Peer victimization and developmental psychopathology in childhood and adolescence Italian psychiatric emergency unit. A single center retrospective observational study.

Peer victimization is a public health concern that affects a significant proportion of children and adolescents. The study evaluated the prevalence of peer victimization among 440 subjects referred to Emergency Department for a psychiatric consultation and analyzed the association with psychopathological symptoms. Sample was divided into two categories (6-13 and 14-18 years old). Logistics regression analysis was performed. Peer victimized were reported in 16.3% of subjects; 27.7% were younger than13 years old and 72.3% were between 14-18 years old, representing the main targets for peer victimization.A significant association was found between being peer victimized and depressive disorder (OR=4.57) in subjects younger than 13 years old and, with post-traumatic stress disorder (PTSD)(OR=6.52) in subjects older than 13 years old. Furthermore, linkage between being peer victimized and obsessive-compulsive disorder (OCD)(OR=4.45) was noted. Increased frequency of repeated hospitalizations was also documented.This is the first Italian study about children and adolescent peer victimization in psychiatric setting, showing a significant higher risk for depressive disorder in subjects younger than 13 years old and PTSD and OCD in subjects older than 13 years old. Investigating experiences of peer victimization provides an early diagnosis and a more efficient treatment plans, guaranteeing an improved clinical outcome.

Epidemiological and Psychopharmacological Study About Off-Label Treatment in Child and Adolescent Psychiatric Emergencies: A Tertiary/Single Center Experience.

OBJECTIVE: The study used an epidemiological and pharmacological description of child and adolescent psychiatric emergencies (CAPEs), during which psychotropic medications are frequently administered as off-label therapies. METHODS: We retrospectively describe CAPE in 190 patients (mean age, 14.7 years) referring in the emergency department of a single tertiary center, from June 2016 to June 2018, focusing on off-label administration rate, most of all in emergency setting. RESULTS: An intrinsic fragility was observed in this population, where 28.4% of patients present a history of self-harm, 24.7% a concomitant neurodevelopmental disorder, and 17.3% a history of substance abuse. Psychomotor agitation was the most frequent referral reason, and it represents an unspecified clinical presentation of several conditions, while self-harm showed a stronger association with depressive disorders (55.2%).Globally, 811 medications were administered both as baseline therapy (67.8% of off-label rate) and/or in the emergency setting, where the off-label rate raised to 78.3%. Benzodiazepines had the highest rate of off-label use (98.2% as baseline therapy, 92.9% in acute context). Nevertheless, in 83.5% cases of acute administrations, a singular oral benzodiazepine (mostly lorazepam) guaranteed psychomotor agitation resolution, with a lower rate of adverse effects in contrast with atypical antipsychotics. CONCLUSIONS: Off-label drug use in CAPEs is a recurrent clinical practice. An international agreement about off-label drugs is crucial to obtain standard long-term pharmacoepidemiological, safety, and efficacy data. Pharmacological pediatric trials and international guidelines are also required to regulate pharmacological treatments of CAPEs, most of all in emergency settings.

Dermoscopic Features of Vulvar Lichen Sclerosus in the Setting of a Prospective Cohort of Patients: New Observations.

OBJECTIVE: Dermoscopic features of vulvar lichen sclerosus (VLS) were investigated in order to determine both vascular and non-vascular features of this disease. MATERIALS AND METHODS: Dermoscopic images of 35 patients affected with histopathologically confirmed VLS were evaluated for the presence of predefined morphological criteria. RESULTS: On dermoscopy, VLS lesions exhibited very sparse vessels, mainly linear, without a specific arrangement. Dotted vessels were observed mostly in the early stage of the disease. Patchy, structureless areas, whitish to white-yellowish to pink-whitish in colour over a diffuse whitish background, were a distinctive and constant dermoscopic feature. Grey-blue dots, usually with a characteristic peppered arrangement, corresponding to dermal melanophages, were also frequently seen. Comedo-like openings and scales were observed, as well as peculiar structures like ice slivers, not identified by histological examination. CONCLUSION: Our findings show that VLS exhibits characteristic dermoscopic patterns that can aid in its clinical diagnosis.

What Is the Key to Improving Renal Transplant Recipients' Awareness of Skin Cancer Risk?

