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The aim of the study is analyze the results after Transanal Endoscopic Microsurgery (TEM) and Trans-Anal Minimally Invasive Surgery (TAMIS) for rectal cancer in terms of Quality of Life (QoL) and anorectal function.The authors have conducted a review of the literature through the PubMed database using the following keywords: "quality of life", "rectal cancer", "transanal surgery", "TEM" and "TAMIS".Six and five studies were included on TEM and TAMIS, respectively, for a total of 619 patients with a follow up of up to five years. QoL and anorectal function were evaluated by questionnaires and anorectal manometry in four out of eleven studies. At postoperative evaluation, patients reported temporary changes (from 3 weeks to 36 months) but no long-term effects on anorectal function and QoL. There were no differences in the postoperative functional outcome between surgery with rigid (TEM) or soft (TAMIS) devices. Some of the studies reported postoperative changes at manometry that were not clinically confirmed by the questionnaires.During TEM and TAMIS the risk of pelvic autonomic nerves damage, that may compromise urinary and sexual function and the risk of permanent sphincter damage with the need to perform a stoma, are very low.Quality of life and anorectal function after TEM or TAMIS for the treatment of rectal tumors are good with no postoperative sequelae at mid-term follow up.Quality of Life (QoL), Rectal cancer, Transanal surgery, Transanal Endoscopic Microsurgery (TEM), Trans-Anal Minimally Invasive Surgery (TAMIS).L’obiettivo della presente revisione della letteratura è quello di analizzare i risultati in termini di qualità di vita e funzione anorettale dopo Transanal Endoscopic Microsurgery (TEM) e Trans-Anal Minimally Invasive Surgery (TAMIS) nel trattamento dei tumori del retto. Gli autori hanno condotto una revisione della letteratura attraverso il database PubMed usando le seguenti parole chiave: “quality of life”, “rectal cancer”, “transanal surgery”, “TEM” e “TAMIS”.Sei e cinque studi, rispettivamente, sono stati inclusi riguardanti la TEM a la TAMIS per un totale di 619 pazienti con un follow up fino a 5 anni. La qualità di vita e la funzione anorettale sono state valutate mediante questionari e manometria anorettale in quattro studi su undici. Nella valutazione postoperatoria della funzione anorettale e della qualità di vita i pazienti hanno riportato modificazioni temporanee (da 3 settimane fino a 36 mesi) ma non effetti a lungo termine. Non ci sono state differenze nei risultati funzionali postoperatori tra la chirurgia con piattaforma rigida (TEM) o morbida (TAMIS). Alcuni studi riportano qualche alterazione alla manometria postoperatoria che comunque non viene confermata dai questionari.Durante la TEM e la TAMIS, il rischio di danno dei nervi pelvici autonomi, che può compromettere le funzioni urinarie e sessuali, e il rischio di danni allo sfintere con la necessità di confezionare una stomia, sono molto bassi.La qualità di vita e la funzione anorettale dopo TEM e TAMIS per il trattamento dei tumori del retto sono buoni, senza sequele postoperatorie ad un follow up a medio termine.

Psychiatric events are thought to be more frequent in people with epileptic seizures than in the general population. However, inter-ictal psychiatric events attributable to epilepsy remain controversial. The aim of the present study was to evaluate the occurrence of psychiatric events in a population of fairly unselected patients with epilepsy and in the general population, and the correlation between psychiatric complaints and selected demographic and disease characteristics. The survey was part of a multicentre prospective cohort study of everyday life risks conducted in eight European countries and comparing referral children and adults with epilepsy referred to secondary/tertiary centers to age- and sex-matched non-epileptic controls. Nine hundred and fifty-one patients with epilepsy and 909 controls were studied. Each patient and his/her control received a diary to record any accident or illness, with severity, circumstances, causes, consequences, and (for the cases) the possible relation to a seizure. The follow-up period ranged between 1 and 2 years. Fifty-eight psychiatric events occurred in 25 patients (2.6%) and 88 in 19 controls (2.1%). Housewives (9.3%) and unemployed persons (4.1%) were mostly affected. No correlation was found between psychiatric events, demographic and disease characteristics. Our results suggest that people with epilepsy if unselected are not at higher risk for psychiatric disorders than the general population. © 2007 British Epilepsy Association.

