Current Pediatric Reviews - Volume 1, Issue 1, 2005

Periventricular leukomalacia is a major neuropathological substrate underlying most of the neurologic morbidity in cerebral palsy. Etiopathogenesis of periventricular leukomalacia is believed to be multifactorial, involving hypoxic-ischemic insults and inflammatory processes. While emphasis was previously placed on hypoxia / ischemia, epidemiological, clinical, experimental and other studies conducted over the last decade have provided evidence for an important role of infective / inflammatory conditions and immune mediators in the pathogenesis of periventricular leukomalacia. Tumor necrosis factor alpha (TNF-a), interleukin-1 beta (IL-1b) and interleukin-2 (IL-2) are overexpressed in affected brains, and receptors for these cytokines are present on many inflammatory and neural cells in the white matter. These findings may be part of a wider network of cytokines, chemokines and other inflammatory factors. There is also evidence for interaction between infective / inflammatory conditions and ischemia / hypoxia as etiopathogenic factors in periventricular leukomalacia / cerebral palsy, as the former may enhance the effects of the latter. These developments in the understanding of the immune responses associated with perinatal brain damage, and the characterization of the implicated cellular and molecular mechanisms may have important implications for neuroprotection strategies aiming at prevention of periventricular leukomalacia and cerebral palsy.

Many issues regarding the definition, phenomenology, categorization and outcome of nonconvulsive (or dialeptic) status epilepticus are still unresolved. Management is often difficult, with highly variable response to treatment. This classically includes oral benzodiazepines or steroids. New insights into pathophysiological mechanisms involved in sustaining epileptic activity or deficits in seizure termination may lead to improved management programs. Relevant synaptic processes implicate functional alterations of GABA, GABA and NMDA receptor complexes. Early results with NMDA blockers (e.g. ketamine) in animal models and pediatric patients are encouraging. Metabolic approaches have included ketogenic diets. Dynamic approaches of electroencephalographic signals may open the way to neuromodulation through electrical resetting techniques applied at critical phases.

Neurodevelopmental disorders are thought of as beginning before birth, and many such as Down syndrome clearly do. Clinically, however, other such disorders may unfold over months (Mental Retardation, Autism, Rett syndrome) or years (Asperger Syndrome, Fragile X, Dyslexia). While structural Magnetic Resonance Imaging (MRI) has uncovered specific regions of white and gray matter abnormalities associated with several of these disorders, the exact relationship between structural changes and alterations in neuronal function and connectivity are still unclear. Over the past decade, functional brain imaging methods such as PET and SPECT have gained widespread clinical acceptance in other medical fields such as Oncology and Psychiatry; while their use in Pediatrics is limited by a reliance on radioactive labeled tracers (radioligand). Functional MRI, on the other hand has several unique advantages in that it is a non-invasive technique with improved spatial resolution that permits a more accurate elucidation of the dynamic brain changes associated with each of these neural based developmental disorders. Since there also exists a spectrum of phenotypic heterogeneity among these disorders, it is important to develop such a diagnostic tool that can first identify underlying biological substrates, and then distinguish successful pharmacological or behavioral interventions. The hope of early diagnosis for these neurodevelopmental disorders may ultimately rely on an integration of comprehensive fMRI brain atlases with specific genetic testing. Discussion. This review focuses in the contributions made by studies employing functional MRI to the understanding of Mental Retardation (Joubert Syndrome, Williams Syndrome,Velocradiofacial Syndrome and Fragile X), Pervasive Developmental Disorder, Autism, and Dyslexia.

Long-chain polyunsaturated fatty acids (LCPUFA) are bioactive compounds that include docosahexaenoic acid (DHA) and arachidonic acid (AA). DHA seems to be necessary to optimize growth and development of infant's neural functions. For preterm infants there is a wide agreement on LCPUFA benefits, while for term infants results are more controversial. There is presently a growing interest in supplementing pregnant and breastfeeding women with DHA. LCPUFA may act as coadjuvants in conditions of functional and organic brain impairments, as well as some inflammatory states, but caution is urged to prevent false expectations. Therefore, pediatricians should be aware of the present scientific evidence concerning dietary LCPUFA supplementations.

