Sleep and Menopause. Hormone Therapy and Sleep Deprivation

This study evaluated the effect of menopause, hormone therapy (HT) and aging on sleep. Further, the mechanisms behind these effects were examined by studying the associations between sleep and the nocturnal profiles of sleep-related hormones. Crosssectional study protocols were used to evaluate sleep in normal conditions and during recovery from sleep deprivation. The effect of initiation of HT on sleep and sleeprelated hormones was studied in a prospective controlled trial. Young, premenopausal and postmenopausal women were studied, and the methods included polysomnography, 24-h blood sampling, questionnaires and cognitive tests of attention. Postmenopausal women were less satisfied with their sleep quality than premenopausal women, but this was not reflected in sleepiness or attention. The objective sleep quality was mainly similar in pre- and postmenopausal women, but differed from young women. The recovery mechanisms from sleep deprivation were relatively well-preserved after menopause. HT offered no advantage to sleep after sleep deprivation or under normal conditions. The decreased growth hormone (GH) and prolactin (PRL) levels after menopause were reversible with HT. Neither menopause nor HT had any effect on cortisol levels. In premenopausal women, HT had only minor effects on PRL and cortisol levels. The temporal link between GH and slow wave sleep (SWS) was weaker after menopause. PRL levels were temporally associated with sleep stages, and higher levels were seen during SWS and lower during rapid-eye-movement (REM) sleep. Sleep quality after menopause is better determined by age than by menopausal state. Although HT restores the decreased levels of GH and PRL after menopause, it offers no advantage to sleep quality under normal conditions or after sleep deprivation.

Sleep-Disordered Breathing in Women

Sleep-disordered breathing (SDB) is underdiagnosed in women, probably due to the different gender-related manifestation. We investigated the differences in presentation, symptoms and co-morbidities of SDB in men and in pre- and postmenopausal women by a clinical, retrospective, cross-sectional study of 601 consecutively referred women and 233 age- and BMI-matched male-female pairs studied with the static-chargesensitive bed (SCSB) and an oximeter. Data on the use of nasal CPAP were gathered from the Paimio hospital database, and the co-morbidity information was based on reimbursed medication data from the National Agency for Medicines and the Social Insurance institution. The abnormal breathing episodes at night were more frequent in men than in women, and in postmenopausal women compared to premenopausal ones. Partial upper airway obstruction was the most common type of SDB in both genders but especially in females. BMI and the major symptoms of SDB were similar in pre- and postmenopausal women, and a menopause effect on symptoms was not found. CPAP adherence did not differ between symptomatic patients with partial upper airway obstruction and those presenting with conventional obstructive sleep apnea. Comorbidities were more frequent in SDB patients than in the general Finnish population. Compared to sleep apnea, partial upper airway obstruction was associated with a threefold prevalence of asthma and/or COPD in both genders, and with a 60% reduced prevalence of hypertension in females matched for age and BMI. Our results emphasize that partial upper airway obstruction is not a milder form of SDB but a different entity, the severity of which is underestimated when using the conventional apnea-hypopnea index. It seems clinically relevant to diagnose and treat the co-morbidities and SDB also in patients with partial upper airway obstruction, especially in elderly and symptomatic women.

Detection of severe obstructive sleep apnea through voice analysis

tThis paper deals with the potential and limitations of using voice and speech processing to detect Obstruc-tive Sleep Apnea (OSA). An extensive body of voice features has been extracted from patients whopresent various degrees of OSA as well as healthy controls. We analyse the utility of a reduced set offeatures for detecting OSA. We apply various feature selection and reduction schemes (statistical rank-ing, Genetic Algorithms, PCA, LDA) and compare various classifiers (Bayesian Classifiers, kNN, SupportVector Machines, neural networks, Adaboost). S-fold crossvalidation performed on 248 subjects showsthat in the extreme cases (that is, 127 controls and 121 patients with severe OSA) voice alone is able todiscriminate quite well between the presence and absence of OSA. However, this is not the case withmild OSA and healthy snoring patients where voice seems to play a secondary role. We found that thebest classification schemes are achieved using a Genetic Algorithm for feature selection/reduction.

