Peculiar lifespan changes of periodic leg movements during sleep in restless legs syndrome

The objective of this observational cohort study was to analyse the age‐related changes of periodic leg movements during sleep using the newest international scoring rules, to expand past analyses, including patients in the paediatric age range, and also to analyse the changes of short‐interval and isolated leg movements during sleep throughout the lifespan. One hundred and sixty‐five patients (84 women) with restless legs syndrome were recruited in the following age groups: 16 preschoolers (≤5 years of age), 29 school‐age children (6–12 years), 19 adolescents (13–17 years), 17 young adults (19–40 years), 47 adults (41–60 years) and 37 seniors (>60 years). Total, periodic, short‐interval and isolated leg movements during sleep and periodicity indexes were obtained by polysomnography. The total index showed (quartic polynomial interpolation) a decrease before 10 years, followed by a steady increase up to 30 years, a relatively stable period until 60 years, and a final increase up to 80 years. This course was almost entirely due to changes in periodic movements. Isolated movements did not change significantly and short‐interval movements showed only an increase in seniors. Our study indicates that, in restless legs syndrome, the total index shows a peculiar and unique course throughout the lifespan, mainly due to periodic movements. These age‐related changes may mirror developmental changes in network complexity known to occur in dopaminergic circuits. These data further confirm the need to better assess the periodicity of leg movements in sleep during the human development period, in order to obtain clinically useful information.     

Computer-assisted detection of nocturnal leg motor activity in patients with restless legs syndrome and periodic leg movements during sleep

STUDY OBJECTIVES: To assess the performance of a new method for automatic detection of periodic leg movements during sleep. METHODS: Leg movements during sleep were visually detected in the tibialis anterior muscles recordings of 15 patients with restless legs syndrome and 15 normal controls. Leg movements were detected automatically by means of a new computer method with which electromyogram signals are first digitally band-pass filtered and then rectified; subsequently, the detection of leg movements is performed by using 2 thresholds: one for the starting point and another to detect the end point of each leg movement. Sensitivity and false-positive rate were obtained; the American Sleep Disorders Association parameters were also computed, and the results analyzed by means of the Kendall W coefficient, the linear correlation coefficient and the Bland-Altman plots. SETTING: N/A. PARTICIPANTS: Fifteen patients with restless legs syndrome and periodic leg movements and 15 controls. MEASUREMENTS AND RESULTS: High values of the Kendall W coefficient of concordance between automatic and visual analysis were found with values close to 1 and the linear correlation coefficient for leg movements index and total leg movements index was > 0.950 (p < .000001). The Bland-Altman plots provided the limits of agreement between visual and computer detection, which were -9.01 and +9.89 for the periodic leg movement index. None of the normal controls was found to have periodic leg movement indexes >5 after automatic analysis. CONCLUSIONS: Our method can be applied to the clinical evaluation of periodic leg movements during sleep, with some caution in patients with a low periodic leg movement indexes. Large-scale research application is possible and can be considered as reliable.     

New approaches to the study of periodic leg movements during sleep in restless legs syndrome

STUDY OBJECTIVES: To describe a new approach for the analysis of quantity, type, and periodicity of the leg motor activity during sleep in patients with restless legs syndrome (RLS) and periodic leg movements (PLM). METHODS: The following parameters were taken into account for LM: duration, amplitude, area under the curve, sleep stage, side, interval, and bilaterality. The analysis of inter-LM intervals was carried out by drawing their distribution graphs. A new index evaluated their periodicity and was validated by means of a Markovian analysis. The differences in inter-LM intervals, LM duration, and area under the curve between normal controls and patients and between the 3 patient subgroups identified on the basis of their periodicity were statistically analyzed. SETTING: N/A. PARTICIPANTS: Sixty-five patients with RLS and periodic LM and 22 young healthy controls. MEASUREMENTS AND RESULTS: The RLS patients' inter-LM interval distribution graph showed a wide peak with a maximum located at around 15 to 30 seconds and extending from 10 to 90 seconds, not present in controls, and another peak for intervals less than 8 seconds, higher than that of controls. Three patient subgroups were identified with different proportions of these 2 peaks, periodicity, and Markovian parameters. Periodicity was not dependent on the periodic leg movement index. Patients showing the peak mainly at around 15 to 30 seconds tended to show slightly longer and higher area under the curve LM than did the other 2 subgroups. CONCLUSIONS: Our new approach seems to be useful in a new qualitative differentiation among patients with PLM, which is not possible by using the simple PLM index.     

