Clinical Director, University of Illinois College of Medicine
There are often underlying problems such as thrombophilias anxiety kava discount 60 caps serpina otc, maternal idiopathic thrombocytopenic purpura anxiety symptoms jaw spasms order serpina 60caps line, vascular maldevelopment anxiety zoloft buy cheap serpina 60 caps on-line, or history of maternal cocaine use anxiety 4th herefords serpina 60 caps line. Infants may present with unilateral, focal seizures or display asymmetric motor function, or they may be asymptomatic. Selective neuronal necrosis can involve specific regions of the cortex, thalamus, brainstem, cerebellum, or hippocampus. An acute global injury such as is seen with uterine rupture or cord prolapse causes injury to the basal ganglia, thalamus, and brainstem, whereas a prolonged partial injury affects mainly the cortex and subcortical white matter. Damage is more extensive in the posterior parietal-occipital region than in the anterior cortical areas. Seizures are a feature of cortical injury, whereas irritability, posturing, and brainstem dysfunction are seen with infarcts affecting the basal ganglia and thalamus. Long-term sequelae of such an injury include cerebral atrophy and multicystic encephalomalacia. Status marmoratus refers to the marbled appearance of the basal ganglia, thalamus, and cerebral cortex in response to the injury. This appearance results from gross shrinkage of the striatum and defects in myelination. It may relate to the type of insult or the density of glutaminergic receptors in the basal ganglia (Johnston, 1995). Although the clinical correlate of this condition in the newborn is not well defined, it is seen in children with choreoathetoid cerebral palsy. Cerebral blood flow is closely autoregulated over a wide range of systemic blood pressure by either vasoconstriction or dilatation of cerebral arterioles. Therefore, rapid changes in cerebral perfusion pressure can occur in response to changes in systemic blood pressure, as well as changes in cerebral Pao2 and Paco2. Injury typically tends to occur in the watershed regions, which in the term newborn are located in the parasagittal regions of the cerebral cortex. The periventricular white matter is the most vulnerable region in preterm newborns. Clinical features of parasagittal injury include hypotonia and weakness, especially in the upper trunk. Cortical infarcts usually occur in the watershed region supplied by the most peripheral branches of the anterior, middle, and posterior cerebral arteries. In patients with hyporeflexia or areflexia, spinal cord pathology should be considered. Although overall cerebral O2 demands are lower in the infant than in the adult, cerebral oxidative metabolism is considerably increased in areas of active neural development that are associated with either synapse formation or activation of enzymes required for ion homeostasis. Glucose is the primary source of energy in cerebral metabolism, and although the newborn brain is capable of utilizing alternative energy substrates such as ketones, lactate, and free fatty acids, glucose uptake mechanisms are relatively underdeveloped (Cremer et al, 1979; Gregoire et al, 1978). Animal studies have shown that this impaired uptake of glucose can impair cerebral metabolism even before oxygen depletion (Yager et al, 1996). Vasoautoregulation in response to increased cerebral blood pressure or flow is relatively underdeveloped in the newborn, thus rendering the infant more vulnerable to ischemic events. The gradual increase in vascularity of the developing brain leads to the creation of watershed areas. These global events lead to patterns of focal injury that are dependent on maturational processes. The similarities between processes essential for brain development and those mediating cellular injury make the immature brain particularly vulnerable to ischemic insult. These similarities include an increased density of glutamate receptors, an increase in glutaminergic synapses in particular regions of the immature brain, and enhanced accumulation of cytosolic calcium after activation of the glutamate receptor. It has been shown that there are proportionately more glutamate receptors in the immature rat brain than in the mature rat brain and that the developing rat brain is much more sensitive to injury than the newborn or adult brain (Yager et al, 1996). Decreased cerebral energy stores lead to membrane pump failure and the subsequent inability to maintain normal ion gradients (Figure 61-3). This is followed by neuronal membrane depolarization and release of neurotransmitters such as glutamate, which increase cytosolic calcium and induce destructive enzymes and free radicals. Reoxygenation after the ischemic episode plays a significant role in cellular injury. In the normal state, glucose and oxygen are the main requirements for brain energy production, which occurs by oxidative phosphorylation. Glucose is taken up by a carrier-mediated diffusion process and phosphorylated to glucose 6-phosphate, the major portion of which enters the glycolytic pathway to form pyruvate. A failure of the pump leads to an influx of sodium into the cell and potassium outside the cell. Associated glial uptake of sodium and water leads to astrocytic swelling that in turn decreases diffusion of oxygen and glucose to the neurons. Accumulation of lactate secondary to anaerobic glycolysis leads to tissue acidosis, which inhibits both vascular autoregulation and phosphofructokinase, the rate-limiting enzyme in glycolysis. In immature animals, hypoglycemia has been shown to be damaging; pretreating animals with glucose decreases the impact of the injury when given before, but not during, the injury (Sheldon et al, 1992; Vannucci and Vannucci, 2000). Excitotoxicity refers to excessive glutamatergic activation that leads to cell injury and death (Olney, 2003). Neuronal injury is initiated by release of glutamate and other excitatory neurotransmitters from the presynaptic neurons. Subsequently, glutamate release occurs by both a reversal of normal glutamate uptake mechanisms by the nerve terminals and glia, and membrane leakage. The density of receptors is higher in regions of active development, and the different subtypes vary in different regions of the brain at different gestational ages. Activation of any of the three subtypes of glutamate-activated postsynaptic neuron receptors leads to an influx of calcium into the postsynaptic neurons.
