Respiratory infections are one of the most common causes of morbidity and mortality among children. After the COVID-19 pandemic, the epidemiology of respiratory tract infections has changed and has been better traced by more frequent and less expensive molecular and antigenic tests. The main aim of this retrospective study was to evaluate the epidemiology of respiratory infections among children hospitalized in Perugia during the epidemic seasons of 2018–2019 and 2023–2024, comparing clinical severity, hospitalization length, diagnostic and therapeutic interventions. We retrospectively analysed hospital records of all patients admitted to our clinic from October 2018 to March 2019 and from October 2023 to March 2024. In the post-COVID-19 era, hospitalizations for respiratory infections increased proportionally to other hospitalization causes, remaining the most common ones. Length of hospital stay was shorter, with no difference based on age, C-Reactive Protein levels or symptoms at admission. A change of respiratory infection epidemiology after the COVID-19 pandemic has been witnessed also in our setting: Respiratory Syncytial Virus and Influenza played a central role, displaying earlier peaks and severe clinical pictures. Increased use of molecular testing allowed for prompt etiological diagnoses, likely contributing to shorter inpatient stays and fewer antibiotic prescriptions, thus reducing economic burden for each patient and promoting improved antibiotic stewardship. In our setting, respiratory infections still accounted for the majority of pediatric hospitalizations during the autumn/winter seasons. A comprehensive testing strategy for etiological diagnosis of respiratory infections in hospitalized patients seemed to be cost-effective by reducing hospital stay and antibiotic prescriptions. This study may inform healthcare policy by emphasizing the importance of etiological diagnosis and the economic burden of inappropriate treatments.

INTRODUCTION:Developmental and epileptic encephalopathies (DEEs), epilepsy-associated neurodevelopmental disorders (NDD), and epileptic syndromes with or without encephalopathy (ES±E) share overlapping genetic architectures where both etiology and seizures impair development. Despite genomic advances, many patients remain pharmacoresistant, and molecular diagnoses seldom translate into targeted treatments. This review connects mechanistic categories to precision therapies, providing a clinical decision-making framework. AREA COVERED:We outline pharmacological and investigational strategies-including antiseizure medications, dietary therapies, and disease-modifying approaches-across major mechanistic categories, including ion channel/receptor dysfunctions, synaptic/signaling defects, metabolic disorders, and neurodegenerative storage diseases. For each condition, potential therapeutic options are interpreted within a hierarchical precision-based framework, ranging from empiric seizure-type-driven treatments to gene-specific molecular interventions. A narrative literature search was conducted across major databases for English-language articles on DEEs, NDD, ES±E, and precision therapeutic approaches published up to early 2026. We categorized potential therapeutic interventions into five hierarchical tiers based on etiological specificity and evidence. Classification, achieved by expert consensus, distinguishes established (Tiers 1-3) from emerging strategies (Tiers 4-5). EXPERT OPINION:Progress depends on early etiological diagnosis and timely, mechanism-informed therapy. Future advances require expanded genomic testing, natural history studies, mechanism-based biomarkers, and innovative trial designs tailored to complex pediatric populations.

Introduction Nocturnal enuresis (NE) is a common pediatric disorder that significantly affects the quality of life of both children and their families. Desmopressin, a first-line pharmacological treatment, is available in two oral formulations: traditional tablets and oral lyophilizate (MELT). Clinical observations suggest that in pediatric patients, MELT may be chewed or swallowed prematurely, especially in younger children, potentially compromising its intended sublingual absorption and efficacy. This study aimed to compare the efficacy of desmopressin tablets vs MELT formulations in pediatric patients with mono-symptomatic NE (MNE). Material and methods This retrospective, observational, single-center study included 536 pediatric patients with MNE, treated at the Enuresis Center, Operative Research Unit of Pediatrics, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy. Patients were assigned to two independent treatment cohorts: MELT (n = 393) and tablet (n = 143). Efficacy was evaluated over 12 weeks using a "dry night calendar." Results A statistically significant difference in efficacy was observed between the two formulations (p = 0.045). In the MELT group, response rates were: non-responders 33.7%, partial responders 43.2%, and full responders 23.2%. In the tablet group, rates were: non-responders 20.8%, partial responders 49%, and full responders 30.2%. Conclusions Patients treated with the tablet formulation demonstrated a superior overall therapeutic response, with a higher rate of optimal response and a lower incidence of no response compared to the MELT formulation.