To assess whether risk factors for Parkinson disease and dementia with Lewy bodies increase rate of defined neurodegenerative disease in idiopathic rapid eye movement (REM) sleep behavior disorder (RBD).Twelve centers administered a detailed questionnaire assessing risk factors for neurodegenerative synucleinopathy to patients with idiopathic RBD. Variables included demographics, lifestyle factors, pesticide exposures, occupation, comorbid conditions, medication use, family history, and autonomic/motor symptoms. After 4 years of follow-up, patients were assessed for dementia or parkinsonism. Disease risk was assessed with Kaplan-Meier analysis, and epidemiologic variables were compared between convertors and those still idiopathic using logistic regression.Of 305 patients, follow-up information was available for 279, of whom 93 (33.3%) developed defined neurodegenerative disease. Disease risk was 25% at 3 years and 41% after 5 years. Patients who converted were older (difference = 4.5 years, p 0.001), with similar sex distribution. Neither caffeine, smoking, nor alcohol exposure predicted conversion. Although occupation was similar between groups, those who converted had a lower likelihood of pesticide exposure (occupational insecticide = 2.3% vs 9.0%). Convertors were more likely to report family history of dementia (odds ratio [OR] = 2.09), without significant differences in Parkinson disease or sleep disorders. Medication exposures and medical history were similar between groups. Autonomic and motor symptoms were more common among those who converted. Risk factors for primary dementia and parkinsonism were generally similar, except for a notably higher clonazepam use in dementia convertors (OR = 2.6).Patients with idiopathic RBD are at very high risk of neurodegenerative synucleinopathy. Risk factor profiles between convertors and nonconvertors have both important commonalities and differences.

Purpose: To investigate the risk of accidents in a cohort of patients with epilepsy and in matched nonepilepsy controls. by type, circumstances, and complications. Methods: A total of 95 1 children and adults with idiopathic, cryptogenic, or remote symptomatic epilepsy and 904 matched controls seen in secondary and tertiary centers in eight European Countries (England. Estonia, Germany, Italy, the Netherlands, Portugal. Russia. and Slovenia) were followed Lip prospectively for 17,484 and 17.206 person-months and asked to report any accident requiring medical attention. its site, and complications. Risk assessment was done by using actuarial methods, relative risks (RRs). and 95% confidence intervals (CIs). Results: During the study period, 199 (21%) patients and 123 (14%) controls reported all accident (p < 0.0001); 24% were seizure related. The Cumulative probability of accidents at 12 and 24 months was 17 and 27% in the cases and 12 and 17% in the controls. The risk was highest for concussions (RR, 2.6; 95% Cl, 1.2-5.8), abrasions (RR, 2.1; 95% Cl, 1.1-4.0), and Wounds (RR, 1.9; Cl, 1.2-3.1). Domestic accidents prevailed in both groups, followed by street and work accidents, and were more common among cases. Compared with controls, patients with epilepsy reported more hospitalization, complications, and medical action. Disease characteristics associated with an increased risk of accidents included generalized epilepsy (conclusions), active epilepsy, and at least monthly seizures (abrasions). Most risks decreased, becoming nonsignificant after excluding, seizure-related events. Conclusions: Patients with epilepsy are at higher risk of accidents and their complications. However, the risk was substantially lower after exclusion of seizure-related events

