Search

Objective: Lennox-Gastaut syndrome (LGS) is a severe form of epilepsy characterized by difficult-to-control seizures and cognitive dysfunction. Previous studies mainly focused on pediatric populations, and little is known about the long-term cognitive outcome in adult patients with LGS. The objective of this study was to investigate the long-term functional and adaptive behavior in adult patients with LGS., Methods: This cross-sectional study enrolled adult patients diagnosed with LGS according to the recently published International League Against Epilepsy (ILAE) diagnostic criteria. The adaptive behavior of participants was assessed using the Vineland Adaptive Behavior Scales, Survey Interview, Second Edition (VABS-II). Demographic, clinical, electroencephalography (EEG), and antiseizure medication (ASM) data were also collected at different timepoints, to investigate their association with VABS-II scores., Results: The study included 38 adult patients with LGS. A low score on the Adaptive Behavior Composite Scale was found in all patients. When considering single VABS-II domains, particularly low scores were found in daily living skills and socialization, whereas slightly higher performances were observed in communication. An earlier age at LGS diagnosis was identified as the most significant predictor of worse adaptive outcomes in adult life. At the time of study evaluation, high seizure frequency, higher EEG background slowing, and multifocal EEG epileptiform abnormalities were significantly associated with lower VABS-II raw scores. Furthermore, in an exploratory correlation analysis with ASM regimen at the study visit, treatment with cannabidiol was associated with higher adaptive behavior scores, whereas benzodiazepine intake correlated with lower scores., Significance: This study provides relevant insights into the long-term challenges faced by adults with Lennox-Gastaut syndrome (LGS), highlighting significant impairments in adaptive behavior as well as the associated clinical and electroencephalography features. Additionally, this study provides a more specific neuropsychological profile in adults with LGS and underscores the importance of comprehensive care approaches that go beyond seizure control in this population., Plain Language Summary: This study examined adults with Lennox-Gastaut syndrome (LGS), a severe type of epilepsy, to understand their long-term abilities to perform daily tasks and adapt socially. We found that these adults have significant difficulties with daily living and social skills, although not all areas were equally affected. They performed somewhat better in communication, particularly in understanding others (receptive communication). Importantly, the younger the age at which LGS was diagnosed, the worse their outcomes were as adults. This study highlights the need for research and treatment approaches that focus not only on controlling seizures but also on improving daily life skills., (© 2024 The Author(s). Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Pain is an unpleasant sensory and emotional experience. Adequate pain control is often challenging, particularly in patients with chronic pain. Despite advances in pain management, drug addiction, overtreatment, or substance use disorders are not rare. Hence the need for further studies in the field. The substantial progress made over the last decade has revealed genes, signalling pathways, molecules, and neuronal networks in pain control thus opening new clinical perspectives in pain management. In this respect, data on the epigenetic modulation of opioid and cannabinoid receptors, key actors in the modulation of pain, offered new perspectives to preserve the activity of opioid and endocannabinoid systems to increase the analgesic efficacy of opioid- and cannabinoid-based drugs. Similarly, upcoming data on cannabidiol (CBD), a non-psychoactive cannabinoid in the marijuana plant Cannabis sativa , suggests analgesic, anti-inflammatory, antioxidant, anticonvulsivant and ansiolitic effects and supports its potential application in clinical contexts such as cancer, neurodegeneration, and autoimmune diseases but also in health and fitness with potential use in athletes. Hence, in this review article, we summarize the emerging epigenetic modifications of opioid and cannabinoid receptors and focus on CBD as an emerging non-psychoactive cannabinoid in pain management in clinical practice, health, and fitness.

Background: The primary aims of our cross-sectional observational study were: (i) to determine the prevalence of depressive symptoms in children and adolescents with epilepsy compared to controls and (ii) to explore the difference in depressive symptoms in patients with epilepsy only and those with epilepsy and primary headache as a comorbidity. The secondary objective was to explore parental stress levels., Methods: 68 pediatric patients aged 6-18 years (44 with epilepsy only and 24 with epilepsy and headache) and 50 controls were recruited. Depressive profile and parental stress were assessed using Children's Depression Inventory, Second Edition (CDI-2) and Parenting Stress Index-Short Form (PSI-SF)., Results: The group with epilepsy showed significantly high depressive symptoms and parental stress compared to controls. The patients with headache in comorbidity experienced more depressive symptoms than those with epilepsy only., Conclusion: Depressive symptoms are more prevalent in patients who have comorbid epilepsy and primary headache; therefore, the neurological/psychological mechanisms underlying this condition should be further investigated. The simultaneous presence of epilepsy, headache and depressive symptoms impacts the quality of life of patients and their parents, increasing parental stress and family management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Pastorino, Olivieri, Viggiano, Meccariello, Roccella, Parisi, Cerulli Irelli, Di Bonaventura, Orsini and Operto.)

Aim: The current study aims to investigate the effect of Executive Functions (EFs) on Health Related Quality of Life (HRQoL) in a cohort of children with self-limited epilepsy with centrotemporal spikes (SeLECTS) and to identify possible factors that impact HRQoL specifically related to epilepsy-related variables and EFs skills., Material and Method: The Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL) and The Behavior Rating Inventory of Executive Function (BRIEF-2 and BRIEF-P) were completed by the parents of 129 patients with SeLECTS. Demographic variables and epilepsy-related variables were collected., Results: Our sample performed in the average range across all the subscales and summary scores of the PedsQL and performed in the normal range of the BRIEF questionnaire. We observed that a lower functioning in EFs was associated with lower overall HRQoL scores. We explored the relationship between epilepsy characteristics and scores on the PedsQL. We found that the use of antiseizure medications (ASMs), longer duration of the treatment, and a higher seizure frequency were associated with a lower HRQoL. Moreover, we observed that executive dysfunction was a significant predictor of reduced HRQoL., Conclusion: Our results suggest the importance of the identification of patients with SeLECTS with a high level of risk for a poor HRQoL. We may now add executive dysfunction to the list of known risk factors for poor HRQoL in children with SeLECTS, along with such factors as seizure frequency, recent seizures, use of ASMs and longer duration of therapy. The early identification of children with SeLECTS at risk of a poor HRQoL could allow the activation of adequate interventions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Male reproduction is under the control of the hypothalamus-pituitary-gonadal (HPG) axis. The endocannabinoid system (ECS) and the kisspeptin system (KS) are two major signaling systems in the central and peripheral control of reproduction, but their possible interaction has been poorly investigated in mammals. This manuscript analyzes their possible reciprocal modulation in the control of the HPG axis., Materials and Methods: Adolescent male rats were treated with kisspeptin-10 (Kp10) and endocannabinoid anandamide (AEA), the latter alone or in combination with the type 1 cannabinoid receptor (CB1) antagonist rimonabant (SR141716A). The hypothalamic KS system and GnRH expression, circulating sex steroids and kisspeptin (Kiss1) levels, and intratesticular KS and ECS were evaluated by immunohistochemical and molecular methods. Non-coding RNAs (i.e., miR145-5p , miR-132-3p , let7a-5p , let7b-5p ) were also considered., Results: Circulating hormonal values were not significantly affected by Kp10 or AEA; in the hypothalamus, Kp10 significantly increased GnRH mRNA and aromatase Cyp19, Kiss1, and Kiss1 receptor (Kiss1R) proteins. By contrast, AEA treatment affected the hypothalamic KS at the protein levels, with opposite effects on the ligand and receptor, and SR141716A was capable of attenuating the AEA effects. Among the considered non-coding RNA, only the expression of miR145-5p was positively affected by AEA but not by Kp10 treatment. Localization of Kiss1+/Kiss1R+ neurons in the arcuate nucleus revealed an increase of Kiss1R-expressing neurons in Kp10- and AEA-treated animals associated with enlargement of the lateral ventricles in Kp10-treated animals. In the brain and testis, the selected non-coding RNA was differently modulated by Kp10 or AEA. Lastly, in the testis, AEA treatment affected the KS at the protein levels, whereas Kp10 affected the intragonadal levels of CB1 and FAAH, the main modulator of the AEA tone. Changes in pubertal transition-related miRNAs and the intratesticular distribution of Kiss1, Kiss1R, CB1, and CB2 following KP and AEA treatment corroborate the KS-ECS crosstalk also showing that the CB1 receptor is involved in this interplay., Conclusion: For the first time in mammals, we report the modulation of the KS in both the hypothalamus and testis by AEA and revealed the KP-dependent modulation of CB1 and FAAH in the testis. KP involvement in the progression of spermatogenesis is also suggested., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Marino, D’Auria, Mele, Pastorino, Di Pietro, D’Angelo, Della Rocca, Operto, Vecchione, Fasano, Pierantoni, Viggiano, Meccariello and Santoro.)

