Characterization of pharmaco-EEG fingerprint and sleep-wake profiles of Lavandula angustifolia Mill. essential oil inhalation and diazepam administration in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Lavandula angustifolia Mill. Essential oil (Lavender EO) has a long history of medicinal use and is particularly claimed to possess anxiolytic and sedative properties. Lavender EO aromatherapy has been used to reduce distress and improve insomnia naturally. Increasing evidence appeared to show similarities between the effects of lavender EO and the anxiolytic drugs, benzodiazepines. However, its effects on sleep-wake and electrical brain patterns in comparison to that of the standard anxiolytic, diazepam, remained to be explored. AIM OF THE STUDY: The aim of this work was to investigate electroencephalography (EEG) profiles and sleep-pattern elicited by lavender EO inhalation compared to that of diazepam, a standard anxiolytic drug in in vivo rat model. MATERIALS AND METHODS: Adult male Wistar rats were anesthetized for electrode implantation on the frontal and parietal skulls. EEG signals were recorded for 180 min following intraperitoneal injection of diazepam (10 mg/kg) or during continuous inhalation of lavender EO (200 µL) or distilled water (control). Fast Fourier transform was used for the analyses of EEG power spectra and sleep-wake parameters. RESULTS: During a 30-60 min period, diazepam and lavender EO significantly increased frontal powers of 0.78-45.31 and 7.03-18.36 Hz, respectively. Both treatments also increased parietal powers with lower magnitudes of significant change. Significant increases in some frequency ranges remained until a 60-90 min period. Sleep-wake analyses also revealed that diazepam significantly reduced time spent in wake, increased time spent in non-rapid eye movement (NREM), increased episode duration of NREM, decreased numbers of wake episode and decreased rapid eye movement (REM) sleep latency. On the other hand, lavender EO only significantly decreased wake episodes and latency to REM sleep. Lavender EO inhalation reduced numbers of wake episode but maintain normal time spent in wake, NREM and REM sleeps. CONCLUSIONS: These findings might suggest beneficial and distinct anxiolytic-like effects of lavender EO for sleep enhancing purposes.

[The effects of quarantine for SARS-CoV-2 on sleep: An online survey]. / Les effets de confinement SARS-CoV-2 sur le sommeil : enquête en ligne au cours de la quatrième semaine de confinement.

OBJECTIVES: Explore the evolution of sleep during the SARS-CoV-2 quarantine period and define associated factors. METHODS: An online survey of patients in quarantine. Questions targeted the conditions of quarantine, sleep related behaviours and exposure to factors known to affect sleep and circadian rhythms (light exposure and sport). RESULTS: In all, 1777 participants were included: 77% women and 72% aged 25-54 years. Quarantine conditions were most frequently in couples with children (36%) and in a house with a garden (51%). Forty-seven percent of participants reported a decrease in sleep quality during quarantine. Factors associated with a reduction in sleep quality by logistic regression were sleep reduction (OR 15.52 P<0.001), going to bed later (OR 1.72 P<0.001), getting up earlier (2.18 P=0.01), an increase in sleep-wake irregularity (OR 2.29 P<0.001), reduced exposure to daylight (OR 1.46 P=0.01) and increased screen use in the evenings (OR 1.33 P=0.04). CONCLUSION: Sleep quality tended to reduce during quarantine and this was associated with changes in sleep behaviours and light exposure, especially in the evening. In order to optimise sleep during quarantine, regular sleep and wake times, at least 1hour exposure to daylight and a reduction of screen use in the evenings are suggested.

Sodium oxybate (Xyrem) treatment in severely sleep-deprived child with Epstein-Barr virus encephalitis with lesion of sleep-wake regulation system: a case report.

We present the effect of exogenous sodium oxybate (GHB) in a severely tormented boy unable to sleep and unable to be anesthetized due to a lesion in the sleep initiation system involving the tracks between the ventrolateral preoptic nucleus and the reticular system. We bypassed the system by using sodium oxybate's effect on the cortical GHB and GABAB receptors involved in the initiation and maintenance of sleep.