Hemangiomas are tumors that demonstrate endothelial hyperplasia and undergo a period of proliferation and involution anxiety 7 cups of tea buy generic serpina 60caps on-line. They have normal endothelial cell turnover and grow accordingly with surrounding structures anxiety physical symptoms buy discount serpina 60 caps. Vascular malformations are further subcategorized by the type of vascular tissue involved (arterial anxiety zone ms fears cheap serpina 60 caps, venous anxiety 9 to 5 buy cheap serpina online, and lymphatic). An effective large left-to-right shunt occurs through the direct arterial-venous connections. A, the branch pulmonary arteries and arch vessels are snared, and a ligature is placed around the ductus arteriosus. To adequately mobilize the descending aorta, the left subclavian artery may need to be divided (as shown). After resection of the ductus arteriosus, the proximal (pulmonary artery) end is oversewn. An alternative strategy is anastomosis of the left subclavian and left common carotid arteries combined with homograft patch augmentation of the inferior surface of the arch. The increased systemic venous return increases right atrial pressures and promotes right-to-left shunting through the foramen ovale. Systolic murmurs may be present secondary to tricuspid valve regurgitation or increased flow across the pulmonary valve. When a malformation is suspected, care must be taken to auscultate areas where malformations are likely, such as the head, liver, and chest. Arteries proximal to the malformation are typically dilated with bounding pulses, whereas those distal are small with diminished pulses. Treatment, if necessary, requires interventional closure or surgical ligation of the anomalous vascular connections. There is a paucity of information, however, regarding the diagnosis and management of fetal and newborn cardiomyopathy. In evaluating a newborn infant with signs of congestive heart failure, structural heart disease should be ruled out. In the absence of structural problems, the diagnosis of cardiomyopathy should be considered. The etiology of neonatal cardiomyopathy includes prenatal infections (with cytomegalovirus, human immunodeficiency virus, enterovirus, or parvovirus); familial or genetic causes; maternal autoimmune disease with anti-Ro or anti-La antibodies; prenatal drug exposure; arrhythmia-induced cardiomyopathy; and twin-twin transfusion. Initial stabilization may require mechanical ventilation, the use of ionotropes, afterload reduction, and diuresis. Long-term treatment is dependent somewhat on the specific cause of the cardiomyopathy, because some forms may be reversible. Cardiac transplantation should be considered if cardiac function is poor or improvement is not noted. Since then, improved understanding of transplant immunology and medical management has made heart transplantation in infants and children an important option in inoperable patients or those with end-stage cardiac disease. In a recent scientific statement from the American Heart Association, the indications for pediatric heart transplantation were defined (adapted from Canter et al, 2007): 1. Progressive deterioration of ventricular function or functional status despite optimal medical care 4. Malignant arrhythmia or survival after cardiac arrest unresponsive to medical therapy, catheter ablation, or an automatic implantable defibrillator 5. Growth failure secondary to severe congestive heart failure unresponsive to conventional medical therapy 7. Unacceptably poor quality of life There are a variety of lesions in the neonate for which cardiac transplantation has been used as primary palliation. In considering transplantation in these patients, there is a balance between the success of palliative surgery and the availability of organs for transplantation. For example, over the past decade, survival of patients undergoing surgical palliation of hypoplastic left heart syndrome has continued to improve (Alsoufi et al, 2007; Gordon et al, 2008). With the availability of infant donors increasing only slightly over this period of time (Table 55-2), the balance for treatment of these newborns has shifted toward surgical palliation with the Norwood or hybrid Norwood procedures. Patients with the other lesions just noted continue to have relatively poor surgical outcomes, suggesting that palliation with heart transplantation may be the best approach. Given the limited availability of organs, however, it should be recognized that some of these infants will not survive to transplantation (Kirklin et al, 2006). The long-term survival of infants who undergo heart transplantation is quite good. The calculated "half-life" of transplant