Airway surgery for obstructive sleep apnea and partial upper airway obstruction during sleep

This study analyzed the feasibility and efficacy of surgical therapies in patients with sleep-disordered breathing ranging from partial upper airway obstruction during sleep to severe obstructive sleep apnea syndrome. The surgical procedures evaluated were tracheostomy, laser-assisted uvulopalatoplasty (LUPP) and uvulopalatopharyngoplasty (UPPP) with laser or ultrasound scalpel. Obstructive sleep apnea and partial upper airway obstruction during sleep were measured with the static charge-sensitive bed (SCSB) and pulse oximeter. The patients with severe obstructive sleep apnea syndrome were treated with tracheostomy. Palatal surgery was performed only if the upper airway narrowing occurred exclusively at the soft palate level in patients with partial upper airway obstruction during sleep. The ultrasound scalpel technique was compared to laser-assisted UPPP. The efficacy of LUPP to reduce partial upper airway obstruction during sleep was assessed and histology of uvulopalatal specimen was compared to body fat distributional parameters and sleep study findings. Tracheostomy was effective therapy in severe obstructive sleep apnea. Partial upper airway obstruction and arterial oxyhemoglobin desaturation index during sleep decreased significantly after LUPP. The minimal retropalatal airway dimension increased and soft palate collapsibility decreased at the level where the velopharyngeal obstruction had occurred before the surgery. Ultrasound scalpel did not offer any significant benefits over the laser-assisted technique, except fewer postoperative haemorrhage events. The loose connective tissue as a manifestation of edema was the only histological finding showing correlation with partial upper airway obstruction parameters of SCSB. Tracheostomy remains a life-saving therapy and also long-term option when adherence to CPAP fails in patients with obstructive sleep apnea syndrome. LUPP effectively reduces partial upper airway obstruction during sleep provided that obstruction at the other levels than the soft palate and uvula were preoperatively excluded. Technically the ultrasound scalpel or laser surgeries are equal. In patients with partial upper airway obstruction the loose connective tissue is more important than fat accumulation in the soft palate. This supports the hypothesis that edema is a primary trigger for aggravation of upper airway narrowing during sleep at the soft palate level and evolution towards partial or complete upper airway obstruction during sleep.

Correlation between the oropharyngo-laryngoscopic findings and the severity of obstructive sleep apnea

Objective: To correlate anatomical and functional changes of the oral cavity, pharynx and larynx to the severity of obstructive sleep apnea syndrome (OSAS). Methods : We conducted a cross-sectional study of 66 patients of both genders, aged between 21 and 59 years old with complaints of snoring and / or apnea. All underwent full clinical evaluation, including physical examination, nasolarybgoscopy and polisonography. We classified individuals into groups by the value of the apnea-hypopnea index (AHI), calculated measures of association and analyzed differences by the Kruskal-Wallis and chi-square tests. Results : all patients with obesity type 2 had OSAS. We found a relationship between the uvula projection during nasoendoscopy and OSAS (OR: 4.9; p-value: 0.008; CI: 1.25-22.9). In addition, there was a major strength of association between the circular shape of the pharynx and the presence of moderate or severe OSAS (OR: 9.4, p-value: 0.002), although the CI was wide (1.80-53.13). The septal deviation and lower turbinate hypertrophy were the most frequent nasal alterations, however unrelated to gravity. Nasal obstruction was four times more common in patients without daytime sleepiness. The other craniofacial anatomical changes were not predictors for the occurrence of OSAS. Conclusion : oral, pharyngeal and laryngeal disorders participate in the pathophysiology of OSAS. The completion of the endoscopic examination is of great value to the evaluation of these patients.

