Daily melatonin intake resets circadian rhythms of a sighted man with non-24-hour sleep-wake syndrome who lacks the nocturnal melatonin rise

Abstract Effects of daily melatonin intake on the circadian rhythms of sleep and wakefulness, rectal temperature and plasma cortisol were examined in a sighted man who had suffered from the non-24-hour sleep-wake syndrome. The subject lacked the nocturnal melatonin rise in plasma, but showed robust circadian rhythms in rectal temperature and plasma cortisol. The sleep-wake rhythm free-ran with a period longer than 24 hours. Daily melatonin intake at 21:00 h concentrated sleep episodes in the nocturnal period (24:00–8:00 h), and increased the length of the episodes. A single oral dose (3 mg) of melatonin increased plasma melatonin levels to about 1300 pg/mL within one hour and remained at pharmacological levels for approximately 6 hours. The trough of rectal temperature and the circadian rise of plasma cortisol were fixed to the early morning. A higher dose of melatonin (6 mg) did not improve the general feature. After the cessation of melatonin intake, the sleep-wake rhythm began to free-run together with the circadian rhythms in rectal temperature and plasma cortisol. It is concluded that daily intake of melatonin at early night time resets the circadian rhythms in a sighted man who lacked the nocturnal melatonin rise and showed free-running circadian rhythms in routine life.     

Thermal regulation disturbance in severely handicapped patients--the second report]

Thirty-three severely handicapped patients were investigated on body temperature regulation by rectal temperature monitoring and hypophyseal hormonal function. The lowest body temperature in the day in the cases with handicaps of prenatal onset tended to be lower than that of peri or postnatal onset. This finding suggests that different causes make regulation disturbance of body temperature in handicapped children. On the other hand, low urine osmolarity in the morning and irregular menstruation were recorded suggesting hypothalamic dysfunction in poor regulation cases.     

Nineteen-hour variation of postural sway, alertness and rectal temperature during sleep deprivation.

Nineteen-hour variation of postural sway, alertness and rectal temperature during sleep deprivation were studied. Alertness decreased gradually at night and remained low until morning. Postural sway in the eyes-closed condition increased during early morning. In six of the eight subjects the greatest sway was observed during the 3-h period when rectal temperature was at its minimum. It is suggested that unbearable sleepiness during sleep deprivation will give rise to measurable impairment of postural balance especially during the time zone of temperature nadir.     

Comparison of Body Temperature Rhythms between Healthy Elderly and Healthy Young Adults

Abstract: The fact that the elderly are usually aware of early sleep onset and early morning awakening shows that the phase of sleep-wake rhythms in the elderly is more advanced than that in young adults. Since it has been suggested that human sleep onset, morning awakening, sleep period and depth of sleep are highly influenced by body temperature rhythms, rectal temperature rhythms were analyzed in 7 healthy elderly and 7 healthy young adults under the condition with time cue. Although a significant 24-hour period was found in the rhythms for all subjects, the phase of the rhythms in the elderly was more advanced than in the young adults. Moreover, a significant inverse correlation was observed between age and acrophase time in the elderly.     

REM latency and core temperature relationships in primary depression

REM latency and rectal and ear canal temperature were studied simultaneously in 11 controls and nine depressed patients; seven of the patients were studied when recovered. REM latency was shorter in the depressed group compared with controls and lengthened with recovery. The nocturnal and ear canal temperatures were higher in the depressed group compared with controls and decreased with recovery. REM latency and the nocturnal rectal temperature were negatively correlated when all the nights of the depressed patients were analyzed (r = -0.44) and when all the nights of the subjects were analyzed (r = -0.44). REM latency and nocturnal ear canal temperatures were negatively correlated when all the nights of the control group were analyzed (r = -0.34). The timing of the temperature rhythm did not appear to be correlated with the REM latency.     

Continuous measurement of temperature in non-24 hour sleep-wake syndrome

Abstract The onset of the low temperature (LT) zone which was defined as a period when the rectal temperature was below its daily mean is a convenient circadian phase marker. In this study, we document three cases of non-24 h sleep-wake syndrome in which identification of the LT zone as an evening circadian phase marker contributed to clinical judgments. We found that the LT zone was correlated well with dim light melatonin onset. Moreover, calculating the LT zone was useful in determining phase position in irregular sleep pattern and in determining the timing of bright light therapy.     

