Latency To N3 Interruption In Arousal Disorders.

STUDY OBJECTIVES: To help expert witnesses in criminal cases using the "sleepwalking defense", we studied the time of first and last interruptions from stage N3 in patients with arousal disorders, including sexsomnia, as well as their determinants. METHODS: The epochs of lights off, sleep onset, first N3 interruption (with and without behaviors), and last N3 interruption were determined by videopolysomnography on two consecutive nights in 163 adults with disorders of arousal, including 46 with and 117 without sexsomnia. RESULTS: The first N3 interruption (independently of concomitant behavior) occurred as early as 8 minutes after sleep onset and within 100 minutes of falling asleep in 95% of cases. The first motor arousal from N3 occurred as early as 25 min after lights off time, a timing more variable between participants (between 30 and 60 minutes after lights off time in 25% of participants and within 60 minutes of falling asleep in 50%). These latencies did not differ between the groups with and without sexsomnia. No correlation was found between these latencies and the young age, sex or clinical severity. The latency of motor arousals was shorter when they were associated with a fast-wave EEG profile and were not preceded by another type of N3 arousal. CONCLUSION: The first motor arousal may occur early in the night in patients with arousal disorders, with or without sexsomnia, suggesting that abnormal behaviors occurring as early as 25 min after lights off time in clinical and criminal cases can be a parasomnia manifestation.

Shift rotation scheme, sleepiness and sleep quality in night-shift workers.

BACKGROUND: Shift rotation schemes can influence workers' tolerance of night-shift work and its impact on health. AIMS: This study was aimed to assess the influence of shift work rotation schemes on sleepiness and sleep quality. METHODS: We conducted a cross-sectional study of 145 male workers, 77 from a ceramic tile factory on a fixed, forward-rotating shift work scheme, and 68 from a dockyard company, working on-call night shifts. Participants self-administered the Epworth Sleepiness Scale (ESS) and the Pittsburgh Sleep Quality Index (PSQI) questionnaires and provided data on demographic and lifestyle variables. We set two logistic regression models to predict the risk of daytime sleepiness and poor sleep quality as a function of night-shift work and on-call night shifts, adjusting for personal and lifestyle covariates. RESULTS: Marital status, body mass index, smoking and alcohol intake did not affect ESS and PSQI scores, nor did they differ between the two cohorts. Night-shift workers from both cohorts were more likely to have a PSQI score ≥6, suggestive of poor sleep quality, with no variation between the two cohorts. ESS scores suggestive of daytime sleepiness were strongly associated with on-call night shifts among dockyard workers for (odds ratio = 13.4; 95% confidence interval 2.9-63.9), in respect the regular, forward-rotating night-shift work among ceramic tile factory workers. DISCUSSION: Daytime sleepiness occurred more frequently among dockyard workers working on-call night shifts. Poor sleep quality occurred more frequently among night-shift workers, but it did not differ between the two companies.

Efficacy and safety of 5-hydroxytryptophan on depression and apathy in Parkinson's disease: a preliminary finding.

BACKGROUND AND PURPOSE: Several studies have indicated that altered serotonergic neurotransmission may contribute to non-motor features commonly associated with Parkinson's disease (PD) such as apathy and depression. 5-hydroxytryptophan (5-HTP) is the intermediate metabolite of L-tryptophan in the production of serotonin. To date, there has been inconsistent research on the use of 5-HTP in PD. The purpose of this study was to compare the effects of 5-HTP with those of placebo on apathy and depressive symptoms in patients with PD. METHODS: A single-center, randomized, double-blind placebo-controlled cross-over trial was employed; 25 individuals were subsequently enrolled into the study. Patients received placebo and 50 mg of 5-HTP daily over a period of 4 weeks. For the assessment of efficacy on depressive and apathy symptoms the Beck Depression Inventory-II (BDI-II), Hamilton Depression Rating Scale (HDRS) and Apathy Scale (AS) were respectively administered at screening, baseline and weeks 4, 8, 12 and 16. Primary efficacy outcomes were the comparison of 5-HTP to placebo in mean change from baseline to weeks 4, 8, 12 and 16 in total score on the AS, BDI-II and HDRS. RESULTS: Repeated-measures analysis revealed a significant improvement of depressive symptoms during the 50-mg 5-HTP treatment compared with placebo as assessed by the HDRS. No effect of 5-HTP was seen on apathy symptoms assessed by the AS. CONCLUSIONS: This study provides preliminary evidence of clinical benefit of 5-HTP for treating depressive symptoms in PD. Larger studies with a longer treatment duration are needed to corroborate these early findings.

