Christian Guilleminault, MD

All Publications

• Long-term Results for Maxillomandibular Advancement to Treat Obstructive Sleep Apnea: A Meta-analysis. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Camacho, M., Noller, M. W., Del Do, M., Wei, J. M., Gouveia, C. J., Zaghi, S., Boyd, S. B., Guilleminault, C. 2019: 194599818815158

  Abstract

  OBJECTIVE: To examine outcomes in the intermediate term (1 to <4 years), long term (4 to <8 years), and very long term (≥8 years) for maxillomandibular advancement (MMA) as treatment for obstructive sleep apnea (OSA).DATA SOURCES: The Cochrane Library, Google Scholar, Embase, Cumulative Index to Nursing and Allied Health, and PubMed/MEDLINE.REVIEW METHODS: Three authors systematically reviewed the international literature through July 26, 2018.RESULTS: A total of 445 studies were screened, and 6 met criteria (120 patients). Thirty-one patients showed a reduction in apnea-hypopnea index (AHI) from a mean 48.3 events/h (95% CI, 42.1-54.5) pre-MMA to 8.4 (95% CI 5.6, 11.2) in the intermediate term. Fifty-four patients showed a reduction in AHI from a mean 65.8 events/h (95% CI, 58.8-72.8) pre-MMA to 7.7 (95% CI 5.9, 9.5) in the long term. Thirty-five showed a reduction in AHI from a mean 53.2 events/h (95% CI 45, 61.4) pre-MMA to 23.1 (95% CI 16.3, 29.9) in the very long term. Improvement in sleepiness was maintained at all follow-up periods. Lowest oxygen saturation improvement was maintained in the long term.CONCLUSION: The current international literature shows that patients with OSA who were treated with MMA maintained improvements in AHI, sleepiness, and lowest oxygen saturation in the long term; however, the mean AHI increased to moderate OSA in the very long term. Definitive generalizations cannot be made, and additional research providing individual patient data for the intermediate term, long term, and very long term is needed.

  View details for DOI 10.1177/0194599818815158

  View details for PubMedID 30598047

• The nocturnal-polysomnogram and "non-hypoxic sleep-disordered-breathing" in children. Sleep medicine Guilleminault, C., Huang, Y., Chin, W., Okorie, C. 2018

  Abstract

  OBJECTIVE: To characterize sleep-disordered breathing patterns not related to hypoxia resulting in fragmented sleep in children.METHODS: We reviewed the polysomnogram (PSG) data of children with sleep complaints who were being evaluated for sleep-disordered breathing and had an apnea-hypopnea-index≤3. These data were compared to the recordings of the same children with nasal CPAP administered for one night and to 60 control subjects (children without any sleep complaints). A subgroup of children was monitored with esophageal manometry, but nasal cannula flow data was recorded in all cases.RESULTS: Abnormal breathing patterns, particularly flow limitation, could be seen with more severity and frequency compared to apnea or hypopnea. The observed abnormal breathing patterns were associated with EEG disturbances.CONCLUSIONS: Patterns such as flow-limitation, mouth-breathing, changes in inspiratory and expiratory time, rib-cage and expiratory muscle activity, transcutaneous CO2 electrode changes and snoring noises are all variables that should be systematically reviewed when analyzing nocturnal PSG. Current scoring guidelines emphasizes apnea-hypopnea and hypoxic-sleep disordered breathing and therefore treatment is often much delayed in this population of children with evidence of abnormal breathing patterns. Analysis of the various patterns of abnormal breathing noted above allows recognition of "non-hypoxic" sleep-disordered-breathing (SDB).

  View details for DOI 10.1016/j.sleep.2018.11.001

  View details for PubMedID 30578113

• Alcohol Consumption as a Moderator of Anxiety and Sleep Quality. The journal of nursing research : JNR Chueh, K., Guilleminault, C., Lin, C. 2018

  Abstract

  BACKGROUND: Although people who sleep poorly may attempt to relieve anxiety for better sleep quality, whether daily alcohol consumption is a factor that moderates anxiety and sleep disturbance is not known.PURPOSE: The aim of the study was to explore (a) the association between anxiety and sleep quality and (b) whether daily alcohol consumption acted as a moderator between anxiety and sleep quality in those who reported sleeping poorly.METHODS: Eighty-four participants aged 20-80 years who reported poor sleep (Pittsburgh Sleep Quality Index > 5) in northern Taiwan were enrolled in this cross-sectional study. A structured questionnaire covering demographics (including daily alcohol consumption), level of anxiety, level of depression, and perceived sleep quality was used to collect data.RESULTS: The participants were mostly women (72.6%). The mean age was 41.81 (SD = 12.62) years; 51.2%, 19.0%, 13.1%, and 14.3%, respectively, had minimal, mild, moderate, and severe anxiety. After adjusting for factors related to sleep quality using multiple regression analysis, receiving sleep therapy, consuming alcohol on a daily basis, and having anxiety were found to be predictors of poor sleep quality. Moreover, daily alcohol consumption was found to moderate the relationship between anxiety and sleep quality.CONCLUSIONS/IMPLICATIONS FOR PRACTICE: People who sleep poorly should avoid misusing alcohol to self-treat poor sleep quality or anxiety and should instead utilize sleep hygiene education and mental healthcare. Daily alcohol consumption may be a moderator between anxiety status and sleep quality.

  View details for DOI 10.1097/JNR.0000000000000300

  View details for PubMedID 30499833

• Sleep-disordered breathing, craniofacial development, and neurodevelopment in premature infants: a 2-year follow-up study. Sleep medicine Huang, Y., Hsu, J., Paiva, T., Chin, W., Chen, I., Guilleminault, C. 2018

  Abstract

  INTRODUCTION: Sleep problems, neuro-developmental development, and sleep-disordered-breathing (SDB), are reported as more prevalent in premature infants than in full-term infants. We investigated the relationship between neuro-development, and SDB in preterm infants at 24 months corrected age (CA) with a narrow palatal presentation over time.METHODS: We enrolled infants 40 weeks or younger at birth collecting obstetric and birth data. Participants were followed up at 6, 12, 18, and 24 months CA. We evaluated craniofacial development by inspecting and photo documenting hard palate; sleep using sleep diary, actigraphy and night-time polysomnography-PSG-; and development using Bayley- Scales-of-Infant-Development and Denver-Developmental-Screening-Test (DDST) at each visit and comparing results at six months and two years.RESULTS: 244 premature infants [139 (57.0%) boys, [at birth: mean gestational age-GA- 31.5±3.2 weeks, 1691.9±593.9g, 40.2±5.2cm], and 30 full term infants (50% boys), [mean GA 39.3±1.0 weeks, 3131.0±390.0g, and 49.38±2.0cm] were enrolled in the study. At 6 and 24 months, 65.2% premature infants had a narrow hard palate (NHP). At 24 months, 79% had an apnea-hypopnea- index (AHI)>1 events/hour at PSG, with a mean AHI of 3.00±2.95. Only 10% of full term infants had NHP at birth and the mean AHI was 0.5±0.2 event/hour at 24 months.CONCLUSION: Preterm infants have a higher occurrence of NHP at birth. At two years of age they have more sleep problems, most commonly associated with obstructive-SDB, and a higher rate of development delays. Frequency of NHP is still abnormally high, suggesting not only abnormal orofacial growth over-time, but also impact of this abnormal growth in the genesis of the obstructive-SDB.

  View details for DOI 10.1016/j.sleep.2018.10.015

  View details for PubMedID 30466820

• Solriamfetol for the treatment of daytime sleepiness in obstructive sleep apnea. Expert review of respiratory medicine Abad, V. C., Guilleminault, C. 2018

  Abstract

  INTRODUCTION: Obstructive sleep apnea (OSA) is highly prevalent and constitutes a major health hazard. Current pharmacotherapy is ineffective in correcting sleep-disordered breathing and is used adjunctively to address residual sleepiness. A new drug, solriamfetol, a selective norepinephrine-dopamine reuptake inhibitor, is the first drug of its class that is being considered by the US Food and Drug Administration (FDA) to treat excessive sleepiness in OSA and narcolepsy patients. Areas Covered: This review covers drug chemistry, pharmacodynamics, pharmacokinetics, and metabolism of solriamfetol. Results of three Phase 3 trials, Treatment of OSA and Narcolepsy Excessive Sleepiness (TONES 3, 4, 5), relevant to OSA patients are summarized. Published abstracts/articles and a 2017 Jazz Investor Presentation provided data. Databases searched included PubMed, Google Scholar, Lexi-Comp, Scopus, Science, and Ovid. Expert Commentary: Solriamfetol shows promise as adjunctive therapy in OSA. It is well tolerated and effective in reducing sleepiness and is an alternative to modafinil or armodafinil. Unlike stimulants like methylphenidate or dextroamphetamine, it does not have cardiac effects, rebound hypersomnia, or withdrawal effects.

  View details for DOI 10.1080/17476348.2018.1541742

  View details for PubMedID 30365900

• Multiple sleep latency test in narcolepsy type 1 and narcolepsy type 2: A 5-year follow-up study JOURNAL OF SLEEP RESEARCH Huang, Y., Guilleminault, C., Lin, C., Chen, C., Chin, W., Chen, T. 2018; 27 (5): e12700

  Abstract

  Excessively sleepy teenagers and young adults without sleep-disordered breathing are diagnosed with either narcolepsy type 1 or narcolepsy type 2, or hypersomnia, based on the presence/absence of cataplexy and the results of a multiple sleep latency test. However, there is controversy surrounding this nomenclature. We will try to find the differences between different diagnoses of hypersomnia from the results of the long-term follow-up evaluation of a sleep study. We diagnosed teenagers who had developed excessive daytime sleepiness based on the criteria of the International Classification of Sleep Disorders, 3rd edition. Each individual received the same clinical neurophysiologic testing every year for 5 years after the initial diagnosis of narcolepsy type 1 (n = 111) or type 2 (n = 46). The follow-up evaluation demonstrated that narcolepsy type 1 (narcolepsy-cataplexy) is a well-defined clinical entity, with very reproducible clinical neurophysiologic findings over time, whereas patients with narcolepsy type 2 presented clear clinical and test variability. By the fifth year of the follow-up evaluation, 17.6% of subjects did not meet the diagnostic criteria of narcolepsy type 2, and 23.9% didn't show any two sleep-onset rapid eye movement periods in multiple sleep latency during the 5-year follow-up. Therefore narcolepsy type 1 (narcolepsy-cataplexy) is a well-defined syndrome, with the presentation clearly related to the known consequences of destruction of hypocretin/orexin neurons. Narcolepsy type 2 covers patients with clinical and test variability over time, thus bringing into question the usage of the term "narcolepsy" to label these patients.

  View details for DOI 10.1111/jsr.12700

  View details for Web of Science ID 000443809300018

  View details for PubMedID 29845680

• Endoscopically-assisted surgical expansion (EASE) for the treatment of obstructive sleep apnea. Sleep medicine Li, K., Quo, S., Guilleminault, C. 2018

  Abstract

  OBJECTIVE: The aim of this retrospective study was to evaluate the results of an outpatient surgical procedure known as endoscopically-assisted surgical expansion (EASE) in expanding the maxilla to treat obstructive sleep apnea (OSA) in adolescent and adults.METHODS: Thirty-three patients (18 males), aged 15-61 years, underwent EASE of the maxilla. All patients completed pre- and post-operative clinical evaluations, polysomnography, questionnaires (Epworth Sleepiness Scale [ESS] and Nasal Obstruction Septoplasty Questionnaire [NOSE]) as well as cone beam computed tomography (CBCT).RESULTS: With EASE, the overall apnea hypopnea index (AHI) improved from 31.6±11.3 to 10.1±6.3. The oxygen desaturation index (ODI) improved from 11.8±9.6 to 1.8±3.7, with reduction of ESS scores from 13.4±4.0 to 6.7±3.1. Nasal breathing improved as demonstrated by reduction of the NOSE scores from 57.8±12.9 to 15.6±5.7. Expansion of the airway from widening of the nasal floor was consistently evident on all postoperative CBCT; the anterior nasal floor expanded 4.9±1.2mm, posterior nasal floor expanded 5.6±1.2mm, and the dental diastema created was 2.3±0.8mm. Mean operative time was 54.0±6.0min. All patients with mild to moderate OSA were discharged the same day; patients with severe OSA were observed overnight. All patients returned to school or work and regular activities within three days.CONCLUSIONS: EASE is an outpatient procedure that improves nasal breathing and OSA by widening the nasal floor in adolescents and adults. Compared to current surgical approaches for maxillary expansion, EASE is considerably less invasive and consistently achieves enlargement of the airway with minimal complications.

  View details for DOI 10.1016/j.sleep.2018.09.008

  View details for PubMedID 30393018

• Neutral supporting mandibular advancement device with tongue bead for passive myofunctional therapy: a long term follow-up study. Sleep medicine Huang, Y., Chuang, L., Hervy-Auboiron, M., Paiva, T., Lin, C., Guilleminault, C. 2018

  Abstract

  BACKGROUNDS: Myofunctional therapy has been reported to be a valid adjunct treatment to OSA, but compliance was mentioned as an issue. We performed a prospective study on age matched randomized children submitted to myofunctional therapy (MFT) or to a functional device used during sleep (passive MFT).METHODS: 110 children 4 to 16 were recruited for the study, 54 children were in the MFT group [A] while 56 were in the "nocturnal device" group [B]. Clinical evaluation, polysomnography and cephalometric X-Rays were performed at baseline, 6 months and 12 months, with clinical follow-up at 3 months.RESULTS: MFT group show very important absence of compliance, at six months only 23 subjects participated and only 10/23 had been compliant with treatment. None came back for research investigation at 12 months. 48/56 of passive MFT children ended the research protocol at 12 months. Comparison of baseline to 6 and 12 months data showed that all children with passive MFT improved (PSG and cephalometrics) and had nasal breathing during sleep at 1 year, and no negative effect of device were noted. The 10 children compliant with MFT showed clear improvement of sleep related breathing with also changes at cephalometric -X-rays.CONCLUSION: Compliance is a major problem of MFT, and MFT will have to take into consideration the absolute need to have continuous parental involvement in the procedure. Passive MFT gives many more positive results, but potential negative effects of device on other jaw will have to be continuously evaluated.

  View details for DOI 10.1016/j.sleep.2018.09.013

  View details for PubMedID 30448089

• From oral facial dysfunction to dysmorphism and the onset of pediatric OSA. Sleep medicine reviews Guilleminault, C., Huang, Y. 2018; 40: 203–14

  Abstract

  The upper airway is a collapsible tube, and its collapsibility increases during sleep. Extrinsic factors such as atypical craniofacial features may increase the risks of airway collapse. We review early development of oral-facial structures and the anatomical variants that may be present at birth and can impact nasal breathing. After birth, there is a continuous interaction between orofacial functions and growth of anatomic features. We review the dysfunctions identified to date that may impact orofacial development leading to sleep-disordered-breathing through changes in the orofacial growth. The identification of risk-factors, ultimately leading to full-blown obstructive sleep apnea, may allow early recognition of these factors and the development of treatments to eliminate early problems or at least decrease their impact.

  View details for DOI 10.1016/j.smrv.2017.06.008

  View details for PubMedID 29103943

• Insomnia in Elderly Patients: Recommendations for Pharmacological Management. Drugs & aging Abad, V. C., Guilleminault, C. 2018

  Abstract

  Chronic insomnia affects 57% of the elderly in the United States, with impairment of quality of life, function, and health. Chronic insomnia burdens society with billions of dollars in direct and indirect costs of care. The main modalities in the treatment of insomnia in the elderly are psychological/behavioral therapies, pharmacological treatment, or a combination of both. Various specialty societies view psychological/behavioral therapies as the initial treatment intervention. Pharmacotherapy plays an adjunctive role when insomnia symptoms persist or when patients are unable to pursue cognitive behavioral therapies. Current drugs for insomnia fall into different classes: orexin agonists, histamine receptor antagonists, non-benzodiazepine gamma aminobutyric acid receptor agonists, and benzodiazepines. This review focuses on Food and Drug Administration (FDA)-approved drugs for insomnia, including suvorexant, low-dose doxepin, Z-drugs (eszopiclone, zolpidem, zaleplon), benzodiazepines (triazolam, temazepam), and ramelteon. We review the indications, dosing, efficacy, benefits, and harms of these drugs in the elderly, and discuss data on drugs that are commonly used off-label to treat insomnia, and those that are in clinical development. The choice of a hypnotic agent in the elderly is symptom-based. Ramelteon or short-acting Z-drugs can treat sleep-onset insomnia. Suvorexant or low-dose doxepin can improve sleep maintenance. Eszopiclone or zolpidem extended release can be utilized for both sleep onset and sleep maintenance. Low-dose zolpidem sublingual tablets or zaleplon can alleviate middle-of-the-night awakenings. Benzodiazepines should not be used routinely. Trazodone, a commonly used off-label drug for insomnia, improves sleep quality and sleep continuity but carries significant risks. Tiagabine, sometimes used off-label for insomnia, is not effective and should not be utilized. Non-FDA-approved hypnotic agents that are commonly used include melatonin, diphenhydramine, tryptophan, and valerian, despite limited data on benefits and harms. Melatonin slightly improves sleep onset and sleep duration, but product quality and efficacy may vary. Tryptophan decreases sleep onset in adults, but data in the elderly are not available. Valerian is relatively safe but has equivocal benefits on sleep quality. Phase II studies of dual orexin receptor antagonists (almorexant, lemborexant, and filorexant) have shown some improvement in sleep maintenance and sleep continuity. Piromelatine may improve sleep maintenance. Histamine receptor inverse agonists (APD-125, eplivanserin, and LY2624803) improve slow-wave sleep but, for various reasons, the drug companies withdrew their products.

  View details for DOI 10.1007/s40266-018-0569-8

  View details for PubMedID 30058034

• Neurocognition, sleep, and PET findings in type 2 vs type 1 narcolepsy. Neurology Huang, Y., Hsiao, I., Liu, F., Hwang, F., Lin, K., Huang, W., Guilleminault, C. 2018; 90 (17): e1478–e1487

  Abstract

  OBJECTIVE: To analyze differences in functional brain images collected in patients with type 2 and type 1 narcolepsy compared to normal controls and the relationship among brain images, objective neuropsychologic tests, and sleep findings.METHODS: Data collection included comprehensive clinical investigation, study of sleep/wake with actigraphy, polysomnography, Multiple Sleep Latency Test, human leukocyte antigen typing, 18F-fluorodeoxyglucose PET, and cognitive tests obtained from 29 patients with type 2 narcolepsy, 104 patients with type 1 narcolepsy, and 26 sex- and age-matched normal control individuals. Conners' Continuous Performance Test (CPT II) and Wisconsin Card-Sorting Task were performed simultaneously with the FDG-PET examination. After analyses of variance, data between patients with type 1 and type 2 narcolepsy were compared by post hoc analysis, and correlation between functional brain imaging findings and results of neurocognitive tests was obtained.RESULTS: All patients with narcolepsy presented with at least 2 sleep-onset REM periods (SOREMP) and subjective sleepiness. Patients with type 2 narcolepsy compared to patients with type 1 narcolepsy had significantly less SOREMP, longer mean sleep latencies, and lower body mass indexes, apnea-hypopnea indexes, and frequency of human leukocyte antigen DQ-Beta1*0602. In patients with type 2 narcolepsy, FDG-PET studies showed significantly less hypermetabolism in the fusiform gyrus, striatum, hippocampus, thalamus, basal ganglia, and cerebellum than in patients with type 1 narcolepsy, and significantly less hypometabolism in the regions of frontal lobe, posterior cingulum, angular gyrus, and part of the parietal lobe; these changes were associated with fewer errors on the CPT.CONCLUSION: Young patients with type 2 narcolepsy have fewer clinical impairments and less distinct brain functional abnormalities than patients with type 1 narcolepsy, who are significantly more affected.

  View details for DOI 10.1212/WNL.0000000000005346

  View details for PubMedID 29602910

• Prevalence of upper respiratory tract infections in habitually snoring and mouth breathing children INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY Kukwa, W., Guilleminault, C., Tomaszewska, M., Kukwa, A., Krzeski, A., Migacz, E. 2018; 107: 37–41

  Abstract

  The aim of the study was to investigate the prevalence of upper respiratory tract infections (URI) - as indicated by rhinosinusitis (RS), ear infections (EI), and antibiotic consumption - in a general pediatric population and evaluate the relationship between these conditions and habitual snoring and mouth breathing during sleep.A population-based cross-sectional study was performed in three medium-sized Polish cities from 2011 to 2015.4837/6963 questionnaires (69.5%) were completed, returned and analyzed. Mean age of studied group was 7.07 ± 0.72 and 7.14 ± 0.73 in girls and boys, respectively. Habitual mouth breathing during sleep (MB) was reported in 907 (18.7%) children and habitual snoring (HS) in 290 (6.0%). 230/290 (79.3%) of children with HS were also MB. Both HS and MB were more prevalent in boys than in girls (p = 0.027 and p < 0.0001, respectively) and neither was associated with BMI (p = 0.11 and p = 0.07, respectively). Habitual snoring and habitual mouth breathing were highly associated with more frequent bouts of rhinosinusitis, ear infections, and antibiotic use (p < 0.0001 for each parameter).Higher rates of rhinosinusitis, ear infections, and antibiotic consumption were similarly associated with HS and MB. MB is over three times more prevalent in the pediatric population relative to HS, therefore it might be considered as a risk factor for URI and may be included in history of URI.

  View details for DOI 10.1016/j.ijporl.2018.01.022

  View details for Web of Science ID 000428492100008

  View details for PubMedID 29501308

• Oropharyngeal and tongue exercises (myofunctional therapy) for snoring: a systematic review and meta-analysis EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY Camacho, M., Guilleminault, C., Wei, J. M., Song, S. A., Noller, M. W., Reckley, L. K., Fernandez-Salvador, C., Zaghi, S. 2018; 275 (4): 849–55

  Abstract

  Oropharyngeal and tongue exercises (myofunctional therapy) have been shown to improve obstructive sleep apnea. However, to our knowledge, a systematic review has not been performed for snoring. The study objective is to perform a systematic review, with a meta-analysis, dedicated to snoring outcomes after myofunctional therapy.PubMed/MEDLINE and three other databases were searched through November 25, 2017. Two authors independently searched the literature. Eligibility (1) patients: children or adults with snoring, (2) intervention: oropharyngeal and/or tongue exercises, (3) comparison: pre and post-treatment data for snoring, (4) outcomes: snoring frequency and snoring intensity, (5) study design: publications of all study designs.A total of 483 articles were screened, 56 were downloaded in their full text form, and nine studies reported outcomes related to snoring. There were a total of 211 patients (all adults) in these studies. The snoring intensity was reduced by 51% in 80 patients from pre-therapy to post-therapy visual analog scale values of 8.2 ± 2.1 (95% CI 7.7, 8.7) to 4.0 ± 3.7 (95% CI 3.2, 4.8). Berlin questionnaire snoring intensity reduced by 36% in 34 patients from 2.5 ± 1.0 (95% CI 2.2, 2.8) to 1.6 ± 0.8 (95% CI 1.3, 1.9). Finally, time spent snoring during sleep was reduced by 31% in 60 patients from 26.3 ± 18.7% (95% CI 21.6, 31.0) to 18.1 ± 20.5% (95% CI 12.9, 23.3) of total sleep time.This systematic review demonstrated that myofunctional therapy has reduced snoring in adults based on both subjective questionnaires and objective sleep studies.

  View details for DOI 10.1007/s00405-017-4848-5

  View details for Web of Science ID 000426758300002

  View details for PubMedID 29275425

• Establishment of nasal breathing should be the ultimate goal to secure adequate craniofacial and airway development in children JORNAL DE PEDIATRIA Torre, C., Guilleminault, C. 2018; 94 (2): 101–3

  View details for DOI 10.1016/j.jped.2017.08.002

  View details for Web of Science ID 000431375700001

  View details for PubMedID 28859912

• Sleep disordered breathing in pregnant women: maternal and fetal risk, treatment considerations, and future perspectives EXPERT REVIEW OF RESPIRATORY MEDICINE Truong, K., Guilleminault, C. 2018; 12 (3): 177–89

  Abstract

  Numerous physiologic and anatomic changes during pregnancy exacerbate or unmask obstructive sleep apnea in women. Left untreated, upper airway flow limitation during pregnancy may lead to dire maternal and fetal health consequences. Areas covered: This review outlines the relationship between sleep disordered breathing (SDB) and gestational hypertension, preeclampsia, and gestational diabetes. It also discusses the implications of SDB on fetal and maternal health and concludes with a review of the emerging literature of treatment options for SDB in pregnancy and its benefit. Expert commentary: Providers should screen, recognize, and treat SDB in pregnant women given its implicated risk on maternal and fetal health. This is particularly true in preeclampsia, a leading cause of maternal and fetal morbidity and mortality where SDB has been shown to add risk and severity. It is important to note that repetitive upper airway flow limitations in pregnancy are associated with surges in nocturnal blood pressure and poor maternal and fetal outcomes, and may be just as detrimental as frank apneas/hypopneas. Future large, prospective, randomized controlled studies on the effects of CPAP are still needed. The epidemiology of SDB in pregnant women needs to be further studied, as well as highlighting the need for systematic, long-term follow ups on mother and infant health post-delivery.

  View details for DOI 10.1080/17476348.2018.1432355

  View details for Web of Science ID 000424815200004

  View details for PubMedID 29363362

• A personal reminiscence of Michel Jouvet: the poet of paradoxical sleep SLEEP MEDICINE Guilleminault, C. 2018; 41: 118

  View details for DOI 10.1016/j.sleep.2017.12.004

  View details for Web of Science ID 000425268700021

• Commentary: Parent-Reported Behavioral and Psychiatric Problems Mediate the Relationship between Sleep-Disordered Breathing and Cognitive Deficits in School-Aged Children FRONTIERS IN NEUROLOGY Barwick, F., Guilleminault, C. 2017; 8: 597

  View details for DOI 10.3389/fneur.2017.00597

  View details for Web of Science ID 000414935600001

  View details for PubMedID 29180980

  View details for PubMedCentralID PMC5693888

• Exploring the Abnormal Modulation of the Autonomic Systems during Nasal Flow Limitation in Upper Airway Resistance Syndrome by Hilbert-Huang Transform FRONTIERS IN MEDICINE Lin, C., Lo, M., Guilleminault, C. 2017; 4: 161

  Abstract

  Patients with nasal flow limitation and upper airway resistance syndrome (UARS) during sleep can present with low blood pressure and disturbing symptoms associated with hypervagotony. We hypothesized that the dynamic changes of the autonomic system related to inspiratory flow limitation can be quantified by the developed analytic technique applied on beat-to-beat heart rate (RR intervals) and finger photoplethysmography (PPG).A breath-by-breath investigation based on the Hilbert-Huang transform was performed to explore autonomic nervous system changes observed during inspiratory flow limitation. Autonomic status was quantified from beat-to-beat heart rate analysis by high frequency (RRHF; 0.15-0.4 Hz), low frequency (RRLF; 0.04-0.15 Hz), and LF/HF ratio of each respiratory cycle. Based on respiratory-related mechanisms contained in the PPG signal, we further quantified the respiratory-related oscillations (PPGres). Based on esophageal pressure and nasal flow measurements, each respiratory cycle was identified and breathing patterns were classified into one of four groups: normal, inspiratory flow limitation cycles without increased effort [FL(-)], minimal inspiratory flow limitation with effort, and inspiratory flow limitation cycles with increased effort [FL(+)]. The resulting quantitative parameters of the identified cycles were calculated.49 UARS patients (12 males; aged 26.8 ± 5.8 years) with apnea-hypopnea index (AHI) 3.1 ± 1.5 per hour and nine aged matched control subjects (3 males; aged 27.8 ± 4.0 years) with AHI 0.8 ± 1.1 per hour were retrospectively identified. Compared to the control group, hyperactivation of the parasympathetic system was noted during stage 2 NREM sleep by RRHF (27.8 ± 18.2 vs 22.5 ± 11.12, p < 0.05) in 49 UARS patients. Analysis of the different classifications of respiratory cycles indicated that during "high" (increased) respiratory efforts, the RRHF and PPGres were significantly higher compared to "normal cycle" and "FL(-)" groups. The RRLF/RRHF (an index of sympathetic activity) was significantly lower in the "FL(+)" group (1.66 ± 0.80) than in the "normal cycle" (1.93 ± 0.97, p < 0.05) and "FL(-)" groups (2.01 ± 1.01, p < 0.05).The proposed algorithm allows quantifying the temporal changes of specific mechanisms of the autonomic system on breath-by-breath basis. With no or very limited impact on oxygen saturation, the hyperactivation of parasympathetic system in associated with inspiratory flow limitation or increased respiratory efforts during stage 2 NREM sleep has been presented in this study.

  View details for DOI 10.3389/fmed.2017.00161

  View details for Web of Science ID 000412023600001

  View details for PubMedID 29034238

  View details for PubMedCentralID PMC5625011

• The preliminary results of the differences in craniofacial and airway morphology between preterm and full-term children with obstructive sleep apnea JOURNAL OF DENTAL SCIENCES Lian, Y., Huang, Y., Guilleminault, C., Chen, K., Hervy-Auboiron, M., Chuang, L., Tsai, A. I. 2017; 12 (3): 253–60

  View details for DOI 10.1016/j.jds.2017.03.005

  View details for Web of Science ID 000423451400009

• Medical comorbidity in narcolepsy: findings from the Burden of Narcolepsy Disease (BOND) study SLEEP MEDICINE Black, J., Reaven, N. L., Funk, S. E., MCGAUGHEY, K., Ohayon, M. M., Guilleminault, C., Ruoff, C. 2017; 33: 13-18

  Abstract

  The objective of this study was to evaluate medical comorbidity patterns in patients with a narcolepsy diagnosis in the United States.This was a retrospective medical claims data analysis. Truven Health Analytics MarketScan® Research Databases were accessed to identify individuals ≥18 years of age with ≥1 diagnosis code for narcolepsy (International Classification of Diseases (ICD)-9, 347.0, 347.00, 347.01, 347.1, 347.10, or 347.11) continuously insured between 2006 and 2010, and controls without narcolepsy matched 5:1 on age, gender, region, and payer. Narcolepsy and control subjects were compared for frequency of comorbid conditions, identified by the appearance of >1 diagnosis code(s) mapped to a Clinical Classification System (CCS) level 1 category any time during the study period, and on specific subcategories, including recognized narcolepsy comorbidities of obstructive sleep apnea (OSA) and depression.The final study group included 9312 subjects with narcolepsy and 46,559 controls (each group: average age, 46.1 years; 59% female). As compared with controls, patients with narcolepsy showed a statistically significant excess prevalence in all the CCS multilevel categories, the only exceptions being conditions originating in the perinatal period and pregnancy/childbirth complications. The greatest excess prevalence in the narcolepsy cohort was seen for mental illness (31.1% excess prevalence; odds ratio (OR) 3.8, 95% confidence interval (CI) 3.6, 4.0), followed by diseases of the digestive system (21.4% excess prevalence; OR 2.7, 95% CI 2.5, 2.8) and nervous system/sense organs (excluding narcolepsy; 20.7% excess prevalence; OR 3.7, 95% CI 3.4, 3.9).In this claims analysis, a narcolepsy diagnosis was associated with a wide range of comorbid medical illness claims, at significantly higher rates than matched controls.

  View details for DOI 10.1016/j.sleep.2016.04.004

  View details for Web of Science ID 000401680000003

  View details for PubMedID 28449892

• Catathrenia (Nocturnal Groaning): A Social Media Survey and State-of-the-Art Review. Journal of clinical sleep medicine Alonso, J., Camacho, M., Chhetri, D. K., Guilleminault, C., Zaghi, S. 2017; 13 (4): 613-622

  Abstract

  Catathrenia is an underrecognized nocturnal vocalization phenomenon that can be a source of perplexity to patients, bed partners, and medical providers. Catathrenia is distinct from both sleep talking (a parasomnia with loud talking during sleep) and snoring (noise due to vibration of upper airway soft tissues related to variations in airway resistance). The objective of this review is to provide an evidence-based resource to help the practitioner reliably evaluate and manage patients with this condition.Data were gathered from: (1) PubMed, Scopus, Web of Science, and Google Scholar; and (2) catathrenia social media groups (Yahoo and Facebook).Data collected were (1) 15 case reports and 17 case series describing 191 patients with catathrenia; (2) questionnaires from 47 catathrenia subjects; (3) 5 audio files.Catathrenia is a noise produced during sleep (distinct from snoring) with identifiable harmonics, a computable main frequency, and high-decibel intensity that involves active adduction and vibration of the vocal cords during expiration. The quality of groaning in catathrenia is monotone, and often presents with a morose or sexual connotation, causing a significant social problem for patients. Although there is no association with risk of physical harm, catathrenia does present a significant disturbance to the bed partner and has been associated with subjective impairments to sleep quality, including unrefreshing sleep and fatigue. Polysomnography can be useful if performed properly to confirm the diagnosis and to evaluate for comorbid sleep disturbances, such as obstructive sleep apnea or parasomnia. Directions for further research could involve consideration of deep breathing exercises, yoga, meditation, or myofunctional therapy to help abate symptoms.

  View details for DOI 10.5664/jcsm.6556

  View details for PubMedID 28095968

• Continuous positive airway pressure therapy in obstuctive sleep apnea: benefits and alternatives EXPERT REVIEW OF RESPIRATORY MEDICINE Cao, M. T., Sternbach, J. M., Guilleminault, C. 2017; 11 (4): 259-272

  Abstract

  Obstructive sleep apnea (OSA) is a highly prevalent condition affecting persons of all age with an increasing public health burden. It is implicated in cardiovascular disease, metabolic syndrome, neurocognitive impairment, reductions in quality of life, and increased motor vehicle accidents. The goals of OSA treatment are to improve sleep and daytime symptoms, and minimize cardiovascular risks.Areas covered: Continuous positive airway pressure (CPAP) is considered the gold standard therapy that delivers pressurized air into the upper airway to relieve obstruction during sleep. Although CPAP is an effective modality of treatment for OSA, adherence to therapy is highly variable. This article highlights the benefits of CPAP therapy, along with alternative treatment options including oral appliance, implantable and wearable devices, and surgery. Expert commentary: CPAP therapy is the gold standard treatment option and should continue to be offered to those who suffer from OSA. Alternative options are available for those who are unable to adhere to CPAP or choose an alternative treatment modality. The most interesting advances have been incorporating orthodontic procedures in conjunction with myofunctional therapy in prepubertal children, raising the possibility of OSA prevention by initiating treatment early in life.

  View details for DOI 10.1080/17476348.2017.1305893

  View details for Web of Science ID 000399464000002

  View details for PubMedID 28287009

• Sound level intensity severely disrupts sleep in ventilated ICU patients throughout a 24-h period: a preliminary 24-h study of sleep stages and associated sound levels ANNALS OF INTENSIVE CARE Elbaz, M., Leger, D., Sauvet, F., Champigneulle, B., Rio, S., Strauss, M., Chennaoui, M., Guilleminault, C., Mira, J. P. 2017; 7

  Abstract

  It is well recognized that sleep is severely disturbed in patients in intensive care units (ICU) and that this can compromise their rehabilitation potential. However, it is still difficult to objectively assess sleep quantity and quality and the determinants of sleep disturbance remain unclear. The aim of this study was therefore to evaluate carefully the impact of ICU sound intensity levels and their sources on ICU patients' sleep over a 24-h period.Sleep and sound levels were recorded in 11 ICU intubated patients who met the criteria. Sleep was recorded using a miniaturized multi-channel ambulatory recording device. Sound intensity levels and their sources were recorded with the Nox-T3 monitor. A 30-s epoch-by-epoch analysis of sleep stages and sound data was carried out. Multinomial and binomial logistic regressions were used to associate sleep stages, wakefulness and sleep-wake transitions with sound levels and their sources.The subjects slept a median of 502.2 [283.2-718.9] min per 24 h; 356.9 [188.6-590.9] min at night (22.00-08.00) and 168.5 [142.5-243.3] during daytime (8 am-10 pm). Median sound intensity level reached 70.2 [65.1-80.3] dBC at night. Sound thresholds leading to disturbed sleep were 63 dBC during the day and 59 dBC during the night. With levels above 77 dBC, the incidence of arousals (OR 3.9, 95% CI 3.0-5.0) and sleep-to-wake transitions (OR 7.6, 95% CI 4.1-14) increased. The most disturbing noises sources were monitor alarms (OR 4.5, 95% CI 3.5-5.6) and ventilator alarms (OR 4.2, 95% CI 2.9-6.1).We have shown, in a small group of 11 non-severe ICU patients, that sound level intensity, a major disturbance factor of sleep continuity, should be strictly controlled on a 24-h profile.

  View details for DOI 10.1186/s13613-017-0248-7

  View details for Web of Science ID 000399233900001

  View details for PubMedID 28255956

• Sleep surgery tool: A medical checklist to review prior to operating. Journal of cranio-maxillo-facial surgery : official publication of the European Association for Cranio-Maxillo-Facial Surgery Camacho, M., Riley, R. W., Capasso, R., O'Connor, P., Chang, E. T., Reckley, L. K., Guilleminault, C. 2017; 45 (3): 381-386

  Abstract

  The objective of this study was to systematically review the international literature for studies providing a preoperative checklist for medical disorders to be evaluated or treated before performing sleep surgery. If no checklist exists, then studies providing recommendations would be used to develop a checklist de novo.Systematic review combined with expert opinion.Four databases, including PubMed/Medline were searched through August 10, 2016.453 potentially relevant studies were screened, 32 were downloaded for full review. No study included a preoperative checklist. No study provided guidance for specific medical disorders to evaluate or screen for prior to sleep surgery. Therefore, we reviewed articles in adults that provided recommendations such as: (1) labs to review, (2) non-operative disorders to evaluate and treat, and (3) comorbidities to optimize prior to performing sleep surgery. These articles were utilized in conjunction with expert opinion to develop a preoperative checklist for surgical guidance.There are several items to review prior to performing sleep surgery on obstructive sleep apnea patients. This systematic review and expert opinion-based checklist provides over twenty items for reviewing prior to performing sleep surgery to reduce the chance of operating prematurely.

  View details for DOI 10.1016/j.jcms.2017.01.001

  View details for PubMedID 28169045

• High Rates of Psychiatric Comorbidity in Narcolepsy: Findings From the Burden of Narcolepsy Disease (BOND) Study of 9,312 Patients in the United States. journal of clinical psychiatry Ruoff, C. M., Reaven, N. L., Funk, S. E., McGaughey, K. J., Ohayon, M. M., Guilleminault, C., Black, J. 2017; 78 (2): 171-176

  Abstract

  To evaluate psychiatric comorbidity patterns in patients with a narcolepsy diagnosis in the United States.Truven Health Analytics MarketScan Research Databases were accessed to identify individuals ≥ 18 years of age with ≥ 1 ICD-9 diagnosis code(s) for narcolepsy continuously insured between 2006 and 2010 and non-narcolepsy controls matched 5:1 (age, gender, region, payer). Extensive subanalyses were conducted to confirm the validity of narcolepsy definitions. Narcolepsy subjects and controls were compared for frequency of psychiatric comorbid conditions (based on ICD-9 codes/Clinical Classification Software [CCS] level 2 categories) and psychiatric medication use.The final population included 9,312 narcolepsy subjects and 46,559 controls (each group, mean age = 46.1 years; 59% female). All categories of mental illness were significantly more prevalent in patients with narcolepsy versus controls, with the highest excess prevalence noted for CCS 5.8 Mood disorders (37.9% vs 13.8%; odds ratio [OR] = 4.0; 95% CI, 3.8-4.2), CCS 5.8.2 Depressive disorders (35.8% vs 13.0%; OR = 3.9; 95% CI, 3.7-4.1), and CCS 5.2 Anxiety disorders (25.1% vs 11.9%; OR = 2.5; 95% CI, 2.4-2.7). Excess prevalence of anxiety and mood disorders (narcolepsy vs controls) was higher in younger age groups versus older age groups. Psychiatric medication usage was higher in the narcolepsy group versus controls in the following categories: selective serotonin reuptake inhibitors (36% vs 17%), anxiolytic benzodiazepines (34% vs 19%), hypnotics (29% vs 13%), serotonin-norepinephrine reuptake inhibitors (21% vs 6%), and tricyclic antidepressants (13% vs 4%) (all P values < .0001).Narcolepsy is associated with significant comorbid psychiatric illness burden and higher psychiatric medication usage compared with the non-narcolepsy population.

  View details for DOI 10.4088/JCP.15m10262

  View details for PubMedID 27835717

• It Is Just Attention-Deficit Hyperactivity Disorder…or Is It? Journal of developmental and behavioral pediatrics Won, D. C., Guilleminault, C., Koltai, P. J., Quo, S. D., Stein, M. T., Loe, I. M. 2017; 38 (2): 169-172

  Abstract

  Carly is a 5-year-old girl who presents for an interdisciplinary evaluation due to behaviors at school and home suggestive of attention-deficit hyperactivity disorder (ADHD). Parent report of preschool teacher concerns was consistent with ADHD. Psychological testing showed verbal, visual-spatial, and fluid reasoning IQ scores in the average range; processing speed and working memory were below average. Carly's behavior improved when her mother left the room, and she was attentive during testing with a psychologist. Tests of executive function (EF) skills showed mixed results. Working memory was in the borderline range, although scores for response inhibition and verbal fluency were average. Parent ratings of ADHD symptoms and EF difficulties were elevated.Carly's parents recently separated; she now lives with her mother and sees her father on weekends. Multiple caregivers with inconsistent approaches to discipline assist with child care while her mother works at night as a medical assistant. Family history is positive for ADHD and learning problems in her father. Medical history is unremarkable. Review of systems is significant for nightly mouth breathing and snoring, but no night waking, bruxism, or daytime sleepiness. She has enlarged tonsils and a high-arched palate on physical examination.At a follow-up visit, parent rating scales are consistent with ADHD-combined type; teacher rating scales support ADHD hyperactive-impulsive type. Snoring has persisted. A sleep study indicated obstructive sleep apnea. After adenotonsillectomy, Carly had significant improvement in ADHD symptoms. She developed recurrence of behavior problems 1 year after the surgery.

  View details for DOI 10.1097/DBP.0000000000000386

  View details for PubMedID 28079611

  View details for PubMedCentralID PMC5401711

• Bimaxillary expansion therapy for pediatric sleep-disordered breathing. Sleep medicine Quo, S. D., Hyunh, N., Guilleminault, C. 2017; 30: 45-51

  Abstract

  The aim of this retrospective study was to evaluate the results of bimaxillary expansion as a treatment option for pediatric sleep-disordered breathing.Forty-five children, aged 3-14 years, with sleep-disordered breathing underwent bimaxillary expansion. They were subjected to baseline clinical evaluations, cephalometric X-rays, and polygraphic sleep studies. Three to six months after bimaxillary expansion, posttreatment sleep studies were performed. Data were analyzed with nonparametric Wilcoxon signed-rank test, and Spearman's correlations were performed to correlate cephalometric facial structures to the effectiveness of treatment.The majority of the children (n = 30) showed improvement in their sleep scores and symptoms after bimaxillary expansion. The initial severity of the obstructive sleep apnea (OSA) indicated by the apnea-hypopnea index (AHI) was a much better predictor of positive results. However, in the "mild OSA" group, patients with smaller MP-SN or counterclockwise mandibular growth, worsened with bimaxillary expansion, while patients with clockwise mandibular growth showed greater improvement; in the "severe OSA" group, patients who initially had shorter mandibular base lengths showed lesser AHI improvements.Bimaxillary expansion can be a treatment option for improving respiratory parameters in children with sleep-disordered breathing. This study also suggests that retrognathia in an anterior growth rotation pattern may not respond to efforts of bimaxillary expansion.

  View details for DOI 10.1016/j.sleep.2016.03.011

  View details for PubMedID 28215262

• Toward a functional definition of ankyloglossia: validating current grading scales for lingual frenulum length and tongue mobility in 1052 subjects. Sleep & breathing = Schlaf & Atmung Yoon, A., Zaghi, S., Weitzman, R., Ha, S., Law, C. S., Guilleminault, C., Liu, S. Y. 2017

  Abstract

  Alterations of the lingual frenulum may contribute to oromyofacial dysfunction, speech and swallowing impediments, underdevelopment of the maxillofacial skeleton, and even predispose to sleep breathing disorder. This study aims to assess the utility of existing instruments for evaluation of restricted tongue mobility, describe normal and abnormal ranges of tongue mobility, and provide evidence in support of a reliable and efficient measure of tongue mobility.A prospective cohort study of 1052 consecutive patients was evaluated during a 3-month period. Age, gender, ethnicity, height, weight, BMI, maximal interincisal mouth opening (MIO), mouth opening with tongue tip to maxillary incisive papillae at roof of mouth (MOTTIP), Kotlow's free-tongue measurement, and presence of severe tongue-tie were recorded. Secondary outcome measures include tongue range of motion deficit (TRMD, difference between MIO and MOTTIP) and tongue range of motion ratio (TRMR, ratio of MOTTIP to MIO).Results indicate that MIO is dependent on age and height; MOTTIP and TRMD are dependent on MIO; Kotlow's free-tongue measurement is an independent measure of free-tongue length and tongue mobility. TRMR is the only independent measurement of tongue mobility that is directly associated with restrictions in tongue function.We propose the use of tongue range of motion ratio as an initial screening tool to assess for restrictions in tongue mobility. "Functional" ankyloglossia can thus be defined and treatment effects followed objectively by using the proposed grading scale: grade 1: tongue range of motion ratio is >80%, grade 2 50-80%, grade 3 < 50%, grade 4 < 25%.

  View details for DOI 10.1007/s11325-016-1452-7

  View details for PubMedID 28097623

• New developments in the management of narcolepsy. Nature and science of sleep Abad, V. C., Guilleminault, C. 2017; 9: 39-57

  Abstract

  Narcolepsy is a life-long, underrecognized sleep disorder that affects 0.02%-0.18% of the US and Western European populations. Genetic predisposition is suspected because of narcolepsy's strong association with HLA DQB1*06-02, and genome-wide association studies have identified polymorphisms in T-cell receptor loci. Narcolepsy pathophysiology is linked to loss of signaling by hypocretin-producing neurons; an autoimmune etiology possibly triggered by some environmental agent may precipitate hypocretin neuronal loss. Current treatment modalities alleviate the main symptoms of excessive daytime somnolence (EDS) and cataplexy and, to a lesser extent, reduce nocturnal sleep disruption, hypnagogic hallucinations, and sleep paralysis. Sodium oxybate (SXB), a sodium salt of γ hydroxybutyric acid, is a first-line agent for cataplexy and EDS and may help sleep disruption, hypnagogic hallucinations, and sleep paralysis. Various antidepressant medications including norepinephrine serotonin reuptake inhibitors, selective serotonin reuptake inhibitors, and tricyclic antidepressants are second-line agents for treating cataplexy. In addition to SXB, modafinil and armodafinil are first-line agents to treat EDS. Second-line agents for EDS are stimulants such as methylphenidate and extended-release amphetamines. Emerging therapies include non-hypocretin-based therapy, hypocretin-based treatments, and immunotherapy to prevent hypocretin neuronal death. Non-hypocretin-based novel treatments for narcolepsy include pitolisant (BF2.649, tiprolisant); JZP-110 (ADX-N05) for EDS in adults; JZP 13-005 for children; JZP-386, a deuterated sodium oxybate oral suspension; FT 218 an extended-release formulation of SXB; and JNJ-17216498, a new formulation of modafinil. Clinical trials are investigating efficacy and safety of SXB, modafinil, and armodafinil in children. γ-amino butyric acid (GABA) modulation with GABAA receptor agonists clarithromycin and flumazenil may help daytime somnolence. Other drugs investigated include GABAB agonists (baclofen), melanin-concentrating hormone antagonist, and thyrotropin-releasing hormone agonists. Hypocretin-based therapies include hypocretin peptide replacement administered either through an intracerebroventricular route or intranasal route. Hypocretin neuronal transplant and transforming stem cells into hypothalamic neurons are also discussed in this article. Immunotherapy to prevent hypocretin neuronal death is reviewed.

  View details for DOI 10.2147/NSS.S103467

  View details for PubMedID 28424564

• Mandibular advancement for adult obstructive sleep apnea: A systematic review and meta-analysis. Journal of cranio-maxillo-facial surgery : official publication of the European Association for Cranio-Maxillo-Facial Surgery Noller, M. W., Guilleminault, C., Gouveia, C. J., Mack, D., Vivian, C., Abdullatif, J., Mangili, S., Liu, S. Y., Zaghi, S., Camacho, M. 2017; 45 (12): 2035–40

  Abstract

  Patients with mandibular insufficiency can be predisposed to obstructive sleep apnea (OSA). The objective of this study was to systematically review the international literature for mandibular advancement surgeries (MAS) as treatment for adult OSA, and then to perform a meta-analysis.Four authors searched five databases from the inception of each database through April 5, 2017. The PRISMA statement was followed.972 studies were screened, 84 were downloaded, and 11 (57 patients) met criteria. In patients with mandibular insufficiency, MAS reduced apnea-hypopnea index (AHI) (50 patients) from 45.9 ± 24.7 to 6.2 ± 10.4 events/h (87% decrease). The lowest oxygen saturation (LSAT) (55 patients) increased from 71.9 ± 14.6% to 89.0 ± 11.0%. The AHI mean difference was -34.8 events/h [95% CI -43.9, -25.8]. The AHI standardized mean difference was -1.8 [95% CI -2.5, -1.2] (indicating a large magnitude of effect). Surgical cure was seen in 75% of those with >16 mm of mandibular advancement vs. 35% of those with <16 mm of advancement [Odds Ratio 5.5; 95% CI 1.06-28.4; Chi Square p = 0.035].The current literature supports isolated mandibular advancement as an efficacious treatment modality for adult OSA in select patients with mandibular insufficiency.

  View details for DOI 10.1016/j.jcms.2017.10.006

  View details for PubMedID 29113702

• The association between ophthalmologic diseases and obstructive sleep apnea: a systematic review and meta-analysis SLEEP AND BREATHING Huon, L., Liu, S. Y., Camacho, M., Guilleminault, C. 2016; 20 (4): 1145-1154

  Abstract

  The purpose of this study was to evaluate the association between obstructive sleep apnea (OSA) and ophthalmologic diseases, specifically glaucoma, nonarteritic anterior ischemic optic neuropathy (NAION), retinal vein occlusion (RVO), central serous chorioretinopathy (CSR), and floppy eyelid syndrome (FES), by performing a systematic review and meta-analysis of published studies.PubMed, Embase, and Scopus databases were searched for observational studies on OSA and its association with select ophthalmologic diseases. Data was pooled for random-effects modeling. The association between OSA and ophthalmologic diseases was summarized using an estimated pooled odds ratio with a 95 % confidence interval.Relative to non-OSA subjects, OSA subjects have increased odds of diagnosis with glaucoma (pooled odds ratio (OR) = 1.242; P < 0.001) and floppy eyelids syndrome (pooled OR = 4.157; P < 0.001). In reverse, the overall pooled OR for OSA was 1.746 (P = 0.002) in the glaucoma group, 3.126 (P = 0.000) in the NAION group, and 2.019 (P = 0.028) in the CSR group. For RVO, one study with 5965 OSA patients and 29,669 controls demonstrated a 1.94-fold odds increase in OSA patients.Our results suggest significant associations between OSA and glaucoma, NAION, CSR, and FES. Screening for OSA should be considered in patients with glaucoma, NAION, CSR, or FES.

  View details for DOI 10.1007/s11325-016-1358-4

  View details for Web of Science ID 000390065300003

  View details for PubMedID 27230013

• Performance of screening questionnaires for obstructive sleep apnea during pregnancy: A systematic review and meta-analysis. Sleep medicine reviews Tantrakul, V., Numthavaj, P., Guilleminault, C., McEvoy, M., Panburana, P., Khaing, W., Attia, J., Thakkinstian, A. 2016

  Abstract

  This review aims to evaluate the performance of obstructive sleep apnea (OSA) screening questionnaires during pregnancy. A systematic review and meta-analysis was performed using MEDLINE Scopus, CINAHL, and the Cochrane library. A bivariate meta-analysis was applied for pooling of diagnostic parameters. Six of the total 4719 articles met the inclusion criteria. The Berlin questionnaire (BQ, N = 604) and Epworth sleepiness scale (ESS, N = 420) were the most frequently used screening tools during pregnancy. The pooled prevalence of OSA during pregnancy was 26.7% (95%CI: 16.9%, 34.4%, I(2) = 83.15%). BQ performance was poor to fair with pooled sensitivity and specificity of 0.66 (95%CI: 0.45, 0.83; I(2) = 78.65%) and 0.62 (95%CI: 0.48, 0.75; I(2) = 81.55%), respectively. BQ performance was heterogeneous depending on type of reference test and pregnancy. Sensitivity increased if diagnosis was based on polysomnography (0.90), and respiratory disturbance index (0.90). However, sensitivity decreased if screening was performed in early pregnancy (≤20 weeks gestation: 0.47), and high-risk pregnancy (0.44). Performance of ESS was poor with pooled sensitivity and specificity of 0.44 (95%CI: 0.33, 0.56; I(2) = 32.8%) and 0.62 (95%CI: 0.48, 0.75; I(2) = 81.55%), respectively. In conclusion, BQ and ESS showed poor performance during pregnancy, hence a new OSA screening questionnaire is needed. Registration: PROSPERO registration CRD42015025848.

  View details for DOI 10.1016/j.smrv.2016.11.003

  View details for PubMedID 28007402

• Rapid maxillary expansion for pediatric obstructive sleep apnea: A systematic review and meta-analysis. Laryngoscope Camacho, M., Chang, E. T., Song, S. A., Abdullatif, J., Zaghi, S., Pirelli, P., Certal, V., Guilleminault, C. 2016

  Abstract

  To perform a systematic review with meta-analysis for sleep study outcomes in children who have undergone rapid maxillary expansion (RME) as treatment for obstructive sleep apnea (OSA).PubMed/MEDLINE and eight additional databases.Three authors independently and systematically reviewed the international literature through February 21, 2016.Seventeen studies reported outcomes for 314 children (7.6 ± 2.0 years old) with high-arched and/or narrow hard palates (transverse maxillary deficiency) and OSA. Data were analyzed based on follow-up duration: ≤3 years (314 patients) and >3 years (52 patients). For ≤3-year follow-up, the pre- and post-RME apnea-hypopnea index (AHI) decreased from a mean ± standard deviation (M ± SD) of 8.9 ± 7.0/hr to 2.7 ± 3.3/hr (70% reduction). The cure rate (AHI <1/hr) for 90 patients for whom it could be calculated was 25.6%. Random effects modeling for AHI standardized mean difference (SMD) is -1.54 (large effect). Lowest oxygen saturation (LSAT) improved from 87.0 ± 9.1% to 96.0 ± 2.7%. Random effects modeling for LSAT SMD is 1.74 (large effect). AHI improved more in children with previous adenotonsillectomy or small tonsils (73-95% reduction) than in children with large tonsils (61% reduction). For >3-year follow-up (range = 6.5-12 years), the AHI was reduced from an M ± SD of 7.1 ± 5.7/hr to 1.5 ± 1.8/hr (79% reduction).Improvement in AHI and lowest oxygen saturation has consistently been seen in children undergoing RME, especially in the short term (<3-year follow-up). Randomized trials and more studies reporting long-term data (≥3-year follow-up) would help determine the effect of growth and spontaneous resolution of OSA. Laryngoscope, 2016.

  View details for DOI 10.1002/lary.26352

  View details for PubMedID 27796040

• Neurocognitive function in patients with residual excessive sleepiness from obstructive sleep apnea: a prospective, controlled study SLEEP MEDICINE Werli, K. S., Otuyama, L. J., Bertolucci, P. H., Rizzi, C. F., Guilleminault, C., Tufik, S., Poyares, D. 2016; 26: 6-11

  Abstract

  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.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.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).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.

  View details for DOI 10.1016/j.sleep.2016.06.028

  View details for Web of Science ID 000390720900002

  View details for PubMedID 28007359

• Inflammatory cytokines in pediatric obstructive sleep apnea MEDICINE Huang, Y., Guilleminault, C., Hwang, F., Cheng, C., Lin, C., Li, H., Lee, L. 2016; 95 (41)

  Abstract

  Pediatric obstructive sleep apnea (OSA) is associated with chronic systemic inflammation and with cognitive impairments. This study aimed to investigate the status of proinflammatory cytokines, particularly interleukin 17 (IL-17) and interleukin 23 (IL-23) and cognition in pediatric OSA.Controls and OSA children participated in the study. Exclusion criteria were adenotonsillectomy, heart, neurological and severe psychiatric diseases, craniofacial syndromes, and obesity. Polysomnogram was followed by serum testing for inflammatory markers and neurocognitive tests such as continuous performance task (CPT) and Wisconsin card sorting test, questionnaires, analyses of plasma high-sensitivity C-reactive protein (HS-CRP), tumor necrosis factor alpha (TNF-α), interleukin 1 (IL-1), interleukin 6 (IL-6), IL-17, and IL-23.Seventy-nine, 4 to 12-year-old subjects in 2 groups ended the study: 47 nonobese OSA children (mean age = 7.84 ± 0.56 years, body mass index [BMI] = 16.95 ± 0.47 kg/m, BMI z-score = 0.15 ± 0.21, and mean apnea-hypopnea index [AHI] = 9.13 ± 1.67 events/h) and 32 healthy control children (mean age = 7.02 ± 0.65 years, with BMI = 16.55 ± 0.58 kg/m, BMI z-score = -0.12 ± 0.27, and mean AHI = 0.41 ± 0.07 event/h) were enrolled. Serum cytokine analyses showed significantly higher levels of HS-CRP, IL-17, and IL-23 in OSA children (P = 0.002, P = 0.024, and P = 0.047). Regression test showed significant influence of HS-CRP, TNF-α, IL-6, IL-17, and specifically IL-23, with the continuous performance test and Wisconsin card sorting test.OSA children have abnormal levels of IL-17, an interleukin related to T helper 17 cells, a T helper cell involved in development of autoimmunity and inflammation. This high expression level may contribute to the complications of pediatric OSA; we also found a significant influence of inflammatory cytokines, particularly IL-23, on abnormal neurocognitive testing.

  View details for DOI 10.1097/MD.0000000000004944

  View details for Web of Science ID 000386354700011

  View details for PubMedID 27741107

  View details for PubMedCentralID PMC5072934

• Brain imaging and cognition in young narcoleptic patients SLEEP MEDICINE Huang, Y., Liu, F., Lin, C. Y., Hsiao, I., Guilleminault, C. 2016; 23: 137-144

  View details for DOI 10.1016/j.sleep.2015.11.023

  View details for Web of Science ID 000388541900020

• Kleine-Levin Syndrome CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS Miglis, M. G., Guilleminault, C. 2016; 16 (6)

  Abstract

  Kleine-Levin syndrome is a rare recurrent hypersomnia associated with symptoms of behavioral and cognitive impairment. This article reviews common presenting symptoms, differential diagnosis, diagnostic workup, and potential treatment options. Current updates on functional imaging studies and long-term neuropsychological studies are reviewed.

  View details for DOI 10.1007/s11910-016-0653-6

  View details for Web of Science ID 000376282500003

  View details for PubMedID 27137943

• Kleine-Levin Syndrome CURRENT TREATMENT OPTIONS IN NEUROLOGY Sum-Ping, O., Guilleminault, C. 2016; 18 (6)

  Abstract

  Kleine-Levin Syndrome [KLS] is often under-recognized and also misdiagnosed. When suspicion for KLS is raised, a thorough clinical evaluation should be performed, including detailed history from family members and a neurologic and psychiatric examination. Additional studies may include PSG, EEG, neuroimaging, as well as serological and CSF studies to rule out alternative diagnoses as clinically indicated. After arriving at a diagnosis of KLS, the foundation of care is supportive. Patients and their families should be provided with education about the disease. During symptomatic periods, patients should be allowed to rest at home under caregiver supervision. Caregivers should pay special attention to the patient's eating habits and mood. Patients should not be allowed to drive or operate heavy machinery during these episodes. In between episodes, avoidance of reported triggers, such as alcohol and infection are encouraged as is maintenance of a regular sleep-wake cycle. Pharmacologic therapy has not been well-studied and for most patients is not necessary. For more severe cases, targeted symptomatic therapy, such as modafinil or amantadine for somnolence or risperidone for psychosis may be considered depending on the patient's symptomatology. Lithium has the best data to support its use as a prophylactic agent and for patients with severe or frequent episodes, may be considered.

  View details for DOI 10.1007/s11940-016-0409-2

  View details for Web of Science ID 000376016800003

  View details for PubMedID 27073070

• Missing teeth and pediatric obstructive sleep apnea SLEEP AND BREATHING Guilleminault, C., Abad, V. C., Chiu, H., Peters, B., Quo, S. 2016; 20 (2): 561-568

  Abstract

  Missing teeth in early childhood can result in abnormal facial morphology with narrow upper airway. The potential association between dental agenesis or early dental extractions and the presence of obstructive sleep apnea (OSA) was investigated.We reviewed clinical data, results of polysomnographic sleep studies, and orthodontic imaging studies of children with dental agenesis (n = 32) or early extraction of permanent teeth (n = 11) seen during the past 5 years and compared their findings to those of age-, gender-, and body mass index-matched children with normal teeth development but tonsilloadenoid (T&A) hypertrophy and symptoms of OSA (n = 64).The 31 children with dental agenesis and 11 children with early dental extractions had at least 2 permanent teeth missing. All children with missing teeth (n = 43) had clinical complaints and signs evoking OSA. There was a significant difference in mean apnea-hypopnea indices (AHI) in the three dental agenesis, dental extraction, and T&A studied groups (p < 0.001), with mean abnormal AHI lowest in the pediatric dental agenesis group. In the children with missing teeth (n = 43), aging was associated with the presence of a higher AHI (R (2) = 0.71, p < 0.0001).Alveolar bone growth is dependent on the presence of the teeth that it supports. The dental agenesis in the studied children was not part of a syndrome and was an isolated finding. Our children with permanent teeth missing due to congenital agenesis or permanent teeth extraction had a smaller oral cavity, known to predispose to the collapse of the upper airway during sleep, and presented with OSA recognized at a later age. Due to the low-grade initial symptomatology, sleep-disordered breathing may be left untreated for a prolonged period with progressive worsening of symptoms over time.

  View details for DOI 10.1007/s11325-015-1238-3

  View details for Web of Science ID 000375434400014

  View details for PubMedID 26330227

• Maxillomandibular Advancement for Treatment of Obstructive Sleep Apnea: A Meta-analysis. JAMA otolaryngology-- head & neck surgery Zaghi, S., Holty, J. C., Certal, V., Abdullatif, J., Guilleminault, C., Powell, N. B., Riley, R. W., Camacho, M. 2016; 142 (1): 58-66

  Abstract

  Maxillomandibular advancement (MMA) is an invasive yet effective surgical option for obstructive sleep apnea (OSA) that achieves enlargement of the upper airway by physically expanding the facial skeletal framework.To identify criteria associated with surgical outcomes of MMA using aggregated individual patient data from multiple studies.The Cochrane Library, Scopus, Web of Science, and MEDLINE from June 1, 2014, to March 16, 2015, using the Medical Subject Heading keywords maxillomandibular advancement, orthognathic surgery, maxillary osteotomy, mandibular advancement, sleep apnea, surgical, surgery, sleep apnea syndrome, and obstructive sleep apnea.Inclusion criteria consisted of studies in all languages of (1) adult patients who underwent MMA as treatment for OSA; (2) report of preoperative and postoperative quantitative outcomes for the apnea-hypopnea index (AHI) and/or respiratory disturbance index (RDI); and (3) report of individual patient data. Studies of patients who underwent adjunctive procedures at the time of MMA (including tonsillectomy, uvulopalatopharyngoplasty, and partial glossectomy) were excluded.Three coauthors systematically reviewed the articles and updated the review through March 16, 2015. The PRISMA statement was followed. Data were pooled using a random-effects model and analyzed from July 1, 2014, to September 23, 2015.The primary outcomes were changes in the AHI and RDI after MMA for each patient. Secondary outcomes included surgical success, defined as the percentage of patients with more than 50% reduction of the AHI to fewer than 20 events/h, and OSA cure, defined as a post-MMA AHI of fewer than 5 events/h.Forty-five studies with individual data from 518 unique patients/interventions were included. Among patients for whom data were available, 197 of 268 (73.5%) had undergone prior surgery for OSA. Mean (SD) postoperative changes in the AHI and RDI after MMA were -47.8 (25.0) and -44.4 (33.0), respectively; mean (SE) reductions of AHI and RDI outcomes were 80.1% (1.8%) and 64.6% (4.0%), respectively; and 512 of 518 patients (98.8%) showed improvement. Significant improvements were also seen in the mean (SD) postoperative oxygen saturation nadir (70.1% [15.6%] to 87.0% [5.2%]; P < .001) and Epworth Sleepiness Scale score (13.5 [5.2] to 3.2 [3.2]; P < .001). Rates of surgical success and cure were 389 (85.5%) and 175 (38.5%), respectively, among 455 patients with AHI data and 44 (64.7%) and 13 (19.1%), respectively, among 68 patients with RDI data. Preoperative AHI of fewer than 60 events/h was the factor most strongly associated with the highest incidence of surgical cure. Nevertheless, patients with a preoperative AHI of more than 60 events/h experienced large and substantial net improvements despite modest surgical cure rates.Maxillomandibular advancement is an effective treatment for OSA. Most patients with high residual AHI and RDI after other unsuccessful surgical procedures for OSA are likely to benefit from MMA.

  View details for DOI 10.1001/jamaoto.2015.2678

  View details for PubMedID 26606321

• Pediatric sleep-disordered breathing: New evidence on its development SLEEP MEDICINE REVIEWS Guilleminault, C., Akhtar, F. 2015; 24: 46-56

  View details for DOI 10.1016/j.smrv.2014.11.008

  View details for Web of Science ID 000364605700005

  View details for PubMedID 26500024

• Mouth breathing, "nasal disuse," and pediatric sleep-disordered breathing SLEEP AND BREATHING Lee, S., Guilleminault, C., Chiu, H., Sullivan, S. S. 2015; 19 (4): 1257-1264

  Abstract

  Adenotonsillectomy (T&A) may not completely eliminate sleep-disordered breathing (SDB), and residual SDB can result in progressive worsening of abnormal breathing during sleep. Persistence of mouth breathing post-T&As plays a role in progressive worsening through an increase of upper airway resistance during sleep with secondary impact on orofacial growth.Retrospective study on non-overweight and non-syndromic prepubertal children with SDB treated by T&A with pre- and post-surgery clinical and polysomnographic (PSG) evaluations including systematic monitoring of mouth breathing (initial cohort). All children with mouth breathing were then referred for myofunctional treatment (MFT), with clinical follow-up 6 months later and PSG 1 year post-surgery. Only a limited subgroup followed the recommendations to undergo MFT with subsequent PSG (follow-up subgroup).Sixty-four prepubertal children meeting inclusion criteria for the initial cohort were investigated. There was significant symptomatic improvement in all children post-T&A, but 26 children had residual SDB with an AHI > 1.5 events/hour and 35 children (including the previous 26) had evidence of "mouth breathing" during sleep as defined [minimum of 44 % and a maximum of 100 % of total sleep time, mean 69 ± 11 % "mouth breather" subgroup and mean 4 ± 3.9 %, range 0 and 10.3 % "non-mouth breathers"]. Eighteen children (follow-up cohort), all in the "mouth breathing" group, were investigated at 1 year follow-up with only nine having undergone 6 months of MFT. The non- MFT subjects were significantly worse than the MFT-treated cohort. MFT led to normalization of clinical and PSG findings.Assessment of mouth breathing during sleep should be systematically performed post-T&A and the persistence of mouth breathing should be treated with MFT.

  View details for DOI 10.1007/s11325-015-1154-6

  View details for Web of Science ID 000365744500020

  View details for PubMedID 25877805

• Sleepiness and Motor Vehicle Crashes in a Representative Sample of Portuguese Drivers: The Importance of Epidemiological Representative Surveys TRAFFIC INJURY PREVENTION Goncalves, M., Peralta, A. R., Monteiro Ferreira, J., Guilleminault, C. 2015; 16 (7): 677-683

  Abstract

  Sleepiness is considered to be a leading cause of crashes. Despite the huge amount of information collected in questionnaire studies, only some are based on representative samples of the population. Specifics of the populations studied hinder the generalization of these previous findings. For the Portuguese population, data from sleep-related car crashes/near misses and sleepiness while driving are missing. The objective of this study is to determine the prevalence of near-miss and nonfatal motor vehicle crashes related to sleepiness in a representative sample of Portuguese drivers.Structured phone interviews regarding sleepiness and sleep-related crashes and near misses, driving habits, demographic data, and sleep quality were conducted using the Pittsburgh Sleep Quality Index and sleep apnea risk using the Berlin questionnaire. A multivariate regression analysis was used to determine the associations with sleepy driving (feeling sleepy or falling asleep while driving) and sleep-related near misses and crashes.Nine hundred subjects, representing the Portuguese population of drivers, were included; 3.1% acknowledged falling asleep while driving during the previous year and 0.67% recalled sleepiness-related crashes. Higher education, driving more than 15,000 km/year, driving more frequently between 12:00 a.m. and 6 a.m., fewer years of having a driver's license, less total sleep time per night, and higher scores on the Epworth Sleepiness Scale (ESS) were all independently associated with sleepy driving. Sleepiness-related crashes and near misses were associated only with falling asleep at the wheel in the previous year. Sleep-related crashes occurred more frequently in drivers who had also had sleep-related near misses.Portugal has lower self-reported sleepiness at the wheel and sleep-related near misses than most other countries where epidemiological data are available. Different population characteristics and cultural, social, and road safety specificities may be involved in these discrepancies. Despite this, Portuguese drivers report sleep-related crashes in frequencies similar to those of drivers in other countries.

  View details for DOI 10.1080/15389588.2015.1013535

  View details for Web of Science ID 000356784700007

  View details for PubMedID 25793312

• Emerging drugs for common conditions of sleepiness: obstructive sleep apnea and narcolepsy EXPERT OPINION ON EMERGING DRUGS Sullivan, S. S., Guilleminault, C. 2015; 20 (4): 571-582

  View details for DOI 10.1517/14728214.2015.1115480

  View details for Web of Science ID 000366612800002

  View details for PubMedID 26558298

• Rapid maxillary expansion (RME) for pediatric obstructive sleep apnea: a 12-year follow-up SLEEP MEDICINE Pirelli, P., Saponara, M., Guilleminault, C. 2015; 16 (8): 933-935

  Abstract

  The objective of this study was to prospectively evaluate the long-term efficacy of rapid maxillary expansion (RME) in a group of children with obstructive sleep apnea (OSA).Thirty-one children diagnosed with OSA were involved in the study. These children had isolated maxillary narrowing and absence of enlarged adenotonsils at baseline. Twenty-three individuals (73% of the initial group) were followed up annually over a mean of 12 years after the completion of orthodontic treatment at a mean age of 8.68 years. Eight children dropped out over time due to either moving out of the area (n = 6) or refusal to submit to regular follow-up (n = 2). Subjects underwent clinical reevaluation over time and repeat polysomnography (PSG) in the late teenage years or in their early 20s. During the follow-up period, eight children dropped out and 23 individuals (including 10 girls) underwent a final clinical investigation with PSG (mean age of 20.9 years). The final evaluation also included computerized tomographic (CT) imaging that was compared with pre- and post-initial treatment findings.Yearly clinical evaluations, including orthodontic and otolaryngological examinations and questionnaire scores, were consistently normal over time, and PSG findings remained normal at the 12-year follow-up period. The stability and maintenance of the expansion over time was demonstrated by the maxillary base width and the distance of the pterygoid processes measured using CT imaging.A subgroup of OSA children with isolated maxillary narrowing initially and followed up into adulthood present stable, long-term results post RME treatment for pediatric OSA.

  View details for DOI 10.1016/j.sleep.2015.04.012

  View details for Web of Science ID 000358087000006

• A Cost-Effectiveness Analysis of Surgery for Middle-Aged Men with Severe Obstructive Sleep Apnea Intolerant of CPAP. Journal of clinical sleep medicine Tan, K. B., Toh, S. T., Guilleminault, C., Holty, J. C. 2015; 11 (5): 525-535

  Abstract

  Obstructive sleep apnea (OSA) is associated with increased cardiovascular morbidity and mortality. Conventional OSA therapy necessitates indefinite continuous positive airway pressure (CPAP). Although CPAP is an effective treatment modality, up to 50% of OSA patients are intolerant of CPAP. We explore whether surgical modalities developed for those intolerant of CPAP are cost-effective.We construct a lifetime semi-Markov model of OSA that accounts for observed increased risks of stroke, cardiovascular disease, and motor vehicle collisions for a 50-year-old male with untreated severe OSA. Using this model, we compare the cost-effectiveness of (1) no treatment, (2) CPAP only, and (3) CPAP followed by surgery (either palatopharyngeal reconstructive surgery [PPRS] or multilevel surgery [MLS]) for those intolerant to CPAP.Compared with the CPAP only strategy, CPAP followed by PPRS (CPAP-PPRS) adds 0.265 quality adjusted life years (QALYs) for an increase of $2,767 (discounted 2010 dollars) and is highly cost effective with an incremental cost-effectiveness ratio (ICER) of $10,421/QALY for a 50-year-old male with severe OSA. Compared to a CPAP-PPRS strategy, the CPAP-MLS strategy adds 0.07 QALYs at an increase of $6,213 for an ICER of $84,199/QALY. The CPAP-PPRS strategy appears cost-effective over a wide range of parameter estimates.Palatopharyngeal reconstructive surgery appears cost-effective in middle-aged men with severe OSA intolerant of CPAP. Further research is warranted to better define surgical candidacy as well as short-term and long-term surgical outcomes.A commentary on this article appears in this issue on page 509.

  View details for DOI 10.5664/jcsm.4696

  View details for PubMedID 25700871

• Gender differences in sleep disordered breathing: implications for therapy EXPERT REVIEW OF RESPIRATORY MEDICINE Won, C., Guilleminault, C. 2015; 9 (2): 221-231

  Abstract

  There are gender differences in the upper airway function and respiratory stability in obstructive sleep apnea (OSA). Hormones are implicated in some gender-related differences, and these differences between men and women appear to mitigate as age increases. In addition, changes in the airway and lung function during pregnancy can contribute to snoring and OSA that might have an adverse effect on the mother and fetus. The limited data available suggest that although the prevalence and severity of OSA may be lower in women, the consequences of the disease are similar, if not worse. Women with OSA may have greater risk for hypertension and endothelial dysfunction, be more likely to develop comorbid conditions such as anxiety and depression and have increased mortality. Therefore, treatment options specifically targeting female presentations and pathophysiology of sleep-disordered breathing (SDB) are expected to result in improved outcomes in women.

  View details for DOI 10.1586/17476348.2015.1019478

  View details for Web of Science ID 000355321300011

  View details for PubMedID 25739831

• The Effect of Nasal Surgery on Continuous Positive Airway Pressure Device Use and Therapeutic Treatment Pressures: A Systematic Review and Meta-Analysis SLEEP Camacho, M., Riaz, M., Capasso, R., Ruoff, C. M., Guilleminault, C., Kushida, C. A., Certal, V. 2015; 38 (2): 279-?

  View details for DOI 10.5665/sleep.4414

  View details for Web of Science ID 000348757800016

  View details for PubMedID 25325439

• The effect of nasal surgery on continuous positive airway pressure device use and therapeutic treatment pressures: a systematic review and meta-analysis. Sleep Camacho, M., Riaz, M., Capasso, R., Ruoff, C. M., Guilleminault, C., Kushida, C. A., Certal, V. 2015; 38 (2): 279-286

  Abstract

  The relationship between nasal surgery and its effect on continuous positive airway pressure (CPAP) device therapeutic treatment pressures and CPAP device use has not been previously systematically examined.To conduct a systematic review and meta-analysis evaluating the effect of isolated nasal surgery on therapeutic CPAP device pressures and use in adults with obstructive sleep apnea (OSA).MEDLINE, Scopus, Web of Science, and The Cochrane Library were searched through July 15, 2014. The MOOSE consensus statement and PRISMA statement were followed.Eighteen studies (279 patients) reported CPAP data after isolated nasal surgery. Seven studies (82 patients) reported preoperative and postoperative mean therapeutic CPAP device pressures and standard deviations (SD), which reduced from 11.6 ± 2.2 to 9.5 ± 2.0 centimeters of water pressure (cwp) after nasal surgery. Pooled random effects analysis demonstrated a statistically significant pressure reduction, with a mean difference (MD) of -2.66 cwp (95% confidence interval (CI), -3.65 to -1.67); P < 0.00001. Eleven studies (153 patients) reported subjective, self-reported data for CPAP use; and a subgroup analysis demonstrated that 89.1% (57 of 64 patients) who were not using CPAP prior to nasal surgery subsequently accepted, adhered to, or tolerated it after nasal surgery. Objective, device meter-based hours of use increased in 33 patients from 3.0 ± 3.1 to 5.5 ± 2.0 h in the short term (<6 mo of follow-up).Isolated nasal surgery in patients with OSA and nasal obstruction reduces therapeutic CPAP device pressures and the currently published literature's objective and subjective data consistently suggest that it also increases CPAP use in select patients.

  View details for DOI 10.5665/sleep.4414

  View details for PubMedID 25325439

• Treatment of upper airway resistance syndrome in adults: Where do we stand? Sleep Science (Sa~o Paulo, Brazil) de Godoy, L. B., Palombini, L. O., Guilleminault, C., Poyares, D., Tufik, S., Togeiro, S. M. 2015; 8 (1): 42-48

  Abstract

  To evaluate the available literature regarding Upper Airway Resistance Syndrome (UARS) treatment.Keywords "Upper Airway Resistance Syndrome," "Sleep-related Breathing Disorder treatment," "Obstructive Sleep Apnea treatment" and "flow limitation and sleep" were used in main databases.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.Randomized controlled trials with larger numbers of patients and long-term follow-up are important to establish UARS treatment options.

  View details for DOI 10.1016/j.slsci.2015.03.001

  View details for PubMedID 26483942

• Pharmacological treatment of sleep disorders and its relationship with neuroplasticity. Current topics in behavioral neurosciences Abad, V. C., Guilleminault, C. 2015; 25: 503-553

  Abstract

  Sleep and wakefulness are regulated by complex brain circuits located in the brain stem, thalamus, subthalamus, hypothalamus, basal forebrain, and cerebral cortex. Wakefulness and NREM and REM sleep are modulated by the interactions between neurotransmitters that promote arousal and neurotransmitters that promote sleep. Various lines of evidence suggest that sleep disorders may negatively affect neuronal plasticity and cognitive function. Pharmacological treatments may alleviate these effects but may also have adverse side effects by themselves. This chapter discusses the relationship between sleep disorders, pharmacological treatments, and brain plasticity, including the treatment of insomnia, hypersomnias such as narcolepsy, restless legs syndrome (RLS), obstructive sleep apnea (OSA), and parasomnias.

  View details for DOI 10.1007/7854_2014_365

  View details for PubMedID 25585962

• Screening of Obstructive Sleep Apnea during Pregnancy: Differences in Predictive Values of Questionnaires across Trimesters JOURNAL OF CLINICAL SLEEP MEDICINE Tantrakul, V., Sirijanchune, P., Panburana, P., Pengjam, J., Suwansathit, W., Boonsarngsuk, V., Guilleminault, C. 2015; 11 (2): 157-163

  Abstract

  Evaluation of Berlin and Stop-Bang questionnaires in detecting obstructive sleep apnea (OSA) across trimesters of pregnancy.Pregnant women from a high-risk pregnancy clinic were recruited to complete sleep evaluations including Berlin and Stop-Bang Questionnaires. Overnight testing with Watch-PAT200 for diagnosis of OSA (cutoff point of apnea-hypopnea index ≥5 events/h) was performed.Seventy-two singleton pregnant women participated in the study. Enrollment consisted of 23, 24, and 25 women during first, second, and third trimesters, respectively. Of 72 pregnancies, 23 patients (31.9%) had OSA. Prevalence of OSA classified by trimesters from first to third was 30.4%, 33.33%, and 32.0%, respectively. Overall predictive values of Berlin and Stop-Bang questionnaires were fair (ROC area under curve, AUC 0.72 for Berlin, p = 0.003; 0.75 for Stop-Bang, p = 0.001). When categorized according to trimesters, predictive values substantially improved in second (AUC: 0.84 for Berlin; 0.78 for Stop-Bang) and third trimesters (AUC: 0.81 for Berlin; 0.75 for Stop-Bang), whereas performances of both questionnaires during first trimester were poorer (AUC: 0.49 for Berlin; 0.71 for Stop-Bang). Multivariate analyses show that pre-pregnancy body mass index (BMI) in first trimester, snore often in second trimester, and weight gain and pregnancy BMI in third trimester were significantly associated with OSA.In high-risk pregnancy, Berlin and Stop-Bang questionnaires were of limited usefulness in the first trimester. However their predictive values are acceptable as pregnancy progresses, particularly in second trimester. OSA in pregnancy seems to be a dynamic process with different predictors association during each trimester.

