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 Blood was withdrawn continuously via a catheter and sampled into 10 min aliquots in an adjoining room.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 processes exert a predominant influence on the 24-h profile of heart rate variability

Adverse cardiovascular events are known to exhibit 24-h variations with a peak incidence in the morning hours and a nonuniform distribution during the night. The authors examined whether these 24-h variations could be related to circadian or sleep-related changes in heart rate (HR) and in HR variability (HRV). To differentiate the effect of circadian and sleep-related influences, independent of posture and of meal ingestion, seven normal subjects were studied over 24 h, once with nocturnal sleep from 2300 to 0700 h and once after a night of sleep deprivation followed by 8 h of daytime sleep from 0700 to 1500 h. The subjects were submitted to constant conditions (continuous enteral nutrition and bed rest). HRV was calculated every 5 min using two indexes: the standard deviation of normal R-R intervals (SDNN) and the ratio of low-frequency to low-frequency plus high-frequency power. Sleep processes exerted a predominant influence on the 24-h profiles of HR and HRV, with lowest HRV levels during slow wave sleep, high levels during REM sleep and intrasleep awakenings, and abrupt increases in HR at each transition from deeper sleep to lighter sleep or awakenings. The circadian influence was smaller, except for SDNN, which displayed a nocturnal increase of 140% whether the subjects slept or not. This study demonstrates that 24-h variations in HR and HRV are little influenced by the circadian clock andare mainly sleep-stage dependent. The results suggest an important role for exogenous factors in the morning increase in cardiovascular events. During sleep, the sudden rises in HR at each transition from deeper sleep to lighter sleep or awakenings might precipitate the adverse cardiac events.     

Improved circadian sleep-wake cycle in infants fed a day/night dissociated formula milk

On the basis of the circadian nutritional variations present in breast milk, and of the implications for the sleep/wake cycle of the nutrients present in infant formula milks, we designed a formula milk nutritionally dissociated into a Day/Night composition. The goal was to improve the bottle-fed infant's sleep/wake circadian rhythm. A total of 21 infants aged 4-20 weeks with sleeping difficulties were enrolled in the three-week duration study. The sleep analysis was performed using an actimeter (Actiwatch) placed on an ankle of each infant to uninterruptedly record movements during the three weeks. The dissociated Day milk, designed to be administered from 06:00 to 18:00, contained low levels of tryptophan (1.5g/100g protein) and carbohydrates, high levels of proteins, and the nucleotides Cytidine 5 monophosphate, Guanosine 5 monophosphate and Inosine 5 monophosphate. The dissociated Night milk, designed to be administered from 18.00 to 06.00, contained high levels of tryptophan (3.4g/100g protein) and carbohydrates, low levels of protein, and the nucleotides Adenosine 5 monophosphate and Uridine 5 monophosphate. Three different milk-feeding experiments were performed in a double-blind procedure covering three weeks. In week 1 (control), the infants received both by day and by night a standard formula milk; in week 2 (inverse control), they received the dissociated milk inversely (Night/Day instead of Day/Night); and in week 3, they received the Day/Night dissociated formula concordant with the formula design. When the infants were receiving the Day/Night dissociated milk in concordance with their environment, they showed improvement in all the nocturnal sleep parameters analyzed: total hours of sleep, sleep efficiency, minutes of nocturnal immobility, nocturnal awakenings, and sleep latency. In conclusion, the use of a chronobiologically adjusted infant formula milk seems to be effective in improving the consolidation of the circadian sleep/wake cycle in bottle-fed infants.     

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.     

Maternal thyroid function in early and late pregnancy.

