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Patients with end-stage renal disease (ESRD) have an annual mortality rate exceeding 20%, although some survive many years. The ESRD population has a high incidence of sleep disorders, including sleep apnea and periodic limb movements in sleep (PLMS). Sleep disorders result in sleep deprivation, which can negatively affect immune function and cardiovascular-related outcomes, common causes of death in patients with ESRD. This study examined predictors of mortality in patients with ESRD with sleep problems. Twenty-nine consecutive patients with ESRD reporting disrupted sleep or daytime sleepiness were studied by all-night polysomnography. All patients were followed up until death, transplantation, or study termination. Among the variables studied, including such previously reported predictors as serum albumin level, urea reduction ratio, and hematocrit, only the PLMS index (PLMSI), arousing PLMSI (APLMSI), and total number of arousals per hour of sleep significantly predicted mortality. The 20-month survival rate with a PLMSI less than 20 was greater than 90% versus 50% for a PLMSI of 20 or greater (exact log-rank, P = 0.007). For the deceased versus survivor groups, mean PLMSI was 119.1 versus 19.8 (P = 0.01) and APLMSI was 48.1 versus 7.8 (P = 0.00006), with a mean survival of 10.3 versus greater than 25.5 months, respectively (P = 0.001). Median survival of patients with a PLMSI greater than 80 was only 6 months. PLMSI, APLMSI, and total arousals per hour of sleep were strongly associated with mortality in patients with ESRD with sleep disorders independent of other factors and may be novel predictors of near-term mortality.

End-stage renal disease (ESRD) is commonly associated with complaints of disturbed sleep and sleep disorders, frequently related to periodic limb movements in sleep (PLMS) or sleep apnea that may result in daytime sleepiness and other sequelae. Improvements in quality of life, including subjective sleep quality, have been reported in ESRD patients treated with recombinant human erythropoietin (rHuEPO). We investigated the objective effects of normalizing hematocrit on sleep disorders, sleep patterns, and daytime ability to remain awake in ESRD patients. Ten hemodialysis patients with sleep complaints while on rHuEPO therapy were studied by polysomnography while moderately anemic (mean hematocrit, 32.3%) and again when hematocrit was normalized (mean hematocrit, 42.3%) by increased rHuEPO dosing. Sleep patterns and associated parameters were monitored. Delivered dialysis dose and iron storage factors were monitored. Maintenance of Wakefulness Testing (MWT) was performed to assess daytime alertness/sleepiness. All 10 subjects experienced highly statistically significant reductions in the total number of arousing PLMS (P = 0.002). Nine of 10 subjects showed reductions in both the Arousing PLMS Index (P < 0.01) and the PLMS Index (P = 0.03) when hematocrit was normalized. Measures of sleep quality showed trends to improved quality of sleep. MWT demonstrated significant improvement in the length of time patients were able to remain awake (9.7 versus 17.1 minutes; P = 0.04). RHuEPO therapy with full correction of anemia reduces PLMS, arousals from sleep, and sleep fragmentation while allowing for more restorative sleep and improved daytime alertness. These findings may explain one mechanism for the improved quality-of-life parameters reported in ESRD patients treated with rHuEPO.

Parasomnias are generally described as disorders of arousal that arise out of stage 3 and 4 nonrapid eye movement (NREM) sleep without identifiable cause. We present a case of a 35-year-old man who during nasal continuous positive airway pressure (nCPAP) treatment for severe obstructive sleep apnea experienced an intense night terror triggered by a residual obstructive apnea during rebound deep sleep. The role of rebound deep sleep was thought to be essential in creating a state of sleep with a high arousal threshold hypothesized to be important for the occurrence of parasomnias. This case supports the clinical wisdom that identifiable sources of arousal can trigger parasomnias.