Does REM sleep behavior disorder change in the progression of Parkinson's disease?

OBJECTIVES/BACKGROUND: Rapid eye movement (REM) Sleep Behavior Disorder (RBD) in Parkinson's disease (PD) may be associated with a malignant phenotype. Despite its prognostic value, little is known about the time course of RBD in PD. In this study, we aimed to ascertain whether or not RBD is a stable feature in PD. In this study, we prospectively evaluated clinical and neurophysiological features of RBD, including REM Sleep Without Atonia (RSWA), in PD patients with RBD at baseline and after three years then assessed whether the changes in measures of RSWA parallel the progression of PD. PATIENTS/METHODS: In sum, 22 (17M, mean age 64.0 ± 6.9 years) moderate-to-advanced PD patients (mean PD duration at baseline:7.6±4.8 years) with RBD, underwent a video-polysomnography (vPSG) recording and clinical and neuropsychological assessment at baseline and after three years. RESULTS: At follow-up, the self-assessed frequency of RBD symptoms increased in six patients, decreased in six and remained stable in 10, while RSWA measures significantly increased in all subjects. At follow-up, patients showed worse H&Y stage (p = 0.02), higher dopaminergic doses (p = 0.05) and they performed significantly worse in phonetic and semantic fluency tests (p = 0.02; p = 0.04). Changes in RSWA correlated significantly with the severity in levodopa-induced dyskinesia (r = 0.61,p = 0.05) and motor fluctuation (r = 0.54,p = 0.03) scores, and with the worsening of executive functions (r = 0.78,p = 0.001) and visuo-spatial perception (r = -0.57,p = 0.04). CONCLUSION: Despite the subjective improvement of RBD symptoms in one-fourth of PD patients, all RSWA measures increased significantly at follow-up, and their changes correlated with the clinical evolution of motor and non-motor symptoms. RBD is a long-lasting feature in PD and RSWA is a marker of the disease's progression.

Italian Association of Sleep Medicine (AIMS) position statement and guideline on the treatment of menopausal sleep disorders.

Insomnia, vasomotor symptoms (VMS) and depression often co-occur after the menopause, with consequent health problems and reductions in quality of life. The aim of this position statement is to provide evidence-based advice on the management of postmenopausal sleep disorders derived from a systematic review of the literature. The latter yielded results on VMS, insomnia, circadian rhythm disorders, obstructive sleep apnea (OSA) and restless leg syndrome (RLS). Overall, the studies show that menopausal hormone therapy (MHT) improves VMS, insomnia, and mood. Several antidepressants can improve insomnia, either on their own or in association with MHT; these include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and mirtazapine. Long-term benefits for postmenopausal insomnia may also be achieved with non-drug strategies such as cognitive behavioral therapy (CBT) and aerobic exercise. Continuous positive airway pressure (CPAP) and mandibular advancement devices (MADs) both reduce blood pressure and cortisol levels in postmenopausal women suffering from OSA. However, the data regarding MHT on postmenopausal restless legs syndrome are conflicting.

REM sleep behavior disorder and periodic leg movements during sleep in ALS.

OBJECTIVE: To assess sleep characteristics and the occurrence of abnormal muscle activity during sleep, such as REM sleep without atonia (RSWA), REM sleep behavior disorder (RBD), and periodic leg movements during sleep (PLMS), in patients with amyotrophic lateral sclerosis (ALS). METHODS: A total of 41 patients with ALS and 26 healthy subjects were submitted to clinical interview and overnight video-polysomnography. RESULTS: A total of 22 patients with ALS (53.6%) reported poor sleep quality. Polysomnographic studies showed that patients with ALS had reduced total sleep time, increased wakefulness after sleep onset, shortened REM and slow-wave sleep, and decreased sleep efficiency, compared to controls. Polysomnographic abnormalities were not different in patients reporting good or poor sleep and were not correlated to clinical and demographic variables. The PLMS index was significantly higher in patients with ALS than in healthy subjects, and 22 patients (53.6%) showed a PLMS index > 15/h, vs 4 (15.4%) controls (P < 0.001). Finally, two patients with ALS (4.9%) had RBD, and two more patients presented RSWA (4.9%), whereas no controls showed abnormalities of REM sleep. CONCLUSION: Patients with ALS frequently present abnormalities of sleep that can be documented both at the clinical interview and at the polysomnographic evaluation, including insomnia, fragmented sleep, and increased PLMS. Moreover, abnormalities of REM sleep can be found in some of these patients.

