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Sydenham's chorea (SC), an autoimmune disorder affecting the central nervous system, is a pivotal diagnostic criterion for acute rheumatic fever. Primarily prevalent in childhood, especially in developing countries, SC manifests with involuntary movements and neuropsychiatric symptoms. Predominantly occurring between ages 5 and 15, with a female bias, SC may recur, particularly during pregnancy or estrogen use. The autoimmune response affecting the basal ganglia, notably against dopamine, underlies the pathophysiology. Clinical management necessitates an integrated approach, potentially involving immunomodulatory therapies. To address discrepancies in SC management, a survey was conducted across Italy, targeting specialists in neurology, pediatrics, child neuropsychiatry, and rheumatology. Of the 51 responding physicians, consensus favored hospitalization for suspected SC, with broad support for laboratory tests and brain MRI. Treatment preferences showed agreement on oral prednisone and IVIG, while opinions varied on duration and plasmapheresis. Haloperidol emerged as the preferred symptomatic therapy. Post-SC penicillin prophylaxis and steroid therapy gained strong support, although opinions differed on duration. Follow-up recommendations included neuropsychological and cardiological assessments. Despite offering valuable insights, broader and more studies are needed in order to guide treatment decisions in this well-known yet challenging complication of acute rheumatic fever, which continues to warrant scientific attention and concerted clinical efforts.

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Hyperekplexia is a neurologic disorder characterized by an exaggerated startle reflex in response to different types of stimuli. Hyperekplexia is defined by the triad of neonatal hypertonia, excessive startle reflexes, and generalized stiffness following the startle. Although uncommon, hyperekplexia can lead to serious consequences such as falls, brain injury, or sudden infant death syndrome.Aim of this study was to identify cases of neonatal hyperekplexia with a confirmed genetic diagnosis and to establish the genotype-phenotype correlation at onset. Articles were selected from 1993 to 2024 and PRISMA Statement was applied including newborns within 28 days of life. So, we retrieved from literature 14 cases of genetically confirmed neonatal hyperekplexia. The onset of clinical manifestations occurred in the first day of life in 8 of 14 patients (57.14%). Clinical findings were muscle stiffness (100%), startle reflex (66.66%), apnea/cyanosis (41.66%), positive nose-tapping test (33.33%), jerks (33.33%), jitteriness (25%), and ictal blinking (25%). Genes involved were GLRA1 in 9 of 14 (64.28%), SLC6A5 in 2 of 14 (14.28%), GPHN in 1 of 14 (7.14%), and GLRB in 2 of 14 (14.28%). Patients showed heterozygous (66.66%) or homozygous (33.33%) status. In 7 of 14 cases (50%), the condition occurred in other family members. A genotype-phenotype correlation was not achievable.Timely diagnosis is crucial to improve the natural history of hyperekplexia avoiding/reducing possible major complications such as sudden infant death syndrome, brain injury, and serious falls. Early differentiation from epilepsy minimizes treatment cost and improves the quality of life of patients.

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BACKGROUND: John M. Opitz, a towering figure in both stature and scientific achievement, left an indelible mark on the fields of genetics, pediatrics, and embryology. Born in 1935 in Hamburg to a Jewish family, Opitz's early life was marked by adversities. Despite these challenges, he pursued a remarkable career, immigrating to the United States at 15 years and becoming a renowned scientist in institutions like Iowa State University and the University of Wisconsin, where he made groundbreaking contributions to clinical genetics. MAIN BODY: A testament to his compassionate nature, Opitz dedicated himself to understanding and treating rare genetic disorders, earning him eponymous recognition in several medical conditions. His impact extended beyond academia, as evidenced by his collaborative efforts with Sicilian universities to advance clinical genetics in Italy. Opitz's teaching style emphasized simplicity, empathy, and meticulous clinical examination, leaving an indelible mark on students and colleagues. CONCLUSION: John M. Opitz's towering intellect, compassionate demeanor, and profound impact on medicine and genetics made him a figure of enduring significance. His legacy lives on through the countless lives he touched, the knowledge he transmitted, and the enduring friendships he forged. In remembering John Opitz, we honor not only a man, but also a myth-a symbol of resilience, humanity, and scientific excellence.

