Síndrome das pernas inquietas (SPI) é um distúrbio do sono com alta prevalência entre pacientes em hemodiálise, nos quais o mecanismo é pouco conhecido. Tem sido postulado que alterações do metabolismo mineral e ósseo relacionadasà doença renal crônica, especialmente o hiperparatireoidismo secundário, possam estar relacionadas à patogênese da SPI. Este trabalho teve como objetivo principal avaliar a SPI antes e após paratireoidectomia (PTX). Além disso, avaliamos dados objetivos do sono por meio de polissonografia, com ênfase em apneia do sono. Estudamos prospectivamente 19 pacientes (6 homens, idade 48 ± 11 anos) com hiperparatireoidismo grave pré e pós-PTX. O diagnóstico e o escore de gravidade da SPI foram avaliados de acordo com o Grupo de Estudo Internacional de SPI. Polissonografia pré e pós-PTX forneceu dados de arquitetura do sono, movimentos periódicos de pernas e apneia do sono, medida por meio do índice de apneia-hipopneia/hora de sono (IAH). SPI foi encontrada em 10 pacientes (53%) e se associou com maiores níveis de fosfato (p=0,005) e maior gravidade da dor (p=0,003). Após a PTX, houve redução dos níveis séricos de paratormônio, fosfato e aumento dos níveis de 25-hidroxivitamina D, calicreína-6 e fetuína-A. A PTX reduziu a SPI para 21% (p=0,044), acompanhada por redução nos escores de gravidade e alívio da dor e do prurido. A análise de regressão logística mostrou que o fosfato pré-PTX permaneceu independentemente associado com SPI (OR=7,28; p=0,035), em modelo ajustado para hemoglobina, idade e sexo. Apneia do sono (IAH > 5) foi encontrada em 11 pacientes pré e 14 pós-PTX (63% vs. 74%, p=0,698). Observamos uma correlação entre o IAH e a relação água corporal extracelular/massa magra (r=0,535, p=0,018), assim como correlação com a circunferência do pescoço pré-PTX (r=0,471, p=0,042). Entretanto, não observamos correlação do IAH com o deslocamento de fluidos da perna direita durante o sono (p=0,09), que aumentou significativamente após PTX (p=0,011). Concluímos que a PTX melhora a SPI, com cura completa ou melhora significativa. Se essa melhora está relacionada à diminuição do paratormônio ou do fósforo necessita de investigação adicional. Além disso, o presente estudo confirma a alta prevalência de apneia do sono entre pacientes em hemodiálise, o que não se modificou com a PTX / Restless legs syndrome (RLS) is a sleep disorder with high prevalence among patients on hemodialysis, which underlying mechanism is still unknown. It has been postulate that bone metabolism disorder, especially secondary hyperparathyroidism may be implicated in the pathogenesis. The present study aimed to evaluate RLS before and after parathyroidectomy (PTX). In addition, we evaluated objective data through polysomnography, focusing on sleep apnea. We prospectively evaluated 19 patients (6 men, aged 48 ± 11 years) with severe hyperparathyroidism pre and post-surgical treatment, parathyroidectomy (PTX). RLS diagnosis and rating scale were accessed based on the International RLS Study Group. Polysomnography pre and post PTX provided data on sleep architecture, periodic leg movements of sleep and apnea-hypopnea index (AHI). RLS was observed in 10 patients (53%), and was associated with higher levels of phosphate (p=0,005) and severe pain (p=0,003). After PTX, there was a reduction of serum parathyroid hormone, serum phosphate, and an increase of 25hydroxyvitamin D, kallicrein-6 and Fetuin-A. PTX improved RLS to 21% (p=0,04), accompanied by a decrease in rating scale, in association with alleviation of pain and pruritus. Logistic regression shows that serum phosphate pre PTX remained independently associated with RLS (HR=7,28; p=0,035), in a model adjusted for hemoglobin, age and gender. Sleep apnea (AHI > 5) was found in 11 patients pre and 14 patients post PTX (63% vs. 74%, p=0,698). There was a correlation between AHI and the relation extracellular water/ lean body mass (r=0,535; p=0,018) as well as a correlation between AHI and neck circumference (r=0,471; p=0,042). However, there was no correlation between AHI and spontaneous rostral fluid shift (p=0,09) that has increased after PTX (p=0,011). We concluded that PTX provided an opportunity to improve RLS. Whether RLS may be improved by reduction of serum phosphorus or parathyroid hormone, merits further investigation. In addition, PTX had no impact on the high prevalence of sleep apnea in this population