(1) Background: The principal aim of our research was to explore the relationship between digital devices use and fine motor skills in children aged three to six years and to explore the effect of some socio-demographic factors. (2) Methods: we enrolled 185 children aged between three to six years. The parents of all the participants fulfilled a questionnaire to explore the digital device use, and their children performed a standardized test to assess fine motor skills (APCM-2). We performed the Spearman correlation test to explore the relationship between different variables. (3) Results: the children spent an average of 3.08 ± 2.30 h/day on digital devices. We did not find a significant association between the time of use of digital devices and fine motor skills ( p = 0.640; r = -0.036). The youngest children experienced digital tools earlier than older ones ( p < 0.001; r = 0.424) and they were also the ones who used digital tools more time afterwards ( p = 0.012; -0.202). The children who had working parents spent more time on digital devices ( p = 0.028; r = 0.164/ p = 0.037; r = 0.154) and used digital devices earlier ( p = 0.023; r = 0.171). (4) Conclusions: This data suggest that it would be useful to monitor the use of digital tools, especially in the very first years of life. Future studies are needed to further explore this topic.

Introduction: Few studies have focused on the long-term effects of the COVID-19 pandemic on mental health. The objective of our work was to evaluate the changes in emotional and behavioral symptoms in patients with neuropsychiatric disorders and the impact on parenting stress 1 year after the first national lockdown., Methods: We enrolled 369 patients aged 1.5-18 years of age referred to the Child and Adolescent Neuropsychiatry Unit of the University Hospital of Salerno (Italy) by their parents. We asked their parents to complete two standardized questionnaires for the assessment of emotional/behavioral symptoms (Child Behavior CheckList, CBCL) and parental stress (Parenting Stress Index, PSI) prior to the pandemic (Time 0), during the first national lockdown (Time 1) and after 1 year (Time 2), and we monitored the changes in symptoms over time., Results: After 1 year from the start of the first national lockdown, we found a significant increase of internalizing problems, anxiety, depression, somatization, and social and oppositional-defiant problems in older children (6-18 years), and a significant increase of somatization, anxiety problems, and sleep problems in younger children (1.5-5 years). We also observed a significant relationship between emotional/behavioral symptoms and parental stress., Conclusion: Our study showed that parental stress levels increased compared to the pre-pandemic months and continues to persist over time, while internalizing symptoms of children and adolescents showed a significant worsening during 1 year follow-up from the first COVID-19 lockdown., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

(1) Background: The aim of our study was to evaluate parental stress after 6 and 12 months of a ketogenic diet, considering demographic and clinical variables (epilepsy type, epilepsy duration, seizure number, antiseizure medications, comorbidities, efficacy, and adverse events). (2) Methods: We consecutively enrolled 36 children aged between 3 and 10 years who had been diagnosed with various types of drug-resistant epilepsy and who were in therapy with a ketogenic diet for better seizure control. A standardized neuropsychological questionnaire (Parenting Stress Index-PSI) was administered to the parents evaluating parental stress at baseline (T0), after 6 (T1) months, and after 12 months (T2). (3) Results: After 6 and 12 months of dietary treatment, Parental Distress and Total Stress mean scores were statistically significantly increased. Post hoc analysis showed no significant changes in the scores between T0 and T1, although there was a significant increase between T1 and T2. We did not find statistically significant relationships between parental stress and the other variables considered. (4) Conclusions: The ketogenic diet can be challenging for parents and can affect the perception of parental stress, especially in the long term. Parents may feel inadequate in their role; therefore, they should be helped and encouraged through additional supports in order to maximize the adherence to diet therapy.

Managing epilepsy in people with an intellectual disability remains a therapeutic challenge and must take into account additional issues such as diagnostic difficulties and frequent drug resistance. Advances in genomic technologies improved our understanding of epilepsy and raised the possibility to develop patients-tailored treatments acting on the key molecular mechanisms involved in the development of the disease. In addition to conventional antiseizure medications (ASMs), ketogenic diet, hormone therapy and epilepsy surgery play an important role, especially in cases of drugresistance. This review aims to provide a comprehensive overview of the mainfactors influencing cognition in children and adolescents with epilepsy and the main therapeutic options available for the epilepsies associated with intellectual disability., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

(1) Introduction: The aim of our research was to explore emotional/behavioral changes in adolescents with neuropsychiatric conditions during the COVID-19 pandemic, and parental stress levels through a standardized assessment, comparing the data collected before and during the first months of lockdown. Moreover, an additional goal was to detect a possible relationship between emotional/behavioural symptoms of adolescents and the stress levels of their parents. (2) Methods: We enrolled 178 Italian adolescents aged between 12-18 that were referred to the Child Neuropsychiatry Unit of the University Hospital of Salerno with different neuropsychiatric diagnoses. Two standardized questionnaires were provided to all parents for the assessment of parental stress (PSI-Parenting Stress Index-Short Form) and the emotional/behavioral problems of their children (Child Behaviour Check List). The data collected from questionnaires administered during the six months preceding the pandemic, as is our usual clinical practice, were compared to those recorded during the pandemic. (3) Results: The statistical comparison of PSI and CBCL scores before/during the pandemic showed a statistically significant increase in all subscales in the total sample. The correlation analysis highlighted a significant positive relationship between Parental Stress and Internalizing/Externalizing symptoms of adolescent patients. Age and gender did not significantly affect CBCL and PSI scores, while the type of diagnosis could affect behavioral symptoms and parental stress. (4) Conclusions: our study suggests that the lockdown and the containment measures adopted during the COVID-19 pandemic could have aggravated the emotional/behavioral symptoms of adolescents with neuropsychiatric disorders and the stress of their parents. Further studies should be conducted in order to monitor the evolution of these aspects over time.

Sydenham's chorea (SC) is a post-streptococcal autoimmune disorder of the central nervous system, and it is a major criterium for the diagnosis of acute rheumatic fever (ARF). SC typically improves in 12-15 weeks, but patients can be affected for years by persistence and recurrencies of both neurological and neuropsychiatric symptoms. We enrolled 48 patients with a previous diagnosis of ARF, with or without SC, in a national multicenter prospective study, to evaluate the presence of neuropsychiatric symptoms several years after SC's onset. Our population was divided in a SC group (n = 21), consisting of patients who had SC, and a nSC group (n = 27), consisting of patients who had ARF without SC. Both groups were evaluated by the administration of 8 different neuropsychiatric tests. The Work and Social Adjustment Scale (WSAS) showed significantly ( p = 0.021) higher alterations in the SC group than in the nSC group. Furthermore, 60.4% (n = 29) of the overall population experienced neuropsychiatric symptoms other than choreic movements at diagnosis and this finding was significantly more common ( p = 0.00) in SC patients (95.2%) than in nSC patients (33.3%). The other neuropsychiatric tests also produced significant results, indicating that SC can exert a strong psychopathological impact on patients even years after its onset.