Summary: Purpose: To assess the risk of illnesses and accidents in patients with epilepsy and to evaluate the proportion of those risks attributable to epilepsy. Methods: Nine hundred fifty-one referral patients with idiopathic, cryptogenic, or remote symptomatic epilepsy and 909 matched controls (relatives or friends) were followed up prospectively for 1–2 years in eight European countries (Italy, Germany, Holland, England, Portugal, Russia, Estonia, and Slovenia). Each patient and control received a diary to keep notes regarding any illness or accident. Patients with epilepsy specifically recorded relations with seizures. Results: Six hundred forty-four patients recorded 2,491 illnesses compared with 1,665 illnesses in 508 controls. The cumulative probability of illness in patients was 49% by 12 months and 86% by 24 months (controls, 39 and 75%; p < 0.0001). One hundred ninety-nine patients and 124 controls had 270 and 140 accidents, respectively. The cumulative probability of accident in the cases was 17 and 27% by 12 and 24 months (controls, 12 and 17%; p < 0.0001). The chance of two or more illnesses or accidents was modestly but significantly greater in the patients. Illnesses and accidents were mostly trivial. Thirty percent of illnesses and 24% of accidents were seizure related. When illnesses and accidents related to seizures were excluded, the chance of illnesses and accidents was fairly similar in the two groups. Conclusions: Patients with idiopathic, cryptogenic, or remote symptomatic epilepsy have a moderately higher risk of illnesses and accidents than do the general population. With few exceptions, the events are trivial. When seizure-related events are excluded, patients with epilepsy are not at any significantly higher risk of illnesses and accidents.

We assessed the validity of an Italian language version of the Epworth sleepiness scale (ESS). The translated ESS was compared to the multiple sleep latency test (MSLT), considered the gold standard for the diagnosis of excessive daytime sleepiness (EDS). Within the context of a multicentric national study on narcolepsy (Gruppo Italiano Narcolessia Studio Epidemiologico Nazionale, GINSEN) involving 17 Italian sleep centres, we compared the two diagnostic tests on 91 prospectively recruited subjects with suspected EDS (34 with narcolepsy, 16 with obstructive sleep apnea syndrome, 19 with idiopathic hypersomnia, and 22 with other sleep, neurologic or psychiatric disorders). ESS scores were inversely correlated with mean sleep latency values, as measured with MSLT (rho = −0.31, p

Sleep has been shown to be a global phenomenon in which the presence of local processes of both activation and deactivation are finely orchestrated. Dysfunctional and independent action of the systems involved in non-rapid eye movement (NREM) sleep and wakefulness is deemed to be at the basis of arousal parasomnias. We show, in a patient with confusional arousals, persistence of sleep in the hippocampal and frontal associative cortices in contrast to the presence of awakening in the motor, cingulate, insular, amygdalar and temporopolar cortices. The clinical features of the confusional arousals in this patient are highly consistent with a dysfunctional coexistence of local cortical arousal and local cortical sleep.

Summary Background Continuous administration of a dopamine agonist could be used to treat patients with restless legs syndrome. Our aim was to investigate the efficacy of transdermal rotigotine in the treatment of idiopathic restless legs syndrome. Methods In this randomised, double-blind, placebo-controlled trial, 458 patients with moderate-to-severe idiopathic restless legs syndrome (average baseline International Restless Legs Syndrome Study Group severity rating scale [IRLS] sum score of 28·1) were randomly assigned to receive transdermal rotigotine 1 mg over 24 h (n=115), 2 mg over 24 h (n=112), or 3 mg over 24 h (n=114), or to receive placebo (n=117). Study medication was delivered via patches, applied once a day for 6 months. Randomisation was done with a computer-generated randomisation list, stratified by centre. Primary efficacy outcomes were absolute change from baseline to end of maintenance in IRLS sum score and in the clinical global impressions (CGI) item 1 score, assessed by analysis of covariance in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00136045. Findings Efficacy analyses were done on 112 patients in the 1 mg group, 109 in the 2 mg group, 112 in the 3 mg group, and 114 in the placebo group. Mean change in IRLS sum score from baseline at the end of the maintenance phase was −13·7 (SE 0·9) in the 1 mg group, −16·2 (0·9) in the 2 mg group, −16·8 (0·9) in the 3 mg group, and −8·6 (0·9) in the placebo group (p vs placebo with each dose). Mean change in CGI item 1 score from baseline at the end of the maintenance phase was −2·09 (0·14) in the 1 mg group, −2·41 (0·14) in the 2 mg group, −2·55 (0·14) in the 3 mg group, and −1·34 (0·14) in the placebo group (p vs placebo with each dose). Skin reactions, mostly mild or moderate, were seen in 145 (43%) of 341 patients who received rotigotine and in two (2%) of 117 who received placebo. Ten patients had serious adverse event that were deemed to be related to rotigotine: elevation of liver enzymes (one patient), worsening of tinnitus (one patient), non-response to anticoagulation (one patient), electrocardiogram changes (one patient), and application-site reactions (six patients). No admissions to hospital were needed for the application-site reactions, and they all resolved within a short time of patch removal without any other therapeutic intervention. The rate of typical dopaminergic side-effects in patients who received rotigotine was low; no signs of augmentation were noted. Interpretation 24 h transdermal delivery of low-dose rotigotine could be used to relieve the night-time and daytime symptoms of restless legs syndrome. Funding Schwarz Biosciences.