Introdução: Apneia Obstrutiva do Sono (AOS) é prevalente em estados edematosos, especialmente em pacientes em hemodiálise (HD). Uma vez que o deslocamento noturno de fluidos (DNF) acarreta piora da AOS, nós elaboramos a hipótese de que a interferência na redistribuição de fluidos pelo uso de meias elásticas compressivas (MEC) atenuaria a gravidade da AOS, por mecanismos diferentes em comparação à terapia padrão para AOS, a pressão positiva em vias aéreas (CPAP). Métodos: este é um estudo randomizado e cross-over, que incluiu 14 pacientes dialíticos com AOS (índice de apneia/hipopneia - IAH > 5 eventos/hora) em exame de polissonografia (PSG), que era realizada em três momentos: basal, titulação de CPAP e após uma semana de uso diário de MEC. Circunferência cervical (CC), bioimpedância elétrica segmentar e variabilidade de frequência cardíaca (VFC) foram avaliadas antes e após cada exame de PSG. Resultados: A idade média foi 53±9 anos (57% de homens) e o índice de massa corporal foi 29,7±6,8 Kg/m². O IAH foi reduzido de 20,8 (14,2; 39,6) no exame basal para 7,9 (2,8; 25,4) durante titulação de CPAP e para 16,7 (3,5; 28,9) eventos/hora após uso de MEC (CPAP vs. basal, p=0,004; MEC vs. basal, p=0,017; e CPAP vs. MEC, p=0.017). Comparando basal, CPAP e MEC, o conteúdo de água noturna em membros inferiores foi menor com MEC (p=0,04), enquanto a água intracelular noturna em tronco foi maior (p=0,03). DNF basal, com CPAP e MEC foi de -183±72, -343±220, e -290±213ml, respectivamente (p=0,006). Houve aumento da circunferência cervical durante a noite durante o exame basal (0,7±0,4 cm), mas houve redução dessa circunferência após titulação com CPAP (-1,0±0,4 cm) e após uso de MEC (-0,4±0,8 cm) (CPAP vs. basal, p<0.0001; MEC vs. basal, p=0.001; CPAP vs. MEC, p=0.01). VFC, avaliada pelos componentes de alta e baixa frequência, demonstrou menor ativação simpática durante o exame de titulação de CPAP: OR: 11 (95% CI: 1,06 - 114,2), p=0,025, mas não com MEC: OR: 7,8 (95% CI: 0,75 - 82,2), p=0,059. Conclusões: tanto o CPAP quanto MEC melhoraram AOS em pacientes em HD, mas por mecanismos distintos: enquanto o CPAP reduziu o edema de vias aéreas superiores, ao exercer pressão local, o uso de MEC reduziu o DNF, ao evitar retenção de fluidos em membros inferiores, acumulando água no componente intracelular do tronco. Ativação simpática foi somente reduzida com uso de CPAP. / Background: Obstructive Sleep Apnea (OSA) is prevalent in edematous states, notably in hemodialysis (HD) patients. Once overnight fluid shift (OFS) augments OSA, we hypothesized that interfering in fluid redistribution by wearing compression stockings (CS) would attenuate OSA severity by different mechanisms in comparison to the standard treatment to OSA, the positive airway pressure (CPAP). Methods: This is a randomized crossover study that included 14 dialytic patients with OSA (apnea/hypopnea index - AHI >5 events/hour) by polysomnography (PSG), which was performed in three moments: at baseline, for CPAP titration, and one week after daily wearing of CS. Neck circumference (NC), segmental bioelectrical impedance and heart rate variability (HRV) were assessed before and after each PSG. Results: Mean age was 53±9 years (57% men) and body mass index was 29.7±6.8 kg/m2. AHI decreased from 20.8 (14.2; 39.6) at baseline to 7.9 (2.8; 25.4) during CPAP titration and to 16.7 (3.5; 28.9) events/hour after wearing CS (CPAP vs. baseline, p=0.004; CS vs. baseline, p=0.017; and CPAP vs. CS, p=0.017). Comparing baseline, CPAP and CS, nocturnal lower limbs water content was lower with CS (p=0.04), while nocturnal intracellular trunk water was higher (p=0.03). OFS at baseline, CPAP and CS was -183±72, -343±220, and -290±213ml, respectively (p=0.006). Overnight NC variation increased at baseline (0.7±0.4 cm), but decreased after CPAP titration (-1.0±0.4 cm) and while wearing CS (-0.4±0.8 cm) (CPAP vs. baseline, p<0.0001; CS vs. baseline, p=0.001; CPAP vs. CS, p=0.01). HRV, assessed by both high and low frequency components, showed a lower sympathetic activation during CPAP titration: OR: 11 (95% CI: 1.06 - 114.2), p=0.025, but not with CS: OR: 7,8 (95% CI: 0.75 - 82.2), p=0.059 Conclusions: Both CPAP and CS improved OSA in HD patients by different mechanisms: while CPAP reduced edema in upper airways by exerting local pressure, wearing CS reduced OFS by avoiding fluid retention in the legs, accumulating water in the intracellular component of the trunk. Sympathetic activation was decreased only with CPAP.

