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Introduction: Changes in the autonomic nervous system due to Obstructive Sleep Apnea (OSA) during the life span have been described. Some pediatric studies have shown cardiovascular effects in children who do not fit the criteria for OSA; namely children with mild sleep disordered breathing. Objective: We investigated heart rate variability (HRV) during sleep in children with chronic snoring and flow limitation events during sleep. Methods: Ten children and adolescents with chronic snoring and an apnea hypopnea index < 1, associated to high Respiratory Index, and 10 controls matched for age, gender, and Tanner stage were monitored following one night of habituation in the sleep laboratory. HRV was studied at each sleep stage. The time and frequency domains were calculated for each 5-min period. Results: All patients were chronic heavy snorers. They presented an apnea hypopnea index = 0.8, respiratory disturbance index = 10.2/h with lowest O2 saturation 96.1 ± 2.4%. The total power of HRV was decreased in all stages (p < 0.05). There was also a decrease in NN50 and pNN50 during all sleep stages compared to healthy controls (p = 0.0003 and p = 0.03, respectively). Conclusion: A reduction in parasympathetic tone was found in the patient group. This may represent an autonomic impairment during sleep in children with mild SDB. A reduction in HRV in children with habitual snoring could be associated with possible increases in cardiovascular risk in adulthood. Significance: The study indicates that children with habitual snoring have important parasympathetic tone changes during sleep.

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Resumen La historia de la apnea obstructiva del sueño es larga y complicada desde sus primeras descripciones en el siglo XIX con el relato de Pickwick en la primera novela de Charles Dickens. La definición de este término por parte de diferentes investigadores resalta la importancia de comprender las entidades asociadas al síndrome, como la hipoventilación alveolar y la somnolencia diurna excesiva. De esta forma, los estudios neurofisiológicos adelantados desde entonces, el desarrollo de la conferencia de la sociedad europea de neurología de 1964, la descripción del síndrome en pacientes pediátricos, la confirmación de la comorbilidad cardiovascular asociada a la enfermedad, la traqueostomía como tratamiento y la creación de implantes de estimuladores del nervio hipogloso -pasando por el descubrimiento de Sullivan de la presión positiva como tratamiento en casa- han sido esenciales para la comprensión de este síndrome.

Abstract The history of obstructive sleep apnea is long and complicated, and some descriptions can be traced back to the early nineteenth century in The Posthumous Papers of the Pickwick Club, the first novel written by Charles Dickens. The definition of this term by different researchers highlights the importance of understanding the entities associated with the syndrome, such as alveolar hypoventilation and excessive daytime sleepiness. Thus, the neurophysiological studies carried out since then, as well as the European Society of Neurology conference held in 1964, the description of the syndrome in pediatric patients, the confirmation of cardiovascular co-morbidity associated with the disease, tracheostomy as treatment and the creation of hypoglossal nerve stimulus implants -including Sullivan's discovery of positive pressure as a home treatment- have been essential for the understanding of this syndrome.

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OBJECTIVE: This study aimed to evaluate neurocognitive function in adult patients with residual excessive sleepiness (RES) after appropriate treatment of obstructive sleep apnea (OSA) with CPAP and good adherence to treatment. METHODS: This was a prospective controlled study. We included patients of both sexes, aged 35-60 years with OSA and an apnea-hypopnea index >20 ev/h, effectively treated with CPAP, but with a residual Epworth Sleepiness Scale score ≥11. The control group consisted of OSA patients adequately treated with CPAP who did not present with excessive sleepiness after treatment. Both groups underwent the following evaluations: polysomnography, multiple sleep latency testing, depression symptoms, and cognitive assessment. RESULTS: Regarding baseline characteristics, the data were matched for age, years of study, and body mass index. Long-term memory result did not show a significant difference between the two groups (RES group 4.7 ± 2.0; control group 6.5 ± 1.9; p = 0.08). The executive functions were the most affected, with alterations in Wisconsin test, number of categories (RES group: 1.6 ± 1.4; control group: 3.0 ± 1.4; p = 0.01), and semantic verbal fluency test (RES group: 13.6 ± 3.3; control group: 16.9 ± 4.3; p = 0.04). CONCLUSION: In summary, the mean depression scale score in the group with residual excessive sleepiness was significantly higher than that in the control group. Patients with residual excessive sleepiness showed impairment of executive functions but no impairments in other cognitive domains.

