P300 latency: abnormal in sleep apnea with somnolence and idiopathic hypersomnia, but normal in narcolepsy

To evaluate cognitive abnormalities in excessive daytime sleepiness (EDS) using cognitive evoked potentials (P300), and to evaluate if P300 measures differentiate among disorders of EDS, a series of EDS subjects were administered a polysomnogram, auditory and visual P300 testing using 31 scalp electrodes, and a multiple sleep latency test. P300 variables were compared with those of normal subjects. Forty normal subjects ages 16 to 65 years, and 69 EDS patients ages 16 to 65 years were used. Of these, 39 had profound obstructive sleep apnea (OSA, Respiratory Disturbance Index or RDI > 80/h sleep) with severe somnolence (Mean Sleep Latency < 5 min). Twenty-two had idiopathic hypersomnia (IH). Eight had narcolepsy. The normals and the three EDS groups did not differ in age. IH and profound OSA patients had longer visual P300 latency than normals or narcolepsy patients (p < 0.05). (p < 0.05). IH and profound OSA patients had longer auditory P300 latency than normals. They had smaller auditory P300 amplitude than narcolepsy patients. There were visual P300 latency topographic differences between normals and profound OSA patients. In conclusion, IH and profound OSA patients show cognitive evoked potential evidence of cognitive dysfunction. Narcolepsy patients do not show such evidence. Visual P300 latency differentiates among disorders of EDS.     

Anamnestic and polygraphic parameters in obstructive sleep apnea syndrome patients with reduced nasal respiration during the day in comparison with obstructive sleep apnea patients with normal nasal respiration

Nasal obstruction is a predictive factor for snoring and may contribute to the development of an obstructive sleep apnea syndrome (OSAS). The aim of this study was to further evaluate the impact of nasal obstruction in OSAS. Therefore, we investigated 2 groups of OSAS-patients, matched pairs concerning gender, age, and BMI: OSAS-patients with nasal obstruction (N, n = 28), total nasal airflow < 500 ccm/s (referred to 150 pa pressure of difference or unilateral nasal resistance > 1 pa/ccm/s), and 28 OSAS-patients without nasal obstruction (control-group K, total nasal airflow > 700 ccm/s [referred to 150 pa pressure of difference or unilateral nasal resistance > 1 pa/ccm/s]). We performed anterior rhinomanometry, lung-function testing, cardio-respiratory polygraphy, and patients answered a standardized questionnaire. We found the following significant differences: 1) N complained more often (n = 17) about dyspnea at night than K (n = 7, p < 0.05, Chi2-test). 2) N had a higher apnea index (20.4 +/- 19.0/h) than K (9.6 +/- 10.0/h, p < 0.05, Student's t-test). There were, however, no significant differences concerning lung function, number of nocturnal hypopneas, nocturnal SaO2 and heart rate. Our results underline the importance of nasal ventilation in the pathogenesis of OSAS. At least in moderate cases of OSAS a therapy of nasal obstruction might be of success in order to abolish nCPAP-therapy or might reduce nasal problems during nCPAP-therapy and thus ameliorate patient's therapy compliance.     

Treatment of otherwise normal children with obstructive sleep apnea

There are many therapeutic approaches to children with OSA. Treatment should be considered only when the severity of the syndrome has been established by objective testing including overnight polysomnography. Anatomic abnormalities, including adenotonsillar hypertrophy, must be defined. Once the severity and underlying cause of OSA have been established, the most appropriate approach can be devised for the individual. Mild cases may simply be observed. Moderate or severe patients whose nasopharynx is obstructed by lymphoid hyperplasia may be treated with adenotonsillectomy. If surgery is declined or contraindicated, nasal CPAP is effective. CPAP is also useful as a temporary measure while weight loss is being effected.     

