Pediatrics_Nelson

Pediatrics_Nelson. The observation period varies with the severity of the injury and may include hospitalization even for children without neurologic deficits who have sustained a concussion. Any patient demonstrating any features of a concussion should be medically evaluated, and disposition (return to play) must be determined by a health care provider (see Table 184-3). The child should be monitored for deterioration over the initial few hours after injury and not left alone. If the child appears well after several hours and is discharged home, parents should be instructed to call their physician for any change in alertness, orientation, or neurologic functioning. An increase in somnolence, headache, or vomiting is cause for concern and neuroimaging.


Pediatrics_Nelson

Pediatrics_Nelson. Patients with intracranial hemorrhage may require emergent surgical intervention for decompression and drainage of the blood collection. Increased ICP may require monitoring, placement of a ventricular drain, and aggressive medical management, including intubation and ventilation, osmotic therapy, and sedation (see later discussion).


Pediatrics_Nelson

Pediatrics_Nelson. Children with concussion without subsequent neurologic deficits have a favorable long-term prognosis, and late sequelae are rare. Children with moderate contusions usually make good recoveries even when neurologic signs persist for weeks. Longterm sequelae may include poor memory, slowing of motor skills, generalized decrease in cognitive skills, behavioral alterations, or attention deficits. Language function, especially in a young child, frequently makes a good recovery. Rehabilitation programs with physical therapy, behavioral management, and appropriate education may be necessary. Poor prognostic signs include a Glasgow Coma Scale score of less than 4 on admission without improvement in 24 hours, absent pupillary light reflexes, and persistent extensor plantar reflexes.


Pediatrics_Nelson

Pediatrics_Nelson. Children with cerebral contusion who survive acute cerebral swelling may improve gradually or may remain vegetative. Extracranial trauma also contributes to the morbidity of these patients (aspiration pneumonia, acute respiratory distress syndrome, sepsis, emboli). Maximal recovery may take weeks or months. Coma lasting for weeks after head trauma may be compatible with a good outcome, although the risk of late sequelae is significant. Patients who remain in a vegetative state for months after head injury are unlikely to improve.


Pediatrics_Nelson

Pediatrics_Nelson. When the cranial sutures are fused, the skull becomes a rigid container enclosing a fixed volume, including the brain (80% to 85%), CSF (10% to 15%), and blood (5% to 10%). The exponential relationship between the volume within a closed container and pressure results in a massive increase in ICP as intracranial volume increases. The brain accommodates increased ICP initially by expelling CSF and blood from the intracranial compartment into the spinal subarachnoid space. When the limits of this accommodation are reached, the brain itself begins to shift in response to the continuing elevation of ICP. Brain shifts may cause herniations across the dural extensions or skull barriers (see Table 184-2). The causes of increased ICP include mass lesion, hydrocephalus, cerebral edema due to trauma or infection and idiopathic intracranial hypertension (Tables 184-5, 184-6).


Pediatrics_Nelson

Pediatrics_Nelson. Mass lesions (brain tumor, abscess, hemorrhage) may produce increased ICP not only by virtue of large size, but by blockage of CSF pathways, blockage of venous outflow, or production of vasogenic cerebral edema. Brain abscesses usually present as mass lesions, producing focal neurologic signs and increased ICP. Symptoms of infection, including fever, malaise, anorexia, and stiff neck, may be subtle or absent. Brain edema around an abscess is usually severe and extends into the surrounding white matter. Children with chronic cardiac or pulmonary disease may embolize infected material to their brains, predisposing them to brain abscesses. Brain tumors in children are most often located in the posterior fossa and can result in elevated ICP due to obstruction of CSF flow through the cerebral aqueduct and fourth ventricle.


Pediatrics_Nelson

Pediatrics_Nelson. Hydrocephalus from congenital abnormalities or due to an intracranial mass is typically characterized by a slowly evolving syndrome of increased ICP extending over weeks or months. CSF is continuously produced by the choroid plexus within the lateral, third, and fourth ventricles. CSF flows from the lateral ventricles through the intraventricular foramen of Monro to the third ventricle, then passes through the cerebral aqueduct to the fourth ventricle. CSF exits the fourth ventricle from the foramen of Magendie and foramina of Luschka. Sub-arachnoid flow occurs superiorly to the cisterns of the brain and inferiorly to the spinal subarachnoid space. Absorption of CSF is accomplished predominantly by the arachnoid villi into the large dural sinuses. Hydrocephalus is due to the obstruction of CSF flow anywhere along its course (see Table 1846). Obstructive hydrocephalus is caused by a block before the CSF flows to the subarachnoid space, usually within the fourth ventricle or at the


