Alterations In Sleep-wake Cycle Research Articles

Night Shift Work Is Associated with Reduced Rate of Humoral Response Following Vaccination for HBV.

Night shift work has been associated with cardiovascular and metabolic disease, endocrine and immunological disorders. Published studies have reported that a reduced total sleep time with sleep-wake cycle alterations were associated with a reduced rate of humoral response following vaccination. Our study aimed to evaluate the association between night shift work and serological status for HBV among workers employed in a university hospital in Rome. We evaluated medical records of 986 HCWs working at Tor Vergata Policlinic of Rome. We screened all study subjects for anti-HBs IgG, anti-HBc IgG and HBsAg. Serological protection for HBV was evaluated in relation to sex, age group, job task, risk setting and night shift work status. Protective titer was found in 856 (86.8%) study participants and the mean titer was significantly high in females, in subjects aged less than 40 years, in night shift workers and in high-risk setting workers. After adjustment for study covariates, night shift work was no longer associated with an HBV-protective titer. This finding suggests that a vaccination strategy for dampening HBV transmission should be carefully addressed in health care workers (HCWs) doing night shift.

Sleep Disorders in Patients With Craniopharyngioma: A Physiopathological and Practical Update

Sleep disorders (SDs) represent an important issue in patients with craniopharyngioma (CP). Nearly 70% of these patients complain of sleep-wake cycle alterations and/or excessive diurnal somnolence due to sleep-related breathing disorders, such as obstructive sleep apnea (OSA) and/or central hypersomnia, including secondary narcolepsy. SDs may severely reduce quality of life, increase disease-related cardiorespiratory and cardiovascular morbidity, and finally play a major role in increased long-term mortality reported on patients with CP. A major risk factor for SDs is represented by the hypothalamic syndrome, which may develop because of direct hypothalamic damage by the tumor itself and/or complications of the treatments, neurosurgery and/or radiotherapy, and typically includes permanent neuroendocrine dysfunctions, morbid obesity, and secondary metabolic disorders. Despite increasing attention to SDs in the general population, and in particular to OSA as a risk factor for cardio-metabolic diseases and excessive daytime somnolence, sleep evaluation is still not routinely proposed to patients with CP. Hence, SDs are often underdiagnosed and undertreated. The aim of this paper is to update current knowledge of the pathogenesis and prevalence of SDs in patients with CP and propose practical algorithms for their evaluation and management in clinical practice. Particular attention is paid to screening and diagnostic tools for appropriate characterization of SDs, identification of risk factors, and potential role of hypothalamic sparing surgery in the prevention of morbid obesity and SDs. Available tools in sleep medicine, including lifestyle interventions, drugs, and respiratory devices, are discussed, as well as the importance of optimal hormone replacement and metabolic interventions. Current limits in the diagnosis and treatment of SDs in patients with CP and possible future avenues for research agenda are also considered.

PER2 C111G polymorphism, cognitive reserve and cognition in subjective cognitive decline and mild cognitive impairment: a 10-year follow-up study.

CLOCK and PER2 genes have been implicated in sleep-wake cycle alterations and neurodegenerative diseases. Our aim was to evaluate the effect of CLOCK T3111C and PER2 C111G on cognitive functioning in subjective cognitive decline (SCD) patients and mild cognitive impairment (MCI) patients at the baseline of a longitudinal study, and the effect of these two polymorphisms on the progression to Alzheimer's disease (AD) of the two groups. Sixty-eight subjects (41 SCD and 27 MCI) who underwent clinical evaluation, neuropsychological assessment, CLOCK and PER2 genotyping at baseline and neuropsychological follow-up every 2years for a mean time of 10years were included. Subjects who developed AD (SCD-c and MCI-c) and non-converters (SCD-nc, MCI-nc) were considered. CLOCK T3111C was detected in 47% of cases (21 SCD, 11 MCI) and PER2 C111G in 19% of cases (eight SCD and five MCI). PER2 G carriers presented lower premorbid intelligence score (P=0.049), fewer years of education (P=0.007) and a lower frequency of family history of AD (P=0.04) than G non-carriers. MCI PER2 G carriers had worse performance in tests assessing memory, executive function, language and visuospatial abilities at baseline. During follow-up, two SCD and 15 MCI subjects progressed to AD: both of the SCD-c subjects presented the PER2 G allele, while none of the SCD PER2 G non-carriers converted to AD (P=0.003). PER2 seems to have a role in cognitive reserve and cognition in SCD and MCI patients. Nevertheless, further studies are needed to assess the role of PER2 C111G on the risk of progression to AD.