BACKGROUND: Previous studies have shown poor compliance rates regarding sun protection among organ transplant recipients. OBJECTIVE: The main objective of the present study was to assess the awareness among renal transplant recipients (RTRs) of their risk of non-melanoma skin cancer (NMSC) development and their sunscreen use. The influence of several potentially relevant variables was also assessed in order to identify possible weak points on which to concentrate efforts in this respect. METHODS: A total of 132 RTRs (92 males and 40 females) were included. The following information was collected and elaborated: (a) demographics; (b) skin phototype; (c) educational level; (d) time elapsed since transplantation; (e) immunosuppressive treatments; (f) previous dermatological visits; (g) patients' awareness of their NMSC risk; (h) use of sunscreen; and (i) previous documented NMSCs or NMSCs found during the study visit. RESULTS: Overall, 65 patients (49.2%) expressed awareness of their susceptibility to skin cancers. A high educational level was the main factor associated with patients' awareness. Thirty-six RTRs (27.3%) reported using sunscreen regularly. High educational level and awareness of personal susceptibility to NMSC development were the most relevant factors associated with sun protection habits. CONCLUSION: The present study showed the low level of sunscreen use among RTRs and their scanty awareness of personal skin cancer risk. Since educational level has been found to be highly related to both awareness of cancer risk and adequate use of sunscreen among RTRs, it is necessary to improve the way education is delivered by dermatologists and nephrologists, especially to subjects with a low educational level.

Level of use and safety of botanical products for itching vulvar dermatoses. Are patch tests useful?

BACKGROUND: Topical remedies based on botanical ingredients are popular. OBJECTIVES: To assess: (i) the usage of botanical substances in subjects affected with itching and chronic vulvar complaints; (ii) the incidence of side-effects associated with their use and the frequency of contact allergy; (iii) the diagnostic usefulness of patch testing. METHODS: Sixty-six patients were provided with a questionnaire to assess the prevalence and type of topical botanical preparations used and the occurrence of adverse reactions. Patients were patch tested with (i) the Italian baseline series, (ii) a topical medicament series, and (iii) a botanical series. RESULTS: Forty-two patients (63.6%) reported the use of natural topical products on the vulva. Seven (16.7%) noted adverse reactions; 27 showed positive reactions with the baseline series; 14 (21.2%) had at least one relevant reaction, mainly to allergens in topical products and cosmetics; and 2 (3%) showed positive reactions to the botanical series. Of the 7 patients complaining of adverse effects of botanical products, 3 (42.8%) showed relevant sensitization. CONCLUSIONS: The use of natural topical products is widespread among women affected with itching vulvar diseases. Contact dermatitis is a possible adverse effect. Botanical series are of questionable usefulness, owing to the wide variety of botanical ingredients.

Symptoms in plasma cell vulvitis: first observational cohort study on type, frequency and severity.

BACKGROUND: Studies assessing symptoms of plasma cell vulvitis (PCV) are lacking. OBJECTIVES: To assess the prevalence and severity of PCV-related symptoms and identify possible associations between patient characteristics, clinical features of PCV and treatments administered before a definitive diagnosis. METHODS: Thirty-six patients affected with PCV were included. Data were collected by direct interview and clinical examination. RESULTS: Thirty patients (83.3%) complained of symptoms: burning was the most frequent (80.6%) while dyspareunia was the severest. Of the symptomatic patients, 73.3% experienced severe symptoms. Severity of symptoms was not associated with age at onset and duration of PCV. Almost 70% of the patients had previously undergone treatments. CONCLUSIONS: Symptoms in PCV are frequent and more than often severe. Neither age at onset nor duration of the disease nor the extent of vulvar involvement were associated with symptom severity. Both the delay in diagnosis and the inappropriate previous treatments seem to indicate frequent misdiagnosis.

Prospective clinical and epidemiologic study of vulvar lichen sclerosus: analysis of prevalence and severity of clinical features, together with historical and demographic associations.

BACKGROUND: Few reports have addressed the associations between clinical, demographic and historical variables of vulvar lichen sclerosus (VLS). OBJECTIVE: To elaborate the prevalence and severity of signs and symptoms and to identify potential factors predicting the severity and course of VLS. METHODS: A prospective cohort of 225 patients affected by VLS was included. Data were collected by direct interview and clinical examination. RESULTS: 98% of patients complained of symptoms, principally itching. Pallor and scarring-sclerosis-atrophy were the most frequent and severe signs. The severity of VLS signs was not associated with age at onset and duration of the disease. About 70% of the patients had previously undergone treatment. CONCLUSIONS: VLS-related symptoms were not associated with the clinical features which resulted less severe. Personal history of autoimmune diseases and familial history of VLS did not influence the age at onset and the severity of VLS. A considerable part of patients had previously received inappropriate treatment.

