Sleep and sleep disorders during pregnancy and postpartum: The Life-ON study.

OBJECTIVE: to prospectively assess sleep and sleep disorders during pregnancy and postpartum in a large cohort of women. METHODS: multicenter prospective Life-ON study, recruiting consecutive pregnant women at a gestational age between 10 and 15 weeks, from the local gynecological departments. The study included home polysomnography performed between the 23rd and 25th week of pregnancy and sleep-related questionnaires at 9 points in time during pregnancy and 6 months postpartum. RESULTS: 439 pregnant women (mean age 33.7 ± 4.2 yrs) were enrolled. Poor quality of sleep was reported by 34% of women in the first trimester of pregnancy, by 46% of women in the third trimester, and by as many as 71% of women in the first month after delivery. A similar trend was seen for insomnia. Excessive daytime sleepiness peaked in the first trimester (30% of women), and decreased in the third trimester, to 22% of women. Prevalence of restless legs syndrome was 25%, with a peak in the third trimester of pregnancy. Polysomnographic data, available for 353 women, revealed that 24% of women slept less than 6 h, and 30.6% of women had a sleep efficiency below 80%. Sleep-disordered breathing (RDI≥5) had a prevalence of 4.2% and correlated positively with BMI. CONCLUSIONS: The Life-ON study provides the largest polysomnographic dataset coupled with longitudinal subjective assessments of sleep quality in pregnant women to date. Sleep disorders are highly frequent and distributed differently during pregnancy and postpartum. Routine assessment of sleep disturbances in the perinatal period is necessary to improve early detection and clinical management.

CAR t-cell therapy in BOlogNa-NEUrotoxicity TReatment and Assessment in Lymphoma (CARBON-NEUTRAL): proposed protocol and results from an Italian study.

OBJECTIVE: To investigate neurotoxicity clinical and instrumental features, incidence, risk factors, and early and long-term prognosis in lymphoma patients who received CAR T-cell therapy. METHODS: In this prospective study, consecutive refractory B-cell non-Hodgkin lymphoma patients who received CAR T-cell therapy were included. Patients were comprehensively evaluated (neurological examination, EEG, brain MRI, and neuropsychological test) before and after (two and twelve months) CAR T-cells. From the day of CAR T-cells infusion, patients underwent daily neurological examinations to monitor the development of neurotoxicity. RESULTS: Forty-six patients were included in the study. The median age was 56.5 years, and 13 (28%) were females. Seventeen patients (37%) developed neurotoxicity, characterized by encephalopathy frequently associated with language disturbances (65%) and frontal lobe dysfunction (65%). EEG and brain FDG-PET findings also supported a predominant frontal lobe involvement. The median time at onset and duration were five and eight days, respectively. Baseline EEG abnormalities predicted ICANS development in the multivariable analysis (OR 4.771; CI 1.081-21.048; p = 0.039). Notably, CRS was invariably present before or concomitant with neurotoxicity, and all patients who exhibited severe CRS (grade ≥ 3) developed neurotoxicity. Serum inflammatory markers were significantly higher in patients who developed neurotoxicity. A complete neurological resolution following corticosteroids and anti-cytokines monoclonal antibodies was reached in all patients treated, except for one patient developing a fatal fulminant cerebral edema. All surviving patients completed the 1-year follow-up, and no long-term neurotoxicity was observed. CONCLUSIONS: In the first prospective Italian real-life study, we presented novel clinical and investigative insights into ICANS diagnosis, predictive factors, and prognosis.

Violent and Complex Behaviors and Non-Restorative Sleep Are the Main Features of Disorders of Arousal in Adulthood: Real Picture or a More Severe Phenotype?

