Valeria Dipasquale

Adrenal Disorders and the Paediatric Brain: Pathophysiological Considerations and Clinical Implications

Various neurological and psychiatric manifestations have been recorded in children with adrenal disorders. Based on literature review and on personal case-studies and case-series we focused on the pathophysiological and clinical implications of glucocorticoid-related, mineralcorticoid-related, and catecholamine-related paediatric nervous system involvement. Childhood Cushing syndrome can be associated with long-lasting cognitive deficits and abnormal behaviour, even after resolution of the hypercortisolism. Exposure to excessive replacement of exogenous glucocorticoids in the paediatric age group (e.g., during treatments for adrenal insufficiency) has been reported with neurological and magnetic resonance imaging (MRI) abnormalities (e.g., delayed myelination and brain atrophy) due to potential corticosteroid-related myelin damage in the developing brain and the possible impairment of limbic system ontogenesis. Idiopathic intracranial hypertension (IIH), a disorder of unclear pathophysiology characterised by increased cerebrospinal fluid (CSF) pressure, has been described in children with hypercortisolism, adrenal insufficiency, and hyperaldosteronism, reflecting the potential underlying involvement of the adrenal-brain axis in the regulation of CSF pressure homeostasis. Arterial hypertension caused by paediatric adenomas or tumours of the adrenal cortex or medulla has been associated with various hypertension-related neurological manifestations. The development and maturation of the central nervous system (CNS) through childhood is tightly regulated by intrinsic, paracrine, endocrine, and external modulators, and perturbations in any of these factors, including those related to adrenal hormone imbalance, could result in consequences that affect the structure and function of the paediatric brain. Animal experiments and clinical studies demonstrated that the developing (i.e., paediatric) CNS seems to be particularly vulnerable to alterations induced by adrenal disorders and/or supraphysiological doses of corticosteroids. Physicians should be aware of potential neurological manifestations in children with adrenal dysfunction to achieve better prevention and timely diagnosis and treatment of these disorders. Further studies are needed to explore the potential neurological, cognitive, and psychiatric long-term consequences of high doses of prolonged corticosteroid administration in childhood.

Breastfeeding and IL-10 levels in children affected by cow’s milk protein allergy: A restrospective study

AIM To assess the protective role of breast-feeding in infants with CMPA-related AEDS as well as IL-10 utility as marker of disease evolution. METHODS 64 breast-feeding children with CMPA-related AEDS (31 males and 33 females; mean age 5.56±2.41months; 21 mild AEDS; 25 moderate AEDS; 18 severe AEDS) and 60 artificial feeding babies (33 males and 27 females; mean age 6.01±2.08months; 26 mild AEDS; 19 moderate AEDS; 15 severe AEDS) were evaluated. In all patients serum IL-10 levels were detected. RESULTS Significant Score Atopic Dermatitis (SCORAD) index point differences between breastfed and not breastfed children (p<0.001) have been detected. The serum IL-10 levels were lower in children with CMPA-related AEDS as compared to the healthy control group (p<0.001). Moreover, a significant inverse correlation between serum IL-10 levels and SCORAD in both enrolled groups has been also noted. In particular, IL-10 levels, in both groups, were significantly lower in children with severe symptoms. Conversely, serum IL-10 levels were significantly increased in children with mild-severe symptoms in both groups. Furthermore, breastfed children, with lower severe symptoms, had higher serum IL-10 levels. Finally, serum total IgE levels were negatively correlated with serum IL-10 levels in both breastfed and non-breastfed children with CMPA-related AEDS (p<0.001). CONCLUSIONS We reported that exclusive breast-feeding induces hyposensitization in children with CMPA-related AEDS and it is associated with minor disease severity and higher serum IL-10 levels, resulting as useful disease-monitor marker.

Pericarditis during infliximab therapy in paediatric ulcerative colitis

Infliximab is a widely used drug for treating inflammatory bowel disease (IBD). This drug is known to rarely cause pericarditis in adult populations.

An overview of the clinical management of cyclic vomiting syndrome in childhood

Abstract This narrative review provides an update on cyclic vomiting syndrome pathogenesis, diagnosis and management, based upon studies published after the 2008 North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) official recommendations. The review began with a comprehensive PubMed/Medline search for “cyclic vomiting syndrome”, “periodic syndromes” and “pediatrics” from 2000 up to October 2017. Additional papers were identified by reviewing the re-ference lists of retrieved publications. Cyclic vomiting syndrome is a severe, debilitating disorder of the brain–gut axis with unclear pathogenesis, that significantly affects long-term quality of life of affected children and their families. The 2008 NASPGHAN recommendations defined the major clinical, diagnostic and therapeutic peculiarities. Over the last 10 years, advancements in pathogenesis and diagnostic criteria have been made, and new prophylactic and therapeutic strategies have been proposed. These aspects are discussed in this manuscript. For the pediatrician, the major aim is to have early clinical suspicion to avoid diagnostic delay and to start adequate, phase-related, symptom-tailored management.

