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The aim of our study is to evaluate objective and subjective vocal outcomes in patients undergoing vagus nerve stimulation (VNS) therapy for drug-resistant epilepsy and to assess the vocal outcome in the known laryngeal dysmotility patterns induced by VNS. We enrolled 16 adult patients without cognitive impairment who had undergone VNS implant for drug-resistant epilepsy at least 1 year prior. They were evaluated by flexible fibreoptic laryngeal examination and Voice Handicap Index questionnaire administration; acoustic and perceptual voice analysis was performed both at rest and during VNS activation. All recruited patients were admitted to the study. The VNS implant systematically determined laryngeal motility alterations, which were in turn mirrored by perceptual, subjective, and/or acoustic analysis voice alterations in all patients. Patients with intact vocal fold function at rest performed worse during acoustic voice analysis in terms of jitter during VNS activation and shimmer at rest when compared to other laryngeal patterns (P= 0.027 and P = 0.034, respectively, Kruskal-Wallis test). Furthermore, VNS activation determined an overall worsening of the perceptual and acoustically analysed voice quality: the grade of hoarseness, instability and breathiness parameters of the GRBASI (grade, roughness, breathiness, asthenia, strain, instability) scale and the jitter, shimmer and noise-to-harmonic ratio of the acoustic analysis worsened significantly during VNS activation (P = 0.001, P = 0.021, P = 0.012, P.001, P = 00.002, P = 0.039, respectively, Wilcoxon test). According to our results, the VNS implant determines a significantly impaired vocal outcome that has a surprisingly mild impact on Voice Handicap Index scores. Such impairment is significantly greater in patients with intact vocal fold function at rest.

Introduction From the beginning of the COVID-19 pandemic, healthcare workers had to face unprecedented emergency needs associated with an extraordinary amount of psychological distress. In this cross-sectional multicenter study, we investigated sleep disturbances, and the level of anxiety and depression among the healthcare and non-healthcare staff of three hospitals in Milan (Italy) during the COVID-19 outbreak. Moreover, we explored potential predisposing factors for affective symptoms and poor sleep. Methods Between June and July 2020, we administered an online questionnaire to evaluate the presence of sleep disorders (Pittsburgh Sleep Quality Index), insomnia (Sleep Condition Indicator), anxiety (State Trait Anxiety Inventory), and depression (Beck Depression Inventory-II). We used univariate and multivariate analysis to evaluate the association between the personal conditions and sleep and affective disorders. Results The 964 participants reported high rates of sleep disorders (80.3%)—mainly insomnia (30.5%)—anxiety (69.7%), and depression (32.8%). The multivariate analysis showed a strong association of sleep disorders, especially insomnia, with female gender (p = 0.004), divorced marital status (p = 0.015), self-isolation (p = 0.037), and chronic diseases (p = 0.003). Anxiety was significantly associated with teleworking (p = 0.001), while depressive symptoms were associated with self-isolation (p = 0.028), modified work schedules (p = 0.03), and chronic diseases (p = 0.027). Conclusion In hospital workers, the high prevalence of sleep and psychiatric symptoms during the COVID-19 outbreak appears to be determined mainly by modifications of personal or work habits. Teleworking was associated with increased anxiety. An accurate planning of hospital activities and a psychological support are needed to prevent and manage sleep and mental disorders.

INTRODUCTION Disorders of arousal (DOA) are parasomnias that emerge from incomplete arousal out of Non-Rem Sleep (NREM) and lead to a broad variety of emotional and motor behaviours. Increasing evidence supports the hypothesis that specific psychopathological traits contribute to the multifactorial origin of these phenomena. The aim of the current multicenter study was to compare the personality profile of children and adolescents with and without DOA using the Junior Temperament and Character Inventory (JTCI). METHODS We enrolled 36 patients with a diagnosis of DOA (mean age of 11 ± 3 years, 64% males), and 36 healthy age and gender matched control subjects (mean age of 11.2 ± 3.6, years, 67% males). Their parents completed the Paris Arousal Disorder Severity Scale (PADSS), the Sleep Disturbance Scale for Children (SDSC) and the JTCI. RESULTS Patients with DOA reached significantly higher levels compared to their control group in total PADSS (p

Background Clinical data regarding use of newer antiseizure medications (ASMs) in an older population are limited. In randomized-controlled, placebo-controlled trials, older patients are under-represented, and protocols deviate markedly from routine clinical practice, limiting the external validity of results. Studies performed in a naturalistic setting are a useful complement to characterize the drug profile. Perampanel is a third-generation ASM and the first and only non-competitive alfa-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor antagonist. Objective The aim of this study was to assess the effectiveness and tolerability of adjunctive perampanel over a 1‐year period in a population of older patients with epilepsy treated in a real-world setting. Methods Older (≥ 65 years of age) patients prescribed add-on perampanel at 12 Italian epilepsy centers were retrospectively identified. Seizure occurrence, adverse events (AEs), and drug withdrawal were analyzed. Effectiveness outcomes included the rates of seizure response (≥ 50% reduction in baseline monthly seizure frequency), seizure freedom, and treatment discontinuation. Safety and tolerability outcomes were the rate of treatment discontinuation due to AEs and the incidence of AEs. Results A total of 92 patients with a median age of 69 (range 65–88) years were included. The median daily dose of perampanel at 12 months was 6 mg (interquartile range 4–6 mg). At 12 months, 53 (57.6%) patients were seizure responders, and 22 (23.9%) patients were seizure free. Twenty (21.7%) patients discontinued perampanel; the reasons for treatment withdrawal were insufficient efficacy (n = 6/20; 30.0%), AEs (n = 12/20; 60.0%), and a combination of both (n = 2/20; 10%). The most common AEs included irritability (8.7%), somnolence (4.3%), and dizziness/vertigo (4.3%). The rate of behavioral and psychiatric AEs was higher in patients with history of psychiatric comorbidities (p = 0.044). There were no differences in the occurrence of behavioral and psychiatric AEs according to the concomitant use of levetiracetam (p = 0.776) and history of cognitive decline (p = 0.332). Conclusions Adjunctive perampanel was associated with improvement in seizure control and good tolerability in a real-life setting and can represent a viable therapeutic option in older patients with epilepsy.

