Clinical and laboratory evaluations of excessive daytime sleepiness.

Sleepiness is common, dangerous, and difficult to quantitate. Sleepiness normally occurs if one tries to be awake during the circadian sleepiness phase or if one obtains insufficient sleep. Certain subjective tests of sleepiness can help the clinician to quantitate historical sleepiness. Objective tests of sleepiness are validated but imperfect predictors of future sleepiness. In spite of the difficulty in measuring sleepiness, a careful clinical evaluation of patients who complain of sleepiness is possible and usually reveals the correct diagnosis.

Subacute encephalomyelitis presenting as stiff-person syndrome: clinical, polygraphic, and pathologic correlations.

A 60-year-old woman presented with stiff-person syndrome (SPS). Treatment with diazepam controlled her painful spasms initially. Two and one-half years after the onset of SPS, new spells of paroxysmal leg jerking and apnea developed. A spell was recorded with simultaneous video and polygraphic techniques that revealed simultaneous firing of motor unit potentials in several muscles (paraspinal, internal hamstring, and abdominal muscles). Apnea was associated with arterial oxygen desaturation. An increase in the dose of diazepam decreased the number and severity of these episodes. Seventeen months later, the patient began to taper the diazepam dose. Shortly thereafter, she had a cardiorespiratory arrest and subsequently died. Autopsy showed small chronic inflammatory foci in the pancreas (some associated with islets) and findings of diffuse encephalomyelitis characterized by perivascular cuffing in the spinal cord, brainstem, thalamus, hippocampus, and amygdala and a dense mononuclear infiltrate in the anterior horns of the lumbar and cervical cord, with relative preservation of axons and myelin. Cell typing showed this infiltrate was polyclonal and reactive. There have been rare cases of SPS associated with encephalomyelitis reported previously. Although the prolonged course in our patient suggested that SPS may have preceded encephalomyelitis, the more likely explanation is that the patient had an unusually long course of encephalomyelitis alone.

Ventilatory dynamics during transient arousal from NREM sleep: implications for respiratory control stability.

The polysomnographic and ventilatory patterns of nine normal adults were measured during non-rapid-eye-movement (NREM) stage 2 sleep before and after repeated administrations of a tone (40-72 dB) lasting 5 s. The ventilatory response to arousal (VRA) was determined in data sections showing electrocortical arousal following the start of the tone. Mean inspiratory flow and tidal volume increased significantly above control levels in the first seven breaths after the start of arousal, with peak increases (64.2% > control) occurring on the second breath. Breath-to-breath occlusion pressure 100 ms after the start of inspiration showed significant increases only on the second and third postarousal breaths, whereas upper airway resistance declined immediately and remained below control for > or = 7 consecutive breaths. These results suggest that the first breath and latter portion of the VRA are determined more by upper airway dynamics than by changes in the neural drive to breathe. Computer model simulations comparing different VRA time courses show that sustained periodic apnea is more likely to occur when the fall in the postarousal increase in ventilation is more abrupt.

Obstructive sleep apnea in patients with human immunodeficiency virus (HIV) disease.

Adenotonsillar hypertrophy has been identified as an early manifestation of human immunodeficiency virus (HIV) disease. Three patients with HIV disease were identified with obstructive sleep apnea (OSA) due to adenotonsillar hypertrophy. In order to examine the relationship between HIV-induced adenotonsillar hypertrophy and OSA, 134 patients with asymptomatic HIV disease were screened with a self-administered sleep survey designed to detect OSA and excessive daytime somnolence. Patients meeting trigger score criteria were studied with overnight polysomnography and nine additional patients were identified with OSA. The only consistent risk factor for OSA in this young and primarily nonobese population was the presence of adenotonsillar hypertrophy, found in 11 of 12 patients with OSA. Three patients had tonsillar biopsy or tonsillectomy and all displayed benign follicular lymphoid hyperplasia. Scores on the Epworth Sleepiness Scale (ESS) were significantly higher for patients with OSA, indicating a greater degree of hypersomnolence (mean ESS scores: OSA+ = 11.4 +/- 3.6, OSA- = 7.8 +/- 4.6, p = 0.012). In our population, patients with HIV disease had a prevalence of OSA of 7%. HIV-induced adenotonsillar hypertrophy is a risk factor for the development of OSA. HIV patients with complaints of excessive daytime sleepiness and snoring who are found to have adenotonsillar hypertrophy on exam should undergo a sleep evaluation to rule out the presence of OSA.