Distinguishing characteristics of delirium in a skilled nursing facility in Spain: Influence of baseline cognitive status.

Mild cognitive impairment (MCI) and dementia (DEM) are prevalent in skilled nursing facilities (SNFs), confounding delirium detection. We report characteristics of delirium in an SNF to ascertain distinguishing features for delirium diagnosis, despite challenges of comorbidity with MCI and DEM. Cross-sectional study of 200 consecutive patients from an SNF in Catalunya, Spain, assessed within the first 24 to 48 admission hours by independent experts with Spanish-Informant Questionnaire on Cognitive Decline in the Elderly (for MCI-DEM), Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) delirium criteria, and Delirium Rating Scale Revised-98 (DRS-R98) for delirium phenomenology. Delirium characteristics were modeled in successive steps, according to the presence of delirium and MCI-DEM, with analysis of variance (ANOVA), receiver operator characteristic analyses, and conditional logistic regression. The final model produced symptoms that represented each of the three delirium core domains (ie, cognitive, higher order thinking, and circadian). The DRS-R98 items rated these symptoms as moderate-severe attention/vigilance, mild-severe language, and moderate-severe sleep-wake cycle alterations. The delirium discriminant accuracy of the three symptoms together was high: 84.6% in the MCI-DEM group to 92.8% in the No MCI-DEM group. Impairments of attention, language, and sleep-wake cycle indicate delirium in SNF patients regardless of the underlying MCI-DEM status. Because delirium is underdetected in SNFs, where nursing staff/patient ratios are low, brief simple tools that measure these symptoms could potentially enhance delirium detection.

A randomized placebo-controlled trial evaluating the effect of melatonin on sleep quality in patients with mild-moderate dementia.

Patients with dementia may suffer from poor sleep quality as well as insomnia and sleep-wake cycle alterations. The main objective of this study was to evaluate the efficacy of melatonin in improving sleep quality. This was a single-center randomized, double-blinded, placebo-controlled study carried out on outpatients with dementia and sleep alterations (according to Diagnostic and Statistical Manual V criteria) from January 2016 to December 2016. Patients aged 65years or over with a diagnosis of mild-moderate dementia (Clinical Dementia Rating 1-2) were included. Patients were randomized to receive either 5mg of melatonin or placebo every night for 8weeks. The primary outcome was sleep quality according to the Pittsburgh Sleep Quality Index (PSQI). Secondary measurements included Mini-Mental State Examination, Neuropsychiatric Inventory (NPI), Geriatric Depression Scale and Katz and Lawton scales for functionality. 40 patients were included (21 in the melatonin group and 19 in the placebo group). Nine patients withdrew from the study, and data of 31 patients were analyzed (16 from the melatonin group and 15 in the placebo group). Baseline characteristics of the population were comparable. PSQI scores improved in both groups at every timepoint compared to baseline, but there were no significant differences between groups. At 8weeks, there was no difference between groups in any of the secondary outcomes except for the sleep sub-item of the NPI, where melatonin group had lower median scores compared to placebo (1, Interquartile Range = 3, vs. 4.4, Interquartile Range = 4.6, p = 0.03). Melatonin administered nightly to older persons with dementia was not effective in improving sleep quality. Clinicaltrials.gov Identifier: NCT03066518.

Parallel recovery of consciousness and sleep in acute traumatic brain injury.

