EXPEHIMENTAL
NEUROLOGY
Obstructive
CHRISTIAN
62, 48-67 (1978)
Sleep Apnea: Electromyographic and Fiberoptic Studies
GUILLEMINAULT, MICHAEL W. HILL, F. BLAIR AND WILLIAM C. DEMENT 1
SIMMONS,
Sleep Disorders Clinic and Research Center and Department of Otolaryngology, Stanford University School of Medicine, Stanford, California 94305 Received October l&1977;
revision received June 19,197s
Seventeen predominantly obstructive sleep apnea patients and four normal controls (all adult males) underwent one or both investigative protocols : (A) A fiberoptic endoscope was introduced intranasally into the pharynx and subjects were monitored continuously and filmed intermittently during wakefulness and sleep. (B) Muscles selected because of their anatomical importance in maintaining the oropharynx during the respiratory cycle were electromyographically implanted intraorally or, in tracheostomy patients, at time of surgery, and subjects were polygraphically monitored during wakefulness and sleep. In both protocols, standard electroencephalogram, chin electromyogram (EMG), electrooculogram (EOG) , and respiration were monitored simultaneously. During fiberoptic studies obstructive apnea during sleep first appeared as a partial or total invagination of the posterolateral pharyngeal walls, while the laryngeal inlet remained patent. EMG recordings showed normal firing patterns in patients during unobstructed sleep. During sleep-induced obstructive apnea, however, a significant decrease or complete disappearance of EMG activity was observed in the palatoglossus, palatopharyngeus, genioglossus, superior and middle constrictors of the pharynx, and stylopharyngeus. The obstruction involves absence, during inspiration, of the activity in the pharyngeal dilators needed to counteract the loads abruptly imposed by intrathoracic negative pressure changes. Abbreviations : EEG-eIectroencephalogram ; EMG-electromyogram ; EOG-electrooculogram; REM, NREM-rapid eye movement, non rapid eye movement; SIDS -sudden infant death syndrome. l This research was supported by National Institute of Neurological and Communicative Disorders and Stroke Grant NS 10727, Public Health Service Research Grant R.R.-70 from the General Clinical Research Centers, and by INSERM to C.G. Information and reprint requests should be addressed to Sleep Disorders Clinic (Dr. Guilleminault) , Stanford University School of Medicine, Stanford, California 94305. Drs. Hill and Simmons are in the Department of Otolaryngology. 48 0014-4886/78/0621-0048$02.00/O Copyright 0 1978 by Academic Press,Inc. All rights of reproduction in any form reserved.
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INTRODUCTION Studies of patients complaining
of excessive
daytime
sleepiness demon-
strated the existence, in a number of these patients, of a predominantly obstructive sleep apnea syndrome (5). During the last several years further investigations combined with multiple nocturnal monitorings have revealed that sleep-induced apnea may precede excessive daytime sleepiness by many years and may result in severe nocturnal hypoxia, cardiac arrhythmias, and hemodynamic changes (1, 15, 16). Questions have been raised about the possible involvement of the sleep apnea syndrome in sudden adult death occurring during sleep, and a possible relationship between the sudden infant death syndrome (SIDS) and sleep apnea has been hypothesized (9, 14). We demonstrated the occurrence of obstructive apneas in infants “near miss for SIDS,” in children, and in adults. Many questions about this complex syndrome remain unanswered. The primary cause of sleep apnea syndromes is, in most cases, unknown. Involvement of the central nervous system has been suspected in the development of diaphragmatic-related apnea ; peripheral and central factors have been thought to contribute to the appearance of obstructive apnea. The precise pathogenesis of periodic upper airway occlusion during sleep, however, is uncertain. It is clear that functional airway obstruction takes place in the upper respiratory passage because treatment by tracheostomy, kept open during sleep, dramatically reverses most of fhe symptoms and pathological findings. Until recently, however, the exact site and mechanism of this functional airway obstruction remained obscure. During the last two years we studied the anatomical dynamics that ,take place in the oral and hypopharynx during sleep in patients with obstructive sleep apnea syndrome using the techniques of fiberoptic direct visual examination and filming during wakefulness and during rapid eye movement (REM) and nonrapid eye movement (NREM) sleep. In addition, we simultaneously recorded, before and after tracheostomy, EMG activity of specific muscles that appear to be involved in the obstructive phenomenon. SUBJECTS
AND
METHODS
The present study involved 17 adult patients with predominantly obstructive sleep apnea syndrome and four normal control subjects. All gave informed consent before participation. Nine sleep apnea patients and two normal controls took part in both phases of the study, i.e., fiberoptic scope and electromyographic (EMG) protocols ; eight patients and two normal controls participated in only one aspect of the study. All participants were male and their ages were 24 to 63 years.
