Commentary on Kayumov L, Pandi Perumal SR, Federoff P, Shapiro CM. Diagnostic values of polysomnograph in forensic medicine. J Forensic Sci 2000 Jan;45(1):191-4.
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Quinine is universally used for the very common symptom of night leg cramps. Patients may not mention it among their medicines, since it is so commonly used and they regulate it themselves. A 68-year-old man suddenly developed extensive bleeding due to severe thrombocytopenia. The diagnosis was initially thought to be a recurrence of idiopathic thrombocytopenic purpura (ITP) that had initially occurred in 1992 and had required splenectomy. Drug-induced thrombocytopenia was also considered, and he was told to stop all of his medicines. Only after three subsequent episodes of severe, symptomatic thrombocytopenia over the next four weeks did he say, upon repeat questioning, that he had continued to take quinine for night leg cramps. Even after a strict warning, he took another quinine tablet that evening, which triggered his fifth episode of severe thrombocytopenia, and confirmed the etiology of quinine-induced thrombocytopenia. The diagnosis thrombocytopenia caused by common drugs can be difficult, requiring persistent, explicit questions.
Nocturnal leg cramps is a common and troublesome problem in elderly individuals, and their etiology is unknown. Treatment with quinine is a common practice, but the effectiveness of the drug is doubtful and adverse drug effects are common. This randomized, double-blind, placebo-controlled study was conducted to evaluate the safety and efficacy of vitamin B complex capsules (fursulthiamine 50 mg, hydroxocobalamin 250 micrograms, pyridoxal phosphate 30 mg, and riboflavin 5 mg) in 28 elderly patients with hypertension who had severe nocturnal leg cramps that disturbed their sleep. Self-reported ratings of leg cramp frequency, duration, and intensity were used to evaluate severity of nocturnal leg cramps. Both the patients taking vitamin B capsules (n = 14) and those taking placebo (n = 14) received medications three times daily, and were examined regularly at 2-week intervals for 3 months. After 3 months, 86% of the patients taking vitamin B had prominent remission of leg cramps, whereas those taking placebo had no significant difference from baseline. Treatment with vitamin B complex significantly reduced the frequency, intensity, and duration of nocturnal leg cramps. Because quinine is not without potential for side effects, and vitamin B complex is a relatively safe and effective alternative, clinicians should reconsider the treatment of choice for nocturnal leg cramps.
The circadian, circasemidian and ultradian features of sleep-wake patterns in narcolepsy are reviewed with respect to the hypotheses that chronobiological disturbances might either be specific to the condition or contribute to its symptomatic profile. The position is taken that, while there are characteristic temporal features associated with the disorder, the chronobiological system is essentially intact, although quantitatively altered. It appears that the fundamental physiopathogenesis involves state boundary control mechanisms, which operate in state transitions, rather than chronobiological mechanisms affecting the timing of the manifestation of symptoms associated with the disease. We review our recent results from sleep-wake schedule studies designed to improve the maintenance of alertness in narcolepsy-cataplexy and report new analyses of subjective sleepiness data. The schedules employed were designed to take preexisting circadian, circasemidian and ultradian sleep-wake patterns of these patients into consideration.
Clinical features of cerebrovascular occlusive disease with the moyamoya network (group 1: twenty-nine children) and those without this network (group 2: nine children) are reported herein. Group 1 was characterized by female preponderance, recurrent and transient ischemic attacks, progression of mental deterioration, rebuild-up after hyperventilation on EEG and wide-spread lesions on CT scan. Group 2 had one or two attacks which led to a rather long-lasting hemiplegia but not to mental deterioration, rare rebuild-up findings on EEG and unilateral focal lesion on CT scan. Precipitating factors for ischemic attacks included deep breathing, changes in body temperature or sleep-waking transition were present in both groups. Etiology in some children was considered to be congenital.