Transtornos do sono: atualização (parte2/2) / Sleep disorders: up to date (2/2)

Este artigo (2/2) compõe uma revisão sobre fundamentos do sono e transtornos do sono (TS), sendo aqui considerados: 1-Incapacidade de dormir na hora desejada-atraso de fase, avanço de fase, ''jet lag'', ritmo sono-vigília irregular, sono/vigília de livre curso, transtornos dos trabalhadores em turnos; 2-Movimentos ou comportamentos anormais durante o sono. Este segundo grupo é aqui subdividido em: A1-Parassonias relacionadas ao sono NREM (Non-rapid eye movement) ­ despertar confusional, sonambulismo, terror noturno, síndrome da cabeça explosiva, alucinações relacionadas ao sono, enurese noturna e parassonias causadas por doenças e medicações; A2-Parassonias relacionadas ao sono REM (rapid eye movement) - transtorno comportamental do sono REM, pesadelos, paralisias recorrentes isoladas do sono, promulgação sono ''dream enactment behavior"; B-Transtornos do movimento relacionados ao sono-bruxismo, síndrome das pernas inquietas, movimentos periódicos das pernas, câimbras do sono, movimentos rítmicos relacionados ao sono, mioclonias proprioespinhais do início do sono, movimentos relacionados à medicação, mioclonias em doenças sistêmicas e mioclonias benignas do sono em bebês.(AU)

This is the second part (2/2) of an article that intends to review major topics regarding sleep fundamentals and sleep disorders (SD), now considering: 1-Circadian rhythm disorders-delayed onset sleep phase disorder, advanced onset sleep phase disorder, jet lag, irregular sleep-wake rhythm, free-running type, shift work type; 2-Abnormal movements or behaviours during sleep. This second category is divided in two groups: A1-NREM (Non-rapid eye movement) parasomnias ­ confusional awakening, sleepwalking, night terrors, explosive head syndrome, sleep-related hallucinations, nocturnal enuresis and parasomnias related to diseases or medications; A2-REM (Rapid eye movement) parasomnias-REM sleep behaviour disorder, nightmares, recurrent isolated sleep paralysis, dream enactment behaviour; B-Sleep related movement disorders-bruxism, restless legs syndrome, periodical limb movement disorders, nocturnal leg cramps, sleep related rhythmic movement disorder, propriospinal myoclonus, movements related to medication use, myoclonus related to systemic diseases and benign myoclonus of sleep.(AU)

Non-24-Hour Sleep-Wake Rhythm Disorder and Melatonin Secretion Impairment in a Patient With Pineal Cyst.

ABSTRACT: We report the case of a 14-year-old girl with a wide non-compressive pineal cyst, associated with the inability to control her sleep-wake schedule. Actigraphic monitoring showed a 24-hour free-running disorder (tau 26.96 hours). A 24-hour serum melatonin curve assay, with concomitant video-polysomnographic and body-core temperature monitoring, was performed. Melatonin curve showed a blunted nocturnal peak, lower total quantity of melatonin, and prolonged melatonin secretion in the morning, with normal temperature profile and sleep parameters. Treatment with melatonin up to 14 mg at bedtime was initiated with complete realignment of the sleep-wake rhythm (tau 23.93 hours). The role of the pineal cyst in the aforementioned alteration of melatonin secretion and free-running disorder remains controversial, but our case supports the utility of monitoring sleep/wake, temperature, and melatonin rhythms in the diagnostic work-up of pineal cysts associated with free-running disorder.

Improvement of a patient's circadian rhythm sleep disorders by aripiprazole was associated with stabilization of his bipolar illness.