Ropinirole decreases periodic leg movements and improves sleep parameters in patients with restless legs syndrome

STUDY OBJECTIVES: Polysomnographic study evaluating the efficacy of ropinirole for the treatment of patients with restless legs syndrome (RLS) suffering from periodic leg movements in sleep (PLMS). DESIGN: Double-blinded, placebo-controlled, parallel-group study. SETTING: 15 tertiary referral centers in the USA. Participants: 65 patients with RLS and PLMS. INTERVENTIONS: Ropinirole (0.25-4.0 mg per day) or placebo for 12 weeks. MEASUREMENTS AND RESULTS: Data from 59 patients were included in the primary endpoint analysis. PLMS per hour decreased more with ropinirole (48.5 to 11.8), compared with placebo (35.7 to 34.2; adjusted treatment difference: -27.2; 95% confidence interval [CI]: -39.1, -15.4; P < .0001). Periodic limb movements with arousal per hour decreased from 7.0 to 2.5 with ropinirole but increased from 4.2 to 6.0 with placebo (adjusted treatment difference: -4.3, 95% CI: -7.6, -1.1; P = .0096). Periodic limb movements while awake per hour decreased from 56.5 to 23.6 with ropinirole but increased from 46.6 to 56.1 with placebo (adjusted treatment difference: -39.5; 95% CI: -56.9, -22.1; P < .0001). Ropinirole treatment significantly improved patients' ability to initiate sleep (P < .05) and the amount of Stage 2 sleep compared with placebo (P < .001). There were also non-significant trends toward increases in total sleep time and sleep efficiency. Sleep adequacy (measured on the subjective Medical Outcomes Study sleep scale) was significantly improved with ropinirole treatment (adjusted treatment difference: 12.1; 95% CI: 1.1, 23.1; P = .0316). In contrast, the placebo group showed a greater increase in Stage 3/4 sleep (P < .01). No serious adverse events occurred in either group. CONCLUSIONS: Ropinirole is effective in the treatment of both the sleep and waking symptoms of RLS.     

Actigraphic assessment of periodic leg movements in patients with restless legs syndrome

The diagnosis of restless legs syndrome (RLS) relies upon diagnostic criteria which are based on history only, and dopaminergic treatment is not normally the first choice of treatment for all patients. It would be worthwhile to identify patients non‐responsive to dopaminergic treatment beforehand, because they may suffer from a restless legs‐like syndrome and may require alternative treatment. We included retrospectively 24 adult patients fulfilling the four essential criteria for restless legs and 12 age‐matched healthy controls. They were investigated by ambulatory actigraphy from both legs over three nights, and patients started treatment with dopamine agonists after this diagnostic work‐up. We examined 12 responders to dopaminergic treatment and 12 non‐responders and studied the association between response to dopaminergic treatment and the periodic limb movement index (PLMI) as assessed with actigraphy. Demographic characteristics, excessive daytime sleepiness and fatigue at baseline were similar in all three groups. Baseline RLS severity was similar between responders and non‐responders [International Restless Legs Severity Scale (IRLS): 25 ± 9 and 24 ± 8]. Group comparisons of PLMI before treatment initiation showed significant differences between the three groups. Post‐hoc pairwise comparisons revealed that healthy controls had significantly lower PLMI (4.9 ± 4.5) than responders (29.3 ± 22.7) and non‐responders (13.3 ± 11.2). Similarly, the PLMI in responders was lower than in non‐responders. PLMI day‐to‐day variability did not differ between responders and non‐responders and there was no correlation between treatment effect, as assessed by the decrease of the IRLS and baseline PLMI. Our retrospective study indicates that actigraphy to assess periodic limb movements may contribute to a better diagnosis of dopamine‐responsive restless legs syndrome.     