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The sleep apnea patients (30 to 63 years of age) presented severe obstructive sleep apnea previously documented by several all-night polygraphic monitorings. Their mean apnea index (number of apneas per sleep-hour) was 96, (The mean apnea index of the normal group was less than 3.) A mean of 93% (range, 88 to 9.5%) of their apneic episodes was obstructive. All patients were heavy snorers and presented with clinical symptomatology typical of the obstructive sleep apnea syndrome previously described (3). The normal control group consisted of four adult males, ages 24 to 43 years. None of them had a sleep disorder, none snored, and all were in general good health. All had been monitored during sleep prior to the study, and sleep apnea syndrome had been ruled out. Two complementary experimental protocols were carried out: (A) fiberoptic endoscope examinations of the pharynx and larynx during wakefulness and sleep ; and (B) selective EMG recordings from muscles of the upper airway. Fiberoptic Studies. Fiberoptic nasal endoscopy was carried out on 14 sleep apneic patients and three control subjects (all male). After achieving topical anesthesia of the nasal mucosa with 4% cocaine or 2% pentocaine, a Machida fiberoptic endoscope was imroduced intranasally into the pharynx. The scope was left in place during wakefulness and while 5 to 8 h nocturnal sleep were monitored. All subjects slept in a hospital bed, at the head of which a 16-mm Bolex camera was attached. The ocular of the Machida endoscope was suspended and securely fixed to a movie camera, or to a video camera to allow cominuous monitoring of the airway dynamics on a portable television monitor. An observer continuously watched the video screen or through the ocular of the camera’s viewfinder (see Fig. 1). Film resolution is greater than that from a videotape, and both techniques have been used during the same night on the same subject. Simultaneous polygraphic recording of electroencephalogram (EEG) ( Ca/As-CI/A1 of the international 10-20 system), digastric electromyogram (EMG) , electrooculogram (EOG) , and measurements from thermistors and abdominal and thoracic strain gauges were obtained in all cases. The continuous monitoring gave simultaneous information as to onset, type, and duration of apnea. Filming was intermittent, linked to one apnea event or to a train of apneas during different sleep stages. A marker automatically indicated on the polygraphic tracing the beginning and ending of filmed sequences. Visual observation and filming were done at several levels in the pharynx. Thus, direct visualization and filming at the site of the vocal cords were possible as well as placement of the scope high in the oropharynx for observation of the posterior part of the tongue. There were
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no complications from advancing and retracting the endoscope manually or using the telescopic lens of the endoscope (see Fig. 1). Electronzyographic Studies. Twelve patients with obstructive sleep apnea and three normal control subjects participated in the EMG study (nine of these patients and two of the controls also underwent t’he fiberoptic protocol repor.ted above). Eight patients were recorded before tracheostomy ; four patients had electrodes implanted at the time of tracheostomy and were studied 36 to 72 h after surgery. Before Tracheosto?~~~~. The recording electrodes were placed intraorally. The area chosen for the recording site was topically anesthesized with 470 xylocaine or 4% cocaine. The electrodes were then placed in position using a 22-gauge spinal needle. A minimum distance of 2 mm was obtained between the muscle ends of the recording electrodes to prevent short circuiting. The free ends of the recording electrodes were brought out through the nose and taped to the skin for later recording. The nasal route was safer than that through the mouth in terms of accidental dislodgment by the tongue and seemed to be less annoying to the patients. After intraoral placement, the free ends were retrieved by placing a catheter through the nose and into the oropharynx. After securing the wires to the catheter, its withdrawal brought the wires through the nasopharynx and out the external nares. After Tracheostomy. Certain muscles cannot be implanted accurately and/or safely either intraorally or percutaneously in an awake patient using topical anesthesia. These muscles (cricopharyngeus, inferior constrictor, and the inferior edges of the middle constrictor) were implanted under direct vision at the time of tracheostomy. The free ends of the electrodes were brought out through the anterior cervical neck skin several centimeters from the tradheostomy site. In these cases the recordings were carried out 36 .to 72 h after surgery with the tracheostomy open and closed (reproducing the typical syndrome). Patients were not monitored immediately following surgery in order to avoid any effect of general anesthesia or postsurgery edema. Recordings were obtained during 5 to S nocturnal hours and included quiet wakefulness and NREM and REM sleep. Before falling asleep, patients were asked to emit sound, swallow, hold their breath, etc., and muscle activity was recorded during these maneuvers. Polygraphic monitoring included standard sleep parameters and maintenance of strain In patients 1 to 4, the palatoglossus, palatogauges and thermistors. pharyngeus, cricopharyngeus, stylohyoid, and genioglossus muscles were simultaneously monitored. Patients 5, 6, 7, and 12 had electrodes implanted in the superior, middle, and inferior constrictors of the pharynx and in the lateral part of the middle constrictor at the level of the stylopharyngeus
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FIBEROPTICS NASOPHARYNGOSCOPE \
POSITION OF SCOPE TIP
\
1 BED
HEADBOARD
FIG. 1. Presentation of setting for fiberoptic scope study. Filming is done in conjunction with polygraphic recording. Video monitoring of the oropharynx is continuous from the adjacent room.
muscle. Control subjects had electrodes placed in the inferior, middle, and superior constrictors of the pharynx-laterally at the level of the stylopharyngeus-and in the genioglossus. Patients 8, 9, 10, and 11 were implanted during tracheostomy under general anesthesia with electrodes placed in the superior, middle, and inferior constrictors of the pharynx and at the level of the stylopharyngeus muscle. Electrodes also were placed in the genioglossusand, in two cases,in the cricopharyngeus. RESULTS Fiberoptic Studies. The presence of the endoscopedid not impair respiration during sleep. No statistical increase in the number of apneas, compared to monitoring on the previous night without endoscopy, was noted. No obstruction was seen in the control subjects during sleep. Contraction of the pharyngeal walls was noted during swallowing. During wakefulness, no obstruction or cause for obstruction was seen in the patient group, and during nonobstructed periods of both NREM and REM sleep, a patent pharynx was clearly visible. On inspiration, the vocal cords abducted widely, then returned to an intermediate position during expiration, as expected. During sleep-related obstructive apnea, the initial and most important feature was the progressive opposition of the lateroposterior
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pharyngeal walls. This closure always started in the oropharynx. Visual observations of the posterior part of the tongue showed that it was not the initator of the obstructive phenomenon in the patients studied. The abrupt collapse of the airway always occurred at the onset of inspiration, and the pharyngeal obstruction looked like a “mismatch” with the respiratory cycle. The pharyngeal contour might or might not be restored to normal at the end of the inspiratory cycle. Some incomplete obstructions, based on polygraphic criteria and termed “hypopnea”, reduced the diameter of the airway, but some airflow persisted, and endoesophageal pressure greatly increased during these episodes. By advancing the scope to the supraglottic area, the laryngeal inlet was seen to be patent during obstructive apnea. The vocal cords exhibited normal inspiratory abduction despite the absence of a normal upward airflow pattern. In our population these fiberoptic studies documented no evidence of glottic obstruction ; the palate was not pushed posteriorly by the tongue during an apneic episode. The lateral and posterior pharyngeal walls collapsed at the level of the oropharynx and produced the obstruction. Figures 2 and 3 present sequences of incomplete and complete pharyngeal collapse during obstructive apnea. The reproductions of filmed sequences indicate rather clearly the posteroanterior progression of the occlusive phenomenon. In one sequence (Fig. 3), the root of the tongue can be seen fairly clearly anteriorly during the occurrence of the obstructive phenomenon, with progressive imagination of the posterolateral pharyngeal walls. Electrow~yograplaic Studies. The EMG findings were not a function of a specific state of sleep (NREM or REM sleep) ; during obstructive apnea similar EMG activity was observed regardless of the sleep state. During sleep, normal controls had a low level of muscle activity in the constrictors; however, a burst of muscle activity was recorded from the electrodes placed laterally at the level of the stylopharyngeus concomitant with inspiration. As shown in Fig. 4, this burst of inspiratory muscle activity was also seen during REM sleep, and even during bursts of rapid eye movements. In sleep apnea patients, during sleep-related obstructive apnea, no change was observed in the E&IG activity of the stylohyoid, the cricopharyngeus, or the inferior constrictor of the pharynx, compared to prior recordings during unobstructed sleep. A significant decrease in EMG activity was recorded during obstructive apnea, however, in the palatoglossus, palatopharyngeus, genioglossus, superior and middle constrictors of the pharynx, and in the lateral part of the middle constrictor at the level of the stylopharyngeus. Figures 5 through 9 show muscle activity during obstructive apneas. In one patient, one muscle fiber was implanted, and complete
7
POSTERIOR PHA~AflYfEAL
FIG. 2. Sequence of incomplete pharyngeal collapse during sleep in a patient with obstructive lapse of the posterolateral walls of the pharynx and the incomplete occlusion of the airway.