INTRODUÇÃO: A literatura confirma a relação existente entre os Distúrbios Respiratórios do Sono (DRS) e os sintomas do Transtorno do Déficit de Atenção/Hiperatividade (TDAH). Há estudos que mostram o efeito dos tratamentos para DRS no comportamento, observando-se, após adenotonsilectomia, melhora nos índices dos testes de comportamento, assim como no desempenho escolar das crianças com TDAH. Considerando-se a relação existente entre a Respiração Oral (RO) e os DRS e entre estes e o TDAH, pretende-se avaliar se ocorrem interferências sintomáticas entre a RO e o TDAH, quando se obtém a reversão da RO em respiração nasal fisiológica, através da utilização do tratamento ortopédico funcional (utilização de placas ortopédicas, orientação para o fechamento labial, ginástica respiratória) e terapia fonoaudiológica. MÉTODOS: Neste estudo longitudinal, realizado entre janeiro de 2004 e janeiro de 2007, acompanhando pacientes com TDAH e RO, de 7 a 13 anos de idade, por 18 meses, no ambulatório de TDAH do Hospital das Clínicas/ FMUSP, comparamos os escores de testes comportamentais para TDAH (Conners e SNAP IV) em dois grupos de pacientes que estavam sendo tratados com metilfenidato, um dos quais recebeu tratamento ortopédico funcional e fonoaudiológico para a RO. RESULTADOS: 1) Não houve diferenças entre o grupo tratado e não tratado para a RO com respeito à idade; 2) Os escores dos questionários no grupo tratado para RO foram significantemente diminuindo (indicando melhora) em todas as variáveis (exceto Conners Pais -conduta anti-social), ao longo do tempo; 3) Os escores dos questionários no grupo tratado para RO foram significantemente menores (indicando melhora) do que os escores do grupo não tratado, para todas as variáveis estudadas, quando se comparam os dois grupos; 4) Esta melhora dos sintomas ocorreu após 12 meses de tratamento para RO e persistiu aos 18 meses; 5) dois dos oito pacientes do grupo tratado puderam interromper o metilfenidato, sendo que todos os pacientes do grupo não tratado ainda utilizam o medicamento. CONCLUSÕES: O Tratamento Ortopédico Funcional para RO, em conjunto com a terapia fonoaudiológica, foi efetivo para a melhora dos sintomas de TDAH em pacientes em tratamento com metilfenidato; a RO e os DRS devem ser investigados e tratados em pacientes com diagnóstico ou suspeita de TDAH, pois podem contribuir para a piora dos sintomas. / INTRODUCTION: A number of studies demonstrate the relationship between Sleep Respiratory Disorders (SRD) and symptoms of the Attention Deficit Hyperactivity Disorder (ADHD). Some of them assess the effect of the treatments for SRD on the behavior; for example, an improvement of the scores in the behavior tests, as well as in the school performance of children with TDAH is observed after adenotonsillectomy Considering the relation between mouth breathing (MB) and SRD and between these and the ADHD, we aimed to evaluate symptomatic interferences between MB and ADHD, through the reversion of MB in physiological nasal breath, by means of functional orthopedics treatment (use of orthopedics plates, orientation for labial closing, respiratory gymnastics) and speech therapy. METHODS: In this longitudinal study, performed between January of 2004 and January of 2007, 16 patients with ADHD and MB, aged 7 to 13 years, and who were being treated with methylphenidate, were followed-up for 18 months, in the outpatient clinic for ADHD at the Hospital das Clínicas da FMUSP. We compared the scores in ADHD tests (Conners and SNAP IV) of two groups of eight patients, one of which received functional orthopedics treatment and speech therapy for MB and the other did not. RESULTS: 1) The two groups were statistically equivalent by age; 2) The scores of the questionnaires in the group of patients treated for MB were significantly lowering (indicating improvement) regarding all the variables (except Conners Parents - antisocial behavior), along the follow-up period; 3) The scores of the questionnaires in the treated group were significantly lower (indicating improvement) of the scores in no treated group, for all the studied variables, when the two groups are compared; 4) This improvement of the symptoms occurred 12 months after the beginning of the treatment for MB and persisted at 18 months; 5) two of the eight patients from the treated group were indicated for interrupting the methylphenidate; however, all patients of the group not treated were still utilizing the medication. CONCLUSIONS: Functional the Orthopedics Treatment for MB, associated with speech therapy, was effective for the improvement of the symptoms of ADHD in patients who were being treated with methylphenidate; MB and SRD must be investigated and treated in patients with diagnosis or suspicion of ADHD, as they can contribute for the worsening of the symptoms.

