Neurology and psychiatry: waking up to opportunities of sleep. : State of the art and clinical/research priorities for the next decade.

In recent years, evidence has emerged for a bidirectional relationship between sleep and neurological and psychiatric disorders. First, sleep-wake disorders (SWDs) are very common and may be the first/main manifestation of underlying neurological and psychiatric disorders. Secondly, SWDs may represent an independent risk factor for neuropsychiatric morbidities. Thirdly, sleep-wake function (SWF) may influence the course and outcome of neurological and psychiatric disorders. This review summarizes the most important research and clinical findings in the fields of neuropsychiatric sleep and circadian research and medicine, and discusses the promise they bear for the next decade. The findings herein summarize discussions conducted in a workshop with 26 European experts in these fields, and formulate specific future priorities for clinical practice and translational research. More generally, the conclusion emerging from this workshop is the recognition of a tremendous opportunity offered by our knowledge of SWF and SWDs that has unfortunately not yet entered as an important key factor in clinical practice, particularly in Europe. Strengthening pre-graduate and postgraduate teaching, creating academic multidisciplinary sleep-wake centres and simplifying diagnostic approaches of SWDs coupled with targeted treatment strategies yield enormous clinical benefits for these diseases.

Parental report of dental pain and discomfort in preschool children is associated with sleep disorders: a cross-sectional study in Brazilian families.

PURPOSE: To evaluate the prevalence of sleep disorders in Brazilian preschool children and its associations with parental report of dental pain and discomfort. METHODS: This cross-sectional study involved 604 Brazilian preschoolers (4-5 years old). Sleep disorders (SD) and the parental report of dental pain and discomfort (DPD) were evaluated using the Brazilian versions of the Sleep Disturbance Scale for Children (SDSC) and the Dental Discomfort Questionnaire (DDQ-B), respectively. Bivariate and multivariate Poisson regression analyses with robust variance were performed to analyze the association between SDSC and DP. RESULTS: Prevalence of SD ranged from 7 to 21%. 7.9% of the children had DPD indicating the need for more invasive dental procedures (DDQ-B ≥ 5). Significant associations were found between DPD and the following SDSC domains: sleep hyperhidrosis (p = 0.024; PRa = 1.38; 95% CI: 1.04-1.83), disorders of initiating and maintaining sleep (p < 0.001; PRa = 1.41; 95% CI: 1.15-1.73), parasomnias (p < 0.001; PRa = 1.82; 95% CI: 1.39-2.37), and sleep-wake transition disorders (p = 0.018; PRa = 1.28; 95% CI: 1.04-1.58). Children with higher prevalence of DPD presented 20% higher prevalence of SD than children lower prevalence of DPD (p = 0.039; PRa = 1.20; 95% CI: 1.01-1.44). CONCLUSION: Preschool children with higher prevalence of DPD are more likely to have SD, such as hyperhidrosis, disorders of initiating and maintaining sleep, parasomnias, and sleep-wake transition.

Identifying the impact of the confinement of Covid-19 on emotional-mood and behavioural dimensions in children and adolescents with attention deficit hyperactivity disorder (ADHD).

The current study examined the impact of the lockdown due to the Covid-19 disease on mood state and behaviours of children and adolescents with ADHD. Nine hundred ninety-two parents of children and adolescents with ADHD filled out an anonymous online survey through the ADHD family association website. The survey investigated the degree of severity of six emotional and mood states (sadness, boredom, little enjoyment/interest, irritability, temper tantrums, anxiety) and five disrupted behaviours (verbal and physical aggression, argument, opposition, restlessness) based on their frequency/week (absent; low: 1-2 days/week; moderate: 3-4 days/week; severe: 5-7 days/week) before and during the lockdown. Important fluctuations were found in all dimensions during the lockdown independently by the severity degree. Subjects with previous low severity degree of these behaviors significantly worsened in almost all dimensions during the lockdown. On the contrary, ADHD patients with moderate and severe degree showed important improvement during the lockdown. Little enjoyment/interests and boredom resulted the dimensions more strongly affected by the condition of restriction, overall in children. Children vs. adolescents showed substantially similar trend but the former resulted significantly more vulnerable to emotive changes. The results provided both the individuation of domains affected, and the indirect benefits produced by restriction condition.

