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Biomedical subjects

C Guilleminault

Publications and source records attributed to C Guilleminault.

At least 181 records · Page 10Linked to original sources
PubMed1994

The Sleep Disorders Questionnaire. I: Creation and multivariate structure of SDQ.

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.

Adult↗
PubMed1994

Stability of cataplexy over several months--information for the design of therapeutic trials.

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.

Catalepsy↗
PubMed1994

Controversies in the diagnosis of narcolepsy.

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.

Adolescent↗
PubMed1994

Twin studies in narcolepsy.

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.

Adult↗
PubMed1994

DQB1*0602 and DQA1*0102 (DQ1) are better markers than DR2 for narcolepsy in Caucasian and black Americans.

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.

Black People↗
PubMed1994

Epidemiology of narcolepsy.

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.

Adult↗
PubMed1994

Load detection in subjects with sleep-induced upper airway obstruction.

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.

Adult↗
PubMed1994

Obstructive sleep apnea and the hyoid: a revised surgical procedure.

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.

Adult↗
PubMed1994

Ambulatory monitoring of blood pressure in patients with sleep-disordered breathing.

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.

Blood Pressure↗
PubMed1994

Traffic accidents in commercial long-haul truck drivers: the influence of sleep-disordered breathing and obesity.

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.

Accidents, Traffic↗
PubMed1994

Sleep fragmentation in normals: a model for sleepiness associated with upper airway resistance syndrome.

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.

Adult↗
PubMed1993

Aging, respiratory efforts during sleep, and pulsus paradoxus.

Forty patients with either obstructive sleep apnea syndrome or a clinical complaint of daytime sleepiness with measured nocturnal increase in upper airway resistance and snoring were investigated during sleep for the presence of pulsus paradoxus, which is defined as a decrease in systolic blood pressure (SBP) of at least 10 mmHg during inspiration. Two thirds of the subjects presented pulsus paradoxus. Age, lowest oxygen saturation (SaO2), and negative inspiratory esophageal pressure nadir (an index of inspiratory effort) were the only studied variables which could statistically dissociate patients presenting pulsus paradoxus. We then divided the patient population into three different subgroups of equal number based upon the degree of decrease in SBP (i.e., > 20 mmHg, < 20 but > 10 mmHg, and < 10 mmHg). In this second analysis, age was the only significant variable that separated the three groups. Lowest SaO2 could not be used to statistically separate subjects with mild to moderate pulsus paradoxus from those without it; and negative inspiratory esophageal pressure measurements could only significantly identify subjects with severe pulsus paradoxus (i.e., > 20 mmHg) from those without any pulsus paradoxus. The variable which correlated best with age was negative inspiratory esophageal pressure nadir (R = 0.83). Our interpretation is that as age increased, negative inspiratory esophageal pressure became less negative, due to the known impact of aging on muscles, and pulsus paradoxus was no longer observed.

Adult↗
PubMed1993

Light therapy as treatment of dyschronosis in brain impaired children.

Fourteen children aged 9 months-4 years with moderate to severe mental retardation and varying neurologic lesions were referred for severe and continuous nocturnal sleep disturbances and very abnormal day/night schedules. All children had previously been given hypnotic medications and behavioral treatments which had little or no effect on nocturnal sleep. The severity of the sleep disturbances significantly affected family life and was a major handicap to the children. All children were treated with light therapy (minimum 4000 lux). Five children responded to treatment and had normal sleep-wake cycles at the most recent post-treatment evaluation (2-5 years after the first treatment). Two of the patients' families were unable to follow the prescribed regimen. Treatment failed in 7 children. One of these seven children spontaneously improved 3 years later. In three of the failure children the neurologic problem progressively worsened, leading to death in one of them. Phototherapy is a treatment worth pursuing in children with very significant sleep/wake disruption which is unresponsive to behavioral or other treatments. It has few side-effects and may lead to normalization of the sleep-wake cycle. Recent improvement in the technology used to monitor the 24-h temperature rhythm over several days and the present commercial availability of "light boxes" should render these therapeutic trials easier than at the time of these initial investigations.

