Melatonin rhythms in delayed sleep phase syndrome

The aim of this study was to compare circadian and sleep characteristics between patients with delayed sleep phase syndrome (DSPS) and healthy controls. The authors studied 8 DSPS patients and 15 normal controls. Serum melatonin concentration was assessed every hour for 24 h under dim light conditions. The sleep phase and the melatonin rhythm in DSPS patients were significantly delayed compared to those in normal controls. Sleep length was significantly greater in DSPS patients compared to that in controls, but the duration of melatonin secretion did not differ between the two groups. The final awakening, relative to melatonin onset, melatonin midpoint, and melatonin offset, was significantly longer in DSPS patients than in controls. By contrast, the timing of sleep onset relative to melatonin rhythm did not differ between the two groups. The authors found a significant positive correlation between sleep phase markers and melatonin phase markers in DSPS. They postulate that a delayed circadian pacemaker may be responsible for delayed sleep phase syndrome. The alteration of phase angle between melatonin rhythm and sleep phase suggested that not only the delay of the circadian clock but also a functional disturbance of the sleep-wake mechanism underlies DSPS.     

Multidimensional analysis of sleep electrophysiological signals

A night sleep polygraphic recording was coded by 20 s epochs, taking into account the recognizible features, summarized into 24 variables. In a 24 dimension space, the values of these variables are the coordinates of a point representative of each 20 s epoch. The coordinates of these points are given by a 24 column data table to which a factor analysis is applied in order to provide a bidimensional representation of the electrophysiological phenomena's evolution in time. Such a representation of the possible combinations of variables illustrates the structure of sleep without any biased ideas about this structure. The results obtained make it possible to consider the classical division of sleep into cycles and stages. Sleep seems to evolve continuously in time between a certain number of typical combinations, which supports the concept of cycle, but never following the same evolution between these combinations, which questions the reality of stages and their similarity from one cycle to the other.The method described seems to reflect more accurately than the classical hypnogram the phenomena of continuous modulation of nervous activity during sleep, and to open interesting possibilities for an analytical automatic treatment of sleep electrophysiological signals.Supported by Grant CRAM Paris No. 1871973 and by International Contract between Consiglio Nazionale delle Ricerche and C.N.R.S.     

Criterion validity of the Pittsburgh Sleep Quality Index: Investigation in a non-clinical sample

The objective of this study was to investigate the reliability and validity of the Pittsburgh Sleep Quality Index (PSQI) in a non-clinical sample consisting of younger and older adults. There has been little research validating the PSQI with respect to multinight recording as with actigraphy, and more validation is needed in samples not specifically selected for clinical disturbance. Also, the degree to which the PSQI scores may reflect depressive symptoms versus actual sleep disturbance remains unclear. One-hundred and twelve volunteers (53 younger and 59 older) were screened for their ability to perform treadmill exercises; inclusion was not based on sleep disturbance or depression. Internal homogeneity was evaluated by correlating PSQI component scores with the global score. Global and component scores were correlated with a sleep diary, actigraphy, and centers for epidemiological studies - depression scale scores to investigate criterion validity. Results showed high internal homogeneity. PSQI global score correlated appreciably with sleep diary variables and the depression scale, but not with any actigraphic sleep variables. These results suggest that the PSQI has good internal homogeneity, but may be less reflective of actual sleep parameters than a negative cognitive viewpoint or pessimistic thinking. The sleep complaints measured may often be more indicative of general dissatisfaction than of any specifically sleep-related disturbance.     

Sleep and wakefulness in Callorhinus ursinus

Sleep and wakefulness of northern fur seals were studied on three subadult bulls carrying the implanted electrodes for recording the electrocorticogram of the two hemispheres, the neck electromiogram, the electrooculogram and the electrocardiogram. The active wakefulness accounted for 32.0 +/- 5.3% of total recording time, the relaxed wakefulness -31.7 +/- 3.1%, the slow wave sleep -30.5 +/- 5.1% and the paradoxical sleep -5.8 +/- 0.9%. The sleep cycle averaged 22,6 +/- 1.2 minutes. Interhemispheric asymmetry of the ECoG slow waves was pronounced in all three animals. Different forms of the asymmetry occupied 15.0 +/- 0.7% of total recording time. Such interhemispheric asymmetry was found in pinnipeds for the first time, in this respect the northern fur seals differ from the Caspean seals but resemble the dolphins.     