Growing evidence indicates a bidirectional relationship between the gut microbiota and sleep disturbances in children, with the microbiota-gut-brain axis (MGBA) mediating this interaction. Sleep, circadian rhythms, and the gut microbiota form an interdependent and developmentally dynamic network that plays a crucial role in neurodevelopment during infancy and childhood. Although the mechanisms underlying this complex interaction have not yet been fully elucidated, emerging evidence suggests that multiple dimensions of sleep-including duration, quality, timing, and regularity-are closely associated with gut microbial composition and function. These findings support the rationale for nutritional and microbiota-targeted interventions during critical developmental windows. However, most mechanistic and taxonomic evidence derives from adult or mixed-age cohorts, while methodological heterogeneity, geographic bias, and the predominance of cross-sectional studies limit causal inference. This review provides an overview of the recent literature investigating the role of the gut microbiota in sleep and sleep disorders in children and summarizes potential microbiota-based therapeutic strategies.

INTRODUCTION:Pediatric focal epilepsies comprise a heterogeneous group of disorders, ranging from self-limited childhood syndromes to severe drug-resistant forms associated with structural, genetic, immune, or unknown etiologies. Despite newer antiseizure medications, pediatric evidence remains largely extrapolated from heterogeneous focal-onset seizure trials, with limited syndrome- or localization-specific data. AREAS COVERED:A structured iterative narrative search of PubMed, Scopus, and Embase was completed in May 2026 and supplemented by section-specific searches and manual reference screening. This review summarizes current and emerging pharmacotherapeutic options for selected representative pediatric focal epilepsies using a syndrome- and localization-oriented approach. We discuss self-limited focal epilepsies of childhood, frontal lobe epilepsy, and temporal lobe epilepsy, highlighting conventional antiseizure medications, newer agents, and investigational or repurposed treatments. Particular attention is given to drug resistance, comorbidities, rational polytherapy, and integration of pharmacological treatment with genetic diagnosis, neuroimaging, and surgical evaluation. EXPERT OPINION:Management is moving from a purely seizure-based approach toward individualized, mechanism-informed care. Newer antiseizure medications expand therapeutic options, particularly in drug-resistant focal epilepsies, but should not delay etiological work-up or timely referral for epilepsy surgery. Future progress will require pediatric condition-specific trials, genotype-driven stratification, real-world data, and targeted therapies.

Epilepsy, particularly drug-resistant epilepsy, remains a significant clinical challenge, with many patients failing to achieve seizure control through conventional antiseizure medications. This unmet need has directed research toward alternative therapeutic targets, including neurosteroid modulation and novel molecular pathways. Soticlestat, a selective inhibitor of cholesterol 24-hydroxylase, is a mechanistically distinct investigational approach to epilepsy treatment by modulating mechanisms beyond those targeted by traditional antiseizure medication. Early-phase clinical trials and preclinical studies demonstrated soticlestat’s potential in reducing seizure frequency and highlighted additional benefits related to quality-of-life improvements in epilepsy patients. However, recent Phase III trials in Dravet syndrome and Lennox-Gastaut syndrome reported mixed results. Beyond seizure control, soticlestat mechanism of action may offer neuroprotective effects, potentially addressing neurodegeneration and neuroinflammation associated with chronic epilepsy, which could support improved cognitive outcomes over time. These findings underscore the need for further research to elucidate the long-term benefits and potential synergy of soticlestat in combination with other antiseizure medications across diverse epilepsy syndromes. While challenges remain, soticlestat offers a promising therapeutic avenue for improving outcomes in DRE and warrants continued investigation as a potential adjunctive treatment.

