134 research outputs found
Insomnia and somnolence in idiopathic RBD : a prospective cohort study
Although some sleep disorders are markers of prodromal Parkinsonâs disease and dementia with Lewy bodies, it is unclear whether
insomnia and somnolence can predict disease. We assessed a large cohort of patients with idiopathic rapid eye movement sleep
behavior disorder and age/sex matched controls, comparing the Epworth sleepiness scale, the Insomnia Severity Index, the
Pittsburgh Sleep Quality Index, and polysomnographic variables. In those with repeated scales, we assessed change over time.
Finally, we assessed whether sleep abnormalities predicted defined neurodegenerative disease. The 151 patients (age = 65.9, 75%
male) completed sleep scales and were included. Epworth scores were similar between patients and controls (7.0+/â4.6 vs. 7.2
+/â4.7, p = 0.77), and did not progress with time (change = +0.46+/â2.1, p = 0.45). Epworth scores were similar between those who
developed neurodegenerative disease and those remaining disease-free (6.7+/â4.4 vs. 7.1+/â4.7, p = 0.70). Pittsburgh Index scores
were higher in patients than controls (7.2+/â3.8 vs. 4.9+/â3.4, p = 0.004), mainly driven by the sleep disturbance/medication
components (reflecting rapid eye movement sleep behavior disorder symptoms/treatment). Baseline Pittsburgh scores did not
predict conversion to neurodegeneration, although sleep duration increased over time in those converting to neurodegenerative
disease (+0.88+/â1.32 h, p = 0.014). Insomnia index scores were higher in patients than controls (10.0+/â5.5 vs. 6.35+/â4.66, p <
0.001), but declined over time (â1.43+/â5.09, p = 0.029) particularly in those converting to neurodegenerative disease. Finally, on
polysomnogram, those with increased tonic rapid eye movement had higher risk of developing defined neurodegenerative disease
(HR = 1.88, p = 0.039). In summary, we found that somnolence and insomnia do not predict neurodegeneration in idiopathic rapid
eye movement sleep behavior disorder. As neurodegeneration progresses through prodromal stages, patients may have increasing
sleep drive and duration
A 12-week open-label, multicenter study evaluating the safety and patient-reported efficacy of sodium oxybate in patients with narcolepsy and cataplexy
Objective: This study aimed to evaluate safety and efficacy of sodium oxybate (SXB) titrated to effect.
Methods: SXB-naive patients who had participated in a randomized SXB clinical trial and had not been
titrated to adequate clinical effect were initiated on open-label SXB at 4.5 g/night and titrated in 1.5-g
increments to 6, 7.5, or 9 g/night or down to 3 g/night, based on individual clinical response. Treatment
was 12 weeks; safety was the primary outcome. Efficacy was evaluated using the Narcolepsy Symptom
Assessment Questionnaire (NSAQ), a five-point scale (âmuch improvedâ to âmuch worseâ) that assessed
changes from baseline in specific symptoms. Response was defined as âmuch improvedâ or âsomewhat
improvedâ overall at weeks 6 and 12.
Results: Of 202 patients, 171 (85%) completed treatment; final doses were 3 g (n = 5), 4.5 g (n = 29), 6 g
(n = 80), 7.5 g (n = 66), and 9 g (n = 22). Adverse events (AEs) were reported in 114 patients (56%), serious
AEs in five (2%). The most common AEs were nausea (10%), headache (7%), and dizziness (5%). Response
rate was 92% at week 6 and 90% at week 12; most patients reported improvements in all individual symptoms.
Overall, 60% of patients rated their symptoms at 12weeks as âmuch improved,â and this improvement
was dose dependent.