Objectives: The aim of our study was to evaluate the effectiveness and tolerability of perampanel (PER) as first add-on and as second line monotherapy in subjects with childhood absence epilepsy., Methods: Our sample consisted of 20 patients with childhood absence epilepsy, aged between 8 and 10, already in therapy with a first antiseizure medication with incomplete seizure control. PER was added as first add-on in a dose ranging from 3 to 8 mg/die with 1- 2 mg/week increments. The patients that were seizure-free were shifted to a PER monotherapy. All patients underwent a standardized neuropsychological evaluation in order to assess non-verbal intelligence and executive functions before adding PER and after 6 months of drug therapy. All parents completed two questionnaires, in order to assess the emotional-behavioral problems and parental stress., Results: 15/20 patients responded to add-on PER and were seizure-free, in 3/20 patients we observed a reduction of seizure frequency <50%, and in the 2 remaining patients the add-on therapy with PER did not lead to a reduction in seizures frequency from baseline. The patients who were seizure-free were switched to PER monotherapy. 9/15 patients remained seizure-free in monotherapy with PER. In the first month of therapy with PER 2/20 patients (10%) reported mild, transient side effects of irritability, headache and dizziness, which did not lead to discontinuation of therapy. Adjunctive treatment with PER did not negatively affect non-verbal intelligence, executive functions, emotional/behavioral symptoms of children and parental stress levels., Significance: Our clinical experience in real life showed that PER appears to be effective in the control of absence seizures in childhood absence epilepsy, with a favorable tolerability profile. PER would seem effective on absence seizures even in monotherapy. Further studies with larger samples, longer follow-up and controlled vs. placebo (or other first choice antiseizure medications) are needed to confirm our data., Competing Interests: GS was employed by Azienda Sanitaria Locale Salerno. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Operto, Orsini, Sica, Scuoppo, Padovano, Vivenzio, de Simone, Rinaldi, Belfiore, Mazza, Aiello, Vetri, Donadio, Labate and Pastorino.)

Whether chemotherapy (ChT) and radiotherapy (RT) determine neurocognitive impairment in acute lymphoblastic leukemia long-term survivors (ALL LTSs) through similar mechanisms affecting the same brain regions is still unknown. We compared neurocognitive alterations, regional brain tissue volumes (by voxel-based morphometry), and functional connectivity of the main default-mode network hubs (by seed-based analysis of resting state functional MRI data), in 13 ALL LTSs treated with RT and ChT (Group A) and 13 treated with ChT only (Group B). Group A performed significantly worse than Group B at the digit span and digit symbol tests ( p = 0.023 and 0.013, respectively). Increased connectivity between the medial prefrontal cortex (the main anterior hub of the default-mode network) and the rolandic operculi was present in Group A compared to Group B, along with the absence of significant differences in regional brain tissue volumes. In these regions, the functional connectivity correlated inversely with the speed of processing scores, independent of treatment group. These results suggest that similar mechanisms may be involved in the neurocognitive deficits in ALL LTS patients, regardless of the treatment group. Further studies are needed to clarify whether these changes represent a direct expression of the mechanisms underlying the cognitive deficits or ineffective compensatory phenomena.

The objective of our study was to evaluate the impact of the COVID-19 pandemic on the emotional and behavioral symptoms in minors with neuropsychiatric disorders and on parental stress through a standardized neuropsychological assessment, comparing the data collected before the pandemic with those collected during the lock-down. Another goal of our study was to analyze the relationship between parental stress and behavioral/emotional symptoms in children. Our study was conducted on 383 families of patients who had already been referred at the Child Neuropsychiatry Unit of the University Hospital of Salerno for different neuropsychiatric conditions. All the parents completed two neuropsychological standardized questionnaires for the assessment of parental stress (PSI-Parenting Stress Index-Short Form) and the emotional/behavioral problems of their children (Child Behaviour CheckList). The data collected during the pandemic were compared with those collected from questionnaires administered during the six months preceding the pandemic, as is our usual clinical practice. The comparison between the mean scores of PSI and CBCL before and after the pandemic showed a statistically significant increase in all subscales analyzed in the total sample. The correlation analysis showed significant positive relationship between the subscale Total Stress of PSI and the subscales Total Problems and Internalizing Problems of CBCL. Our study suggested that the COVID-19 pandemic and the corresponding measures adopted led to an increase in internalizing and externalizing symptoms in children and adolescents with neuropsychiatric disorder. Similarly, parental stress increased during COVID-19 and ahigher level of stress in parents can be related to the internalizing symptoms of their children.

Introduction: The goal of the present study was to comparatively analyze Social Cognition skills in a pediatric population diagnosed with Migraine or Epilepsy, compared to Typically Developing children (TD). The secondary aim was to relate Social Cognition skills with other migraine- or epilepsy-related variables and with executive and cognitive functions., Materials and Methods: In our cross-sectional observational study 119 children and adolescents (aged 6-16) with Migraine or Focal Epilepsy and 61 TD peers were recruited. Both the clinical groups and TD peers performed a neuropsychological evaluation through standardized test to assess Theory of Mind (TM), Emotion Recognition through facial expression (ER), executive function and non-verbal cognitive abilities., Results: Children and adolescents with Migraine or Focal Epilepsy showed comparable scores between each other, however their scores were significantly lower than their TD peers, in both ER and TM. Social Cognition skills were significantly related to executive functions., Conclusion: Our study suggests that some chronic neurological conditions in childhood, such as Migraine and Epilepsy, may be associated with difficulties in Social Cognition skills, and that these difficulties may be related to a deficit in executive functions. The relationship between these two higher cognitive abilities should be further explored in future studies. Our results also suggest the importance of monitoring cognitive abilities in pediatric patients with Migraine or Epilepsy, in order to detect early impairment and ensure the necessary support., (© 2022 Published by Elsevier Ltd on behalf of European Paediatric Neurology Society.)