Objectives Little is known about the evolution of epilepsy in individuals with tuberous sclerosis complex (TSC) in adulthood. This study aims at describing the characteristics of epilepsy in adult TSC patients attending a single multidisciplinary clinic. Materials and Methods We collected data about epilepsy (age at onset, seizure types, history of infantile spasms (IS), epilepsy diagnosis and outcome), genetic and neuroradiological findings, cognitive outcome and psychiatric comorbidities. Results Out of 257 adults with TSC, 183 (71.2%) had epilepsy: 121 (67.2%) were drug‐resistant; 59 (32.8%) seizure‐free, at a median age of 18 years. 22% of the seizure‐free patients (13/59) discontinued medication. Median age at seizure onset was 9 months. Seventy‐six patients (41.5%) had a history of IS. TSC2 pathogenic variants (p = 0.018), cortical tubers (p

Sleep disorders are frequent in tuberous sclerosis complex (TSC) during the developmental age but are not well characterized. Forty-six TSC patients and 46 healthy age- and sex-matched controls were enrolled. Their parents completed the Sleep Disturbances Scale for Children (SDSC) and the Child Behavior Checklist (CBCL). A total of 17.4% of the TSC patients obtained a total pathologic score at the SDSC versus 4.4% in the control group (p = 0.024). 45.7% of individuals with TSC reported a pathologic score in at least one of the factors. We found a statistically significant difference between the TSC cohort and healthy controls for most of the CBCL scales scores. A significant relationship was found between the Total SDSC score and the Total CBCL score (R-square = 0.387, p

ObjectiveRecent scientific literature has widely described a possible major role of smell dysfunction as a specific symptom of coronavirus disease 2019. This systematic review may provide a more holistic approach to current knowledge of the disease.MethodsA systematic review was completed using Embase, PubMed and Web of Science databases that considered original articles focused on olfactory evaluation in coronavirus disease 2019 patients, published between March and May 2020, in English language.ResultsFrom the 483 research papers initially identified, 32 original studies were selected, comprising a total of 17 306 subjects with a laboratory confirmed diagnosis of coronavirus disease 2019. Individual study sample sizes ranged from 6 to 6452 patients. This comprehensive analysis confirmed that olfactory disorders represent an important clinical feature in coronavirus disease 2019, with a prevalence of 11–100 per cent in included patients, although there was heterogeneity in terms of assessment tools and population selection criteria.ConclusionThe results indicate that an accurate clinical evaluation should be carried out using structured questionnaires and tests with olfactory substances.

BackgroundTuberous Sclerosis Complex (TSC) and Neurofibromatosis type 1 (NF1) are neurocutaneous disorders commonly characterized by neuropsychiatric comorbidities. The TAND (Tuberous Sclerosis Associated Neuropsychiatric Disorders) Checklist is currently used to quickly screen for behavioural, psychiatric, intellectual, academic, neuropsychological and psychosocial manifestations in patients with TSC. We administered the authorized Italian version of the TAND Checklist to the parents of 42 TSC patients and 42 age- and sex-matched NF1 patients, for a total of 84 individuals, aged 4–20 years.Aims of this study: - to test the overall usability of the TAND Checklist in NF1, −to compare the results between children and adolescents with TSC and NF1, and -to examine the association between neuropsychiatric manifestations and severity of the phenotype in terms of epilepsy severity in the TSC cohort and disease severity according to the modified version of the Riccardi severity scale in the NF1 cohort.ResultsTSC cohort:35.6% had Intellectual Disability (ID), 11.9% Specific Learning Disorders (SLD), 50.0% Attention Deficit Hyperactivity Disorder (ADHD) and 16.6% anxious/mood disorder. 33.3% had a formal diagnosis of Autism Spectrum Disorder (ASD). Paying attention and concentrating (61.9%), impulsivity (54.8%), temper tantrums (54.8%), anxiety (45.2%), overactivity/hyperactivity (40.5%), aggressive outburst (40.5%), absent or delayed onset of language (40.5%), repetitive behaviors (35.7%), academic difficulties (> 40%), deficits in attention (61.9%) and executive skills (50.0%) were the most commonly reported problems.NF1 cohort:9.5% had ID, 21.4% SLD, 46.6% ADHD, and 33.3% anxious/mood disorder. No one had a diagnosis of ASD. Commonly reported issues were paying attention and concentrating (59.5%), impulsivity (52.4%), anxiety (50.0%), overactivity/hyperactivity (38.1%), temper tantrums (38.1%), academic difficulties (> 40%), deficits in attention (59.5%), and executive skills (38.1%).Neuropsychiatric features in TSCvsNF1:Aggressive outburst and ASD features were reported significantly more frequently in TSC than in NF1.Neuropsychiatric manifestations and phenotype severity:Depressed mood, absent or delayed onset of language, repetitive language, difficulties in relationship with peers, repetitive behaviors, spelling, mathematics, dual-tasking, visuo-spatial tasks, executive skills, and getting disoriented were significantly different among TSC patients with different epilepsy severity. No statistically significant differences in the NF1 subgroups were noted for any of the items in the checklist.ConclusionThe TAND Checklist used for TSC is acceptable and feasible to complete in a clinical setting, and is able to detect the complexity of neuropsychiatric involvement in NF1 as well. NF1 is mainly characterized by an ADHD profile, anxiety problems and SLD, while ASD features are strongly associated with TSC. In conclusion, the TAND Checklist is a useful and feasible screening tool, in both TSC and NF1.

Individuals with comorbidities are at higher risk of coronavirus disease 2019 (COVID-19) and worse outcome, but little information has been available about patients with genetic diseases and COVID-19. This study aims at evaluating the presence and outcome of COVID-19 in a cohort of Italian patients with tuberous sclerosis complex (TSC) and/or lymphangioleiomyomatosis (LAM), and at reviewing the possible effects of mTOR inhibitors on SARS-CoV-2 infection. We included 102 unselected individuals with a diagnosis of TSC and/or LAM assessed between January 1, 2020 and April 24, 2020 (29% children, 71% adults). Twenty-six patients were on mTOR inhibitors. Demographic data, TSC manifestations, presence, and outcomes in individuals with confirmed or suspected SARS-CoV-2 infection were evaluated. Health status and outcomes of all patients on mTOR inhibitors were assessed. One patient with severe TSC had polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection, was admitted to ICU, and died. Nine additional patients either met the definition of suspect case or presented with at least two of the most common symptoms of SARS-CoV-2 infection. All recovered fully. None of the patients treated with mTOR inhibitors for their underlying comorbidities was diagnosed with COVID-19, and those who showed suspicious respiratory symptoms recovered fully. This cohort study provides preliminary information on COVID-19 in people with TSC in Italy and suggests feasibility to systematically evaluate the role of mTOR inhibitors in SARS-CoV-2 infection.

Vagus nerve stimulation for refractory epilepsy may induce laryngeal side effects such as dysphonia and dysphagia. Careful tuning of the stimulation parameters and collaboration between epileptologists and otolaryngologists can help significantly reduce side effects.