Estimation of dynamic chemoresponsiveness in wakefulness and non-rapid-eye-movement sleep.

We developed a method for quantifying dynamic chemoresponsiveness on the basis of the ventilatory response to pseudorandom binary CO2 stimulation. The dynamic chemoreflex gain (GD) and effective time delay (TDeff) relating breath-to-breath fluctuations in alveolar PCO2 to ventilation were evaluated at frequencies between 0 and 0.05 Hz. Application of the method to simulated "data" showed that estimation errors in GD and TDeff were most likely to be minimized in the range of 0.01-0.03 Hz, corresponding to periodicities of 30-100 s. Estimation of TDeff was generally more susceptible to error than that of GD because of the limited time resolution of the breath-by-breath measurements. In eight awake normal adults, we compared estimates of GD derived from the pseudorandom binary CO2 stimulation test with peripheral and central hypercapnic sensitivities deduced from single-breath and Read rebreathing measurements in the same subject. GD at 0.02 Hz was highly correlated with peripheral hypercapnic sensitivity but poorly correlated with central hypercapnic sensitivity, underscoring the importance of the peripheral chemoreflexes in mediating ventilatory responses to phasic stimuli. Application of the procedure to a different group of 10 healthy volunteers during wakefulness and stage 2 sleep showed decreases in GD in 8 subjects but increases in 2 subjects. However, for the group as a whole, GD and TDeff did not change significantly between wakefulness and sleep. The proposed method may provide information more pertinent to periodic breathing than traditional CO2 response tests do, since the chemoreflex responses to phasic variations in blood gases are likely to be important in determining ventilatory control during sleep.

Assessment of accuracy and analysis time of a novel device to monitor sleep and breathing in the home.

Obstructive sleep apnea is increasingly recognized as a common and debilitating disorder. As a result, a variety of diagnostic technologies have evolved to potentially decrease cost and improve access and ease of assessment. In this study we compared the Healthdyne NightWatch (NW) System (a home sleep diagnostic methodology) to standard polysomnography (PSG) in two sleep centers. Two separate studies were completed. NW was compared to a simultaneously obtained PSG in 30 patients (IN-LAB study). Seventy additional patients were studied in both the home with NW and in the laboratory with PSG (HOME-LAB study). The NW system records eye movement, leg movement, SaO2, nasal-oral airflow, chest and abdominal wall motion, body position and heart rate on a solid state recorder, which permits sleep staging based on body and eye movement and standard respiratory assessment. For the PSG, standard paper recording techniques were used. The IN-LAB study revealed a correlation between NW and PSG for total sleep time of r = 0.72, with NW tending to score some awake time as nonrapid eye movement sleep. The correlation for apnea-hypopnea index (AHI) was r = 0.94 between systems, with a sensitivity of 100% and specificity of 63.6% at an AHI threshold of 10. The HOME-LAB study demonstrated understandably poor correlations between NW and PSG for most measures of sleep, which is likely a product of night-to-night variability in sleep, home versus laboratory effects and the differences in sleep staging methodology. However, the correlation for AHI was r = 0.92, with a sensitivity of 90.7% and a specificity of 70.4% at an AHI threshold of 10. Using a new methodology to assess agreement between diagnostic systems, we observed 78.6% diagnostic agreement between NW and PSG in the HOME-LAB study, with NW underestimating AHI 4.3% of the time and overestimating it in 17.1% of cases. This may relate to night-to-night variability in AHI or greater NW computer sensitivity to subtle hypopneas. We conclude that NW provides an accurate determination of AHI in both the home and laboratory, using limited instrumentation. The analysis time for NW is also reduced compared to PSG, and patients generally prefer the NW evaluation.

