Antonia Versace

Hereditary tyrosinemia type 1 (HT1) is a rare metabolic disorder caused by fumarylacetoacetate hydrolase deficiency, leading to the accumulation of toxic metabolites such as fumarylacetoacetate (FAA) and succinylacetone (SA). We report an 11-year-old boy with poorly controlled HT1 who presented with a severe neurovisceral crisis after suboptimal adherence to nitisinone (NTBC) therapy, characterized by abdominal pain, hypertension, paralytic ileus, seizures, and profound hyponatremia. Biochemical evaluation revealed markedly elevated urinary δ-aminolevulinic acid (ALA), consistent with a porphyria-like metabolic decompensation, together with inappropriately increased plasma copeptin in the setting of hypotonic hyponatremia and clinical euvolemia, fulfilling diagnostic criteria for the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Optimization of NTBC therapy combined with tailored fluid management resulted in complete clinical and biochemical recovery. This case supports a pathophysiological link between acute disruption of the heme–porphyrin pathway and inappropriate antidiuretic hormone secretion. In HT1, this susceptibility may be further amplified by FAA- and SA-mediated oxidative stress, mitochondrial dysfunction, and heme depletion, with an additional contribution from SA-associated renal tubular impairment. Overall, our findings underscore SIADH as a potentially underrecognized cause of acute hyponatremia in HT1 and highlight the importance of strict NTBC adherence and early monitoring of urinary ALA during metabolic decompensation.

Many headaches at night arise due to primary headache disorders, which occur independently of other symptoms and are not caused by another medical condition. Primary headache disorders with nighttime attacks can include tension-type headaches, migraines, hypnic headaches, and cluster headaches. A hypnic headache is sometimes called an “alarm clock headache” because symptoms tend to arise at the same time of night. Apart from considering primary headaches, secondary causes of nighttime headaches should be considered and ruled out, in particular headaches secondary to intracranial hypertension, temporomandibular joint issues (like bruxism) and sleep apnea. Treatments vary based on headache type but often include a combination of medications and prevention strategies. This review article covers the basics of nighttime primary headaches in children, including pathophysiology, etiology, clinical features of the different forms and their treatment. It will also discuss the differences in headache features between children and adults.

Introduction: While influenza-associated encephalopathy (IAE) in children remains a serious concern, recent evidence suggests a shift in its epidemiology, with a possible decline in incidence and severity over time. Methods: This retrospective review includes patients aged 0–18 admitted to a tertiary hospital in Northern Italy between November 2023 and February 2025. Inclusion criteria were a positive influenza test, influenza-like symptoms, and neurological involvement. Findings are interpreted alongside current literature. Results: Twenty-five unvaccinated children met criteria for IAE (11 in 2023/24; 14 in 2024/25). Neurological comorbidities were present in 40%. All patients had pathological EEGs. Lumbar puncture was performed in 40%, with abnormalities in 33%. Brain imaging was conducted in 56% of cases, revealing findings in 15%. All received oseltamivir; 60% were also treated with dexamethasone. Severe complications occurred in 16%, while 12% had persistent symptoms or required therapy at discharge. After adjusting for seasonal peak timing, no significant inter-seasonal difference was observed. Discussion: Although IAE continues to present serious risks, recent trends suggest a changing burden. The lack of vaccination among cases underscores the need for prevention. Study limitations include its single-center design and the absence of long-term follow-up. Broader prospective studies are needed.

Background: Lower airway diseases in children are one of the major causes of hospitalisation. This study aimed to evaluate the characteristics of children admitted to a tertiary pediatric hospital diagnosed with lower airway disease and to identify differences between age groups and the two years of the study. Methods: In this single-centre retrospective observational study, demographic and clinical information about children hospitalised in the emergency pediatric ward and diagnosed with lower respiratory disease from 1 June 2021 to 30 June 2023 were retrospectively reviewed. Results: A total of 410 episodes of hospitalisation for lower airway diseases were registered. In 83.9% of cases, the patient needed hospitalisation for respiratory failure, and children <1 year of age were at higher risk. Rhinovirus and respiratory syncytial virus (RSV) were the leading causes of lower respiratory tract infections. No death has been recorded. In 8.8% of cases, the patient was admitted to the Pediatric Intensive Care Unit. In 2021–2022, we recorded more hospitalisations for bronchiolitis with RSV as the primary pathogen detected and more patients were admitted to the hospital for respiratory failure. In 2022–2023, we registered more admissions for bacterial pneumonia and the need for intravenous therapy. Conclusions: Lower respiratory tract diseases are frequent in the pediatric population, and the risk of respiratory failure is higher. Analysing the differences between the two years of study, we underline how the COVID-19 pandemic has changed the epidemiology of acute respiratory infections in children.

Background/Objectives: To face antimicrobial resistance, antimicrobial stewardship programs (ASPs) have been implemented in the pediatric age, but the area of urgency remains understudied. We aimed to assess the impact of an educational program on optimizing antibiotic appropriateness in a pediatric ED. Methods: We conducted a pre-post observational study with an audit, intervention, and feedback given to prescribers. We recorded all systemic antibiotic prescriptions for children attending our pediatric ED from January to March and from July to September 2020. The study’s team assigned a score to each prescription, regarding the appropriate molecule, dose, and duration of therapy, according to the diagnosis. From April to June 2020, we held weekly meetings focusing on different pediatric infectious diseases, with interaction between one to three ED physicians and the infectious disease (ID) specialist of the study’s team. We then distributed synthetic digital guidelines adapted to our reality to all prescribers. Results: Optimal antibiotic prescriptions increased after the intervention, with statistical significance (p < 0.001) in four main aspects (overall adequacy: 13% PRE vs. 43% POST; need of antibiotics: 53% vs. 68%; adequacy of the spectrum: 55% vs. 63%; adequacy of the chosen molecule: 54% vs. 62%). We observed an improvement in all the main infectious diseases and concerns all the ED physicians. The prescription of first-choice drugs increased in specific and common illnesses such as otitis and pharyngotonsillitis. Conclusions: An antimicrobial stewardship program is a relevant method for improving the appropriateness of antimicrobial use also in the complex setting of a pediatric ED.