Pulmonary hypertension in patients with obstructive sleep apnea syndrome

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is associated with an increased cardiovascular morbidity, including pulmonary hypertension. Little is known about factors influencing the degree of pulmonary hypertension and left ventricular dysfunction in patients with OSAS, especially in the absence of concomitant lung disease. METHODS: Right heart catheterization, arterial blood gas analysis, and pulmonary function tests were performed in 92 consecutive patients (81 men and 11 women; mean +/- SD age, 53.1 +/- 11.0 years) with polysomnographically verified OSAS, in whom clinically significant lung disease was excluded. RESULTS: Eighteen patients (20%) had mild pulmonary hypertension; 8 (44%) of them also had increased pulmonary capillary wedge pressures (Ppew). Left ventricular dysfunction was associated with arterial hypertension. Only Ppcw (r = 0.51; P < .001) and the percentage of time during sleep spent with an oxygen saturation below 90% (as an indicator of the severity of OSAS) (r = 0.34; P = .003) were significantly and independently associated with pulmonary artery pressure. CONCLUSIONS: Obstructive sleep apnea syndrome can cause mild pulmonary hypertension, even in the absence of pulmonary disease. In these patients, pulmonary hypertension is of the postcapillary type, or-in patients with normal left ventricular function-strongly related to the severity of OSAS. Our findings indicate that OSAS may constitute an important, and independent, risk factor for pulmonary hypertension.     

Obstructive sleep apnea in patients with coronary heart disease

Patients with obstructive sleep apnea have an increased cardiovascular morbidity and mortality, those with co-existent coronary artery disease being particularly at risk. The object of our study was to evaluate the prevalence of obstructive sleep apnea in patients with coronary artery disease. 153 patients (117 men, 36 women) with verified coronary artery disease were given a highly sensitive standardized questionnaire. The 59 patients with pathological results were then checked with a 6-channel non-laboratory monitoring system. 22.2% of all patients had a respiratory disturbance index (RDI) above 5/h. and 14.4% above 10/h. 13.3% had a pathological RDI and additionally suffered from excessive daytime sleepiness. Patients with coronary artery disease have a high prevalence of obstructive sleep apnea and should consequently be screened for this sleep-related breathing disorder.     

Evaluation of patients with sleep apnea after tracheotomy

OBJECTIVE: To determine the effect of tracheotomy on polysomnographic and arterial blood gas data in patients with obstructive sleep apnea (OSA). DESIGN: A retrospective study of all patients who underwent tracheotomy and were studied polysomnographically at the Johns Hopkins Sleep Disorders Center, Baltimore, Md, since 1981. SETTING: A regional sleep disorders center. PATIENTS: Twenty-eight patients (8 women and 20 men), aged 22 through 77 years. Patients were categorized into 2 groups on the basis of whether they had already undergone tracheotomy before polysomnography. Group 1 patients all had a polysomnographic diagnosis of OSA before tracheotomy. They were further subdivided on the basis of whether cardiopulmonary decompensation had been absent (group 1a, n=10) or present (group 1b, n=13). Group 2 patients (n=5) had undergone tracheotomy to treat upper airway obstruction that developed after non-apnea-related upper aerodigestive tract surgeries. INTERVENTION: Tracheotomy. MAIN OUTCOME MEASURES: Nocturnal non-rapid eye movement, apnea-hypopnea index, percentage oxyhemoglobin saturation, and arterial blood gas data. RESULTS: Patients with OSA underwent tracheotomy as definitive treatment for the apnea (n=15), to prevent postoperative upper airway compromise after uvulopalatopharyngoplasty (n=7), and to treat upper airway compromise after non-apnea-related upper aerodigestive tract surgeries (n=6). Tracheotomy alleviated apnea in all 10 patients with uncomplicated sleep apnea (group 1a). For patients with OSA complicated by cardiopulmonary decompensation (group 1b), tracheotomy improved but did not eliminate sleep apnea in 7 of the 13 patients, despite overall improvement in arterial blood gas values. For patients whose sleep apnea had not been diagnosed polysomnographically before tracheotomy (group 2), tracheotomy was still required to treat OSA that had previously not been recognized. CONCLUSIONS: Tracheotomy effectively treated patients with uncomplicated OSA, but was much less effective in treating patients with OSA and cardiopulmonary decompensation. In patients who underwent tracheotomy in conjunction with other upper aerodigestive tract surgeries, concomitant obstructive sleep apnea often required continued use of a tracheotomy to maintain upper airway patency.     

