Current Pediatric Reviews - Volume 2, Issue 1, 2006

Neonatal brain injury is common, essential to appropriate treatment and prevention is a thorough understanding of the pathogenesis. Two articles in this issue of the journal focus on this important topic. Dr. Xanthou analyses the mechanism through which proinflammatory cytokines and chemokines may lead to neuro-degeneration and brain damage. The vunerability of preterm infants to white matter damage, due to immature oligodendrocytes and deficient endogenous protective mechanisms, is described. Therapeutic possibilities of modifying or blocking the activity of proinflammatory cyokines and chemokines in preventing brain damage are discussed. Dr. Torrance and colleagues describe mechanisms of hypoxic ischaemic reperfusion injury and promising pharmacological neuro-protective strategies. In addition, they discuss beneficial effects of early intervention of combination therapy with moderate hypothermia. Dr. Penberthy and colleagues discuss a possible advance in the diagnosis of attention deficit/hyperactivity deficit. Although, neither traditional nor quantitative EEG has revealed persuasive or consistent patterns of EEG abnormalities, they highlight that an advanced quantitative EEG analysis has yielded promising results in small preliminary studies. The impact of preventative measures is reviewed in several articles. Drs. Mann and Lee emphasise that in the UK approximately 28 children die per year from cycle injuries, usually directly attributable to head injuries. They note that helmets reduced the risk of severe brain injury by 74% and also result in reduction in upper and mid facial injuries. This is without a reduction in cycling activity. The case for introduction of legislation in more countries to maximise helmet wearing by young cyclists is emphasised. Nosocomial infections are a major cause of mortality and morbidity particularly amongst vulnerable patients. There are many preventative strategies including health care personnel education and isolation. Dr. Saez-Llorens reminds us that hand washing is the single most effective measure to prevent nosocomial infection. Supine sleeping position has been associated with a reduction in sudden infant death syndrome, but is associated with an increase in referrals for positional or non-synostotic plagiocephaly (NSP). The review highlights that NSP is common and most mild to moderate cases revert to normal by the age of two years. Infants at increased risk are described, including those who are less active, which may explain why developmental delay is sometimes associated with NSP. Many drugs given to children have side-effects. Dr. Schou reviews the role of knemometry in the assessment of growth suppressive effects of glucocorticoid treatment and describes the effects of exogenous glucocorticoids on different components of the lower leg. Epilepsy is a common problem in childhood. Although many efficacious drugs are available, Dr. Verrotti and colleagues remind us that endocrinological side-effects can occur. Two comprehensive reviews of the presentation, investigation and management of clinical conditions are also included. Drs. Polyxeni and Papadopoulou discuss idiopathic hypercalciuria, the most common cause of urolithiasis in children. They highlight that although this complex metabolic disease is considered to be of genetic origin, no specific gene or polymorphisms have been identified. Drs. Barese and Goebel review chronic granulomatous disease (CGD) in childhood. They discuss that current efforts to develop curative therapies include allogeneic bone marrow transplantation for CGD patients with HLA identical sibling donors and transplantation of autologous gene corrected hematopoietic stem cells for patients who lack suitable marrow donors.

During perinatal asphyxia the inflammatory response to tissue injury and the production of cytokines occur after the excitotoxic cascade, at the reperfusion state, as hypoxia upregulates numerous proinflammatory genes of cytokines and chemokines. During perinatal infections CD14 and TLRs expressed on various cells bind to pathogen derived molecules and induce the synthesis of proinflammatory cytokines and chemokines. When the infection is located in uterus these inflammatory mediators enter the fetal circulation by crossing the placenta. Subsequently they cross the blood-brain barrier and cause local inflammation in the fetal brain. In experimental studies as well as in clinical, epidemiologic and neuropathologic studies concerning the newborn infant, an association between perinatal asphyxia and/or infection, cytokines, chemokines and brain damage has been found. In this review we analyse the mechanisms through which proinflammatory cytokines and chemokines may lead to neurodegeneration and brain damage. Particular emphasis is given to the white matter damage of the brain of preterm infants. Preterm infants are more vulnerable to brain damage because of their immature vascular ependymal factors, immature oligodendrocytes and deficient endogenous protective mechanisms. The methods used to modify or block the activity of proinflammatory cytokines and chemokines in order to prevent brain damage are being discussed.