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OBJECTIVE: To evaluate the available literature regarding Upper Airway Resistance Syndrome (UARS) treatment. METHODS: Keywords "Upper Airway Resistance Syndrome," "Sleep-related Breathing Disorder treatment," "Obstructive Sleep Apnea treatment" and "flow limitation and sleep" were used in main databases. RESULTS: We found 27 articles describing UARS treatment. Nasal continuous positive airway pressure (CPAP) has been the mainstay therapy prescribed but with limited effectiveness. Studies about surgical treatments had methodological limitations. Oral appliances seem to be effective but their efficacy is not yet established. CONCLUSION: Randomized controlled trials with larger numbers of patients and long-term follow-up are important to establish UARS treatment options.

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STUDY OBJECTIVES: Inspiratory flow limitation (IFL) during sleep occurs when airflow remains constant despite an increase in respiratory effort. This respiratory event has been recognized as an important parameter for identifying sleep breathing disorders. The purpose of this study was to investigate how much IFL normal individuals can present during sleep. DESIGN: Cross-sectional study derived from a general population sample. SETTING: A "normal" asymptomatic sample derived from the epidemiological cohort of São Paulo. PATIENTS AND PARTICIPANTS: This study was derived from a general population study involving questionnaires and nocturnal polysomnography of 1,042 individuals. A subgroup defined as a nonsymptomatic healthy group was used as the normal group. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: All participants answered several questionnaires and underwent full nocturnal polysomnography. IFL was manually scored, and the percentage of IFL of total sleep time was considered for final analysis. The distribution of the percentage of IFL was analyzed, and associated factors (age, sex, and body mass index) were calculated. There were 95% of normal individuals who exhibited IFL during less than 30% of the total sleep time. Body mass index was positively associated with IFL. CONCLUSIONS: Inspiratory flow limitation can be observed in the polysomnography of normal individuals, with an influence of body weight on percentage of inspiratory flow limitation. However, only 5% of asymptomatic individuals will have more than 30% of total sleep time with inspiratory flow limitation. This suggests that only levels of inspiratory flow limitation > 30% be considered in the process of diagnosing obstructive sleep apnea in the absence of an apnea-hypopnea index > 5 and that < 30% of inspiratory flow limitation may be a normal finding in many patients.

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PURPOSE: Obstructive sleep apnea (OSA) is a risk factor for cardiovascular disease. Strong associations have been reported among sleep duration, hypertension, obesity, and cardiovascular mortality. The authors hypothesize that sleep duration may play a role in OSA severity. The aim of this study is to analyze sleep duration in OSA patients. METHODS: Patients who underwent overnight polysomnography were consecutively selected from the Sleep Clinic of Universidade Federal de São Paulo database between March 2009 and December 2010. All subjects were asked to come to the Sleep Clinic at 8:00 a.m. for a clinical evaluation and actigraphy. Anthropometric parameters such as weight, height, hip circumference, abdominal circumference, and neck circumference were also measured. RESULTS: One hundred thirty-three patients were divided into four groups based on total sleep time, sleep efficiency, sleep latency, and wake after sleep onset: very short sleepers (n = 11), short sleepers (n = 21), intermediate sleepers (n = 56), and sufficient sleepers (n = 45). Apnea-hypopnea index (AHI) was higher in very short sleepers (50.18 ± 30.86 events/h) compared with intermediate sleepers (20.36 ± 14.68 events/h; p = 0.007) and sufficient sleepers (23.21 ± 20.45 events/h; p = 0.02). Minimal and mean arterial oxygen saturation and time spent below 90 % oxygen saturation exhibited worse values in very short sleepers. After adjustment for gender, age, AHI, and body mass index, mean oxygen saturation was significantly associated to total sleep time (p = 0.01). CONCLUSIONS: In conclusion, the present study suggests that sleep duration may be associated to low mean oxygen saturation in OSA patients.

