Seizures in Children with SARS-CoV-2 Infection: Epidemiological, Clinical and Neurophysiological Characterization.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may present with a wide variety of symptoms, including neurological manifestations. We investigated clinical, demographic, laboratory, neurophysiological and imaging characteristics of SARS-CoV-2-positive children with seizures and analyzed differences between children admitted during the periods with prevalent circulation of the Alpha/Delta and Omicron variants, respectively. Patients' characteristics were analyzed according to the presence or absence of seizures and then according to the SARS-CoV-2 variants. Five-hundred and four SARS-CoV-2-positive patients were included: 93 (18.4%) with seizures and 411 (81.6%) without. Patients with seizures were older, had more commonly an underlying epilepsy and had more frequently altered C-reactive protein than those without seizures. Electroencephalography was abnormal in 5/38 cases. According to the SARS-CoV-2 variant, seizures were recorded in 4.7% of the total number of hospitalized patients during the Alpha/Delta period, and in 16.9% of patients admitted during the Omicron period. During the Alpha/Delta variants, seizures were more commonly observed in patients with epilepsy compared to those observed during the Omicron period. Our findings suggest that although SARS-CoV-2 may potentially trigger seizures, they are generally not severe and do not require intensive care admission.

Liver and Pancreatic Involvement in Children with Multisystem Inflammatory Syndrome Related to SARS-CoV-2: A Monocentric Study.

Liver and pancreatic involvement in children with Multisystem Inflammatory Syndrome related to SARS-CoV-2 (MIS-C) has been poorly investigated so far. We reviewed a cohort of MIS-C patients to analyze the prevalence of acute liver injury (ALI) and pancreatic injury and their correlation with clinical outcomes. Demographic, clinical, laboratory and imaging features of children with MIS-C at admission and during hospital stay were prospectively collected. Fifty-five patients (mean age 6.5 ± 3.7 years) were included. At admission, 16 patients showed ALI and 5 had increased total serum lipase. During observation, 10 more patients developed ALI and 19 more subjects presented raised pancreatic enzymes. In comparison to those with normal ALT, subjects with ALI were significantly older (p = 0.0004), whereas pancreatic involvement was associated to a longer duration of hospital stay compared with patients with normal pancreatic enzymes (p = 0.004). Time between hospital admission and onset of ALI was shorter compared to the onset of raised pancreatic enzymes (3.2 ± 3.9 versus 5.3 ± 2.7 days, respectively; p = 0.035). Abdominal ultrasound showed liver steatosis in 3/26 (12%) and hepatomegaly in 6/26 (16%) patients with ALI; 2 patients presented enlarged pancreas. Although liver and pancreatic involvement is commonly observed in MIS-C patients, it is mild in most cases with a complete recovery.

Brugada Pattern in a Child with Severe SARS-CoV-2 Related Multisystem Inflammatory Syndrome.

This report presents the first case of Brugada pattern complicated by a supraventricular arrhythmia in a child with SARS-CoV-2 related Multisystem Inflammatory Syndrome in Children (MIS-C). A 7-year-old boy came to our Emergency Department with 7 days of abdominal pain and fever. MIS-C was diagnosed on the basis of the clinical, laboratory and instrumental tests. On admission, ECG showed type 1 Brugada pattern in the right precordial leads. During hospitalization the onset of supraventricular arrhythmias complicated the clinical picture. This case underlines management complexity of supraventricular arrhythmic events, different from atrial fibrillation, in patients with Brugada pattern in the context of a systemic inflammatory condition with significant cardiac involvement. All potential therapeutic choices should be considered to ensure the best outcomes.

Is Covid-19 lockdown related to an increase of accesses for seizures in the emergency department? An observational analysis of a paediatric cohort in the Southern Italy.