  View details for DOI 10.5664/jcsm.4464

  View details for Web of Science ID 000352140800011

  View details for PubMedID 25406273

• Nasopharyngeal airway stenting devices for obstructive sleep apnoea: A systematic review and meta-analysis. journal of laryngology and otology Kumar, A. R., Guilleminault, C., Certal, V., Li, D., Capasso, R., Camacho, M. 2015; 129 (1): 2-10

  Abstract

  To systematically review outcomes of adults with obstructive sleep apnoea treated with nasopharyngeal airway stenting devices.Medline, Scopus, Web of Science and the Cochrane Library databases were searched, and data on device use and tolerability, sleepiness, oxygen saturation, apnoea index, apnoea-hypopnoea index, and sleep quality were collected.Of 573 potential studies, 29 were retrieved for detailed evaluation and 16 met the study criteria. Polysomnography data for patients treated with nasal trumpets as an isolated therapy were pooled for meta-analysis. The mean apnoea index ± standard deviation, for 53 patients, decreased from 32.4 ± 15.9 to 9.0 ± 7.2 episodes per hour (p < 0.00001). The mean apnoea-hypopnoea index, for 193 patients, decreased from 44.1 ± 18.9 to 22.7 ± 19.3 episodes per hour (p < 0.00001). The mean lowest oxygen saturation, for 193 patients, increased from 66.5 ± 14.2 to 75.5 ± 13.9 per cent (p < 0.00001).Some studies have demonstrated limited effectiveness and low tolerability of nasopharyngeal airway stenting devices, while other studies have shown a significant benefit in treating obstructive sleep apnoea, with a high level of patient acceptance. Nasal trumpets have been successful in decreasing airway obstruction in the short term.

  View details for DOI 10.1017/S0022215114003119

  View details for PubMedID 25544266

• Sleep and breathing in premature infants at 6 months post-natal age BMC PEDIATRICS Huang, Y., Paiva, T., Hsu, J., Kuo, M., Guilleminault, C. 2014; 14

  View details for DOI 10.1186/s12887-014-0303-6

  View details for Web of Science ID 000346802900001

• High rates of medical comorbidity in narcolepsy: findings from the burden of narcolepsy disease (BOND) study of 9312 patients in the United States 22nd Congress of the European-Sleep-Research-Society Black, J., Reaven, N., Funk, S., MCGAUGHEY, K., Ohayon, M., Guilleminault, C., Ruoff, C. WILEY-BLACKWELL. 2014: 152–152

  View details for Web of Science ID 000349960600398

• An fMRI study of cerebrovascular reactivity and perfusion in obstructive sleep apnea patients before and after CPAP treatment. Sleep medicine Prilipko, O., Huynh, N., Thomason, M. E., Kushida, C. A., Guilleminault, C. 2014; 15 (8): 892-898

  Abstract

  Cerebrovascular reactivity is impaired in patients suffering from obstructive sleep apnea syndrome (OSAS) as demonstrated by transcranial Doppler studies. We use magnetic resonance imaging techniques to investigate the anatomical distribution of cerebrovascular reactivity changes in patients with OSAS, as well as their evolution after therapeutic and sham continuous positive airway pressure (CPAP) treatment.Twenty-three men with moderate or severe obstructive sleep apnea were compared to a healthy control group (n=7) using a breath-holding functional magnetic resonance imaging task and the flow-sensitive alternating inversion recovery (FAIR) imaging before and after 2months of therapeutic (active) or sub-therapeutic (sham) CPAP treatment.Significantly higher cerebrovascular reactivity was found in healthy controls as compared to patients in bilateral cortical and subcortical brain regions. Cerebrovascular reactivity increased with therapeutic CPAP in the thalamus and decreased with sham CPAP in medial frontal regions in OSAS patients. Duration of nocturnal hypoxemia and body mass index negatively correlated with cerebrovascular reactivity, particularly in the medial temporal lobe structures, suggesting a possible pathophysiological mechanism for hippocampal injury. There was no difference in perfusion between patients and control group, and no effect of CPAP or sham-CPAP treatment on perfusion in patients.Observed cerebrovascular reactivity changes were neither homogeneous throughout the brain nor followed vascular territories, but rather corresponded to underlying neuronal networks, establishing a relationship between cerebrovascular reactivity and surrounding neuronal activity.

  View details for DOI 10.1016/j.sleep.2014.04.004

  View details for PubMedID 24916094

• Changes in salivary cortisol levels in pediatric patients with obstructive sleep apnea syndrome after adenotonsillectomy SLEEP MEDICINE Jeong, J., Guilleminault, C., Park, C., Son, H., Lee, H., Hwang, S., Choi, Y. 2014; 15 (6): 672-676

  Abstract

  Obstructive sleep apnea syndrome (OSAS) activates the stress response system, including the hypothalamic-pituitary-adrenocortical (HPA) axis. The salivary cortisol, as an index of free circulating cortisol levels, may be used as a measure of HPA axis activity. We examined the change in the salivary cortisol level in pediatric OSAS patients before and after adenotonsillectomy (AT).Forty-eight subjects from 80 subjects suspicious of having OSAS were diagnosed with OSAS by overnight PSG, 34 of 48 OSAS patients undergoing AT, and 13 of 34 OSAS patients were finally enrolled prospectively for this study. Before and three months after the AT, the saliva was collected at night before PSG (n-sCor) and in the early morning after PSG (m-sCor) for the measurements of the salivary cortisol level.Children in the study population (n=13) were divided into mild (1< or = AHI <5, n=5), moderate (5 < or = AHI <10, n=3), and severe (AHI > or =10, n=5) OSAS groups. The mean preoperative AHI in the children was 14.7, and the mean postoperative AHI was 0.33. The percentage of children with AHI <1 after AT was 92.3%. Postoperative m-sCor, the difference of cortisol level (sub-sCor: m-sCor minus n-sCor), and the ratio of cortisol level (r-sCor: m-sCor/n-sCor) showed significant difference postoperatively.AT was associated with improvements in PSG and subjective symptoms in pediatric OSAS patients. In addition, these improvements were significantly related to normalization of salivary cortisol level after AT. Although further study on salivary cortisol levels needs to be done, the measurement of salivary cortisol level before and after AT may predict the outcome of AT as a treatment of OSAS.

  View details for DOI 10.1016/j.sleep.2013.12.019

  View details for Web of Science ID 000338621200014

  View details for PubMedID 24813395

• The Burden of Narcolepsy Disease (BOND) study: health-care utilization and cost findings. Sleep medicine Black, J., Reaven, N. L., Funk, S. E., McGaughey, K., Ohayon, M., Guilleminault, C., Ruoff, C., Mignot, E. 2014; 15 (5): 522-529

  Abstract

  The aim of this study was to characterize health-care utilization, costs, and productivity in a large population of patients diagnosed with narcolepsy in the United States.This retrospective, observational study using data from the Truven Health Analytics MarketScan® Research Databases assessed 5years of claims data (2006-2010) to compare health-care utilization patterns, productivity, and associated costs among narcolepsy patients (identified by International Classification of Diseases, Ninth Revision (ICD9) narcolepsy diagnosis codes) versus matched controls. A total of 9312 narcolepsy patients (>18years of age, continuously insured between 2006 and 2010) and 46,559 matched controls were identified.Compared with controls, narcolepsy subjects had approximately twofold higher annual rates of inpatient admissions (0.15 vs. 0.08), emergency department (ED) visits w/o admission (0.34 vs. 0.17), hospital outpatient (OP) visits (2.8 vs. 1.4), other OP services (7.0 vs. 3.2), and physician visits (11.1 vs. 5.6; all p<0.0001). The rate of total annual drug transactions was doubled in narcolepsy versus controls (26.4 vs. 13.3; p<0.0001), including a 337% and 72% higher usage rate of narcolepsy drugs and non-narcolepsy drugs, respectively (both p<0.0001). Mean yearly costs were significantly higher in narcolepsy compared with controls for medical services ($8346 vs. $4147; p<0.0001) and drugs ($3356 vs. $1114; p<0.0001).Narcolepsy was found to be associated with substantial personal and economic burdens, as indicated by significantly higher rates of health-care utilization and medical costs in this large US group of narcolepsy patients.

  View details for DOI 10.1016/j.sleep.2014.02.001

  View details for PubMedID 24768358

• BURDEN OF NARCOLEPSY DISEASE (BOND) STUDY: VALIDATION OF USING A SINGLE DIAGNOSIS CODE TO DEFINE PRESENCE OF AN ORPHAN CONDITION IN MEDICAL CLAIMS DATA Villa, K., Reaven, N., Funk, S., MCGAUGHEY, K., Ohayon, M., Guilleminault, C., Ruoff, C., Black, J. ELSEVIER SCIENCE INC. 2014: A202–A203

  View details for Web of Science ID 000341082001239

• Tracheostomy as treatment for adult obstructive sleep apnea: a systematic review and meta-analysis. Laryngoscope Camacho, M., Certal, V., Brietzke, S. E., Holty, J. C., Guilleminault, C., Capasso, R. 2014; 124 (3): 803-811

  Abstract

  To systematically review outcomes for polysomnography, sleepiness, and mortality in patients who undergo tracheostomy for the treatment of adult obstructive sleep apnea (OSA).MEDLINE, Scopus, and the Cochrane Library were searched from inception to March 2013, followed by extensive hand searching for the identification of relevant English language studies that met predefined criteria.Adult studies of tracheostomies or tracheotomies as treatment for OSA with outcomes for apnea index (AI), apnea-hypopnea index (AHI), oxygen desaturation index (ODI), effect on daytime sleepiness or mortality were identified, abstracted and pooled (as appropriate). Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed.The systematic search identified 18 relevant studies that were primarily case series, using retrospective review. Posttracheostomy AI improved from 73.0 ± 27.1 to 0.2 ± 1.2/h and an AI mean difference of -83.47 (95% CI, -106.07 to -60.87; P < 0.0001). Mean AHI decreased from 92.0 ± 34.8 to 17.3 ± 20.5/h and an AHI mean difference -79.82 (95% CI, -63.74 to -95.90; P < 0.0001) compared with preoperative status was observed. Postsurgically, there was a development of central apneas; however, the central AI demonstrated near normalization to a mean of 2.1 ± 3.5/h after 14 weeks. ODI decreased from 78.2 ± 25.8/h to 20.8 ± 25.5/h. Four studies demonstrated a statistically significant improvement in subjective sleepiness posttracheostomy. Postoperative statistically significant reductions in overall and in cardiovascular mortality compared with untreated historical cohorts was reported.Tracheostomies significantly decrease apnea index, oxygen desaturation index, sleepiness, and mortality in OSA subjects.NA. Laryngoscope, 124:803-811, 2014.

  View details for DOI 10.1002/lary.24433

  View details for PubMedID 24549987

• Narcolepsy-Cataplexy and Schizophrenia in adolescent Sleep Medicine Huang, Y., Guilleminault, C., Chen, C., Lai, P., Hwang, F. 2014; 15: 15-22
• Kleine-Levin syndrome: a review. Nature and science of sleep Miglis, M. G., Guilleminault, C. 2014; 6: 19-26

  Abstract

  Kleine-Levin syndrome is a recurrent hypersomnia associated with symptoms of hyperphagia, hypersexuality, and cognitive impairment. This article reviews the current available research and describes common clinical symptoms, differential diagnosis, and acceptable workup and treatment. Although deficits have traditionally been thought to resolve between episodes, functional imaging studies and long-term neuropsychological testing in select patients have recently challenged this notion. This may suggest that Kleine-Levin syndrome is not as benign as previously considered.

  View details for DOI 10.2147/NSS.S44750

  View details for PubMedID 24470783

  View details for PubMedCentralID PMC3901778

• Volumetric brain morphometry changes in patients with obstructive sleep apnea syndrome: effects of CPAP treatment and literature review FRONTIERS IN NEUROLOGY Huynh, N. T., Prilipko, O., Kushida, C. A., Guilleminault, C. 2014; 5

  View details for DOI 10.3389/fneur.2014.00058

  View details for Web of Science ID 000209629300058

• Scoring respiratory event in sleep medicine: Who is the driver= Biology or medical insuranceThomas RJ , Guilleminault C, Indu A, Rapoport DM Sleep Meedicine Thomas, R. R., Guilleminault, C., Indu, A., Rapoport, D. 2014; 10: 1245-47
• Correlation of Salivary Alpha Amylase Level and Adenotonsillar Hypertrophy with Sleep Disordered Breathing in Pediatric Subjects JOURNAL OF CLINICAL SLEEP MEDICINE Park, C., Guilleminault, C., Park, H., Cho, J., Lee, H., Son, H., Hwang, S. 2014; 10 (5): 559-566

  Abstract

  Obstructive sleep apnea syndrome (OSAS) and sleep disordered breathing (SDB) can affect the sympathetic adrenomedullary system (SAM). As a biomarker of SAM activity, salivary α-amylase (sAA) in pediatric subjects was evaluated whether it has any correlation with polysomnographic (PSG) parameters related to SDB.Sixty-seven children who attended our clinic during 1 year were enrolled prospectively and underwent clinical examinations and in-lab polysomnography. The sAA was measured at 2 points--at night before PSG and in the early morning after PSG.Subjects were divided into control (n = 26, apneahypopnea index [AHI] < 1) and OSAS (n = 41, AHI ≥ 1) groups. The OSAS group was subdivided according to AHI (mild-moderate, 1 ≤ AHI < 10; severe, AHI ≥ 10). The sAA subtraction and ratio (p = 0.014 and p < 0.001, respectively) were significantly higher in severe OSAS than in the mild-moderate and control groups. Although oxygen desaturation index (ODI) and AHI were significantly associated with sAA, sAA in the OSAS group was not related to lowest oxygen saturation or adenotonsillar hypertrophy.sAA was well related to polysomnographic (PSG) parameters related to SDB, such as AHI and ODI. Therefore, screening test for sAA in children suspected to have SBD may help to identify OSAS patients from control.

  View details for DOI 10.5664/jcsm.3712

  View details for Web of Science ID 000341135100015

  View details for PubMedID 24812542

  View details for PubMedCentralID PMC4013385

• Treatment Outcomes of Adenotonsillectomy for Children with Obstructive Sleep Apnea: A Prospective Longitudinal Study SLEEP Huang, Y., Guilleminault, C., Lee, L., Lin, C., Hwang, F. 2014; 37 (1): 71-76

  Abstract

  To evaluate the efficacy of adenotonsillectomy (AT) in the treatment of children with obstructive sleep apnea (OSA) in a 3-y prospective, longitudinal study with analysis of risk factors of recurrence of OSA.An investigation of children (6 to 12 y old) with OSA documented at entry and followed posttreatment at 6, 12, 24, and 36 mo with examination, questionnaires, and polysomnography. Multivariate generalized linear modeling and hierarchical linear models analysis were used to determine contributors to suboptimal long-term resolution of OSA, and Generalized Linear Models were used for analysis of risk factors of recurrence.Of the 135 children, 88 terminated the study at 36 months post-AT. These 88 children (boys = 72, mean age = 8.9 ± 2.7 yersus boys 8.9 ± 2.04 y, girls: 8.8 ± 2.07 y; body mass index [BMI] = 19.5 ± 4.6 kg/m(2)) had a preoperative mean apnea-hypopnea index (AHI0) of 13.54 ± 7.23 and a mean postoperative AHI at 6 mo (AHI6) of 3.47 ± 8.41 events/h (with AHI6 > 1 = 53.4% of 88 children). A progressive increase in AHI was noted with a mean AHI36 = 6.48 ± 5.57 events/h and AHI36 > 1 = 68% of the studied group. Change in AHI was associated with changes in the OSA-18 questionnaire. The residual pediatric OSA after AT was significantly associated with BMI, AHI, enuresis, and allergic rhinitis before surgery. From 6 to 36 mo after AT, recurrence of pediatric OSA was significantly associated with enuresis, age (for the 24- to 36-mo period), postsurgery AHI6 (severity), and the rate of change in BMI and body weight.Adenotonsillectomy leads to significant improvement in apnea-hypopnea index, though generally with incomplete resolution, but a worsening over time was observed in 68% of our cases.

  View details for DOI 10.5665/sleep.3310

  View details for Web of Science ID 000332471500008

  View details for PubMedID 24470697

  View details for PubMedCentralID PMC3902877

• Narcolepsy-cataplexy and schizophrenia in adolescents SLEEP MEDICINE Huang, Y., Guilleminault, C., Chen, C., Lai, P., Hwang, F. 2014; 15 (1): 15-22

  Abstract

  Despite advances in the understanding of narcolepsy, little information the on association between narcolepsy and psychosis is available, except for amphetamine-related psychotic reactions. Our case-control study aimed to compare clinical differences and analyze risk factors in children who developed narcolepsy with cataplexy (N-C), schizophrenia, and N-C followed by schizophrenia.Three age- and gender-matched groups of children with N-C schizophrenia (study group), N-C (control group 1), and schizophrenia only (control group 2) were investigated. Subjects filled out sleep questionnaires, sleep diaries, and quality of life scales, followed by polysomnography (PSG), multiple sleep latency tests (MSLT), routine blood tests, HLA typing, genetic analysis of genes of interest, and psychiatric evaluation. The risk factors for schizophrenia also were analyzed.The study group was significantly overweight when measuring body mass index (BMI) (P=.016), at narcolepsy onset compared to control group 1, and the study group developed schizophrenia after a mean of 2.55±1.8 years. Compared to control group 2, psychotic symptoms were significantly more severe in the study group, with a higher frequency of depressive symptoms and acute ward hospitalization in 8 out of 10 of the subjects. They also had poorer long-term response to treatment, despite multiple treatment trials targeting their florid psychotic symptoms. All subjects with narcolepsy were HLA DQ B1(∗)0602 positive. The study group had a significantly higher frequency of DQ B1(∗)-03:01/06:02 (70%) than the two other groups, without any significant difference in HLA-DR typing, tumor necrosis factor α (TNF-α) levels, hypocretin (orexin) receptor 1 gene, HCRTR1, and the hypocretin (orexin) receptor 2 gene, HCRTR2, or blood infectious titers.BMI and weight at onset of narcolepsy as well as a higher frequency of DQ B1(∗)-03:01/06:02 antigens were the only significant differences in the N-C children with secondary schizophrenia; such an association is a therapeutic challenge with long-term persistence of severe psychotic symptoms.

  View details for DOI 10.1016/j.sleep.2013.09.018

  View details for Web of Science ID 000329220600004

  View details for PubMedID 24268496

• Volumetric Brain Morphometry Changes in Patients with Obstructive Sleep Apnea Syndrome: Effects of CPAP Treatment and Literature Review. Frontiers in neurology Huynh, N. T., Prilipko, O., Kushida, C. A., Guilleminault, C. 2014; 5: 58-?

  Abstract

  Obstructive sleep apnea syndrome (OSAS) is a frequent breathing disorder occurring during sleep that is characterized by recurrent hypoxic episodes and sleep fragmentation. It remains unclear whether OSAS leads to structural brain changes, and if so, in which brain regions. Brain region-specific gray and white matter volume (GMV and WMV) changes can be measured with voxel-based morphometry (VBM). The aims of this study were to use VBM to analyze GMV and WMV in untreated OSAS patients compared to healthy controls (HC); examine the impact of OSAS-related variables (nocturnal hypoxemia duration and sleep fragmentation index) on GMV and WMV; and assess the effects of therapeutic vs. sham continuous positive airway pressure (CPAP) treatment. We discuss our results in light of previous findings and provide a comprehensive literature review.Twenty-seven treatment-naïve male patients with moderate to severe OSAS and seven healthy age- and education-matched HC were recruited. After a baseline fMRI scan, patients randomly received either active (therapeutic, n = 14) or sham (subtherapeutic, n = 13) nasal CPAP treatment for 2 months.Significant negative correlations were observed between nocturnal hypoxemia duration and GMV in bilateral lateral temporal regions. No differences in GMV or WMV were found between OSAS patients and HC, and no differences between CPAP vs. sham CPAP treatment effects in OSAS patients.It appears that considering VBM GMV changes there is little difference between OSAS patients and HC. The largest VBM study to date indicates structural changes in the lateral aspect of the temporal lobe, which also showed a significant negative correlation with nocturnal hypoxemia duration in our study. This finding suggests an association between the effect of nocturnal hypoxemia and decreased GMV in OSAS patients.

  View details for DOI 10.3389/fneur.2014.00058

  View details for PubMedID 24808886

• Kleine-Levin Syndrome: a review Nat.Science Sleep Miglis, M. G., Guilleminault, C. 2014; 6: 19-26
• Inspiratory Flow Limitation in a Normal Population of Adults in Sao Paulo, Brazil SLEEP Palombini, L. O., Tufik, S., Rapoport, D. M., Ayappa, I. A., Guilleminault, C., de Godoy, L. B., Castro, L. S., Bittencourt, L. 2013; 36 (11): 1663-1668

  Abstract

  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.Cross-sectional study derived from a general population sample.A "normal" asymptomatic sample derived from the epidemiological cohort of São Paulo.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.N/A.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.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.

  View details for DOI 10.5665/sleep.3122

  View details for Web of Science ID 000326537800011

  View details for PubMedID 24179299

• Sleep-Disordered Breathing in Ehlers-Danlos Syndrome: A Genetic Model of OSA. Chest Guilleminault, C., Primeau, M., Chiu, H., Yuen, K. M., Leger, D., Metlaine, A. 2013; 144 (5): 1503-1511

  Abstract

  The objective of this study was to investigate the presence of sleep-disordered breathing (SDB) in patients with Ehlers-Danlos syndrome. Ehlers-Danlos syndrome is a genetic disorder characterized by cartilaginous defects, including nasal-maxillary cartilages.A retrospective series of 34 patients with Ehlers-Danlos syndrome and complaints of fatigue and poor sleep were evaluated by clinical history, physical examination, polysomnography (PSG), and, in some cases, anterior rhinomanometry. Additionally, a prospective clinical investigation of nine patients with Ehlers-Danlos syndrome was performed in a specialized Ehlers-Danlos syndrome clinic.All patients with Ehlers-Danlos syndrome evaluated had SDB on PSG. In addition to apneas and hypopneas, SDB included flow limitation. With increasing age, flow limitation decreased in favor of apnea and hypopnea events, but clinical complaints were similar independent of the type of PSG finding. In the subgroup of patients who underwent nasal rhinomanometry, increased nasal resistance was increased relative to normative values. Nasal CPAP improved symptoms. Patients with Ehlers-Danlos syndrome presenting to the medical clinic had symptoms and clinical signs of SDB, but they were never referred for evaluation of SDB.In patients with Ehlers-Danlos syndrome, abnormal breathing during sleep is commonly unrecognized and is responsible for daytime fatigue and poor sleep. These patients are at particular risk for SDB because of genetically related cartilage defects that lead to the development of facial structures known to cause SDB. Ehlers-Danlos syndrome may be a genetic model for OSA because of abnormalities in oral-facial growth. Early recognition of SDB may allow treatment with orthodontics and myofacial reeducation.

  View details for DOI 10.1378/chest.13-0174

  View details for PubMedID 23929538

• Correlation of salivary cortisol level with obstructive sleep apnea syndrome in pediatric subjects SLEEP MEDICINE Park, C., Guilleminault, C., Hwang, S., Jeong, J., Park, D., Maeng, J. 2013; 14 (10): 978-984

  Abstract

  Obstructive sleep apnea syndrome (OSAS) is associated with stress system activation involving the hypothalamic-pituitary-adrenocortical (HPA) axis. The relationships among salivary cortisol, a measure of the HPA axis, and objective parameters of polysomnography (PSG) and subjective sleep symptoms were examined.Our prospective study enrolled 80 children who had a physical examination, underwent overnight PSG, and completed the Korean version of the modified pediatric Epworth sleepiness scale (KMPESS) and OSA-18 (KOSA-18) questionnaires. Saliva was collected at night before PSG and in the early morning after PSG.Subjects (N=80) were divided into control (n=32, apnea-hypopnea index [AHI]<1) and OSAS (n=48, AHI⩾1) groups; the OSAS group was subdivided into mild (1⩽AHI<5) and moderate to severe (AHI⩾5) groups. Although salivary cortisol before PSG (n-sCor) did not show a significant change with OSAS severity, salivary cortisol after PSG (m-sCor) significantly decreased with OSAS severity. This decrease resulted in a salivary cortisol ratio (r-sCor) that was significantly different between the control group and the two OSAS subgroups. The m-sCor and sub-sCor of the total group as well as the m-sCor, sub-sCor, and r-sCor of the OSAS group were negatively related to the oxygen desaturation index (ODI). The m-sCor and r-sCor in the OSAS group also were related to subjective sleep symptoms (quality of life [QOL] by KOSA-18).Among the four salivary cortisol parameters, r-sCor was negatively associated with OSAS severity, ODI, and QOL (KOSA-18), which may indicate a chronically stressed HPA axis. These results demonstrate that salivary cortisol may be a useful biomarker of OSAS.

  View details for DOI 10.1016/j.sleep.2013.05.012

  View details for Web of Science ID 000324103600009

  View details for PubMedID 23891237

• Sex-Related Differences in Narcolepsy Burden of Illness: Burden of Narcolepsy Disease (BOND) Database Analysis 42nd Annual Meeting of the Child-Neurology-Society Black, J., Reaven, N., Funk, S., McGaughey, K., Ohayon, M., Guilleminault, C., Ruoff, C. WILEY-BLACKWELL. 2013: S40–S40

  View details for Web of Science ID 000327914200138

• Age-Related Healthcare Utilization and Comorbidity: Data from the Burden of Narcolepsy Disease (BOND) Database 42nd Annual Meeting of the Child-Neurology-Society Black, J., Reaven, N., Funk, S., McGaughey, K., Ohayon, M., Guilleminault, C., Ruoff, C. WILEY-BLACKWELL. 2013: S39–S39

  View details for Web of Science ID 000327914200134

• Usefulness of Adenotonsillar Size for Prediction of Severity of Obstructive Sleep Apnea and Flow Limitation OTOLARYNGOLOGY-HEAD AND NECK SURGERY Hwang, S., Guilleminault, C., Park, C., Kim, T., Hong, S. 2013; 149 (2): 326-334

  Abstract

  Adenotonsillar hypertrophy is considered the most common cause of pediatric obstructive sleep apnea syndrome (OSAS). This study aimed to evaluate the relationships between tonsil/adenoid size, parameters of polysomnography, and subjective sleep symptoms.Case-control studies.Tertiary care center.A 4-point tonsil grading method and adenoid-nasopharynx (AN) ratio were used to categorize tonsil and adenoid size, respectively. Sleep questionnaires (Korean version of the Obstructive Sleep Apnea-18 [KOSA-18]) and full-attended polysomnography were performed.The subjects (n = 70) were divided into a control group (n = 31, apnea-hypopnea index [AHI] <1) and an OSAS group (n = 39, AHI ≥ 1), which was subdivided into mild and moderate to severe groups. Tonsil/adenoid size showed a statistically significant difference between control and OSAS groups, but these differences had no clinical significance. In addition, tonsil/adenoid size did not differ significantly among 2 OSAS severity subgroups. Only adenoid size in the total and OSAS groups was related to quality of life (QOL) by the KOSA-18. The AN ratio was related to lowest oxygen saturation only in the OSAS group, especially in the moderate to severe OSAS group, but tonsil size was related to flow limitation in total and supine positions in the control group. In the control group, flow limitation was not associated with QOL.Tonsil/adenoid size did not predict the severity of AHI. Nevertheless, adenoid size might be related to lowest oxygen saturation, which is thought to be related to subjective symptoms. Although flow limitation was related to tonsil size but not to QOL in the control group, further research will be needed to understand the importance of flow limitation and upper airway resistance syndrome in the pediatric population.

  View details for DOI 10.1177/0194599813490892

  View details for Web of Science ID 000322243000023

  View details for PubMedID 23715686

• Critical role of myofascial reeducation in pediatric sleep-disordered breathing. Sleep medicine Guilleminault, C., Huang, Y. S., Monteyrol, P. J., Sato, R., Quo, S., Lin, C. H. 2013; 14 (6): 518-525

  Abstract

  Limited studies suggest that pubertal development may lead to a recurrence of sleep-disordered breathing (SDB) despite previous curative surgery. Our study evaluates the impact of myofunctional reeducation in children with SDB referred for adenotonsillectomy, orthodontia, and myofunctional treatment in three different geographic areas.A retrospective investigation of children with polysomnographic analysis following adenotonsillectomy were referred for orthodontic treatment and were considered for myofunctional therapy. Clinical information was obtained during pediatric and orthodontic follow-up. Polysomnography (PSG) at the time of diagnosis, following adenotonsillectomy, and at long-term follow-up, were compared. The PSG obtained at long-term follow-up was scored by a single-blinded investigator.Complete charts providing the necessary medical information for long-term follow-up were limited. A subgroup of 24 subjects (14 boys) with normal PSG following adenotonsillectomy and orthodontia were referred for myofunctional therapy, with only 11 subjects receiving treatment. Follow-up evaluation was performed between the 22nd and 50th month after termination of myofunctional reeducation or orthodontic treatment if reeducation was not received. Thirteen out of 24 subjects who did not receive myofunctional reeducation developed recurrence of symptoms with a mean apnea-hypopnea index (AHI)=5.3±1.5 and mean minimum oxygen saturation=91±1.8%. All 11 subjects who completed myofunctional reeducation for 24months revealed healthy results.Despite experimental and orthodontic data supporting the connection between orofacial muscle activity and oropharyngeal development as well as the demonstration of abnormal muscle contraction of upper airway muscles during sleep in patients with SDB, myofunctional therapy rarely is considered in the treatment of pediatric SDB. Absence of myofascial treatment is associated with a recurrence of SDB.

  View details for DOI 10.1016/j.sleep.2013.01.013

  View details for PubMedID 23522724

• Accurate scoring of the apnea-hypopnea index using a simple non-contact breathing sensor JOURNAL OF SLEEP RESEARCH Beattie, Z. T., Hayes, T. L., Guilleminault, C., Hagen, C. C. 2013; 22 (3): 356-362

  Abstract

  Sleep apnea is a serious condition that afflicts many individuals and is associated with serious health complications. Polysomnography, the gold standard for assessing and diagnosing sleep apnea, uses breathing sensors that are intrusive and can disrupt the patient's sleep during the overnight testing. We investigated the use of breathing signals derived from non-contact force sensors (i.e. load cells) placed under the supports of the bed as an alternative to traditional polysomnography breathing sensors (e.g. nasal pressure, oral-nasal thermistor, chest belt and abdominal belt). The apnea-hypopnea index estimated using the load cells was not different than that estimated using standard polysomnography leads (t44  = 0.37, P = 0.71). Overnight polysomnography sleep studies scored using load cell breathing signals had an intra-class correlation coefficient of 0.97 for the apnea-hypopnea index and an intra-class correlation coefficient of 0.85 for the respiratory disturbance index when compared with scoring using traditional polysomnography breathing sensors following American Academy of Sleep Medicine guidelines. These results demonstrate the feasibility of using unobtrusive load cells installed under the bed to measure the apnea-hypopnea index.

  View details for DOI 10.1111/jsr.12023

  View details for Web of Science ID 000318813600016

  View details for PubMedID 23363404

• The impact of sleep duration in obstructive sleep apnea patients SLEEP AND BREATHING Risso, T. T., Poyares, D., Rizzi, C. F., Pulz, C., Guilleminault, C., Tufik, S., de Paola, A. A., Cintra, F. 2013; 17 (2): 837-843

  Abstract

  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.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.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).In conclusion, the present study suggests that sleep duration may be associated to low mean oxygen saturation in OSA patients.

  View details for DOI 10.1007/s11325-012-0774-3

  View details for Web of Science ID 000319075800060

  View details for PubMedID 23099474

• Healthcare Utilization and Costs in Narcolepsy: Findings from the Burden of Narcolepsy Disease (BOND) Study of 9,312 Patients in the United States 65th Annual Meeting of the American-Academy-of-Neurology (AAN) Black, J., Reaven, N., Funk, S., McGaughey, K., Ohayon, M., Guilleminault, C., Ruoff, C. LIPPINCOTT WILLIAMS & WILKINS. 2013

  View details for Web of Science ID 000332068606063

• Teenage sleep-disordered breathing: Recurrence of syndrome SLEEP MEDICINE Guilleminault, C., Huang, Y., Quo, S., Monteyrol, P., Lin, C. 2013; 14 (1): 37-44

  Abstract

  The study aims to better understand the reappearance of sleep apnoea in adolescents considered cured of obstructive sleep apnoea (OSA) following adenotonsillectomy and orthodontic treatment.The study employs a retrospective analysis of 29 adolescents (nine girls and 20 boys) with OSA previously treated with adenotonsillectomy and orthodontia at a mean age of 7.5years. During follow-up at 11 and 14years of age, patients were clinically evaluated, filled the Pediatric Sleep Questionnaire (PSQ) and had systematic cephalometric X-rays performed by orthodontists. Polysomnographic (PSG) data were compared at the time of OSA diagnosis, following surgical and orthodontic treatment and during pubertal follow-up evaluation.Following the diagnosis of OSA and treatment with adenotonsillectomy and rapid maxillary expansion (Apnea-Hypopnea Index (AHI) 0.4±0.4), children were re-evaluated at a mean age of 11years. During follow-up at 14years, all children had normal body mass indices (BMIs). Teenagers were subdivided into two groups based on complaints: Nine asymptomatic subjects (seven girls and two boys) and 20 subjects with decline in school performance, presence of fatigue, indicators of sleep-phase delays and, less frequently, specific symptoms of daytime sleepiness and snoring. Presence of mouth breathing, abnormal AHI and RDI and significant reduction of posterior airway space (PAS) was demonstrated during repeat polysomnography and cephalometry. Compared to cephalometry obtained at a mean of 11years of age, there was a significant reduction of PAS of 2.3±0.4mm at a mean age of 14years.Previously suggested recurrence of OSA during teenage years has again been demonstrated in this small group of subjects. Prospective investigations are needed to establish frequency of risk, especially in non-orthodontically treated children.

  View details for DOI 10.1016/j.sleep.2012.08.010

  View details for Web of Science ID 000313727100008

  View details for PubMedID 23026504

• Pediatric obstructive sleep apnea and the critical role of oral-facial growth: evidences FRONTIERS IN NEUROLOGY Huang, Y., Guilleminault, C. 2013; 3

  View details for DOI 10.3389/fneur.2012.00184

  View details for Web of Science ID 000209628900003

• Correlation of salivary cortisol level with obstructive sleep apnea syndrome in pediatric subjects Sleep Medicine Park, S. C., Guilleminault, C., Hwang, S. H., Jeong, J. H., Park, D. S., Maeng, J. H. 2013; 14: 978-984
• Usefulness of adenotonsillar size for prediction of severity of obstructive sleep apnea and flow limitation Otolaryngol. Head-Neck Surg Hwang, S. H., Guilleminault, C., Parck, C. S., Kim, T. W., Hong, S. C. 2013; 149: 326-334
• Defending Sleepwalkers with science and an illustrative case. Journal of Clinical sleep medicine Cartwright, R., Guilleminault, c. 2013; 9: 721-726
• Sleep-disordered breathing in Ehlers Danlos Syndrome (a genetic model of OSA) chest Guilleminault, c. 2013; 144: 1503-1511
• Central sleep apnea: effect on stroke volume in heart failure Am.J.Respir. Crit. Care Med Cao, M., Lin, C., Guilleminault, C. 2013; 187: 1-2
• . Inspiratory flow limitation in a normal population of adults in Sao Paolo, Brazil SLEEP Palombini, L., Tufik, S., Rapoport, D., Ayappa, I., Guilleminault, C., de Godoy, L., Castro, L., Bittencourt, L. 2013; 36: 1663-1668
• Accurate scoring of the apnea-hypopnea index using a simple non-contact breathing sensor. journal of sleep research Beattie , Z. T., Hayes, T. L., Guilleminault, c., Hagen, C. C. 2013; 22: 356-362
• Pediatric sleep apnea and the critical role of oral facial growth: evidences Frontier in neurology Huang, y., Guilleminault, C. 2013; 3: 184
• Nonepileptic paroxysmal sleep disorders. Handbook of clinical neurology Frenette, E., Guilleminault, C. 2013; 112: 857-860

  Abstract

  Events occurring during nighttime sleep in children can be easily mislabeled, as witnesses are usually not immediately available. Even when observers are present, description of the events can be sketchy, as these individuals are frequently aroused from their own sleep. Errors of perception are thus common and can lead to diagnosis of epilepsy where other sleep-related conditions are present, sometimes initiating unnecessary therapeutic interventions, especially with antiepileptic drugs. Often not acknowledged, paroxysmal nonepileptic behavioral and motor episodes in sleep are encountered much more frequently than their epileptic counterpart. The International Classification of Sleep Disorders (ICSD) 2nd edition displays an extensive list of such conditions that can be readily mistaken for epilepsy. The most prevalent ones are reviewed, such as nonrapid eye movement (NREM) sleep parasomnias, comprised of sleepwalking, confusional arousals and sleep terrors, periodic leg movements of sleep, repetitive movement disorders, benign neonatal myoclonus, and sleep starts. Apnea of prematurity is also briefly reviewed. Specific issues regarding management of these selected disorders, both for diagnostic consideration and for therapeutic intervention, are addressed.

  View details for DOI 10.1016/B978-0-444-52910-7.00006-4

  View details for PubMedID 23622294

• The Effects of CPAP Treatment on Task Positive and Default Mode Networks in Obstructive Sleep Apnea Patients: An fMRI Study PLOS ONE Prilipko, O., Huynh, N., Schwartz, S., Tantrakul, V., Kushida, C., Paiva, T., Guilleminault, C. 2012; 7 (12)

  Abstract

  Functional magnetic resonance imaging studies enable the investigation of neural correlates underlying behavioral performance. We investigate the effect of active and sham Continuous Positive Airway Pressure (CPAP) treatment on working memory function of patients with Obstructive Sleep Apnea Syndrome (OSAS) considering Task Positive and Default Mode networks (TPN and DMN).An experiment with 4 levels of visuospatial n-back task was used to investigate the pattern of cortical activation in 17 men with moderate or severe OSAS before and after 2 months of therapeutic (active) or sub-therapeutic (sham) CPAP treatment.Patients with untreated OSAS had significantly less deactivation in the temporal regions of the DMN as compared to healthy controls, but activation within TPN regions was comparatively relatively preserved. After 2 months of treatment, active and sham CPAP groups exhibited opposite trends of cerebral activation and deactivation. After treatment, the active CPAP group demonstrated an increase of cerebral activation in the TPN at all task levels and of task-related cerebral deactivation in the anterior midline and medial temporal regions of the DMN at the 3-back level, associated with a significant improvement of behavioral performance, whereas the sham CPAP group exhibited less deactivation in the temporal regions of Default Mode Network and less Task Positive Network activation associated to longer response times at the 3-back.OSAS has a significant negative impact primarily on task-related DMN deactivation, particularly in the medial temporal regions, possibly due to nocturnal hypoxemia, as well as TPN activation, particularly in the right ventral fronto-parietal network. After 2 months of active nasal CPAP treatment a positive response was noted in both TPN and DMN but without compete recovery of existing behavioral and neuronal deficits. Initiation of CPAP treatment early in the course of the disease may prevent or slow down the occurrence of irreversible impairment.

  View details for DOI 10.1371/journal.pone.0047433

  View details for Web of Science ID 000312588200002

  View details for PubMedID 23227139

• Effects of Continuous Positive Airway Pressure on Neurocognitive Function in Obstructive Sleep Apnea Patients: The Apnea Positive Pressure Long-term Efficacy Study (APPLES) SLEEP Kushida, C. A., Nichols, D. A., Holmes, T. H., Quan, S. F., Walsh, J. K., Gottlieb, D. J., Simon, R. D., Guilleminault, C., White, D. P., Goodwin, J. L., Schweitzer, P. K., Leary, E. B., Hyde, P. R., Hirshkowitz, M., Green, S., McEvoy, L. K., Chan, C., Gevins, A., Kay, G. G., Bloch, D. A., Crabtree, T., Dement, W. C. 2012; 35 (12): 1593-U40

  Abstract

  To determine the neurocognitive effects of continuous positive airway pressure (CPAP) therapy on patients with obstructive sleep apnea (OSA).The Apnea Positive Pressure Long-term Efficacy Study (APPLES) was a 6-month, randomized, double-blind, 2-arm, sham-controlled, multicenter trial conducted at 5 U.S. university, hospital, or private practices. Of 1,516 participants enrolled, 1,105 were randomized, and 1,098 participants diagnosed with OSA contributed to the analysis of the primary outcome measures.Active or sham CPAP MEASUREMENTS: THREE NEUROCOGNITIVE VARIABLES, EACH REPRESENTING A NEUROCOGNITIVE DOMAIN: Pathfinder Number Test-Total Time (attention and psychomotor function [A/P]), Buschke Selective Reminding Test-Sum Recall (learning and memory [L/M]), and Sustained Working Memory Test-Overall Mid-Day Score (executive and frontal-lobe function [E/F])The primary neurocognitive analyses showed a difference between groups for only the E/F variable at the 2 month CPAP visit, but no difference at the 6 month CPAP visit or for the A/P or L/M variables at either the 2 or 6 month visits. When stratified by measures of OSA severity (AHI or oxygen saturation parameters), the primary E/F variable and one secondary E/F neurocognitive variable revealed transient differences between study arms for those with the most severe OSA. Participants in the active CPAP group had a significantly greater ability to remain awake whether measured subjectively by the Epworth Sleepiness Scale or objectively by the maintenance of wakefulness test.CPAP treatment improved both subjectively and objectively measured sleepiness, especially in individuals with severe OSA (AHI > 30). CPAP use resulted in mild, transient improvement in the most sensitive measures of executive and frontal-lobe function for those with severe disease, which suggests the existence of a complex OSA-neurocognitive relationship.Registered at clinicaltrials.gov. Identifier: NCT00051363.Kushida CA; Nichols DA; Holmes TH; Quan SF; Walsh JK; Gottlieb DJ; Simon RD; Guilleminault C; White DP; Goodwin JL; Schweitzer PK; Leary EB; Hyde PR; Hirshkowitz M; Green S; McEvoy LK; Chan C; Gevins A; Kay GG; Bloch DA; Crabtree T; Demen WC. Effects of continuous positive airway pressure on neurocognitive function in obstructive sleep apnea patients: the Apnea Positive Pressure Long-term Efficacy Study (APPLES). SLEEP 2012;35(12):1593-1602.

  View details for DOI 10.5665/sleep.2226

  View details for Web of Science ID 000313000600005

  View details for PubMedID 23204602

  View details for PubMedCentralID PMC3490352

• Usage of four-phase high-resolution rhinomanometry and measurement of nasal resistance in sleep-disordered breathing LARYNGOSCOPE Toh, S., Lin, C., Guilleminault, C. 2012; 122 (10): 2343-2349

  Abstract

  To investigate the ease of use of four-phase high-resolution rhinomanometry (HRR), a new way of measuring nasal resistance, in measuring change in nasal resistance from supine to inclined position in a clinical sleep laboratory setting, and to correlate findings with continuous positive airway pressure (CPAP) tolerance.Retrospective review of clinical charts.Forty successively seen Caucasian subjects diagnosed with sleep-disordered breathing (SDB) with complete charts were analyzed. Using four-phase HRR and acoustic rhinometry, nasal resistance and minimal cross-sectional area of the nasal cavity were objectively measured with the patient in the supine position and repeated in the inclined position (30° from the horizontal plane), respectively.From the supine to inclined position, reduction in total nasal resistance was observed in 87.5% (35 out of 40). There was a mean reduction of nasal resistance by 37.1 ± 21.6%. Five (12.5%) out of 40 subjects showed no change or mild increase in nasal resistance. Subjects with nasal resistance unresponsive to the inclined position change tended to have difficulty using nasal CPAP based on downloaded compliance card data.Four-phase HRR and acoustic rhinometry are tests that can be easily performed by sleep specialists to characterize nasal resistance in SDB patients and determine changes in resistance with positional changes. In this study, we found that patients who did not demonstrate a decrease in nasal resistance with inclined position were more likely to be noncompliant with nasal CPAP. These measurements may help us objectively identify patients who might have trouble tolerating nasal CPAP.

  View details for DOI 10.1002/lary.23441

  View details for Web of Science ID 000309060200039

  View details for PubMedID 22777838

• Death, nasomaxillary complex, and sleep in young children EUROPEAN JOURNAL OF PEDIATRICS Rambaud, C., Guilleminault, C. 2012; 171 (9): 1349-1358

  Abstract

  This is an investigation of anatomical and sleep history risk factors that were associated with abrupt sleep-associated death in seven children with good pre-mortem history. Seven young children with abrupt deaths and information on health status, sleep history, death scene report, and autopsy performed in a specialized unit dedicated to investigation of abrupt death in young children were investigated Seven age and gender matched living children with obstructive-sleep-apnea (OSA) were compared to the findings obtained from the dead children. Two deaths results from accidents determined by the death scene and five were unexplained at the death scene. History revealed presence of chronic indicators of abnormal sleep in all cases prior death and history of an acute, often mild, rhinitis just preceding death in several. Four children, including three infants, were usually sleeping in a prone position. Autopsy demonstrated variable enlargement of upper airway soft tissues in all cases, and in all cases, there were features consistent with a narrow, small nasomaxillary complex, with or without mandibular retroposition. All children were concluded to have died of hypoxia during sleep. Our OSA children presented similar complaints and similar facial features. Anatomic risk factors for a narrow upper airway can be determined early in life, and these traits are often familial. Their presence should lead to greater attention to sleep-related complaints that may be present very early in life and indicate impairment of well been and presence of sleep disruption. Further investigation should be performed to understand the role of upper airway infection in the setting of anatomically small airway in apparently abrupt death of infants and toddlers.

  View details for DOI 10.1007/s00431-012-1727-3

  View details for Web of Science ID 000307701100008

  View details for PubMedID 22492014

• Treatment outcomes of adenotonsillectomy for children with obstructive sleep apnoea: a prospective longitudinal study 21st Congress of the European-Sleep-Research-Society Huang, Y. S., Tsai, M. H., Guilleminault, C. WILEY-BLACKWELL. 2012: 242–242

  View details for Web of Science ID 000307963201134

• Hiding in plain sight Risk factors for REM sleep behavior disorder NEUROLOGY Sullivan, S. S., Schenck, C. H., Guilleminault, C. 2012; 79 (5): 402-403

  View details for DOI 10.1212/WNL.0b013e31825dd3c0

  View details for Web of Science ID 000307161100008

  View details for PubMedID 22744669

• Acute and Chronic Sleep Loss: Implications on Age-Related Neurocognitive Impairment SLEEP Cao, M., Guilleminault, C. 2012; 35 (7): 901-902

  View details for DOI 10.5665/sleep.1944

  View details for Web of Science ID 000305997300004

  View details for PubMedID 22754034

• Periodic Leg Movement, Nasal CPAP, and Expiratory Muscles CHEST Seo, W. H., Guilleminault, C. 2012; 142 (1): 111-118

  Abstract

  Periodic leg movements (PLMs) may appear during nasal CPAP titration, persisting despite the elimination of hypopneas.Systematic recordings of expiratory abdominal muscles on the right and left sides with surface electromyographic (EMG) electrodes lateral to navel, and close from the lateral side of abdomen, were added during nasal CPAP titration for treatment of obstructive sleep apnea (OSA). Positive airway pressure was titrated during nocturnal polysomnography, based on analysis of the flow curve derived from the CPAP equipment and EEG analysis, including persistence of phases A2 and A3 of the cyclic alternating pattern (CAP). The requirement was to eliminate American Association of Sleep Medicine (AASM)-defined hypopnea and also flow limitation and abnormal EEG patterns. When CPAP reached valid results, it was lowered at the time of awakening by 2 or 3 cm H(2)O, and titration was performed again. Data collected during a 7-month period on adults with a prior diagnosis of OSA who had received treatment with nasal CPAP regardless of age and sex were rendered anonymous and were retrospectively rescored by a blinded investigator.Eighty-one successively seen patients with PLMs during CPAP titration were investigated. Elimination of AASM-defined hypopnea was not sufficient to eliminate the PLMs observed during the titration; higher CPAP eliminated flow limitation and CAP phases A2 and A3 and persisting PLMs. PLMs were associated with simultaneous EMG bursts in expiratory abdominal muscles.The presence of PLMs during CPAP titration indicates the persistence of sleep-disordered breathing. PLMs during CPAP titration are related to the presence of abdominal expiratory muscle activity.

  View details for DOI 10.1378/chest.11-1563

  View details for Web of Science ID 000306209800020

  View details for PubMedID 22241760

• Orthodontics and sleep-disordered breathing SLEEP AND BREATHING Ruoff, C. M., Guilleminault, C. 2012; 16 (2): 271-273

  View details for DOI 10.1007/s11325-011-0534-9

  View details for Web of Science ID 000301737400002

  View details for PubMedID 21559930

• Sleep-disordered breathing in premenopausal women: Differences between younger (less than 30 years old) and older women SLEEP MEDICINE Tantrakul, V., Park, C., Guilleminault, C. 2012; 13 (6): 656-662

  Abstract

  To compare clinical manifestations and polysomnographic data of sleep-disordered breathing (SDB) in younger (less than 30 years old) versus older premenopausal women.A cohort of 420 premenopausal women diagnosed with SDB in a university sleep clinic during a 5-year period underwent systematic collection of clinical and polysomnographic variables.One-hundred and fifteen (27.4%) women were younger than 30 (mean 24.5 ± 3.5 years), while 305 (72.6%) were older than 30 (mean 39.5 ± 5.7 years). The younger premenopausal women had less severe SDB with a trend towards upper-airway resistance syndrome. Despite similar daytime consequences, snoring was less common in the younger group. Both groups of premenopausal women frequently had insomnia and nasal abnormalities or craniofacial-deficiency.Recognizing the different clinical features and understanding the different polysomnographic presentation of SDB in young premenopausal women are crucial to detecting and treating this syndrome.

  View details for DOI 10.1016/j.sleep.2012.02.008

  View details for Web of Science ID 000306304700017

  View details for PubMedID 22608672

• Sleepiness and fatigue following traumatic brain injury: a clear relationship? SLEEP MEDICINE Siebern, A. T., Guilleminault, C. 2012; 13 (6): 559-560

  View details for DOI 10.1016/j.sleep.2012.03.003

  View details for Web of Science ID 000306304700002

  View details for PubMedID 22608678

• Pharmacotherapy of obstructive sleep apnea EXPERT OPINION ON PHARMACOTHERAPY Lin, C. M., Huang, Y. S., Guilleminault, C. 2012; 13 (6): 841-857

  Abstract

  Obstructive sleep apnea syndrome is a common public health problem in the general population. The important health-related consequences of obstructive sleep apnea include cardiovascular disorders, such as myocardial infarction and hypertension, stroke, sudden death and difficult blood sugar control related to diabetes mellitus. The current main treatment options include body weight loss, continuous positive airway pressure, oral appliances and surgical treatment. The effects of pharmacotherapy on sleep apnea continue to be controversial and supplemental only. Current medications for sleep apnea mainly act through reducing risk factors, treating predisposing endocrine disorders, improving residual sleepiness post management and controlling associated hypertension and metabolic disorders.This article discusses the pharmacotherapy of sleep apnea, including ventilatory stimulants, serotoninergic and REM sleep suppressant agents, acetylcholinesterase inhibitors, medications for predisposing endocrine disorders, stimulants, associated sleep apnea health problems and sleep apnea patient anesthetic precaution. Weight loss is not a direct pharmacological approach and is only briefly mentioned.At present, there is no appropriate pharmacological treatment for obstructive sleep apnea. There are adjunct treatments such as anti-allergy treatment, and, if residual sleepiness is present, nonamphetaminic stimulants can help. Usage of these stimulants will, however, produce negative effects in an anticipated rate of about 10% of subjects taking these medications.

  View details for DOI 10.1517/14656566.2012.666525

  View details for Web of Science ID 000301837600007

  View details for PubMedID 22424320

• Beneficial effect of donepezil on obstructive sleep apnea: A double-blind, placebo-controlled clinical trial SLEEP MEDICINE Sukys-Claudino, L., Moraes, W., Guilleminault, C., Tufik, S., Poyares, D. 2012; 13 (3): 290-296

  Abstract

  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.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.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).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.

  View details for DOI 10.1016/j.sleep.2011.09.014

  View details for Web of Science ID 000301695600012

  View details for PubMedID 22281004

• Relationship between Kleine-Levin Syndrome and Upper Respiratory Infection in Taiwan SLEEP Huang, Y., Guilleminault, C., Lin, K., Hwang, F., Liu, F., Kung, Y. 2012; 35 (1): 123-129

  Abstract

  In Kleine-Levin Syndrome (KLS), new episodes of hypersomnia are often preceded by an acute flu-like syndrome or upper airway infection 3 to 5 days before onset. This study investigated the relationship between the occurrence of mild upper respiratory tract infections (URIs) in the general population and the occurrence and seasonality and hypersomnic episodes in KLS patients.This investigation was a longitudinal clinical study. Based on data obtained from the National Health Research Institutes between 2006 and 2007, the timing of hypersomnic episodes in 30 KLS patients were compared with calendar reports of URI events, and the results compared with age-matched general Taiwanese population.Clinical symptoms, physical examination, polysomnographic recording, SPECT study, and laboratory tests affirming KLS during both periods of hypersomnic attack and non-attack were collected. Every symptomatic episode was then followed up. The cross-correlation function (CCF) and bivariate correlations analysis were performed to see the relationship between KLS and URIs.A positive finding of CCF analysis and significant bivariate correlations were found between KLS episodes and URI in the general population (r = 0.456*). In onset of hypersomnia, significant correlations existed among "acute upper respiratory infections" (r = 0.446*), "acute bronchitis and bronchiolitis" (r = 0.462*), and "pharyngitis and nasopharyngitis" (r = 0.548*) subtypes of infections. A positive correlation between higher reports of symptomatic hypersomnia and URI also existed in a given season. A positive nonsignificant trend for "allergic rhinitis" (r = 0.400) was also found.The agent behind URI or its consequence (such as fever) is associated with increased incidence of KLS episodes and may explain periodic symptomatic recurrences.

  View details for DOI 10.5665/sleep.1600

  View details for Web of Science ID 000298741100016

  View details for PubMedID 22215926

• Patterns in pharyngeal airflow associated with sleep-disordered breathing SLEEP MEDICINE Powell, N. B., Mihaescu, M., Mylavarapu, G., Weaver, E. M., Guilleminault, C., Gutmark, E. 2011; 12 (10): 966-974

  Abstract

  To establish the feasibility of a noninvasive method to identify pharyngeal airflow characteristics in sleep-disordered breathing.Four patients with sleep-disordered breathing who underwent surgery or used positive airway pressure devices and four normal healthy controls were studied. Three-dimensional CT imaging and computational fluid dynamics modeling with standard steady-state numerical formulation were used to characterize pharyngeal airflow behavior in normals and pre-and post-treatment in patients. Dynamic flow simulations using an unsteady approach were performed in one patient.The pre-treatment pharyngeal airway below the minimum cross-sectional area obstruction site showed airflow separation. This generated recirculation airflow regions and enhanced turbulence zones where vortices developed. This interaction induced large fluctuations in airflow variables and increased aerodynamic forces acting on the pharyngeal wall. At post-treatment, for the same volumetric flow rate, airflow field instabilities vanished and airflow characteristics improved. Mean maximum airflow velocity during inspiration reduced from 18.3±5.7 m/s pre-treatment to 6.3±4.5 m/s post-treatment (P=0.002), leading to a reduction in maximum wall shear stress from 4.8±1.7 Pa pre-treatment to 0.9±1.0 Pa post-treatment (P=0.01). The airway resistance improved from 4.3±1.4 Pa/L/min at pre-treatment to 0.7±0.7 Pa/L/min at post-treatment (P=0.004). Post-treatment airflow characteristics were not different from normal controls (all P ≥ 0.39).This study demonstrates that pharyngeal airflow variables may be derived from CT imaging and computational fluid dynamics modeling, resulting in high quality visualizations of airflow characteristics of axial velocity, static pressure, and wall shear stress in sleep-disordered breathing.

  View details for DOI 10.1016/j.sleep.2011.08.004

  View details for Web of Science ID 000299196000006

  View details for PubMedID 22036604

• Oral Appliances and Sleep-Disordered Breathing CHEST Ruoff, C. M., Guilleminault, C. 2011; 140 (5): 1110-1111

  View details for DOI 10.1378/chest.11-1375

  View details for Web of Science ID 000296928500003

  View details for PubMedID 22045873

• Comparison of agomelatine and escitalopram on nighttime sleep and daytime condition and efficacy in major depressive disorder patients INTERNATIONAL CLINICAL PSYCHOPHARMACOLOGY Quera-Salva, M., Hajak, G., Philip, P., Montplaisir, J., Keufer-Le Gall, S., Laredo, J., Guilleminault, C. 2011; 26 (5): 252-262

  Abstract

  Agomelatine, an MT1/MT2 receptor agonist and 5-HT2C receptor antagonist antidepressant, is known to have beneficial effects on subjective sleep in major depressive disorder patients. This international multicenter, randomized, double-blind study compared the effects of agomelatine (25-50 mg/day) and escitalopram (10-20 mg/day) on sleep polysomnographic parameters in major depressive disorder patients treated up to 24 weeks. A total of 138 outpatients were randomly allocated to agomelatine (n=71) or escitalopram (n=67). Treatment with agomelatine was associated with a reduction in sleep latency from week 2 onward. The difference between treatments was significant on all evaluations. Rapid eye movement latency was increased with escitalopram compared with agomelatine, with significant between-group differences at every visit. Agomelatine preserved the number of sleep cycles, whereas it was decreased with escitalopram with significant between-group differences at every visit. Assessments on visual analogue scales indicated that treatment with agomelatine improved morning condition, and reduced daytime sleepiness compared with escitalopram.17-item Hamilton depression rating scale total score was reduced in both groups, agomelatine was statistically noninferior to escitalopram at 6 weeks. Both treatments were well tolerated. This study showed that the clinical effects of agomelatine on sleep and wake parameters are different from that of escitalopram.

  View details for DOI 10.1097/YIC.0b013e328349b117

  View details for Web of Science ID 000293732000003

  View details for PubMedID 21829106

• Current hypopnea scoring criteria underscore pediatric sleep disordered breathing SLEEP MEDICINE Lin, C., Guilleminault, C. 2011; 12 (7): 720-729

  Abstract

  This is a retrospective study comparing 2007 American Academy of Sleep Medicine (AASM) pediatric scoring criteria and Stanford scoring criteria of pediatric polysomnograms to characterize the impact different scoring systems have upon the diagnosis of sleep disordered breathing in children.The diagnostic and post-treatment nocturnal polysomnograms (PSGs) of children (age 2-18 years) consecutively referred to an academic sleep clinic for evaluation of suspected sleep disordered breathing (SDB) for 1 year were independently analyzed by a single researcher using AASM and Stanford scoring criteria in a blinded fashion.A total of 209 (83 girls) children with suspected SDB underwent clinical evaluation and diagnostic PSG. Analysis of the diagnostic PSGs using the Stanford and AASM criteria classified 207 and 39 studies as abnormal, respectively. The AASM scoring criteria classified 19% of subjects as having obstructive sleep apnea (OSA) while the Stanford criteria diagnosed 99% of the subjects with OSA who were referred for evaluation of suspected sleep disordered breathing. There was a positive correlation between SDB-related clinical symptoms and anatomic risk factors for SDB. Scatter-plot analyses showed that the AASM apnea hypopnea index (AHI) was not only significantly lower compared to the Stanford AHI but also skewed in distribution. Ninety-nine children were restudied with PSG (9 were initially diagnosed with SDB with AASM criteria, whereas all 99 were diagnosed with SDB with Stanford criteria). All 99 children had been treated and had a post-treatment clinical evaluation and post-treatment PSG during the study period. All 99 children evaluated after treatment showed improvement in clinical presentation, Stanford AHI, and oxygen saturation during sleep.The AASM scoring criteria classified 19% of subjects as having OSA while the Stanford criteria diagnosed 99% of the subjects with OSA who were referred for evaluation of suspected sleep disordered breathing. The primary factor differentiating the AASM and Stanford criteria was the scoring of hypopneas. The AASM definition of hypopnea may be detrimental to the recognition of SDB in children.

  View details for DOI 10.1016/j.sleep.2011.04.004

  View details for Web of Science ID 000293937700017

  View details for PubMedID 21700494

• REM-related bradyarrhythmia syndrome SLEEP MEDICINE REVIEWS Holty, J. C., Guilleminault, C. 2011; 15 (3): 143-151

  Abstract

  Cardiac arrhythmias during sleep are relatively common and include a diverse etiology, from benign sinus bradycardia to potentially fatal ventricular arrhythmias. Predisposing factors include obstructive sleep apnea and cardiac disease. Rapid eye movement (REM)-related bradyarrhythmia syndrome (including sinus arrest and complete atrioventricular block with ventricular asystole) in the absence of an underlying cardiac or physiologic sleep disorder was first described in the early 1980s. Although uncertain, the underlying pathophysiology likely reflects abnormal autonomic neural-cardiac inputs during REM sleep. The autonomic nervous system (ANS) is a known key modulator of heart rate fluctuations and rhythm during sleep and nocturnal heart rate reflects a balance between the sympathetic-parasympathetic systems. Whether the primary trigger for REM-related bradyarrhythmias reflects abnormal centrally mediated control of the ANS during REM sleep or anomalous baroreflex parasympathetic influences is unknown. This review focuses on the salient features of the REM-related bradyarrhythmia syndrome and explores potential mechanisms with a particular assessment of the relationship between the ANS and nocturnal heart rate fluctuations.

  View details for DOI 10.1016/j.smrv.2010.09.001

  View details for Web of Science ID 000291175000002

  View details for PubMedID 21055981

• Circadian Rhythms, Melatonin and Depression CURRENT PHARMACEUTICAL DESIGN Salva, M. A., Hartley, S., Barbot, F., ALVAREZ, J. C., Lofaso, F., Guilleminault, C. 2011; 17 (15): 1459-1470

  Abstract

  The master biological clock situated in the suprachiasmatic nuclei of the anterior hypothalamus plays a vital role in orchestrating the circadian rhythms of multiple biological processes. Increasing evidence points to a role of the biological clock in the development of depression. In seasonal depression and in bipolar disorders it seems likely that the circadian system plays a vital role in the genesis of the disorder. For major unipolar depressive disorder (MDD) available data suggest a primary involvement of the circadian system but further and larger studies are necessary to conclude. Melatonin and melatonin agonists have chronobiotic effects, which mean that they can readjust the circadian system. Seasonal affective disorders and mood disturbances caused by circadian malfunction are theoretically treatable by manipulating the circadian system using chronobiotic drugs, chronotherapy or bright light therapy. In MDD, melatonin alone has no antidepressant action but novel melatoninergic compounds demonstrate antidepressant properties. Of these, the most advanced is the novel melatonin agonist agomelatine, which combines joint MT1 and MT2 agonism with 5-HT(2C) receptor antagonism. Adding a chronobiotic effect to the inhibition of 5-HT(2C) receptors may explain the rapid impact of agomelatine on depression, since studies showed that agomelatine had an early impact on sleep quality and alertness at awakening. Further studies are necessary in order to better characterize the effect of agomelatine and other novel melatoninergic drugs on the circadian system of MDD patients. In summary, antidepressants with intrinsic chronobiotic properties offer a novel approach to treatment of depression.

  View details for Web of Science ID 000295455800007

  View details for PubMedID 21476953

• The nasomaxillary complex, the mandible, and sleep-disordered breathing SLEEP AND BREATHING Kim, J. H., Guilleminault, C. 2011; 15 (2): 185-193

  Abstract

  This study aims to use clinical scales in a standardized fashion in evaluating the frequency of a high and narrow hard palate and/or small and retroplaced mandible in children with polysomnographically demonstrated sleep-disordered breathing (SDB).This is a retrospective review of clinical and polysomnographic data from children (2-17 years old) with SDB. Exclusion criteria were obesity, presence of a syndromic disorder, and incomplete chart information. Data on demographics, reason for referral, sleep history, Mallampati scale, size of the tonsils (Friedman scale), bite occlusion (dental positioning), and correlating clinical presentation and comparative physical exam of nasomaxillary and mandibular features (using subjective grading scales) were collected, as were results of pre- and post- treatment polysomnography.Data from 400 children were analyzed. With increasing age, fewer referrals were made for abnormal breathing during sleep and more were made for daytime impairment and generally poor sleep. There were 290 children (72.6%) who had tonsils graded 3+ or 4+, but 373 (93.3%) had craniofacial features considered to be risk factors for SDB, including small mandible and/or high and narrow hard palate associated with a narrow nasomaxillary complex. Mean pretreatment apnea-hypopnea index (AHI) was 14.6 ± 17.1 and AHI was similar in the three age groups. Initial treatment was adenotonsillectomy. Follow-up was obtained in 378 subjects, and 167 cases demonstrated residual AHI. Incomplete response to adenotonsillectomy was seen more often in children with Mallampati scale scores of 3 and 4.Non-obese children with SDB had different initial clinical complaints based on age. Independently of age, facial anatomic structures limiting nasal breathing and those considered to be risk factors for SDB were commonly seen in the total group. Clinical assessment of craniofacial features considered as risk factors for SDB and more particularly a Mallampati scale score of 3 or 4 can be useful in identifying children who may be more at risk for limited response to adenotonsillectomy, suggesting a subsequent need for post-surgery polysomnography.

  View details for DOI 10.1007/s11325-011-0504-2

  View details for Web of Science ID 000290939000006

  View details for PubMedID 21394611

• Hypocretin Antagonists in Insomnia Treatment and Beyond CURRENT PHARMACEUTICAL DESIGN Ruoff, C., Cao, M., Guilleminault, C. 2011; 17 (15): 1476-1482

  Abstract

  Hypocretin neuropeptides have been shown to regulate transitions between wakefulness and sleep through stabilization of sleep promoting GABAergic and wake promoting cholinergic/monoaminergic neural pathways. Hypocretin also influences other physiologic processes such as metabolism, appetite, learning and memory, reward and addiction, and ventilatory drive. The discovery of hypocretin and its effect upon the sleep-wake cycle has led to the development of a new class of pharmacologic agents that antagonize the physiologic effects of hypocretin (i.e. hypocretin antagonists). Further investigation of these agents may lead to novel therapies for insomnia without the side-effect profile of currently available hypnotics (e.g. impaired cognition, confusional arousals, and motor balance difficulties). However, antagonizing a system that regulates the sleep-wake cycle while also influencing non-sleep physiologic processes may create an entirely different but equally concerning side-effect profile such as transient loss of muscle tone (i.e. cataplexy) and a dampened respiratory drive. In this review, we will discuss the discovery of hypocretin and its receptors, hypocretin and the sleep-wake cycle, hypocretin antagonists in the treatment of insomnia, and other implicated functions of the hypocretin system.

  View details for Web of Science ID 000295455800009

  View details for PubMedID 21476951

• Adeno-tonsillectomy and rapid maxillary distraction in pre-pubertal children, a pilot study SLEEP AND BREATHING Guilleminault, C., Monteyrol, P., Huynh, N. T., Pirelli, P., Quo, S., Li, K. 2011; 15 (2): 173-177

  Abstract

  When both narrow maxilla and moderately enlarged tonsils are present in children with obstructive sleep apnea, the decision of which treatment to do first is unclear. A preliminary randomized study was done to perform a power analysis and determine the number of subjects necessary to have an appropriate response. Thirty-one children, 14 boys, diagnosed with OSA based on clinical symptoms and polysomnography (PSG) findings had presence of both narrow maxillary complex and enlarged tonsils. They were scheduled to have both adeno-tonsillectomy and RME for which the order of treatment was randomized: group 1 received surgery followed by orthodontics, while group 2 received orthodontics followed by surgery. Each child was seen by an ENT, an orthodontist, and a sleep medicine specialist. The validated pediatric sleep questionnaire and PSG were done at entry and after each treatment phase at time of PSG. Statistical analyses were ANOVA repeated measures and t tests.The mean age of the children at entry was 6.5 ± 0.2 years (mean ± SEM). Overall, even if children presented improvement of both clinical symptoms and PSG findings, none of the children presented normal results after treatment 1, at the exception of one case. There was no significant difference in the amount of improvement noted independently of the first treatment approach. Thirty children underwent treatment 2, with an overall significant improvement shown for PSG findings compared to baseline and compared to treatment 1, without any group differences.This preliminary study emphasizes the need to have more than subjective clinical scales for determination of sequence of treatments.

  View details for DOI 10.1007/s11325-010-0419-3

  View details for Web of Science ID 000290939000004

  View details for PubMedID 20848317

• Pharmacological Treatment of ADHD and the Short and Long Term Effects on Sleep CURRENT PHARMACEUTICAL DESIGN Huang, Y., Tsai, M., Guilleminault, C. 2011; 17 (15): 1450-1458

  Abstract

  There is growing research focusing on the sleep problems of children with attention-deficit/hyperactivity disorder (ADHD) in recent years. High incidence of sleep disorders in children with ADHD may be associated with a substantial impact on their quality of life and exacerbation of ADHD symptoms. The core symptoms of ADHD can be effectively treated by various medications, including methylphenidate (MPH), amphetamine, pemoline, and the newly FDA-approved extended-release α2 adrenergic agonists. However, most of them are known to affect patients' sleep because of their pharmacological actions on dopaminergic and/or noradrenergic release in the central nervous system. Previous studies have found increased incidence of insomnia and sleep disturbances in ADHD children treated with CNS (central nervous system) stimulants. In contrast, recent prospective, double-blind, placebo-controlled trials concluded that MPH, by objective polysomnographic or actigraphic measurements, did not cause significant sleep problems in children or adolescents with ADHD. Given the fact that sleep quality and core symptoms of ADHD are highly correlated, it is imperative that we understand the effects of ADHD medications on sleep while prescribing either CNS stimulants or non-CNS stimulants. Here we will concisely review the pharmacological treatments of ADHD, and provide the relevant data discussing their short- and long-term effects on sleep.

  View details for Web of Science ID 000295455800006

  View details for PubMedID 21476954

• A Review of Sodium Oxybate and Baclofen in the Treatment of Sleep Disorders CURRENT PHARMACEUTICAL DESIGN Brown, M. A., Guilleminault, C. 2011; 17 (15): 1430-1435

  Abstract

  Studies examining GABA(B) receptor agonists have reported effects on sleep including decreased sleep onset latency (SOL), increased sleep consolidation and increases in slow wave sleep (SWS). γ-hydroxybutyrate (GHB) is proposed to act as a GABA(B) receptor agonist; however, the mechanism of action of GHB is controversial. In addition, the GABA(B) receptor agonist, baclofen, has also been proposed to exert similar effects on sleep. The aim of this paper is to provide a review of the human clinical studies of sodium oxybate and baclofen regarding sleep and the treatment of sleep disorders including narcolepsy and insomnia, as well as other disorders involving disrupted sleep such as fibromyalgia.

  View details for Web of Science ID 000295455800003

  View details for PubMedID 21476957

• Pharmacological Treatment of Obstructive Sleep Apnea CURRENT PHARMACEUTICAL DESIGN Abad, V. C., Guilleminault, C. 2011; 17 (15): 1418-1429

  Abstract

  Obstructive sleep apnea (OSA) is a growing public health hazard fueled by the obesity epidemic and an aging population. Untreated sleep apnea can result in significant consequences both in the short-term and long-term. We need to educate the public to recognize the symptoms of sleep apnea and to publicize that effective treatments are available. Positive airway pressure therapy remains the gold standard currently in treating OSA. Alternative treatments include an oral appliance or surgical options. This paper discusses the pharmacologic treatment of sleep apnea: goals include medications to address the ventilatory control of breathing, treat co-morbid diseases, treat associated health problems/complaints, address special issues, such as anesthetic precautions, and propose future targets.

  View details for Web of Science ID 000295455800002

  View details for PubMedID 21476959

• Hypocretin and Its Emerging Role as a Target for Treatment of Sleep Disorders CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS Cao, M., Guilleminault, C. 2011; 11 (2): 227-234

  Abstract

  The neuropeptides hypocretin-1 and -2 (orexin A and B) are critical in the regulation of arousal and maintenance of wakefulness. Understanding the role of the hypocretin system in sleep/wake regulation has come from narcolepsy-cataplexy research. Deficiency of hypocretin results in loss of sleep/wake control with consequent unstable transitions from wakefulness into non-rapid eye movement (REM) and REM sleep, and clinical manifestations including daytime hypersomnolence, sleep attacks, and cataplexy. The hypocretin system regulates sleep/wake control through complex interactions between monoaminergic/cholinergic wake-promoting and GABAergic sleep-promoting neuronal systems. Research for the hypocretin agonist and the hypocretin antagonist for the treatment of sleep disorders has vigorously increased over the past 10 years. This review will focus on the origin, functions, and mechanisms in which the hypocretin system regulates sleep and wakefulness, and discuss its emerging role as a target for the treatment of sleep disorders.

  View details for DOI 10.1007/s11910-010-0172-9

  View details for Web of Science ID 000287926100016

  View details for PubMedID 21170610

• Sedative antidepressants and insomnia REVISTA BRASILEIRA DE PSIQUIATRIA dos Santos Moraes, W. A., Burke, P. R., Coutinho, P. L., Guilleminault, C., Bittencourt, A. G., Tufik, S., Poyares, D. 2011; 33 (1): 91-95

  Abstract

  The present review addresses the relationship between sleep and depression and how serotonergic transmission is implicated in both conditions.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.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.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.

  View details for Web of Science ID 000289741400018

  View details for PubMedID 21537726

• The Association between Obstructive Sleep Apnea and Neurocognitive Performance-The Apnea Positive Pressure Long-term Efficacy Study (APPLES) SLEEP Quan, S. F., Chan, C. S., Dement, W. C., Gevins, A., Goodwin, J. L., Gottlieb, D. J., Green, S., Guilleminault, C., Hirshkowitz, M., Hyde, P. R., Kay, G. G., Leary, E. B., Nichols, D. A., Schweitzer, P. K., Simon, R. D., Walsh, J. K., Kushida, C. A. 2011; 34 (3): 303-U207

  Abstract

  To determine associations between obstructive sleep apnea (OSA) and neurocognitive performance in a large cohort of adults.Cross-sectional analyses of polysomnographic and neurocognitive data from 1204 adult participants with a clinical diagnosis of obstructive sleep apnea (OSA) in the Apnea Positive Pressure Long-term Efficacy Study (APPLES), assessed at baseline before randomization to either continuous positive airway pressure (CPAP) or sham CPAP.Sleep and respiratory indices obtained by laboratory polysomnography and several measures of neurocognitive performance.Weak correlations were found for both the apnea hypopnea index (AHI) and several indices of oxygen desaturation and neurocognitive performance in unadjusted analyses. After adjustment for level of education, ethnicity, and gender, there was no association between the AHI and neurocognitive performance. However, severity of oxygen desaturation was weakly associated with worse neurocognitive performance on some measures of intelligence, attention, and processing speed.The impact of OSA on neurocognitive performance is small for many individuals with this condition and is most related to the severity of hypoxemia.

  View details for Web of Science ID 000287917600010

  View details for PubMedID 21358847

  View details for PubMedCentralID PMC3041706

• Task Positive and Default Mode Networks during a Parametric Working Memory Task in Obstructive Sleep Apnea Patients and Healthy Controls SLEEP Prilipko, O., Huynh, N., Schwartz, S., Tantrakul, V., Kim, J. H., Peralta, A. R., Kushida, C., Paiva, T., Guilleminault, C. 2011; 34 (3): 293-U193

  Abstract

  Functional magnetic resonance imaging (fMRI) studies enable the investigation of neural correlates underlying behavioral performance. We investigate the working memory (WM) function of patients with untreated obstructive sleep apnea (OSA) from the view point of task positive and default mode networks (TPN and DMN, respectively) and compare the results to those of healthy controls (HC).A parametric fMRI experiment with 4 levels of visuospatial N-back task was used to investigate the pattern of cortical activation in 17 men with untreated moderate or severe OSA and 7 age-matched HC. Categorical and parametrical analysis of the data was performed. Multiple regression analysis of fMRI data of OSA patients was performed with AHI, nocturnal desaturation time, and BMI as covariates.OSA patients demonstrate compensatory spatial recruitment of the TPN (maximal at 3-back) and of the DMN (maximal at 2-back). HC had a different patten of spatial recruitment and deactivation of the DMN at the maximal load of task (3-back). Nocturnal desaturation had significant positive correlation with BOLD signal in bilateral frontal, temporal, and occipital regions, and negative correlations in bilateral frontal and left parietal regions; whereas BMI showed only negative correlations with BOLD signal, predominantly in the PFC. AHI was positively correlated with BOLD signal in bilateral frontal regions.Both TPN and DMN are affected in OSA patients, with nocturnal desaturation affecting both networks; whereas BMI appears to be the major negative factor influencing the TPN and has a significant negative correlation with behavioral performance.

  View details for Web of Science ID 000287917600009

  View details for PubMedID 21358846

• Upper-airway resistance syndrome. Handbook of clinical neurology Guilleminault, C., Los Reyes, V. D. 2011; 98: 401-409

  View details for DOI 10.1016/B978-0-444-52006-7.00026-5

  View details for PubMedID 21056201

• Sleep epidemiology 30 years later: Where are we? SLEEP MEDICINE Ohayon, M. M., Guilleminault, C., Chokroverty, S. 2010; 11 (10): 961-962

  View details for DOI 10.1016/j.sleep.2010.10.001

  View details for Web of Science ID 000286022600001

  View details for PubMedID 21084223

• Epidemiology of sleep-related complaints associated with sleep-disordered breathing in Bangkok, Thailand SLEEP MEDICINE Suwanprathes, P., Won, C., Komoltri, C., Nana, A., Kotchabhakdi, N., Guilleminault, C. 2010; 11 (10): 1025-1030

  Abstract

  This study assesses the prevalence of and risk factors for sleep-related complaints in Bangkok, Thailand.A representative sample of the Bangkok population was selected based on results of the 2000 Census. A total of 4680 participants underwent face-to-face interview with a 49-question sleep inventory.Four percent of the total sampled (5.3% of men and 3.5% of women) complained of habitual snoring (>3 nights/week) and excessive daytime sleepiness (>3 days/week) for at least 3 months. These subjects were significantly (p<0.0001) older (41.4 vs. 36.7 years), had greater BMI (26.0 vs. 22.8 kg/m(2)), neck size (34.7 vs. 32.5 cms), and waist circumference (88.0 vs. 78.7 cms). They reported significantly shorter nocturnal sleep time, greater frequency of sleep disturbances and awakenings, unrefreshing sleep, choking during sleep, night sweats, nocturia, and bruxism. There was also a greater prevalence of cardiovascular and endocrine diseases. Multivariate analysis showed that male gender; BMI; waist size; and reports of witnessed apneas, unrefreshing sleep and night sweats were significant predictors of snoring and daytime sleepiness.This is the first epidemiologic study investigating sleep-related complaints and associated health morbidities in the Thai population.

  View details for DOI 10.1016/j.sleep.2010.04.007

  View details for Web of Science ID 000286022600010

  View details for PubMedID 20643577

• An epidemiologic study of sleep problems among adolescents in North Taiwan SLEEP MEDICINE Huang, Y., Wang, C., Guilleminault, C. 2010; 11 (10): 1035-1042

  Abstract

  To investigate the prevalence of sleep problems and their association with daytime sleepiness among Taiwanese adolescents by use of a validated questionnaire.This is a cross-sectional, community based study with self-reported sleep questionnaires. Completed questionnaires from 1939 adolescent subjects from schools in Lin-Kou district (Taipei, Taiwan) (96.7% responded); 1906 valid questionnaires (62.3% girls) were analyzed. The randomly selected classes included elementary grade 6 (age range: 12-13 years), junior high school (age range: 14-16 years) and senior high school students (age range: 17-18 years).The mean sleep duration on weekdays was 7.35±1.23 h and on weekends 9.38±1.62 h. Weeknight sleep decreased significantly with increasing school grade (6.87±1.14 h for high school seniors). There was a trend towards increased daytime sleepiness for students in higher school grade levels. Daytime sleepiness directly correlated with shorter total sleep time (TST) on weekdays, longer TST on weekends, snoring, insomnia and nightmares. Coffee intake, smoking, periodic leg movement/restless legs syndrome, body mass index (BMI), mouth breathing and breathing problems were indirect factors that induced daytime sleepiness. Pearson correlation showed no significant correlation between the TST during the weekday and BMI (-0.047, p=0.079) or body weight (BW) (-0.048, p=0.072). But it showed significant negative correlation (-0.103, p=0.0001) for increasing total sleep time on the weekend and decreasing BMI.Daytime sleepiness correlated with the shorter TST on weekdays, longer TST on weekends, snoring, insomnia and nightmares. There is no significant correlation between the weekday TST and BMI or BW. Meals and food intake of children are still traditional and have not changed as much in Taiwan as in some other western countries, and compared to a similar survey performed 12 years ago in Taiwan among junior high school students, sleep duration was not significantly different but reduced due to school demands.