Illegal immigration: the puzzling role of several risk factors for rhabdomyolysis

A 14-year-old boy presented with low-grade fever, widespread myalgia and difficulty in walking and standing 2 days after the undocumented trip which brought him from western Africa to Italy. His serum creatine phosphokinase was markedly elevated. He was diagnosed with rhabdomyolysis and was volume-restored with normal saline and bicarbonate-containing fluid. Anamnesis revealed illegal, not well-specified, forced consumption in his fatherland, and very bad conditions of the trip (prolonged immobility, dehydration, hypothermia). Workup included a respiratory microbiological panel which was positive for Chlamydia pneumoniae. Other microbiological agents were excluded. After 3 weeks, he recovered complete motility. Undocumented immigrants may present several risk factors for rhabdomyolysis that give to this group of individuals a higher risk of developing this disorder.

Standard Polymeric Formula Tube Feeding in Neurologically Impaired Children: A Five-Year Retrospective Study

Malnutrition is frequent in neurologically impaired (NI) children. Enteral feeding via gastrostomy tube is increasingly being used to provide adequate nutrition. Our aim was to assess the outcomes of exclusive gastrostomy tube feeding with standard polymeric formula in children with NI, severe oro-motor dysfunction, and malnutrition, and to investigate the role of the underlying NI-associated disease. A five-year retrospective study from January 2013 to November 2017 was conducted. The primary aim was to assess the nutritional outcomes of exclusive gastrostomy tube feeding with standard polymeric formula in malnourished NI children. The secondary aim was to investigate gastrostomy complications and the impact of the underlying NI-associated disease on the nutritional outcomes. We enrolled 110 consecutive children with NI. Of these patients, 34.5% (N = 38) were categorized as malnourished and started exclusive enteral feeding with a standard (1.0 kcal/mL) polymeric formula (Nutrini, Nutricia) after percutaneous endoscopic gastrostomy (PEG) placement. Seventy-three percent of patients (N = 28) had cerebral palsy (CP); other diagnoses included metabolic (13%, N = 5) and genetic (13%, N = 5) diseases. Tricep skinfold thickness had significantly improved in all patients at 12-months follow-up, while body weight and body mass index showed significant increases mainly in children with CP. No serious complications occurred. We found that standard polymeric formula via gastrostomy tube represents a safe and efficient nutritional intervention in children with NI and malnutrition.

Bowel Preparation and Factors Correlated with Patients and Parents

The quality of the colonic cleansing greatly influences the success rate of colonoscopy, both in terms of diagnostic and therapeutic potentialities. Different bowel cleansing solutions are available for children, but no standard regimens have been realized yet, as well as a standardized approach to an inadequately prepared colon discovered on intubation. Suboptimal colonic preparation can occur in up to one-third of colonoscopies. Colonic cleansing quality has to be properly reported in colonoscopy reports.

A loss-of-function homozygous mutation in DDX59 implicates a conserved DEAD-box RNA helicase in nervous system development and function

We report on a homozygous frameshift deletion in DDX59 (c.185del: p.Phe62fs*13) in a family presenting with orofaciodigital syndrome phenotype associated with a broad neurological involvement characterized by microcephaly, intellectual disability, epilepsy, and white matter signal abnormalities associated with cortical and subcortical ischemic events. DDX59 encodes a DEAD‐box RNA helicase and its role in brain function and neurological diseases is unclear. We showed a reduction of mutant cDNA and perturbation of SHH signaling from patient‐derived cell lines; furthermore, analysis of human brain gene expression provides evidence that DDX59 is enriched in oligodendrocytes and might act within pathways of leukoencephalopathies‐associated genes. We also characterized the neuronal phenotype of the Drosophila model using mutant mahe, the homolog of human DDX59, and showed that mahe loss‐of‐function mutant embryos exhibit impaired development of peripheral and central nervous system. Taken together, our results support a conserved role of this DEAD‐box RNA helicase in neurological function.

Pharmacological treatments and infectious diseases in pediatric inflammatory bowel disease

ABSTRACT Introduction: The incidence of pediatric inflammatory bowel disease (IBD) is rising, as is the employment of immunosuppressive and biological drugs. Most patients with IBD receive immunosuppressive therapies during the course of the disease. These molecules are a double-edged sword; while they can help control disease activity, they also increase the risk of infections. Therefore, it is important that pediatricians involved in primary care, pediatric gastroenterologists, and infectious disease physicians have a thorough knowledge of the infections that can affect patients with IBD. Areas covered: A broad review of the major infectious diseases that have been reported in children and adolescents with IBD was performed, and information regarding surveillance, diagnosis and management were updated. The possible correlations with IBD pharmacological tools are discussed. Expert commentary: Opportunistic infections are possible in pediatric IBD, and immunosuppressive and immunomodulator therapy seems to play a causative role. Heightened awareness and vigilant surveillance leading to prompt diagnosis and treatment are important for optimal management.

Gastrointestinal and nutritional issues in children with neurological disability

Neurological disability is often associated with feeding and gastrointestinal disorders leading to malnutrition and growth failure. Assessment of nutritional status represents the first step in the clinical evaluation of children with neurological disability. The European Society of Gastroenterology, Hepatology, and Nutrition (ESPGHAN) recently issued a consensus statement on gastrointestinal and nutritional management in children with neurological disability. Here we critically review and address implications of this consensus for clinical practice, including assessment and monitoring of nutritional status, definition of nutritional requirements, diagnosis and treatment of gastro‐oesophageal reflux disease, and indications for and modalities of nutritional support. There is a strong evidence base supporting the ESPGHAN guidelines; their application is expected to lead to better management of this group of children.