Chemical control of breathing in patients with obstructive sleep apnea

The authors have studied chemical control of breathing in 37 normocapnic patients with OSA. These patients had increased apnea-hypopnea index (AHI = 51 +/- 22), obesity (BMI = 32.4 +/- 5.6 kg/m2) and normal lung function tests. Control group consisted of 20 healthy subjects with normal weight (BMI = 23.1 +/- 2.4 kg/m2). Respiratory responses (ventilatory and P0.1) to hypercapnic and hypoxic stimulation during rebreathing tests were measured with computerized methods. The obtained results in OSA patients were compared with the data of the control group. The results exceeding mean values of the control group above 1.64 SD were recognized as hyperreactive responses. The majority e.g. 26 patients (OSA-N) had normal respiratory responses during hypercapnic stimulation. delta V/delta PCO2 = 16.8 +/- 4.5 L/min/kPa, P0.1/delta PCO2 = 3.5 +/- 2.4 cm H2O/kPa/. In remaining 11 patients (OSA-H) respiratory responses were significantly increased delta V/delta PCO2 = 39.1 +/- 18.8 L/min/kPa, P0.1/delta PCO2 = 8.6 +/- 3.9 cm H20/kPa). During isocapnic hypoxic stimulation majority e.g. 25 patients (OSA-H) had significantly increased respiratory responses delta V/delta SaO2 = 3.28 +/- 1.63 L/min/%, delta P0.1/delta SaO2 = 0.54 +/- 0.43 cm H2O/%/. In remaining 12 patients (OSA-N) respiratory responses were within normal limits delta V/SaO2 = 1.2 +/- 0.28 L/min/%, delta P0.1/ delta SaO2 = 0.21 +/- 0.07 cm H2O/%/. The above results indicated, that majority OSA patients (67.5%) had increased ventilatory and P0.1 responses to hypoxic stimulation. Among them also 11 patients had increased respiratory responses to hypercapnia. It seems, that increased respiratory responses to hypoxic stimulus in OSA patients are symptoms of protective reaction to hypoxaemia occurring during repetitive sleep apnoea and reveals increased neuro-muscular output.     

The relationship between the severity of sleep apnea syndrome and 24-h blood pressure values in patients with obstructive sleep apnea

Analysis of the nucleotide sequence in the 5' flanking region of bacteriophage T4 gene 25 revealed three potential Shine and Dalgarno sequences, SD1, SD2 and SD3, with a spacing of 8, 17 and 27 nucleotides from the initiation codon of this gene, respectively. Results of our experiments in the bacteriophage T7 expression system clearly demonstrate that the SD3 sequence is required for efficient expression of gene 25. We propose the existence of a stem-loop structure that includes SD1 and SD2 sequences and brings the SD3 sequence to a favourable spacing with the initiation codon of gene 25. Since the predicted secondary structure in the translational initiation region of gene 25 is relatively unstable and the SD3 sequence, GAGG, is more typical than the SD1 sequence, GAG, we suggest that this structure could control the level of gene expression.     

Cardiovascular effects of mibefradil in hypertensive patients with obstructive sleep apnea

OBJECTIVE: Hypertension is often seen in obstructive sleep apnea (OSA) and is characterized by increased sympathetic activity, depressed baroreflex and accentuated vascular responsiveness. The objective of this study was to investigate the effects of the new T-selective calcium channel blocker mibefradil on invasively measured blood pressure (BP) and heart rate in hypertensive patients with OSA. METHODS: The present study was a double-blind, randomized and placebo-controlled before and after trial in two parallel groups. Fifty-three men aged 23 69 years with systemic hypertension and OSA were recruited from the Outpatient Department of the Marburg University Sleep Laboratory and hospitalized for 10 days. Mibefradil (50 mg) or placebo were given orally in the morning for 8 days. The main outcome measure was the mean arterial (radial) BP monitored continuously during nocturnal sleep and during standardized daytime physical and psychological performance testing. RESULTS: Mibefradil lowered mean arterial BP and heart rate with (SD) during the entire measurement period compared with placebo: -7.25 (9.59) vs -2.11 (8.43) mmHg (P=0.039) and -4.83 (5.94) vs -1.34 (4.13) bpm (P=0.022), respectively. Both effects were observed during nocturnal sleep and performance testing, including graded exercise. Adverse events did not differ compared with placebo. CONCLUSION: Mibefradil is an effective but well-tolerated antihypertensive that also lowers heart rate over 24 h in OSA, in conditions known to increase BP.     