Disorders of arousal (DoA) are NREM parasomnias characterized by motor and emotional behaviors emerging from incomplete arousals from deep sleep. DoA are largely present in pediatric populations, a period during which they are labeled as self-limited manifestations. However, an extensive literature has shown that DoA can persist in adulthood, with different characteristics from childhood DoA. Adult DoA patients usually report excessive daily sleepiness, sleep-related violence during DoA episodes or potentially harmful behaviors, which are rare in childhood. The semeiological features of DoA episodes in adulthood may complicate differential diagnoses with other motor manifestations during sleep, in particular sleep-related hypermotor epilepsy. However, it cannot be excluded that adults with DoA attending sleep centers constitute a more severe phenotype, thus not being representative of adult DoA in the general population. Video-polysomnographic studies of DoA document a spectrum of motor patterns of different complexities, the simplest of which may often go unnoticed. Despite the different complexities of the episodes, neurophysiologic studies showed the co-existence of deep sleep and wakefulness during DoA episodes or even before their onset. These aspects make DoA an ideal model to investigate the mechanisms regulating local sleep, sleep arousal and cognitive functions including spatial and temporal orientation, attention or memory.

Influence of chronotype on the incidence and severity of perinatal depression in the "Life-ON" study.

BACKGROUND: Perinatal depression (PND) is a severe complication of pregnancy, but there are no established risk factors predicting the disease. Evening chronotype has been associated with unhealthy lifestyle habits and adverse outcomes during pregnancy. In this study, we aimed to clarify whether chronotype can predict symptoms and/or occurrence of PND. METHODS: Two hundred ninety-nine women were followed-up from the first trimester of pregnancy until 6 months postpartum. Chronotype was assessed at baseline using the MEQ, while mood was repeatedly assessed by depression rating scales (EPDS, HDRS, MADRS). The influence of time and chronotype on EPDS, HDRS and MADRS, was estimated by constructing multilevel linear mixed regression models. A Cox proportional-hazard regression model was built to evaluate the association between chronotype and incidence of depression. RESULTS: Chronotype modulated PND symptom severity depending on time of assessment, with evening chronotypes having a higher risk for developing PND symptoms, as assessed by EPDS, at postpartum visits V4 (5-12 days) and V5 (19-26 days). These also had less healthy lifestyle habits and were more likely to suffer from gestational diabetes mellitus and undergo cesarean delivery as compared to other chronotypes. LIMITATIONS: Only a minority of women were classified as evening chronotypes. The long follow-up phase of the study led to missing data. CONCLUSIONS: Pregnant evening chronotypes show unhealthy lifestyle habits and sociodemographic characteristics commonly associated with a higher risk for PND. They also have a higher risk of developing PND symptoms in the first month after delivery. Chronotype should therefore be routinely assessed during pregnancy to identify women potentially at risk for developing PND.

EEG Activation Does Not Differ in Simple and Complex Episodes of Disorders of Arousal: A Spectral Analysis Study.

Purpose: Disorders of arousal (DoA) are characterized by incomplete awakening from NREM sleep, with the admixture of both deep sleep and wake EEG activity. Previous observations suggested that changes in EEG activity could be detected in the seconds preceding DoA episodes. The aims of this work were to characterize the topography of EEG spectral changes prior to DoA episodes and to investigate whether or not behavioral complexity could be predicted by changes in EEG immediately preceding behavioral onsets. Patients and Methods: We collected 103 consecutive video-polysomnographic recordings of 53 DoA adult patients and classified all episodes as simple, rising and complex arousal movements. For each episode, a 5-second window preceding its motor onset ("pre-event") and a 60-second window from 2 to 3 minutes before the episodes ("baseline") were compared. Subsequently, a between-group comparison was performed for the pre-event of simpler versus the more complex episodes. Results: Spectral analysis over 325 DoA episodes showed an absolute significant increase prior to DoA episodes in all frequency bands excluding sigma, which displayed the opposite effect. In normalized maps, the increase was relatively higher over the central/anterior areas for both slow and fast frequency bands. No significant differences emerged from the comparison between simpler and more complex episodes. Conclusion: Taken together, these results show that deep sleep and wake-like EEG rhythms coexist over overlapping areas before DoA episodes, suggesting an alteration of local sleep mechanisms. Episodes of different complexity are preceded by a similar EEG activation, implying that they possibly share a similar pathophysiology.

Frontal predominant encephalopathy with early paligraphia as a distinctive signature of CAR T-cell therapy-related neurotoxicity.