recipients younger than 1 year of age was 15. It is interesting that there appears to be a survival advantage in newborns who receive their transplant before 1 month of age versus those between 1 and 12 months (del Rio, 2000). Although the mechanism of the improved survival in the younger neonates is not known, it may reflect an immunologic window where in graft rejection and transplant coronary artery disease are limited. Klitzner Advances in both electrophysiology and fetal echocardiography over the past two decades have substantially enhanced our ability to diagnose and treat arrhythmias in the fetus and newborn. This chapter outlines many of the advances and can serve as a guide to the most modern approaches to the issue of rhythm disturbances in the perinatal period. After a brief introduction to the pathophysiology of arrhythmias, the chapter is divided into sections on the neonate and fetus.
It was suggested by the authors that more than 50% of invasive procedures might be avoided using this technique anxiety symptoms flushed face discount serpina 60caps line. The rate of fetal trauma and morbidity associated with cordocentesis is less than 2% (Parer anxiety symptoms brain zaps purchase serpina overnight delivery, 1988; van Kamp et al anxiety free buy genuine serpina on line, 2005) anxiety 1st trimester order serpina 60 caps free shipping. Cordocentesis should be performed with blood available for intravascular intrauterine transfusion if necessary. Such blood should be type O, RhD negative, cytomegalovirus negative, and less than 72 hours from collection; extended crossmatch is often performed with maternal blood type. The transfusion is generally administered at approximately 20 mL per kg estimated fetal weight with a target of 40 to 50% hematocrit. For a full discussion and algorithm for management of pregnant patients with RhD alloimmunization, see Moise, 2008b. This hyperbilirubinemia reflects the severity of hemolysis and its effects on the fetal liver. Neonatal exchange transfusion, amniocentesis, selective early induction of delivery, and intrauterine fetal blood transfusions all have contributed to the declining neonatal death rate from Rh incompatibility. In persons with type A and type B blood, naturally occurring anti-B and anti-A isoantibodies largely are IgM molecules that do not cross the placenta. In contrast, the alloantibodies present in persons with type O blood also include IgG antibodies that can traverse the placenta (Abelson and Rawson, 1961). Laboratory features include evidence of minimal to moderate hyperbilirubinemia and, occasionally, some degree of anemia. The peripheral blood smear is characterized by marked spherocytosis that is indistinguishable from that seen in hereditary spherocytosis (see Hereditary Spherocytosis, later). Additional follow-up at 2 to 3 weeks of age to check for anemia in these infants is essential. Minor Blood Group Incompatibility With the sharp decline of hemolytic disease caused by Rh incompatibility, the proportion of cases caused by Rh c, Rh E, Kell, Duffy, and Kidd incompatibility has increased from the previous estimates of 1% to 3%, to as high as 20% (for Kell sensitization) (Geifman-Holtzman et al, 1997; Moise, 2008a). With some antibodies such as Kell, antibody titer and amniocentesis findings may underestimate the severity of fetal hemolysis. Inherited mutations in components of the membrane cytoskeleton (spectrin, ankyrin, or band 3) weaken the stability of the interactions between the cytoskeleton and the membrane lipid bilayer, promoting vesiculation and loss of bits of the bilayer, thus leading to progressive loss of membrane surface area (Gallagher and Glader, 2009). Removal of the spleen after 5 years of age allows spherocytes to have a near-normal life span despite their cytoskeletal defects and abnormal shape. Twenty-eight percent to 43% of infants are anemic at birth (Hgb <15 gm/dL) (Perrotta et al, 2008). Neonatal hemolysis or hyperbilirubinemia appears in approximately half of all affected infants (Stamey and Diamond, 1957). In fact it is often the exaggerated neonatal hyperbilirubinemia that raises the suspicion of an underlying hemolytic disorder. In many cases, other family members are affected in a pattern consistent with autosomal dominant inheritance. In 20% to 30% of cases, recessive inheritance is noted, but only homozygotes express the clinical features of spherocytosis. Occasionally, the appearance of a new case of spherocytosis in a previously unaffected family is due to spontaneous mutation. In this situation, evaluation of the family for other persons affected with spherocytosis may point to a hereditary rather than an acquired cause. The