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Purpose: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) usually causes a mild disease in children and the most serious consequence is multisystem inflammatory syndrome in children (MIS-C). Currently, there are no data about the protective role of vaccination performed by parents on children regarding the development of MIS-C. The aim of our study is to establish whether parental vaccination is related to MIS-C and the protective value of SARS-CoV-2 vaccination performed by parents against the occurrence of MIS-C in their children. Materials and Methods: Our retrospective single center study included 124 patients aged 1 month to 18 years admitted to emergency department from April 2020 to March 2022 for coronavirus disease 2019 disease. Results: Parental vaccination was negatively correlated with the development of MIS-C: 4% of patients with both parents vaccinated developed MIS-C, while patients with no parent vaccinated to have developed MIS-C were 20%. Conclusion: Parental vaccination could be an important factor influencing the course of the disease and reduces the probability that a child would develop MIS-C by 83% if both parents vaccinated.

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In Sicily (Italy), respiratory syncytial virus (RSV), rhinovirus (HRV), and influenza virus triggered epidemics among children, resulting in an increase in acute respiratory tract infections (ARTIs). Our objective was to capture the epidemiology of respiratory infections in children, determining which pathogens were associated with respiratory infections following the lockdown and whether there were changes in the epidemiological landscape during the post-SARS-CoV-2 pandemic era. MATERIALS AND METHODS: We analyzed multiplex respiratory viral PCR data (BioFire® FilmArray® Respiratory Panel 2.1 Plus) from 204 children presenting with respiratory symptoms and/or fever to our Unit of Pediatrics and Pediatric Emergency. RESULTS: Viruses were predominantly responsible for ARTIs (99%), with RSV emerging as the most common agent involved in respiratory infections, followed by human rhinovirus/enterovirus and influenza A. RSV and rhinovirus were also the primary agents in coinfections. RSV predominated during winter months, while HRV/EV exhibited greater prevalence than RSV during the fall. Some viruses spread exclusively in coinfections (human coronavirus NL63, adenovirus, metapneumovirus, and parainfluenza viruses 1-3), while others primarily caused mono-infections (influenza A and B). SARS-CoV-2 was detected equally in both mono-infections (41%) and coinfections (59%). CONCLUSIONS: Our analysis underlines the predominance of RSV and the importance of implementing preventive strategies for RSV.

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PURA syndrome is a congenital developmental disorder caused by de novo mutations in the PURA gene, which encodes a DNA/RNA-binding protein essential for transcriptional and translational regulation. We present the case of an 11-year-old patient with a de novo frameshift variant in the PURA gene, identified through whole exome sequencing (WES). In addition to the classical PURA deficiency phenotype, our patient exhibited pronounced sialorrhea and seizures, which were effectively treated with the ketogenic diet (KD). Our integrative approach, combining a literature review and bioinformatics data, has led to the first documented clinical case showing improvement in both sialorrhea and seizures with KD treatment, a phenomenon not previously reported. Although a direct relationship between the de novo PURA mutation and the KD was not established, we identified a novel frameshift deletion associated with a new clinical phenotype.

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This perspective discusses how to best define "e-cigarette use" among youth in a way that is relevant to individual and human health. Commonly-used definitions of youth e-cigarette use have been adapted from measures validated for tobacco cigarette smoking among adults, but may not carry the same meaning for a different product (with a much lower risk profile and very different patterns of use) and a different population (whose use is more often transient and experimental, rather than frequent and persistent). We discuss strengths and weaknesses of different definitions, and recommend improvements in defining youth e-cigarette use. We find that current literature employs a range of definitions of e-cigarette use, from lifetime use ("even a puff") to daily use. More lenient measures capture more potentially at-risk youth, but much of this is transient experimentation that has negligible risks in and itself, if not persistent. More stringent measures such as daily use are more relevant to individual and public health. Future research should examine possible improvements to definitions which include intensity of use (e.g., number of puffs per day) and persistence/duration of use, either via self-report or technology-assisted data capture.