Brain Diseases↗
PubMed1993

Canine cataplexy is preferentially controlled by adrenergic mechanisms: evidence using monoamine selective uptake inhibitors and release enhancers.

Narcolepsy is currently treated with anti-depressants to control REM-related symptoms such as cataplexy and with amphetamine-like stimulants for the management of sleepiness. Both stimulant and antidepressant drugs presynaptically enhance monoaminergic transmission but both classes of compounds lack pharmacological specificity. In order to determine which monoamine is selectively involved in the therapeutic effect of these compounds, we examined the effects of selective monoamine uptake inhibitors and release enhancers on cataplexy using a canine model of the human disorder. A total of 14 compounds acting on the adrenergic (desipramine, nisoxetine, nortriptyline, tomoxetine, viloxazine), serotoninergic (fenfluramine, fluoxetine, indalpine, paroxetine, zimelidine) and dopaminergic (amfonelic acid, amineptine, bupropion, GBR 12909) systems were tested. Some additional compounds interesting clinically but with less pharmacological selectivity, i.e., cocaine, dextroamphetamine, methylphenidate, nomifensine and pemoline, were also included in the study. All compounds affecting noradrenergic transmission completely suppressed canine cataplexy at low doses in all dogs tested, whereas compounds which predominantly modified serotoninergic and dopaminergic transmission were either inactive or partially active at high doses. Our results demonstrate the preferential involvement of adrenergic systems in the control of cataplexy and, presumably, REM sleep atonia. Our findings also demonstrate that canine narcolepsy is a useful tool in assessing the pharmacological specificity of antidepressant drugs.

Adrenergic Agents↗
PubMed1993

Does snoring intensity predict flow limitation or respiratory effort during sleep?

We tested whether snoring sound intensity could be an accurate predictor of the degree of respiratory effort or the decrease of inspiratory volume during partially obstructed breathing in sleep. Six snorers were investigated with nocturnal polygraphic monitoring including measurement of esophageal pressure (Pes), airflow (pneumotachometer and face mask, indicating tidal volume [VT]), and snoring sound intensity (SSI) measured in decibels. SSI was a poor predictor of flow limitation during snoring. Considerable between- and within-subject variance did not allow establishment of models for the interdependence between VT and SSI. The increase in peak-negative inspiratory efforts was better predicted by SSI. Individual multiple correlation analyses of Pes on SSI indicated a positive interdependence in all subjects. Calculation of ecological correlations with subject means of Pes and SSI was performed. SSI significantly predicted the level of peak-negative inspiratory effort during obstructed, noisy breathing for a given subject. Monitoring of snoring sound intensity may be a useful indicator identifying subjects performing high peak negative inspiratory efforts with obstructed, noisy breathing during sleep.

Analysis of Variance↗
PubMed1993

Upper airway resistance in infants at risk for sudden infant death syndrome.

To investigate the relationship between sudden infant death syndrome and upper airway obstruction, we studied 14 term infants at a mean age of 11 weeks who had been identified as being at risk for sudden infant death syndrome on the basis of clinical and family histories and polygraphic monitoring. Respiratory efforts during sleep were investigated by esophageal pressure monitoring (all 14 infants) and by monitoring of flow with a pneumotachometer (6 infants). During apparently normal sleep, increased respiratory efforts were shown by intermittent increases in the magnitude of the negativity of esophageal pressure. Mild changes in tidal volume occurred occasionally, always at the lowest monitored esophageal pressure of a breath sequence. These tidal volume decreases had no impact on oxygen saturation but led to a short arousal and decreased respiratory efforts, followed by a return to normal breathing. Occasionally the abnormal increase in upper airway resistance did not lead to an immediate arousal but instead to a short obstructive apnea that was then followed by an arousal. This investigation indicates the importance of arousal mechanisms in maintaining normal breathing during sleep. Any disruption of the arousal mechanisms during sleep (including sleep fragmentation caused by repetitive arousals) may place these infants with increased upper airway resistance at risk for obstructive apnea during sleep.

Airway Resistance↗