Effect of Yokukansan on sleep disturbance and neuropathic pain in chronic constriction injury using a rat model

Sleep and Biological Rhythms - Patients with chronic pain develop peripheral neuropathy and experience sleep disturbance. Yokukansan is used to treat insomnia and control neuropathic pain. We...     

Persistence of the Nocturnal Thyrotropin Surge and Preservation of the Sleep-Related Variations of TSH in African Trypanosomiasis

The aim of this work was to study the nycthemeral and sleep-related variations of thyrotropin (TSH) in sleeping sickness (Human African trypanosomiasis). Six untreated patients were studied during 24 hours using 10 min blood sampling and polygraphic sleep recordings. These patients were compared to 5 healthy African subjects. The patients were selected during a medical investigation in Congo. Sleeping sickness was diagnosed clinically and confirmed by the detection of Trypanosoma brucei gambiense in the blood, the cerebrospinal fluid, or in a lymph node puncture, and by a serologic immunofluorescence test. Blood was withdrawn continuously via a catheter and sampled into 10 min aliquots in an adjoining room. TSH was measured by a commercial IRMA kit. Sleep was recorded by continuous polysomnography and scored visually. The integrity of the sleep-wake cycle varied greatly among patients, ranging from major disruption with insomnia to almost undisturbed nocturnal sleep. Mean TSH levels were slightly higher in the patients than in the controls, although the difference was not significant. The nocturnal surge was preserved in all but one patient and its amplitude was not different between patients and controls. There were more TSH pulses in the patients, maybe due to fragmented sleep with many awakenings. The relationships between sleep structure and TSH variations were preserved, with decreasing TSH levels during slow-wave sleep and increasing levels after awakenings. We conclude that contrarily to other biological rhythms, the nycthemeral pattern of TSH is preserved in the sleeping sickness patients. The TSH nocturnal surge persisted, unlike in other nonthyroidal illnesses. The relationhsips between TSH variations and sleep structure are also preserved, demonstrating the robustness of this association.     

Persistence of the Nocturnal Thyrotropin Surge and Preservation of the Sleep-Related Variations of TSH in African Trypanosomiasis

The aim of this work was to study the nycthemeral and sleep-related variations of thyrotropin (TSH) in sleeping sickness (Human African trypanosomiasis). Six untreated patients were studied during 24 hours using 10 min blood sampling and polygraphic sleep recordings. These patients were compared to 5 healthy African subjects. The patients were selected during a medical investigation in Congo. Sleeping sickness was diagnosed clinically and confirmed by the detection of Trypanosoma brucei gambiense in the blood, the cerebrospinal fluid, or in a lymph node puncture, and by a serologic immunofluorescence test. Blood was withdrawn continuously via a catheter and sampled into 10 min aliquots in an adjoining room. TSH was measured by a commercial IRMA kit. Sleep was recorded by continuous polysomnography and scored visually. The integrity of the sleep-wake cycle varied greatly among patients, ranging from major disruption with insomnia to almost undisturbed nocturnal sleep. Mean TSH levels were slightly higher in the patients than in the controls, although the difference was not significant. The nocturnal surge was preserved in all but one patient and its amplitude was not different between patients and controls. There were more TSH pulses in the patients, maybe due to fragmented sleep with many awakenings. The relationships between sleep structure and TSH variations were preserved, with decreasing TSH levels during slow-wave sleep and increasing levels after awakenings. We conclude that contrarily to other biological rhythms, the nycthemeral pattern of TSH is preserved in the sleeping sickness patients. The TSH nocturnal surge persisted, unlike in other nonthyroidal illnesses. The relationhsips between TSH variations and sleep structure are also preserved, demonstrating the robustness of this association.     