Relationships between headache and sleep in a non-clinical population of children and adolescents.

BACKGROUND: Headache and sleep are related in different ways and alterations of chronobiological mechanisms are involved in headache. We investigated the relationships between headache and sleep quality in a large non-clinical population of children and adolescents and evaluated the relationship between headache and circadian typologies. METHODS: A total of 1073 children and adolescents (50.9% males; mean age=10.56; range=8-15 years) were recruited from four schools in Rome. They filled out the questionnaires individually in classrooms, after brief group instruction about answer formats. The questionnaires included (a) a self-report headache questionnaire to collect information on different aspects of headache attacks based on the International Classification of Headache Disorders-2nd edition (ICHD-2); (b) the School Sleep Habits Survey that incorporated questions about sleep habits, the Sleep-Wake Problems Behaviour Scale (SWPBS), the Sleepiness Scale (SLS) and the Morningness/Eveningness Questionnaire (MEQ). RESULTS: According to ICHD-2 criteria, we classified 70 (6.5%) children as Migraine Group (MG), 135 (12.7%) as Non-Migraine Headache Group (NMG), and the remaining 868 (80.8%) were classified as Headache-Free Group (HFG). No clear differences have been found between MG and NMG regarding the frequency of the attacks, although MG showed a significantly increased frequency of long-lasting attacks. The modality of onset of pain and the location of pain was similar in both groups. The most frequent triggering factor for headache in MG and NMG was "a bad sleep" (32.2%) followed by emotional distress (27.8%). No differences have been found between MG, NMG and HFG in sleep schedule or sleep duration. MG and NMG showed significantly higher scores on the SWPBS vs. HFG, while MG presented higher scores on the SLS compared to NMG and HFG. MG presented lower MEQ scores, indicating a more pronounced eveningness. CONCLUSIONS: The relationships between headache and sleep problems are evident even in a non-clinical population of children and adolescents, with MG showing poorer sleep quality, sleepiness and a tendency toward eveningness.

Comorbidity of Attention Deficit Hyperactivity Disorder and Generalized Anxiety Disorder in children and adolescents.

The aim of the study is to explore the impact of Generalized Anxiety Disorder (GAD) comorbidity in children with Attention Deficit Hyperactivity Disorder (ADHD). Six hundred children with ADHD (mean age = 9.12 years), recruited from 2013 to 2017, participated in the study. A total of 96 (16%) children with ADHD displayed a comorbidity with GAD. ADHD + GAD were compared to 504 ADHD children without GAD in terms of cognitive and psychiatric profile, ADHD subtype and family psychiatric history. The ADHD + GAD, predominantly represented from ADHD combined (72.6%), displayed higher psychiatry comorbidity, in particular with depressive disorders, and were associated with higher rates of maternal depression, of ADHD in fathers, and bipolar disorders in second degree relatives. Moreover, younger preschool-primary school age children with ADHD + GAD showed significant higher frequency of depressive disorders versus younger preschool-primary children with ADHD without GAD. ADHD + GAD comorbidity represents a more complex clinical condition compared to ADHD without GAD, characterized by the higher frequency of multiple comorbidities and by a psychiatric family with higher rates of mood and disruptive disorders.

World Association of Sleep Medicine (WASM) 2016 standards for recording and scoring leg movements in polysomnograms developed by a joint task force from the International and the European Restless Legs Syndrome Study Groups (IRLSSG and EURLSSG).