BACKGROUND: The World Health Organization (WHO) declared a global pandemic of Covid-19 on 11 March 2020. The lockdown caused a lifestyle changes: an increase in the use of mobile media devices (MMDs), sleep and psychiatric disorders, incorrect habits regarding food and physical activities. We investigate prevalence of admission for seizures at our emergency department (ED), during Italian lockdown, comparing with that of the same period of the previous year (2019), and the relationship with some lifestyle changes. METHODS: In this observational study, patients (4-14 years) with seizures that accessed at our ED, during Italian lockdown, were eligible. Non-epileptic events and febrile seizures were excluded. We describe two groups: patients with new-onset seizures and not. Moreover, a questionnaire concerning use of MMDs and sleep habits was administered. RESULTS: Fifty-seven patients were included; median age 8.03 years. Considering only paediatric medical emergencies, the prevalence of accesses for seizures was 2.6% (CI 95% 0.020-0.034), while the incidence was 0.94% (CI 95% 0.006-0.0149). There was a statistically significant difference with prevalence of previous years, χ2 102.21 (p = 0.0001). We also reported a difference in daily screen time (DST) (p = 0.001) and total sleep time (TST) (p = 0.045), in all population, between period pre- and during lockdown. A negative correlation between DST and seizures latency (Spearman's ρ -0.426, p = 0.038) was found. In the two groups, the results were partially overlapping. CONCLUSIONS: During lockdown period, we assisted to an increase of accesses for seizures. It is conceivable that a sleep time change and/or higher MMD use could act as triggers for seizures.

Short stature and primary ovarian insufficiency possibly due to chromosomal position effect in a balanced X;1 translocation.

BACKGROUND: Primary ovarian insufficiency (POI) is defined as a primary ovarian defect characterized by absent menarche (primary amenorrhea), a decrease in the initial primordial follicle number, high follicle-stimulating hormone (FSH) levels and hypoestrogenism. Although the etiology of a majority of POI cases is not yet identified, several data suggest that POI has a strong genetic component. Conventional cytogenetic and molecular analyses have identified regions of the X chromosome that are associated with ovarian function, as well as POI candidate genes, such as FMR1 and DIAPH2. Here we describe a 10.5-year-old girl presenting with high FSH and luteinizing hormone (LH) levels, pathologic GH stimulation arginine and clonidine tests, short stature, pterygium, ovarian dysgenesis, hirsutism and POI. RESULTS: Cytogenetic analysis demonstrated a balanced reciprocal translocation between the q arms of chromosomes X and 1, with breakpoints falling in Xq21 and 1q41 bands. Molecular studies did not unravel any chromosome microdeletion/microduplication, and no XIST-mediated inactivation was found on the derivative chromosome 1. Interestingly, through immunofluorescence assays, we found that part of the Xq21q22 trait, translocated to chromosome 1q41, was late replicating and therefore possibly inactivated in 30 % metaphases both in lymphocytes and skin fibroblasts, in addition to a skewed 100 % inactivation of the normal X chromosome. These findings suggest that a dysregulation of gene expression might occur in this region. Two genes mapping to the Xq translocated region, namely DIAPH2 and FMR1, were found overexpressed if compared with controls. CONCLUSIONS: We report a case in which gonadal dysgenesis and POI are associated with over-expression of DIAPH2 gene and of FMR1 gene in wild type form. We hypothesize that this over-expression is possibly due to a phenomenon known as "chromosomal position effect", which accounts for gene expression variations depending on their localization within the nucleus. For the same effect a double mosaic inactivation of genes mapping to the Xq21-q22 region, demonstrated by immunofluorescence assays, may be the cause of a functional Xq partial monosomy leading to most Turner traits of the proband's phenotype.

Management of adults with paediatric-onset chronic liver disease: strategic issues for transition care.

Advances in the management of children with chronic liver disease have enabled many to survive into adulthood with or without their native livers, so that the most common of these conditions are becoming increasingly common in adult hepatology practice. Because the aetiologies of chronic liver disease in children may vary significantly from those in adulthood, adults with paediatric-onset chronic liver disease may often present with clinical manifestations unfamiliar to their adulthood physician. Transition of medical care to adult practice requires that the adulthood medical staff (primary physicians and subspecialists) have a comprehensive knowledge of childhood liver disease and their implications, and of the differences in caring for these patients. Pending still unavailable Scientific Society guidelines, this article examines causes, presentation modes, evaluation, management, and complications of the main paediatric-onset chronic liver diseases, and discusses key issues to aid in planning a program of transition from paediatric to adult patients.