ARYEPIGLOTTIC FOLD
sleep apnea. Note the progressive
COI-
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FIG. 6. Recordings from a 38-year-old obstructive sleep apneic patient during stage 2 NREM sleep. Channel l-EMG recorded with bipolar electrodes implanted in the palatopharyngeus ; channel Z-EMG recorded with bipolar electrodes in the palatoglossus; channel 3-thermistor.
FIG. 7. Recording 3 days postsurgery with tracheostomy closed in a 53-year-old obstructive sleep apneic patient. The patient is in stage ‘2 NREM sleep. One muscle fiber was implanted in the right stylopharyngeus. Pharyngeal EMG electrodes were implanted under general anesthesia during tracheostomy surgery. Channel I-EEG ((L/As), channel 2-EOG, channel 3-digastric EMG, channel 4-bipolar electrodes implanted in the right stylopharyngeus, channel S-EMG obtained from a third electrode implanted in the same area and referred to a neutral electrode. (Several batches of electrodes were implanted in the same muscles at the time of surgery because some could become dislodged during the two postsurgery days.) Channel 6-EMG from the proximity of the inferior constrictor of the pharynx. Respiration was analyzed from recordings obtained from nasal thermistor and abdominal strain gauge (channels 7 and 8). Note the sudden stylopharyngeal EMG silence during the obstructive apnea.
FIG. 8. Example of obstructive hypopnea during sleep in a 36-year-old male with obstructive sleep apnea. Channel 7 (from the top) monitored EMG activity of the genioglossus and channel 8 EMG ofthe middle constrictor of the pharynx. Note the dissociation of EMG activity in the two muscles; the middle constrictor of the pharynx stops firing, but the genioglossus is still active.
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silence was obtained during the obstruction. In this case the electrodes were implanted at the time of tracheostomy surgery under general anesthesia. The electrodes were believed to be accurately placed in the stylopharyngeus. During the all-night recording patients also experienced incomplete obstruction (obstructive hypopnea), shown in Fig. 2. Figure 8 shows electromyographic tracings from the genioglossus and the middle constrictor of the pharynx during an hypopneic event. As Fig. 8 shows, there was complete EMG silence in the middle constrictor, but bursts of EMG activity persisted in the genioglossus. Obstructive sleep apneic patients have some central apneic events, involving the diaphragm, as well as obstructive episodes. Figure 10 shows EMG activity from the genioglossus and the inferior constrictor of the pharynx during one of these central events ; complete muscle inhibition was recorded in the genioglossus. DISCUSSION In 1967, Schwartz and Escande, in a fiberoptic study during sleep in one Pickwickian patient,2 reported (11) that the site of the obstruction during sleep apnea was located in the oropharynx. This, however, was considered controversial for the following decade. We reported similar observations in one obstructive sleep apneic patient (12). Smirne and Comi (13) reported serial X-ray studies in two Pickwickians and one control subject during sleep and wakefulness. Those authors observed during sleep a slight collapse of the pharyngeal wall and interruption of the air column at the level of the soft palate between the base of the tongue and the pharyngeal walls. Weitzman et al. (17) and our group (2, 4) obtained films and videotapes during all-night monitoring that indicated the oropharynx as the site of the obstruction. Remmers et al. (8), measuring supraglottic pressure, also suggested that the oropharynx may be the site of obstruction. But Krieger and colleagues (6), after fiberoptic evaluations of a Pickwickian patient in 1976, located the obstruction at the vocal cord level. Our fiberoptic studies in 14 non-Pickwickian, predominantly obstructive sleep apneic patients indicated that, in this population, the site of the obstruction was supraglottic, in the oropharynx, and that the posterolateral pharyngeal walls were the first to invaginate. Speculation has arisen about the mechanism involved in this obstruction. Weitzman et al. suggested the possibility of an active contraction of the constrictors of the pharynx (17). Also, the role of the tongue in the obstruction has been considered. Sauer2As defined by Burwell, C., E. Robin, R. Whaley, obesity associated with alveolar hypoventilation, Med. 21: 811-818.
and A. Dickelman. 1956. Extreme a Pickwickian syndrome. Am. 1.
FIG. 9. Recording in a S-year-old obstructive sleep apneic patient during stage 2 NREM sleep. Channels 4 and 6 are EMGs recorded from bipolar electrodes implanted in the middle constrictor of the pharynx. Note the marked decrease in muscle activity during this mixed apnea.
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GUILLEMINAULT
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land and Harper (10) reported a loss of genioglossal muscle activity in snorers during sleep. Remmers et al. (8) related genioglossal EMG activity to the “occluded/ventilatory cycle” and measurement of supraglottic pressure. Our results, in the studied population, do not support all the previous assumptions. All oropharyngeal muscles studied demonstrated decreased activity during obstructive apnea ; when respiration resumed muscle activity was recorded at maximum intensity. This finding contradicts hyperactivity of pharyngeal constrictors as the primary factor in sleep-induced obstruction. Our fiberoptic studies demonstrated no vocal cord involvement and confirmed much of the previous data implicating the oropharynx as the site of the obstruction. Most of our observations negate singular involvement of the tongue. Indeed, the pharyngeal walls seem to be the initiator of the obstructive phenomenon. The root of the tongue can be seen in Fig. 3, and invagination (“sucking-in”) of the posterolateral walls apparently precedes movement of the tongue. One could question whether the correlation between esophageal pressure and EMG activity reported by Remmers et al. (8) would have been higher had those authors recorded not only the genioglossus but the pharyngeal constrictors as well, and then selected the middle constrictor of the pharynx as an index of EMG activity. It is interesting to note that EMG activity was completely abolished in the lead in the middle constrictor shown in Fig. 8, with persistence of genioglossal activity, while airflow decreased considerably during obstructive hypopnea (see also Fig. 2). It could be argued that obstruction remains incomplete because of the persistence of genioglossal activity, but that argument also favors the primacy of the pharyngeal walls in the obstruction. Obstruction may eventually incorporate the tongue, but its activity cannot be considered a reliable index of obstruction. It should also be emphasized that when central apnea is monitored, supposedly involving a sudden diaphragmatic inhibition, total inhibition of the genioglossus is observed (see Fig. 10). One of the questions raised by this finding is not why genioglossal activity abruptly ceases during a central apnea, as the respiratory apparatus can be considered as a centrally controlled functional unit, but why there is dissociated diaphragmatic and oropharyngeal muscle activity. From our studies we have elaborated the “tent hypothesis.” Recordings during sleep show that the superior and middle constrictors of the pharynx both decrease EMG activity during obstruction, but the inferior constrictor demonstrates no change in EMG activity before, during, or after obstructive apnea during sleep. The “pharyngeal tent” in our hypothesis refers specifically to the superior and middle constrictors. This tent is transfixed by a thin muscle at the junction of the superior and middle constrictors which then spreads widely beneath the mucous membrane-the stylo-
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Stylopharyngeus
FIG. 11. Anatomical presentation of the constrictors pharyngeus. Left, rostra1 ; right, caudal.