  View details for DOI 10.1016/j.sleep.2010.04.009

  View details for Web of Science ID 000286022600012

  View details for PubMedID 20724214

• Obstructive Sleep Apnea and Chronic Opioid Use LUNG Guilleminault, C., Cao, M., Yue, H. J., Chawla, P. 2010; 188 (6): 459-468

  Abstract

  The use of opioids has been associated with development of sleep-disordered breathing, including central apneas, nocturnal oxygen desaturations, and abnormal breathing patterns. We describe sleep-disordered breathing and its subsequent treatment in a group of obstructive sleep apneic patients on chronic opioid therapy. Clinical evaluation followed by diagnostic overnight polysomnogram was performed in subjects on chronic opioid therapy who met the study criteria. All subjects had an initial CPAP titration followed by a repeat clinical evaluation. Subjects with an apnea-hypopnea index (AHI) ≥ 5 continued to report symptoms and had follow-up titration with bilevel positive therapy; then bilevel positive-pressure therapy with a back-up rate was then performed. Age-, sex-, and disease-severity-matched obstructive sleep apnea patients served as controls. Forty-four study participants, including a large group of women (50%), and 44 controls were enrolled in the study. Opioid subjects had AHI = 43.86 ± 1.19, with a central apnea index of 0.64 ± 1.36. Two abnormal breathing patterns were seen, including decreased inspiratory effort during an obstructive event and longer than expected pauses in breathing. Despite adequate titration with CPAP and bilevel positive-pressure therapy, nocturnal awakenings and central apnea awakenings persisted (AHI and central apnea indices of 13.81 ± 2.77 and 11.52 ± 2.12, respectively). Treatment with bilevel positive-pressure therapy with a back-up rate controlled the problem. Nonobese OSA patients with opioid intake have obstructive breathing with a different pattern. In this study, bilevel positive-pressure therapy with a back-up rate was the most effective treatment.

  View details for DOI 10.1007/s00408-010-9254-3

  View details for Web of Science ID 000285104200002

  View details for PubMedID 20658143

• Maxillomandibular advancement for the treatment of obstructive sleep apnea: A systematic review and meta-analysis SLEEP MEDICINE REVIEWS Holty, J. C., Guilleminault, C. 2010; 14 (5): 287-297

  Abstract

  The reported efficacy of maxillomandibular advancement (MMA) for the treatment of obstructive sleep apnea (OSA) is uncertain. We performed a meta-analysis and systematic review to estimate the clinical efficacy and safety of MMA in treating OSA. We searched Medline and bibliographies of retrieved articles, with no language restriction. We used meta-analytic methods to pool surgical outcomes. Fifty-three reports describing 22 unique patient populations (627 adults with OSA) met inclusion criteria. Additionally, 27 reports provided individual data on 320 OSA subjects. The mean apnea-hypopnea index (AHI) decreased from 63.9/h to 9.5/h (p<0.001) following surgery. Using a random-effects model, the pooled surgical success and cure (AHI <5) rates were 86.0% and 43.2%, respectively. Younger age, lower preoperative weight and AHI, and greater degree of maxillary advancement were predictive of increased surgical success. The major and minor complication rates were 1.0% and 3.1%, respectively. No postoperative deaths were reported. Most subjects reported satisfaction after MMA with improvements in quality of life measures and most OSA symptomatology. We conclude that MMA is a safe and highly effective treatment for OSA.

  View details for DOI 10.1016/j.smrv.2009.11.003

  View details for Web of Science ID 000282561700002

  View details for PubMedID 20189852

• Families with sleepwalking SLEEP MEDICINE Cao, M., Guilleminault, C. 2010; 11 (7): 726-734

  Abstract

  Studies on families with sleepwalking are uncommonly published but can give further information on the phenotype of patients with chronic sleepwalking.Out of 51 individuals referred for chronic sleepwalking during a 5-year period, we obtained sufficient information on 7 families with direct relatives who reported sleepwalking with or without sleep terrors. Among 70 living direct family members, we obtained questionnaire responses from 50 subjects and identified 34 cases with a history of sleepwalking. Of the 50 subjects, 16 completed only questionnaires, while all the others also completed a clinical evaluation and nocturnal sleep recordings.There was a positive history of sleepwalking on either the paternal or maternal side of the family over several generations in our 7 families. Thirty-three clinically evaluated subjects had evidence of sleep-disordered breathing (SDB), with associated craniofacial risk factors for SDB (particularly maxillary and/or mandibular deficiencies). There was a complete overlap with the report of parasomnias and the presence of SDB. In cases with current sleepwalking, treatment of SDB coincided with clear improvement of the parasomnia.All of our subjects with parasomnias presented with familial traits considered as risk factors for SDB. These anatomical risk factors are present at birth and even subtle SDB can lead to sleep disruption and instability of NREM sleep. The question raised is: are factors leading to chronic sleep disruption the familial traits responsible for familial sleepwalking?

  View details for DOI 10.1016/j.sleep.2010.01.011

  View details for Web of Science ID 000280914500019

  View details for PubMedID 20598633

• Expert opinion on pharmacotherapy of narcolepsy EXPERT OPINION ON PHARMACOTHERAPY Zaharna, M., Dimitriu, A., Guilleminault, C. 2010; 11 (10): 1633-1645

  Abstract

  Narcolepsy is a neurodegenerative disorder resulting in the instability of the sleep-wake cycle and marked by low levels of hypocretin in cerebrospinal fluid. Sleep instability is marked by brisk, sleep-onset REM periods and sleep fragmentation, while the waking state is interrupted by the intrusion of REM sleep and sometimes accompanied by cataplectic attacks.Current pharmacologic interventions that aim to address three primary features of this disorder; excessive daytime sleepiness (EDS), cataplexy and automatic behaviors, and sleep fragmentation. We review and compare the use of traditional and new stimulants in the treatment of EDS. For the treatment of cataplexy and automatic behaviors, serotonergic and noradrenergic agents are considered. The role of gamma-hydroxybutyrate (GHB) is also explored in its ability to reduce daytime sleepiness and catapletic attacks and to consolidate sleep. Findings are based on a PubMed literature search of clinical and basic science research papers spanning 1977-2009.A comprehensive understanding of the various existing and promising future treatments for narcolepsy. For each of these treatments, we evaluate risks versus benefits of treatment, and proposed pharmacologic mechanisms of action. We conclude with a review of new treatment approaches, including thyrotropin-releasing hormone (TRH), histamine agonists, immunotherapy and hypocretin replacement therapies.Narcolepsy is an autoimmune, neurodegenerative disorder that results in significant sleep-wake instability with or without cataplectic attacks. Current treatments aim symptomatically to reconsolidate the sleep and waking states and to reduce daytime attacks of cataplexy. Future treatments aim primarily towards correcting the causal deficiency of hypocretin or preventing the autoimmune response that results in the loss of hypocretin cells.

  View details for DOI 10.1517/14656566.2010.484021

  View details for Web of Science ID 000279678800004

  View details for PubMedID 20426704

• Surgical Options for the Treatment of Obstructive Sleep Apnea MEDICAL CLINICS OF NORTH AMERICA Holty, J. C., Guilleminault, C. 2010; 94 (3): 479-?

  Abstract

  Obstructive sleep apnea (OSA) is a prevalent condition characterized by repetitive airway obstruction during sleep with associated increased morbidity and mortality. Although CPAP is the preferred treatment, poor compliance is common. Patients intolerant of conventional OSA medical treatment may benefit from surgical therapy to alleviate pharyngeal obstruction. Case series suggest that maxillomandibular advancement has the highest surgical efficacy (86%) and cure rate (43%). Soft palate surgical techniques are less successful, with uvulopalatopharyngoplasty having an OSA surgical success rate of 50% and cure rate of 16%. Further research is needed to more thoroughly assess clinical outcomes (eg, quality of life, morbidity), better identify key preoperative patient and clinical characteristics that predict success, and confirm long-term effectiveness of surgical modalities to treat OSA.

  View details for DOI 10.1016/j.mcna.2010.02.001

  View details for Web of Science ID 000278853600005

  View details for PubMedID 20451028

• Kleine-Levin Syndrome: Current Status MEDICAL CLINICS OF NORTH AMERICA Huang, Y., Lakkis, C., Guilleminault, C. 2010; 94 (3): 557-?

  Abstract

  Kleine-Levin Syndrome is a periodic hypersomnia characterized by recurrent episodes of hypersomnia and other symptoms. This article reviews the research to date, outlines the clinical symptoms, and describes current testing and treatment. It concludes that the cause remains unknown and no treatment is effective in preventing recurrence, although modafinil may reduce duration of symptomatic episode.

  View details for DOI 10.1016/j.mcna.2010.02.011

  View details for Web of Science ID 000278853600009

  View details for PubMedID 20451032

• Preface Sleep Medicine-A Challenging Field With Many New Findings MEDICAL CLINICS OF NORTH AMERICA Dimitriu, A., Guilleminault, C. 2010; 94 (3): XI-XIV

  View details for DOI 10.1016/j.mcna.2010.03.009

  View details for Web of Science ID 000278853600001

  View details for PubMedID 20451024

• Opioid Medication and Sleep-disordered Breathing MEDICAL CLINICS OF NORTH AMERICA Yue, H. J., Guilleminault, C. 2010; 94 (3): 435-?

  Abstract

  There has been a growing recognition of chronic pain that may be experienced by patients. There has been a movement toward treating these patients aggressively with pharmacologic and nonpharmacologic modalities. Opioids have been a significant component of the treatment of acute pain, with their increasing use in cases of chronic pain, albeit with some controversy. In addition to analgesia, opioids have many accompanying adverse effects, particularly with regard to stability of breathing during sleep. This article reviews the existing literature on the effects of opioids on sleep, particularly sleep-disordered breathing.

  View details for DOI 10.1016/j.mcna.2010.02.007

  View details for Web of Science ID 000278853600002

  View details for PubMedID 20451025

• Sleep, noise and health: Review NOISE & HEALTH Zaharna, M., Guilleminault, C. 2010; 12 (47): 64-69

  Abstract

  Sleep is a physiologic recuperative state that may be negatively affected by factors such as psychosocial and work stress as well as external stimuli like noise. Chronic sleep loss is a common problem in today's society, and it may have significant health repercussions such as cognitive impairment, and depressed mood, and negative effects on cardiovascular, endocrine, and immune function. This article reviews the definition of disturbed sleep versus sleep deprivation as well as the effects of noise on sleep. We review the various health effects of chronic partial sleep loss with a focus on the neuroendocrine/hormonal, cardiovascular, and mental health repercussions.

  View details for DOI 10.4103/1463-1741.63205

  View details for Web of Science ID 000286478000003

  View details for PubMedID 20472951

• Impact of the novel antidepressant agomelatine on disturbed sleep-wake cycles in depressed patients HUMAN PSYCHOPHARMACOLOGY-CLINICAL AND EXPERIMENTAL Quera-Salva, M., Lemoine, P., Guilleminault, C. 2010; 25 (3): 222-229

  Abstract

  Disturbance of sleep-wake cycles is common in major depressive disorder (MDD), usually as insomnia, but also as hypersomnia or reduced daytime alertness. Agomelatine, an MT(1) and MT(2) receptor agonist and 5-HT(2C) receptor antagonist, represents a novel approach in MDD, with proven antidepressant efficacy and a positive impact on the sleep-wake cycle. We review the effects of agomelatine 25/50 mg/day on objective and subjective measures of the sleep-wake cycle in MDD.Agomelatine improved all aspects of the sleep-wake cycle from as early as 1 week in randomized trials versus selective serotonin reuptake inhibitors and venlafaxine, particularly getting off to sleep and quality of sleep, with an improvement in daytime alertness.Agomelatine's effect on sleep architecture in MDD has been measured by polysomnography (PSG). There were significant improvements in sleep efficiency, slow-wave sleep (SWS), and the distribution of delta activity throughout the night, but no change in amount or latency of rapid eye movement (REM) sleep. Furthermore, the slow-wave sleep was resynchronized to the first sleep cycle of the night.Agomelatine, a novel antidepressant, improves disturbed sleep-wake cycles in MDD. The improvement of both nighttime sleep and daytime functioning with agomelatine are promising features of this antidepressant regarding the management of MDD.

  View details for DOI 10.1002/hup.1112

  View details for Web of Science ID 000277385000004

  View details for PubMedID 20373473

• Upper airway changes with a mandibular advancement device. Expert review of respiratory medicine Yue, H., Lin, C., Guilleminault, C. 2010; 4 (1): 25-28

  View details for PubMedID 20387290

• Sleep disordered breathing in children INDIAN JOURNAL OF MEDICAL RESEARCH Sinha, D., Guilleminault, C. 2010; 131 (2): 311-320

  Abstract

  Sleep disordered breathing (SDB) is increasingly being recognised as a cause of morbidity even in young children. With an estimated prevalence of 1 to 4 per cent, SDB results from having a structurally narrow airway combined with reduced neuromuscular tone and increased airway collapsibility. SDB in children differs from adults in a number of ways, including presenting symptoms and treatment. Presentation may differ according to the age of the child. Children have a more varied presentation from snoring and frequent arousals to enuresis to hyperactivity. Those with Down syndrome, midface hypoplasia or neuromuscular disorders are at higher risk for developing SDB. First line definitive treatment in children involves tonsillectomy and adenoidectomy. Rapid maxillary expansion, allergy treatment and continuous positive airway pressure (CPAP) are other options. As untreated SDB results in complications as learning difficulties, memory loss and a long term increase in risk of hypertension, depression and poor growth, it is important to diagnose SDB.

  View details for Web of Science ID 000275635200022

  View details for PubMedID 20308756

• Chapter 34: the history of sleep medicine. Handbook of clinical neurology Pelayo, R., Hodgson, N., Guilleminault, C. 2010; 95: 547-556

  View details for DOI 10.1016/S0072-9752(08)02134-9

  View details for PubMedID 19892137

• Comparison of hypopnea definitions in lean patients with known obstructive sleep apnea hypopnea syndrome (OSAHS) SLEEP AND BREATHING Guilleminault, C., Hagen, C. C., Huynh, N. T. 2009; 13 (4): 341-347

  Abstract

  In the interest of improving inter-rater reliability and standardization between sleep laboratories, hypopnea definitions were recently changed to place less emphasis on arousal scoring and more emphasis on oxygen desaturations. We sought to determine whether these changes would affect detection and treatment of OSAHS in lean patients-a group known to desaturate less-than-obese patients.Thirty-five lean subjects (15 male, 20 women, five post-menopausal) diagnosed OSAHS and a documented benefit from treatment had diagnostic polysomnograms (PSG) originally scored using the American Academy of Sleep Medicine (AASM) rule from 1999 (referred to as "Rule C"). These patients had appropriate clinical care based on those results. PSG records were then re-scored in a randomized and blinded fashion utilizing hypopnea Rule A and B of the 2007 AASM guidelines.Baseline mean (SD) apnea hypopnea indices (AHI) for rules A, B, and C were 6.4 (3.1), 20.6 (8.2), and 26.9 (7.3), respectively (p < 0.0001). Mean (SD) BMI was 24.4 (1.0). By design, all subjects were treatment responders. Eighty-six percent with CPAP, 83% with oral appliance, and 100% with surgical intervention reported resolution of their initial daytime or sleep complaint. Post-treatment AHIs for rules A, B, and C were 0.8 (0.9), 1.8 (1.2) and 2.3 (1.6; p < 0.001). In all three scoring conditions, the AHI was reduced significantly with treatment (p < 0.001). A repeated measures ANOVA of the difference between scoring methods indicated statistically significant differences between all three strategies at both pre- and post-treatment (p < 0.001). Sleepiness on the Epworth sleepiness scale decreased from a mean of 10.9 (2.3) to 5.7 (1.3) with treatment (p < 0.001). This change in subjective rating of sleepiness was more strongly correlated with rules B and C (r = 0.6) and more modestly correlated with Rule A scoring (r = 0.4).Response to treatment was more tightly correlated with arousal based scoring rules B and C in this group of lean subjects. The1999 hypopnea rule was used at baseline to detect this cohort of patients with OSAHS that ultimately benefitted from treatment. Rule B detected OSAHS and correlated well with response to treatment, but many more were categorized as mild (5 < AHI < 15) at baseline. Since 40% of the subjects had an AHI less than 5 with Rule A, lack of sensitivity should be considered before applying Rule A to the scoring of sleep studies in lean patients.

  View details for DOI 10.1007/s11325-009-0253-7

  View details for Web of Science ID 000270978900005

  View details for PubMedID 19418083

• Reaction time performance in upper airway resistance syndrome versus obstructive sleep apnea syndrome SLEEP MEDICINE Stoohs, R. A., Philip, P., Andries, D., Finlayson, E. V., Guilleminault, C. 2009; 10 (9): 1000-1004

  Abstract

  Patients with obstructive sleep apnea syndrome (OSAS) are known to have an increased risk for motor vehicle crashes. They suffer from sleep-related respiratory abnormality causing repetitive arousal leading to daytime sleepiness. In turn, it has been demonstrated that sleepiness can impair human psychomotor performance causing slowing of reaction times (RTs). Patients with OSAS present with RTs comparable to young adults under the influence of blood alcohol concentrations above the legally permitted level to drive a motor vehicle. Vigilance related risk levels in patients with upper airway resistance syndrome (UARS) and potential deficits in psychomotor performance are unknown.We designed a study to compare psychomotor performance in UARS and compared it to patients with OSAS. Forty-seven UARS patients were matched by gender and age with 47 OSAS patients. All subjects completed a standardized vigilant attention task utilizing reaction time before undergoing polygraphic sleep studies.Patients with UARS presented worse psychomotor performance on most test metrics than patients with OSAS.Our study results may suggest that patients with UARS may also present an increased risk for motor vehicle crashes as previously demonstrated in OSAS patients.

  View details for DOI 10.1016/j.sleep.2008.11.005

  View details for Web of Science ID 000271339000013

  View details for PubMedID 19410510

• Treatment options for obstructive sleep apnea CURRENT TREATMENT OPTIONS IN NEUROLOGY Abad, V. C., Guilleminault, C. 2009; 11 (5): 358-367

  Abstract

  Sleep apnea is a major public health problem that afflicts 9% of women and 24% of men 30 to 60 years of age. It is highly treatable, but when untreated, it has been associated with (but not necessarily linked to) increased probability of cerebral and coronary vascular disease, congestive heart failure, metabolic dysfunction, cognitive dysfunction, excessive daytime sleepiness, motor vehicle accidents, reduced productivity, and decreased quality of life. The gold standard for treatment in adults is positive airway pressure (PAP) therapy: continuous PAP (CPAP), bilevel PAP, autotitrating CPAP, or autotitrating bilevel PAP. Measures to increase compliance with PAP therapy include medical or surgical treatment of any underlying nasal obstruction, setting appropriate pressure level and airflow, mask selection and fitting, heated humidification, desensitization for claustrophobia, patient and partner education, regular follow-up with monitoring of compliance software, and attendance of support groups (eg, AWAKE). Adjunctive treatment modalities include lifestyle or behavioral measures and pharmacologic therapy. Patients with significant upper airway obstruction who are unwilling or unable to tolerate PAP therapy may benefit from surgery. Multilevel surgery of the upper airway addresses obstruction of the nose, oropharynx, and hypopharynx. A systematic approach may combine surgery of the nose, pharynx, and hypopharynx in phase 1, whereas skeletal midface advancement or tracheotomy constitutes phase 2. Clinical outcomes are reassessed through attended diagnostic polysomnogram performed 3 to 6 months after surgery. Oral appliances can be used for patients with symptomatic mild or moderate sleep apnea who prefer them to PAP therapy or for whom PAP therapy has failed or cannot be tolerated. Oral appliances also may be used for patients with severe obstructive sleep apnea who are unable or unwilling to undertake PAP therapy or surgery. For children, the main treatment modality is tonsillectomy and adenoidectomy, with or without turbinate surgery. Children with craniofacial abnormalities resulting in maxillary or mandibular insufficiency may benefit from palatal expansion or maxillary/mandibular surgery. PAP therapy may be used for children who are not surgical candidates or if surgery fails.

  View details for DOI 10.1007/s11940-009-0040-6

  View details for Web of Science ID 000268871400005

  View details for PubMedID 19744402

• Emerging drugs for insomnia: new frontiers for old and novel targets EXPERT OPINION ON EMERGING DRUGS Sullivan, S. S., Guilleminault, C. 2009; 14 (3): 411-422

  Abstract

  Insomnia is the most prevalent sleep disorder, with up to 50% of the US adult population reporting symptoms of insomnia on a weekly basis and approximately 12% with insomnia disorder. Comorbid conditions such as depression and anxiety are frequent. Insomnia is more common with older age, female gender and socioeconomic status. Traditionally, therapy has focused on GABA(A) receptor agonists, and off-label antidepressant and antihistamine use.With increased understanding of complex neural networks involved in sleep and wake, hypnotics are being developed to target a broader variety of receptors with increasing selectivity. This review summarizes promising compounds in Phase II and III trials with evidence supporting efficacy for treatment of insomnia.5-HT(2A) and 5-HT(2C) antagonists, melatonergic (MT1/MT2) agonists, orexin receptor (OX1/OX2) antagonists, as well as GABA(A) receptor agonists are reviewed and summarized. Data are collected from PubMed and Pharmaprojects database searches, company websites, recent scientific meeting presentations and abstracts.A variety of drugs targeting several pathways, including GABA(A) agonism, MT1/MT2 agonism, 5-HT(2A) antagonism, OX1/OX2 antagonism and others, are in Phase II and III trials. More work should be done to understand the impact of these drugs in certain populations and in the context of comorbid conditions.

  View details for DOI 10.1517/14728210903171948

  View details for Web of Science ID 000270014900003

  View details for PubMedID 19708818

• Neurologic Aspects of Sleep Apnea: Is Obstructive Sleep Apnea a Neurologic Disorder? SEMINARS IN NEUROLOGY Guilleminault, C., Ramar, K. 2009; 29 (4): 368-371

  Abstract

  The upper airway caliber is determined by afferent sensory input to the brainstem respiratory centers and efferent motor neural output to the upper airway structures. Upper airway caliber is altered in obstructive sleep apnea. The mechanosensory receptors of the upper airway are capable of responding to changes in airway pressure, airflow, temperature, and to the upper airway muscle tone itself. Application of topical anesthesia change chronic snorers in apneic patients during sleep and prolong sleep apnea in obstructive sleep apnea (OSA) patients. Respiratory-related evoked potential are significantly reduced in OSA patients during non-rapid eye movement sleep indicating a sleep-related blunted cortical response to inspiratory occlusion. Histologic investigations of palatopharyngeal muscles from OSA patients show evidence of motor neuron lesions and actual damage to the muscles. Currently demonstrated local neurologic impairment and lesions can explain the development of sleep apneas and hypopneas.

  View details for DOI 10.1055/s-0029-1237122

  View details for Web of Science ID 000269984500009

  View details for PubMedID 19742412

• Narcolepsy: Action of Two gamma-Aminobutyric Acid Type B Agonists, Baclofen and Sodium Oxybate PEDIATRIC NEUROLOGY Huang, Y., Guilleminault, C. 2009; 41 (1): 9-16

  Abstract

  This study was performed to evaluate the actions of baclofen and sodium oxybate, two medications with gamma-aminobutyric acid type B (GABA(B)) receptor agonist properties, on symptoms of narcolepsy in drug-naïve teenagers. Twenty-six narcoleptic teenagers with recent onset of narcolepsy-cataplexy syndrome who were human leukocyte antigen DQB1 0602 positive were matched for age and sex and received either baclofen or sodium oxybate. If deemed necessary to combat excessive daytime sleepiness, the alerting agent modafinil was also prescribed. Clinical evaluation was performed weekly, and visual analog sleepiness score and cataplexy logs were collected weekly. The Epworth Sleepiness Scale or the Pediatric Daytime Sleepiness Scale, polysomnography, and the Multiple Sleep Latency Test were recorded at baseline and after 3 months of drug intake. The dose of baclofen demonstrating an effect on nocturnal sleep without negative side effects was determined and maintained. Both drugs increased total sleep time and delta waves during sleep, but only sodium oxybate had an effect on daytime sleepiness and cataplexy at 3 months. Improvement of total nocturnal sleep time had no beneficial effect on daytime sleepiness. The mechanism by which sodium oxybate improves cataplexy and sleepiness is inferred to be due to properties beyond direct GABA(B) agonist action.

  View details for DOI 10.1016/j.pediatrneurol.2009.02.008

  View details for Web of Science ID 000267196300002

  View details for PubMedID 19520267

• Rebound cataplexy after withdrawal from antidepressants SLEEP MEDICINE Broderick, M., Guilleminault, C. 2009; 10 (4): 403-404

  View details for DOI 10.1016/j.sleep.2008.06.004

  View details for Web of Science ID 000266788000002

  View details for PubMedID 18692440

• Pediatric sleep disorders: How can sleep-medicine make a difference? SLEEP MEDICINE REVIEWS Cao, M., Guilleminault, C. 2009; 13 (2): 107-110

  View details for DOI 10.1016/j.smrv.2008.11.002

  View details for Web of Science ID 000264943400001

  View details for PubMedID 19233696

• Chronic Sleep Complaints in Premenopausal Women and Their Association with Sleep-Disordered Breathing LUNG Tantrakul, V., Guilleminault, C. 2009; 187 (2): 82-92

  Abstract

  In clinical practice, we have found that premenopausal women have delayed diagnosis of sleep-disordered breathing (SDB).During a 4-year period, we systematically collected the clinical and polysomnographic variables for all women referred for sleep complaints using preestablished questionnaires, scales, clinical grid, polygraphic montage, and scoring criteria. The variables collected on premenopausal SDB women were analyzed and compared to those of postmenopausal women within 5 years of menopause.Of 977 women, 316 were premenopausal with SDB. Complaints of chronic insomnia and sleepwalking were the most common reasons for referral, had been present for a mean of 6.4 +/- 5.4 years, and had lead to unsuccessful symptomatic treatment. The normal-weight premenopausal SDB group had anatomically small upper airways, while those with body mass index (BMI) >/= 25 kg/m(2) complained more frequently of snoring and daytime sleepiness and their clinical presentation was closer to those of the postmenopausal SDB comparison group. Premenopausal women often had a low apnea-hypopnea index (AHI), but there was a discrepancy between the low AHI and the amount of continuous positive airway pressure (CPAP) needed to control the SDB, and there was a need for higher pressures in overweight premenopausal SDB women (mean 9.1 +/- 1.9 and 10.1 +/- 2.6 cmH(2)O).Normal-weight premenopausal SDB women often present with atypical sleep complaints of chronic insomnia and parasomnias. Clinical attention paid to craniofacial features and use of specific scales such as Mallampati help with the suspicion of the presence of SDB, and a low AHI is unrelated to the positive clinical impact of nasal CPAP treatment.

  View details for DOI 10.1007/s00408-009-9137-7

  View details for Web of Science ID 000266211100002

  View details for PubMedID 19219502

• Scheduled Bright Light for Treatment of Insomnia in Older Adults JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Friedman, L., Zeitzer, J. M., Kushida, C., Zhdanova, I., Noda, A., Lee, T., Schneider, B., Guilleminault, C., Sheikh, J., Yesavage, J. A. 2009; 57 (3): 441-452

  Abstract

  To determine whether bright light can improve sleep in older individuals with insomnia.Single-blind, placebo-controlled, 12-week, parallel-group randomized design comparing four treatment groups representing a factorial combination of two lighting conditions and two times of light administration.At-home light treatment; eight office therapy sessions.Thirty-six women and fifteen men (aged 63.6+/-7.1) meeting primary insomnia criteria recruited from the community.A 12-week program of sleep hygiene and exposure to bright ( approximately 4,000 lux) or dim light ( approximately 65 lux) scheduled daily in the morning or evening for 45 minutes.Within-group changes were observed for subjective (sleep logs, questionnaires) and objective (actigraphy, polysomnography) sleep measures after morning or evening bright light.Within-group changes for subjective sleep measures after morning or evening bright light were not significantly different from those observed after exposure to scheduled dim light. Objective sleep changes (actigraphy, polysomnography) after treatment were not significantly different between the bright and dim light groups. Scheduled light exposure was able to shift the circadian phase predictably but was unrelated to changes in objective or subjective sleep measures. A polymorphism in CLOCK predicted morningness but did not moderate the effects of light on sleep. The phase angle between the circadian system (melatonin midpoint) and sleep (darkness) predicted the magnitude of phase delays, but not phase advances, engendered by bright light.Except for one subjective measure, scheduled morning or evening bright light effects were not different from those of scheduled dim light. Thus, support was not found for bright light treatment of older individuals with primary insomnia.

  View details for DOI 10.1111/j.1532-5415.2008.02164.x

  View details for Web of Science ID 000263859600008

  View details for PubMedID 19187411

  View details for PubMedCentralID PMC2743069

• Sleep-disordered breathing and chronic atrial fibrillation SLEEP MEDICINE Braga, B., Poyares, D., Cintra, F., Guilleminault, C., CIRENZA, C., Horbach, S., Macedo, D., Silva, R., Tufik, S., de Paola, A. A. 2009; 10 (2): 212-216

  Abstract

  Little has been known about the prevalence of sleep apnea in patients with atrial fibrillation (AF). Studies have suggested that the prevalence of AF is increasing in patients with sleep-disordered breathing. We hypothesize that the prevalence of OSA is higher in chronic persistent and permanent AF patients than a sub-sample of the general population without this arrhythmic disorder.Evaluate the frequency of Obstructive Sleep Apnea in a sample of chronic AF compared to a sub-sample of the general population.Fifty-two chronic AF patients aged (60.5 +/- 9.5, 33 males) and 32 control (aged 57.3 +/- 9.6, 15 males). All subjects were evaluated by a staff cardiologist for the presence of medical conditions and were referred for polysomnography. The differences between groups were analyzed by ANOVA for continuous variables, and by the Chi-square test for dichotomous variables. Statistical significance was established by alpha=0.05.There were no differences in age, gender, BMI, sedentarism, presence of hypertension, type 2 diabetes mellitus, abdominal circumference, systolic and diastolic blood pressure, and sleepiness scoring between groups. Despite similar BMI, AF patients had a higher neck circumference compared to control group (39.9cm versus 37.7cm, p=0.01) and the AF group showed higher percentage time of stage 1 NREM sleep (6.4% versus 3.9%, p=0.03). Considering a cut-off value for AHI >= 10 per hour of sleep, the AF group had a higher frequency of OSA compared to the control group (81.6% versus 60%, p=0.03). All the oxygen saturation parameters were significantly worse in the AF group, which had lower SaO(2) nadir (81.9% versus 85.3%, p=0.01) and mean SaO(2) (93.4% versus 94.3%, p=0.02), and a longer period of time below 90% (26.4min versus 6.7min, p=0.05).Sleep-disordered breathing is more frequent in chronic persistent and permanent AF patients than in age-matched community dwelling subjects.

  View details for DOI 10.1016/j.sleep.2007.12.007

  View details for Web of Science ID 000264683300010

  View details for PubMedID 18280206

• Sleep and psychiatry ZHURNAL NEVROLOGII I PSIKHIATRII IMENI S S KORSAKOVA Abad, V. C., Guilleminault, C. 2009; 109 (9): 102-?

  View details for Web of Science ID 000270866800022

  View details for PubMedID 19908413

• DIFFERENCES IN CEREBRAL ACTIVATION ON A VISUO-SPATIAL WORKING MEMORY TASK]IN OBSTRUCTIVE SLEEP APNEA PATIENTS AND HEALTHY CONTROLS 23rd Annual Meeting of the Associated-Professional-Sleep-Societies (APSS) Prilipko, O., Huynh, N., Tantrakul, V., Leary, E., Nichols, D., Henry, M., Kushida, C., Guilleminault, C. AMER ACAD SLEEP MEDICINE. 2009: A225–A225

  View details for Web of Science ID 000265542001041

• FMRI STUDY OF CPAP TREATMENT ON VERBAL MEMORY ENCODING IN OBSTRUCTIVE SLEEP APNEA PATIENTS IN COMPARISON TO HEALTHY CONTROLS 23rd Annual Meeting of the Associated-Professional-Sleep-Societies (APSS) Huynh, N. T., Prilipko, O., Tantrakul, V., Nichols, D., Leary, E., Kushida, C., Guilleminault, C. AMER ACAD SLEEP MEDICINE. 2009: A224–A224

  View details for Web of Science ID 000265542001036

• Resting Energy Expenditure in Adults With Sleep Disordered Breathing ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY Kezirian, E. J., Kirisoglu, C. E., Riley, R. W., Chang, E., Guilleminault, C., Powell, N. B. 2008; 134 (12): 1270-1275

  Abstract

  To examine the association between sleep disordered breathing severity and resting energy expenditure (REE).Cross-sectional.University-based academic medical center.Two hundred twelve adults with signs or symptoms of sleep disordered breathing underwent medical history, physical examination, level I attended polysomnography, and determination of REE using an indirect calorimeter.Mean REE.Seventy-one percent (151 of 212) of the study population were male, and the mean (SD) age was 42.3 (12.6) years. The mean (SD) body mass index, calculated as weight in kilograms divided by height in meters squared, was 28.3 (7.3). The mean (SD) apnea-hypopnea index was 25.4 (27.2), and the lowest oxygen saturation during the sleep study was 86.9% (9.5%). The mean (SD) REE was 1763 (417) kcal/d. Analysis of variance and univariate regression analysis showed an association between REE and several measures of sleep disordered breathing severity that persisted after adjustment for age, sex, and self-reported health status in multiple regression analysis. Only REE and the apnea-hypopnea index demonstrated an independent association after additional adjustment for body mass index (or body weight and height separately). This association did not differ between individuals with normal vs elevated body mass index.Sleep disordered breathing severity is associated with REE. Although this association is largely confounded by body weight, there is an independent association with the apnea-hypopnea index.

  View details for Web of Science ID 000261740100004

  View details for PubMedID 19075121

• Is there a link between alertness and fatigue in patients with traumatic brain injury? NEUROLOGY Chaumet, G., Quera-Salva, M., MacLeod, A., Hartley, S., Taillard, J., Sagaspe, P., Mazaux, J., Azouvi, P., Joseph, P., Guilleminault, C., Bioulac, B., Leger, D., Philip, P. 2008; 71 (20): 1609-1613

  Abstract

  Many patients with traumatic brain injury (TBI) report chronic fatigue, and previous studies showed a potential relationship between sleepiness and fatigue in these patients. Our study first looked at the impact of objective and subjective sleepiness on fatigue in patients with TBI. We then investigated how fatigue could affect driving performance in these patients.Nocturnal polysomnography, the Fatigue Severity Scale (FSS), the Epworth Sleepiness Scale (ESS), and five 40-minute maintenance of wakefulness tests (MWT) were collected in 36 patients with TBI. Fitness to drive was assessed in a subsample of 22 patients compared to 22 matched controls during an hour simulated driving session.In patients with TBI, FSS, ESS, and mean MWT scores (+/-SD) were 27 +/- 10, 8 +/- 4, and 35 +/- 7 minutes vs 15 +/- 2.5, 5 +/- 3, and 37 +/- 5 minutes in controls. Patients with TBI reported more chronic fatigue (W = 99, p < 0.001) than controls, and, unlike in controls, the level of chronic fatigue was correlated to their MWT scores. Patients' driving performances were worse than the controls' (W = 79, p < 0.001). The best predictive factors of driving performance were fatigue scores and body mass index (multiple R = 0.458, 41.8% of explained variance).In patients with TBI, chronic fatigue is significantly related to subjective and objective levels of alertness, even though these levels are not highly pathologic. This might suggest that a small level of sleepiness (i.e., MWT scores between 33 and 39 minutes) worsens fatigue in these patients. Chronic fatigue and body mass index could predict driving simulator performance in patients with TBI.

  View details for DOI 10.1212/01.wnl.0000334753.49193.48

  View details for Web of Science ID 000260795700009

  View details for PubMedID 19001250

• Prospective Randomized Study of Patients with Insomnia and Mild Sleep Disordered Breathing SLEEP Guilleminault, C., Davis, K., Huynh, N. T. 2008; 31 (11): 1527-1533

  Abstract

  Patients with insomnia may present with mild and often unrecognized obstructive sleep apnea (OSA).To evaluate both subjective and objective outcomes of patients with complaints of insomnia and mild OSA who receive surgical treatment for OSA versus behavioral treatment with cognitive behavioral therapy for insomnia (CBT-I).Prospective study with crossover design of 30 patients with complaints of insomnia and mild OSA. Thirty subjects, matched for age and gender, were randomized with stratification to receive either CBT-I or surgical treatment of OSA as primary treatment. Patients were reassessed after completing the initial intervention and reassigned if agreeable to the alternative treatment option and assessed again on completion of both treatment arms. Outcome measures included clinical impression, Epworth Sleepiness Scale (ESS) score, Fatigue Severity Scale (FSS) score, and polysomnography (PSG) results.Surgery resulted in greater improvements in total sleep time (TST), slow wave sleep and REM sleep duration, respiratory disturbance index, apnea-hypopnea index, minimum oxygen saturation, FSS, and ESS. CBT-I also improved TST and resulted in shorter sleep latency.Surgical intervention for the management of patients with complaints of insomnia and mild OSA demonstrated greater improvement in both subjective and objective outcome measures. Initial treatment of underlying OSA in patients with insomnia was more successful in improving insomnia than CBT-I alone. However CBT-I as initial treatment improved TST compared to baseline; following surgical intervention, it had the additional benefit of further increasing TST and helped to control sleep onset difficulties that may be related to conditioning due to unrecognized symptoms of mild OSA.

  View details for Web of Science ID 000260550100011

  View details for PubMedID 19014072

• Maintenance of Wakefulness Test, Obstructive Sleep Apnea Syndrome, and Driving Risk ANNALS OF NEUROLOGY Philip, P., Sagaspe, P., Taillard, J., Chaumet, G., Bayon, V., Coste, O., Bioulac, B., Guilleminault, C. 2008; 64 (4): 410-416

  Abstract

  Sleepiness at the wheel is a major risk factor for traffic accidents. Because of the potential medical and legal implications, in this study, we evaluated the correlation between subjective and objective measures of sleepiness and driving performances in patients suffering from excessive daytime sleepiness.Thirty-eight untreated sleep apnea patients (mean age +/- standard deviation, 51 +/- 9 years; mean apnea-hypopnea index +/- standard deviation, 41 +/- 25), and 14 healthy control subjects (mean age +/- standard deviation, 46 +/- 9 years) were included in the study. Nocturnal polysomnography, mean sleep latency as measured by four 40-minute Maintenance of Wakefulness Test (MWT) trials, Epworth Sleepiness Scale, Karolinska Sleepiness Scale, and the number of inappropriate line crossings during a 90-minute real-life driving session were analyzed.The number of inappropriate line crossings correlated with MWT scores (Spearman's Rho: r = -0.339; p < 0.05), Karolinska Sleepiness Scale scores measured at halfway in total driving distance (Rho: r = 0.367; p < 0.01), and Epworth Sleepiness Scale (Rho: r = 0.389; p < 0.01). We found a significant difference in the number of inappropriate line crossings among the four groups defined by MWT scores (very sleepy [0-19 minutes], sleepy [20-33 minutes], alert [34-40 minutes], and controls) (Kruskal-Wallis test: H = 11.319; p < 0.01). Very sleepy and sleepy patients had more inappropriate line crossings than the control drivers (p < 0.05).In addition to subjective sleepiness scales, the MWT can be used to assess driving ability in untreated sleep apnea patients.

  View details for DOI 10.1002/ana.21448

  View details for Web of Science ID 000260845000009

  View details for PubMedID 18688799

• Delta sleep instability in children with chronic arthritis 11th Brazilian Congress on Sons Lopes, M. C., Guilleminault, C., Rosa, A., Passarelli, C., Roizenblatt, S., Tufik, S. ASSOC BRAS DIVULG CIENTIFICA. 2008: 938–43

  Abstract

  The objective of the present study was to evaluate the expression of a cyclic alternating pattern (CAP) in slow wave sleep (SWS) in children with the well-defined chronic syndrome juvenile idiopathic arthritis (JIA). Twelve patients (9-17 years of age), 7 girls, with JIA were compared to matched controls by age, pubertal stage and gender. After one night of habituation in the sleep laboratory, sleep measurements were obtained by standard polysomnography with conventional sleep scoring and additional CAP analyses. The sleep parameters of the JIA and control groups were similar for sleep efficiency (91.1 +/- 6.7 vs 95.8 +/- 4.0), sleep stage in minutes: stage 1 (16.8 +/- 8.5 vs 17.8 +/- 4.0), stage 2 (251.9 +/- 41 vs 262.8 +/- 38.1), stage 3 (17.0 +/- 6.0 vs 15.1 +/- 5.7), stage 4 (61.0 +/- 21.7 vs 77.1 +/- 20.4), and rapid eye movement sleep (82.0 +/- 27.6 vs 99.0 +/- 23.9), respectively. JIA patients presented nocturnal disrupted sleep, with an increase in short awakenings, but CAP analyses showed that sleep disruption was present even during SWS, showing an increase in the overall CAP rate (P < 0.01). Overall CAP rate during non-rapid eye movement sleep was significantly higher in pediatric patients who were in chronic pain. This is the first study of CAP in pediatric patients with chronic arthritis showing that CAP analyses can be a powerful tool for the investigation of disturbance of SWS in children, based on sleep EEG visual analysis.

  View details for Web of Science ID 000261171400018

  View details for PubMedID 19030715

• Neurological aspects of obstructive sleep apnea. Annals of the New York Academy of Sciences Broderick, M., Guilleminault, C. 2008; 1142: 44-57

  Abstract

  Obstructive sleep apnea is often regarded as a structural disorder causing narrowing of the airway. This article reviews the neurological aspects of obstructive sleep apnea, including the upper airway reflex, cortical arousal thresholds, and motor function as they pertain to the pathophysiology of disease. We also discuss the relationship of obstructive sleep apnea to other neurological diseases.

  View details for DOI 10.1196/annals.1444.003

  View details for PubMedID 18990120

• Nasal obstruction in children with sleep-disordered breathing ANNALS ACADEMY OF MEDICINE SINGAPORE Sullivan, S., Li, K., Guilleminault, C. 2008; 37 (8): 645-648

  Abstract

  Nasal obstruction secondary to pathological enlargement of inferior nasal turbinates contributes to sleep-disordered breathing (SBD) in prepubertal children, but treatments designed to address turbinate enlargement are often not performed. The aims of these studies are: (1) to appreciate the contribution to SDB of untreated enlarged nasal turbinates in prepubertal children; and (2) to report our experience with treatment of enlarged nasal turbinates in young children with SDB.Children with enlarged nasal turbinates who underwent adenotonsillectomy (T&A) had significantly less improvement in postoperative apnoea-hypopnoea index (AHI) compared to those treated with concomitant turbinate reduction. Children in the untreated turbinate hypertrophy group subsequently underwent radiofrequency ablation of the inferior nasal turbinates; following this procedure, AHI was no different than AHI of those without hypertrophy.In an analysis of safety and effectiveness of radiofrequency treatment of the nasal turbinates, we found the procedure to be a well-tolerated component of SDB treatment.We conclude that radiofrequency (RF) treatment of inferior nasal turbinates is a safe and effective treatment in young prepubertal children with SDB. When indicated, it should be included in the treatment plan for prepubertal children with SDB. However, the duration of effectiveness is variable and therapy may need to be repeated if turbinate hypertrophy recurs.

  View details for Web of Science ID 000259787600004

  View details for PubMedID 18797556

• Orthodontic expansion treatment and adenotonsillectomy in the treatment of obstructive sleep apnea in prepubertal children (Retracted article. See vol. 33, pg. 8, 2010) SLEEP Guilleminault, C., Quo, S., Huynh, N. T., Li, K. 2008; 31 (7): 953-957

  Abstract

  Rapid maxillary expansion and adenotonsillectomy are proven treatments of obstructive sleep apnea (OSA) in children. Our goal was to investigate whether rapid maxillary expansion should be offered as an alternative to surgery in select patients. In addition, if both therapies are required, the order in which to perform these interventions needs to be determined.Prepubertal children with moderate OSA clinically judged to require both adenotonsillectomy and orthodontic treatment were randomized into 2 treatment groups. Group 1 underwent adenotonsillectomy followed by orthodontic expansion. Group 2 underwent therapies in the reverse sequence.Thirty-two children (16 girls) in an academic sleep clinic.Clinical evaluation and polysomnography were performed after each stage to assess efficacy of each treatment modality.The 2 groups were similar in age, symptoms, apnea-hypopnea index, and lowest oxygen saturation. Two children with orthodontic treatment first did not require subsequent adenotonsillectomy. Thirty children underwent both treatments. Two of them were still symptomatic and presented with abnormal polysomogram results following both therapies. In the remaining 28 children, all results were significantly different from those at entry (P = 0.001) and from single therapy (P = 0.01), regardless of the order of treatment. Both therapies were necessary to obtain complete resolution of OSA.In our study, 87.5% of the children with sleep-disordered breathing had both treatments. In terms of treatment order, 2 of 16 children underwent orthodontic treatment alone, whereas no children underwent surgery alone to resolve OSA. Two children who underwent both treatments continued to have OSA.

  View details for Web of Science ID 000257293800006

  View details for PubMedID 18652090

• Sleep and rheumatologic disorders SLEEP MEDICINE REVIEWS Abad, V. C., Sarinas, P. S., Guilleminault, C. 2008; 12 (3): 211-228

  Abstract

  Arthritis is the leading cause of chronic illness in the United States. Seventy-two percent of the adults aged 55 years and older with arthritis report sleep difficulties. This review discusses sleep disorders associated with rheumatoid arthritis, juvenile rheumatoid arthritis, Sjogren's syndrome, systemic lupus erythematosus, scleroderma, Behcet's disease, seronegative spondyloarthropathies, osteoarthritis, sarcoidosis, and fibromyalgia. We describe the inter-relationship between sleep complaints, disease activity, depression, sleep deprivation, and cytokines. An algorithm for evaluation and treatment of sleep disorders associated with rheumatologic diseases is proposed.

  View details for DOI 10.1016/j.smrv.2007.09.001

  View details for Web of Science ID 000257451500005

  View details for PubMedID 18486034

• NREM sleep instability in children with sleep terrors: The role of slow wave activity interruptions CLINICAL NEUROPHYSIOLOGY Bruni, O., Ferri, R., Novelli, L., Finotti, E., Miano, S., Guilleminault, C. 2008; 119 (5): 985-992

  Abstract

  To evaluate NREM sleep instability, as measured by the cyclic alternating pattern (CAP), in children with sleep terrors (ST) vs. normal controls.Ten boys (mean age: 8.5 years, range 5-13) meeting the following inclusion criteria: (a) complaint of ST several times a month, (b) a history of ST confirmed by a third person, and (c) a diagnosis of ST according to the ICSD-2 criteria. Eleven age-matched control children with parental report of at least 8.5h of nightly sleep, absence of known daytime consequences of sleep disorders were recruited by advertisement from the community. Sleep was visually scored for sleep macrostructure and CAP using standard criteria.Sleep macrostructure showed only a significantly increased number of awakenings per hour and reduced sleep efficiency in ST subjects. CAP parameters analysis revealed several significant differences in ST vs. controls: an increase of total CAP rate in SWS, of A1 index in SWS and of the mean duration of A phases while B phases had a decreased duration, exclusively in SWS. The normalized CAP interval-distribution graphs showed significant differences in SWS with interval classes 10< or = i < 35s higher in children with ST and intervals classes above 50s higher in normal controls.Children with ST showed faster alternations of the amplitude of slow EEG bursts during SWS. This abnormally fast alternation of the EEG amplitude in SWS is linked to the frequent intrusion of CAP B phases interrupting the continuity of slow delta activity and could be considered as a neurophysiological marker of ST.This abnormal alternation of the EEG amplitude in SWS is associated with the occurrence of parasomnias and might be considered as a neurophysiological marker of disorders of arousal.

  View details for DOI 10.1016/j.clinph.2008.01.015

  View details for Web of Science ID 000255716200003

  View details for PubMedID 18313981

• Polysomnography in Kleine-Levin syndrome NEUROLOGY Huang, Y., Lin, Y., Guilleminault, C. 2008; 70 (10): 795-801

  Abstract

  Cause and pathogenesis of the Kleine-Levin syndrome (KLS), a recurrent hypersomnia affecting mainly male adolescents, remain unknown, with only scant information on the sleep characteristics during episodes. We describe findings obtained with polysomnography (PSG) and Multiple Sleep Latency Test (MSLT) and correlation obtained between clinical and PSG findings from different episodes.Nineteen patients (17 male) were investigated with PSG and MSLT. Ten patients had data during both symptomatic episode and asymptomatic interval. The analyses considered day of onset of symptoms and relationship between this time of onset and day of recording during the symptomatic period.When PSG was performed early (before the end of the first half of the symptomatic period), an important reduction in slow wave sleep (SWS) was always present with progressive return to normal during the second half (with percentages very similar to those monitored during the asymptomatic period) despite persistence of clinical symptoms. REM sleep remained normal in the first half of the episode but decreased in the second half: the differences between first and second half of episodes were significant for SWS (p = 0.014) and REM sleep (p = 0.027). The overall mean sleep latency at MSLT was 9.51 +/- 4.82 minutes and 7 of 17 patients had two or more sleep onset REM periods during the symptomatic period.Important changes in sleep occur over time during the symptomatic period, with clear impairment of slow wave sleep at symptom onset. But Multiple Sleep Latency Test (MSLT) is of little help in defining sleep problems and findings from the MSLT do not correlate with symptom onset.

  View details for Web of Science ID 000253776100009

  View details for PubMedID 18316691

• Surgical treatment of obstructive sleep apnea: upper airway and maxillomandibular surgery. Proceedings of the American Thoracic Society Won, C. H., Li, K. K., Guilleminault, C. 2008; 5 (2): 193-199

  Abstract

  Upper airway surgery is an important treatment option for patients with obstructive sleep apnea (OSA), particularly for those who have failed or cannot tolerate positive airway pressure therapy. Surgery aims to reduce anatomical upper airway obstruction in the nose, oropharynx, and hypopharynx. Procedures addressing nasal obstruction include septoplasty, turbinectomy, and radiofrequency ablation (RF) of the turbinates. Surgical procedures to reduce soft palate redundancy include uvulopalatopharyngoplasty, uvulopalatal flap, laser-assisted uvulopalatoplasty, and RF of the soft palate with adenotonsillectomy. More significant, however, particularly in cases of severe OSA, is hypopharyngeal or retrolingual obstruction related to an enlarged tongue, or more commonly due to maxillomandibular deficiency. Surgeries in these cases are aimed at reducing the bulk of the tongue base or providing more space for the tongue in the oropharynx so as to limit posterior collapse during sleep. These procedures include genioglossal advancement, hyoid suspension, distraction osteogenesis, tongue RF, lingualplasty, and maxillomandibular advancement. Successful surgery depends on proper patient selection, proper procedure selection, and experience of the surgeon. Most surgeries are done in combination and in a multistep manner, with maxillomandibular advancement typically being reserved for refractory or severe OSA, or for those with obvious and significant maxillomandibular deficiency. Although not without risks and not as predictable as positive airway pressure therapy, surgery remains an important therapeutic consideration in all patients with OSA. Current research aims to optimize the success of these procedures by identifying proper candidates for surgery, as well as to develop new invasive procedures for OSA treatment.

  View details for DOI 10.1513/pats.200708-121MG

  View details for PubMedID 18250212

• Placebo and modafinil effect on sleepiness in obstructive sleep apnea PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY Bittencourt, L. R., Lucchesi, L. M., Rueda, A. D., Garbuio, S. A., Palombini, L. O., Guilleminault, C., Tufik, S. 2008; 32 (2): 552-559

  Abstract

  Previous studies have evaluated the effect of modafinil on residual excessive daytime sleepiness (EDS) in patients with obstructive sleep apnea syndrome (OSAS) under effective CPAP treatment. Even though those trials also used placebo groups, we suppose that the placebo effect might influence the patients' response to modafinil.Twenty sleepy patients with OSAS under CPAP treatment were selected. All of them had Epworth Sleepiness Scale (ESS) >10. Following baseline evaluation (T1), all subjects were instructed to take placebo for 7 days. After this single-blind placebo phase and second evaluation (T2), patients were randomly allocated to placebo or modafinil treatment for 21 days in a double-blind protocol. Patients underwent a final evaluation (T3) on the last day of drug intake. The evaluations at T1, T2 and T3 consisted of: medical and laboratory examinations, nocturnal polysomnography, ESS, maintenance of wakefulness test (MWT) and complex reaction time (CRT-NY). In addition, in T2 and T3 the change of illness severity scale (CGI-C) and the evaluation of quality of life (SF-36) were applied.The comparison between the two groups during the three periods studied, showed the following results: in the modafinil group, ESS score did not change during the initial placebo period, but there was a significant reduction during the modafinil treatment period (p=0.0006); in the placebo group a significant reduction occurred during the initial placebo period (p=0.05), and no further change was observed in the treatment (placebo) period. A significant difference was found between the two groups after the placebo period (T2) (p=0.02). Three patients (33%) of the modafinil group and 9 patients (81%) of the placebo group were classified as placebo-responsive (X2: p=0.039). In the treatment period, reaction time was significantly reduced in the modafinil group compared to the placebo group (p<0.02). There was a trend toward improvement in overall clinical condition and also in some domains of SF-36 in the modafinil group.In summary, our study confirms that modafinil used adjunctively with CPAP therapy improves subjective daytime sleepiness in patients with OSAS who were regular users of CPAP therapy but still experienced sleepiness. Moreover, it could help in the improvement of objective measures of behavioral alertness and reduce functional impairments. The usefulness of a blinded placebo period for systematic investigation of placebo role in studies based on subjective response is a point that should be considered in this type of drug trial.

  View details for DOI 10.1016/j.pnpbp.2007.10.016

  View details for Web of Science ID 000253847000034

  View details for PubMedID 18053628

• Cardiovascular complications of obstructive sleep apnea. Expert review of respiratory medicine Ramar, K., Guilleminault, C. 2008; 2 (1): 63-74

  Abstract

  Obstructive sleep apnea (OSA) is a common disorder with an increasing public health burden. It is characterized by repeated upper airway narrowing and closure, leading to apneas, hypopneas and increased respiratory effort-related arousals. Continuous positive airway pressure is an effective modality of treatment for OSA. Apart from being responsible for daytime sleepiness and cognitive impairment, OSA has been implicated in various systemic diseases, particularly of the cardiovascular system. This article reviews some of the extensive literature implicating OSA in the development of cardiovascular diseases and describes the intermediary pathophysiologic mechanisms involved. Repetitive nocturnal oxygen desaturation and reoxygenation and increased intrathoracic pressure changes related to OSA result in the intermediary pathophysiologic mechanisms that affect the neural, humoral, thrombotic, inflammatory and metabolic pathways responsible for the development of cardiovascular disorders. This review also examines evidence that suggests that OSA may be a specific cause of certain cardiovascular disorders.

  View details for DOI 10.1586/17476348.2.1.63

  View details for PubMedID 20477223

• Catathrenia: Parasomnia or uncommon feature of sleep disordered breathing? SLEEP Guilleminault, C., Hagen, C. C., Khaja, A. M. 2008; 31 (1): 132-139

  Abstract

  We report a series of seven consecutive cases of catathrenia (sleep related groaning) that differ from limited previous reports in the literature with regard to sleep stage and response to treatment.Catathrenia was recently defined as a parasomnia in the International Classification of Sleep Disorders Diagnostic and Coding Manual (ICSD-2), but there is debate about its classification, and its response to CPAP is unknown.We present 7 consecutive patients presenting with catathrenia over a 5-year period. They were all young women, ranging in age from 20 to 34 years with a body mass index (BMI) <25. They underwent standard clinical evaluation, questionnaires, physical exam, craniofacial evaluations, and nocturnal polysomnography. All seven were titrated on continuous passive airway pressure (CPAP) treatment for sleep disordered breathing then offered surgical treatment if unable to tolerate or adhere to CPAP recommendations.Groaning was present throughout all stages of sleep. The mean (SD) AHI and RDI were 3.2 (0.56) and 13.1 (2.4) respectively. CPAP resolved groaning in all cases. 5 patients (71%) elected subsequent surgical intervention. Three of the 4 that followed up after surgery required adjuvant oral appliance treatment, but all four ultimately had resolution of groaning.Catathrenia may have subtypes related to sleep stage specificity or presence of sleep disordered breathing. In our heterogeneous group of non-obese women with a normal AHI and elevated RDI, CPAP and select soft tissue surgeries of the upper airway (often augmented with an oral appliance) successfully treated nocturnal groaning.

  View details for Web of Science ID 000252264000017

  View details for PubMedID 18220087

• Neurological Aspects of Obstructive Sleep Apnea Meredith Broderick and Christian Guilleminault YEAR IN NEUROLOGY 2008 Broderick, M., Guilleminault, C. 2008; 1142: 44-57

  View details for DOI 10.1196/annals.1444.003

  View details for Web of Science ID 000260858700003

• Evolution of narcolepsy symptoms in families 22nd Annual Meeting of the Associated-Professional-Sleep-Societies Ohayon, M. M., Guilleminault, C., Black, J., Wells, C., Krystal, A. D. AMER ACAD SLEEP MEDICINE. 2008: A213–A213

  View details for Web of Science ID 000255419001079

• Pre-eclampsia and nasal CPAP: Part 1. Early intervention with nasal CPAP in pregnant women with risk-factors for pre-eclampsia: Preliminary findings SLEEP MEDICINE Guillerninault, C., Palombini, L., Poyares, D., Takaoka, S., Huynh, N. T., El-Sayed, Y. 2007; 9 (1): 9-14

  Abstract

  Pre-eclampsia is a leading cause of maternal-fetal morbidity and mortality. Significant overlap exists between the risk factors for pre-eclampsia and sleep-disordered breathing. Nasal continuous positive airway pressure (CPAP) has been proposed as therapy for pre-eclampsia. This prospective, longitudinal study was designed to characterize sleep-related breathing patterns in pregnant women with pre-eclampsia risk factors, and to describe the effects of early nasal CPAP therapy in these patients.Twelve pregnant women with pre-eclampsia risk factors underwent polysomnography to characterize sleep-related breathing abnormalities and baseline blood pressure determination. Patients with airflow-limitation underwent nasal CPAP titration and were treated with optimal pressures. Periodic assessments of CPAP compliance and tolerance, sleep quality, and blood pressure control were performed until delivery or pre-eclampsia onset. CPAP retitration was performed between weeks 20 and 22 of pregnancy.Mean respiratory disturbance index was 8.5+/-2.6 events/h of sleep, and initial nasal CPAP pressures were 5-6 cm H(2)O with an increase to 6-9 cm H2O after recalibration. All subjects with chronic hypertension maintained blood pressures below 140/90 with a mean diurnal blood pressure of 122+/-2.5 mmHg over 83+/-1.5 mmHg. Patient characteristics of obesity and prior pre-eclampsia were associated with pregnancies complicated by spontaneous abortion, premature delivery, or pre-eclampsia.Early application of nasal CPAP in pregnant women alleviated sleep-related breathing disturbances but was not sufficient to prevent negative pregnancy outcomes. Obesity and prior pre-eclampsia appeared to be important factors and were associated with the worst complications. However, nasal positive pressure may still be beneficial to decrease severity of outcomes, particularly if individualized to patient risk factors, more particularly hypertension at pregnancy onset.

  View details for DOI 10.1016/j.sleep.2007.04.020

  View details for Web of Science ID 000252696300003

  View details for PubMedID 17644420

• Cyanotic breath-holding spells in children respond to adenotonsillectomy for sleep-disordered breathing JOURNAL OF SLEEP RESEARCH Guilleminault, C., Huang, Y., Chan, A., Hagen, C. C. 2007; 16 (4): 406-413

  Abstract

  Children with breath-holding (BH) spells may demonstrate sleep-disordered breathing (SDB) during polysomnography. We studied five young children with cyanotic spells retrospectively and found both SDB and a response to adenotonsillectomy. We therefore proceeded with a prospective investigation of treatment for SDB in children with comorbid cyanotic spells. Nineteen children with cyanotic BH spells were identified and enrolled in the prospective study. Parents chose either treatment or observation. Fourteen children underwent complete SDB evaluation and treatment trials while five selected observation only (control group). Sleep and sleep-surgery specialist evaluation and polysomnography revealed the presence of a narrow upper-airway and an abnormal respiratory disturbance index in all 14 children. Nasal CPAP was not successful, but adenotonsillectomy performed near 14 months of age eliminated SDB. BH spells were eliminated 1 month after surgery, while they persisted to the end of the study (24 months of age) in the control group. In conclusion, the presence of cyanotic BH should prompt investigation and polysomnography for possible SDB. Independent treatment of SDB may hasten resolution of BH spells in these cases.

  View details for Web of Science ID 000251203300009

  View details for PubMedID 18036086

• Pre-eclampsia and nasal CPAP: Part 2. Hypertension during pregnancy, chronic snoring, and early nasal CPAP intervention SLEEP MEDICINE Poyares, D., Guilleminault, C., Hachul, H., Fujita, L., Takaoka, S., Tufik, S., Sass, N. 2007; 9 (1): 15-21

  Abstract

  To evaluate the potential benefit of nasal continuous positive airway pressure (CPAP) administration in pregnant women recognized to have hypertension early in pregnancy.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.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.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.

  View details for DOI 10.1016/j.sleep.2007.04.019

  View details for Web of Science ID 000252696300004

  View details for PubMedID 17644475

• Non-REM sleep instability in patients with major depressive disorder: Subjective improvement and improvement of non-REM sleep instability with treatment (Agomelatine) SLEEP MEDICINE Lopes, M. C., Quera-Salva, M., Guilleminault, C. 2007; 9 (1): 33-41

  Abstract

  To assess the importance of non-rapid eye movement (NREM) sleep disturbance in major depressive disorder (MDD) patients using cyclic alternating pattern (CAP) analysis, and to determine the usefulness of CAP analysis in evaluating treatment effect.Baseline sleep-staging data and CAP analysis of NREM sleep was compared in 15 MDD patients (Hamilton depression scale score>20) and normal controls. Longitudinal evaluation of sleep changes using similar analysis during a treatment trial was also performed.A single-blinded researcher scored and analyzed the sleep of MDD and age-matched normal controls at baseline and during a treatment trial using the international scoring system as well as CAP analysis.MDD patients had evidence of disturbed sleep with both analyses, but CAP analysis revealed more important changes in NREM sleep of MDD patients at baseline than did conventional sleep staging. There was a significant decrease in CAP rate, time, and cycle and disturbances of phase A subtype of CAP. NREM abnormalities, observed by CAP analysis, during the treatment trial paralleled subjective responses. Analysis of subtype A phase of CAP demonstrated better sleep improvement.CAP analysis demonstrated the presence of more important NREM sleep disturbances in MDD patients than did conventional sleep staging, suggesting the involvement of slow wave sleep (SWS) in the sleep impairment of MDD patients. Improvement of NREM sleep paralleled subjective mood improvement and preceded REM sleep improvement. CAP analysis allowed objective investigation of the effect of treatment on sleep disturbances.

  View details for DOI 10.1016/j.sleep.2007.01.011

  View details for Web of Science ID 000252696300007

  View details for PubMedID 17826314

• Improvement in subjective sleep in major depressive disorder with a novel antidepressant, agomelatine: Randomized, double-blind comparison with venlafaxine JOURNAL OF CLINICAL PSYCHIATRY Lemoine, P., Guilleminault, C., Alvarez, E. 2007; 68 (11): 1723-1732

  Abstract

  Patients with major depressive disorder (MDD) experience sleep disturbances that may be worsened by some antidepressant drugs early in treatment. The aim of this study was to assess the subjective quality of sleep of patients receiving agomelatine, a new antidepressant with melatonergic MT(1) and MT(2) receptor agonist and 5-HT(2C) antagonist properties, compared with that of patients receiving venlafaxine, a serotonin-norepinephrine reuptake inhibitor.This double-blind, randomized study involved 332 patients with MDD (DSM-IV criteria), lasted 6 weeks, and compared the effects of agomelatine 25-50 mg/day and venlafaxine 75-150 mg/day, with a possible dose adjustment at 2 weeks. Subjective sleep was assessed with the Leeds Sleep Evaluation Questionnaire (LSEQ), and the main efficacy criterion was the "getting to sleep" score. Antidepressant efficacy was assessed with the 17-item Hamilton Rating Scale for Depression (HAM-D) and the Clinical Global Impressions (CGI) global improvement scale. The study was performed between November 2002 and June 2004.After 6 weeks, the antidepressant efficacy of agomelatine was similar to that of venlafaxine. The LSEQ "getting to sleep" score was significantly better with agomelatine (70.5 +/- 16.8 mm) than with venlafaxine (64.1 +/- 18.2 mm); the between-treatment difference at the last visit was 6.36 mm (p = .001), and the difference was already significant at week 1. Secondary sleep items, including LSEQ quality of sleep (p = .021), sleep awakenings (p = .040), integrity of behavior (p = .024), and sum of HAM-D items 4, 5, and 6 (insomnia score) (p = .044), were also significantly improved compared to venlafaxine, as was the CGI global improvement score (p = .016). Incidence of adverse events was 52.1% with agomelatine and 57.1% with venlafaxine, and withdrawals due to adverse events were more common with venlafaxine than with agomelatine (13.2% vs. 4.2%).Agomelatine showed similar antidepressant efficacy with earlier and greater efficacy in improving subjective sleep than venlafaxine in MDD patients.

  View details for Web of Science ID 000251179200012

  View details for PubMedID 18052566

• Major depressive disorder, sleep EEG and agomelatine: an open-label study INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY Salva, M. Q., Vanier, B., Laredo, J., Hartley, S., Chapotot, F., Moulin, C., Lofaso, F., Guilleminault, C. 2007; 10 (5): 691-696

  Abstract

  This open study evaluates the effect of agomelatine, a melatonergic receptor agonist and 5-HT2C antagonist antidepressant, on sleep architecture in patients suffering from major depressive disorder. Fifteen outpatients with a baseline HAMD score > or = 20 were treated with 25 mg/d agomelatine for 42 d. Polysomographic studies were performed at baseline, day 7, day 14, and day 42. Sleep efficiency, time awake after sleep onset and the total amount of slow-wave sleep (SWS) increased at week 6. The increase of SWS was predominant during the first sleep cycle. The amount of SWS decreased throughout the first four sleep cycles from day 7 and delta ratio increased from day 14 onwards. No change in rapid eye movement (REM) latency, amount of REM or REM density was observed and agomelatine was well tolerated. In conclusion agomelatine improved sleep continuity and quality. It normalized the distribution of SWS sleep and delta power throughout the night.

  View details for DOI 10.1017/S1461145707007754

  View details for Web of Science ID 000250063600012

  View details for PubMedID 17477886

• Sleep-disordered breathing and C-reactive protein: A commentary SLEEP Ohayon, M. M., Guilleminault, C. 2007; 30 (6): 679-679

  View details for Web of Science ID 000247321400001

  View details for PubMedID 17580589

• The cyclic alternating pattern demonstrates increased sleep instability and correlates with fatigue and sleepiness in adults with upper airway resistance syndrome SLEEP Guilleminault, C., Lopes, M. C., Hagen, C. C., da Rosa, A. 2007; 30 (5): 641-647

  Abstract

  To clarify the relationship between sleep instability and subjective complaints in patients with upper airway resistance syndrome (UARS).Thirty subjects (15 women) with UARS and 30 age- and sex-matched controls in a prospective, single-blind, case-control study. Blinded cyclic alternating pattern (CAP) electroencephalogram analysis and scales of fatigue and sleepiness were completed.Mann-Whitney U tests for independent, nonparametric variables between groups and chi2 tests for nonparametric variables with defined standard values.Patients with UARS had significantly more complaints of fatigue and sleepiness, compared with controls, demonstrated on their Fatigue Severity Scale (P < 0.001) and Epworth Sleepiness Scale (P < 0.001). By design, the mean apnea-hypopnea index was normal in both groups, whereas the respiratory disturbance index was greater in patients with UARS than in those without (14.5 +/- 3.0 vs 9 +/- 5.2, respectively [P < 0.001]). CAP analysis demonstrated abnormal non-rapid eye movement sleep with abnormally increased CAP rate, electroencephalogram arousals, A2 index, and A3 index. Decreased A1 index in controls was consistent with their more normal progression of sleep. CAP rate correlated with both the Epworth Sleepiness Scale (r = 0.38, P < 0.01) and the Fatigue Severity Scale (r = 0.51, P < 0.0001), and there was a positive trend between the Fatigue Severity Scale and phase A2 index (r = 0.29, P < 0.05).Compared with age- and sex-matched controls, patients with UARS have higher electroencephalogram arousal indexes and important non-rapid eye movement sleep disturbances that correlate with subjective symptoms of sleepiness and fatigue. These disturbances are identifiable with sensitive measures such as CAP analysis but not with traditional diagnostic scoring systems.

  View details for Web of Science ID 000246747800016

  View details for PubMedID 17552380

• The role of hypnotics in continuous positive airway pressure compliance CHEST Pelayo, R., Guilleminault, C. 2007; 131 (5): 1616-1616

  View details for DOI 10.1378/chest.06-3036

  View details for Web of Science ID 000246544700062

  View details for PubMedID 17494823

• Sleepy driver near-misses may predict accident risks SLEEP Powell, N. B., Schechtman, K. B., Riley, R. W., Guilleminault, C., Chiang, R. P., Weaver, E. M. 2007; 30 (3): 331-342

  Abstract

  To quantify the prevalence of self-reported near-miss sleepy driving accidents and their association with self-reported actual driving accidents.A prospective cross-sectional internet-linked survey on driving behaviors.Dateline NBC News website.Results are given on 35,217 (88% of sample) individuals with a mean age of 37.2 +/- 13 years, 54.8% women, and 87% white. The risk of at least one accident increased monotonically from 23.2% if there were no near-miss sleepy accidents to 44.5% if there were > or = 4 near-miss sleepy accidents (P < 0.0001). After covariate adjustments, subjects who reported at least one near-miss sleepy accident were 1.13 (95% CI, 1.10 to 1.16) times as likely to have reported at least one actual accident as subjects reporting no near-miss sleepy accidents (P < 0.0001). The odds of reporting at least one actual accident in those reporting > or = 4 near-miss sleepy accidents as compared to those reporting no near-miss sleepy accidents was 1.87 (95% CI, 1.64 to 2.14). Furthermore, after adjustments, the summary Epworth Sleepiness Scale (ESS) score had an independent association with having a near-miss or actual accident. An increase of 1 unit of ESS was associated with a covariate adjusted 4.4% increase of having at least one accident (P < 0.0001).A statistically significant dose-response was seen between the numbers of self-reported sleepy near-miss accidents and an actual accident. These findings suggest that sleepy near-misses may be dangerous precursors to an actual accident.

  View details for Web of Science ID 000245305900012

  View details for PubMedID 17425230

• Maintenance of wakefulness test as a predictor of driving performance in patients with untreated obstructive sleep apnea SLEEP Sagaspe, P., Taillard, J., Chaumet, G., Guilleminault, C., Coste, O., Moore, N., Bioulac, B., Philip, P. 2007; 30 (3): 327-330

  Abstract

  To determine the ability of Maintenance of Wakefulness Test (MWT) to predict simulated driving performance in patients suffering from sleep apnea syndrome.Study involving one hour of simulated driving, one night of polysomnography (PSG), and a 4 x 40-minute MWT.Sleep laboratory.Thirty male patients with untreated obstructive sleep apnea syndrome (OSAS) (mean age [+/- SD] = 51 +/- 8 years, range 34-62; mean body mass index (BMI) [+/- SD] = 29 +/- 3, range 24-37; mean apnea/hypopnea index (AHI) [+/- SD] = 43 +/- 24, range 14-96). As defined by MWT mean sleep latency, 23.3% of the patients were sleepy (0-19 min), 33.3% were alert (20-33 min), and 43.4% were fully alert (34-40 min).Nocturnal PSG, mean sleep latency at 4 x 40-minute MWT trials, Epworth Sleepiness Scale (ESS), and standard deviation from the center of the road (SDS) on driving simulator.Mean MWT scores inversely correlated with SDS during the simulated driving session (Pearson's r = -0.513, P < 0.01). We found a significant effect of MWT groups (sleepy, alert, or fully alert) on SDS (ANOVA, F(2, 29) = 5.861, P < 0.01). Post hoc tests revealed that the sleepy group had a higher SDS than the fully alert group (P = 0.006). ESS, AHI, microarousal index, and total sleep time did not predict simulated driving performance.A pathological MWT mean sleep latency (0-19 min) is associated with simulated driving impairment. Before MWT can be used to predict the driving ability of untreated patients with OSAS, further studies are needed to confirm that pathological MWT scores are associated with real driving impairment.

  View details for Web of Science ID 000245305900011

  View details for PubMedID 17425229

• Adenotonsillectomy and obstructive sleep apnea in children: A prospective survey OTOLARYNGOLOGY-HEAD AND NECK SURGERY Guilleminault, C., Huang, Y., Glamann, C., Li, K., Chan, A. 2007; 136 (2): 169-175

  Abstract

  Prospective survey of children up to 14 years of age with OSA submitted to adenotonsillectomy.Clinical evaluation, with questionnaires and clinical scales evaluating facial structures including tonsils and Mallampati scales and otolaryngologic evaluation; nocturnal polysomnography and repeat evaluation three to five months postsurgery.Of 207 successively seen children, 199 had follow-up polysomnography, and 94 had still abnormal sleep recording. Multivariate analysis indicates that Mallampati scale score 3 and 4, retro-position of mandible, enlargement of nasal inferior turbinates at +3 (subjective scale 1 to 3), and deviated septum were significantly associated with persistence of abnormal polysomnography (with high 95% CI for Mallampati scale and deviated septum).Mallampati scale scores are resultant of several facial factors involving maxilla, mandible, and oral versus oral breathing but add information on risk of partial response to adenotonsillectomy.Adenotonsillectomy may not resolve obstructive sleep apnea in children.

  View details for DOI 10.1016/j.otohns.2006.09.021

  View details for Web of Science ID 000244052200002

  View details for PubMedID 17275534

• Effect of atrial overdrive pacing on obstructive sleep apnea in patients with systolic heart failure SLEEP MEDICINE Sharafkhaneh, A., Sharafkhaneh, H., Bredikus, A., Guilleminault, C., Bozkurt, B., Hirshkowitz, M. 2007; 8 (1): 31-36

  Abstract

  Obstructive sleep apnea (OSA) is associated with cardiovascular disease. Preliminary studies suggested breathing improvement in patients with apnea and heart disease when atrial overdrive pacing was applied during sleep. However, more recent studies do not show significant beneficial effect for atrial overdrive pacing in OSA. To further investigate this relationship, we conducted a randomized clinical trial evaluating the effect of atrial overdrive pacing on sleep-related breathing events in subjects with OSA and systolic heart failure.We screened 33 subjects with symptoms consistent with OSA. On a screening overnight polysomnography (PSG), 15 subjects with mean age of 74 years (standard deviation (SD) 6.6) and ejection fraction of 38% (SD 14.4%) had OSA defined as having an apnea/hypopnea index (AHI) of > or =15 per hour of sleep. These subjects underwent additional PSGs including a night with atrial overdrive pacing (O), a night with pacemaker rate set at 40-50 beats per minutes (N), and a positive airway pressure titration night. The O and N nights were consecutive and the order was randomized. For O, the pacemaker rate was set at 15 beats higher than the average nightly heart rate (determined from the screening night).At baseline, mean AHI was 34.8 (15.5) and mean SaO(2) nadir was 85% (3.2%). Average heart rate was significantly higher on O nights compared to N nights (p<0.005). The apnea index (AI) was statistically lower on O nights compared to N nights (18+/-16.6 vs. 24+/-18.9, p<0.05). However, AHI and minimum and average O(2) saturations did not differ significantly between O and N nights. Interestingly, AHI improved statistically significantly on O nights in younger subjects.While statistically reliable, the small pacing-related reduction in sleep-disordered breathing (SDB) events is of unknown clinical significance. By contrast, continuous positive airway pressure (CPAP) dramatically improved AHI, AI, respiratory arousal index, and O(2) saturation. Thus our data suggest that overdrive pacing exerts a mild effect on respiratory events in some heart failure patients with OSA; however, atrial overdrive pacing was not therapeutically effective for improving airway patency and sleep-related respiratory function.

  View details for DOI 10.1016/j.sleep.2006.06.012

  View details for Web of Science ID 000244399100006

  View details for PubMedID 17157066

• Narcolepsy spectrum in probands' families and the general population 21st Annual Meeting of the American-Professional-Sleep-Societies Ohayon, M., Guilleminault, C., Black, J., Wells, C. AMER ACAD SLEEP MEDICINE. 2007: A226–A227

  View details for Web of Science ID 000246224900670

• An epidemiologic study of self-reported sleep problems and daytime sleepiness among adolescents in north Taiwan 21st Annual Meeting of the American-Professional-Sleep-Societies Huang, Y., Gau, S., Guilleminault, C. AMER ACAD SLEEP MEDICINE. 2007: A73–A73

  View details for Web of Science ID 000246224900213

• The clinical manifestation of sleep-disordered breathing in children and adolescent 21st Annual Meeting of the American-Professional-Sleep-Societies Kim, J., Won, C., Guilleminault, C. AMER ACAD SLEEP MEDICINE. 2007: A86–A86

  View details for Web of Science ID 000246224900252

• Attention-deficit/hyperactivity disorder with obstructive sleep apnea: A treatment outcome study SLEEP MEDICINE Huang, Y., Guilleminault, C., Li, H., Yang, C., Wu, Y., Chen, N. 2007; 8 (1): 18-30

  Abstract

  Children diagnosed with attention-deficit/hyperactivity disorder (ADHD), based on Diagnostic and Statistical Manual of Mental Disorders, Fourth edition (DSM-IV) criteria, may also have obstructive sleep apnea (OSA), but it is unclear whether treating OSA has similar results as methylphenidate (MPH), a commonly used treatment for ADHD.This study enrolled 66 school-age children, referred for and diagnosed with ADHD, and 20 healthy controls. Polysomnography (PSG) performed after ADHD diagnosis showed the presence of mild OSA. After otolaryngological evaluation, parents and referring physicians of the children could select treatment of ADHD with MPH, treatment of OSA with adenotonsillectomy or no treatment. Systematic follow-up was performed six months after initiation of treatment, or diagnosis if no treatment. All children had pre- and post-clinical interviews; pediatric, neurologic, psychiatric and neurocognitive evaluation; PSG; ADHD rating scale, child behavior checklist (CBCL) filled out by parents and teacher; test of variables of attention (TOVA); and the quality of life in children with obstructive sleep disorder questionnaire (OSA-18).ADHD children had an apnea-hypopnea index (AHI)>1<5 event/hour; 27 were treated with MPH, 25 had adenotonsillectomy, and 14 had no treatment. The surgical and MPH groups improved more than the non-treatment group. When comparing MPH to post-surgery, the PSG and questionnaire sleep variables, some daytime symptoms (including attention span) and TOVA subscales (impulse control, response time and total ADHD score) improved more in the surgical group than the MPH group. The surgical group had an ADHD total score of 21.16+/-7.13 on the ADHD rating scale (ADHD-RS) post-surgery compared to 31.52+/-7.01 pre-surgery (p=0.0001), and the inattention and hyperactivity subscales were also significantly lower (p=0.0001). Finally, the results were significantly different between surgically and MPH-treated groups (ADHD-RS p=0.007). The surgical group also had a TOVA ADHD score lower than -1.8 and close to those obtained in normal controls.A low AHI score of >1 considered abnormal is detrimental to children with ADHD. Recognition and surgical treatment of underlying mild sleep-disordered breathing (SDB) in children with ADHD may prevent unnecessary long-term MPH usage and the potential side effects associated with drug intake.