The impact of managed care has been dramatic in child psychiatric services. This paper describes the clinical evolution of child mental health services in the US in the context of managed care. The paper notes the lack of information guiding the safety and effectiveness of treatment, and the authors argue that there are both clinical and ethical reasons for managed care organizations to share data about their beneficiaries' treatment outcomes in an effort to improve the safety and quality of psychiatric care to children and adolescents. The authors make recommendations for changes in public accountability and call for collaboration between all parties to occur without further delay.

Approximately 1 in 6 children have special health care needs and half of those have functional limitations or disabilities. Such children use health and related services on average two to eight times more often than children without these conditions. Health care systems and clinical practices are poorly designed to deliver high quality health care to children with chronic conditions. Reform efforts such as the Medical Home and the Improving Chronic Care Model have been shown to improve clinical outcomes but more progress is needed. This paper argues that establishing clinical goals and measuring health outcomes in the care of children with chronic conditions should focus on the nature and extent of functional limitations in a wide range of domains. The International Classification of Functioning, Disability, and Health (ICF) provides a conceptually-driven diagnostic and statistical manual that can be used at the clinical and public health levels to assess and monitor functional outcomes. The newly released ICF-Children and Youth Version has been designed specifically for children up to 18 years of age. The results of functional classification with the ICF can be integrated with medical and mental health diagnoses in a multi-axial assessment of the patient, providing a standardized and therapeutically relevant description of the individual with chronic conditions through a number of domains or axes. Each functional problem requires its own plan for intervention. Functional classification is compatible with other reform efforts, such as the Medical Home initiative. Routine use of functional assessment and classification in the care of children with chronic conditions will lead to a comprehensive or “wholistic” approach to the child and family.

Evidence-based practice provides a five-step framework for providing high quality healthcare. This review takes the reader through the basics of the five steps (ask a question, acquire some information, appraise the evidence, apply the results and assess performance) in the setting of acute paediatric medicine. It shows how even frontline clinicians can provide diagnoses, treatments and prognostic information based on the best evidence, acknowledging patient and family needs and integrating clinical expertise.

There have been significant advances in the treatment of neuroblastoma and rhabdomyosarcoma, but the clinical results are still poor, especially after tumor relapse. In addition to this, rhabdomyosarcoma does worse if localized tumors occur in unfavorable sites. Therefore, new chemotherapeutic agents have been sought, and the effects of 9- dimethylaminomethyl-10-hydroxycampthothecin (topotecan) and 7-ethyl-10-(4-[1-piperidino]-1-piperidino)-carbonylcamptothecin hydrochloride (irinotecan) were studied preclinically and clinically during the past decade not only in adults but also in children. Irinotecan and topotecan inhibit DNA topoisomerase I, which is an essential nuclear enzyme that relaxes torsionally strained duplex DNA, enabling replication and transcription. These agents were reported to be effective against various human malignancies in adults. Among these camptothecin derivatives, topotecan and irinotecan are the most widely used clinically, and at present irinotecan appears to be more promising in the treatment of childhood solid tumors such as rhabdomyosarcoma and neuroblastoma. The recommended dose and administration schedule differ among clinical trials.. For example, 1-day, 3-day, and 10-day regimens have been used. In the present article, the clinical effectiveness of topotecan and irinotecan with different administration schedules are reviewed in the US, French and Japanese literature, and the authors propose which agent and which administration schedule of these agents are the most effective in the treatment of pediatric solid tumors.