A case of a childhood onset developmental encephalopathy with a novel de novo truncating variant in the Membrane Protein Palmitoylated 5 (MPP5) gene.

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.

Distinct neurodevelopmental and epileptic phenotypes associated with gain- and loss-of-function GABRB2 variants.

BACKGROUND: Variants in GABRB2, encoding the ß2 subunit of the γ-aminobutyric acid type A (GABAA) receptor, can result in a diverse range of conditions, ranging from febrile seizures to severe developmental and epileptic encephalopathies. However, the mechanisms underlying the risk of developing milder vs more severe forms of disorder remain unclear. In this study, we conducted a comprehensive genotype-phenotype correlation analysis in a cohort of individuals with GABRB2 variants. METHODS: Genetic and electroclinical data of 42 individuals harbouring 26 different GABRB2 variants were collected and accompanied by electrophysiological analysis of the effects of the variants on receptor function. FINDINGS: Electrophysiological assessments of α1ß2γ2 receptors revealed that 25/26 variants caused dysfunction to core receptor properties such as GABA sensitivity. Of these, 17 resulted in gain-of-function (GOF) while eight yielded loss-of-function traits (LOF). Genotype-phenotype correlation analysis revealed that individuals harbouring GOF variants suffered from severe developmental delay/intellectual disability (DD/ID, 74%), movement disorders such as dystonia or dyskinesia (59%), microcephaly (50%) and high risk of early mortality (26%). Conversely, LOF variants were associated with milder disease manifestations. Individuals with these variants typically exhibited fever-triggered seizures (92%), milder degrees of DD/ID (85%), and maintained ambulatory function (85%). Notably, severe movement disorders or microcephaly were not reported in individuals with loss-of-function variants. INTERPRETATION: The data reveals that genetic variants in GABRB2 can lead to both gain and loss-of-function, and this divergence is correlated with distinct disease manifestations. Utilising this information, we constructed a diagnostic flowchart that aids in predicting the pathogenicity of recently identified variants by considering clinical phenotypes. FUNDING: This work was funded by the Australian National Health & Medical Research Council, the Novo Nordisk Foundation and The Lundbeck Foundation.

Etiology and duration of the disease in the assessment of intellectual functioning of pediatric patients with epilepsy: An observational study.

Childhood epilepsy can be frequently associated with impaired cognitive functioning. Previous research has suggested an increased risk of cognitive impairment that may be related to the etiology, the electro-clinical pattern and the load of anti-seizure medications (ASMs). The aim of this study was to evaluate the impact of different clinical features on the global intellectual functioning in a cohort of children and adolescents with epilepsy. We studied eighty patients diagnosed and followed in a tertiary care center. These factors were examined: 1. Etiology of epileptic syndrome; 2. Type of seizure; 3. Number of ASMs; 4. Seizure frequency; 5. Age at seizure onset; 6. Total duration of epilepsy; and 7. Active duration of epilepsy. Multiple regression analysis showed that the etiology and the total duration of epilepsy were the best indicators of intellectual functioning. The present data indicate that children with symptomatic epilepsy (SE) have lower IQ scores (M = 63.5), while children with self-limited focal epilepsy and generalized idiopathic epilepsy, i.e. age-related epileptic syndromes (ARES), have a higher IQ (M = 100.0; p < 0.01). Children with epilepsy of unknown etiology (UEE) (M = 75.1; p < 0.05) are positioned at an intermediate level between the SE and the ARES group (p < 0.01). Increased duration of epilepsy was associated with decreased intellectual functioning. In conclusion, knowledge about the risks associated with etiologic factors and the duration of the disease may guide the definition of optimal neuropsychological rehabilitation strategies.

EEG Features in Autism Spectrum Disorder: A Retrospective Analysis in a Cohort of Preschool Children.