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INTRODUCTION/OBJECTIVES: Previous publications have shown beneficial effects of cholinergic medication on obstructive sleep apnea (OSA) in Alzheimer's disease (AD) patients. We hypothesized that cholinergic medication could also improve OSA in non-AD patients. The present study evaluated the effects of donepezil on OSA in non-AD patients. METHODS: A randomized, double-blind, placebo-controlled study was conducted. The final sample consisted of 21 male patients with mild to severe OSA and AHI >10 divided into two groups, a donepezil-treated group (n=11) and a placebo-treated group (n=10). The dosage was one tablet/day (5 mg) for the first two weeks and two tablets/day (10 mg) for the last two weeks. Polysomnography and sleepiness evaluations were performed at baseline and after one month of treatment. Groups were compared using two-way ANOVA for repeated measures with treatment-group and treatment-time as the main factors and time-treatment as an interaction effect. RESULTS: Considering the effect of the interaction with time-treatment, there was a significant improvement in the obstructive apnea/hypopnea index, desaturation index, percentage of time with O(2) saturation ≤3% lower than baseline, lowest oxygen saturation, and the Epworth Sleepiness Scale (ESS) scores with donepezil treatment (p<0.05). Sleep efficiency significantly decreased (p<0.01). CONCLUSIONS: Donepezil treatment improved obstructive sleep apnea index, oxygen saturation, and sleepiness in parallel with a reduction in sleep efficiency. Our findings support the concept that cholinergic transmission may influence breathing regulation in OSA patients.

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OBJECTIVE: The present review addresses the relationship between sleep and depression and how serotonergic transmission is implicated in both conditions. METHOD: Literature searches were performed in the PubMed and MedLine databases up to March 2010. The terms searched were "insomnia", "depression", "sedative antidepressants" and "serotonin". In order to pinpoint the sedative antidepressants most used to treat insomnia, 34 ISI articles, mainly reviews and placebo-controlled clinical trials, were selected from 317 articles found in our primary search. RESULTS: Sleep problems may appear months before the diagnosis of clinical depression and persist after the resolution of depression. Treatment of insomnia symptoms may improve this comorbid disease. Some antidepressant drugs can also result in insomnia or daytime sleepiness. Serotonin (5-HT) demonstrates a complex pattern with respect to sleep and wakefulness that is related to the array of 5-HT receptor subtypes involved in different physiological functions. It is now believed that 5HT2 receptor stimulation is subjacent to insomnia and changes in sleep organization related to the use of some antidepressants. CONCLUSION: Some drugs commonly prescribed for the treatment of depression may worsen insomnia and impair full recovery from depression. 5-HT2 receptor antagonists are promising drugs for treatment strategies since they can improve comorbid insomnia and depression.

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OBJECTIVE: The present review addresses the relationship between sleep and depression and how serotonergic transmission is implicated in both conditions. METHOD: Literature searches were performed in the PubMed and MedLine databases up to March 2010. The terms searched were "insomnia", "depression", "sedative antidepressants" and "serotonin". In order to pinpoint the sedative antidepressants most used to treat insomnia, 34 ISI articles, mainly reviews and placebo-controlled clinical trials, were selected from 317 articles found in our primary search. RESULTS: Sleep problems may appear months before the diagnosis of clinical depression and persist after the resolution of depression. Treatment of insomnia symptoms may improve this comorbid disease. Some antidepressant drugs can also result in insomnia or daytime sleepiness. Serotonin (5-HT) demonstrates a complex pattern with respect to sleep and wakefulness that is related to the array of 5-HT receptor subtypes involved in different physiological functions. It is now believed that 5HT2 receptor stimulation is subjacent to insomnia and changes in sleep organization related to the use of some antidepressants. CONCLUSION: Some drugs commonly prescribed for the treatment of depression may worsen insomnia and impair full recovery from depression. 5-HT2 receptor antagonists are promising drugs for treatment strategies since they can improve comorbid insomnia and depression.