Periodic leg movements during sleep in narcoleptic patients with or without restless legs syndrome

We compared periodic and non‐periodic leg movements during sleep and polysomnography in patients with narcolepsy with cataplexy (NC) with or without restless legs syndrome (RLS) with matched idiopathic RLS (iRLS) and control subjects. We enrolled 100 patients with NC: 17 having RLS were compared with 34 sex‐ and age‐matched patients without RLS and with 17 normal controls and 17 iRLS subjects. Periodic leg movements were highest in iRLS and lowest in controls, with those in NC with RLS very close to iRLS, but higher than those in NC without RLS. The periodicity indexes showed the highest value in iRLS followed by NC with or without RLS and, finally, by controls. The inter‐leg movement intervals peaked between 10 and 50 s in NC with RLS and in iRLS, the former did not display the nocturnal gradual decrease of periodic leg movements typical of iRLS. Periodic leg movements during sleep and polysomnography displayed specific features in RLS and NC, respectively, with NC with RLS showing an intermediate pattern. Even if RLS is only detected by targeted interview in NC, its frequency and impact on night‐time sleep architecture and continuity suggest that this condition should be routinely searched for in NC.     

Sequence analysis of leg movements during sleep with different intervals (<10, 10–90 and >90 s) in restless legs syndrome

The aim of this study was to define the time structure of leg movements during sleep occurring with an intermovement interval (onset‐to‐onset) shorter than 10 s in patients with restless legs syndrome and controls, and to compare it to the structure of movements with intervals of 10–90 s or >90 s. Polysomnographic recordings of 141 untreated patients and 68 age‐matched normal controls were analysed. All movements were detected and classified into three categories, separated by intervals of <10, 10–90 or >90 s. The number of movements included in each category was significantly higher in patients than in controls. The movements with an interval of >90 s occurred steadily during the night, whereas the hourly distribution of movements with intervals of <10 or 10–90 s was decreasing or bell‐shaped in patients or controls, respectively. Movements with an interval of <10 s tended to have a shorter duration and constituted shorter sequences than movements with intervals of 10–90 or >90 s. The time structure features of the three categories of movements considered in this study were found to be clearly different. This, together with previous observations on the differential effects of dopamine agonists on movements with different intervals, suggests that movements with intervals of <10 and >90 s are regulated by neurotransmitter mechanisms different from those modulating movements with an interval of 10–90 s.     

Different periodicity and time structure of leg movements during sleep in narcolepsy/cataplexy and restless legs syndrome

STUDY OBJECTIVES: To analyze periodic leg movements (PLM) during sleep in patients with narcolepsy and compare the results with those obtained in normal controls and subjects with restless legs syndrome (RLS). METHODS: We recruited 40 HLA DQB1*0602-positive patients with narcolepsy/cataplexy, 22 with RLS, and 22 controls. The time structure of their polysomnographically recorded LMs was analyzed by means of an approach particularly able to consider their periodicity. MEASUREMENTS AND RESULTS: Nineteen patients with narcolepsy had a PLM index greater than 15. The distribution of inter-LM intervals was clearly bimodal in RLS and narcoleptics, with 1 peak at 2 to 4 seconds and another at around 22 to 26 seconds; in the range 22 to 40 seconds, patients with RLS had values significantly higher than patients with narcolepsy. All periodicity parameters were significantly lower in the narcolepsy group. Finally, the distribution of the number of PLM per hour of sleep was bell shaped in normal controls and patients with narcolepsy, whereas patients with RLS showed a progressive decrease throughout the night. CONCLUSION: Most narcoleptic patients show a high number of LMs that are significantly less periodic than those of patients with RLS. PLM are in functional interrelationship with the cyclic alternating pattern, which is reduced in patients with narcolepsy; decreased arousal fluctuations during sleep may be one of the factors influencing the reduction in periodicity of LMs during sleep in narcolepsy.     