Therapeutic options in pediatric non alcoholic fatty liver disease: current status and future directions.

The epidemics of overweight and obesity has resulted in a significant increase of non alcoholic fatty liver disease (NAFLD), a potentially progressive condition. Currently, obesity related hepatopathy represents therefore the main cause of pediatric chronic liver disease. The first choice treatment at all ages is weight loss and/or lifestyle changes, however compliance is very poor and a pharmacological approach has become necessary. In the present article we present a systematic literature review focusing on established pediatric NALFD drugs (ursodeoxycholic acid, insulin sensitizers, and antioxidants) and on innovative therapeutic options as well.Regarding the former ones, a pediatric pilot study highlighted that ursodeoxycholic acid is not efficient on transaminases levels and bright liver. Similarly, a recent large scale, multicenter randomized clinical trial (TONIC study) showed that also insulin sensitizers and antioxidant vitamin E have scarce effects on serum transaminase levels. Among a large series of novel therapeutic approaches acting on recently proposed different pathomechanisms, probiotics seem hitherto the most interesting and reasonable option for their safety and tolerability. Toll-like receptors modifiers, Pentoxifylline, and Farnesoid X receptors agonists have been still poorly investigated, and will need further studies before becoming possible promising innovative therapeutic strategies.

Diagnosis of nonalcoholic fatty liver disease in children and adolescents: position paper of the ESPGHAN Hepatology Committee.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children and adolescents in the United States, and most probably also in the rest of the industrialized world.As the prevalence of NAFLD in childhood increases with the worldwide obesity epidemic, there is an urgent need for diagnostic standards that can be commonly used by pediatricians and hepatologists. To this end, we performed a PubMed search of the adult and pediatric literature on NAFLD diagnosis through May 2011 using Topics and/or relevant Authors as search words. According to the present literature, NAFLD is suspected based on the association of fatty liver combined with risk factors (mainly obesity), after the exclusion of other causes of liver disease. The reference but imperfect standard for confirming NAFLD is liver histology. The following surrogate markers are presently used to estimate degree of steatosis and liver fibrosis and risk of progression to end-stage liver disease: imaging by ultrasonography or magnetic resonance imaging, liver function tests, and serum markers of liver fibrosis.NAFLD should be suspected in all of the overweight or obese children and adolescents older than 3 years with increased waist circumference especially if there is a NAFLD history in relatives. The typical presentation, however, is in children ages 10 years and older. The first diagnostic step in these children should be abdominal ultrasound and liver function tests, followed by exclusion of other liver diseases. Overweight/obese children with normal ultrasonographic imaging and normal liver function tests should still be monitored due to the poor sensitivity of these tests at a single assessment.Indications for liver biopsy include the following: to rule out other treatable diseases, in cases of clinically suspected advanced liver disease, before pharmacological/surgical treatment, and as part of a structured intervention protocol or clinical research trial.

Effects of Lactobacillus rhamnosus strain GG in pediatric obesity-related liver disease.

OBJECTIVE: Various lines of evidence suggest that malfunctioning of the gut-liver axis contributes to hepatic damage of rodents and humans with nonalcoholic fatty liver disease. We evaluated the effects of short-term probiotic treatment in children with obesity-related liver disease who were noncompliant with lifestyle interventions. PATIENTS AND METHODS: Twenty obese children (age 10.7 ± 2.1 years) with persisting hypertransaminasemia and ultrasonographic (US) bright liver were enrolled in this double-blind, placebo-controlled pilot study. At baseline, patients underwent clinical and laboratory anthropometric evaluation, measurement of the US hepatorenal ratio, standard liver function tests, oral glucose tolerance test, serum tumor necrosis factor-alpha, the glucose hydrogen breath test, and evaluation of serum antibodies to antipeptidoglycan-polysaccharide polymers. After exclusion of causes of liver disease other than obesity, patients received either probiotic Lactobacillus rhamnosus strain GG (12 billion CFU/day) or placebo for 8 weeks. RESULTS: Multivariate analysis after probiotic treatment revealed a significant decrease in alanine aminotransferase (average variation vs placebo P = 0.03) and in antipeptidoglycan-polysaccharide antibodies (average variation vs placebo P = 0.03) irrespective of changes in BMI z score and visceral fat. Tumor necrosis factor-alpha, and US bright liver parameters remained fairly stable. CONCLUSIONS: Probiotic L rhamnosus strain GG warrants consideration as a therapeutic tool to treat hypertransaminasemia in hepatopathic obese children noncompliant with lifestyle interventions.