Sleep in chronic chorea patients after therapy with sodium valproate

In previous researches spontaneous nocturnal sleep in chronic chorea showed short total sleep time, prolonged sleep latency, several awakenings, reduction of REM sleep time, decrease in slow waves sleep, strong increase in sleep spindles. Some of these alterations improved after therapy with lithium, haloperidol and lithium, pimozide. Since the concentration of GABA has been found to be reduced in patients with Huntington's chorea, we studied the effect of sodium valproate, a drug that enhances GABA inhibition in cerebral cortex, on nocturnal sleep of six patients with chronic chorea, aged 35 to 60 years (mean 47,3). Nocturnal polygraphic records (EEG, EOG, EMG of chin muscles) were carried out after two consecutive adjustative nights, both before therapy and after sixty days of treatment with sodium valproate (800-2000 mg four times a day, orally). Moreover, chorea, finger dexterity and gait were each rated once a week by three members of the research team and by one independent observer, using a five points rating scale from 0 (normal) to 4 (very severely abnormal). Before therapy the sleep parameters were in accordance with our previous results in chronic choreic patients. After two months therapy we observed a statistically significant (P less than 0.05) reduction of awakenings and of wake time. Sodium valproate produced no objective change in any of the parameters of motor function studied. If singularly examined, however, a reduction of chorea was obtained only in a patient, whose favourable response to therapy was also demonstrated by the normalization of other sleep parameters. These data stress the importance of sleep study in extrapyramidal disorders and suggest a different involvement of GABA-mediated transmission in various patients with chronic chorea.     

Polygraphic findings in bird-like face syndrome with favorable spontaneous evolution

The syndrome characterized by acquired micrognathia, hypersomnia and periodic apneas during sleep is a rare consequence of mandibular underdevelopment. The pathogenesis is ascribed to incomplete obstruction of the upper airways associated with a hypoexcitability of the respiratory center. Tracheostomy, with the placement of a permanent tracheal cannula, has proved to be the only treatment producing clinical remission of the syndrome. Polygraphic findings were described in a case spontaneously recovered of hypersomnia and periodic apneas with acquired micrognathia due to a bilateral mastoiditis occurring in early childhood. In this patient three polygraphic recordings were carried out during diurnal and nocturnal sleep; another night sleep was recorded after a spontaneous improvement. In the early three recordings there is a prevalence of light sleep over slow-waves sleep and REM sleep is reduced in nocturnal sleep. There is a lot of periodic apneas during sleep stages. During apneas we observe an increase of heart frequency in NonREM sleep and a decrease in REM sleep. In the recording after clinical recovery we observe an improvement of sleep parameters and a disappearing of apneas in NonREM sleep. A temporary hyposensibility of respiratory centers is considered to be a possible interpretation of clinical and polygraphic improvement.     

Poor Sleep in Patients with Multiple Sclerosis

Background

Poor sleep is a frequent symptom in patients with multiple sclerosis (MS). Sleep may be influenced by MS-related symptoms and adverse effects from immunotherapy and symptomatic medications. We aimed to study the prevalence of poor sleep and the influence of socio-demographic and clinical factors on sleep quality in MS- patients.

Methods

A total of 90 MS patients and 108 sex-and age- matched controls were included in a questionnaire survey. Sleep complaints were evaluated by Pittsburgh Sleep Quality Index (PSQI) and a global PSQI score was used to separate good sleepers (≤5) from poor sleepers (>5). Excessive daytime sleepiness, the use of immunotherapy and antidepressant drugs, symptoms of pain, depression, fatigue and MS-specific health related quality of life were registered. Results were compared between patients and controls and between good and poor sleepers among MS patients.

Results

MS patients reported a higher mean global PSQI score than controls (8.6 vs. 6.3, p = 0.001), and 67.1% of the MS patients compared to 43.9% of the controls (p = 0.002) were poor sleepers. Pain (p = 0.02), fatigue (p = 0.001), depression (p = 0.01) and female gender (p = 0.04) were associated with sleep disturbance. Multivariate analyses showed that female gender (p = 0.02), use of immunotherapy (p = 005) and a high psychological burden of MS (p = 0.001) were associated with poor sleep among MS patients.

Conclusions

Poor sleep is common in patients with MS. Early identification and treatment of modifiable risk factors may improve sleep and quality of life in MS.     

On the Influence of Freight Trains on Humans: A Laboratory Investigation of the Impact of Nocturnal Low Frequency Vibration and Noise on Sleep and Heart Rate

Background

A substantial increase in transportation of goods on railway may be hindered by public fear of increased vibration and noise leading to annoyance and sleep disturbance. As the majority of freight trains run during night time, the impact upon sleep is expected to be the most serious adverse effect. The impact of nocturnal vibration on sleep is an area currently lacking in knowledge. We experimentally investigated sleep disturbance with the aim to ascertain the impact of increasing vibration amplitude.

