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Early-life exposure to environmental toxins like tobacco can permanently re-program body structure and function. Here, we investigated the long-term effects on mouse adult sleep phenotype exerted by early-life exposure to nicotine or to its principal metabolite, cotinine. Moreover, we investigated whether these effects occurred together with a reprogramming of the activity of the hippocampus, a key structure to coordinate the hormonal stress response. Adult male mice born from dams subjected to nicotine (NIC), cotinine (COT) or vehicle (CTRL) treatment in drinking water were implanted with electrodes for sleep recordings. NIC and COT mice spent significantly more time awake than CTRL mice at the transition between the rest (light) and the activity (dark) period. NIC and COT mice showed hippocampal glucocorticoid receptor (GR) downregulation compared to CTRL mice, and NIC mice also showed hippocampal mineralocorticoid receptor downregulation. Hippocampal GR expression significantly and inversely correlated with the amount of wakefulness at the light-to-dark transition, while no changes in DNA methylation were found. We demonstrated that early-life exposure to nicotine (and cotinine) concomitantly entails long-lasting reprogramming of hippocampal activity and sleep phenotype suggesting that the adult sleep phenotype may be modulated by events that occurred during that critical period of life.

Background Measures to contain the Covid-19 pandemic led to significant lifestyle changes for children and adolescents mainly related to the closure of schools and recreational activities, reduced social interaction, and increased family concerns. Methods A cross-sectional online survey of 78 questions investigating social determinants of health, mood changes, symptoms of anxiety, increase in sleep disorders and unusual repetitive movements was offered to parents living in Italy with children ≤18 years; including families of children with disabilities, autism spectrum disorders, chronic diseases, and specific learning disabilities. The survey was conducted on the Qualtrics platform 6 months after the beginning of the pandemic and distributed in hospitals and paediatricians’ waiting rooms as well as through social networks. The primary outcomes were the increase in sleep disorders among children and adolescents. Possible risk factors were investigated through multivariable regression. Results Six thousand two hundred ten volunteer parents responded to the questions concerning mood changes, sleep disorders and unusual repetitive movements, and were included in the present study. The majority were female (91.8%) and Italian (97.0%). 72.7% answered that their children had become more nervous, worried, or sad (80.2% in children with learning disabilities); 77.6% reported feelings of loneliness and 69.3% more difficulties in children falling asleep, 30.2% in staying asleep, and 18.7% an increase in nightmares and/or sleep terrors. Statistical analysis identified socioeconomic status, parent’s job loss, food insecurity, family attitude toward the pandemic, and children’s mood swing, feelings of loneliness, or missing outdoor activities, as major risk factors for sleep disorders. Conclusion The first Covid-19 lockdown impacted children’s and adolescents’ health through an increase in sleep disorders. In the following phases of the pandemic, this evidence may be useful to investigate and treat these disorders as well as make decisions about containment health policies concerning this age group.

Disorders of arousal (DoA) and sleep-related hypermotor epilepsy (SHE) are sleep-related events characterized by complex, often bizarre, and violent behaviors. DoA are involuntary motor manifestations of various complexities occurring during incomplete awakening from non-rapid eye movement sleep. SHE is a focal epilepsy characterized by stereotyped hyperkinetic or/and asymmetric tonic/dystonic seizures usually arising from non-rapid eye movement sleep. Even if many aspects regarding DoA and SHE have been clarified, the differential diagnosis remains challenging, because DoA and SHE share some semiologic features and genetic background. The clinical history, collected from the patient and his/her witness, represents the first and common milestone in the diagnosis. Validated questionnaires constitute suitable screening tools that could guide further analysis. The worldwide availability of homemade video recordings has increased the possibility of adding more objective information to the clinical history alone. The confirmed diagnosis relies on video-polysomnographic recording although it requires time, economic resources, and specific skills for the analysis. In this review we propose a simple diagnostic algorithm for the differential diagnosis between DoA and SHE in adults, based on the most updated knowledge, from the simpler tool to the most specific and tailored one.