BACKGROUND: The management of epilepsy in older adults has become part of daily practice because of an aging population. Older patients with epilepsy represent a distinct and more vulnerable clinical group as compared with younger patients, and they are generally under-represented in randomized placebo-controlled trials. Real-world studies can therefore be a useful complement to characterize the drug's profile. Brivaracetam is a rationally developed compound characterized by high-affinity binding to synaptic vesicle protein 2A and approved as adjunctive therapy for focal seizures in adults with epilepsy. OBJECTIVE: The aim of this study was to assess the 12-month effectiveness and tolerability of adjunctive brivaracetam in older patients (≥65 years of age) with epilepsy treated in a real-world setting. METHODS: The BRIVAFIRST (BRIVAracetam add-on First Italian netwoRk STudy) was a 12-month retrospective multicenter study including adult patients prescribed adjunctive brivaracetam. Effectiveness outcomes included the rates of seizure response (≥50% reduction in baseline seizure frequency), seizure freedom, and treatment discontinuation. Safety and tolerability outcomes included the rate of treatment discontinuation due to adverse events and the incidence of adverse events. Data were compared for patients aged ≥65 years of age ('older') vs those aged

Objective: Post-stroke epilepsy (PSE) is one of the most common causes of acquired epilepsy and accounts for about 10-15% of all newly diagnosed epilepsy cases. However, evidence about the clinical profile of antiseizure medications in the PSE setting is currently limited. Brivaracetam (BRV) is a rationally developed compound characterized by high-affinity binding to synaptic vesicle protein 2A. The aim of this study was to assess the 12-month effectiveness and tolerability of adjunctive BRV in patients with PSE treated in a real-world setting. Methods: This was a subgroup analysis of patients with PSE included in the BRIVAracetam add-on First Italian netwoRk Study (BRIVAFIRST). The BRIVAFIRST was a 12-month retrospective, multicentre study including adult patients prescribed adjunctive BRV. Effectiveness outcomes included the rates of seizure response (≥50% reduction in baseline seizure frequency), seizure‐freedom, and treatment discontinuation. Safety and tolerability outcomes included the rate of treatment discontinuation due to adverse events (AEs) and the incidence of AEs. Results: Patients with PSE included in the BRIVAFIRST were 75 and had a median age of 57 (interquartile range, 42-66) years. The median daily doses of BRV at 3, 6, and 12 months from starting treatment were 100 (100-150) mg, 125 (100-200) mg and 100 (100-200) mg, respectively. At 12 months, 32 (42.7%) patients had a reduction in their baseline seizure frequency by at least 50%, and the seizure freedom rates was 26/75 (34.7%). During the 1-year study period, 10 (13.3%) patients discontinued BRV. The reasons of treatment withdrawal were insufficient efficacy in 6 (8.0%) patients and poor tolerability in 4 (5.3%) patients. Adverse events were reported by 13 (20.3%) patients and were rated as mild in 84.6% and moderate in 15.4% of cases. Significance: Adjunctive BRV was efficacious and generally well-tolerated when used in patients with PSE in clinical practice. Adjunctive BRV can be a suitable therapeutic option for patients with PSE.

The maintenance of seizure control over time is a clinical priority in patients with epilepsy. The aim of this study was to assess the sustained seizure frequency reduction with adjunctive brivaracetam (BRV) in real-world practice. Patients with focal epilepsy prescribed add-on BRV were identified. Study outcomes included sustained seizure freedom and sustained seizure response, defined as a 100% and a ≥50% reduction in baseline seizure frequency that continued without interruption and without BRV withdrawal through the 12-month follow-up. Nine hundred ninety-four patients with a median age of 45 (interquartile range = 32-56) years were included. During the 1-year study period, sustained seizure freedom was achieved by 142 (14.3%) patients, of whom 72 (50.7%) were seizure-free from Day 1 of BRV treatment. Sustained seizure freedom was maintained for ≥6, ≥9, and 12months by 14.3%, 11.9%, and 7.2% of patients from the study cohort. Sustained seizure response was reached by 383 (38.5%) patients; 236 of 383 (61.6%) achieved sustained ≥50% reduction in seizure frequency by Day 1, 94 of 383 (24.5%) by Month 4, and 53 of 383 (13.8%) by Month 7 up to Month 12. Adjunctive BRV was associated with sustained seizure frequency reduction from the first day of treatment in a subset of patients with uncontrolled focal epilepsy.

The aim of the present study is to detect the presence of SARS-CoV-2 of patients affected by COVID-19 in olfactory mucosa (OM), sampled with nasal brushing (NB) and biopsy, and to assess whether a non-invasive procedure, such as NB, might be used as a large-scale procedure for demonstrating SARS-CoV-2 presence in olfactory neuroepithelium. Nasal brushings obtained from all the COVID-19 patients resulted positive to SARS-CoV-2 immunocytochemistry while controls were negative. Double immunofluorescence showed that SARS-CoV-2 positive cells included supporting cells as well as olfactory neurons and basal cells. OM biopsies showed an uneven distribution of SARS-CoV-2 positivity along the olfactory neuroepithelium, while OM from controls were negative. SARS-CoV-2 was distinctively found in sustentacular cells, olfactory neurons, and basal cells, supporting what was observed in NB. Ultrastructural analysis of OM biopsies showed SARS-CoV-2 viral particles in the cytoplasm of sustentacular cells. This study shows the presence of SARS-CoV-2 at the level of the olfactory neuroepithelium in patients affected by COVID-19. For the first time, we used NB as a rapid non-invasive tool for assessing a potential neuroinvasion by SARS-CoV-2 infection.

Background: People with epilepsy have a higher prevalence of behavioral and neuropsychiatric comorbidities compared to the general population and those with other chronic medical conditions, although the underlying clinical features remain unclear. The goal of the current study was to characterize behavioral profiles of adolescents with epilepsy, assess the presence of psychopathological disorders, and investigate the reciprocal interactions among epilepsy, psychological functioning, and their main clinical variables. Methods: Sixty-three adolescents with epilepsy were consecutively recruited at the Epilepsy Center, Childhood and Adolescence Neuropsychiatry Unit of Santi Paolo e Carlo hospital in Milan (five of them were excluded) and assessed with a specific questionnaire for psychopathology in adolescence, such as the Questionnaire for the Assessment of Psychopathology in Adolescence (Q-PAD). Q-PAD results were then correlated with the main clinical data. Results: 55.2% (32/58) of patients presented at least one emotional disturbance. Body dissatisfaction, anxiety, interpersonal conflicts, family problems, uncertainty about the future, and self-esteem/well-being disorders were frequently reported. Gender and poor control of seizures are associated with specific emotional features (p < 0.05). Conclusions: These findings highlight the importance of screening for emotional distress, recognition of the impairments, and provision of adequate treatment and follow-up. A pathological score on the Q-PAD should always require the clinician to investigate the presence of behavioral disorders and comorbidities in adolescents with epilepsy.

