Current Pediatric Reviews - Volume 4, Issue 4, 2008

Disorders of neuronal migration are a heterogeneous group of disorders of nervous system development. One of the most frequent disorders is lissencephaly characterized by a paucity of normal gyri and sulci resulting in a “smooth brain”. There are two pathologic subtypes: classical and cobblestone. Classical lissencephaly results from an arrest of neuronal migration, whereas cobblestone lissencephaly results from overmigration. Another important neuronal migration disorder is heterotopia characterized by a cluster of normal neurons in abnormal locations and it is divided into three main groups: periventricular nodular heterotopia, subcortical heterotopia and marginal glioneural heterotopia. Polymicrogyria develops at the last stages of neuronal migration to the earliest phases of cortical organization; bilateral frontoparietal form is characterized by bilateral, symmetric polymicrogyria in the frontoparietal regions. Bilateral perisylvian polymicrogyria results in a clinical syndrome manifested by mild mental retardation, epilepsy and pseudobulbar palsy. Schizencephaly is another important disorder of neuronal migration whose clinical characteristics are extremely variable. Focal cortical dysplasia represents one of most severe causes of epilepsy in children. This review reports the main clinical, genetical, neuroradiological aspects of these disorders.

Cystic periventricular leukomalacia (PVL) is one of the most severe and frequent cause of cerebral palsy in children surviving preterm birth. The pathogenesis of PVL yet is not completely understood. The majority of the theories consider the necrotic foci to be hypoxic-ischemic lesions, resulting from impaired perfusion at the vascular border zones between ventriculopedal and ventriculofugal arteries, as the latter are poorly developed in preterm infants. Besides periventricular vascular anatomic factors and pressure-passive cerebral circulation the intrinsic vulnerability of cerebral white matter (a particular vulnerability of rapidly differentiating oligodendroglial cells) of preterm infants plays an important role. An alternative view focuses on the role of intrauterine infection and the fetal inflammatory response syndrome. Hypocarbia has been identified as an independent risk factor for PVL in many studies. As far as the pathogenesis of PVL is complex and likely multifactorial, the influence of hypocarbia on subsequent white matter damage is most striking in postnatal acquired and late onset cystic PVL. This review analyses clinical trials demonstrating an association between hypocarbia and PVL. Physiological studies on cerebrovascular autoregulation and animal studies presented in this review try to elucidate the underlying mechanisms.

Chronic daily headache (CDH) affects 2 to 4% of adolescent females and 0.8 to 2% of adolescent males. Chronic daily headache is diagnosed when headaches occur more than 4 hours a day, for greater than or equal to 15 headache days per month, over a period of 3 consecutive months, without an underlying pathology. It is manifested by severe intermittent headaches, that are migraine-like, as well as a chronic baseline headache. Silberstein and Lipton divided patients into four diagnostic categories: transformed migraine, chronic tension-type headache, new dailypersistent headache, and hemicrania continua. The second edition of the International Classification of Headache Disorders did not comprise any CDH category as such, but provided criteria for all four types of CDH: chronic migraine, chronic tension-type headache, new daily-persistent headache, and hemicrania continua. The International Headache Society. Children and adolescents with chronic daily headache frequently have sleep disturbance, pain at other sites, dizziness, medication-overuse headache and a psychiatric comorbidity (anxiety and mood disorders). Chronic daily headache frequently results in school absence. Successful approaches to treatment include reassurance, education, use of preventative medication, avoidance of analgesics, and helping the child work its way back into a functional daily routine and a regular school schedule.

The medical, surgical and psychosocial management of individuals affected by disorders of sex development (DSD) is currently under scrutiny. Patients who possess a 46,XY chromosomal complement (i.e., those affected by 46,XY DSD) pose particular challenges to healthcare professionals because this group is most likely to report dissatisfaction with their sex of rearing as they progress from childhood through adulthood. The current review examines satisfaction with sex of rearing, degree of concordance between masculine/feminine behavior and sex of rearing, and sexual orientation in adults affected by 46,XY DSD, reared male or female. Such individuals may present with female external genitalia, ambiguous external genitalia or a micropenis. The impact of potentially confounding variables such as physical health, fertility and sexual function on psychosexual development in persons affected by DSD is considered when such data are available. Finally, observations from non-DSD clinical populations and animal models are discussed, including their appropriateness for informing healthcare professionals about behavioral outcomes in DSD patients. Rodent models that support the aromatization hypothesis or the independent influence of genes on the Y chromosome for brain/behavior masculinization do not generalize to human psychosexual development; however, the nonhuman primate literature is more instructive for understanding the direct impact of androgens on human gender development. Finally, discussion pertaining to the predominance of male gender development in cases of 5α-RD-2 and 17β-HSD-3 deficiencies is offered.

Epidermolysis bullosa (EB) refers to a group of genodermatoses that present with skin fragility. Patients with this condition present life-long blistering and bullae formation in their skin and mucosal membranes as a response to minor friction or trauma. A revised classification has recently been published and three major types of EB we are identified: simplex, junctional and dystrophic. In each of these subtypes a spectrum of clinical manifestations can be found, varying from very mild to disfiguring and disabling disease. Pediatricians are likely to be the first to encounter patients with EB. Patients may be born with findings suggestive of EB or develop these shortly after. The initial severity of presentation does not indicate prognosis, so clinical classification early on is discouraged. Regardless of the subtype of EB, pediatricians should be aware of the constellation of findings they might encounter when caring for these patients. Although many of the efforts are going to be directed to prevention of skin lesions and wound care, this is not a condition that is limited to the skin. Patients may develop systemic compromise, involving eyes, teeth, oral mucosa, gastrointestinal tract, genitourinary tract and respiratory, cardiovascular, musculoskeletal and hematological systems. In the absence of a cure for EB, efforts are targeted towards prevention and treatment of complications and towards improving patients' quality of life. In order to do this, pediatricians should be aware of possible complications, recognize them promptly and provide appropriate care.