of the pharynx
and stylo-
pharyngeus (see Figs. 11 and 12). It draws the sides of the upper pharynx cranially and laterally, thereby increasing the transverse dimension of the pharynx. It is a pharyngeal dilator. As far as we could tell, decreasedEMG activity occurs in this dilator as well as in the constrictors. One could hypothesize that under normal conditions reflex reinforcement of EMG activity in the pharyngeal dilators occurs during inspiration to counteract the load suddenly imposed by the diaphragm and other accessory inspiratory muscles and by sudden intrathoracic negative pressure changes. This “burst” of muscle activity would need to coordinate with all other respiratory movements. If it does not, or if it occurs at the wrong time (mismatched), obstruction could occur. This schemeis supported by our observations, but we must acknowledge that we have not recorded all muscles involved in the control of the jaw, some of which, although located distantly, may contribute to change in
FIG. 12. Schematic representation of the superior and middle constrictors of the pharynx (the “tent”) and the stylopharyngeus (“string of the tent”, shaded) which “dilate” the tent and hold it out.
66
GUILLEMINAULT
activity
of the genioglossus,
for example,
ET
AL.
as demonstrated
by Lowe
et al.
(7). Additionally, this scheme does not explain the primary event responsible for the loss of muscle activity in the pharyngeal dilators. Our hypothesis is that changes in oxygen and carbon dioxide blood concentrations during sleep, and-perhaps initially-specifically during REM sleep in certain genetically predispoied individuals, may interact with the activity of the brain stem neuronal network responsible for motor control of the airway and its coordination of inspiration and expiration. The motor defect observed during obstructive apnea would not then be primary in the pathogenesis of the obstruction but a consequence of a broader dysfunction involving control of ventilation during sleep and various sleep states. Animal studies, observing the chronic effect of mild hypercapnia and hypoxemia on specific neurons during sleep, may further our knowledge of this issue. ACKNOWLEDGMENT The authors thank Stephen C. Coburn and Wayne Flagg for their technical assistance during these studies. REFERENCES 1. COCCAGNA, G., M. MANTOVANI, F. BRIGNANI, C. PARCHI, AND E. LUGAFCESI. 1972. Continuous recording of the pulmonary and systemic arterial pressure during sleep in syndromes of hypersomnia with periodic breathing. Bull. Physiopathol. Respir. 8 : 1217-1227. 2. GUILLEMINAULT, C. 1978. State of the art: Sleep and control of breathing. Chest 73 (2 Suppl) : 293-299. 3. GUILLEMINAULT, C., F. L. ELDRIDGE, A. TILKIAN, F. B. SIMMONS, AND W. C. DEMENT. 1977. Sleep apnea syndrome due to upper airway obstruction: A review of 25 cases. Arch. Intern. Med. 13,7: 296-300. 4. GUILLEMINAULT, C., M. HILL, F. B. SIMMONS, AND W. C. DEMENT. 1977. Fiberoptic scope studies in obstructive sleep apneic patients. Abstract of paper presented at the Meeting of the Association for the Psychophysiological Study of Sleep, Houston, Texas. 5. GUILLEMINAULT, C., A. TILKIAN, AND W. C. DEMENT. 1976. The sleep apnea syndromes. Ann. Rev. Med. 27: 465-484. 6. KRIEGER, J., D. KURTZ, AND N. ROESLIN. 1976. Observation fibroscopique directe au tours des apukes bypniques chez un sujet Pickwickien. NOUV. Presse Med. 5: 2890. A. A., S. C. GURZA, AND B. J. SESSLE. 1977. Regulation of genioglossus and masseter muscle activity in man. Arch Oral Biol. 22: 579-584. 8. REMMERS, J. E., W. J. DEGROOT, E. K. SAUERLAND, AND A. M. ANCH. 1978. Neural and mechanical factors controlling pharyngeal occlusion during sleep. Pages 211-217 in C. GUILLEMINAULT AND W. C. DEMENT, Eds., Sleep APttea Syndromes. Alan R. Liss, Inc., New York. 9. ROBINSON, R. R. 1974. SIDS 1974. The Canadian Foundation for the Study of Infant Death, Toronto, Canada. 7. LOWE,
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E. D., AND R. M. HARPER. 1976. The human tongue during sleep: Electromyographic activity of the genioglossus muscle. Exj. Nezcrol. 51 : 160170. SCHWARTZ, B., AND J. ESCANDE. 1976. Etude cinematographique de la respiration hypnique Pickwickienne. Rev. Neural. 116 : 667-678. SIMMONS, F. B., C. GUILLEMINAULT, W. C. DEMENT, A. G. TILKIAN, AND M. HILL. 1977. Surgical management of airway obstructions during sleep. Laryngoscope 87: 326-338. SMIRNE, S., AND G. COMI. 1975. The obstructive mechanism in Pickwickian syndrome : A serial X-ray study. Sleep Res. 4 : 237. STEINSCHNEIDER, A. 1972. Prolonged apnea and the SIDS : Clinical and laboratory observations. Pediatrics 51) : 646-654. TILKIAN, A. G., C. GUILLEMINAULT, J. S. SCHROEDER, K. L. LEHRMAN, F. B. SIMMONS, AND W. C. DEMENT. 1976. Hemodynamics in sleep-induced apnea: Studies during wakefulness and sleep. Ann. Interu. Med. 85 : 714-719. TILKIAN, A. G., C. GUILLEMINAULT, J. S. SCHROEDER, K. L. LErranrAN, F. B. SIMMONS, AND W. C. DEMENT. 1977. Sleep-induced apnea syndrome: Prevalence of cardiac arrhythmias and their reversal after tracheostomy. Am. J.
10. SAUERLAND,
11.
12. 13. 14. 15.
16.
Med.
63:
17. WEITZMAN,
348-358.
E. D., C. POLLAK, B. BOROWIECKI, B. BURACK, R. SHPRINTZEN, AND 1977. The hypersomnia sleep-apnea syndrome (HSA) : Site and mechanism of upper airway obstruction. Sleep Res. 6: 182. S. RAKOFF.