This observational study aims to characterize, from a socio-demographic and psychopathological perspective, a sample of children with Functional Neurological Disorders (FND). Thirteen paediatric patients (below 18 years old) with FND and their parents completed a battery of anamnestic and neuropsychological tests, assessing socio-demographic status, cognitive level, behavioural and emotional issues, depression, anxiety, alexithymic traits and dissociative symptoms. Five patients presented movement disorders (tremor, myoclonus and gait disorder), three patients psychogenic non-epileptic seizures and five patients sensitivity disturbances (pain, anaesthesia and paraesthesia). Cognitive profile was normal in 11 patients; academic performance was good in nine patients, but three had a diagnosis of Specific Learning Difficulty or Attention Deficit Hyperactivity Disorder. Precipitating events occurred in 11 patients. At the self-report questionnaires, mean scores close to the clinical cut off were documented with respect to affective and somatic problems. At the parent-report questionnaires, clinically significant mean scores were observed in the subscales assessing anxious–depressive symptoms and somatic complaints. We speculate that paediatric FND patients, although acknowledging the relevance of somatic symptoms, have difficulties in recognizing internal emotional states (that, instead, are easily recognized by their parents). The case of one FND patient was described. These preliminary data might help identifying different clinical phenotypes of paediatric FND.

The authors will present a comprehensive account of the neurological aspects of SARS-CoV-2 infection. The aim is to provide a practical clinical book which will serve as a guide for clinicians from all specialties involved in the management of COVID-19 patients. The authors share the extensive clinical experience gained in major hospitals in Lombardy, the first European region to face the COVID-19 emergency in 2020. All are recognized international experts in their respective fields and have been involved in the management of COVID-19 cases from the very beginning of the Italian SARS-CoV-2 outbreak. The text begins with a description of pathobiological and pathophysiological aspects related to the involvement of the nervous system, moving on to the discussion of the neurological complications observed in COVID-19 patients; these range from central to peripheral symptoms, and can occur in the acute or post-acute phases of the disease. Further topics are: neuropathology, seizures and EEG, neuroimaging, delirium, encephalomyelitis, stroke, psychopathology and psychiatry, neuropsychology and cognitive impairment, neuromuscu-lar disorders, and the impact of COVID-19 on other pre-existing neurological disorders. In addi-tion, the book will discuss the new developments in teleneurology approaches, which have been a direct response to the ongoing pandemic. Finally, the possible neurological complications of the COVID-19 vaccines and the neurological complications in children will be considered.Each chapter will present a critical review of the existing literature concerning the specific subject matter, followed by practical clinical recommendations, as well as personal considerations based on the experience gained by each author during the course of the COVID-19 pandemic.Neurology of COVID-19 will be an original and innovative reference book for clinicians of all the specialties involved in the management of patients with SARS-CoV-2 infection. ________________________________________________ List of chapters ________________________________________________

Rationale Juvenile myoclonic epilepsy (JME) and juvenile absence epilepsy (JAE) are generalized epileptic syndromes presenting in the same age range. To explore whether uneven network dysfunctions may underlie the two different phenotypes, we examined drug-naive patients with JME and JAE at the time of their earliest presentation. Methods Patients were recruited based on typical JME (n = 23) or JAE (n = 18) presentation and compared with 16 age-matched healthy subjects (HS). We analyzed their awake EEG signals by Partial Directed Coherence and graph indexes. Results Out-density and betweenness centrality values were different between groups. With respect to both JAE and HS, JME showed unbalanced out-density and out-strength in alpha and beta bands on central regions and reduced alpha out-strength from fronto-polar to occipital regions, correlating with photosensitivity. With respect to HS, JAE showed enhanced alpha out-density and out-strength on fronto-polar regions. In gamma band, JAE showed reduced Global/Local Efficiency and Clustering Coefficient with respect to HS, while JME showed more scattered values. Conclusions Our data suggest that regional network changes in alpha and beta bands underlie the different presentation distinguishing JME and JAE resulting in motor vs non-motor seizures characterizing these two syndromes. Conversely, impaired gamma-activity within the network seems to be a non-local marker of defective inhibition.

Objective: This research involved the parents of ADHD students to explore how their children coped with online distance learning during COVID-19 pandemic and what implications this schooling method had on their emotional and behavioral well-being. Method: Data were collected during lockdown using an online questionnaire addressed to 100 mothers and were compared with 184 matched controls from a national survey launched in the same period. Results: Attention span, spontaneous commitment, and autonomy in distance learning was found to be more limited in ADHD group. Compared to controls, 21.7% of ADHD students were not assessed and 40.9% did not receive grades. Behavioral changes were reported in both groups (64.2%), represented mainly by restlessness, aggressiveness, and anxiety. Conclusion: Distance education increases academic difficulties, especially in ADHD pupils. The effects of lockdown should be adequately evaluated upon school reopening and appropriate recovery interventions should be planned.

Borderline intellectual functioning (BIF) is a multifactorial condition in which both genetic and environmental factors are likely to contribute to the clinical outcome. Abnormal cortical development and lower IQ scores were shown to be correlated in BIF children, but the genetic components of this condition and their possible connection with intelligence and brain morphology have never been investigated in BIF. The synaptosomal-associated protein of 25 kD (SNAP-25) is involved in synaptic plasticity, neural maturation, and neurotransmission, affecting intellectual functioning. We investigated SNAP-25 polymorphisms in BIF and correlated such polymorphisms with intelligence and cortical thickness, using socioeconomic status and environmental stress as covariates as a good proxy of the variables that determine intellectual abilities. Thirty-three children with a diagnosis of BIF were enrolled in the study. SNAP-25 polymorphisms rs363050, rs363039, rs363043, rs3746544, and rs1051312 were analyzed by genotyping; cortical thickness was studied by MRI; intelligence was measured using the WISC-III/IV subscales; environmental stressors playing a role in neuropsychiatric development were considered as covariate factors. Results showed that BIF children carrying the rs363043(T) minor allele represented by (CT + TT) genotypes were characterized by lower performance Perceptual Reasoning Index and lower full-scale IQ scores (p = 0.04) compared to those carrying the (CC) genotype. This association was correlated with a reduced thickness of the left inferior parietal cortex (direct effect = 0.44) and of the left supramarginal gyrus (direct effect = 0.56). These results suggest a link between SNAP-25 polymorphism and intelligence with the mediation role of brain morphological features in children with BIF.