Splitting of the behavioural activity phase has been found in nocturnal rodents with suprachiasmatic nucleus (SCN) coupling disorder. A similar phenomenon was observed in the sleep phase in the diurnal human discussed here, suggesting that there are so-called evening and morning oscillators in the SCN of humans. The present case suffered from bipolar disorder refractory to various treatments, and various circadian rhythm sleep disorders, such as delayed sleep phase, polyphasic sleep, separation of the sleep bout resembling splitting and circabidian rhythm (48 h), were found during prolonged depressive episodes with hypersomnia. Separation of sleep into evening and morning components and delayed sleep-offset (24.69-h cycle) developed when lowering and stopping the dose of aripiprazole (APZ). However, resumption of APZ improved these symptoms in 2 weeks, accompanied by improvement in the patient's depressive state. Administration of APZ may improve various circadian rhythm sleep disorders, as well as improve and prevent manic-depressive episodes, via augmentation of coupling in the SCN network.

CNS Drug Development, Lessons Learned, Part 4: The Role of Brain Circuitry and Genes-Tasimelteon as an Example.

This is the fourth in a series of columns discussing the rational and targeted development of drugs to affect specific central nervous system (CNS) circuits in specific ways based on knowledge gained by molecular biology and the human genome project. The first column in this series described 6 CNS drugs with novel mechanisms of action developed over the last 25 years. The second column discussed differences between syndromic diagnoses as exemplified by the third through the fifth editions of the Diagnostic and Statistical Manual of Mental Disorders (DSM III through DSM-5) and the new approach to psychiatric diagnoses championed by the National Institute of Mental Health in their Research Domain Criteria Initiative. The third column reviewed the last 9 years of drug development contrasting the development of drugs in other therapeutic areas (eg, cancer) with psychiatric and related CNS-active drugs. This column extends the discussion of modern drug development for psychiatric and other CNS-related indications, using the development of tasimelteon as an example of how modern drug development focuses rationally on novel targets of interest while simultaneously achieving "specificity." Tasimelteon, which is indicated for the treatment of non-24-hour sleep-wake disorder, was developed to be a selective agonist at the melatonin MT1 and MT2 receptors, with limited or no effects at other pharmacologically relevant receptors and enzymes to minimize the potential for off-target effects (eg, nuisance side effects), toxicity, drug-drug interactions, and effects on oxidative drug metabolizing enzymes. The next column in this series will continue the discussion of the development of CNS drugs with novel mechanisms of action, using suvorexant, which targets orexin-1 and orexin-2 receptors, to illustrate the preclinical and human studies that were carried out to assess its safety as part of a successful new drug application.

Protective effect of blue-light shield eyewear for adults against light pollution from self-luminous devices used at night.

We investigated sleep quality and melatonin in 12 adults who wore blue-light shield or control eyewear 2 hours before sleep while using a self-luminous portable device, and assessed visual quality for the two eyewear types. Overnight melatonin secretion was significantly higher after using the blue-light shield (P < 0.05) than with the control eyewear. Sleep efficacy and sleep latency were significantly superior for wearers of the blue-light shield (P < 0.05 for both), and this group reported greater sleepiness during portable device use compared to those using the control eyewear. Participants rated the blue-light shield as providing acceptable visual quality.

Pharmacological interventions for sleepiness and sleep disturbances caused by shift work

BACKGROUND: Shift work results in sleep-wake disturbances, which cause sleepiness during night shifts and reduce sleep length and quality in daytime sleep after the night shift. In its serious form it is also called shift work sleep disorder. Various pharmacological products are used to ameliorate symptoms of sleepiness or poor sleep length and quality. OBJECTIVES: To evaluate the effects of pharmacological interventions to reduce sleepiness or to improve alertness at work and decrease sleep disturbances whilst of work, or both, in workers undertaking shift work. METHODS: Search methods: We searched CENTRAL, MEDLINE, EMBASE, PubMed and PsycINFO up to 20 September 2013 and ClinicalTrials.gov up to July 2013. We also screened reference lists of included trials and relevant reviews. Selection criteria: We included all eligible randomised controlled trials (RCTs), including cross-over RCTs, of pharmacological products among workers who were engaged in shift work (including night shifts) in their present jobs and who may or may not have had sleep problems. Primary outcomes were sleep length and sleep quality while of work, alertness and sleepiness, or fatigue at work. Data collection and analysis: Two authors independently selected studies, extracted data and assessed risk of bias in included trials. We performed meta-analyses where appropriate. ...