Conclusions: The SXB safety profile was consistent with parent trials. Ninety percent of patients
reported improvements as measured by the NSAQ
Sleep deprivation reveals altered brain perfusion patterns in somnambulism
BACKGROUND:
Despite its high prevalence, relatively little is known about the pathophysiology of somnambulism. Increasing evidence indicates that somnambulism is associated with functional abnormalities during wakefulness and that sleep deprivation constitutes an important drive that facilitates sleepwalking in predisposed patients. Here, we studied the neural mechanisms associated with somnambulism using Single Photon Emission Computed Tomography (SPECT) with 99mTc-Ethylene Cysteinate Dimer (ECD), during wakefulness and after sleep deprivation.
METHODS:
Ten adult sleepwalkers and twelve controls with normal sleep were scanned using 99mTc-ECD SPECT in morning wakefulness after a full night of sleep. Eight of the sleepwalkers and nine of the controls were also scanned during wakefulness after a night of total sleep deprivation. Between-group comparisons of regional cerebral blood flow (rCBF) were performed to characterize brain activity patterns during wakefulness in sleepwalkers.
RESULTS:
During wakefulness following a night of total sleep deprivation, rCBF was decreased bilaterally in the inferior temporal gyrus in sleepwalkers compared to controls.
CONCLUSIONS:
Functional neural abnormalities can be observed during wakefulness in somnambulism, particularly after sleep deprivation and in the inferior temporal cortex. Sleep deprivation thus not only facilitates the occurrence of sleepwalking episodes, but also uncovers patterns of neural dysfunction that characterize sleepwalkers during wakefulness
EEG functional connectivity prior to sleepwalking : evidence of interplay between sleep and wakefulness
Study Objectives: Although sleepwalking (somnambulism) affects up to 4% of adults, its pathophysiology remains poorly understood. Sleepwalking can be
preceded by fluctuations in slow-wave sleep EEG signals, but the significance of these pre-episode changes remains unknown and methods based on EEG
functional connectivity have yet to be used to better comprehend the disorder.
Methods: We investigated the sleep EEG of 27 adult sleepwalkers (mean age: 29 ± 7.6 years) who experienced a somnambulistic episode during slow-wave
sleep. The 20-second segment of sleep EEG immediately preceding each patientâs episode was compared with the 20-second segment occurring 2 minutes
prior to episode onset.
Results: Results from spectral analyses revealed increased delta and theta spectral power in the 20 seconds preceding the episodesâ onset as compared to
the 20 seconds occurring 2 minutes before the episodes. The imaginary part of the coherence immediately prior to episode onset revealed (1) decreased delta
EEG functional connectivity in parietal and occipital regions, (2) increased alpha connectivity over a fronto-parietal network, and (3) increased beta connectivity
involving symmetric inter-hemispheric networks implicating frontotemporal, parietal and occipital areas.
Conclusions: Taken together, these modifications in EEG functional connectivity suggest that somnambulistic episodes are preceded by brain processes
characterized by the co-existence of arousal and deep slee
Regional cerebral blood flow during wakeful rest in older subjects with mild to severe obstructive sleep apnea
Objectives: To evaluate changes in regional cerebral blood flow (rCBF) during wakeful rest in older
subjects with mild to severe obstructive sleep apnea (OSA) and healthy controls, and to identify
markers of OSA severity that predict altered rCBF.
Design: High-resolution 99mTc-HMPAO SPECT images during wakeful rest.
Setting: Research sleep laboratory affiliated with a University hospital.
Participants: Fifty untreated OSA patients aged between 55 and 85 years divided into mild, moderate
and severe OSA and 20 age-matched healthy controls.
Interventions: N/A
Measurements: Using statistical parametrical mapping, rCBF was compared between groups and
correlated with clinical, respiratory and sleep variables.
Results: Whereas no rCBF change was observed in mild and moderate groups, participants with severe
OSA had reduced rCBF compared to controls in the left parietal lobules, precentral gyrus, bilateral
postcentral gyri, and right precuneus. Reduced rCBF in these regions and in areas of the bilateral
frontal and left temporal cortex was associated with more hypopneas, snoring, hypoxemia, and
sleepiness. Higher apnea, micro-arousal, and body mass indexes were correlated to increased rCBF in
the basal ganglia, insula, and limbic system.