NEUROLOGY
Obstructive
CHRISTIAN
62, 48-67 (1978)
Sleep Apnea: Electromyographic and Fiberoptic Studies
GUILLEMINAULT, MICHAEL W. HILL, F. BLAIR AND WILLIAM C. DEMENT 1
SIMMONS,
Sleep Disorders Clinic and Research Center and Department of Otolaryngology, Stanford University School of Medicine, Stanford, California 94305 Received October l&1977;
revision received June 19,197s
Seventeen predominantly obstructive sleep apnea patients and four normal controls (all adult males) underwent one or both investigative protocols : (A) A fiberoptic endoscope was introduced intranasally into the pharynx and subjects were monitored continuously and filmed intermittently during wakefulness and sleep. (B) Muscles selected because of their anatomical importance in maintaining the oropharynx during the respiratory cycle were electromyographically implanted intraorally or, in tracheostomy patients, at time of surgery, and subjects were polygraphically monitored during wakefulness and sleep. In both protocols, standard electroencephalogram, chin electromyogram (EMG), electrooculogram (EOG) , and respiration were monitored simultaneously. During fiberoptic studies obstructive apnea during sleep first appeared as a partial or total invagination of the posterolateral pharyngeal walls, while the laryngeal inlet remained patent. EMG recordings showed normal firing patterns in patients during unobstructed sleep. During sleep-induced obstructive apnea, however, a significant decrease or complete disappearance of EMG activity was observed in the palatoglossus, palatopharyngeus, genioglossus, superior and middle constrictors of the pharynx, and stylopharyngeus. The obstruction involves absence, during inspiration, of the activity in the pharyngeal dilators needed to counteract the loads abruptly imposed by intrathoracic negative pressure changes. Abbreviations : EEG-eIectroencephalogram ; EMG-electromyogram ; EOG-electrooculogram; REM, NREM-rapid eye movement, non rapid eye movement; SIDS -sudden infant death syndrome. l This research was supported by National Institute of Neurological and Communicative Disorders and Stroke Grant NS 10727, Public Health Service Research Grant R.R.-70 from the General Clinical Research Centers, and by INSERM to C.G. Information and reprint requests should be addressed to Sleep Disorders Clinic (Dr. Guilleminault) , Stanford University School of Medicine, Stanford, California 94305. Drs. Hill and Simmons are in the Department of Otolaryngology. 48 0014-4886/78/0621-0048$02.00/O Copyright 0 1978 by Academic Press,Inc. All rights of reproduction in any form reserved.
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INTRODUCTION Studies of patients complaining
of excessive
daytime
sleepiness demon-
strated the existence, in a number of these patients, of a predominantly obstructive sleep apnea syndrome (5). During the last several years further investigations combined with multiple nocturnal monitorings have revealed that sleep-induced apnea may precede excessive daytime sleepiness by many years and may result in severe nocturnal hypoxia, cardiac arrhythmias, and hemodynamic changes (1, 15, 16). Questions have been raised about the possible involvement of the sleep apnea syndrome in sudden adult death occurring during sleep, and a possible relationship between the sudden infant death syndrome (SIDS) and sleep apnea has been hypothesized (9, 14). We demonstrated the occurrence of obstructive apneas in infants “near miss for SIDS,” in children, and in adults. Many questions about this complex syndrome remain unanswered. The primary cause of sleep apnea syndromes is, in most cases, unknown. Involvement of the central nervous system has been suspected in the development of diaphragmatic-related apnea ; peripheral and central factors have been thought to contribute to the appearance of obstructive apnea. The precise pathogenesis of periodic upper airway occlusion during sleep, however, is uncertain. It is clear that functional airway obstruction takes place in the upper respiratory passage because treatment by tracheostomy, kept open during sleep, dramatically reverses most of fhe symptoms and pathological findings. Until recently, however, the exact site and mechanism of this functional airway obstruction remained obscure. During the last two years we studied the anatomical dynamics that ,take place in the oral and hypopharynx during sleep in patients with obstructive sleep apnea syndrome using the techniques of fiberoptic direct visual examination and filming during wakefulness and during rapid eye movement (REM) and nonrapid eye movement (NREM) sleep. In addition, we simultaneously recorded, before and after tracheostomy, EMG activity of specific muscles that appear to be involved in the obstructive phenomenon. SUBJECTS
AND
METHODS
The present study involved 17 adult patients with predominantly obstructive sleep apnea syndrome and four normal control subjects. All gave informed consent before participation. Nine sleep apnea patients and two normal controls took part in both phases of the study, i.e., fiberoptic scope and electromyographic (EMG) protocols ; eight patients and two normal controls participated in only one aspect of the study. All participants were male and their ages were 24 to 63 years.