Background: Vitamin D exerts multiple pleiotropic effects beyond its role in calcium-phosphate metabolism. Growing evidence suggests an association between hypovitaminosis D and sleep disorders, thus increasing the interest in the role of this vitamin in the regulatory mechanisms of the sleep-wake cycle. Objective: The study aimed to explore and summarize the current knowledge about the role of vitamin D in sleep regulation and the impact of vitamin D deficiency on sleep disorders. Methods: The main regulatory mechanisms of vitamin D on sleep are explained in this study. The literature was scanned to identify clinical trials and correlation studies showing an association between vitamin D deficiency and sleep disorders. Results: Vitamin D receptors and the enzymes that control their activation and degradation are expressed in several areas of the brain involved in sleep regulation. Vitamin D is also involved in the pathways of production of Melatonin, the hormone involved in the regulation of human circadian rhythms and sleep. Furthermore, vitamin D can affect sleep indirectly through non-specific pain disorders, correlated with alterations in sleep quality, such as restless legs syndrome and obstructive sleep apnea syndrome. Conclusions: : Vitamin D has both a direct and an indirect role in the regulation of sleep. Although vitamin D deficiency has been associated to sleep disorders, there is still scant evidence to concretely support the role of vitamin D supplementation in the prevention or treatment of sleep disturbances; indeed, more intervention studies are needed to better clarify these aspects.

Individuals with Chronic Obstructive Pulmonary Disease (COPD) experience sleep disturbances due to the impact of respiratory symptoms on sleep quality. We explored whether sleep disturbances in COPD are linked to heterogeneity of airway constriction.The impact of breathing problems on sleep quality was measured in consecutive COPD outpatients with the COPD and Asthma Sleep Impact Scale (CASIS) questionnaire. Impulse oscillometry technique (IOS) was employed to assess heterogeneity of airway constriction. Subjects with a previous or concomitant diagnosis of asthma or obstructive sleep apnea (OSA) were excluded.Fifty COPD subjects (M/F 40/10; age: 71 +/- 8 yrs, Body Mass Index (BMI): 26.2 +/- 4.7 kg/m(2), Forced Expiratory Volume in the first second (FEV1): 65 +/- 25% predicted; mean +/- SD) were enrolled. The mean CASIS score was 36 +/- 3.3, and the R5-R20 value was 0.2 +/- 0.15 kPa s L-1. The CASIS score was significantly higher in subjects with increased R5-R20 (>0.07 kPa s L-1) (39 +/- 24; p = 0.02) compared to normal R5-R20 (21 +/- 17). When subjects were categorized on the basis of lung function in severely versus non severely obstructed (FEV1 50% predicted) or air trappers versus non air trappers (Residual Volume, RV >= or

Recent contributions have reported sleep disorders as one of the health impairment outcomes of workaholism. A possible factor affecting the sleep-wake cycle might be the intensive use of smartphones. The current study aimed to explore the role of intensive smartphone use in the relationship between workaholism and the sleep-wake cycle. Two serial multiple mediation models were tested on a sample of 418 employees, who filled self-report questionnaires measuring workaholism, use of smartphones, sleep quality and daytime sleepiness, using conditional process analysis for testing direct and indirect effects. Results supported our hypotheses regarding two serial multiple mediation models&mdash, that intensive smartphone use and poor sleep quality mediated the relationship between workaholism and daytime sleepiness, and that smartphone use and daytime sleepiness mediated the relationship between workaholism and poor quality of sleep. Although the use of a cross-sectional design and the snowball technique for collecting data can be considered as possible limitations, the current study is one of the first to document the potential detrimental role of the intensive smartphone use on the workaholism-sleep disorders relationship.

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.