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BACKGROUND: Cerebrospinal fluid myelin oligodendrocyte glycoprotein IgG (CSF MOG-IgG) are found in a proportion of patients with MOG antibody-associated disorder (MOGAD) and have been associated with severe disease presentations. However, most studies did not systematically investigate the role of MOG-IgG intrathecal synthesis (ITS). METHODS: We retrospectively studied 960 consecutive patients with paired serum and CSF samples screened for MOG-IgG using a live cell-based assays. MOG-IgG-specific antibody index (AIMOG) was systematically calculated using serum and CSF titres to assess MOG-IgG ITS, and clinical features were compared between MOG-IgG CSF+/CSF- and ITS+/ITS- patients. RESULTS: MOG-IgG were found in 55/960 patients (5.7%; serum+/CSF-: 58.2%, serum+/CSF+: 34.5%; serum-/CSF+: 7.3%). Serum/CSF MOG-IgG titres showed a moderate correlation in patients without ITS (ρ=0.47 (CI 0.18 to 0.68), p<0.001), but not in those with ITS (ρ=0.14 (CI -0.46 to -0.65), p=0.65). There were no clinical-paraclinical differences between MOG-IgG CSF+ vs CSF- patients. Conversely, patients with MOG-IgG ITS showed pyramidal symptoms (73% vs 32%, p=0.03), spinal cord involvement (82% vs 39%, p=0.02) and severe outcome at follow-up (36% vs 5%, p=0.02) more frequently than those without MOG-IgG ITS. A multivariate logistic regression model indicated that MOG-IgG ITS was an independent predictor of a poor outcome (OR: 14.93 (CI 1.40 to 19.1); p=0.03). AIMOG correlated with Expanded Disability Status Scale (EDSS) scores at disease nadir and at last follow-up (p=0.02 and p=0.01). CONCLUSIONS: Consistently with physiopathology, MOG-IgG ITS is a promising prognostic factor in MOGAD, and its calculation could enhance the clinical relevance of CSF MOG-IgG testing, making a case for its introduction in clinical practice.

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Background: type 1 neurofibromatosis (NF1) is the most common neurocutaneous disorder, and it is an inherited condition that causes a tumour predisposition. Central nervous system (CNS) manifestations are a significant cause of morbidity and mortality in NF1. We provide a pictorial review of neuroradiological features of NF1, with emphasis on magnetic resonance imaging (MRI), and we assess the frequency of those features on a cohort of NF1 patients. Methods: we retrospectively evaluated all patients with a diagnosis of NF1 who underwent MRI of the spine and brain in our centre over a period of almost 5 years. A total of 74 patients were enrolled, 28 males and 46 females, with a mean age of 21 ± 12.67 years. The frequency of CNS manifestations encountered in our cohort of NF1 patients was assessed and compared with the data found in other studies published in the literature. Results: many of our findings were in line with the literature, and possible interpretations for those that turned out to be different were suggested in the discussion. Conclusion: imaging plays a central role in the diagnosis and management of NF1, and the knowledge of CNS manifestations could be critical for its early detection and identification, such as for treatment planning and prognostic implications.

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Wilson's disease (WD) is a biallelic disease-causing variant in the ATP7B gene on chromosome 13q14.3 that results in copper accumulation in many organs, particularly the liver and brain. The phenotypic spectrum is wide and symptoms at onset can be heterogeneous. We describe two Sicilian siblings, a young man and his elder sister, both compound heterozygous for the variants c.1286-2A>G and c.2668G>A (p.Val890Met) in the ATB7B gene. The male patient presented with liver cirrhosis, which quickly progressed to end-stage liver disease (Child-Pugh score = C10), while his sister had moderate steatotic liver disease (SLD). Our findings highlight that SLD may not always be related to obesity in overweight patients, especially when there are other potential risk factors such as a family history of chronic liver disease, or the persistence of high transaminase despite the adoption of adequate dietary and pharmacological intervention. Screening for conditions such as WD could identify patients at risk of developing SLD and avoid delays in diagnosis. Phenotypic variability in WD is considerable; therefore, further studies are needed to identify which WD patients have a greater risk of developing SLD and determine factors that can predict the severity of the disease.