  View details for DOI 10.1016/j.sleep.2006.05.016

  View details for Web of Science ID 000244399100005

  View details for PubMedID 17157069

• Pramipexole: new use for an old drug - the potential use of pramipexole in the treatment of restless legs syndrome. Neuropsychiatric disease and treatment Benbir, G., Guilleminault, C. 2006; 2 (4): 393-405

  Abstract

  Restless legs syndrome (RLS) is characterized by paraesthesias-dysesthesias and motor restlessness worsening at rest-in the evening, with at least temporary relief by activity. Its etiology is unknown, though it could be secondary to various conditions. It is well known, however, that dopamine plays a crucial role in the pathophysiology of RLS, as dopaminergic agonists achieve marked improvement. Pramipexole is a nonergoline compound with selectivity for D3 dopamine receptors. This drug is very effective in the treatment of idiopathic and secondary RLS and in treatment-resistant patients, as shown by double-blind, placebo-controlled studies in adults. In children, studies are much more limited, and RLS is often misdiagnosed as "growing pain" or attention deficit hyperactivity disorder. Pramipexole has been successful in open studies, eliminating clinical symptoms. This medication has the advantage of being free of the frequently encountered problems seen with ergot derivatives. The side-effects are limited, particularly at the dosages usually prescribed for RLS treatment: They are much lower than in Parkinson's disease, and inappropriate sleepiness and sleep attacks, particularly while driving, or compulsive behavior have not been seen. Compared with the adverse reactions of levodopa, including tolerance, rebound, and augmentation phenomena in RLS, which led to usage of dopamine agonists as first line of treatment for RLS, pramipexole has had one of the best profiles. Augmentation can still be noted with the drug, but after longer usage time compared with many other dopamine agonists. Although excessive daytime sleepiness has been noted, sleep attacks have not been encountered in RLS patients treated with pramipexole.

  View details for PubMedID 19412489

• Vascular endothelial dysfunction in patients with mild obstructive sleep apnea syndrome. Wiener medizinische Wochenschrift Duchna, H., Stoohs, R., Guilleminault, C., Christine Anspach, M., Schultze-Werninghaus, G., Orth, M. 2006; 156 (21-22): 596-604

  Abstract

  We investigated endothelial dysfunction, an early manifestation of atherosclerosis, in patients with mild obstructive sleep apnea syndrome (OSAS) (5/h < AHI < 15/h).Endothelium-dependent and -independent vasodilatory function was tested in 10 patients with mild OSAS, 12 healthy controls and 20 subjects with moderate to severe OSAS using the hand vein compliance technique.Maximum endothelium-dependent vasodilation to bradykinin (Emax) was significantly blunted in patients with mild OSAS (68.6 +/- 30.2 %) compared to healthy controls (94.8 +/- 9.5 %; p < 0.05; moderate to severe OSAS: 57.1 +/- 23.4 %; p = 0.33). Mean endothelium-independent venodilation was not altered. After 160.7 +/- 82.2 nights of CPAP therapy, mean Emax was significantly improved to 90.8 +/- 23.8 % (p < 0.01 vs. baseline; p = 0.7 vs. healthy controls) in 7 patients with mild OSAS.Systemic endothelium-dependent venodilation is markedly reduced in subjects with mild OSAS, which may imply adverse cardiovascular consequences. CPAP-treatment leads to a sustained restoration of endothelial dysfunction in these patients and is thus highly recommended.

  View details for PubMedID 17160377

• A double-blind, placebo-controlled, crossover study of sildenafil in obstructive sleep apnea ARCHIVES OF INTERNAL MEDICINE Roizenblatt, S., Guilleminault, C., Poyares, D., Cintra, F., Kauati, A., Tufik, S. 2006; 166 (16): 1763-1767

  Abstract

  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.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.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.In patients with severe obstructive sleep apnea, a single 50-mg dose of sildenafil at bedtime worsens respiratory and desaturation events.

  View details for Web of Science ID 000240593400014

  View details for PubMedID 16983056

• Chronic snoring and sleep in children: A demonstration of sleep disruption PEDIATRICS Lopes, M. C., Guilleminault, C. 2006; 118 (3): E741-E746

  Abstract

  Chronic snoring that does not adhere to the criteria for a diagnosis of obstructive sleep apnea syndrome may be associated with learning and behavioral problems. We investigated the sleep structure of chronic snorers who had an apnea-hypopnea index of < 1 event per hour and analyzed the cyclic alternating pattern.Fifteen successively seen chronic snorers (9.8 +/- 4 years) with an apnea-hypopnea index of <1 and 15 aged-matched control subjects (10.3 +/- 5 years) underwent an investigation of their sleep with the determination of non-apneic-hypopneic breathing abnormalities polysomnographic scoring using current criteria and analysis of the cyclic alternating pattern.Chronic snorers have evidence of flow limitations and tachypnea during sleep even if they do not present with apneas, hypopneas, and decrease in oxygen saturations. They also present with abnormal cyclic alternating pattern rates and changes in phase A of cyclic alternating pattern compared with control subjects.An apnea-hypopnea index value cannot be the sole determinant in evaluating sleep-disordered breathing in children. Children who have chronic snoring and do not respond to the criteria for obstructive sleep apnea syndrome can present with an abnormal sleep electroencephalogram as evidenced by a significant increase in cyclic alternating pattern rates, with a predominance of abnormalities in slow wave sleep.

  View details for DOI 10.1542/peds.2005-3046

  View details for Web of Science ID 000240959100101

  View details for PubMedID 16950965

• Antidepressant efficacy of agomelatine 25-50 mg versus venlafaxine 75-150 mg: two randomized, double blind studies 19th Congress of the European-College-of-Neuropsychopharmacology Kennedy, S. H., Guilleminault, C. ELSEVIER SCIENCE BV. 2006: S319–S320

  View details for Web of Science ID 000240771301013

• Antihypertensive treatment and endothelium-dependent venodilation in sleep-disordered breathing SLEEP AND BREATHING Duchna, H., Orth, M., Schultze-Werninghaus, G., Guilleminault, C., Stoohs, R. A. 2006; 10 (3): 115-122

  Abstract

  Sleep-disordered breathing (SDB) is associated with nitric oxide-mediated endothelial dysfunction and increased risk and prevalence of cardiovascular disease, namely, arterial hypertension. A substantial number of patients do not comply with nasal continuous positive airway pressure (nCPAP) treatment. These individuals have a persisting increased cardiovascular risk. Antihypertensive drugs have shown to improve nitric oxide-mediated endothelial dysfunction. We therefore designed a study to test the hypothesis that antihypertensive drug treatment in hypertensive patients with SDB can have beneficial effects on nitric oxide-mediated endothelial function in the absence of treatment with nCPAP. Six patients with SDB and treated arterial hypertension, six normotensive patients with SDB, and six healthy controls received sleep studies and an assessment of venodilation using the dorsal hand vein technique. Polygraphic measures using standard overnight sleep studies and dose-response curves to the endothelium-dependent vasodilator bradykinin were obtained. Maximum nitric-oxide-mediated dilation to bradykinin was significantly higher in patients with SDB who had received antihypertensive drug treatment compared to normotensive SDB patients. Nitric oxide-mediated dilation in hypertensive patients with SDB was similar to nitric oxide-mediated dilation in healthy controls. After treatment of normotensive patients with SDB using nCPAP, nitric oxide-mediated dilation in normotensive SDB patients was comparable to nitric oxide-mediated dilation in SDB patients with antihypertensive drug treatment and normal controls. Hypertensive patients with SDB present a normal nitric oxide-mediated endothelial function under antihypertensive treatment.

  View details for DOI 10.1007/s11325-006-0057-y

  View details for Web of Science ID 000244342100002

  View details for PubMedID 16607560

• Chronic fatigue, unrefreshing sleep and nocturnal polysomnography SLEEP MEDICINE Guilleminault, C., Poyares, D., da Rosa, A., Kirisoglu, C., Almeida, T., Lopes, M. C. 2006; 7 (6): 513-520

  Abstract

  To investigate the complaint of unrefreshing sleep with study of sleep electroencephalogram (EEG) in patients with chronic fatigue.Fourteen successively seen patients (mean age: 41.1 9.8) who complained of chronic fatigue but denied sleepiness and agreed to participate were compared to 14 controls (33.6+/-10.2 years) who were monitored during sleep recorded in parallel. After performing conventional sleep scoring we applied Fast Fourier Transformation (FFT) for the delta 1, delta 2, theta, alpha, sigma 1, sigma 2, beta EEG frequency bands. The presence of non-rapid eye movement (NREM) sleep instability was studied with calculation of cyclic alternating pattern (CAP) rate. Two-way analysis of variance (ANOVA) was performed to analyze FFT results and Mann-Whitney U-test to compare CAP rate in both groups of subjects.Slow wave sleep (SWS) percentage and sleep efficiency were lower, but there was a significant increase in delta 1 (slow delta) relative power in the chronic fatigue group when compared to normals (P<0.01). All the other frequency bands were proportionally and significantly decreased compared to controls. CAP rate was also significantly greater in subjects with chronic fatigue than in normals (P=0.04). An increase in respiratory effort and nasal flow limitation were noted with chronic fatigue.The complaints of chronic fatigue and unrefreshing sleep were associated with an abnormal CAP rate, with increase in slow delta power spectrum, affirming the presence of an abnormal sleep progression and NREM sleep instability. These specific patterns were related to subtle, undiagnosed sleep-disordered breathing.

  View details for DOI 10.1016/j.sleep.2006.03.016

  View details for Web of Science ID 000241212400007

  View details for PubMedID 16934523

• Emerging pharmacotherapeutic agents for insomnia: a hypnotic panacea? EXPERT OPINION ON PHARMACOTHERAPY Navab, P., Guilleminault, C. 2006; 7 (13): 1731-1738

  Abstract

  The burden of insomnia has had a significant effect not only on the socioeconomic matrix, but also the medical terrain, as signified by the increased morbidity and mortality of its associated psychiatric and organic sequelae. To this end, a plethora of pharmacotherapeutic agents have been recently introduced that address the vital need to combat insomnia and prevent the perpetuation in its chronic form. The previously and currently dispensed barbiturates and benzodiazepines, respectively, have paved the way for newer agents that are purported to be just as effective, or even more so, with a favourable profile in all domains of sleep. In assessing both published clinical studies and unpublished reports conducted on these emerging agents, this article profiles the most contemporary, therapeutic options in lieu of older hypnotics, over-the-counter medications and supplements. Furthermore, this paper aims to indicate both the future course of hypnotics and the developments currently in progress.

  View details for DOI 10.1517/14656566.7.13.1731

  View details for Web of Science ID 000240151300004

  View details for PubMedID 16925500

• Medical therapy for obstructive sleep apnea: A review by the medical therapy for obstructive sleep apnea task force of the standards of practice committee of the American academy of sleep medicine SLEEP Veasey, S. C., Guilleminault, C., Strohl, K. P., Sanders, M. H., Ballard, R. D., Magalang, U. J. 2006; 29 (8): 1036-1044

  Abstract

  A significant number of patients with obstructive sleep apnea neither tolerate positive airway pressure (PAP) therapy nor achieve successful outcomes from either upper airway surgeries or use of an oral appliance. The purpose of this paper, therefore, was to systematically evaluate available peer-reviewed data on the effectiveness of adjunctive medical therapies and summarize findings from these studies. A review from 1985 to 2005 of the English literature reveals several practical findings. Weight loss has additional health benefits and should be routinely recommended to most overweight patients. Presently, there are no widely effective pharmacotherapies for individuals with sleep apnea, with the important exceptions of individuals with hypothyroidism or with acromegaly. Treating the underlying medical condition can have pronounced effects on the apnea/hypopnea index. Stimulant therapy leads to a small but statistically significant improvement in objective sleepiness. Nonetheless, residual sleepiness remains a significant health concern. Supplemental oxygen and positional therapy may benefit subsets of patients, but whether these therapies reduce morbidities as PAP therapy does will require rigorous randomized trials. PAP therapy has set the bar high for successful treatment of sleep apnea and its associated morbidities. Nonetheless, we should strive towards the development of universally effective pharmacotherapies for sleep apnea. To accomplish this, we require a greater knowledge of the neurochemical mechanisms underlying sleep apnea, and we must use this infrastructure of knowledge to design well-controlled, adequately powered studies that examine, not only effects on the apnea/hypopnea index, but also the effects of pharmacotherapies on all health related outcomes shown beneficial with PAP therapy.

  View details for Web of Science ID 000240046400007

  View details for PubMedID 16944672

• Daytime sleepiness with and without cataplexy in Chinese-Taiwanese patients SLEEP MEDICINE Huang, Y., Tafti, M., Guilleminault, C. 2006; 7 (5): 454-457

  Abstract

  Investigation of Chinese-Taiwanese patients with excessive sleepiness, but no association with other sleep disorders, and with the presence or absence of cataplexy.Thirty-five patients, successively referred between 2002 and 2004, underwent polysomnography (PSG), repeat multiple sleep latency test (MSLT), and human leukocyte antigen (HLA) typing. Three patients without cataplexy also had cerebrospinal fluid (CSF) hypocretin measurements.DQB1*0602 was associated with cataplexy in over 90% of Chinese-Taiwanese cases. Absence of cataplexy and <2 sleep-onset REM periods (SOREMPs) was seen in only two subjects, but presence of two SOREMPs did not dissociate DQB1*0602 positive and negative or cataplexy positive and negative subjects. As a group, narcoleptics with cataplexy had a higher number of SOREMPs, and the mean sleep latency was much shorter in narcoleptics with cataplexy than in the non-cataplectic patients, independent of the number of SOREMPs.Chinese-Taiwanese patients with cataplexy present with similar HLA findings as Black and Caucasian patients, but the presence of two or more SOREMPs in Chinese-Taiwanese patients is not a sufficient diagnostic tool to identify narcolepsy. When cataplexy is not present, description of PSG nd HLA findings may be a better approach than using a label with little scientific significance, allowing for better collection of patients' phenotype.

  View details for DOI 10.1016/j.sleep.2006.05.009

  View details for Web of Science ID 000239947200009

  View details for PubMedID 16815745

• The Apnea Positive Pressure Long-term Efficacy Study (APPLES): rationale, design, methods, and procedures. Journal of clinical sleep medicine Kushida, C. A., Nichols, D. A., Quan, S. F., Goodwin, J. L., White, D. P., Gottlieb, D. J., Walsh, J. K., Schweitzer, P. K., Guilleminault, C., Simon, R. D., Leary, E. B., Hyde, P. R., Holmes, T. H., Bloch, D. A., Green, S., McEvoy, L. K., Gevins, A., Dement, W. C. 2006; 2 (3): 288-300

  Abstract

  To assess the size, time course, and durability of the effects of long-term continuous positive airway pressure (CPAP) therapy on neurocognitive function, mood, sleepiness, and quality of life in patients with obstructive sleep apnea.Randomized, double-blinded, 2-arm, sham-controlled, multicenter, long-term, intention-to-treat trial of CPAP therapy.Sleep clinics and laboratories at 5 university medical centers and community-based hospitals. Patients or Participants: Target enrollment is 1100 randomly assigned subjects across 5 clinical centers.Active versus sham (subtherapeutic) CPAP. Measurements and Results: A battery of conventional and novel tests designed to evaluate neurocognitive function, mood, sleepiness, and quality of life.The Apnea Positive Pressure Long-term Efficacy Study (APPLES) is designed to study obstructive sleep apnea and test the effects of CPAP through a comprehensive, controlled, and long-term trial in a large sample of subjects with obstructive sleep apnea.

  View details for PubMedID 17561541

• Cyclic alternating pattern as a sign of brain instability during sleep NEUROLOGIA Ferre, A., Guilleminault, C., Lopes, M. C. 2006; 21 (6): 304-311

  Abstract

  During the last 20 years, the fact that the role of microarousal arousal is very involved in the pathophysiology of sleep disorders has been widely demonstrated. However, in spite of this, the nature of microarousal is still under debate. The awakening system forms a part of the relationship between activation system and sleep maintenance, thus providing the natural evolution of sleep and defending it from the stimuli of the external world. The awakening system, that includes the concept of microarousal, can appear isolated or periodically, then receiving the name of cyclic alternating pattern (CAP). CAP may be affected by different factors that can alter its periodicity, thus offering quantitative information on sleep instability. It can also serve as another new tool to understand human sleep and as complementary information supplied by the sleep macrostructure and microarousal study. This study aims to explain the concept of CAP and its pathophysiology studied up to the present.

  View details for Web of Science ID 000239387500005

  View details for PubMedID 16799905

• [Cardiovascular comorbidities and obstructive sleep apnea]. Arquivos brasileiros de cardiologia Cintra, F. D., Poyares, D., Guilleminault, C., Carvalho, A. C., Tufik, S., De Paola, A. A. 2006; 86 (6): 399-407

  View details for PubMedID 16810413

• A case-control sleep study in children with polyarticular juvenile rheumatoid arthritis JOURNAL OF RHEUMATOLOGY Passarelli, C. M., Roizenblatt, S., Len, C. A., Moreira, G. A., Lopes, M. C., Guilleminault, C., Tufik, S., Hilario, M. O. 2006; 33 (4): 796-802

  Abstract

  To investigate the relationship between clinical manifestations and sleep abnormalities in patients with juvenile rheumatoid arthritis (JRA).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.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).Pain symptoms and disability are related to sleep fragmentation in patients with active polyarticular JRA.

  View details for Web of Science ID 000236745200026

  View details for PubMedID 16511937

• The effect of CNS activation versus EEG arousal during sleep on heart rate response and daytime tests CLINICAL NEUROPHYSIOLOGY Guilleminault, C., Abad, V. C., Philip, P., Stoohs, R. 2006; 117 (4): 731-739

  Abstract

  To induce a heart rate change in normal subjects using auditory stimulation without inducing EEG arousals and to assess the effects on daytime functioning and compare results to auditory stimulation leading to short EEG arousals.Six normal young men initially randomized into two groups (A and B) underwent 4 nights of nocturnal polysomnography (normal sleep on night 1, auditory stimulation without EEG arousal or normal sleep on nights 2 and 3 using Latin square design, and auditory stimulation with EEG arousal on night 4). MSLT and PVT were performed during days following nights 2-4.MSLT and PVT results showed significant differences after EEG arousal compared to stimulation without EEG arousal and to normal sleep; there were no significant differences after normal sleep compared to stimulation without EEG arousal. RR interval showed significant differences during undisturbed sleep compared to stimulation without EEG arousal and to stimulation with EEG arousal; RR interval without EEG arousal also differed significantly from RR interval with EEG arousal.Activation of the brain-stem can lead to autonomic nervous system (ANS) response without objective consequences the next day.ANS responses induced by auditory stimulation during sleep without EEG arousal do not have the same effects on daytime sleepiness and performance as sleep fragmentation associated with EEG arousals.

  View details for DOI 10.1016/j.clinph.2005.08.035

  View details for Web of Science ID 000236663800005

  View details for PubMedID 16458068

• Upper airway resistance syndrome: A long-term outcome study JOURNAL OF PSYCHIATRIC RESEARCH Guilleminault, C., Kirisoglu, C., Poyares, D., Palombini, L., Leger, D., Farid-Moayer, M., Ohayon, M. M. 2006; 40 (3): 273-279

  Abstract

  This prospective study aimed to assess symptomatic evolution of patients diagnosed with Upper Airway Resistance Syndrome (UARS) four and half years after the initial UARS diagnosis. For this purpose, 138 UARS patients were contacted by mail between 43 and 69 months after the initial evaluation; 105 responded to the letter and 94 patients accepted to undergo new clinical and polysomnographic evaluations. Initial and follow-up polysomnographic recordings were scored using the same criteria.Of the 94 patients who completed the follow-up examination, none of them were using nasal CPAP. It was related to refusal by insurance providers to provide equipment based on initial apnea-hypopnea index (AHI) in 90/94 subjects. Percentage of patients with sleep related-complaints significantly increased over the four and half year period: daytime fatigue, insomnia and depressive mood increased by 12 to 20 times. Reports of sleep maintenance sleep onset insomnia and depressive mood was significantly increased. Hypnotic, antidepressant and stimulant prescription increased from initial to follow-up visit (from 11.7% to 61.7%; from 3.2% to 25.5% and from 0% to 9.6%, respectively) with antidepressant given as much for sleep disturbance as mood disorder. The polysomnography results at follow-up showed that 5 subjects had AHI compatible with Obstructive Sleep Apnea Syndrome (OSAS) but overall, respiratory disturbance index had no significant change. Total sleep time was significantly reduced compared to initial visit.Many UARS patients remained untreated following initial evaluation. Worsening of symptoms of insomnia, fatigue and depressive mood were seen with absence of treatment of UARS.

  View details for DOI 10.1016/j.jpsychires.2005.03.007

  View details for Web of Science ID 000235856500013

  View details for PubMedID 16473570

• Sleepwalking, a disorder of NREM sleep instability SLEEP MEDICINE Guilleminault, C., Kirisoglu, C., Da Rosa, A. C., Lopes, C., Chan, A. 2006; 7 (2): 163-170

  Abstract

  Thirty-two chronic sleepwalkers who were part of a larger, previously reported sleepwalking group all achieved control of sleepwalking after undergoing treatment for an associated sleep disorder. In the current study, all records were blindly scored to perform a cyclic alternating pattern (CAP) analysis.Thirty-two young adult chronic sleepwalkers had polysomnography (PSG) on initial nights without sleepwalking events, as did age-matched normal controls and patients with mild sleep-disordered breathing (SDB). More than 90% of these patients with mild SDB had upper airway resistance syndrome (UARS). Ten randomly selected PSGs for sleepwalkers and matched controls also had quantitative electroencephalographic (EEG) analysis using Fast Fourier Transformation (FFT) with determination of delta power for each non-rapid eye movement (NREM)-REM sleep cycle.Compared to normal controls, an investigation of CAP in sleepwalkers demonstrated the presence of an abnormal CAP rate with a decrease in phase A1 and an increase in phases A2 and A3 on non-sleepwalking nights. The results of CAP analysis in sleepwalkers were similar to those obtained in age-matched UARS patients. Furthermore, the analysis of the first four NREM-REM sleep cycles reconfirmed the presence of an important decrease in delta power in sleep cycles 1 and 2 during a non-sleepwalking night in sleepwalkers compared to normal controls.The presence of both 'hypersynchronous slow delta' and 'burst of delta waves' have been reported in sleepwalkers, but their significance is controversial. These EEG patterns are similar to phase A1 (and possibly A2) of the CAP. Proper analysis of the sleep EEG of sleepwalkers should integrate CAP analysis. Sleepwalkers on a non-sleepwalking night present instability of NREM sleep, as demonstrated by this analysis. This instability is similar to the one noted in UARS patients. Subtle sleep disorders associated with chronic sleepwalking constitute the unstable NREM sleep background on which sleepwalking events occur. A subtle associated sleep disorder should be systematically searched for and treated in the presence of sleepwalking with abnormal CAP.

  View details for DOI 10.1016/j.sleep.2005.12.006

  View details for Web of Science ID 000236490900011

  View details for PubMedID 16459139

• Stroke and treatment with nasal CPAP EUROPEAN JOURNAL OF NEUROLOGY Palombini, L., Guilleminault, C. 2006; 13 (2): 198-200

  Abstract

  Stroke patients present a high prevalence of obstructive sleep apnea (OSA) and those with OSA have a higher mortality after 1 year and poorer functional outcome compared with others. The aim of this study was to prospectively evaluate the acceptance of nasal continuous positive airway pressure (CPAP) by recent stroke patients with OSA. Recruitment of non-comatose stroke patients with sufficient consciousness for diagnostic evaluation of OSA was performed and they were treated at home with nasal CPAP after hospital calibration and training on the usage of CPAP. Initial evaluation and regular follow-up of the home trial of auto-CPAP was carried out for a duration of 8 weeks. Of 50 initially recruited patients, 32 (100%) responded to the minimum cognitive criteria but seven patients (22%) only used nasal CPAP for 8 weeks. Subject dropout was related to difficulties with CPAP usage as perceived by patient and family members, facial weakness, motor impairment and increase difficulties and discomfort with usage of full-face mask. The majority of OSA stroke patients rejected CPAP treatment. Better education and support of patients and families, and special training sessions in rehabilitation services, will be needed to improve compliance.

  View details for Web of Science ID 000235470200016

  View details for PubMedID 16490054

• The effect of donepezil on sleep and REM sleep EEG in patients with Alzheimer disease: A double-blind placebo-controlled study SLEEP dos Santos Moraes, W. A., Poyares, D. R., Guilleminault, C., Ramos, L. R., Ferreira Bertolucci, P. H., Tufik, S. 2006; 29 (2): 199-205

  Abstract

  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.Randomized, double-blind, placebo-controlled design.Two sleep research centers, University Hospital.Thirty-five patients with mild to moderate Alzheimer disease, allocated to 2 groups: donepezil treated (n=17) and placebo treated (n=18).Patients were administered donepezil or placebo.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.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).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.

  View details for Web of Science ID 000240123500012

  View details for PubMedID 16494088

• The Apnea Positive Pressure Long-term Efficacy Study (APPLES): Rationale, Design, Methods, and Procedures JOURNAL OF CLINICAL SLEEP MEDICINE Kushida, C. A., Nichols, D. A., Quan, S. F., Goodwin, J. L., White, D. P., Gottlieb, D. J., Walsh, J. K., Schweitzer, P. K., Guilleminault, C., Simon, R. D., Leary, E. B., Hyde, P. R., Holmes, T. H., Bloch, D. A., Green, S., McEvoy, L. K., Gevins, A., Dement, W. C. 2006; 2 (3): 288-300

  View details for Web of Science ID 000209775800006

• Agomelatine: a preliminary review of a new antidepressant CNS Drug Zupancic M, Guilleminault C 2006; 20: 981-92
• Pharmacological management of sleep apnoea EXPERT OPINION ON PHARMACOTHERAPY Abad, V. C., Guilleminault, C. 2006; 7 (1): 11-23

  Abstract

  Obstructive sleep apnoea poses a significant health hazard that is associated with leading causes of mortality and morbidity. Nasal continuous positive airway pressure is the primary treatment modality, with surgical treatments as alternatives. Oral appliances and pharmacological therapy remain adjunctive modalities. Non-specific treatments include weight loss, postural therapy and behavioural measures. Pharmacotherapy goals include the reduction of risk factors for sleep apnoea; correction of underlying predisposing metabolic diseases, such as hypothyroidism or acromegaly; treatment of associated symptoms, including excessive daytime sleepiness; and prevention of apnoeas/hypopnoeas. This paper reviews data supporting the treatment of sleep apnoea with various pharmacological agents, including intranasal corticosteroids, decongestant sprays, nicotine therapy, opiate antagonists, methylxanthine derivatives, oestrogen and progesterone, testosterone, thyroid hormone, growth hormone therapy for acromegaly, beta-blockers, alpha-adrenergic agonists, angiotensin-converting enzyme inhibitors, glutamate antagonists, acetazolamide, selective serotonin re-uptake inhibitors, tricyclic antidepressants, physostigmine, modafinil and TNF-alpha antagonists, in addition to supplemental oxygen, and carbon dioxide inhalation. Some of these drugs have received very little testing and are the subject of few research articles.

  View details for DOI 10.1517/14656566.7.1.11

  View details for Web of Science ID 000234420300002

  View details for PubMedID 16370918

• Daytime sleepiness with and without cataplexy in Chinese-Taiwanese Sleep Med. Huang YS, Tafti M, Guilleminault C 2006; 7: 454-457
• Heart rate variability during sleep in patients with vasovagal syncope PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY Cintra, F., Poyares, D., Do Amaral, A., De Marchi, G., Barreto, S., Tufik, S., De Paola, A., Guilleminault, C. 2005; 28 (12): 1310-1316

  Abstract

  There are a few studies showing no significant heart rate variability (HRV) over a 24-hour period in vasovagal syncope (VVS) patients, but no research has examined HRV and its sympathetic and parasympathetic components during rapid eye movement (REM) and non-REM sleep. The authors hypothesized that REM sleep might be a critical state in which VVS patients would show abnormal responses.To analyze the sympathetic and parasympathetic components of HRV during REM and SWS in patients with VVS compared to normal subjects, and in patients with positive HUTT compared to negative ones.Thirty-seven VVS patients and 20 normal age-matched controls were submitted to polysomnography with 24-hour Holter monitoring to assess HRV. Time and frequency domain techniques were carefully performed for 24 hours and during Stages 3 and 4 of REM and non-REM sleep. Variation of sympathetic activity index (VSAI) was defined as the difference in the low frequency (LF) component of HRV between REM and Stages 3 and 4 of non-REM sleep. An analysis of variance was performed to compare patients and controls; patients with positive and negative head-up tilt testing.The LF component was lower in syncope compared to normal patients (1,769.54 +/- 1,738.17, 3,225.37 +/- 2,585.05, respectively, P = 0.03). There was a significant decrease in VSAI in the syncope group compared to the control group (-539.39 +/- 1,930.78, 1,268.10 +/- 2,420.20, respectively, P = 0.01). The other sleep variables analyzed including very LF, high frequency, low frequency/high frequency and time domain parameters did not reach statistical significance. Syncope patients also showed an increase in slow wave sleep (28.2 +/- 10.5, 19.7 +/- 7.8, P = 0.01).VVS patients exhibited sympathetic suppression during REM sleep. Possible mechanisms are discussed in this article.

  View details for Web of Science ID 000234255300008

  View details for PubMedID 16403163

• Is obstructive sleep apnea syndrome a neurological disorder? A continuous positive airway pressure follow-up study ANNALS OF NEUROLOGY Guilleminault, C., Huang, Y. S., Kirisoglu, C., Chan, A. 2005; 58 (6): 880-887

  Abstract

  Abnormal sensory responses have been found in the upper airway of obstructive sleep apnea patients, but no long-term study has been published previously regarding the evolution of obstructive sleep apnea syndrome and persistence of abnormal pharyngeal sensory evaluation in response to continuous positive airway pressure (CPAP) treatment. Over 5 years, we managed healthy, nonobese subjects compliant with nasal CPAP. Only 47 subjects completed this prospective study, due to protocol requirements. They underwent regular clinical evaluation, subjective scales, four polysomnographies without nasal CPAP, recalibration of nasal CPAP with polysomnography, regular downloading of home data, and a palatal two-point discrimination study. None of the subjects presented normal results at any checkpoint when they had been without CPAP for two or three nights. By the completion of the study, all subjects required an increase in nasal CPAP (1-7 cm H(2)O) and demonstrated abnormal two-point palatal discrimination compared with control subjects. Despite initial control of clinical symptoms with regular usage of nasal CPAP in subjects without weight change, abnormal sensory palatal evaluation was present at the conclusion of the study. Obstructive sleep apnea syndrome involves abnormal upper airway sensory input, which may be responsible for the development of apneas and hypopneas. These neurological lesions are persistent despite nasal CPAP treatment.

  View details for DOI 10.1002/ana.20654

  View details for Web of Science ID 000233703900009

  View details for PubMedID 16240364

• Is OSAS a neurologic disorder? 18th World Congress of Neurology Guilleminault, C., Huang, Y. S., Kirisoglu, C., Chan, A. ELSEVIER SCIENCE BV. 2005: S32–S32

  View details for Web of Science ID 000235088000132

• Non-REM-sleep instability in recurrent sleepwalking in pre-pubertal children SLEEP MEDICINE Guilleminault, C., Lee, J. H., Chan, A., Lopes, M. C., Huang, Y. S., da Rosa, A. 2005; 6 (6): 515-521

  Abstract

  We questioned whether or not the sleep of pre-pubertal children with recurrent sleepwalking was different from that recorded in normal children.Twelve pre-pubertal chronic sleepwalkers were compared to age- and gender-matched normal children. All children had a clinical evaluation covering pediatric, sleep, neuropsychiatric and otolaryngological fields. Two standardized sleep questionnaires were administered, and a minimum of two successive polysomnograms were performed with monitoring of sleep electroencephalographic (EEG) and cardiorespiratory variables. The research investigations were performed on nights without sleepwalking to search for the presence of other sleep disorders, including upper airway resistance syndrome (UARS). Sleep was scored using standard atlases, but it was also evaluated for the cyclic alternating pattern (CAP) rate.All sleepwalkers presented with either obstructive sleep apnea (n=2) or UARS (n=10). Compared to normal children, sleepwalkers had shorter total sleep time but no significant change in wake after sleep onset when considering all arousals > 3 s. CAP analysis showed a significantly higher CAP rate than in controls.Chronic sleepwalkers have instability of non-rapid eye movement (NREM) sleep detectable only by the calculation of CAP rate. Instability of NREM sleep was seen even on nights without sleepwalking and is probably related to the presence of the associated sleep disorders. We hypothesize that chronic NREM-sleep instability is a risk factor for occurrence of sleepwalking when further sleep disruption is triggered by external events.

  View details for DOI 10.1016/j.sleep.2005.03.003

  View details for Web of Science ID 000233577000006

  View details for PubMedID 15994122

• An animal model of a spontaneously reversible obstructive sleep apnea syndrome in the monkey NEUROBIOLOGY OF DISEASE Philip, P., Gross, C. E., Taillard, J., Bioulac, B., Guilleminault, C. 2005; 20 (2): 428-431

  Abstract

  The anatomies of the tongue and uvula in monkeys share many similarities with humans, such that this species has the closest approximation to the human upper airway than any other species. In this study, we investigated the feasibility of using small monkeys as experimental animals for an obstructive sleep apnea model. Monkeys received intradermal injections of liquid collagen in the uvula, tongue, and lateral pharyngeal walls every 2 weeks. Polysomnography was performed bi-monthly in order to control the impact of injections on breathing events, respiratory effort (as measured by esophageal pressure), and sleep. Before injections, the three animals showed normal breathing during sleep with a mean of 4.8 +/- 2.0 events/h. After injections, a mean of 27.9 +/- 19.7 hypopneas/h was recorded (P = 0.023). Total sleep time was significantly reduced, with a decrease of REM sleep and stage II sleep; however, stage I sleep increased. Collagen injections in monkey's upper airways can create sleep-disordered breathing and abnormal sleep, as seen in sleep apneic patients.

  View details for DOI 10.1016/j.nbd.2005.03.024

  View details for Web of Science ID 000233096700025

  View details for PubMedID 15886006

• Pediatric autopsy and informed parental consent ARCHIVES DE PEDIATRIE Rambaud, C., Guilleminault, C. 2005; 12 (10): 1478-1482

  Abstract

  In French legal terminology, the definition of autopsy is "organs'withholding". This phrase is ambiguous, meaning both removing the organs for their macroscopic exam and their retention for subsequent histology. The autopsy of a child requires an informed consent from both parents. The issue is that the pathologist who performs the autopsy is not the one who delivers the information and gets the parents' consent: therefore, he does not know what they were told and what they actually agreed upon.A questionnaire was sent to 3 groups of paediatricians (N=891) to approach their knowledge regarding autopsy.Among 362 paediatricians who answered the questionnaire, 57.2% never attended an autopsy and procedures were badly known. They did not know whether or not organs, were systematically sampled especially brain. Regarding the possibility of conservation of organs, a majority thought that one should not solely answer to parents'queries (63.8%) but rather that one should point out every possibility, without giving the ins and outs (60.8%). The majority favoured organs retention and use for research.We make 3 suggestions: to register autopsy in the Natioanal Securite Sociale nomenclature, to establish information and consent forms for organs'removal, retention and disposal, and to offer parents the possibility of an interview with the pathologist before and/or after the autopsy, in association with the paediatrician.

  View details for DOI 10.1016/j.arcped.2005.06.004

  View details for Web of Science ID 000233213900006

  View details for PubMedID 16061365

• Long-term effects of nasal continuous positive airway pressure on vasodilatory endothelial function in obstructive sleep apnea syndrome. Sleep & breathing = Schlaf & Atmung Duchna, H., Orth, M., Schultze-Werninghaus, G., Guilleminault, C., Stoohs, R. A. 2005; 9 (3): 97-103

  Abstract

  Obstructive sleep apnea syndrome (OSAS) is associated with a dysfunction of vascular endothelial cells. The aim of this study was to investigate long-term improvement of endothelial dysfunction in OSAS with nasal continuous positive airway pressure (nCPAP) treatment. We investigated endothelium-dependent and endothelium-independent vasodilatory function in patients with OSAS using the hand vein compliance technique. Dose-response curves to endothelium-dependent vasodilator bradykinin were obtained in 16 subjects with OSAS before and after 6 months of nCPAP therapy and in 12 control subjects without OSAS. Maximum dilation (Emax) to bradykinin, being impaired in all OSAS patients, was completely restored with nCPAP. Mean Emax to bradykinin rose from 54.9+/-18.5 to 108.2+/-28.7% with 164.4+/-90.0 nights of nCPAP therapy (p<0.0001; Emax healthy controls, 94.8+/-9.5%). At treatment follow-up, endothelium-dependent vasodilatory capacity was not significantly different in nCPAP-treated OSAS patients vs healthy controls. Mean vasodilation with endothelium independently acting nitroglycerin was not altered initially and did not change with nCPAP therapy indicating that nCPAP restored endothelial cell function and not unspecific, endothelium-independent factors. These results suggest that regular nocturnal nCPAP treatment leads to a sustained restoration of OSAS-induced impaired endothelium-dependent nitric oxide-mediated vasodilation, suggesting an improvement of systemic endothelial dysfunction in patients studied.

  View details for PubMedID 16021522

• Heart rate variability, sympathetic and vagal balance and EEG arousals in upper airway resistance and mild obstructive sleep apnea syndromes SLEEP MEDICINE Guilleminault, C., Poyares, D., Rosa, A., Huang, Y. S. 2005; 6 (5): 451-457

  Abstract

  We questioned the role of respiratory events in obstructive sleep apnea syndrome (OSAS) and of upper airway resistance syndrome (UARS) on heart rate (HR) during sleep, paying specific attention to the termination of the abnormal breathing events and examining the presence of arousals or termination with only central nervous system (CNS) activation.Twenty patients, 10 with UARS and 10 with mild OSAS, were studied. A nocturnal polysomnogram was performed including measurement of respiratory variables and pulse transit time (PTT). According to the presence or absence of a PTT event indicative of autonomic nervous system (ANS) activation, 148 events were extracted after having been randomly chosen in each represented sleep stage, with or without an electroencephalogram (EEG) arousal >1.5s. RR interval (RRI) in electrocardiogram (ECG) recordings, as well as heart rate variability, was calculated during 60 and 120s, respectively. Period amplitude analysis (PAA) was applied for RR-interval analysis, and fast Fourier transformation (FFT) was applied to perform HR variability analysis.Visually scored EEG arousal was significantly associated with an increase in sympathetic index of heart rate, while PTT was associated with a drop in parasympathetic index, after the respiratory events. Patients with mild OSAS presented persistently shorter RRI when compared to patients with UARS. The latter also exhibited a significant decrease in parasympathetic index (High Frequency (HF)) at the termination of a respiratory event.The HF component was only significantly decreased in patients with UARS, which indicates a predominant involvement of the parasympathetic tone in patients with UARS in comparison to those with OSAS.

  View details for DOI 10.1016/j.sleep.2005.03.014

  View details for Web of Science ID 000232676100012

  View details for PubMedID 15994124

• SPECT findings in the Kleine-Levin syndrome SLEEP Huang, Y. S., Guilleminault, C., Kao, P. F., Liu, F. Y. 2005; 28 (8): 955-960

  Abstract

  The Kleine-Levin Syndrome, is a rare disorder with onset during teenage years, but little is known on etiopathogenesis. Seven subjects with Kleine-Levin Syndrome accumulated over time had systematic SPECT studies during (n=5) and out (n=7) of the symptomatic period.Seven boys with symptom onset between 11 and 17 years of age and at least 2 episodes per year were followed for a mean of 6 years.Electroencephalogram awake-asleep, computed tomography scan, and magnetic resonance imaging studies were performed before Tc-99m ECD single photon emission tomography (SPECT) obtained during day 4 or 5 (n=5) and at least 1 month away from the symptomatic period (n=7).All imaging tests except SPECT were normal. Hypoperfusion of both thalami were seen during the symptomatic period that completely disappeared during the asymptomatic period. Hypoperfusion in other regions were also noted in some, but not all subjects. They persisted during the asymptomatic period in 2 cases over the temporal lobe (2/7 cases), frontal lobe (1/7 cases), and basal ganglia (1/7 cases). The largest amount of persistent hypoperfusion was seen in the subject with longest clinical evolution.Hypoperfusion of the thalamus is a consistent finding during the symptomatic period, but perfusion abnormalities may persist even during the asymptomatic period. The longer the duration of the syndrome, the more extended the hypoperfusion regions during the asymptomatic period.

  View details for Web of Science ID 000231273900008

  View details for PubMedID 16218078

• Pediatric obstructive sleep apnea syndrome ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE Guilleminault, C., Lee, J. H., Chan, A. 2005; 159 (8): 775-785

  Abstract

  To review evidence-based knowledge of pediatric obstructive sleep apnea syndrome (OSAS).We reviewed published articles regarding pediatric OSAS; extracted the clinical symptoms, syndromes, polysomnographic findings and variables, and treatment options, and reviewed the authors' recommendations.Orthodontic and craniofacial abnormalities related to pediatric OSAS are commonly ignored, despite their impact on public health. One area of controversy involves the use of a respiratory disturbance index to define various abnormalities, but apneas and hypopneas are not the only abnormalities obtained on polysomnograms, which can be diagnostic for sleep-disordered breathing. Adenotonsillectomy is often considered the treatment of choice for pediatric OSAS. However, many clinicians may not discern which patient population is most appropriate for this type of intervention; the isolated finding of small tonsils is not sufficient to rule out the need for surgery. Nasal continuous positive airway pressure can be an effective treatment option, but it entails cooperation and training of the child and the family. A valid but often overlooked alternative, orthodontic treatment, may complement adenotonsillectomy.Many complaints and syndromes are associated with pediatric OSAS. This diagnosis should be considered in patients who report the presence of such symptoms and syndromes.

  View details for Web of Science ID 000230948900014

  View details for PubMedID 16061787

• Erectile dysfunction, obstructive sleep apnea syndrome and nasal CPAP treatment SLEEP MEDICINE Goncalves, M. A., Guilleminault, C., Ramos, E., Palha, A., Paiva, T. 2005; 6 (4): 333-339

  Abstract

  To evaluate the effect of one month of continuous positive airway pressure (CPAP) in a subgroup of obstructive sleep apnea (OSA) patients with erectile dysfunction (ED) and compare this subgroup with age- and body mass index (BMI)-matched OSA patients without ED.Prospective general, sleep, psychiatric and sexologic evaluations were conducted. Epworth Sleepiness Scale (ESS), Beck Depression Inventory (BDI), Sleep Disorders Questionnaire (SDQ), Quality of Life SF-36, and polysomnography were used. Seventeen OSA patients with ED were compared prior to CPAP treatment and during CPAP treatment with age- and BMI-matched OSA patients without ED. Parametric and non-parametric statistics, chi-square, Fisher exact test and multiple regression analyses were performed.Ninety-eight men (BMI=28.8 kg/m2, apnea-hypopnea index (AHI)=49.6 events/h, ESS=14.8, BDI=8.4, and lowest SaO2=75.3%) were divided into subgroups of lowest SaO2>80% (A) and lowest SaO2< or =80% (B). (A) Forty-six men had a mean lowest SaO2 of 85.7%+/-2.9, AHI=29.5+/-17.6, age=46.3+/-9.3 years, ESS=13.6+/-4.2, BMI=25.8+/-4.8. Seven of the patients had ED. (B) Fifty-two men had a mean lowest SaO2=60.10+/-10.0%, AHI=67.4+/-24.5, BDI=9.0+/-6.9, age=47.4+/-9.4 years, ESS=16.2+/-4.4, BMI=31.4+/-5.1. Twenty-one of the patients had ED (chi2: P=0.006). Significant variables for ED were lowest SaO2 and age (r=0.17). CPAP-treated subgroup: ED subjects had significantly lower SaO2, ESS, BDI and SF-36 subscale scores than OSA controls. Nasal CPAP eliminated the differences between groups, and ED was resolved in 13 out of 17 cases.ED in OSAS is related to nocturnal hypoxemia, and about 75% of OSAS patients with ED treated with nasal CPAP showed remission at one-month follow-up, resulting in significant improvement in quality of life.

  View details for DOI 10.1016/j.sleep.2005.03.001

  View details for Web of Science ID 000230690000008

  View details for PubMedID 15946896

• [Violent behavior during sleep]. Revista brasileira de psiquiatria Poyares, D., Almeida, C. M., Silva, R. S., Rosa, A., Guilleminault, C. 2005; 27: 22-26

  Abstract

  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.

  View details for PubMedID 16082451

• Fatigue, sleep restriction and driving performance ACCIDENT ANALYSIS AND PREVENTION Philip, P., Sagaspe, P., Moore, N., Taillard, J., Charles, A., Guilleminault, C., Bioulac, B. 2005; 37 (3): 473-478

  Abstract

  We ran a randomized cross-over design study under sleep-deprived and non-sleep-deprived driving conditions to test the effects of sleep restriction on real driving performance. The study was performed in a sleep laboratory and on an open French highway. Twenty-two healthy male subjects (age = 21.5 +/- 2 years; distance driven per year = 12,225 +/- 4739 km (7641 +/- 2962 miles) [mean +/- S.D.]) drove 1000 km (625 miles) over 10 h during five 105 min sessions on an open highway. Self-rated fatigue and sleepiness before each session, number of inappropriate line crossings from video recordings and simple reaction time (RT) were measured. Total crossings increased after sleep restriction (535 crossings in the sleep-restricted condition versus 66 after non-restricted sleep (incidence rate ratio (IRR): 8.1; 95% confidence interval (95% CI): 3.2-20.5; p < 0.001)), from the first driving session. The interaction between the two factors (conditionxtime of day) was also significant (F(5, 105) = 3.229; p < 0.05). Increasing sleepiness score was associated with increasing crossings during the next driving session in the sleep-restricted (IRR: 1.9; 95% CI: 1.4-2.4) but not in the non-restricted condition (IRR: 1.0; 95% CI: 0.8-1.3). Increasing self-perceived fatigue was not associated with increasing crossings in either condition (IRR: 0.95; 95% CI: 0.93-0.98 and IRR: 1.0; 95% CI: 0.98-1.02). Rested subjects drove 1000 km with four shorts breaks with only a minor performance decrease. Sleep restriction induced important performance degradation even though time awake (8h) and session driving times (105 min) were relatively short. Major inter-individual differences were observed under sleep restriction. Performance degradation was associated with sleepiness and not fatigue. Sleepiness combined with fatigue significantly affected RT. Road safety campaigns should encourage drivers to avoid driving after sleep restriction, even on relatively short trips especially if they feel sleepy.

  View details for DOI 10.1016/j.aap.2004.07.007

  View details for Web of Science ID 000228310000011

  View details for PubMedID 15784201

• HD-16: a new quality of life instrument specifically designed for insomnia SLEEP MEDICINE Leger, D., Scheuermaier, K., Raffray, T., Metlaine, A., Choudat, D., Guilleminault, C. 2005; 6 (3): 191-198

  Abstract

  To design a new quality of life (QoL) instrument specifically for insomnia.Based on severe insomniacs' interviews, we have built a new quality of life scale that has been tested in one group of 240 severe insomniacs, in one group of 422 mild insomniacs and in one group of 391 good sleepers. Ten steps led to the construction of a specific QoL scale.Five dimensions have been validated as both relevant and independent from each other. Sixteen items out of the 43 initially tested were retained and significantly different within the groups in each dimension. Based on the 16 items selected, we called the scale Hotel Dieu 16 (HD-16). We have therefore verified the score's specificity (correlation score of +0.36) and the reliability of the scale (Cronbach coefficient alpha=0.78).HD-16 may be used as a focused instrument to better assess an insomniac's quality of life.

  View details for DOI 10.1016/j.sleep.2005.03.013

  View details for Web of Science ID 000229262000001

  View details for PubMedID 15854848

• Adult chronic sleepwalking and its treatment based on polysomnography BRAIN Guilleminault, C., Kirisoglu, C., Bao, G., Arias, V., Chan, A., Li, K. K. 2005; 128: 1062-1069

  Abstract

  Adult sleepwalking affects 2.5% of the general population and may lead to serious injuries. Fifty young adults with chronic sleepwalking were studied prospectively. Clinical evaluation, questionnaires from patients and bed partners, and polysomnography were obtained on all subjects in comparison with 50 age-matched controls. Subjects were examined for the presence of psychiatric anxiety, depression and any other associated sleep disorder. Isolated sleepwalking or sleepwalking with psychiatric disorders was treated with medication. All other patients with other sleep disorders were treated only for their associated problem. Prospective follow-up lasted 12 months after establishment of the most appropriate treatment. Patients with only sleepwalking, treated with benzodiazepines, dropped out of follow-up testing and reported persistence of sleepwalking, as did patients with psychiatric-related treatment. Chronic sleepwalkers frequently presented with sleep-disordered breathing (SDB). All these patients were treated only for their SDB, using nasal continuous positive airway pressure (CPAP). All nasal CPAP-compliant patients had control of sleepwalking at all stages of follow-up. Non-compliant nasal CPAP patients had persistence of sleepwalking. They were offered surgical treatment for SDB. Those successfully treated with surgery also had complete resolution of sleepwalking. Successful treatment of SDB, which is frequently associated with chronic sleepwalking, controlled the syndrome in young adults.

  View details for DOI 10.1093/brain/awh481

  View details for Web of Science ID 000228635300016

  View details for PubMedID 15817520

• Neuromuscular disorders and sleep. Current neurology and neuroscience reports Oztura, I., Guilleminault, C. 2005; 5 (2): 147-152

  Abstract

  Neuromuscular disorders are caused by the primary involvement of the motor unit. In these patients, sleep-disordered breathing (SDB) due to respiratory muscle weakness is often encountered during sleep. Because there is a tendency to overlook this disorder, all patients with neuromuscular disorders should be questioned about SDB. Overnight polysomnography is the best investigation for SDB and nocturnal desaturations. In the management of these patients, noninvasive intermittent positive pressure ventilation results in improvement of SDB and breathing.

  View details for PubMedID 15743553

• Comparison of pleural pressure and transcutaneous diaphragmatic electromyogram in obstructive sleep apnea syndrome SLEEP Stoohs, R. A., Blum, H. C., Knaack, L., Butsch-Von-Der-Heydt, B., Guilleminault, C. 2005; 28 (3): 321-329

  Abstract

  Based on studies of the impact of esophageal pressure on cardiovascular variables during sleep, this signal can be used to refine the severity level in the clinical diagnosis of obstructive sleep apnea syndrome. We hypothesized that relative changes in diaphragmatic electromyogram (EMG) can reflect short-term changes in esophageal pressure durng obstructive apneas and hypopneas.Diaphragmatic EMG was sampled at 0.25 kHz; diaphragmatic EMG waveform was band-pass filtered and digitally converted; the electrocardiogram artifact was eliminated; using a gating procedure, the waveform was fast-Fourier transformed and digitally rectified; and a moving average of 200 milliseconds was calculated. For each inspiratory effort during apnea or hypopnea, we calculated maximum diaphragmatic EMG and esophageal pressure. Data were normalized calculating the percentage difference between the first obstructed and each subsequent inspiratory effort during the respiratory event.Sleep disorders laboratory.9 patients with moderate obstructive sleep apnea syndrome presenting with apneas and hypopneas during sleep.None.861 respiratory events were scored, and the evolution between esophageal pressure and diaphragmatic EMG were compared. Normalized data showed a good correlation between the 2 measures during apneas and hypopneas. There was a significant difference between the percentage increase in esophageal pressure and diaphragmatic EMG for apneas and hypopneas (esophageal pressure, apnea: 118.1% +/- 118.5%, hypopnea: 76.1% +/- 74.3%, P = .000; diaphragmatic EMG, 123.5% +/- 131.7%, hypopnea: 73.3% +/- 74.2%, P = .000). No significant differences for apnea or hypopnea were noted between the 2 measures under investigation.Diaphragmatic EMG may be clinically useful to describe relative changes in respiratory effort under conditions of apnea and hypopnea during sleep and to reliably dissociate central from obstructive events where esophageal pressure monitoring is not readily available.

  View details for Web of Science ID 000227349000009

  View details for PubMedID 16173653

• The scoring of arousals in healthy term infants (between the ages of 1 and 6 months) JOURNAL OF SLEEP RESEARCH Ariagno, R., Bentele, K., Bardini, M. R., Brouillette, R., Bruni, O., Challamel, M. J., Curzi-dascalova, L., Dalmaz, Y., Donzelli, G., Dubru, J. M., Fagioli, I., Ferber, R., Ficca, G., Franco, P., Francois, G., Gaultier, C., Gingras, J., Groswasser, J., Guilleminault, C., Hoppenbrouwers, T., Horne, R., Hunt, K., Jorch, G., Kahn, A., Katz-Salomon, M., Keens, T., Lagercrantz, H., Lecendreux, M., Marcus, C., Milrad, J., Mirmiran, M., Mitchell, E., Navelet, Y., Peirano, P., Piumelli, R., Plouin, P., Poets, C., Ravet, F., Rivarola, M. R., Ronchetti, M., Salzarulo, P., Taylor, B., Thach, B., Urschitz, M., Veccherini, M. F., Maria, P. V., Wulbrand, H., Zotter, H. 2005; 14 (1): 37-41

  Abstract

  Various definitions of arousals have been used in infants. An international group of experts has worked on a consensus for the scoring of arousals in healthy infants, aged between 1 and 6 months. This opinion paper summarizes the consensus statement on the scoring of arousal. The paper reviews recommended techniques for the recording of arousal in infants. Scoring includes the differentiation between subcortical activation, with no visible change n the electroencephalograph (EEG) recording, and cortical arousals associated with EEG changes. The arousals are further scored as spontaneous or induced, according to environmental conditions. Potential limitations to the method are discussed, with the hope that this document could contribute to promote further progresses in the scoring of infants arousals from sleep.

  View details for Web of Science ID 000227316500006

  View details for PubMedID 15743332

• Cyclic alternating pattern in peripubertal children SLEEP Lopes, M. C., Rosa, A., Roizenblatt, S., Guilleminault, C., Passarelli, C., Tufik, S., Poyares, D. 2005; 28 (2): 215-219

  Abstract

  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.Descriptive study.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.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%).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.

  View details for Web of Science ID 000226905000009

  View details for PubMedID 16171246

• The upper airway syndrome: clinical relevance and pathophysiology REVUE DES MALADIES RESPIRATOIRES Guilleminault, C., Leger, D. 2005; 22 (1): 27-30

  View details for Web of Science ID 000228071600007

  View details for PubMedID 15968754

• Sleep and psychiatry. Dialogues in clinical neuroscience Abad, V. C., Guilleminault, C. 2005; 7 (4): 291-303

  Abstract

  Psychiatric disorders constitute 15.4% of the disease burden in established market economies. Many psychiatric disorders are associated with sleep disturbances, and the relationship is often bidirectional. This paper reviews the prevalence of various psychiatric disorders, their clinical presentation, and their association with sleep disorders. Among the psychiatric disorders reviewed are affective disorders, psychosis, anxiety disorders (including posttraumatic stress disorder), substance abuse disorders, eating disorders, and attention deficit/hyperactivity disorders. The spectrum of associated sleep disorders includes insomnia, hypersomnia, nocturnal panic, sleep paralysis, hypnagogic hallucinations, restless legs/periodic limb movements of sleep, obstructive sleep apnea, and parasomnias. The effects on sleep of various psychotropic medications utilized to treat the above psychiatric disorders are summarized.

  View details for PubMedID 16416705

  View details for PubMedCentralID PMC3181745

• History of the Development of Sleep Medicine in the United States JOURNAL OF CLINICAL SLEEP MEDICINE Shepard, J. W., Buysse, D. J., Chesson, A. L., Dement, W. C., Goldberg, R., Guilleminault, C., Harris, C. D., Iber, C., Mignot, E., Mitler, M. M., Moore, K. E., Phillips, B. A., Quan, S. F., Rosenberg, R. S., Roth, T., Schmidt, H. S., Silber, M. H., Walsh, J. K., White, D. P. 2005; 1 (1): 61-82

  Abstract

  Sleep Medicine has only recently been recognized as a specialty of medicine. Its development is based on an increasing amount of knowledge concerning the physiology of sleep, circadian biology and the pathophysiology of sleep disorders. This review chronicles the major advances in sleep science over the past 70 years and the development of the primary organizations responsible for the emergence of Sleep Medicine as a specialty, sleep disorders as a public health concern and sleep science as an important area of research.

  View details for Web of Science ID 000209775200013

• C-reactive protein and sleep-disordered breathing SLEEP Guilleminault, C., Kirisoglu, C., Ohayon, M. M. 2004; 27 (8): 1507-1511

  Abstract

  Over a 2-month period, to evaluate serum levels of C-reactive protein (CRP) in new patients with obstructive sleep apnea syndrome (OSAS), upper airway resistance syndrome (UARS), and absence of important comorbidity, as well as in normal controls.Cross-sectional analysis.Sleep disorders clinic.239 successively monitored subjects: 156 subjects were diagnosed with OSAS, 39 with UARS, and 54 controls.none.Clinical information (neurologic, general medical, and otolaryngology examination), body mass index, neck circumference, hip-waist ratio, Epworth Sleepiness Scale, 3 fatigue scales, Sleep Disorders Questionnaire, serum CRP, and polysomnography were collected. Analysis of variance indicated a significant difference between the groups for diastolic blood pressure, respiratory disturbance index, lowest SaO2, and body mass index. The mean serum CRP level was normal in all 3 groups. Only 15 (14 OSAS and 1 UARS) out of 239 subjects had high serum CRP values. CRP levels were significantly correlated with body mass index, esophageal pressures, hip-waist ratio, neck circumference, and blood pressure. Only body mass index was significantly associated with high CRP values; multiple regression showed: adjusted R2 = 0.115, beta = 0.345, P <.001. When men and women were considered separately, body mass index was again significantly associated with high CRP levels.Obesity is a risk factor for high serum CRP levels in patients with sleep-disordered breathing, as in the general population.

  View details for Web of Science ID 000226076000014

  View details for PubMedID 15683141

• Does benign "primary snorting" ever exist in children? CHEST Guilleminault, C., Lee, J. H. 2004; 126 (5): 1396-1398

  View details for Web of Science ID 000225214700002

  View details for PubMedID 15539698

• Emerging drugs for narcolepsy. Expert opinion on emerging drugs Abad, V. C., Guilleminault, C. 2004; 9 (2): 281-291

  Abstract

  Narcolepsy is characterised by excessive daytime sleepiness, usually associated with cataplexy, hypnagogic hallucinations, sleep paralysis and fragmented nocturnal sleep. Although uncommon, it results in significant disability. Most cases occur sporadically, but genetic factors probably form a susceptibility background on which unknown environmental triggers act. The hypocretin system is strongly implicated in the development of narcolepsy. Cerebrospinal fluid levels of hypocretin-1 are significantly reduced in narcoleptic subjects with cataplexy. Despite the advances in our understanding of narcolepsy, current therapy is primarily symptomatic. Stimulants (standard and novel) combat excessive daytime sleepiness. Antidepressants (tricyclics, dual-action or selective serotonin re-uptake inhibitors) and sodium oxybate are anticataplexy agents. Hypnagogic hallucinations and sleep paralysis respond to antidepressants. Sodium oxybate consolidates sleep. Novel and experimental treatments include histamine antagonists, hypocretin agonists, slow-wave sleep enhancers, intravenous gamma-globulin, tramadol and corticosteroids.

  View details for PubMedID 15571485

• Upper airway resistance syndrome-one decade later CURRENT OPINION IN PULMONARY MEDICINE Bao, G., Guilleminault, C. 2004; 10 (6): 461-467

  Abstract

  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.

  View details for Web of Science ID 000224924300002

  View details for PubMedID 15510051

• "Back to sleep" and unexplained death in infants SLEEP Rambaud, C., Guilleminault, C. 2004; 27 (7): 1359-1366

  Abstract

  Investigation of body position in infants with sudden and apparently unexplained death. Determination of the upper airway space of the infants in different positions by computed tomography (CT) scan. Comparison of the CT scan, the body position at death scene, and the autopsy results.Prospective investigation on all infants referred to a specialized center investigating abrupt and apparently unexplained death of infants.Full-term infants with sudden and clinically unexplained death. Four extra infants studied at different postmortem times to verify absence of change in measurement in postmortem CT scan over time.Position of infant when found dead. CT scan of upper airway in 3 positions (prone face down, prone head rotated, supine nose up), presence or absence of upper airway obstruction, level and length of the obstruction, presence or absence of cause of death, and presence or absence of small maxillomandibular complex at autopsy.Twenty-seven children had unexpected crib deaths (17 of them determined to be sudden infant death syndrome at autopsy). Fourteen children were found dead in the prone position; for 8 of them, this was their normal sleeping position. Airway occlusion behind the base of tongue was seen on CT scan in 24 of the 27 infants (89%) when placed prone head down; in 13 (48%) when placed prone with the head rotated to the side, and in 5 (18%) infants in the supine position. Four infants had mild facial dysplasia and had been found dead in the supine position; in 3 of them, sudden infant death syndrome was found to be the cause of death. The stability of CT scan findings over time was demonstrated after death in 3 different body positions.Supine sleeping position may not be necessarily protective when small jaws are present, and sleeping position may also be a factor in abrupt deaths in infants even if "explained by autopsy."

  View details for Web of Science ID 000225093100015

  View details for PubMedID 15586789

• Meta-analysis of quantitative sleep parameters from childhood to old age in healthy individuals: Developing normative sleep values across the human lifespan SLEEP Ohayon, M. M., Carskadon, M. A., Guilleminault, C., Vitiello, M. V. 2004; 27 (7): 1255-1273

  Abstract

  The purposes of this study were to identify age-related changes in objectively recorded sleep patterns across the human life span in healthy individuals and to clarify whether sleep latency and percentages of stage 1, stage 2, and rapid eye movement (REM) sleep significantly change with age.Review of literature of articles published between 1960 and 2003 in peer-reviewed journals and meta-analysis.65 studies representing 3,577 subjects aged 5 years to 102 years.The research reports included in this meta-analysis met the following criteria: (1) included nonclinical participants aged 5 years or older; (2) included measures of sleep characteristics by "all night" polysomnography or actigraphy on sleep latency, sleep efficiency, total sleep time, stage 1 sleep, stage 2 sleep, slow-wave sleep, REM sleep, REM latency, or minutes awake after sleep onset; (3) included numeric presentation of the data; and (4) were published between 1960 and 2003 in peer-reviewed journals.In children and adolescents, total sleep time decreased with age only in studies performed on school days. Percentage of slow-wave sleep was significantly negatively correlated with age. Percentages of stage 2 and REM sleep significantly changed with age. In adults, total sleep time, sleep efficiency, percentage of slow-wave sleep, percentage of REM sleep, and REM latency all significantly decreased with age, while sleep latency, percentage of stage 1 sleep, percentage of stage 2 sleep, and wake after sleep onset significantly increased with age. However, only sleep efficiency continued to significantly decrease after 60 years of age. The magnitudes of the effect sizes noted changed depending on whether or not studied participants were screened for mental disorders, organic diseases, use of drug or alcohol, obstructive sleep apnea syndrome, or other sleep disorders.In adults, it appeared that sleep latency, percentages of stage 1 and stage 2 significantly increased with age while percentage of REM sleep decreased. However, effect sizes for the different sleep parameters were greatly modified by the quality of subject screening, diminishing or even masking age associations with different sleep parameters. The number of studies that examined the evolution of sleep parameters with age are scant among school-aged children, adolescents, and middle-aged adults. There are also very few studies that examined the effect of race on polysomnographic sleep parameters.

  View details for Web of Science ID 000225093100005

  View details for PubMedID 15586779

• Periodic leg movements in prepubertal children with sleep disturbance DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY Martinez, S., Guilleminault, C. 2004; 46 (11): 765-770

  Abstract

  This study's aims were to determine: (1) prevalence of periodic leg movements (PLMs) in walking prepubertal children consulting a sleep clinic for any sleep disorder; (2) associations between PLMs and other sleep and medical disorders; and (3) the response of other sleep disorders to treatment with the dopamine agonist pramipexol. Clinical evaluation and polysomnography were carried out for a period of 12 months on 252 consecutively seen, prepubertal children with sleep disorders (156 males, 96 females; aged 15mo to 11y, mean 7y 1mo, SD3y 10mo). Sleep disorders unrelated to PLMs were treated, and six children received pramipexol for PLMs. Follow-up included clinical evaluation and polysomnography. Twenty-three per cent of children were diagnosed with PLMs on the basis of polysomnography. The presence of PLMs had usually been unrecognized clinically. The only clinical symptom that could be related to periodic limb movement disorder was a report of leg pains at morning awakening. Only two of 58 children had PLMs without other clinical or polysomnographic findings. Comorbidity seen with PLMs included neuropsychiatric syndromes (n=20), isolated sleep disordered breathing (SDB; n=29), and several other comorbid conditions (n=7). Seven of 11 children seen with attention-deficit-hyperactivity disorder also had PLMs. Surgery for SDB was associated with subsequent cessation of PLMs in 15 of 29 children. Five out of six children with PLMs who received pramipexol were able to tolerate the drug and experienced a complete disappearance of their PLMs. Presence of chronic fatigue, sleepiness, disrupted nocturnal sleep, and difficulties in falling asleep should lead to a systematic search for PLMs that is independent of associated syndromes. Isolated treatment of SDB might help eliminate some, but not all, PLMs.

  View details for DOI 10.1017/S0012162204001318

  View details for Web of Science ID 000225066000008

  View details for PubMedID 15540638

• Somnambulism (sleepwalking) EXPERT OPINION ON PHARMACOTHERAPY Remulla, A., Guilleminault, C. 2004; 5 (10): 2069-2074

  Abstract

  Somnambulism is an arousal parasomnia consisting of a series of complex behaviours that result in large movements in bed or walking during sleep. It occurs in 2-14% of children and 1.6-2.4% of adults. Occasional benign episodes are managed conservatively. However, recurrent sleepwalking with a risk of injury to self or others mandates immediate treatment with pharmacotherapy while awaiting work-up. The most commonly used medications are benzodiazepines, particularly clonazepam, with tricyclic antidepressants and serotonin selective re-uptake inhibitors also administered. Treatment of underlying causes such as obstructive sleep apnoea, upper airway resistance syndrome, restless legs syndrome and periodic limb movements, is currently the best approach and usually eliminates somnambulism in children and adults.

  View details for Web of Science ID 000224228800003

  View details for PubMedID 15461542

• Effectiveness of mirtazapine in the treatment of Sleep Apnea Hypopnea Syndrome (SAHS) SLEEP MEDICINE Castillo, J. L., Menendez, P., Segovia, L., Guilleminault, C. 2004; 5 (5): 507-508

  Abstract

  Several drugs have been described as possible treatments for Sleep Apnea/Hypopnea Syndrome (SAHS) but the data available does not support their use. In an animal model of central apnea the use of mirtazapine produced a significant reduction of apneas. We present a male patient, 82 years old, with excessive daytime sleepiness and loud snoring during at least 10 years. An overnight polysomnography (PSG) revealed an apnea/hypopnea index of 54.9 events per hour of sleep with a minimum pulse oximetric saturation (SaO(2)) of 78% and an arousal index of 40.4 per hour. A nasal CPAP titration in the second half of the night showed suppression of apneas with a CPAP level of 8 cmH(2)O. The patient refused to use the CPAP device and began with 15 mg of mirtazapine at bedtime. A second PSG performed after 3 months of mirtazapine showed a significant reduction in the apnea/hypopnea index (9.3 events per hour of sleep; 81% minimal oxygen saturation (SaO(2))). Clinically, the patient and his wife reported a clear reduction of excessive daytime sleepiness and an improvement in self-reported functioning and well-being without any important side effects. This successful case appears to be the first report with mirtazapine in human SAHS and supports the need for an appropriate clinical trial with this drug.

  View details for DOI 10.1016/j.sleep.2004.06.004

  View details for Web of Science ID 000224018100014

  View details for PubMedID 15341898

• Neurological perspective on obstructive and nonobstructive sleep apnea SEMINARS IN NEUROLOGY Abad, V. C., Guilleminault, C. 2004; 24 (3): 261-269

  Abstract

  One of every 15 adults in the United States has at least moderate sleep apnea. The true prevalence is higher, as approximately 0.3 to 5% of adults with sleep apnea are undiagnosed. Sleep apnea has major health consequences; therefore, neurologists must recognize and treat sleep apnea syndromes appropriately. There are three main categories of sleep apnea: obstructive sleep apnea (OSA), central sleep apnea (CSA), and mixed sleep apnea. OSA results from upper airway obstruction, and CSA is due to lack of inspiratory muscle effort; mixed apnea results from a combination of these factors. Sleep apnea syndromes can present within the spectrum of "typical" neurological complaints, including forgetfulness, headaches, sleepiness, fatigability, seizures, and muscle and nerve weakness. A good sleep history, a nocturnal polysomnogram, and multiple sleep latency test are important in elucidating the diagnosis and validating the complaints of sleepiness. The gold standard for treatment of OSA is positive airway pressure, although some patients may benefit from surgical interventions designed to bypass the site of airway obstruction. With CSA, treatment is directed toward the underlying disorder. Patients with CSA may also benefit from several types of nasal positive airway pressure treatment, while some require mechanical ventilation.

  View details for Web of Science ID 000224248200006

  View details for PubMedID 15449219

• Sleep disorders in Taiwanese children with attention deficit/hyperactivity disorder JOURNAL OF SLEEP RESEARCH Huang, Y. S., Chen, N. H., Li, H. Y., Wu, Y. Y., Chao, C. C., Guilleminault, C. 2004; 13 (3): 269-277

  Abstract

  To assess obstructive sleep apnea syndrome (OSAS) and periodic limb movement disorder (PLMD) in children with attention deficit/hyperactivity disorder (ADHD) compared with a control group. The ADHD was diagnosed based on Diagnostic and Statistical Manual, version IV (DSM-IV) criteria on successively seen elementary school children aged 6-12 years referred to a psychiatric clinic for suspected ADHD. A standardized interview (Kiddie-SADS-E), parents and teacher questionnaires, neuropsychological testing, and nocturnal polysomnography were completed for each child. Eighty-eight children (77 boys) with ADHD and 27 controls were involved in the study. Fifty children with ADHD (56.8%) had an apnea-hypopnea index (AHI) >1 event h(-1) and 17 (19.3%) had an AHI >5 event h(-1). Nine children (10.2%) had a periodic limb movement index (PLMI) >5 events h(-1). There is one child with AHI >1 and none with a PLMI > 5 in the control group. In the test of variables of attention (TOVA), the response time was significantly worse in ADHD with sleep disorders than those without them. The child behavior checklist (CBCL) showed a significant difference between groups in the hyperactivity subscale. The diagnostic criteria for ADHD based on DSM-IV do not differentiate between children with or without sleep disorders. Evaluation of sleep disorders should be considered before starting drug treatment for ADHD.

  View details for Web of Science ID 000223642500009

  View details for PubMedID 15339263

• Obstructive Sleep Apnea. Current treatment options in neurology Guilleminault, C., Abad, V. C. 2004; 6 (4): 309-317

  Abstract

  Obstructive sleep apnea (OSA) is a major public health problem in the US that afflicts at least 2% to 4% of middle-aged Americans and incurs an estimated annual cost of 3.4 billion dollars. At Stanford, we utilize a multispecialty team approach combining the expertise of sleep medicine specialists (adult and pediatric), maxillofacial and ear, nose, and throat surgeons, and orthodontists to determine the most appropriate therapy for complicated OSA patients. The major treatment modality for children with OSA is tonsillectomy and adenoidectomy with or without radiofrequency treatment of the nasal inferior turbinate. Children with craniofacial anomalies resulting in maxillary or mandibular insufficiency may benefit from palatal expansion or more invasive maxillary/mandibular surgery. Continuous positive airway pressure (PAP) therapy is used in children with OSA who are not surgical candidates or have failed surgery. As a last resort, tracheotomy may be used in patients with persistent or severe OSA who do not respond to other measures. The cornerstone of treatment in adults utilizes PAP: continuous PAP, bilevel PAP, or auto PAP. Treatment of nasal obstruction, appropriate titration, attention to mask-fit issues, desensitization for claustrophobia, use of heated humidification for nasal dryness and nasal pain with continuous PAP, patient education, regular follow-up, use of compliance software (in selected individuals), and referral to support groups (AWAKE) are measures that can improve patient compliance. Adjunctive treatment modalities include lifestyle/behavioral/pharmacologic measures. Oral appliances can be used in patients with symptomatic mild sleep apnea or upper airway resistance syndrome. Patients who are unwilling or unable to tolerate continuous PAP or who have obvious upper airway obstruction may benefit from surgery. Surgical success depends on appropriate patient selection, the procedure performed, and the experience of the surgeon. Phase I surgeries have a success rate of 50% to 60%, whereas phase II surgeries have a success rate greater than 90%.

  View details for PubMedID 15157408

• Rapid maxillary expansion in children with obstructive sleep apnea syndrome SLEEP Pirelli, P., Saponara, M., Guilleminault, C. 2004; 27 (4): 761-766

  Abstract

  To evaluate the effect of rapid maxillary expansion on children with nasal breathing and obstructive sleep apnea syndrome.Recruitment of children with maxillary contraction, without of adenoid hypertrophy, with a body mass index < 24 kg/m2, with obstructive sleep apnea syndrome demonstrated by polysomnography, and whose parents signed informed consent. Otolaryngologic and orthognathic-odontologic evaluation with clinical evaluation, anterior rhinometry and nasal fibroscopy, panoramic radiographs, anteroposterior and laterolateral telecephalometry were performed at entry and follow-up. Intervention: Rapid maxillary expansion (ie, active phase of treatment) was performed for 10 to 20 days; maintenance of device (for consolidation) and orthodontic treatment on teeth lasted 6 to 12 months.31 children (19 boys), mean age 8.7 years, participated in the study. The mean apnea-hypopnea index was 12.2 events per hour. At the 4-month follow-up, the anterior rhinometry was normal, and all children had an apnea-hypopnea index < 1 event per hour. The mean cross-sectional expansion of the maxilla was 4.32 +/- 0.7 mm. There was a mean increase of the pyriform opening of 1.3 +/- 0.3 mm.Rapid maxillary expansion may be a useful approach in dealing with abnormal breathing during sleep.

  View details for Web of Science ID 000223169300023

  View details for PubMedID 15283012

• Obstructive sleep apnea syndrome, sleepiness, and quality of life CHEST Goncalves, M. A., Paiva, T., Ramos, E., Guilleminault, C. 2004; 125 (6): 2091-2096

  Abstract

  To evaluate the addition of short arousals of > 3 s on indexes of sleep-disordered breathing (SDB) and subjective sleepiness in patients with obstructive sleep apnea (OSA), and to evaluate the quality of life and reported difficulty driving with arousal index and indexes of SDB.Data was collected from a general clinical evaluation, and evaluations using the Epworth sleepiness scale (ESS), the sleep disorders questionnaire, the Beck depression inventory (BDI), the Medical Outcomes Study 36-item short form health survey (SF-36), a questionnaire on driving difficulties and accidents, and polysomnography.A total of 135 male subjects (mean [+/- SD] age, 52 +/- 12.1 years; mean body mass index [BMI], 27.8 +/- 5.6 kg/m(2); mean apnea-hypopnea index [AHI], 48.7 +/- 26.8 events per hour) were studied. Of these subjects, 70.4% acknowledged having driven while sleepy. ESS scores correlated significantly with the arousal index and AHI, and negatively with the lowest arterial oxygen saturation. The "physical functioning," "general health," and "role physical" subscales of the SF-36 correlated with the arousal index. No significant correlation was seen in multiple regression analyses after adjusting for age and BMI, using "reports of sleepiness while driving" as the dependent variable.Several subjective complaints and subscales of the SF-36 correlated significantly with a frequency of SDB-related arousal of > 3 s. Patients perceived that an organic health problem had been impairing their quality of life more than an emotional problem, despite elevated scores on the BDI. However, if sleepiness while driving was common in OSA patients, it was not significant. Many clinical and polysomnographic variables may be considered as possible independent variables in the regression analysis. Other unrelated factors have a greater impact. To relate sleepiness while driving only to the usually studied variables in OSA patients is an oversimplification.

  View details for Web of Science ID 000222253100023

  View details for PubMedID 15189926

• Chronic benzodiazepine usage and withdrawal in insomnia patients JOURNAL OF PSYCHIATRIC RESEARCH Poyares, D., Guilleminault, C., Ohayon, M. M., Tufik, S. 2004; 38 (3): 327-334

  Abstract

  We studied the sleep of patients with insomnia during continuous and very long-term use of benzodiazepines (BZDs), and after withdrawal. A group of 25 patients (mean age 44.3+/-11.8 years) with persistent insomnia, who had been taking BZDs nightly for 6.8+/-5.4 years was selected. The control group was comprised of 18 age-matched healthy individuals. Sleep stage parameters were analyzed during Night 1 (while taking BZDs), Night 2 (first night after completing BZD withdrawal), and Night 3 (15 days after gradual BZD withdrawal). Sleep data for control subjects was monitored in parallel. Sleep EEGs of the patients were analyzed using Period Amplitude Analysis (PAA), during Nights 1 and 3 only. During BZD use, a significant reduction of Total Sleep Time (TST) and increased sleep latency were found in the insomniac group when compared to controls. We found an increase in stage 2 non-REM (NREM) sleep, and a reduction in Slow Wave Sleep (SWS) when comparing to night 3 (after withdrawal). Sleep EEGs analysis showed an increase in sigma band and decrease in delta count in stages 2, 3, 4 NREM and REM sleep in the BZD group when comparing to night 3 (after withdrawal). During the BZD withdrawal period, six out of nine subjects taking lorazepam failed withdrawal. In the remaining 19 subjects, gradual withdrawal of BZDs was associated with immediate worsening of nocturnal sleep, as indicated by sleep parameters. However, 15 days after withdrawal (Night 3), some of the sleep structure parameters of patients were not significantly different from baseline (while taking BZDs), except for a significant increase in SWS and in delta count throughout most sleep stages, and a decrease in stage 2 NREM sleep. These values were not different from those shown by control subjects. REM sleep parameters showed no significant variation across the experimental conditions. Subjective sleep quality was significantly improved on Night 3 compared with Night 1. Conclusions: Chronic intake of BZDs may be associated with poor sleep in this population. A progressive 15-day withdrawal did not avoid an immediate worsening of sleep parameters. But at the end of the protocol, SWS, delta count, and sleep quality were improved compared to those recorded during the chronic BZD intake, despite the lack of change in sleep efficiency.

  View details for DOI 10.1016/j.jpsychires.2003.10.003

  View details for Web of Science ID 000220334800014

  View details for PubMedID 15003439

• A prospective study of nocturia and the quality of life of elderly patients with obstructive sleep apnea or sleep onset insomnia JOURNAL OF PSYCHOSOMATIC RESEARCH Guilleminault, C., Lin, C. M., Goncalves, M. A., Ramos, E. 2004; 56 (5): 511-515

  Abstract

  To prospectively evaluate the relationship between obstructive sleep apnea syndrome (OSAS), nocturia and quality of life in elderly patients free of the urologic and medical conditions that lead to increased nocturia.Prospective study of nocturia in men 65 years and older with isolated OSAS or sleep onset insomnia. After a 7-day nocturia evaluation and nocturnal polysomnography, Epworth Sleepiness Scale (ESS), Beck Depression Inventory (BDI), Quality of Life (SF-36) were administered.OSAS patients with frequent nocturia had significantly greater body mass index (BMI), greater apnea-hypopnea index (AHI), lower lowest oxygen saturation and lower SF-36 subscale scores. Treatment with nasal continuous positive airway pressure (CPAP) for OSAS and behavioral techniques for insomnia improved ESS and BDI scores for all three groups. SF-36 subscale scores improved more in subjects with multiple nocturia. AHI and BMI explain 38% of the variance for nocturia.Nasal CPAP reduces OSA and nocturia and improves quality of life of elderly patients.

  View details for DOI 10.1016/S0022-3999(04)00021-2

  View details for Web of Science ID 000222168800007

  View details for PubMedID 15172207

• Obstructive sleep apnea syndromes MEDICAL CLINICS OF NORTH AMERICA Guillerminault, C., Abad, V. C. 2004; 88 (3): 611-?

  View details for DOI 10.1016/j.mcna.2004.01.002

  View details for Web of Science ID 000221049600005

  View details for PubMedID 15087207

• Maxillomandibular expansion for the treatment of sleep-disordered breathing: Preliminary result LARYNGOSCOPE Guilleminault, C., Li, K. K. 2004; 114 (5): 893-896

  Abstract

  To assess the outcomes of maxillomandibular expansion (MME) by distraction osteogenesis (DO) for the treatment of sleep-disordered breathing (SDB).This was a prospective study of six consecutive patients with SDB. All of the patients have maxillary and mandibular constriction and were treated with MME. Variables examined include age, sex, body mass index (BMI), polysomnographic results (PSG), Epworth Sleepiness Scale (ESS), and the extent of the widening of the maxilla and mandible.All six patients (4 males) completed MME for the treatment of SDB. The mean age was 22.2 +/- 11.4 years. The mean maxillary expansion was 10.3 +/- 3.0 mm, and the mean mandibular expansion was 9.5 +/- 2.9 mm. ESS improved from 10.2 +/- 1.9 to 5 +/- 2.9. The mean apnea/ hypopnea index (AHI) improved from 13.2 +/- 15.6 to 4.5 +/- 5.8 events per hour, and the mean lowest oxygen saturation (LSAT) improved from 88.2 +/- 2.9% to 91.3 +/- 3.3%. The mean esophageal pressure improved from -20 +/- 11.3 cm H2O to -8 +/- 3.6 cm H2O. No complications were encountered, and the follow-up period was 18.1 +/- 9.8 months.: The result suggests that MME improves SDB in patients with maxillary and mandibular constriction and can be a valid treatment.