Introdução- Obstrução das vias aeríferas superiores associadas a mudanças nos padrões de sono, estão diretamente relacionados a problemas de crescimento e aprendizagem, o que interfere com a qualidade de vida das crianças com este quadro. Métodos de expansão maxilar já mostraram efeito favorável sobre a função respiratória. Aparelhos removíveis intra-orais têm sido usados no tratamento do ronco e apneia do sono, buscando reequilibrar a postura da mandíbula e da língua para melhorar a função respiratória. O objetivo deste trabalho é avaliar as dimensões da faringe, o crescimento craniofacial e os sintomas respiratórios obstrutivos em crianças com ronco e aumento das tonsilas faríngeas e palatinas em tratamento com um aparelho ortodôntico e ortopédico bucal. Métodos- Quarenta crianças de 6 a 9 anos de idade com tonsilas faríngeas e palatinas graus 3 e 4 e apresentando maxila atrésica e sobressaliência anterior foram divididos em dois grupos aleatórios: 24 pacientes tratados com o aparelho oral e 16 controles não tratados. As dimensões da faringe foram medidas por faringometria acústica. Cefalometria avaliou o crescimento facial, incluindo os valores relacionados com a apnéia do sono. Os pais preencheram questionários sobre os sintomas respiratórios da criança. Os pacientes foram reavaliados após 6 meses, em ambos os grupos. Resultados: A faringometria acústica confirmou um aumento volumétrico de 3,1 cm3 (d.p. ± 2,5) na faringe, no grupo de estudo e uma redução volumétrica de -1,2 cm3 (d.p. ± 1,3) no não tratado (p <0,001). A área mínima de colapsibilidade no grupo de estudo apresentou incremento de 1,1 cm2 (dp ± 0,2) para 1,3 cm2 (d.p. ± 0,2) e uma redução no grupo controle de 1,5 cm2 (dp ± 0,3) para 1,3 cm2 (d.p. ± 0,3) estatisticamente significante (p <0,001). A cefalometria comprovou crescimento craniofacial mais favorável no grupo de estudo, em comparação aos controles, incluindo os valores relacionados a apnéia do sono, como ANB, MMPA e H-ML (p <0,001) . O questionário de sintomas confirmou uma melhoria no padrão de respiração e sono no grupo tratado. Conclusão- As crianças que foram submetidos a esse protocolo de tratamento apresentaram aumento de dimensões da faringe, direção de crescimento mais favorável, e uma melhora na respiração e qualidade do sono / Introduction- Airway obstruction due to associated changes in sleep patterns are directly related to problems of growth and learning, which interfer with the quality of life for these children. Maxillary expansion methods have shown favorable effect on respiratory function. Intra-oral removable appliances have been used in the treatment of snoring and sleep apnea, seeking to rebalance the posture of the jaw and tongue to improve breathing function. The purpose of this thesis is evaluate the facial growth, pharyngeal dimensions and respiratory symptoms in snoring children with enlarged tonsils and adenoids under treatment with an orthodontic and orthopedic oral appliance. Methods- Forty snoring children ages 6 to 9 years old with tonsil and adenoid enlargement grades 3 and 4 and presenting constricted maxilla were divided into two randomized groups: 24 patients treated with the oral appliance and 16 untreated controls. Pharyngeal size was measured by acoustic pharyngometry. Cephalometry evaluated the facial growth including values related to sleep apnea. Pharyngeal size was measured by acoustic pharyngometry. Parents filled out questionnaires about their child\'s respiratory symptoms. Patients were re-evaluated after 6 months, in both groups Results- Acoustic pharyngometry confirmed a volumetric gain of 3.1 cm3 (s.d. ±2.5) in the pharynx at the study group and a volumetric reduction of -1.2 cm3 (s.d. ±1.3) at the untreated (p<0.001). The minimum area on collapsibility at the study group showed an increment from1.1 cm2 (s.d.±0.2) to 1.3 cm2 (s.d.±0.2) and a reduction on the control group from 1.5 cm2 (s.d.±0.3) to 1.3 cm2 (s.d.±0.3) statistically significant (p<0.001). Cephalometry showed a more favorable facial growth on the study group compared to controls, including values related to sleep apnea prediction such as ANB, MMPA and H-ML (p<0.001). The symptoms questionnaire confirmed an improvement on the breathing pattern at the group treated. Conclusions- Children who underwent this treatment protocol presented more favorable growth direction, enlargement of pharyngeal dimensions, and an improvement in breathing and sleep