Methodology/Principal Findings

The impacts of various amplitudes of horizontal vibrations on sleep disturbance and heart rate were investigated in a laboratory study. Cardiac accelerations were assessed using a combination of polysomnography and ECG recordings. Sleep was assessed subjectively using questionnaires. Twelve young, healthy subjects slept for six nights in the sleep laboratory, with one habituation night, one control night and four nights with a variation of vibration exposures whilst maintaining the same noise exposure. With increasing vibration amplitude, we found a decrease in latency and increase in amplitude of heart rate as well as a reduction in sleep quality and increase in sleep disturbance.

Conclusions/Significance

We concluded that nocturnal vibration has a negative impact on sleep and that the impact increases with greater vibration amplitude. Sleep disturbance has short- and long-term health consequences. Therefore, it is necessary to define levels that protect residents against sleep disruptive vibrations that may arise from night time railway freight traffic.     

A longitudinal large-scale objective sleep data analysis revealed a seasonal sleep variation in the Japanese population

In the contemporary era, when life habits are largely determined by social needs and individual preferences, sleep is nevertheless affected by seasonal environmental changes. Japan has large seasonal and geographical alterations of photoperiod and climate. Japan does not adopt the daylight saving time (DST) system, making it a suitable country for the study of seasonal variations in natural human sleep. The aim of this study was to analyze the seasonal changes in the sleep properties (timing and quality) and identify their relationship with environmental changes. Here, we report an analysis of objective sleep data of 691 161 nights collected from 1856 Japanese participants (age 20–79 years, male 91%, female 9%) for 3 years using contactless biomotion sensors. Sleep onset time did not show clear seasonal variation, but sleep offset time showed a seasonal change with a single latest peak in winter. Seasonal variation was larger during weekends than during weekdays. Sleep offset time well correlated with sunrise time but was different in spring and autumn even when the sunrise time was same, suggesting the role of temperature difference. Sleep quality, estimated by wake time after sleep onset and sleep efficiency, showed seasonal changes with the lowest trough around mid-summer. In conclusion, despite profound social influences, the timing and quality of sleep showed seasonal fluctuation indicating that they were influenced by climate factors even in the developed country.     

Is sleeping sickness a circadian disorder? The serotonergic hypothesis.

Patients with human African trypanosomiasis (HAT, sleeping sickness), due to the inoculation of Trypanosoma brucei gambiense or rhodesiense by the tsetse fly, are "sleepy by day and restless by night." The first 24 h polysomnographic recording (electroencephalogram [EEG], electromyogram [EMG], electrooculogram [EOG]), showing a disappearance of the 24 h rhythmicity of sleep and wakefulness, was performed in 1988. Thereafter, our team recorded 18 patients and 6 control volunteers at bed rest during 24 h sessions. Blood samples were taken hourly from 8 of the patients through a venous catheter and every 10 minutes from the remaining 10 patients. Plasma cortisol, prolactin, growth hormone (GH), melatonin, and plasma renin activity were analyzed. No disruptions of the circadian rhythms of sleep and wakefulness were described in the 6 healthy African subjects, and there also were no disturbances of 24 h hormone profiles. The patients experienced a dysregulation of the circadian rhythmicity of sleep and wakefulness that was proportional to the severity of the disease. Sleep onset rapid eye movement (REM) episodes were more frequent in the most severely sick patients, who also showed major disruptions in the 24 h plasma hormonal profiles, with intermediate profiles being observed at earlier stages of the sickness. However, the relationship between hormonal secretions and the states of vigilance persisted. Contrary to the other hormones, melatonin secretion remained undisturbed. These findings indicate that, at the stage of meningoencephalitis, HAT represents a dysregulation of the sleep-wake cycle and sleep structure, rather than a hypersomnia; this dysregulation is proportional to the degree of severity of the clinical and biological symptoms. It is accompanied by a circadian dysrhythmia of hormonal secretions, although the relationship between hormone pulses and sleep states is preserved. We therefore favor the involvement of the serotonergic raphe nuclei-suprachiasmatic nuclei liaison in the reversible disturbance of the circadian rhythms of the sleep-wake cycle and of hormonal secretions.     

Knee Pain and Low Back Pain Additively Disturb Sleep in the General Population: A Cross-Sectional Analysis of the Nagahama Study

Introduction

Association of knee and low back pain with sleep disturbance is poorly understood. We aimed to clarify the independent and combined effects of these orthopedic symptoms on sleep in a large-scale general population.