Thyroid function was investigated during and after pregnancy in 12 healthy euthyroid women. During pregnancy, serum total T4 (TT4) levels were significantly elevated and nearly stable, while thyroxine-binding globulin (TBG) levels progressively increased till the 7th month. A slight elevation, though not significant, of free T4 (fT4) was recorded in early pregnancy. In the following months, fT4, free T3 (fT3) and the T4/TBG ratio progressively diminished, reaching a plateau at the 7th month. Serum TSH levels, measured by an ultrasensitive immunofluorometric assay, were comparable to postpartum values during the first trimester and showed a moderate upward trend with the progression of pregnancy. The evaluation of 24-hour TSH profiles was performed in 5 women during the first trimester of pregnancy. In all women, the circadian rhythm of TSH was present with a normal nocturnal surge, though anticipated in 1 case. In summary (1) during the first trimester of pregnancy, the increased thyroid activity does not seem to be only sustained by pituitary TSH which remains unmodified; the negative correlation between TSH and hCG levels might suggest that hCG also stimulates the gland to increase thyroid hormone output, and the presence of a normal TSH circadian rhythm indicates that the central mechanism of neuroregulation of the pituitary-thyroid axis is preserved in early pregnancy, and (2) in late pregnancy, a marked decrease in free thyroid hormone fractions is accompanied by serum TSH levels still in the normal range, indicating a modification of thyroid homeostasis which might recognize various etiological factors.     

Longitudinal Study of Mothers' Sleep-Wake Behaviors and Circadian Time Patterns from Late Pregnancy to Postpartum - Monitoring of Wrist Actigraphy and Sleep Logs

This longitudinal study investigated sleep-wake behavior patterns during and after pregnancy, using an actimeter worn on the non-dominant wrist and a sleep log. Records were obtained from ten mothers, from the 34th week of gestation until the 15th week postpartum. Ten non-pregnant women were used as a control group, data being collected from them for 2 weeks. The sleep-wake behavior after delivery, obtained from wrist actigraphy, was greater in the postpartum period. Total sleep time, sleep efficiency, and circadian amplitude decreased in the weeks immediately following parturition, but wake after sleep onset increased. Subsequently, all the sleep and circadian variables improved slightly, but they had not returned to the levels of the non-pregnant control group even by the 15th postpartum week. The length of daytime naps increased, in order to make up for nocturnal sleep deprivation when the number of awakenings during nighttime had increased. There were significant positive correlations between total sleep time, sleep efficiency, wake after sleep onset, and the length of daytime naps, but the numbers of awakenings at night and daytime naps did not show this correlation. The total sleep time indicated by sleep logs tended to be greater than that indicated by actigraphy, but wake after sleep onset tended to be underestimated by the sleep logs. The implications of these results are discussed.     

Sleep enhances nocturnal plasma ghrelin levels in healthy subjects

Ghrelin, an endogenous ligand of the growth hormone secretagogue receptor, has been shown to promote slow-wave sleep (SWS, non-REM sleep stages 3 and 4). Plasma levels of ghrelin are dependent on food intake and increase in sleeping subjects during the early part of the night. It is unknown whether sleep itself affects ghrelin levels or whether circadian networks are involved. Therefore, we studied the effect of sleep deprivation on nocturnal ghrelin secretion. In healthy male volunteers, plasma levels of ghrelin, cortisol, and human growth hormone (hGH) were measured during two experimental sessions of 24 h each: once when the subjects were allowed to sleep between 2300 and 0700 and once when they were kept awake throughout the night. During sleep, ghrelin levels increased during the early part of the night and decreased in the morning. This nocturnal increase was blunted during sleep deprivation, and ghrelin levels increased only slightly until the early morning. Ghrelin secretion during the first hours of sleep correlated positively with peak hGH concentrations. We conclude that the nocturnal increase in ghrelin levels is more likely to be caused by sleep-associated processes than by circadian influences. During the first hours of sleep, ghrelin might promote sleep-associated hGH secretion and contribute to the promotion of SWS.     

Longitudinal Study of Mothers’ Sleep-Wake Behaviors and Circadian Time Patterns from Late Pregnancy to Postpartum – Monitoring of Wrist Actigraphy and Sleep Logs

This longitudinal study investigated sleep-wake behavior patterns during and after pregnancy, using an actimeter worn on the non-dominant wrist and a sleep log. Records were obtained from ten mothers, from the 34th week of gestation until the 15th week postpartum. Ten non-pregnant women were used as a control group, data being collected from them for 2 weeks. The sleep-wake behavior after delivery, obtained from wrist actigraphy, was greater in the postpartum period. Total sleep time, sleep efficiency, and circadian amplitude decreased in the weeks immediately following parturition, but wake after sleep onset increased. Subsequently, all the sleep and circadian variables improved slightly, but they had not returned to the levels of the non-pregnant control group even by the 15th postpartum week. The length of daytime naps increased, in order to make up for nocturnal sleep deprivation when the number of awakenings during nighttime had increased. There were significant positive correlations between total sleep time, sleep efficiency, wake after sleep onset, and the length of daytime naps, but the numbers of awakenings at night and daytime naps did not show this correlation. The total sleep time indicated by sleep logs tended to be greater than that indicated by actigraphy, but wake after sleep onset tended to be underestimated by the sleep logs. The implications of these results are discussed.     