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BACKGROUND: The main objective of this study was to evaluate the neurological consequences of delayed pyridoxine administration in patients diagnosed with Pyridoxin Dependent Epilepsies (PDE). MATERIALS AND METHODS: We reviewed 29 articles, comprising 52 genetically diagnosed PDE cases, ensuring data homogeneity. Three additional cases were included from the General Pediatric Operative Unit of San Marco Hospital. Data collection considered factors like age at the first seizure's onset, EEG reports, genetic analyses, and more. Based on the response to first-line antiseizure medications, patients were categorized into four distinct groups. Follow-up evaluations employed various scales to ascertain neurological, cognitive, and psychomotor developments. RESULTS: Our study includes 55 patients (28 males and 27 females), among whom 15 were excluded for the lack of follow-up data. 21 patients were categorized as "Responder with Relapse", 11 as "Resistant", 6 as "Pyridoxine First Approach", and 2 as "Responders". The neurological outcome revealed 37,5 % with no neurological effects, 37,5 % showed complications in two developmental areas, 15 % in one, and 10 % in all areas. The statistical analysis highlighted a positive correlation between the time elapsed from the administration of pyridoxine after the first seizure and worse neurological outcomes. On the other hand, a significant association was found between an extended latency period (that is, the time that elapsed between the onset of the first seizure and its recurrence) and worse neurological outcomes in patients who received an unfavorable score on the neurological evaluation noted in a subsequent follow-up. CONCLUSIONS: The study highlights the importance of early recognition and intervention in PDE. Existing medical protocols frequently overlook the timely diagnosis of PDE. Immediate administration of pyridoxine, guided by a swift diagnosis in the presence of typical symptoms, might improve long-term neurological outcomes, and further studies should evaluate the outcome of PDE neonates promptly treated with Pyridoxine.

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BACKGROUND: In response to the imperative need for standardized support for adolescent Gender Dysphoria (GD), the Italian Academy of Pediatrics, in collaboration with the Italian Society of Pediatrics, the Italian Society for Pediatric Endocrinology and Diabetes, Italian Society of Adolescent Medicine and Italian Society of Child and Adolescent Neuropsychiatry is drafting a position paper. The purpose of this paper is to convey the author's opinion on the topic, offering foundational information on potential aspects of gender-affirming care and emphasizing the care and protection of children and adolescents with GD. MAIN BODY: Recognizing that adolescents may choose interventions based on their unique needs and goals and understanding that every individual within this group has a distinct trajectory, it is crucial to ensure that each one is welcomed and supported. The approach to managing individuals with GD is a multi-stage process involving a multidisciplinary team throughout all phases. Decisions regarding treatment should be reached collaboratively by healthcare professionals and the family, while considering the unique needs and circumstances of the individual and be guided by scientific evidence rather than biases or ideologies. Politicians and high court judges should address discrimination based on gender identity in legislation and support service development that aligns with the needs of young people. It is essential to establish accredited multidisciplinary centers equipped with the requisite skills and experience to effectively manage adolescents with GD, thereby ensuring the delivery of high-quality care. CONCLUSION: Maintaining an evidence-based approach is essential to safeguard the well-being of transgender and gender diverse adolescents.

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INTRODUCTION: GNAO1 encephalopathy is characterized by severe hypotonia, psychomotor retardation, epilepsy, and movement disorders. Genetic variations in GNAO1 have been linked to neurological symptoms including movement disorders like dystonia. The correlation between the E246K mutation in the Gα subunit and aberrant signal transduction of G proteins has been established but no data are reported regarding the efficacy of medical treatment with tetrabenazine. METHODS: Molecular modeling studies were performed to elucidate the molecular mechanisms underlying this mutation. We developed drug efficacy models using molecular dynamic simulations that replicated the behavior of wild-type and mutated proteins in the presence or absence of ligands. RESULTS AND DISCUSSION: We demonstrated that the absence of the mutation leads to normal signal transduction upon receptor activation by the endogenous ligand, but not in the presence of tetrabenazine. In contrast, the presence of the mutation resulted in abnormal signal transduction in the presence of the endogenous ligand, which was corrected by the drug tetrabenazine. Tetrabenazine was identified as a promising therapeutic option for pediatric patients suffering from encephalopathy due to an E246K mutation in the GNAO1 gene validated through molecular dynamics. This is a potential first example of the use of this technique in a rare neurological pediatric disease.