Purpose : Epilepsy affects not only physical functioning but also neurocognitive, emotional, and social skills. In chronic epilepsy, cognitive impairment and executive dysfunction are closely related to seizure frequency and severity, making them useful predictive markers for clinical and therapeutic management. This study explores the clinical correlation between childhood absence epilepsy (CAE) and developmental coordination disorder (DCD) through a comprehensive assessment protocol. Methods : Nineteen children diagnosed with CAE, according to ILAE criteria, were compared with twenty-one typically developing children. Assessments included evaluations of motor coordination using the Movement Assessment Battery for Children 2nd edition and visual-motor integration with the Beery-Buktenica Developmental Test of Visual- Motor Integration. Results : Significant differences in motor coordination and visual-motor integration were observed between the CAE group and controls, with a higher prevalence of DCD in the CAE group (73.68% vs 4.76%). Moreover, a correlation between the duration of CAE and the severity of DCD was found, suggesting a potential cumulative effect over time. These findings underscore the significant impact of CAE on motor coordination and visual-motor integration skills, independent of age, gender, or intellectual abilities. Additionally, they highlight the importance of early identification and intervention for DCD in children with CAE to address long-term motor impairment and optimize outcomes. Conclusion : This research contributes to understanding the shared neurobiological mechanisms underlying epilepsy and DCD, emphasizing the importance of comprehensive assessment and targeted interventions to support affected children's development and quality of life.

Background: Epilepsy is a complex neurological disorder in which growing evidence supports a significant role for the microbiota-gut-brain axis (MGBA) in modulating neuroinflammation, neuronal excitability, and treatment responsiveness. Beyond their traditional role in inducing ketosis, dietary therapies may influence epilepsy by modulating gut microbial ecology, intestinal barrier integrity, immune signaling, and microbiota-derived metabolites. Methods: This narrative review critically examines current clinical and experimental evidence regarding the relationship between epilepsy, gut microbiota, and dietary interventions. Particular attention was given to ketogenic dietary therapies, the Modified Atkins Diet (MAD), low-glycemic-index treatment (LGIT), Mediterranean dietary patterns, restrictive diets, and microbiota-targeted supplementation, including probiotics, prebiotics, and postbiotics. Results: Available evidence suggests that patients with epilepsy exhibit alterations in gut microbial composition associated with impaired short-chain fatty acid production, intestinal inflammation, and altered neuroimmune regulation. Ketogenic and microbiota-supportive dietary approaches may modulate these pathways beyond ketosis alone, potentially contributing to seizure reduction through integrated metabolic, inflammatory, and microbial mechanisms. Emerging evidence also supports a role for probiotics, prebiotics, and postbiotics in modulating gut-brain communication and neuroinflammatory signaling, although current clinical data remain limited. Conclusions: Dietary therapies in epilepsy should no longer be viewed exclusively as metabolic interventions aimed at inducing ketosis, but rather as potential modulators of the microbiota-gut-brain axis and neuroimmune homeostasis. While further mechanistic and clinical studies are needed, microbiota-targeted nutritional approaches may represent valuable complementary strategies to be integrated alongside conventional antiseizure therapies within more personalized models of epilepsy management.

BACKGROUND/OBJECTIVES:This study examined whether exposure to white noise improves reading and writing performance in children with Specific Learning Disorder (SLD), with and without comorbid Attention-Deficit/Hyperactivity Disorder (ADHD). METHODS:Thirty children aged 8-13 years (mean age = 9.4) with SLD, 12 of whom also had ADHD, were recruited from the Centro di Riabilitazione San Raffaele Pisana (Rome). Each child completed two standardized reading and writing assessments, four weeks apart, under two auditory conditions (with vs. without white noise) in randomized order. The primary outcomes were reading speed and accuracy, while the secondary outcome was writing accuracy. RESULTS:Among the 26 completers, white noise significantly improved nonword reading speed and accuracy, showed a trend toward improved passage-reading accuracy, and reduced accuracy in nonword writing. Benefits were different in children with SLD + ADHD compared to those with SLD only. CONCLUSIONS:These findings indicate task-specific effects of white noise and suggest potential applications for targeted educational interventions.