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The sleep apnea patients (30 to 63 years of age) presented severe obstructive sleep apnea previously documented by several all-night polygraphic monitorings. Their mean apnea index (number of apneas per sleep-hour) was 96, (The mean apnea index of the normal group was less than 3.) A mean of 93% (range, 88 to 9.5%) of their apneic episodes was obstructive. All patients were heavy snorers and presented with clinical symptomatology typical of the obstructive sleep apnea syndrome previously described (3). The normal control group consisted of four adult males, ages 24 to 43 years. None of them had a sleep disorder, none snored, and all were in general good health. All had been monitored during sleep prior to the study, and sleep apnea syndrome had been ruled out. Two complementary experimental protocols were carried out: (A) fiberoptic endoscope examinations of the pharynx and larynx during wakefulness and sleep ; and (B) selective EMG recordings from muscles of the upper airway. Fiberoptic Studies. Fiberoptic nasal endoscopy was carried out on 14 sleep apneic patients and three control subjects (all male). After achieving topical anesthesia of the nasal mucosa with 4% cocaine or 2% pentocaine, a Machida fiberoptic endoscope was imroduced intranasally into the pharynx. The scope was left in place during wakefulness and while 5 to 8 h nocturnal sleep were monitored. All subjects slept in a hospital bed, at the head of which a 16-mm Bolex camera was attached. The ocular of the Machida endoscope was suspended and securely fixed to a movie camera, or to a video camera to allow cominuous monitoring of the airway dynamics on a portable television monitor. An observer continuously watched the video screen or through the ocular of the camera’s viewfinder (see Fig. 1). Film resolution is greater than that from a videotape, and both techniques have been used during the same night on the same subject. Simultaneous polygraphic recording of electroencephalogram (EEG) ( Ca/As-CI/A1 of the international 10-20 system), digastric electromyogram (EMG) , electrooculogram (EOG) , and measurements from thermistors and abdominal and thoracic strain gauges were obtained in all cases. The continuous monitoring gave simultaneous information as to onset, type, and duration of apnea. Filming was intermittent, linked to one apnea event or to a train of apneas during different sleep stages. A marker automatically indicated on the polygraphic tracing the beginning and ending of filmed sequences. Visual observation and filming were done at several levels in the pharynx. Thus, direct visualization and filming at the site of the vocal cords were possible as well as placement of the scope high in the oropharynx for observation of the posterior part of the tongue. There were
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no complications from advancing and retracting the endoscope manually or using the telescopic lens of the endoscope (see Fig. 1). Electronzyographic Studies. Twelve patients with obstructive sleep apnea and three normal control subjects participated in the EMG study (nine of these patients and two of the controls also underwent t’he fiberoptic protocol repor.ted above). Eight patients were recorded before tracheostomy ; four patients had electrodes implanted at the time of tracheostomy and were studied 36 to 72 h after surgery. Before Tracheosto?~~~~. The recording electrodes were placed intraorally. The area chosen for the recording site was topically anesthesized with 470 xylocaine or 4% cocaine. The electrodes were then placed in position using a 22-gauge spinal needle. A minimum distance of 2 mm was obtained between the muscle ends of the recording electrodes to prevent short circuiting. The free ends of the recording electrodes were brought out through the nose and taped to the skin for later recording. The nasal route was safer than that through the mouth in terms of accidental dislodgment by the tongue and seemed to be less annoying to the patients. After intraoral placement, the free ends were retrieved by placing a catheter through the nose and into the oropharynx. After securing the wires to the catheter, its withdrawal brought the wires through the nasopharynx and out the external nares. After Tracheostomy. Certain muscles cannot be implanted accurately and/or safely either intraorally or percutaneously in an awake patient using topical anesthesia. These muscles (cricopharyngeus, inferior constrictor, and the inferior edges of the middle constrictor) were implanted under direct vision at the time of tracheostomy. The free ends of the electrodes were brought out through the anterior cervical neck skin several centimeters from the tradheostomy site. In these cases the recordings were carried out 36 .to 72 h after surgery with the tracheostomy open and closed (reproducing the typical syndrome). Patients were not monitored immediately following surgery in order to avoid any effect of general anesthesia or postsurgery edema. Recordings were obtained during 5 to S nocturnal hours and included quiet wakefulness and NREM and REM sleep. Before falling asleep, patients were asked to emit sound, swallow, hold their breath, etc., and muscle activity was recorded during these maneuvers. Polygraphic monitoring included standard sleep parameters and maintenance of strain In patients 1 to 4, the palatoglossus, palatogauges and thermistors. pharyngeus, cricopharyngeus, stylohyoid, and genioglossus muscles were simultaneously monitored. Patients 5, 6, 7, and 12 had electrodes implanted in the superior, middle, and inferior constrictors of the pharynx and in the lateral part of the middle constrictor at the level of the stylopharyngeus
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FIBEROPTICS NASOPHARYNGOSCOPE \
POSITION OF SCOPE TIP
\
1 BED
HEADBOARD
FIG. 1. Presentation of setting for fiberoptic scope study. Filming is done in conjunction with polygraphic recording. Video monitoring of the oropharynx is continuous from the adjacent room.
muscle. Control subjects had electrodes placed in the inferior, middle, and superior constrictors of the pharynx-laterally at the level of the stylopharyngeus-and in the genioglossus. Patients 8, 9, 10, and 11 were implanted during tracheostomy under general anesthesia with electrodes placed in the superior, middle, and inferior constrictors of the pharynx and at the level of the stylopharyngeus muscle. Electrodes also were placed in the genioglossusand, in two cases,in the cricopharyngeus. RESULTS Fiberoptic Studies. The presence of the endoscopedid not impair respiration during sleep. No statistical increase in the number of apneas, compared to monitoring on the previous night without endoscopy, was noted. No obstruction was seen in the control subjects during sleep. Contraction of the pharyngeal walls was noted during swallowing. During wakefulness, no obstruction or cause for obstruction was seen in the patient group, and during nonobstructed periods of both NREM and REM sleep, a patent pharynx was clearly visible. On inspiration, the vocal cords abducted widely, then returned to an intermediate position during expiration, as expected. During sleep-related obstructive apnea, the initial and most important feature was the progressive opposition of the lateroposterior
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pharyngeal walls. This closure always started in the oropharynx. Visual observations of the posterior part of the tongue showed that it was not the initator of the obstructive phenomenon in the patients studied. The abrupt collapse of the airway always occurred at the onset of inspiration, and the pharyngeal obstruction looked like a “mismatch” with the respiratory cycle. The pharyngeal contour might or might not be restored to normal at the end of the inspiratory cycle. Some incomplete obstructions, based on polygraphic criteria and termed “hypopnea”, reduced the diameter of the airway, but some airflow persisted, and endoesophageal pressure greatly increased during these episodes. By advancing the scope to the supraglottic area, the laryngeal inlet was seen to be patent during obstructive apnea. The vocal cords exhibited normal inspiratory abduction despite the absence of a normal upward airflow pattern. In our population these fiberoptic studies documented no evidence of glottic obstruction ; the palate was not pushed posteriorly by the tongue during an apneic episode. The lateral and posterior pharyngeal walls collapsed at the level of the oropharynx and produced the obstruction. Figures 2 and 3 present sequences of incomplete and complete pharyngeal collapse during obstructive apnea. The reproductions of filmed sequences indicate rather clearly the posteroanterior progression of the occlusive phenomenon. In one sequence (Fig. 3), the root of the tongue can be seen fairly clearly anteriorly during the occurrence of the obstructive phenomenon, with progressive imagination of the posterolateral pharyngeal walls. Electrow~yograplaic Studies. The EMG findings were not a function of a specific state of sleep (NREM or REM sleep) ; during obstructive apnea similar EMG activity was observed regardless of the sleep state. During sleep, normal controls had a low level of muscle activity in the constrictors; however, a burst of muscle activity was recorded from the electrodes placed laterally at the level of the stylopharyngeus concomitant with inspiration. As shown in Fig. 4, this burst of inspiratory muscle activity was also seen during REM sleep, and even during bursts of rapid eye movements. In sleep apnea patients, during sleep-related obstructive apnea, no change was observed in the E&IG activity of the stylohyoid, the cricopharyngeus, or the inferior constrictor of the pharynx, compared to prior recordings during unobstructed sleep. A significant decrease in EMG activity was recorded during obstructive apnea, however, in the palatoglossus, palatopharyngeus, genioglossus, superior and middle constrictors of the pharynx, and in the lateral part of the middle constrictor at the level of the stylopharyngeus. Figures 5 through 9 show muscle activity during obstructive apneas. In one patient, one muscle fiber was implanted, and complete
7
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FIG. 2. Sequence of incomplete pharyngeal collapse during sleep in a patient with obstructive lapse of the posterolateral walls of the pharynx and the incomplete occlusion of the airway.