Conclusions: While older individuals with severe OSA had hypoperfusions in the sensorimotor and
parietal areas, respiratory variables and subjective sleepiness were correlated with extended regions of
hypoperfusion in the lateral cortex. Interestingly, OSA severity, sleep fragmentation and obesity
correlated with increased perfusion in subcortical and medial cortical regions. Anomalies with such a
distribution could result in cognitive deficits and reflect impaired vascular regulation, altered neuronal
integrity, and/or undergoing neurodegenerative processes
Correlation of changes in patient-reported quality of life with physician-rated global impression of change in patients with narcolepsy participating in a clinical trial of sodium oxybate : a post hoc analysis
Introduction: Narcolepsy patients report lower
health-related quality of life (HRQoL) than the
general population, as measured by the Short Form-36 Health Survey (SF-36). This analysis
evaluated whether changes in SF-36 correlated
with physician-rated Clinical Global Impression
of Change (CGI-C).
Methods: Data were from 209 of 228 narcolepsy patients participating in an 8-week
clinical trial of sodium oxybate. Changes from
baseline for SF-36 subscales (Physical Functioning, Role Physical, Bodily Pain, General Health,
Vitality, Social Functioning, Role Emotional,
and Mental Health) and the summary scores
were evaluated for correlation with CGI-C
overall and by treatment group. Correlations
were calculated using the Pearson product-moment correlation coefficient (r).
Results: Correlations described an inverse relationship in scores, but a direct relationship in
improvement; lower CGI-C scores (i.e., better)
were associated with higher SF-36 subscale
scores (i.e., improved HRQoL). Moderate and
significant correlations were observed for Vitality (r = -0.464; P\0.0001) and Role Physical
(r = -0.310; P\0.0001) subscales, but weak
correlations were observed with other subscales
including summary scores. Correlations were
stronger at higher sodium oxybate doses for
most SF-36 subscales. Conclusion: Some aspects of HRQoL, measured
by the SF-36, may be associated with narcolepsy. In particular, Vitality (indicative of
energy and tiredness) and Role Physical (impact
of physical function on daily roles) moderately correlated with overall change in status
observed by clinicians. However, lack of strong
correlations between SF-36 and CGI-C indicates
differences in patient and clinician perspectives
of disease, and suggest a need for broader
assessment of the impact of narcolepsy and its
treatment on patients
Short-term heart rate variability in a population-based sample of 10-year-old children
Heart rate variability (HRV) is a non-invasive quantitative marker of cardiac autonomic function derived from continuous electrocardiogram (ECG) recordings. Normative HRV values and development factors have not been established in pediatric populations. The objective was to derive referent time- and frequency-domain HRV values for a population-based sample of children. Children aged 9-11 years (N = 1,036) participated in the QuĂ©bec Longitudinal Study of Child Development cohort cardiovascular health screening. Registered nurses measured anthropometrics (height, weight) and children wore an ambulatory Holter monitor to continuously record an ECG signal. HRV variables included time (SDNN, pNN50, RMSSD, SDANN) and frequency (HF, LF, LF/HF ratio) domain variables. Normative HRV values, stratified by age, sex, and heart rate, are presented. Greater heart rate (ÎČ avg = -0.60, R avg (2) = 0.39), pubertal maturation (ÎČ avg = -0.11, R avg (2) = 0.01), later ECG recording times (ÎČ avg = -0.19, R avg (2) = 0.07), and higher diastolic blood pressure (ÎČ avg = -0.11, R avg (2) = 0.01) were significantly associated with reduced HRV in 10-year-old children. The normative HRV values permit clinicians to monitor, describe, and establish pediatric nosologies in primary care and research settings, which may improve treatment of diseases associated with HRV in children. By better understanding existing values, the practical applicability of HRV among clinicians will be enhanced. Lastly, developmental (e.g., puberty) and procedural (e.g., recording time) factors were identified that will improve recording procedures and interpretation of results
Gray matter hypertrophy and thickening with obstructive sleep apnea in middle-aged and older adults
Rationale: Obstructive sleep apnea causes intermittent hypoxemia, hemodynamic fluctuations,
and sleep fragmentation, all of which could damage cerebral gray matter that can be indirectly
assessed with neuroimaging.