Non-pharmacological management of periodic limb movements during hemodialysis session in patients with uremic restless legs syndrome

Restless legs syndrome (RLS) is very common in hemodialysis patients. RLS induces motor excitability and discomfort during rest periods, and those symptoms have also been observed during hemodialysis sessions. The aim of the study was to assess whether a single bout of exercise could reduce periodic limb movements (PLM) occurring during hemodialysis. Eighteen hemodialysis patients were eligible and participated in the study. Using the RLS criteria and further verified by the presence of PLM during sleep, patients were divided to non-RLS and RLS groups. Three scenarios were studied during three different sessions: 1) light exercise, including cycling for 45 minutes with no added resistance, 2) heavy exercise, including cycling for 45 minutes with a resistance set at 60% of their exercise capacity, and 3) no exercise, including rest for the same period of time. In all sessions, PLM per hour of hemodialysis (PLM/hHD) was recorded. A single bout of either light or heavy exercise was equally effective in significantly reducing PLM/hHD in patients with RLS compared with the no-exercise scenario, whereas in non-RLS patients, no effect was observed. Independent of intensity, a single bout of intradialytic exercise reduces PLM/hHD in hemodialysis patients with RLS. Further research is needed to establish the acute role of exercise in ameliorating the RLS symptoms.     

Interaction effect of obstructive sleep apnea and periodic limb movements during sleep on heart rate variability

We aimed at assessing cardiac autonomic function by heart rate variability during sleep in patients with obstructive sleep apnea and periodic limb movements during sleep, and to compare it with that of patients with obstructive sleep apnea only, periodic limb movements during sleep only, and controls. We also aimed at investigating the interaction effect between apnea–hypopnea index and periodic limb movement index on heart rate variability. Four groups of patients (n = 42 each, total = 168) were identified based on the presence/absence of obstructive sleep apnea and periodic limb movements during sleep: + obstructive sleep apnea/? periodic limb movements during sleep (5 ≤ apnea–hypopnea index < 30 events per hr), ? obstructive sleep apnea/+ periodic limb movements during sleep (periodic limb movement index > 15 events per hr), + obstructive sleep apnea/+ periodic limb movements during sleep, ? obstructive sleep apnea/? periodic limb movements during sleep (controls). All groups were matched for age, sex and body mass index. Time‐ and frequency‐domain heart rate variability measures were calculated over 5‐min periods of stable stage 2 non‐rapid eye movement sleep. In patients with both obstructive sleep apnea and periodic limb movements during sleep, LFnu and LF/HF ratio were higher than in those with obstructive sleep apnea only, periodic limb movements during sleep only, and controls, while HFnu was the lowest among the four groups. LFnu, HFnu and LF/HF ratio were significantly and independently associated with minimal oxygen saturation in the + obstructive sleep apnea/+ periodic limb movements during sleep group. There was a significant interaction effect between apnea–hypopnea index and periodic limb movement index on LF/HF ratio (p = 0.038) in patients with obstructive sleep apnea. Patients with elevated apnea–hypopnea index and elevated periodic limb movement index exhibited higher sympathovagal balance compared with those with high apnea–hypopnea index and low periodic limb movement index, and compared with those with low apnea–hypopnea index (regardless of periodic limb movement index). Increased sympathetic activation and decreased parasympathetic control appear to be related to the severity of oxygen desaturation. Apnea–hypopnea index and periodic limb movement index had interactive effects on increased sympathovagal balance in patients with obstructive sleep apnea.     

Age-related changes in cardiac autonomic control during sleep

Aging is commonly associated with decreased sleep quality and increased periodic breathing (PB) that can influence heart rate variability (HRV). Cardiac autonomic control, as inferred from HRV analysis, was determined, taking into account the sleep quality and breathing patterns. Two groups of 12 young (21.1 +/- 0.8 years) and 12 older (64.9 +/- 1.9 years) volunteers underwent electroencephalographic, cardiac, and respiratory recordings during one experimental night. Time and frequency domain indices of HRV were calculated in 5-min segments, together with electroencephalographic and respiratory power spectra. In the elderly, large R-R oscillations in the very-low frequency (VLF) range emerged, that reflected the frequency of PB observed in 18% of the sleep time. PB occurred more frequently during rapid eye movement sleep (REM) sleep and caused a significant (P < 0.02) increase in the standard deviation of normal R-R intervals (SDNN) and absolute low-frequency (LF) power. With normal respiratory patterns, SDNN, absolute VLF, LF, and high frequency (HF) power fell during each sleep stage (P < 0.01) compared with young subjects, with no significant sleep-stage dependent variations. An overall decrease (P < 0.01) in normalized HF/(LF + HF) was observed in the elderly, suggesting a predominant loss of parasympathetic activity which may be related to decreased slow-wave sleep duration. These results indicate that two distinct breathing features, implying different levels of autonomic drive to the heart, influence HRV in the elderly during sleep. The breathing pattern must be considered to correctly interpret HRV in the elderly.     