BACKGROUND: The effect of carotid endarterectomy in lowering the risk of stroke ipsilateral to severe atherosclerotic carotid-artery stenosis is offset by complications during or soon after surgery. We compared surgery under general anaesthesia with that under local anaesthesia because prediction and avoidance of perioperative strokes might be easier under local anaesthesia than under general anaesthesia. METHODS: We undertook a parallel group, multicentre, randomised controlled trial of 3526 patients with symptomatic or asymptomatic carotid stenosis from 95 centres in 24 countries. Participants were randomly assigned to surgery under general (n=1753) or local (n=1773) anaesthesia between June, 1999 and October, 2007. The primary outcome was the proportion of patients with stroke (including retinal infarction), myocardial infarction, or death between randomisation and 30 days after surgery. Analysis was by intention to treat. The trial is registered with Current Control Trials number ISRCTN00525237. FINDINGS: A primary outcome occurred in 84 (4.8%) patients assigned to surgery under general anaesthesia and 80 (4.5%) of those assigned to surgery under local anaesthesia; three events per 1000 treated were prevented with local anaesthesia (95% CI -11 to 17; risk ratio [RR] 0.94 [95% CI 0.70 to 1.27]). The two groups did not significantly differ for quality of life, length of hospital stay, or the primary outcome in the prespecified subgroups of age, contralateral carotid occlusion, and baseline surgical risk. INTERPRETATION: We have not shown a definite difference in outcomes between general and local anaesthesia for carotid surgery. The anaesthetist and surgeon, in consultation with the patient, should decide which anaesthetic technique to use on an individual basis. FUNDING: The Health Foundation (UK) and European Society of Vascular Surgery.

Background and purpose To carry out an observational epidemiological survey (Studio Morfeo), to determine: (1) the frequency of insomnia in a large Italian population presenting directly to the general physician (GP); (2) the impact of insomnia on the quality of life, on the use of health-care resources and on co-morbidity. Patients and methods The study was accomplished by GPs, trained by sleep specialists accredited by the Italian Association of Sleep Medicine. Only patients spontaneously presenting to their GP for medical problems were surveyed. Each GP was asked to enroll at least five patients across a routine week of medical activity including both morning and afternoon clinics. The first patient of each weekday was recruited after obtaining written consent. According to the responses to the sleep-related questions, patients were classified into three categories: (1) no insomnia, (2) level 1 insomnia with absence of day-time dysfunction and (3) level 2 insomnia with presence of day-time dysfunction. Results A total of 3284 patients were enrolled by 738 GPs in this Italian survey. Insomnia was reported by 64% of all interviewed patients, with 20% classified as level 1 and 44% as level 2. Logistic analysis indicated that depression (odds ratio, 2.70), involvement of >1 organ systems (odds ratio, 1.24), female gender (odds ratio, 1.19), unemployment (odds ratio, 1.18), low education (odds ratio, 1.18) and increasing age (odds ratio, 1.02) were the major risk factors for insomnia. Conclusions Our findings indicate that insomnia is a frequent disturbance in the Italian primary care population, is associated with high risk of co-morbid conditions, and results in increased use of health-care resources.