Methods

Cross-sectional data about sleep and knee/low back pain were collected for 9,611 community residents (53±14 years old) by a structured questionnaire. Sleep duration less than 6 h/d was defined as short sleep. Sleep quality and the presence of knee and low back pain were evaluated by dichotomous questions. Subjects who complained about knee or low back pains were graded by tertiles of a numerical response scale (NRS) score and a Roland-Morris disability questionnaire (RDQ) score respectively. Multivariate regression analyses were performed to determine the correlates of short sleep duration and poor sleep quality.

Results

Frequency of participants who complained of the orthopedic symptoms was as follows; knee pain, 29.0%; low back pain, 42.0% and both knee and low back pain 17.6%. Both knee and low back pain were significantly and independently associated with short sleep duration (knee pain: odds ratio (OR) = 1.19, p<0.01; low back pain: OR = 1.13, p = 0.01) and poor sleep quality (knee pain: OR = 1.22, p<0.01; low back pain; OR = 1.57, p<0.01). The group in the highest tertile of the NRS or RDQ score had the highest risk for short sleep duration and poor sleep quality except for the relationship between the highest tertile of the RDQ score and short sleep duration.(the highest tertile of the NRS: OR for short sleep duration = 1.31, p<0.01; OR for poor sleep quality = 1.47, p<0.01; the highest tertile of the RDQ: OR for short sleep duration = 1.11, p = 0.12; OR for poor sleep quality = 1.81, p<0.01) Further, coincident knee and low back pain raised the odds ratios for short sleep duration (either of knee or low back pain: OR = 1.10, p = 0.06; both knee and low back pain: OR = 1.40, p<0.01) and poor sleep quality (either of knee or low back pain: OR = 1.61, p<0.01; both knee and low back pain: OR = 2.17, p<0.01).

Conclusion

Knee and low back pains were independently associated with short sleep duration and poor sleep quality. Further, they additively increased the correlation with these sleep problems in the general population.     

Disruptions in sleep–wake cycles in community-dwelling cancer patients receiving palliative care and their correlates

Significant disruptions in sleep–wake cycles have been found in advanced cancer patients in prior research. However, much remains to be known about specific sleep–wake cycle variables that are impaired in patients with a significantly altered performance status. More studies are also needed to explore the extent to which disrupted sleep–wake cycles are related to physical and psychological symptoms, time to death, maladaptive sleep behaviors, quality of life and 24-h light exposure. This study conducted in palliative cancer patients was aimed at characterizing patients’ sleep–wake cycles using various circadian parameters (i.e. amplitude, acrophase, mesor, up-mesor, down-mesor, rhythmicity coefficient). It also aimed to compare rest–activity rhythm variables of participants with a performance status of 2 vs. 3 on the Eastern Cooperative Oncology Group scale (ECOG) and to evaluate the relationships of sleep–wake cycle parameters with several possible correlates. The sample was composed of 55 community-dwelling cancer patients receiving palliative care with an ECOG of 2 or 3. Circadian parameters were assessed using an actigraphic device for seven consecutive 24-h periods. A light recording and a daily pain diary were completed for the same period. A battery of self-report scales was also administered. A dampened circadian rhythm, a low mean activity level, an early mean time of peak activity during the day, a late starting time of activity during the morning and an early time of decline of activity during the evening were observed. In addition, a less rhythmic sleep–wake cycle was associated with a shorter time to death (from the first home visit) and with a lower 24-h light exposure. Sleep–wake cycles are markedly disrupted in palliative cancer patients, especially, near the end of life. Effective non-pharmacological interventions are needed to improve patients’ circadian rhythms, including perhaps bright light therapy.     

The relationship between chronotype,sleep disturbance,severity of fibromyalgia,and quality of life in patients with fibromyalgia

ABSTRACT

Patients with fibromyalgia (FM) report high levels of sleep disturbance and chronic diffuse musculoskeletal pain. These patients experience diminished quality of life (QoL) due to pain and other comorbidities. Chronotype preferences have been suggested as a potential factor connecting increased severity of FM, sleep disturbances, and poor overall QoL. The present study is the first study examining the possible association between chronotype preferences, sleep disturbance, severity of FM, and QoL in patients with FM.

One hundred drug-free patients diagnosed with FM participated in this cross-sectional study. Of them, 79 (79%) were females and 21 (21%) were males. The mean age was 41.65 ± 9.17 years (range: 21–62 years). The severity of FM symptoms, chronotype preferences, and QoL was evaluated using the Fibromyalgia Impact Questionnaire (FIQ), Morningness-Eveningness Questionnaire (MEQ), and World Health Organization Questionnaire on Quality of Life: Short Form (WHOQOL-BREF). The participants’ anxiety/depressive symptoms and sleep problems were assessed using the Hospital Anxiety and Depression Scale (HADS) and Pittsburgh Sleep Quality Index (PSQI).