  View details for Web of Science ID 000221537900020

  View details for PubMedID 15126751

• Efficacy of automated continuous positive airway pressure in children with sleep-related breathing disorders in an attended setting PEDIATRICS Palombini, L., Pelayo, R., Guilleminault, C. 2004; 113 (5): E412-E417

  Abstract

  The purpose of this study was to evaluate the safety and efficacy of automated continuous positive airway pressure (Auto-CPAP) in children. Sleep-related breathing disorders (SRBDs) include the clinical spectrum of symptomatic chronic snoring, upper airway resistance syndrome, and obstructive sleep apnea. This spectrum occurs in adults and children. Less data are available for children despite recognition of the condition's prevalence. CPAP has been an established treatment for adults and children. Treatment with Auto-CPAP has been available for adults but has not been reported previously in children.A group of 14 children (8 months to 12 years old) was evaluated prospectively with baseline polysomnographic study and CPAP titration performed with Auto-CPAP under sleep technologist supervision.The results demonstrated that Auto-CPAP is sensitive and effective for children with obstructive sleep apnea in an attended setting. There was 1 subject who did not seem to tolerate Auto-CPAP, but when she was switched to conventional CPAP, she did not tolerate that either. In this subject, the mask never fit well. She was excluded from the analysis. All other patients had a decrease in the number of abnormal breathing events during sleep. The respiratory disturbance index decreased from a mean of 12.6 (SD: 12.4) to 2.6 (SD: 2.7) events per hour. The lowest oxygen saturation improved from a mean of 86% (SD: 10.8) to 93.6% (SD: 3.9).We conclude that Auto-CPAP is safe and effective in an attended environment. Auto-CPAP did not eliminate all the abnormal respiratory events. In subjects 1 and 14, the final respiratory index improved but remained >5 events per hour (5.9 and 7.7, respectively). We suspect that this was because of problems with the masks leaking, which illustrates the importance of follow-up and possible need for retitration in some patients. Proper mask fit is essential for successful treatment. Additional work is needed to evaluate its utility in the home setting. This study was designed to evaluate Auto-CPAP titration in an attended environment. It did not indicate information about the effectiveness in an unattended or home setting. We demonstrate that Auto-CPAP is able to detect abnormal breathing events during sleep in children and may provide the necessary pressure to correct these events. Auto-CPAP can be used safely for pressure titration in an attended setting. Auto-CPAP devices from different manufactures are commercially available for adults. These different devices may have different algorithms and sensitivities to detect abnormal breathing episodes. This study was performed with only 1 specific model of Auto-CPAP. Our results should not be extrapolated to other Auto-CPAP devices without empirical confirmation of the devices' ability to detect and correct events in children. Auto-CPAP can be an alternative treatment for SRBDS in the pediatric population. These results allow for speculation of possible applications for Auto-CPAP in children. A potential advantage of Auto-CPAP includes permitting the initiation of treatment while awaiting a standard CPAP titration. The variable pressure response of Auto-CPAP allows for treatment under different situations such as upper airway infections, different sleeping positions, and changes in weight. As the child grows, the amount of positive pressure needed to maintain airway patency may change. Auto-CPAP may be able to adjust to these changing pressure requirements. Auto-CPAP does not eliminate the need for periodic office visits and evaluations of the clinical course.

  View details for Web of Science ID 000221169200058

  View details for PubMedID 15121982

• Twenty minutes versus forty-five minutes morning bright light treatment on sleep onset insomnia in elderly subjects JOURNAL OF PSYCHOSOMATIC RESEARCH Kirisoglu, C., Guilleminault, C. 2004; 56 (5): 537-542

  Abstract

  To compare the efficacy of 20 min versus 45 min light exposure for relieving psychophysiological insomnia in the elderly.Prospective recruitment of subjects 60 years and older with psychophysiological insomnia. Random distribution to 20 or 45 min of daily exposure to 10,000 lux for 60 days. Sleep latency, total sleep time, fatigue and activity were measured at baseline and 3 and 6 months posttreatment. Blind analysis of data and comparison were performed using repeated-measure analysis of variance, independent samples t test and Wilcoxon rank signed test.At 3 months, improvement was significantly higher in the 45-min versus 20-min condition. At 6 months, variables returned toward baseline in the 20-min but not in the 45-min condition.Twenty minutes of bright light treatment leads to a lesser treatment response than 45 min at 3-month follow-up and to a return toward baseline at 6-month follow-up that was not seen with a 45-min exposure.

  View details for DOI 10.1016/j.jpsychores.2004.02.005

  View details for Web of Science ID 000222168800010

  View details for PubMedID 15172210

• Review of rapid eye movement behavior sleep disorders. Current neurology and neuroscience reports Abad, V. C., Guilleminault, C. 2004; 4 (2): 157-163

  Abstract

  The spectrum of rapid eye movement behavior disorders (RBD) spans various age groups, with the greatest prevalence in elderly men. Major diagnostic features include harmful or potentially harmful sleep behaviors that disrupt sleep continuity and dream enactment during rapid eye movement sleep. In RBD patients, the polysomnogram during rapid eye movement sleep demonstrates excessive augmentation of chin electromyogram or excessive chin or limb phasic electromyogram twitching. RBD may be associated with various neurodegenerative disorders, such as multiple system atrophy, Parkinson's disease, and dementia with Lewy bodies. Other co-morbid conditions may include narcolepsy, agrypnia excitata, sleepwalking, and sleep terrors. RBD is hypothesized to be caused by primary dysfunction of the pedunculo-pontine nucleus or other key brainstem structures associated with basal ganglia pathology or, alternatively, from abnormal afferent signals in the basal ganglia leading to dysfunction in the midbrain extrapyramidal area/ pedunculo-pontine nucleus regions.

  View details for PubMedID 14984689

• Pediatric sleep pharmacology: you want to give my kid sleeping pills? PEDIATRIC CLINICS OF NORTH AMERICA Pelayo, R., Chen, W., Monzon, S., Guilleminault, C. 2004; 51 (1): 117-?

  Abstract

  There is a need for greater information about the pharmacologic management of sleep disorders in children. Pharmacologic guidelines must be developed specifically for sleep disorders in children. Ideally, these guidelines should be approved by the Food and Drug Administration for a specific sleep disorder or for the pediatric age range. This approval prevents physicians from being forced to prescribe medications as an "off label" indication. Development of easy-to-swallow, chewable, or liquid forms of these medications would be well received by parents everywhere. When these are not available, instructions for compounding these medications into a suspension by pharmacists are needed. Integration of behavioral and pharmacologic treatments may yield better patient outcomes. This approach requires pediatricians to have a comprehensive understanding of clinical sleep disorders in children. Training programs should play the lead role in enhancing pediatricians' knowledge of the pharmacologic treatment of sleep disorders in children.

  View details for DOI 10.1016/S0031-3955(03)00179-2

  View details for Web of Science ID 000189167700008

  View details for PubMedID 15008585

• A prospective study on the surgical outcomes of children with sleep-disordered breathing SLEEP Guilleminault, C., Li, K., Quo, S., Inouye, R. N. 2004; 27 (1): 95-100

  Abstract

  To prospectively evaluate the outcome of surgical treatment decisions made by a multidisciplinary team for children aged 18 months to 12 years with sleep-disordered breathing (SDB).A multidisciplinary team evaluated children referred to a sleep clinic for suspicion of SDB using polysomnography, questionnaires, and clinical evaluations. Suggestions for treatment (surgical, medical, or orthodontic) were made and sent to referring providers. A follow-up evaluation, which included a repeat of all of the tests performed at baseline, was performed 3 months after treatment (and at 6 months for a subgroup of subjects). The clinical outcome of the recommended versus the performed treatment was compared.56 successively evaluated children.Based on insurance plans, 11 children were treated by a surgeon on the multidisciplinary team, who followed all treatment recommendations. After treatment, 1 of the 11 children still had SDB. Forty-five children were referred to other specialists. Only 1 of these children had the team's treatment recommendations implemented. Twenty-six of the 45 children had residual symptoms. Twelve children had polysomnographic abnormalities with or without symptoms or snoring. Sixteen children (28.6%) underwent a second surgical procedure.There are misconceptions in the pediatric and otolaryngologic communities about the rationale for the surgical treatment of SDB. Interactions between mouth breathing, maxillofacial growth, and clinical symptoms associated with SDB are not well understood. Multidisciplinary evaluations of the anatomic abnormalities of children with SDB lead to better overall treatment.

  View details for Web of Science ID 000223168600015

  View details for PubMedID 14998243

• Breathing patterns in prepubertal children with sleep-related breathing disorders ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE Guilleminault, C., Li, K., Khramtsov, A., Palombini, L., Pelayo, R. 2004; 158 (2): 153-161

  Abstract

  To investigate abnormal breathing patterns during sleep in prepubertal children using nonstandard polysomnographic patterns in association with an apnea-hypopnea scoring technique.Study participants included 400 children with suspected sleep-related breathing disorders and 60 control children. We analyzed clinical signs and symptoms at entry into the study and 3 months after otolaryngological treatment. We determined the frequency of predefined breathing patterns during sleep through blind analysis of polysomnograms obtained once in control subjects and twice in children referred to our clinic (before and after adenotonsillectomy), using the nasal cannula-pressure transducer system, mouth thermistor, esophageal manometry, microphone, and pulse oximetry. We also determined the relationship between breathing patterns during sleep and residual postsurgery symptoms. Further analysis was performed of symptoms and polysomnographic patterns in those children who underwent new treatment interventions due to persistence of symptoms and abnormal polysomnogram findings.Tachypnea, persistently elevated breathing effort, progressively increased breath effort, and discrete flattening of nasal airflow monitored with the nasal cannula-pressure transducer system without oxygen saturation decreases help determine disorder as much as apneas and hypopneas. Abnormal, nonstandard breathing patterns were associated with the same symptoms as those in children with apnea and hypopnea and were more commonly present when there was incomplete resolution of initial symptoms that led treating practitioners to request further treatment.Currently published polysomnographic scoring recommendations overlook common breathing abnormalities during sleep that are associated with clinical complaints.

  View details for Web of Science ID 000188763300010

  View details for PubMedID 14757607

• Abnormal blood pressure in prepubertal children with sleep-disordered breathing PEDIATRIC RESEARCH Guilleminault, C., Khramsov, A., Stoohs, R. A., Kushida, C., Pelayo, R., Kreutzer, M. L., Chowdhuri, S. 2004; 55 (1): 76-84

  Abstract

  The purpose of this study was to investigate the association between low blood pressure (BP) with mild symptoms of orthostatism, sleep-disordered breathing (SDB) and tilt test results in 7- to 12-y-old children. A retrospective chart review of 301 children, ages 7 to 12 y, was initially performed to evaluate the frequency of abnormal BP measurements. Then a prospective study was performed on 7- to 12-y-old prepubertal children with SDB, looking for both abnormal BP and mild orthostatism. All children had polysomnography. Those identified with abnormal (high or low) BP measurements (called "BP outliers") were studied with a new polysomnogram followed by a head-up tilt test as an indicator of autonomic activity. Four of the children with low BP were treated with nasal continuous positive airway pressure and received a second head-up tilt test 3.5 to 7 mo after starting treatment. The prospective study included 78 children, eight of whom were BP outliers. Seven of these outliers had low BP. Compared with all of the SDB subjects, SDB subjects with low BP and indicators of mild orthostatic hypotension had a significantly higher incidence of craniofacial dysmorphism, symptoms of SDB early in life, chronically cold extremities, and dizziness on standing up (chi2, p = 0.01 to 0.0001). They had a significantly greater drop in BP without evidence of autonomic neuropathy than all other children on head-up tilt testing (Kruskal-Wallis ANOVA with Bonferroni adjustment, p = 0.001 to 0.0001). However, the normotensive SDB controls also had significantly different BP drops than the normal controls (p = 0.0001). The four children placed on nasal continuous positive airway pressure had a nonsignificant trend toward normalization of tilt test response. SDB in prepubertal children can lead to different abnormal stimulation of the autonomic nervous system, with different impacts on BP. The severity and frequency of oxygen saturation drops during sleep, nonhypoxic increases in respiratory effort, and the duration of abnormal breathing are suspected of playing a role in the difference in autonomic nervous system stimulation.

  View details for DOI 10.1203/01.PDR.0000099791.29621.62

  View details for Web of Science ID 000187502400011

  View details for PubMedID 14605262

• Non-invasive estimation of esophageal pressure based on intercostal EMG monitoring 26th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society Stoohs, R. A., Blum, H. C., Knaack, L., Guilleminault, C. IEEE. 2004: 3867–3869

  View details for Web of Science ID 000225461801008

• Attention-deficit/hyperactivity-disorder with and without obstructive sleep apnea-outcome of methylphenidate and surgical treatment 18th Annual Meeting of the Associated-Professional-Sleep-Societies Huang, Y., Chen, N., Li, H., Yang, C., Chen, H., Guilleminault, C. AMER ACAD SLEEP MEDICINE. 2004: 103–103

  View details for Web of Science ID 000223169400230

• Evolution of PSG sleep parameters with age 18th Annual Meeting of the Associated-Professional-Sleep-Societies Ohayon, M., Carskadon, M., Guilleminault, C., Vitiello, W. V. AMER ACAD SLEEP MEDICINE. 2004: 134–135

  View details for Web of Science ID 000223169400298

• Effects of CNS activation on arousal and autonomic nervous system 18th Annual Meeting of the Associated-Professional-Sleep-Societies Guilleminault, C., Abad, V., Stoohs, R. AMER ACAD SLEEP MEDICINE. 2004: 40–40

  View details for Web of Science ID 000223169400089

• Fatigue and sleepiness associated with OSAS and UARS 18th Annual Meeting of the Associated-Professional-Sleep-Societies Kirisoglu, C., Abad, V., Guilleminault, C. AMER ACAD SLEEP MEDICINE. 2004: 192–193

  View details for Web of Science ID 000223169400426

• C-reactive protein in non-obese and obese obstructive sleep apnea subjects 18th Annual Meeting of the Associated-Professional-Sleep-Societies Kirisoglu, C., Abad, V., Guilleminault, C. AMER ACAD SLEEP MEDICINE. 2004: 193–193

  View details for Web of Science ID 000223169400428

• Sleep disordered breathing: Surgical outcomes in prepubertal children LARYNGOSCOPE Guilleminault, C., Li, K. K., Khramtsov, A., Pelayo, R., Martinez, S. 2004; 114 (1): 132-137

  Abstract

  To evaluate the treatment outcomes of sleep disordered breathing (SDB) in prepubertal children 3 months following surgical intervention.Retrospective investigation of 400 consecutively seen children with SDB who were referred to otolaryngologists for treatment.After masking the identities and conditions of the children, the following were tabulated: clinical symptoms, results of clinical evaluation and polysomnography at entry, the treatment chosen by the otolaryngologists, and clinical and polysomnographic results 3 months after surgery.Treatment ranged from nasal steroids to various surgical procedures. Adenotonsillectomy was performed in only 251 of 400 cases (68%). Four cases included adenotonsillectomy in conjunction with pharyngoplasty (closure of the tonsillar wound by suturing the anterior and posterior pillar to tighten the airway). Persistent SDB was seen in 58 of 400 children (14.5%), and an additional 8 had persistent snoring. Best results were with adenotonsillectomy.SDB involves obstruction of the upper airway, which may be partially due to craniofacial structure involvement. The goal of surgical treatment should be aimed at enlarging the airway, and not be solely focused on treating inflammation or infection of the lymphoid tissues. This goal may not be met in some patients, thus potentially contributing to residual problems seen after surgery. The possibility of further treatment, including collaboration with orthodontists to improve the craniofacial risk factors, should be considered in children with residual problems.

  View details for Web of Science ID 000225916200022

  View details for PubMedID 14710009

• The effects of trazodone on sleep in patients treated with stimulant antidepressants SLEEP MEDICINE Kaynak, H., Kaynak, D., Gozukirmizi, E., Guilleminault, C. 2004; 5 (1): 15-20

  Abstract

  To evaluate the effects of trazodone on subjective and objective measures of sleep in depressed insomnia patients treated with selective serotonin reuptake inhibitors (SSRIs). SSRIs can exacerbate or cause new insomnia while alleviating other symptoms of depression. Trazodone has been reported to be an effective hypnotic for patients with antidepressant-associated insomnia.Twelve female patients were given either 100 mg trazodone or placebo for 7 days in a double-blind crossover design with a 7-day washout period. Polysomnographic recordings were repeated on the 3rd, 9th and 17th, 23rd nights after treatment with trazodone or placebo. Sleep was assessed by Pittsburgh sleep quality index (PSQI) at the beginning and end of the study. Psychological evaluation was done by Hamilton depression rating scale (HDRS).Trazodone significantly increased total sleep time, percentage of stages 3+4, sleep efficiency index, sleep continuity index and decreased percentage of stage 1, number of awakenings, stage shifts compared to the baseline. This improvement was also obtained after 7 days of treatment. The PSQI score was reduced to 5+/-1.6 at the end of the study. HDRS was reduced to 11.5+/-4.5 with trazodone and to 12.2+/-3 with placebo.Trazodone is effective in the treatment of antidepressant-associated insomnia.

  View details for DOI 10.1016/j.sleep.2003.06.006

  View details for Web of Science ID 000189355100004

  View details for PubMedID 14725822

• Non-invasive estimation of esophageal pressure based on intercostal EMG monitoring. Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference Stoohs, R. A., Blum, H. C., Knaack, L., Guilleminault, C. 2004; 5: 3867-3869

  Abstract

  Recording of esophageal pressure waveform is an important clinical tool to identify patients with sleep-disordered breathing. Commonly, esophageal pressure probes are not tolerated by patients undergoing sleep monitoring. We therefore developed a technique to non-invasively estimate esophageal pressure based on recording of intercostal EMG monitoring. A three step approach to modification of the intercostal EMG signal was created to closely match results obtained from esophageal pressure recording. The algorithm was then tested on 10 subjects with sleep-disordered breathing undergoing full polysomnography with simultaneous monitoring of esophageal pressure and intercostal EMG. Analysis of correlations between esophageal pressure and intercostal EMG were computed by sleep stages. The overall correlation coefficient in all subjects combined was r=0.896, p<0.00001. The results indicate that this method can be used reliably in clinical sleep studies where esophageal pressure recordings cannot be performed.

  View details for PubMedID 17271140

• Pregnancy, sleep disordered breathing and treatment with nasal continuous positive airway pressure SLEEP MEDICINE Guilleminault, C., Kreutzer, M., Chang, J. L. 2004; 5 (1): 43-51

  Abstract

  To investigate the tolerance, compliance and problems associated with usage of nasal continuous positive airway pressure (CPAP) by pregnant women with sleep disordered breathing (SDB).Twelve pregnant women diagnosed with SDB received polysomnography (PSG) at entry, CPAP titration, repeat PSG at 6 months gestation (GA) and home monitoring of cardio-respiratory variables at 8 months GA. Compliance was verified by the pressure at the mask. Results from the Epworth sleepiness scale, fatigue scale and visual analogue scales (VAS) for sleepiness, fatigue, and snoring were compared over time.All of the subjects had full term pregnancies and healthy infants. Nightly compliance was at least 4 h initially and 6.5 h at 6 months GA. Nasal CPAP significantly improved all scales compared to entry. VAS scores remained lower at 6 months GA compared to entry. Re-adjustment of CPAP pressure was needed in six subjects at 6 months GA.Nasal CPAP is a safe and effective treatment of SDB during pregnancy.

  View details for DOI 10.1016/j.sleep.2003.07.001

  View details for Web of Science ID 000189355100008

  View details for PubMedID 14725826

• Long-term follow-up and mechanisms of Obstructive Sleep Apnea (OSA) and related syndromes through infancy and childhood 8th International Congress of Paediatric Otorhinolaryngology Contencin, P., Guilleminault, C., Manach, Y. ELSEVIER IRELAND LTD. 2003: S119–S123

  Abstract

  Although tonsil and adenoid (T&A) enlargement in children is a leading cause of it, Obstructive Sleep Apnea (OSA) may occur at any age. But even after T&A surgery, some children experience recurrent apneic episodes. The reasons for possible recurrence are unclear.To quantify the prevalence of recurrent OSA after T&A surgery and find out a common cause of OSA in children from the neonatal period to adulthood.A retrospective report of apneic patients followed in a tertiary-care center is presented. Telephone interviews of parents were performed 3 years after T&A surgery. The questionnaire included night and day symptoms related to sleep-disordered breathing (SDB). A literature review was performed about associated causes of upper airway stenosis.Out of 59 children who were included to follow up, 5 (8.5%) experienced residual or recurrent symptoms of SDB. The literature suggests the role of skeletal abnormalities in this process through nasal or pharyngeal stenosis. Major craniofacial anomalies are a well-known cause of obstruction. Thickened soft tissue has to be ruled out. Minor stenoses or neuromuscular disorders are less often diagnosed although they seem to be involved as well.A longitudinal follow-up of apneic children is able to reveal recurrence of SDB after adenotonsillectomy and often allows the understanding of mechanisms of upstream-induced recurrent pharyngeal obstructions.

  View details for DOI 10.1016/j.ijport.2003.08.009

  View details for Web of Science ID 000187789900018

  View details for PubMedID 14662182

• Diagnosis and treatment of sleep disorders: a brief review for clinicians. Dialogues in clinical neuroscience Abad, V. C., Guilleminault, C. 2003; 5 (4): 371-388

  Abstract

  Sleep disorders encompass a wide spectrum of diseases with significant individual health consequences and high economic costs to society. To facilitate the diagnosis and treatment of sleep disorders, this review provides a framework using the International Classification of Sleep Disorders, Primary and secondary insomnia are differentiated, and pharmacological and nonpharmacological treatments are discussed. Common circadian rhythm disorders are described in conjunction with interventions, including chronotherapy and light therapy. The diagnosis and treatment of restless legs syndrome/periodic limb movement disorder is addressed. Attention is focused on obstructive sleep apnea and upper airway resistance syndrome, and their treatment. The constellation of symptoms and findings in narcolepsy are reviewed together with diagnostic testing and therapy, Parasomnias, including sleep terrors, somnambulism, and rapid eye movement (REM) behavior sleep disorders are described, together with associated laboratory testing results and treatment.

  View details for PubMedID 22033666

  View details for PubMedCentralID PMC3181779

• Effect of fatigue on performance measured by a driving simulator in automobile drivers JOURNAL OF PSYCHOSOMATIC RESEARCH Philip, P., Taillard, J., KLEIN, E., Sagaspe, P., Charles, A., Davies, W. L., Guilleminault, C., Bioulac, B. 2003; 55 (3): 197-200

  Abstract

  To identify risk factors of performance decrement in automobile drivers.114 drivers (age <30 years, n=57; age > or =30 years, n=57) who stopped at a rest stop area on a freeway were recruited for the study. They filled out a questionnaire on their journey, sleep/wake patterns and performed a 30-min test on a driving simulator. The test evaluates, by computerized analysis, the lateral deviation of a virtual car from an appropriate trajectory on a virtual road. A sex/age matched control group was recruited in the community. Control subjects were studied at the same time of day as the index case driver. Controls had normal sleep wake schedule, absence of long driving and performed the same driving test.Drivers performed significantly worse than controls on the driving test. Age and duration of driving were the main factors associated with decreased performance.Our driving simulator can identify fatigue generated by driving but results must be considered in relation with age of subjects.

  View details for DOI 10.1016/S0022-3999(02)00496-8

  View details for Web of Science ID 000185034100003

  View details for PubMedID 12932791

• Sleep and respiratory stimulus specific dampening of cortical responsiveness in OSAS 8th International Symposium on Sleep and Breathing Afifi, L., Guilleminault, C., Colrain, I. M. ELSEVIER SCIENCE BV. 2003: 221–34

  Abstract

  The application of inspiratory occlusion stimuli produces cortical responses called respiratory-related evoked potentials (RREPs). During wakefulness the RREP waveform consists of early P1 and Nf components, an N1 and a P300. During non-REM sleep the predominant component is an N550, best seen in the averages of elicited K-complexes. Obstructive sleep apnea syndrome (OSAS) patients have been previously shown to have a normal wake RREP but to have a reduced amplitude N550 and a smaller proportion of elicited K-complexes than controls. The present study tested the hypothesis that this reflects a sleep-specific dampening peculiar to inspiratory effort-related stimuli, by assessing both respiratory and auditory evoked potentials (AEPs) during wakefulness and non-REM sleep in OSAS patients and controls. Auditory tones were presented in an oddball sequence during wakefulness and as a monotonous series during stage 2 sleep. Inspiratory occlusions, delivered for 500 msec via an nCPAP mask were also presented during wakefulness and stage 2 sleep, every three to five breaths. Data were collected from ten OSAS patients and ten controls. There were no significant differences in the amplitudes of the auditory N1 and P3 or the respiratory P1, Nf, N1 or P3 components during wakefulness. The amplitude of the auditory N550 and the proportion of elicited K-complexes did not differ between groups for auditory stimuli presented during stage 2 sleep. The respiratory N550 and K-complex elicitation rate were both significantly reduced in the OSAS group, despite there being no differences in the mask occlusion pressure response to the occlusion. The results confirm a blunted cortical response to inspiratory occlusions that is specific to sleep. The absence of significant group differences in the responses to auditory stimuli highlight that the sleep-related differences seen in OSAS patients are specific to the processing of inspiratory effort related stimuli.

  View details for DOI 10.1016/S1569-9048(03)00084-3

  View details for Web of Science ID 000184484100013

  View details for PubMedID 12853013

• Anterior cervical spine fusion and sleep disordered breathing NEUROLOGY Guilleminault, C., Li, K. K., Philip, P., Kushida, C. A. 2003; 61 (1): 97-99

  Abstract

  The authors reviewed 12 patients who developed obstructive sleep apnea (OSA) syndrome in association with anterior cervical spine fusion. Four subsequent patients were studied prospectively before C2 to C4 anterior fusion and documented to have OSA by questionnaire, visual analogue scales, polysomnography, and multiple sleep latency tests. The authors found that placement of the anterior cervical plates reduced the size of the upper airway. Symptoms and objective findings were controlled with nasal continuous positive airway pressure.

  View details for Web of Science ID 000183978800020

  View details for PubMedID 12847164

• An adjunctive method of radiofrequency volumetric tissue reduction of the tongue for OSAS OTOLARYNGOLOGY-HEAD AND NECK SURGERY Riley, R. W., Powell, N. B., Li, K. K., Weaver, E. M., Guilleminault, C. 2003; 129 (1): 37-42

  Abstract

  Temperature-controlled radiofrequency volumetric reduction (TCRF), a minimally invasive procedure, has been used to treat tongue base obstruction in Obstructive Sleep Apnea Syndrome (OSAS). An adjunctive method was objectively evaluated.A prospective, nonrandomized clinical study was undertaken on 20 consecutive OSAS patients with isolated tongue base obstruction. Under local anesthesia, multiple lesions of the ventral tongue (genioglossus insertion) and dorsal tongue were given at each treatment session. A visual analog scale was used to assess changes in speech and swallowing. Polysomnography and Epworth Sleepiness Scale (ESS) were used to assess outcome. Patients were maintained on nasal continuous positive airway pressure after each treatment.Patients received a mean 4.6 +/- 0.6 treatments for a mean total of 7915 +/- 1152 joules. There was no significant change in speech or swallowing at 3 months after completion of treatment. Patients reported a significant decrease in sleepiness with a mean change in ESS from 12.4 +/- 2.9 to 7.3 +/- 3.0 (P < 0.001). Mean apnea/hypopnea index decreased from 35.1 +/- 18.1 to 15.1 +/- 17.4 (P < 0.001). Transient mild to moderate pain and swelling occurred after each treatment. There were no significant complications (ulceration, paresthesia, infection).TCRF can successfully treat the OSAS patient with tongue base obstruction. Combined treatment of the ventral (genioglossus insertion) and dorsal tongue appears safe and may improve outcome with less total energy when compared with traditional dorsal-only applications.

  View details for DOI 10.1016/S0194-5998(03)00482-0

  View details for Web of Science ID 000184368300007

  View details for PubMedID 12869914

• Sleepwalking, sleep-disordered breathing, and restless leg 17th Annual Meeting of the Associated-Professional-Sleep-Societies Chang, J. L., Guilleminault, C., Palombini, L. AMER ACAD SLEEP MEDICINE. 2003: A126–A126

  View details for Web of Science ID 000182841100312

• Anterior cervical spine fusion and sleep disordered breathing: An unreported complication 17th Annual Meeting of the Associated-Professional-Sleep-Societies Chen, W., Guilleminault, C., Li, K. AMER ACAD SLEEP MEDICINE. 2003: A356–A357

  View details for Web of Science ID 000182841100900

• Treatment of sleep disordered breathing with nasal continuous positive airway pressure in pregnancy 17th Annual Meeting of the Associated-Professional-Sleep-Societies Kreutzer, M. L., Chang, J. L., Guilleminault, C. AMER ACAD SLEEP MEDICINE. 2003: A262–A262

  View details for Web of Science ID 000182841100660

• Preliminary observations on the effects of sleep time in a sleep restriction paradigm SLEEP MEDICINE Guilleminault, C., Powell, N. B., Martinez, S., Kushida, C., Raffray, T., Palombini, L., Philip, P. 2003; 4 (3): 177-184

  Abstract

  To evaluate of the effect of 7 days of sleep restriction--with sleep placed at the beginning of night or early morning hours - on sleep variables, maintenance of wakefulness test, and serum leptin.After screening young adults with questionnaires and actigraphy for 1 week, eight young adult males were recruited to participate in a sleep restriction study. The subjects were studied for baseline data for 2.5 days, with 8.5 h per night in bed, and then over 7 days of sleep restriction to 4 h per night with a 22:30 h bedtime for half the group and a 02:15 h bedtime for the other half. At the end of study, after one night of ad libitum sleep, subjects again had 2 days of 8.5 h in bed. Wakefulness was continuously verified and tests, including Maintenance of Wakefulness (MWT), were performed during the scheduled wake time. Blood was drawn six times throughout the 24 h of the 7th day of sleep restriction and after 2 days of the post-restriction schedule.There was individual variability in response to sleep restriction, but independent of group distribution, MWT was significantly affected by sleep restriction, with the early morning sleep group having less decrease in MWT score. Sleep efficiency was also better in this group, which also had shorter sleep latency. Independent of group distribution there was a greater increase in the percentage of slow wave sleep than rapid eye movement sleep, despite a clear internal variability and variability between subjects. Peak serum leptin was significantly decreased with 7 days of sleep restriction for all subjects.Sleep restriction to 4 h affected all subjects, but there were individual and group differences in MWT and sleep data. In this group of young adult males (mean age 19 years), there was a better overall adaptation to the early morning sleep, perhaps related to the general tendency in most adolescents to present some phase-delay during late teen-aged years.

  View details for DOI 10.1016/S1389-9457(03)00061-3

  View details for Web of Science ID 000188839200004

  View details for PubMedID 14592319

• Competency-based goals for sleep and chronobiology in undergraduate medical education SLEEP Strohl, K. P., Veasey, S., Harding, S., Skatrud, J., Berger, H. A., Papp, K. K., Dunagan, D., Guilleminault, C. 2003; 26 (3): 333-336

  Abstract

  Sleep and circadian rhythms are biologic processes operative in health and disease, but as yet there is no articulated curriculum for undergraduate medical education.A multidisciplinary expert-opinion approach was utilized to assess and define education objectives and the potential for implementation.N/A.National Institutes of Health Sleep Academic Awardees.N/A.Four competencies with examples of instruction objectives were identified relating to sleep processes and sleep need, the impact of sleep and sleep disorders on human illness, the sleep history, and the application of sleep physiology and pathophysiology to patent care. Various strategies and tools are currently available for implementation and assessment of learning objectives for these knowledge and skills.The core competencies can be designed to improve physician knowledge and skills in recognizing and intervening in sleep problems and disorders. Learning objectives can be immediately incorporated into most medical school curricula. At the same time, these competencies serve as an important bridge across multiple medical content areas and disciplines and between undergraduate and postgraduate training.

  View details for Web of Science ID 000182439100018

  View details for PubMedID 12749555

• Fatigue, sleep restriction, and performance in automobile drivers: A controlled study in a natural environment SLEEP Philip, P., Sagaspe, P., Taillard, J., Moore, N., Guilleminault, C., Sanchez-Ortuno, M., Akerstedt, T., Bioulac, B. 2003; 26 (3): 277-280

  Abstract

  To test the neurobehavioral consequences of sleep restriction combined with fatigue from long-distance driving (1000 Km/600 miles).Counterbalanced study involving 3 experimental conditions: laboratory after controlled habitual sleep (8.5 hours), driving after controlled habitual sleep (8.5 hours) (Road 1), and driving after reduced sleep (2 hours) (Road 2).Sleep laboratory and open French highway.10 male participants (mean age 22 years, range 18-24 years, mean driving distance per year 15000 Km/9000 miles) free of sleep disorders.Simple reaction time, prospective self-assessment of performance, and instantaneous fatigue and sleepiness ratings measured at 2-hour intervals.A two-way repeated ANOVA with time of day and condition indicated a significant main effect for time of day (p < 0.05). The interaction between the two factors (condition * time of day) was also significant (p < 0.05). The effects of time of day were significant only in the condition of driving after sleep restriction, (p < 0.05). Under sleep restriction, some drivers presented an increase of 650 milliseconds compared to the laboratory condition, representing an increase of 23 meters in breaking distance at a speed of 75 miles per hour. Correlation analyses showed a significant linear correlation between self-assessment and reaction time in the laboratory condition (r = -0.58, p < 0.01) but not in the road conditions. Self-ratings during the breaks showed a significant increase in instantaneous self-rated fatigue and sleepiness between Road 1 and Road 2 conditions (Wilcoxon's test, Z = - 6.47, p < 0.0001 and Z = - 6.26, p < 0.0001).Sleep restriction combined with fatigue significantly affects reaction time. The lack of correspondence between reaction time and prospective self-evaluation of performance suggests that self-monitoring in real conditions is poorly reliable.

  View details for Web of Science ID 000182439100008

  View details for PubMedID 12749545

• Validation: A dangerous and difficult claim to make SLEEP MEDICINE Ohayon, M. M., Guilleminault, C. 2003; 4 (2): 99-99

  View details for DOI 10.1016/S1389-9457(03)00007-8

  View details for Web of Science ID 000188839100003

  View details for PubMedID 14592340

• A 12-month, open-label, multicenter extension trial of orally administered sodium oxybate for the treatment of narcolepsy SLEEP Black, J., Guilleminault, C., Bogan, R., Feldman, N., Hagaman, M., Hertz, G., Iyer, V., Kathawalla, S., Lankford, A., Mitler, M., Hayduk, R., Sahota, P., Roth, T., Scharf, M., Scrima, L., SCHWARTZ, J., Zammit, G. 2003; 26 (1): 31-35

  Abstract

  To evaluate the long-term safety and efficacy of nightly sodium oxybate for the treatment of narcolepsy.A multicenter, 12-month, open-label trial.118 narcolepsy patients previously enrolled in a 4-week double-blind sodium oxybate trial. Interventions: Patients were administered 6 g sodium oxybate nightly, taken in equally divided doses at bedtime and 2.5 to 4 hours later. The study protocol permitted the dose to be increased or decreased in 1.5-g increments at 2-week intervals based on efficacy response or adverse experiences but staying within the range of 3 to 9 g nightly.Narcolepsy symptoms and adverse events were recorded in daily diaries. Safety measures included physical and laboratory examinations repeated at 6 and 12 months. The primary efficacy measure was the change in weekly cataplexy attacks from baseline. Secondary measures included daytime sleepiness using the Epworth Sleepiness Scale (ESS), inadvertent naps/sleep attacks, nighttime awakenings, and the overall change in disease severity as rated by the investigators (Clinical Global Impression of Change; CGI-c).Sodium oxybate, in doses of 3 to 9 g nightly, produced overall improvements in narcolepsy symptoms, which were significant at 4 weeks and maximal after 8 weeks. Reported improvements included a significant decrease in frequency of cataplexy attacks (p < 0.001); diminished daytime sleepiness (p < 0.001); and patient descriptions of nocturnal sleep quality, level of alertness, and ability to concentrate (for each p < 0.001). Adverse events were generally mild and patients showed no evidence of tolerance.Sodium oxybate is an effective and well-tolerated treatment for narcolepsy.

  View details for Web of Science ID 000181724800008

  View details for PubMedID 12627729

• Upper airway resistance syndrome, insomnia, and functional somatic syndromes CHEST Guilleminault, C., Dave, R. 2003; 123 (1): 12-14

  View details for Web of Science ID 000180491100006

  View details for PubMedID 12527594

• Arousal and upper airway resistance (UAR) SLEEP MEDICINE Guilleminault, C., Poyares, D. 2002; 3: S15-S20

  Abstract

  The objective of this study is to investigate upper airway resistance (UAR) in infants and children and presence/absence of electroencephalogram (EEG) arousal.Polysomnography with nasal cannula/pressure transducer and esophageal manometry; pattern recognition of sleep disordered breathing (SDB) in children. Identification of visually scored arousals in response to SDB. Power spectrum analysis of EEG associated with SDB.Several breathing patterns and change in heart rate (HR) can be seen with abnormal UAR during sleep. SDB may end with or without visual arousal. Power spectrum analysis shows different EEG patterns with termination of UAR and SDB. HR is also variably modified.Airway reopening and decline in UAR is associated with variable central nervous system activation and only intermittently with arousals.

  View details for Web of Science ID 000208301500004

  View details for PubMedID 14592373

• Work and rest sleep schedules of 227 European truck drivers. Sleep medicine Philip, P., Taillard, J., Léger, D., Diefenbach, K., Akerstedt, T., Bioulac, B., Guilleminault, C. 2002; 3 (6): 507-511

  Abstract

  To investigate the sleep-wake behavior and performance of a random sample of European truck drivers.The drivers completed a questionnaire concerning sleep-wake habits and disorders experienced during the previous 3 months. In addition, they were asked to complete a sleep and travel log that included their usual work and rest periods during the previous two days. They answered questions concerning working conditions and reported their caffeine and nicotine intake during their trips.A total of 227 drivers, mean age 37.7+/- 8.4 years (96.2% acceptance rate), participated in the study. The drivers were found to have a fairly consistent total nocturnal sleep time during their work week, but on the last night at home prior to the new work week there was an abrupt earlier wake-up time associated with a decrease in nocturnal sleep time. Of the drivers, 12.3% had slept less than 6 h in the 24 h previous to the interview and 17.1% had been awake more than 16 h.Shifting sleep schedules between work and rest periods can generate long episodes of wakefulness. This type of sleep deprivation is rarely investigated. Its is usually not taken into consideration when creating work schedules, but affects the performance of drivers. Unsuspected shifts occur at the onset of a new workweek. Sleep hygiene education for professional drivers is still far from perfect.

  View details for PubMedID 14592146

• Arousal, EEG spectral power and pulse transit time in LIARS and mild OSAS subjects CLINICAL NEUROPHYSIOLOGY Poyares, D., Guilleminault, C., Rosa, A., Ohayon, M., Koester, U. 2002; 113 (10): 1598-1606

  Abstract

  Upper airway resistance syndrome (UARS) and obstructive sleep apnea syndrome (OSAS) are associated with arousals and autonomic activation. Pulse transit time (PTT) has been used to recognize transient arousals. We examined the accuracy of PTT to recognize arousals, and the relationship between PTT deflection and visual and non-visual arousals.Ten UARS and 10 mild OSAS subjects were studied via polysomnography including measurement of esophageal pressure. Electroencephalogram (EEG) spectral power was obtained from central leads. Seven types of events were identified, depending upon the presence or absence of: a sleep-related respiratory event (SRRE), i.e. apnea, hypopnea, and abnormal breathing effort; a PTT signal; or a visually scored arousal (>1.5s).One thousand four hundred forty-six events were identified in 20 subjects. Fifty-nine percent of all SRREs were associated with a PTT signal and a visual EEG arousal. Nineteen percent of SRREs had no EEG arousals at their termination, and 7.4% had no associated PTT signal. Delta power was significantly increased when non-visual EEG arousals were scored. The time delay for PTT was determined by the presence or absence of EEG arousal. The sensitivity of PTT to recognize EEG arousal was 90.4% and the specificity was 16.8%. The sensitivity and specificity of PTT to recognize SRRE was 90.7 and 21.9%, respectively.These results preclude the use of PTT by itself. SRREs induce an activation with positive PTT response but without arousal in 14% of cases. This PTT response, however, is much slower than that occurring with arousal. UARS and mild OSAS do not respond in the same way to SRREs, particularly during rapid eye movement sleep.

  View details for Web of Science ID 000178783400010

  View details for PubMedID 12350436

• Sleep/wake cycles in the dark: sleep recorded by polysomnography in 26 totally blind subjects compared to controls CLINICAL NEUROPHYSIOLOGY Leger, D., Guilleminault, C., Santos, C., Paillard, M. 2002; 113 (10): 1607-1614

  Abstract

  To evaluate subjective sleep difficulties and nocturnal sleep with polysomnography in 26 completely blind subjects, living in normal social environments and to compare the findings with those of matched controls.Twenty-six blind individuals with no light perception and free-running melatonin rhythms, as assessed by measurements of urinary and salivary 6-sulfatoxymelatonin, were polygraphically monitored. Actigraphy and Braille sleep logs were obtained from the individuals for 14 days. Their sleep was compared to that of matched controls.Blind individuals were 'free-running' despite normal and regular social interaction. Each had ordinary working conditions and/or a family life with seeing spouse and children. Actigraphy obtained on 14 successive days showed the presence of small amount of daytime 'sleep' - 24.7+/-25.1 min per day. Total sleep time, sleep latency, sleep efficiency, and total REM sleep were significantly lower than in matched controls. Working blind subjects had a slightly higher total sleep time than those retired and unemployed. Congenital blindness, acquired blindness, presence of bilateral prosthetic eyes or presence of normal human eyes did not produce different nocturnal sleep and 'free-running' pattern results.Reduced total sleep time and other sleep abnormalities were associated with the complaint of daytime sleepiness and poor sleep in blind subjects. The abnormalities of sleep, which may be related to the free-running condition, present an additional challenge for these subjects, who are already severely impaired by their complete lack of vision.

  View details for Web of Science ID 000178783400011

  View details for PubMedID 12350437

• Medical and socio-professional impact of insomnia SLEEP Leger, D., Guilleminault, C., Bader, G., Levy, E., Paillard, M. 2002; 25 (6): 625-629

  Abstract

  Insomnia, a highly prevalent disorder with direct and indirect economic and professional consequences, affects daytime functioning, behavior, and quality of life. Several studies have shown that insomnia affects the workforce and is associated with an increased risk of accidents. Insomnia may also play a role in other disorders. Our study attempted to evaluate the socio-professional correlates of insomnia by comparing a group of insomniacs to a group of good sleepers.With a questionnaire focused on the socio-professional and medical consequences of insomnia, we surveyed a group of severe insomniacs and a group of good sleepers. Persons with psychiatric disorders according to the DSM-IV minimum criteria for anxiety and depression were eliminated from each group. After screening, 240 insomniacs and 391 good sleepers remained and were then compared.Compared to good sleepers, severe insomniacs reported more medical problems, had more physician-office visits, were hospitalized twice as often, and used more medication. Severe insomniacs had a higher rate of absenteeism, missing work twice as often as did good sleepers. They also had more problems at work (including decreased concentration, difficulty performing duties, and more work-related accidents).Our study showed that insomnia has socio-professional consequences and is correlated with lower medical status.

  View details for Web of Science ID 000177831900004

  View details for PubMedID 12224841

• Two-point palatal discrimination in patients with upper airway resistance syndrome, obstructive sleep apnea syndrome, and normal control subjects CHEST Guilleminault, C., Li, K., Chen, N. H., Poyares, D. 2002; 122 (3): 866-870

  Abstract

  To compare the results of a two-point palatal discrimination response in normal subjects (n = 15), patients with obstructive sleep apnea syndrome (OSAS) [n = 15], and patients with upper airway resistance syndrome (UARS) [n = 15] matched for age, sex, and body mass index.Comparison study of three subject groups.A sleep-disorders clinic.Participants were selected based on clinical questionnaire, clinical evaluation, and polysomnography.Polysomnography involving measurement of flow limitation with a nasal cannula pressure transducer system and of respiratory effort with esophageal pressure was performed in order to recognize the presence, absence, and types of sleep-disordered breathing. The 45 subjects were submitted to a two-point palatal discrimination study during wakefulness performed by an investigator blinded to the polysomnogram results.Patients with OSAS had a clear impairment of their palatal sensory input with a significant decrement in two-point discrimination, but patients with UARS and normal control subjects had similar responses. Patients with UARS exhibited at least intermittent snoring in most cases.The normal responses seen in patients with UARS indicate that these patients are more capable of transmitting sensory inputs than patients with OSAS. This may be one element explaining the difference in arousal response previously documented in UARS compared to OSAS.

  View details for Web of Science ID 000177990300020

  View details for PubMedID 12226025

• Temperature-controlled radiofrequency tongue base reduction for sleep-disordered breathing: Long-term outcomes OTOLARYNGOLOGY-HEAD AND NECK SURGERY Li, K. K., Powell, N. B., Riley, R. W., Guilleminault, C. 2002; 127 (3): 230-234

  Abstract

  Our goal was to evaluate the long-term outcomes of temperature-controlled radiofrequency reduction of the tongue base in sleep-disordered breathing.The 18 patients from our initial pilot study were reevaluated. Clinical examinations, polysomnography (PSG), questionnaires, visual analog scales, and a comparative SF-36 were used to assess long-term outcomes.Sixteen of the original 18 patients completed this study; 2 patients were lost to follow-up. The mean follow-up was 28 months. There was a mean weight increase of 3.1 +/- 7.9 kg. The original pretreatment Respiratory Disturbance Index (RDI) was a mean of 39.5 with a mean mean oxygen saturation nadir (LSAT) of 81.9%, and the posttreatment RDI was a mean of 17.8 with a mean LSAT of 88.3%. Follow-up PSG data showed a persistent improvement of the mean Apnea Index compared with pretreatment (5.4 vs 22.1) without significant changes compared with posttreatment (4.1). However, there were changes in the follow-up Hypopnea Index (HI) of 22.9 compared with the pretreatment and posttreatment HI values of 17.4 and 13.6, respectively. This resulted in a relapse of the RDI from a posttreatment value of 17.8 to 28.7. The LSAT also worsened from 88.3% to 85.8%. However, there was no significant deterioration in the quality-of-life measurements by SF-36 or in daytime sleepiness by Epworth Sleepiness Scale.The success of temperature-controlled radiofrequency tongue base reduction for sleep-disordered breathing may reduce with time. PSG demonstrated that long-term relapse is primarily reflected in the HI without significant detrimental effects on the patient's quality of life (SF-36) and sleepiness (Epworth Sleepiness Scale). Continual evaluation of this treatment modality is warranted.

  View details for DOI 10.1067/mhn.2002.126900

  View details for Web of Science ID 000178169000016

  View details for PubMedID 12297815

• Chronic insomnia, postmenopausal women, and sleep disordered breathing - Part 1. Frequency of sleep disordered breathing in a cohort JOURNAL OF PSYCHOSOMATIC RESEARCH Guilleminault, C., Palombini, L., Poyares, D., Chowdhuri, S. 2002; 53 (1): 611-615

  Abstract

  A cohort of postmenopausal women complaining of chronic insomnia for over 6 months and free of hypnotic intake was recruited mostly from the community. Three hundred and ninety-four women were included. The following questions were addressed: How many presents sleep disordered breathing (SDB)? Which type of SDB (upper airway resistance syndrome [UARS] or obstructive sleep apnea syndrome [OSAS]) is the most frequent? Is there a specific upper airway anatomical abnormality in SDB patients predisposing to the syndrome?Subjects were recruited in the community or referred by the Sleep Clinic and all had complaint of chronic poor sleep.First step. Questionnaires, visual analog scales, clinical interview, clinical evaluation with work-up, actigraphy, and ambulatory monitoring were used. Second step. Otolaryngologic evaluation, ambulatory sleep monitoring, and reading of results were used. Subjects negative for SDB at ambulatory monitoring had polysomnography (PSG) with pressure transducer/nasal cannula system and esophageal manometry measurements.Population. Three hundred and ninety-four individuals responded to all entry criteria. Ambulatory monitoring identified 194 subjects with OSAS. Two hundred individuals were not recognized with SDB and were submitted to PSG. This further testing showed that 68 subjects had normal breathing, 62 had UARS, and 100 mild OSAS. Based on otolaryngological evaluation, subjects were classified based on the presence or absence of narrow upper airway, and the location of narrowing was assessed.A total of 326 postmenopausal women complaining of chronic insomnia had a SDB, usually with low apnea-hypopnea index (AHI). This total represents about 83% of the studied women. Questions of the role of SDB in the complaint of chronic insomnia are raised.

  View details for Web of Science ID 000177230200013

  View details for PubMedID 12127179

• Chronic insomnia, premenopausal women and sleep disordered breathing - Part 2. Comparison of nondrug treatment trials in normal breathing and UARS post menopausal women complaining of chronic insomnia JOURNAL OF PSYCHOSOMATIC RESEARCH Guilleminault, C., Palombini, L., Poyares, D., Chowdhuri, S. 2002; 53 (1): 617-623

  Abstract

  The question addressed here is: Can a discrete sleep disordered breathing (SDB) play a role in the insomnia complaint of postmenopausal chronic insomniacs? To respond to the query, two groups of individuals derived from a cohort of postmenopausal chronic insomniacs recruited mostly from the community were enlisted in a treatment protocol. These subjects were all individuals identified with normal breathing (n=68) and all those recognized with Upper Airway Resistance Syndrome (UARS) (n=62) pooled from a cohort of 349 postmenopausal insomniacs. TREATMENT PROTOCOL: The 62 UARS were allocated to either treatment of chronic insomnia by behavioral approaches or treatment of SDB. Based on ENT evaluation, health professionals in charge of patients selected either treatment with nasal CPAP or treatment of nasal turbinates. A stratification correction was performed to obtain a near equal number of both treatment modalities in each of the two subgroups. The 68 individuals with normal breathing were randomly allocated to immediate behavioral treatment of insomnia or delay treatment of insomnia. The delay treatment received a list of 10 sleep hygiene recommendations by mail.Questionnaires, visual analog scales (VAS), Epworth Sleepiness Scale (ESS), clinical interviews, clinical evaluation with oto-laryngologic clinical assessment of a presence/absence of narrow upper airway and location of narrowing. Actigraphy and polysomnography (PSG) with pressure transducer/and nasal cannula system and esophageal manometry. DATA ANALYSES: All recording data were scored blind to patient's condition.Two subjects in the SBD-CPAP treated group (Group B) and two subjects in the delayed treatment group (Group D) dropped out. Total sleep time was improved compared to baseline in all groups, including the delayed treatment group. One group was significantly better (ANOVA, P=.05) with a more important delta score compared to baseline, and this was the behaviorally treated non-SDB. Sleep latency was significantly decreased in the behaviorally treated group (with or without SBD), P=.05, compared to SBD-treated and delayed treatment groups. Sleep latency was, however, improved in all groups. VAS for "quality of sleep" was higher at 6 months in all the groups when compared to "baseline" values. VAS for "daytime fatigue" showed significant differences among the four groups (ANOVA, P=.01); the overall score at the end of treatment was significantly better in the SDB-treated group than the other three groups. SBD was treated either by radio frequency on nasal turbinate or by nasal CPAP. CPAP-treated patients had a lower VAS score than nasal turbinate treatment, but the difference was only a trend. The delta improvement (6-month baseline condition) in "daytime fatigue" of each subgroup was calculated and compared within and between groups. Despite the small number of subjects, the turbinate-treated subgroup was significantly different from Groups B, C and D (ANOVA, P=.05). When a similar comparison was made with the nasal CPAP group, there was only a nonsignificant trend when compared to Groups B, C and D.Abnormal breathing during sleep significantly enhanced complaints of daytime fatigue in postmenopausal chronic insomniacs and this complaint improved with SDB treatment. This improvement is significantly better compared to SDB insomniacs treated with a behavioral regimen. Behavioral treatment, however, gave the best response in the non-SDB chronic insomnia group and improved better long sleep latency even in the SDB group. These results suggest the need to find an appropriate treatment for SBD even if mild and to recognize the role of SDB in relation to symptoms seen with chronic insomnia.

  View details for Web of Science ID 000177230200014

  View details for PubMedID 12127180

• Obstructive sleep apnea and maxillomandibular advancement: An assessment of airway changes using radiographic and nasopharyngoscopic examinations JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY Li, K. K., Guilleminault, C., Riley, R. W., Powell, N. B. 2002; 60 (5): 526-530

  Abstract

  The study aim was to evaluate the resultant changes in the upper airway after maxillomandibular advancement (MMA) for obstructive sleep apnea.Twelve patients were evaluated before and after MMA using fiberoptic nasopharyngoscopy (NPG) with Müller maneuver. An inspiratory force meter was used to ensure the consistency of the inspiratory efforts between the 2 examinations. Preoperative and postoperative lateral cephalometric radiographs were also compared.Decrease in the airway obstruction was shown by the lateral cephalometric radiograph as well as by fiberoptic NPG during passive respiration. Fiberoptic NPG with Müller maneuver also revealed a decrease in airway collapsibility. Although the retrodisplacement of the tongue base was improved, the improvement in lateral pharyngeal wall stability was the most striking.MMA achieved expansion of the upper airway. In addition, MMA decreased the collapsibility of the airway, especially the lateral pharyngeal walls. These findings may explain the highly successful outcomes of MMA for the treatment of obstructive sleep apnea.

  View details for DOI 10.1053/joms.2002.31849

  View details for Web of Science ID 000175407700012

  View details for PubMedID 11988930

• Can valerian help insomnia patients after BZD withdrawal? Poyares, D., Guilleminault, C., Ohayon, M. M., Moraes, W. D., Tufik, S. AMER ACAD SLEEP MEDICINE. 2002: A483–A484

  View details for Web of Science ID 000174927200688

• Two-point palatal discrimination response is normal in Upper Airway Resistance Syndrome and reduced in Obstructive Sleep Apnea Syndrome Robinson, A., Li, K., Robinson, A., Guilleminault, C. AMER ACAD SLEEP MEDICINE. 2002: A221–A222

  View details for Web of Science ID 000174927200298

• Can valerian improve the sleep of insomniacs after benzodiazepine withdrawal? PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY Poyares, D. R., Guilleminault, C., Ohayon, M. M., Tufik, S. 2002; 26 (3): 539-545

  Abstract

  The authors studied the sleep of patients with insomnia who complained of poor sleep despite chronic use of benzodiazepines (BZDs). The sample consisted of 19 patients (mean age 43.3+/-10.6 years) with primary insomnia (DSM-IV), who had taken BZDs nightly, for 7.1+/-5.4 years. The control group was composed of 18 healthy individuals (mean age 37+/-8 years). Sleep electroencephalogram (EEG) of the patients was analyzed with period amplitude analysis (PAA) and associated algorithms, during chronic BZD use (Night 1), and after 15 days of a valerian placebo trial (initiated after washout of BZD, Night 2). Sleep of control subjects was monitored in parallel.Valerian subjects reported significantly better subjective sleep quality than placebo ones, after BZD withdrawal, despite the presence of a few side effects. However, some of the differences found in sleep structure between Night 1 and Night 2 in both the valerian and placebo groups may be due to the sleep recovery process after BZD washout. Example of this are: the decrease in Sleep Stage 2 and in sigma count; the increase in slow-wave sleep (SWS), and delta count, which were found to be altered by BZD ingestion. There was a significant decrease in wake time after sleep onset (WASO) in valerian subjects when compared to placebo subjects; results were similar to normal controls. Nonetheless, valerian-treated patients also presented longer sleep latency and increased alpha count in SWS than control subjects.The decrease in WASO associated with the mild anxiolytic effect of valerian appeared to be the major contributor to subjective sleep quality improvement found after 2-week of treatment in insomniacs who had withdrawn from BDZs. Despite subjective improvement, sleep data showed that valerian did not produce faster sleep onset; the increase in alpha count compared with normal controls may point to residual hyperarousabilty, which is known to play a role in insomnia. Nonetheless, we lack data on the extent to which a sedative drug can improve alpha sleep EEG. Thus, the authors suggest that valerian had a positive effect on withdrawal from BDZ use.

  View details for Web of Science ID 000174698300017

  View details for PubMedID 11999905

• Associations between symptoms of inattention, hyperactivity, restless legs, and periodic leg movements SLEEP Chervin, R. D., Archbold, K. H., Dillon, J. E., Pituch, K. J., Panahi, P., Dahl, R. E., Guilleminault, C. 2002; 25 (2): 213-218

  Abstract

  Attention-deficit/hyperactivity disorder (ADHD) has shown associations with restless legs syndrome (RLS) and periodic leg movements during sleep (PLMS) among small samples of referred children, but whether RLS or PLMS are common more generally among hyperactive children has not been well studied.Cross-sectional survey.Two university-affiliated but community-based general pediatrics clinics.N=866 children (469 boys), aged 2.0 to 13.9 years (mean 6.8+/-3.2 years), with clinic appointments.N/A.A validated Pediatric Sleep Questionnaire assessed for PLMS (a 6-item subscale), restless legs, growing pains, and several potential confounds of an association between behavior and PLMS or RLS. Parents also completed two common behavioral measures, a DSM-IV-derived inattention/hyperactivity scale (IHS) and the hyperactivity index (HI, expressed as a t-score) of the Conners' Parent Rating Scale.Restless legs were reported in 17% (95% C.I. [15, 20]) of the subjects. Positive HI scores (>60) were found in 13% [11, 16] of all subjects, 18% [12, 25] of children with restless legs, and 11% [9, 14] of children without restless legs (chi-square p<0.05). Odds ratios between HI>60 and each of the following were: a one-s.d. increase in the overall PLMS score, 1.6 [1.4, 1.9]; restless legs, 1.9 [1.1, 3.2]; and growing pains, 1.9 [0.9, 3.6] (all age and sex-adjusted). Results were similar for high IHS scores (>1.25). The associations between each behavioral measure and the PLMS score retained significance after statistical adjustment for sleepiness, snoring, restless sleep in general, or stimulant use.Inattention and hyperactivity among general pediatric patients are associated with symptoms of PLMS and RLS. If either condition contributes to hyperactivity, the magnitude of association suggests an important public health problem.

  View details for Web of Science ID 000174275400010

  View details for PubMedID 11902431

• Rapid Eye Movement Sleep-related Parasomnias. Current treatment options in neurology Lee, M. K., Guilleminault, C. 2002; 4 (2): 113-120

  Abstract

  Among the rapid eye movement (REM) sleep-related parasomnias, the most common and important disorder for which patients present is REM sleep behavior disorder (RBD). Rapid eye movement sleep behavior disorder is often undiagnosed for many years, despite the sometimes bizarre and harmful behaviors involved. Complete evaluation and accurate diagnosis are essential for proper management. This includes medical, sleep/wake, psychiatric, and neurologic histories. Although they may raise feelings of guilt or shame, questions related to sexual and violent behaviors should be directed towards the identified patient as well as their bed partners. Objective studies should include nocturnal polysomnogram with audiovisual monitoring of behavior, electromyography (EMG) of all limbs, and seizure montage. Brain imaging, clinical electroencephalogram (EEG), neuropsychometric testing, and actigraphy may be used adjunctively. Clinicians should have a high index of suspicion for other neurologic conditions, especially neurodegenerative disorders and narcolepsy, because many patients with RBD have these conditions. Rapid eye movement sleep behavior disorder may actually precede symptoms and signs associated with other neurologic disorders, so close follow-up is recommended. Medications that may be causing or exacerbating RBD should be withdrawn, if possible. Clonazepam is very effective in reducing the symptoms of RBD. This treatment is generally well tolerated and may be used long-term. Discontinuation of clonazepam usually leads to relapse of symptoms. Safety-related issues should be discussed with patients and their families.

  View details for PubMedID 11827643

• Technical protocol for the use of esophageal manometry in the diagnosis of sleep-related breathing disorders SLEEP MEDICINE Kushida, C. A., Giacomini, A., Lee, M. K., Guilleminault, C., Dement, W. C. 2002; 3 (2): 163-173

  Abstract

  A time-tested protocol for intrathoracic pressure monitoring during sleep is described. This method of esophageal manometry uses a fluid-filled catheter to measure variations in transmitted intrathoracic pressure with respiration. Esophageal manometry is an invaluable tool for the sleep specialist in the diagnosis of sleep-related breathing disorders, especially for detecting cases of upper airway resistance syndrome and for distinguishing subtle central apneas from obstructive events. The methods for scoring esophageal pressure, the indications and contraindications for esophageal manometry, the use of esophageal manometry as the 'gold standard' for the measurement of respiratory effort, and directions for future research are also discussed.

  View details for Web of Science ID 000208301700014

  View details for PubMedID 14592238

• Sleep and EEG power spectrum in post encephalitis hypersomnia: a case report SLEEP MEDICINE Poyares, D., Guilleminault, C., Rosa, A. 2002; 3 (2): 155-158

  Abstract

  The nocturnal recordings of breathing, and sleep and daytime multiple sleep latency tests over the 5 year follow-up of a patient with post encephalitis hypersomnia are presented. EEG power spectrum analysis was performed on the last polysomnographic recording, and the results were compared with those obtained for a matched control subject. The patient presented initially a hypoventilation syndrome controlled by nasal bilevel positive pressure at night. The syndrome progressively improved, but daytime sleepiness stayed unchanged with limited help from stimulants. Fast Fourier transformation analysis of the last nocturnal recording demonstrates a decrease in absolute power for all frequency bands in all sleep stages, but a cyclical presence of the NREM/REM.

  View details for Web of Science ID 000208301700012

  View details for PubMedID 14592236

• Atlas, rules, and recording techniques for the scoring of cyclic alternating pattern (CAP) in human sleep SLEEP MEDICINE Terzano, M. G., Parrino, L., Smerieri, A., Chervin, R., Chokroverty, S., Guilleminault, C., Hirshkowitz, M., Mahowald, M., Moldofsky, H., Rosa, A., Thomas, R., Walters, A. 2002; 3 (2): 187-199

  View details for Web of Science ID 000208301700020

  View details for PubMedID 14592244

• Atypical sexual behavior during sleep PSYCHOSOMATIC MEDICINE Guilleminault, C., Moscovitch, A., Yuen, K., Poyares, D. 2002; 64 (2): 328-336

  Abstract

  This article reports a case series of atypical sexual behavior during sleep, which is often harmful to patients or bed partners.Eleven subjects underwent clinical evaluation of complaints of sleep-related atypical sexual behavior. Complaints included violent masturbation, sexual assaults, and continuous (and loud) sexual vocalizations during sleep. One case was a medical-legal case. Sleep logs, clinical evaluations, sleep questionnaires, structured psychiatric interviews, polysomnography, actigraphy, home electroencephalographic monitoring during sleep, and clinical electroencephalographic monitoring while awake and asleep were used to determine clinical diagnoses.Atypical sexual behaviors during sleep were associated with feelings of guilt, shame, and depression. Because of these feelings, patients and bed partners often tolerated the abnormal behavior for long periods of time without seeking medical attention. The following pathologic sleep disorders were demonstrated on polysomnography: partial complex seizures, sleep-disordered breathing, stage 3 to 4 non-rapid eye movement (REM) sleep parasomnias, and REM sleep behavior disorder. These findings were concurrent with morning amnesia.The atypical behaviors were related to different syndromes despite the similarity of complaints from bed partners. In most cases the disturbing and often harmful symptoms were controlled when counseling was instituted and sleep disorders were treated. In some cases treatment of seizures or psychiatric disorders was also needed. Clonazepam with simultaneous psychotherapy was the most common successful treatment combination. The addition of antidepressant or antiepileptic medications was required in specific cases.

  View details for Web of Science ID 000174551600017

  View details for PubMedID 11914450

• Sleepy driving: Accidents and injury 105th Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery Powell, N. B., Schechtman, K. B., Riley, R. W., Li, K., Guilleminault, C. MOSBY-ELSEVIER. 2002: 217–27

  Abstract

  The study goals were to evaluate the associated risks of driving and to assess predictors of accidents and injury due to sleepiness.A cross-sectional Internet-linked survey was designed to elicit data on driving habits, sleepiness, accidents, and injuries during the preceding 3 years. Statistical analysis included logistic models with covariate-adjusted P values of <0.01 (odds ratios and 95% confidence intervals or limits). Independent accident predictors were sought.Responses from 10,870 drivers were evaluated. The mean +/- SD age was 36.9 +/- 13 years; 61% were women and 85% were white. The Epworth Sleepiness Scale overall baseline score was 7.4 +/- 4.2 (for drivers with no accidents) and ranged to 12.7 +/- 7.2 (for drivers with > or = 4 accidents) (P = < 0.0001). Twenty-three percent of all respondents experienced > or = 1 accident. Among respondents who reported > or = 4 accidents, a strong association existed for the most recent accident to include injury (P < 0.0001). Sleep disorders were reported by 22.5% of all respondents, with a significantly higher prevalence (35%, P = 0.002) for drivers who had been involved in > or = 3 accidents.Factors of sleepiness were strongly associated with a greater risk of automobile accidents. Predictors were identified that may contribute to accidents and injury when associated with sleepiness and driving.

  View details for DOI 10.1067/mhn.2002.122699

  View details for Web of Science ID 000175371100003

  View details for PubMedID 11956528

• Inattention, hyperactivity, and symptoms of sleep-disordered breathing PEDIATRICS Chervin, R. D., Archbold, K. H., Dillon, J. E., Panahi, P., Pituch, K. J., Dahl, R. E., Guilleminault, C. 2002; 109 (3): 449-456

  Abstract

  Inattention and hyperactivity are frequent among children with sleep-disordered breathing (SDB) and often improve when SDB is treated. However, the frequency of SDB symptoms among inattentive and hyperactive children has received little study.Cross-sectional survey.Two university-affiliated but community-based general pediatrics clinics.Patients consisted of N = 866 children (469 boys), aged 2.0 to 13.9 years (mean: 6.8 plus minus 3.2 years), with clinic appointments.A validated Pediatric Sleep Questionnaire assessed for habitual snoring (1 item), snoring severity (a 4-item subscale), sleepiness (4 items), and overall risk of SDB (16 items). Parents also completed 2 common behavioral measures, an inattention/hyperactivity scale (IHS) derived from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and the hyperactivity index (HI, expressed as a t score) of the Conners' Parent Rating Scale.Habitual snoring was reported in 16% (95% confidence interval [CI]: 13, 19) of the participants. High HI scores (>60) were found in 13% (95% CI: 11, 16) of all participants, 22% (95% CI: 15, 29) of habitual snorers, and 12% (95% CI: 9, 14) of nonsnorers. Odds ratios between HI >60 and each of the following were: habitual snoring, 2.2 (95% CI: 1.4, 3.6); 1 additional positive symptom-item on the snoring scale, 1.3 (95% CI: 1.1, 1.5); 1 additional positive item on the sleepiness scale, 1.6 (95% CI: 1.4, 2.0); and a 1-standard deviation increase in the overall SDB score, 1.7 (95% CI: 1.4, 2.0; all odds ratios age- and sex-adjusted). Results were similar for high IHS scores (>1.25). Stratification by age and sex showed that most of the association with snoring (but not sleepiness) derived from boys <8 years old.Inattention and hyperactivity among general pediatric patients are associated with increased daytime sleepiness and---especially in young boys---snoring and other symptoms of SDB. If sleepiness and SDB do influence daytime behavior, the current results suggest a major public health impact.

  View details for Web of Science ID 000174202800023

  View details for PubMedID 11875140

• A randomized, double blind, placebo-controlled multicenter trial comparing the effects of three doses of orally administered sodium oxybate with placebo for the treatment of narcolepsy SLEEP Black, J., Guilleminault, C., Bogan, R., Emsellem, H., Feldman, N., Hagaman, M., Hertz, G., Iyer, V., Kathawalla, S., Lankford, D., Mitler, M., Hayduk, R., Pascualy, R., Sahota, P., Roth, T., Scharf, M., Scrima, L., SCHWARTZ, J., Zammit, G. 2002; 25 (1): 42-49

  Abstract

  To evaluate and compare the efficacy and safety of three doses of sodium oxybate and placebo for the treatment of narcolepsy symptoms.A multicenter, double blind, placebo-controlled trial.N/A.Study subjects were 136 narcolepsy patients with 3 to 249 (median 21) cataplexy attacks weekly.Prior to baseline measures, subjects discontinued anticataplectic medications. Stable doses of stimulants were permitted. Subjects were randomized in blinded fashion to receive 3, 6, or 9 g doses of sodium oxybate or placebo taken in equally divided doses upon retiring to bed and 2.5-4 hours later for 4 weeks.Disease symptoms and adverse events were recorded in daily diaries. The primary measure of efficacy was the change from baseline in weekly cataplexy attacks. Secondary measures included daytime sleepiness using the Epworth Sleepiness Scale (ESS), inadvertent daytime naps/sleep attacks and nighttime awakenings. Investigators assessed changes in disease severity using Clinical Global Impression of Change (CGI-c). Compared to placebo, weekly cataplexy attacks were decreased by sodium oxybate at the 6 g dose (p=0.0529) and significantly at the 9 g dose (p=0.0008). The ESS was reduced at all doses, becoming significant at the 9 g dose (p=0.0001). The CGI-c demonstrated a dose-related improvement, significant at the 9 g dose (p=0.0002). The frequency of inadvertent naps/sleep attacks and the nighttime awakenings showed similar dose-response trends, becoming significant at the 9 g dose (p=0.0122 and p=0.0035, respectively). Sodium oxybate was generally well-tolerated at all three doses. Nausea, headache, dizziness and enuresis were the most commonly reported adverse events.Sodium oxybate significantly improved symptoms in patients with narcolepsy and was well tolerated.

  View details for Web of Science ID 000173415100008

  View details for PubMedID 11833860

• Distraction osteogenesis in adult obstructive sleep apnea surgery: A preliminary report JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY Li, K. K., Powell, N. B., Riley, R. W., Guilleminault, C. 2002; 60 (1): 6-10

  Abstract

  This study evaluated the potential application of distraction osteogenesis (DO) for skeletal expansion in the management of adult patients with obstructive sleep apnea syndrome (OSAS).Five consecutive adult patients (3 male, 2 female) underwent a DO procedure with intraoral distraction devices for the management of OSAS. The surgical procedures were mandibular advancement (n = 4, with 3 bilateral advancement and 1 unilateral advancement) and simultaneous maxillomandibular advancement (n = 1). Starting 7 days after surgery, the distraction devices were activated 4 times daily at a rate of 1.0 mm/d until the desired skeletal expansion was achieved. All of the patients underwent pre- and postoperative radiographic analysis and polysomnography. The distraction devices were removed 3 months after the completion of the distraction process.The amount of skeletal advancement by distraction ranged from 5.5 to 12.5 mm, with the mean distance being 8.1 mm. The postoperative polysomnographic results showed improvement of OSAS in all 5 patients with an improvement of the mean RDI from 49.3 events per hour to 6.6 events per hour. The lowest oxygen saturation improved from 79.8% to 85.8%. The mean follow-up period was 12 months. Complications included localized inflammation at the distraction device site (n = 2), temporary temporomandibular joint (TMJ) discomfort during distraction process (n = 1), and temporary paresthesia of the inferior alveolar nerve distribution (n = 2). A moderate amount of pain during the activation of the distraction devices was reported (n = 3) and was adequately treated with analgesics. None of the complications led to permanent problems.This limited case series shows that DO is applicable in selected adult patients for skeletal advancement in the treatment of OSAS. However, there are disadvantages with the use of DO, and further investigations are necessary to determine the potential of this technique.

  View details for DOI 10.1053/joms.2002.29049

  View details for Web of Science ID 000173121900004

  View details for PubMedID 11756997

• Sleep-disordered Breathing in Neuromuscular Disease. Current treatment options in neurology Guilleminault, C., Shergill, R. P. 2002; 4 (2): 107–12

  Abstract

  Patients with neuromuscular disorders involving respiratory muscles (upper airway muscles, respiratory accessory muscles, diaphragm, even abdominal muscles that stabilize the chest) have more significant problems with breathing during sleep, especially during REM sleep, than during wakefulness. There are means of appropriately treating sleep disordered breathing and improving the quality of life of these patients. Treatment helps to avoid daytime symptoms and additional autonomic nervous system dysfunction. The treatment involves support of breathing during sleep. It must be adjusted to the severity of the problem during sleep, which implies systematic investigation and treatment based on polygraphic recordings during sleep. Patients, even when stable, need to be monitored during sleep at least once a year and more often if symptomatic, ie, appearance of any daytime symptom or frequent upper respiratory infection or indication of daytime CO(2) retention.

  View details for PubMedID 11827642

• Upper airway resistance syndrome in children: a clinical review. Seminars in pediatric neurology Guilleminault, C., Khramtsov, A. 2001; 8 (4): 207-215

  Abstract

  Upper airway resistant syndrome (UARS) is more common in children than is obstructive sleep apnea syndrome (OSAS). Age will color the symptoms associated with the syndrome. UARS must be looked for in families with adult sleep-disordered breathing. Polygraphic recording during sleep will show flow limitation with usage of nasal cannula/pressure transducer system, but the abnormal breathing during sleep may be indicated also by burst of tachypnea without saturation drops. Esophageal pressure monitoring may be the only way to confirm a suspected diagnosis. A mild developmental anomaly of the craniofacial skeleton is often seen in these children even in the presence of enlarged tonsils and adenoids. Children with sleep-disordered breathing should have a maxillomandibular examination to assess the need for orthodontic treatment to expand the oral cavity.

  View details for PubMedID 11768783

• [Disorders of wakefulness and sleep in blind patients]. Revue neurologique Léger, D., Stal, V., Quera-Salva, M. A., Guilleminault, C., Paillard, M. 2001; 157 (11): S135-9

  Abstract

  The goal of this paper was to summarize three studies focused on sleep/wake disorders in blind subjects. The first study was an epidemiology survey performed in 1073 blind subjects in comparison with non-blind controls. The blind had more episodes of insomnia and free running rhythms. They also took more sleeping pills and complained of more daytime somnolence. The seriousness of the sleep disorders was related to the seriousness of the blindness. In the second study, 78 blind children were compared with seeing children. They had more insomnia and more parasomnias but there was not any more free running. Finally, polysomnography was performed in 26 free running blind subjects in comparison with 26 controls. Total sleep time and sleep efficiency were lower in the blind. Sleep latency was increased and REM sleep was disturbed (longer latency and percentage decreases). There was no difference concerning slow wave sleep. Factorial analysis showed that factors such as being born blind, having ocular prosthesis, being single or having children had no influence on sleep. Working did however have an influence.

  View details for PubMedID 11924026

• Atlas, rules, and recording techniques for the scoring of cyclic alternating pattern (CAP) in human sleep SLEEP MEDICINE Terzano, M. G., Parrino, L., Sherieri, A., Chervin, R., Chokroverty, S., Guilleminault, C., Hirshkowitz, M., Mahowald, M., Moldofsky, H., Rosa, A., Thomas, R., Walters, A. 2001; 2 (6): 537-553

  View details for Web of Science ID 000208301300008

• Sleep/wake disorders in the blind. 15th Congress of the French-Society-for-Sleep-Research/7th Meeting of the Sleep-Group of the Society-of-French-Speaking-Lung-Specialists Leger, D., Stal, V., Quera-Salva, M. A., Guilleminault, C., Paillard, M. MASSON EDITEUR. 2001: S135–S139

  View details for Web of Science ID 000172849600029

• New insights into the pathogenesis and treatment of narcolepsy. Current opinion in pulmonary medicine Brooks, S. N., Guilleminault, C. 2001; 7 (6): 407-410

  Abstract

  Narcolepsy is a complex neurologic disorder, which has significant negative impacts on the lives of those who have it. Although the disorder is treatable, traditional methods do not alleviate symptoms completely and often produce unwanted side effects. Fortunately, recent advances in the understanding of narcolepsy offer the promise of improved treatments in the foreseeable future.

  View details for PubMedID 11706317

• Atlas, rules, and recording techniques for the scoring of cyclic alternating pattern (CAP) in human sleep. Sleep medicine Terzano, M. G., Parrino, L., Sherieri, A., Chervin, R., Chokroverty, S., Guilleminault, C., Hirshkowitz, M., Mahowald, M., Moldofsky, H., Rosa, A., Thomas, R., Walters, A. 2001; 2 (6): 537-553

  View details for PubMedID 14592270

• Radiofrequency treatment of turbinate hypertrophy in subjects using continuous positive airway pressure: A randomized, double-blind, placebo-controlled clinical pilot trial LARYNGOSCOPE Powell, N. B., Zonato, A. I., Weaver, E. M., Li, K., Troell, R., Riley, R. W., Guilleminault, C. 2001; 111 (10): 1783-1790

  Abstract

  To estimate the treatment effect of temperature-controlled radiofrequency (TCRF) reduction of turbinate hypertrophy in patients with sleep-disordered breathing (SDB) treated with nasal continuous positive airway pressure (CPAP), and to assess the impact of study design on this estimate.Prospective, randomized, double-blind, placebo-controlled clinical pilot trial.Twenty-two CPAP-treated patients with SDB with turbinate hypertrophy were randomly assigned to either TCRF turbinate treatment (mean energy 415 +/- 37 J/turbinate; n = 17) or placebo control (n = 5). Changes in nasal obstruction were evaluated between pretreatment and 4 weeks post-treatment. The primary outcome assessed changes in the blinded examiners' findings of nasal obstruction on a visual analogue scale (VAS). Secondary outcomes included blinded patients' and unblinded examiner assessments of nasal obstruction (VAS), nightly CPAP use, adherence, and tolerance, along with sleepiness and general health status scales. The treatment group findings were subtracted from the changes in the placebo group to yield treatment effect.The primary outcome treatment effect by VAS was -0.9 cm (95% confidence interval [CI], -2.4, 0.7), and beyond the placebo effect of -1.5 cm (95% CI: -3.4, 0.3). The secondary treatment effect of the unblinded examiner was -3.0 cm (95% CI, -4.9, -1.1). A beneficial treatment effect was also seen on every secondary outcome except general health status, but only self-reported CPAP adherence (P = .03) was statistically significant.TCRF turbinate treatment appears to benefit nasal obstruction and CPAP treatment for SDB. Placebo control and double blinding are critical for establishing the true treatment effect. A future definitive trial is feasible to establish statistical significance of these findings.

  View details for Web of Science ID 000171422900023

  View details for PubMedID 11801946

• Medications for the treatment of narcolepsy. Expert opinion on emerging drugs Black, J., Guilleminault, C. 2001; 6 (2): 239-247

  Abstract

  Narcolepsy is a syndrome of unknown aetiology characterised by excessive daytime sleepiness (often severe) usually in association with cataplexy (brief episodes of partial or complete muscle paralysis) and often with other uncommon symptoms. Due to limited disease-specific knowledge, medication treatment for this condition has focussed on specific symptom amelioration rather than improving or eliminating underlying disease mechanisms. Such treatment generally consists of stimulants for daytime sleepiness and anticataplectic medication for cataplexy; hence, both types of agents are reviewed in this article. Recent discoveries, including the finding that canine familial narcolepsy is caused by a single gene defect in the hypocretin receptor, coupled with the findings in human narcoleptics of undetectable hypocretin levels in the CSF and of severe hypocretin-containing neuronal atrophy in brains of deceased narcoleptics, have shifted the focus of narcolepsy treatment research to the hypocretin system. The hope is that a single agent can be developed to provide effective treatment for all symptoms of narcolepsy. While the mechanism of action in narcolepsy is unknown, gamma-hydroxybutyrate (GHB) is proving to be such an agent. Interestingly, GHB is not known to impact hypocretin pathways in the brain, yet specific research exploring this possible interaction has not been performed. The market for medications limited to use by narcoleptics is small because of the relatively low prevalence of narcolepsy; however, the prevalence of clinically important daytime sleepiness and/or fatigue is surprisingly high. New agents that effectively manage the sleepiness of narcolepsy thus have a much larger potential for appropriate use in treating sleepiness and fatigue in the general population. This fact has recently been demonstrated by the tremendous success of modafinil, a drug introduced to the market a little over 2 years ago, which was developed to treat sleepiness in narcolepsy but now is used in a much larger patient population.