Major vascular injuries during laparoscopic procedures are rare but potentially life-threatening if not promptly diagnosed and treated. We report a case in which the placement of a trocar during a laparoscopic cholecystectomy caused damage to the right renal artery and led to the development of a pseudoaneurysm. The pseudoaneurysm of the right renal artery then eroded into the inferior vena cava resulting in an arteriovenous fistula that eventually caused right renal failure, systolic and diastolic hypertension, and congestive heart failure. The recognition of this complication was delayed and the patient was referred for surgery 5 years after the laparoscopic procedure. He then successfully underwent right nephrectomy, resection of the pseudoaneurysm, and closure of the fistula.

We report the case of a 34-year old patient who first complained of fever, confusion and transient ophthalmoplegia and then developed akinetic mutism, frontal lobe, pyramidal tract and extrapyramidal signs. Clinical and electrophysiological data support a diagnosis of encephalitis lethargica. Magnetic resonance imaging showed hyperintensive lesions in various brain regions. The patient responded to corticosteroid treatment. Two years after the onset of the first clinical signs he had recovered completely and today, after 5 years, he shows no sign of disease.

Study objectives: To verify the existence of a symptomatic form of restless legs syndrome (RLS) secondary to multiple sclerosis (MS) and to identify possible associated risk factors. Design: Prospective, multicenter, case-control epidemiologic survey. Settings: Twenty sleep centers certified by the Italian Association of Sleep Medicine. Patients: Eight hundred and sixty-one patients affected by MS and 649 control subjects. Interventions: N/A. Measures and results: Data regarding demographic and clinical factors, presence and severity of RLS, the results of hematologic tests, and visual analysis of cerebrospinal magnetic resonance imaging studies were collected. The prevalence of RLS was 19% in MS and 4.2% in control subjects, with a risk to be affected by RLS of 5.4 (95%confidence interval: 3.56-8.26) times greater for patients with MS than for control subjects. In patients with MS, the following risk factors for RLS were significant: older age; longer MS duration; the primary progressive MS form; higher global, pyramidal, and sensory disability; and the presence of leg jerks before sleep onset. Patients with MS and RLS more often had sleep complaints and a higher intake of hypnotic medications than patients with MS without RLS. RLS associated with MS was more severe than that of control subjects. Conclusions: RLS is significantly associated with MS, especially in patients with severe pyramidal and sensory disability. These results strengthen the idea that the inflammatory damage correlated with MS may induce a secondary form of RLS. As it does in idiopathic cases, RLS has a significant impact on sleep quality in patients with MS; therefore, it should be always searched for, particularly in the presence of insomnia unresponsive to treatment with common hypnotic drugs.

International audience; Idiopathic REM sleep behaviour disorder (iRBD) is a powerful early sign of Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. This provides an unprecedented opportunity to directly observe prodromal neurodegenerative states, and potentially intervene with neuroprotective therapy. For future neuroprotective trials, it is essential to accurately estimate phenoconversion rate and identify potential predictors of phenoconversion. This study assessed the neurodegenerative disease risk and predictors of neurodegeneration in a large multicentre cohort of iRBD. We combined prospective follow-up data from 24 centres of the International RBD Study Group. At baseline, patients with polysomnographically-confirmed iRBD without parkinsonism or dementia underwent sleep, motor, cognitive, autonomic and special sensory testing. Patients were then prospectively followed, during which risk of dementia and parkinsonsim were assessed. The risk of dementia and parkinsonism was estimated with Kaplan-Meier analysis. Predictors of phenoconversion were assessed with Cox proportional hazards analysis, adjusting for age, sex, and centre. Sample size estimates for disease-modifying trials were calculated using a time-to-event analysis. Overall, 1280 patients were recruited. The average age was 66.3 ± 8.4 and 82.5% were male. Average follow-up was 4.6 years (range = 1-19 years). The overall conversion rate from iRBD to an overt neurodegenerative syndrome was 6.3% per year, with 73.5% converting after 12-year follow-up. The rate of phenoconversion was significantly increased with abnormal quantitative motor testing [hazard ratio (HR) = 3.16], objective motor examination (HR = 3.03), olfactory deficit (HR = 2.62), mild cognitive impairment (HR = 1.91-2.37), erectile dysfunction (HR = 2.13), motor symptoms (HR = 2.11), an abnormal DAT scan (HR = 1.98), colour vision abnormalities (HR = 1.69), constipation (HR = 1.67), REM atonia loss (HR = 1.54), and age (HR = 1.54). There was no significant predictive value of sex, daytime somnolence, insomnia, restless legs syndrome, sleep apnoea, urinary dysfunction, orthostatic symptoms, depression, anxiety, or hyperechogenicity on substantia nigra ultrasound. Among predictive markers, only cognitive variables were different at baseline between those converting to primary dementia versus parkinsonism. Sample size estimates for definitive neuroprotective trials ranged from 142 to 366 patients per arm. This large multicentre study documents the high phenoconversion rate from iRBD to an overt neurodegenerative syndrome. Our findings provide estimates of the relative predictive value of prodromal markers, which can be used to stratify patients for neuroprotective trials.