Environmental risk factors for REM sleep behavior disorder: a multicenter case-control study.

OBJECTIVE: Idiopathic REM sleep behavior disorder is a parasomnia characterized by dream enactment and is commonly a prediagnostic sign of parkinsonism and dementia. Since risk factors have not been defined, we initiated a multicenter case-control study to assess environmental and lifestyle risk factors for REM sleep behavior disorder. METHODS: Cases were patients with idiopathic REM sleep behavior disorder who were free of dementia and parkinsonism, recruited from 13 International REM Sleep Behavior Disorder Study Group centers. Controls were matched according to age and sex. Potential environmental and lifestyle risk factors were assessed via standardized questionnaire. Unconditional logistic regression adjusting for age, sex, and center was conducted to investigate the environmental factors. RESULTS: A total of 694 participants (347 patients, 347 controls) were recruited. Among cases, mean age was 67.7 ± 9.6 years and 81.0% were male. Cases were more likely to smoke (ever smokers = 64.0% vs 55.5%, adjusted odds ratio [OR] = 1.43, p = 0.028). Caffeine and alcohol use were not different between cases and controls. Cases were more likely to report previous head injury (19.3% vs 12.7%, OR = 1.59, p = 0.037). Cases had fewer years of formal schooling (11.1 ± 4.4 years vs 12.7 ± 4.3, p < 0.001), and were more likely to report having worked as farmers (19.7% vs 12.5% OR = 1.67, p = 0.022) with borderline increase in welding (17.8% vs 12.1%, OR = 1.53, p = 0.063). Previous occupational pesticide exposure was more prevalent in cases than controls (11.8% vs 6.1%, OR = 2.16, p = 0.008). CONCLUSIONS: Smoking, head injury, pesticide exposure, and farming are potential risk factors for idiopathic REM sleep behavior disorder.

[Cancer risk among shift workers: a review]. / Rischio oncogeno nei lavoratori a turni: analisi della letteratura.

INTRODUCTION: According to IARC, shift work resulting in disruption of circadian rhythm is a probable human carcinogen (Group 2A). METHODS: We examined the scientific literature on the carcinogenic risk among shift workers for risk assessment purposes. RESULTS: Clock genes polymorphisms might contribute with suppression of melatonin synthesis, immuno-suppression from sleep deprivation, individual habits associated with shift work, and low vitamin D levels, in increasing risk of breast cancer, prostate cancer and lymphoma among shift workers. CONCLUSION: Although the epidemiological evidence seems scanty, the hypothesis that shift work-related sleep deprivation would contribute to increasing cancer risk seems based on solid ground.

Vagal nerve stimulation improves cerebellar tremor and dysphagia in multiple sclerosis.

Vagus nerve stimulation (VNS), an adjunctive approach for the treatment of epilepsy, was performed in three multiple sclerosis (MS) patients displaying postural cerebellar tremor (PCT) and dysphagia. Following VNS, improvement of PCT and dysphagia was manifested over a period of two and three months, respectively. In view of the involvement of the main brainstem visceral component of the vagus, the nucleus tractus solitarius (NTS), in modulating central pattern generators (CPGs) linked to both olive complex pathway and swallowing, improvement is likely to be VNS related. The results obtained suggest an additional therapeutic application for VNS and may represent a novel form of treatment in patients with severe MS.

Increase in 20-50 Hz (gamma frequencies) power spectrum and synchronization after chronic vagal nerve stimulation.

OBJECTIVE: Though vagus nerve stimulation (VNS) is an important option in pharmaco-resistant epilepsy, its mechanism of action remains unclear. The observation that VNS desynchronised the EEG activity in animals suggested that this mechanism could be involved in VNS antiepileptic effects in humans. Indeed VNS decreases spiking bursts, whereas its effects on the EEG background remain uncertain. The objective of the present study is to investigate how VNS affects local and inter regional syncronization in different frequencies in pharmaco-resistant partial epilepsy. METHODS: Digital recordings acquired in 11 epileptic subjects 1 year and 1 week before VNS surgery were compared with that obtained 1 month and 1 year after VNS activation. Power spectrum and synchronization were then analyzed and compared with an epileptic group of 10 patients treated with AEDs only. RESULTS: VNS decreases the synchronization of theta frequencies (P < 0.01), whereas it increases gamma power spectrum and synchronization (< 0.001 and 0.01, respectively). CONCLUSIONS: The reduction of theta frequencies and the increase in power spectrum and synchronization of gamma bands can be related to VNS anticonvulsant mechanism. In addition, gamma modulation could also play a seizure-independent role in improving attentional performances. SIGNIFICANCE: These results suggest that some antiepileptic mechanisms affected by VNS can be modulated by or be the reflection of EEG changes.