Respiratory sinus arrhythmia during sleep in children with upper airway obstruction

Upper airway obstruction during adulthood is associated with cardiovascular morbidity; cardiovascular consequences of childhood upper airway obstruction are less well established. This study aimed at investigating the effect of childhood upper airway obstruction on respiratory sinus arrhythmia as a measure of cardiac vagal modulation during night‐time sleep. Overnight polysomnography was conducted in 40 healthy children (20 M; age: 7.5 ± 2.6 years; body mass index percentile: 60.7 ± 26.4%) and 40 children with upper airway obstruction (24 M; age: 7.5 ± 2.7 years; body mass index percentile: 65.8 ± 31.9%). We used the phase‐averaging technique to compute respiratory sinus arrhythmia amplitude and phase delay. To study sleep stage effects and the effect of upper airway obstruction, respiratory sinus arrhythmia was measured during all artefact‐free sleep episodes, and after exclusion of respiratory events. A significant increase in respiratory sinus arrhythmia amplitude and phase delay was observed during stage 4 sleep as compared with rapid eye movement sleep in both groups (amplitude: controls = 0.10 ± 0.03 versus 0.07 ± 0.02 s, P < 0.01, respectively, and upper airway obstruction = 0.07 ± 0.03 versus 0.05 ± 0.03 s, P < 0.05, respectively; phase delay: controls = 3.1 ± 0.1 versus 3.0 ± 0.1 rad, P < 0.05, respectively, and upper airway obstruction = 3.13 ± 0.04 versus 3.04 ± 0.08 rad, P < 0.01, respectively). A significant association between respiratory sinus arrhythmia and apnea/hypopnea index was observed during stage 2 sleep in children with upper airway obstruction. Compared with healthy controls, a significant decrease in respiratory sinus arrhythmia amplitude during stage 2 sleep was observed in children with upper airway obstruction (0.09 ± 0.03 versus 0.06 ± 0.03 s, P < 0.05). However, this difference was not apparent when respiratory events were excluded from analysis. Importantly, respiratory sinus arrhythmia showed a strong negative correlation with body mass index. In conclusion, night‐time respiratory sinus arrhythmia in children is sleep stage dependent and normal during quiet sleep in children with relatively mild upper airway obstruction.     

Sleep‐disordered breathing in children is associated with impairment of sleep stage‐specific shift of cardiac autonomic modulation

We examined the effects of sleep stages and sleep‐disordered breathing (SDB) on autonomic modulation in 700 children. Apnea hypopnea index (AHI) during one 9 h night‐time polysomnography was used to define SDB. Sleep stage‐specific autonomic modulation was measured by heart rate variability (HRV) analysis of the first available 5 min RR intervals from each sleep stage. The mean [standard deviation (SD)] age was 112 (21) months (49% male and 25% non‐Caucasian). The average AHI was 0.79 (SD = 1.03) h^?1, while 73.0%, 25.8% and 1.2% of children had AHI <1 (no SDB), 1–5 (mild SDB) and ≥5 (moderate SDB), respectively. In the no SDB group, the high frequency (HF) and root mean square SD (RMSSD) increased significantly from wake to Stage 2 and slow wave sleep (SWS), and then decreased dramatically when shifting into rapid eye movement (REM) sleep. In the moderate SDB group, the pattern of HRV shift was similar to that of no SDB. However, the decreases in HF and RMSSD from SWS to REM were more pronounced in moderate SDB children [between‐group differences in HF (?24% in moderate SDB versus ?10% in no SDB) and RMSSD (?27% versus ?12%) were significant (P < 0.05)]. The REM stage HF is significantly lower in the moderate SDB group compared to the no SDB group [mean (standard error): 4.49 (0.43) versus 5.80 (0.05) ms², respectively, P < 0.05]. Conclusions are that autonomic modulation shifts significantly towards higher parasympathetic modulation from wake to non‐rapid eye movement sleep, and reverses to a less parasympathetic modulation during REM sleep. However, the autonomic modulation is impaired among children with moderate SDB in the directions of more reduction in parasympathetic modulation from SWS to REM sleep and significantly weaker parasympathetic modulation in REM sleep, which may lead to higher arrhythmia vulnerability, especially during REM sleep.     