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BACKGROUND: Point-of-care ultrasound (POCUS) is becoming increasingly crucial in the Pediatric Emergency Department for objective patient examination. However, despite its growing interest and wide-ranging applications, POCUS remains relatively unexplored in general pediatric training and education. Many physicians still find it challenging to comprehend and implement. METHODS: A theoretical-practical POCUS course for pediatric residents was conducted at the University of Catania, Italy. The course's effectiveness and practical impact on residents was assessed through a pre-post training survey. The first part of the questionnaire focused on the self-perceived time needed to learn how to recognize the following conditions using POCUS: (i) Pleural effusion (ii) Lung consolidation (iii) Pneumothorax (PNX) (iv) Cardiac contractility (v) Pericardial effusion (vi) Perisplenic effusion (vii) Morison's pouch effusion (viii) Douglas' pouch effusion (ix) Filling and collapsibility of the inferior vena cava. In the second part, we compared the potential role of POCUS in (i) Reducing the use of ionizing radiation in children (ii) Increasing the sense of security in diagnosis and treatment decisions making and (iii) Increasing the residents' confidence level with POCUS after the course on a 1-to-10 rating scale. RESULTS: Seventy-two residents participated in the study. The statistical analysis showed significant pre-post differences in almost all the items considered, except for "cardiac contractility" and "PNX". Furthermore, the perceived potential role of POCUS in reducing ionizing radiation usage and the sense of security in diagnosis and treatment decisions showed statistically significant differences (p < 0.05) before and after the course. Data analysis also revealed a consistently high confidence level with POCUS after the course. CONCLUSIONS: The results highlight the importance of including a POCUS track course in pediatric post-graduate programs due to its simplicity, rapid learning time, and clinical usefulness. Based on these findings, it would be recommended to increase the teaching hours dedicated to the recognition of pneumothorax and cardiology POCUS examination. Emphasizing POCUS training in pediatric education can enhance patient care and diagnostic accuracy while minimizing radiation exposure.

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Background: Motor Imagery (MI) is a cognitive process consisting in mental simulation of body movements without executing physical actions: its clinical use has been investigated prevalently in adults with neurological disorders. Objectives: Review of the best-available evidence on the use and efficacy of MI interventions for neurorehabilitation purposes in common and rare childhood neurological disorders. Methods: systematic literature search conducted according to PRISMA by using the Scopus, PsycArticles, Cinahl, PUBMED, Web of Science (Clarivate), EMBASE, PsychINFO, and COCHRANE databases, with levels of evidence scored by OCEBM and PEDro Scales. Results: Twenty-two original studies were retrieved and included for the analysis; MI was the unique or complementary rehabilitative treatment in 476 individuals (aged 5 to 18 years) with 10 different neurological conditions including, cerebral palsies, stroke, coordination disorders, intellectual disabilities, brain and/or spinal cord injuries, autism, pain syndromes, and hyperactivity. The sample size ranged from single case reports to cohorts and control groups. Treatment lasted 2 days to 6 months with 1 to 24 sessions. MI tasks were conventional, graded or ad-hoc. MI measurement tools included movement assessment batteries, mental chronometry tests, scales, and questionnaires, EEG, and EMG. Overall, the use of MI was stated as effective in 19/22, and uncertain in the remnant studies. Conclusion: MI could be a reliable supportive/add-on (home-based) rehabilitative tool for pediatric neurorehabilitation; its clinical use, in children, is highly dependent on the complexity of MI mechanisms, which are related to the underlying neurodevelopmental disorder.