Complaints about sleep and daytime alertness are common in ESRD patients. Eight consecutive ESRD patients with a sleep complaint were studied with all-night polysomnography. All were found to have significant sleep apnea with a mean apnea/hypopnea index (AHI) of 64 +/- 41.6 episodes per hour of sleep (range 7.5 to 140/hr of sleep). The majority of apneas were of the central or mixed variety causing severe fragmentation of sleep and frequent awakenings. Treatment was attempted with nasal continuous positive airway pressure (NCPAP). NCPAP was highly successful in six of the eight patients, reducing the mean AHI to normal or near normal levels (6.0 +/- 3.8/hr of sleep, P < 0.02 vs. baseline). The quality of sleep was significantly improved with statistically significant decreases in light stage 1 sleep, and nocturnal oxygenation improved with statistically significant increases in low SaO2 values. Five of six responders reported that they awoke feeling more alert and fewer times from sleep. The etiology of sleep apnea in ESRD is unknown although the frequent central apneas suggest a dysfunction of central respiratory control resulting from the effects of renal failure. Sleep-related complaints in patients with ESRD are likely to result from sleep apnea, a sleep disorder that can be diagnosed with polysomnography and treated with NCPAP.

Pupil diameter was measured in light and dark conditions every half hour for 6.5-10 h in 3 normal controls and 3 narcoleptics. Mean pupillary diameter was significantly smaller in the narcoleptic group than in the normal group. Pupil activity was correlated with pupil diameter only in the dark condition in narcoleptics. Pupil diameter varied with a circa 90 min periodicity in the narcoleptics but not in the normal controls. These results indicate firstly, that one-time assessment of pupil size is insufficient; and secondly, that the appearance of these rhythms may be the result of a defect in arousal mechanisms of narcoleptics which usually play an inhibitory role.

The measurement and interpretation of nocturnal penile tumescence (NPT) studies depend on appropriate measurement techniques, knowledge of the conditions during which NPT was recorded, and a lack of preconceived notions about the relationship of penile circumference to penile rigidity. This case report illustrates several of the most common problems in the measurement and interpretation of NPT that could result in a false positive finding.

The effectiveness of codeine as a treatment for the excessive daytime sleepiness of narcolepsy was studied in two experimental trials. In an open trial of codeine in five narcoleptic subjects, dramatic clinical improvement was reported. However, all-night polysomnography and maintenance of wakefulness tests before and after codeine showed no significant differences. A double-blind placebo-codeine trial was conducted in which eight narcoleptic subjects received codeine for 1 week and placebo for 1 week in a random order. During the week they kept a diary, and on the sixth evening and for 10 h following awakening on the seventh day they were monitored by radiotelemetry in the sleep laboratory for electroencephalogram, electro-oculogram, and electromyogram. The results were analyzed for sleep stages as well as four levels of wakefulness. The results showed no significant differences in any of the objective sleep or wakefulness parameters. However, the diaries showed significantly fewer naps during the week on codeine as compared with the placebo week. Eighteen of 27 narcoleptic patients treated with codeine report clinical improvement. Codeine consistently results in subjective clinical improvement. However, this is not reflected in the objective measures generally used to assess daytime sleepiness.

A review of the sleep of 31 patients 45 years old or older undergoing nocturnal penile tumescence studies showed that 19 had a previously undiagnosed sleep disorder. Of the patients 9 had periodic leg movements in sleep, 9 had sleep apnea and 1 had both disorders. In 10 of these patients the sleep disorders affected nocturnal penile tumescence by disrupting sleep and causing brief periods of detumescence, movement artifacts and delays in the tumescing phase of nocturnal penile tumescence. These disruptions resulted in an apparently abnormal nocturnal penile tumescence that appeared as if the patient had difficulty in achieving or maintaining an erection. The nocturnal penile tumescence disruptions may have reflected only a disruption of the necessary conditions for normal nocturnal penile tumescence to occur, namely adequate sleep and rapid eye movement sleep. The results strongly suggest that failure to measure concurrent sleep parameters and screen for occult sleep disorders could result in the incorrect diagnosis of abnormal nocturnal penile tumescence.