The Effect of Photoperiod on Plasma Levels of Melanin-Concentrating Hormone in the Trout

The neurohypophysial melanin-concentrating hormone, MCH, plays a role in adaptive colour change in teleost fishes, inducing pallor when the fish is placed in pale-coloured surroundings. The present study shows that its plasma concentration, measured in groups of white-adapted fish, is not uniformly high throughout the day but follows a clear diurnal pattern. Over a 24 h cycle, plasma concentrations rise gradually during the morning to reach peak values around the middle of the photophase, after which they decline significantly before night. Lowest concentrations are observed during the dark period. This pattern was observed under a long photoperiod in summer and a short photoperiod in winter. The peak was shifted within a week of changing the onset of either light or dark. When dawn was delayed by 6 h for fish held on a long photoperiod, the usual morning rise in hormone titres was suppressed but, with the advent of light, hormone concentrations rose more rapidly than usual to reach peak values at about the normal time. If the dawn was advanced by 6 h for fish held under short photoperiod conditions, then peak concentrations were attained 6 h precociously. Fish from a long photoperiod placed in constant light showed a pattern of MCH release which approximated to the normal over the first 24 h period but plasma values then became raised and periodicity was no longer discernible. Plasma hormone concentrations were much reduced in trout kept in black coloured tanks in which nocturnal and daytime values differed, but significant differences during the photophase were not demonstrable. The results suggest that an illuminated white background can initiate the early morning release of MCH, and that an endogenous pacemaker underlies the pattern of MCH secretion.     

Correlation between the circadian sleep propensity rhythm and hormonal rhythms under ultra-short sleep–wake cycle

The aim of this study was to clarify effects of hormonal and temperature rhythms on circadian fluctuations of sleep propensity. Ten healthy females underwent 24-h sleep deprivation and entered the circadian sleep propensity assessment setting under the ultra-short sleep-wake schedule. During the experiment, sleep propensity rhythm, rectal temperature, and 24-h serum hormone profiles (melatonin, cortisol and thyroid-stimulating hormone) were investigated. The circadian sleep propensity rhythms had two apparent peaks (afternoon and nocturnal peaks) and a trough (nocturnal sleep gate). The timings of the nocturnal sleep gate and the nocturnal peak were correlated exclusively with temperature and melatonin rhythms (P < 0.05), while that of the afternoon peak was significantly correlated with habitual wake time and melatonin rhythm. These results indicate that the circadian sleep propensity rhythm is influenced not only by the circadian pacemaker, but also by sleep habit.     

Diurnal and sleep-wake dependent variations of soluble TNF- and IL-2 receptors in healthy volunteers

There is very little published information on the diurnal variation of cytokines and their receptors, in healthy individuals during normal sleep-wake patterns or during sustained wakefulness. The aim of the current investigation was to characterize concentrations of soluble tumor necrosis factor receptors (sTNF-Rs) and interleukin-2 receptor (sIL-2R) during normal sleep and wakefulness, as well as during a 24 h vigil. Plasma levels of the sTNF-R p55, sTNF-R p75, and sIL-2R did not differ significantly between nocturnal sleep and nocturnal wakefulness. Rhythmic analysis (2-h intervals) revealed significant diurnal variations for both sTNF-R p55 and sTNF-R p75, but not levels of sIL-2R. Diurnal variations of both sTNF-Rs were characterized by a single cosine curve with an average peak near 06:00 h in the morning. This peak occurred well before that of cortisol, and fluctuated inversely with the diurnal rhythm of temperature. These diurnal variations in sTNF-Rs levels are consistent with the hypothesis that the TNF system plays a role in normal diurnal temperature regulation.     

A sighted man with non-24-hour sleep-wake syndrome shows damped plasma melatonin rhythm

Abstract Twenty-four-hour profiles of plasma melatonin, cortisol and rectal temperature were measured longitudinally in a sighted man who has been suffering from sleep disorders for more than 10 years. The sleep-wake rhythm of this subject free-ran, despite his routine life, and occasionally showed a sign of internal desyn-chronization, where sleep was lengthened up to 30 h. These states were classified into the non-24-hour sleep-wake syndrome. Plasma melatonin concentrations in the subjective night remained at a low level and showed a damped circadian rhythm. At the same time, robust circadian rhythms were detected in plasma cortisol and rectal temperature, indicating that the circadian pacemaker was intact. The causal relationship between the damping of nocturnal melatonin rise and a failure of entrainment of the sleep-wake cycle is discussed.     