The period of freerunning circadian rhythms is significantly shorter and the fraction of sleep is significantly larger in human females than in males, as long as the rhythms run internally synchronized. The sex difference in the period could be a property either of the whole circadian system or of only one of the oscillators in a multi-oscillator system. The sex difference in the sleep fraction could be a fixed property of the sleep-wake rhythm or could depend on interactions in the multi-oscillator system. To investigate these questions, a sample of 33 long-term experiments, in which the rhythms ran internally synchronized in one section and internally desynchronized in another section, were analyzed. The periods of rhythms in rectal temperature were different in females and males during internal synchronization, but became identical during internal desynchronization. In contrast, sex differences in sleep-wake periods were more pronounced when the rhythms were desynchronized than when they were internally synchronized. This result provides evidence that the sex difference in periodicity is a property only of the sleep-wake rhythm; the intrinsic periods of temperature rhythms are identical in females and males, whereas those of sleep-wake rhythms are distinctly shorter in females than in males. In the state of internal synchronization, the joint period is a compromise between the intrinsic periods of the rhythms involved, and therefore it shows a small but significant sex difference. Moreover, the transition from internally synchronized to desynchronized rhythms is combined with a highly significant reduction in the sleep fraction, which is considerably greater in females than in males. These results suggest that the occurrence of internal desynchronization strongly affects the sleep-wake rhythm, and that the influence of rhythm disorders is considerably greater in females than in males.
Alterations in sleep organization were longitudinally studied in 6 new cases of fatal familial insomnia (FFI) by 24 h polygraphic recording. All patients showed an early reduction in sleep spindles and K complexes, and a drastic reduction in total sleep time and disruption of the cyclic sleep organization. Complete abolition of NREM sleep and persistence of only brief residual periods of REM sleep without atonia were features characteristic of the 3 patients with a short (less than 1 year) clinical course, and lacking in the 3 cases with a longer (more than 2 years) disease course. In the latter, sudden transitions from waking to NREM or REM sleep occurred, sometimes recurring periodically. Our findings confirm that impairment of sleep-wake regulation is a consistent distinctive feature of FFI.
Sleep disorders in amygdala-kindled cats differ according to the sleep or waking state in which seizures occur and the time lapse between seizures and polygraphic recordings. Twelve-hour polygraphic recordings were initiated at the following times: (i) before kindling (N = 8 cats); (ii) just after kindled convulsions during waking, slow-wave sleep (SWS), rapid-eye-movement sleep (REMS), or in transition from SWS to REMS (N = 8 cats per state), and (iii) 24 h after state-specific seizures (N = 8 cats per state). Rapid onset SWS and delayed REMS occurred in records started immediately after seizures in waking, SWS, or REMS; in contrast, seizures during transitions from SWS to REMS produced early onset REMS and SWS. Finally, records begun 24 h after seizures always revealed prolonged sleep onset and generalized sleep suppression regardless of the state in which seizures occurred. The timing of seizures and of polygraphic recordings may explain discrepancies in the literature on the type of sleep disorders seen in secondary generalized temporal lobe epilepsy.
Chronic exposure to mild unpredictable stress causes subsensitivity to rewards (anhedonia). These effects are reversible by chronic treatment with antidepressant drugs, and have been proposed as an animal model of depression. In the present study, sleep architecture, particularly the rapid eye movement (REM) component, was mapped in rats following exposure to chronic mild stress. The study used a unique large scale automated sleep system to record and analyze the sleep signals from 32 rats simultaneously. The effects of stress on sleep were maximal following 21 days of stress, at which time the stressed animals demonstrated decreases in active waking and deep sleep, and disruptions of REM sleep. The changes in REM sleep included increases in the duration of and transitions into REM sleep over the sleep part of the sleep-wake cycle, and most importantly, a reduced latency to the onset of the first REM period. These sleep abnormalities, and in particular the decrease in REM latency, are consistent with those reported in endogenous depression. The results provide further support for the validity of the chronic mild stress paradigm as an animal model to study the mechanisms underlying endogenous depression.
Biological circadian clocks oscillate with an approximately 24-hour period, are ubiquitous, and presumably confer a selective advantage by anticipating the transitions between day and night. The circadian rhythms of sleep, melatonin secretion and body core temperature are thought to be generated by the suprachiasmatic nucleus of the hypothalamus, the anatomic locus of the mammalian circadian clock. Autosomal semi-dominant mutations in rodents with fast or slow biological clocks (that is, short or long endogenous period lengths; tau) are associated with phase-advanced or delayed sleep-wake rhythms, respectively. These models predict the existence of familial human circadian rhythm variants but none of the human circadian rhythm disorders are known to have a familial tendency. Although a slight 'morning lark' tendency is common, individuals with a large and disabling sleep phase-advance are rare. This disorder, advanced sleep-phase syndrome, is characterized by very early sleep onset and offset; only two cases are reported in young adults. Here we describe three kindreds with a profound phase advance of the sleep-wake, melatonin and temperature rhythms associated with a very short tau. The trait segregates as an autosomal dominant with high penetrance. These kindreds represent a well-characterized familial circadian rhythm variant in humans and provide a unique opportunity for genetic analysis of human circadian physiology.
