Melatonin Secretion Pattern in Critically Ill Patients:A Pilot Descriptive Study

Critically ill patients have abnormal circadian and sleep homeostasis. This may be associated with higher morbidity and mortality. The aims of this pilot study were (1) to describe melatonin secretion in conscious critically ill mechanically ventilated patients and (2) to describe whether melatonin secretion and sleep patterns differed in these patients with and without remifentanil infusion. Eight patients were included. Blood-melatonin was taken every 4th hour, and polysomnography was carried out continually during a 48-hour period. American Academy of Sleep Medicine criteria were used for sleep scoring if sleep patterns were identified; otherwise, Watson’s classification was applied. As remifentanil was periodically administered during the study, its effect on melatonin and sleep was assessed. Melatonin secretion in these patients followed a phase-delayed diurnal curve. We did not observe any effect of remifentanil on melatonin secretion. We found that the risk of atypical sleep compared to normal sleep was significantly lower (p<0.001) under remifentanil infusion. Rapid Eye Movement (REM) sleep was only observed during the nonsedation period. We found preserved diurnal pattern of melatonin secretion in these patients. Remifentanil did not affect melatonin secretion but was associated with lower risk of atypical sleep pattern. REM sleep was only registered during the period of nonsedation

Sleep spindle alterations in patients with Parkinson's disease

The aim of this study was to identify changes of sleep spindles (SS) in the EEG of patients with Parkinson's disease (PD). Five sleep experts manually identified SS at a central scalp location (C3-A2) in 15 PD and 15 age- and sex-matched control subjects. Each SS was given a confidence score, and by using a group consensus rule, 901 SS were identified and characterized by their (1) duration, (2) oscillation frequency, (3) maximum peak-to-peak amplitude, (4) percent-to-peak amplitude, and (5) density. Between-group comparisons were made for all SS characteristics computed, and significant changes for PD patients vs. control subjects were found for duration, oscillation frequency, maximum peak-to-peak amplitude and density. Specifically, SS density was lower, duration was longer, oscillation frequency slower and maximum peak-to-peak amplitude higher in patients vs. controls. We also computed inter-expert reliability in SS scoring and found a significantly lower reliability in scoring definite SS in patients when compared to controls. How neurodegeneration in PD could influence SS characteristics is discussed. We also note that the SS morphological changes observed here may affect automatic detection of SS in patients with PD or other neurodegenerative disorders (NDDs)

Signaling mechanisms that regulate actin-based motility processes in the nervous system

Actin-based motility is critical for nervous system development. Both the migration of neurons and the extension of neurites require organized actin polymerization to push the cell membrane forward. Numerous extracellular stimulants of motility and axon guidance cues regulate actin-based motility through the rho GTPases (rho, rac, and cdc42). The rho GTPases reorganize the actin cytoskeleton, leading to stress fiber, filopodium, or lamellipodium formation. The activity of the rho GTPases is regulated by a variety of proteins that either stimulate GTP uptake (activation) or hydrolysis (inactivation). These proteins potentially link extracellular signals to the activation state of rho GTPases. Effectors downstream of the rho GTPases that directly influence actin polymerization have been identified and are involved in neurite development. The Arp2/3 complex nucleates the formation of new actin branches that extend the membrane forward. Ena/VASP proteins can cause the formation of longer actin filaments, characteristic of growth cone actin morphology, by preventing the capping of barbed ends. Actin-depolymerizing factor (ADF)/cofilin depolymerizes and severs actin branches in older parts of the actin meshwork, freeing monomers to be re-incorporated into actively growing filaments. The signaling mechanisms by which extracellular cues that guide axons to their targets lead to direct effects on actin filament dynamics are becoming better understood.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66422/1/j.1471-4159.2002.01185.x.pd

Consciousness in Neurocritical Care Cohort Study Using fMRI and EEG (CONNECT-ME): Protocol for a Longitudinal Prospective Study and a Tertiary Clinical Care Service