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Objectives: To investigate the quality of sleep and the psychological profiles of a large cohort of Italian patients with burning mouth syndrome (BMS) and to clarify the relationships between these variables and pain. Methods: In this case–control study, 200 patients with BMS vs an equal number of age- and sex-matched healthy controls, recruited in 10 universities, were enrolled. The Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Hamilton Rating Scale for Depression (HAM-D), Hamilton Rating Scale for Anxiety (HAM-A), Numeric Pain Intensity Scale (NRS) and Total Pain Rating Index (T-PRI) were administered. Descriptive statistics, including the Mann–Whitney U test and hierarchical multiple linear regression analysis, were used. Results: Poor sleep quality (PSQI≥5) was present in 78.8% (160) patients with BMS. BMS patients had statistically higher scores in all items of the PSQI and ESS than the healthy controls (p&nbsp

Introduction: Impaired sleep has been reported as an important nonmotor feature in dystonia, but so far, self-reported complaints have never been compared with nocturnal video-polysomnographic (PSG) recording, which is the gold standard to assess sleep-related disorders. Methods: Twenty patients with idiopathic isolated cervical dystonia and 22 healthy controls (HC) underwent extensive clinical investigations, neurological examination, and questionnaire screening for excessive daytime sleepiness and sleep-related disorders. A full-night video PSG was performed in both patients and HC. An ad hoc montage, adding electromyographic leads over the muscle affected with dystonia, was used. Results: When compared to controls, patients showed significantly increased pathological values on the scale assessing self-reported complaints of impaired nocturnal sleep. Higher scores of impaired nocturnal sleep did not correlate with any clinical descriptors but for a weak correlation with higher scores on the scale for depression. On video-PSG, patients had significantly affected sleep architecture (with decreased sleep efficiency and increased sleep latency). Activity over cervical muscles disappears during all the sleep stages, reaching significantly decreased values when compared to controls both in nonrapid eye movements and rapid eye movements sleep. Conclusions: Patients with cervical dystonia reported poor sleep quality and showed impaired sleep architecture. These features however cannot be related to the persistence of muscle activity over the cervical muscles, which disappears in all the sleep stages, reaching significantly decreased values when compared to HC.

Nocturnal frontal lobe epilepsy (NFLE) is a focal epilepsy with seizures arising mainly during sleep and characterized by complex, often bizarre, motor behavior or sustained dystonic posturing. First described in 1981, it was initially considered a motor disorder of sleep and was named nocturnal paroxysmal dystonia (NPD). The unusual seizure semiology, onset during sleep, and often uninformative scalp EEG and brain MRI make it difficult to distinguish NPD attacks from other non-epileptic nocturnal paroxysmal events, namely parasomnias. The long-debated epileptic origin of the condition was finally demonstrated in 1990 and the term NFLE introduced. Even though many aspects of parasomnias and NFLE have been clarified in the last two decades, the differential diagnosis remains a challenge for clinicians. To address controversial issues and define the diagnostic criteria for NFLE, a Consensus Conference was held in Bologna, Italy in 2014. Major points of agreement emerged on: (i) the relationship of the seizures with sleep and not with the circadian pattern of seizure occurrence; (ii) the possible extrafrontal origin of hypermotor seizures, without substantial differences in seizure semiology. In the wake of the Consensus, the syndrome was renamed Sleep-Related Hypermotor Epilepsy (SHE).

Objective:To assess the long-term outcome of sleep-related hypermotor epilepsy (SHE).Methods:We retrospectively reconstructed a representative cohort of patients diagnosed with SHE according to international diagnostic criteria, sleep-related seizures ≥75% and follow-up ≥5 years. Terminal remission (TR) was defined as a period of ≥5 consecutive years of seizure freedom at the last follow-up. We used Kaplan-Meier estimates to calculate the cumulative time-dependent probability of TR and to generate survival curves. Univariate and multivariate Cox regression analyses were performed.Results:We included 139 patients with a 16-year median follow-up (2,414 person-years). The mean age at onset was 13 ± 10 years. SHE was sporadic in 86% of cases and familial in 14%; 16% of patients had underlying brain abnormalities. Forty-five percent of patients had at least 1 seizure in wakefulness lifetime and 55% had seizures only in sleep (typical SHE). At the last assessment, 31 patients achieved TR (TR group, 22.3%), while 108 (NTR group, 77.7%) still had seizures or had been in remission for p = 0.028; p = 0.043). Absence of any underlying brain disorder (hazard ratio 4.21, 95% confidence interval 1.26–14.05, p = 0.020) and typical SHE (hazard ratio 2.76, 95% confidence interval 1.31–5.85, p = 0.008) were associated with TR.Conclusions:Our data show a poor prognosis of SHE after a long-term follow-up. Its outcome is primarily a function of the underlying etiology.