Background: Neuroinflammation is a key component in the etiopathogenesis of neurological diseases and brain aging. This process involves the brain immune system that modulates synaptic functions and protects neurons from infection or damage. Hence, the knowledge of neuroinflammation related pathways and modulation by drugs or natural compounds is functional to developing therapeutic strategies aimed at preserving, maintaining and restoring brain health., Objective: This review article summarizes the basics of neuroinflammation and related signaling pathways, the success of the dietary intervention in clinical practice and the possible development of RNA-based strategies for treating neurological diseases., Methods: Pubmed search from 2012 to 2022 with the keywords neuroinflammation and molecular mechanisms in combination with diet, miRNA and non-coding RNA., Results: Glial cells-play a crucial role in neuroinflammation, but several pathways can be activated in response to different inflammatory stimuli, inducing cell death by apoptosis, pyroptosis or necroptosis. The dietary intervention has immunomodulatory effects and could limit the inflammatory process induced by microglia and astrocytes. Thus by inhibiting neuroinflammation and improving the symptoms of a variety of neurological diseases, diet exerts pleiotropic neuroprotective effects independently from the spectrum of pathophysiological mechanisms underlying the specific disorder. Furthermore, data from animal models revealed that altered expression of specific noncoding RNAs, in particular microRNAs, contributes to neuroinflammatory diseases; consequently, RNA-based strategies may be promising to alleviate the consequences of neuroinflammation., Conclusion: Further studies are needed to identify the molecular pathways and the new pharmacological targets in neuroinflammation to lay the basis for more effective and selective therapies to be applied, in parallel to dietary intervention, in the treatment of neuroinflammation-based diseases., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: The aim of this study was to identify the presence of emotional and behavioral symptoms in children and adolescents with epilepsy, to measure the stress levels in their parents, and to determine if and how parental stress was linked to emotional and behavioral symptoms of their children. Methods: We conducted a cross-sectional observational study including 103 children and adolescents with different form of epilepsy and 93 sex-/age-matched controls. Parental stress and emotional and behavioral symptoms were assessed through two standardized questionnaires: the Parenting Stress Index (PSI) and the Child Behavior Checklist (CBCL), respectively. We also considered the following variables: age, sex, maternal education level, family history of psychiatric disorders, duration of epilepsy, seizure frequency, seizure type, and number of antiseizure medications. Results: The statistical comparison showed that the epilepsy group obtained significantly higher scores than controls in almost all the CBCL and the PSI scales ( p < 0.05). The correlation analysis revealed a significant relationship between the PSI Total Stress scale and the following CBCL scales: total problems, internalizing problems, and externalizing problems ( p < 0.05). An earlier age of seizure onset was related to a greater presence of externalizing problems, total problems, and total stress ( p < 0.05). Conclusion: In the epilepsy group, we found higher levels of parental stress and higher presence of emotional and behavioral symptoms compared to controls, mainly represented by internalizing problems (anxiety and depression symptoms). Therefore, it is important to precociously detect these symptoms and monitor them over time, in order to prevent psychiatric problems. In addition, parents of children with epilepsy should be offered psychological support to cope with parental stress and to improve the relationship with their children., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Operto, Pastorino, Pippa, Padovano, Vivenzio, Scuoppo, Pistola and Coppola.)

Background: The aim of our study was to compare adaptive skills, emotional/behavioral problems, and parental stress among children with different severity levels of Autism Spectrum Disorder (ASD) symptoms. Methods: This study included a sample of 88 subjects with ASD (mean age = 6.00 ± 2.70). All subjects underwent standardized neuropsychological tests for the assessment of symptoms of the autism spectrum (Autism Diagnostic Observation Schedule-Second Edition), adaptive level (The Vineland Adaptive Behavior Scales, Survey Interview, 2nd edition), behavioral and emotional problems (Child Behavior CheckList CBCL), and parental stress (Parental Stress Index Short Form-PSI-SF). Non-parametric statistical methods (Kruskal-Wallis test and Mann-Whitney U -test for post hoc analysis) and linear regression analysis were used in this study. Results: C hildren who had higher severity levels of ASD symptoms had less adaptive functioning; younger children showed more severe symptoms of ASD; older children had better communication skills. The presence of greater adaptive difficulties was related to a greater presence of internalizing problems. An increase in parental stress levels was related to an higher severity of ASD symptoms, fewer adaptive skills, and a greater presence of internalizing and externalizing problems. Conclusion: This study suggests that the adaptive behavior should be considered in order to planning a habilitation intervention in children with autism. It is also important to monitor emotional/behavioral problems and parental stress levels in order to provide parenting support and improve the family quality of life., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Operto, Pastorino, Scuoppo, Padovano, Vivenzio, Pistola, Belfiore, Rinaldi, de Simone and Coppola.)

Introduction: The main of the present study was to assess the effectiveness and tolerability of perampanel (PER) in association with 1 or 2 concomitant antiseizure medications (ASMs) in patients with epilepsy throughout a follow-up period of 24 months or longer in a real-world setting., Methods: This retrospective, observational, multi-center study collected data from both underage (<18 years old) and adult patients who had started PER in association with 1 or 2 ASMs. Only patients who had started PER and were followed up for at least 24 months were included. Response to treatment was analyzed at the 24-, 36-, and 48-month visits by considering the last visit undergone by patients. Subgroup analyses were performed according to age, gender, and epilepsy type and patients were categorized following PER treatment in concomitance with 1 or 2 ASMs to evaluate the factors affecting the achievement of seizure freedom (SF) at the 24-month FU., Results: Ninety-four patients were included (mean age 36.89 years; 51.1% female). At the 24-month follow-up visit, 90 (95.74%) patients were still receiving PER concomitantly with 1 or 2 ASMs. The mean PER dose was 6.02 mg/day and SF was achieved by 33 (35.1%) patients. A significantly higher SF rate was found in patients who had started PER with only 1 ASM when compared to those who had started PER with 2 concomitant ASMs. Effectiveness was maintained also in the subgroups of patients with a 36- or 48-month follow-up visit. Adult patients had a higher final daily dosage of PER than underage patients. Logistic regression found that the lowest number of previously failed ASMs was associated with a higher SF rate (p = 0.036)., Conclusion: Perampanel demonstrated a good effectiveness in association with 1 or 2 ASMs in both pediatric and adult patients, without having to use a high dose of the drug. The possibility to present SF was higher when PER was added early. Finally, the maintenance of effectiveness was observed also in the subgroups of patients with a follow-up of 36 and 48 months., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Perampanel (PER) is a non-competitive AMPA glutamate receptor antagonist approved for focal and generalized seizures as add-on therapy. PER does not seem to negatively affect the cognitive profile in children and adolescents, but its influence on visuospatial abilities is still to be assessed. The aim of our study was to assess visuospatial skills through a standardized neuropsychological evaluation in adolescents taking PER for 12 months. Methods: Our sample included 46 adolescents aged 12-18 years with focal and generalized drug-resistant epilepsy already in therapy with one or two antiseizure medications. Changes in visuospatial perception and memory were assessed by the Rey-Osterrieth Complex Figure Test at baseline (before taking PER) and after 12 months of pharmacological treatment. Executive functions and non-verbal intelligence were also assessed at baseline. Results: After 12 months of PER therapy, the mean scores on the Rey-Osterrieth Complex Figure Test remained almost unchanged for both visuospatial perception and visuospatial memory skills. At baseline, visuospatial memory was related to executive function, and visuospatial perception was related to executive function and non-verbal intelligence. Conclusions: Adjunctive treatment with PER did not negatively affect visuospatial skills. No adverse event effects have been reported after 12 months of follow-up, and this suggests a good tolerability in the middle-to-long term., Competing Interests: FO and GP participated at advisory boards and scientific meetings for Eisai. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Operto, Vivenzio, Scuoppo, Padovano, Roccella, Quatrosi and Pastorino.)