Objective The COVID-19 pandemic has strongly affected daily habits and psychological wellbeing, and many studies point to large modifications in several sleep and sleep-related domains. Nevertheless, pre-sleep arousal during the pandemic has been substantially overlooked. Since hyperarousal represents one of the main factors for the development and the perpetuation of chronic insomnia disorder, the assessment of variables associated with high levels of pre-sleep arousal during the pandemic is clinically relevant. The study aimed to assess the prevalence and predictors of perceived sleep quality and pre-sleep arousal in an Italian sample during the COVID-19 lockdown. Methods We used an online survey to collect self-reported sociodemographic, environmental, clinical, sleep, and sleep-related data. Our final sample included 761 participants. Results Beyond a high frequency of poor sleep quality, depressive and stress symptoms, our results show that almost half of the sample suffered from clinically relevant levels of at least one component (ie, cognitive, somatic) of pre-sleep arousal. Subjects with greater pre-sleep arousal exhibited poorer sleep quality. Also, sleep quality was strongly associated with somatic and cognitive pre-sleep arousal. Regarding the predictors of sleep and sleep-related measures, depressive and event-related stress symptoms were the main factors associated with both poor sleep quality and pre-sleep arousal components. Moreover, specific sociodemographic and environmental variables were uniquely related to sleep quality, cognitive or somatic pre-sleep arousal. Conclusions These findings suggest that the assessment of specific sleep-related factors (ie, pre-sleep arousal), together with more global measures of sleep quality, may be crucial to depict the complex impact of the pandemic on sleep, and to help prevent and counteract the spread of insomnia symptoms.

BACKGROUND AND PURPOSE: Some epilepsy syndromes (sleep-related epilepsies, SREs) have a strong link with sleep. Comorbid sleep disorders are common in patients with SRE and can exert a negative impact on seizure control and quality of life. Our purpose was to define the standard procedures for the diagnostic pathway of patients with possible SRE (scenario 1) and the general management of patients with SRE and comorbidity with sleep disorders (scenario 2).METHODS: The project was conducted under the auspices of the European Academy of Neurology, the European Sleep Research Society and the International League Against Epilepsy Europe. The framework entailed the following phases: conception of the clinical scenarios; literature review; statements regarding the standard procedures. For the literature search a stepwise approach starting from systematic reviews to primary studies was applied. Published studies were identified from the National Library of Medicine's MEDLINE database and Cochrane Library.RESULTS: Scenario 1: Despite a low quality of evidence, recommendations on anamnestic evaluation and tools for capturing the event at home or in the laboratory are provided for specific SREs. Scenario 2: Early diagnosis and treatment of sleep disorders (especially respiratory disorders) in patients with SRE are likely to be beneficial for seizure control.CONCLUSIONS: Definitive procedures for evaluating patients with SRE are lacking. Advice is provided that could be of help for standardizing and improving the diagnostic approach of specific SREs. The importance of identifying and treating specific sleep disorders for the management and outcome of patients with SRE is underlined.