Chimeric antigen receptor (CAR) T-cell therapy is an emerging highly effective treatment for refractory haematological malignancies. Unfortunately, its therapeutic benefit may be hampered by treatment-related toxicities, including neurotoxicity. Early aggressive treatment is paramount to prevent neurological sequelae, yet it potentially interferes with the anti-cancer action of CAR T-cells. We describe four CAR T-cells infused patients who presented with reiterative writing behaviours, namely paligraphia, as an early manifestation of neurotoxicity, and eventually developed frontal predominant encephalopathy (one mild, three severe). Paligraphia may represent an early, specific, and easily detectable clinical finding of CAR T-cell therapy-related neurotoxicity, potentially informing its management.

Disorders of arousal in 4 older men: evidence from clinical practice.

STUDY OBJECTIVES: To describe clinical and video-polysomnographic features of disorders of arousal (DoA) in older adults. METHODS: Four consecutive male patients with nocturnal motor behaviors underwent a clinical interview, neurologic examination, laboratory tests, brain magnetic resonance imaging, and nocturnal in-laboratory or 24- to 48-hour home video polysomnography. The patients repeated an evaluation after 6 months of follow-up, including a 48-hour home video polysomnography in 2 patients. RESULTS: The patients were aged 65-72 years, and 1 patient has Parkinson disease. Sleep-related behavioral episodes had begun from 12-55 years before our observation. Three patients presented with a positive family history for DoA. Sleep motor episodes were described as suddenly raising the head or trunk, sitting in bed, screaming, speaking, gesturing, and sleepwalking (in 1 patient). When questioned, all patients seemed confused, rarely reporting any dream-like content. We recorded 25 DoA episodes of different intensity and complexity arising from nonrapid eye movement sleep. The semiology of the episodes was similar to that described in younger patients, consisting of sleep terrors and confusional arousals. All patients presented with physiological rapid eye movement sleep muscle atonia. Medication therapy reduced the frequency of the episodes in 2/4 patients. CONCLUSIONS: DoA may begin in adulthood and persist or arise in older adults, sometimes causing sleep-related injuries. Motor patterns of DoA in older adults are similar to those of younger patients. A combined clinical examination and video polysomnography recording are crucial in establishing a definitive diagnosis of nocturnal motor behavior in all older adults and especially in those affected by neurodegenerative diseases. CITATION: Loddo G, Fragiacomo F, Mainieri G, et al. Disorders of arousal in 4 older men: evidence from clinical practice. J Clin Sleep Med. 2022;18(1):129-136.

The Arousal Disorders Questionnaire: a new and effective screening tool for confusional arousals, Sleepwalking and Sleep Terrors in epilepsy and sleep disorders units.

BACKGROUND: Arousal Disorders (DoA) include Confusional Arousals, Sleepwalking and Sleep Terrors. DoA diagnosis is mainly clinical but no validated questionnaires exist for DoA screening according to the criteria of the International Classification of Sleep Disorders, Third Edition. Recently our group proposed the Arousal Disorders Questionnaire (ADQ) as a new diagnostic tool for DoA diagnosis. The objective of this study was to evaluate the diagnostic accuracy of the ADQ in a sleep and epilepsy center. METHODS: One interviewer blinded to clinical and video-polysomnographic (VPSG) data administered the ADQ to 150 patients consecutively admitted to our Sleep and Epilepsy Centers for a follow-up visit. The final diagnosis, according to VPSG recordings of at least one major episode, classified patients either with DoA (DoA group) or with other sleep-related motor behaviors confounding for DoA (nDoA group). RESULTS: 47 patients (31%) composed the DoA group; 56 patients with REM sleep behavior disorder, 39 with sleep-hypermotor epilepsy, six with night eating syndrome, and two with drug-induced DoA composed the nDoA group. The ADQ had a sensitivity of 72% (95% CI: 60-82) and a specificity of 96% (95% CI: 89-98) for DoA diagnosis; excluding the items regarding consciousness and episode recall, sensitivity was 83% (95% CI: 71-90) and specificity 93% (95% CI: 86-97). CONCLUSIONS: The ADQ showed good accuracy in screening patients with DoA in a sleep and epilepsy center setting. Diagnostic criteria related to cognition and episode recall reduced ADQ sensitivity, therefore a better definition of these criteria is required, especially in adults.