ARYEPIGLOTTIC FOLD
sleep apnea. Note the progressive
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FIG. 6. Recordings from a 38-year-old obstructive sleep apneic patient during stage 2 NREM sleep. Channel l-EMG recorded with bipolar electrodes implanted in the palatopharyngeus ; channel Z-EMG recorded with bipolar electrodes in the palatoglossus; channel 3-thermistor.
FIG. 7. Recording 3 days postsurgery with tracheostomy closed in a 53-year-old obstructive sleep apneic patient. The patient is in stage ‘2 NREM sleep. One muscle fiber was implanted in the right stylopharyngeus. Pharyngeal EMG electrodes were implanted under general anesthesia during tracheostomy surgery. Channel I-EEG ((L/As), channel 2-EOG, channel 3-digastric EMG, channel 4-bipolar electrodes implanted in the right stylopharyngeus, channel S-EMG obtained from a third electrode implanted in the same area and referred to a neutral electrode. (Several batches of electrodes were implanted in the same muscles at the time of surgery because some could become dislodged during the two postsurgery days.) Channel 6-EMG from the proximity of the inferior constrictor of the pharynx. Respiration was analyzed from recordings obtained from nasal thermistor and abdominal strain gauge (channels 7 and 8). Note the sudden stylopharyngeal EMG silence during the obstructive apnea.
FIG. 8. Example of obstructive hypopnea during sleep in a 36-year-old male with obstructive sleep apnea. Channel 7 (from the top) monitored EMG activity of the genioglossus and channel 8 EMG ofthe middle constrictor of the pharynx. Note the dissociation of EMG activity in the two muscles; the middle constrictor of the pharynx stops firing, but the genioglossus is still active.
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silence was obtained during the obstruction. In this case the electrodes were implanted at the time of tracheostomy surgery under general anesthesia. The electrodes were believed to be accurately placed in the stylopharyngeus. During the all-night recording patients also experienced incomplete obstruction (obstructive hypopnea), shown in Fig. 2. Figure 8 shows electromyographic tracings from the genioglossus and the middle constrictor of the pharynx during an hypopneic event. As Fig. 8 shows, there was complete EMG silence in the middle constrictor, but bursts of EMG activity persisted in the genioglossus. Obstructive sleep apneic patients have some central apneic events, involving the diaphragm, as well as obstructive episodes. Figure 10 shows EMG activity from the genioglossus and the inferior constrictor of the pharynx during one of these central events ; complete muscle inhibition was recorded in the genioglossus. DISCUSSION In 1967, Schwartz and Escande, in a fiberoptic study during sleep in one Pickwickian patient,2 reported (11) that the site of the obstruction during sleep apnea was located in the oropharynx. This, however, was considered controversial for the following decade. We reported similar observations in one obstructive sleep apneic patient (12). Smirne and Comi (13) reported serial X-ray studies in two Pickwickians and one control subject during sleep and wakefulness. Those authors observed during sleep a slight collapse of the pharyngeal wall and interruption of the air column at the level of the soft palate between the base of the tongue and the pharyngeal walls. Weitzman et al. (17) and our group (2, 4) obtained films and videotapes during all-night monitoring that indicated the oropharynx as the site of the obstruction. Remmers et al. (8), measuring supraglottic pressure, also suggested that the oropharynx may be the site of obstruction. But Krieger and colleagues (6), after fiberoptic evaluations of a Pickwickian patient in 1976, located the obstruction at the vocal cord level. Our fiberoptic studies in 14 non-Pickwickian, predominantly obstructive sleep apneic patients indicated that, in this population, the site of the obstruction was supraglottic, in the oropharynx, and that the posterolateral pharyngeal walls were the first to invaginate. Speculation has arisen about the mechanism involved in this obstruction. Weitzman et al. suggested the possibility of an active contraction of the constrictors of the pharynx (17). Also, the role of the tongue in the obstruction has been considered. Sauer2As defined by Burwell, C., E. Robin, R. Whaley, obesity associated with alveolar hypoventilation, Med. 21: 811-818.
and A. Dickelman. 1956. Extreme a Pickwickian syndrome. Am. 1.
FIG. 9. Recording in a S-year-old obstructive sleep apneic patient during stage 2 NREM sleep. Channels 4 and 6 are EMGs recorded from bipolar electrodes implanted in the middle constrictor of the pharynx. Note the marked decrease in muscle activity during this mixed apnea.
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land and Harper (10) reported a loss of genioglossal muscle activity in snorers during sleep. Remmers et al. (8) related genioglossal EMG activity to the “occluded/ventilatory cycle” and measurement of supraglottic pressure. Our results, in the studied population, do not support all the previous assumptions. All oropharyngeal muscles studied demonstrated decreased activity during obstructive apnea ; when respiration resumed muscle activity was recorded at maximum intensity. This finding contradicts hyperactivity of pharyngeal constrictors as the primary factor in sleep-induced obstruction. Our fiberoptic studies demonstrated no vocal cord involvement and confirmed much of the previous data implicating the oropharynx as the site of the obstruction. Most of our observations negate singular involvement of the tongue. Indeed, the pharyngeal walls seem to be the initiator of the obstructive phenomenon. The root of the tongue can be seen in Fig. 3, and invagination (“sucking-in”) of the posterolateral walls apparently precedes movement of the tongue. One could question whether the correlation between esophageal pressure and EMG activity reported by Remmers et al. (8) would have been higher had those authors recorded not only the genioglossus but the pharyngeal constrictors as well, and then selected the middle constrictor of the pharynx as an index of EMG activity. It is interesting to note that EMG activity was completely abolished in the lead in the middle constrictor shown in Fig. 8, with persistence of genioglossal activity, while airflow decreased considerably during obstructive hypopnea (see also Fig. 2). It could be argued that obstruction remains incomplete because of the persistence of genioglossal activity, but that argument also favors the primacy of the pharyngeal walls in the obstruction. Obstruction may eventually incorporate the tongue, but its activity cannot be considered a reliable index of obstruction. It should also be emphasized that when central apnea is monitored, supposedly involving a sudden diaphragmatic inhibition, total inhibition of the genioglossus is observed (see Fig. 10). One of the questions raised by this finding is not why genioglossal activity abruptly ceases during a central apnea, as the respiratory apparatus can be considered as a centrally controlled functional unit, but why there is dissociated diaphragmatic and oropharyngeal muscle activity. From our studies we have elaborated the “tent hypothesis.” Recordings during sleep show that the superior and middle constrictors of the pharynx both decrease EMG activity during obstruction, but the inferior constrictor demonstrates no change in EMG activity before, during, or after obstructive apnea during sleep. The “pharyngeal tent” in our hypothesis refers specifically to the superior and middle constrictors. This tent is transfixed by a thin muscle at the junction of the superior and middle constrictors which then spreads widely beneath the mucous membrane-the stylo-
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Stylopharyngeus
FIG. 11. Anatomical presentation of the constrictors pharyngeus. Left, rostra1 ; right, caudal.