This article will review the use of electroencephalographic (EEG) data in children with Attention Deficit/Hyperactivity Disorder (ADHD) or symptoms indicative of ADHD, both in research directed at determining the pathophysiology of ADHD, as well as research attempting to use the EEG as a diagnostic tool. In addition, we briefly review concepts important in quantitative analysis of EEG data. Overall, although some studies show enhancement of certain frequency bands relative to others within groups of ADHD children compared to normal controls, to date neither traditional nor quantitative EEG has revealed pervasive or consistent patterns of EEG abnormalities with sufficient specificity or sensitivity to separate children with ADHD from normal subjects. An exciting and promising recent development in this area of research involves advanced quantitative EEG analysis that has revealed an index shown, in small preliminary studies, to clearly and reliably differentiate ADHD from non-ADHD males. The use of EEG as a diagnostic tool for ADHD warrants further study, including additional large studies to help determine and clarify the specificity and sensitivity of the multiple EEG measures in differentiating ADHD and its subtypes from non-ADHD and other medical and psychiatric disorders.

Although the supine sleep position in infants has greatly reduced SIDS incidence, it has been associated with an increase in referrals of positional, or non-synostotic, plagiocephaly (NSP). Deformation of the soft infant skull may occur in response to the exertion of gravity on the cranium lying on a firm surface, particularly in the presence of a favoured head position. NSP is characterised by patent cranial sutures and unilateral or central occipital flattening, often with associated compensational changes in other parts of the cranium. Differentiation between lambdoid synostosis and NSP can largely be made using clinical examination. The condition is common and most mild to moderate cases of NSP revert to the normal range by the age of two years. At increased risk are males, firstborns, non-singletons, premature infants, less active infants, those exposed to intrauterine crowding or a difficult delivery, supine sleepers and infants with neck rotation abnormalities. It is unclear at present whether developmental delays that are sometimes associated with NSP are causal or resultant of plagiocephaly. Treatment involves keeping pressure off the flattened part of the skull and treating neck rotation abnormalities. Prevention revolves around early awareness of the head shape and varying the head-lying position from birth.

Despite ongoing research and new insights into the pathophysiological pathways of neonatal hypoxic-ischemic reperfusion brain injury, effective treatment is not yet available. This review briefly covers the mechanisms of hypoxicischemic reperfusion injury and focuses on promising pharmacological neuroprotective strategies which may become available for clinical use in the near future. Furthermore, the beneficial effects of early intervention and combination therapy with moderate hypothermia are discussed.

Cycling is a healthy activity for children, but accidents do occur and can result in death or disability. In the UK, around 28 children per year die from cycle injuries and most of these are directly attributable to head injury, and figures for permanent brain injury are around 1,000 children a year. What are the potential benefits of legislation on helmet usage and reduction in injury? Early studies from 1996 showed that helmets reduced the risk of severe brain injury by 74%. Subsequent studies in other countries have confirmed these initial findings, and a meta-analysis using 16 studies by Attewell in 2001 showed clear benefits of helmets in reducing injury including when there has been a motor vehicle impac; a situation that is more likely to lead to serious injury than a fall from a bike. Furthermore, upper and mid facial injuries are reduced by helmet usage and Thompson et al. have demonstrated a protective effect of 65%. Legislation for compulsory wearing of cycle helmets has been introduced in many countries including over one-third of States in USA, with significant reductions in head injury rates and deaths. Initial concerns about a reduction of cycling activity have not been confirmed. There is a good case for continued introduction of legislation to maximise helmet wearing by young cyclists.

A nosocomial infection (NI) is an infection contracted in a hospital or other health-care facility. An essential requirement for the diagnosis of NI is the lack of evidence of infection (subclinical or within the incubation period) on admission to the hospital. The onset of a NI usually begins 48-72 hours after hospitalization or can be longer in infections with long or variable incubation period such as hepatitis or varicella. Owing to the number and constant variability of factors that contribute to the development and persistence of NIs within the hospital environment, these conditions represent an important public health issue. NIs add to the length of hospital stay, contribute to the economic burden for the family and the institution and are responsible for the increased mortality associated with hospitalization. Accordingly, hospital-acquired infections are a true challenge for both the treating clinician as well as health authorities and administrators of tertiary medical institutions. The introduction of new technologies, especially in PICU and NICU, health-care equipment and immune status characteristics are some factors related with the development of nosocomial infections. Indeed, the study of factors associated with these hospital-acquired infections is crucial for their prevention in our patients. Hand washing is the single most effective measure to prevent the development of NIs with great results. Cleaning of surfaces and recommendations for inanimate objects, health-care personnel education in aseptic technique practices and isolation measures are a part of goals to prevent the spread of nosocomial infections.