Seizures, when prolonged or repeated, leading to status epilepticus (SE), represent a medical emergency, requiring prompt treatment. In these conditions, the use of continuous midazolam (MDZ) infusion is often reserved for established or refractory SE and considered an anesthesiologic treatment, while evidence on its early use in non-intensive settings is still limited. To verify this approach in daily practice, we retrospectively collected data on about 42 episodes of pediatric SE or acute repetitive seizures (ARSs), treated with continuous MDZ infusion in non-intensive setting. Collected data include demographical information, previous history of epilepsy, instrumental examinations (electroencephalography [EEG] and brain magnetic resonance imaging [MRI]), comorbidities, anti-seizure medications (ASMs), information about the event, other treatments (first- and second-line), information about MDZ infusion, and need for other third-line treatment and/or intensive care unit (ICU) transfer. Infusion durations and rates varied widely, but in most cases (38/42) low dose (<.23 mg/kg/h) were employed. The treatment was effective in 84.2% of cases, achieving both clinical and EEG response. No adverse events (AEs) were reported. The need for a second-line treatment (particularly levetiracetam [LEV] and phenobarbital [PB]) was associated with a worse outcome. Another third-line treatment was needed in 9.5% of cases. Patients (21.4%) were transferred to ICU; a higher risk of ICU admission was reported in patients with precipitating factors (infection, surgery, hypertension and suboptimal anti-seizure medication [ASM] serum levels), and those receiving MDZ infusion at higher rates and/or co-treated with PB. Overall, our study suggests that low-dose continuous MDZ infusion is an effective and safe strategy for treatment of pediatric SE and ARSs in non-intensive settings.

Background Heterozygous variants in FBXW7 have recently been recognized as a cause of a rare neurodevelopmental disorder with variable developmental delay, neurological manifestations, and multisystem involvement. The breadth of clinical variability and penetrance remains incompletely defined.Cases presentation We report a retrospective multicenter case series of seven previously unreported individuals (five males, two females) with heterozygous FBXW7 variants identified through clinical genetic testing, aged 5-9 years at last evaluation (median 6 years). Six variants occurred de novo and one was inherited. Neurodevelopmental involvement was present in six individuals and was characterized by global developmental delay and language impairment; hypotonia was observed in all seven. Formal intellectual disability was documented in four cases, while one individual showed preserved cognitive functioning with predominant behavioral difficulties. Epileptic seizures occurred in four individuals, whereas three had no history of epilepsy. Brain MRI was available for six individuals and was normal in four, whereas two showed structural anomalies involving the corpus callosum. Extracerebral features were variably reported, most commonly constipation and recurrent respiratory/otolaryngological infections. Comparison with previously reported individuals confirmed the core neurodevelopmental phenotype and further refined the spectrum.Conclusions This case series expands the phenotypic spectrum associated with FBXW7-related neurodevelopmental disorder and highlights variable expressivity and incomplete penetrance, including clinically relevant variants presenting with mild or atypical phenotypes. These findings support considering FBXW7 across a broad range of neurodevelopmental presentations and inform genetic counseling.