Pain symptoms and sleep problems among school-aged children. Long-term prevalence changes, and pain symptoms as predictors of later mental health

Children’s pain symptoms and sleep problems are among the most common health complaints. They distract children from activities, decrease the quality of life, contribute to a significant economic burden, and have shown continuity into adulthood. The main aims of this thesis were to investigate long-term changes in the prevalence of pain symptoms and sleep problems among Finnish school-aged children, and the later mental health of those who in childhood experience pain. Prevalence, co-occurrence, and associated psychosocial factors of pain symptoms and sleep problems were also assessed. In study I, prevalence changes in eight-year-old children’s pain symptoms and sleep problems were investigated in three cross-sectional population-based samples (years 1989: n=1038, 1999: n=1035, and 2005: n=1030). In study II, cross-sectional associations between pain symptoms, sleep problems, and psychosocial factors were assessed among 13-18-year-old adolescents (n=2476). In studies III and IV, associations between pain symptoms at age eight (n=6017), and register-based data on antidepressant use and severe suicidality by age 24, were examined in a nationwide birth cohort. Pain symptoms and sleep problems were common and often co-occurred. A considerable number of children’s pain symptoms remained unrecognized by the parents. The prevalence of pain symptoms, sleep problems, and multiple concurrent symptoms approximately doubled from 1989 to 2005. Psychiatric difficulties or demographic factors did not explain the increase. Psychosocial factors that were associated with pain, sleep problems, and a higher number of symptoms, were female sex, psychological difficulties, emotional symptoms, smoking, victimization, and feeling not cared about by teachers. In longitudinal analyses, the child’s own report of headache, and to a smaller degree the parental report of the child’s abdominal pain predicted later antidepressant use. Parental report of the child’s abdominal pain predicted severe suicidality among males. If one of the symptoms is present, health care professionals should inquire about other symptoms as well. Questions should be directed to the children, not only to their parents. Inquiring about psychiatric difficulties, substance use, victimization, and relations with teachers should be included as a part of the assessment. Further studies are needed to clarify the reasons that underlie the increased prevalence rates, and the factors that may increase or decrease the risk for later mental health problems among pain-suffering children.

Association between Information and Communication Technology Usage and the Quality of Sleep among School-Aged Children during a School Week

ilm OKM 2013

Electrical status epilepticus during sleep. Continuous spikes and waves during sleep