Abstract The prevalence of self-reported obstructive sleep apnea syndrome (OSAS), habitual snoring (HS), daytime sleepiness (DS) and restless legs syndrome (RLS), and their associations with cardiovascular risk factors and depressive symptoms as well as the natural course and associated factors of habitual snoring and restless legs syndrome over a ten-year period were studied. Two different birth cohorts in Northern Finland were investigated. In the Oulu 35 longitudinal research programme study subjects participated in two subsequent surveys conducted in 1996–1998 and 2007–2008 (61–63 and 72–73 years old subjects, respectively). The Oulu 45 study population was examined in 2001–2002 (56–57 years old subjects). The data were gathered by questionnaires, as well as laboratory and clinical measurements. In the Oulu35 study, of the 831 baseline participants, 593 (73%) participated in the first follow-up in 1996–1998 and 457 (55%) participated in both follow-up studies. In the Oulu 45 study, the target population comprised 1 332 subjects, 995 (75%) of whom participated. The prevalence of OSAS was 8% in the 56–57 year-old population, 4% in the 61–63 year old population, and 3% in the 72–73 year old population. These figures were 31%, 26% and 19% for HS, 16%, 9% and 11% for DS, and 18%, 21% and 15% for RLS, respectively. In a ten-year period, half of those who snored in 1996–1998 stopped snoring, and half of those who suffered from restless legs 3–7 nights/week in 1996–98 suffered from this syndrome less than once a week in 2007–2008. The 10-year incidence of new cases of both HS and RLS was 7%. In subjects aged 56–57 and 61–63, the components of the metabolic syndrome and depressive symptoms associated with OSAS and HS, while in the follow-up study, the role of these associations diminished. Male gender was the strongest predictor of the new cases of HS, while depressive symptoms and waist circumference predicted the permanence or incidence of HS. Depressive symptoms, DS and, weakly, waist circumference were associated with RLS in both the 56–57 year-old and in 61–63 year-old populations. Depressive symptoms were also predictive of the permanence and incidence of new RLS cases. Waist circumference also predicted new cases of RLS in the 72–73 year-old population. Sleep disorders were quite common in 56–73 year-old subjects and their prevalence seemed to diminish as subjects aged. The components of metabolic syndrome associated with sleep disorders in middle-aged subjects, but these associations lost their significance in older age groups. Depressive symptoms predicted incidence of restless legs syndrome. / Tiivistelmä Tutkimuksessa selvitettiin unenaikaisten hengityshäiriöiden, päiväaikaisen väsymyksen ja levottomien jalkojen esiintyvyyttä ja yhteyksiä sydän- ja verisuonitautien riskitekijöihin sekä depressioon. Jokaöisen kuorsaamisen ja levottomien jalkojen luonnollista kulkua ja siihen vaikuttavia tekijöitä selvitettiin 10 vuoden seuranta-aikana. Tutkimusaineisto koostui kahdesta eri-ikäisestä pohjoissuomalaisesta väestöstä. Oulu35-seurantatutkimukset tehtiin vuosina 1996–1998 ja 2007–2008 (61–63- ja 72–73-vuotiaat tutkittavat). Oulu45-poikkileikkaustutkimus tehtiin vuosina 2001–2002 (56–57-vuotiaat tutkittavat). Aineisto kerättiin kyselylomakkeilla, laboratorio- ja kliinisillä tutkimuksilla. Oulu35-tutkimuksessa 593 henkilöä (73&#160;%) 831 kutsutusta osallistui ensimmäiseen seurantatutkimukseen v. 1996–1998 ja molempiin seurantatutkimuksiin osallistui 457 (55&#160;%) henkilöä. Oulu45 -tutkimukseen osallistui 995 henkilöä (75&#160;%) 1332 kutsutusta. Obstruktiivisen uniapnean esiintyvyys 56–57-vuotiaalla väestöllä oli 8&#160;%, 61–63-vuotiailla 4&#160;% ja 72–73-vuotiailla 3&#160;%. Jokaöisen kuorsaamisen esiintyvyys oli vastaavissa ikäluokissa 31&#160;%, 26&#160;% ja 19&#160;%, päiväaikaisen väsymyksen 16&#160;%, 9&#160;% ja 11&#160;% ja levottomien jalkojen 18&#160;%, 21&#160;% ja 15&#160;%. Kymmenen vuoden seurannassa jokaöinen kuorsaaminen vähentyi puoleen niillä henkilöillä, jotka kuorsasivat v. 1996–1998. Vastaavasti 10 vuoden kuluttua niillä henkilöillä, joilla esiintyi levottomia jalkoja 3–7 yönä viikossa v. 1996–1998, esiintyvyys oli vähentynyt alle 1 kertaan viikossa puolella tutkituista. 