Circadian fluctuations in the muscular efficiency of athletes: with sleep versus sleep deprivation

The influence of time of day on muscular performance was studied. From part of the results of two different studies (EAS et EPS), the effects of sleep deprivation were appreciated. Seven times over the 24-h period, developed torque and myoelectric activity were estimated during maximal isometric voluntary contractions using an isokinetic dynamometer: elbow flexion for EAS in standardised sleep, and knee extension for EPS in complete sleep deprivation. The results showed nycthemeral changes in torque in both conditions (p < 0.005), with maximal values recorded at the beginning of night. Although during sleep deprivation (EPS) the rhythm followed neurophysiological factors, during EAS, this rhythm was accounted for by the variations in the contractile state of muscle.     

Identification of Trypanosome Proteins in Plasma from African Sleeping Sickness Patients Infected with T. b. rhodesiense

Control of human African sleeping sickness, caused by subspecies of the protozoan parasite Trypanosoma brucei, is based on preventing transmission by elimination of the tsetse vector and by active diagnostic screening and treatment of infected patients. To identify trypanosome proteins that have potential as biomarkers for detection and monitoring of African sleeping sickness, we have used a ‘deep-mining” proteomics approach to identify trypanosome proteins in human plasma. Abundant human plasma proteins were removed by immunodepletion. Depleted plasma samples were then digested to peptides with trypsin, fractionated by basic reversed phase and each fraction analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). This sample processing and analysis method enabled identification of low levels of trypanosome proteins in pooled plasma from late stage sleeping sickness patients infected with Trypanosoma brucei rhodesiense. A total of 254 trypanosome proteins were confidently identified. Many of the parasite proteins identified were of unknown function, although metabolic enzymes, chaperones, proteases and ubiquitin-related/acting proteins were found. This approach to the identification of conserved, soluble trypanosome proteins in human plasma offers a possible route to improved disease diagnosis and monitoring, since these molecules are potential biomarkers for the development of a new generation of antigen-detection assays. The combined immuno-depletion/mass spectrometric approach can be applied to a variety of infectious diseases for unbiased biomarker identification.     

Actigraphy in human African trypanosomiasis as a tool for objective clinical evaluation and monitoring: a pilot study

Background

Human African trypanosomiasis (HAT) or sleeping sickness leads to a complex neuropsychiatric syndrome with characteristic sleep alterations. Current division into a first, hemolymphatic stage and second, meningoencephalitic stage is primarily based on the detection of white blood cells and/or trypanosomes in the cerebrospinal fluid. The validity of this criterion is, however, debated, and novel laboratory biomarkers are under study. Objective clinical HAT evaluation and monitoring is therefore needed. Polysomnography has effectively documented sleep-wake disturbances during HAT, but could be difficult to apply as routine technology in field work. The non-invasive, cost-effective technique of actigraphy has been widely validated as a tool for the ambulatory evaluation of sleep disturbances. In this pilot study, actigraphy was applied to the clinical assessment of HAT patients.

Methods/Principal Findings

Actigraphy was recorded in patients infected by Trypanosoma brucei gambiense, and age- and sex-matched control subjects. Simultaneous nocturnal polysomnography was also performed in the patients. Nine patients, including one child, were analyzed at admission and two of them also during specific treatment. Parameters, analyzed with user-friendly software, included sleep time evaluated from rest-activity signals, rest-activity rhythm waveform and characteristics. The findings showed sleep-wake alterations of various degrees of severity, which in some patients did not parallel white blood cell counts in the cerebrospinal fluid. Actigraphic recording also showed improvement of the analyzed parameters after treatment initiation. Nocturnal polysomnography showed alterations of sleep time closely corresponding to those derived from actigraphy.