Assessment of attention parameters in sleep apnea patients

In the current study the modality-shift paradigm was applied to examine attention deficits in sleep-apnea patients. The reaction times of ipsi- and crossmodal light and sound stimuli were measured on 34 patients presenting symptoms of sleep-apnea. Some of the simple reaction times of ipsimodal (light-light; sound-sound) and crossmodal (light-sound; sound-light) stimuli correlated with mean or with minimal oxygen saturation, but did not correlate with the frequency or duration of obstructive apneas and hypopneas. However, results are different if the amount of modality-shift effect is taken into consideration. Significant correlations were found for the maximal duration of obstructive apneas and hypopneas as well as for mean oxygen saturation.     

Assessment of ventilatory neuromuscular drive in patients with obstructive sleep apnea

The presence of abnormalities of the respiratory center in obstructive sleep apnea (OSA) patients and their correlation with polysomnographic data are still a matter of controversy. Moderately obese, sleep-deprived OSA patients presenting daytime hypersomnolence, with normocapnia and no clinical or spirometric evidence of pulmonary disease, were selected. We assessed the ventilatory control and correlated it with polysomnographic data. Ventilatory neuromuscular drive was evaluated in these patients by measuring the ventilatory response (VE), the inspiratory occlusion pressure (P.1) and the ventilatory pattern (VT/TI, TI/TTOT) at rest and during submaximal exercise, breathing room air. These analyses were also performed after inhalation of a hypercapnic mixture of CO2 (delta P.1/delta PETCO2, delta VE/delta PETCO2). Average rest and exercise ventilatory response (VE: 12.2 and 32.6 l/min, respectively), inspiratory occlusion pressure (P.1: 1.5 and 4.7 cmH2O, respectively), and ventilatory pattern (VT/TI: 0.42 and 1.09 l/s; TI/TTOT: 0.47 and 0.46 l/s, respectively) were within the normal range. In response to hypercapnia, the values of ventilatory response (delta VE/delta PETCO2: 1.51 l min-1 mmHg-1) and inspiratory occlusion pressure (delta P.1/delta PETCO2: 0.22 cmH2O) were normal or slightly reduced in the normocapnic OSA patients. No association or correlation between ventilatory neuromuscular drive and ventilatory pattern, hypersomnolence score and polysomnographic data was found; however a significant positive correlation was observed between P.1 and weight. Our results indicate the existence of a group of normocapnic OSA patients who have a normal awake neuromuscular ventilatory drive at rest or during exercise that is partially influenced by obesity.     

Fluoroscopic MR of the pharynx in patients with obstructive sleep apnea

PURPOSE: The purpose of our study was to introduce an ultrafast MR imaging technique of the pharynx as a diagnostic tool for viewing the mechanism of obstruction in patients with obstructive sleep apnea. METHODS: Six healthy volunteers and 16 patients with obstructive sleep apnea were examined on a 1.5-T whole-body imager using a circular polarized head coil. Ultrafast two-dimensional fast low-angle shot sequences were obtained in midsagittal and axial projections during transnasal shallow respiration at rest, during simulation of snoring, and during performance of the Müller maneuver. All patients underwent physical examination, transnasal fiberoptic endoscopy, and polysomnography. RESULTS: Five to six images were obtained per second with an in-plane resolution of 2.67 x 1.8 mm and 2.68 x 2.34 mm, allowing visualization of motion of the tongue, soft palate, uvula, and posterior pharyngeal surface. MR findings correlated well with results of clinical examination. The length of obstruction in the oropharynx, which cannot be ascertained by transnasal endoscopy of the pharynx, was clearly visible MR images. Differences between patients with obstructive sleep apnea and healthy subjects in terms of the degree of obstruction in the velopharynx and oropharynx depicted on MR images during the Müller maneuver were highly significant. CONCLUSION: We believe that ultrafast MR imaging is a reliable noninvasive method for use in the evaluation of obstructive sleep apnea.     

Are thyroid function tests necessary in patients with suspected sleep apnea?