OBJETIVO: Esta atualização aborda a relação entre sono e depressão e como a transmissão serotoninérgica está envolvida em ambas condições. MÉTODO: Foi realizada uma busca na literatura no PubMed e MedLine até março de 2010 com os termos "insônia", "depressão", "antidepressivos sedativos" e "serotonina". A fim de contemplar os antidepressivos sedativos mais utilizados no tratamento da insônia, 34 artigos ISI, principalmente revisões e estudos clínicos placebo-controlados, foram selecionados entre 317 artigos encontrados na busca inicial. RESULTADOS: Alterações de sono podem aparecer meses antes do diagnóstico clínico de depressão e persistir após a resolução da depressão. O tratamento dos sintomas de insônia pode melhorar essa doença associada. Alguns antidepressivos também podem levar à insônia ou sonolência diurna. A serotonina (5-HT) demonstra um padrão complexo no que diz respeito ao sono e vigília, o que está relacionado com a variedade de subtipos do receptor 5-HT envolvidos em diferentes funções fisiológicas. Acredita-se, atualmente, que a estimulação do receptor 5-HT2 esteja envolvida nas alterações da organização do sono e insônia relacionada a alguns antidepressivos. CONCLUSÃO: Alguns medicamentos normalmente prescritos para o tratamento de depressão podem piorar a insônia e dificultar a completa recuperação da depressão. Os antagonistas do receptor 5-HT2 são drogas promissoras para o tratamento, pois podem melhorar a insônia e depressão associadas.

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BACKGROUND: There is an association between Alzheimer disease and sleep-disordered breathing. Donepezil is the drug most frequently used to treat cognitive symptoms in Alzheimer disease. This study evaluates the effects of donepezil on obstructive sleep apnea in patients with Alzheimer disease. METHODS: Randomized, double-blind, placebo-controlled design. Twenty-three patients with mild-to-moderate Alzheimer disease and apnea-hypopnea index (AHI) > 5/h were allocated to two groups: donepezil treated (n = 11) and placebo treated (n = 12). Polysomnography and cognitive evaluation using Alzheimer disease assessment scale-cognitive (ADAS-cog) subscale were performed at baseline and after 3 months. Cognitive and sleep data were analyzed using analysis of variance. RESULTS: AHI and oxygen saturation improved significantly after donepezil treatment compared to baseline and placebo (p < 0.05). Rapid eye movement (REM) sleep duration increased after donepezil treatment (p < 0.05). ADAS-cog scores improved after donepezil treatment, although they did not correlate with REM sleep increase and sleep apnea improvement (p < 0.01). CONCLUSIONS: Donepezil treatment improved AHI and oxygen saturation in patients with Alzheimer disease. Treatment also increased REM sleep duration and reduced ADAS-cog scores. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00480870.

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OBJECTIVES: To evaluate the potential benefit of nasal continuous positive airway pressure (CPAP) administration in pregnant women recognized to have hypertension early in pregnancy. METHODS: This is a randomized study comparing the addition of nasal CPAP treatment to standard prenatal care to standard prenatal care alone in hypertensive women treated with alpha-methyl dopa during early pregnancy. Pregnant women with hypertension were recruited by their obstetricians and completed baseline sleep questionnaires and visual analogue scales on snoring and sleepiness. Subjects were then randomized to receive either CPAP with standard prenatal care (treatment group) or standard prenatal care alone (control group) with routine obstetric follow-up. Nocturnal polysomnography was performed in all patients randomized to the treatment group for initial CPAP titration. Periodic assessment of blood pressure control and CPAP compliance was performed by the same specialist at each scheduled follow-up visit. RESULTS: In the control group (n=9), a progressive rise in blood pressure with a corresponding increase in alpha-methyl dopa doses was observed, beginning at the sixth month of pregnancy. There was also an increase in the number of non-scheduled post-natal visits during the first postpartum month. Pre-eclampsia occurred in one subject; the remaining eight patients had normal pregnancies and infant deliveries. In the treatment group (n=7), blood pressure was noted to decrease significantly as compared to the control group with associated decreases in doses of antihypertensive medications at six months of gestation. All treated patients experienced uncomplicated pregnancies and delivered infants with higher APGAR scores at one minute post-delivery compared to those of controls. CONCLUSION: In pregnant women with hypertension and chronic snoring, nasal CPAP use during the first eight weeks of pregnancy combined with standard prenatal care is associated with better blood pressure control and improved pregnancy outcomes.