ABSTRACT Maria Peltola Electrical status epilepticus during sleep – Continuous spikes and waves during sleep Department of Clinical Neurophysiology, University of Turku Department of Clinical Neurophysiology and Department of Pediatric Neurology, Children’s Hospital, Helsinki University Central Hospital Annales Universitatis Turkuensis, Medica-Odontologica, Turku, Finland, 2014 Background: Electrical status epilepticus during sleep (ESES) is an EEG phenomenon of frequent spikes and waves occurring in slow sleep. ESES relates to cognitive deterioration in heterogeneous childhood epilepsies. Validated methods to quantitate ESES are missing. The clinical syndrome, called epileptic encephalopathy with continuous spikes and waves during sleep (CSWS) is pharmacoresistant in half of the patients. Limited data exists on surgical treatment of CSWS. Aims and methods: The effects of surgical treatment were studied by investigating electroclinical outcomes in 13 operated patients (nine callosotomies, four resections) with pharmacoresistant CSWS and cognitive decline. Secondly, an objective paradigm was searched for assessing ESES by the semiautomatic quantification of spike index (SI) and measuring spike strength from EEG. Results: Postoperatively, cognitive deterioration was stopped in 12 (92%) patients. Three out of four patients became seizure-free after resective surgery. Callosotomy resulted in greater than 90% reduction of atypical absences in six out of eight patients. The preoperative propagation of ESES from one hemisphere to the other was associated with a good response. Semiautomatic quantification of SI was a robust method when the maximal interspike interval of three seconds was used to determine the “continuous” discharge in ten EEGs. SI of the first hour of sleep appeared representative of the whole night SI. Furthermore, the spikes’ root mean square was found to be a stable measure of spike strength when spatially integrated over multiple electrodes during steady NREM sleep. Conclusions: Patients with pharmacoresistant CSWS, based on structural etiology, may benefit from resective surgery or corpus callosotomy regarding both seizure outcome and cognitive prognosis. The semiautomated SI quantification, with proper userdefined settings and the new spatially integrated measure of spike strength, are robust and promising tools for quantifying ESES. Keywords: Electrical status epilepticus during sleep, ESES, continuous spikes and waves during sleep, CSWS, epilepsy surgery, spike index, spike strength, RMS TIIVISTELMÄ Maria Peltola Unenaikainen sähköinen status epilepticus Kliininen neurofysiologia, Turun yliopisto Kliininen neurofysiologia ja lastenneurologia, Lasten ja nuorten sairaala, Helsingin yliopistollinen keskussairaala Annales Universitatis Turkuensis, Medica-Odontologica, Turku, Suomi, 2014 Tausta: Sähköinen status epilepticus unessa (ESES) on aivosähkökäyrä (EEG)-ilmiö, jossa hidasaaltounen aikana esiintyy tiheä piikkihidasaaltopurkaus. ESES:n kvantifioimiseen ei ole olemassa validoituja menetelmiä. ESES on liitetty kognitiivisen tason laskuun ja tällöin puhutaan CSWS (continuous spikes and waves during sleep) - oireyhtymästä. CSWS ei vastaa lääkehoitoon puolella potilaista ja sen epilepsiakirurgisesta hoidosta on olemassa vain vähän tietoa. Tavoitteet ja menetelmät: Selvitimme retrospektiivisesti epilepsiakirurgian vaikusta elektrokliinisiin löydöksiin 13:lla lääkeresistenttiä CSWS-oireyhtymää sairastavalla lapsella, joilla oli rakenteellinen aivojen poikkeavuus. Toinen tavoite oli löytää objektiivinen puoliautomaattinen tapa mitata purkauksen määrää ja piikkien voimakkuutta EEG:stä. Tulokset: Kognitiivisen tason jatkuva heikentyminen loppui 12 (92 %) potilaalla leikkauksen jälkeen. Kolme neljästä resektiopotilaasta tuli kohtauksettomaksi. Kallosotomian jälkeen kuudella kahdeksasta potilaasta päivittäiset kohtaukset vähenivät yli 90 %:lla. Purkauksen leviäminen leikkausta edeltävästi vain yhdestä hemisfääristä toiseen liittyi hyvään leikkaushoitovasteeseen. Piikki-indeksi, jossa käytetään jatkuvan purkauksen määritelmänä maksimissaan kolmea sekuntia piikkien välillä, osoittautui luotettavaksi menetelmäksi ESES:n kvantifioimiseen. Useammasta elektrodista integroitu piikkien neliöllinen keskiarvo oli piikin voimakkuuden vakaa mitta häiriintymättömässä NREM-unessa. Päätelmät: Lääkehoidolle vastaamatonta CSWS:ää sairastavat potilaat, joilla on rakenteellinen aivopoikkeavuus ja yhdensuuntainen purkauksen leviämismalli, näyttävät kohtausten vähenemisen lisäksi hyötyvän epilepsiakirurgiasta kognitiivisesti. Puoliautomaattinen piikki-indeksin kvantifiointi sopivilla käyttäjäasetuksilla ja uusi spatiaalisesti integroitu piikin voimakkuuden mittari ovat stabiileja ja lupaavia ESES:n kvantitatiivisia mittareita. Avainsanat: Unenaikainen sähköinen status epilepticus, ESES, CSWS, epilepsiakirurgia, piikki-indeksi, piikin voimakkuus, neliöllinen keskiarvo

Rapid eye movement (REM) sleep deprivation reduces rat frontal cortex acetylcholinesterase (EC 3.1.1.7) activity