Cardiac autonomic dynamics during sleep are lost in patients with TIA and stroke

Ischaemic stroke is accompanied by important alterations of cardiac autonomic control, which have an impact on stroke outcome. In sleep, cardiac autonomic control oscillates with a predominant sympathetic modulation during REM sleep. We aimed to assess cardiac autonomic control in different sleep stages in patients with ischaemic stroke. Forty‐five patients enrolled in the prospective, multicentre SAS‐CARE study but without significant sleep‐disordered breathing (apnea–hypopnea index < 15/hr) and without atrial fibrillation were included in this analysis. The mean age was 56 years, 68% were male, 76% had a stroke (n = 34, mean National Institutes of Health Stroke Scale [NIHSS] score of 5, 11 involving the insula) and 24% (n = 11) had a transitory ischaemic attack. Cardiac autonomic control was evaluated using three different tools (spectral, symbolic and entropy analysis) according to sleep stages on short segments of 250 beats in all patients. Polysomnographic studies were performed within 7 days and 3 months after the ischaemic event. No significant differences in cardiac autonomic control between sleep stages were observed in the acute phase and after 3 months. Predominant vagal modulation and decreased sympathetic modulation were observed across all sleep stages in ischaemic stroke involving the insula. Patients with ischaemic stroke and transitory ischaemic attack present a loss of cardiac autonomic dynamics during sleep in the first 3 months after the ischaemic event. This change could represent an adaptive phenomenon, protecting the cardiovascular system from the instabilities of autonomic control, or a risk factor for stroke, which precedes the ischaemic event.     

Heart rate variability and apnea during sleep in Down's syndrome

Autonomic system dysfunction has been reported to occur frequently in patients with Down's syndrome (DS) and is constituted mainly by an imbalance between the sympathetic and vagal systems. The analysis of heart rate variability (HRV) during sleep is a quantitative reliable method for studying such a mechanism, but it has not yet been extensively and adequately applied in DS. In this study, HRV during sleep was evaluated in seven DS patients and in six normal controls, by also controlling for the presence of sleep apnea or arousal. The main results were an increased sympathetic function (low-frequency component of HRV) and a decreased vagal activity (high-frequency component of HRV) in DS with respect to normal controls, during apnea-free periods. Moreover, the presence of apnea, in DS, induced a further significant increase in low-frequency and very low-frequency components of HRV during sleep Stage 2. This study provides additional evidence of a brainstem dysfunctioning in DS, responsible for the abnormal imbalance between the sympathetic and vagal systems and confirms the brainstem involvement already suggested in the literature in order to explain brainstem-auditory evoked potential abnormalities and central sleep apnea in these patients.     

Sleep/wake abnormalities in patients with periodic leg movements during sleep: Factor analysis on data from 24-h ambulatory polygraphy