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder that can be associated with intellectual disability (ID) and epilepsy (E). The etiology and the pathogenesis of this disorder is in most cases still to be clarified. Several studies have underlined that the EEG recordings in children with these clinical pictures are abnormal, however the precise frequency of these abnormalities and their relationship with the pathogenic mechanisms and in particular with epileptic seizures are still unknown. We retrospectively reviewed 292 routine polysomnographic EEG tracings of preschool children (age < 6 years) who had received a first multidisciplinary diagnosis of ASD according to DSM-5 clinical criteria. Children (mean age: 34.6 months) were diagnosed at IRCCS E. Medea (Bosisio Parini, Italy). We evaluated: the background activity during wakefulness and sleep, the presence and the characteristics (focal or diffuse) of the slow-waves abnormalities and the interictal epileptiform discharges. In 78.0% of cases the EEG recordings were found to be abnormal, particularly during sleep. Paroxysmal slowing and epileptiform abnormalities were found in the 28.4% of the subjects, confirming the high percentage of abnormal polysomnographic EEG recordings in children with ASD. These alterations seem to be more correlated with the characteristics of the underlying pathology than with intellectual disability and epilepsy. In particular, we underline the possible significance of the prevalence of EEG abnormalities during sleep. Moreover, we analyzed the possibility that EEG data reduces the ASD clinical heterogeneity and suggests the exams to be carried out to clarify the etiology of the disorder.

Epilepsia partialis continua associated with the p.Arg403Cys variant of the DNM1L gene: an unusual clinical progression with two episodes of super-refractory status epilepticus with a 13-year remission interval.

Dynamin-1-like (DNM1L) is a gene located on chromosome 12p11.21 that encodes for dynamin-related protein (DRP1), a GTPase involved in mitochondrial and peroxisomal fusion, which plays a pivotal role in brain development. The missense variant, p.Arg403Cys, is clinically associated with childhood-onset super-refractory status epilepticus, with either subsequent poor neurological outcome or death (described in 13 patients). We present a 20-year-old girl carrying this mutation with a history of two episodes of super-refractory focal myoclonic status epilepticus which manifested as epilepsia partialis continua (EPC) with a 13-year interval, during which she displayed moderate intellectual disability, social and school reintegration, without complete control of myoclonic manifestations. The first status, which occurred at the age of six, was associated with transient left side thalamic involvement and the second episode with right side transient basal ganglia hyperintensity on MRI. After the second status, a persistent vegetative state with both drug-resistant epilepsia partialis continua and reticular myoclonus endured; the MRI showed progressive brain atrophy. In contrast to previous published cases, this new case of childhood-onset DNM1L encephalopathy demonstrated biphasic clinical progression. The main features of our patient were EPC, super-refractory status epilepticus, and transient and migrating subcortical thalamic hyperintensity on MRI at onset. The unusual clinical course is also noticeable, indicating possible epigenetic and/or protective factors, without underestimating the progressive and genetic basis of this encephalopathy. Precise characterization of seizures and whole-exome sequencing are crucial in order to establish early diagnosis.

Seizure Outcome of Temporal Lobe Epilepsy Surgery in Adults and Children: A Systematic Review and Meta-Analysis.

BACKGROUND: Temporal lobe epilepsy (TLE) surgery is associated with the best seizure outcome in adults, although its long-term results remain suboptimal. Retrospective pediatric studies suggest better figures whose determinants are poorly understood. OBJECTIVE: To conduct a systematic review and meta-analysis of studies on the efficacy of TLE surgery in children (age younger than 18 years) and adults. METHODS: We searched MEDLINE, Embase, and Cochrane Library for TLE surgery original research from January 1, 1990, until May 12, 2020. The outcome measures were seizure freedom since surgery and seizure freedom either at last or longest follow-up. We meta-analyzed the proportion of children and adults achieving either Engel I/International League Against Epilepsy (ILAE) 1 or Engel IA/ILAE 1A outcome by follow-up duration, type of surgery, histopathology, neuroimaging, quality of the studies, and publication period. We used a random effects model with Freeman-Tukey double arcsine transformation of proportions. RESULTS: From 40 409 records identified, we included 277 studies (30 848 patients). The proportions of patients achieving Engel I/ILAE 1 and Engel IA/ILAE 1A outcomes were 0.74 (95% CI, 0.69-0.78) and 0.61 (0.48-0.74) for children and 0.69 (0.67-0.71) and 0.56 (0.52-0.60) for adults. Histopathology significantly influenced Engel I/ILAE 1 outcome in adults but not in children ( P < .0001), while the type of surgery significantly influenced Engel I/ILAE 1 outcome in children but not in adults. CONCLUSION: The proportion of seizure freedom after TLE surgery was higher in children, although not significantly. Histopathology and the surgical approach can influence seizure outcome, with age-related variability.