Neurological and neuropsychiatric disorders, particularly drug-resistant epilepsies and rare genetic syndromes such as CDKL5 deficiency disorder, pose significant therapeutic challenges. Ganaxolone (GNX), a synthetic neurosteroid and positive allosteric modulator of GABA-A receptors, has emerged as a promising treatment option due to its unique pharmacological properties. This review explores GNX's pharmacokinetic profile, preclinical evidence, and clinical applications. Preclinical studies have demonstrated its efficacy in reducing seizure frequency and severity across various epilepsy models, including amygdala kindling and status epilepticus, as well as its neuroprotective effects in hypoxic-ischemic encephalopathy. Clinical trials have confirmed GNX's benefits, particularly in CDD, where it significantly reduces seizure frequency, leading to its FDA and EMA approval. Additionally, GNX has shown potential in focal epilepsy, status epilepticus, and other drug-resistant epilepsies, although with variable results. Beyond epilepsy, GNX's modulation of GABAergic signaling suggests potential applications in neuropsychiatric conditions. Its favorable safety profile further supports its therapeutic value.

OBJECTIVES:Migraine is the most common etiology of episodic vertigo in pediatric populations. The characteristics of migraine headaches in children differ from those in adults, with initial manifestations frequently presenting as periodic syndromes. Sleep disorders are prevalent among individuals with migraines. Headaches may not be present in early childhood, and children may not easily report aura or phono-photophobia. Therefore, it is essential to identify clinical and anamnesic elements that can support the etiopathogenetic hypothesis of migraine in the assessment of episodic idiopathic vertigo. The objective of this study was to assess the validity of research concerning sleep disorders in children experiencing episodic vertigo, with the aim of providing evidence for a connection to migraine. METHODS:The study included 25 participants diagnosed with episodic idiopathic vertigo, including 13 females and 12 males, aged between 5 and 14 years. A range of anamnestic parameters was analyzed, including the presence, type, and age of onset of sleep disorders; the presence, characteristics, and age of onset of headaches; and the presence of a family history of migraine. The data were compared with those of a control group matched for age and sex, which was affected by dysfunctional dysphonia and had no history of vertigo. The comparison of percentage values concerning the parameters under examination was conducted using the chi-square statistic test with Yates correction. A t-test was employed to compare the means and standard deviations. The significance limit is established for p values ≤ 0.05. RESULTS:Sleep disorders were present in 15 out of 25 patients (60 %) with episodic vertigo, compared to 3 out of 25 (12 %) in the control group (p = 0.001). Somniloquy is the most prevalent disorder. Headache was reported by 12 out of 25 recruited patients (48 %), with 8 cases classified as migraine-type, 1 as tension-type, and 3 as mixed or indefinite-type. In the control group, 4 out of 25 (16 %) reported headaches, including 1 migraine-type, 2 tension-type, and 1 mixed or indefinite-type (p = 0.03). A family history of migraine was identified in 19 (76 %) of the 25 patients and in 7 (28 %) of the 25 subjects in the control group (p = 0.001). The average age of onset for sleep disorders was 6.28 ± 1.67 years, while for headaches it was 9.25 ± 3.01 years (p = 0.01). The comparative analysis of symptom distribution by patient age indicates that all patients with sleep disorders reported this clinical manifestation by the age of eight years. Conversely, only 26.6 % of these patients reported experiencing the headache for the first time at the same age. CONCLUSIONS:Children with episodic idiopathic vertigo exhibit a high prevalence of sleep disorders, alongside a significant correlation with headaches and a familial history of migraine. In younger patients, migraine symptoms, particularly headache, necessary for diagnosing vestibular migraine, are frequently absent or unreported. Studies on sleep disorders in children experiencing episodic idiopathic vertigo indicate a correlation with migraine.

Artificial intelligence(AI)is promising for supporting and optimizing clinical practice in various fields while simul-taneously arousing excitement and concerns about its ben-efits and limitations[1].Even in the field of epilepsy,the application of AI techniques has enabled the development of highly relevant tools for both diagnostic and therapeutic purposes.In particular,the diagnostic domain is on the verge of benefiting from AI-assisted tools that can enhance already widely utilized methodologies,such as electroencephalo-gram(EEG)pattern analysis,neuroimaging data interpreta-tion and the integration of wearable or remote monitoring devices.Similarly,the therapeutic approach stands to gain significantly from AI-driven methodologies,which have the potential to redefine the boundaries of personalized medi-cine,seizure management and decision-making in neurosur-gical interventions.