Background Epilepsy is a main feature of Mowat Wilson Syndrome (MWS), a congenital malformation syndrome caused by ZEB2 variants. The aim of this study was to investigate the long-term evolution of the electroclinical phenotype of MWS in a large population. Methods Forty-individuals with a genetically confirmed diagnosis were enrolled. Three age groups were identified (t1 = 0–4; t2 = 5–12; t3 = >13 years); clinical data and EEG records were collected, analyzed, and compared for age group. Video-EEG recorded seizures were reviewed. Results Thirty-six of 40 individuals had epilepsy, of whom 35/35 aged >5 years. Almost all (35/36) presented focal seizures at onset (mean age at onset 3.4 ± 2.3 SD) that persisted, reduced in frequency, in 7/22 individuals after the age of 13. Absences occurred in 22/36 (mean age at onset 7.2 ± 0.9 SD); no one had absences before 6 and over 16 years old. Paroxysmal interictal abnormalities in sleep also followed an age-dependent evolution with a significant increase in frequency at school age (p = 0.002) and a reduction during adolescence (p = 0.008). Electrical Status Epilepticus during Sleep occurred in 14/36 (13/14 aged 5–13 years old at onset). Seven focal seizure ictal video-EEGs were collected: all were long-lasting and more visible clinical signs were often preceded by prolonged electrical and/or subtle (erratic head and eye orientation) seizures. Valproic acid was confirmed as the most widely used and effective drug, followed by levetiracetam. Conclusions Epilepsy is a major sign of MWS with a characteristic, age-dependent, electroclinical pattern. Improvement with adolescence/adulthood is usually observed. Our data strengthen the hypothesis of a GABAergic transmission imbalance underlying ZEB2-related epilepsy.

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition, whose etiology remains poorly understood in most cases. Several genetic, epigenetic and environmental factors have been implicated in ASD pathogenesis and numerous studies have provided evidences for increased levels of oxidative stress and reduced antioxidant capacity in patients with ASD. Recent clinical trials explored supplementation with antioxidant agents as a potential therapeutic strategy for ASD, investigating the impact of this treatment on behavioral symptoms and on most common comorbidities of the disease, including sleep disturbances. Among all medical conditions associated to ASD, sleep problems are highly prevalent and are supposed to be positively related to the severity of the disease. Moreover, studies on animal models support the hypothesis of a relationship between oxidative stress and sleep deprivation. The aim of this review is to summarize the current state of the literature on the effect of antioxidant treatment on sleep disturbances in patients with ASD. Twenty-one articles were included in final synthesis. Of them, 15 studies involved Melatonin, 1 Tryptophan and 5 focused on supplementation with other antioxidant agents (namely Coenzyme Q10, L-Carnosine, Luteolin and Quercetin). Despite the high prevalence of comorbid sleep troubles in ASD, there is a paucity of data on the efficacy of antioxidant agents in those patients. Further research is needed to better define the role of antioxidants agents as adjunctive therapy in the management sleep disorders in children and adolescents affected with ASD.

Ruxolitinib is a highly potent JAK2 inhibitor approved for the treatment of myelofibrosis (idiopathic or post-polycythemia vera or post-essential thrombocythemia) and, more recently, for polycythemia vera with an inadequate response to or intolerant of hydroxyurea. The most common adverse events of ruxolitinib include immunosuppression with an increased risk of reactivation of silent infections and increased non-melanoma skin cancer. The known neurological side effects of ruxolitinib are dizziness and headache, but no neurological paroxysmal episodes have been recorded. This report deals with an 80-year-old outpatient woman with polycythemia vera turned into myelofibrosis who experienced neurological episodes of hypoesthesia and weakness of right arm and leg during ruxolitinib treatment.

Transient loss of consciousness initially diagnosed as epileptic seizures and then documented as paroxysmal atrioventricular block. Cardiac resynchronization and defibrillator therapy guided by a multimodality approach.

AIM To improve the genetic, clinical, and neuroradiological characterization of cerebellar involvement in tuberous sclerosis complex (TSC) and determine whether cerebellar lesions could be a reliable biomarker of neurological impairment. METHOD This retrospective cohort study, held at two tertiary paediatric university centres, was conducted on patients with a confirmed diagnosis of TSC who underwent brain magnetic resonance imaging between October 2009 and May 2016. The study population consisted of 112 patients with TSC (median age 10y; range 5mo-38y; 61 females, 51 males). RESULTS The results from multivariable statistical analysis indicated that cerebellar involvement (34 out of 112 patients, none carrying a TSC1 mutation) was the most powerful predictor of supratentorial cortical tuber load; however, cerebellar involvement was not the best predictor of clinical phenotype when supratentorial tuber load and TSC2 mutations were taken into consideration. The association between cerebellar lesions and a more severe clinical and neuroradiological phenotype was statistically significant and may be due to its strong association with TSC2 mutations and higher cortical tuber load. INTERPRETATION Cerebellar involvement is not the best predictor of neurobehavioural outcome, including TSC-related autism, after adjusting for TSC2 and the number of cortical tubers. Its role in the TSC clinical phenotype needs to be investigated further. WHAT THIS PAPER ADDS Cerebellar involvement is a powerful predictor of supratentorial cortical involvement and a potential biomarker of disease severity. Cerebellar lesions significantly correlate with a more severe clinical and neuroradiological phenotype. Cerebellar involvement is not the best predictor of neurobehavioural outcome.

Recent results show that in mainland Italian children with Autism spectrum disorder (ASD), HLA-G coding alleles distribution is skewed and an association between HLA-G*01:05N and ASD is present. Herein, in an independent cohort of Sardinian ASD (sASD) children and their relatives, we verify whether HLA-G allele association with ASD could be confirmed in this genetically peculiar insular population. One hundred children with a diagnosis of ASD, born in Sardinia and of Sardinian descent, 91 of their mothers, and 40 of their healthy siblings were enrolled. DNA sequencing analysis of HLA-G exon 2, 3 and 4 was used to obtain HLA-G allelic frequencies. Alleles distribution was compared with that of continental ASD children and with a control group of Caucasoid couples of multiparous women and their partners from Brazil and Denmark. Skewing of HLA-G allele distribution was replicated in sASD children; in particular, the HLA-G*01:03 allele, associated with reduced fetal tolerogenicity and development of myeloid leukemia, was more common in both ASD groups compared to controls (pc = 1 × 10−3; OR:3.5, 95%CI: 1.8–6.8). However, given the lack of data on HLA-G*01:03 allelic distribution among Sardinian healthy subjects, we cannot exclude a population effect. These data confirm an association of HLA-G locus with ASD development, particularly with those alleles linked to a lower expression of tolerogenic HLA-G protein, thus warranting further studies on HLA-G polymorphism distribution in different ASD populations.