This report presents the results of the work by a joint task force of the International and European Restless Legs Syndrome Study Groups and World Association of Sleep Medicine that revised and updated the current standards for recording and scoring leg movements (LM) in polysomnographic recordings (PSG). First, the background of the decisions made and the explanations of the new rules are reported and then specific standard rules are presented for recording, detecting, scoring and reporting LM activity in PSG. Each standard rule has been classified with a level of evidence. At the end of the paper, Appendix 1 provides algorithms to aid implementation of these new standards in software tools. There are two main changes introduced by these new rules: 1) Candidate LM (CLM), are any monolateral LM 0.5-10 s long or bilateral LM 0.5-15 s long; 2) periodic LM (PLM) are now defined by runs of at least four consecutive CLM with an intermovement interval ≥10 and ≤ 90 s without any CLM preceded by an interval <10 s interrupting the PLM series. There are also new options defining CLM associated with respiratory events. The PLM rate may now first be determined for all CLM not excluding any related to respiration (providing a consistent number across studies regardless of the rules used to define association with respiration) and, subsequently, the PLM rate should also be calculated without considering the respiratory related events. Finally, special considerations for pediatric studies are provided. The expert visual scoringof LM has only been altered by the new standards to require accepting all LM > 0.5 s regardless of duration, otherwise the technician scores the LM as for the old standards. There is a new criterion for the morphology of LM that applies only to computerized LM detection to better match expert visual detection. Available automatic scoring programs will incorporate all the new rules so that the new standards should reduce technician burden for scoring PLMS.

Effectiveness and tolerability of perampanel in children and adolescents with refractory epilepsies-An Italian observational multicenter study.

PURPOSE: To evaluate the efficacy and tolerability of Perampanel (PER) in children and adolescents with refractory epilepsies in daily clinical practice conditions. PATIENTS AND METHODS: This Italian multicenter retrospective observational study was performed in 16 paediatric epilepsy centres. Inclusion criteria were: (i) ≤18 years of age, (ii) history of refractory epilepsy, (iii) a follow-up ≥5 months of PER add-on therapy. Exclusion criteria were: (i) a diagnosis of primary idiopathic generalized epilepsy, (ii) variation of concomitant AEDs during the previous 4 weeks. Response was defined as a ≥50% reduction in monthly seizure frequency compared with the baseline. RESULTS: 62 patients suffering from various refractory epilepsies were included in this study: 53% were males, the mean age was 14.2 years (range 6-18 years), 8 patients aged <12 years. Mean age at epilepsy onset was 3.4 years and the mean duration of epilepsy was 10.8 years (range 1-16), which ranged from 2 seizures per-month up to several seizures per-day (mean number=96.5). Symptomatic focal epilepsy was reported in 62.9% of cases. Mean number of AEDs used in the past was 7.1; mean number of concomitant AEDs was 2.48, with carbamazepine used in 43.5% of patients. Mean PER daily dose was 7.1mg (2-12mg). After an average of 6.6 months of follow-up (5-13 months), the retention rate was 77.4% (48/62). The response rate was 50%; 16% of patients achieved ≥75% seizure frequency reduction and 5% became completely seizure free. Seizure aggravation was observed in 9.7% of patients. Adverse events were reported in 19 patients (30.6%) and led to PER discontinuation in 4 patients (6.5%). The most common adverse events were behaviour disturbance (irritability and aggressiveness), dizziness, sedation and fatigue. CONCLUSION: PER was found to be a safe and effective treatment when used as adjunctive therapy in paediatric patients with uncontrolled epilepsy.

Sleep characteristics in healthy children from birth to 6 years of age in the urban area of Rome.