Hydrops foetalis is defined as a state of excessive fluid accumulation in the extravascular compartment of the foetus, leading to widespread soft tissue oedema and / or accumulation of fluid in the foetal body cavities. The prognosis of hydrops foetalis is highly dependent on the underlying pathology and early diagnosis is essential to identify treatable cases. The classification of immune and non-immune hydrops foetalis describes the difference between Rhesus haemolytic disease of the newborn and other aetiologies leading to hydrops foetalis. With improved diagnosis and treatment of Rhesus iso-immunisation, non-immune factors have become more frequent. Distinction between anaemic and non-anaemic hydrops foetalis provides a far more useful differentiation between aetiologies. This approach is used to discuss differential diagnosis, work-up and therapeutic options in hydrops foetalis. A structured multidisciplinary work-up will facilitate early diagnosis and assist in making treatment decisions.

Autoimmune hepatitis is a severe and unresolving inflammatory disease of the liver of unknown etiology carrying high morbidity and mortality. All ages and genders are concerned with a peak of incidence in girls in prepubertal age, even if the disease has been diagnosed as early as 6 months. Autoimmune hepatitis may be classified in two major subgroups on a presence of a specific set of autoantibodies: anti-smooth muscle mostly with anti-actin specificity and / or by antinuclear antibody in type 1 and anti-liver-kidney microsome and / or the anti-liver cytosol in type 2. The histological hallmark is “interface hepatitis”, with a mononuclear cell infiltrate in the portal tracts, variable degrees of necrosis, and progressive fibrosis. The disease follows a chronic but fluctuating course usually progressing to cirrhosis and liver failure. The most frequent type onset is similar to that of an acute viral hepatitis with acute liver failure in some patients; about a third of patients have an insidious onset with progressive fatigue and jaundice while 10-15% are asymptomatic and are accidentally discovered by the finding of hepatomegaly and / or an increase of serum aminotransferase activity. Corticosteroids alone or in conjunction with azathioprine are the treatment of choice inducing remission in over 90% of patients. An alternative therapeutic strategy is cyclosporine. Withdrawal of immunosuppression is associated with high risk of relapse. Liver transplantation manages patients with decompensated liver disease unresponsive to “rescue” medical treatment.

Background: Contributing factors in bronchopulmonary dysplasia (BPD) in neonatal infants includes inflammation and oxygen radicals. Nitric oxide (NO - 2), an important mediator of inflammation can lead to cell injury or induce proinflammatory cytokines. Glucocorticoids are known to decrease the transcription of inducible NO synthetase. Objective: To investigate if there are altered serum (NO 2) nitrite, a products of NO metabolism levels in very low birth weight infants with BPD and respiratory distress syndrome (RDS) as compared to healthy newborns before and after dexamethasone treatment. Methods: We clinically evaluated neonatal infants and obtained samples from 31 infants diagnosed with BPD (N=15), RDS (N=6), prematurity without respiratory distress syndrome (N=6), and full term (FT) neonates (N=4). Levels of nitrite were measured using the Greiss Reagent, and absorbance was determined at 550nm. Results: The highest levels of NO- 2 were obtained in the BPD patients (9-253 μM), mean = 110 μM, with low APGAR scores at 1 minute from 0 to 5. RDS patients with low APGAR scores at 1 minute from 5 to 7, also had high levels (8-93 μM), mean=54 μM and patients with prematurity with normal APGAR scores at 1 minute from 6 to 9 had relatively low NO- 2 levels (29-76 μM), mean = 41mM. Dexamethasone treatment (0.5 mg/kg/d) of 12 hrs. for 3-8 days) in premature infants with low APGAR scores dramatically decreased from 85-253 μM to 10-146μM (p<0.05). In 2 of the severe BPD a rise in NO levels after dexamethasone correlated with severe systemic infection. NO - 2 levels in FT patients (21 - 37μM), (mean=30 μM). Control serum samples from 16 infants randomly selected had NO levels of (8-53 μM), mean = 28 μM). Supported by a fellow-in-training grant* and Von Pirquet Awardsd from ACAAI.