mainstay of treatment during the newborn period is directed toward management of hyperbilirubinemia, which often is present and may not peak until the infant is several days of age. A common occurrence is the appearance of a transient but severe anemia during the first 20 days of life due to underproduction of Immune Hemolytic Anemia Due to Maternal Disease Maternal autoimmune hemolytic anemia or lupus erythematosus during pregnancy may be associated with passive transfer of IgG antibody to the fetus. Treatment with prednisone in the mother may reduce both maternal hemolysis and the risk of neonatal morbidity. As in other cases of neonatal hemolysis, treatment is focused on prevention of severe hyperbilirubinemia and kernicterus. In cases of bacterial sepsis, both the direct and indirect bilirubin levels may be elevated. Documentation of infection as the cause of hemolysis is made by the presence of other clinical and laboratory evidence of neonatal infections. Hemolysis caused by infections may present early in the neonatal period, or it can be delayed for several weeks. The hemolytic component of this disorder is secondary to the deposition of fibrin within the vascular walls. Abnormalities of the placental microcirculation or macrovascular anomalies such as an umbilical vein varix are rare causes of congenital schistocytic anemia (Batton et al, 2000). Careful monitoring of affected infants after discharge from the nursery is warranted. Splenectomy is the definitive treatment for hereditary spherocytosis, but this is not recommended before 5 years of age because of the increased risk of overwhelming sepsis with encapsulated organisms such as Streptococcus pneumoniae (Diamond, 1969) that occurs following splenectomy in infants and young children. Guidelines regarding the indications for total or partial splenectomy have been reviewed (Bader-Meunier et al, 2001; BoltonMaggs et al, 2004). Heterozygotes usually exhibit elliptocytes on the blood smear, but in the vast majority of instances hemolysis is absent. Transient poikilocytosis and hemolysis may occur during the newborn period in infants destined ultimately to have asymptomatic elliptocytosis (Austin and Desforges, 1969). Precipitating factors can include infection, exposure to medications that are potent oxidants, or to other agents such as fava beans, naphthalene, or certain petrochemical-derived substances. Rarely, hemolytic anemia is chronic rather than episodic and is present even in the absence of obvious exposure to oxidant stress.
If poor fixation and following are noted after 3 months of age anxiety symptoms 9 days purchase serpina 60caps with visa, a significant eye or brain abnormality is suspected anxiety and pregnancy purchase generic serpina pills, and referral is advisable (American Academy of Pediatrics anxiety care plan buy 60 caps serpina otc, 2003) anxiety symptoms tongue cheap serpina 60 caps. On inspection, the pediatrician may grossly visualize a white lesion in the pupillary space or identify an abnormal red reflex. The differential diagnosis for leukocoria includes vision- and life-threatening conditions, and leukocoria in an infant or older child requires urgent ophthalmologic evaluation. In one series, 60% of 71 children less than age 10 who presented to a tertiary referral center with leukocoria had cataracts and 28% had retinoblastoma (Haider et al, 2008). Note central dense opacity surrounded by clearer lens and poor pupillary dilation. In contrast with adult-onset cataracts, which in most cases are removed at the preference of the patient, visually significant congenital cataracts must be surgically removed before 6 to 8 weeks of age to prevent irreversible vision loss from dense amblyopia (see the earlier discussion of visual development) (Birch et al, 2009; Lundvall and Kugelberg, 2002). Therefore, it is essential that all newborns and young infants have screening eye examinations by a pediatrician, because visual prognosis is directly tied to timely ophthalmologic referral. Cataracts can develop or progress with time, so examination for an abnormal red reflex should be repeated at each well-child visit even if prior exam findings appeared normal. Nystagmus is an ominous sign of poor visual prognosis and adds even greater urgency for surgical intervention. Treatment does not end with surgery, because these infants are left aphakic (without a lens) and must receive optical correction with special contact lenses. Glasses, including bifocals, may be required in addition to aphakic contacts but may produce excessive optical aberrations when used as the sole means of refractive correction. Compliance with contacts, glasses, and, in the case of monocular