Search

Background: Membrane Protein Palmitoylated 5 (MPP5) is a highly conserved apical complex protein, essential for cell polarity. Defects in neuronal cell polarity are associated with neurologic disorders. Only three patients with heterozygous MPP5 de novo variants have been reported so far, with global developmental delay, behavioral changes and in only one case epileptic seizures., Objective: To describe a new patient with a novel truncating de novo mutation in MPP5 and to characterize in detail the epileptic phenotype and electroencephalographic features of the encephalopathy., Methods: We identified a novel truncating de novo mutation in MPP5 in a 44 year old patient by exome sequencing (p.Ser498Phefs*15). We retrospectively analyzed his clinical and instrumental data along a thirty-year follow up., Result: Our patient presents with generalized tonic-clonic seizures, myoclonic and clonic seizures, non-epileptic myoclonus, tremor, severe intellectual disability, mild face dysmorphic traits, and psychosis., Discussion and Conclusion: We present a case of a childhood onset developmental encephalopathy with a likely-pathogenic variant in the MPP5 gene.. This represents the first complete description of the epileptic syndrome associated with the MPP5 gene., Competing Interests: Declaration of Competing Interest None of the authors has any conflict of interest to disclose. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Previous research suggests that adolescent norms and behaviours may be influenced by peers. The aim of this study was to investigate social clustering of health outcomes among school friendship groups., Methods: Cross-sectional surveys were collected from Oct 26, 2022, to March 30, 2023, in four secondary schools in Scotland's central belt, and all Secondary 2 (12-13 years) and Secondary 4 (14-15 years) students were invited to take part. Schools self-selected into the study, between 6% and 27% had a free school meal registration (Scotland average 25%). The survey asked about health and about friendships in school. The outcomes of interest were binary indicators of: mental health and self-esteem using validated scales, smoking, drinking without parents knowing (DWPK), and trying drugs. Ethics approval for the study was given by the University of Glasgow (200190035) and all participants gave consent via an online form. We used Auto-Logistic Actor Attribute Models (ALAAMs) to model the association between features of individuals' social networks and their health outcomes. We specified a model for each health outcome separately including parameters: indegree, outdegree, and simple contagion, and combined using meta-analysis., Findings: Response rate was 74% (n=1097; 50% boys, 46% girls, 4% other). Based on self-report measures, 40% participants had poor mental health, 15% had low self-esteem, 6% smoked regularly, 4% tried drugs, and 18% were drinking without parents knowing. Preliminary unadjusted analysis found evidence of social contagion for mental health. Odds of poor mental health for each additional friend with poor mental health was 1·15 (95% CI 1·05-1·26). There was no evidence of contagion for self-esteem (1·13, 0·95-1·34), smoking (1·14, 0·46-2·82), DWPK (0·88, 0·71-1·10), and having tried drugs (0·91, 0·38-2·19). Some networks had low or zero prevalence of the outcomes, increasing the uncertainty in the pooled estimate for the contagion parameter., Interpretation: A cross-sectional study cannot differentiate between social contagion and selecting similar friends, and low prevalence and social desirability bias might have masked associations. However, the unique combination of social network data with advanced statistical modelling gives initial findings on the potential communicable nature of mental health and health behaviours in adolescence. Preliminary results indicate preventive approaches in schools could benefit from social network methods., Funding: Medical Research Council (MRC) and Chief Scientist Office (CSO)., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Nature-based play benefits children's health and development. However, the delivery of this in early learning and childcare centres (ELC) is extremely diverse, and implementation is not well understood. We applied a systems science perspective to understand the factors crucial to implementing nature-based outdoor play in ELC settings. Through Group Model Building workshops with 20 participants in managerial and practitioner roles, crucial factors were appraised using Causal Loops Diagrams. Twelve thematic causal loops emerged. Network analysis was employed to analyse the diagram. Exponential Random graph models explained the diagram construction process. Centrality measures alongside conditional uniform tests identified six leverage factors: use of outdoor space, culture of being outdoors, ELC culture of outdoor play, perceived child safety and enjoyment, educator confidence and educator agency. This research brings novel and practically relevant evidence about the important factors, and interdependencies, involved in the implementation of outdoor play practice within ELC settings., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Descriptions of electroencephalographic (EEG) patterns in Aicardi syndrome (AIC) have to date referred to small cohorts of up to six cases and indicated severe derangement of electrical activity in all cases. The present study was conducted to describe the long-term EEG evolution in a larger AIC cohort, followed for up to 23 years, and identify possible early predictors of the clinical and EEG outcomes., Methods: In a retrospective study, two experienced clinical neurophysiologists systematically reviewed all EEG traces recorded in 12 AIC cases throughout their follow-up, from epilepsy onset to the present. Clinical outcome was assessed with standardized clinical outcome scales., Results: Analysis of the data revealed two distinct AIC phenotypes. In addition to the "classical severe phenotype" already described in the literature, we identified a new "mild phenotype". The two phenotypes show completely different EEG features at onset of epilepsy and during its evolution, which correspond to different clinical outcomes., Conclusions: Data from our long-term EEG and clinical-neuroradiological study allowed us to describe two different phenotypes of AIC, with different imaging severity and, in particular, different EEG at onset, which tend to remain constant over time., Significance: Together, these findings might help to predict long-term clinical outcomes., 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 © 2022 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Aim: Mowat-Wilson Syndrome (MWS) is a genetic rare disease. Epilepsy is present in 70-75% of Patients and an age-dependent electroclinical pattern has been described. Up to date, there are studies with overnight sleep EEGs, probably because of the severe intellectual disability (ID) and hyperactivity of these Patients. Our purpose was to verify the hypothesis that MWS Patients might have electrical status epilepticus in slow wave sleep (ESES pattern)., Methods: A retrospective analysis of anamnestic and electrographic data was performed on 7 consecutive MWS Patients followed between 2007 and 2016. Only Patients with at least one overnight sleep EEG were included in the study., Results: Five out of 7 Patients had overnight sleep EEG studies and were included in this study. All of them had an anterior ESES pattern with spike-and-wave index>85%. The architecture of sleep was abnormal. An ESES related regression of cognitive and motor functions with impact on daily activities (ESES-related syndrome) was demonstrated in 3 out of 5 (60%) Patients. In two Patients marked improvement of cognitive and motor performances was observed when the epileptiform activity during sleep was successfully controlled or it was spontaneously reduced., Conclusions: The clinical significance of the ESES pattern is hard to assess in MWS Patients due to severe ID, but changing in behaviour or in motor and cognitive functions should mandate sleep EEG investigation and, if ESES is present, an appropriate treatment should be tried. Furthermore, overnight sleep EEG recordings, if regularly performed in the follow up, might help to understand if ESES pattern hampers the cognitive and communicative profile in MWS., (Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Restoration efforts in the Mediterranean Basin have been changing from a silvicultural to an ecological restoration approach. Yet, to what extent the projects are guided by ecological restoration principles remains largely unknown. To analyse this issue, we built an on-line survey addressed to restoration practitioners. We analysed 36 restoration projects, mostly from drylands (86%). The projects used mainly soil from local sources. The need to comply with legislation was more important as a restoration motive for European Union (EU) than for non-EU countries, while public opinion and health had a greater importance in the latter. Non-EU countries relied more on non-native plant species than EU countries, thus deviating from ecological restoration guidelines. Nursery-grown plants used were mostly of local or regional provenance, whilst seeds were mostly of national provenance. Unexpected restoration results (e.g. inadequate biodiversity) were reported for 50% of the projects and restoration success was never evaluated in 22%. Long term evaluation (>6years) was only performed in 31% of cases, and based primarily on plant diversity and cover. The use of non-native species and species of exogenous provenances may: i) entail the loss of local genetic and functional trait diversity, critical to cope with drought, particularly under the predicted climate change scenarios, and ii) lead to unexpected competition with native species and/or negatively impact local biotic interactions. Absent or inappropriate monitoring may prevent the understanding of restoration trajectories, precluding adaptive management strategies, often crucial to create functional ecosystems able to provide ecosystem services. The overview of ecological restoration projects in the Mediterranean Basin revealed high variability among practices and highlighted the need for improved scientific assistance and information exchange, greater use of native species of local provenance, and more long-term monitoring and evaluation, including functional and ecosystem services' indicators, to improve and spread the practice of ecological restoration., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: To study neuropsychological functions in children with idiopathic epilepsy at onset of treatment and after 1 year of therapy and to identify factors associated with cognitive impairment., Methods: 43 Subjects aged 5.2-16.9 years with newly diagnosed idiopathic epilepsy were enrolled and started treatment with valproate or carbamazepine. At admission and after 12 months, all patients underwent clinical examinations, the Child Behavioural Checklist, EEG and a neuropsychological test battery. The results of each test were correlated to demographic, clinical, electrophysiological and therapeutic variables., Results: Except for attention, all neuropsychological functions were normal at admission and after 12 months. An improvement with time was noted for memory (p<0.05) and logical-executive functions (p<0.01). Attentive deficit was worse at 12 months (53.5% vs. 32.6%). Low socio-economic level and emotional and behavioural disturbances were the only factors negatively correlated to intelligence, memory and attention. Compared to valproate, carbamazepine was most commonly implicated., Discussion: Idiopathic epilepsy can affect attention, even before starting treatment. Emotional and behavioural difficulties and a low socio-economical status are associated with cognitive impairment., (Copyright © 2010 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