Autonomic nervous system (ANS) measures have been used frequently as measures of activation or arousal. However, their relationship to standard measures of alertness--the Multiple Sleep Latency Test (MSLT) and Stanford Sleepiness Scale (SSS)--and to the quantity and quality of prior sleep has not been determined. In this study, the direct pupil light reflex (PLR) was measured with the MSLT and SSS to determine how ANS activity varies with daytime sleepiness and how all three measures were related to prior nocturnal sleep in a group of patients with obstructive sleep apnea. When the effects of age and time of day were partialed out, PLR data suggest that increased sleepiness as measured by MSLT is significantly correlated with increased parasympathetic activity (r = -0.60, p less than 0.01) and not with decreased sympathetic activity (r = -0.24, not significant). These partial correlations were significantly different (p less than 0.05). Increased sleepiness as measured by the SSS was significantly correlated with decreased sympathetic activity (r = -0.46, p less than 0.05) and not with increased parasympathetic activity (r = -0.00, not significant). These partial correlations were significantly different (p less than 0.02). In the group of sleep apnea patients, the PLR suggests that increased number of apneas and hypopneas (sleep fragmentation) was significantly correlated with both decreased sympathetic activity and increased parasympathetic activity. These findings suggest that ANS activity is related to daytime sleepiness and to the quality of prior sleep.

Periodic leg movements in sleep are shown to be a common finding in patients with OSA and may become evident or increase in severity after treatment of the OSA with NCPAP. Periodic leg movements in sleep were measured during baseline polysomnography, a NCPAP treatment trial, and a repeat NCPAP recording in 33 patients treated with NCPAP for OSA. During baseline PSG, nine patients had five or more PLMS per hour of sleep (index), while 14 patients had a PLMSI of 5 or more during the NCPAP trial and the repeat NCPAP recording. Among those patients with a PLMSI of 5 or more during repeat NCPAP studies, the PLMSI showed a significant increase from baseline to initial NCPAP (16.9 +/- 25.3 vs 39.3 +/- 29.4; p less than 0.001) and from baseline to repeat NCPAP (16.9 +/- 25.3 vs 42.9 +/- 39.8; p less than 0.05). The number of PLMS associated with electroencephalographic arousal also increased significantly from baseline to initial NCPAP (4.3 +/- 7.4 vs 9.7 +/- 8.9; p less than 0.05) and from baseline to repeat NCPAP (4.3 +/- 7.4 vs 16.5 +/- 18.6; p less than 0.05). The 14 patients with a PLMSI of 5 or more on the repeat NCPAP had significantly more stage 1 sleep and less REM sleep than 19 patients with a PLMSI of less than 5. Bilateral anterior tibialis EMG must be measured during NCPAP recordings in order to recognize sleep disruption caused by PLMS.

Changes in the sleep and daytime alertness of the elderly are common and are secondary to a variety of causes. These changes cannot be attributed solely to the aging process. The role of occult sleep disorders in producing these changes in significant, and severe sleep disruption in the healthy elderly is almost always secondary to a sleep disorder such as sleep apnea. A number of precautions must be kept in mind when interpreting studies of sleep in the elderly.

Recent evidence suggests that endogenous opiates may be involved in the pathophysiology of narcolepsy. To test this theory, the effect of 0.8 mg naloxone hydrochloride on pupil size and subjective alertness was measured in normal and narcoleptic subjects. Naloxone resulted in significant pupillary constriction in the normal but not in the narcoleptic subjects. The extent of contraction of the pupil light reflex was reduced significantly in the narcoleptic but not in the normal subjects. There was no effect on subjective ratings of alertness on the Stanford Sleepiness Scale or the visual analogue scale in either group. The naloxone-related miosis in the normal group confirms that naloxone is not a pure opiate antagonist. The lack of naloxone-related miosis in the narcoleptics suggests that narcoleptic individuals do not respond to naloxone as do normal individuals. However, this difference can not be definitely attributed to the antagonism of endogenous opiates. The reduction of the extent of contraction of the light reflex suggests that naloxone caused an increase in supranuclear inhibition of parasympathetic pupil reflex activity. However, this finding may have resulted from mechanical limitations of a small pupil or technical limitations of the recording equipment. This study does not support previous reports that naloxone causes an increase in subjective alertness in narcoleptics.