Catathrenia (nocturnal groaning): an abnormal respiratory pattern during sleep

Catathrenia (nocturnal groaning) is a rare condition characterized by monotonous irregular groans occurring during sleep. Ten patients (five women; mean age: 27 ± 7.4 years, range: 15–41) with sleep-related groaning persisting for years or decades and normal daytime fibreoptic laryngoscopy and respiratory function tests underwent videopolysomnographic recording (VPSG) analysing their respiratory patterns during sleep. After the VPSG, all patients were clinically followed up for a mean period of 4.9 ± 3.5 years. On VPSG, all patients showed nocturnal groaning during NREM sleep and particularly during REM sleep stages. Groaning was associated with disproportionate prolonged expiration causing reduced breathing rate without oxygen desaturation. The breathing pattern with prolonged expiration and sound production alternated with a normal respiratory pattern without groaning. Endoesophageal pressure during groaning showed mildly positive swings at the initial phase of expiration suggesting a partial mild expiratory upper airway obstruction. At the end of the follow-up period, all patients reported persistent nocturnal groaning but no other clinical manifestations. Groaning confined to sleep alternating with normal breathing and the absence of long-term clinical consequences suggest that catathrenia is because of an abnormality of the internal respiratory drive system, possibly related to persistence of a neonatal (vestigial) type of breathing pattern.     

Nocturnal heart rate and volitional lifestyle in the elderly

The relationship between the level of volitional lifestyle and nocturnal heart rate (HR) in the elderly was investigated. Twenty high- and low-volitional elderly individuals (n = 10 each; mean age 73.2 years) participated in the study. Heart rate during nocturnal sleep was recorded at their homes using an ambulatory polysomnographic system. High-volitional individuals showed a lower HR throughout the night and less variability during rapid eye movement sleep. These findings suggest that a volitional lifestyle of the elderly has a beneficial effect on autonomic activity during sleep.     

Sleepiness/alertness among healthy evening and morning type individuals

Objective: The aim of this study was to determine the level of sleepiness/alertness among different chronotypes.Background: The Horne-Ostberg Morningness-Eveningness Questionnaire (MEQ) has allowed the characterization of chronotypes that are associated with a number of biological factors including: body temperature, cortisol rhythm, sleep patterns, and architecture.Methods: Fifty-six consecutive normal volunteers underwent an 8-h polysomnogram followed by a multiple sleep latency test (MSLT). Each subject also completed the MEQ and the Sleep/Wake Activity Inventory.Results: Evening types (ET) reported significantly later bedtimes and risetimes than both morning types (MT) and neither types (NT, P<0.05). On nocturnal polysomnography, the ET documented significantly longer latencies to stage 1 and persistent sleep when compared to both the NT and MT (P<0.01). There were no significant differences in the level of sleepiness on the MSLT across the different chronotypes. However, the pattern of sleepiness differed among them. While ET and NT showed differential sleep latencies across nap opportunities, MT showed no evidence of circadian variation on their level of sleepiness.Conclusions: There were no overall differences in daytime sleepiness/alertness across chronotypes. However, a differential pattern of sleep latencies was noted on the MSLT.     

Body core temperature and depression during total sleep deprivation in depressives

Endogenously depressed patients were subjected to a total sleep deprivation (TSD) schedule of sleep-TSD-sleep-TSD. They were simultaneously treated with the antidepressant drug clomipramine. Self- and observer-rated depression was measured daily. Continuously measured rectal temperature (RT) data were available for the second TSD. It was found that a higher nocturnal minimum RT during this TSD was associated with a positive clinical response.     

Disrupted sleep and circadian patterns in frontotemporal dementia

Background:  A study of the pattern of Sleep/Wake disturbance in frontotemporal dementia (FTD).
Methods:  Sleep diaries and prolonged actigraphy were used to record the activity, sleep and wake of 13 patients with a clinical diagnosis of FTD. These were compared with diaries and actigraphy from normal age/sex matched controls and also to a population with probable Alzheimer's disease (AD).
Results:  There was significant sleep/wake disturbance in FTD. This occurred throughout the course of the illness and the nature of the sleep disturbance was different to patients with AD. FTD subjects showed increased nocturnal activity and decreased morning activity compared with controls, suggesting possible phase delay. Sleep diary data confirmed decreased sleep efficiency and decreased total sleep in all FTD patients.
Conclusions:  We describe significant sleep disturbance in non-institutionalized patients with FTD and suggest that early sleep disturbance may help differentiate between FTD and AD.     