Background: Migraine is one of the most frequent primary headaches in childhood. The role of thrombotic predisposition in its pathogenesis is debated. Our aim was to analyse the cardiovascular risk factors and family history of major thrombotic events in children with migraine. Methods: A retrospective, single-centre study was performed over 12 years. Our headache centre record database was screened for migraine with aura (MA) and migraine without aura (MO) on the basis of the ICHD-II (until 2013) and III criteria. A control group of otherwise healthy children was recruited. Descriptive and multivariate analyses are provided; significance was set at p < 0.05. Results: Migraine was diagnosed in 930 children (24.7% MA); 73.3% were 9–14 years old. Children with MA were older (p < 0.001). A family history of cerebral ischemic events at ≤50 years old was more commonly reported by children with MA than those with MO (p < 0.001) and those in the control group (p = 0.001). Children with MA showed a higher risk of a family history of cerebral ischemic events at ≤50 years old than children with MO (OR: 2.6) and those in the control group (OR: 3.1). When comparing the family history of DVT, we observed a significantly increased risk for MA vs. MO (OR: 2.9). Conclusion: A family history of cerebral ischemic events at ≤50 years old leads to an increased risk of MA. Further studies are needed to explore such an association.

Background. The orofacial pain syndromes (OFPs) are a heterogeneous group of syndromes characterized by painful attacks involving the orofacial structures. They may be summarily subdivided into two great categories: (1) orofacial pain mainly attributed to dental disorders such as dentoalveolar and myofascial orofacial pain or temporomandibular joint (TM) pain; (2) orofacial pain mainly attributed to non-dental pain as neuralgias, facial localization of primary headaches or idiopathic orofacial pain. The second group is uncommon, often described by single case reports, can often show overlapping symptoms with the first group, and represents a clinical challenge, carrying the risk of undervaluation and possibly invasive odontoiatric treatment. We aimed to describe a clinical pediatric series of non-dental orofacial pain and better to underline some topographic and clinical features associated with them. We retrospectively collected the data of children admitted to our headache centers (Bari, Palermo, Torino) from 2017 to 2021. Our inclusion criterion was the presence of non-dental orofacial pain following the topographic criteria of 3° International Classification of Headache Disorders (ICHD-3), and exclusion criteria included the pain syndromes attributed to the dental disorders and pain syndromes due to the secondary etiologies Results. Our sample comprised 43 subjects (23/20 M/F, in the range of ages 5–17). We classified them int: 23 primary headaches involving the facial territory during attacks, 2 facial trigeminal autonomic cephalalgias, 1 facial primary stabbing headache, 1 facial linear headache, 6 trochlear migraines, 1 orbital migraine 3 red ear syndrome and 6 atypical facial pain. All patients described debilitating pain for intensity (moderate/severe), 31 children had episodic attacks, and 12 had continuous pain. Almost all received drugs for acute treatment (less than 50% were satisfied), and some received non-pharmacological treatment associated with drug therapy Conclusion. Although rare OFP can occur in pediatric age, it can be debilitating if unrecognized and untreated, affecting the psychophysical well-being of young patients. We highlight the specific characteristics of the disorder for a more correct and earlier identification during the diagnostic process, already difficult in pediatric age, and to define the approach and possible treatment to prevent negative outcomes in adulthood.

The natural history of vertically acquired HCV infection is ill defined. The aim of this study was to outline the natural course of vertical HCV infection in a cohort of untreated children, including rate of spontaneous viral clearance, frequency and features of HCV-related autoimmune disorders. Children with vertical HCV infection were prospectively followed from the first month of life with regular clinical and laboratory assessments. Statistical analysis was performed using Prism 5.0. Forty-five children (median age 12 years, interquartile range 6.9–15.5) were studied. Genotype 1 was predominant (53.3 %). Spontaneous viral clearance was achieved by 12 patients (26.7 %) and associated with genotype 3. Alanine-amino-transferase levels were increased in most children in the first 2 years of life with higher values in those who later cleared the infection. All children were asymptomatic for liver disease. Transient elastography (32 patients) showed mild or moderate fibrosis in nine and two cases, respectively. Non-organ-specific autoantibodies were detected in 24 children (53.3 %) independently of viremia; of these, one developed type-1 diabetes. Cryoglobulinemia was associated with genotype 1 infection and found in 15 subjects (33.3 %): two had low C4 levels and persistent proteinuria. Conclusions: Vertically acquired HCV infection may result in spontaneous clearance in up to 27 % of children. Resolution of infection is higher with genotype 3, usually occurs in preschool age and persists over time. Chronic infection is generally asymptomatic, although hepatomegaly and mild fibrosis may develop. Autoantibodies and cryoglobulins are frequent, whereas the associated clinical manifestations are rare.