Introduction: Visuospatial abilities are fundamental for good school achievements and good daily functioning. Previous studies showed an impairment of visuospatial skills in pediatric patients with epilepsy; pharmacological treatment, although indispensable for the seizure control, could further affect cognitive functions. The aim of our study was to evaluate the visuospatial skills in children and adolescents with different forms of epilepsy well-controlled by antiseizure monotherapy, both at baseline and after one year follow-up, through a standardized neuropsychological assessment., Methods: We recruited 207 children and adolescents (mean age = 10.35 ± 2.39 years) with epilepsy, well controlled by monotherapy with levetiracetam, valproic acid, ethosuximide, oxcarbazepine or carbamazepine and 45 age/sex-matched controls. All the participants performed the Rey-Osterrieth Complex Figure, a standardized test for visuospatial perception and visuospatial memory assessment, at baseline and after 12 month of drug therapy. Age, sex, executive functions, non-verbal intelligence, age at onset of epilepsy, epilepsy duration, epilepsy type, lobe and side of seizure onset were considered in our analysis. EEG, seizure frequency, and drug dose were also recorded., Results: At baseline, the epilepsy group performed significantly worse than controls in the Immediate Recall test but not the Direct Copy test, without differences between epilepsy subgroups. Immediate Recall scores were related to age of seizure onset and epilepsy duration and executive functions. The re-assessment after 1 year showed that the Immediate Recall mean scores were not significantly changed in the levetiracetam and oxcarbazepine group, while they significantly worsened in the valproic acid, ethosuximide and carbamazepine groups. The Immediate Recall scores were correlated to age, age at onset of epilepsy, epilepsy duration, and executive functions., Conclusions: Children with epilepsy may exhibit visuospatial memory impairment compared to their peer, that may be correlated to some features of the epilepsy itself and to the impairment of executive functions. Different antiseizure medications can affect visuospatial memory differently, so it is important monitoring this aspect in pediatric patients., Competing Interests: Declaration of competing interest None of the authors has any conflict of interest to disclose., (Copyright © 2021 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Background: The aim of our study was to trace a specific neuropsychological profile, to investigate emotional-behavioral problems and parental stress in children with Autism Spectrum Disorder Level 1/High functioning (ASD-HF), Specific Learning Disorders (SLD) and Attention Deficit/Hyperactivity Disorder (ADHD) disorders and to highlight similarities and differences among the three groups., Methods: We retrospectively collected the data from a total of 62 subjects with ASD-HF ( n = 19) ADHD ( n = 21), SLD ( n = 22) and 20 typical development. All the participants underwent neuropsychological standardized test for the evaluation of cognitive profile (Wechsler Intelligence Scale for Children Fourth Edition-WISC-IV), behavioral and emotional problems (Child Behavior CheckList CBCL), and parental stress (Parental Stress Index Short Form-PSI-SF). The scores of the ASD-HF, ADHD, and SLD groups were compared using non-parametric statistic methods (Kruskall-Wallis H test and U Mann-Whitney for post-hoc analysis)., Results: The ASD-HF group were significantly higher in all areas of the WISC-IV than the other two clinical groups. The SLD group performed significantly lower than ASD-HF in Working Memory Index. The SLD group showed lower scores on the somatic problems subscale than the other two groups. In the Difficult Child subscale of the PSI-SF, parents of ADHD children scored lower than the mothers of SLD subjects and higher than the fathers of SLD subjects. In all three groups there are specific deficiencies compared to the control group in the cognitive profile, behavioral and emotional problems, and parental stress., Conclusions: Our comparative analysis highlighted similarities and differences in three groups of children with different neurodevelopmental disorders, helping to better define cognitive, behavioral, and emotional characteristics of these children and parental stress of their parents.

Introduction: The purpose of our study was to perform a comparative analysis of social cognition in children and adolescents with epilepsy, autism spectrum disorder (ASD), specific learning disorder (SLD) and in typical development (TD) controls. The secondary aim was to relate social cognition to some clinical and demographic characteristics. Methods: Our work is a transversal observational study. The recruits were 179 children and adolescents aged between 6 and 18 years diagnosed with epilepsy, ASD, or SLD and 32 subjects with TD. All the participants underwent neuropsychological assessment of Emotion Recognition (ER) and Theory of Mind (ToM) skills. Results: All three clinical groups performed significantly worse than controls in ER and ToM. The ASD group achieved significantly lower performance than the other groups; however, the scores of SLD and epilepsy groups were comparable. The ER performances are related to non-verbal intelligence only in the group with epilepsy. Conclusion: Children and adolescents with focal epilepsy, SLD, or ASD may present a deficit of varying extent in emotion recognition and ToM, compared with TD peers. These difficulties are more pronounced in individuals with ASD, but impairment worthy of clinical attention also emerges in individuals with SLD and epilepsy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Pastorino, Operto, Padovano, Vivenzio, Scuoppo, Pastorino, Roccella, Vetri, Carotenuto and Coppola.)

The ketogenic diet, used for over a century as an alternative therapy for the control of drug-resistant seizures in both children and adults, has recently drawn increasing interest in various neurological or psychiatric disorders other than epilepsy. In particular, there are a few preliminary studies in mood and neurodevelopmental disorders such as anxiety, depression and autism spectrum disorders. Mood disorders in comorbidity with epilepsy are commonly seen in adolescents and young adults both at the onset and during the course of the epileptic disorder. The rationale for the use of the ketogenic diet is based on the potential mood stabilizing effects through level modifications of metabolites such as dopamine and serotonin and the regulation of GABA/glutamatergic neurotransmission, mitochondrial function and oxidative stress. In this review, epilepsies with a higher risk of mood disorders in adolescents will be considered. A brief overview of the various types of ketogenic diet that can currently be offered to young patients in order to improve palatability and compliance with the diet, is also included. The efficacy and tolerability of the ketogenic diet options for the treatment of mood disorders, with or without drug therapy including mood stabilizers and antidepressant drugs, are as well discussed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Operto, Matricardi, Pastorino, Verrotti and Coppola.)