of the pharynx
and stylo-
pharyngeus (see Figs. 11 and 12). It draws the sides of the upper pharynx cranially and laterally, thereby increasing the transverse dimension of the pharynx. It is a pharyngeal dilator. As far as we could tell, decreasedEMG activity occurs in this dilator as well as in the constrictors. One could hypothesize that under normal conditions reflex reinforcement of EMG activity in the pharyngeal dilators occurs during inspiration to counteract the load suddenly imposed by the diaphragm and other accessory inspiratory muscles and by sudden intrathoracic negative pressure changes. This “burst” of muscle activity would need to coordinate with all other respiratory movements. If it does not, or if it occurs at the wrong time (mismatched), obstruction could occur. This schemeis supported by our observations, but we must acknowledge that we have not recorded all muscles involved in the control of the jaw, some of which, although located distantly, may contribute to change in
FIG. 12. Schematic representation of the superior and middle constrictors of the pharynx (the “tent”) and the stylopharyngeus (“string of the tent”, shaded) which “dilate” the tent and hold it out.
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activity
of the genioglossus,
for example,
ET
AL.
as demonstrated
by Lowe
et al.
(7). Additionally, this scheme does not explain the primary event responsible for the loss of muscle activity in the pharyngeal dilators. Our hypothesis is that changes in oxygen and carbon dioxide blood concentrations during sleep, and-perhaps initially-specifically during REM sleep in certain genetically predispoied individuals, may interact with the activity of the brain stem neuronal network responsible for motor control of the airway and its coordination of inspiration and expiration. The motor defect observed during obstructive apnea would not then be primary in the pathogenesis of the obstruction but a consequence of a broader dysfunction involving control of ventilation during sleep and various sleep states. Animal studies, observing the chronic effect of mild hypercapnia and hypoxemia on specific neurons during sleep, may further our knowledge of this issue. ACKNOWLEDGMENT The authors thank Stephen C. Coburn and Wayne Flagg for their technical assistance during these studies. REFERENCES 1. COCCAGNA, G., M. MANTOVANI, F. BRIGNANI, C. PARCHI, AND E. LUGAFCESI. 1972. Continuous recording of the pulmonary and systemic arterial pressure during sleep in syndromes of hypersomnia with periodic breathing. Bull. Physiopathol. Respir. 8 : 1217-1227. 2. GUILLEMINAULT, C. 1978. State of the art: Sleep and control of breathing. Chest 73 (2 Suppl) : 293-299. 3. GUILLEMINAULT, C., F. L. ELDRIDGE, A. TILKIAN, F. B. SIMMONS, AND W. C. DEMENT. 1977. Sleep apnea syndrome due to upper airway obstruction: A review of 25 cases. Arch. Intern. Med. 13,7: 296-300. 4. GUILLEMINAULT, C., M. HILL, F. B. SIMMONS, AND W. C. DEMENT. 1977. Fiberoptic scope studies in obstructive sleep apneic patients. Abstract of paper presented at the Meeting of the Association for the Psychophysiological Study of Sleep, Houston, Texas. 5. GUILLEMINAULT, C., A. TILKIAN, AND W. C. DEMENT. 1976. The sleep apnea syndromes. Ann. Rev. Med. 27: 465-484. 6. KRIEGER, J., D. KURTZ, AND N. ROESLIN. 1976. Observation fibroscopique directe au tours des apukes bypniques chez un sujet Pickwickien. NOUV. Presse Med. 5: 2890. A. A., S. C. GURZA, AND B. J. SESSLE. 1977. Regulation of genioglossus and masseter muscle activity in man. Arch Oral Biol. 22: 579-584. 8. REMMERS, J. E., W. J. DEGROOT, E. K. SAUERLAND, AND A. M. ANCH. 1978. Neural and mechanical factors controlling pharyngeal occlusion during sleep. Pages 211-217 in C. GUILLEMINAULT AND W. C. DEMENT, Eds., Sleep APttea Syndromes. Alan R. Liss, Inc., New York. 9. ROBINSON, R. R. 1974. SIDS 1974. The Canadian Foundation for the Study of Infant Death, Toronto, Canada. 7. LOWE,
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E. D., AND R. M. HARPER. 1976. The human tongue during sleep: Electromyographic activity of the genioglossus muscle. Exj. Nezcrol. 51 : 160170. SCHWARTZ, B., AND J. ESCANDE. 1976. Etude cinematographique de la respiration hypnique Pickwickienne. Rev. Neural. 116 : 667-678. SIMMONS, F. B., C. GUILLEMINAULT, W. C. DEMENT, A. G. TILKIAN, AND M. HILL. 1977. Surgical management of airway obstructions during sleep. Laryngoscope 87: 326-338. SMIRNE, S., AND G. COMI. 1975. The obstructive mechanism in Pickwickian syndrome : A serial X-ray study. Sleep Res. 4 : 237. STEINSCHNEIDER, A. 1972. Prolonged apnea and the SIDS : Clinical and laboratory observations. Pediatrics 51) : 646-654. TILKIAN, A. G., C. GUILLEMINAULT, J. S. SCHROEDER, K. L. LEHRMAN, F. B. SIMMONS, AND W. C. DEMENT. 1976. Hemodynamics in sleep-induced apnea: Studies during wakefulness and sleep. Ann. Interu. Med. 85 : 714-719. TILKIAN, A. G., C. GUILLEMINAULT, J. S. SCHROEDER, K. L. LErranrAN, F. B. SIMMONS, AND W. C. DEMENT. 1977. Sleep-induced apnea syndrome: Prevalence of cardiac arrhythmias and their reversal after tracheostomy. Am. J.
10. SAUERLAND,
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12. 13. 14. 15.
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17. WEITZMAN,
348-358.
E. D., C. POLLAK, B. BOROWIECKI, B. BURACK, R. SHPRINTZEN, AND 1977. The hypersomnia sleep-apnea syndrome (HSA) : Site and mechanism of upper airway obstruction. Sleep Res. 6: 182. S. RAKOFF.