Seizures with paroxysmal arousals in sleep-related hypermotor epilepsy (SHE): Dissecting epilepsy from NREM parasomnias.

OBJECTIVE: Sleep-related hypermotor epilepsy (SHE) is a focal epilepsy characterized by seizures occurring mostly during sleep, ranging from brief seizures with paroxysmal arousals (SPAs) to hyperkinetic seizures and ambulatory behaviors. SPAs are brief and stereotypic seizures representing the beginning of a major seizure. Distinguishing SPAs from disorders of arousal (DOAs) and their briefest episodes called simple arousal movements (SAMs) is difficult. We performed a characterization of SPAs and SAMs to identify video-polysomnographic (VPSG) features that can contribute to the diagnosis of SHE or DOA. METHODS: Fifteen SHE, 30 DOA adult patients, and 15 healthy subjects underwent full-night VPSG. Two neurologist experts in sleep disorders and epilepsy classified all the sleep-related movements and episodes recorded. For each SPAs and SAMs, sleep stage at onset, duration, limb involvement, progression, and semiology have been identified. RESULTS: A total of 121 SPAs were recorded, emerging mostly during stage 1-2 non-rapid eye movement (NREM) sleep (median duration: 5 seconds). At the beginning, the SPAs motor pattern was hyperkinetic in 78 cases (64%), involving more than three non-contiguous or all body parts. The standard was a constant progression of movements during SPAs without any motor arrests. In DOA patients a total of 140 SAMs were recorded (median duration: 12 seconds) mostly emerging during stage 3 NREM sleep. In SAMs, we did not observe any tonic/dystonic or hypermotor patterns or stereotypy; motor arrest was present over the course of about half of the episodes. In comparison with both DOA and healthy subjects, SHE patients showed a higher number of sleep-related movements per night and a reduction of sleep efficiency. SIGNIFICANCE: SPAs and SAMs present different semiological and clinical features. Their recognition could be useful to drive the diagnosis when major episodes are not recorded during VPSG in patients with a clear clinical history of SHE or DOA.

Inside the clinical evaluation of sleepiness: subjective and objective tools.

PURPOSE: To critically review the available tools for evaluating excessive daytime sleepiness (EDS) in clinical practice. METHODS: Objective tests and subjective scales were divided into three groups in accordance with the different dimensions of sleepiness they measure, namely physiological, manifest, and introspective. Strengths, weaknesses, and limitations of each test have been analysed and discussed along with the available recommendations for their use in clinical practice. RESULTS: The majority of the tests developed for sleepiness evaluation do not have practical usefulness outside the research setting. The suboptimal correlation between different tests mainly depends on the different dimensions of sleepiness they analyse. Most importantly in-laboratory tests poorly correlate with sleepiness in real-life situations and, to date, none is able to predict the risk of injuries related to EDS, especially on an individual level. CONCLUSIONS: There exists not the one best test to assess EDS, however, clinicians can choose a more specific test to address a specific diagnostic challenge on the individual level. The development of novel performance tests with low cost and easy to administer is advisable for both screening purposes and fitness for duty evaluations in populations at high risk of EDS-related injuries, for example professional drivers.

Clinical Features and Pathophysiology of Disorders of Arousal in Adults: A Window Into the Sleeping Brain.