  View details for PubMedID 15989524

• Sleep-disordered breathing and hypotension AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE Guilleminault, C., Faul, J. L., Stoohs, R. 2001; 164 (7): 1242-1247

  Abstract

  We investigated the presence of low blood pressure (BP) in 4,409 subjects referred for overnight polysomnography. A low resting arterial BP (systolic BP < 105 mm Hg, diastolic BP < 65 mm Hg) was present in 101 subjects (2.3%). Low BP was more prevalent in subjects with upper airway resistance syndrome (UARS) (23%) than in subjects with obstructive sleep apnea syndrome (OSAS) (0.06%), parasomnia (0.7%), restless leg syndrome (0.9%), or psychological insomnia (0.9%). In order to investigate BP homeostasis, we conducted polysomnography followed by tilt-table testing on 15 subjects with orthostatic intolerance (OI) and UARS, five normotensive subjects with UARS, five subjects with insomnia and low BP, 15 subjects with OSAS, and 15 healthy control subjects. Fifteen subjects with UARS and OI and 15 healthy controls also underwent 24-h ambulatory BP monitoring. Subjects with OI and UARS had lower mean daytime systolic (119 +/- 28 mm Hg) and diastolic (75 +/- 18 mm Hg) BP than did control subjects (131 +/- 35 mm Hg and 86 +/- 19 mm Hg, respectively) (p < 0.05). During tilt-table testing, subjects with UARS and a history of OI had a greater decrease in systolic BP (27 +/- 3 mm Hg) than did control subjects (7.5 +/- 1.6 mm Hg), subjects with OSAS (6.8 +/- 1.2 mm Hg), normotensive subjects with UARS (7.2 +/- 0.84 mm Hg), or hypotensive insomniacs (7.4 +/- 1.1 mm Hg) (p < 0.01). We conclude that approximately one fifth of subjects with UARS have low BP and complain of OI. Tilt-table testing may be indicated to confirm orthostatic intolerance in subjects with UARS.

  View details for Web of Science ID 000172013200032

  View details for PubMedID 11673217

• Daily consequences of insomnia: impact on quality of life REVUE NEUROLOGIQUE Leger, D., Stal, V., Guilleminault, C., Raffray, T., Dib, M., Paillard, M. 2001; 157 (10): 1270-1278

  Abstract

  Insomnia is not only a disease of sleep, it has also daily consequences: fatigue, irritability, impaired daytime functioning. These complaints are regent reported by the patients, however the objective tests assessing alertness in insomnia are usually not impaired when compared with good sleepers. We wanted to appreciate more accurately the daily consequences of insomnia, in terms of quality of life. 240 severe insomniacs (according to the DSM-IV criterias) and 391 good sleepers received a questionnaire on quality of life items. Depressed and anxious patients were excluded from this group. The questionnaire was built by a multidisciplinary group, based on insomniac's interviews. It was primarily tested in a small sample and then proposed in the entire group. Insomniac's quality of life appeared to be significantly impaired in comparison with good sleepers. They experienced more fatigue and more sleepiness during the daytime. They reported more attention disorders and memory complaints. They seemed to be more irritable and sensitive to the environment. At work they made more mistakes and had more sic leave. They also had poorer relationships with relatives and family than good sleepers.

  View details for Web of Science ID 000172234100007

  View details for PubMedID 11885520

• Sleep-disordered breathing. A view at the beginning of the new Millennium. Dental clinics of North America Guilleminault, C., QUO, S. D. 2001; 45 (4): 643-656

  Abstract

  Obstructed sleep apnea syndrome and UARS are often missed in clinical practice. The pediatric population presenting with UARS or mild OSAS is the most commonly ignored because the symptoms are insidious. Often, their craniofacial morphology is not as altered as in the adult population because the effects of airway obstruction may not have been fully established. This is, however, the group in which trials aimed at redistributing bone growth and functional readaptations may be attempted. Dentists and orthodontists have the greatest opportunity to see these young individuals and may help identify them and participate in treatment options. Undoubtedly, functional appliances are not the ideal solution, but if used appropriately with the goal of enlarging the upper airway, they may obviate the need for aggressive surgical treatments later in life. Orthopedic palatal and transverse expansion appliances can widen the jaw bases at the level of the basal bone. Orthodontically uprighting lingually tipped teeth to widen the alveolar bone housing the teeth can help improve the oropharyngeal space indirectly by altering the resting posture of the tongue. These measures in conjunction with other simultaneous, noninvasive modalities may prove to be effective.

  View details for PubMedID 11699234

• Misinterpretation of sleep-breathing disorder by periodic limb movement disorder. Sleep & breathing = Schlaf & Atmung Stoohs, R. A., Blum, H. C., Suh, B. Y., Guilleminault, C. 2001; 5 (3): 131-137

  Abstract

  We report a case of misinterpretation of sleep-disordered breathing due to periodic limb movement disorder. A 67-year-old man was diagnosed with sleep-disordered breathing and subsequently placed on treatment with nasal continuous positive airway pressure (CPAP). The initial diagnostic evaluation did not include measurement of anterior tibialis electromyogram. The respiratory disturbance index of the initial evaluation was 23. After a brief period of nasal CPAP use, the patient discontinued the treatment because no significant change in daytime alertness was noted and signs of CPAP-related insomnia appeared. The patient was restudied polysomnographically with monitoring of anterior tibialis electromyograms. This study identified 392 leg movements of which 65% were associated with brief EEG arousal from sleep. Double-blind analysis of respiratory disturbance and leg movements yielded a total number of 360 arousals in the overnight recording. Eighty-five percent of all respiratory events could be associated with central hypoventilation following periodic limb movement-associated EEG arousal. No significant hypoxia was recorded with these events. We hypothesize that chemoreceptor stimulation secondary to EEG arousal during sleep is responsible for this central hypoventilation. This case report highlights that recording and scoring of leg movements must be an integral part of polysomnographic evaluations.

  View details for PubMedID 11868152

• Comparison of actigraphic, polysomnographic, and subjective assessment of sleep parameters in sleep-disordered patients SLEEP MEDICINE Kushida, C. A., Chang, A., Gadkary, C., Guilleminault, C., Carrillo, O., Dement, W. C. 2001; 2 (5): 389-396

  View details for Web of Science ID 000208301200003

• Variability of respiratory effort in relation to sleep stages in normal controls and upper airway resistance syndrome patients. Sleep medicine Guilleminault, C., Poyares, D., Palombini, L., Koester, U., Pelin, Z., Black, J. 2001; 2 (5): 397-405

  Abstract

  Investigation of the role of sleep states on the respiratory effort of controls and subjects with upper airway resistance syndrome (UARS) using nasal cannula/pressure transducer system and esophageal manometry.One night's monitoring of sleep and breathing, including the determination of peak end inspiratory esophageal pressure (respiratory effort) with esophageal manometry and flow limitation with nasal cannula. Analysis of the data, breath-by-breath, using visual inspection and a computerized program. Setting - a university sleep laboratory. Patients were nine men with UARS and nine control men matched for age, ethnicity, and body mass index.A modulation of respiratory effort by sleep state and stages is seen in all subjects, the lowest noted during REM sleep and the highest associated with Slow Wave Sleep. When total nocturnal breaths are investigated, a significant difference between peak end inspiratory esophageal pressure [(Pes)-considered as an index of respiratory effort] is noted between normal subjects and UARS. Two specific breathing patterns, seen primarily in UARS patients, are NREM sleep stage dependent. Crescendos (defined as more negative peak end inspiratory Pes with each successive abnormal breath) occur mostly during stages 1-2 NREM sleep, while segments consisting of regular and continuous, breath-after-breath, high respiratory efforts are associated with Slow Wave Sleep. Depending on sleep stage, visually scored arousal response displays differences in Pes negativity. The termination of the abnormal breathing pattern, always well defined with Pes, is not necessarily associated with a pattern of 'flow limitation' at the nasal cannula tracing, even when a visually scored EEG arousal is present.UARS patients have significantly more breaths, with more negative peak end inspiratory Pes, than do control subjects. The modulation of peak end inspiratory Pes (an index of respiratory effort) by sleep stage and state differs in UARS patients and control subjects. The nasal cannula/pressure transducer system may not detect all abnormal breathing pattern during sleep. As indicated by the visual sleep scoring, repetitive arousals may lead to more or less severe sleep fragmentation.

  View details for PubMedID 14592389

• Pattern analysis of sleep-deprived human EEG JOURNAL OF SLEEP RESEARCH Kim, H., Guilleminault, C., Hong, S., Kim, D., Kim, S., Go, H., Lee, S. 2001; 10 (3): 193-201

  Abstract

  Progress during the past decade in non-linear dynamics and instability theory has provided useful tools for understanding spatio-temporal pattern formation. Procedures which apply principle component analysis (using the Karhunen-Loeve decomposition technique) to the multichannel electroencephalograph (EEG) time series have been developed. This technique shows localized changes of cortical functioning; it identifies increases and decreases of the activity of localized cortical regions over time while the subject performs a simple task or test. It can be used to demonstrate the change in cortical dynamics in response to a continuous challenge. Using 16 EEG electrodes, the technique provides spatio-temporal information not obtained with power spectrum analysis, and includes the weighted information given with omega complexity. As an application, we performed a pattern analysis of sleep-deprived human EEG data in 20 healthy young men. Electroencephalograph recordings were performed on subjects for <2 min, with eyes closed after normal sleep and after 24 h of experimentally-induced sleep deprivation. The significant changes in the eigenvector components indicated the relative changes of local activity in the brain with progressive sleep deprivation. A sleep deprivation effect was observed, which was hemispherically correlated but with opposite directional dynamics. These changes were seen in the temporo-parietal regions bilaterally. The application of the technique showed that the simple test task was performed with a limited unilateral hemispheric involvement at baseline, but needed a much larger cortical participation with decreased frontal activity and increased coherence and bilateral hemispheric involvement. The calculations performed demonstrated that the same weighted changes as those obtained with omega complexity were shown, but the technique had the added advantage of showing the localized directional changes of the principle eigenvector at each studied electrode, pointing out the cortical localized region affected by the sleep deprivation and toward which direction the environmental challenge induced the spatial change. This methodology may allow the evaluation of changes in local dynamics in brain activity in normal and pathological conditions.

  View details for Web of Science ID 000170906900004

  View details for PubMedID 11696072

• Comparison of actigraphic, polysomnographic, and subjective assessment of sleep parameters in sleep-disordered patients. Sleep medicine Kushida, C. A., Chang, A., Gadkary, C., Guilleminault, C., Carrillo, O., Dement, W. C. 2001; 2 (5): 389-396

  Abstract

  Comparison of polysomnography (PSG)-derived sleep parameters (total sleep time, sleep efficiency, and number of awakenings) to those derived from actigraphy and subjective questionnaires.Actigraphy is commonly used to assist sleep specialists in the diagnosis of various sleep and circadian-rhythm disorders. However, few validation studies incorporate large sample sizes, typical sleep clinic patients, or comparisons with subjective reports of sleep parameters.Clinical series with 100 consecutive sleep-disordered patients (69 men, 31 women, mean age of 49+/-14.7 years) at a tertiary sleep disorders center. Sensitivity, specificity, and accuracy measures were obtained from epoch-by-epoch comparison of PSG and actigraphic data. Subjective sleep parameter data were derived from questionnaires given to subjects in the morning following their recording night.We found that total sleep time and sleep efficiency did not significantly differ between PSG data and the combined data obtained from actigraphy and subjective reports. Using a high-threshold (low-wake-sensitivity) actigraphic algorithm, the number of awakenings was not significantly different from those detected by PSG.We recommend the use of subjective data as an adjunct to actigraphic data in estimating total sleep time and sleep efficiency in sleep-disordered patients, especially those with disorders of excessive somnolence.

  View details for PubMedID 14592388

• Variability of respiratory effort in relation to sleep stages in normal controls and upper airway resistance syndrome patients SLEEP MEDICINE Guilleminault, C., Poyares, D., Palombini, L., Koester, U., Pelin, Z., Black, J. 2001; 2 (5): 397-406

  View details for Web of Science ID 000208301200004

• [Obstructive sleep apnea syndrome: a cardiovascular risk factor?]. Zeitschrift fur Kardiologie Duchna, H. W., Guilleminault, C., Stoohs, R. A., Orth, M., de Zeeuw, J., Schultze-Werninghaus, G., Rasche, K. 2001; 90 (8): 568-575

  Abstract

  Obstructive sleep apnea syndrome (OSAS) is frequently associated with cardiovascular disease. We investigated endothelium-dependent and endothelium-independent nitric oxide-mediated vasodilatory function in normotensive patients with OSAS using the hand vein compliance technique.Dose-response curves to the endothelium-dependent vasodilator bradykinin were obtained in 23 male subjects with OSAS and 12 male control subjects of comparable age, height, and weight.Mean (+/- SD) maximum dilation (Emax) to bradykinin was significantly lower in OSAS patients than in controls (59.8 +/- 26.0 vs. 94.8 +/- 9.5%, p < 0.0001). Mean vasodilation with nitroglycerin was not diminished in the OSAS group (90.7 +/- 30.5 vs. 100.3 +/- 12.9% in controls; n.s.). In 11 OSAS patients, a follow-up investigation was performed after at least 2 months of treatment with nasal continuous positive airway pressure (CPAP): Emax to bradykinin rose from 54.5 +/- 19.2% to 111.5 +/- 25.1% after treatment (p < 0.001). Mean vasodilation to nitroglycerin was unchanged.These results suggest that endothelium-dependent nitric oxide-mediated vasodilation is impaired in patients with OSAS due to an impaired function in the endothelial cells. This impairment is reversible with CPAP treatment.

  View details for PubMedID 11569627

• Vascular endothelial dysfunction in patients with obstructive sleep apnoea syndrome ZEITSCHRIFT FUR KARDIOLOGIE Duchna, H. W., Guilleminault, C., Stoohs, R. A., Orth, M., de Zeeuw, J., Schultze-Werninghaus, G., Rasche, K. 2001; 90 (8): 568-575

  View details for Web of Science ID 000170791000005

• Excessive daytime sleepiness - A challenge for the practising neurologist BRAIN Guilleminault, C., Brooks, S. N. 2001; 124: 1482-1491

  Abstract

  The complaint of excessive daytime sleepiness, commonly encountered in neurological practice, may arise from a variety of disorders. The list of possibilities spans virtually every major area of medicine, neurology and psychiatry. A clear, detailed history is invaluable in negotiating these numerous diagnostic considerations; however, the symptom may be expressed in terms that do not directly denote somnolence (e.g. 'tiredness' or 'fatigue'). Accurate diagnosis is important, not only because of the negative impacts of sleepiness and its root causes on health and social function, but because excessive sleepiness is generally remediable with appropriate treatment. As our understanding of the neurological underpinnings of alertness and sleepiness deepens, improved treatment methods are bound to emerge.

  View details for Web of Science ID 000170453400002

  View details for PubMedID 11459741

• Sleep and wakefulness in somnambulism - A spectral analysis study JOURNAL OF PSYCHOSOMATIC RESEARCH Guilleminault, C., Poyares, D., Abat, F., Palombini, L. 2001; 51 (2): 411-416

  Abstract

  The sleep structure and the dynamics of EEG slow-wave activity (SWA) were investigated in 12 young adults and age- and gender-matched controls.Polysomnography was performed in subjects with well-documented chronic sleepwalking and in matched controls. Blinded visual scoring was performed using the international criteria from the Rechtschaffen and Kales atlas [A manual of standardized technology, techniques and scoring systems for sleep stages of human subjects. Los Angeles: UCLA Brain Information Service, Brain Research Institute, 1968.] and by determining the presence of microarousals as defined in the American Sleep Disorders Association (ASDA) atlas [Sleep 15 (1992) 173.]. An evaluation of SWA overnight was performed on total nocturnal sleep to determine if a difference existed between groups of subjects, since sleepwalking usually originates with slow-wave sleep. Investigation of the delta power in successive nonoverlapping 4-second windows in the 32 seconds just prior to EMG activity associated with a confusional arousal was also conducted. One central EEG lead was used for all analyses.Somnambulistic individuals experienced more disturbed sleep than controls during the first NREM-REM sleep cycle. They had a higher number of ASDA arousals and presented lower peak of SWA during the first cycle that led to a lower SWA decline overnight. When the investigation focused on the short segment immediately preceding a confusional arousal, they presented an important increase in the relative power of low delta (0.75-2 Hz) just prior to the confusional arousal.Sleepwalkers undergo disturbed nocturnal sleep at the beginning of the night. The increased power of low delta just prior to the confusional arousal experienced may not be related to Stages 3-4 NREM sleep. We hypothesize that it may be translated as a cortical reaction to brain activation.

  View details for Web of Science ID 000170720200001

  View details for PubMedID 11516762

• Genetics, control of breathing, and sleep-disordered breathing: a review SLEEP MEDICINE Gaultier, C., Guilleminault, C. 2001; 2 (4): 281-295

  View details for Web of Science ID 000208301100002

• Sleep-disordered breathing and upper-airway anomalies in first-degree relatives of ALTE children PEDIATRIC RESEARCH Guilleminault, C., Pelayo, R., Leger, D., Philip, P., Ohayon, M. 2001; 50 (1): 14-22

  Abstract

  From 1985 through 1995, 348 infants aged 3 wk-3 mo were referred to the Stanford Sleep Clinic for "apparent life-threatening events" (ALTE). A small group of 48 infants with no history of sleep-disordered breathing (SDB) was also recruited and used as controls (they comprised group C). We conducted a systematic investigation of relatives (parents, siblings, and grandparents) of the infants, including a clinical evaluation, craniofacial investigation, and the completion of an extensive (189-question) validated sleep/wake questionnaire. All data were calculated before the subdivision of ALTE infants into two groups. The subdivision was based on a blind scoring of the infants' polygraphic recordings; 42.5% of the infants were negative for SDB (Group A), whereas 57.5% of the infants were positive for SDB (Group B). Groups A and C were not significantly different from each other. Forty-three percent of the relatives of Group B infants had been treated for SDB (with nasal CPAP, surgical or dental appliance treatments) compared with 7.1% of Group A relatives. Clinical investigation indicated a significantly higher presence of small upper airways in the families of infants with SDB. About twice as many relatives reported the presence of asthma in Group B compared with Group A. Naso-oro-maxillomandibular anatomic traits that may lead to small upper airways in parents may be risk factors for abnormal breathing during sleep in their infants.

  View details for Web of Science ID 000169458600004

  View details for PubMedID 11420413

• Is there a link between subjective daytime somnolence and sickness absenteeism? A study in a working population JOURNAL OF SLEEP RESEARCH Philip, P., Taillard, J., Niedhammer, I., Guilleminault, C., Bioulac, B. 2001; 10 (2): 111-115

  Abstract

  A number of studies have highlighted the increasing incidence and financial cost of sleep-related disorders in the general population, but little research has been carried out on the impact of subjective daytime somnolence on health status. The existence of a survey of the health of employees of the French National Gas and Electricity Board has allowed us to investigate this question and measure the link between subjective daytime somnolence and sickness absenteeism, used here as a general health indicator. In order to evaluate the quality of sleep over the previous 3 months, a questionnaire was given to each participant. The association between subjective daytime somnolence and absence as a result of sickness was explored using the data of sickness absenteeism provided by the company's social security department during a 12-month follow-up period. Of our 1105 subjects, 6.7% reported severe subjective daytime somnolence of 3 days or more a week and 30% of our study population had at least one spell of sickness absence during the 12-month period of follow-up. A strong association was observed between subjective daytime somnolence and sickness absence, which remained significant even after adjustment for potential confounding variables (age, sex, employment grade, sleep symptoms and self-reported diseases). The odds-ratio for absence as a result of sickness during the follow-up period associated with subjective daytime somnolence of 3 days or more a week was 2.2 (95% CI: 1.3--3.8). Employees suffering from severe subjective daytime somnolence lose more working days for health reasons than their more alert colleagues. This may have long-term implications for employees' health.

  View details for Web of Science ID 000169246200004

  View details for PubMedID 11422725

• Uvulopalatopharyngoplasty, maxillomandibular advancement, and the velopharynx LARYNGOSCOPE Li, K. K., Troell, R. J., Riley, R. W., Powell, N. B., Koester, U., Guilleminault, C. 2001; 111 (6): 1075-1078

  Abstract

  To evaluate the presence of velopharyngeal insufficiency (VPI) symptoms and the associated changes of the velopharyngeal anatomy in patients who underwent maxillomandibular advancement (MMA) for persistent obstructive sleep apnea (OSA) after uvulopalatopharyngoplasty (UPPP).Preoperative and postoperative cephalometric radiographs were analyzed to assess the anatomic changes of the velopharynx. In addition, a questionnaire survey was sent to the patients between 6 to 12 months after MMA. The questionnaires evaluated the presence and extent of VPI symptoms, including nasal regurgitation while eating or drinking as well as hypernasal speech. A 10-cm visual analog scale (VAS 0-10) was included to assess the impact of VPI symptoms on the patient's quality of life. In the patients who reported VPI symptoms, telephone interviews were conducted 1 year after the survey to evaluate the changes in VPI symptoms over time.Fifty-two of the 65 questionnaires were returned. Five patients (9.6%) reported nasal regurgitation of liquids when drinking hastily, with 2 patients reporting the occurrences as occasional and 3 patients reporting as rare. The impact of these symptoms on the patient's quality of life was minimal (VAS 0.6 +/- 0.4). Regurgitation of food or hypernasal speech was not reported. The telephone interviews 1 year later revealed that the symptoms have completely resolved in all 5 patients. Comparison of the preoperative and postoperative cephalometric radiographs demonstrated the pharyngeal depth increase was 48% of the amount of maxillary advancement and the functional pharyngeal length increased 53% of the maxillary advancement. The functional depth of the pharynx after MMA was significantly greater in the patients with VPI symptoms (P=.01).The results of this study suggest that patients who undergo MMA for persistent OSA after UPPP have a low risk of developing VPI. If symptoms occur postoperatively, they are mild and have minimal effect on the patient's quality of life; moreover, the symptoms usually resolve over time.

  View details for Web of Science ID 000169102900025

  View details for PubMedID 11404624

• Sleep and daytime sleepiness in upper airway resistance syndrome compared to obstructive sleep apnoea syndrome EUROPEAN RESPIRATORY JOURNAL Guilleminault, C., Kim, Y. D., Chowdhuri, S., Horita, M., Ohayon, M., Kushida, C. 2001; 17 (5): 838-847

  Abstract

  This study has investigated differences in the nocturnal sleep and daytime sleepiness among patients with obstructive sleep apnoea syndrome (OSAS), upper airway resistance (UARS), sleep hypopnoea syndrome, and normal control subjects, using sleep scoring and spectral activity analysis of the electroencephalogram (EEG). Twelve nonobese males with UARS aged 30-60 yrs were recruited. These subjects were strictly matched for age and body mass index with twelve OSAS patients, 12 sleep hypopnoea syndrome patients, and 12 normal controls, all male. Daytime sleepiness was evaluated using the Epworth Sleepiness Scale (ESS) and the Multiple Sleep Latency Test (MSLT). The macrostructure of sleep was determined using international criteria and spectral analysis of the sleep EEG was obtained from a central lead. The sleep macrostructure of OSAS and UARS patients was significantly different from that of controls. These patients were also sleepier during the daytime than controls. Complaints of tiredness and daytime sleepiness, ESS and MSLT scores were similar in the different patient groups. Mild dysmorphia was present in all three patient groups. However, nocturnal sleep was significantly different among the different groups. OSAS patients had significantly more awake time during sleep than the UARS patients. The spectral activity of the total sleep time of the patient groups also differed significantly from that of controls. When the sleep spectral activity of UARS and OSAS patients were compared, OSAS patients had less slow wave sleep activity than UARS patients. UARS patients had a significantly higher absolute power in the 7-9 Hz bandwidth than OSAS patients. The absolute delta power over the different sleep cycles was also different between controls and patients, and between UARS and OSAS patients. There are clear differences in the macrostructure and spectral activity of sleep between upper airway resistance and obstructive sleep apnoea syndrome patients, demonstrated by differences in the cortical activity recorded in the central lead during sleep. Despite these nocturnal sleep differences, the tests of subjective daytime sleepiness are not significantly different.

  View details for Web of Science ID 000170209000002

  View details for PubMedID 11488314

• CPAP treatment does not affect glucose-insulin metabolism in sleep apneic patients SLEEP MEDICINE Smurra, M., Philip, P., Taillard, J., Guilleminault, C., Bioulac, B., Gin, H. 2001; 2 (3): 207-213

  View details for Web of Science ID 000208301000004

• The road to danger: The comparative risks of driving while sleepy 104th Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery Powell, N. B., Schechtman, K. B., Riley, R. W., Li, K., Troell, R., Guilleminault, C. JOHN WILEY & SONS INC. 2001: 887–93

  Abstract

  A large sector of the population of the United States has sleep deprivation directly leading to excessive daytime sleepiness. The prevalence of excessive daytime sleepiness in this population ranges from 0.3% to 13.3%. The consequences of even 1 to 2 hours of sleep loss nightly may result in decrements in daytime functions resulting in human error, accidents, and catastrophic events. The magnitude of risks in the workplace or on the highways resulting from sleepiness is not fully understood or appreciated by the general population. Hence, to more clearly emphasize the magnitude of these risks, we question whether mild sleep deprivation may have the same effect as alcohol on reaction times and driving performance.Nonrandomized prospective cohort investigation.Sixteen healthy matched adult subjects (50% women) were stratified into two groups, sleep deprived and alcohol challenged. The sleep-deprived group was further subdivided into acute (one night without sleep) and chronic (2 h less sleep nightly for 7 d) sleep deprivation. Each group underwent baseline reaction time testing and then drove on a closed course set up to test performance. Seven days later, the group repeated this sequence after either sleep deprivation or alcohol intake.There were no significant between-group differences (sleep deprivation or alcohol challenged) in the changes before and after intervention for all 11 reaction time test metrics. Moreover, with few exceptions, the magnitude of change was nearly identical in the two groups, despite a mean blood alcohol concentration of 0.089 g/dL in the alcohol-challenged group. On-track driving performances were similar (P =.724) when change scores (hits and errors) between groups were compared (baseline minus final driving trial).This comparative model suggests that the potential risks of driving while sleepy are at least as dangerous as the risks of driving illegally under the influence of alcohol.

  View details for Web of Science ID 000168618900023

  View details for PubMedID 11359171

• The narcolepsy diagnosis: Comparison between the Sleep-EVAL system and clinicians Black, J., Ohayon, M., Okun, M., Guilleminault, C., Mignot, E., Zarcone, V. AMER ACAD SLEEP MEDICINE. 2001: A328–A328

  View details for Web of Science ID 000168230900574

• Circadian firing pattern of 95 patients with automatic implantable cardioverter defibrillators (AICDs) Yuen, K. M., Colrain, I., Koester, U., Chowdhuri, S., Guilleminault, C. AMER ACAD SLEEP MEDICINE. 2001: A199–A199

  View details for Web of Science ID 000168230900336

• How age and daytime activities are related to insomnia in the general population: Consequences for older people JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Ohayon, M. M., Zulley, J., Guilleminault, C., Smirne, S., Priest, R. G. 2001; 49 (4): 360-366

  Abstract

  To determine the role of activity status and social life satisfaction on the report of insomnia symptoms and sleeping habits.Cross-sectional telephone survey using the Sleep-EVAL knowledge base system.Representative samples of three general populations (United Kingdom, Germany, and Italy).13,057 subjects age 15 and older: 4,972 in the United Kingdom, 4,115 in Germany, and 3,970 in Italy. These subjects were representative of 160 million inhabitants.Clinical questionnaire on insomnia and investigation of associated pathologies (psychiatric and neurological disorders).Insomnia symptoms were reported by more than one-third of the population age 65 and older. Multivariate models showed that age was not a predictive factor of insomnia symptoms when controlling for activity status and social life satisfaction. The level of activity and social interactions had no influence on napping, but age was found to have a significant positive effect on napping.These results indicate that the aging process per se is not responsible for the increase of insomnia often reported in older people. Instead, inactivity, dissatisfaction with social life, and the presence of organic diseases and mental disorders were the best predictors of insomnia, age being insignificant. Healthy older people (i.e., without organic or mental pathologies) have a prevalence of insomnia symptoms similar to that observed in younger people. Moreover, being active and satisfied with social life are protective factors against insomnia at any age.

  View details for Web of Science ID 000168331300002

  View details for PubMedID 11347777

• Patient's perception of the facial appearance after maxillomandibular advancement for obstructive sleep apnea syndrome JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY Li, K. K., Riley, R. W., Powell, N. B., Guilleminault, C. 2001; 59 (4): 377-380

  Abstract

  The goal of this study was to evaluate the patient's perception of the facial appearance after maxillomandibular advancement (MMA) surgery for obstructive sleep apnea syndrome (OSAS).During a 14-month period, 58 patients underwent MMA for OSAS. All of the patients underwent preoperative and postoperative cephalometric analysis. Between 6 and 12 months after surgery, a questionnaire was mailed to each patient. The questionnaire asked the patient to evaluate subjectively their postoperative facial appearance. Visual analog scale ([VAS] 0 to 10) was used to assess the extent of the facial changes.Forty-four (76%) patients (39 men, 6 women) responded to the questionnaire. Cephalometric analysis revealed that 40 patients had maxillomandibular protrusion postoperatively. Forty-two (96%) of the 44 patients reported changes in their facial appearance (VAS, 4.8 +/- 2.5). Twenty-four (55%) patients reported favorable facial changes (ie, they were more attractive [15 patients] and/or more youthful). Fourteen patients gave neutral responses (ie, they were no more or no less attractive). Four patients gave unfavorable responses (ie, they were less attractive after surgery).The results suggest that most patients who underwent MMA for OSAS noted moderate changes in their facial appearance. Despite significant maxillomandibular protrusion based on the postoperative cephalometric analysis, more than 90% of the patients gave either positive or neutral responses to the changes in their facial appearance.

  View details for DOI 10.1053/joms.2001.21870

  View details for Web of Science ID 000167764700004

  View details for PubMedID 11289166

• SF-36: Evaluation of quality of life in severe and mild insomniacs compared with good sleepers PSYCHOSOMATIC MEDICINE Leger, D., Scheuermaier, K., Philip, P., Paillard, M., Guilleminault, C. 2001; 63 (1): 49-55

  Abstract

  Despite many studies, the impact of chronic insomnia on daytime functioning is not well understood. The aim of our study was to detect this impact by evaluating quality of life (QoL) using a validated instrument, the 36-item Short Form Health Survey of the Medical Outcomes Study (SF-36), in three matched groups of severe insomniacs, mild insomniacs, and good sleepers selected from the general population.Three matched groups of 240 severe insomniacs, 422 mild insomniacs, and 391 good sleepers were recruited from the general French population after eliminating those with DSM-IV criteria for anxiety or depression. All subjects were asked to complete the SF-36. Scores for each QoL dimension were calculated and compared statistically among the three groups.Severe insomniacs had lower QoL scores in eight dimensions of the SF-36 than mild insomniacs and good sleepers. Mild insomniacs had lower scores in the same eight dimensions when compared with good sleepers. No dimension was significantly more altered than the other.The mental health status and role of emotional QoL dimensions were worse in severe and mild insomniacs than in good sleepers. This result held even though we screened for psychiatric diseases, which shows a clear interrelation between insomnia and emotional state. General health status was also worse in severe and mild insomniacs than in good sleepers. However, we could conclude only that insomnia was related to a worse health status and not whether it was a cause or consequence of this worse health status. Finally, the degradation of QoL scores was correlated with the severity of insomnia.

  View details for Web of Science ID 000166843200006

  View details for PubMedID 11211064

• Idiopathic hypersomnia: a neurological dilemma. Sleep medicine reviews Guilleminault, C., Brooks, S. 2001; 5 (5): 347–49

  View details for DOI 10.1053/smrv.2001.0210

  View details for PubMedID 12530997

• CPAP treatment does not affect glucose-insulin metabolism in sleep apneic patients. Sleep medicine Smurra, M., Philip, P., Taillard, J., Guilleminault, C., Bioulac, B., Gin, H. 2001; 2 (3): 207–13

  Abstract

  Objective: We investigated glucose metabolism and insulin resistance in non-obese and moderately overweight sleep apnea patients, as well as their response to nasal CPAP treatment.Methods: A group of subjects with glucose intolerance was screened for sleep disordered breathing by clinical interview and ambulatory recordings. Ten subjects were found to have untreated sleep apnea and were asked to participate in further investigation. This included nocturnal polysomnography, oral glucose tolerance test and indirect calorimetry. Subjects then had calibration of nasal CPAP with polysomnography. Two months after start of treatment, all subjects were restudied as at baseline. In parallel, six obstructive sleep apnea syndrome (OSAS) subjects, diagnosed through the sleep clinic, were matched for gender, age and oxygen desaturation index with the other group, and had a euglycemic hyperinsulinemic clamp at baseline and after 2 months of nasal CPAP.Results: The first ten patients showed no change in total glucose oxidation, glucose oxidation by weight or by fat free mass, or insulin energetic expenditure, despite nocturnal usage of nasal CPAP. Similarly, when comparing baseline to the treatment at 2 months, the six OSAS patients had no change in mean glycemia, insulin, C peptide and hemoglobin (Hgb) A1C measurements. No difference in the amount of glucose infused during the duration of the clamp was noted either.Conclusion: Our data do not support the existence of a significant relationship between glucose and insulin metabolism and obstructive sleep apnea. Obesity, when present, is the important variable.

  View details for PubMedID 11311683

• Risk factors for sleep bruxism in the general population CHEST Ohayon, M. M., Li, K. K., Guilleminault, C. 2001; 119 (1): 53-61

  Abstract

  Sleep bruxism can have a significant effect on the patient's quality of life. It may also be associated with a number of disorders. However, little is known about the epidemiology of sleep bruxism and its risk factors in the general population.Cross-sectional telephone survey using the Sleep-EVAL knowledge based system.Representative samples of three general populations (United Kingdom, Germany, and Italy) consisting of 158 million inhabitants.Thirteen thousand fifty-seven subjects aged > or = 15 years (United Kingdom, 4,972 subjects; Germany, 4,115 subjects; and Italy, 3,970 subjects).None.Clinical questionnaire on bruxism (using the International Classification of Sleep Disorders [ICSD] minimal set of criteria) with an investigation of associated pathologies (ie, sleep, breathing disorders, and psychiatric and neurologic pathologies).Grinding of teeth during sleep occurring at least weekly was reported by 8.2% of the subjects, and significant consequences from teeth grinding during sleep (ie, muscular discomfort on awakening, disturbing tooth grinding, or necessity of dental work) were found in half of these subjects. Moreover, 4.4% of the population fulfilled the criteria of ICSD sleep bruxism diagnosis. Finally, subjects with obstructive sleep apnea syndrome (odds ratio [OR], 1.8), loud snorers (OR, 1.4), subjects with moderate daytime sleepiness (OR, 1.3), heavy alcohol drinkers (OR, 1.8), caffeine drinkers (OR, 1.4), smokers (OR, 1.3), subjects with a highly stressful life (OR, 1.3), and those with anxiety (OR, 1.3) are at higher risk of reporting sleep bruxism.Sleep bruxism is common in the general population and represents the third most frequent parasomnia. It has numerous consequences, which are not limited to dental or muscular problems. Among the associated risk factors, patients with anxiety and sleep-disordered breathing have a higher number of risk factors for sleep bruxism, and this must raise concerns about the future of these individuals. An educational effort to raise the awareness of dentists and physicians about this pathology is necessary.

  View details for Web of Science ID 000166766300014

  View details for PubMedID 11157584

• Genetics, control of breathing, and sleep-disordered breathing: a review. Sleep medicine Gaultier, C., Guilleminault, C. 2001; 2 (4): 281–95

  View details for PubMedID 11438245

• Obstructive sleep apnea surgery: Patient perspective and polysomnographic results OTOLARYNGOLOGY-HEAD AND NECK SURGERY Li, K. K., Riley, R. W., Powell, N. B., Gervacio, L., Troell, R. J., Guilleminault, C. 2000; 123 (5): 572-575

  Abstract

  The goal of this study was to assess the outcomes of obstructive sleep apnea (OSA) surgery based on the patient perspective and polysomnographic data.Fifty-six patients with severe OSA completed the 2-phase reconstructive protocol. A minimum of 6 months after the phase II surgery and after the postoperative polysomnography, questionnaires with visual analog scales (VAS 0-10) were mailed to the patients to assess their perceptions of treatment results.Forty-two (75%) questionnaires were returned. The mean patient age was 46.3 years. The mean respiratory disturbance index improved from 58.7 to 10.0. The mean lowest oxygen saturation improved from 76.3 to 87.3%. All 42 patients reported improved sleep (VAS 8.7). Although 10 patients reported changes in speech, the changes were insignificant, with 9 of the patients scoring 0 on the VAS (VAS 0.08 +/-0.3). Five patients reported changes in swallowing, and their VAS scores were 0.5, 0.9, 1.0, 2.7, and 6.9 (mean VAS 2.4+/-2.7). Forty patients (95%) were satisfied with their results and would undergo the reconstruction again.Surgical airway reconstruction for severe OSA is a highly effective treatment option base on the objective as well as the subjective assessment.

  View details for Web of Science ID 000165222600010

  View details for PubMedID 11077343

• Obstructive sleep apnea syndrome: A comparison between Far-East Asian and white men LARYNGOSCOPE Li, K. K., Kushida, C., Powell, N. B., Riley, R. W., Guilleminault, C. 2000; 110 (10): 1689-1693

  Abstract

  To investigate the possible differences between Far-East Asian men and white men in obstructive sleep apnea syndrome (OSAS).Prospective nonrandomized controlled study.This study compared consecutive Far-East Asian men with OSAS (n = 50) with two selected groups of White men with OSAS (n = 50 in each group). One group of white men was controlled for age, respiratory disturbance index (RDI), and minimum oxygenation saturation (LSAT). Another group was controlled for age and body mass index (BMI). Cephalometric analysis was performed on all subjects.The majority of the Far-East Asian men were found to be nonobese (mean BMI, 26.7 +/- 3.8) but had severe OSAS (mean RDI, 55.1 +/- 35.1). When controlled for age, RDI, and LSAT, the white men were substantially more obese (mean BMI, 29.7 +/- 5.8, P = .0055). When controlled for age and BMI, the white men had less severe illness (RDI, 34.1 +/- 17.9, P = .0001). Although the posterior airway space and the distance from the mandibular plane to hyoid bone were less abnormal in the Far-East Asian men, the cranial base dimensions were significantly decreased.The majority of the Far-East Asian men in this study were found to be nonobese, despite the presence of severe OSAS. When compared with white men, Far-East Asian men were less obese but had greater severity of OSAS. There may be differences in obesity and craniofacial anatomy as risk factors in these two groups.

  View details for Web of Science ID 000089709500020

  View details for PubMedID 11037826

• Normal pregnancy, daytime sleeping, snoring and blood pressure SLEEP MEDICINE Guilleminault, C., Querra-Salva, M., Chowdhuri, S., Poyares, D. 2000; 1 (4): 289-297

  View details for Web of Science ID 000208300700006

• Maxillomandibular advancement for persistent obstructive sleep apnea after phase I surgery in patients without maxillomandibular deficiency LARYNGOSCOPE Li, K. K., Riley, R. W., Powell, N. B., Guilleminault, C. 2000; 110 (10): 1684-1688

  Abstract

  To assess the outcomes of maxillomandibular advancement (MMA) for the treatment of persistent obstructive sleep apnea syndrome (OSA) after phase I reconstruction in patients who do not have maxillomandibular deficiency.From January 1997 to September 1998, 25 patients previously treated with phase I reconstruction (uvulopalatoplasty, genioglossus advancement, and/or hyoid suspension) who did not have maxillary and mandibular deficiencies underwent MMA for persistent OSA. Variables examined include age, sex, body mass index (BMI), respiratory disturbance index (RDI), lowest oxygen saturation (LSAT), and cephalometric data. In addition, a minimum of 6 months after surgery, questionnaires containing a 10-cm visual analogue scale (0 = no change, 10 = drastic change) were mailed to the patients. The questionnaire subjectively assessed the patient's perception of the facial appearance after surgery, whether there was pain or discomfort of the temporomandibular joint, the overall satisfaction with the treatment outcomes, and whether the patient would recommend the operation to other patients.Nineteen (76%) questionnaires were completed and returned by 15 men and 4 women. The mean age was 45.3 +/- 6.6 years and the mean BMI was 33.1 +/- 7.1 kg/m2. The mean RDI improved from 63.6 +/- 20.8 to 8.1 +/- 5.9 events per hour, and the mean LSAT improved from 73.3 +/- 13.2% to 88.1 +/- 4.1%. One patient was defined as an incomplete responder (RDI >20). One patient reported transient pain and discomfort of the temporomandibular joint. Although all of the patients felt that there were changes in their facial appearance after surgery, 18 of the 19 patients gave either a neutral or a favorable response to their facial esthetic results. All of these patients were satisfied with the overall outcomes and would recommend the treatment to others.MMA is a highly effective treatment for persistent OSA after phase I surgery in patients who otherwise do not have maxillomandibular deficiency. The patient satisfaction is extremely high. Furthermore, previous concerns of unfavorable postoperative facial esthetics and temporomandibular joint dysfunction do not appear to be significant.

  View details for Web of Science ID 000089709500019

  View details for PubMedID 11037825

• Primary pulmonary hypertension with central sleep apnea - Sudden death after bilevel positive airway pressure therapy JAPANESE CIRCULATION JOURNAL-ENGLISH EDITION Shiomi, T., Guilleminault, C., Sasanabe, R., Oki, Y., Hasegawa, R., Otake, K., Banno, F., Usui, K., Maekawa, M., Kanayama, H., Takahashi, R., Kobayashi, T. 2000; 64 (9): 723-726

  Abstract

  An obese 23-year-old man with sleep-disordered breathing and primary pulmonary hypertension (PPH) had been administered oral beraprost sodium, anticoagulant warfarin, and home oxygen therapy, at another hospital as treatment for the PPH, but he had not experienced any symptomatic improvement. The patient had a body mass index of 32.4kg/m2, and complained of fatigue, shortness of breath on exertion, excessive daytime sleepiness, and snoring. Arterial blood gas analysis showed a PaO2 and a PaCO2 of 70.9 and 31.2mmHg, respectively. A polysomnographic study revealed central sleep apnea with an apnea-hypopnea index (AHI) of 29.7episodes/h. The patient showed improvement of daytime sleepiness after starting nocturnal nasal bilevel positive airway pressure (BiPAP) therapy for the central sleep apnea, but his pulmonary hypertension, measured in the daytime, worsened. The patient died suddenly while walking to the bathroom in the morning 1 month after initiation of BiPAP therapy. It is necessary to consider the possibility of sudden death when nasal BiPAP therapy is given to a PPH patient with central sleep apnea.

  View details for Web of Science ID 000089023100015

  View details for PubMedID 10981861

• Upper airway resistance syndrome - Central electroencephalographic power and changes in breathing effort AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE Black, J. E., Guilleminault, C., Colrain, I. M., Carrillo, O. 2000; 162 (2): 406-411

  Abstract

  Upper airway resistance syndrome (UARS) is defined by excessive daytime sleepiness and tiredness, and is associated with increased breathing effort. Its polygraphic features involve progressive increases in esophageal pressure (Pes), terminated by arousal (AR) as defined by the American Sleep Disorders Association (ASDA). With the arousal there is an abrupt decrease in Pes, called Pes reversal. However, Pes reversal can be seen without the presence of an AR. We performed spectral analysis on electroencephalographic data from a central lead for both AR and nonarousal (N-AR) events obtained from 15 UARS patients (eight men and seven women). Delta band activity was increased before and surrounding Pes reversal regardless of the presence or absence of AR. In the period after Pes reversal, alpha, sigma, and beta activity showed a greater increase in AR events than in N-AR events. The Pes measures were identical leading up to the point of reversal, but showed a longer-lasting and significantly greater decrease in respiratory effort after an AR. The data indicate that substantial electroencephalographic changes can be identified in association with Pes events, even when ARs cannot be detected according to standard criteria; however, visually identifiable electroencephalographic arousals clearly have a greater impact on ongoing inspiratory effort.

  View details for Web of Science ID 000088829200012

  View details for PubMedID 10934061

• Problems associated with switch to modafinil - a novel alerting agent in narcolepsy EUROPEAN JOURNAL OF NEUROLOGY Guilleminault, C., Aftab, F. A., Karadeniz, D., Philip, P., Leger, D. 2000; 7 (4): 381-384

  Abstract

  Modafinil is a novel medication recently approved for the treatment of narcolepsy and idiopathic hypersomnia. Commonly, patients had already been prescribed medications for their syndrome. This report outlines difficulties encountered in the clinical practice of switching patients to modafinil. Naïve subjects accepted modafinil best. Subjects withdrawn from amphetamine had the most problems and failure to withdraw. Venlafaxine hydrochloride combined well with modafinil to control cataplectic attacks. Usage of a progressive withdrawal protocol may ease the difficulties observed.

  View details for Web of Science ID 000088697000002

  View details for PubMedID 10971596

• Long-term efficacy and safety of modafinil (PROVIGIL (R)) for the treatment of excessive daytime sleepiness associated with narcolepsy SLEEP MEDICINE Mitler, M. M., Harsh, J., Hirshkowitz, M., Guilleminault, C. 2000; 1 (3): 231-243

  View details for Web of Science ID 000208300500008

• Upper airway resistance syndrome and its treatment 3rd Symposium on Diagnosis and Treatment of Sleep Breathing Disorders Guilleminault, C., Kim, Y. D., Palombini, L., Li, K., Powell, N. AMER ACAD SLEEP MEDICINE. 2000: S197–S200

  Abstract

  Although upper airway resistance syndrome (UARS) is being recognized by a growing number of specialists, its prevalence remains unknown. UARS is associated with nocturnal and daytime complaints and oro-naso-maxillo-mandibular signs. Spectrum analysis of the nocturnal sleep EEG from the central leads indicates significant differences in absolute power in the 12-14 Hz and the 7-9 Hz bands of UARS patients compared to controls. The 0.5-2.0 Hz band also appears to be involved when analyses performed on matched controls are compared to results obtained in subjects treated with nasal CPAP. Several treatment avenues--nasal CPAP, dental devices, surgical procedures, and radiofrequency thermal ablation--have been used for the treatment of UARS. The number of subjects treated have been too low and the protocols too limited to arrive at appropriate outcome recommendations, but many of the approaches have shown positive results, suggesting the possibility of several treatment avenues.

  View details for Web of Science ID 000087868200026

  View details for PubMedID 10893102

• Radiofrequency (pacing and thermic effects) in the treatment of sleep-disordered breathing 3rd Symposium on Diagnosis and Treatment of Sleep Breathing Disorders Guilleminault, C., Chervin, R., Palombini, L., Powell, N. AMER ACAD SLEEP MEDICINE. 2000: S182–S186

  Abstract

  Radiofrequency, whether it is used for pacing or for its thermal liberation properties, has been investigated as a treatment for sleep-disordered breathing. Diaphragmatic pacing has a long history. The problems associated with pacing, which are related to patient selection, equipment failure, disturbances at the electrode/nerve interface, neuromuscular function failure, muscle fatigue, and the physiological consequences of stimulation, will have to be resolved with XIIth nerve stimulation. Radiofrequency thermal ablation has been applied on the tongue of an animal model. In man, turbinates, soft palate tissue and the base of tongue have been treated. These feasibility studies have demonstrated that obstructive sleep apnea syndrome and upper airway resistance syndrome can be completely controlled using radiofrequency thermal ablation in some subjects. These results can be obtained without complications related to speech, taste or swallowing. The treatment can be administered as an outpatient procedure, but many applications are needed, and treatment may span 6 months. Too high a level of radiofrequency will cause pain or otherwise avoidable complications. The determination of which patients will benefit most from these procedures will require further multi-center, placebo-controlled studies.

  View details for Web of Science ID 000087868200022

  View details for PubMedID 10893098

• Morbidly obese patients with severe obstructive sleep apnea: Is airway reconstructive surgery a viable treatment option? LARYNGOSCOPE Li, K. K., Powell, N. B., Riley, R. W., Zonato, A., Gervacio, L., Guilleminault, C. 2000; 110 (6): 982-987

  Abstract

  To evaluate the outcomes of airway reconstructive surgery for the treatment of severe obstructive sleep apnea in the morbidly obese patient.Retrospective review of consecutively treated patients. Variables examined include age, sex, body mass index (BMI), respiratory disturbance index (RDI), lowest oxygen saturation (LSAT), cephalometric data, and complications.Twenty-one patients (13 men) with a mean age of 42.6 +/- 7.9 years and mean BMI of 45 +/- 5.4 kg/m2 were identified. The mean RDI improved from 83 +/- 30.1 to 10.6 +/- 10.8 events per hour with an improved mean apnea index from 38.4 +/- 31.3 to 1.2 +/- 1.8 events per hour. The mean LSAT improved from 63.9 +/- 17.7% to 86 +/- 7.9%. The mean BMI at the 6-month postoperative polysomnographic recording was 43 +/- 4.3 kg/m2 (P < .001). Seventeen patients (81%) were successfully treated (RDI < 20 and with minimal desaturation < 90%). The mean follow-up was 21.8 +/- 15.4 months (range, 7-66 mo). Coexisting obesity-hypoventilation syndrome was related to treatment failure in two patients. One patient noted recurrence of daytime fatigue after significant weight gain 4 years after surgery and the polysomnographic recordings demonstrated the recurrence of obstructive sleep apnea.Airway reconstruction is an effective treatment for severe obstructive sleep apnea in the morbidly obese patient. Careful patient selection and identifying potential coexisting obesity-hypoventilation syndrome, as well as counseling on weight reduction and avoiding continual weight gain will improve treatment outcomes. Key Words: Obstructive sleep apnea, sleep-disordered breathing, obstructive sleep apnea surgery, obesity, maxillomandibular advancement.

  View details for Web of Science ID 000087494900019

  View details for PubMedID 10852518

• Is sleep-disordered breathing an independent risk factor for hypertension in the general population (13,057 subjects)? JOURNAL OF PSYCHOSOMATIC RESEARCH Ohayon, M. M., Guilleminault, C., Priest, R. G., Zulley, J., Smirne, S. 2000; 48 (6): 593-601

  Abstract

  OBJECTIVES Sleep-disordered breathing has been hypothesized to have a close relationship with hypertension but previous studies have reported mixed results. This is an important health issue that requires further clarification because of the potential impact on the prevention and control of hypertension.The relationship between hypertension and three forms of sleep-disordered breathing (chronic snoring, breathing pauses and obstructive sleep apnea syndrome (OSAS)) was assessed using representative samples of the non-institutionalized population of the UK, Germany and Italy (159 million inhabitants). The samples were comprised of 13,057 individuals aged 15-100 years who were interviewed about their sleeping habits and their sleep symptoms over the telephone using the Sleep-EVAL system.OSAS was found in 1.9% (95% CI: 1.2% to 2.3%) of the UK sample, 1.8% (95% CI: 1.4% to 2.2%) of the German sample and 1.1% (95% CI: 0.8% to 1.4%) of the Italian sample. OSAS was an independent risk factor (odds ratio (OR): 9.7) for hypertension after controlling for possible confounding effects of age, gender, obesity, smoking, alcohol consumption, life stress, and, heart and renal disease.Results from three of the most populated countries in Western Europe indicate that OSAS is an independent risk factor for hypertension. Snoring and breathing pauses during sleep appeared to be non-significant predictive factors.

  View details for Web of Science ID 000089430300012

  View details for PubMedID 11033380

• Apparent life-threatening events, facial dysmorphia and sleep-disordered breathing EUROPEAN JOURNAL OF PEDIATRICS Guilleminault, C., Pelayo, R., Leger, D., Philip, P. 2000; 159 (6): 444-449

  Abstract

  A standardized clinical evaluation and questionnaire was, beginning in 1985, applied to infants referred for an apparent life-threatening event (ALTE). All children who underwent this "core evaluation protocol" during a 10-year period were reviewed. Documentation of clinical complaints, symptoms and signs of sleep-disordered breathing, sleep/wake evaluation, systematic evaluation of the face and naso-oro-pharynx, nocturnal polygraphic recording, and systematic follow-up was conducted. A total of 346 infants had complete data sets, with a smaller group of 46 age-matched healthy infants as controls. A scorer blind to the clinical data analyzed the polygraphic investigation and divided the 346 referred into two groups. Group A, 42.6% of the population, included infants with no abnormal findings based on nocturnal polygraphic recording. These infants were no different from controls at initial evaluation and during follow-up. Group B, 57.4% of the population, included infants who had obstructive breathing during sleep which became more obvious over time. Two-thirds of these infants not only had clinical symptoms of sleep-disordered breathing but also had mild facial dysmorphia that could be seen clearly at 6 months of age.A subgroup of infants with apparent life-threatening events present an indication of a sleep-disordered breathing syndrome which is associated with a mild dysmorphia. This mild facial dysmorphia needs to be recognized early to distinguish these infants from other infants with apparent life-threatening events and to initiate appropriate treatment.

  View details for Web of Science ID 000087421900010

  View details for PubMedID 10867851

• High (or abnormal) upper airway resistance REVUE DES MALADIES RESPIRATOIRES Guilleminault, C., Black, J. E., Palombini, L. 2000; 17: S43-S50

  View details for Web of Science ID 000088250000007

• [The upper airway high resistance (or abnormal resistance) syndrome]. Revue des maladies respiratoires Guilleminault, C., Black, J. E., Palombini, L. 2000; 17: S43-50

  View details for PubMedID 10939103

• Upper airway resistance syndrome is a distinct syndrome AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE Guilleminault, C., Chowdhuri, S. 2000; 161 (5): 1412-1413

  View details for Web of Science ID 000086945400002

  View details for PubMedID 10806128

• Randomized trial of modafinil as a treatment for the excessive daytime somnolence of narcolepsy 49th Annual Meeting of the American-Academy-of-Neurology Becker, P. M., Jamieson, A. O., Jewel, C. E., Bogan, R. K., James, D. S., Sutton, J. T., Corser, B., Mayleben, D. W., Bernard, S. H., Dinner, D. S., Emsellem, H., Knight, E., Erwin, C. W., Krystal, A. D., Radtke, R. A., Farrow, S., Odynski, T., PINTO, J., Steljes, D., Feldman, N. T., O'Brien, M., Fredrickson, P. A., Kaplan, J., Lin, S. C., Burger, C., Fry, J. M., Guilleminault, C., Black, J., Green, P. M., Schmitigal, L., Gross, P. T., Dignan, S., Harsh, J., Hartwig, G., Haynes, J. B., Hageman, M., Porter-Shirley, K., Hertz, G., Hirshkowitz, M., Moore, C. A., Iyer, V., Mahowald, M. M., Ullevig, C., Mitler, M. M., Hayduk, R., Erman, M. K., Pascualy, R., Stolz, S., Parman, D., Richter, R. W., Gruenau, S. P., Webster, J. J., Ristanovic, R. K., Bergen, D., Kanner, A., Dyonzak, J., Rogers, A. E., Aldrich, M. S., Rosenberg, R., Richardson, T., Lee, J., Sahota, P. K., Dexter, J. D., Burger, R. C., Sangal, R. B., Sangal, J. M., Belisle, C., Schmidt, H. S., Parisot, P. A., Schmidt-Nowara, W. W., Jessup, C., Schwartz, J. R., Schwartz, E. R., Veit, C., Blakely, L., Scrima, L., Miller, B. R., Shettar, S. M., May, R. S., Wilkerson, K. E., Stafford, C., Grogan, W. A., Tearse, R., Thein, S. G., Colontonio, L., Vern, B. A., Mercer, P. J., Merritt, S. L., Walsleben, J. A., O'Malley, M. B., Rapoport, D. M., WINOKUR, A., Szuba, M. D., Civil, R. H., Dobbins, T. W., Kribbs, N. B., Laughton, W. B., Nelson, M. T., Wang, L. X. LIPPINCOTT WILLIAMS & WILKINS. 2000: 1166–75

  View details for Web of Science ID 000085785700028

• Surgery and obstructive sleep apnea: Long-term clinical outcomes 102nd Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery Riley, R. W., Powell, N. B., Li, K. K., Troell, R. J., Guilleminault, C. MOSBY-ELSEVIER. 2000: 415–21

  Abstract

  Outcome data on the surgical treatment of obstructive sleep apnea are, in general, based on short-term follow-up (<6-9 months). This examination was undertaken to assess long-term results.Forty patients who underwent soft tissue and skeletal surgery were the subjects of this review. Methods of evaluation included polysomnographic variables (respiratory disturbance index [RDI], low oxyhemoglobin desaturation [LSAT]), body mass index, quality-of-life assessments, roentgenographic analysis, and complications. Statistical analysis used the SAS 6.12 system.Thirty-six of 40 patients (90%) showed long-term clinical success. The mean preoperative RDI, nasal continuous positive airway pressure RDI, and long-term RDI were 71.2 +/- 27.0, 7.6 +/- 5.2 and 7.6 +/- 5.1, respectively. The mean preoperative LSAT, nasal continuous positive airway pressure LSAT, and long-term LSAT were 67. 5% +/- 14.8%, 87.1% +/- 3.2%, and 86.3% +/- 3.9%, respectively. The mean follow-up was 50.7 +/- 31.9 months. The patients showed a statistically significant long-term weight gain (P = 0.0002) compared with their 6-month postoperative level (body mass index 31. 4 +/- 6.7 vs 32.2 +/- 6.3). There was a positive correlation with the amount of skeletal advancement and clinical outcome.Comprehensive evaluation and surgical treatment can result in successful long-term clinical outcome.

  View details for Web of Science ID 000085832100019

  View details for PubMedID 10699820

• Prevalence of insomnia in a survey of 12 778 adults in France JOURNAL OF SLEEP RESEARCH Leger, D., Guilleminault, C., Dreyfus, J. P., Delahaye, C., Paillard, M. 2000; 9 (1): 35-42

  Abstract

  This study was an epidemiological questionnaire survey of a representative sample of the French population that included 12 778 individuals and in which adapted DSM-IV criteria for the definition of insomnia were used. Our goals were not only to assess the prevalence of 'insomnia' using these criteria, but also to compare the results obtained with those of prior studies using different definitions of 'insomnia'. The aim of this study was also to identify where areas of agreement and disagreement existed, as we believe that it is important to emphasize these points because DSM-IV recommendations are supposedly reflected in clinical practice. Seventy-three per cent of the individuals surveyed complained of a nocturnal sleep problem, but only 29% reported at least one sleep problem three times per week for a month, and 19% (2428 subjects) had at least one sleep problem three times per week for a month and complained of daytime consequences (DSM-IV criteria). Only 9% had two or more nocturnal sleep problems with daytime consequences and were classified as 'severe insomniacs'. Our study indicates that if DSM-IV criteria are used, the diagnosis of 'insomnia' is lower than in other epidemiological studies. The DSM criteria have an advantage in that they emphasize the daytime consequences of nocturnal sleep disturbances, which seem to be responsible for the most important socio-economic costs of the problem.

  View details for Web of Science ID 000086267800006

  View details for PubMedID 10733687

• Comparison of postoperative pain between laser-assisted uvolopalatoplasty, uvulopalatopharyngoplasty, and radiofrequency volumetric tissue reduction of the palate 102nd Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery Troell, R. J., Powell, N. B., Riley, R. W., Li, K. K., Guilleminault, C. MOSBY-ELSEVIER. 2000: 402–9

  Abstract

  This study compares the posttreatment discomfort between laser-assisted uvulopalatoplasty (LAUP), uvulopalatopharyngoplasty (UPPP), and radiofrequency volumetric tissue reduction (RFVTR) of the palate through the use of visual analog pain scales and a quantitative assessment of the analgesic medication taken.In one group, LAUP (n = 10) or UPPP (n = 9) was used to treat patients' snoring or sleep-disordered breathing (SDB), and the other group underwent RFVTR (n = 22).The mean numbers of days with pain after RFVTR, LAUP, and UPPP were 2.6, 13.8, and 14.3 days, respectively. Narcotic analgesics were required in the RFVTR, LAUP, and UPPP groups in 9%, 100%, and 100% of the subjects, respectively. The mean number of these days requiring narcotic pain medications for RFVTR, LAUP, and UPPP was 0.2, 11.8, and 12.4 days, whereas the total narcotic equivalent was 0.3, 7.4 and 29.6 days, respectively.RFVTR of the soft palate produced less posttreatment pain than LAUP or UPPP. LAUP and UPPP appeared to show little difference in the severity or duration of posttreatment discomfort.

  View details for Web of Science ID 000085832100017

  View details for PubMedID 10699818

• An unreported risk in the use of home nasal continuous positive airway pressure and home nasal ventilation in children - Mid-face hypoplasia CHEST Li, K. K., Riley, R. W., Guilleminault, C. 2000; 117 (3): 916-918

  Abstract

  We report the case of a 15-year-old boy with obstructive sleep apnea and obesity who was treated since the age of 5 with nasal continuous positive airway pressure. Due to the long-term use of a nasal mask, the child developed a mid-face hypoplasia. Chronic use of a nasal mask for home ventilation in children should always be associated with regular evaluations of maxillomandibular growth.

  View details for Web of Science ID 000085884000055

  View details for PubMedID 10713032

• Radiofrequency volumetric reduction of the palate: An extended follow-up study OTOLARYNGOLOGY-HEAD AND NECK SURGERY Li, K. K., Powell, N. B., Riley, R. W., Troell, R. J., Guilleminault, C. 2000; 122 (3): 410-414

  Abstract

  The goal was to evaluate the effect of radiofrequency (RF) of the palate on speech, swallowing, taste, sleep, and snoring 12 to 18 months after treatment.Twenty-two patients were evaluated by clinical examination, questionnaires, and visual analog scales. The patients with relapse of snoring were offered further RF treatment.After a mean follow-up of 14 months, no adverse effect was reported. Subjective snoring scores relapsed by 29% overall. Nine patients (41%) noted relapse of snoring from 2.1 +/- 1. 1 to 5.7 +/- 2.7 (P < 0.001). Eight of the patients underwent further RF treatment with a reduction of snoring from 5.8 +/- 2.9 to 3.3 +/- 3.1 (P = 0.01).The success of RF volumetric reduction of the palate diminishes with time, as with other surgical procedures of the palate. However, the minimal invasiveness of the RF provided a high patient acceptance for retreatment, and relapse of snoring can be improved.

  View details for Web of Science ID 000085832100018

  View details for PubMedID 10699819

• Hypersomnia after head-neck trauma - A medicolegal dilemma NEUROLOGY Guilleminault, C., Yuen, K. M., Gulevich, M. G., Karadeniz, D., Leger, D., Philip, P. 2000; 54 (3): 653-659

  Abstract

  To evaluate the severity of daytime sleepiness in patients with a history of head trauma who complain of daytime somnolence, to investigate polygraphic abnormalities during nocturnal sleep, and to determine whether daytime sleepiness was the cause or consequence of the head trauma.The authors performed a systematic evaluation of 184 patients comprised of clinical interviews, sleep disorders questionnaires, sleepiness and depression scales, medical and neurologic evaluations, sleep logs with actigraphy, nocturnal polysomnography, and the Multiple Sleep Latency Test (MSLT). Assessments of sleepiness before the accident were based on bed partner interviews, coworker and employer reports, health reports, driving records, and employment history that included absenteeism.Post-traumatic complaint of somnolence was associated with variable degrees of impaired daytime functioning in more than 98% of patients. Patients who were in a coma for 24 hours, who had a head fracture, or who had immediate neurosurgical interventions were likely to have scores > 16 points on the Epworth Sleepiness Scale (ESS) and < or = 5 minutes on the MSLT. Pain at night was an important factor in nocturnal sleep disruption and daytime sleepiness. Sleep-disordered breathing was a common finding and was the only finding in whiplash patients with daytime sleepiness. Extensive evaluation of pretrauma behavior supported the conclusion that the onset of symptomatic sleep-disordered breathing was associated with the trauma. The patients who showed a "compulsive presleep behavior" were severely impaired in performing their daily activities.A systematic approach is required when dealing with patients complaining of hypersomnia following a head-neck trauma.

  View details for Web of Science ID 000085160300021

  View details for PubMedID 10680799

• A clinical investigation of obstructive sleep apnea syndrome (OSAS) and upper airway resistance syndrome (UARS) patients SLEEP MEDICINE Guilleminault, C., Black, J. E., Palombini, L., Ohayon, M. 2000; 1 (1): 51-56

  View details for Web of Science ID 000208300300007

• Postoperative airway findings after maxillomandibular advancement for obstructive sleep apnea syndrome LARYNGOSCOPE Li, K. K., Riley, R. W., Powell, N. B., Zonato, A., Troell, R., Guilleminault, C. 2000; 110 (2): 325-327

  Abstract

  To evaluate the upper airway characteristics in the early postoperative period after maxilomandibular advancement for obstructive sleep apnea syndrome.Nasopharyngolaryngoscopy was performed before and 48 hours after surgery on 70 consecutive patients who underwent maxillomandibular advancement for obstructive sleep apnea syndrome. The preoperative and the postoperative evaluations were performed by the same examiner for consistency.Mild to moderate lateral pharyngeal wall edema was identified in 70 consecutive patients. Fourteen patients (20%) had edema as well as ecchymosis involving the pyriform sinus and aryepiglottic fold. Four of these patients (6%) were also noted to have hypopharyngeal hematoma involving the pyriform sinus, aryepiglottic fold, arytenoid, and false vocal cord that partially obstructed the airway. These four patients were closely monitored for 1 to 2 additional days for possible expanding hematoma leading to airway compromise. None of these patients were found to have airway difficulty, and the minimum oxygen saturation was more than 90% throughout the hospitalization. All four patients were discharged uneventfully, and the hematoma resolved completely within 10 days.Although postoperative edema was expected after maxillomandibular advancement, hypopharyngeal hematoma was unexpected. Although none of our patients had evidence of airway difficulty, the possibility of an expanding hypopharyngeal hematoma should be considered in patients complaining of breathing difficulty after maxillomandibular advancement surgery.

  View details for Web of Science ID 000085224200026

  View details for PubMedID 10680939

• A clinical investigation of obstructive sleep apnea syndrome (OSAS) and upper airway resistance syndrome (UARS) patients. Sleep medicine Guilleminault, C., Black, J. E., Palombini, L., Ohayon, M. 2000; 1 (1): 51–56

  Abstract

  Objective: (i) Evaluation of the clinical differences and similarities presented by patients diagnosed as OSAS and UARS subjects. (ii) Evaluation of the ability of a sleep disorders specialist to dissociate the two syndromes based upon clinical evaluation.Population: 314 subjects were included. They were referred to a sleep disorders clinic with complaints of loud snoring during a 3 month period.Method: The evaluation consisted of: (i) Clinical interview and evaluation. (ii) Administration of validated questionnaires (Sleep Disorders Questionnaire and Epworth Sleepiness Scale). (iii) Establishment of clinical diagnostic and results of polygraphic recording.Results: After clinical evaluation and polygraphic recordings (performed within 3 weeks of initial evaluation) patients were subdivided into two groups: 176 OSAS and 128 UARS. The misclassification of patients by specialists correlated with body mass index (BMI) measurement, with an over classification of patient as OSAS when a high BMI was noted and vice-versa for UARS. The only significant difference between OSAS and UARS patients was an older age and a wider neck circumference in the OSAS group than in UARS patients.Conclusion: Clinical presentation including daytime sleepiness complaint and ESS score is similar for patients with and without drop of oxygen saturation below 90% during sleep. There was always a male predominance within both syndromes, but more women were diagnosed with UARS than with OSAS.

  View details for PubMedID 10733620

• Long-Term Results of Maxillomandibular Advancement Surgery. Sleep & breathing = Schlaf & Atmung Li, K. K., Powell, N. B., Riley, R. W., Troell, R. J., Guilleminault, C. 2000; 4 (3): 137-140

  Abstract

  Surgery is a major modality in the treatment of obstructive sleep apnea syndrome (OSAS), and maxillomandibular advancement (MMA) has been shown to be the most effective surgical option. However, despite the successful short-term (6-9 months) results reported by various investigators, little is known of the long-term clinical outcomes. A review of our long-term clinical results demonstrated that MMA achieves long-term cure in most patients. Aging and minor weight gain did not appear to have a significant adverse effect on the long-term results; however, major weight gain did seem to have a significant negative impact on the long-term outcomes. Therefore, long-term follow-up with proper counseling on weight maintenance or reduction is essential in improving long-term results.

  View details for PubMedID 11868133

• Long-term efficacy and safety of modafinil (PROVIGIL((R))) for the treatment of excessive daytime sleepiness associated with narcolepsy. Sleep medicine Mitler, M. M., Harsh, J., Hirshkowitz, M., Guilleminault, C. 2000; 1 (3): 231–43

  Abstract

  Objectives: To assess the long-term efficacy and safety of modafinil in patients with excessive daytime sleepiness (EDS) associated with narcolepsy.Background: Modafinil has been shown to be effective and well tolerated for treating EDS associated with narcolepsy in two large-scale, well-controlled, 9-week clinical trials.Methods: Four hundred and seventy eight adult patients with a diagnosis of narcolepsy who had completed one of two 9-week, double-blind, placebo-controlled, multicenter, clinical trials of modafinil were enrolled in two 40-week, open-label, extension studies. A flexible-dose regimen (i.e. 200, 300, or 400 mg daily) was followed in one study. In the second study, patients received 200 mg/day for 1 week, followed by 400 mg/day for 1 week. Investigators then prescribed either 200- or 400-mg doses for the duration of the study. Efficacy was evaluated using Clinical Global Impression of Change (CGI-C) scores, the Epworth Sleepiness Scale (ESS), and the 36-item Medical Outcomes Study health survey (SF-36). Adverse events were recorded. Data from the two studies were combined.Results: The majority of patients ( approximately 75%) received 400 mg of modafinil daily. Disease severity improved in >80% of patients throughout the 40-week study. At weeks 2, 8, 24, and 40, disease severity was 'much improved' or 'very much improved' in 49, 58, 59, and 58% of patients, respectively. The mean (+/-SEM) ESS score improved significantly from 16.5+/-0.2 at open-label baseline to 12.4+/-0.2 at week 2 and remained at that level through week 40 (P<0.001). Quality of life scores at weeks 4, 8, 24, and 40 were significantly improved versus open-label baseline scores for six of the eight SF-36 domains (P<0.001). The most common treatment-related adverse events were headache (13%), nervousness (8%), and nausea (5%). Most adverse events were mild to moderate in nature. A total of 341 patients (71%) completed the studies. Forty-three patients (9.0%) discontinued treatment because of adverse events.Conclusions: Modafinil is effective for the long-term treatment of EDS associated with narcolepsy and significantly improves perceptions of general health. Modafinil is well tolerated, with no evidence of tolerance developing during 40 weeks of treatment.

  View details for PubMedID 10828434

• Suspicion of sleep-disordered breathing: which test to perform? Sleep medicine Guilleminault, C. 2000; 1 (1): 73–75

  View details for PubMedID 10733628

• Vascular reactivity in obstructive sleep apnea syndrome AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE Duchna, H. W., Guilleminault, C., Stoohs, R. A., Faul, J. L., Moreno, H., Hoffman, B. B., Blaschke, T. F. 2000; 161 (1): 187-191

  Abstract

  The obstructive sleep apnea syndrome (OSAS) is associated with cardiovascular disease and systemic hypertension. Because systemic arterial blood pressure is proportional to venodilation and venous return to the heart, we hypothesized that altered vascular responsiveness might exist in the veins of subjects with OSAS. We therefore investigated venodilator responses in awake, normotensive subjects with and without OSAS, using the dorsal hand vein compliance technique. Dose-response curves to bradykinin and nitroglycerin were obtained from 12 subjects with OSAS and 12 matched control subjects. Maximal dilation (E(max)) to bradykinin was significantly lower in the OSAS group (62.1% +/- 26.1%) than in the control group (94.3% +/- 10.7%) (p < 0.005). Vasodilation to nitroglycerin tended to be lower in the OSAS group (78.6% +/- 31.8%) than the control group (100.3% +/- 12.9%), but this effect did not reach statistical significance. When six of the OSAS subjects were retested after 60 d of treatment with nasal continuous positive airway pressure (CPAP), E(max) to bradykinin rose from 60.3% +/- 20. 3% to 121.4% +/- 26.9% (p < 0.01). Vasodilation to nitroglycerin also increased, but this effect did not reach statistical significance. These results demonstrate that a blunted venodilatory responsiveness to bradykinin exists in OSAS. This effect appears to be reversible with nasal CPAP therapy.

  View details for Web of Science ID 000084820200032

  View details for PubMedID 10619819

• Upper airway resistance syndrome OTO-RHINO-LARYNGOLOGIA NOVA Guilleminault, C., Chowdhuri, S. 2000; 10 (3-4): 119-125

  View details for Web of Science ID 000165694100006

• Normal pregnancy, daytime sleeping, snoring and blood pressure. Sleep medicine Guilleminault, C., Querra-Salva, M., Chowdhuri, S., Poyares, D. 2000; 1 (4): 289–97

  Abstract

  Objective: Investigation of daytime sleepiness, blood pressure changes and presence of sleep disordered breathing, in healthy young women during pregnancy.Methods: Young, healthy pregnant women between 18 and 32 years of age, seen in three different prenatal care clinics, were enlisted in a prospective study divided in two parts: part 1 of the study consisted of completing a standardized questionnaire on past and present sleep disorders. It also included filling out visual analog scales (VAS) for daytime sleepiness and snoring by the subject and bed partner. Blood pressure measurement was performed at 9 AM as per the WHO protocol. Similar data were collected again at the 6-month prenatal visit and at the 3-month post-delivery visit. At the 6-month visit, ambulatory monitoring of nocturnal sleep using a portable six-channel recorder (Edentrace((R))) was performed at home. Part 2 involved a subgroup of subjects that were randomly selected after stratification based on results of VAS and ambulatory monitoring. It included 1 night of nocturnal polysomnography with esophageal manometry and 24 h of ambulatory BP monitoring with portable equipment with cuff inflation every 30 min.Results: Of the 267 women who participated in part 1 of the study, only 128 consented to enroll in part 2, from which 26 were selected to undergo polysomnography. At the 6-week prenatal visit 37.45% of the subjects reported daytime sleepiness of variable severity. At the 6-month visit, this was noted in 52% of the subjects. Bed-partners reported chronic, loud snoring prior to pregnancy in 3.7% of the study population, but this increased to 11.8% at the 6-month visit. Blood pressure (BP) remained below the pathological range, i.e. less than 150/95 mm Hg, during the entire pregnancy. However, ambulatory monitoring indicated that 37 women, including the loud chronic snorers, had some minor SaO(2) drops during sleep and this same group presented the largest increase in BP between the 6th week and the 6th month prenatal visits. Part 2 included 26 women, 13 from the above identified 37 women and 13 from the rest of the group, chosen randomly, age and body mass index (BMI) matched. Polysomnography did identify two abnormal breathing patterns during sleep: (1) esophageal pressure 'crescendos' associated predominantly with stage 1 and 2 NREM sleep, and (2) 'abnormal sustained efforts' seen predominantly with delta sleep. These abnormal breathing patterns were noted during a significantly longer time during sleep. This group of women with the abnormal breathing patterns were not only chronic snorers but also had significantly higher systolic and diastolic BP increases when compared to the 13 other non-snorers. Six out of the 13 snorers were 'non-dippers' at the 24-h BP recording.Conclusion: Abnormal breathing during sleep (that is frequently, but not always, associated with loud, chronic snoring, and may be a consequence of edema induced by hormonal changes associated with pregnancy), can be seen in otherwise healthy young pregnant women. It may contribute to the symptom of daytime sleepiness. The changes in blood pressure noted were of no pathological significance in our population but could be an added risk factor in high-risk pregnancies.

  View details for PubMedID 11040461

• Narcolepsy in children: a practical guide to its diagnosis, treatment and follow-up. Paediatric drugs Guilleminault, C., Pelayo, R. 2000; 2 (1): 1-9

  Abstract

  Narcolepsy is a neurological syndrome characterised by daytime somnolence and cataplexy which often begins in childhood. Failing to recognise the condition may lead to mislabelling a child as lazy or depressed. The diagnostic criteria for narcolepsy vary with age. In children 8 years and older a Multiple Sleep Latency Test with an average latency of less than 8 minutes, and 2 or more sleep onset REM episodes supports the diagnosis. Human leucocyte antigen (HLA) marker DQbeta1 -0602 has been associated with narcolepsy. The current evidence supports the hypothesis that transmission of narcolepsy is multifactorial. with at least two genes, one of which is non-HLA related. The goal of all therapeutic approaches in narcolepsy is to control the narcoleptic symptoms and allow the patient to continue to fully participate in personal and academic activities. This usually requires a combination of behavioural therapy along with medication. Medications for patients with excessive sleepiness are usually stimulants, including amphetamines. However, a novel wake promoting agent, modafinil, is now available. Cataplexy can be controlled by medications with noradrenergic reuptake-blocking properties, such as clomipramine and fluoxetine, through their active metabolites. Increased awareness of narcolepsy is important to allow earlier diagnosis. Research on the effects different medications have, specifically on children with narcolepsy, has been very limited.

  View details for PubMedID 10937454

• The sleep tutorial. Studies in health technology and informatics Paiva, T., Guilleminault, C., Sagalés, T., Billiard, M., Zulley, J., Challamel, M. J., Louis, J., Besset, A., Philip, P., Levy, P., Rosa, A., Penzel, T. 2000; 78: 193-206

  Abstract

  A multimedia Sleep tutorial for General Practitioners was implemented from scratch. The implementation had into account the following features: 1) Specific needs of GPs evaluated in 3 different countries, related with Tutorial contents and technical features; 2) Multinational authorship from European experts; 3) Multilingual possibilities; 4) User friendliness and easy navigation. The tutorial was implemented and tested and its gama version is now available for commercialization.

  View details for PubMedID 11151597

• A comparison of Asian and white patients with obstructive sleep apnea syndrome LARYNGOSCOPE Li, K. K., Powell, N. B., Kushida, C., Riley, R. W., Adornato, B., Guilleminault, C. 1999; 109 (12): 1937-1940

  Abstract

  To evaluate the possible differences between Asian and white patients with obstructive sleep apnea syndrome.A retrospective review of Asian and white patients during a 12-month period was conducted. Patients with respiratory disturbance index (RDI) > or = 15 based on polysomnography were included in the study. Variables examined include age, sex, body mass index (BMI), RDI, lowest oxygen saturation (LSAT), and cephalometric analysis data.Fifty-eight Asian patients (53 men) and 293 white patients (260 men) were studied. The Asians were younger (44.1 +/- 9.8 vs. 47.5 +/- 11.6 y, P = .02), and the mean BMI (kg/m2) was 26.6 +/- 3.7 in the Asians and 30.7 +/- 5.9 in the whites (P < .001). The mean RDI was similar (56.6 +/- 34.9 vs. 55.6 +/- 26.9, P = NS), but the mean LSAT was lower in the whites (77.7 +/- 9.9% vs. 70.0 +/- 15.6%, P < .001). Based on the cephalometric data, the Asians have maxillomandibular protrusion, narrower cranial base angle, larger posterior airway space, and more superiorly positioned hyoid bone compared with the whites.Although male gender was found to be an important risk factor for obstructive sleep apnea syndrome in both Asian and white patients, obesity may be a less significant risk factor in the Asians because the majority of our Asian patients were nonobese. There was also variability in the craniomandibular factors that contributed to obstructive sleep apnea syndrome in the two groups.

  View details for Web of Science ID 000084030700007

  View details for PubMedID 10591350

• Validation of the sleep-EVAL system against clinical assessments of sleep disorders and polysomnographic data SLEEP Ohayon, M. M., Guilleminault, C., Zulley, J., Palombini, L., Raab, H. 1999; 22 (7): 925-930

  Abstract

  To validate the Sleep-EVAL expert system, a computerized tool designed for the assessment of sleep disorders, against polysomnographic data and clinical assessments by sleep specialists.Patients were interviewed twice, once by a physician using Sleep-EVAL and again by a sleep specialist. Polysomnographic data were also recorded to ascertain diagnoses. Agreement between diagnoses generated by Sleep-EVAL and those formulated by sleep specialists was determined via the kappa statistic.Sleep disorder centers at Stanford University (USA) and Regensburg University (Germany).105 patients aged 18 years or over.NA.Sleep-EVAL made an average of 1.32 diagnoses per patient, compared with 0.93 for the sleep specialists. Overall agreement on any sleep-breathing disorder was 96.9% (Kappa .94). More than half of the patients were diagnosed with obstructive sleep apnea syndrome (OSAS); the agreement rate for this specific diagnosis was 96.7% (Kappa .93).The findings indicate that the Sleep-EVAL system is a valid instrument for the recognition of major sleep disorders, particularly insomnia and OSAS.

  View details for Web of Science ID 000083566100010

  View details for PubMedID 10566910

• Evaluation of obstructive sleep apnea by polysomnography prior to pediatric adenotonsillectomy ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY Pelayo, R., Powell, N., Guilleminault, C. 1999; 125 (11): 1282-1283

  View details for Web of Science ID 000083519700020

  View details for PubMedID 10555707

• Overview of phase II surgery for obstructive sleep apnea syndrome. Ear, nose, & throat journal Li, K. K., Riley, R. W., Powell, N. B., Troell, R., Guilleminault, C. 1999; 78 (11): 851-?