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BACKGROUND: Sildenafil prolongs the action of cyclic guanosine monophosphate and nitric oxide by inhibiting cyclic guanosine monophosphate-specific phosphodiesterase 5. It is largely used for erectile dysfunction, a highly prevalent condition in obstructive sleep apnea. Because nitric oxide promotes upper airway congestion, muscle relaxation, and pulmonary vasodilation, the aim of this study was to establish the impact of a single 50-mg dose of sildenafil on the sleep of patients with severe obstructive sleep apnea. METHODS: Thirteen [corrected] middle-aged men with severe obstructive sleep apnea were consecutively selected for this double-blind, placebo-controlled, crossover study. Exclusion criteria were obesity, cardiovascular and/or respiratory disease, and conditions that interfere with sleep. All-night polysomnography was preceded by a single 50-mg dose of sildenafil or matching placebo randomly administered at bedtime, after a washout period of 1 week. RESULTS: In comparison to placebo, a single 50-mg dose of sildenafil significantly increased the percentage of total sleep time with an arterial oxygen saturation of less than 90% (mean +/- SD, 15.6% +/- 9.6% vs 7.9% +/- 3.3%, [corrected] P < .01), without a difference in the nadir of oxygen desaturation. The mean arterial oxygen saturation also decreased (92.1% +/- 1.9% vs 93.8% +/- 1.3%, P = .03), [corrected] and the desaturation index increased (30.3 +/- 14.5 [corrected] events per hour vs 18.5 +/- 9.1 [corrected] events per hour, P < .001). There was an increase in apnea-hypopnea index (48.1 +/- 20.8 [corrected] events per hour vs 32.3 +/- 11.3 [corrected] events per hour, P = .001), [corrected] involving mostly obstructive events. CONCLUSION: In patients with severe obstructive sleep apnea, a single 50-mg dose of sildenafil at bedtime worsens respiratory and desaturation events.

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A síndrome da apnéia obstrutiva do sono (SAHOS) é uma condição prevalente na população, associada a maior risco cardiovascular, freqüentemente não-diagnosticada. O reconhecimento da síndrome requer alto grau de suspeita clínica, especialmente por cardiologistas, e pode ser confirmada por meio da polissonografia. O tratamento da síndrome com o uso de CPAP (pressão positiva na via aérea superior) é altamente eficaz, melhorando o padrão respiratório durante o sono, instituindo o sono reparador e, dessa forma, otimizando a qualidade de vida desses pacientes, além de atenuar ou reverter muitas das complicações cardiovasculares relacionadas a SAHOS. Este artigo aborda a fisiopatologia e os aspectos clínicos das comorbidades cardiovasculares associadas à síndrome.

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OBJECTIVE: To investigate the relationship between clinical manifestations and sleep abnormalities in patients with juvenile rheumatoid arthritis (JRA). METHODS: Twenty-one patients with active polyarticular JRA and 20 healthy controls were enrolled consecutively. Pain and functional impairment were assessed with standardized, validated Brazilian questionnaires. Sleep evaluation was based on parent reporting of their child's sleep habits and polysomnography; subjects underwent an adaptation night in the sleep laboratory. Sleep architecture was analyzed and spectral analysis of non-rapid eye movement (REM) sleep was carried out by electroencephalography. RESULTS: Patients with JRA exhibited higher indexes of periodic leg movements (PLM; p = 0.02), isolated leg movements (LM), and arousals, as well as increases in alpha activity in non-REM sleep (all p < 0.01), in spite of similar frequency of sleep complaints in comparison to controls. Among JRA patients, greater alpha activity in non-REM sleep was observed in the participants with greater joint involvement assessed by the Escola Paulista de Medicina-Pediatric Range of Motion Scale (p = 0.03) or joint count (p = 0.02). Correlation was observed between morning stiffness and PLM and/or LM (rS = 0.75, Sr = 0.74, p < 0.001 for both), and between self-rating scores of pain and alpha activity in non-REM sleep (rS = 0.74, p < 0.001). CONCLUSION: Pain symptoms and disability are related to sleep fragmentation in patients with active polyarticular JRA.