Introduction: Lennox-Gastaut syndrome (LGS) is a severe pediatric epilepsy syndrome characterized by multiple drug-resistant seizure types. Children with LGS usually experience cognitive regression, and LGS is almost always associated with moderate to severe cognitive impairment. Rufinamide (RFM) was approved by the European Medicines Agency in 2007 for the adjunctive treatment of seizures associated with LGS in patients ≥4 years of age. The primary objective of our study was to assess cognitive, adaptive, and behavior functioning of patients with LGS after 12 months of RFM therapy., Methods: This was an observational, multicenter, prospective study involving 16 patients diagnosed with LGS aged between 7 and 58 years (mean = 22 ± 16.3). Fourteen of 16 patients were already on therapy with 3 antiseizure drugs and 2/16 with 4 antiseizure drugs; RFM has been added with 100 mg/week increments up to a dose of 300-2400 mg/day. The participants and their parents underwent a neuropsychological evaluation for the assessment of intellectual, adaptive, and emotional/behavioral functioning (Leiter International Performance Scale-Revised (LEITER-R), Vineland, and Child Behavior CheckList (CBCL), respectively) before the RFM introduction (baseline) and 12 months after the RFM therapy (T2). Physical and neurological examination, electroencephalography (EEG) recording, seizure type and frequency, and adverse reactions were also considered., Results: After 12 months, the total intelligence quotient (IQ) assessed by LEITER-R did not show statistical significant changes, such as there were no statistically significant changes in adaptive functions, assessed by Vineland. Furthermore, there were no statistically significant changes in internalizing and externalizing problems assessed by CBCL., Conclusion: Adjunctive treatment with RFM did not negatively affect cognitive, adaptive function, and emotional profile in patients with LGS after 1 year of follow-up., Competing Interests: Declaration of competing interest P.S. has received speaker fees and participated at advisory boards for BioMarin, Zogenyx, GW Pharmaceuticals, and has received research funding by ENECTA BV, GW Pharmaceuticals, Kolfarmasrl., Eisai. M.E. participated at advisory boards for GW Pharmaceuticals and Eisai. G.C. participated at advisory boards and scientific meetings for Eisai. F.F.O and G.M.G.P. participated at advisory boards for Eisai., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Several studies have documented learning disabilities (LDs) in subjects with epilepsy, who have been shown to be at greater risk of mild neuropsychological damage, with the consequent risk of academic failure. This retrospective study aimed to investigate the peculiarities of reading and writing disorders in subjects with idiopathic epilepsy. The reading and writing performance of 35 children affected by reading and writing disorders and idiopathic epilepsy (R/WD + E group) has been compared with the performance of 37 children with only reading and writing disorders (R/WD group). A comparison group of 22 typical developing healthy children (TDC group) was also included in the study. As expected, the TDC group reached better performances in the reading and writing tests administered. Between R/WD + E and R/WD groups, there was a substantial analogy in reading and writing disabilities. The differences between the two clinical groups concern writing ability in sentences dictation and verbal and visuospatial short-term memory in digit span and memory-for-location (MFL) tests., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background : Over the past decade, the use of digital tools has grown and research evidence suggests that traditional media and new media offer both benefits and health risks for young children. The abilities to understand and use language represent two of the most important competencies developed during the first 3 years of life through the interaction of the child with people, objects, events, and other environmental factors. The main goal of our study is to evaluate the relationship between digital devices use and language abilities in children between 8 and 36 month, also considering the influence of several factors. Materials and Methods : We conducted a cross-sectional observational study on digital devices use and language abilities in260 children (140 males = 54%) aged between 8 and 36 months (mean = 23.5 ± 7.18 months). All the parents completed a self-report questionnaire investigating the use of digital devices by their children, and a standardized questionnaire for the assessment of language skills (MacArthur-Bates). Linear regression analysis was used to evaluate the relation between different variables. Subsequent moderation analysis were performed to verify the influence of other factors. Results : We found a statistically significant negative relation between the total daily time of exposure to digital devices and the Actions and Gestures Quotient (ß = -0.397) in children between 8 and 17 months, and between the total daily time of exposure to digital devices and Lexical Quotient (ß = -0.224) in children between 18 and 36 months. Gender, level of education/job of parents, modality of use/content of digital device did not significantly affect the result of the regression analysis. Conclusion : In our study we found that a longer time of exposure to digital devices was related to lower mimic-gestural skills in children from 8-17 months and to lower language skills in children between 18 and 36 months, regardless of age, gender, socio-economic status, content, and modality of use. Further studies are needed to confirm and better understand this relation, but parents and pediatricians are advised to limit the use of digital devices by children and encourage the social interaction to support the learning of language and communication skills in this age group.

Objectives: Deficits in facial emotion recognition and Theory of Mind are frequent in patients with epilepsy. Although this evidence, studies on pediatric age are few and the relation between these abilities and other cognitive domain remains to be better elucidated. The purpose of our study is to evaluate facial emotion recognition and Theory of Mind in children and adolescents with focal epilepsy, and correlate them with intelligence and executive functions., Materials and Methods: Our work is a cross-sectional observational study. Sixty-two children and adolescents aged between 7-16 years diagnosed by focal epilepsy and 32 sex/age-matched controls were recruited. All participants were administered a standardized battery tests to assess social cognition (NEPSY-II), executive functions (EpiTrack Junior) and cognitive non-verbal level (Raven Progressive Matrices)., Results: Emotion recognition mean score was significantly lower in the epilepsy group than in the controls to Student's t-test (p<0.05). Epilepsy group showed an impairment in happiness, sadness, anger and fear recognition, compared to controls (p<0.05). Theory of Mind mean score was also significantly lower in epilepsy group than controls (p<0.05). Deficits in emotion recognition seemed to be related to low age at onset of epilepsy, long duration of disease, low executive functions and low non-verbal intelligence. Deficits in Theory of Mind seemed to be related to a high seizure frequency., Conclusions: Our results suggest that children and adolescents with focal epilepsy had deficit in facial emotion recognition and Theory of Mind, compared to their peer. Both these difficulties seem to be related to some features of epilepsy itself. Our results also suggest that deficits in facial emotion recognition are potentially related to difficulties in executive functions and non-verbal intelligence. More studies are needed to confirm these hypotheses., Competing Interests: Declaration of competing interest None of authors has any conflict of interest to disclose., (Copyright © 2020 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

A large body of literature reports the higher prevalence of epilepsy in subjects with Autism Spectrum Disorder (ASD) compared to the general population. Similarly, several studies report an increased rate of Subclinical Electroencephalographic Abnormalities (SEAs) in seizure-free patients with ASD rather than healthy controls, although with varying percentages. SEAs include both several epileptiform discharges and different non-epileptiform electroencephalographic abnormalities. They are more frequently associated with lower intellectual functioning, more serious dysfunctional behaviors, and they are often sign of severer forms of autism. However, SEAs clinical implications remain controversial, and they could represent an epiphenomenon of the neurochemical alterations of autism etiology. This paper provides an overview of the major research findings with two main purposes: to better delineate the state-of-the-art about EEG abnormalities in ASD and to find evidence for or against appropriateness of SEAs pharmacological treatment in ASD.

Background: Some recent studies suggest that children and adolescents with different neurodevelopmental disorders perform worse in emotions recognition through facial expressions (ER) compared with typically developing peers. This impairment is also described in children with Specific Learning Disorders (SLD), compromising their scholastic achievement, social functioning, and quality of life. The purpose of our study is to evaluate ER skills in children and adolescents with SLD compared to a control group without learning disorders, and correlate them with intelligence and executive functions., Materials and Methods: Our work is a cross-sectional observational study. Sixty-three children and adolescents aged between 8 and 16 years, diagnosed with SLD, and 32 sex/age-matched controls without learning disorders were recruited. All participants were administered standardized neuropsychological tests, evaluating facial emotion recognition (NEPSY-II), executive functions (EpiTrack Junior), and intelligence profile (WISC-IV)., Results: Emotion recognition mean score was significantly lower in the SLD group than in the controls group on the Mann-Whitney U test for unpaired samples ( p < 0.001). The SLD group performed significantly lower than the control group in their abilities to identify neutral expressions, happiness, sadness, anger, and fear compared to controls ( p < 0.001). ER scores were positively correlated to the executive functions scores. There was no correlation with the Total Intelligence Quotient scores but there is a significant positive correlation with Working Memory Index and Processing Speed Index measured by WISC.IV., Conclusion: Our study showed that children and adolescents with Specific Learning Disorders have facial emotion recognition impairment when compared with a group of peers without learning disorders. ER abilities were independent of their global intelligence but potentially related to executive functions.

Developmental dyslexia is a reading disorder unrelated to intellectual disability, inadequate teaching systems or poor motivation for schooling. The first attempts to understand such difficulty of learning to read, connected the problem to a primary 'visual defect'. Since then, several models have been developed. In the last decades, autopsy and histopathological studies on the brain of developmental dyslexics provided neuroanatomical evidence of structural and morphological differences between the normal and dyslexic brains. Furthermore, neuroimaging studies allowed to understand the neural systems of reading and dyslexia. According to more recent studies, developmental dyslexia appears as a language-related neurodevelopmental disorder with a deficit in phonological decoding and visuospatial organization of the language code. Therefore, dyslexia is viewed as a multicomponential and complex disorder. Consequently, rehabilitation should be aimed at both the recovery of linguistic decoding processes and the improvement of visuo-spatial and attentional processes. This brief overview should be a valuable tool for a deeper understanding of dyslexic disorder. Literature searches in Medline, PsycINFO, EMBASE, Scopus, PubMed, Web of Science identified one hundred articles focusing attention on how this disorder has been considered over the years., Competing Interests: Conflict of interest: The authors declare no potential conflict of interest., (©Copyright: the Author(s).)