Thyroid evaluation is frequently performed in patients with sleep apnea because of a suspected causal relationship between hypothyroidism and obstructive sleep apnea (OSA). The aim of this study was to determine the actual prevalence of hypothyroidism in patients referred for polysomnography and evaluate whether its rate was higher in patients with OSA than those without OSA. Ultrasensitive thyroid stimulating hormone (TSH) was performed on 255 of 279 consecutive patients referred for polysomnography from the neurology service of a large HMO. Hypothyroidism was detected in 1.6% (4/243) of all patients, 1.5% (3/194) of patients referred to evaluate OSA, and 2.0% of patients referred to evaluate the presence of periodic leg movement disorder (PLMD)/narcolepsy/parasomnia. There was no significant difference in rates of hypothyroidism in patients with documented OSA (2.9%, 3/103) compared to those without OSA (0.7%, 1/135). Two of the four patients with elevated TSHs had previously documented hypothyroidism and were on thyroxine replacement. Rates of hyperthyroidism were as high or higher than those of hypothyroidism in all groups. We conclude that thyroid screening does not appear to be appropriate for patients with suspected, or confirmed, OSA in the absence of signs or symptoms consistent with hypothyroidism or unless they are in a high risk group (women over the age of 60).     

Frontal lobe-related cognitive functions in patients with sleep apnea syndrome before and after treatment

Impairments of cognitive executive functions has been previously suspected to occur in Sleep Apnea Syndrome (SAS), as suggested by some neuropsychological studies. However such functions have not been assessed directly. In the present study, ten patients with SAS were evaluated with various focused frontal lobe-related tests in comparison with ten matched normal controls. Such tasks explored attention, short term memory spans, learning abilities, planning and programming capacities, categorizing activities and verbal fluency. Patients were found with a significant decreased ability to initiate new mental processes and to inhibit automatic ones in conjunction with a tendency for perseverative errors. They were also affected with deficits of verbal and visual learning abilities and they had reduced spans. Patients were submitted to continuous positive airway pressure (CPAP) and further reevaluated after 4-6 months of treatment. Patients were found to have normalized most of their cognitive executive and learning disabilities, except for all the short-term memory tests which remained unchanged. These findings are discussed in light of data from the literature concerning cognitive impairments described for patients with isolated daytime sleepiness versus hypoxemia, as illustrated in other pathological or physiological circumstances. The contribution of frontal lobe-related systems in short-term memory functions is also taken into account.     

Maxillomandibular advancement surgery in patients with obstructive sleep apnea: mandibular morphology and stability

Causal associations between various craniofacial morphologic variables and obstructive sleep apnea have been inferred and serve to justify many treatments. The purposes of this study were to examine the presurgical and postsurgical mandibular morphology of patients with obstructive sleep apnea who were undergoing maxillomandibular advancement and to assess the stability of the observed changes. Various mandibular morphologic variables of 32 male subjects were measured on presurgical, immediately postsurgical, and short-term and long-term postsurgical radiographs. The results demonstrated that presurgical mandibular morphology was not significantly different from that of control samples derived from the literature. The presurgical mandibular plane-hyoid measurement was an average of 11.4 mm greater than that in matched controls. On average, surgery resulted in a significantly longer mandible, a greater gonial angle, and a reduced mandibular plane-hyoid distance, although the response of the hyoid was quite variable. The surgical changes in mandibular length were relatively stable over the long-term. Obstructive sleep apnea did not appear to be related to abnormal presurgical mandibular morphology in this sample.     

Automobile accidents in patients with sleep apnea syndrome. An epidemiological and mechanistic study