Chronobiology, cognitive function and depressive symptoms in surgical patients.

Biological rhythms are essential for the regulation of many life processes. Disturbances of the circadian rhythm are known to affect human health, performance and well-being and the negative consequences are numerous and widespread. Cognitive dysfunction, fatigue, pain, sleep disturbances and mood disorders, such as anxiety and depression, are common problems arising around the time of surgery or in the course of a cancer diagnosis and subsequent treatment period. The importance of investigating prevention or treatment possibilities in these populations is significant due to the extent of the problems and the derived consequences on morbidity and mortality. Genetic predisposition to these problems is also an issue in focus. In this thesis we initially investigated whether the specific clock gene genotype PER(5/5) was associated with the development of postoperative cognitive dysfunction one week after non-cardiac surgery. We did not find any association, although this could have been due to the size of the study. Yet, if PER3(5/5) is associated with a higher incidence of postoperative cognitive dysfunction, the risk seems to be only modestly increased and by less than 10%. Melatonin is a hormone with well-known chronobiotic and hypnotic effects. In addition, exogenous melatonin is also known to have anxiolytic, analgesic, antidepressant and positive cognitive effects. Based on the lack of studies investigating these effects of melatonin, we conducted the MELODY trial in which we investigated the effect of 6 mg oral melatonin on depressive symptoms, anxiety, sleep, cognitive function and fatigue in patients with breast cancer in a three month time period after surgery. Melatonin had an effect on reducing the risk of developing depressive symptoms and also increased sleep efficiency perioperatively and total sleep time postoperatively. No effect was found on anxiety, sleep quality, sleepiness, general well-being or pain, however melatonin seemed to positively influence the ability to complete trial participation compared to placebo. Postoperative cognitive dysfunction was not a problem in this limited population. With regard to safety in our study, melatonin treatment for three months did not cause any serious adverse effects. Finally, we systematically reviewed the literature on the prophylactic or therapeutic effect of melatonin for depression or depressive symptoms in adult patients and assessed the safety of melatonin in these studies. The quantity, size and quality of trials investigating this question were not high and there was no clear evidence of an effect, although some studies were positive. In conclusion, further research is warranted with regard to the prophylactic effect and treatment effect of melatonin in depression, depressive symptoms, cognitive disturbances and symptom clusters of cancer patients in general. In addition, more hypothesis-generating studies with regard to the genetic heritability of POCD are needed.

Impacts of shift work on sleep and circadian rhythms.

Shift work comprises work schedules that extend beyond the typical "nine-to-five" workday, wherein schedules often comprise early work start, compressed work weeks with 12-hour shifts, and night work. According to recent American and European surveys, between 15 and 30% of adult workers are engaged in some type of shift work, with 19% of the European population reportedly working at least 2 hours between 22:00 and 05:00. The 2005 International Classification of Sleep Disorders estimates that a shift work sleep disorder can be found in 2-5% of workers. This disorder is characterized by excessive sleepiness and/or sleep disruption for at least one month in relation with the atypical work schedule. Individual tolerance to shift work remains a complex problem that is affected by the number of consecutive work hours and shifts, the rest periods, and the predictability of work schedules. Sleepiness usually occurs during night shifts and is maximal at the end of the night. Impaired vigilance and performance occur around times of increased sleepiness and can seriously compromise workers' health and safety. Indeed, workers suffering from a shift work sleep-wake disorder can fall asleep involuntarily at work or while driving back home after a night shift. Working on atypical shifts has important socioeconomic impacts as it leads to an increased risk of accidents, workers' impairment and danger to public safety, especially at night. The aim of the present review is to review the circadian and sleep-wake disturbances associated with shift work as well as their medical impacts.