To investigate whether the progressive recuperation of consciousness was associated with the reconsolidation of sleep and wake states in hospitalized patients with acute traumatic brain injury (TBI). This study comprised 30 hospitalized patients (age 29.1 ± 13.5 years) in the acute phase of moderate or severe TBI. Testing started 21.0 ± 13.7 days postinjury. Consciousness level and cognitive functioning were assessed daily with the Rancho Los Amigos scale of cognitive functioning (RLA). Sleep and wake cycle characteristics were estimated with continuous wrist actigraphy. Mixed model analyses were performed on 233 days with the RLA (fixed effect) and sleep-wake variables (random effects). Linear contrast analyses were performed in order to verify if consolidation of the sleep and wake states improved linearly with increasing RLA score. Associations were found between scores on the consciousness/cognitive functioning scale and measures of sleep-wake cycle consolidation (p < 0.001), nighttime sleep duration (p = 0.018), and nighttime fragmentation index (p < 0.001). These associations showed strong linear relationships (p < 0.01 for all), revealing that consciousness and cognition improved in parallel with sleep-wake quality. Consolidated 24-hour sleep-wake cycle occurred when patients were able to give context-appropriate, goal-directed responses. Our results showed that when the brain has not sufficiently recovered a certain level of consciousness, it is also unable to generate a 24-hour sleep-wake cycle and consolidated nighttime sleep. This study contributes to elucidating the pathophysiology of severe sleep-wake cycle alterations in the acute phase of moderate to severe TBI.

The role of neurosteroids in the pathogenesis of hepatic encephalopathy

Hepatic Encephalopathy (HE) represents a neuropsychiatric syndrome caused by acute or chronic liver failure. Hyperammonemia plays a pivotal role in the development of HE through modulation of neurotransmission, oxidative stress, neuroinflammation, mitochondrial dysfunction, and energy deficit. Neurosteroids contribute significantly to increased GABAergic tone in HE. Ammonia, in combination with manganese and proinflammatory cytokines, stimulate neurosteroid synthesis by up-regulation of translocator protein, a component of multiprotein complex that stimulate cholesterol transport into astrocytic mitochondria. Cholesterol serves as a substrate for the synthesis of neurosteroids allopregnanolone and tetrahydro-deoxycorticosterone. After release from astrocytes, allopregnanolone and tetrahydro-deoxycorticosterone potentiate GABAergic transmission by positive allosteric modulation of GABAA receptor, thus contributing to cognitive deficit and alterations in sleep-wake cycle. Additional potential mechanisms of neurosteroid action in HE include modulation of serotoninergic, cholinergic, glutamatergic, glycinergic, and opioid receptor activities, as well as modulation of gene expression. This review aimed to summarize current knowledge of the role of neurosteroids in the pathogenesis of HE.

Electric stimulation of the tuberomamillary nucleus affects epileptic activity and sleep–wake cycle in a genetic absence epilepsy model

Deep brain stimulation (DBS) is a promising approach for epilepsy treatment, but the optimal targets and parameters of stimulation are yet to be investigated. Tuberomamillary nucleus (TMN) is involved in EEG desynchronization-one of the proposed mechanisms for DBS action. We studied whether TMN stimulation could interfere with epileptic spike-wave discharges (SWDs) in WAG/Rij rats with inherited absence epilepsy and whether such stimulation would affect sleep-wake cycle. EEG and video registration were used to determine SWD occurrence and stages of sleep and wake during three-hours recording sessions. Stimulation (100Hz) was applied in two modes: closed-loop (with previously determined interruption threshold intensity) or open-loop mode (with 50% or 70% threshold intensity). Closed-loop stimulation successfully interrupted SWDs but elevated their number by 148 ± 54% compared to baseline. It was accompanied by increase in number of episodes but not total duration of both active and passive wakefulness. Open-loop stimulation with amplitude 50% threshold did not change measured parameters, though 70% threshold stimulation reduced SWDs number by 40 ± 9%, significantly raised the amount of active wakefulness and decreased the amount of both slow-wave and rapid eye movement sleep. These results suggest that the TMN is unfavorable as a target for DBS as its stimulation may cause alterations in sleep-wake cycle. A careful choosing of parameters and control of sleep-wake activity is necessary when applying DBS in epilepsy.