Conclusions/Significance

The data indicate that actigraphy can be an interesting tool for HAT evaluation, providing valuable clinical information through simple technology, well suited also for long-term follow-up. Actigraphy could therefore objectively contribute to the clinical assessment of HAT patients. This method could be incorporated into a clinical scoring system adapted to HAT to be used in the evaluation of novel treatments and laboratory biomarkers.     

Circadian Eating and Sleeping Patterns in the Night Eating Syndrome

Objective: To compare the eating and sleep‐wake patterns of persons with the night eating syndrome (NES) with those of matched control subjects. Research Methods and Procedures: Forty‐six overweight/obese NES subjects (mean age 43.3 ± 9.8 years; 32 women) and 43 similar controls (mean age 39.0 ± 11.0 years; 28 women) wore wrist actigraphs for 7 days and completed sleep and food diaries at home. Results: There was no difference between the total energy intake of the NES and the control subjects, but the pattern of energy intake differed greatly. Relative to control subjects, the temporal pattern of food intake of night eaters was delayed. Food intake after the evening meal, as a proportion of the 24‐hour intake, was more than 3‐fold greater in NES subjects than in controls (34.6 ± 10.1% vs. 10.0 ± 6.9%, p = 0.001). NES subjects had sleep onset, offset, and total sleep duration times comparable with those of controls. NES subjects reported more nocturnal awakenings than did controls (1.5 ± 1.0 per night vs. 0.5 ± 0.5; p < 0.001), and their actigraphically monitored arousals occurred earlier during sleep (at 128 minutes after sleep onset vs. 193 minutes, p = 0.01). NES subjects consumed food on 74% of the awakenings vs. 0% for the controls. Discussion: The pattern of cumulative energy intake of the night eaters suggests a phase delay in energy consumption relative to sleep‐wake times. NES may involve a dissociation of the circadian control of eating relative to sleep.     

Association of sickness absence with poor sleep and depressive symptoms in shift workers

A cross-sectional study was conducted to evaluate the contribution of daily sleep habits and depressive symptoms to sickness absences of shift workers. A self-administered questionnaire that solicited answers about sleep, symptoms of depression, sickness absence, diseases/injuries, and lifestyle factors was submitted to a sample of 522 rotating shift workers between the ages of 18-59 (mean 27) yrs of an electric equipment manufacturing company. The seven features of sleep queried were daily hours of sleep, time to fall asleep, awakening during sleep, early morning awakening, sleep well at night, sufficiency of sleep, and excessive daytime sleepiness at work. The responses were assessed over the subject's previous 1-yr period. Each sleep feature, except daily sleeping hours, was dichotomized by the following responses: (1) taking more than 30min to fall asleep (difficulty initiating sleep; DIS), (2) awakening during sleep almost every day (difficulty maintaining sleep; DMS), (3) early morning awakening almost every day (EMA), (4) sleeping very poorly or not so well at night, (5) definite or somewhat insufficient nightly sleep, and (6) excessive daytime sleepiness at work almost every day (EDS). Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) scale. Sickness absence was calculated by asking subjects "How many days in total have you been absent from work due to sickness, including paid vacation, in the last 1-yr period?" The responses were divided into three groups that included no (0 days) sickness absences (reference group, n=235 subjects), 1 to 4 days (short-term, n=199 subjects), and 5 days or more (long-term, n = 88 subjects). Compared to the prevalence of sleep features of the reference group, workers with short-term absence showed a significantly higher prevalence of EMA with an odds ratio (OR) of 5.3, 95% confidence interval (CI) 1.3-22.0. Long-term absence was significantly associated with DMS (OR = 2.1, 95%CI 1.0-4.6), EMA (OR = 5.6, 95%CI 1.0-28.7), sleeping poorly at night (OR= 2.6, 95%CI 1.4-5.0), and high depressive symptoms (OR = 2.0, 95%CI 1.0-3.7) according to the CES-D score of >16, after adjusting for multiple confounding variables. These data point to an association between both the parameters of poor sleep and symptoms of deep depression when self-reported sickness absence is frequent. The association is particularly strong with long-term absence in male shift workers.     