Introduction: Disorders of Arousal (DoA) are NREM parasomnias that have been typically regarded as self-limited childhood manifestations. It is now clear that DoA can persist in adults, often presenting with distinctive characteristics. So far, few studies have described the clinical course and characteristics of DoA in adulthood, therefore a large part of their semiology is ignored. The aim of this study is to describe the clinical manifestations of DoA in an adult population and to provide a pathophysiological interpretation of their features. Methods: We screened our database for all 1,600 adult (≥15 years) patients with sleep-related motor behaviors between 1995 and 2016. We identified 45 patients with typical DoA episodes, of whom a complete history, neurological examination and diagnostic video-polysomnography (VPSG) were available. All patients provided a detailed description of their episodes (with particular regards to semiology, frequency, and association with stressful life events) in different life periods. VPSG recordings were reviewed and DoA episodes were identified and assigned to three different categories according to their complexity. Results: Our population was composed of 45 adult patients ranging between 15 and 76 years. Sleepwalking was reported by 86% of patients, possibly associated with complex interactions with the environment and violent behaviors in 53% of cases; distressing mental contents were reported by 64%. Recall of the episodes was reported in 77% of patients. Non-restorative sleep was reported in 46% of patients. Stress was a potential episode trigger in 80% of patients. VPSG recordings documented 334 DoA episodes. According to our classification of motor patterns, 282 episodes (84%) were Simple Arousal Movements (SAMs), 34 (10%) Rapid Arousal Movements (RAMs) and 18 (5%) Complex Arousal Movements (CAMs). Discussion: Our study confirms that DoA in adulthood present with distinctive characteristics, such as non-restorative sleep, violence and complex, or bizarre behaviors. Alternative classifications of DoA based on motor patterns could be useful to characterize DoA episodes in adults, as different motor patterns often coexist in the same individual and minor episodes are more common but generally underreported by patients. Prospective studies are needed for a definitive characterization of DoA in adulthood throughout the life course.

Is the Epworth Sleepiness Scale a useful tool for screening excessive daytime sleepiness in commercial drivers?

The significant social and economic impact of excessive daytime sleepiness makes sleep evaluation a primary medical need in commercial drivers. However, the best screening tool is still matter of debate. In our cohort of 221 commercial drivers, only ten (4.5%) had Epworth Sleepiness Scale scores indicative of excessive daytime sleepiness. These findings and the lack of concordance in estimating excessive daytime sleepiness among commercial drivers in previous studies using the same psychometric measure indicate that the Epworth Sleepiness Scale is not a reliable tool. This may be due to the low internal consistency of the scale in non-clinical samples and the possible intentional underscoring of sleepiness due to a perceived threat of driver's license suspension. Moreover, the reliability of the Epworth Sleepiness Scale results may be strongly influenced by the administration setting. The clinical application of inexpensive less time-consuming new tools like performance tests should be considered for the objective evaluation of excessive daytime sleepiness in commercial drivers.

Specific motor patterns of arousal disorders in adults: a video-polysomnographic analysis of 184 episodes.

OBJECTIVE: To compile an objective accurate description of the motor patterns of adult arousal disorders (ADs). METHODS: We reviewed 59 nocturnal video-polysomnographic (VPSG) recordings of 30 adult patients (>15 years) with a history of sleepwalking (SW). We scrutinized the semeiology of all 184 episodes recorded, classifying them into three groups according to three semeiological motor patterns characterized by increasing intensity and complexity: simple arousal movements (pattern I), characterized by head flexion/extension, head flexion/extension and limb movement or head flexion/extension and partial trunk flexion/extension; rising arousal movements (pattern II), characterized by a complete trunk flexion with patient sitting up in bed; and complex arousal with ambulatory movements (pattern III) characterized by SW. The VPSG recordings were compared to those of 10 healthy controls. RESULTS: AD patients presented with 169 pattern I, 37 pattern II, and nine pattern III episodes. Pattern I developed into pattern II in 17 cases and into pattern II followed by pattern III in five patients. Pattern II developed into pattern III in four patients. Onset was abrupt in 55% of the episodes. Episodes lasted a mean (±standard deviation) of 33 ± 35 s. Movements tended to halt temporarily during 72% of the episodes. We recorded 248 movements during sleep in the healthy controls, none of whom presented with AD patterns. CONCLUSION: We identified three specific motor patterns in AD patients not previously reported and not observed in healthy controls. Identification of these patterns could be important for diagnosis and serve as the basis for a new definition of AD in adults.

Survival of Dialysis Patients with Restless Legs Syndrome: A 15-Year Follow-Up Study.