Why the dim light melatonin onset (DLMO) should be measured before treatment of patients with circadian rhythm sleep disorders.

Treatment of circadian rhythm sleep disorders (CRSD) may include light therapy, chronotherapy and melatonin. Exogenous melatonin is increasingly being used in patients with insomnia or CRSD. Although pharmacopoeias and the European food safety authority (EFSA) recommend administering melatonin 1-2 h before desired bedtime, several studies have shown that melatonin is not always effective if administered according to that recommendation. Crucial for optimal treatment of CRSD, melatonin and other treatments should be administered at a time related to individual circadian timing (typically assessed using the dim light melatonin onset (DLMO)). If not administered according to the individual patient's circadian timing, melatonin and other treatments may not only be ineffective, they may even result in contrary effects. Endogenous melatonin levels can be measured reliably in saliva collected at the patient's home. A clinically reliably DLMO can be calculated using a fixed threshold. Diary and polysomnographic sleep-onset time do not reliably predict DLMO or circadian timing in patients with CRSD. Knowing the patient's individual circadian timing by assessing DLMO can improve diagnosis and treatment of CRSD with melatonin as well as other therapies such as light or chronotherapy, and optimizing treatment timing will shorten the time required to achieve results.

[Melatonin as a regulator of human sleep and circadian systems].

Melatonin(N-acetyl-5-methoxytryptamine) is synthesized from tryptophan and is intensively secreted into the blood only in darkness (nighttime) by the pineal gland. Melatonin is not only the most reliable marker of internal circadian phase but also a potent sleep-promoting and circadian phase regulatory agent in humans. There is evidence that daytime administered melatonin is able to exhibit short-acting hypnagogic effect and phase-shifting of the circadian rhythms such that sleep timing and associated various physiological functions realign at a new desired phase. Under favor of these properties, melatonin and melatonin receptor agonists have been shown to be potent therapeutic agents for the treatment of circadian rhythm sleep disorders and some type of insomnia.

Treatment of delirium with risperidone in cancer patients.

AIM: Antipsychotic medications have frequently been regarded as the treatment of choice for delirium. This study examined the clinical efficacy of risperidone for the treatment of delirium in cancer patients, combined with a repeated assessment of underlying medical severity levels. METHODS: The study included consecutive referrals of 29 delirious cancer patients (mean age, 68.9 ± 12.5 years; male, 69%) to the psychiatric consultation service. Risperidone was given orally once per day (mean dosage, 1.4 ± 1.3 mg/day). Study participants were assessed using quantitative standardized scales of cognitive function, delirium, and physical impairment at baseline and at the end of the study (seventh day). RESULTS: Risperidone with routine clinical management was effective for the treatment of delirium: 48% of the patients responded and 38% achieved remission. The reduction of delirium severity occurred in 79% of the patients. Changes in delirium severity were unrelated to age, gender, general cognitive dysfunction, or to severity of attendant medical conditions. In addition to changes in agitation and perceptional disturbances, risperidone was also effective for other specific delirium symptoms. CONCLUSIONS: Risperidone with routine clinical management is effective in the treatment of delirium in advanced cancer patients, independent of changes in the underlying medical condition.

Is shift work making your patient sick? Emerging theories and therapies for treating shift work disorder.