The diagnosis of a subtelomeric rearrangement has immediate impact on counseling, particularly in the case of familial rearrangements. However, the existence of subtelomeric imbalances with absent phenotypic effects may hamper genetic counseling, particularly when the rearrangement has not been previously described. We report on a new subtelomeric polymorphism, consisting of a familial subtelomeric rearrangement of chromosome 19 resulting in distal trisomy for 21q, detected in a child with Angelman Syndrome (AS) due to an UBE3A mutation. This report shows that new, previously unknown, benign subtelomeric variants may complicate the correct clinical diagnosis.

Objective: To investigate the relevance of serum topiramate (TPM) levels (SL) monitoring in the clinical management of epileptic patients., Methods: Twenty-seven patients with different epileptic syndromes on TPM therapy were studied. TPM was used as add-on in 26 patients, only in one as monotherapy de novo; one case changed from TPM as add-on to TPM monotherapy. The mean follow-up time was 11 months. TPM SL were measured by fluorescence polarization immunoassay., Results: We analyzed the TPM SL in 43 samples from 27 patients. Mean TPM dose was 3.9mg/kg, mean TPM SL 13.43mumol/l. The mean level to dose ratio (LDR) was 3.63mumol/l/mg/kg. Four patients became seizure-free, all with TPM dosages lower than the mean. Eleven patients had at least 50% seizure reduction. The comedication with enzyme-inducing AED significantly reduced TPM SL and LDR. On the other hand, the influence of valproic acid (VPA) on TPM LDR was not univocal. Indeed, patients younger than 15 years showed SL values lower than the adults did, although not significant., Conclusion: We could not detect a direct relationship between high TPM SL and efficacy neither between high TPM SL and tolerability. However, the data we collected seem to favour the hypothesis that high TPM dosage and SL might be associated to a greater probability to reduce seizure severity.