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STUDY OBJECTIVE: Examine the effects of donepezil on sleep and rapid eye movement (REM) sleep electroencephalogram (EEG) in patients with Alzheimer disease, using polysomnography, and the correlation between REM sleep EEG parameters and cognitive scores. DESIGN: Randomized, double-blind, placebo-controlled design. SETTINGS: Two sleep research centers, University Hospital. PARTICIPANTS: Thirty-five patients with mild to moderate Alzheimer disease, allocated to 2 groups: donepezil treated (n=17) and placebo treated (n=18). INTERVENTION: Patients were administered donepezil or placebo. OUTCOME MEASURES: Polysomnography with REM sleep EEG spectral analysis and cognitive evaluation using the Alzheimer Disease Assessment Scale, cognitive subscale, were performed at baseline and after 3 and 6 months. Slowing ratio was the ratio between slow and fast EEG frequency bands. Cognitive and sleep data were analyzed using analysis of variance. Correlations between cognitive improvement and REM sleep EEG were also calculated. RESULTS: REM sleep increased significantly after 3 and 6 months of donepezil treatment compared with baseline and placebo (p < .01). Overall theta (p = .04), frontal theta (p < .01) and frontal delta (p = .03) absolute power during REM sleep decreased after 6 months of donepezil treatment. The occipital slowing ratio decreased during treatment (p = .04). REM sleep overall and frontal and centroparietal alpha absolute power significantly correlated with the cognitive improvement rate on the Alzheimer Disease Assessment Scale, cognitive subscale (r = 0.75, r = 0.71, r = 0.78); p < .01). CONCLUSIONS: Donepezil treatment enhanced REM sleep and reduced slow frequencies of REM sleep EEG, suggesting a possible action upon REM sleep-related cholinergic neurons in patients with Alzheimer disease. Furthermore, REM sleep alpha power may predict the cognitive response to donepezil.

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STUDY OBJECTIVES: The aim of this study is to complement the data on the expression and characteristics of cyclic alternating pattern (CAP) events in children, specifically in the peripubertal age group of 8 to 12 years and to analyze the association of CAP events with arousals. The study of CAP and arousal is a useful tool for assessing sleep instability and fragmentation in children. DESIGN: Descriptive study. PARTICIPANTS: Ten sex-matched healthy children, aged 8 to 12 years, underwent standard polysomnography after 1 adaptation night in the sleep laboratory. Sleep stages, CAP, and arousals were analyzed according to standard international rules. RESULTS: The mean CAP rate was 62.1% +/- 10.8% and the mean CAP cycle duration, 24.6 +/- 2.1 minutes. CAP A1 phase was the most numerous (85.5% +/- 3.9%), whereas the A2 phase was 9.1% +/- 4.7%, and the A3 phase as 5% +/- 2.3%, (P < .01). Differences between boys and girls were detected by analysis of variance, namely increases of phase A2 and A3 subtypes in girls (P < .001). Stronger phase A1 subtype expression in slow-wave sleep was verified in both sexes. Positive correlation between electroencephalogram arousals and the sum of phase A2 and A3 subtypes was also present. The overall CAP rate is higher in this age group than the rate previously reported in children aged 6 to 10 years (62.1% +/- 10.8% vs 33.4% +/- 5.3%). CONCLUSIONS: Our study provides normative data on CAP in children aged 8 to 12 years and indicates that age and Tanner stages must both be considered when investigating peripubertal children.

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Cases of violent behavior during sleep have been reported in the literature. However, the incidence of violent behavior during sleep is not known. One epidemiological study showed that approximately 2% of the general population, predominantly males, presented violent behavior while asleep. In the present study, the authors describe clinical and medico-legal aspects involved in violent behavior investigation. Violent behavior refers to self-injury or injury to another during sleep. It happens most frequently following partial awakening in the context of arousal disorders (parasomnias). The most frequently diagnosed sleep disorders are REM behavior disorder and somnambulism. Violent behavior might be precipitated by stress, use of alcohol or drugs, sleep deprivation or fever.

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