Rapid eye movement (REM) sleep deprivation induces several behavioral changes. Among these, a decrease in yawning behavior produced by low doses of cholinergic agonists is observed which indicates a change in brain cholinergic neurotransmission after REM sleep deprivation. Acetylcholinesterase (Achase) controls acetylcholine (Ach) availability in the synaptic cleft. Therefore, altered Achase activity may lead to a change in Ach availability at the receptor level which, in turn, may result in modification of cholinergic neurotransmission. To determine if REM sleep deprivation would change the activity of Achase, male Wistar rats, 3 months old, weighing 250-300 g, were deprived of REM sleep for 96 h by the flower-pot technique (N = 12). Two additional groups, a home-cage control (N = 6) and a large platform control (N = 6), were also used. Achase was measured in the frontal cortex using two different methods to obtain the enzyme activity. One method consisted of the obtention of total (900 g supernatant), membrane-bound (100,000 g pellet) and soluble (100,000 g supernatant) Achase, and the other method consisted of the obtention of a fraction (40,000 g pellet) enriched in synaptic membrane-bound enzyme. In both preparations, REM sleep deprivation induced a significant decrease in rat frontal cortex Achase activity when compared to both home-cage and large platform controls. REM sleep deprivation induced a significant decrease of 16% in the membrane-bound Achase activity (nmol thiocholine formed min-1 mg protein-1) in the 100,000 g pellet enzyme preparation (home-cage group 152.1 ± 5.7, large platform group 152.7 ± 24.9 and REM sleep-deprived group 127.9 ± 13.8). There was no difference in the soluble enzyme activity. REM sleep deprivation also induced a significant decrease of 20% in the enriched synaptic membrane-bound Achase activity (home-cage group 126.4 ± 21.5, large platform group 127.8 ± 20.4, REM sleep-deprived group 102.8 ± 14.2). Our results suggest that REM sleep deprivation changes Ach availability at the level of its receptors through a decrease in Achase activity

Cardiovascular and respiratory changes during slow-wave sleep in rats are associated with electrocorticogram desynchronization

In awake rats a single recurrent larger tidal volume (deep breaths) occurs at regular intervals, followed by oscillations in arterial pressure and heart rate. In the present study we recorded the changes in blood pressure, heart rate and ventilation during the wakefulness-sleep cycle identified by electrocorticographic records in order to determine whether the deep breaths and cardiovascular oscillations were associated with changes in the electrocorticogram. During several episodes of slow-wave sleep (SWS) in 7 rats the deep breaths and oscillations in arterial pressure and heart rate were preceded by SWS desynchronization. The interval between deep breaths during SWS was 71 ± 4 s, the period between initial desynchronization and the generation of deep breaths was 3.98 ± 0.45 s and the duration of SWS desynchronization was 11 ± 0.65 s. Hypotension (-16 ± 1 mmHg) and tachycardia (+15 ± 5 bpm) were observed during deep breaths in the SWS state. These data indicate that the oscillations in arterial pressure and heart rate during SWS are associated with deep breaths, which in turn are preceded by desynchronization of the electrocorticogram in this state of sleep

Assessment of ventilatory neuromuscular drive in patients with obstructive sleep apnea

The presence of abnormalities of the respiratory center in obstructive sleep apnea (OSA) patients and their correlation with polysomnographic data are still a matter of controversy. Moderately obese, sleep-deprived OSA patients presenting daytime hypersomnolence, with normocapnia and no clinical or spirometric evidence of pulmonary disease, were selected. We assessed the ventilatory control and correlated it with polysomnographic data. Ventilatory neuromuscular drive was evaluated in these patients by measuring the ventilatory response (VE), the inspiratory occlusion pressure (P.1) and the ventilatory pattern (VT/TI, TI/TTOT) at rest and during submaximal exercise, breathing room air. These analyses were also performed after inhalation of a hypercapnic mixture of CO2 (DP.1/DPETCO2, DVE/DPETCO2). Average rest and exercise ventilatory response (VE: 12.2 and 32.6 l/min, respectively), inspiratory occlusion pressure (P.1: 1.5 and 4.7 cmH2O, respectively), and ventilatory pattern (VT/TI: 0.42 and 1.09 l/s; TI/TTOT: 0.47 and 0.46 l/s, respectively) were within the normal range. In response to hypercapnia, the values of ventilatory response (DVE/DPETCO2: 1.51 l min-1 mmHg-1) and inspiratory occlusion pressure (DP.1/DPETCO2: 0.22 cmH2O) were normal or slightly reduced in the normocapnic OSA patients. No association or correlation between ventilatory neuromuscular drive and ventilatory pattern, hypersomnolence score and polysomnographic data was found; however a significant positive correlation was observed between P.1 and weight. Our results indicate the existence of a group of normocapnic OSA patients who have a normal awake neuromuscular ventilatory drive at rest or during exercise that is partially influenced by obesity