Objectives: To investigate whether markers of obstructive sleep apnea severity are associated
with gray matter changes among middle-aged and older individuals.
Methods: Seventy-one subjects (ages: 55 to 76; apneaâhypopnea index: 0.2 to 96.6 events/h)
were evaluated with magnetic resonance imaging. Two techniques were used: 1) voxel-based
morphometry, which measures gray matter volume and concentration; 2) FreeSurfer automated
segmentation, which estimates the volume of predefined cortical/subcortical regions and cortical
thickness. Regression analyses were performed between gray matter characteristics and markers
of obstructive sleep apnea severity (hypoxemia, respiratory disturbances, sleep fragmentation).
Measurements and Main Results: Subjects had few symptoms, i.e. sleepiness, depression,
anxiety and cognitive deficits. While no association was found with voxel-based morphometry,
FreeSurfer revealed increased gray matter with obstructive sleep apnea. Higher levels of
hypoxemia correlated with increased volume and thickness of the left lateral prefrontal cortex as
well as increased thickness of the right frontal pole, the right lateral parietal lobules, and the left
posterior cingulate cortex. Respiratory disturbances positively correlated with right amygdala
volume while more severe sleep fragmentation was associated with increased thickness of the
inferior frontal gyrus.
Conclusions: Gray matter hypertrophy and thickening were associated with hypoxemia,
respiratory disturbances, and sleep fragmentation. These structural changes in a group of middle-aged and older individuals may represent adaptive/reactive brain mechanisms attributed to a
presymptomatic stage of obstructive sleep apnea
The long-term treatment of restless legs syndrome/WillisâEkbom disease: evidence-based guidelines and clinical consensus best practice guidance: a report from the International Restless Legs Syndrome Study Group
AbstractA Task Force was established by the International Restless Legs Syndrome Study Group (IRLSSG) to develop evidence-based and consensus-based recommendations for the long-term pharmacologic treatment of restless legs syndrome/WillisâEkbom disease (RLS/WED). The Task Force reviewed the results of all studies of RLS/WED treatments with durations of 6months or longer presented at meetings over the past 2years, posted on Web sites of pharmaceutical companies, or published in peer-reviewed journals, asking the questions, âWhat is the efficacy of this treatment in patients with RLS/WED?â and âWhat is the safety of this treatment in patients with RLS/WED?âThe Task Force developed guidelines based on their review of 61 papers meeting inclusion criteria, and using a modified evidence-grading scheme. Pregabalin has been established as effective for up to 1year in treating RLS/WED (Level A evidence). Pramipexole, ropinirole, and rotigotine have been established as effective for up to 6months in treating RLS/WED (Level A). The following drugs have been established as probably effective (Level B) in treating RLS/WED for durations ranging from 1 to 5years: gabapentin enacarbil, pramipexole, and ropinirole (1year); levodopa (2years); and rotigotine (5years). Because of associated safety concerns, pergolide and cabergoline should not be used in the treatment of RLS/WED unless the benefits clearly outweigh the risks. Other pharmacologic therapies have insufficient evidence to support their long-term use in treating RLS/WED.The IRLSSG Task Force also developed consensus-based strategies for the prevention and treatment of complications (such as augmentation, loss of efficacy, excessive daytime sleepiness, and impulse control disorders) that may develop with the long-term pharmacologic treatment of RLS/WED. The use of either a dopamine-receptor agonist or α2ÎŽ calcium-channel ligand is recommended as the first-line treatment of RLS/WED for most patients, with the choice of agent dependent on the patientâs severity of RLS/WED symptoms, cognitive status, history, and comorbid conditions
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