Functional non-retentive fecal incontinence (FNRFI) is a common problem in pediatric age. FNRFI is defined as unintended loss of stool in a 4-year-old or older child after organic causes have been excluded. FNRFI tends to affects up to 3% of children older than 4 years, with males being affected more frequently than females. Clinically, children affected by FNRFI have normal intestinal movements and stool consistency. Literature data show that children with fecal incontinence have increased levels of separation anxiety, specific phobias, general anxiety, attention-deficit/hyperactivity disorder (ADHD), and oppositional defiant disorder. In terms of possible relationship between incontinence and sleep, disorders of sleep organization have been observed in the pathogenesis of enuresis so generating the hypothesis that the orexinergic system may have a crucial role not only for the sleep organization per se but also for the sphincterial control in general. This study aimed to focus on specific neurophysiological aspects to investigate on the possible relationship between sleep organizational abnormalities and FNRFI. Specifically, we aimed to measure orexin serum levels in children with FNRFI and assess their polysomnographic sleep macrostructure patterns. Two study groups were considered: FNFRI ( n = 45) and typically developed (TD) ( n = 45) group. In both groups, sleep patterns and respiratory events were assessed by polysomnographic recordings (PSG) during a period of two nights at least, and plasma levels of Orexin-A were measured in each participant. The findings of this initial investigation seem to support a major role of Orexin-A in sleep organization alterations in children with FNFRI. Also, our data suggest that sleep habits evaluation should be considered as screening and complementary tool for the diagnosis of fecal incontinence in children.

Objectives: Perampanel (PER) is a noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor antagonist recently approved for focal and generalized epilepsies as an add-on therapy. It is well tolerated and effective as treatment of various pediatric epilepsy syndromes; PER does not seem to negatively affect the cognitive profile of children and adolescents, but its influence on executive functions is still to be assessed., Methods: Our sample included 37 children aged 12-18 years, with focal pharmacoresistant epilepsy already in therapy with 2 or 3 antiepileptic drug (AED); PER was added with 1 mg/week increments up to a dose of 2-4 mg/day. Changes in executive functions were assessed by the EpiTrack Junior test. Emotional and behavioral aspects were evaluated through the interview for parents Child Behavior Checklist (CBCL). Both tests were performed before taking PER and after 6 and 12 months of treatment., Results: After 12 months of PER in 22/30 patients, global score of the EpiTrack Junior test remained almost unchanged; in 7/30 patients, this score improved. The CBCL did not show significant changes in emotional or behavioral problems., Conclusions: Adjunctive treatment with PER did not negatively affect executive functions that could also be improved. No emotional/behavioral negative effects have been reported, and this suggests a good tolerability in the middle/long term., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: Cognitive abilities and executive functions in children and adolescents are important indicators of quality of life as well as academic and social achievements. Cognitive and executive functioning are often impaired in patients with epilepsy and can be exacerbated by seizures and antiseizure drugs. The aim of our observational retrospective study was to assess executive functioning in patients with pediatric epilepsy, currently taking a single antiseizure medication., Materials and Methods: Records of 172 children and adolescents aged between 6 and 18 years (mean age = 12 ± 3.4 years) with newly diagnosed epilepsy who had not yet commenced an antiepileptic treatment were included in the study. Longitudinal changes in executive functioning were assessed using the EpiTrack Junior test at baseline, before the introduction of antiepileptic monotherapy, and at 3-month, 6-month, and 9-month follow-up visits. All patients commenced a single antiepileptic treatment (levetiracetam n = 54; valproic acid n = 52; ethosuximide n = 20; oxcarbazepine n = 22; carbamazepine n = 24). Age, sex, seizure types, and seizure baseline frequency were also recorded., Results: Relative to baseline, Epitrack Junior mean scores deteriorated at the 9-month follow-up visit for patients taking valproic acid, ethosuximide, and carbamazepine, but this was only statistically significant for patients taking carbamazepine. In contrast, mean scores improved for subjects taking levetiracetam and oxcarbazepine at the 9-month follow-up visit relative to baseline, but this was only statistically significant for patients taking levetiracetam., Conclusions: Levetiracetam was the only antiseizure medication that led to slight improvements in executive functioning; whereas carbamazepine led to deteriorations in cognitive functioning. Further research using double-blinded, placebo-controlled trials are needed to confirm these results., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Fragile X syndrome (FXS) is a genetic syndrome with intellectual disability due to the loss of expression of the FMR1 gene located on chromosome X (Xq27.3). This mutation can suppress the fragile X mental retardation protein (FMRP) with an impact on synaptic functioning and neuronal plasticity. Among associated sign and symptoms of this genetic condition, sleep disturbances have been already described, but few polysomnographic reports in pediatric age have been reported. This multicenter case-control study is aimed at assessing the sleep macrostructure and at analyzing the presence of EEG abnormalities in a cohort of FXS children. We enrolled children with FXS and, as controls, children with typical development. All subjects underwent at least 1 overnight polysomnographic recording (PSG). All recorded data obtained from patients and controls were compared. In children with FXS, all PSG-recorded parameters resulted pathological values compared to those obtained from controls, and in FXS children only, we recorded interictal epileptiform discharges (IEDs), as diffuse or focal spikes and sharp waves, usually singles or in brief runs with intermittent or occasional incidence. A possible link between IEDs and alterations in the circadian sleep-wake cycle may suggest a common dysregulation of the balance between inhibitory and excitatory pathways in these patients. The alteration in sleep pattern in children with FXS may negatively impact the neuropsychological and behavioral functioning, adding increasing burn of the disease on the overall management of these patients. In this regard, treating physicians have to early detect sleep disturbances in their patients for tailored management, in order to prevent adjunctive comorbidities., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2019 Marco Carotenuto et al.)

Introduction: Psychogenic nonepileptic seizures (PNES) are observable abrupt paroxysmal changes in behavior or consciousness that resemble epileptic seizures, but without concurrent electroencephalographic abnormalities., Methods: In this manuscript, we reviewed literature concerning pediatric PNES and focused on those articles published in the last 10 years, in order to try to understand what the state of the art is at the moment, particularly as regards relationship and differential diagnosis with epilepsy., Results: Psychogenic nonepileptic seizures have been extensively described in literature mainly in adults and less frequently in children. Despite the potential negative impact of a misdiagnosis (unnecessary investigations and antiepileptic drugs, structured pathological behavioral patterns), in literature there is little information regarding the real prevalence, clinical features, treatment, and outcome of PNES in children and adolescents., Conclusion: Psychogenic nonepileptic seizures are common but frequently missed entity in pediatric population. Diagnosis could be difficult, especially in those children who have both epileptic and nonepileptic seizures; video EEG and home video can help clinicians in diagnosis. More studies are needed to better classify PNES in children and facilitate diagnosis and treatment., (© 2019 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.)

Background: Obstructive sleep apnea syndrome (OSAS) affects up to 4% of a pediatric population, with many comorbidities in the medium-long term. Functional alterations in the prefrontal cortex (PFC) may explain why OSAS impacts aspects such as executive functions, memory, motor control, attention, visual-spatial skills, learning, and mood regulation. Emotional intelligence (EI) is a complex neuropsychological function that could be impaired in many clinical conditions., Purpose: The aim of the study is to evaluate the difference in emotional intelligence skills among children with OSAS and healthy subjects (nOSAS)., Methods: 129 children (72 males; mean age 7.64 ± 1.98 years) affected by OSAS were compared to 264 non-OSAS (nOSAS) children (138 males; mean age 7.98 ± 2.13) similar for gender, age, and socioeconomic status. In order to assess the emotional quotient, the Bar-On Emotional Quotient Inventory: Youth Version (EQ-i:YV) was used., Results: The comparison for means and standard deviation between OSAS children and nOSAS children for EQ-i:YV scores showed significant differences for Interpersonal, Adaptability, and Stress Management scales and EQ Total score., Conclusions: Our findings highlighted the role of intermittent hypoxia in the genesis of the effects of sleep-related respiratory disorders, which involves also aspects different from physical impairments., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2019 Francesca Felicia Operto et al.)