10 vuoden ilmaantuvuus sekä jokaöiselle kuorsaamiselle että levottomille jaloille oli 7&#160;%. Metabolisen oireyhtymän osatekijät ja depressiiviset oireet olivat yhteydessä obstruktiiviseen uniapneaan ja jokaöiseen kuorsaamiseen sekä 56–57-vuotiailla että 61–63-vuotiailla. Kymmenen vuoden seurannassa näiden tekijöiden vaikutus näytti kuitenkin vähentyvän. Miessukupuoli ennusti vahvimmin jokaöisen kuorsaamisen ilmaantuvuutta. Myös depressiiviset oireet ja vyötärönympärys ennustivat jokaöisen kuorsaamisen ilmaantuvuutta ja pysyvyyttä. Depressiiviset oireet, päiväaikainen väsymys ja vyötärönympärys olivat yhteydessä levottomien jalkojen esiintyvyyteen sekä 56–57- että 61–63-vuotiaassa että väestössä. Depressiiviset oireet ennustivat myös levottomien jalkojen ilmaantuvuutta ja tilan pysyvyyttä ja vyötärönympärys levottomien jalkojen ilmaantuvuutta 72–73-vuotiaana. Unihäiriöt olivat varsin yleisiä 56–73-vuotiaissa väestöissä, ja niiden ilmaantuvuus näyttäisi vähentyvän iän mukana. Metabolisen oireyhtymän osatekijät olivat yhteydessä unihäiriöihin keski-ikäisillä, mutta vanhemmissa ikäluokissa näiden yhteyksien merkitys väheni. Depressiiviset ennustivat levottomat jalat -oireyhtymän ilmaantuvuutta.

L’objectif de ce travail de thèse a été d’étudier la réactivité autonomique cardiaque à des stimulations aversives au cours du sommeil et les phénomènes pouvant la moduler. Pour ce faire, nous avons utilisé une technique d’analyse temps-fréquence de la variabilité du signal RR (inverse de la fréquence cardiaque), basée sur des transformées en ondelettes de ce signal, lors de stimuli nociceptifs chez des sujets sains et en réponse à des évènements respiratoires obstructifs chez des patients apnéiques. Notre première étude suggère que la réactivité autonomique cardiaque en réaction à des stimuli nociceptifs est dépendante d’une activation sympathique qui est préservée dans tous les stades du sommeil. De plus, bien que cette réactivité cardiaque soit présente même lorsque la stimulation ne donne pas lieu à une réaction d’éveil, elle est plus importante si la stimulation est suivie d’une réaction d’éveil cortical, et ceci quelque soit le stade de sommeil. La deuxième étude, réalisée chez des patients apnéiques, montre que la réactivité autonomique en réponse aux évènements respiratoires obstructifs est dépendante essentiellement de la réactivité sympathique qui est modulée par le processus de réaction d’éveil plutôt que par les stades de sommeil ou par la sévérité des évènements respiratoires. Enfin, la troisième étude révèle qu’un niveau d’activité sympathique cardiaque élevé avant les stimulations nociceptives ou pendant les évènements respiratoires obstructifs peut favoriser l’apparition de réactions d’éveil. En conclusion, nos résultats sont en faveur du maintien de la réactivité sympathique cardiaque à des évènements aversifs au cours du sommeil et ceci dans tous les stades de sommeil. Cette réactivité sympathique est essentiellement modulée par le processus qui mène à la réaction d’éveil cortical, processus auquel semble participer un niveau sympathique basal élevé / The aim of this work was to study cardiac autonomic reactivity to aversive stimulations during sleep and the phenomena that could modulate this reactivity. We used time-frequency method of RR intervals variability (or heart rate variability), based on wavelet transform during nociceptive stimulations in healthy subjects and obstructive respiratory events in apnoeic patients. Our first study showed that the cardiac autonomic reactivity to nociceptive stimulations is sympathetically-driven cardiac activation in reaction, and preserved during all sleep stages. Furthermore, albeit cardiac reactivity persisted even in the absence of arousals, it was higher when a cortical arousal followed the noxious stimulus whatever the sleep stages. Our second work showed, in apnoeic patients, that cardiac autonomic reactivity in response to obstructive respiratory events was also dependent on sympathetic reactivity, mainly modulated by arousal process rather than sleep stages or severity of respiratory events. At last, our third work showed that cardiac sympathetic level before nociceptive stimuli or during respiratory events could favour cortical arousal. In conclusion, cardiac sympathetic reactivity in response to aversive stimuli during sleep is preserved during all sleep stages. This sympathetic reactivity is modulated by arousal process rather than sleep stages or severity of respiratory events. Cardiac sympathetic activity during sleep could take part in arousal process, by favouring cortical arousal