Prospective Evaluation of Ghrelin and Des-Acyl Ghrelin Plasma Levels in Children with Newly Diagnosed Epilepsy: Evidence for Reduced Ghrelin-to-Des-Acyl Ghrelin Ratio in Generalized Epilepsies.

Children with epilepsy and identified as responders to antiseizure medications (ASMs) were found to present markedly higher ghrelin plasma levels when compared to drug-resistant patients. However, it was undetermined if this phenotype could be influenced by the ASMs. Here, we prospectively investigated total ghrelin and des-acyl ghrelin (DAG) plasma levels by enzyme-linked immunosorbent assay before and after ASM administration. Inclusion criteria were: (i) subject with a suspicion of epilepsy; (ii) age ranging from 0 to 16 years; and (iii) informed consent signed by parents or caregivers. Exclusion criteria were acute or chronic metabolic disorders with occasional convulsions but without epilepsy. Fifty patients were followed over a period of one year in Italian neuropediatric centers. Apart from a few exceptions, the majority of children were responsive to ASMs. No differences were found in total ghrelin and DAG levels before and after the treatment, but total ghrelin levels were significantly lower in children with generalized epilepsy compared to those with combined focal and generalized epilepsy. Moreover, the ghrelin-to-DAG ratio was also markedly lower in generalized epilepsies compared to all the other types of epilepsy. Finally, ghrelin was unchanged by ASMs, including the first (e.g., carbamazepine), second (levetiracetam), and third (lacosamide) generation of anticonvulsants.

Dyspareunia in vulvar lichen sclerosus: an overview of a distressing symptom.

BACKGROUND: Dyspareunia is a symptom of vulvar lichen sclerosus (VLS). This study specifically addressed prevalence and severity of dyspareunia in patients affected with VLS as well as the factors that can influence its occurrence. Changes in the severity of dyspareunia with treatment were also explored. METHODS: In this retrospective, cohort study we included VLS patients who had undergone any topical treatment for 12 weeks, between January 2011 and March 2016, at our Vulva Unit; demographics, history and clinical features recorded at baseline and at treatment completion were elaborated. RESULTS: The study included 177 patients; among the 90 patients who reported having sexual activity 56.7% complained of dyspareunia; the frequency and severity of dyspareunia was higher among the patients who had not previously been treated with topical corticosteroids than among those who had undergone previous treatments; the patients complaining of dyspareunia reported significantly higher scores for itching and burning compared with those who did not have painful intercourses; after the treatment, 52.5%, 78.4% and 64.3% of the patients reported an improvement ≥75% compared with baseline in dyspareunia, itching and burning scores, respectively. CONCLUSIONS: Dyspareunia occurred in more than half VLS patients. The patients who complained of dyspareunia had a more severe overall symptom profile than those who did not report having painful intercourses. The objective severity of VLS did not seem to significantly affect dyspareunia occurrence and severity. Dyspareunia was found to be the symptom most resistant to treatment, however early treatment can be expected to reduce its occurrence and severity.

Gender differences in genital lichen sclerosus: data from a multicenter Italian study on 729 consecutive cases.

BACKGROUND: Studies specifically conducted to assess gender differences in genital lichen sclerosus (GLS) are not available. This multicenter study aimed to identify possible gender-related differences on GLS clinical features, history and course, through collecting data from a large mixed-sex sample of patients. METHODS: This was a cross-sectional study on 729 subjects (53.8% females, 46.2% males) affected with GLS, consecutively observed within a network of 15 Italian dermatology units. The following information was specifically collected: clinical features and severity of symptoms related to GLS, extragenital involvement, previous therapies, diagnostic suspicion at referral, type of referring physicians, development of genital squamous-cell carcinoma (SCC). RESULTS: Females complained of symptoms more frequent and severe than men; pallor and scarring-sclerosis-atrophy were the most frequent features without gender differences; itching-related signs were more frequent in females than in males as well as extragenital involvement; prior to receiving a definitive diagnosis, females received treatment more frequently than males; 40% of patients were referred with a misdiagnosis; the highest rate of correct suspected diagnosis at referral came from dermatologists than from other physicians; duration of the disease was found to predispose to SCC development. CONCLUSIONS: Our findings highlighted several gender differences on clinical presentation and symptom profile of GLS. In spite of some characteristic features, misdiagnosis at referrals was frequent.