BACKGROUND: Restless legs syndrome, also known as Willis/Ekbom disease (RLS/WED), is a sleep-related, sensorimotor disorder with a high prevalence among end-stage renal disease (ESRD) patients undergoing haemodialysis (HD) (about 15-40%). Whether RLS/WED in uremic patients influences cardiovascular morbidity and mortality remains a matter of controversy. The aim of this study was to evaluate the relationship of RLS/WED and mortality in a population of chronically dialyzed patients. METHOD: In 1996, we studied 128 patients with ESRD undergoing HD; 47 subjects (36.7%) complained RLS/WED symptoms. Fifteen years later we evaluated the mortality of this population. No clinical follow-up examination of the uremic population was made. The Kaplan-Maier curves in dialysis patients with or without RLS/WED (control group matched for age) were constructed for all-cause mortality and compared using log-rank test. RESULTS: The Kaplan-Maier curves disclosed a lower mortality rate in the uremic patients with RLS/WED than in those without RLS/WED (p = 0.04). In our analysis, the mortality rate was not influenced by RLS/WED severity (p = 0.11) or gender (p = 0.15). No difference among the causes of death was found in the 2 groups. CONCLUSIONS: Our study suggests that mortality in ESRD patients is not influenced by concomitant RLS/WED. After a 15-year follow-up, survival rates in our cohort were significantly longer in uremic subjects with RLS/WED than in those without RLS/WED. Finally, we found no relationship between RLS/WED severity and mortality.

Technique and Preliminary Analysis of Drug-Induced Sleep Endoscopy With Online Polygraphic Cardiorespiratory Monitoring in Patients With Obstructive Sleep Apnea Syndrome.

Importance: Drug-induced sleep endoscopy is a diagnostic technique that allows dynamic evaluation of the upper airway during artificial sleep. The lack of a standardized procedure and the difficulties associated with direct visual detection of obstructive events result in poor intraobserver and interobserver reliability, especially when otolaryngology surgeons not experienced in the technique are involved. Objectives: To describe a drug-induced sleep endoscopy technique implemented with simultaneous polygraphic monitoring of cardiorespiratory parameters (DISE-PG) in patients with a diagnosis of obstructive sleep apnea syndrome and discuss the technique's possible advantages compared with the standard procedure. Design, Setting, and Participants: This prospective cohort study included 50 consecutive patients with obstructive sleep apnea syndrome who underwent DISE-PG from March 1, 2013, to June 30, 2014. A standard protocol was adopted, and all the procedures were carried out in an operation room by an experienced otolaryngology surgeon under the supervision of an anesthesiologist. Endoscopic and polygraphic obstructive respiratory events were analyzed offline in a double-blind setting and randomized order. Main Outcomes and Measures: The feasibility and safety of the DISE-PG technique, as well as its sensitivity in detecting respiratory events compared with that of the standard drug-induced sleep endoscopy procedure. Results: All 50 patients (43 men and 7 women; mean [SD] age, 51.1 [12.1] years) underwent DISE-PG without technical problems or patient difficulties regarding the procedure. As expected, polygraphic scoring was more sensitive than endoscopic scoring in identifying obstructive events (mean [SD] total events, 13.3 [6.8] vs 5.3 [3.6]; mean [SD] difference, 8.8 [5.6]; 95% CI, 7.3 to 10.4; Cohen d, -1.5). This difference was most pronounced in patients with a higher apnea-hypopnea index (AHI) at baseline (mean [SD] difference for AHI >30, 27.1% [31.0%]; 95% CI, -36.2% to 90.4%; Cohen d, 0.2; for AH I >40, 76.0% [35.5%]; 95% CI, 4.6% to 147.4%; Cohen d, 0.5; for AHI >50, 92.2% [37.2%]; 95% CI, 17.3% to 167.1%; Cohen d, 0.6) and a high percentage of hypopneas (≥75% of all obstructive events) at baseline (mean [SD] difference, 20.2% [5.4%]; 95% CI, 9.2% to 31.3%; Cohen d, 1.1). No other anthropomorphic or polygraphic features at baseline were associated with the differences between the DISE-PG and baseline home sleep apnea test. Conclusions and Relevance: The DISE-PG technique is feasible, safe, and more sensitive at detecting an obstructed breathing pattern than is drug-induced sleep endoscopy alone. The DISE-PG technique could be helpful for accurate comprehension of upper airway obstructive dynamics (ie, degree of obstruction and multilevel pattern) and a nonobstructive breathing pattern (ie, central apneas).

Chronobiology, sleep-related risk factors and light therapy in perinatal depression: the "Life-ON" project.