Effect of sleep on nocturnal bronchoconstriction and ventilatory patterns in asthmatics

To assess the effect of sleep on airflow resistance and patterns of ventilation in asthmatic patients with nocturnal worsening, 10 adult subjects (6 asthmatic patients with nocturnal worsening, 4 normal controls) were monitored overnight in the sleep laboratory on two separate occasions. During 1 night, subjects were allowed to sleep normally, whereas during the other night all sleep was prevented. The six asthmatic patients demonstrated progressive increases in lower airway resistance (Rla) on both nights, but the rate of increase was twofold greater (P less than 0.0001) during the sleep night compared with the sleep prevention night. However, overnight decrements in forced expired volume in 1 s (FEV1) were similar over the 2 nights. The asthmatic patients maintained their minute ventilation as Rla increased during sleep, demonstrating a stable tidal volume with a mild increase in respiratory frequency. We conclude that in asthmatic patients with nocturnal worsening 1) Rla increases and FEV1 falls overnight regardless of sleep state, 2) sleep enhances the observed overnight increases in Rla, and 3) sleep does not abolish compensatory ventilatory responses to spontaneously occurring bronchoconstriction.     

Thyrotropin nyctohemeral pattern in primary depression : Differences between unipolar and bipolar women

The nyctohemeral patterns of serum thyrotropin (TSH) levels were studied in thirteen female patients suffering from primary affective illness (5 bipolars and 8 unipolars); they were compared to the nyctohemeral profiles obtained in six normal female subjects. The periodogram analysis showed striking differences in TSH circadian rhythms between unipolar and bipolar patients. The nyctohemeral TSH patterns in bipolar patients were similar to those obtained in controls. Unipolar patients, compared to controls, had a significantly lower 24-hour TSH mean, a lower sleep-wake ratio of TSH and an absence of nocturnal rise of TSH. The alterations of the circadian rhythm of TSH secretion observed in the depressive phase of unipolar illness may be a relevant neuroendocrine indicator of hypothalamic-pituitary dysfunction in primary depressive illness.     

Effects of Age and Gender on Sleep Habits and Sleep Trouble for Aged People

The healthy 455 subjects above 60 years of age were questioned on their sleep habit inventory and the morningness-eveningness questionnaire. We analyzed the effects of age and sex on sleep habits and sleep-related trouble. Bedtimes on weekdays and weekends became earlier with aging, and women went to bed significantly later than men did. The length of sleep on weekdays slightly increased with aging, and it was longer for men than for women. The number of urinations and awakenings during nocturnal sleep and the amount of daytime napping increased with aging. The score on morningness-eveningness shifted toward the morning type with aging. In comparison with men, women had significantly longer sleep latency; and a higher percentage of subjects who reported that they sleep for only a short time, have sleep trouble, have received medical treatment for their sleep trouble, and take sleep medication. From these results, we deduced that the phase of sleep shifted forward in subjects above 60 years of age, and they showed frequent interruptions during nocturnal sleep and long daytime napping. We discussed the factor of gender difference in sleep in relation to social and cultural factors, particularly the household activities of women.     

Effects of Age and Gender on Sleep Habits and Sleep Trouble for Aged People

The healthy 455 subjects above 60 years of age were questioned on their sleep habit inventory and the morningness-eveningness questionnaire. We analyzed the effects of age and sex on sleep habits and sleep-related trouble. Bedtimes on weekdays and weekends became earlier with aging, and women went to bed significantly later than men did. The length of sleep on weekdays slightly increased with aging, and it was longer for men than for women. The number of urinations and awakenings during nocturnal sleep and the amount of daytime napping increased with aging. The score on morningness-eveningness shifted toward the morning type with aging. In comparison with men, women had significantly longer sleep latency; and a higher percentage of subjects who reported that they sleep for only a short time, have sleep trouble, have received medical treatment for their sleep trouble, and take sleep medication. From these results, we deduced that the phase of sleep shifted forward in subjects above 60 years of age, and they showed frequent interruptions during nocturnal sleep and long daytime napping. We discussed the factor of gender difference in sleep in relation to social and cultural factors, particularly the household activities of women.     