The participants were classified according to their MEQ scores as evening type (score: 16–41), neither type (score: 42–58), and morning type (score: 59–86). It was found that there were significant differences in the FIQ score between the three groups (p < .001). It was determined that the total PSQI score was significantly higher in the evening type than the other two types (p < .05). It was found that there were significant differences in the general health, physical health, psychological, and environmental domain scores of the WHOQOL-BREF between the three groups (p < .05). It was detected that there were significant correlations between MEQ scores, WHOQOL-BREF subscale scores, FIQ scores, HADS-A and HADS-D scores, and PSQI scores. According to hierarchical regression analysis, eveningness preference explained an additional 21.9% of the variation in FM severity, thereby causing a statistically significant change in R-squared.

Our results indicated that eveningness preference was directly related to increased FM symptom severity and poorer QoL. Based on these findings, neglecting to take chronotype preference into account may not result in optimal response to standard treatment for some patients with FM.     

Sleep Disruption and Daytime Sleepiness Correlating with Disease Severity and Insulin Resistance in Non-Alcoholic Fatty Liver Disease: A Comparison with Healthy Controls

Background & Aims

Sleep disturbance is associated with the development of obesity, diabetes and hepatic steatosis in murine models. Hepatic triglyceride accumulation oscillates in a circadian rhythm regulated by clock genes, light-dark cycle and feeding time in mice. The role of the sleep-wake cycle in the pathogenesis of human non-alcoholic fatty liver disease (NAFLD) is indeterminate. We sought to detail sleep characteristics, daytime sleepiness and meal times in relation to disease severity in patients with NAFLD.

Methods

Basic Sleep duration and latency, daytime sleepiness (Epworth sleepiness scale), Pittsburgh sleep quality index, positive and negative affect scale, Munich Chronotype Questionnaire and an eating habit questionnaire were assessed in 46 patients with biopsy-proven NAFLD and 22 healthy controls, and correlated with biochemical and histological parameters.

Results

In NAFLD compared to healthy controls, time to fall asleep was vastly prolonged (26.9 vs. 9.8 min., p = 0.0176) and sleep duration was shortened (6.3 vs. 7.2 hours, p = 0.0149). Sleep quality was poor (Pittsburgh sleep quality index 8.2 vs. 4.7, p = 0.0074) and correlated with changes in affect. Meal frequency was shifted towards night-times (p = 0.001). In NAFLD but not controls, daytime sleepiness significantly correlated with liver enzymes (ALAT [r = 0.44, p = 0.0029], ASAT [r = 0.46, p = 0.0017]) and insulin resistance (HOMA-IR [r = 0.5, p = 0.0009]) independent of cirrhosis. In patients with fibrosis, daytime sleepiness correlated with the degree of fibrosis (r = 0.364, p = 0.019).

Conclusions

In NAFLD sleep duration was shortened, sleep onset was delayed and sleep quality poor. Food-intake was shifted towards the night. Daytime sleepiness was positively linked to biochemical and histologic surrogates of disease severity. The data may indicate a role for sleep-wake cycle regulation and timing of food-intake in the pathogenesis of human NAFLD as suggested from murine models.     

Improvement of Sleep Disturbance and Neurocognitive Function after Parathyroidectomy in Patients with Primary Hyperparathyroidism