Aims and Objectives: To facilitate individualized assessment of unresponsive patients in the intensive care unit for signs of preserved consciousness after acute brain injury.Background: Physicians and neuroscientists are increasingly recognizing a disturbing dilemma: Brain-injured patients who appear entirely unresponsive at the bedside may show signs of covert consciousness when examined by functional MRI (fMRI) or electroencephalography (EEG). According to a recent meta-analysis, roughly 15% of behaviorally unresponsive brain-injured patients can participate in mental tasks by modifying their brain activity during EEG- or fMRI-based paradigms, suggesting that they are conscious and misdiagnosed. This has major ethical and practical implications, including prognosis, treatment, resource allocation, and end-of-life decisions. However, EEG- or fMRI-based paradigms have so far typically been tested in chronic brain injury. Hence, as a novel approach, CONNECT-ME will import the full range of consciousness paradigms into neurocritical care.Methods: We will assess intensive care patients with acute brain injury for preserved consciousness by serial and multimodal evaluation using active, passive and resting state fMRI and EEG paradigms, as well as state-of-the-art clinical techniques including pupillometry and sophisticated clinical rating scales such as the Coma Recovery Scale-Revised. In addition, we are establishing a biobank (blood, cerebrospinal fluid and brain tissue, where available) to facilitate future genomic and microbiomic research to search for signatures of consciousness recovery.Discussion: We anticipate that this multimodal approach will add vital clinical information, including detection of preserved consciousness in patients previously thought of as unconscious, and improved (i.e., personalized) prognostication of individual patients. Our aim is two-fold: We wish to establish a cutting-edge tertiary care clinical service for unresponsive patients in the intensive care unit and lay the foundation for a fruitful multidisciplinary research environment for the study of consciousness in acute brain injury. Of note, CONNECT-ME will not only enhance our understanding of consciousness disorders in acute brain injury but it will also raise awareness for these patients who, for obvious reasons, have lacked a voice so far.Trial registration: The study is registered with clinicaltrials.org (ClinicalTrials.gov Identifier: NCT02644265)

Increased Motor Activity During REM Sleep Is Linked with Dopamine Function in Idiopathic REM Sleep Behavior Disorder and Parkinson Disease

STUDY OBJECTIVES: Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by impaired motor inhibition during REM sleep, and dream-enacting behavior. RBD is especially associated with α-synucleinopathies, such as Parkinson disease (PD). Follow-up studies have shown that patients with idiopathic RBD (iRBD) have an increased risk of developing an α-synucleinopathy in later life. Although abundant studies have shown that degeneration of the nigrostriatal dopaminergic system is associated with daytime motor function in Parkinson disease, only few studies have investigated the relation between this system and electromyographic (EMG) activity during sleep. The objective of this study was to investigate the relationship between the nigrostriatal dopamine system and muscle activity during sleep in iRBD and PD. METHODS: 10 iRBD patients, 10 PD patients with PD, 10 PD patients without RBD, and 10 healthy controls were included and assessed with (123)I-N-omega-fluoropropyl-2-beta-carboxymethoxy-3beta-(4-iodophenyl) nortropane ((123)I-FP-CIT) Single-photon emission computed tomography (SPECT) scanning ((123)I-FP-CIT SPECT), neurological examination, and polysomnography. RESULTS: iRBD patients and PD patients with RBD had increased EMG-activity compared to healthy controls. (123)I-FP-CIT uptake in the putamen-region was highest in controls, followed by iRBD patients, and lowest in PD patients. In iRBD patients, EMG-activity in the mentalis muscle was correlated to (123)I-FP-CIT uptake in the putamen. In PD patients, EMG-activity was correlated to anti-Parkinson medication. CONCLUSIONS: Our results support the hypothesis that increased EMG-activity during REM sleep is at least partly linked to the nigrostriatal dopamine system in iRBD, and with dopamine function in PD. CITATION: Zoetmulder M, Nikolic M, Biernat H, Korbo L, Friberg L, Jennum P. Increased motor activity during rem sleep is linked with dopamine function in idiopathic REM sleep behavior disorder and Parkinson disease. J Clin Sleep Med 2016;12(6):895–903