Objectives This research investigates level of empowerment, decisional skills, and the perceived relationship with the clinician, of women in childbirth age, also in relationship with clinical variables such as epilepsy type, seizure frequency, therapy, and pregnancy status. In particular, as concerning therapy, we were interested in women who take valproic acid (VPA), for its specific balance of risks and benefits, especially in pregnant women. Methods The sample is composed of 60 women with epilepsy (6 were excluded), who underwent a standardized clinical protocol for assessment of level of empowerment, decisional skills, and of their judgment about how they feel to be involved by their clinician in medical decision making. Results Overall, the sample does not show signs of low empowerment level nor of abnormal decision-making patterns. The type of epilepsy, the frequency of seizures, and the treatment type (VPA versus no VPA) do not impact on empowerment, on decision styles, nor on medical relationship, with the only exception of a specific decision style, the avoidant style, that is more frequent in women treated with VPA with respect to those taking other therapies. Interestingly, regarding VPA dosage, we found that women taking equal or more than 700 mg/day of VPA have lower scores on empowerment in all dimensions compared with women with a VPA dosage lower than 700 mg/day. Conclusions Shared decision making including improved decision quality, more informed choices and better treatment concordance, should be a central part of epilepsy care. In addition, for clinicians it would be useful to have specific tools to know if the patient has really understood the risks and benefits of antiepileptic drugs (AEDs), particularly VPA, and all treatment alternatives.

Summary Aims Irritability has been described as a frequent adverse event in patients affected by epilepsy and treated with perampanel (PER), levetiracetam (LEV), and less frequently with valproic acid (VPA). Since the questionnaire for irritability (I‐EPI) is a validated instrument to measure this psychiatric manifestation in patients affected by epilepsy, in this study we aimed at investigating the effect of PER as first add‐on therapy on I‐EPI. Moreover, we compared the effectiveness and I‐EPI scores obtained at 12‐month follow‐up visits in patients treated by PER, LEV, or VPA in order to measure irritability as a consequence of these treatments. Methods We collected data from 17 patients treated by PER, 16 patients treated by LEV, and 16 patients under VPA treatment followed for 12 months. Results We did not document significant changes of I‐EPI questionnaire between baseline and follow‐up in the PER group. As concerning the comparison of I‐EPI among PER, LEV, and VPA groups, we documented lower global scores in PER than both LEV (P < 0.05) and VPA (P < 0.05) groups. Moreover, patients under PER treatment showed lower scores than LEV and VPA (P < 0.05) in I‐EPI items measuring the gentle personality, anxiety of having epileptic seizures in front of others, and irritability in thinking that they can have an epileptic seizure. Conclusions This retrospective study described a stable and possibly lower degree of irritability in patients starting PER than LEV and VPA treatments, although we documented the comparable effectiveness of PER, LEV, and VPA as first add‐on treatments in patients affected by uncontrolled epileptic seizures. However, the small sample of patients included in this study and the absence of I‐EPI scores obtained at baseline visits in LEV and VPA groups require further investigations to confirm this preliminary evidence.

In March 2020, northern Italy became the second country worldwide most affected by Covid-19 and the death toll overtook that in China. Hospital staff soon realized that Covid-19 was far more severe than expected from the few data available at that time. The Covid-19 pandemic forced hospitals to adjust to rapidly changing circumstances. We report our experience in a general teaching hospital in Milan, the capital of Lombardy, the most affected area in Italy. First, we briefly describe Lombardy's regional Covid-19-related health organizational changes as well as general hospital reorganization. We also provide a multidisciplinary report of the main clinical, radiological and pathological Covid-19 findings we observed in our patients.

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.

Background: Purified cannabidiol (CBD) was administered to highly refractory patients with Dravet (DS) or Lennox–Gastaut (LGS) syndromes in an ongoing expanded access program (EAP). Herein, we report interim results on CBD safety and seizure outcomes in patients treated for a 12-month period.Material and Methods: Thirty centers were enrolled from December 2018 to December 2019 within the open-label prospective EAP up to a maximum of 25 mg/kg per day. Adverse effects and liver function tests were assessed after 2 weeks; 1, 3, and 6 months of treatment; and periodically thereafter. Seizure endpoints were the percentage of patients with ≥50 and 100% reduction in seizures compared to baseline.Results: A total of 93 patients were enrolled and included in the safety analysis. Eighty-two patients [27 (32.9%) DS, 55 (67.1%) LGS] with at least 3 months of treatment have been included in the effectiveness analysis; median previously failed antiseizure medications was eight. Pediatric and adult patients were uniformly represented in the cohort. At 3-month follow-up, compared to the 28-day baseline period, the percentage of patients with at least a 50% reduction in seizure frequency was 40.2% (plus 1.2% seizure-free). Retention rate was similar according to diagnosis, while we found an increased number of patients remaining under treatment in the adult group. CBD was mostly coadministered with valproic acid (62.2%) and clobazam (41.5%). In the safety dataset, 29 (31.2%) dropped out: reasons were lack of efficacy [16 (17.2%)] and adverse events (AEs) [12 (12.9%)], and one met withdrawal criteria (1.1%). Most reported AEs were somnolence (22.6%) and diarrhea (11.9%), followed by transaminase elevation and loss of appetite.Conclusions: CBD is associated with improved seizure control also in a considerable proportion of highly refractory patients with DS and LGS independently from clobazam use. Overall, CBD safety and effectiveness are not dose-related in this cohort.

To date only five patients with 8p23.2-pter microdeletions manifesting a mild-to-moderate cognitive impairment and/or developmental delay, dysmorphisms and neurobehavioral issues were reported. The smallest microdeletion described by Wu in 2010 suggested a critical region (CR) of 2.1 Mb including several genes, out of which FBXO25, DLGAP2, CLN8, ARHGEF10 and MYOM2 are the main candidates. Here we present seven additional patients with 8p23.2-pter microdeletions, ranging from 71.79 kb to 4.55 Mb. The review of five previously reported and nine Decipher patients confirmed the association of the CR with a variable clinical phenotype characterized by intellectual disability/developmental delay, including language and speech delay and/or motor impairment, behavioral anomalies, autism spectrum disorder, dysmorphisms, microcephaly, fingers/toes anomalies and epilepsy. Genotype analysis allowed to narrow down the 8p23.3 candidate region which includes only DLGAP2, CLN8 and ARHGEF10 genes, accounting for the main signs of the broad clinical phenotype associated to 8p23.2-pter microdeletions. This region is more restricted compared to the previously proposed CR. Overall, our data favor the hypothesis that DLGAP2 is the actual strongest candidate for neurodevelopmental/behavioral phenotypes. Additional patients will be necessary to validate the pathogenic role of DLGAP2 and better define how the two contiguous genes, ARHGEF10 and CLN8, might contribute to the clinical phenotype.

Ring chromosome 20 [r(20)] syndrome is a rare condition characterized by a non-supernumerary ring chromosome 20 replacing a normal chromosome 20. It is commonly seen in a mosaic state and is diagnosed by means of karyotyping. r(20) syndrome is characterized by a recognizable epileptic phenotype with typical EEG pattern, intellectual disability manifesting after seizure onset in otherwise normally developing children, and behavioral changes. Despite the distinctive phenotype, many patients still lack a diagnosis—especially in the genomic era—and the pathomechanisms of ring formation are poorly understood. In this review we address the genetic and clinical aspects of r(20) syndrome, and discuss differential diagnoses and overlapping phenotypes, providing the reader with useful tools for clinical and laboratory practice. We also discuss the current issues in understanding the mechanisms through which ring 20 chromosome causes the typical manifestations, and present unpublished data about methylation studies. Ultimately, we explore future perspectives of r(20) research. Our intended audience is clinical and laboratory geneticists, child and adult neurologists, and genetic counselors.