Disorders of arousals are common sleep disorders characterized by complex motor behaviours that arise episodically out of slow-wave sleep. Psychological distress has long been associated with disorders of arousal, but this link remains controversial, especially in children andadolescents. The aim of this multi-centre study wasto characterize behavioural and emotional problems in a sample of children/adolescents with disorders of arousal, and toexplore their relationship with the severity of nocturnal episodes. The parents of 41 children/adolescents with a diagnosis of disorders of arousal (11.5±3.3years old, 61% males)and of a group of 41 age- and gender-matched control participants filled in the Child Behavior Checklist, along with the Sleep Disturbance Scale for Children and the Paris Arousal Disorders Severity Scale. Multilevel t-tests revealedsignificantly higher total scores and sub-scores of the Child Behavior Checklist for the patient group compared with the control group. Thirty-four percent of the patients obtained pathological total scores, and 12% of them borderline scores. The severity of emotional/behavioural problems in the patient group was positively correlated with the severity of the nocturnal episodes. Interestingly, children/adolescents with disorders of arousal also obtained higher excessive daytime sleepiness and insomnia symptoms sub-scores at the Sleep Disturbance Scale for Children. These results confirmed the hypothesis that behavioural/emotional problems are surprisingly common in children/adolescents with disorders of arousal. Further studies are warranted to investigate the causal relationship between pathological manifestations, subtler sleep abnormalities, and diurnal emotional/behavioural problems in children/adolescents with disorders of arousal.

STUDY OBJECTIVES: Narcolepsy type 1 (NT1) is a chronic neurological disorder typically arising during adolescence and young adulthood. Recent studies demonstrated that NT1 presents with age-specific features, especially in children. With this study we aimed to describe and to compare the clinical pictures of NT1 in different age groups. METHODS: In this cross-sectional, multicenter study, 106 untreated patients with NT1 enrolled at the time of diagnosis underwent clinical evaluation, a semistructured interview (including the Epworth Sleepiness Scale), nocturnal video-polysomnography, and the Multiple Sleep Latency Test. Patients were enrolled in order to establish 5 age-balanced groups (childhood, adolescence, adulthood, middle age, and senior). RESULTS: The Epworth Sleepiness Scale score showed a significant increase with age, while self-reported diurnal total sleep time was lower in older and young adults, with the latter also complaining of automatic behaviors in more than 90% of patients. Children reported the cataplexy attacks to be more frequent (> 1/d in 95% of patients). “Recalling an emotional event,” “meeting someone unexpectedly,” “stress,” and “anger” were more frequently reported in adult and older adult patients as possible triggers of cataplexy. Neurophysiological data showed a higher number of sleep-onset rapid eye movement periods on the Multiple Sleep Latency Test in adolescent compared to senior patients and an age-progressive decline in sleep efficiency. CONCLUSIONS: Daytime sleepiness, cataplexy features and triggers, and nocturnal sleep structure showed age-related difference in patients with NT1; this variability may contribute to diagnostic delay and misdiagnosis. CITATION: Lividini A, Pizza F, Filardi M, et al. Narcolepsy type 1 features across the life span: age impact on clinical and polysomnographic phenotype. J Clin Sleep Med. 2021;17(7):1363–1370.

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.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.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, p0.001), 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).Smoking, head injury, pesticide exposure, and farming are potential risk factors for idiopathic REM sleep behavior disorder.