Periodic Leg Movements (PLM) in sleep occur in a wide variety of sleep/wake disorders but their relationship with sleep disturbance, and notably with the concomitant existence of a 'restless legs' syndrome (RLS) remains unclear. We performed 24-h ambulatory polygraphy in a population of 54 consecutive, unselected patients with PLMs (Coleman's index greater than 5/h) who complained of different sleep disorders. A Principal Component Analysis (PCA) was conducted on seven variables from the sample, namely PLM index, patient's age, sleep stage changes per hour, sleep depth index (SWS+PS/TST), diurnal sleep time, number of awakenings exceeding 2 min and presence of a RLS. PCA yielded four independent factors. The PLM index and the changes of sleep stage clustered in a single factor, linking therefore sleep fragmentation to the frequency of PLMs. The second factor appeared to reflect a circadian sleep/wake disorder, combining diurnal sleep time with the number of long night awakenings. The third factor was mainly loaded by the patients' age and the sleep depth index, thus reflecting a well known relationship. Finally, the variable reflecting the existence of a RLS appeared isolated in a single factor, independent from the three previously described. These results confirm and extend the link between PLMs and sleep fragmentation, as well as the recently described dissociation between PLMs and diurnal somnolence. On the other hand, our analysis suggests that in PLM patients the concomitant existence of a RLS is not related to the frequency of occurrence of PLMs, at least when these latter are quantified independently of their arousal index.     

Usefulness of cardiac parasympathetic index in CPAP‐treated patients with obstructive sleep apnea: A preliminary study

Cardiac autonomic indexes, including cardiac parasympathetic index and cardiac sympathetic index, have been reported to accurately identify patients with sleep disorders such as obstructive sleep apnea. Our study aimed to assess cardiac autonomic indexes in patients with obstructive sleep apnea before and during a single full‐night continuous positive airway pressure therapy using a combined approach. Our simultaneous heart rate variability‐polysomnographic study included 16 never‐treated obstructive sleep apnea patients. Two patients dropped out. Patients underwent combined recordings in two consecutive days, at baseline and during a single full‐night of acute continuous positive airway pressure treatment. We calculated cardiac parasympathetic index and cardiac sympathetic index as night/day ratio for high‐frequency and low‐frequency heart rate variability spectral components, respectively. Continuous positive airway pressure treatment significantly reduced cardiac autonomic indexes values in comparison with baseline values (cardiac parasympathetic index: p < .0001; cardiac sympathetic index: p = .001). After acute continuous positive airway pressure treatment, the percentage of decrease of cardiac parasympathetic index was greater than that of cardiac sympathetic index (51.02 ± 15.72 versus 34.64 ± 26.93). A positive statistical correlation was also found between decrease of cardiac parasympathetic index and decrease of apnea–hypopnea index after continuous positive airway pressure (p < .001). This study improves the knowledge on cardiac autonomic modulation during acute continuous positive airway pressure therapy in obstructive sleep apnea. Our results demonstrate that both autonomic indexes decreased significantly after a single‐night of acute continuous positive airway pressure therapy. Cardiac parasympathetic index more than cardiac sympathetic index was related to decrease of apnea–hypopnea index after continuous positive airway pressure therapy, thus representing a potential help in everyday clinical practice.     

Forearm and leg amino acid metabolism in the basal state and during combined insulin and amino acid stimulation after a 3‐day fast

Aim: Fasting is characterized by a progressive loss of protein, but data on protein kinetics are unclear and few have studied the effects of re‐feeding. The present study was designed to test the hypothesis that a combined infusion of insulin and amino acids after fasting would induce compensatory increases in protein synthesis and reductions in protein breakdown at the whole body level and in muscle. Methods: We included 10 healthy male volunteers and studied them twice: (1) in the post‐absorptive state and (2) after 72 h of fasting. Amino acid kinetics was measured using labelled phenylalanine and tyrosine, whole body energy expenditure was assessed and urea nitrogen synthesis rates were calculated. Results: After fasting we observed an increase in arterial blood concentration of branched chain amino acids and a decrease in gluconeogenic amino acids (P < 0.05). Isotopically determined whole body, forearm and leg phenylalanine fluxes were unaltered apart from a 30% decrease in phenylalanine‐to‐tyrosine conversion (2.0 vs. 1.4 μmol kg^?1 h^?1, P < 0.01). During infusion of insulin and amino acids, amino acid concentrations increased. Conclusion: Our data indicate that after a 72‐h fast basal and insulin/amino acid‐stimulated regional phenylalanine fluxes in leg and forearm muscle are unaltered. During fasting concentrations of gluconeogenic amino acids decrease and hepatic and/or renal phenylalanine‐to‐tyrosine conversion decreases. Thus, as opposed to glucose and lipid metabolism, fasting does not induce insulin resistance as regards amino acid metabolism.