Background. The novel coronavirus (SARS-COV-2) and related syndrome (COVID-19) has required a worldwide measure of quarantine with severe consequences for millions of people. Methods. Since psychopathological consequences related to social restrictions have been reported, a systematic review according to Cochrane Collaboration guidelines and the PRISMA Statement was performed to quantify the effects of quarantine on mental health of adults. Major databases - Pubmed, Scopus, Embase, PsycInfo, and Web of Science- were researched for observational studies with data on mental health indexes related to quarantine or isolation for epidemic infections. Results. Twenty-one independent studies were included for 82,312 subjects. Conclusions. The results showed that at least 20% of people exposed to these conditions reported a psychological distress, with a prevalence of PTSD, depression and, less often, generalized anxiety. Important methodological bias weakens the conclusion of most studies, opening to the need of further research on mental health after quarantine and related risk/buffering factors.

Background: Given the paucity of data concerning the care of adolescents attending an emergency department (ED) for mental disorders, we performed an observational study with the aim to describe psychotropic drug use in an Italian ED. Methods: A retrospective chart review of adolescents (13&ndash, 17 years) visited in the ED of the San Paolo University Hospital in Milan for mental disorders between January and June 2018 was conducted. Information concerning age, gender, type of disorder, psychotropic drug use in the ED and outcome of the visit were analyzed, using an anonymous patient code. Results: A total of 1298 adolescents, 13&ndash, 17 years old, were visited in the ED, 56 (4%) of whom had a diagnosis of mental disorder (34 females and 22 males). The most common disorder was anxiety (21 patients), followed by predominant psychomotor disorder (13 patients). In all, 30 adolescents received a psychotropic drug. Benzodiazepines were the most commonly used drugs (73% of the subjects), and delorazepam was administered/prescribed to 17 adolescents, despite the fact that evidence on its safety, efficacy, and its off-label use in the pediatric population is lacking. Conclusions: One out of two adolescents attending the ED for an acute episode of mental disorder received a psychotropic drug prescription, mainly in an off-label manner. More evidence is needed to guide the pharmacological management of acute episodes of mental disorders.

Background Rett syndrome is a complex genetic disorder with age-specific manifestations and over half of the patients surviving into middle age. However, little information about the phenotype of adult individuals with Rett syndrome is available, and mainly relies on questionnaires completed by caregivers. Here, we assess the clinical manifestations and management of adult patients with Rett syndrome and present our experience in transitioning from the paediatric to the adult clinic. Methods We analysed the medical records and molecular data of women aged ≥18 years with a diagnosis of classic Rett syndrome and/or pathogenic variants in MECP2, CDKL5 and FOXG1, who were in charge of our clinic. Results Of the 50 women with classic Rett syndrome, 94% had epilepsy (26% drug-resistant), 20% showed extrapyramidal signs, 40% sleep problems and 36% behavioural disorders. Eighty-six % patients exhibited gastrointestinal problems; 70% had scoliosis and 90% low bone density. Breathing irregularities were diagnosed in 60%. None of the patients had cardiac issues. CDKL5 patients experienced fewer breathing abnormalities than women with classic Rett syndrome. Conclusion The delineation of an adult phenotype in Rett syndrome demonstrates the importance of a transitional programme and the need of a dedicated multidisciplinary team to optimise the clinical management of these patients.

Background: Knowledge is increasing about TSC-Associated Neuropsychiatric Disorders (TAND), but little is known about the potentially confounding effects of intellectual ability (IA) on the rates of TAND across age, sex, and genotype. We evaluated TAND in (a) children vs. adults, (b) males vs. females, and (c) TSC1 vs. TSC2 mutations, after stratification for levels of IA, in a large, international cohort.Methods: Individuals of any age with a documented visit for TSC in the 12 months prior to enrolment were included. Frequency and percentages of baseline TAND manifestations were presented by categories of IA (no intellectual disability [ID, intelligence quotient (IQ)>70]; mild ID [IQ 50–70]; moderate-to-profound ID [IQ

Background Seizures in individuals affected by tuberous sclerosis complex (TSC) commonly develop in the first year of life, are often preceded by a progressive deterioration of the electroencephalogram (EEG), and likely influence developmental outcome. Although early diagnosis of TSC has offered a tremendous opportunity to monitor affected patients before seizure onset, reports of the neurological manifestations of TSC in infants before seizure onset are still scarce. Here we describe early EEG activity, clinical and genetic data and developmental assessment in a group of TSC infants, with the aim of identifying possible prognostic factors for neurodevelopmental outcome. Methods We report on six infants diagnosed with TSC pre- or perinatally, who underwent serial Video-EEG recordings during the first two years of life. EEGs were classified based on distribution and intensity of interictal epileptiform discharges, and Vigabatrin was introduced in case of ictal discharges. Psychomotor development, cognitive functioning and behavioral problems were assessed through standardized scales. Molecular testing included analysis for point mutations and deletions/duplications in TSC1 and TSC2. Results EEG abnormalities appeared at a mean age of 4 months. Four of the six patients developed seizures. EEG abnormalities preceded the onset of clinical seizures in all of them. The two individuals with good seizure control showed normal development, while the other two exhibited psychomotor delays. The patients who did not develop seizures had normal development. A pathogenic variant in the TSC2 gene was detected in all patients but one. The one without a mutation identified did not develop seizures and showed normal neurodevelopment. Of note, the two patients presenting with the worst outcome (that is, poor seizure control and intellectual/behavioral disability) both carried pathogenic variants in the GAP domain of TSC2. Conclusion Our report supports the importance of EEG monitoring before seizure onset in patients with TSC, and the correlation between prompt seizure control and positive neurodevelopmental outcome, regardless of seizure type. Our results also indicate a possible role of the genetic background in influencing the outcome.

Background: Transcranial Direct Current Stimulation (tDCS) combined with traditional rehabilitative techniques has not been widely applied to Rett Syndrome (RTT). The aim of this study was to examine the effects of combined cognitive traditional training with tDCS applied to attention and language measures in subjects with RTT. Methods: 31 subjects with RTT were randomly allocated into two groups: non-sham tDCS (n = 18) and sham tDCS (n = 13). The former received the integrated intervention non-sham tDCS plus cognitive empowerment during the treatment phase. The latter received sham stimulation plus cognitive empowerment. All participants underwent neurological and cognitive assessment to evaluate attention and language measures: before integrated treatment (pre-test phase), at the conclusion of the treatment (post-test phase), and at 1 month after the conclusion of the treatment (follow-up phase). Results: the results indicated longer attention time in the non-sham tDCS group compared to the sham tDCS group with a stable trend also in the follow-up phase, an increase of the number of vowel/phoneme sounds in the non-sham tDCS group, and an improvement in the neurophysiological parameters in the non-sham tDCS group. Conclusions: This study supports the use of tDCS as a promising and alternative approach in the RTT rehabilitation field.