Lennox-Gastaut syndrome (LGS) is one of the most severe, yet one of the most discussed, childhood-onset developmental and epileptic encephalopathies (DEEs). Dissent among epileptologists on the definition and minimum set of electroclinical features derives from the high etiological heterogeneity within the syndrome, which could make its prevalence overestimated. However, in recent years, our diagnostic strategies, including both high-resolution magnetic resonance imaging and next-generation sequencing techniques, have enabled us to disentangle many cases previously classified as "idiopathic." In addition, some electroencephalographic and circulating biomarkers have been identified that could predict disease progression and treatment response if confirmed in larger patient populations. As our diagnostic capacity increases, so do our treatment strategies. Although progress has been made, the implementation of better clinical trial designs, individualized treatments, and therapies that address the genetic roots of the disease remains necessary in clinical practice. A lot is being done in this direction, thanks to the involvement of families and the creation of international networks, such as the ERNs, which are rapidly promoting collaboration among highly specialized centers and the establishment of disease registries to shed light on the natural history of LGS. Yet, many unmet needs still afflict patients and their families, including uncertainties arising from the transition process and a lack of administrative support and comprehensive care as patients transition into adulthood. This article summarizes these key challenges in diagnosing, treating, and caring for patients with LGS, as well as the roadmap to enhanced future care discussed during the international LGS meeting held in Genoa.

CDKL5 Deficiency Disorder (CDD) is a rare and severe neurodevelopmental condition marked by profound developmental delays, early-onset epilepsy, and significant impairments in motor and communication skills. The outcomes in CDD are shaped by various factors, including early-onset epilepsy and environmental influences. Genotype-phenotype correlations reveal that specific CDKL5 mutations impact developmental milestones, although considerable variability persists. Recent advancements have introduced novel antiseizure medications and emerging treatments such as gene therapy and targeted molecular interventions. Despite these promising developments, managing CDD effectively requires a comprehensive approach that integrates pharmacological treatments with neuro-rehabilitation strategies. Research has progressed in developing validated tools for assessing motor and language abilities in CDD, but monitoring neurodevelopment remains challenging due to the absence of longitudinal studies and standardized measures. This study delves into the developmental delays associated with CDD, providing an in-depth analysis of its clinical characteristics, pathogenetic mechanisms, and genetic background. It aims to uncover the pathways disrupted by CDKL5 mutations and their effects on neuronal development and function. Additionally, the study reviews potential therapeutic strategies to mitigate CDD's impact, offering a comprehensive overview of interventions to enhance patient outcomes.

Child maltreatment is a widespread global issue involving any form of harm or neglect by a parent or caregiver, leading to various forms of physical or emotional damage, with approximately 150 million affected children globally. This study discusses the potential mechanism of the hypothalamic-pituitary-adrenal axis dysfunction and cortisol hormone changes in linking child maltreatment to mental health disorders. It also discusses supportive strategies to prevent mental diseases and counteract the biological embedding of these conditions, emphasizing the need for comprehensive interventions to address the long-term impact of child maltreatment on mental health. Articles were selected using established methods previously described. Key information was obtained from scientific articles published during the past 20 years, including original studies, systematic reviews, and meta-analyses. Articles search was performed using top academic search engines. While research on hypothalamic-pituitary-adrenal axis response to stress in maltreated children is ongoing and far from conclusive, its impact and implications for physiological functioning and the predisposition to psychopathology are significant. Childhood maltreatment increases the risk of psychiatric illnesses, severity of diseases, and poor treatment responses. Childhood maltreatment manifests as disruptions to hypothalamic-pituitary-adrenal axis functioning, with the extent varying based on factors, such as the age of onset, parental responsiveness, and the type and characteristics of maltreatment. The complex interplay of these factors contributes to the diversity of hypothalamic-pituitary-adrenal axis responses to stress in maltreated children, creating a spectrum of physiological functioning and vulnerability to psychopathology.