Objective: To assess maternal and paternal stress in two groups of children with different types of epilepsy, at the time of diagnosis and after one year of follow-up., Methods: We investigated parental stress in a sample of 85 children aged between 2 and 14 years, divided into two groups based on the diagnosis: Group 1 (50 patients) with childhood absence epilepsy or idiopathic focal epilepsy with rolandic discharges and Group 2 (35 patients) with different forms of drug-resistant epilepsy. Parents independently completed the Parental Stress Index-Short Form at Time 0, when they received the diagnosis and patients started therapy, and at Time 1, after 1 year of follow-up., Results: We found high levels of stress in both mothers and fathers at Time 0, without statistically significant differences between the two groups. At Time 1, stress values were unchanged in Group 1 mothers; conversely, the levels of stress in Group 1 fathers reduced, with average values that all fell within the "normal range." In Group 2, stress levels were reduced both in mothers and in fathers at Time 1, compared to Time 0, but equally fell into the "pathological range," for both parents., Conclusion: In our study, the diagnosis of the epilepsy itself tended to increase parental stress, apparently regardless of the severity of the epilepsy; even after a period of follow-up, when the epilepsy was better controlled, overall parental stress remained high. It might have been related to feelings of parental inadequacy or concerns about issues such as safety or the outcome for the child., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Benign epilepsy with centrotemporal spikes (BECTS) is a common epileptic syndrome in childhood, characterized by brief and infrequent partial motor seizures, with or without generalization and mostly recurring during sleep. Because of its favorable efficacy, tolerability, and safety profile, levetiracetam (LEV) monotherapy is often administered in these patients. Long-term effects of LEV therapy and its influence on cognitive functions remain controversial., Purpose: This evaluated the changes in the cognitive profile of children with BECTS treated with LEV monotherapy for 2 years, compared with a control group of children with specific learning disabilities., Method: Our patient cohort included 20 children aged 8-14 years diagnosed as having BECTS and administered LEV monotherapy and 10 age/sex-matched controls with specific learning disabilities. All participants underwent a standardized test for assessing cognitive profile (Wechsler Intelligence Scale for Children - Fourth Edition [WISC-IV]) before drug therapy and after 2 years of treatment. Average LEV blood level and electroencephalographic (EEG) recordings were periodically monitored. Several factors such as age, sex, response to therapy, and EEG pattern changes were considered. Statistical analysis was performed using Student's t-test for paired and independent samples. p < 0.05 was considered statistically significant., Results: Children administered LEV for 24 months showed a mild but statistically significant improvement in overall cognitive abilities. Verbal skills, visual-perceptual reasoning, working memory, and processing speed showed slight but significant improvement. In the control group, cognitive profile remained substantially unchanged at 2-year follow-up., Conclusions: Not only do our data suggest a nonworsening of the cognitive profile in BECTS with LEV but, on the contrary, cognitive scores also improved over time, unlike the control group., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To describe (a) the observed cognitive, emotional, and behavioral phenotype in a cohort of male children with 47,XYY syndrome and (b) stress levels in their parents., Methods: We conducted a cross-sectional observational study of 11 boys diagnosed with 47,XYY syndrome and compared them with 11 age-matched boys with normal karyotype (46,XY). The participants performed standardized assessments of cognitive function, emotional state, and behavioral features; the parents completed a questionnaire evaluating parental stress. All data were analyzed using parametric and nonparametric statistical methods., Results: All of the boys exhibited a normal cognitive profile. However, emotional-behavioral profiling revealed that internalizing and externalizing problems were more prevalent in the 47,XYY group. In addition, the stress levels of the parents of the 47,XYY group were reportedly higher than those of the parents of the 46,XY group. We also found that the time of the diagnosis had an effect on the mothers' stress levels; that is, postnatal fetal 47,XYY diagnosis was associated with higher maternal stress, whereas prenatal fetal 47,XYY diagnosis was not., Conclusions: Generally, 47,XYY syndrome is associated with certain cognitive, emotional, and behavioral features. High stress levels have been reported by the mothers of 47,XYY boys who had been diagnosed postnatally because of unexpected developmental delay and/or learning difficulties. The present study highlights the need to better define the neuropsychiatric phenotype of 47,XYY children; namely, the effect of the chromosomal abnormality on their cognitive function and emotional-behavioral (internalizing and externalizing) features. This study could improve prenatal counseling and pediatric surveillance.

Introduction: Rett syndrome (RTT) is a severe X-linked neurodevelopmental disorder that primarily affects girls, with an incidence of 1:10,000-20,000. The diagnosis is based on clinical features: an initial period of apparently normal development (ages 6-12 months) followed by a rapid decline with regression of acquired motor skills, loss of spoken language and purposeful hand use, onset of hand stereotypes, abnormal gait, and growth failure. The course of the disease, in its classical form, is characterized by four stages. Three different atypical variants of the disease have been defined. Epilepsy has been reported in 60%-80% of patients with RTT; it differs among the various phenotypes and genotypes and its severity is an important contributor to the clinical severity of the disease., Methods: In this manuscript we reviewed literature on RTT, focusing on the different genetic entities, the correlation genotype-phenotype, and the peculiar epileptic phenotype associated to each of them., Results: Mutations in MECP2 gene, located on Xq28, account for 95% of typical RTT cases and 73.2% of atypical RTT. CDKL5 and FOXG1 are other genes identified as causative genes in atypical forms of RTT. In the last few years, a lot of new genes have been identified as causative genes for RTT phenotype., Conclusions: Recognizing clinical and EEG patterns in different RTT variants may be useful in diagnosis and management of these patients., (© 2019 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.)

Objective: The objective of the study was to explore stress levels in the parents of children with idiopathic epilepsy at different time points of the disease, specifically, at the time of diagnosis, during follow-up, and 1 and 2 years after discontinuation of antiepileptic drugs., Methods: Our study included 50 patients between 5 and 14 years of age, who were diagnosed with childhood absence epilepsy or idiopathic focal epilepsy with Rolandic paroxysms. Parents of the participants independently completed the Parenting Stress Index-Short Form at the time of initial diagnosis, and when the children started antiepileptic drugs (Time 0), and at 1 year (Time 1) and 2 years (Time 2) after discontinuation of therapy., Results: At Time 0, parental stress levels were increased, both in mothers and fathers, with average scores in the "clinical range" of the parental distress (PD), dysfunctional parent-child interaction (P-CDI), and total stress (TS) scales. At Time 1, the scores on these scales remained high. At Time 2, a mild reduction in the stress scores was observed in both parents, despite values remaining in the "clinical range" for all the scales., Conclusions: Results suggested that parents of children with epilepsy were not reassured about the child's condition, even after clinical improvement. Parental stress levels remained higher than expected, even 2 years after the discontinuation of therapy and freedom from seizures. This was probably due to concerns with the reappearance of new seizures or a more severe type of epilepsy with the discontinuation of drug(s), and feelings of inadequacy with their parental role(s)., (Copyright © 2019 Elsevier Inc. All rights reserved.)