Background: The new coronavirus (SARS-CoV-2) shows several similarities with previous outbreaks of Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) Aim of this systematic review and meta-analysis is to provide evidence of the psychopathologic burden on health care workers (HCWs) of the first two deadly coronavirus outbreaks to get lessons for managing the current burden of COVID-19 outbreak Method: According to Cochrane Collaboration guidelines and the PRISMA Statement, the study quantified the effects of frontline work on mental health of HCWs Major databases — Pubmed, Scopus, Embase, Medline, and Web of Science — were searched for observational and case-control studies evaluating mental health indexes reported by front-line work This study computed the percentage of sample that reported clinically significant levels of psychiatric symptoms Cohen’s d was used for comparing mental health outcomes of health care workers directly involved in addressing pandemic emergency with a control group that was not directly exposed to such conditions Pooled effect sizes (dw) were estimated whenever at least three independent studies yielded data Heterogeneity of findings and bias of publication were estimated as well Findings: Fifteen studies have been selected for a total of 7,393 HCWs From 9 6% to 51% of HCWs reported symptoms of Post-Traumatic Stress Disorder (PTSD) and from 20% to 75% reported psychiatric symptoms, with a prevalence of anxiety and depression From one to the three years after outbreak, from 2% to 19% reported PTSD symptoms and from 5% to 90% psychiatric symptoms Interestingly, HWCs who were directly involved in pandemic emergency showed significantly higher depressive and anxious symptoms (dw = 66 ( 46– 85);p < 001) than ones who were not directly exposed Similarly, the direct involvement significantly affected the severity of PTSD symptoms (dw = 30 ( 21– 39);p < 001) Conclusion: Health care professionals in general and most of all frontline workers showed an association with a likely risk of developing psychiatric disorders following outbreaks and for at least three years later Mental health interventions for professionals exposed to COVID-19 need to be immediately implemented Further studies are warranted to investigate long-term consequences carefully, and to look for mediating and buffering factors as well The role of clinical psychologists and psychiatrists in delivering adequate interventions is critically important © Copyright © 2020 Galli, Pozzi, Ruggiero, Mameli, Cavicchioli, Barbieri, Canevini, Priori, Pravettoni, Sani and Ferrucci

An adverse social environment is a major risk factor for borderline intellectual functioning (BIF), a condition characterized by an intelligence quotient (IQ) within the low range of normality (70–85) with difficulties in the academic achievements and adaptive behavior. Children with BIF show impairments in planning, language, movement, emotion regulation, and social abilities. Moreover, the BIF condition exposes children to an increased risk of school failures and the development of mental health problems, and poverty in adulthood. Thus, an early and effective intervention capable of improving the neurodevelopmental trajectory of children with BIF is of great relevance. Aim The present work aims to report the results of a randomized controlled trial (RCT) in which an intensive, integrated and innovative intervention, the movement cognition and narration of the emotions (MCNT) was compared to standard speech therapy (SST) for the treatment of children with BIF. Methods This was a multicenter, interventional, single blind RCT with two groups of children with BIF: the experimental treatment (MCNT) and the treatment as usual (SST). A mixed factorial ANOVA was carried out to assess differences in the effectiveness between treatments. Primary outcome measures were: WISC III, Child Behavior Checklist (CBCL), Vineland II, and Movement ABC. Results MCNT proved to be more effective than SST in the increment of full-scale IQ (p = 0.0220), performance IQ (p < 0.0150), socialization abilities (p = 0.0220), and behavior (p = 0.0016). No improvement was observed in motor abilities. Both treatments were linked to improvements in verbal memory, selective attention, planning, and language comprehension. Finally, children in the SST group showed a significant worsening in their behavior. Conclusion Our data show that an intensive and multimodal treatment is more effective than a single domain treatment for improving intellectual, adaptive and behavioral functioning in children with BIF. These improvements are relevant as they might represent protective factors against the risk of school failure, poverty and psychopathology to which children with BIF are exposed in the adult age. Limitations of the study are represented by the small number of subjects and the lack of a no-treatment group. Clinical Trial Registration ISRCTN Registry (isrctn.com), identifier ISRCTN81710297.

Healthcare transition from childhood to adulthood is required to ensure continuity of care of an increasing number of individuals with chronic conditions surviving into adulthood. The transition for patients with tuberous sclerosis complex (TSC) is complicated by the multisystemic nature of this condition, age-dependent manifestations, and high clinical variability and by the presence of intellectual disability in at least half of the individuals. In this article, we address the medical needs regarding each TSC-related manifestation in adulthood, and the services and support required. We review existing models of transition in different chronic conditions, discuss our experience in transitioning from the pediatric to the adult TSC Clinic at our Institution, and propose general rules to follow when establishing a transition program for TSC. Although a generalizable transition model for TSC is likely not feasible for all Institutions, a multidisciplinary TSC clinic is probably the best model, developed in accordance with the resources available and country-specific healthcare systems. Coordination of care and education of the adult team should be always sought regardless of the transition model.

Sleep and epilepsy interact with each other in a complex bidirectional way. The main objective of this study was to characterize and determine the prevalence of sleep and behavioral disorders among Italian children and adolescents with epilepsy. We asked 84 consecutive parents/caregivers of patients with epilepsy aged between 6 and 17 years old to fill out the Sleep Disturbances Scale for Children (SDSC) and Child Behavior Checklist (CBCL). An abnormal total sleep score was found in 20 subjects with epilepsy (23.8%), compared with 4 (4.4%) of control group (P .001). Forty-eight patients (57.1%) had an abnormal score in at least one SDSC factor: disorders in initiating and maintaining sleep (DIMS; 13.1%), sleep breathing disorders (SBD; 13.1%), disorders of arousal (DA; 5.9%), sleep-wake transition disorders (SWTD; 15.5%), disorders of excessive somnolence (DOES; 20.2%), and sleep hyperhidrosis (SHY; 5.9%). Patients with epilepsy showed higher prevalence of behavioral/emotional disturbances in all CBCL domains but one compared with patients without epilepsy. The SDSC and CBCL total scores showed a significant correlation (R-square = 0.256; P .001). Sleep and behavioral/emotional disorders are common in epilepsy during childhood and adolescence. The SDSC could be a valid tool to screen sleep disturbances in this group of patients.