The current survey is an attempt to evaluate age-specific sleep characteristics and to identify the presence of sleep problems in Italian normally developing preschool-aged children. A cross-sectional survey by parental interview on sleep behavior was carried out on 2,889 children (from birth to 6 years). Groups were formed based on age level. Results showed a developmental trend of some sleep characteristics, regarding mainly the length of sleep and rating of night wakings. Comparison with other studies showed that the children in this study had a later sleep onset time and slept less than children of the same age living in some other countries. These dissimilarities may be due to sociocultural and climate differences. Sleep problems (sleep latency longer than 30 minutes or disruptive night wakings) were found in 35% of children less than 2 years old, in 23% of 2-3-year-olds and in 14% of 4-6-year-olds. Children with sleep problems slept significantly less (on average 30-40 minutes across all age levels, required parental presence at time of sleep onset and shared their parents' bed more frequently than those without sleeping problems.

Sleep disorders in children with neurologic diseases.

Pediatric neurologic diseases are often associated with different kinds of sleep disruption (mainly insomnia, less frequently hypersomnia or parasomnias). Due to the key-role of sleep for development, the effort to ameliorate sleep patterns in these children could have important prognostic benefits. Study of sleep architecture and organization in neurologic disorders could lead to a better comprehension of the pathogenesis and a better treatment of the disorders. This article focuses on the following specific neurologic diseases: nocturnal frontal lobe epilepsy and abnormal motor behaviors of epileptic origin, evaluating differential diagnosis with parasomnias; achondroplasia, confirming the crucial role of craniofacial deformity in determining sleep-disordered breathing; neuromuscular diseases, mainly Duchenne's muscular dystrophy and myotonic dystrophy; cerebral palsy, evaluating either the features of sleep architecture and the importance of the respiratory problems associated; headaches, confirming the strict relationships with sleep in terms of neurochemical and neurobehavioral substrates; and finally a review on the effectiveness of melatonin for sleep problems in children with neurologic syndromes and mental retardation, blindness, and epilepsy.

Sleep disorders in tuberous sclerosis: a polysomnographic study.

Overnight polysomnography was performed in 10 subjects with tuberous sclerosis (TS) and partial epilepsy in order to investigate the relationships between sleep organization, sleep disorders and epilepsy. Sleep architecture abnormalities were observed in 9 cases. Compared with ten healthy age-matched controls, the TS group showed a shorter total sleep time, a reduced sleep efficiency, a higher number of awakenings and stage transitions, an increased wake after sleep onset and stage 1 and a decreased REM sleep. Children with seizures showed a more disrupted sleep architecture compared with seizure-free children. Sleep disorders in TS were mainly due to sleep-related epileptic events and were more evident in children who showed large bifrontal or temporal tubers on MRI.

Flunarizine in therapy-resistant infantile epilepsies.

An open add-on trial with flunarizine has been carried out in 27 cases of therapy resistant infantile epilepsies: 15 partial and 12 generalized epilepsies. Etiology was an hypoxic-ischemic encephalopathy (HIE) in 13 cases, cerebral malformations in 10 cases and 4 various prenatal and perinatal cases. After a 2 months baseline period, flunarizine was given in addition to the previous therapy in a 5 mg once daily dose. A single blind versus placebo study was carried out in another series of 16 cases. Better results were found in HIE cases than in malformative cases, and in cases with perinatal HIE than in cases with prenatal hypoxic encephalopathy. The improvement in symptomatic generalized epilepsies was more evident than in symptomatic partial epilepsies. Drowsiness was the only side effect reported.

Short temperament questionnaire for children aged 8-12 years in the city of Rome.

The assessment of temperament is usually measured by means of parental questionnaires. Since temperament questionnaires in children aged 8-12 years do not exist in Italy we planned a study to develop an Italian questionnaire. Initially we tried to adapt Hegvik et al.'s questionnaire and delivered 389 questionnaires to the mothers of children aged 8-12 years, but most of them were given back uncompleted, essentially because they often described behavior not usually observed in Italian children. Then we prepared a new, short (30 items) questionnaire which we distributed to 431 mothers of children aged 8-12 years. This new questionnaire was completed by 98.76% of mothers and a high three week rating-re-rating reliability for the different temperamental characteristics under assessment was proved. We believe that this new questionnaire is reliable for temperament assessment in Italian children aged 8 to 12 years, living in a big city environment in Central Italy.