Effect of nasal continuous positive airway pressure on cardiac output and oxygen delivery in patients with congestive heart failure.

We studied the acute hemodynamic effects of increasing nasal continuous positive airway pressure (CPAP) in 13 patients with acute decompensation of congestive heart failure. Heart rate, respiratory rate, pulmonary capillary wedge pressure, right atrial pressure, systemic blood pressure, and thermodilution cardiac outputs were measured at baseline, during, and after application of nasal CPAP at increasing pressures of 5, 10, and 15 cm H2O. Cardiac index, stroke volume, and oxygen delivery were calculated. Based on a significant change in cardiac output greater than or equal to 400 ml, seven patients were classified as responders, whereas six patients were considered to be nonresponders. In responders, significant increases were noted in cardiac index (2.5 +/- 0.7 to 2.9 +/- 0.9 L/min/m2), stroke volume (49 +/- 15 to 57 +/- 16 ml), and oxygen delivery (10.3 +/- 5.1 to 12.3 +/- 6.0 ml/min/kg) without a change in pulmonary capillary wedge pressure. In contrast, the nonresponders showed no significant change in any of the hemodynamic parameters. Improvement in cardiac output could not be predicted by any of the baseline hemodynamic or clinical variables, nor was it related to random variations since all variables returned to baseline after cessation of CPAP. Increase in stroke volume without a change in pulmonary capillary wedge pressure (preload) suggests either improved inotropic function of the left ventricle or reduced left ventricular afterload with CPAP. Thus, CPAP may offer a new noninvasive adjunct to improving left ventricular function and augmenting cardiac performance in a subset of patients with congestive heart failure.

Occlusion and narrowing of the pharyngeal airway in obstructive sleep apnea: evaluation by ultrafast spoiled GRASS MR imaging.

Morphologic abnormalities of the pharyngeal airway are frequently found in patients with obstructive sleep apnea. These structural alterations in the pharyngeal airway can be detected in awake patients by using rapid imaging techniques. Ten patients with clinically proved obstructive sleep apnea had ultrafast spoiled gradient-recalled acquisition in the steady state (GRASS) MR imaging of the pharyngeal airway to determine the presence of occlusions and/or narrowings. Twelve sequential images were obtained at one midsagittal plane and at eight transverse planes through the pharyngeal airway. The scans were obtained at the rate of one image per 1.04 sec while the patient was breathing quietly. Occlusions or narrowings of the pharyngeal airways were detected on MR images in all patients. The site(s) of the occlusions and the site(s) and extent of the narrowings varied. Six patients had occlusions and four had narrowings of one or more sites. This study shows that ultrafast spoiled GRASS MR imaging can be used to evaluate patients with obstructive sleep apnea during tidal breathing and is useful for determining the presence of occlusions and narrowings of the pharyngeal airway.

Dynamic study of the upper airway with ultrafast spoiled GRASS MR imaging.

Dynamic magnetic resonance (MR) imaging of the upper airway was not possible previously because of poor temporal resolution. Recently, a rapid technique has been developed that provides the means to obtain multiple images at different section locations with sufficient image quality and temporal resolution to allow a comprehensive, dynamic study of the upper airway. The authors describe an ultrafast spoiled GRASS (gradient-recalled acquisition in the steady state) pulse sequence for dynamic studies of the upper airway. The authors believe that this procedure has potential for identifying and characterizing upper airway abnormalities such as nonfixed occlusions and/or narrowings that may exist in patients with obstructive sleep apnea.

Effects of alterations in pulmonary function and sleep variables on survival in patients with amyotrophic lateral sclerosis.