PURPOSE OF REVIEW The aim is to review sleep disturbances in different movement disorders, mainly Parkinson's disease, and highlight current concepts on merging the boundaries between movement disorders and dissociative states of being. RECENT FINDINGS Since the observation that rapid eye movement sleep behavior disorder (RBD) may be an early marker of neurodegeneration, many studies focused on this disorder for the opportunity to explore the pathogenetic mechanisms underlying movement disorder and future neuroprotective therapies. It is also increasingly evident that this disorder is a possible marker for incoming dementia and for a general worst prognosis. Mechanisms of excessive daytime sleepiness in Parkinson's disease are still to be clarified and, if the role of hypocretin neuron loss is still doubtful, attention is moving to the role of monoaminergic system disruption. The role of dopamine in circadian rhythm regulation is opening new scenarios, namely the disruption of clock genes expression. Finally, the close relationship between sleep and movement disorder is emerging also in primarly sleep disorders. SUMMARY Recent studies provided new insights into the links between sleep and movement disorder that may simplify the diagnostic process and shed light on the underlying pathophysiological mechanisms.

Aim: Although there have been frequent clinical reports about sleep disturbances in children with learning disabilities, no data are available about the prevalence of sleep disturbances in children with developmental dyslexia (DD). This study evaluated sleep disturbances in children with DD referred to a hospital clinic and compared their scores with healthy controls.Methods: We consecutively enrolled 147 children (66% male) aged 10.26 ± 2.63 years referred by clinical paediatricians to the Clinic for Child and Adolescent Neuropsychiatry at the Second University of Naples with DD and 766 children without DD (60% male) aged 10.49 ± 2.39 years recruited from schools in the same urban area. Sleep disturbances were assessed with the Sleep Disturbances Scale for Children (SDSC), which was filled out by the childrens’ main carers.Results: Compared to the controls, the children with DD showed significantly higher rates of above threshold scores on the total SDSC score (pConclusion: Sleep disorders were significantly more frequent in children with DD than in healthy controls. A possible relationship between dyslexia and sleep disorders may have relevant clinical implications.

Background: Patients with mood disorders show a high dependence of behavior on the molecular characteristics of the biological clock. CLOCK rs1801260 gene polymorphism influences circadian behavior in bipolar disorder (BD), with∗C carriers showing a delayed sleep onset and worse insomnia. Sleep phase delay and insomnia associate with suicide in the general population. Methods: We investigated the effects of rs1801260, and of exposure to stressful life events, on current suicidal ideation and history of suicide attempts in 87 depressed patients with BD. Results: rs1801260∗C carriers currently showed worse Hamilton Depression Rating Scale scores for suicide and worse ratings for depressive cognitive distortions. Previous history of attempted suicide associated with exposure to higher stressful events in the early life, with rs1801260∗C carriers showing a higher dependency of the modeled probability of attempting suicide on the severity of exposure to early stress. Discussion: CLOCK rs1801260 modulated the relationship between early stress, adult history of attempted suicide and current suicide ideation. Factors affecting the biological clock can influence "non-clock" core psychopathological features of mood disorders.