  Abstract

  Maxillomandibular advancement is an extremely effective surgical procedure for the treatment of obstructive sleep apnea syndrome. When properly executed, it is associated with minimal morbidity and is well accepted by patients. It is a treatment option that achieves long-term care.

  View details for PubMedID 10581838

• Overview of phase I surgery for obstructive sleep apnea syndrome. Ear, nose, & throat journal Li, K. K., Powell, N. B., Riley, R. W., Troell, R., Guilleminault, C. 1999; 78 (11): 836-?

  Abstract

  It is well established that obstructive sleep apnea syndrome is associated with increased morbidity and mortality. Surgical therapy has been demonstrated to be a viable treatment option for cure. Thorough presurgical evaluation with the identification of the type of airway abnormality is mandatory to allow for the utilization of a surgical protocol that results in improved clinical outcomes. Phase I surgical protocol is designed to apply specific surgical procedures to alleviate the obstruction(s) present. Following a logical, stepwise surgical approach in airway reconstruction will minimize surgical interventions and avoid unnecessary operations. The incorporation of a risk-management protocol will minimize treatment complications while achieving cure.

  View details for PubMedID 10581836

• A comparative model: Reaction time performance in sleep-disordered breathing versus alcohol-impaired controls Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery Powell, N. B., Riley, R. W., Schechtman, K. B., Blumen, M. B., Dinges, D. F., Guilleminault, C. JOHN WILEY & SONS INC. 1999: 1648–54

  Abstract

  Patients with sleep-disordered breathing have reaction time deficits that may lead to catastrophic accidents and loss of life. Although safety guidelines do not exist for unsafe levels of sleepiness, they have been established for unsafe levels of alcohol consumption. Since reaction time performance is altered in both, we prospectively used seven measures of reaction time performance as a comparative model in alcohol-challenged normal subjects with corresponding measures in subjects with sleep-disordered breathing.Institutional Review Board-approved, nonrandomized prospective controlled study.Eighty healthy volunteers (29.1+/-7.5 y of age, 56.3% female subjects) performed four reaction time trials using a psychomotor test at baseline and at three subsequent rising alcohol-influenced time points. The same test without alcohol was given to 113 subjects (47.2+/-10.8 y of age, 19.3% female subjects) with mild to moderate sleep-disordered breathing.Mean blood alcohol concentrations (BACs) in the alcohol-influenced subjects at baseline and three trials were 0, 0.057, 0.080, and 0.083 g/dL. The sleep-disordered subjects had mean respiratory disturbance indices of 29.2 events per hour of sleep. On all seven reaction time measures, their performance was worse than that of the alcohol subjects when BACs were 0.057 g/dL. For three of the measures, the sleep-disordered subjects performed as poorly as or worse than the alcohol subjects when alcohol levels were 0.080 g/dL. These results could not be explained by sex or age differences.The data demonstrate that sleep-disordered subjects in this study (with a mean age of 47 y) with mild to moderate sleep-disordered breathing had worse test reaction time performance parameters than healthy, nonsleepy subjects (with a mean age of 29 y) whose BAC is illegally high for driving a commercial motor vehicle in California. This comparative model points out the potential risks of daytime sleepiness in those with sleep-disordered breathing relative to a culturally accepted standard of impairment.

  View details for Web of Science ID 000083050300019

  View details for PubMedID 10522937

• Obstructive sleep apnoea in a puerperal patient with Hallermann-Streiff syndrome EUROPEAN RESPIRATORY JOURNAL Shiomi, T., Guilleminault, C., Izumi, H., Yamada, S., Murata, K., Kobayashi, T. 1999; 14 (4): 974-977

  Abstract

  A 26 yr old puerperal female with Hallermann-Streiff syndrome developed serious obstructive sleep apnoea syndrome during pregnancy. She underwent an elective Caesarean section delivery, but ending the pregnancy did not improve her clinical symptoms. By treating her with nasal continuous positive airway pressure, a worsening of her headaches and glaucoma was prevented. The administration of acetazolamide controlled all of her symptoms. Treatment with nasal ventilation is the best initial approach. It is also important to assure normal oxygenation before pregnancy since the foetus may suffer from the severe deprivation that may occur in these patients.

  View details for Web of Science ID 000083614800042

  View details for PubMedID 10573253

• Sleep disorders in children with blindness ANNALS OF NEUROLOGY Leger, D., Prevot, E., Philip, P., Yence, C., Labaye, N., Paillard, M., Guilleminault, C. 1999; 46 (4): 648-651

  Abstract

  To evaluate the frequency and type of sleep disorders seen in blind children compared with matched controls, a 42-item questionnaire was used on 156 children (77 blind children) ranging from 3 to 18 years of age. A total of 17.4% of blind children reported sleeping less than 7 hours per night on weekdays compared with 2.6% of controls, with blind children awakening much earlier. Blind children had more sleep complaints, and 13.4% of blind subjects had daily episodes of involuntary sleepiness compared with 1.3% of controls. Blindness has an impact on sleep and alertness that adds to the primary disability.

  View details for Web of Science ID 000082914500014

  View details for PubMedID 10514103

• Prevalence of sleep/wake disorders in persons with blindness CLINICAL SCIENCE Leger, D., Guilleminault, C., Defrance, R., Domont, A., Paillard, M. 1999; 97 (2): 193-199

  Abstract

  Blind individuals are not only handicapped by their loss of vision, but are also affected because the loss of sight may have a secondary impact on functioning of their biological clock. The objective of the present study was to determine the impact of visual loss on sleep/wake disorders. A prospective 48-item questionnaire survey was distributed to blind individuals through the French Association Valentin Haüy, which serves blind persons. A control group matched by age, sex, geographical location and professional activity/non-activity was obtained from a panel of 20000 households representative of the French population, and this group also completed the questionnaire. From a potential blind population of 1500 subjects, 1073 questionnaires (71.5%) were completed and usable for analysis, and from a potential 1000 control subjects, 794 (79. 4%) of the questionnaires were returned and analysed. Criteria outlined in the Diagnostic and Statistical Manual of Mental Disorders, 4th revision, and the International Classification of Sleep/Wake Disorders (1990) were used to determine pathology. Individuals determined to be 'totally blind' and 'almost blind' (i.e. with less than 10% vision left in only one eye) presented a significantly higher occurrence of sleep/wake disorders than controls. Nocturnal sleep disruption, daytime somnolence, and (to a lesser degree) a 'free-running' condition are significantly more common in blind individuals. There is an increased use of sleeping pills, and a higher incidence of inappropriate involuntary daily naps. In conclusion, individuals with blindness report a significant curtailment of total sleep time and hence resulting daytime somnolence, which impacts on daytime activities. A 'free-running' condition is also a common sleep/wake impairment that may compound the handicap of blindness.

  View details for Web of Science ID 000082064200008

  View details for PubMedID 10409474

• Long distance driving and self-induced sleep deprivation among automobile drivers SLEEP Philip, P., Taillard, J., Guilleminault, C., Salva, M. A., Bioulac, B., Ohayon, M. 1999; 22 (4): 475-480

  Abstract

  To evaluate the sleep hygiene and prevalence of sleep deprivation among a large sample of automobile drivers.From the 15th of June to the 4th of August 1996, with the help of the French highway patrol, we randomly stopped automobile drivers at the toll booths of Bordeaux and Biarritz. All subjects completed a validated questionnaire on sleep/wake habits during the year. After answering the questionnaire, subjects completed a graphic travel and sleep log of the three days preceding the interview.We randomly stopped 2196 automobile drivers. Ninety-one percent of the sample (mean age 43 +/- 13 years) agreed to participate in the survey.Fifty percent of the drivers decreased their total sleep time in the 24 hours before the interview compared with their regular self-reported sleep time. 12.5% presented a sleep debt > 180 minutes, and 2.7% presented a sleep debt > 300 minutes. Being young, commuting to work, driving long distances, starting the trip at night, being an "evening" person, being a long sleeper during the week, and sleeping in on the week-end were risk factors significantly associated with sleep debt.The results of the study highlight variables (long-distance driving, youth, sleep restriction) that are frequently associated with sleep-related accidents.

  View details for Web of Science ID 000081994900007

  View details for PubMedID 10389223

• Sleep-related violence, injury, and REM sleep behavior disorder in PD NEUROLOGY Bernath, O., Guilleminault, C. 1999; 52 (9): 1924-1924

  View details for Web of Science ID 000080758500052

  View details for PubMedID 10371559

• Radiofrequency tongue base reduction in sleep-disordered breathing: A pilot study 102nd Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery Powell, N. B., Riley, R. W., Guilleminault, C. MOSBY-ELSEVIER. 1999: 656–64

  Abstract

  This pilot study investigates the new technology of radiofrequency energy (RFe), as applied to the tongue base, for the purpose of assessing feasibility, safety, and possible efficacy in the treatment of sleep-disordered breathing (SDB).Eighteen patients with SDB, in whom at least palatopharyngoplasty had failed, were entered in this study. The mean respiratory disturbance index was 39.6, with a mean nadir oxygen (SaO2) of 81.9%. A radiofrequency electrode delivered energy to the subsurface tongue base with local anesthetic. Polysomnography, quantitative speech and swallowing studies, questionnaires, and visual analog scales were used to assess outcomes. MRI assessed changes in tongue volume.Separate RFe treatments (mean 5.5) at 4-week intervals were given (mean 1543 J for 9 minutes at 80 degrees C), for a mean energy total of 8490 J per patient. The posttreatment mean respiratory disturbance index was 17.8, and the SaO2 nadir was 88.3%. Weight increased slightly; speech and swallowing did not change. Questionnaires and visual analog scale scores showed improvement in study variables. Tongue volume was reduced by a mean of 17%. Pain was controlled by hydrocodone for 3 to 4 days. One infection was seen and resolved with incision and drainage.This pilot study demonstrates feasibility, safety, and efficacy in reducing tongue volume using RFe. Additional cumulative energy may improve the cure rate for SDB.

  View details for Web of Science ID 000080179300007

  View details for PubMedID 10229589

• Prevalence and pathologic associations of sleep paralysis in the general population NEUROLOGY Ohayon, M. M., Zulley, J., Guilleminault, C., Smirne, S. 1999; 52 (6): 1194-1200

  Abstract

  Previous epidemiologic data on sleep paralysis (SP) came from small specific samples. The true prevalence and associated factors of SP in the general population remain unknown.A representative sample of the noninstitutionalized general population of Germany and Italy age > or =15 years (n = 8,085) was surveyed by telephone using the Sleep-EVAL questionnaire and the Sleep Questionnaire of Alertness and Wakefulness.Overall, 6.2% (5.7 to 6.7%) of the sample (n = 494) had experienced at least one SP episode in their lifetime. At the time of the interview, severe SP (at least one episode per week) occurred in 0.8% of the sample, moderate SP (at least one episode per month) in 1.4%, and mild SP (less than one episode per month) in 4.0%. Significant predictive variables of SP were anxiolytic medication, automatic behavior, bipolar disorders, physical disease, hypnopompic hallucinations, nonrestorative sleep, and nocturnal leg cramps.SP is less common in the general population than was previously reported. This study indicates that the disorder is often associated with a mental disorder. Users of anxiolytic medication were nearly five times as likely to report SP, even after we controlled for possible effects of mental and sleep disorders.

  View details for Web of Science ID 000079728900016

  View details for PubMedID 10214743

• High (or abnormal) upper airway resistance REVUE DES MALADIES RESPIRATOIRES Guilleminault, C., Black, J. E., Palombini, L. 1999; 16 (2): 173-180

  View details for Web of Science ID 000080017800007

  View details for PubMedID 10339760

• Night terrors, sleepwalking, and confusional arousals in the general population: Their frequency and relationship to other sleep and mental disorders JOURNAL OF CLINICAL PSYCHIATRY Ohayon, M. M., Guilleminault, C., Priest, R. G. 1999; 60 (4): 268-276

  Abstract

  Arousal parasomnias (night terrors, sleepwalking, and confusional arousals) have seldom been investigated in the adult general population. Clinical studies of parasomnias, however, show that these disorders may be indicators of underlying mental disorders and may have serious consequences.A representative sample of the United Kingdom population (N = 4972) was interviewed by telephone with the Sleep-EVAL system.Night terrors were reported by 2.2% (95% CI = 1.8% to 2.6%) of the sample, sleepwalking by 2.0% (1.6% to 2.4%), and confusional arousals by 4.2% (3.6% to 4.8%). The rate of these 3 parasomnias decreased significantly with age, but no gender difference was observed. Multivariate models identified the following independent factors as associated with confusional arousals (odds ratio [OR]): age of 15-24 years (OR = 4.1), shift work (OR = 2.1), hypnagogic hallucinations (OR = 3.3), deep sleep (OR = 1.6), daytime sleepiness (OR = 1.9), sleep talking (OR = 1.7), daily smoking (OR = 1.7), adjustment disorder (OR = 3.1), and bipolar disorder (OR = 13.0). Factors associated with night terrors were subjective sense of choking or blocked breathing at night (OR = 5.1), obstructive sleep apnea syndrome (OR = 4.1), alcohol consumption at bedtime (OR = 3.9), violent or injury-causing behaviors during sleep (OR = 3.2), hypnagogic hallucinations (OR = 2.2), and nightmares at least 1 night per month (OR = 4.0). Factors associated with sleepwalking were age of 15-24 years (OR = 5.2), subjective sense of choking or blocked breathing at night (OR = 5.1), sleep talking (OR = 5.0), and a road accident in the past year (OR = 3.9) after controlling for possible effects of sleep deprivation, life stress, and mental and sleep disorders.Arousal parasomnias, especially night terrors and confusional arousals, are often the expression of a mental disorder. Other life or medical conditions, such as shift work or excessive need of sleep for confusional arousals and stressful events for sleepwalking, may also trigger parasomnias. Prevalence rates are based on self-reported data and, consequently, are likely underestimated.

  View details for Web of Science ID 000079921300021

  View details for PubMedID 10221293

• Cardiovascular changes associated with spontaneous and evoked K-complexes NEUROSCIENCE LETTERS Monstad, P., Guilleminault, C. 1999; 263 (2-3): 211-213

  Abstract

  This study examines the relationship between blood pressure and spontaneous and sound-evoked K-complexes (KCs) during stage 2 NREM sleep, in 8 volunteers studied by intraarterial blood pressure (BP) monitoring and polysomnography. A robust oscillation of blood pressure with a period of 16-30 s (Mayer waves) was seen in all subjects. Spontaneous KCs predominantly occurred during a drop (downward slope) in blood pressure. Randomly administered sound stimuli were more likely to evoke a KC if the stimulus was given during a downward slope of BP. During the last 20 s prior to a sound-evoked KC, the mean drop in systolic BP was 0.3 mmHg, and evoked and spontaneous K-complexes were preceded by a mean drop in BP of 1.9 and 2.7 mmHg, respectively. Finally, K-complexes, either spontaneous or evoked, during the first 6 s, induced a rise in systolic BP. The results indicate that if the BP falls during stage 2 NREM sleep, there is a greater likelihood that an external stimulus will evoke a K-complex and that spontaneous K-complexes may occur more frequently as well. Spontaneous and evoked K-complexes may play a role in the control of BP during NREM sleep.

  View details for Web of Science ID 000079504800035

  View details for PubMedID 10213173

• The snoring spectrum - Acoustic assessment of snoring sound intensity in 1,139 individuals undergoing polysomnography CHEST Wilson, K., Stoohs, R. A., Mulrooney, T. F., Johnson, L. J., Guilleminault, C., Huang, Z. 1999; 115 (3): 762-770

  Abstract

  To quantify the snoring sound intensity levels generated by individuals during polysomnographic testing and to examine the relationships between acoustic, polysomnographic, and clinical variables.The prospective acquisition of acoustic and polysomnographic data with a retrospective medical chart review.A sleep laboratory at a primary care hospital.All 1,139 of the patients referred to the sleep laboratory for polysomnographic testing from 1980 to 1994.The acoustic measurement of snoring sound intensity during sleep concurrent with polysomnographic testing.Four decibel levels were derived from snoring sound intensity recordings. L1, L5, and L10 are measures of the sound pressure measurement in decibels employing the A-weighting network that yields the response of the human ear exceeded, respectively, for 1, 5, and 10% of the test period. The Leq is a measure of the A-weighted average intensity of a fluctuating acoustic signal over the total test period. L10 levels above 55 dBA were exceeded by 12.3% of the patients. The average levels of snoring sound intensity were significantly higher for men than for women. The levels of snoring sound intensity were associated significantly with the following: polysomnographic testing results, including the respiratory disturbance index (RDI), sleep latency, and the percentage of slow-wave sleep; demographic factors, including gender and body mass; and clinical factors, including snoring history, hypersomnolence, and breathing stoppage. Men with a body mass index of > 30 and an average snoring sound intensity of > 38 dBA were 4.1 times more likely to have an RDI of > 10.Snoring sound intensity levels are related to a number of demographic, clinical, and polysomnographic test results. Snoring sound intensity is closely related to apnea/hypopnea during sleep. The noise generated by snoring can disturb or disrupt a snorer's sleep, as well as the sleep of a bed partner.

  View details for Web of Science ID 000079110400032

  View details for PubMedID 10084490

• The prevalence of depressive disorders in the United Kingdom BIOLOGICAL PSYCHIATRY Ohayon, M. M., Priest, R. C., Guilleminault, C., Caulet, M. 1999; 45 (3): 300-307

  Abstract

  The prevalence of major psychiatric disorders in the general population is difficult to pinpoint owing to widely divergent estimates yielded by studies employing different criteria, methods, and instruments. Depressive disorders, which represent a sizable mental health care expense for the public purse, are no exception to the rule.The prevalence of depressive disorders was assessed in a representative sample (n = 4972) of the U.K. general population in 1994. Interviews were performed over the telephone by lay interviewers using an expert system that tailored the questionnaire to each individual based on prior responses. Diagnoses and symptoms lists were based on the DSM-IV.Five percent (95% confidence interval = 4.4-5.6%) of the sample was diagnosed by the system with a depressive disorder at the time of the interview, with the rate slightly higher for women (5.9%) than men (4.2%). Unemployed, separated, divorced, and widowed individuals were found to be at higher risk for depression. Depressive subjects were seen almost exclusively by general practitioners (only 3.4% by psychiatrists). Only 12.5% of them consulted their physician seeking mental health treatment, and 15.9% reported being hospitalized in the past 12 months.The study indicates that mental health problems in the community are seriously underdetected by general practitioners, and that these professionals are highly reluctant to refer patients with depressive disorders to the appropriate specialist.

  View details for Web of Science ID 000078518800010

  View details for PubMedID 10023506

• Validation of a cataplexy questionnaire in 983 sleep-disorders patients SLEEP Anic-Labat, S., Guilleminault, C., Kraemer, H. C., Meehan, J., Arrigoni, J., Mignot, E. 1999; 22 (1): 77-87

  Abstract

  Our goal was to validate a self-administered narcolepsy questionnaire focusing on cataplexy. Nine hundred and eight three consecutive subjects entering the Stanford Sleep Disorder Clinic completed the questionnaire. Clinic physicians reported on the presence or absence of "clear-cut" cataplexy. Responses to 51 cataplexy-related questionnaire items were compared between subjects with clear-cut cataplexy (n = 63) and all other patients (n = 920). As previously reported, a large portion of the non-narcoleptic population was found to experience muscle weakness with various intense emotions (1.8% to 18.0%) or athletic activities (26.2% to 28.8%). Factor analysis and Receiver Operating Characteristic Curve (ROC) analysis were used to determine the most predictive items for clear-cut cataplexy. Most strikingly, cataplexy was best differentiated from other types of muscle weakness when triggered by only three typical situations: "when hearing and telling a joke," "while laughing," or "when angry." Face or neck, rather than limbs, were also more specifically involved in clear-cut cataplexy. Other items, such as length of attacks, bilaterality, and alteration in consciousness, were poorly predictive. A simple decision tree was constructed to isolate high-(91.7%) and low-(0.6%) risk groups for cataplexy. This questionnaire will be used to increase diagnostic consistency across clinical centers, thus providing more homogenous subject pools for clinical and basic research studies.

  View details for Web of Science ID 000081155300010

  View details for PubMedID 9989368

• Cervical positional effects on snoring and apneas. Sleep research online : SRO Kushida, C. A., Rao, S., Guilleminault, C., Giraudo, S., Hsieh, J., Hyde, P., Dement, W. C. 1999; 2 (1): 7-10

  Abstract

  We examined the effects of cervical position on the Obstructive Sleep Apnea Syndrome (OSAS) through the use of a custom-designed cervical pillow which promoted neck extension. Twelve subjects with OSAS were recruited from a tertiary sleep disorder clinic population. Of the twelve subjects, three had mild cases of OSAS, four had moderate cases, and the remaining five had severe cases. The subjects used their usual pillows during two consecutive recorded baseline nights in our laboratory. The subjects then used the cervical pillow for five days at home, and returned for two consecutive recorded nights at our laboratory while using the cervical pillow. During the nights in our laboratory, the subjects completed questionnaires, were videotaped to record head and body position, and had their breathing parameters recorded during sleep. Subjects with mild OSAS cases had a non-significant improvement in the severity of their snoring and a significant improvement in their respiratory disturbance index with the cervical pillow, while subjects with moderate OSAS cases showed no improvement in these parameters. Subjects with severe OSAS cases showed slight improvement in some measures of their abnormal respiratory events during the experimental period.

  View details for PubMedID 11382876

• Power spectral sleep EEG findings in patients with obstructive sleep apnea and upper airway resistance syndromes 14th International Congress of EEG and Clinical Neurophysiology Guilleminault, C., Kim, Y. D., Horita, M., Tsutumi, M., Pelayo, R. ELSEVIER SCIENCE BV. 1999: 113–120

  View details for Web of Science ID 000085689700013

  View details for PubMedID 10689453

• Central sleep apnea Otolaryngologic clinics of North America Guilleminault, Robinson 1998; 31 (6): 1049-1065

  Abstract

  A central sleep apnea is the absence of respiratory effect, and, this, the absence of airflow during sleep. Central hypopnea, a related disorder, is also discussed. The sensory component of central sleep apnea; defects involving the integrative and executive neurons; non-neurologic causes of central sleep apneas, including chronic obstructive pulmonary disease and congestive heart failure; diagnosis; treatment; and other topics are reviewed.

  View details for PubMedID 9838017

• Radiofrequency volumetric tissue reduction for treatment of turbinate hypertrophy: A pilot study OTOLARYNGOLOGY-HEAD AND NECK SURGERY Li, K. K., Powell, N. B., Riley, R. W., Troell, R. J., Guilleminault, C. 1998; 119 (6): 569-573

  Abstract

  Ideal treatment for nasal obstruction caused by turbinate hypertrophy remains in question. Medical therapy is often ineffective. Surgical procedures have associated morbidity including pain, bleeding, crusting, adhesion, infection, and dryness. Radiofrequency has recently been shown to be safe and effective in volumetric tissue reduction of the tongue in the animal model and of the palate in human beings. We prospectively evaluate the safety and effectiveness of radiofrequency volumetric tissue reduction (RFVTR) for the treatment of nasal obstruction caused by inferior turbinate hypertrophy.Twenty-two consecutive patients with nasal obstruction and associated inferior turbinate hypertrophy refractory to medical therapy were evaluated for RFVTR. The study design limited the region of treatment to the anterior third of the inferior turbinate. The procedures were performed in an ambulatory facility with patients under local anesthesia. Clinical examinations, patient questionnaires, and visual analog scales were used to assess treatment outcomes.No adverse effects were encountered, including bleeding, crusting, dryness, infection, adhesion, or a worsening of obstruction. Mild edema was noted in all patients but was of short duration (24 to 48 hours). Posttreatment discomfort was well controlled with acetaminophen. Eight weeks after treatment, nasal breathing improved in 21 of 22 patients, with a 58.5% reduction in severity and a 56.5% decrease in the frequency of nasal obstruction.The results of this study demonstrate that RFVTR of the hypertrophic inferior turbinate is associated with minimal adverse effects. Furthermore, this new treatment modality achieves subjective improvement in patients with symptoms of nasal obstruction. However, because of the small sample size and short follow-up, future investigations are needed to fully evaluate the use of RFVTR in the treatment of nasal obstruction caused by turbinate hypertrophy.

  View details for Web of Science ID 000077409400003

  View details for PubMedID 9852527

• Sleep and neuromuscular disease: bilevel positive airway pressure by nasal mask as a treatment for sleep disordered breathing in patients with neuromuscular disease JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY Guilleminault, C., Philip, P., Robinson, A. 1998; 65 (2): 225-232

  Abstract

  Investigation of the therapeutic effects of bilevel positive airway pressure delivered by nasal mask in patients with neuromuscular disease.20 patients with neuromuscular disease were evaluated for symptoms of nocturnal sleep disruption. These symptoms included daytime tiredness, fatigue, sleepiness, and complaints of insomnia. The patients were studied with nocturnal polysomnograms and daytime multiple sleep latency tests (MSLT). Their immediate and long term responses to bilevel positive airway pressure were also investigated. The study took place at the Stanford University Sleep Disorders Clinic. Some of the polygraphic evaluations were performed with portable equipment in the patients' homes. The reported population comprised 20 patients, all of whom had progressive neuromuscular disease. Five of the patients were women. Four patients had muscular dystrophy, six had myotonic dystrophy, and two patients each had mitochondrial myopathy and glycogen storage disease. Two patients had post-traumatic lesions, one bulbar and the other phrenic. The remaining patients had vascular myopathy, unclassified myopathy, syringomyelia, and slow evolving spinocerebellar degeneration.19 of the 20 patients accepted some form of non-invasive ventilation. All but one of these were initially maintained on bilevel positive airway pressure spontaneous (S) mode, although one patient required a switch to the timed (T) mode within a year. The mean expiratory positive airway pressure (EPAP) used was 4.5 with a range of 4 to 5 cm H2O. The mean inspiratory positive airway pressure (IPAP) was 11.5, range 9 to 14 cm H2O. Before treatment the MSLTs were < or = 8 minutes in 11 of the patients. The overall mean score was 8.2 (SD) 1.3 minutes. After long term treatment the mean MSLT was 12.5 (SD 2) minutes and the mean ESS score was 7 (SD 3). During the mean 3.5 years of follow up, three patients needed supplemental oxygen at a flow of 0.5 to 1.0 l/min bled into their masks. Three patients with myotonic dystrophy presented continued daytime somnolence despite apparent adequate treatment of their sleep disordered breathing. This required the addition of stimulant medication to their regimen. During this time three additional subjects had to be switched to nasal mask intermittent positive pressure ventilation delivered by traditional volume cycled home ventilator (volume controlled NIPPV).Bilevel positive airway pressure delivered by nasal mask may be used successfully to treat sleep disordered breathing associated with neuromuscular disease. This device can be employed to assist nocturnal ventilation by either the spontaneous or timed mode. In the United States it is less expensive and easier to institute than volume controlled NIPPV and may be as efficacious as this mode if close surveillance and regular reevaluation of the patient's status is maintained.

  View details for Web of Science ID 000075084700018

  View details for PubMedID 9703177

• Sleep-disordered breathing in children ANNALS OF MEDICINE Guilleminault, C., Pelayo, R. 1998; 30 (4): 350-356

  Abstract

  The first series of children with obstructive sleep apnoea syndrome was reported in 1976. Later it became apparent that children may have breathing disorders during sleep without frank apnoea or 'hypopnoeas'. This pattern could be detected by measuring the oesophageal pressure. This led to the concept of sleep-disordered breathing as a spectrum that combines obstructive sleep apnoea syndrome and the upper airway resistance syndrome. Studies that do not take into account this spectrum may misclassify symptomatic patients as 'primary snorers'. The exact prevalence of sleep-disordered breathing in children is unknown but may be as high as 11%. There is a familial predisposition to sleep-disordered breathing. Nasal obstruction and mouth breathing influence facial growth, which may further lead to difficulty in breathing while asleep. Symptoms include an increase in total sleep time, nonspecific behavioural difficulties, hyperactivity, irritability, bed-wetting and morning headaches. Clinical signs include failure to thrive, increased respiratory effort with nasal flaring and suprasternal or intercostal retractions. Also, abnormal paradoxical inward motion of the chest may occur during sleep. Excessive daytime sleepiness and obesity are not always present. Untreated children may develop cardiovascular complications. The condition is treatable with continuous or bilevel positive airway pressure, and may be cured with surgery.

  View details for Web of Science ID 000076083500003

  View details for PubMedID 9783833

• ... And if the polysomnogram was faulty? PEDIATRIC PULMONOLOGY Guilleminault, C., Pelayo, R. 1998; 26 (1): 1-3

  View details for Web of Science ID 000075128900001

  View details for PubMedID 9710272

• Radiofrequency volumetric tissue reduction of the palate in subjects with sleep-disordered breathing CHEST Powell, N. B., Riley, R. W., Troell, R. J., Li, K., Blumen, M. B., Guilleminault, C. 1998; 113 (5): 1163-1174

  Abstract

  To evaluate pain, swallowing, speech, edematous response, tissue shrinkage, sleep, snoring, and safety (energy limits and adverse effects) following radiofrequency (RF) treatment to the palate in 22 subjects with sleep-disordered breathing.This investigation is a prospective nonrandomized study. Polysomnography, radiographic imaging, and infrared thermography, along with questionnaires and visual analog scales, were used to evaluate the effects of RF treatment to the palate.Treatments were delivered on an outpatient basis at Stanford University Medical Center.Twenty-two healthy patients (18 men), with a mean age of 45.3+/-9.1 years, were enrolled. All were snorers seeking treatment and met predetermined criteria: a respiratory disturbance index < or = 15, oxygen saturation > or = 85%, and a complaint of daytime sleepiness.RF was delivered to the submucosa of the palate with a custom-fabricated electrode for a mean duration of 141+/-30 s with a mean of 3.6+/-1.2 treatments per patient. Reduction of their snoring scores determined the end point of the study.Neither speech nor swallowing was adversely affected. Pain was of short duration (0 to 48 h) and was controlled with acetaminophen. There were no infections. Although there was documented edema at 24 to 48 h, there were no clinical airway compromises. Polysomnographic data showed improvement in esophageal pressure measurements of the mean nadir and the 95th percentile nadir (p=0.031, p=0.001) respectively, as well as the mean sleep efficiency index (p=0.002). Radiographic imaging showed a mean shrinkage of 5.5+/-3.7 mm (p< or =0.0001). Subjective snoring scores fell by a mean of 77% (8.3+/-1.8 to 1.9+/-1.7, p=0.0001) accompanied by improved mean Epworth sleepiness scores (8.5+/-4.4 to 5.2+/-3.3, p=0.0001).The results of this investigation allowed the formulation of safety parameters for RF in this defined population with mild sleep-disordered breathing. There was a documented tissue reduction and improvement in symptoms in all subjects. However, given the small sample size and short-term follow-up, these results should be confirmed by further investigation.

  View details for Web of Science ID 000073591500009

  View details for PubMedID 9596289

• Narcolepsy and idiopathic hypersomnolence CLINICS IN CHEST MEDICINE Choo, K. L., Guilleminault, C. 1998; 19 (1): 169-?

  Abstract

  Narcolepsy is among the leading causes of excessive daytime sleepiness. Its classic form associates daytime sleepiness with cataplexy, sleep paralysis, hypnopompic hallucinations, and nocturnal disrupted sleep. This form is associated with HLA DQ betal-0602 in about 85% to 90% of affected subjects, independently of their ethnicity. But the definition of the variants of narcolepsy remains controversial, despite the fact that, in some cases, narcolepsy may be limited to daytime sleepiness. In its classic form, it is associated with two or more sleep onset rapid eye movement periods at the Multiple Sleep Latency Test. This test, performed after nocturnal polysomnography, can be helpful in diagnosing narcolepsy, in the absence of a convincing history of partial or complete attacks of cataplexy--a pathognomonic symptom. Investigation of narcoleptic Dobermans has indicated that a muscarinic cholinergic hypersensitivity exists in the brain of affected animals and abnormalities involve also the dopaminergic system. Despite its prevalence of 0.03% to 0.05%, it is still a neurologic entity often missed. Investigations of families of narcoleptics, including monozygotic twins, indicate that this syndrome is polygenic in nature with association of environmental factors. As the peak of onset of disabling symptoms occurs between 15 and 25 years of age, it is important to improve the treatment of this lifelong, disabling illness. Stimulants medications, independently of their mode of action, are prescribed to help daytime sleepiness, and tricyclic antidepressant drugs or serotonergic reuptake blockers are used on the other symptoms. But these medications have a limited efficacy. Short naps at regular intervals during the day are a strong therapeutic adjuvent.

  View details for Web of Science ID 000072887900014

  View details for PubMedID 9554226

• Psychotropic medication consumption patterns in the UK general population JOURNAL OF CLINICAL EPIDEMIOLOGY Ohayon, M. M., Caulet, M., Priest, R. G., Guilleminault, C. 1998; 51 (3): 273-283

  Abstract

  The prevalence of psychotropic medication consumption was assessed in the UK by surveying a representative sample of 4972 non-institutionalized individuals 15 years of age or older (participation rate, 79.6%). A questionnaire was administered over the telephone with the help of the Sleep-Eval Expert System. Topics covered included: type and name of medication, indication, dosage, duration of intake, and medical specialty of prescriber. Also collected were data pertaining to sociodemographics, physical illnesses, and DSM-IV mental disorders. Overall, 3.5% [95% CI: 3-4] of the sample reported current use of psychotropic medication. Consumption was higher among women [4.6% (3.8-5.4)] than men [2.3% (1.7-2.9)], and among the elderly (> or = 65 years of age). The distribution of psychotropics was: hypnotics 1.5%, antidepressants 1.1%, and anxiolytics 0.8%. The median duration of psychotropic intake was 52 weeks. General practitioners were the most common prescribers of psychotropics (over 80% for each class of drug). Nearly half the antidepressant users were diagnosed by the system with a DSM-IV anxiety disorder, and one-fifth the anxiolytic users with a depressive disorder. A marked improvement in sleep quality was reported by half the subjects using a psychotropic for sleep-enhancing purposes. Psychotropic users were more likely than non-users to report episodes of memory loss, vertigo, or anomia. Psychotropic medication consumption is lower and patterns of psychotropic prescription differ in the UK compared with other European and North American countries. Results suggest that physicians may not be sufficiently trained to deal with the overlap between general practice and psychiatry.

  View details for Web of Science ID 000072147700012

  View details for PubMedID 9495693

• Normative data on snoring: a comparison between younger and older adults EUROPEAN RESPIRATORY JOURNAL Stoohs, R. A., Blum, H. C., Haselhorst, M., Duchna, H. W., Guilleminault, C., Dement, W. C. 1998; 11 (2): 451-457

  Abstract

  Snoring is a common sleep-related behaviour. Increased body mass index (BMI), cranio-facial anatomical features, and older age have been linked to the occurrence of snoring. While mostly middle-aged populations have been studied for the occurrence of snoring and sleep-related breathing abnormality, this study was designed to assess the subjective report of snoring and the objective measurement of snoring at the two extremes of human age. The study design called for measurement of snoring in two age groups (college students; n=155 and older subjects; mean age 64.1 yrs n=134) with a mean age difference of 45 yrs. Snoring was assessed with a validated recording device. A validated questionnaire was used to subjectively assess snoring and obtain relevant sleep-related information. Students and older subjects differed in the self-report of snoring. While 83% of students reported "never" or "rarely" snoring only 35% of older subjects fell into these categories. Measurement of snoring during sleep revealed that students spent more time during sleep with continuous snoring than older subjects. In older subjects, a reduction in continuous snoring was accompanied by an increase in apnoeic snoring. Subjective snoring frequency correlated with continuous snoring in students only. A positive family history of snoring increased the odds ratio for self-reported snoring but not for recorded snoring. It has been shown that snoring frequency can vary depending on age and that the congruency between perceived snoring frequency and recorded snoring is influenced by the age of an individual.

  View details for Web of Science ID 000072605900033

  View details for PubMedID 9551753

• Investigations into the neurologic basis of narcolepsy Roundtable Discussion on Current Issues in the Diagnosis and Management of Narcolepsy Guilleminault, C., Heinzer, R., Mignot, E., Black, J. LIPPINCOTT WILLIAMS & WILKINS. 1998: S8–S15

  Abstract

  The understanding of narcolepsy has been enhanced by neurophysiologic investigations in humans and by pharmacologic and biochemical studies using the canine model of narcolepsy. Repetitive microsleeps have a more deleterious effect on performance than several short complete naps during the day. Under normal living conditions, the nocturnal sleep of narcoleptic patients is disrupted, and the spectral analysis of central EEG leads shows less delta power density per epoch than it does in age-matched controls, who have an absence or decrease of the usual decay in delta power across the night. Cataplexy is associated with a drop in H-reflex, even during partial cataplectic attacks. Monitoring of heart rate and intra-arterial blood pressure during cataplexy in humans shows a decrease in heart rate and an increase in blood pressure with onset of cataplexy, but the change in heart rate is secondary to the change in blood pressure. Investigations of narcoleptic Doberman pinschers have implicated several neurotransmitters in the brainstem and amygdala. In vivo dialysis and in situ injections of carbachol indicate that the pontine reticular formation is not the only muscarinic cholinergic region involved, but data support the existence of a multisynaptic descending pathway involved in the muscle atonia of cataplexy. Carbachol injections into the basal forebrain induce status cataplecticus. Experimental findings suggest a hypersensitivity of the overall muscarinic cholinergic system and that this hypersensitive cholinergic system is linked to the limbic system. An increase in the postsynaptic D2 dopaminergic receptor is observed in the amygdala of narcoleptic dogs compared with controls, with impairment of dopamine release. The associated findings suggest that an abnormal cholinergic-dopaminergic interaction could underlie the pathophysiology of narcolepsy.

  View details for Web of Science ID 000072168200003

  View details for PubMedID 9484417

• HLA-DQB1*0602 homozygosity increases relative risk for narcolepsy but not disease severity in two ethnic groups TISSUE ANTIGENS Pelin, Z., Guilleminault, C., Risch, N., GRUMET, F. C., Mignot, E. 1998; 51 (1): 96-100

  Abstract

  Narcolepsy is a neurological disorder known to be tightly associated with HLA-DQA1*0102 and DQB1*0602. In this study, we have examined if homozygosity for DQB1*0602 increases disease susceptibility and/or severity. Patients diagnosed at Stanford University (n=160) or enrolled in a multicenter clinical trial (n=509) were included in this analysis. In both African-Americans and Caucasian-Americans with or without cataplexy, a significantly higher than expected number of subjects were DQB1*0602 homozygotes. Relative risks were 2-4 times higher in DQB1*0602 homozygotes vs heterozygotes across all patient groups. In contrast, symptom severity did not differ between DQB1*0602 homozygous and heterozygous subjects. These results indicate that HLA-DQB1*0602 homozygosity increases susceptibility to narcolepsy but does not appear to influence disease severity.

  View details for Web of Science ID 000071134000012

  View details for PubMedID 9459509

• Randomized trial of modafinil for the treatment of pathological somnolence in narcolepsy 121st Annual Meeting of the American-Neurological-Association Mitler, M. M., Guilleminault, C., Harsh, J. R., Hirshkowitz, M., Becker, P. M., Jamieson, A. O., Jewel, C. E., Bogan, R. K., James, D. S., Sutton, J. T., Corser, B., Mayleben, D. W., Bernard, S. H., Dinner, D. S., Emsellem, H., Knight, E., Chase, C., Erwin, C. W., Krystal, A. D., Radtke, R. A., Farrow, S., Odynski, T., PINTO, J., Steljes, D., Feldman, N. T., O'Brien, M., Fredrickson, P. A., Kaplan, J., Lin, S. C., Burger, C., Fry, J. M., Black, J., Green, P. M., Schmitigal, L., Gross, P. T., Dignan, S., Harsh, J., Hartwig, G., Haynes, J. B., Hageman, M., Porter-Shirley, K., Hertz, G., Moore, C. A., Iyer, V., Mahowald, M. M., Ullevig, C., Hayduk, R., Erman, M. K., Pascualy, R., Stolz, S., Parman, D., Richter, R. W., Gruenau, S. P., Webster, J. A., Ristanovic, R. K., Bergen, D., Kanner, A., Dyonzak, J., Rogers, A. E., Aldrich, M. S., Rosenberg, R., Richardson, T., Lee, J., Sahota, P. K., Dexter, J. D., Burger, R. C., Sangal, R. B., Sangal, J. A., Belisle, C., Schmidt, H. S., Parisot, P. A., Schmidt-Nowara, W. W., Jessup, C., Schwartz, J. R., Schwartz, E. R., Veit, C., Blakely, L., Scrima, L., Miller, B. R., Shettar, S. M., May, R. S., Wilkerson, K. E., Stafford, C., Grogan, W. A., Tearse, R., Thein, S. G., Colontonio, L., Vern, B. A., Mercer, P. J., Merritt, S. L., Walsleben, J. A., O'Malley, M. B., Rapoport, D. M., WINOKUR, A., Szuba, M. D., Civil, R. H., Dobbins, T. W., Kribbs, N. B., Laughton, W. B., Nelson, M. T., Wang, L. X. WILEY-LISS. 1998: 88–97

  View details for Web of Science ID 000071504600011

• The European Neurological Network 10th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society Penzel, T., Guilleminault, C., Kesper, K., Paiva, T., Peter, J. H., Zulley, J. IEEE. 1998: 1318–1320

  View details for Web of Science ID 000079210400361

• Narcolepsy in prepubertal children ANNALS OF NEUROLOGY Guilleminault, C., Pelayo, R. 1998; 43 (1): 135-142

  Abstract

  Narcolepsy was diagnosed in 51 children (29 boys). The age range was 2.1 to 11.8 years (mean, 7.9 +/- 3.1 years). A mean of three referrals was made before narcolepsy was considered. In 10 children, cataplexy was the presenting symptom. Thirty-eight children acknowledged sleep paralysis and 30 acknowledged hypnagogic hallucinations. All children had sleep studies; 31 exhibited rapid eye movement at sleep onset. The mean sleep latency was 1.5 minutes +/- 39 seconds on the Multiple Sleep Latency Test. All children had at least two sleep-onset rapid eye movement sleep episodes in this test. Forty-six children were HLA class II-positive for DQw6, and 45 were also positive for DRw15. Thirty (65%) families refused referrals to support and counseling groups. Teachers often refused to acknowledge a medical problem. During follow-up, all children presented at least once with depressive symptoms in reaction to their syndrome. Narcolepsy should be considered when evaluating children with behavioral and depressive symptoms.

  View details for Web of Science ID 000071504600021

  View details for PubMedID 9450782

• Nocturnal wandering and violence: Review of a sleep clinic population JOURNAL OF FORENSIC SCIENCES Guilleminault, C., Leger, D., Philip, P., Ohayon, M. M. 1998; 43 (1): 158-163

  Abstract

  Sleep consists of two complex states--NREM and REM sleep--and disturbances of the boundaries between the states of sleep and wakefulness may result in violence. We investigated our population for reports of violence associated with sleep. REM behavior disorder is rarely associated with injury to the sufferer or others. NREM sleep related nocturnal wandering associated with self-inflicted injuries has variable etiologies. In the elderly, it is associated with dementia. In young individuals, it may be associated with mesio-temporal or mesio-frontal foci and an indication of a complex partial seizure. It also may be related to abnormal alertness and is associated with excessive daytime sleepiness, micro-sleeps, and hypnagogic hallucinations in sleep disorders such as narcolepsy or sleep disordered breathing.

  View details for Web of Science ID 000071623100023

  View details for PubMedID 9456536

• How sleep and mental disorders are related to complaints of daytime sleepiness ARCHIVES OF INTERNAL MEDICINE Ohayon, M. M., Caulet, M., Philip, P., Guilleminault, C., Priest, R. G. 1997; 157 (22): 2645-2652

  Abstract

  Daytime sleepiness is widespread and has negative impacts on the public sector.To ascertain the incidence and prevalence of daytime sleepiness and associated risk factors in the general population.In 1994, a representative sample of the non-institutionalized British population aged 15 years or older was interviewed via telephone using an expert computer-assisted program designed to facilitate surveys of this type (Sleep-Eval, M. M. Ohayon, Montreal, Quebec). Subjects were classified into 3 groups based on the severity of their daytime sleepiness. We completed 4972 interviews (acceptance rate, 79.6%).Severe daytime sleepiness was reported in 5.5% (95% confidence interval, 4.9%-6.1%) of the sample, and moderate daytime sleepiness in another 15.2% (95% confidence interval, 14.2%-16.2%). Associated factors with severe daytime sleepiness included female sex, middle age, napping, insomnia symptoms, high daily caffeine consumption, breathing pauses or leg pain in sleep, depressive disorder (based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria), falling asleep while reading or watching television, and motor vehicle crashes or accidents involving use of machinery. Moderate daytime sleepiness was associated with female sex, napping, insomnia symptoms, arthritis or heart disease, and gross motor movements during sleep.It is likely that daytime sleepiness deleteriously affects work activities, social and/or marital life, and exhibits a negative socioeconomic impact. In addition, the risk of a motor vehicle crash appears to be higher in this specific population: twice as many subjects operating a motor vehicle or using machine tools reported having a crash or accident, respectively, in the previous year in the groups with severe daytime sleepiness or moderate daytime sleepiness than did the general population with no daytime sleepiness. The high prevalence rates of daytime sleepiness and multiplicity of related factors mandate further scrutiny by public health officials.

  View details for Web of Science ID A1997YJ52300015

  View details for PubMedID 9531234

• Prevalence and correlates of nocturnal desaturations in a sample of elderly people JOURNAL OF SLEEP RESEARCH Philip, P., Dealberto, M. J., Dartigues, J. F., Guilleminault, C., Bioulac, B. 1997; 6 (4): 264-271

  Abstract

  We designed an epidemiological study to estimate the prevalence and correlates of nocturnal desaturations in a sample of elderly subjects from the general population. Sleep-related respiratory disturbances were assessed by questionnaire and MESAM IV (MADAUS electronic sleep apnoea monitor) ambulatory monitoring. An oxygen desaturation index (ODI), oxygen desaturation being defined as a decrease in SaO2 of or exceeding 4%, was then computed from these data. An oxygen desaturation index > or = 10 was observed in 27.0% of the 293 subjects studied (mean age 76.6+/-5.7 y, median=75 y, min.=69, max.=99), an oxygen desaturation index > or = 30in 4.4%. Multivariate analysis identified as correlates to an oxygen desaturation index > or = 10: male gender (OR=1.80; P=0.04), a high body mass index (BMI) in men (OR=1.20 per kg m2; P=0.0009), and advanced age in women (OR=1.09 per y; P=0.02). A positive association was found between loud snoring (OR=1.75; P=0.06) and an oxygen desaturation index > or = 10. However, there was no statistically significant relationship between an oxygen desaturation index > or = 10 and either daytime somnolence (OR=1.50; P=0.19) or trouble getting to sleep (OR=0.59; P=0.09). We found no significant relationship in our sample between oxygen desaturation index and arterial hypertension or cardiac dysrhythmia. Previous studies on younger populations have reported different results. It may well be the advanced age of our sample that explains these inconsistencies. For the elderly persons we studied our results underline the relatively high prevalence of sleep-related respiratory disturbances. However, these may be of less consequence than in younger populations.

  View details for Web of Science ID 000071940500008

  View details for PubMedID 9493527

• Surgical treatment of obstructive sleep apnea. Sleep medicine reviews Guilleminault, C. 1997; 1 (2): 75-?

  View details for PubMedID 15310514

• Obstructive sleep apnea surgery: Risk management and complications OTOLARYNGOLOGY-HEAD AND NECK SURGERY Riley, R. W., Powell, N. B., Guilleminault, C., Pelayo, R., Troell, R. J., Li, K. K. 1997; 117 (6): 648-652

  Abstract

  Hypoxemia, hypertension, airway obstruction, and death have been associated with surgery for obstructive sleep apnea syndrome (OSAS). Patient analysis was undertaken to identify potential factors that could affect risk-management outcome.One hundred eighty-two consecutively treated patients with OSAS undergoing 210 procedures were evaluated. Fifty-four factors were analyzed.Group characteristics included a mean age of 48.2 years, a mean respiratory disturbance index of 42.3, and a mean low oxyhemoglobin desaturation (LSAT) of 77.5%. Surgery included a combination of uvulopalatopharyngoplasty (162 patients; 77%) and maxillofacial procedures (173 patients; 82%). Patients with a respiratory disturbance index greater than 40 and an LSAT less than 80% (117 patients; 64%) were maintained on nasal continuous positive airway pressure. Thirty-nine patients (18.6% had difficult intubations. There was a positive correlation (p > 0.001) of difficult intubations, neck circumference (> 45.6 cm) and skeletal deficiency (Sella-Nasion-Point B < 75 degrees). All tubes were removed with the patient awake in the operating room with two transient episodes of airway obstruction. One hundred forty-eight of the patients (70.5%) required postoperative intravenous antihypertensive medications. Patients with a preoperative history of hypertension had a significantly increased risk (p > 0.01) of requiring intraoperative and postoperative intravenous antihypertensive medications. The mean hospital stay was 2.2 days (SD +/- 0.9). Analgesia was achieved with intravenous morphine sulfate or meperidine HCl (intensive care unit) and oral oxycodone (non-intensive care unit). There were no significant oxyhemoglobin desaturations, irrespective of severity of OSAS or obesity (mean LSAT day 1, 94.8% (SD +/- 2.4); mean LSAT day 2, 95.5% (SD +/- 1.6)). Complications included postoperative bleeding (n = 4), infection (n = 5), seroma (n = 3), arrhythmia (n = 4), angina (n = 1), and loss of skeletal fixation (n = 1).Intraoperative airway risks can be reduced by use of fiberoptic intubation in patients with increased neck circumference and skeletal deficiency. Patients with OSAS are at a significantly increased risk for hypertension. Nasal continuous positive airway pressure eliminated the postoperative risk of hypoxemia, which allowed the use of adequate parenteral or oral analgesics.

  View details for Web of Science ID 000071083200014

  View details for PubMedID 9419093

• A predictive morphometric model for the obstructive sleep apnea syndrome ANNALS OF INTERNAL MEDICINE Kushida, C. A., Efron, B., Guilleminault, C. 1997; 127 (8): 581-?

  Abstract

  Mathematical formulas have been used to clinically predict whether patients will develop the obstructive sleep apnea syndrome (OSAS). However, these models do not take into account the disproportionate craniofacial anatomy that accompanies OSAS independently of obesity.To determine the accuracy of a morphometric model, which combines measurements of the oral cavity with body mass index and neck circumference, in predicting whether a patient has OSAS.6-month prospective study.University-based tertiary referral sleep clinic and research center.300 consecutive patients evaluated for sleep disorders for the first time.Body mass index, neck circumference, and oral cavity measurements were obtained, and a model value was calculated for each patient. Polysomnography was used to determine the number of abnormal respiratory events that occurred during sleep. Sleep apnea was defined as more than five episodes of apnea or hypopnea per hour of sleep.The morphometric model had a sensitivity of 97.6% (95% CI, 95% to 98.9%), a specificity of 100% (CI 92% to 100%), a positive predictive value of 100% (CI, 98.5% to 100%), and a negative predictive value of 88.5% (CI, 77% to 95%). No significant discrepancies were revealed in tests of intermeasurer and test-retest reliability.The morphometric model provides a rapid, accurate, and reproducible method for predicting whether patients in an ambulatory setting have OSAS. The model may be clinically useful as a screening tool for OSAS rather than as a replacement for polysomnography.

  View details for Web of Science ID A1997YB41900001

  View details for PubMedID 9341055

• DSM-IV and ICSD-90 insomnia symptoms and sleep dissatisfaction BRITISH JOURNAL OF PSYCHIATRY Ohayon, M. M., Caulet, M., Priest, R. G., Guilleminault, C. 1997; 171: 382-388

  Abstract

  The complex nature of insomnia and its relationship with organic and mental disorders render diagnosis problematic for epidemiologists and physicians.A representative UK sample (non-institutionalised, > 14 years old) was interviewed by telephone (n = 4972; 79.6% participation rate) with the Sleep-EVAL system. Subjects fell into three groups according to presence of insomnia symptom(s) and/or sleep dissatisfaction.Insomnia symptoms occurred in 36.2% of subjects. Most of these (75.9%), however, reported no sleep dissatisfaction. In comparison, those also with sleep dissatisfaction had higher prevalence of sleep and mental disorders and longer duration of insomnia symptoms, and were more likely to take sleep-promoting medication, dread bedtime, and complain of light sleep, poor night-time sleep and daytime sleepiness.Insomnia sufferers differ as to whether they are satisfied or dissatisfied with sleep. Although insomnia symptoms are common in the general population, sleep disturbances among sleep-dissatisfied individuals are more severe. Sleep dissatisfaction seems a better indicator of sleep pathology than insomnia symptoms.

  View details for Web of Science ID A1997YA83000018

  View details for PubMedID 9373431

• Diaphragm pacing for respiratory insufficiency JOURNAL OF CLINICAL NEUROPHYSIOLOGY Chervin, R. D., Guilleminault, C. 1997; 14 (5): 369-377

  Abstract

  Diaphragm pacing (DP) by electrical stimulation of the phrenic nerve offers important advantages to a highly select group of patients with respiratory paralysis. The patient wears an external radiofrequency (RF) transmitter over an implanted receiver, and a stimulating current is induced without the need for any transcutaneous wires. We review the conditions and requirements of patients who may benefit most from DP. We outline the preoperative evaluation and procedures for surgical implantation. We discuss the risk of diaphragmatic fatigue posed by initiation of DP and the use of gradual conditioning to limit this problem. Other problems encountered by patients in the course of DP can be minimized by well-instructed home caregivers and by systematic medical follow-up. Although a few patients derive considerable benefit from DP, many patients with respiratory paralysis are better treated by less invasive means such as nasal bilevel positive airway pressure or intermittent positive pressure ventilation, which we also review.

  View details for Web of Science ID 000073045400003

  View details for PubMedID 9415384

• Chronic headaches and sleep disorders ARCHIVES OF INTERNAL MEDICINE Paiva, T., Farinha, A., MARTINS, A., Batista, A., Guilleminault, C. 1997; 157 (15): 1701-1705

  Abstract

  Headaches and sleep problems are common complaints in the daily practice of the general practitioner. Since the relationship between headaches and sleep complaints is complex, clear models of interaction are needed for adequate diagnosis and treatment.All subjects, successively seen in a headache clinic during a defined period, were subdivided based on the time of onset of cephalalgia. Subjects who reported onset of headache on a long-term basis, during the nocturnal or early morning (before final awakening) period, were systematically studied by a headache clinic and a sleep disorders center. This subgroup represented 17% of the total headache group.Although the results of the headache clinic study did not differentiate this subgroup from the other patients, the sleep disorders center's interviews and questionnaires demonstrated a significant impact of the sleep disorders on headache and daytime function. Nocturnal monitoring during sleep identified specific sleep disorders in 55% of the subjects with onset of headache during the nocturnal sleep period. Follow-up after treatment of the sleep disorder showed that all subjects with an identifiable sleep disorder reported either an improvement or absence of their headache. The subjects identified with periodic limb movement syndrome were mostly those who reported only an improvement in their sleep and still needed treatment for their headaches. The question of the interaction and association of sleep-related headache and periodic limb movement syndrome is unresolved.Headaches occurring during the night or early morning are often related to a sleep disturbance.

  View details for Web of Science ID A1997XP05800012

  View details for PubMedID 9250231

• HLA DR15 (DR2) and DQB1*0602 typing studies in 188 narcoleptic patients with cataplexy NEUROLOGY Rogers, A. E., Meehan, J., Guilleminault, C., GRUMET, F. C., Mignot, E. 1997; 48 (6): 1550-1556

  Abstract

  Narcolepsy is considered a homogeneous clinical entity when excessive daytime sleepiness and cataplexy are present. Cataplexy is a polymorphic symptom that can be very mild and is thus subjectively defined. The Multiple Sleep Latency Test (MSLT) is widely used as a diagnostic test for narcolepsy. A short mean sleep latency and multiple sleep onset REM periods (SOREMPs) are typically observed in narcoleptic patients. The discovery of a tight association of narcolepsy with HLA class II antigens offers a unique opportunity to explore the respective value of the MSLT or of the presence of clear-cut cataplexy in defining an etiologically homogeneous group of narcoleptic patients. In this study, we carried out HLA typing for DR15(DR2) and DQB1*0602 in 188 narcoleptic patients with cataplexy in three ethnic groups (24 Asians, 61 Blacks, and 103 Caucasians). These results confirm the importance of DQB1*0602 typing rather than DR15 (DR2) typing in Black narcoleptic patients and demonstrate that the presence of clear-cut cataplexy is a better predictor for DQB1*0602 positivity than the presence of abnormal MSLT results.

  View details for Web of Science ID A1997XE09100015

  View details for PubMedID 9191765

• Objective measurement of sleepiness in summer vacation long-distance drivers ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY Philip, P., Ghorayeb, I., Leger, D., Menny, J. C., Bioulac, B., Dabadie, P., Guilleminault, C. 1997; 102 (5): 383-389

  Abstract

  The study investigated whether sleepiness at the wheel is a problem in non-commercial drivers going on summer vacation. All drivers, who stopped at a rest area on a large European freeway while one of the interviewers was available, were systematically approached and asked to respond to a questionnaire. All subjects who had driven at least 400 km (240 miles), whose age was between 20 and 46 years of age, and who agreed to participate were asked to undergo a longer investigation that included a short sleep/wake diary describing overall sleep habits during the year, a sleep/wake log covering the days just prior to departure, an analog visual scale indicating sleepiness at time of interview, and a polygraphically monitored two nap sleep test (TNST). A control group was recruited that consisted of subjects of the same age range, normal sleep habits, and normal nocturnal sleep time before administration of the TNST. One hundred and four drivers (2 women) participated between 08:00 and 20:00 h. The total group was subdivided into 6 subgroups based upon the time of day of their investigation (08:00-10:00 h, 10:01-12:00 h, etc.). The control group included 50 men with 50-55% of control subjects, relative to the total number of index-cases, in each subgroup. Eighty-eight percent (n = 92) of studied drivers had experienced acute sleep deprivation within one day prior to departure due to the planned long driving. The TNST demonstrated that, overall, drivers had a significantly shorter sleep latency in nap 1 and nap 2 than controls, had a significantly longer sleep duration in nap 1 and nap 2, and there was a significant correlation between the sleep debt prior to departure and the sleep stage reached during the TNST. It is concluded that the TNST is a test which allows the objective study of sleepiness in drivers without the burden of the multiple sleep latency test. Many drivers are excessively sleepy when making long summer vacation journeys.

  View details for Web of Science ID A1997XF44600001

  View details for PubMedID 9191581

• Radiofrequency volumetric reduction of the tongue - A porcine pilot study for the treatment of obstructive sleep apnea syndrome CHEST Powell, N. B., Riley, R. W., Troell, R. J., Blumen, M. B., Guilleminault, C. 1997; 111 (5): 1348-1355

  Abstract

  To investigate, in an animal model, the feasibility of radiofrequency (RF) volumetric tongue reduction for the future purpose of determining its clinical applications in obstructive sleep apnea syndrome (OSAS).The study was performed in three stages, one in vitro bovine stage and two in vivo porcine stages. The last stage was a prospective investigation with histologic and volumetric analyses to establish outcomes.Laboratory and operating room of veterinary research center.A homogeneous population of porcine animal models, including seven in stage 2 and 12 in stage 3.RF energy was delivered by a custom-fabricated needle electrode and RF generator to the tongue tissue of both the in vitro and in vivo models.Microultransonic crystals were used to measure three-dimensional changes (volumetric reduction). Lesion size correlated well with increasing RF energy delivery (Sperman correlation coefficient of 0.986; p = 0.0003). Histologic assessments done serially over time (1 h through 3 weeks) showed a well-circumscribed lesion with a normal healing progression and no peripheral damage to nerves. Volumetric analysis documented a very mild initial edematous response that promptly tapered at 24 h. At 10 days after RF, a 26.3% volume reduction was documented at the treatment site (circumscribed by the microultrasonic crystals).RF, in a porcine animal model, can safely reduce tongue volume in a precise and controlled manner. Further studies will validate the use of RF in the treatment of OSAS.

  View details for Web of Science ID A1997WY49900038

  View details for PubMedID 9149593

• Extensive HLA class II studies in 58 non-DRB1*15 (DR2) narcoleptic patients with cataplexy TISSUE ANTIGENS Mignot, E., Kimura, A., Lattermann, A., Lin, X., Yasunaga, S., MUELLERECKHARDT, G., Rattazzi, C., Lin, L., Guilleminault, C., Dement, W. C., Underhill, P. 1997; 49 (4): 329-341

  Abstract

  Narcolepsy is a sleep disorder that has been shown to be tightly associated with HLA DR15 (DR2). In this study, 58 non-DR15 patients with narcolepsy-cataplexy were typed at the HLA DRB1, DQA1 and DQB1 loci. Subjects included both sporadic cases and narcoleptic probands from multiplex families. Additional markers studied in the class II region were the promoters of the DQA1 and DQB1 genes, two CA repeat polymorphisms (DQCAR and DQCARII) located between the DQA1 and DQB1 genes, three CA repeat markers (G51152, T16CAR and G411624R) located between DQB1 and DQB3 and polymorphisms at the DQB2 locus. Twenty-one (36%) of these 58 non-DR15 narcoleptic patients were DQA1*0102 and DQB1*0602, a DQ1 subtype normally associated with DRB1*15 in DR2-positive narcoleptic subjects. Additional microsatellite and DQA1 promoter diversity was found in some of these non-DR15 but DQB1*0602-positive haplotypes but the known allele specific codons of DQA1*0102 and DQB1*0602 were maintained in all 21 cases. The 37 non-DQA1*0102/DQB1*0602 subjects did not share any particular HLA DR or DQ alleles. We conclude that HLA DQA1*0102 and DQB1*0602 are the most likely primary candidate susceptibility genes for narcolepsy in the HLA class II region.

  View details for Web of Science ID A1997WV41100002

  View details for PubMedID 9151385

• Passive constriction of the upper airway during central apneas: Fiberoptic and EMG investigations RESPIRATION PHYSIOLOGY Guilleminault, C., Hill, M. H., SIMMONS, F. B., Powell, N., Riley, R., Stoohs, R. 1997; 108 (1): 11-22

  Abstract

  We studied five adult male patients with central sleep apnea syndrome (> 75% of the monitored events being central) during sleep using a fiberoptic scope and EMG monitoring of the superior and middle constrictors of the pharynx and the genioglossus and geniohyoid muscles. The fiberoptic investigation revealed a spontaneous decrease in the size of the airway during central apneas, without negative intrathoracic pressure or activation of the superior and middle pharyngeal constrictor muscles. We found a mean maximum decrease of 71 +/- 7% in the cross-sectional area of the airway and an absence of superior-middle pharyngeal constrictor EMG discharge. We did not observe any complete collapses of the airway.

  View details for Web of Science ID A1997XA56700002

  View details for PubMedID 9178373

• Snoring and breathing pauses during sleep: Telephone interview survey of a United Kingdom population sample BRITISH MEDICAL JOURNAL Ohayon, M. M., Guilleminault, C., Priest, R. G., Caulet, M. 1997; 314 (7084): 860-863

  Abstract

  To determine the prevalence of snoring, breathing pauses during sleep, and obstructive sleep apnoea syndrome and determine the relation between these events and sociodemographic variables, other health problems, driving accidents, and consumption of healthcare resources.Telephone interview survey directed by a previously validated computerised system (Sleep-Eval).United Kingdom.2894 women and 2078 men aged 15-100 years who formed a representative sample of the non-institutionalised population.Interview responses.Forty per cent of the population reported snoring regularly and 3.8% reported breathing pauses during sleep. Regular snoring was significantly associated with male sex, age 25 or more, obesity, daytime sleepiness or naps, night time awakenings, consuming large amounts of caffeine, and smoking. Breathing pauses during sleep were significantly associated with obstructive airways or thyroid disease, male sex, age 35-44 years, consumption of anxiety reducing drugs, complaints of non-restorative sleep, and consultation with a doctor in the past year. The two breathing symptoms were also significantly associated with drowsiness while driving. Based on minimal criteria of the International classification of Sleep Disorders (1990), 1.9% of the sample had obstructive sleep apnoea syndrome. In the 35-64 year age group 1.5% of women (95% confidence interval 0.8% to 2.2%) and 3.5% of men (2.4% to 4.6%) had obstructive sleep apnoea syndrome.Disordered breathing during sleep is widely underdiagnosed in the United Kingdom. The condition is linked to increased use of medical resources and a greater risk of daytime sleepiness, which augments the risk of accidents. Doctors should ask patients and bed partners regularly about snoring and breathing pauses during sleep.

  View details for Web of Science ID A1997WQ02800023

  View details for PubMedID 9093095

• Nasal obstruction and obstructive sleep apnea: A review ALLERGY AND ASTHMA PROCEEDINGS Kushida, C. A., Guilleminault, C., Clerk, A. A., Dement, W. C. 1997; 18 (2): 69-71

  Abstract

  Several groups of investigators have assessed the impact of nasal obstruction on the obstructive sleep apnea syndrome. These studies evaluated patients with either naturally occurring partial nasal obstruction (e.g., allergic rhinitis, septal deviation) or experimentally induced nasal occlusion. The results of these studies are summarized and discussed in this article.

  View details for Web of Science ID A1997WW54000003

  View details for PubMedID 9134062

• Comparison of the results of the Epworth Sleepiness Scale and the multiple Sleep Latency Test JOURNAL OF PSYCHOSOMATIC RESEARCH Chervin, R. D., Aldrich, M. S., Pickett, R., Guilleminault, C. 1997; 42 (2): 145-155

  Abstract

  The Epworth Sleepiness Scale (ESS), which asks patients to estimate the likelihood that they would doze off or fall asleep in sedentary situations, has been proposed to be a quick, inexpensive way to assess sleepiness. We analyzed relations among ESS scores, mean sleep latencies on the Multiple Sleep Latency Test (MSLT), and subjective assessments of severity of sleepiness in 60 patients (34 women) with suspected excessive daytime sleepiness. Mean scores were 14.2 +/- 5.9 on the ESS and 8.3 +/- 5.2 minutes on the MSLT. ESS scores correlated negatively, but not strongly, with MSLT scores (rho = -0.37, p = 0.0042) and ESS scores of 14 and above predicted a low mean sleep latency on the MSLT. The ESS score correlated with the degree to which patients complained of sleepiness and may be useful as an otherwise elusive link between patients' complaints and their objective findings on MSLT.

  View details for Web of Science ID A1997WK44200004

  View details for PubMedID 9076642

• How a general population perceives its sleep and how this relates to the complaint of insomnia SLEEP Ohayon, M. M., Caulet, M., Guilleminault, C. 1997; 20 (9): 715-723

  Abstract

  The traditional indicators of insomnia (i.e. difficulty initiating sleep, difficulty maintaining sleep, nonrestorative sleep, early morning awakening) were assessed in a representative sample of 1,722 French-speaking Montrealers (Canada) aged 15 to 100 years. These subjects were interviewed over the telephone (81.3% of contacted sample) by means of the Sleep-Eval software. Subjects were classified as either satisfied or dissatisfied with quality of sleep (SQS or DQS), with or without insomnia indicators (+I or -I). Sociodemographics, sleep-wake schedules, evening activities, medication intake, recent medical consultations, and social life were also investigated. DQS subjects composed 17.8% of the population (DQS + I: 11.2%; DQS - I: 6.5%), and 21.7% of subjects were classified as either DQS + I or SQS + I. Overall, 3.8% of subjects reported using a sleep-enhancing medication. Nonrestorative sleep did not significantly distinguish SQS and DQS subjects. The complaint of nonrestorative sleep is not a useful indicator of insomnia, despite its inclusion in all medical classifications. DQS - I and SQS + I subjects defy traditional classifications. A better understanding of sleep complaints and more accurate classifications will help physicians identify patients with insomnia and meet their needs more appropriately.

  View details for Web of Science ID A1997YH47100005

  View details for PubMedID 9406323

• HLA DQB1*0602 is associated with cataplexy in 509 narcoleptic patients SLEEP Mignot, E., Hayduk, R., Black, J., GRUMET, F. C., Guilleminault, C. 1997; 20 (11): 1012-1020

  Abstract

  Narcolepsy is a sleep disorder associated with HLA DR15 (DR2) and DQB1*0602. We HLA typed 509 patients enrolled in a clinical trial for the drug modafinil and analyzed the results in relation to cataplexy, a symptom of narcolepsy characterized by muscle weakness triggered by emotions. The patients were either subjects with cataplexy who had a mean sleep latency (SL) of less than 8 minutes and two or more sleep onset rapid eye movement (REM) periods (SOREMPs) during a multiple sleep latency test, or narcoleptic patients without cataplexy but with a mean SL shorter than 5 minutes and two or more SOREMPs. The respective values of DRB1*15 (DR2) and DQB1*0602 as markers for narcolepsy were first compared in different ethnic groups and in patients with and without cataplexy. DQB1*0602 was found to be a more sensitive marker for narcolepsy than DRB1*15 across all ethnic groups. DQB1*0602 frequency was strikingly higher in patients with cataplexy versus patients without cataplexy (76.1% in 421 patients versus 40.9% in 88 patients). Positivity was highest in patients with severe cataplexy (94.8%) and progressively decreased to 54.2% in patients with the mildest cataplexy. A voluntary 50-item questionnaire focusing on cataplexy was also analyzed in 212 of the 509 HLA-typed patients. Subjects with definite cataplexy as observed by an experienced clinician were more frequently HLA DQB1*0602-positive than those with doubtful cataplexy, and the manifestations of cataplexy were clinically more typical in DQB1*0602-positive patients. These results show that the HLA association is as tight as previously reported (85-95%) when cataplexy is clinically typical or severe. We also found that patients with mild, atypical, or no cataplexy have a significantly increased DQB1*0602 frequency (40-60%) in comparison with ethnically matched controls (24%). These results could be explained by increased disease heterogeneity in the noncataplexy group or by a direct effect of the HLA DQB1*0602 genotype on the clinical expression of narcolepsy.

  View details for Web of Science ID 000071355600011

  View details for PubMedID 9456467

• Sleep-disordered breathing and hypertension: Past lessons, future directions SLEEP Guilleminault, C., Robinson, A. 1997; 20 (9): 806-811

  Abstract

  That obstructive sleep apnea syndrome is an independent risk factor for the development of hypertension was established in the 1970s, and recent works on large samples have confirmed this fact. Investigations of the mechanisms that may lead to the development of hypertension with sleep-disordered breathing will allow not only confirmation of the relationship but also creation of better treatment. There is a multigenic basis of blood pressure regulation, and genetic factors play a role in the development of sleep-disordered breathing. Genes that may have little role in the physiologic variation of blood pressure may be more important in the manifestation of pathology. And one hypothesis is that genes involved in the development of a morphotype may also have a role in the development of hypertension. Furthermore, sleep-disordered breathing may be associated with abnormal sympathetic discharge during sleep, as shown by microneurography. This mechanism may explain how a sleep disorder leads to hypertension, but impairment of vascular endothelial controls may also be involved. Investigation of vascular endothelial vasodilation as demonstrated by forearm plethysmography or the dorsal hand vein technique indicates that impairment of endothelium-dependent vasodilation during wake is associated with sleep-disordered breathing. This endothelium-dependent vasodilation appears to be more frequently impaired than the endothelium-independent vasodilation, and the former impairment can be reversed by nasal continuous positive airway pressure. These findings are supportive fo the role of sleep-disordered breathing in the development of hypertension in man.

  View details for Web of Science ID A1997YH47100015

  View details for PubMedID 9406332

• Circadian rhythms and enhanced athletic performance in the National Football League SLEEP Smith, R. S., Guilleminault, C., Efron, B. 1997; 20 (5): 362-365

  Abstract

  Circadian rhythms produce daily changes in critical elements of athletic performance. We explored the significance of performing at different circadian times in the National Football League (NFL) over the last 25 seasons. West Coast (WC) NFL teams should have a circadian advantage over East Coast (EC) teams during Monday Night Football (MNF) games because WC teams are essentially playing closer to the proposed peak athletic performance time of day. Retrospective data analysis was applied to all games involving WC versus EC teams playing on MNF with start times of 9:00 p.m. Eastern Standard Time (EST) from the 1970-1994 seasons. Logistic regression analysis of win-loss records relative to point spreads and home-field advantage was examined. West Coast teams win more often (p < 0.01) and by more points per game than EC teams. West Coast teams are performing significantly (p < 0.01) better than is predicted by the Las Vegas odds (the point spread). This apparent advantage enhances home-field advantage for WC teams and essentially eliminates the beneficial effects of home-field advantage for EC teams during MNF games. These results support the presence of an enhancement of athletic performance at certain circadian times of the day.

  View details for Web of Science ID A1997XN93300007

  View details for PubMedID 9381059

• Why are there two reports on the methodologies of epidemiologic studies in sleep disorders? SLEEP Guilleminault, C. 1997; 20 (12): 1075-1076

  View details for Web of Science ID 000071931700001

  View details for PubMedID 9493914

• Rapid shift in peak melatonin secretion associated with improved performance in short shift work schedule SLEEP Quera-Salva, M. A., Guilleminault, C., Claustrat, B., Defrance, R., Gajdos, P., McCann, C. C., De Lattre, J. 1997; 20 (12): 1145-1150

  Abstract

  We studied the performance and adaptability of 40 nurses (median age 35 years), 20 on permanent day shift and 20 on permanent night shift with fast rotation of work and days off, matched for age, gender, and socio-familial responsibilities. For 15 days prior to the study, subjects maintained sleep logs and trained for performance tests. Questionnaires were administered to evaluate adaptability to shift work. During the experimental phase, sleep/wake patterns were monitored using sleep logs and activity/inactivity with wrist actigraphy. Performance levels were measured with the four choice reaction time and memory test for seven letters, eight times/day during the wake period, days on and off. On the last day of work and first day off, 6-sulfatoxy-melatonin levels were assayed from urine samples collected every 2 hours. Estimated total sleep time during the 15-day experimental period was not significantly different in the dayshift and nightshift nurses. Night nurses shifted regularly to daytime activities on days off and, as a group, were significantly sleep deprived on work days with napping on the job in 9 of the 20 night shift nurses (mean of 114+/-45 minutes per shift) and a significant performance decrement during the work period. Further analysis revealed two subgroups of night nurses: The majority (14 nurses) had a mean peak of 6-sulfatoxy-melatonin at 0718 hours on days off and no peak during night work while the other 6 night shift nurses presented a fast melatonin shift with two clear peaks on both work and days off. Comparison of performance scores revealed that all nurses performed similarly on days off. Daytime nurses and fast-shifting night nurses had similar scores on work days, while nonshifting night nurses had significantly lower scores at work. Despite similar gender, age, social conditions, and light exposure levels, a minority of the nurses studied possessed the physiological ability to adapt to a fast-shifting sleep-wake schedule of more than 8 hours and were able to perform appropriately in both conditions. This shift was associated with a change in the acrophase of 6-sulfatoxy-melatonin.

  View details for Web of Science ID 000071931700011

  View details for PubMedID 9493924

• Prevalence of nightmares and their relationship to psychopathology and daytime functioning in insomnia subjects SLEEP Ohayon, M. M., Morselli, P. L., Guilleminault, C. 1997; 20 (5): 340-348

  Abstract

  A representative sample of 5,622 subjects between 15 and 96 years of age from the noninstitutionalized general population of France were interviewed by telephone concerning their sleeping habits and sleep disorders. The interviews were conducted using the Sleep-Eval knowledge-based system, a nonmonotonic, level 2 expert system with a causal reasoning mode. Questions investigated nightmares, based on the Diagnostic and Statistical Manual, fourth edition (DSM-IV), definition, psychopathological traits, and included 12 other groups of information, including sociodemographics, sleep-wake schedule, daytime functioning, psychiatric and medical history, and drug intake. The data from 1,049 subjects suffering from insomnia were considered for this analysis. Bivariate analyses, logistic regression analysis using the method of indicator contrasts for the investigation of independent variables, and calculation of significant odds ratios were performed. Nightmares were reported in 18.3% of the surveyed insomniac population and were two times higher in women than in men. The following factors were found to be significantly associated with nightmares 1) sleep with many awakenings, 2) abnormally long sleep onset, 3) daytime memory impairment following poor nocturnal sleep, 4) daytime anxiety following poor nocturnal sleep, and 5) being a woman. There was a strong association between the report of nightmares in women and the presence of either a depressive disorder, anxiety disorder, or both disorders together. When the effects of major psychiatric disorders were controlled for, nightmares were significantly associated with being a woman, feeling depressed after a poor night's sleep, and complaining of a long sleep latency. Nightmares can lead to a negative conditioning toward sleep and to chronic sleep complaints. Considering the frequency of nightmares in an adult insomniac population and the significant relationship between nightmares and certain subgroups, nightmares should receive more attention in patients, especially women complaining of disrupted sleep, as high rates of psychiatric disorders were found in this specific group.

  View details for Web of Science ID A1997XN93300003

  View details for PubMedID 9381055

• An international study on sleep disorders in the general population: Methodological aspects of the use of the Sleep-EVAL system SLEEP Ohayon, M. M., Guilleminault, C., Paiva, T., Priest, R. G., Rapoport, D. M., Sagales, T., Smirne, S., Zulley, J. 1997; 20 (12): 1086-1092

  Abstract

  The comparability among epidemiological surveys of sleep disorders has been encumbered because of the array of methodologies used from study to study. The present international initiative addresses this limitation. Many such studies using the exact same methodology are being completed in six European countries (France, the United Kingdom, Germany, Italy, Portugal, and Spain), two Canadian cities (metropolitan areas of Montreal and Toronto), New York State, and the city of San Francisco. These surveys have been undertaken with the aim of documenting the prevalence of sleep disorders in the general population according to criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) and the International Classification of Sleep Disorders (ICSD-90). Data are gathered over the telephone by lay interviewers using the Sleep-EVAL expert system. This paper describes the methodology involved in the realization of these studies. Sample design and selection procedures are discussed.

  View details for Web of Science ID 000071931700003

  View details for PubMedID 9493916

• Survey of habitual snoring in centenarians JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Shiomi, T., Guilleminault, C., Kayukawa, Y., Wakida, Y., Okamoto, Y., Kobayashi, T. 1997; 45 (1): 84-86

  Abstract

  To ascertain whether centenarians in the surveyed group would be nonhabitual snorers.A cross-sectional survey of centenarians residing in the Aichi Prefecture of Japan.A total of 103 centenarians (21 men and 82 women).Questionnaire on sleep habits, breathing, and snoring.Nineteen centenarians (18.4%; 5 men and 14 women) were habitual snorers and two (1.9%) were suspected of having sleep apnea syndrome because of the presence of heavy snoring and nocturnal respiratory arrest.Most centenarian subjects were nonsnorers and without breathing pauses during sleep; their snoring rates were no different from those of younger aged older adults in the same population.

  View details for Web of Science ID A1997WB73300015

  View details for PubMedID 8994494

• Should everyone be monitored for upper-airway resistance and how? Proceedings of the 4th International Symposium on Sleep and Respiration Guilleminault, C., Kushida, C., Stoohs, R., Ohayon, M., Wilson, K., Clerk, A. AMER ACAD SLEEP MEDICINE. 1996: S260–S262

  Abstract

  Preliminary data indicate that the use of a morphometric model, an expert system with standardized questions, and an evaluation of snoring can be effective tools for diagnosing upper-airway sleep-disordered breathing (UASDB) in many cases. This eliminates the need for many sleep recordings.

  View details for Web of Science ID A1996WP54300033

  View details for PubMedID 9085526

• Recognition of sleep-disordered breathing in children PEDIATRICS Guilleminault, C., Pelayo, R., Leger, D., Clerk, A., Bocian, R. C. 1996; 98 (5): 871-882

  Abstract

  To determine whether upper airway resistance syndrome (UARS) can be recognized and distinguished from obstructive sleep apnea syndrome (OSAS) in prepubertal children based on clinical evaluations, and, in a subgroup of the population, to compare the efficacy of esophageal pressure (Pes) monitoring to that of transcutaneous carbon dioxide pressure (tcPCO2) and expired carbon dioxide (CO2) measurements in identifying UARS in children.A retrospective study was performed on children, 12 years and younger, seen at our clinic since 1985. Children with diagnoses of sleep-disordered breathing were drawn from our database and sorted by age and initial symptoms. Clinical findings, based on interviews and questionnaires, an orocraniofacial scale, and nocturnal polygraphic recordings were tabulated and compared. If the results of the first polygraphic recording were inconclusive, a second night's recording was performed with the addition of Pes monitoring. In addition, simultaneous measurements of tcPCO2 and endtidal CO2 with sampling through a catheter were performed on this second night in 76 children. These 76 recordings were used as our gold standard, because they were the most comprehensive. For this group, 1848 apneic events and 7040 abnormal respiratory events were identified based on airflow, thoracoabdominal effort, and Pes recordings. We then analyzed the simultaneously measured tcPCO2 and expired CO2 levels to ascertain their ability to identify these same events.The first night of polygraphic recording was inconclusive enough to warrant a second recording in 316 of 411 children. Children were identified as having either UARS (n = 259), OSAS (n = 83), or other sleep disorders (n = 69). Children with small triangular chins, retroposition of the mandible, steep mandibular plane, high hard palate, long oval-shaped face, or long soft palate were highly likely to have sleep-disordered breathing of some type. If large tonsils were associated with these features, OSAS was much more frequently noted than UARS. In the 76 gold standard children, Pes, tcPCO2, and expired CO2 measurements were in agreement for 1512 of the 1848 apneas and hypopneas that were analyzed. Of the 7040 upper airway resistance events, only 2314 events were consonant in all three measures. tcPCO2 identified only 33% of the increased respiratory events identified by Pes; expired CO2 identified only 53% of the same events.UARS is a subtle form of sleep-disordered breathing that leads to significant clinical symptoms and day and nighttime disturbances. When clinical symptoms suggest abnormal breathing during sleep but obstructive sleep apneas are not found, physicians may, mistakenly, assume an absence of breathing-related sleep problems. Symptoms and orocraniofacial information were not useful in distinguishing UARS from OSAS but were useful in distinguishing sleep-disordered breathing (UARS and OSAS) from other sleep disorders. The analysis of esophageal pressure patterns during sleep was the most revealing of the three techniques used for recognizing abnormal breathing patterns during sleep.