Prevalence and long-term course of macro-aspartate aminotransferase in children.

OBJECTIVES: To investigate the prevalence, association with clinical conditions, and long-term course of macro-aspartate aminotransferase (macro-AST). STUDY DESIGN: Forty-four children with an isolated elevation of serum AST were screened for macro-AST with electrophoresis and % polyethylene glycol (PEG) precipitable activity (PPA). RESULTS: All children were healthy, except they had elevated AST values. Seventeen children (38.6%) were macro-AST-positive. They had higher AST values than the 27 children who were macro-AST-negative (P = .001). Values <67.1% PPA and >82.2% PPA were associated with a very low probability of being macro-AST-positive and macro-AST-negative, respectively. Thirty-eight children underwent clinical and laboratory follow-up (mean, 4.7 +/- 3.8; range, 1-16 years). All remained symptom-free. AST levels decreased significantly only in children who were macro-AST-negative (P = .006). Macroenzyme persisted in 6 of the 9 children who were macro-AST-positive after 6.0 +/- 4.1 years. CONCLUSIONS: Macro-AST was present in more than one-third of children with an isolated increase of AST levels. The lack of pathological correlates in a long period argues for the benign nature of this phenomenon in childhood. We suggest that our %PPA thresholds can be used as a screening test and that electrophoresis be reserved for confirming positive screen test results and cases in which %PPA levels are of intermediate discriminant accuracy.

Per-rectal portal scintigraphy is complementary to ultrasonography and endoscopy in the assessment of portal hypertension in children with chronic cholestasis.

UNLABELLED: We evaluated the clinical usefulness of 99mTc-pertechnetate per-rectal portal scintigraphy (PPS) in the assessment of portal circulation in children with chronic cholestasis. METHODS: PPS percentage shunt index (%SI) (the amount of radionuclide that shunts the liver and reaches the systemic blood after injection in the rectum) was measured in 22 children (mean age, 7.2 +/- 4.9 y) and compared with established clinical, laboratory, and endoscopic and imaging parameters of portal hypertension (PH). Fourteen children had surgically treated biliary atresia, and 8 had chronic intrahepatic cholestasis. Six clinically well children served as control subjects. RESULTS: The %SI was 14.3 +/- 3.1 and 34.7 +/- 18.8 in controls and in patients, respectively (P < 0.01). A cutoff of 19% correctly allocated 100% of controls and 86% of patients. Mean %SI values were significantly higher in patients with biliary atresia, a high risk of pretransplantation death, esophageal varices (EV) at endoscopy, and an abnormal value for the ratio of lesser omentum thickness to abdominal aorta diameter (LO/Ao) at ultrasonography. Correlations between %SI values and several ultrasonographic continuous variables were statistically significant only for LO/Ao ratios (r = 0.51; P = 0.005) and spleen longitudinal diameters (r = 0.53; P = 0.01). The presence of EV could correctly be predicted only when values of %SI were greater than 30% (100% specificity; 56% sensitivity). Endoscopic and PPS findings agreed for a diagnosis of PH with EV in 3 of 7 patients with normal or borderline ultrasonographic LO/Ao ratios. PPS patterns and %SI values became normal in 3 children who underwent liver transplantation. CONCLUSION: In children with chronic cholestasis, PPS may be an advantageous, minimally invasive tool complementary to ultrasonography and endoscopy for better assessment and follow-up of PH before and after liver transplantation.