"Shift work" is a term that applies to a wide array of nontraditional work schedules. Shift work disorder (SWD) is a circadian rhythm sleep disorder experienced by a subset of shift workers that is characterized by excessive sleepiness during work and/or insomnia during scheduled sleep times. It is estimated to affect up to 2 million Americans, and is associated with increased morbidity and mortality from metabolic risk factors, cardiovascular and gastrointestinal diseases, depression, accidents, and some kinds of cancers. Patient history is all that is needed to make a diagnosis with the International Classification of Sleep Disorders-Second Edition criteria as described herein. Circadian rhythm disorders, in which an underlying misalignment of circadian rhythm with the sleep-wake cycle occurs, may be treated by behavioral and pharmacologic approaches, including the use of hypnotics to improve the duration of sleep. However, evidence is limited with these approaches in patients diagnosed with SWD. Other treatment options may include pharmacologic interventions such as modafinil and armodafinil, which have shown efficacy in this population. Combined therapy can reduce insomnia and excessive sleepiness, and improve attention and alertness during work shifts and the subsequent commute home.

The role of adenosine in the regulation of sleep.

This paper presents an overview of the current knowledge about the role of adenosine in the sleep-wake regulation with a focus on adenosine in the central nervous system, regulation of adenosine levels, adenosine receptors, and manipulations of the adenosine system by the use of pharmacological and molecular biological tools. The endogenous somnogen prostaglandin (PG) D(2) increases the extracellular level of adenosine under the subarachnoid space of the basal forebrain and promotes physiological sleep. Adenosine is neither stored nor released as a classical neurotransmitter and is thought to be formed inside cells or on their surface, mostly by breakdown of adenine nucleotides. The extracellular concentration of adenosine increases in the cortex and basal forebrain during prolonged wakefulness and decreases during the sleep recovery period. Therefore, adenosine is proposed to act as a homeostatic regulator of sleep and to be a link between the humoral and neural mechanisms of sleep-wake regulation. Both the adenosine A(1) receptor (A(1)R) and A(2A)R are involved in sleep induction. The A(2A)R plays a predominant role in the somnogenic effects of PGD(2). By use of gene-manipulated mice, the arousal effect of caffeine was shown to be dependent on the A(2A)R. On the other hand, inhibition of wake-promoting neurons via the A(1)R also mediates the sleep-inducing effects of adenosine, whereas activation of A(1)R in the lateral preoptic area induces wakefulness, suggesting that A(1)R regulates the sleep-wake cycle in a site-dependent manner. The potential therapeutic applications of agonists and antagonists of these receptors in sleep disorders are briefly discussed.

Melatonin: pharmacological aspects and clinical trends.

Melatonin, N-acetyl-5-methoxytryptamine, the major hormone produced by the pineal gland under the influence of the dark/light cycle, has been shown to have a large number of therapeutic possibilities. It has been utilized in several countries for circadian rhythm disorders, sleep disturbances, jet lag, and sleep-wake cycle disturbances in blind people, and shift workers. In our mechanism of act, the G(i) protein-coupled metabotropic melatonin receptors MT1 and MT2 are the primary mediators of the physiological actions of melatonin. This hormone plays an important role in the regulation of physiological and neuroendocrine functions, such as synchronization of seasonal reproductive rhythms and entrainment of circadian cycles. In addition to its chronobiological role, several pharmacological effects of melatonin have been reported in mammals including sedative, antioxidant, anxiolytic, antidepressant, anticonvulsant, and analgesic activities. There is some evidence from clinical trials that melatonin can be helpful in that event. Current trends of pharmacological functions of melatonin pointed out its use in the treatment of neurodegenerative and neoplastic diseases. These effects and uses of melatonin are mentioned but further confirmatory studies are needed in most of them.

[Sleep-wake cycle in chemotherapy patients: a retrospective study]. / Il ritmo sonno-veglia nel paziente sottoposto a chemioterapia: uno studio retrospettivo.