Objective: To compare distributions of body mass index (BMI) between individuals with different habitual sleep patterns. Methods: We performed cross-sectional analyses of 40,197 Swedish adults (64% women), who reported sleep duration and quality, weight, height, and possible confounding factors in 1997. Using quantile regression, we estimated associations between sleep patterns and selected percentiles of the distribution of BMI. Results: While the medians were similar, larger adjusted values of BMI were estimated in the upper part of the distribution among men and women with short sleep (≤5 h) compared with medium-length sleep (6-8 h). For example, in men, the 90th percentile of BMI was 0.80 kg/m2 (95% confidence interval: 0.17-1.43 kg/m2) higher among short sleepers. In women, long sleepers (≥9 h) also showed larger values in the upper part of the BMI distribution; the 90th percentile was 1.23 kg/m2 (0.42-2.04 kg/m2) higher than in medium-length sleepers. In male long sleepers, smaller values were estimated in the lower part of the BMI distribution; the 10th percentile was 0.84 kg/m2 lower (0.35-1.32 kg/m2) than in medium-length sleepers. The 90th percentile of BMI in women with poor-quality compared with good-quality sleep was larger by 0.82 kg/m2 (0.47-1.16 kg/m2); the 10th percentile was smaller by 0.17 kg/m2 (0.02-0.32 kg/m2). Conclusions: Short, long or poor-quality sleepers showed larger, or smaller, values at the tails of the BMI distribution, but similar medians. Hence, unfavorable sleep patterns and BMI were associated only in a subset of this study population.

Gender differences in brain structure and function may lead to differences in the clinical expression of neurological diseases, including Parkinson's disease (PD). Few studies reported gender-related differences in the burden of non-motor symptoms (NMS) in treated PD patients, but this matter has not been previously explored in drug-naïve PD patients. This study is to assess gender differences in the prevalence of NMS in a large sample of early, drug-naïve PD patients compared with age and sex-matched healthy controls. Two hundred early, drug-naïve PD patients and ninety-three age and sex-matched healthy controls were included in the study. Frequency of NMS was evaluated by means of the Non-Motor Symptoms Questionnaire. The difference in gender distribution of NMS was evaluated with the χ (2) exact test; multiple comparisons were corrected with the Benjamini-Hochberg method. Male PD patients complained of problems having sex and taste/smelling difficulties significantly more frequently than female PD patients. Furthermore, men with PD complained more frequently of dribbling, sadness/blues, loss of interest, anxiety, acting during dreams, and taste/smelling difficulties as compared to healthy control men, while female PD patients reported more frequently loss of interest and anxiety as compared with healthy control women. This study shows specific sex-related patterns of NMS in drug-naïve PD. In contrast with previous data, female PD patients did not present higher prevalence of mood symptoms as compared to male PD patients. Comparison with healthy controls showed that some NMS classically present in premotor and early stage of disease (i.e., acting out during dreams, taste/smelling difficulties) are more frequent in male than in female patients.

BACKGROUND: Impairment of sleep quality and quantity has been described in critically ill patients. Delirium, an organ dysfunction that affects outcome of the critically ill patients, is characterized by an acute onset of impaired cognitive function, visual hallucinations, delusions, and illusions. These symptoms resemble the hypnagogic hallucinations and wakeful dreams seen in patients with neurological degenerative disorders and suffering of disorders of rapid eye movement (REM) sleep. We assessed the characteristics of sleep disruption in a cohort of surgical critically ill patients examining the hypothesis that severe impairments of rapid eyes movement (REM) sleep are associated to delirium. METHODS: Surgical patients admitted to the intensive care units of the San G. Battista Hospital (University of Turin) were enrolled. Once weaning was initiated, sleep was recorded for one night utilizing standard polysomnography. Clinical status, laboratory data on admission, co-morbidities and duration of mechanical ventilation were recorded. Patients were a priori classified as having a "severe REM reduction" or "REM reduction" if REM was higher or lower than 6% of the total sleep time (TST), respectively. Occurrence of delirium during intensive care unit (ICU) stay was identified by CAM-ICU twice a day. Multivariate forward stepwise logistic regression analysis was performed with sleep ("severe REM reduction" vs. "REM reduction") as the a priori dependent factor. RESULTS: REM sleep amounted to 44 (16-72) minutes [11 (8-55) % of the TST] in 14 patients ("REM reduction") and to 2.5 (0-36) minutes [1 (0-6) % of the TST] in the remaining 15 patients ("severe REM reduction") (P = 0.0004). SAPS II on admission was higher in " severely REM deprived" then in "REM deprived" patients. Delirium was present in 11 patients (73.3%) of the patients with "severe REM reduction" and lasted for a median of 3 (0-11) days before sleep assessment, while only one patient having "REM reduction" developed delirium that lasted for 1 day. The factors independently associated with a higher risk of developing "severe REM reduction" were delirium and daily dosage of lorazepam. CONCLUSION: The present study shows that while all critically ill patients present a profound fragmentation of sleep with a high frequency of arousals and awakenings and a reduction of REM sleep, a percentage of patients present an extremely severe reduction of REM sleep. Delirium and daily dosage of lorazepam are the factors independently associated to extremely severe REM sleep reduction.