BACKGROUND: A hypnogram shows how sleep travels through its various stages in the course of a night. The sleep stage changes can be quantified to study sedative drug effects. METHODS: Hypnograms from 21 patients with primary insomnia were collected during a randomized, placebo-controlled crossover study of 20 mg temazepam. A separate daytime session was performed to determine the pharmacokinetics of 20 mg temazepam and its effect on saccadic eye movement and electroencephalogram. A first-order Markov model was developed to describe the probability of sleep stage changes as a function of time after drug intake and time after last sleep stage change. The influence of temazepam concentration on the probability to change sleep stage was incorporated into the model. RESULTS: Transitions between sleep stages were profoundly influenced by the time of the night and by the time since the last change of sleep stage. Temazepam reduced the time spent awake. This effect could be attributed to four mechanisms: (1) transition to "deeper" sleep was facilitated, (2) transition to "lighter" sleep was inhibited, (3) regardless of sleep stage, the transition to wake state was inhibited, and (4) return to sleep was facilitated. Daytime sensitivities to temazepam, measured with the surrogate markers saccadic peak velocity and electroencephalogram beta activity, each correlated with one of the transition probabilities influenced by temazepam. CONCLUSIONS: By the development of a Markov model for these non-ordered six categorical data, the effect of temazepam on the sleep-wake status could be interpreted in terms of known mechanisms for sleep generation and benzodiazepine pharmacology.
STUDY OBJECTIVES: Because sleep and wakefulness differ from each other by the amount of body movement, it has been claimed that the two states can be accurately distinguished by wrist actigraphy. Our objective was to test this claim in lengthy polysomnographic (psg) and actigraphic (acf) samples that included night and day components. DESIGN: Fourteen healthy young (21-35 years) and old (70-72 years) men and women lived in a laboratory without temporal cues for 7 days. Each subject continuously wore sleep-recording electrodes as well as 2 wrist-movement recorders. Act measurements were converted to predictions of sleep and wakefulness by simple-threshold and multiple-regression methods. Psg served as the gold standard for calculation of predictive values (PV, the probability that an act prediction is correct by psg criteria). SETTING: N/A. PARTICIPANTS: N/A. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: The 7-day act recordings showed clear circadian cycles of high and low activity that respectively corresponded to subjective days, when subjects were wakeful, and subjective nights when they slept. Lower act levels corresponded to deeper states of psg sleep. Logistic regression on a 20-minute moving average of act gave the highest overall PV's. Nevertheless, the mean PV for sleep (PVS) was only 62.2% in complete, day + night samples. PVS was 86.6% in night samples. Act successfully predicted wakefulness during subjective nights (PVW = 89.6) and accurately measured circadian period length and the extent of sleep-wake consolidation, but it overestimated sleep rate and sleep efficiency. Act systematically decreased before sleep onset and increased before awakening, but reliable transitions among joint psg/act states (the Markov-1 property) were not demonstrated. CONCLUSIONS: Low PV's and overestimation of sleep currently disqualify actigraphy as an accurate sleep-wake indicator. Actigraphy may, however, by useful for measuring circadian period and sleep-wake consolidation and has face validity as a measure of rest/activity.
This review article: (1) describes the circadian distribution of ictal and interictal events; (2) differentiates transitional arousal, non-rapid eye movement and rapid eye movement sleep components and their substrates; (3) suggests the means by which the neural generators of these seizure-prone vs. seizure-resistant sleep and arousal states modulate the timing of different seizure manifestations; (4) considers clinical and mechanistic findings for the reciprocal effects of seizures and antiepileptic drugs upon the sleep-wake cycle; and (5) assesses clinical and basic mechanisms of sleep deprivation effects upon seizures.
Amygdala-kindled kittens exhibit frequent epileptiform EEG transients, often in conjunction with phasic arousal events of sleep [k-complexes, pontogeniculo-occipital (PGO) waves, and/or sleep spindles]. In this study, paroxysmal microarousals occurred throughout the sleep-wake cycle after kindling, but were most frequent during seizure-prone states of slow-wave sleep (SWS) and the transition into rapid-eye-movement sleep (REM). Their incidence correlated with interictal sleep fragmentation as well as onset of spontaneous convulsions. Results could reflect transsynaptic kindling effects on brainstem and forebrain arousal mechanisms with which amygdala is reciprocally connected. Increased discharge rates of neural generators for normal EEG and behavioral arousal could disrupt sleep at some times and recruit epileptic neurons in the kindled focus to precipitate seizures at others. Alternatively, epileptiform EEG paroxysms were accompanied by subtle behavioral stereotypes (a head nod, limb elevation, eye twitch, lip smack, or a combination of these). Behavioral correlates were elements of partial kindled seizures, suggesting that paroxysmal microarousals may be subclinical seizures. Whether or not the microarousals are true seizures, our findings may link ictal onset and interictal sleep disorders to a subclinical paroxysmal arousal disorder and suggest a common epileptic mechanism.