AIM: To compare the pregnancy outcome, in particular gestational age and birth weight in women with systemic lupus erythematosus (SLE) diagnosed before and after pregnancy, and to review data on presence or absence of the antiphospholipid (aPL) antibody and flares of disease activity. METHOD: Case histories were reviewed of women with a diagnosis of SLE and an obstetric event attending Monash Medical Centre (MMC) over an eight year period (1988-96). Fifty-four pregnancies in 28 women were studied, with 44 occurring after the diagnosis of SLE (Group 1) and ten prior to the diagnosis of SLE (Group 2). RESULTS: In Group 1 there were 25 live births (63%) with 16 full term and nine premature deliveries, 12 spontaneous abortions, three foetal deaths in utero and four elective terminations. In Group 2 there were seven live births (70%), two spontaneous abortions and one foetal death in utero. The mean gestational age of live births was 35.8 weeks and 39.2 weeks respectively (p < 0.001). The mean birth weight of live births was 2448 g and 3030 g respectively (p < 0.023). a PL antibodies were positive in eight of 26 women tested with three live births and were negative in 18 of 26 women with 12 live births. Flares of disease activity occurred in 17 of 28 pregnancies. CONCLUSION: Pregnancy in women with a predisposition to SLE have a high risk of an adverse outcome. Clinical disease confers an additional risk. The mean gestational age and birth weight were significantly less in women with established disease. Mild flares in disease activity resulted in a favourable outcome while renal flares had a worse outcome.     

Neuropsychological functioning and determinants of morning alertness in patients with obstructive sleep apnea syndrome

Neuropsychological functioning is reported to be impaired in patients suffering from obstructive sleep apnea syndrome (OSAS). This syndrome is characterized by nocturnal respiratory disturbances, blood oxygen desaturations, sleep fragmentation, and excessive daytime sleepiness. Opinions are divided concerning the exact relationship between the observed cognitive deficits, nocturnal hypoxia, sleep disruption, and impaired daytime alertness. In the present study, morning neuropsychological function of 26 moderate to severe middle-aged sleep apneics is compared to that of 22 primary insomniacs. There were no performance differences on a range of neuropsychological tests among the two patient groups. In addition, the data suggest that morning alertness impairment, which is closely associated with a lack of slow wave sleep (SWS) and rapid eye movement (REM) sleep, is of major importance in inducing poorer cognitive performance in patients with moderate to severe sleep apnea.     

Pharyngeal critical pressure in patients with obstructive sleep apnea syndrome. Clinical implications

Current evidence suggests that patients with obstructive sleep apnea (OSA) may have greater pharyngeal critical pressure (Pcrit), which reflects the increase in upper airway collapsibility. The contribution of Pcrit to the severity of OSA and to the efficacious continuous positive pressure (nCPAPeff) therapy has never been extensively described and no data are available about the interaction of Pcrit, age, and anthropometric variables. To determine the relationship between Pcrit, severity of the disease, nCPAPeff, and anthropometric variables we measured Pcrit in a group of 106 patients with OSA. Pharyngeal critical pressure was derived from the relationship between maximal inspiratory flow and nasal pressure, Pcrit representing the extrapolated pressure at zero flow. Upper airway resistance (Rus) was determined as the reciprocal of the slope (DeltaPn/DeltaVImax cm H2O/L/s) in the regression equation. In a subgroup of 68 patients, during the diagnostic night, we measured as indices of respiratory effort, the maximal inspiratory esophageal pressure (Pes) at the end of apnea (Pesmax), the overall increase from the minimum to the maximum (DeltaPes), and the rate of increase of Pes during apnea (RPes). As a group, the mean Pcrit was 2.09 +/- 0.1 cm H2O (range, 0 to 4.5) and the mean Rus was 11.1 +/- 0.5 cm H2O/L/s. Although men have greater Pcrit, pharyngeal collapsibility was influenced neither by neck size nor by body mass index (BMI). Although there was a significant relationship between Pcrit and apnea plus hypopnea index (AHI) (r = 0.23, p = 0.02), neck circumference was the stronger predictor of apnea frequency, with Pcrit contributing only to the 3% of the variance. In the group of patients as a whole, a model including AHI, BMI, Rus, and Pcrit explained the 36% of the variance in nCPAPeff, with a greater contribution of AHI, Pcrit accounting for only 3% of the variation. In patients for whom the measure of respiratory effort was obtained, 42% of the variance in nCPAPeff was explained by RPes (33%) and BMI. From these results we conclude that Pcrit alone does not yield a diagnostically accurate estimation of OSA severity and nCPAPeff. Although individual collapsibility may predispose to pharyngeal collapse, upper airway occlusion may require the combination of several factors, including obesity, upper airway structure, and abnormalities in muscle control.