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Les technologies du sommeil connaissent une révolution numérique à laquelle nous avons apporté une validation avec pour objectif une meilleure analyse des troubles du sommeil en Unité de Soins Intensifs, dans la maladie d’Alzheimer et dans l’évaluation de l’hypovigilance en vol de longue durée en milieu militaire. Ainsi, nous avons évalué le temps de sommeil sur 24 heures en relation avec les nuisances sonores en soins intensifs. Cette évaluation a été réalisée à l’aide d’un nouveau polysomnographe l’Actiwave couplé à un polygraphe Nox T3 qui ont permis d’enregistrer les cycles du sommeil et les niveaux sonores sur les 24 heures dans une Unité de Soins Intensif. Nous avons montré que l’Actiwave est un outil performant pour enregistrer le sommeil dans de telles conditions. Combiné au Nox T3, il permet d’explorer l’impact des niveaux sonores sur la qualité et quantité du sommeil. Nous avons retrouvé un Temps Total de Sommeil médian de 6 heures par nuit et de 2,5 heures pendant la journée, la qualité de sommeil étant plus perturbée que sa quantité. Nous avons démontré que 60% des éveils intra-sommeil étaient associés à un bruit supérieur à 77 dB et identifié les sources sonores principales qui agissent sur la pathogénèse des troubles du sommeil en Unité de Soins Intensif, à savoir les alarmes des respirateurs mécaniques avec un risque relatif de 10.9 (9.8-11.9) et les alarmes des constantes vitales avec un risque relatif de 9.8 (8.6-11.3). Une deuxième étude, l’évaluation de l’hypovigilance en vol de longue durée, a été réalisée à l’aide de l’ActiWave. Pour cela, nos équipes ont conçu un algorithme d’analyse automatique de détection du sommeil. Nous avons montré que l’ActiWave est un polysomnographe fiable en conditions extrêmes, l’analyse automatique montrant une bonne concordance avec l’analyse manuelle de deux experts du sommeil (Kappa>80%). Nous démontrons donc qu’il est possible de coder automatiquement les stades de sommeil à l’aide du ratio (+)/ sur la région occipitale O1-M2 vs C3-M2 (p<0.05). Nous avons validé un nouvel actimètre le MotionWatch 8 pour l’évaluation du temps de sommeil chez 208 patients présentant la maladie d’Alzheimer. Ce travail a permis de montrer que le MotionWatch 8 est un outil fiable avec de bonnes sensibilité et spécificité dans l’évaluation des troubles du sommeil chez ces patients. Le Temps Total de Sommeil est dans la norme (TTS moyen 7h35 minutes) et est significativement associé au score d’apathie (7h46 minutes vs 7h26 minutes ; p=0.04). Le marqueur chrono-biologique SIJ est également associé à l’apathie (p=0.04) ainsi qu’aux troubles cognitifs (p=0.02). Finalement, la fragmentation de rythmes veille/sommeil (VIJ) est associée au score du handicap de la maladie d’Alzheimer (p=0.02). Dans une quatrième étude, nous nous sommes intéressés à la nouvelle technologie de télé-observance dans le traitement du syndrome d’apnées du sommeil par pression positive continue, qui permet d’alerter le médecin de la compliance du patient. Nous avons validé un nouveau dispositif médical de télé-observance du traitement du syndrome d’apnées du sommeil, le NOWAPI. Nous montrons que le NOWAPI mesure avec précision et de manière fiable les niveaux de pressions et de débits des PPC disponibles sur le marché et qu’il permet de calculer les indicateurs d'observance des patients souffrants du syndrome d’apnées du sommeil (IAH Nowapi de 2,5 (-1.4 ; 3.6)/h vs IAH Polygraphie respiratoire de 2,3 (1.2 ;3.4)/h). En conclusion, les études présentées ici mettent en exergue l’importance de l’innovation technologique dans le domaine du sommeil pour une meilleure prise en charge des patients. A l’ère du 21ème siècle, une nouvelle médecine commence à émerger, la médecine 2.0, avec pour corollaire l’eSanté. (...) / Scientific research into sleep over the past thirty years has progressed so speedily that it is now possible to speak of “Sleep Medicine”. This specialty is placed incontestably at the frontier of Science and Medicine. The issues have been recently