The effects of immediate-release melatonin on circadian rest-activity profiles, cognition, and mood were investigated in ten elderly individuals with self-reported sleep-wake disturbances. Melatonin (6 mg), administered 2 hr before habitual bedtime, enhanced the rest-activity rhythm and improved sleep quality as observed in a reduction in sleep onset latency and in the number of transitions from sleep to wakefulness. However, total sleep time was not significantly increased nor was wake within sleep significantly reduced. The ability to remember previously learned items improved along with a significant reduction in depressed moods. No side effects or contraindications were reported by any of our participants during the 10 day trials. These data suggest that melatonin can safely improve some aspects of sleep, memory, and mood in the elderly in short-term use.
Eighteen EEG long-term recordings were carried out in patients with generalized fits of different etiologies using a mobile 4-channel monitoring system in order to observe individual patterns of epileptic activity. In patients with idiopathic tonic-clonic seizures (A) no connection of frequency of spike-wave bursts with the sleep-wakefulness cycle was observed. In patients suffering from fits of organic nature (B) a peak of paroxysms was obtained in the hours before sleep onset, whereas in patients with absence seizures (C) a maximum was found in the morning hours after awakening. In patients with idiopathic fits (tonic-clonic and absence seizures) the minimum of bursts was observed in REM sleep, whereas stage 0 (tonic-clonic) and stage 1 (absence) were most prone to discharges. Patients with secondary generalized epilepsy had most spike-wave bursts in deep sleep. In the absence seizure group the transitional periods within the light non-REM-sleep stages were more susceptible to paroxysms than the retained stages. In patients with idiopathic grand mal seizures, the highest frequency of paroxysmal discharges was found during time spent awake in the night when retained over a longer period of time. The group including cases with attacks of organic nature did not show any preference to shifting times or preservation episodes of sleep stages.
STUDY OBJECTIVES: To evaluate the relationship between sleep structure and continuous positive airway pressure (CPAP) delivered by an automatic CPAP (auto-CPAP) machine in patients with obstructive sleep apnea syndrome (OSAS). DESIGN: Nocturnal polysomnography was performed during CPAP administration by an auto-CPAP machine (Autoset Clinical 1; ResMed; Sydney, Australia). SETTING: Sleep-disorders center in a research institute. PATIENTS: Fifteen subjects with newly diagnosed OSAS deserving home CPAP treatment. MEASUREMENTS AND RESULTS: During the night, in most cases, the lowest CPAP level was recorded during a prolonged nonrapid eye movement (NREM) sleep period uninterrupted by arousals, whereas the highest level during wake-sleep transitions or NREM sleep fragmented by arousals. In four subjects, rapid eye movement sleep was always associated with increasing CPAP. Sleep efficiency was negatively correlated with CPAP variability, evaluated as the SD of the mean nocturnal CPAP level averaged epoch by epoch (r = 0.63, p < 0.02). Eighty-eight percent of rapid CPAP augmentations (increases by at least 2 cm H(2)O in less-than-or-equal 2 min) were observed during sleep-wake transitions or after arousals/awakenings (Ar/Aw); 63% of such Ar/Aw were not preceded by any detectable respiratory abnormality. CONCLUSIONS: CPAP levels and variations during auto-CPAP application may be mainly related to sleep continuity and efficiency. The recording of a highly variable pressure during auto-CPAP administration in an unattended environment must raise the question whether the patient's sleep quality was acceptable. A poor sleep quality during an autotitration night could lead to an undesirable overestimation of the CPAP level needed for use with fixed-level CPAP machines.
Facility of memory formation and retrieval is affected by sleep-wake state. This paper discusses memory function while individuals are awake, but sleepy, at the transitions in state (i.e., wake to sleep and sleep to wake), and in REM and NREM sleep. The basal state of arousal at the time of memory function seems to be critical and the sleepy state, state transitions, and NREM sleep seem to define a continuum of arousal with respect to memory function. While different memory systems have been described, the effect of sleep-wake state on memory systems appears to be non-specific. Finally there is a shift in neurobiology from the NREM to REM state and memory function also appears to change in REM sleep.