[Resection surgery in malignant neoplasms of the exocrine pancreas: our experience, 1987-1994]. / La chirurgia resettiva nelle neoplasie maligne del pancreas esocrino: nostra esperienza 1987-1994.

From 1987 to 1994, 24 patients underwent resection for pancreatic cancer; they represented 24% of all patients observed in that period. Surgical procedures were a pancreatoduodenectomy (PD) in 20 cases, a distal pancreatectomy in 4 cases, a palliative intervention in 61 cases, an exploratory laparotomy in 13 cases and a video laparoscopy in 2 cases. Adjuvant treatments were given in addition to resection in 20 patients. In the 20 patients undergoing PD, mortality was 20% and morbidity 20%. There was no mortality and no morbidity in distal pancreatectomy. The 1-year survival in pancreatoduodenectomy was 50% and 0% for distal pancreatectomy. Pancreatic resection, radical and palliative, whenever technically possible, represents the treatment of choice for pancreatic cancer.

[Billiopancreatic diversion with preservation of the duodenal bulb and transitory gastroplasty in the treatment of morbid obesity. Our experience]. / La diversione bilio-pancreatica con conservazione del bulbo duodenale e gastroplastica transitoria nel trattamento dell'obesità patologica. Nostra esperienza.

We present our experience in malabsorbitive procedure in bariatric surgery based on Biliopancreatic Diversion (BPD) with transitory gastroplasty. Since 1995 we operated on 74 patients with BPD coupled with gastroplasty which is transitory due to the presence of a band in polidioxanone (PDS). The technique, proposed by Vassallo et al. in 1992, involve the respect of the duodenal bulb (5 centimeter from the pylorous) making an end-to-side duodeno-ileal isoperistaltic anastomosis. The initial excess weight loss was satisfactory (69.8% +/- 11.4% after 1 year) and it kept being stable during all the follow-up (75.2% +/- 6.4% after 5 years). The mortality was absence. We didn't observe ipoalbuminemia, diarrhea or halitosis in any patients. Only 1 patient (1.3%) developed an anastomotic ulcer. After 5 years follow-up we observed 2 cases (12.5%) of chronic hypochromic anemia and 1 case (6.2%) of hypocalcemia. We didn't perform any restorative operation. We consider this technique a good malabsortive procedure able to obtain a satisfactory and stable weight loss, with a low incidence of complications. Moreover it could be applied in patients previously treated by an ineffective gastroplasty.

[Evaluation of the results after 5 year from a vertical banded gastroplasty: our experience]. / Risultati a 5 anni della gastroplastica verticale secondo MacLean: nostra esperienza.

BACKGROUND AND AIMS: vertical banded gastroplasty (GPV) is the most frequently performed restrictive procedure for morbid obesity, but long-term follow-up is almost nonexistent. A poor outcome after GPV and a low quality of life has been reported. The aim of the study was to determine long-term outcome after 5 years follow-up. METHODS: 225 GPV were performed from 1995 to 2002. Patients were followed every month in the first three months, after 6 and 12 months, and subsequently every year. RESULTS: No mortality was observed. One gastric fistula, treated with medical therapy, was the single related complication observed. Vomiting occurred in 21.2% of patients. After 2 years 74.5% of patients had a BMI < 35, with a decrease of IEW = 50% (IEW% L 54.1%, 56.4%, and 57.1% after 12, 24 and 60 months, respectively). After 5 years, the results were unsatisfactory in 17.1% of patients; 8 patients underwent bariatric re-operation with good results. CONCLUSIONS: GPV represents a safe procedure with a low incidence of complications, with poor results in 17.1% of patients. Pre-operative identification of non responders is achievable with "BIB test". In the responders significant dietary changes are complained.