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PURPOSE: Our study aimed to evaluate the effectiveness of corticosteroids on seizure control in drug-resistant epilepsies (DREs). Our primary goal was to assess the response to steroids for various underlying etiologies, interictal electroencephalographic (EEG) patterns and electroclinical seizure descriptions. Our second goal was to compare steroid responsiveness to different treatment protocols. METHODS: This is a retrospective multicentre cohort study conducted according to the STROBE guidelines (Strengthening the Reporting of Observational Studies in Epidemiology). The following data were collected for each patient: epilepsy etiology, interictal EEG pattern, seizure types and type of steroid treatment protocol administered. RESULTS: Thirty patients with DRE were included in the study. After 6 months of therapy, 62.7 % of patients experienced reduced seizure frequency by 50 %, and 6.6 % of patients experienced complete seizure cessation. Findings associated with favourable response to steroids included structural/lesional etiology of epilepsy, immune/infectious etiology and focal interictal abnormalities on EEG. Comparing four different steroid treatment protocols, the most effective for seizure control was treatment with methylprednisolone at the dose of 30 mg/kg/day administered for 3 days, leading to greater than 50 % seizure reduction at 6 months in 85.7 % of patients. Treatment with dexamethasone 6 mg/day for 5 days decreased seizure frequency in 71.4 % of patients. Hydrocortisone 10 mg/kg administered for 3 months showed a good response to treatment in 71 %. CONCLUSIONS: In our study, two-thirds of patients with DRE experienced a significant seizure reduction following treatment with steroids. We suggest considering steroids as a potential therapeutic option in children with epilepsy not responding to conventional antiseizure medicines (ASM).

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BACKGROUND: Currently, there is no evidence that MRI produces harmful effects on premature newborns, as well as short-term and long-term safety issues regarding radiofrequency fields and loud acoustic environment, while the examination that is being performed has not been clearly investigated. MRI of the brain conducted on preterm infants should be part of the diagnostic workup, when necessary. This article is intended to evaluate the short-term safety of MRI performed in preterm infants, when required, by analyzing all vital parameters available before, during, and after the MRI procedures. METHODS: We conducted a systematic review of the literature on electronic medical databases (PubMed and ClinicalTrials.gov) following the Preferred Reported Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We included all preterm infants who underwent MRI whose clinical, hemodynamic, and respiratory parameters were reported. The quality of the included articles was assessed using QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies) tool. RESULTS: Six studies were included with a total of 311 preterm infants. No severe adverse event, such as death, occurred during MRI procedures. Vital signs remained stable in about two-thirds of all patients. CONCLUSIONS: Given the general clinical safety of MRI, we suggest it as a tool to be used in preterm infants in Neonatal Intensive Care Units, when necessary. We further suggest the development of standard protocols to guide the use of MRI in preterm infants to maximize the clinical safety of the procedure.

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Glucose transporter type 1 deficiency syndrome (GLUT-1DS) is characterized by alterations in glucose translocation through the blood-brain barrier (BBB) due to mutation involving the GLUT-1 transporter. The fundamental therapy is ketogenic diet (KD) that provide an alternative energetic substrate - ketone bodies that across the BBB via MCT-1 - for the brain. Symptoms are various and include intractable seizure, acquired microcephalia, abnormal ocular movement, movement disorder, and neurodevelopment delay secondary to an energetic crisis for persistent neuroglycopenia. KD is extremely effective in controlling epileptic seizures and has a positive impact on movement disorders and cognitive impairment. Cases of KD resistance are rare, and only a few of them are reported in the literature, all regarding seizure. Our study describes a peculiar case of GLUT-1DS due to a new deletion involving the first codon of SLC2A1 gene determining a loss of function with a resistance to KD admitted to hospital due to intractable episodes of dystonia. This patient presented a worsening of symptomatology at higher ketonemia values but without hyperketosis and showed a complete resolution of symptomatology while maintaining low ketonemia values. Our study proposes an in-silico genomic and proteomic analysis aimed at explaining the atypical response to KD exhibited by our patient. In this way, we propose a new clinical and research approach based on precision medicine and molecular modelling to be applied to patients with GLUT-1DS resistant to first-line treatment with ketogenic diet by in silico study of genetic and altered protein product.

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