Localization of fast MEG waves in patients with brain tumors and epilepsy.

It was investigated if single dipole analysis of spontaneous fast waves (>8 Hz) can be used to determine the location of the epileptic focus. Automatic dipole analysis was applied to MEG data of 25 patients with intracranial tumors and epilepsy. The frequency range of 8-50 Hz was divided into standard EEG bands. MEG results were overlaid on the MRI scans of the patients. Dipoles describing fast wave fields were located in the parietal/occipital cortex, and not at tumor border zones. In the cases that the dipoles were lateralized there was no clear preference to be located ipsi or contralateral to the tumor. However the generators of epileptic activity in these patients are thought to be located in the border areas of the tumors. Therefore it seems unlikely that the dipole locations describing fast waves are related to the epileptic zones in patients with brain tumors and epilepsy. A remarkable finding is that lateralized dipoles tend to be located in the right hemisphere and not in the left hemisphere. This appears to reflect an asymmetry of possibly normal background activity.

Correlation between cerebral perfusion and hyperventilation enhanced focal spiking activity.

Single photon emission computed tomography (SPECT) has frequently been used to investigate cerebral brain perfusion (CBP) occurring ictally and inter-ictally in epileptic patients. Several studies have addressed the multimodal analysis of the modifications occurring in cerebral areas involved in seizure activity, by correlating SPECT with electroencephalografic (EEG) recordings during ictal and inter-ictal epileptiform lateralized discharges (IELDs). Although these studies have yielded interesting results, variations in regional CBP (rCBP) observed during ictal events are difficult to interpret since the areas of altered rCBP might reflect not only events restricted to the epileptogenic focus, but also large fluctuations determined by seizure spread. Inter-ictal rCBP correlates with the area generating the local EEG epileptogenic activity in a limited percentage of studies. Hyperventilation (HPV) represents a well established EEG activation procedure aimed at enhancing epileptiform discharges. Since HPV-enhanced IELDs may help analyze the CBP pathophysiology in inter-ictal epilepsy, in the present study we investigate this specific aspect co-registering EEG with SPECT in subjects affected by partial epilepsy responding to HPV with IELD enhancement without seizure precipitation. This study suggests a correlation between localized increase in rCBP and HPV-induced IELDs and provides a tool to discuss uncommon aspects of the physiology of rCBP during the inter-ictal state in the epileptogenic areas.

Hippocampal theta activity after systemic administration of a non-peptide delta-opioid agonist in freely-moving rats: relationship to D1 dopamine receptors.

Hippocampal theta activity was acquired and processed off-line from digitized EEG recordings after subcutaneous (s.c.) administration of the non-opioid delta agonist BW 373U86 (0.5-2.5 mg/kg) in freely-moving rats. Relative theta power spectral analysis, implemented by a signal processing software, showed that BW 373U86 induced a dose-dependent increase in the slow component of theta band (Type 2 theta), while movement-related fast theta band (Type 1 theta) failed to show significant changes. Moreover, the increase in relative Type 2 theta power showed a maximal change at 1 mg/kg of BW 373U86, while higher doses, although effective in increasing relative Type 2 theta, induced locomotion and irregularly increased Type 1 hippocampal theta activity. The administration of 10.0 mg/kg of the delta antagonist Naltrindole (NLI) 30 min before BW 373U86, abolished hippocampal Type 2 theta increase. The rise of relative Type 2 theta power induced by BW 373U86 (1-2.5 mg/kg) was greatly attenuated by 0.1 mg/kg of the selective dopamine (DA) D1 antagonist SCH 23390. Administration of 0.1 mg/kg of SCH 23390 alone did not modify hippocampal Type 2 theta. These results indicate that delta receptors modulate the expression of hippocampal Type 2 theta and dopamine, through D1 receptors, exerts a permissive role on this influence.