cataracts, aggressive amblyopia treatment is essential for a successful visual outcome. Such children are also at risk for developing aphakic glaucoma, which may present after years, can be very difficult to treat, and is sightthreatening. There is evidence that very early cataract surgery increases the risk of glaucoma, and the optimal timing may lie between 3 and 6 weeks of age (Chak and Rahi, 2008; Khan and A1-Dahmesh, 2009; Michaelides et al, 2007; Swamy et al, 2007). The etiologic distribution of congenital cataracts is approximately one third inherited; one third associated with systemic genetic, metabolic, or maternal infectious disorders; and one third idiopathic. Genetic inheritance is most commonly autosomal dominant and rarely autosomal or X-linked recessive (Francis et al, 2000; Hejtmancik and Smaoui, 2003). Multiple genes are involved in lens development, and numerous genetic loci have been identified (Hejtmancik and Smaoui, 2003). Marked variability can be present even within the same pedigree, and children with a family history should be examined early by a pediatric ophthalmologist. The same is true of children diagnosed with one of the numerous systemic conditions associated with cataracts. The incidence is between 1 in 15,000 and 1 in 20,000 live births, with approximately 350 newly diagnosed cases in the United States per year (Moll et al, 1997; Seregard et al, 2004). Untreated retinoblastoma is almost uniformly fatal, and long-term survival for disease diagnosed after it has spread outside the eye is under 50% (Chantada et al, 1999; Leander et al, 2007). In contrast, 5-year survival rates are greater than 90% when timely recognition and referral to centers specializing in retinoblastoma treatment occur (Abramson, 1982; Abramson et al, 2003; MacCarthy et al, 2006; Moll et al, 1997; Sanders et al, 1988; Seregard et al, 2004). The most common presenting sign was leukocoria (54%), followed by strabismus (19%), poor vision (4%), family history with request for early exam (5%), and red eye (5%). In most reports, a majority of cases are diagnosed between 1 and 2 years of age, but the earliest reported date has been in utero, and in a series of 400 cases reported by Shield et al, 8. In the series reported by Abramson et al (2003), the disease presenting sign was identified first by a family member or friend in 80% of cases, a pediatrician in 8%, and an ophthalmologist in 10%. Among patients presenting with leukocoria, the sign was first identified by the family in 90% of cases. These findings stress the importance of routine red reflex testing for all children seen by pediatricians, beginning with newborns. Any child found to have leukocoria should be referred to an ophthalmologist for urgent evaluation. Involved structures can include the cornea, iris, ciliary body, lens, retina, choroid, and optic nerve (Gregory-Evans et al, 2004). A chorioretinal or optic nerve head coloboma, depending on the size, will appear as an abnormal red reflex or leukocoria. The visual prognosis depends on whether the central macula is involved, and children may have good central vision despite upper visual field defects if the macula is spared. Long term, there is a variable risk of complicating retinal detachment or choroidal neovascularization associated with retinal and optic nerve colobomas (Daufenbach et al, 1998; Gregory-Evans et al, 2004; Guirgis and Lueder, 2003). There are numerous genetic loci, chromosomal aberrations, ocular abnormalities, and systemic findings associated with coloboma. Once referral occurs, diagnosis of retinoblastoma can often be made by visualization using indirect ophthalmoscopy with scleral depression, frequently during examination under anesthesia. Treatment modalities include enucleation, chemotherapy, focal destructive therapies such as retinal laser photocoagulation or cryotherapy, and radiation, including brachytherapy, stereotactic conformal radiotherapy, and accelerated proton beam irradiation (Balmer et al, 2006). Forty percent of patients have an inherited, disease-causing germline mutation, which acts in an autosomal dominant fashion with 90% penetrance (Balmer et al, 2006). Such children, as well as those with spontaneous germline mutations, are also at increased risk of developing nonocular tumors at a rate of 1% per year, or 50% by 50 years of age (Abramson, 1999). A discussion of the risk of retinoblastoma in relatives of affected parents or children is beyond the scope of this chapter. However, children with a positive family history may require serial examinations under anesthesia by an ophthalmologist and referral for genetic counseling.
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