Breathing abnormalities and nocturnal hypoventilation occur in patients with amyotrophic lateral sclerosis (ALS). A prospective study was undertaken to determine the relationship of pulmonary function test abnormalities with quality of sleep and survival in 21 patients with ALS. Results of spirometry including determination of maximal respiratory pressures and arterial blood gases were compared with several formal polysomnographic variables and then also with 18-month survival. The patients had mild to moderate pulmonary function deficits, but the quality of sleep was best related to age (mean age, 58.5 years). The results of pulmonary function tests and arterial blood gas measurements did not correlate well with the presence of nocturnal breathing events or survival time, but the maximal inspiratory pressure was 86% sensitive for predicting the presence of a nocturnal oxygen saturation nadir of 80% or less and 100% sensitive for predicting 18-month survival. Although obstructive breathing events occurred, the primary explanation for the decline in nocturnal oxygen saturation was hypoventilation. We conclude that routine pulmonary function tests may be useful for screening for reductions in nocturnal oxygen saturation and also may have prognostic value. Further studies may determine whether treatment of nocturnal hypoventilation will have an effect on survival in patients with ALS who have breathing impairment.

Sleep disorders and upper airway obstruction in adults.

The OSA syndrome, described over 100 years ago, was rediscovered in 1966. It is a common disorder, especially among fat, middle-aged men. Stentorian snoring and diurnal somnolence are the cardinal manifestations and should always lead to an examination during sleep. That examination (polysomnography) can demonstrate the pathognomonic events--repetitive apneas occurring in sleep--which signal the failure of the sleeping brain to maintain the patency of the supraglottic airway. All evidence points to the problem being an abnormal pharyngeal airway, one which has a shape or size or compliance that allows inspiratory collapse as the normal loss of pharyngeal dilator muscle tone occurs with sleep. The apneas are asphyxic events terminated by arousals which fragment sleep continuity and lead to the daytime sleepiness. Because the snoring occurs during sleep, the arousals are unremembered, and the sleepiness can develop so gradually that the patient may forget what normal alertness is like. It is important to interview the patient's spouse or partner. Besides obesity and maleness, other risk factors for OSA are diseases that have an impact on the configuration or effective compliance of the pharyngeal passageway. Recent studies support the clinical intuition that sleep apnea is undesirable. Sleepiness leads to accidents. The hypoxemia occurring during apnea can lead to potentially fatal cardiac dysrhythmias. A number of reports suggest that snoring and sleep apnea are associated with an increased risk of stroke, myocardial ischemia, and infarction. Finally, there are now two papers showing a significantly decreased probability of 5-year survival in patients with symptomatic sleep apnea. The good news is that treatment with tracheostomy or NCPAP improves mortality rates to normal. Approximately 90 per cent of patients can tolerate a night's initial trial with CPAP. Long-term acceptance of CPAP has now been reviewed in a number of studies, and it appears to be about 65 to 70 per cent.

Fast-CT evaluation of the upper airway during wakefulness in patients with obstructive sleep apnea.

Fast-CT scanning was used to study the dynamic changes in the upper airway (UA) during quiet tidal ventilation (VT) in 25 patients with obstructive sleep apnea (OSA). Ten fast-CT scans were sequentially obtained over one respiratory cycle from the level of the hard palate to the hypopharynx with the patients awake in the supine position. The patients were 44 +/- 2 years old, weighed 104 +/- 5 kg, and had moderately severe OSA with an apnea plus hypopnea index (AHI) of 59 +/- 7 per hour. Maximum and minimum UA cross-sectional areas (Amax -Amin) were determined for each UA level and percent reductions in UA size or collapsibility index (CI) were computed as (Amax -Amin)*100/Amax. The lower velo-pharynx was the narrowest (Amin = 80 +/- 12 mm2) and most collapsible segment of the UA (Cl = 55 +/- 5%). Amin was less than 25, 50, or 75 mm2 in 64%, 76%, and 88% of the patients, respectively. Significant narrowing was confined to the proximal segment (levels 1 to 4) in the majority, with the remaining patients having narrowing in both the proximal and distal segments. None of the patients had major narrowing confined to the distal segment alone. Mean UA cross-sectional area (Amean) was generally largest at end-inspiration and smallest at end-expiration. In conclusion, fast-CT has documented substantial changes in UA cross-sectional area during quiet VT in awake supine patients with OSA. The velopharyngeal (retropalatal) segment was the narrowest and most collapsible region. Maximal narrowing was greatest at end-expiration, consistent with relaxation of UA dilator muscle activity.