ObjectiveTo investigate the frequency of the nontraditional symptoms of sleep disturbance and impaired cognitive functioning in patients with primary hyperparathyroidism (PHPT) and to assess changes in such patients after parathyroidectomy.MethodsIn this study, we used formal neurocognitive assessment of patients undergoing parathyroidectomy for PHPT. The Brief Sleep Disturbance Inventory assessed sleep disturbance, and Stroop tests evaluated for cognitive impairment. Study patients underwent preoperative and postoperative neurocognitive testing.ResultsFifty-five patients underwent neurocognitive evaluation; the 43 women and 12 men had a mean age of 63 years. Sleep disturbance was assessed in all 55 patients, whereas evaluation for cognitive impairment was performed in 47. Sleep disturbance was identified preoperatively in 24 (44%) of the 55 patients. This disorder affected 17 (31%) of 55 patients postoperatively (P < 0.01). Impaired executive functioning was found at baseline in 6 (13%) of 47 patients and decreased to 1 (2%) of 47 postoperatively (P < 0.01), whereas impaired cognitive processing speed was detected in 12 (26%) of 47 patients at baseline and decreased to 3 (6%) of 47 after parathyroidectomy (P < 0.01). Eight patients did not meet the National Institutes of Health consensus statement criteria for parathyroidectomy; 4 of these patients had preoperative impairment of sleep or cognitive functioning, 3 of whom showed improvement postoperatively.ConclusionSleep disturbance and neurocognitive impairment occur in patients with PHPT, and these disorders improve after parathyroidectomy. Further objective evaluation of nontraditional symptoms in patients diagnosed as having PHPT is warranted. (Endocr Pract. 2007;13:338-344)     

Polysomnographic sleep, growth hormone insulin-like growth factor-I axis, leptin, and weight loss

Short sleep appears to be strongly associated with obesity and altered metabolic function, and sleep and growth hormone (GH) secretion seems interlinked. In obesity, both the GH-insulin-like-growth-factor-I (GH-IGF-I) axis and sleep have been reported to be abnormal, however, no studies have investigated sleep in relation to the GH-IGF-I axis and weight loss in obese subjects. In this study polygraphic sleep recordings, 24-h GH release, 24-h leptin levels, free-IGF-I, total-IGF-I, IGF-binding protein-3 (IGFBP-3), acid-labile subunit (ALS), cortisol and insulin sensitivity were determined in six severely obese subjects (BMI: 41+/-1 kg/m(2), 32+/-2 years of age), cross-sectional at baseline, and longitudinal after a dramatically diet-induced weight loss (36+/-7 kg). Ten age- and gender-matched nonobese subjects served as controls. Sleep duration (360+/-17 vs. 448+/-15 min/night; P<0.01), 24-h GH (55+/-9 vs. 344+/-55 mU/l.24 h; P<0.01), free-IGF-I (2.3+/-0.42 vs. 5.7+/-1.2 microg/l; P<0.01), and total-IGF-I (186+/-21 vs. 301+/-18 microg/l; P<0.01) were significantly decreased and 24-h leptin levels were increased (35+/-5 vs. 12+/-3 microg/l; P<0.01) in obese subjects at pre-weight loss compared with nonobese subjects After diet-induced weight loss the differences in GH, free IGF-I, and leptin were no longer present between previously obese and nonobese subjects, whereas a significant difference in sleep duration and total IGF-I levels persisted. Rapid eye movement (REM) sleep, non-REM sleep, IGFBP-3, ALS, and cortisol levels were similar in obese and nonobese subjects. Sleep duration, 24-h GH, and IGF-I levels were decreased and 24-h leptin levels were increased in obese subjects. We conclude that hyposomatotropism and hyperleptinemia in obesity are transient phenomena reversible with weight loss, whereas short sleep seems to persist after weight has been reduced dramatically.     

Evidence of Associations between Cytokine Genes and Subjective Reports of Sleep Disturbance in Oncology Patients and Their Family Caregivers

The purposes of this study were to identify distinct latent classes of individuals based on subjective reports of sleep disturbance; to examine differences in demographic, clinical, and symptom characteristics between the latent classes; and to evaluate for variations in pro- and anti-inflammatory cytokine genes between the latent classes. Among 167 oncology outpatients with breast, prostate, lung, or brain cancer and 85 of their FCs, growth mixture modeling (GMM) was used to identify latent classes of individuals based on General Sleep Disturbance Scale (GSDS) obtained prior to, during, and for four months following completion of radiation therapy. Single nucleotide polymorphisms (SNPs) and haplotypes in candidate cytokine genes were interrogated for differences between the two latent classes. Multiple logistic regression was used to assess the effect of phenotypic and genotypic characteristics on GSDS group membership. Two latent classes were identified: lower sleep disturbance (88.5%) and higher sleep disturbance (11.5%). Participants who were younger and had a lower Karnofsky Performance status score were more likely to be in the higher sleep disturbance class. Variation in two cytokine genes (i.e., IL6, NFKB) predicted latent class membership. Evidence was found for latent classes with distinct sleep disturbance trajectories. Unique genetic markers in cytokine genes may partially explain the interindividual heterogeneity characterizing these trajectories.