Objective: This controlled study investigated associations between comorbidity and medication in patients with polysomnographically confirmed idiopathic REM sleep behavior disorder (iRBD), using a large multicenter clinic-based cohort. Methods: Data of a self-administered questionnaire on comorbidity and medication use of 318 patients with iRBD and 318 matched controls were analyzed. Comparisons between cases and controls were made using logistic regression analysis. Results: Patients with iRBD were more likely to report depression (odds ratio [OR] 2.0, 95% confidence interval [CI] 1.3–2.9) and concomitant antidepressant use (OR 2.2, 95% CI 1.4–3.6). Subanalysis of antidepressant agents revealed that the increased use of antidepressants in iRBD was due to selective serotoninergic reuptake inhibitors (OR 3.6, 95% CI 1.8–7.0) and not due to other antidepressant classes. Patients with iRBD reported more lifetime antidepressant use than comorbid depression (antidepressant use: OR 1.9, 95% CI 1.1–3.3; depression: OR 1.6, 95% CI 1.0–2.5). Patients with iRBD reported more ischemic heart disease (OR 1.9, 95% CI 1.1–3.1). This association did not change substantially when adjusting for cardiovascular risk factors (OR 2.3, 95% CI 1.3–3.9). The use of inhaled glucocorticoids was higher in patients with iRBD compared to controls (OR 5.3, 95% CI 1.8–15.8), likely reflecting the higher smoking rate in iRBD (smoking: OR 15.3, 95% CI 2.0–118.8; nonsmoking: OR 2.4, 95% CI 0.4–13.2) and consequent pulmonary disease. Conclusions: This large study confirms the association between comorbid depression and antidepressant use in iRBD. In addition, there was an unexpected association of iRBD with ischemic heart disease that was not explained by cardiovascular risk factors.

Patients with idiopathic REM sleep behavior disorder (iRBD) are at very high risk of developing neurodegenerative synucleinopathies, which are disorders with prominent autonomic dysfunction. Several studies have documented autonomic dysfunction in iRBD, but large-scale assessment of autonomic symptoms has never been systematically performed. Patients with polysomnography-confirmed iRBD (318 cases) and controls (137 healthy volunteers and 181 sleep center controls with sleep diagnoses other than RBD) were recruited from 13 neurological centers in 10 countries from 2008 to 2011. A validated scale to study the disorders of the autonomic nervous system in Parkinson's disease (PD) patients, the SCOPA-AUT, was administered to all the patients and controls. The SCOPA-AUT consists of 25 items assessing the following domains: gastrointestinal, urinary, cardiovascular, thermoregulatory, pupillomotor, and sexual dysfunction. Our results show that compared to control subjects with a similar overall age and sex distribution, patients with iRBD experience significantly more problems with gastrointestinal, urinary, and cardiovascular functioning. The most prominent differences in severity of autonomic symptoms between our iRBD patients and controls emerged in the gastrointestinal domain. Interestingly, it has been reported that an altered gastrointestinal motility can predate the motor phase of PD. The cardiovascular domain SCOPA-AUT score in our study in iRBD patients was intermediate with respect to the scores reported in PD patients by other authors. Our findings underline the importance of collecting data on autonomic symptoms in iRBD. These data may be used in prospective studies for evaluating the risk of developing neurodegenerative disorders.

Objective: To compare the frequency of proxy-reported REM sleep behavior disorder (RBD) among relatives of patients with polysomnogram-diagnosed idiopathic RBD (iRBD) in comparison to controls using a large multicenter clinic-based cohort. Methods: A total of 316 patients with polysomnography-confirmed iRBD were recruited from 12 RBD study group centers, along with 316 controls matched on sex and age group. All subjects completed a self-administered questionnaire that collected proxy-reported information on family history of tremor, gait trouble, balance trouble, Parkinson disease, memory loss, and Alzheimer disease. The questionnaire also included a single question that asked about possible symptoms of RBD among first-degree relatives (siblings, parents, and children). Results: A positive family history of dream enactment was reported in 13.8% of iRBD cases compared to 4.8% of controls (odds ratio [OR] = 3.9, 95% confidence interval [CI] 2.0–7.7). ORs were increased for both siblings (OR = 6.1, 95% CI 2.1–18.1) and parents (OR = 3.2, 95% CI 1.4–7.8). We found no significant difference in sex, current age (65.3 ± 10.2 vs 66.9 ± 10.2 years), or age at self-reported RBD onset (55.2 ± 11.7 vs 56.6 ± 15.1 years) in possible familial vs sporadic iRBD. No differences were found in family history of tremor, walking and balance troubles, Parkinson disease, memory loss, or Alzheimer disease. Conclusion: We found increased odds of proxy-reported family history of presumed RBD among individuals with confirmed iRBD. This suggests the possibility of a genetic contribution to RBD.