Neuroethologic differences in sleep deprivation induced by the single- and multiple-platform methods

It has been proposed that the multiple-platform method (MP) for desynchronized sleep (DS) deprivation eliminates the stress induced by social isolation and by the restriction of locomotion in the single-platform (SP) method. MP, however, induces a higher increase in plasma corticosterone and ACTH levels than SP. Since deprivation is of heuristic value to identify the functional role of this state of sleep, the objective of the present study was to determine the behavioral differences exhibited by rats during sleep deprivation induced by these two methods. All behavioral patterns exhibited by a group of 7 albino male Wistar rats submitted to 4 days of sleep deprivation by the MP method (15 platforms, spaced 150 mm apart) and by 7 other rats submitted to sleep deprivation by the SP method were recorded in order to elaborate an ethogram. The behavioral patterns were quantitated in 10 replications by naive observers using other groups of 7 rats each submitted to the same deprivation schedule. Each quantification session lasted 35 min and the behavioral patterns presented by each rat over a period of 5 min were counted. The results obtained were: a) rats submitted to the MP method changed platforms at a mean rate of 2.62 ± 1.17 platforms h-1 animal-1; b) the number of episodes of noninteractive waking patterns for the MP animals was significantly higher than that for SP animals (1077 vs 768); c) additional episodes of waking patterns (26.9 ± 18.9 episodes/session) were promoted by social interaction in MP animals; d) the cumulative number of sleep episodes observed in the MP test (311) was significantly lower (chi-square test, 1 d.f., P<0.05) than that observed in the SP test (534); e) rats submitted to the MP test did not show the well-known increase in ambulatory activity observed after the end of the SP test; f) comparison of 6 MP and 6 SP rats showed a significantly shorter latency to the onset of DS in MP rats (7.8 ± 4.3 and 29.0 ± 25.0 min, respectively; Student t-test, P<0.05). We conclude that the social interaction occurring in the MP test generates additional stress since it increases the time of forced wakefulness and reduces the time of rest promoted by synchronized sleep.

Inspiratory flow-volume curve in snoring patients with and without obstructive sleep apnea

We analyzed the flow-volume curves of 50 patients with complaints of snoring and daytime sleepiness in treatment at the Pneumology Unit of the University Hospital of Brasília. The total group was divided into snorers without obstructive sleep apnea (OSA) (N = 19) and snorers with OSA (N = 31); the patients with OSA were subdivided into two groups according to the apnea/hypopnea index (AHI): AHI<20/h (N = 14) and AHI>20/h (N = 17). The control group (N = 10) consisted of nonsmoking subjects without complaints of snoring, daytime sleepiness or pulmonary diseases. The population studied (control and patients) consisted of males of similar age, height and body mass index (BMI); spirometric data were also similar in the four groups. There was no significative difference in the ratio of forced expiratory and inspiratory flows (FEF50%/FIF50%) in any group: control, 0.89; snorers, 1.11; snorers with OSA (AHI<20/h), 1.42, and snorers with OSA (AHI>20/h), 1.64. The FIF at 50% of vital capacity (FIF50%) of snoring patients with or without OSA was lower than the FIF50% of the control group (P<0.05): snorers 4.30 l/s; snorers with OSA (AHI<20/h) 3.69 l/s; snorers with OSA (AHI>20/h) 3.17 l/s and control group 5.48 l/s. The FIF50% of patients with severe OSA (AHI>20/h) was lower than the FIF50% of snorers without OSA (P<0.05): 3.17 l/s and 4.30 l/s, respectively. We conclude that 1) the FEF50%/FIF50% ratio is not useful for predicting OSA, and 2) FIF50% is decreased in snoring patients with and without OSA, suggesting that these patients have increased upper airway resistance (UAR).