Usefulness of a morning routine EEG recording in patients with juvenile myoclonic epilepsy

OBJECTIVE: To evaluate if a standard awake EEG recording in the morning is superior to afternoon awake EEG session in detecting generalized epileptiform discharges (GEDs) in patients with juvenile myoclonic epilepsy (JME). METHODS: The study group included 29 consecutive patients (23 women; mean age 22.3+/-6.3 years; age at onset of JME 15.4+/-3.4 years) with JME. Out of 29 patients 5 were untreated, 9 patients were treated with valproate, 8 with lamotrigine, 6 with levetiracetam and 1 patient with valproate plus phenobarbital. Two routine consecutive interictal EEG recordings were performed at 9a.m. and at 3p.m., respectively, while the subject was awake, on the same day after a a regular nocturnal sleep at own home. RESULTS: The morning EEG recording showed GEDs (i.e., generalized polispike and waves, photoparoxysmal response, or both). in 20/29 patients. In 15 of these 20 patients, the afternoon recording was normal and this difference was statistically significant (p < or = 0.001). Moreover, there was a striking reduction of GEDs in three of the remaining five patients. Nine/29 patients had both morning and afternoon EEG recording normal. CONCLUSIONS: The results of this study have illustrated a significant greater rate of detection of generalized epileptiform abnormalities by performing standard awake EEG in the morning in comparison with an afternoon session.     

Madopar HBS in Parkinson patients with nocturnal akinesia

Madopar Hydrodynamically Balanced System (HBS), a new sustained-release levodopa preparation, was used to control severe nightly disabilities in 15 outpatients suffering from Parkinson's disease in an advanced state and with long-term levodopa therapy. This medication was given ante noctem in addition to an otherwise unchanged daily regimen of levodopa administration. In 13 patients a considerable diminution in nocturnal akinesia and in the frequency of waking up was reached with a mean dosage of 308 mg of Madopar HBS. Early morning akinesia was only slightly alleviated in four patients. The nocturnal off-period pain disappeared in one patient. Adverse effects consisted of nocturnal dyskinesia in two patients and early morning dystonia in another two patients. The regular use of sleeping pills was clearly reduced after Madopar HBS therapy.     

Melatonin in relation to body measures, sex, age, season and the use of drugs in patients with major affective disorders and healthy subjects

Serum melatonin levels over a 24 hr period were studied in 30 acutely ill patients with major depressive episode, 24 patients with a history of unipolar or bipolar major affective disorder in remission and 33 healthy subjects. A significant negative correlation (-0.45) between body height and maximum nocturnal serum melatonin level was found. Maximum serum melatonin levels during the night were lower in both patient groups than in the healthy controls. No difference was found between maximum nocturnal serum melatonin levels in 26 patients investigated when ill and again in remission. We thus propose low nocturnal melatonin to be a trait-dependent marker for major depressive disorder. A difference in the morning but not night melatonin levels was found between samples taken during the dark, winter season versus samples taken during the bright, spring-summer season. Melatonin levels were not lower in females than in males, when melatonin levels were adjusted for body height. Similar results were found when the nocturnal areas under the curve for melatonin were analyzed.     

Effect of melatonin on sleep and rectal temperature of young healthy evening types.

The present study assessed in healthy nocturnal juveniles the presence or absence of the hypnotic action of exogenous melatonin and its effect on core temperature by oral administration of exogenous melatonin at a pharmacologically low dose 15 min before going to bed at the normal time. Both sleep latency and the number of instances of waking up after falling asleep tended to decrease, while the amount of Stage 2 sleep increased significantly. However, no hypothermic action regarding the rectal temperature for changes in the circadian phase were observed. According to those results, it is possible that exogenous melatonin has some direct hypnotic action on habitual night sleep, although the extent of this action is considered to be relatively weak.     

Nocturia, nocturnal polyuria, and sleep quality in the elderly

Nocturia is a common symptom in the elderly, which profoundly influences general health and quality of life. One consequence of nocturia is sleep deterioration, with increased daytime sleepiness and loss of energy and activity. Accidents, e.g., fall injuries, are increased both at night and in the daytime in elderly persons with nocturia. Nocturia is caused by nocturnal polyuria, a reduced bladder capacity, or a combination of the two. Nocturnal polyuria can be caused by numerous diseases, such as diabetes insipidus, diabetes mellitus, congestive heart failure, and sleep apnoea. In the nocturnal polyuria syndrome (NPS), the 24-h diuresis is normal or only slightly increased, while there is a shift in diuresis from daytime to night. NPS is caused by a disturbance of the vasopressin system, with a lack of nocturnal increase in plasma vasopressin or, in some cases, no detectable levels of the hormone at any time of the 24-h period. The calculated prevalence of NPS is about 3% in an elderly population, with no gender difference. In NPS, there are serious sleep disturbances, partly due to the need to get up for micturition, but there is also increased difficulty in falling asleep after nocturnal awakenings and increased sleepiness in the morning. The treatment of NPS may include avoidance of excessive fluid intake, use of diuretics medication in the afternoon rather than the morning, and desmopressin orally at bedtime.