Chronic granulomatous disease (CGD) is a genetic immunodeficiency that commonly presents in infancy and early childhood. Currently, life expectancy is beyond the fourth decade of life if the disease is promptly diagnosed and treated. CGD is characterized by increased susceptibility to recurrent and often life-threatening infections caused by bacteria and fungi. The hallmark of the disease is the formation of inflammatory granulomas, which can cause obstruction of the hollow viscera. Therapeutic management of CGD patients relies on the early and aggressive treatment of acute infections, as well as lifelong antibiotic and antifungal prophylaxis. Interferon gamma has a role in the prevention and management of intractable infections. Current efforts for the development of curative therapies focus on allogeneic bone marrow transplantation for CGD patients with HLA-identical sibling donors, and transplantation of autologous genecorrected hematopoietic stem cells for patients who lack suitable marrow donors. Significant recent achievements in these fields provide a realistic hope for a lifelong cure of CGD.

Exogenous glucocorticoids are commonly used in the treatment of various conditions including asthma, rhinitis, and a range of renal, gastrointestinal and malignant diseases in children. Glucocorticoid treatment has numerous systemic side effects beside the beneficial effects. An important and well described side effect is growth suppression. Knemometry, i.e. measurement of the lower leg length, is a well established method for assessment of short term growth. The present article reviews the role of knemometry in the assessment of growth suppressive effects of glucocorticoid treatment, and the present data on lower leg growth during glucocorticoid treatment are summarized. Our knowledge on the effects of exogenous glucocorticoids in the different components (bones, cartilage, cutis and subcutis, etc.) of the lower leg is reviewed, and integrated with recent studies assessing such effects by new methods.

Epilepsy is a neurological disorder commonly seen in pediatric age. A large number of anti epileptic Drugs are now available for the treatment of this disease; although many of these drugs have good efficacy in the treatment of both partial and generalized epilepsies, their use can be associated with various endocrinological side effects. During treatment are commonly observed changes in serum levels of many hormones, such as insulin, luteinizing hormone, follicle stimulating hormone, corticotrophin and the main sexual hormones. Therefore, in epileptic patients treated with antiepileptic, it is common to observe a number of clinical problems like abnormalities in pubertal development, weight gain, gonad dysfunction, hypothyroidism, etc. Both seizures and drugs could compromise hormonal balance in epileptic patients, but it is not yet clear to distinguish their effects. The aim of this review is to focus on the main endocrinological abnormalities induced by antiepileptic drugs, in order to achieve a critical analysis of the recent researches on this topic and to offer practical advice for a better care of epileptic children.

Idiopathic Hypercalciuria (IH), a heterogenous disorder, is the most common cause of urolithiasis in children. IH patients present frequently with gross or microscopic hematuria, abdominal pain and a variety of urinary tract complaints (frequency-dysuria syndrome, enuresis, recurrent tract infection), with-noncalculus manifestation more prevalent than stone disease. Recently, osteopenia has been found in a high percentage of IH children even at the time of diagnosis. IH is characterized by urinary calcium excretion greater than 4mg/kg/day with normocalcemia in the absence of any other causes of hypercalciuria such as vitamin D intoxication, primary hyperparathyroidism, hyperthyroidism, immobilization, endogenous or exogenous glucocorticoid excess, distal renal tubular acidosis and furesemide medication. This complex metabolic disease is considered to be of genetic origin, as in some cases, it seems to be inherited in an autosomal dominant pattern. A variety of genes participating in the mechanisms of Ca homeostasis, have attracted the interest of researchers in order to elucidate the pathogenetic mechanism of the disease and thus determining the appropriate treatment for any distinct patient. However, no specific gene or polymorphisms are yet identified. Furthermore, studies on the pathophysiology of IH distinguish two prominent types of IH: the absorptive, characterized by increased intestinal Ca absorption, and the renal, characterized by decreased tubular Ca reabsorption. The distinction between renal and absorptive type could direct towards the better therapeutic protocol. Generally, the main goal of treatment applied on hypercalciuric children should be to alleviate and finally eliminate the symptoms of the disease, to prevent renal stone formation or recurrence and to permit the acquisition of the optimal bone mass. Initial management of those patients consists primarily of high fluid intake and dietary salt restriction. If the symptoms persist, thiazide diuretics prescription is ideal, especially for IH patients of renal type.