During the last fifteen years better hygienic standards led to an increased consumption of natural rubber latex (NRL) gloves for the protection of medical staff. At the same time case reports about an IgE-mediated allergy to NRL sometimes causing life-threatening anaphylactic reactions came up. This allergy was different from the well-known type IV reactions caused by latex additives. Health care workers and patients with multiple surgery surgeries were identified as high risk groups. For unknown reasons patients with spina bifida (SB) showed the highest prevalence of NRL-specific IgE-antibodies. A pre-existing atopy increased the risk of latex sensitization. Allergic reactions were caused mainly by medical procedures, especially surgeries, if latex gloves and other latex containing devices were used. Meanwhile some allergenic proteins in NRL (named Hev b in accordance with the rubber tree Hevea brasiliensis) could be identified. Patients in different risk groups showed distinct prevalences of sensitization to these allergens. The way of the allergen uptake (aerogen or by direct mucosal contact during surgeries) played an important role in the sensitization to different allergens. Most of the latex allergens like Hev b 1, Hev b 3, Hev b 6.02 have been totally sequenced. Since the sequence of all registrated allergens (Hev b 1 - Hev b 13) is known, it was possible to localize in Hev b 1, Hev b 5 and Hev b 6.01 several IgE binding sites as well as T cell epitopes. Cross-reacting antibodies between NRL and numerous fruit were described and for some proteins structural homologies were well characterized. For the in vitro diagnosis of NRL allergy serologic tests with improved extracts and recombinant allergens (for instance ImmunoCAPTM system) are available. NRL protein extracts for skin prick tests were difficult to standardize. The use of natural extracts in combination with recombinant latex allergens could be one possible future perspective for skin testing. The problem of NRL allergy is still not resolved but significant progress has been made in its prevention. In high risk patients like persons with spina bifida a primary prophylaxis was performed with success, but also secondary or tertiary prophylaxis allows safe operations without symptoms of NRL allergy.

Eosinophilic esophagitis (EoE) is a disease based on a clinico-pathologic diagnosis which involves a localized eosinophilic inflammation of the esophagus. There has been a significant increase in the incidence of diagnosis of pediatric EoE over the past 10 years due, in part, to a greater recognition of the disease among gastroenterologists, allergists and pathologists. EoE is defined by the presence of 15 or more eosinophils per high-powered field on esophagastroduodenoscopic biopsies isolated to the esophagus associated with characteristic clinical symptoms which do not respond to gastric acid-blockade. While the exact mechanism of EoE is unknown, food allergens are thought to play a significant role. When available, a combination of skin prick and atopy patch testing may be useful when attempting to identify IgE and non-IgE based food allergens in patients with EoE. Effective treatment options include dietary restrictions and various steroid formulations. A multidisciplinary approach is essential for a timely diagnosis and successful treatment strategies in patients with EoE.

The National Institute for Clinical Excellence (NICE) uses economic evaluation as the means to assess new treatments: this is a process unfamiliar to many clinicians. High technology treatments used in paediatric intensive care are expensive and have been subject to economic evaluation. A systematic review of the literature was performed for economic evaluations of treatments used for critically ill children with cardio-pulmonary failure. Of 3604 potentially eligible studies identified, there were 16 cost minimisation studies addressing applicable treatments but only 9 cost effectiveness or cost utility evaluations were found and subjected to review. Three studies dealt with the UK trial of extracorporeal membrane oxygenation (ECMO) for neonates, two studies addressed ECMO and transplantation in paediatric cardiac patients, two studies evaluated ECMO in mixed paediatric respiratory failure populations and two studies assessed the cost effectiveness of inhaled nitric oxide in neonatal respiratory failure. There are inherent problems in performing economic studies in this paediatric field. However, economic evaluation with adherence to guidelines is recommended. Given recent NHS reforms, it is clear that economic evaluation will remain an important focus of debate and is likely to become more prevalent rather than less.

As the result of the use of blood culture vials for seeding joint and bone exudates, and nucleic acid amplification methods, Kingella kingae is emerging as an important pathogen in patients <3 years of age. The organism is carried asymptomatically in the oropharynx of young children, coinciding with the age of increased attack rate of invasive disease, and propagates through close personal contact. Carriage of K. kingae is a dynamic process with frequent turnover of strains after weeks or months of continuous or intermittent colonization. Colonizing K. kingae enters the bloodstream through breaches in the respiratory mucosa and disseminates to bones, joints, or the endocardium. Daycare attendance increases the risk for K. kingae acquisition and transmission, and outbreaks of invasive disease have been reported among children in daycare. The most common manifestations of K. kingae disease in children are skeletal system infections (in 56% of patients), bacteremia (in 39%), pneumonia (in 4%), and endocarditis (in 1%). The clinical presentation is often subtle and laboratory tests are frequently normal, requiring a high index of suspicion. The organism is susceptible to most antibiotics, and with the exception of cases of endocarditis, invasive K. kingae infections usually run a benign uncomplicated clinical course.