AIM: Over 50% of cancer patients suffer from insomnia, nearly twice the estimated prevalence in the general population. However, this widespread problem has received far less attention compared to cancer pain and fatigue. The aim of this study was to determine whether certain factors can alter the sleep-wake cycle in this patient subgroup and whether altered nyctohemeral sleep rhythms may negatively impact on quality of life. METHODS: The medical records of 101 patients treated at the Cancer Center, San Giovanni Battista Hospital, Turin, and who had died of cancer in 2007, were reviewed. Extracted from each record were data on: patient age, sex, primary tumor site, presence of pain, concomitant conditions, concomitant medications, type of therapy, chemotherapeutic (CT) scheme, survival, and side effects. The sample was divided into two subgroups defined as inducers or non-inducers, depending on whether the patient had taken medications or not to treat insomnia. Significant differences between the two groups for these variables were tested using statistical analysis. RESULTS: A statistically significant difference between the two groups emerged for anxiety-depression syndromes (P=0.00001), the number of sleeping pills taken in association with a concurrent anxiety-depression syndrome (P=0.01463), and side effects (P=0.0015). There was a statistically significant difference between the inducer and the non-inducer groups for female sex (one-tailed Fisher's exact test; P=0.04170) but the difference was marginal on Fisher's two-tailed test (P=0.06121). No statistically significant differences between the two groups were found for mean age (P=0.61281), median age (P=0.9996), primary tumor site, concomitant conditions (P=0.4205), survival (P=0.5704), presence of pain (P=0.53300) or type of therapy (P=0.6466). CONCLUSION: Sleep disturbances are a common complaint of cancer patients but have only recently attracted greater attention as the diagnosis of cancer has increased. Sleep disturbances are not an isolated problem but rather lead to a vicious circle of insomnia and fatigue where it is not always possible to distinguish between cause and effect. Future studies are needed to gain insight into the underlying mechanisms and a better understanding of what causes alterations in circadian rhythm.

Sleep and rhythm consequences of a genetically induced loss of serotonin.

BACKGROUND: A genetic deficiency in sepiapterin reductase leads to a combined deficit of serotonin and dopamine. The motor phenotype is characterized by a dopa-responsive fluctuating generalized dystonia-parkinsonism. The non-motor symptoms are poorly recognized. In particular, the effects of brain serotonin deficiency on sleep have not been thoroughly studied. OBJECTIVE: We examine the sleep, sleep-wake rhythms, CSF neurotransmitters, and melatonin profile in a patient with sepiapterin reductase deficiency. PATIENT: The patient was a 28-year-old man with fluctuating generalized dystonia-parkinsonism caused by sepiapterin reductase deficiency. METHODS: A sleep interview, wrist actigraphy, sleep log over 14 days, 48-h continuous sleep and core temperature monitoring, and measurement of CSF neurotransmitters and circadian serum melatonin and cortisol levels before and after treatment with 5-hydroxytryptophan (the precursor of serotonin) and levodopa were performed. RESULTS: Before treatment, the patient had mild hypersomnia with long sleep time (704 min), ultradian sleep-wake rhythm (sleep occurred every 11.8 +/- 5.3 h), organic hyperphagia, attentionlexecutive dysfunction, and no depression. The serotonin metabolism in the CSF was reduced, and the serum melatonin profile was flat, while cortisol and core temperature profiles were normal. Supplementation with 5-hydroxytryptophan, but not with levodopa, normalized serotonin metabolism in the CSF, reduced sleep time to 540 min, normalized the eating disorder and the melatonin profile, restored a circadian sleep-wake rhythm (sleep occurred every 24 +/- 1.7 h, P < 0.0001), and improved cognition. CONCLUSION: In this unique genetic paradigm, the melatonin deficiency (caused by a lack of its substrate, serotonin) may cause the ultradian sleep-wake rhythm.

A novel approach to treating morning sleep inertia in narcolepsy.

We describe an adolescent with narcolepsy who presented with inability to awaken from sleep to attend early morning classes at school. After he did not respond to traditional therapies, a nicotine patch was prescribed with success. We present our experience with this unconventional treatment, which may benefit others with inability to awaken from sleep that is refractory to standard treatments.