  View details for Web of Science ID A1996VR46600003

  View details for PubMedID 8909480

• Sleep and neuromuscular disease: Frequency of sleep-disordered breathing in a neuromuscular disease clinic population NEUROLOGY LABANOWSKI, M., SCHMIDTNOWARA, W., Guilleminault, C. 1996; 47 (5): 1173-1180

  Abstract

  We investigated 60 adult and pediatric patients (33 male, 27 female) with various neuromuscular disorders for sleep-disordered breathing in a clinic population at a local altitude of 1,500 m. Measurements included a questionnaire concerning symptoms of sleep and daytime function, a disability index, and pulmonary function tests. We used an EdenTrace monitor for 1 night to evaluate breathing during sleep and calculated mean and minimum oxygen saturation (SpO2), total apneas, hypopneas, and respiratory disturbance index (RDI). We had validated the EdenTrace II monitor prior to the study. The majority of the patients had symptoms of daytime dysfunction. The frequency of sleep-disordered breathing in this population was much higher (42% with RDI > 15) than frequencies indicated in recent population-based surveys. Spirometry revealed no positional effect in this population. Statistical analysis comparing RDI with disability index, pulmonary function tests, age, sex, body mass index, and Epworth Sleepiness Scales identified no strong correlates that could be used as predictors of sleep-disordered breathing in this population. Sleep studies using ambulatory equipment such as the EdenTrace II are an easy and effective means of identifying sleep-disordered breathing in patients with neuromuscular disorders and, given the high frequency of sleep-disordered breathing in our sample, should be performed on most patients with neuromuscular disorders if sleep-disordered breathing is to be identified early.

  View details for Web of Science ID A1996VR42500010

  View details for PubMedID 8909425

• Sleep-disordered breathing and systemic hypertension in the older male JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Stoohs, R. A., Gingold, J., Cohrs, S., Harter, R., Finlayson, E., Guilleminault, C. 1996; 44 (11): 1295-1300

  Abstract

  To investigate the relationship between sleep-disordered breathing (SDB) and essential hypertension in a population of older male hypertensives.One-hundred forty consecutive older hypertensive males.Monitoring of sleep-related breathing abnormality with a portable sleep apnea monitor (level III device). Assessment of complaints related to sleep quality using a validated questionnaire. Systemic arterial blood pressure according to WHO standards and biochemical analyses. SDB was defined as more than 10 abnormal respiratory events per hour of sleep.Prospective investigation on a retrospective cohort.Veterans Administrations hypertension clinic.SDB was diagnosed in 80% of this older, hypertensive, male population. Thirty-four percent of all study subjects presented with severe SDB, with more than 30 abnormal respiratory events per hour of sleep. Subjects with SDB were significantly heavier (BMI = 30.0 +/- 5.2 kg/m2) than subjects without SDB (BMI = 26.8 +/- 5.1 kg/m2, P = .004). Furthermore, subjects with SDB slept significantly longer (by a mean of 46 minutes/night, P = .027) and complained significantly more often of daytime sleepiness than subjects without SDB (P = .018). Fifty percent of all 140 subjects snored more than 10% of the total sleep time, and 26% snored for more than one-third of the night. No significant differences in blood pressure values were observed in subjects with compared with subjects without sleep-disordered breathing. However, a considerable number of subjects presenting with hypertensive blood pressure values despite treatment could be identified. Subjects presenting with hypertensive blood pressure values had a significantly higher severity index of SDB than subjects with normotensive blood pressure values (P = .047).This investigation supports data showing that undiagnosed SDB is a common phenomenon in older male individuals, leading to impaired daytime functioning and impairment of overall quality of life. More importantly, our data suggests that untreated SDB may have an adverse effect on the efficacy of antihypertensive treatment in hypertensive individuals with sleep-disordered breathing.

  View details for Web of Science ID A1996VR27100002

  View details for PubMedID 8909343

• Developmental aspects of sleep and breathing. Current opinion in pulmonary medicine Guilleminault, C., Robinson, A. 1996; 2 (6): 492-499

  Abstract

  The developmental aspects of sleep and breathing are rarely treated as one subject. This report attempts to link the fields of sleep research and developmental pulmonology in a comprehensive description of development and control of sleep and breathing from gestation to adulthood. Unfortunately, much of the investigation in this area is basic physiology and was done some time ago. Although this subject matter need not be updated, some of these references are older; however, this may be new information for the pulmonologist. The second part of this report details the pathophysiologic mechanisms behind the development of sleep-disordered breathing in children and adults. In fact, developmental abnormalities that occur in childhood may recrudesce in adulthood. We conclude with a discussion of the familial and genetic aspects of sleep-disordered breathing and consider the place of sudden infant death syndrome in the spectrum of these disorders.

  View details for PubMedID 9363191

• Objective patient compliance in long-term use of nCPAP EUROPEAN RESPIRATORY JOURNAL Fleury, B., Rakotonanahary, D., HAUSSERHAUW, C., Lebeau, B. 1996; 9 (11): 2356-2359

  Abstract

  Concerns remain regarding patient compliance with nasal continuous positive airway pressure (nCPAP). Poor objective compliance during the first months of treatment has been reported, but no data are available among chronically treated patients. Use of nCPAP, in 17 chronically treated obstructive sleep apnoea patients (820+/-262 days) was evaluated objectively using a pressure monitor (MC+; Sefam, France). Two consecutive recording periods of 30 sessions of treatment were scheduled at the patient's home. To minimize the potential bias caused by the introduction of the monitor, only the pressure data obtained at the end of the second period of recording (T2) were analysed. During the 28.1+/-2.6 monitored days, the mean effective daily rate of use was 7.1+/-1.1 h, 97% of the rate indicated by the standard in-built time counter. The prescribed pressure was observed during 95% of the machine run time. The nCPAP system was used for 94% of the monitored days. Sixty percent of the patients used their device every day. These preliminary results suggest that, contrary to reported compliance during the early period of the treatment, objective use of nasal continuous positive airway pressure therapy in chronically treated patients is satisfactory.

  View details for Web of Science ID A1996VT87500028

  View details for PubMedID 8947085

• Hypnagogic and hypnopompic hallucinations: Pathological phenomena? BRITISH JOURNAL OF PSYCHIATRY Ohayon, M. M., Priest, R. G., Caulet, M., Guilleminault, C. 1996; 169 (4): 459-467

  Abstract

  Hypnagogic and hypnopompic hallucinations are common in narcolepsy. However, the prevalence of these phenomena in the general population is uncertain.A representative community sample of 4972 people in the UK, aged 15-100, was interviewed by telephone (79.6% of those contacted). Interviews were performed by lay interviewers using a computerised system that guided the interviewer through the interview process.Thirty-seven per cent of the sample reported experiencing hypnagogic hallucinations and 12.5% reported hypnopompic hallucinations. Both types of hallucinations were significantly more common among subjects with symptoms of insomnia, excessive daytime sleepiness or mental disorders. According to this study, the prevalence of narcolepsy in the UK is 0.04%.Hypnagogic and hypnopompic hallucinations were much more common than expected, with a prevalence that far exceeds that which can be explained by the association with narcolepsy. Hypnopompic hallucinations may be a better indicator of narcolepsy than hypnagogic hallucinations in subjects reporting excessive daytime sleepiness.

  View details for Web of Science ID A1996VL64400011

  View details for PubMedID 8894197

• Blindness and sleep patterns LANCET Leger, D., Guilleminault, C., Defrance, R., Domont, A., Paillard, M. 1996; 348 (9030): 830-831

  View details for Web of Science ID A1996VH98900062

  View details for PubMedID 8814013

• Determinants of sleepiness in automobile drivers JOURNAL OF PSYCHOSOMATIC RESEARCH Philip, P., Ghorayeb, I., Stoohs, R., Menny, J. C., Dabadie, P., Bioulac, B., Guilleminault, C. 1996; 41 (3): 279-288

  Abstract

  Governmental agencies do not systematically investigate the presence of daytime sleepiness as a determinant of driving accidents. We surveyed automobile drivers traveling on summer vacations and driving long distances on a European highway. We evaluated their subjective daytime sleepiness while driving and any sleep deprivation just prior to departure. Five-hundred sixty-seven automobile drivers (mean age 37.7 +/- 11 years) were interviewed at a roadside rest-stop. Questions covered the sleep/wake schedule during the year, sleep habits, and the presence of symptoms frequently associated with sleep-disordered breathing. Sleep behavior just prior to departure was compared to the usual sleep schedule during the year. Fifty percent of the responders had a sleep restriction just prior to departure (mean -203 minutes) compared to usual total sleep time during the year; 10% had no nocturnal sleep prior to departure. Drivers younger than 30 years were significantly more acutely sleep deprived than other drivers. Economic migrants (subjects with low economic status) also experienced significant acute sleep restriction.

  View details for Web of Science ID A1996VK73400010

  View details for PubMedID 8910250

• Rapid shift in sleep time and acrophase of melatonin secretion in short shift work schedule SLEEP QUERASALVA, M. A., Defrance, R., Claustrat, B., Delattre, J., Guilleminault, C. 1996; 19 (7): 539-543

  Abstract

  Tolerance to shift work and adaptability to shifting schedules is an issue of growing importance in industrialized society. We studied 40 registered nurses, 20 on fixed day-shifts and 20 on fixed night-shifts, to assess whether workers with rapidly shifting schedules were able to adapt their melatonin secretion and sleep-wake cycles. The day-shift worked 5 days with 2 days off and the night-shift worked 3 nights with 2 off. All night-shift personnel acknowledged shifting back to daytime schedules on their days off. Sleep-wake was determined by sleep logs and actigraphy. To measure 6-sulfatoxymelatonin levels, urine was collected at 2-hour intervals on the last work day and on the last day off. Night-shift workers slept significantly more on days off. Napping on the job occurred in 9/20 night-shift workers (mean 114 minutes) between 3 and 6 a.m. The acrophase of 6-sulfatoxymelatonin in day-shift nurses occurred at similar times on workdays and off days. In night-shift nurses, the acrophase was about 7 a.m. on days off, but had a random distribution on workdays. Further analysis revealed two subgroups of night-shift nurses: six subjects (group A).demonstrated a rapid shift in melatonin secretion (acrophase at near 12 noon on work days and at near 7 a.m. on days off) while 14 nurses (group B) did not shift. Group A nurses slept more in the daytime on work days and their total sleep time was the same as day-shift nurses. Group A was slightly younger and was composed solely of women (there were nine women and five men in group B). Age may be a factor in the ability to adapt to rapidly shifting schedules.

  View details for Web of Science ID A1996VM16500003

  View details for PubMedID 8899932

• A reversible uvulopalatal flap for snoring and sleep apnea syndrome SLEEP Powell, N., Riley, R., Guilleminault, C., Troell, R. 1996; 19 (7): 593-599

  Abstract

  Velopharyngeal incompetence (VPI) is a recognized complication of uvulopalatopharyngoplasty (UPPP) for obstructive sleep apnea. A new uvulopalatal flap (UPF) technique that modifies the UPPP and reduces this risk is presented. The technique achieves the same anatomic results as the UPPP but is reversible. To evaluate clinical outcomes of this new procedure, selected variables were compared in patients who underwent UPPP and UPF procedures. Eighty patients were examined (59/80 UPF, 21/80 UPPP) in a prospective and consecutive manner. Subjects underwent polysomnography and extensive airway evaluations. The characteristics of all patients, at baseline, were evaluated. The study variables included age, sex, body mass index (BMI), palatal length (PNS P) in millimeters, respiratory disturbance index (RDI), lowest oxygen saturation during sleep and a subjective snoring scale. Sixty-seven of the 80 patients underwent simultaneous hypopharyngeal surgery. Data were analyzed with a SAS program. No statistical difference existed between groups. The postoperative character of the palate and the change in snoring scores were the same in all patients (p = 0.584). A positive correlation existed between improvement in the snoring score and the amount of tissue removed or repositioned in the patients treated with UPF (correlation coefficient = 0.370, p = 0.004). In contrast, there was a negative correlation in the UPPP group for the same parameters (correlation coefficient = -0.195, P = 0.409). This suggests there was a difference between these two groups despite the fact that the baseline and postoperative lengths, as well as tissue removed or repositioned, were equivalent. This further suggests that the UPF may reduce snoring to a greater extent than the UPPP. No significant complications were seen in either group. There was no evidence of VPI, even in the early postoperative period. The new reported procedure is reversible and conservative and reduces the risk of VPI. Snoring is improved, which is consistent with a decrease in airway resistance or obstruction.

  View details for Web of Science ID A1996VM16500011

  View details for PubMedID 8899940

• Central sleep apnea NEUROLOGIC CLINICS Guilleminault, C., Robinson, A. 1996; 14 (3): 611-?

  Abstract

  A central sleep apnea is the absence of respiratory effect, and, thus, the absence of airflow during sleep. Central hypopnea, a related disorder, is also discussed. The sensory component of central sleep apnea; defects involving the integrative and executive neurons; non-neurologic causes of central sleep apneas, including chronic obstructive pulmonary disease and congestive heart failure; diagnosis; treatment; and other topics are reviewed in detail.

  View details for Web of Science ID A1996VC23300007

  View details for PubMedID 8871979

• Obstructive sleep apnea and related disorders NEUROLOGIC CLINICS Chervin, R. D., Guilleminault, C. 1996; 14 (3): 583-?

  Abstract

  OSAS, a common cause of disrupted sleep and EDS, result from repetitive closure of the upper airway during sleep. It probably represents the most severe syndrome related to obstruction of the upper airway; less severe forms include UARS, a syndrome characterized by the need for increased effort to breath but no prominent apneas or hypopneas, and primary snoring. Initial clues to the presence of OSAS and related disorders are derived from the history and include loud snoring, EDS or insomnia, and witnessed apneas. Some patients, especially women, may complain mostly of tiredness or fatigue, and children may present with behavioral abnormalities. Obesity, a large neck circumference, and a crowded oropharynx are common on physical examination. Nonobese patients, in particular, often have retrognathia, a high-arched narrow palate, macroglossia, enlarged tonsils, temporomandibular joint abnormalities, or chronic nasal obstruction. The clinical suspicion of obstructed nocturnal breathing is confirmed by overnight polysomnography, and an MSLT may be used to assess sleepiness. Esophageal manometry during polysomnography facilitates diagnosis of UARS. Treatment most commonly consists of nasal CPAP or BPAP, although problems with compliance make surgical treatment preferable in some cases. Although UPPP eliminates sleep apnea only in a minority of patients, combining UPPP with maxillofacial procedures appears to improve outcomes. Other treatments such as the use of dental appliances or medications, weight loss, and positional therapy may be useful as adjunctive therapy for moderate to severe OSAS or as primary treatments for UARS or mild OSAS.

  View details for Web of Science ID A1996VC23300006

  View details for PubMedID 8871978

• A laboratory validation study of the diagnostic mode of the Autoset(TM) system for sleep-related respiratory disorders SLEEP Fleury, B., Rakotonanahary, D., HAUSSERHAUW, C., Lebeau, B., Guilleminault, C. 1996; 19 (6): 502-505

  Abstract

  We performed a validation study of the diagnostic mode of the Autoset system (ResMed, Australia) on a group of 44 snorers (10 women). We compared the result of the Autoset's automatic analysis of nasal airflow (using nasal prongs) to those of an in-laboratory polysomnographic study with a Fleisch facemask pneumotachograph. For the first 29 patients, the Autoset software was set to recognize only apneas; for the remaining 15, the software was modified to recognize both apneas and hypopneas. Relative to polysomnography, the Autoset overestimated the number of apneas. Oral breathing or displacement of the nasal prongs partially explained these differences. A significant correlation was found between the apnea indices (AI) assessed by the two methods (r = 0.98). For an AI of 20/hour the Autoset was 100% sensitive and 88% specific. The Autoset significantly underestimated the number of hypopneas compared to the polysomnograph with pneumotachograph (62.9 +/- 4.7 vs. 85.5 +/- 73.1, P = 0.04), although for an apnea-hypopnea index of 20, Autoset was 100% sensitive and 88% specific. The lack of linearity of Autoset's volume evaluation at low volumes could explain most of the differences. Our results indicate that the Autoset system, in its diagnostic mode, is a useful tool for identifying patients with significant obstructive sleep apnea syndrome. The system is less useful in patients with mild to moderate sleep disordered breathing, where it may give erroneous results.

  View details for Web of Science ID A1996VD27800009

  View details for PubMedID 8865509

• IgH (mu-switch and gamma-1) region restriction fragment length polymorphism in human narcolepsy JOURNAL OF CLINICAL IMMUNOLOGY Singh, S. M., George, C. F., OTT, R. N., Rattazzi, C., Guilleminault, C., Dement, W. C., Mignot, E. 1996; 16 (4): 208-215

  Abstract

  Predisposition to narcolepsy involves genetic factors both in humans and in a canine model of the disorder. In humans, narcolepsy is strongly associated with HLA DR15 and DQB1*0602. In Dobermans and Labradors, narcolepsy is transmitted as a single autosomal recessive gene with full penetrance (canarc-1). Canine narcolepsy is not linked with DLA, the canine equivalent of HLA, but co-segregates with a DNA segment with high homology with the mu immunoglobulin heavy-chain (IgH) switch-like region (S mu). To determine if the IgH locus is involved in genetic predisposition to human narcolepsy, restriction fragment length polymorphisms specific for the IgM and IgG cluster within this locus were studied in sporadic cases of the disease, as well as in five families with two or more affected individuals. Comparisons were made between control populations and both familial and sporadic cases and for patients with and without HLA-DR15 and DQB1*0602. RFLP analysis at the S mu and gamma-1 loci, which cover over 200 kb of 14q32.3, indicates that there is no evidence for any association between the IgH region and human narcolepsy.

  View details for Web of Science ID A1996VA01500004

  View details for PubMedID 8840222

• Insulin resistance and sleep-disordered breathing in healthy humans AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE Stoohs, R. A., Facchini, F., Guilleminault, C. 1996; 154 (1): 170-174

  Abstract

  Fifty healthy, normotensive individuals (34 women) with a mean age of 44.3 +/- 13.2 yr and a mean body mass index of 27.1 +/- 5.4 kg/m2 were tested for the presence or absence of insulin resistance and sleep-disordered breathing. The hypothesis of this investigation was that insulin resistance is associated with sleep-disordered breathing. In vivo insulin action with determination of steady-state plasma glucose (SSPG) and insulin was measured using simultaneous intravenous infusion of somatostatin, glucose, and insulin via a Harvard pump. Determination of sleep-disordered breathing was performed through clinical assessment and portable nocturnal monitoring using a validated sleep apnea recorder. Individuals with > or = 10 hypoxic respiratory events per hour of sleep were significantly more insulin-resistant than subjects without sleep-breathing disorders. After adjusting the relationship between insulin resistance and sleep-disordered breathing for potential confounding variables, it was found that this relationship was entirely dependent on body mass.

  View details for Web of Science ID A1996UW82700029

  View details for PubMedID 8680675

• Blood pressure ''dipping'' and ''non-dipping'' in obstructive sleep apnea syndrome patients SLEEP Suzuki, M., Guilleminault, C., Otsuka, K., Shiomi, T. 1996; 19 (5): 382-387

  Abstract

  Obstructive sleep apnea syndrome (OSAS) has been associated with a higher than normal cardiovascular morbidity and mortality. Some OSAS patients lack the sleep-related, nocturnal decrease, or "dip," in blood pressure which is seen in normal individuals. These subjects, called "non-dippers," may be at greater risk for cardiovascular problems. We studied 40 OSAS patients (including 3 women) and 6 control subjects, all identified by polysomnography, for nocturnal blood pressure "dipping." We performed a second nocturnal polysomnogram to determine their apnea and hypopnea indices, (A + H)I, and oxygen saturation levels at the beginning of the study and then initiated 48 hours of ambulatory blood pressure monitoring, with data points collected every 30 minutes. Controls, which included one hypertensive subject, were all dippers. Nineteen OSAS subjects (48% of OSAS individuals) were systolic non-dippers and only 9 of them (22.5%) were diastolic non-dippers. We considered the following clinical variables as potential predictors of non-dipping: age, body mass index, respiratory disturbance index, years of reported loud snoring by bed partners, lowest oxygen saturation during nocturnal sleep, and percentage of sleep time spent with oxygen saturation below 90%. Multiple regression analyses indicated respiratory disturbance index as the only significant variable for systolic (p = 0.04) and diastolic (p = 0.03) blood pressure non-dipping. When we forced the following two nonsignificant variables into the model, they showed a very meager impact: number of years with reported loud snoring (p = 0.4 and p = 0.5, respectively for systolic and diastolic blood pressure non-dipping) and age (p = 0.5 and p = 0.6). The calculated model explained only a low percentage of the variance with an r2 of 0.25 and 0.26 for systolic and diastolic blood pressure non-dipping, respectively. Analysis of hypertension/normotension and dipping/non-dipping failed to show a significant relationship in the studied population. Fifty percent of the normotensive OSAS subjects were non-dippers and 43% of the hypertensive OSAS subjects were also non-dippers. We found a relationship between increasing respiratory disturbance index and increasing average 24-hour systolic blood pressure only when OSAS subjects were non-dippers and hypertensive.

  View details for Web of Science ID A1996UZ88100005

  View details for PubMedID 8843529

• Augmented very low frequency component of heart rate variability during obstructive sleep apnea SLEEP Shiomi, T., Guilleminault, C., Sasanabe, R., Hirota, I., Maekawa, M., Kobayashi, T. 1996; 19 (5): 370-377

  Abstract

  After documenting the presence of obstructive sleep apnea syndrome (OSAS) through polysomnographic monitoring, we performed simultaneous ambulatory recordings of electrocardiogram, oronasal airflow, and pulse oximetry on 12 OSAS patients with normal autonomic nervous function for a period of 24 hours. The power spectrum of heart rate variability was investigated before and during treatments using dental appliances. Freuquency domain analysis showed that the very low frequency component of heart rate (0.008-0.04 Hz) was increased in OSAS patients and that a very low frequency peak appeared during episodes of obstructive sleep apnea. The increase in very low frequency identification was synchronized with episodes of absence of air exchange or hypoxemia (decreased arterial oxygen saturation) that occurred repeatedly at a cycle length of 25-120 seconds in our subjects. Frequency domain analysis of heart rate variability before and during prosthetic mandibular advancement treatment showed that only the very low frequency was significantly decreased during prosthetic mandibular advancement treatment, whereas the other frequencies, i.e. high, low, and ultralow frequency component values, showed no significant changes. Time domain analysis of heart rate variability before and during prosthetic mandibular advancement treatment showed no significant changes in any of these parameters. Frequency domain analysis of heart rate variability during nocturnal sleep, especially investigation of very low frequency and very low frequency peak, can be a noninvasive low-cost approach to diagnose and even better monitor subjects undergoing treatment at home, particularly considering that R-R intervals can be extracted from pulse oximetry and that analysis software programs are already commercially available.

  View details for Web of Science ID A1996UZ88100003

  View details for PubMedID 8843527

• Sleep fragmentation as a risk factor for hypertension in middle-aged nonapneic snorers CHEST Lofaso, F., Coste, A., Gilain, L., Harf, A., Guilleminault, C., Goldenberg, F. 1996; 109 (4): 896-900

  Abstract

  Although a high prevalence of hypertension has been observed in snorers, whether there is a direct link between hypertension and snoring remains controversial. It has recently been demonstrated that an abnormal amount of breathing effort during snoring is responsible for sleep fragmentation even in the absence of sleep apnea syndrome criteria. We hypothesized that sleep fragmentation during snoring may be a direct risk factor for the development of hypertension. On the basis of polysomnographic data, 105 nonapneic patients between 40 and 65 years of age referred for snoring with social impairment were selected and categorized as snorers with (n=55) or without sleep fragmentation (n=50) based on whether the arousals index was 10 or greater or less than 10/h of sleep, respectively. Sleep distribution did not differ between the two groups, except for a longer duration of wake after sleep onset (58 +/- 43 min vs 42 +/- 38 min) and a shorter duration of slow-wave sleep in the group with sleep fragmentation (72 +/- 34 min vs 97 +/- 34 min). Although there were no statistically significant differences between the snorers with and without sleep disruption in terms of age (51.3 +/- 7.7 vs 48.6 +/- 6.0 years), body mass index (26.9 +/- 4.0 vs 27.2 +/- 5.5 kg/m2), sex ratio, respiratory indexes during sleep, daytime sleepiness, and daytime tiredness, prevalence of systemic hypertension was significantly higher in the sleep-fragmented group (20/55 vs 7/50). This significant difference persisted (16/51 vs 6/49) when patients using antihypertensive drugs with possible effects on the CNS were excluded. Our data suggest that sleep fragmentation is common in patients who seek medical help for snoring with social impairment and may play a role in the development of hypertension.

  View details for Web of Science ID A1996UE72400013

  View details for PubMedID 8635367

• Prevalence of DSM-IV mood disorders in the general population of UK Ohayon, M. M., Priest, R. G., Guilleminault, C., Caulet, M. ELSEVIER SCIENCE INC. 1996: 558–58

  View details for Web of Science ID A1996UE89300543

• The effect of triazolam and flunitrazepam - Two benzodiazepines with different half-lives - On breathing during sleep CHEST Schneider, H., Grote, L., Peter, J. H., Cassel, W., Guilleminault, C. 1996; 109 (4): 909-915

  Abstract

  We performed a double-blind single-dose placebo/hypnotics crossover study randomized within groups to test the potential problems that a group of normal subjects, including subjects who snore, may face using hypnotic medications. Two benzodiazepine hypnotics--triazolam, 0.25 mg, and flunitrazepam, 2 mg tablets--were considered. Subjects were monitored with nocturnal polysomnography, including esophageal pressure (Pes) monitoring as a measure of respiratory efforts, and were given daytime performance tests. Results were analyzed for the total nocturnal sleep period and also by thirds of the night in consideration of the different half-lives of the studied drugs. Three specific respiratory variables were evaluated: mean breathing frequency for selected unit of time, "Delta Pes" (esophageal pressure at peak end-expiration minus Pes at peak end-inspiration) expressed in cm H2O, and the ratio of Delta Pes/Delta TI (inspiratory time), taken as an index of respiratory drive calculated for each respiratory cycle. There was no significant increase in either the respiratory disturbance index or the oxygen desaturation index (number of drops in arterial oxygen saturation of 4% or more per hour of sleep, as measured by pulse oximetry). There was a significant increase in mean breathing frequency with flunitrazepam compared with placebo, as well as a significantly larger percentage of time during sleep with Delta Pes above 10 cm H2O (taken as a cutoff point for normal respiratory effort) with both triazolam and flunitrazepam compared with placebo. These respiratory changes, even if significant, were minor but may become a liability in association with specific abnormalities.

  View details for Web of Science ID A1996UE72400015

  View details for PubMedID 8635369

• EEG frequency changes during sleep apneas SLEEP Svanborg, E., Guilleminault, C. 1996; 19 (3): 248-254

  Abstract

  To study the effect of transient, apnea-induced hypoxemia on electrocortical activity, five patients with severe obstructive sleep apnea syndrome (OSAS) were investigated during nocturnal sleep. Polysomnographic and simultaneous digitized electro encephalographic (EEG) recordings for topographic and compressed spectral array analysis were made. The EEG recordings were timed exactly to respiratory events. During nonrapid eye movement (NREM) apnea, delta band amplitude increased, starting on average 13 seconds after the apnea onset. Average differences were 268% between initial and maximal values and 202% between initial and final values. In contrast, significant increases in delta amplitudes between the onset and end of REM apneas did not occur, although some caused deep oxygen desaturations. Changes in delta activity were not correlated to NREM apnea duration or degree of desaturation. These results indicate that the increased delta activity during NREM apneas may not be caused by arterial hypoxemia. It could instead be due to either an arousal mechanism, since arousals may be preceded by slow waves in EEG, or to a breakthrough of slow-wave-sleep activity. The sleep disturbance in severe OSAS may create such a propensity for slow-wave sleep that stages pass much more rapidly than in normal persons.

  View details for Web of Science ID A1996UH78800011

  View details for PubMedID 8723384

• Cognitive function in patients with sleep apnea after acute nocturnal nasal continuous positive airway pressure (CPAP) treatment: Sleepiness and hypoxemia effects JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY VALENCIAFLORES, M., Bliwise, D. L., Guilleminault, C., Cilveti, R., Clerk, A. 1996; 18 (2): 197-210

  Abstract

  Patients with sleep apnea are typically hypersomnolent during the daytime and may demonstrate higher order cognitive dysfunction. A persistent problem in interpreting impaired neuropsychological test performance in such patients is whether the observed deficits can be explained wholly by impaired vigilance. We examined 37 sleep apnea patients prior to and immediately subsequent to successful sleep apnea treatment with nasal continuous positive airway pressure (CPAP). Patients were evaluated immediately after morning awakening in the sleep lab. A brief neuropsychological evaluation, was administered at that time. Following this, alertness was measured with a 30-min polysomnographically determined sleep latency test. Both test (approximately 50 min in duration) were performed once following a baseline (diagnostic) night in the sleep lab and once in the morning following a CPAP (therapeutic) night in the lab. Subgroup analyses indicted that while vigilance impairment can account for some of the decreased test performance seen in sleep apnea (auditory verbal learning) the effects of severe nocturnal hypoxemia appear to affect other function (sustained attention in repetitive arithmetic calculations) that were not easily modified by treatment. Thus, performance on the recall trial of the Rey Auditory Verbal Learning Test increased from pre-CPAP to post-CPAP for the increased alertness group but decreased significantly for the decreased alertness group. On the Wilkinson Addition Test, non-hypoxemic patients showed statistically significant improvement in problems correctly solved from pre-CPAP to post-CPAP, but the hypoxemic patients showed only a marginal increase. These results are compatible with other studies suggesting that patients having sleep apnea may incur deficits as a result of both decreased vigilance and hypoxemia, and that at least some of these deficits are immediately reversible.

  View details for Web of Science ID A1996UR52400004

  View details for PubMedID 8780955

• Upper airway resistance syndrome, nocturnal blood pressure monitoring, and borderline hypertension CHEST Guilleminault, C., Stoohs, R., Shiomi, T., Kushida, C., Schnittger, I. 1996; 109 (4): 901-908

  Abstract

  Upper airway resistance syndrome (UARS) is a sleep-disordered breathing syndrome characterized by complaints of daytime fatigue and/or sleepiness, increased upper airway resistance during sleep, frequent transient arousals, and no significant hypoxemia. Of a population of 110 subjects (58 men) diagnosed as having UARS, we investigated acute systolic and diastolic BP changes seen during sleep in two different samples. First, six patients from the original subject pool were found to have untreated chronic borderline high BP, and were subjected to 48 h of continuous ambulatory BP monitoring before treatment and another 48 h of BP monitoring 1 month after the start of nasal-continuous positive airway pressure (N-CPAP) treatment. Five of six subjects used their equipment on a regular basis and had their chronic borderline high BP completely controlled. No change in BP values was seen in the last subject, who discontinued N-CPAP after 3 days. A second protocol investigated seven normotensive subjects drawn from the initial subject pool. Continuous radial artery BP recording was performed during nocturnal sleep with simultaneous polygraphic recording of sleep/wake variables and respiration. BP changes were studied during periods of increased respiratory efforts and at the time of alpha EEG arousals. Increases in systolic and diastolic BP were noted during the breaths with the greatest inspiratory efforts without significant hypoxemia. A further increase in BP was noted in association with arousals. Three of these subjects also underwent echocardiography during sleep, which demonstrated a leftward shift of the interventricular septum with pulsus paradoxus in association with peak end-inspiratory esophageal pressure more negative than -35 cm H2O. Our study indicates that, in the absence of classic apneas, hypopneas, and repetitive significant drops in oxygen saturation (below 90%), repetitive increases in BP can occur as a result of increased airway resistance during sleep. It also shows that, in some patients with both UARS and borderline high BP, high BP can be controlled with treatment of UARS. We conclude that abnormal upper airway resistance during sleep, often associated with snoring, can play a role in the development of hypertension.

  View details for Web of Science ID A1996UE72400014

  View details for PubMedID 8635368

• Overestimation of sleep latency by patients with suspected hypersomnolence SLEEP Chervin, R. D., Guilleminault, C. 1996; 19 (2): 94-100

  Abstract

  The latency to sleep onset has been reported to be overestimated by chronic insomniacs. Observing that some patients evaluated for suspected hypersomnolence complain of insomnia and others fail to report that they are sleepy, we wondered whether overestimation of sleep latency could be occurring in these subjects as well. Since polysomnography (PSG) only provides one sleep onset with which to assess a patient's estimation, we investigated the use of the multiple sleep latency test (MSLT) for this purpose. Among 147 patients who had an MSLT, 137 of whom had a preceding PSG, overestimation of sleep latency occurred on 78% and 74% of the respective tests. The magnitude of overestimation averaged 3 minutes and 27 minutes, respectively, and was not dependent on diagnosis. Subjects who had reported a history of difficulty falling asleep, compared to those who did not, tended to show equivalent objective sleep latencies, longer subjective nocturnal sleep latencies and less overall accuracy in their estimates. Those who denied having a problem with excessive daytime sleepiness (EDS) showed objective sleep latencies nearly identical to those who complained of EDS but had only a trend toward higher overestimation on the MSLT. Overestimation of sleep latency is therefore more readily part of an explanation for why hypersomnolent patients sometimes complain of insomnia than it is for failure to recognize EDS. The MSLT as well as nocturnal recordings can provide data with which to assess overestimation of sleep latency.

  View details for Web of Science ID A1996UC74600002

  View details for PubMedID 8855030

• Adult psychophysiologic insomnia and positive history of childhood insomnia SLEEP Philip, P., Guilleminault, C. 1996; 19 (3): S16-S22

  Abstract

  Sixty-five adults diagnosed with "psychophysiologic chronic insomnia" following the criteria of the Association of Sleep Disorders Centers were investigated. They were subdivided into two groups based on whether onset of the insomnia had occurred in childhood or adulthood. Fifty similar-aged patients with obstructive sleep apnea syndrome (OSAS) were also investigated and served as a contrast group. All subjects were given polygraphic recordings and structured interviews, and all completed sleep questionnaires after reviewing the questions with an investigator. On many indices evaluating subjective daytime alertness and well-being, the psychophysiologic insomnia patients had scores similar to the OSAS patients. There were no significant differences between the childhood-onset and adult-onset psychophysiologic insomnia patients on most of the investigated items. However, the childhood-onset psychophysiologic insomniinacs had moderately but significantly higher reports of nightmares. This group also reported having had longer sleep latencies, significantly more "fear of the dark" and more frequent nightmares during childhood than the adult-onset group. These statistically significant findings reflected only a moderate increase in subjective scores, however, and in general the childhood-onset and adult-onset psychophysiologic insomnia patients were very similar.

  View details for Web of Science ID A1996UJ76400003

  View details for PubMedID 8723371

• Development of circadian rhythmicity of temperature in full-term normal infants NEUROPHYSIOLOGIE CLINIQUE-CLINICAL NEUROPHYSIOLOGY Guilleminault, C., Leger, D., Pelayo, R., Gould, S., Hayes, B., Miles, L. 1996; 26 (1): 21-29

  Abstract

  Twelve full-term infants (7 girls and 5 boys) with normal neurological, behavioral and somatic development were followed at regular intervals during the first 5 months of life to appreciate the development of circadian rectal temperature rhythmicity. Activity and temperature (oral at birth, rectal thereafter) were monitored for a minimum of 60 hours on seven separate occasions: at birth, 3 weeks, 6 weeks, 8 weeks, 10 weeks, 16 weeks and 20 weeks of age. Activity was measured using an actigraph worn on the infant's wrist, and rectal temperature was measured using a rectal probe attached to a portable microprocessor (Vitalog TM). Data points were collected every 2 minutes. No fewer than ten infants were monitored at each session, and no infant missed more than one session. Missing recordings were due to equipment malfunctions, probe expulsions and minor health problems. Six infants out of 12 were successfully monitored at each of the first four sessions, from birth to 8 weeks of age inclusively, and two subjects were successfully monitored at all seven sessions. Periodic regression analysis was performed by least squares curve fit with secondary analysis of variance. Analysis of covariance was performed on repeated measures. There was no evidence of rectal temperature circadian rhythmicity at 3 weeks. Two infants demonstrated a circadian rhythmicity at 6 weeks, and all infants had a circadian rhythmicity at 10 weeks post-natal age. At the time of the first observance of circadian rhythmicity of rectal temperature, the mean delta in temperature from peak to trough was 0.6 +/- 0.3 degrees C. This delta was greater at the 16th week, with a mean value of 1.2 +/- 0.3 degrees C. The trough was seen during the first part of the long nocturnal inactivity period. Circadian rhythmicity of rectal temperature was always observed in the studied subjects before the establishment of a consolidated, long daytime wake period.

  View details for Web of Science ID A1996UK72800004

  View details for PubMedID 8657095

• Tiredness and somnolence despite initial treatment of obstructive sleep apnea syndrome (what to do when an OSAS patient stays hypersomnolent despite treatment) From Snoring to Sleep Apnea Syndrome: Therapeutic Approach, Second Conference Guilleminault, C., Philip, P. AMER ACAD SLEEP MEDICINE. 1996: S117–S122

  Abstract

  From a database of 4,129 patients with sleep-disordered breathing (SDB), we found 207 subjects (43 women) that still complained of daytime tiredness, fatigue, and/or sleepiness despite treatment. In 25 subjects the sleepiness developed 1 to 36 months following treatment and was related to noncompliance (8 subjects), significant weight increase and/or inappropriate treatment (10 subjects), or development of new medical problems (7 subjects). In the remaining 182 subjects, sleepiness was noted within 1 month after what was judged appropriate treatment for SDB. In this group, the reason for persistent complaint was divided into four categories: 1) inappropriate treatment as a result of not using the measurement of esophageal pressure (Pes) in the initial diagnosis (41 subjects), 2) nonfunctional treatment (3 subjects), 3) associated narcolepsy-like syndrome (2 subjects), and 4) emergence of obesity and/or periodic leg movements as significant factors (135 subjects). The 135 subjects in this last category could be subdivided into three subgroups: 1) younger subjects, severely overweight with lower mean nocturnal saturated arterial oxygen (SaO2) values; 2) older subjects, of normal weight, with high numbers of periodic leg movements (PLM); and 3) moderately overweight subjects, with a combination of PLM and lower mean SaO2 values than expected. Treatments were aimed at eliminating the identified problems; they included standard medications for PLM and nasal bilevel positive airway pressure (BiPAP) for low SaO2 measurements. These treatments were not effective in specific cases, and stimulant medications had to be prescribed.

  View details for Web of Science ID A1996WE74500012

  View details for PubMedID 9122568

• ASSESSMENT OF SLEEPINESS IN CLINICAL-PRACTICE NATURE MEDICINE Chervin, R. D., Guilleminault, C. 1995; 1 (12): 1252-1253

  View details for Web of Science ID A1995TH78600034

  View details for PubMedID 7489403

• HOME NASAL CONTINUOUS POSITIVE AIRWAY PRESSURE IN INFANTS WITH SLEEP-DISORDERED BREATHING JOURNAL OF PEDIATRICS Guilleminault, C., Pelayo, R., Clerk, A., Leger, D., BOCIAN, R. C. 1995; 127 (6): 905-912

  Abstract

  To review our experience with home nasal continuous positive airway pressure (CPAP) in infants with small upper airways and abnormal breathing during sleep.Seventy-four infants with sleep-disordered breathing and narrow upper airways, as identified by nocturnal polygraphic recording and endoscopic evaluation, were treated at home with nasal CPAP. Infants with craniofacial anomalies and trisomy 21, and infants who had been referred to us as having had "apparent life-threatening events," made up the majority of the population. Because of the rapid growth of infants, regular follow-up visits were scheduled to adjust CPAP and mask size.Seventy-two infants were successfully treated at home with nasal CPAP; there were two failures. Follow-up lasted from 5 months to 12 years. Compliance was not a problem, but home nasal CPAP was prescribed only for infants who lived close to our center and whose families and pediatricians were willing to support compliance.Home nasal CPAP requires careful, in-laboratory titration and regular follow-up to adjust both pressure and mask size. With the support of families and pediatricians, home nasal CPAP can be an effective treatment for infants with upper airway respiratory problems during sleep. In many cases, it can provide an interim solution, enabling physicians to plan surgery at an appropriate time and giving infants time to grow before having to undergo surgical stress.

  View details for Web of Science ID A1995TK14900009

  View details for PubMedID 8523187

• FORENSIC SLEEP MEDICINE - NOCTURNAL WANDERING AND VIOLENCE SLEEP Guilleminault, C., Moscovitch, A., Leger, D. 1995; 18 (9): 740-748

  Abstract

  Forty-one subjects between 12 and 63 years of age with a complaint of nocturnal wandering were reviewed retrospectively, and a prospective investigation of their compliance to treatment was performed. Twenty-nine of 41 subjects committed violence against themselves or others ("violent group"). Clinical investigation of their problem involved polysomnography, wake and sleep EEGs and ambulatory EEG recording in the home environment. The nocturnal wandering may have started from NREM sleep or REM sleep, and violence was observed in both of these sleep states. Arousal from sleep may have been triggered by sleep-disordered breathing or may have been related to temporal lobe abnormalities, and, in some cases, no abnormal polygraphic features were noted. Violence was always preceded by many instances of nocturnal wandering that had received little clinical attention. Temporal lobe abnormalities, a rare cause of nocturnal wandering, were present only in the "violent" group. This group also had a higher percentage of men than the "nonviolent" group. In both groups, the frequency of nocturnal wandering increased with an increase in daytime stressors. Pharmacological and psychiatric treatment approaches were beneficial in both groups.

  View details for Web of Science ID A1995TH48600006

  View details for PubMedID 8638066

• PROLONGED CONFUSION WITH NOCTURNAL WANDERING ARISING FROM NREM AND REM-SLEEP - A CASE-REPORT SLEEP Kushida, C. A., Clerk, A. A., Kirsch, C. M., Hotson, J. R., Guilleminault, C. 1995; 18 (9): 757-764

  Abstract

  A 51-year-old man with Machado-Joseph disease had a 3-year history of prolonged confusion following nightly nocturnal wandering. Polysomnography with videotape monitoring revealed 19- to 120-minute sleepwalking episodes emerging from non-rapid eye movement (NREM) sleep and occasionally from rapid eye movement (REM) sleep, followed by 22-47 minutes of prolonged confusion and disorientation. The patient also had a periodic limb movement disorder and obstructive sleep apnea syndrome. Excessive daytime sleepiness was evident by results from the Epworth Sleepiness Scale and Multiple Sleep Latency Test. A sleep-deprived electroencephalogram (EEG) and a polysomnogram with an expanded EEG montage before and during these episodes revealed no epileptiform activity. A contrast-enhanced brain magnetic resonance imaging (MRI) scan demonstrated findings consistent only with Machado-Joseph disease. The patient improved with a combination of temazepam and carbidopa-levodopa.

  View details for Web of Science ID A1995TH48600008

  View details for PubMedID 8638068

• FORENSIC SLEEP MEDICINE AND NOCTURNAL WANDERING SLEEP Guilleminault, C., Kushida, C., Leger, D. 1995; 18 (9): 721-723

  View details for Web of Science ID A1995TH48600002

  View details for PubMedID 8638062

• CORRELATES OF SLEEP LATENCY ON THE MULTIPLE SLEEP LATENCY TEST IN A CLINICAL POPULATION ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY Chervin, R. D., Kraemer, H. C., Guilleminault, C. 1995; 95 (3): 147-153

  Abstract

  The multiple sleep latency test (MSLT) is commonly used as an objective measure of sleepiness. We retrospectively correlated MSLT scores from 147 patients with other information relating to sleepiness, namely demographic information, data from nocturnal polysomnograms (PSGs), and subjective assessments. The only variable that showed a valid and statistically significant correlation with the MSLT score was sleep latency on the PSG. The results were largely similar within subgroups focusing on (1) individuals with the ability to fall asleep on every nap, (2) subjects with abnormally short MSLT scores, (3) nap attempts that were successful, and (4) patients with particular diagnoses. We conclude that the mean sleep latency on the MSLT, in a clinical population, does not correlate well with a number of variables expected to influence sleepiness. While the validated utility of the MSLT in separating patients from normals or in identifying narcolepsy is not disputed, the accuracy of the MSLT as a measure of sleepiness appears to be limited.

  View details for Web of Science ID A1995RW40300001

  View details for PubMedID 7555905

• FAMILIAL AGGREGATES IN OBSTRUCTIVE SLEEP-APNEA SYNDROME CHEST Guilleminault, C., Partinen, M., Hollman, K., Powell, N., Stoohs, R. 1995; 107 (6): 1545-1551

  Abstract

  Obstructive sleep apnea syndrome (OSAS) was diagnosed in157 subjects based on clinical symptoms, physical evaluation, cephalometric x-ray films, and polysomnography. These index cases identified 844 living first-degree relatives. Mailings were sent to 792 (94%). The mailing consisted of two identical questionnaires, one for the family member of the index case and one to be given to a friend (not a relative) of approximately the same age. In response, we received 531 (63%) questionnaires from relatives and 198 (25%) questionnaires from age-matched nonrelated friends, which were used as a control group. A more extensive investigation was performed on first-degree relatives of the index group living in the San Francisco Bay Area or vicinity. Two hundred seventy-nine relatives (100%) were identified. One hundred sixty-six subjects (59%) as well as 69 age-matched friends (ie, 41% of the 166 relatives and 25% of the potential total group) agreed to participate in further studies. These subjects had interviews, clinical investigations, and nonattended ambulatory monitoring. Cephalometric x-ray films could be obtained on only 22 of 166 participating relatives and 6 of 69 friends. Body mass index was not a differentiating measure between relatives and friends. Odds ratios (ORs) were calculated from the questionnaiare data. The report of tiredness, fatigue, and sleepiness did not distinguish family members from friends. The OR, however, progressively increases when there is a positive history of near nightly loud snoring (OR = 1.78; 95% confidence interval [CI] 1.25-2.54) or a positive history of daytime sleepiness in conjunction with near nightly loud snoring (OR = 3.11; 95% CI = 1.94-4.99). The investigation in the Bay Area indicated that, when first-degree relatives were compared with friends, the complaint of daytime tiredness, sleepiness, or both with the presence of a high and narrow(ogival) hard palate sharply differentiated between friends and relatives (OR = 10.9, 95, CI = 5.31-22.5). An Epworth Sleepiness Scale score of 9 or greater with the presence of another symptom associated with OSAS, and a respiratory disturbance index greater than 5 (number of apneas and hypopneas per hour of sleep > 5) gave an OR of 45.6 (95% CI = 18.8-11.0). Disproportionate craniofacial anatomy was common in familial groups with OSAS. Craniofacial familial features can be a strong indicator of risk for the development of OSAS.

  View details for Web of Science ID A1995RD45100015

  View details for PubMedID 7781344

• AROUSAL, INCREASED RESPIRATORY EFFORTS, BLOOD-PRESSURE AND OBSTRUCTIVE SLEEP-APNEA JOURNAL OF SLEEP RESEARCH Guilleminault, C., Stoohs, R. 1995; 4: 117-124

  View details for Web of Science ID A1995RK09400024

• SLEEP AND SLEEP-DISORDERED BREATHING IN COMMERCIAL LONG-HAUL TRUCK DRIVERS CHEST Stoohs, R. A., BINGHAM, L. A., Itoi, A., Guilleminault, C., Dement, W. C. 1995; 107 (5): 1275-1282

  Abstract

  We have performed a study assessing the prevalence of sleep-disordered breathing in a large US trucking company using a validated portable monitor (MESAM-4) and a validated symptom questionnaire. Three hundred eighty-eight drivers with a mean age of 36 years filled out the questionnaire. One hundred fifty-nine drivers with a mean age of 35 years spent the night at the terminal hub where they underwent monitoring for identification of sleep-disordered breathing. The drivers also had blood pressure recorded while awake, seated, and after 15 min of quiet rest. Seventy-eight percent of the drivers had an oxygen desaturation index (ODI) > or = 5 per hour of sleep; 10% had an ODI > or = 30 per hour of sleep. There was a significant difference in the body mass index (BMI) between drivers with ODI < 5 and drivers with ODI > or = 5 (25.7 +/- 6.0 kg/m2 in drivers with ODI < 5 vs 29.0 +/- 6.3 kg/m2 in drivers with ODI > or = 5, p < 0.001). Sixteen percent of all drivers tested were hypertensive. Twelve percent were unaware of their hypertension. Hypertensive drivers were significantly more overweight (p < 0.0001), slept more restlessly (p < 0.04), took more naps (p < 0.03), and woke up more frequently during the night (p < 0.005). About 20% of drivers presented symptoms indicating very regular sleep disturbances. Drivers who had been with the company for more than 1 year were more likely to present daytime fatigue, daytime tiredness, unrestorative sleep, hypertension, and higher BMI. Long-haul truck drivers have very irregular sleep/wake schedules and a high prevalence of sleep-disordered breathing. Chronic sleep/wake disruption and partial, prolonged sleep deprivation may worsen sleep-disordered breathing. This combination of problems may impact significantly on the daytime alertness of truckers.

  View details for Web of Science ID A1995QY14600020

  View details for PubMedID 7750318

• NONDRUG TREATMENT TRIALS IN PSYCHOPHYSIOLOGICAL INSOMNIA ARCHIVES OF INTERNAL MEDICINE Guilleminault, C., Clerk, A., Black, J., LABANOWSKI, M., Pelayo, R., Claman, D. 1995; 155 (8): 838-844

  Abstract

  Due to a variety of potential problems with long-term hypnotic use, patients and treating physicians often try to avoid drugs in the treatment of psychophysiologic insomnia and to use nondrug treatment strategies, but these treatments must bring relief within a limited amount of time to be acceptable to patients.Thirty patients participated in the study. All had, for a minimum of 6 months, the complaint of less than 6 hours total sleep time per night in conjunction with either: (1) spending more than 30 minutes in bed before falling asleep, or (2) awakening during the night within 2 hours of sleep onset with difficulty returning to sleep. All subjects had the associated complaint of daytime impairment and none had used hypnotics for at least 3 months. Patients were randomly assigned to three parallel treatment groups: structured sleep hygiene, structured sleep hygiene with late afternoon moderate exercise, and structured sleep hygiene with early morning light therapy. Patients responded to questionnaires and filled out sleep logs. In addition, they underwent clinical evaluation, structured interviews, nocturnal monitoring, and actigraphy. The analyzed variables before and at the end of treatment were those derived from sleep logs and actigraphy.All subjects showed a trend toward improvement, independent of the treatment received, but only the "structured sleep hygiene with light treatment" showed statistically significant improvement at the end of the trial.Patients with chronic psychophysiologic insomnia may benefit from a nondrug treatment approach. Light therapy appears particularly promising.

  View details for Web of Science ID A1995QU59400008

  View details for PubMedID 7717792

• SLEEP ONSET - SCORING CRITERIA IN PATIENTS WITH SLEEP-APNEA SYNDROME CLINICAL ELECTROENCEPHALOGRAPHY VALENCIAFLORES, M., Bliwise, D. L., Guilleminault, C. 1995; 26 (2): 108-112

  Abstract

  It has been suggested that in patients with sleep apnea syndrome (SAS) modified scoring criteria may improve accuracy in the determination of sleep onset in the Multiple Sleep Latency Test (MSLT). Scoring in 30-sec epochs according to the standard criteria requires more than 50% of the epoch asleep to score sleep latency (SL). In patients with SAS, short apneas with arousals could prevent the accurate determination of SL. This study compared three time-duration epochs (5-sec, 10-sec, 30-sec) for scoring SL in patients with SAS. Sleep onset during a single sleep latency test, the morning subsequent to a nocturnal polysomnogram, was determined by the criterion of at least 50% of the epoch asleep. Neuropsychological evaluation was performed immediately after the single sleep latency test. There was no statistically significant difference in time to fall asleep as defined by 10-sec and 30-sec epochs, but SL defined by 5-sec epochs was significantly shorter than SL defined by 10-sec and 30-sec epochs. Wilkinson Addition Test correct score correlated better with SL as defined by 30-sec epochs. The results imply that the level of sleepiness measured by 30-sec epochs may be more useful to appreciate behavior and performance.

  View details for Web of Science ID A1995QR00800006

  View details for PubMedID 7781189

• UPPER AIRWAY SLEEP-DISORDERED BREATHING IN WOMEN ANNALS OF INTERNAL MEDICINE Guilleminault, C., Stoohs, R., Kim, Y. D., Chervin, R., Black, J., Clerk, A. 1995; 122 (7): 493-501

  Abstract

  To investigate the various clinical presentations of sleep-disordered breathing in women.A retrospective case-control study.A sleep disorders clinic.334 women, aged 18 years and older, seen between 1988 and 1993, who were diagnosed with upper airway sleep-disordered breathing. Controls were 60 women with insomnia and 100 men with sleep-disordered breathing.Clinical, anatomic, and polygraphic information.The mean lag time (+/- SD) in women between the appearance of symptoms and a positive diagnosis was 9.7 +/- 3.1 years; among participants 30 to 60 years of age, the duration of untreated symptoms differed (P < 0.001) between women and men. Sleep-disordered breathing was blamed for divorce or social isolation by 40% of the case patients. Abnormal maxillomandibular features were noted in 45% of the women with disordered breathing. Dysmenorrhea and amenorrhea (which disappeared after treatment with nasal continuous positive airway pressure) were reported in 43% of premenopausal women compared with 13% of persons in the control group of women with insomnia. Thirty-eight women (11.4%) with upper airway sleep-disordered breathing had a respiratory disturbance index of less than 5 and were significantly younger, had a smaller neck circumference, and had a lower body mass index than women with a respiratory disturbance index of 5 or more.Physicians should revise their understanding of upper airway sleep-disordered breathing so that they notice women with certain craniofacial features, a low body mass index, a small neck circumference, and a respiratory disturbance index of less than 5. These revisions may enable more rapid diagnosis and treatment of women with sleep-disordered breathing.

  View details for Web of Science ID A1995QP00800003

  View details for PubMedID 7872583

• OBSTRUCTIVE SLEEP-APNEA TRENDS IN THERAPY WESTERN JOURNAL OF MEDICINE Riley, R. W., Powell, N. B., Guilleminault, C., Clerk, A., Troell, R. 1995; 162 (2): 143-148

  Abstract

  The National Commission on Sleep Disorders Research, in its report to Congress, concluded that the primary care community generally does not understand sleep disorders. Obstructive sleep apnea carries a risk of substantial morbidity and mortality. Excessive daytime sleepiness results from fragmented sleep and microarousals associated with apneic events. It causes poor work performance and increases the incidence of automobile accidents due to driving while drowsy. The commission estimates that the loss of productivity in the United States from excessive daytime sleepiness is more than $20 billion per year. Obstructive sleep apnea is strongly associated with hypertension, myocardial infarction, and stroke. Risk factors for obstructive sleep apnea include male sex, obesity, older age, craniofacial anomalies, and familial risk. Treatment is based on documenting the disorder by polysomnography. Medical management of the syndrome includes weight loss and nasal continuous positive airway pressure. A network of follow-up and support is necessary to maintain compliance. Surgical treatment is reserved for those for whom nasal airway pressure treatment fails. A surgical protocol is presented that demonstrates efficacy equal to nasal airway pressure treatment. Primary care physicians should assume the responsibility of identifying patients at risk for obstructive sleep apnea and refer them appropriately.

  View details for Web of Science ID A1995QJ19700005

  View details for PubMedID 7725686

• THE EFFECT OF ELECTRICAL-STIMULATION ON OBSTRUCTIVE SLEEP-APNEA SYNDROME CHEST Guilleminault, C., Powell, N., Bowman, B., Stoohs, R. 1995; 107 (1): 67-73

  Abstract

  Patients with severe obstructive sleep apnea polygraphically documented underwent electrical stimulation treatment trials. Submental and intraoral stimulations were applied during waking and during nocturnal sleep. The stimulation was applied using a custom-designed neuromuscular electrical stimulator (EdenTec Corp) providing symmetric biphasic constant voltage pulses. Pulse duration of each phase was set to 80 microseconds based on a subjective evaluation of pulse durations from 80 to 300 microseconds to minimize sensation while generating equivalent motor responses. Pulse repetition rate was set to 50 pulses per second. Cephalometric radiographs and endoscopies were obtained with and without stimulations during waking. Most commonly, stimulations induced alpha EEG arousals. Submental subcutaneous stimulation induced good contractions of platysmal muscles but had no impact on the upper airway. Intraoral stimulation induced clear tongue muscle movements but with change of shape of the upper airway and posterior movements of the tongue. Each time a breakage of apnea was noted, it was associated with a time-linked alpha EEG arousal. The results obtained by us and others do not, at this time, give convincing support for the use of electrical stimulation using submental surface or intraoral electrodes as a viable approach for effective control of obstructive sleep apnea syndrome symptoms.

  View details for Web of Science ID A1995QC15800017

  View details for PubMedID 7813315

• Arousal, increased respiratory efforts, blood pressure and obstructive sleep apnoea. Journal of sleep research Guilleminault, C., Stoohs, R. 1995; 4 (S1): 117–24

  Abstract

  The roles of hypoxaemia, of mechanical changes related to partial or complete airway obstruction and of arousals during sleep in the haemodynamic and heart rate changes seen in association with sleep-disordered breathing have been questioned. Several experiments have been performed by these authors to investigate the role of arousals and mechanical changes in the blood pressure changes associated with sleep disordered breathing. Investigation of the role of arousals. Two different populations were used in this study; one of normal, young volunteers without sleep-disordered breathing monitored at baseline (normal sleep) who were submitted to auditory stimulation during sleep, causing sleep fragmentation, and another of obstructive sleep apnoeic patients who were monitored at baseline and after nasal CPAP treatment. Before treatment and after one month of treatment while still being treated with nasal CPAP, these subjects were submitted to the same auditory stimulation and sleep fragmentation as normal controls. The studied variables were systolic and diastolic blood pressure and heart rate. In normal controls, auditory induced arousals lead to an increase in diastolic as well as systolic blood pressure. The increase was related to the type of arousal but was also noted with K complexes to a lesser degree. In OSAS patients under treatment with nasal CPAP, similar increases were noted with auditory stimulation. Compared to baseline hypoxaemia and hyperventilation periods, however, the haemodynamic increase was, at its highest, only one-third of the mean pressure monitored during the baseline, end-of-apnoea hyperventilation period with EEG arousals. Investigation of the role of nasal CPAP on blood pressure (BP) while patients had no hypoxaemia (SaO2>92%) but still showed increased respiratory efforts indicated a persistence of higher systolic and diastolic pressures than when nasal CPAP completely eliminated increased efforts. Possible long-term impact of arousals and mechanical changes. A last study was performed on patients with upper airway resistance syndrome (UARS). Out of 112 patients, 6 were identified using the World Health Organization (WHO) protocol and ambulatory monitoring as having borderline high BP (140-160//90-98). Subjects were calibrated with nasal CPAP and were asked to use their equipment on a nightly basis. The CPAP machines were equipped with counters that could accurately measure the number of hours that the device was used. Patients were their own controls and were re-monitored one month later. Four subjects used their nasal CPAP at least 6 nights per week and more than 5 hours per night. One patient used his CPAP approximately 3 nights per week and more than 4 hours per night. One patient used his CPAP a total of 3 nights in the whole month. Blood pressure was unchanged in the patient who failed to use his CPAP, but was normalized in the 5 others, as were nocturnal recordings.

  View details for PubMedID 10607187

• CLINICAL ASPECTS AND FEATURES OF CATAPLEXY NEGATIVE MOTOR PHENOMENA Guilleminault, C., Gelb, M. 1995; 67: 65-77

  View details for Web of Science ID A1995BE11Z00006

  View details for PubMedID 8848983

• DQB1-ASTERISK-0602 AND DQA1-ASTERISK-0102 (DQ1) ARE BETTER MARKERS THAN DR2 FOR NARCOLEPSY IN CAUCASIAN AND BLACK-AMERICANS 4th International Conference on Narcolepsy Mignot, E., Lin, X., Arrigoni, J., Macaubas, C., Olive, F., Hallmayer, J., Underhill, P., Guilleminault, C., Dement, W. C., GRUMET, F. C. AMER SLEEP DISORDERS ASSOC. 1994: S60–S67

  Abstract

  In the present study, we tested 19 Caucasian and 28 Black American narcoleptics for the presence of the human leucocyte antigen (HLA) DQB1*0602 and DQA1*0102 (DQ1) genes using a specific polymerase chain reaction (PCR)-oligotyping technique. A similar technique was also used to identify DRB1*1501 and DRB1*1503 (DR2). Results indicate that all but one Caucasian patient (previously identified) were DRB1*1501 (DR2) and DQB1*0602/DQA1*102 (DQ1) positive. In Black Americans, however, DRB1*1501 (DR2) was a poor marker for narcolepsy. Only 75% of patients were DR2 positive, most of them being DRB1*1503, but not DRB1*1501 positive. DQB1*0602 was found in all but one Black narcoleptic patient. The clinical and polygraphic results for this patient were typical, thus confirming the existence of a rare, but genuine form of DQB1*0602 negative narcolepsy. These results demonstrate that DQB1*0602/DQA1*0102 is the best marker for narcolepsy across all ethnic groups.

  View details for Web of Science ID A1994QD08100013

  View details for PubMedID 7701202

• EPIDEMIOLOGY OF NARCOLEPSY 4th International Conference on Narcolepsy Hublin, C., Partinen, M., Kaprio, J., Koskenvuo, M., Guilleminault, C. AMER SLEEP DISORDERS ASSOC. 1994: S7–S12

  Abstract

  The prevalence of narcolepsy is usually presented at about 50/100,000. There are, however, marked differences of about 2,500-fold between the lowest and the highest reported prevalence. This discrepancy is at least partly explained by differences in the study populations and methods. There are, however, no earlier population-based epidemiological studies with polygraphically confirmed diagnoses. We studied the occurrence of symptoms resembling the two main manifestations of narcolepsy, i.e. abnormal sleep tendency and emotion-associated muscular weakness, in an adult twin cohort (n = 16,179) with a questionnaire. A total of 3.2% met the minimal diagnostic criteria of the International Classification of Sleep Disorders for narcolepsy. Eleven questionnaire items assessing the main manifestations of narcolepsy formed a measure called the Ullanlinna Narcolepsy Scale (UNS), which has been validated. The UNS score was calculated for 11,354 subjects. Those (n = 75) having a UNS score equal or higher than the lowest value in a narcolepsy patient group were studied. Thirty-one of them (fulfilling also the minimal diagnostic criteria) were interviewed, and those suspected of having narcolepsy (n = 5) were evaluated in the sleep laboratory. In three subjects the narcolepsy diagnosis was verified (all dizygotic, nonfamilial and human leukocyte antigen DR2/DQB-0602 positive), giving a prevalence of 0.026% in the adult Finnish (Caucasian) population.

  View details for Web of Science ID A1994QD08100003

  View details for PubMedID 7701204

• OBSTRUCTIVE SLEEP-APNEA AND THE HYOID - A REVISED SURGICAL-PROCEDURE OTOLARYNGOLOGY-HEAD AND NECK SURGERY Riley, R. W., Powell, N. B., Guilleminault, C. 1994; 111 (6): 717-721

  Abstract

  Obstructive sleep apnea syndrome results from a loss of muscular activity of pharyngeal dilators and airway collapse at the hypopharynx-base of tongue or the oropharynx-soft palate. The hyoid arch and its muscle attachments strongly affect hypopharyngeal airway patency and resistance. On the basis of these concepts and previous experience, a modified hyoid suspension procedure is presented. Fifteen consecutively treated surgical patients underwent an isolated modified hyoid suspension procedure to correct hypopharyngeal obstruction. Oropharyngeal-palatal obstruction had previously been corrected or was thought not to be a component of the obstruction. Treatment outcomes were based on objective polysomnographic data and subjective clinical correction of excessive daytime sleepiness. The polysomnographic data included analysis of the respiratory disturbance index and lowest oxyhemoglobin desaturation. On the basis of these criteria, 12 of 15 patients (75%) had correction of their excessive daytime sleepiness and marked improvement in their sleep disorder breathing. The mean preoperative respiratory disturbance index was 44.7 +/- 22.6, and the lowest oxyhemoglobin desaturation was 82% +/- 6%. The postoperative respiratory disturbance index and lowest oxyhemoglobin desaturation were 12.8 +/- 6.9 and 86% +/- 5%, respectively. The modified hyoid suspension procedure appears to offer significant adjunctive treatment for hypopharyngeal obstruction in obstructive sleep apnea syndrome.

  View details for Web of Science ID A1994PX41300004

  View details for PubMedID 7991249

• CONTROVERSIES IN THE DIAGNOSIS OF NARCOLEPSY 4th International Conference on Narcolepsy Guilleminault, C., Mignot, E., Partinen, M. AMER SLEEP DISORDERS ASSOC. 1994: S1–S6

  Abstract

  The diagnosis of narcolepsy can be problematic. Most sleep laboratories use polygraphic testing to establish the diagnosis. One polygraphic recording followed by a single multiple sleep latency test (MSLT) is used to differentiate the causes of syndromes with complaints of daytime somnolence. Prospective investigations have demonstrated that patients with periodic leg movements or upper airway resistance syndrome may present abnormal sleep latencies and more than one sleep onset rapid eye movement period (SOREMP) during MSLT. On the other hand, investigations of patients with daytime sleepiness and cataplexy have shown that the MSLT may not show more than one SOREMP. The combination of history of cataplexy and more than one SOREMP during MSLT is the best clinical determinant of narcolepsy. History of daytime sleepiness and presence of more than one SOREMP during MSLT, however, is a poorer discriminant of narcolepsy than history of cataplexy, particularly in an aging population.

  View details for Web of Science ID A1994QD08100002

  View details for PubMedID 7701189

• TWIN STUDIES IN NARCOLEPSY 4th International Conference on Narcolepsy Partinen, M., Hublin, C., Kaprio, J., Koskenvuo, M., Guilleminault, C. AMER SLEEP DISORDERS ASSOC. 1994: S13–S16

  Abstract

  The genetic basis of narcolepsy is reflected by the strong association to human leukocyte antigen DR2 (most specifically to DQB1-0602) and the occasional familial occurrence, with several modes of transmission. At present, 12 monozygotic pairs with at least one affected twin have been reported. Of the three pairs considered concordant, the only well-documented pair is DR2 negative. Of the nine discordant pairs five are well documented, and all of these are DR2 positive. We performed a questionnaire study using a validated measure of narcoleptic symptoms (the Ullanlinna narcolepsy scale or UNS). The questionnaire was sent to 2,191 monozygotic twin pairs included in the Finnish Twin Cohort. In 225 pairs neither of the twins responded. In 1,550 pairs both twins responded, but in the answers of 228 pairs there were some missing data concerning the UNS items. Not a single case suggestive of narcolepsy was found. Narcolepsy in monozygotic twins is very rare. These facts support the hypothesis of a multifactorial etiology with a strong influence of nongenetic environmental factors.

  View details for Web of Science ID A1994QD08100004

  View details for PubMedID 7701193

• TRAFFIC ACCIDENTS IN COMMERCIAL LONG-HAUL TRUCK DRIVERS - THE INFLUENCE OF SLEEP-DISORDERED BREATHING AND OBESITY SLEEP Stoohs, R. A., Guilleminault, C., Itoi, A., Dement, W. C. 1994; 17 (7): 619-623

  Abstract

  This study assesses a possible independent effect of sleep-related breathing disorders on traffic accidents in long-haul commercial truck drivers. The study design included integrated analysis of recordings of sleep-related breathing disorders, self-reported automotive and company-recorded automotive accidents. A cross-sectional population of 90 commercial long-haul truck drivers 20-64 years of age was studied. Main outcome measures included presence or absence, as well as severity, of sleep-disordered breathing and frequency of automotive accidents. Truck drivers identified with sleep-disordered breathing had a two-fold higher accident rate per mile than drivers without sleep-disordered breathing. Accident frequency was not dependent on the severity of the sleep-related breathing disorder. Obese drivers with a body mass > or = 30 kg/m2 also presented a two-fold higher accident rate than nonobese drivers. We conclude that a complaint of excessive daytime sleepiness is related to a significantly higher automotive accident rate in long-haul commercial truck drivers. Sleep-disordered breathing with hypoxemia and obesity are risk factors for automotive accidents.

  View details for Web of Science ID A1994PR32700008

  View details for PubMedID 7846460

• MODAFINIL BINDS TO THE DOPAMINE UPTAKE CARRIER SITE WITH LOW-AFFINITY SLEEP Mignot, E., Nishino, S., Guilleminault, C., Dement, W. C. 1994; 17 (5): 436-437

  View details for Web of Science ID A1994PE28600006

  View details for PubMedID 7991954

• Ambulatory monitoring of blood pressure in patients with sleep-disordered breathing. Journal of cardiovascular risk Chervin, R. D., Guilleminault, C. 1994; 1 (2): 127-131

  Abstract

  Patients with obstructive sleep apnea and other sleep-related breathing disorders that cause sleep disruption frequently present with abnormal circadian blood pressure patterns or frank hypertension. Ambulatory blood pressure monitoring has been useful in research documenting nocturnal hypertension and the normalization of blood pressure when sleep apnea is treated. In practice, similar measurements can provide a clue to the presence of an undiagnosed sleep disorder and can be valuable in following the blood pressure response to the treatment of sleep-disordered breathing.

  View details for PubMedID 7606623

• THE PREVALENCE OF NARCOLEPSY - AN EPIDEMIOLOGIC-STUDY OF THE FINNISH TWIN COHORT ANNALS OF NEUROLOGY Hublin, C., Kaprio, J., Partinen, M., Koskenvuo, M., Heikkila, K., KOSKIMIES, S., Guilleminault, C. 1994; 35 (6): 709-716

  Abstract

  We investigated the prevalence of narcolepsy using a well-defined white population previously used for epidemiological investigations: the Finnish Twin Cohort. The Cohort consists of 13,888 monozygotic and dizygotic twin pairs born before 1958. There were 16,179 individuals who participated in the study, with a 77.3% response rate. The study methodology included a questionnaire covering sleep and alertness, the Ullanlinna Narcolepsy Scale (UNS), a scale specifically developed and tested for the study, telephone interviews, and finally, clinical evaluation, polygraphic recording, and HLA blood typing. Seventy-five subjects were selected for telephone interviews and laboratory evaluations based on data from both questionnaires. Five of them were strongly suspected of narcolepsy, but laboratory data identified only 3. All were dizygotic (fraternal) twins discordant for the disease with a negative family history and presence of DR2 DQw1 (i.e., DRw15 DQw6, new World Health Organization classification). The prevalence of narcolepsy in the Finnish population is 0.026% (95% confidence interval, 0.0-0.06). This prevalence is lower than that reported in studies performed without polygraphic recording and is close to that reported in 1945 in the black U.S. population. The tools developed to perform this study, the largest population study of its kind yet performed, can now be used for other population investigations.

  View details for Web of Science ID A1994NQ97300011

  View details for PubMedID 8210228

• DEFINITION OF THE SUDDEN-INFANT-DEATH-SYNDROME BRITISH MEDICAL JOURNAL Rambaud, C., Guilleminault, C., Campbell, P. E. 1994; 308 (6941): 1439-1439

  View details for Web of Science ID A1994NP42000050

  View details for PubMedID 7993420

• STABILITY OF CATAPLEXY OVER SEVERAL MONTHS - INFORMATION FOR THE DESIGN OF THERAPEUTIC TRIALS SLEEP Gelb, M., Guilleminault, C., Kraemer, H., Lin, S., Moon, S., Dement, W. C., Mignot, E. 1994; 17 (3): 265-273

  Abstract

  Twenty-seven narcoleptic patients severely affected with cataplexy completed four symptom diaries over a 4-month period in order to clarify some of the controversies surrounding assessment of anticataplectic medications. The home diary method was found to be a viable model for the assessment of anticataplectic activity. Assessment of reliability in 1-, 2-, 3-, 4-, 5- and 10-day intervals indicated that reliability increases with the number of days included. A 10-day design was found to be optimal. Reliability decreased, however, with each successive diary over the 4-month period. Power analysis indicates that two groups of 30-40 subjects in a parallel design, or one group of 30-40 subjects in a crossover design, would be sufficient to demonstrate a significant therapeutic anticataplectic effect in most cases. A "first diary effect" was observed, suggesting that a training period prior to the actual trial might improve reliability. Whether the patient was treated or untreated with stimulant medications did not affect severity or fluctuation of cataplexy, suggesting that both groups of patients could be included in therapeutic trials. No time-of-day fluctuation was observed in the daily distribution of cataplexy attacks. Sudden increases in cataplexy were often, although not always, caused by unusual emotional events or sleepiness. The finding of a long-lasting "precataplectic" feeling or "aura" pointed to the need to carefully clarify the symptom prior to beginning a therapeutic trial.

  View details for Web of Science ID A1994NQ80400010

  View details for PubMedID 7939127

• SLEEP FRAGMENTATION IN NORMALS - A MODEL FOR SLEEPINESS ASSOCIATED WITH UPPER AIRWAY-RESISTANCE SYNDROME SLEEP Philip, P., Stoohs, R., Guilleminault, C. 1994; 17 (3): 242-247

  Abstract

  Eight young adults underwent 1 night of auditory sleep fragmentation followed by four naps of the multiple sleep latency test and performance testing the next day. A latin-square design was used to compare results with baseline. Efforts were made to eliminate effects of learning on repeated performance tests. A mean of 303 arousals, lasting a mean of 11 seconds, disrupted nocturnal sleep. This sleep fragmentation was induced to mimic as closely as possible the nocturnal sleep disruption seen in subjects with upper airway resistance syndrome. There was a significant disruption of nocturnal sleep architecture with a significant overall decrease in slow-wave sleep (SWS) and a significant but more moderate decrease in rapid eye movement (REM) sleep during the fragmented night. The most interesting finding related to analysis by thirds of the night, which indicated an important increase over time in arousal threshold during SWS followed by REM sleep. This threshold increase was associated with a parallel increase in dB(A) levels needed to induce an arousal. Stages 1 and 2 nonrapid eye movement (NREM) sleep were less affected by the stimulation, but the amount of stage 1 NREM sleep decreased from the beginning to the end of the night, again indicating an increase in pressure to sleep. Following 1 night of sleep fragmentation, subjects had significantly shorter sleep latencies on the multiple sleep latency test for naps 2, 3 and 4. There was a significant relationship between percent nocturnal SWS and mean sleep latencies. The selected performance tests were not affected by 1 night of sleep fragmentation, despite the obvious sleepiness.

  View details for Web of Science ID A1994NQ80400007

  View details for PubMedID 7939124

• LOAD DETECTION IN SUBJECTS WITH SLEEP-INDUCED UPPER AIRWAY-OBSTRUCTION AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE Clerk, A. A., Duncan, S. R., Guilleminault, C. 1994; 149 (3): 727-730

  Abstract

  Respiratory flow-resistive load detection in obese patients has been shown to be impaired. We tested the hypothesis that there is no difference in inspiratory flow-resistive load detection measured in nonobese obstructive sleep apnea patients, nonobese snorers, and normal control subjects. Eleven male obstructive sleep apnea patients and seven male snorers were investigated and compared with 10 normal male control subjects. Severely obese patients (body mass index, BMI > 35 kg/m2) were excluded. Patients were investigated by nocturnal polysomnography with measurement of esophageal pressure (Pes). Awake pulmonary function tests were performed before the investigation. Airway resistance (Raw) and lung volumes were measured with plethysmography. Resistive loads were investigated according to Tapper and associates (13) and Killian and associates (12). Resistances were applied for the duration of one inspiratory cycle and a minimum of two breaths allowed between each resistive load. Six different resistances plus background shams were presented 10 times in random order. Flow, pressure, and subject response were recorded with a calibrated multichannel recorder. Subjects signaled detected changes of inspiratory resistance with a hand-held signaling device. The probability of detecting a particular resistance was calculated as the ratio of correct identification to the number of presentations (i.e., 10). The resistance corresponding to a 0.5 probability of detection was determined. The Weber fraction (wf) calculated as delta R/R(apparatus) +Raw. There were no differences between nonobese subjects and controls in terms of resistive load detection.

  View details for Web of Science ID A1994NP71900028

  View details for PubMedID 8118643

• THE SLEEP DISORDERS QUESTIONNAIRE-I - CREATION AND MULTIVARIATE STRUCTURE OF SDQ SLEEP Douglass, A. B., Bornstein, R., NINOMURCIA, G., Keenan, S., Miles, L., Zarcone, V. P., Guilleminault, C., Dement, W. C. 1994; 17 (2): 160-167

  Abstract

  The development of the Sleep Disorders Questionnaire (SDQ) from the Sleep Questionnaire and Assessment of Wakefulness (SQAW) of Stanford University is described in detail. The extraction of the best question items from the SQAW and their subsequent rewording in the SDQ to insure greater completion rates are described. Two item test-retest reliability studies are reported on 71 controls and on 130 sleep-disorder patients, which confirmed adequate reliability. To create multivariate scoring scales, SDQ was then given in a multicenter study to 519 persons, 435 of whom were sleep-disorder patients with full polysomnography. Canonical Discriminant Function Analysis was employed, which resulted in four clinical-diagnostic scales: SA for sleep apnea, NAR for narcolepsy, PSY for psychiatric sleep disorder and PLM for periodic limb movement disorder. Each was adjusted for male and female responses and transformed to a percentile using the observed distribution of raw scores. Using Receiver Operating Characteristics analysis, cutoff points were determined for each scale to maximize its sensitivity and specificity. Positive and negative predictive values were also calculated. The SA and NAR scales proved to be the most discriminating.

  View details for Web of Science ID A1994NJ63400007

  View details for PubMedID 8036370

• DIAPHRAGM PACING - REVIEW AND REASSESSMENT SLEEP Chervin, R. D., Guilleminault, C. 1994; 17 (2): 176-187

  View details for Web of Science ID A1994NJ63400010

  View details for PubMedID 8036373

• SLEEP-APNEA AND HYPERTENSION IN COMMERCIAL TRUCK DRIVERS 3rd International Conference on Sleep and Breathing Stoohs, R. A., Guilleminault, C., Dement, W. C. AMER SLEEP DISORDERS ASSOC. 1993: S11–S14

  View details for Web of Science ID A1993MW45700007

  View details for PubMedID 8177995

• EXCESSIVE DAYTIME SOMNOLENCE IN WOMEN WITH ABNORMAL RESPIRATORY EFFORTS DURING SLEEP 3rd International Conference on Sleep and Breathing Guilleminault, C., Stoohs, R., Clerk, A., Simmons, J., LABANOWSKI, M. AMER SLEEP DISORDERS ASSOC. 1993: S137–S138

  Abstract

  An abnormal level of respiratory efforts, indicated by significant increase in peak negative esophageal pressure (Pes), can be associated with daytime somnolence in snoring pre-menopausal women. No drop in oxygen saturation (SaO2) or visual evidence of transient electroencephalographic (EEG) arousals can be found at repeat polysomnography. Nasal continuous positive airway pressure (CPAP) titrated on Pes measurements eliminates somnolence.

  View details for Web of Science ID A1993MW45700051

  View details for PubMedID 8011017

• SELECTED CARDIOVASCULAR RISK-FACTORS IN PATIENTS WITH OBSTRUCTIVE SLEEP-APNEA - EFFECT OF NASAL CONTINUOUS POSITIVE AIRWAY PRESSURE (N-CPAP) 3rd International Conference on Sleep and Breathing Stoohs, R. A., Facchini, F. S., Philip, P., VALENCIAFLORES, M., Guilleminault, C. AMER SLEEP DISORDERS ASSOC. 1993: S141–S142

  View details for Web of Science ID A1993MW45700053

  View details for PubMedID 8178008