driven by the advances in the technology of recording biological parameter and analysis of the data, in parallel with a deeper understanding of the physiopathology and therapeutic advances in sleep disorders. The subject of this thesis lies at the crossover of two areas of professional expertise; sleep technology and bio-engineering, with notably the aim of validating new tools in research as well as in the diagnosis and treatment of sleep disorders. We have tested a miniaturized polysomnographic new technology, the Actiwave, capable of detecting sleep and alert states in extreme conditions, notably in patients hospitalized in Intensive Care Units and in aircraft pilots in long duration military flights. In intensive care units, we have explored the relation between sleep and noise in the immediate environment of the patients. In brief, Total Sleep Time was not disturbed whereas the sleep quality was altered. Wake episodes after sleep onset were mostly associated with noise over 77 dB, and the main disturbances were triggered by the alarms of breathing machines and those from vital parameters. In military flights of long duration, we have explored the presence of hypovigilance episodes. This allowed us to validate the Actiwave for polysomnography in extreme conditions. In a third study, we have analyzed the sleep patterns in a total of 202 patients with Alzheimer’s disease by using a new actimeter, the MotionWatch8. We have shown that the latter device has a good sensitivity and specificity or evaluating sleep-wake parameters in these patients. In particular, we find that the TST is in the normal range and is associated with the aptathy score. The SIJ score is associated with the apathy score and also with the cognitive impairments. Finally, the sleep fragmentation is associated with the disability status. In a last study, we explored the parameter of sleep apneas in patients with SAS using the NOWAPI. We validated this new device by demonstrating that it provides on-line reliable data about pressure and flow levels of various CPAP. In conclusion, this thesis considers possible future avenues of research into sleep technology and discusses the crucial importance of a scientific approach capable of leading the development of appropriate and lasting diagnostic and therapeutic tools. The next step will be the era of the 2.0 medicine for which I am developing the iSommeil application that will allow patients to be the actual actors of their disease and also to facilitate the diagnostic and the prevention of sleep disorders.

Background: Although the negative impact of sleep apnea on the clinical course of acute ischemic stroke (AIS) is well known, data regarding non-invasive ventilation in acute patients are scarce. Several studies have shown its tolerability and safety, yet no controlled randomized sequential phase studies exist that aim to establish the efficacy of early non-invasive ventilation in AIS patients. Methods/design: We decided to examine our hypothesis that early non-invasive ventilation with auto-titrating bilevel positive airway pressure (auto-BPAP) positively affects short-term clinical outcomes in AIS patients. We perform a multicenter, prospective, randomized, controlled, third rater- blinded, parallel-group trial. Patients with AIS with proximal arterial obstruction and clinically suspected sleep apnea will be randomized to standard stroke care alone or standard stroke care plus auto-BPAP. Auto-BPAP will be initiated within 24 hours of stroke onset and performed for a maximum of 48 hours during diurnal and nocturnal sleep. Patients will undergo unattended cardiorespiratory polygraphy between days three and five to assess sleep apnea. Our primary endpoint will be any early neurological improvement on the NIHSS at 72 hours from randomization. Safety, tolerability, short-term and three-months functional outcomes will be assessed as secondary endpoints by un-blinded and blinded observers respectively. Discussion: We expect that this study will advance our understanding of how early treatment with non-invasive ventilation can counterbalance, or possibly reverse, the deleterious effects of sleep apnea in the acute phase of ischemic stroke. The study will provide preliminary data to power a subsequent phase III study.

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