Obstructive sleep apnea syndrome in patients with class II malocclusion.

This study was designed to analyze the effect of class II malocclusion as a factor in the development of obstructive sleep apnea syndrome. Although mandibular retrusion has been reported coincidentally with obstructive sleep apnea syndrome many times, no causal relationship has been established. No previous study has analyzed the occurrence of obstructive sleep apnea syndrome in patients with class II malocclusion without sleep complaints. In this study, we selected 12 patients with class II malocclusion who required surgical mandibular-lengthening or repositioning procedures. These patients were surveyed for sleep habits or sleep complaints and then studied with overnight polysomnography for sleeping or breathing abnormalities. None of these patients had obstructive sleep apnea syndrome. From this sample population, an incidence of obstructive sleep apnea syndrome of no more than 26.5% in the surgical population of patients with class II malocclusion can be extrapolated.

Paraplegic energy expenditure during negotiation of architectural barriers.

Long-leg braces are often used by persons with paraplegia to negotiate architectural barriers, and thereby increase their wheelchair mobility. Such barriers include ramps, stairways, and narrow corridors requiring multiple turns. This study was designed to measure the energy expenditure during such activities for two long-leg orthoses: standard braces without a dorsiflexion stop and Scott-Craig braces. Energy expenditure was measured in eight subjects by indirect spirometry using Douglas bag collection and Haldane analysis. Data obtained were used to calculate oxygen consumption per minute, volume of oxygen per turn, step, or meter, and calories per minute during each activity. Using Scott-Craig braces on one day and standard braces on another day, each subject negotiated five 90 degrees turns and two 180 degree turns, ten 15.24 cm steps, both up and down, and an 11.9 m ramp inclined 12 degrees, both up and down. Milliliters of oxygen consumed per kilogram of body weight per turn, step, or meter were recorded for Scott-Craig braces, standard braces, and normal walking. All of these activities required a high expenditure of energy. No significant difference was apparent between the standard and the Scott-Craig braces for any activity.

Energy expenditure of paraplegic patients standing and walking with two knee-ankle-foot orthoses.

To determine which kind of knee-ankle-foot orthosis (KAFO) is more efficient, we measured energy expenditure in standing, walking with a walker, and walking with crutches by eight subjects using the Scott-Craig KAFO and a single-stopped long-leg KAFO. All subjects had complete motor paralysis below the level of their lesion and had been fully trained to use KAFOs. Every subject used both types of KAFO, and energy expenditure--per minute and per meter traveled--was measured by oxygen consumption. No significant difference in energy expenditure appeared during standing. During ambulation, however, mean energy expenditure was less with the Scott-Craig KAFO than with the single-stopped type: 31% less kcal/m with a walker and 25% less kcal/min with crutches. These results suggest that the Scott-Craig KAFO is more energy-efficient than the single-stopped long-leg KAFO.

Symptomatic pectus deformities of the chest.

Aspects of pulmonary mechanics and exercise tolerance were investigated in 8 young male patients with pectus deformities, 5 of whom presented with the chief complaint of exercise limitation. Results of pulmonary mechanics studies did not adequately explain patient symptoms. Lung volumes were only mildly reduced. There was no evidence of airway obstruction. Measures of lung compliance were normal in 6 patients studied. Results of exercise studies did reveal significant abnormalities in symptomatic and asymptomatic patients; tidal volume at maximal effort expressed as a percentage of vital capacity was diminished, suggesting restriction of ventilation. Oxygen uptakes in the 4 symptomatic patients were normal at lesser work loads but progressively exceeded predicted values at greater work loads, suggesting an abnormally elevated work of breathing during vigorous exertion. Three asymptomatic patients demonstrated a normal linear pattern of increase in oxygen uptake with increasing work load. Respiratory symptoms in some patients with pectus deformities appear to have a physiologic basis. Our data suggest a dynamic restrictive pulmonary process as an explanation for these symptoms.