Increased REM Sleep Associated with Melatonin Deficiency after Pinealectomy: A Case Study

The objectives of the investigation were to assess hypersomnia, which progressively appeared in a young patient after a pinealectomy, chemotherapy, and radiotherapy for a typical germinoma, as well as the potential benefit of melatonin administration in the absence of its endogenous secretion. 24 h ambulatory polysomnography and the Multiple Sleep Latency Test (MSLT) were performed; in addition, daily plasma melatonin, cortisol, growth hormone, prolactin, and rectal temperature profiles were determined before and during melatonin treatment (one 2 mg capsule given nightly at 21:00 h for 4 weeks). MSLT showed abnormal sleep latency and two REM sleep onsets. Nighttime total sleep duration was lengthened, mainly as a consequence of an increased REM sleep duration. These parameters were slightly modified by melatonin replacement. Plasma melatonin levels, which were constantly nil in the basal condition, were increased to supraphysiological values with melatonin treatment. The plasma cortisol profile showed nycthemeral variation within the normal range, and the growth hormone profile showed supplementary diurnal peaks. Melatonin treatment did not modify the secretion of either hormone. The plasma prolactin profile did not display a physiological nocturnal increase in the basal condition; however, it did during melatonin treatment, with the rise coinciding with the nocturnal peak of melatonin concentration. A 24 h temperature rhythm of normal amplitude was persistent, though the mean level was decreased and the rhythm was dampened during melatonin treatment. The role of radiotherapy on the studied parameters cannot be excluded; the findings of this case study suggest that the observed hypersomnia is not the result of melatonin deficiency alone. Overall, melatonin treatment was well tolerated, but the benefit on the sleep abnormality, especially on daytime REM sleep, was minor, requiring the re‐introduction of modafinil treatment.     

Increased REM sleep associated with melatonin deficiency after pinealectomy: a case study

The objectives of the investigation were to assess hypersomnia, which progressively appeared in a young patient after a pinealectomy, chemotherapy, and radiotherapy for a typical germinoma, as well as the potential benefit of melatonin administration in the absence of its endogenous secretion. 24 h ambulatory polysomnography and the Multiple Sleep Latency Test (MSLT) were performed; in addition, daily plasma melatonin, cortisol, growth hormone, prolactin, and rectal temperature profiles were determined before and during melatonin treatment (one 2 mg capsule given nightly at 21:00 h for 4 weeks). MSLT showed abnormal sleep latency and two REM sleep onsets. Nighttime total sleep duration was lengthened, mainly as a consequence of an increased REM sleep duration. These parameters were slightly modified by melatonin replacement. Plasma melatonin levels, which were constantly nil in the basal condition, were increased to supraphysiological values with melatonin treatment. The plasma cortisol profile showed nycthemeral variation within the normal range, and the growth hormone profile showed supplementary diurnal peaks. Melatonin treatment did not modify the secretion of either hormone. The plasma prolactin profile did not display a physiological nocturnal increase in the basal condition; however, it did during melatonin treatment, with the rise coinciding with the nocturnal peak of melatonin concentration. A 24 h temperature rhythm of normal amplitude was persistent, though the mean level was decreased and the rhythm was dampened during melatonin treatment. The role of radiotherapy on the studied parameters cannot be excluded; the findings of this case study suggest that the observed hypersomnia is not the result of melatonin deficiency alone. Overall, melatonin treatment was well tolerated, but the benefit on the sleep abnormality, especially on daytime REM sleep, was minor, requiring the re-introduction of modafinil treatment.     

The effect of sleep upon human circadian rhythms

Subjects who slept for 4 h from 0000, and for a second 4 h variously distributed over the day, have provided values for rectal temperature and for urinary excretion of water, potassium, sodium, chloride, phosphate, creatinine, calcium and urate in the sleeping subject at all hours of the 24. These are compared with similar values in the wakeful subject. Temperature was lower during sleep at all hours except 1000 and 1200, and the difference was maximal shortly before 0000. At all hours potassium excretion was lower and phosphate excretion higher during sleep. Cosinor analysis of the different variables in the sleeping subject is compared with that in subjects following nycthemeral habits, and the interaction between endogenous rhythms and external influences such as sleep is discussed. The phasing of the temperature and urinary rhythms was essentially normal by the end of the observations. By contrast in a subject who slept at irregular hours mimicking the habits of an air pilot a free-running rhythm unrelated to the habits of sleep emerged. When he was finally living again on normal time his temperature and urinary acrophases had moved to the middle of the night. Phosphate excretion was largely exogenous, falling consistently when subjects rose after 8 h, but not after 4 h of sleep.