Metabolomics-based technologies map in vivo biochemical changes that may be used as early indicators of pathological abnormalities prior to the development of clinical symptoms in neurological conditions. Metabolomics may also reveal biochemical pathways implicated in tissue dysfunction and damage and thus assist in the development of novel targeted therapeutics for neuroinflammation and neurodegeneration. Metabolomics holds promise as a non-invasive, high-throughput and cost-effective tool for early diagnosis, follow-up and monitoring of treatment response in multiple sclerosis (MS), in combination with clinical and imaging measures. In this review, we offer evidence in support of the potential of metabolomics as a biomarker and drug discovery tool in MS. We also use pathway analysis of metabolites that are described as potential biomarkers in the literature of MS biofluids to identify the most promising molecules and upstream regulators, and show novel, still unexplored metabolic pathways, whose investigation may open novel avenues of research.
Background A retrospective study was conducted in order to investigate and describe the characteristics of Immunoglobulin A vasculitis (IgAV), previously known as Henoch-Schӧnlein purpura, in the paediatric population of a community-based healthcare delivery system in the Italian region of Abruzzo. Methods This is a population-based retrospective chart review of the diagnosis of IgAV in children ages 0 to 18, admitted to the Department of Paediatrics of Chieti and Pescara between 1 January 2000 and 31 December 2016. All children enrolled presented with clinical symptoms and laboratory findings and met the EULAR/PRINTO/PRES 2008 criteria. Results Two-hundred-eight children met the criteria for IgAV, with the highest incidence reported among children below 7-years of age. A correlation with recent infections was found in 64% of the cohort; the onset was more frequently during the winter and fall. Purpura had a diffuse distribution in the majority of patients; joint impairment was the second most frequent symptom (43%), whereas the gastrointestinal tract was involved in 28% of patients. Conclusions Hereby, we confirm the relative benignity of IgAV in a cohort of Italian children; with regards to renal involvement, we report a better outcome compared to other studies. However, despite the low rate of renal disease, we observed a wide use of corticosteroids, especially for the treatment of persistent purpura.
Brivaracetam (BRV), which is considered to be the second generation of the drug of levetiracetam (LEV), 1 is a new antiseizure medication (ASM). It is a 2S)-2-[(4R)-2-oxo-4-propylpyrrolidin-1-yl] butanamide with four different diastereomers 2 capable of binding to SV2A vesicles with high affinity. 3 It was discovered as part of a program established by UCB Pharma to identify selective, high-affinity SV2A ligands that have higher antiepileptic properties than LEV. 2,4,5 Brivaracetam has a 10-30 times greater affinity and selectivity than LEV 6,7 and, compared to the latter, shows greater permeability of the blood-brain barrier in rodent models. 8 In recent years, it has been tested as an ASM in adult and pediatric patients. Most of the studies on the tolerability and efficacy of BRV concern the adult population; the data on the pediatric population are still sparse. The purpose of this review is to provide a comprehensive overview of the available data published about its efficacy and tolerability at the pediatric age.
Multiple sclerosis (MS) and type 1 diabetes (T1D) are chronic conditions that result from dysfunction of the immune system. Their common root in autoimmunity stimulates interest in the exploration of similarities and differences between the two diseases. Genetic susceptibility is relevant, creating a substrate, on which environmental factors act as a trigger of an aberrant immune response. Despite being both T-cell mediated disorders with a strong involvement of the humoral arm, immunomodulation is a mainstay of MS management, whereas hormone replacement therapy remains the principal approach for T1D. T1D is usually diagnosed in children and adolescents, while MS is typical of young adults. This difference has implications for disease progression and treatment. The SARS-CoV-2 pandemic and its effect on immunity may affect the prevalence of these conditions, as well as their clinical manifestation.
Glucose is the most important substrate for proper brain functioning and development, with an increased glucose consumption in relation to the need of creating new brain structures and connections. Therefore, alterations in glucose homeostasis will inevitably be associated with changes in the development of the Nervous System. Several studies demonstrated how the alteration of glucose homeostasis - both hyper and hypoglycemia- may interfere with the development of brain structures and cognitivity, including deficits in intelligence quotient, anomalies in learning and memory, as well as differences in the executive functions. Importantly, differences in brain structure and functionality were found after a single episode of diabetic ketoacidosis suggesting the importance of glycemic control and stressing the need of screening programs for type 1 diabetes to protect children from this dramatic condition. The exciting progresses of the neuroimaging techniques such as diffusion tensor imaging, has helped to improve the understanding of the effects, outcomes and mechanisms underlying brain changes following dysglycemia, and will lead to more insights on the physio-pathological mechanisms and related neurological consequences about hyper and hypoglycemia.
The growing interest in metabolomics has spread to the search for suitable predictive biomarkers for complications related to the emerging issue of pediatric obesity and its related cardiovascular risk and metabolic alteration. Indeed, several studies have investigated the association between metabolic disorders and amino acids, in particular branched-chain amino acids (BCAAs). We have performed a revision of the literature to assess the role of BCAAs in children and adolescents’ metabolism, focusing on the molecular pathways involved. We searched on Pubmed/Medline, including articles published until February 2022. The results have shown that plasmatic levels of BCAAs are impaired already in obese children and adolescents. The relationship between BCAAs, obesity and the related metabolic disorders is explained on one side by the activation of the mTORC1 complex—that may promote insulin resistance—and on the other, by the accumulation of toxic metabolites, which may lead to mitochondrial dysfunction, stress kinase activation and damage of pancreatic cells. These compounds may help in the precocious identification of many complications of pediatric obesity. However, further studies are still needed to better assess if BCAAs may be used to screen these conditions and if any other metabolomic compound may be useful to achieve this goal.
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