The Melatonergic System in Mood and Anxiety Disorders and the Role of Agomelatine: Implications for Clinical Practice

Melatonin exerts its actions through membrane MT1/MT2 melatonin receptors, which belong to the super family of G-protein-coupled receptors consisting of the typical seven transmembrane domains. MT1 and MT2 receptors are expressed in various tissues of the body either as single ones or together. A growing literature suggests that the melatonergic system may be involved in the pathophysiology of mood and anxiety disorders. In fact, some core symptoms of depression show disturbance of the circadian rhythm in their clinical expression, such as diurnal mood and other symptomatic variation, or are closely linked to circadian system functioning, such as sleep-wake cycle alterations. In addition, alterations have been described in the circadian rhythms of several biological markers in depressed patients. Therefore, there is interest in developing antidepressants that have a chronobiotic effect (i.e., treatment of circadian rhythm disorders). As melatonin produces chronobiotic effects, efforts have been aimed at developing agomelatine, an antidepressant with melatonin agonist activity. The present paper reviews the role of the melatonergic system in the pathophysiology of mood and anxiety disorders and the clinical characteristics of agomelatine. Implications of agomelatine in “real world” clinical practice will be also discussed.

Delirium in hospitalized patients: Cohort observational in infirmary of medical clinic

Objectives: To determine prevalence, incidence and risk factors of delirium in hospitalized patients in the infirmary of medical clinic of the Lauro Wanderley University Hospital. Method: An observational cohort study evaluating 140 patients over 18 years between admission and discharge. The survey instrument was the Confusion Assessment Method. Results: The prevalence of delirium was 5.7% (8/140) and the incidence, 2.1%. In patients with delirium were observed alteration of sleep-wake cycle (6/75%), altered level of consciousness (6/75%), disorganized thinking (5/62, 5%) and psychomotor retardation (5/62 5%). There was a significant association of delirium and age, mechanical restraint in bed, prior history of cognitive impairment, auditory and visual sensory deficit, psychiatric hospitalization, poor health status and mortality. Conclusions: The prevalence of delirium at admission was lower than that found in other studies, but it was a predictor factor of hospital mortality.

Postoperative Delirium

Delirium is a global impairment of upper brain functions caused by an organic substrate. It is frequently observed in the postoperative period, particularly in elderly people. Vascular and orthopedic surgery and long-duration surgery are associated with a higher incidence of postoperative delirium. When it occurs, postoperative delirium makes patient management much more difficult, increases costs, and, above all, causes severe discomfort to the patient. Delirium is also associated with higher postoperative mortality and morbidity, and with delayed functional recovery, but it is still unclear whether worse prognosis is directly caused by delirium or results from the neurological damage of which delirium is simply a symptom. Drug therapy should be part of a complex approach to prevent and treat this complication. Neuroleptics like haloperidol and droperidol, and benzodiazepines are usually employed in order to control symptoms like agitation, restlessness, and altered perceptions. Atypical neuroleptics, like risperidone, have not yet been studied in postoperative delirium, although some case reports in which they were successfully used have been published. Physiostigmine is effective in delirium caused by anticholinergic syndrome; vitamins may be useful in alcoholics; melatonin use has been suggested in order to prevent and treat delirium by normalizing sleep-wake cycle alterations. Environmental interventions are often costless and may be very useful to prevent and treat postoperative delirium in patients at risk.

WAR-RELATED POST-TRAUMATIC STRESS DISORDER

Post-Traumatic Stress Disorder (PTSD) follows a psychologically distressing event outside the usual human experience. Characteristic symptoms: re-experiencing the traumatic event, avoidance of stimuli associated with the event or numbing of general responsiveness and increased arousal. Using semi-structured questionnaires, we studied background, war traumas and physical/psycho-cmotional reactions in 163 Bosnian and 30 Croatian refugees (mainly mothers & children) in an Italian Red Cross camp. Results. Adults: PTSD in most, with psychiatric relevance in 16. Infants: csp. physical ailments (poor appetite; vomiting; colic; diarrhoea; constipation; alterations in sleep wake cycle, mood, and development), all worsening when psychological disturbances in mothers increased. Children >3 yrs: frequent PTSD with insomnia, restlessness, repetitive play, moodiness, psychosomatic symptoms. Adolescents: PTSD with defence mechanisms against anxiety (rationalisation and idealisation). Conclusions: infants better defended from traumas providing mothers act as a protective shield. Releasing tension through play is often ineffective in protecting Children. Adolescents' idealisation process tends to exasperate the contrapposition between friends and enemies, undermining their sense of reality and their personal identity.