, obese men, although its existence in women as well as in lean individuals is increasingly recognized. Despite the early recognition of the strong association between OSA and obesity, and OSA and cardiovascular problems, sleep apnoea has been treated as a 'local abnormality' of the respiratory track rather than as a 'systemic illness'. In 1997, we first reported that the pro-inflammatory cytokines interleukin (IL)-6 and tumour necrosis factor-alpha (TNF alpha) were elevated in patients with disorders of excessive daytime sleepiness (EDS) and proposed that these cytokines were mediators of daytime sleepiness. Also, we reported a positive correlation between IL-6 or TNF alpha plasma levels and the body mass index (BMI). In subsequent studies, we showed that IL-6, TNF alpha, leptin and insulin levels were elevated in sleep apnoea independently of obesity and that visceral fat, was the primary parameter linked with sleep apnoea. The association of OSA with insulin resistance and diabetes type 2 has been confirmed since then in several epidemiological and clinical studies. Furthermore, our findings that women with polycystic ovary syndrome (PCOS, a condition associated with hyperandrogenism and insulin resistance) were much more likely than controls to have sleep disordered breathing (SDB) and daytime sleepiness support the pathogenetic role of insulin resistance in OSA. Other findings that support the view that sleep apnoea and sleepiness may be manifestations of a serious metabolic disorder, namely the Metabolic or Visceral Obesity Syndrome, include: obesity without sleep apnoea is associated with daytime sleepiness; PCOS and diabetes type 2 are independently associated with EDS after controlling for SDB, obesity and age; and increased prevalence of sleep apnoea in postmenopausal women, with hormonal replacement therapy associated with a significantly reduced risk for OSA. In conclusion, accumulating evidence provides support to our model of the bi-directional, feedforward, pernicious association between sleep apnoea, sleepiness, inflammation and insulin resistance, all promoting atherosclerosis and cardiovascular disease.

The Natural History of Health and Symptoms in Narcolepsy: A to-year Longitudinal Study

This longitudinal study investigated, over a 10-year period, reported changes in people with narcolepsy (a disorder of excessive daytime sleepiness). The issues of the functional impact of symptoms; stimulant medication status; body mass index, and concomitant illnesses were examined. The study also documented, using retrospective report, environmental factors influencing narcolepsy severity, and reported time of worst symptom severity following narcolepsy onset. In 1991, 127 people with diagnosed narcolepsy and cataplexy completed a wide-ranging questionnaire. In 2001, attempts were made to recontact these participants and 67 were traceable. Of these, 47 people, (18 males, 29 females; mean age 61.76 years, age range 31-86 years) returned a revised questionnaire. The reported impact of excessive daytime sleepiness (EDS) on the ability to carry out day-to-day activities showed minor increases in severity over the 10-year period in this older narcolepsy sample, and this could not be attributed to major changes in medication status. It is argued that the underlying severity of EDS does not increase with time, but rather that the interaction of EDS with the ageing process increases its detrimental impact. Improvements in the functional impact of sleep paralysis, hallucinations and automatic behaviour were reported. There was no evidence that any narcolepsy symptom became substantially worse with time for most people with the disorder. The influence of environmental factors on symptoms was inconsistent within the group. The elevated body mass index, stable over time, suggested that excess weight may be a trait often associated with narcolepsy, possibly linked to hypocretin deficiency.

Arousals de origen respiratorio y síndrome de aumento de resistencia de la vía aérea superior: aspectos fisiopatológicos y diagnósticos

The description of Upper Airway Resistance Syndrome (UARS) let us to recognize the importance of the pair 'respiratory effort-arousal' on sleep-disordered breathing pathophysiology. First part of this paper reviews knowledge about respiratory arousal pathophysiology. Arousal response is normally needed to end obstructive respiratory episodes, but it is also the cause of sleep fragmentation. Among respiratory stimuli able to provoke arousal (respiratory effort, hypoxemia and hypercapnia), respiratory effort is the most constant. Neurophysiological mechanisms involved in arousal, sleep and vegetative consequences, and the possible role of non visible arousals, are also discussed. In UARS, because of the absence of apnea/hypopnea and significative O2 desaturations, arousals are induced by the increased respiratory effort. Diagnosis needs the simultaneous recording of polysomnography and esophageal pressure. Some symptoms and signs of UARS are similar to those of Obstructive Sleep Apnea Syndrome. However, UARS shows any differences: a lower Body Mass Index, less constant snoring, males and females are similarly affected or higher frequency of craniofacial abnormalities. Diagnostic difficulties may be due to confusion between hypopneas and episodes of increased resistance of upper airway, or to the lack of definitive diagnostic criteria. Finally, differential diagnosis needs a broad knowledge of disorders of excessive daytime sleepiness.

Disorders of excessive daytime sleepiness—an update

Disorders of excessive daytime sleepiness (EDS) constitute a major health hazard, since impaired alertness may lead to accidents and poor quality of life, and some of them are associated with increased cardiovascular morbidity and mortality. Many disorders of EDS are neurological diseases (e.g. narcolepsy and periodic limb movements in sleep, PLMS). The largest group of disorders causing EDS consists of sleep-related disturbances of breathing, where neuroregulatory mechanisms play a major role in pathophysiology. Many patients with neurodegenerative and neuromuscular diseases suffer from sleep disturbances associated with EDS. Therefore, neurologists must be acquainted with the differential diagnosis of EDS and the major categories of sleep disorders causing it. The present update focuses on major sleep disorders causing EDS, and approaches the topic from the neurologist's perspective. Rather than being an extensive review, this update includes recent data on epidemiology, pathophysiology, diagnosis and treatment of obstructive sleep apnea and related conditions (incresed upper airway resistance syndrome, central sleep apnea), as well as of narcolepsy and PLMS. Also included are recent data concerning EDS in neurodegenerative (Alzheimer's disease, Parkinson's disease, multiple system atrophy) and neuromuscular disorders.

Elevation of Plasma Cytokines in Disorders of Excessive Daytime Sleepiness: Role of Sleep Disturbance and Obesity

Elevation of Plasma Cytokines in Disorders of Excessive Daytime Sleepiness: Role of Sleep Disturbance and Obesity