Alternating hemiplegia of childhood is a neurological disorder characterized by episodes of hemiplegia, various non-epileptic paroxysmal events and global neurological impairment. Characterization of the evolution and outcome into adulthood has not been sufficiently investigated. The goal of this study was to elucidate the natural history of alternating hemiplegia within a large cohort of 157 patients, as part of the European Network for Research on Alternating Hemiplegia project. A questionnaire was formulated to determine the severity of both paroxysmal and global neurological impairment and address progression of the disorder by allocating data to specific age epochs up to and over 24 years of age. Patients in early age groups were consistently present in subsequent later age groups and for each patient, data were collected for each corresponding age epoch. The study was based on predominantly retrospective and, for a period of 2 years, prospective data. At inclusion, patients were aged from 9 months to 52 years. The median age at diagnosis was 20 months. All patients experienced hemiplegic attacks; 86.5% reported episodes of bilateral weakness, 88% dystonic attacks, 53% epileptic seizures, 72% developed chorea and/or dystonia and 92% mental retardation. When data over the course of the illness were examined for the whole cohort, the severity of symptoms did not appear to change, with the exception of abnormal ocular movements and hypotonia that regressed, but did not disappear into adulthood (from 86 to 36% and 76 to 36%, respectively). No statistically significant correlation between a history of severe paroxysmal hemiplegic/dystonic episodes and a worse neurological outcome was identified. Seven patients died, some of whom experienced severe plegic attacks or epileptic seizures at the time of death. History of severe plegic/dystonic attacks was not found to be an aggravating factor for deceased patients. Our results provide evidence that the natural history of alternating hemiplegia is highly variable and unpredictable for individual patients. However, we did not find evidence to support a steadily progressive and degenerative course of the disorder when patients were analysed as a group. For a minority of patients, a risk of sudden death was associated with more severe neurological impairment. The European Network for Research on Alternating Hemiplegia Registry, validated by our study, includes all major neurological signs and symptoms of alternating hemiplegia and may thus be used as a precedent for the progressive inclusion and follow-up of patients as well as a reference for genetic studies and treatment trials.

Objectives: Our objectives were to test the hypothesis that, in the geriatric population, chronic airway obstruction is associated with a higher prevalence of sleep disturbances; to identify the main correlates of sleep disturbances, and to verify whether asthma and COPD patients have different patterns of sleep disturbances. Methods: The EPESE questionnaire was administered to 734 patients aged 65 years and over with asthma or chronic obstructive pulmonary disease (cases) and 1237 individuals of comparable age who were free of respiratory disease but not of other chronic conditions (controls). Four sleep disturbances were quantified: difficulty in falling asleep, nocturnal awakening, morning tiredness, and early awakening. Multidimensional assessment of demographic data, personal history, clinical, and functional status was performed. Independent correlates of sleep disturbances were identified by logistic regression analysis. Results: One or more sleep disturbances were reported by 445 cases and 697 controls (60.6% vs. 56.4%, ns). Morning tiredness and early awakenings were more prevalent among cases (38% vs. 27.8%, p