BACKGROUND: Perinatal depression (PND) has an overall estimated prevalence of roughly 12 %. Untreated PND has significant negative consequences not only on the health of the mothers, but also on the physical, emotional and cognitive development of their children. No certain risk factors are known to predict PND and no completely safe drug treatments are available during pregnancy and breastfeeding. Sleep and depression are strongly related to each other because of a solid reciprocal causal relationship. Bright light therapy (BLT) is a well-tested and safe treatment, effective in both depression and circadian/sleep disorders. METHODS: In a 3-year longitudinal, observational, multicentre study, about 500 women will be recruited and followed-up from early pregnancy (10-15 gestational week) until 12 months after delivery. The primary aim of the present study is to systematically explore and characterize risk factors for PND by prospective sleep assessment (using wrist actigraphy, polysomnography and various sleep questionnaires) and bloodbased analysis of potential markers during the perinatal period (Life-ON study). Secondary aims are to explore the relationship between specific genetic polymorphisms and PND (substudy Life-ON1), to investigate the effectiveness of BLT in treating PND (substudy Life-ON2) and to test whether a short term trial of BLT during pregnancy can prevent PND (substudy Life-ON3). DISCUSSION: The characterization of specific predictive and risk factors for PND may substantially contribute to improve preventive medical and social strategies for the affected women. The study results are expected to promote a better understanding of the relationship between sleep disorders and the development of PND and to confirm, in a large sample of women, the safety and efficacy of BLT both in prevention and treatment of PND. TRIAL REGISTRATION: ClinicalTrials.gov NCT02664467 . Registered 13 January 2016.

Sleep-readiness signals in insomniacs and good sleepers.

Sleep is preceded by physiological and behavioural events that inform the subject that it is time to sleep. Our hypothesis is that insomniacs do not adequately recognize such signals, thus missing the best time to go to bed. Eighty-seven chronic insomniac participants and 76 age-matched good sleeper controls were recruited. Semi-structured interviews focused on three aspects of nocturnal sleep: features, habitual activities and signals that they usually rely on in order to decide their readiness to sleep. The results showed that insomniacs relied more than good sleepers on external signals (time) than on bodily ones to decide to go to sleep.

Short- and Long-Term Stroke Risk after Urgent Management of Transient Ischaemic Attack: The Bologna TIA Clinical Pathway.

BACKGROUND: Rapid management can reduce the short stroke risk after transient ischaemic attack (TIA), but the long-term effect is still little known. We evaluated 3-year vascular outcomes in patients with TIA after urgent care. METHODS: We prospectively enrolled all consecutive patients with TIA diagnosed by a vascular neurologist and referred to our emergency department (ED). Expedited assessment and best secondary prevention was within 24 h. Endpoints were stroke within 90 days, and stroke, myocardial infarction, and vascular death at 12, 24 and 36 months. RESULTS: Between August 2010 and July 2013, we evaluated 686 patients with suspected TIA; 433 (63%) patients had confirmed TIA. Stroke at 90 days was 2.07% (95% confidence interval (CI), 1.1-3.9) compared with the ABCD2-predicted risk of 9.1%. The long-term stroke risk was 2.6% (95% CI, 1.1-4.2), 3.7% (95% CI, 1.6-5.9) and 4.4% (95% CI, 1.9-6.8) at 12, 24 and 36 months, respectively. The composite outcome of stroke, myocardial infarction, and vascular death was 3.5% (95% CI, 1.7-5.1), 4.9% (95% CI, 2.5-7.4), and 5.6% (95% CI, 2.8-8.3) at 12, 24, and 36 months, respectively. CONCLUSIONS: TIA expedited management driven by vascular neurologists was associated with a marked reduction in the expected early stroke risk and low long-term risk of stroke and other vascular events.

A restless abdomen and propriospinal myoclonus like at sleep onset: an unusual overlap syndrome.

We report for the first time the association between restless abdomen, a phenotypic variant of restless legs syndrome in which symptoms are limited to the abdomen, and propriospinal myoclonus at sleep onset causing severe insomnia. The treatment with a low-dosage of dopaminergic drug (pramipexole) induced the immediate disappearance of both symptoms, which was documented by video-polysomnography.