STUDY OBJECTIVES: Restless legs syndrome (RLS) prevalence estimates range from 0% to 52% in Parkinson disease (PD), but the causal relationship between the two disorders is still debated. The present study aims to evaluate RLS prevalence in de novo PD subjects, its incidence during the first 4 years from diagnosis, and possible relationships with clinical, laboratory, and neuroradiological data. METHODS: One hundred nine newly diagnosed, drug-naïve PD subjects were evaluated at the time of PD diagnosis, and after 2- and 4-years. RLS diagnosis was performed with the RLS Diagnostic Index at each visit. Motor features, additional non-motor symptoms (NMS), and concomitant dopaminergic and nondopaminergic treatments were also gathered. Moreover, at baseline, 65 subjects were randomly selected to undergo a FP-CIT SPECT to study dopamine transporter availability. RESULTS: RLS prevalence rose from 4.6% at baseline evaluation to 6.5% after 2 years and to 16.3% after 4 years (P = 0.007). A multinomial logistic stepwise regression model selected NMS Questionnaire items more likely to be associated with RLS at diagnosis (insomnia, OR = 15.555; P = 0.040) and with occurrence of RLS during follow-up (dizziness, OR = 1.153; P = 0.022; and daytime sleepiness; OR = 9.557; P = 0.001), as compared to patients without RLS. Older age was more likely associated to increased RLS occurrence during follow-up in a random effect logistic regression model (OR = 1.187; P = 0.036). A multinomial logistic stepwise model found increased dopaminergic transporter availability of affected caudate and putamen to be more likely associated with RLS presence at diagnosis (n = 5; OR = 75.711; P = 0.077), and RLS occurrence during follow-up (n = 16; OR = 12.004; P = 0.059), respectively, as compared to patients without RLS (n = 88). CONCLUSIONS: RLS is present since PD diagnosis, and increases in prevalence during the course of PD. PD subjects with RLS have higher age at PD onset, more preserved dopaminergic pathways, and worse sleep and cardiovascular disturbances.

Menopause in the female life cycle is a special period due to important hormonal, physical and psychological changes. Sleep disruption represents a common complaint for midlife and menopausal women, related to primary sleep disorders, including insomnia, sleep disordered breathing, restless legs syndrome (RLS), mood and anxiety disorder, other medical illness, hormonal-related vasomotor symptoms, and aging per se. Aims of our study were to evaluate the prevalence of sleep disorders in a sample of pre and post menopausal women, and to investigate the relationship between sleep and other medical disorders, and life habits. Among workers in the six participant centers, we enrolled 334 women, aged between 40 and 60 years, that completed a questionnaire that included screening on menarche, menstrual cycle, fertility, parity, menopause, life habits, personal medical and sleep history and related treatment, and self-administered scales for sleep quality (PSQI), excessive daytime sleepiness [Epworth Sleepiness Scale (ESS)], mood disorder [Beck Depression Inventory (BDI)], Berlin Questionnaire for sleep disordered breathing (SDB), IRLS diagnostic interview and Rating Scale. Menopausal and perimenopausal women showed an increased prevalence of poor sleep, high risk of SDB, and mood disorder; menopausal women also reported increased RLS severity. Mood disorder had a significant impact on night sleep measures and excessive daytime sleepiness, as well as on RLS severity, and had a greater prevalence in hypertensive women. Sleep disturbances are frequent in menopausal women. Their aetiology is unclear, but probably multifactorial, and many factors contribute to the sleep disruption. Our data suggest the importance of correctly investigate and address sleep problems associated with menopause, through sleep history, and a sleep study could be obtained if clinically warranted. Pharmacological and behavioural treatment strategies should then be aimed at improving sleep and life quality in perimenopausal and menopausal women.