Pediatrics_Nelson

Pediatrics_Nelson. of CSF flow anywhere along its course (see Table 1846). Obstructive hydrocephalus is caused by a block before the CSF flows to the subarachnoid space, usually within the fourth ventricle or at the level of the aqueduct. Impairment of CSF flow within the subarachnoid space or impairment of


Pediatrics_Nelson

Pediatrics_Nelson. Hydrocephalus Infarction with edema Hemorrhage Tumor Abscess Cyst Inflammatory mass Arterial ischemic stroke Intracranial venous sinus thrombosis Hyponatremia Diabetic ketoacidosis Dialysis dysequilibrium syndrome Reye syndrome Fulminant hepatic encephalopathy Pulmonary insufficiency with hypercarbia Lead intoxication Idiopathic intracranial hypertension (pseudotumor cerebri) Drugs Withdrawal of long-term steroid administration Endocrinologic disturbance Obesity


Pediatrics_Nelson

Pediatrics_Nelson. Idiopathic intracranial hypertension (pseudotumor cerebri) Drugs Withdrawal of long-term steroid administration Endocrinologic disturbance Obesity Obstruction of CSF Intraventricular foramina (Monro) pathways obstruction Parasellar mass (craniopharyngioma, germinoma, pituitary tumor) Intraventricular tumor (ependymoma) Tuberous sclerosis with subependymal giant cell astrocytoma Aqueduct of Sylvius (cerebral aqueduct) obstruction Aqueductal stenosis Midbrain or pineal region tumor Postinfectious or postinflammatory Posthemorrhagic Impaired flow from the fourth ventricle foramina of Luschka and Magendie Basilar impression Platybasia Dandy-Walker malformation Arnold-Chiari malformation Bone lesions of the cranial base (achondroplasia, rickets) Overproduction of Choroid plexus papilloma CSF


Pediatrics_Nelson

Pediatrics_Nelson. Overproduction of Choroid plexus papilloma CSF Defective Hypoplasia of the arachnoid villi reabsorption of CSF Postinfectious or posthemorrhagic (extraventricular destruction of arachnoid villi or obstruction or subarachnoid fibrosis communicating Extensive cerebral sinovenous thrombosis hydrocephalus) CSF, Cerebrospinal fluid. absorption is known by the misnomer communicating hydrocephalus, where there is actually extraventricular obstruction of CSF flow (external hydrocephalus). Hydrocephalus caused by overproduction of CSF without true obstruction is seen in choroid plexus papillomas, which account for 2% to 4% of childhood intracranial tumors.


Pediatrics_Nelson

Pediatrics_Nelson. Bacterial meningitis may produce increased ICP by blockage of CSF pathways, toxic cerebral edema, increase in cerebral blood flow, or multifocal cerebral infarctions (Chapter 100). Most children with bacterial meningitis can undergo LP safely because the brain swelling is diffuse and distributed evenly throughout the brain and spinal CSF compartments. A few patients with meningitis, however, develop transtentorial herniation within a few hours of LP. Focal neurologic signs, poorly reactive pupils, and a tense fontanelle are contraindications to LP in a patient with suspected bacterial meningitis.


Pediatrics_Nelson

Pediatrics_Nelson. Idiopathic intracranial hypertension (pseudotumor cerebri) is a cause of increased ICP with normal brain imaging.Patients exhibit a daily debilitating headache associated withdiplopia, abducens palsy, transient visual obscurations, and papilledema. If untreated, permanent visual field loss may develop.The syndrome has been associated with ingestion of medications(tetracycline, vitamin A, oral contraceptive agents) and endocrinedisturbances (thyroid disease, Addison disease). Most commonly,this condition is idiopathic and affects children who are otherwise well except for being overweight, with rapid weight gain being a predisposing factor. Treatment including acetazolamideor other diuretic, topiramate, or corticosteroids, is generally effective. Weight loss and cessation of triggering medications are alsomainstays of treatment. Infrequently, chronic papilledema frompersistent idiopathic intracranial hypertension produces visualimpairment, and more aggressive management is required


Pediatrics_Nelson

Pediatrics_Nelson. medications are alsomainstays of treatment. Infrequently, chronic papilledema frompersistent idiopathic intracranial hypertension produces visualimpairment, and more aggressive management is required (opticnerve fenestration) to preserve visual function.


Pediatrics_Nelson

Available @ StudentConsult.com

Pediatrics_Nelson. Available @ StudentConsult.com


Pediatrics_Nelson

Pediatrics_Nelson. The symptoms and signs of increased ICP include headache,vomiting, lethargy, irritability, altered consciousness, sixthnerve palsy, strabismus, diplopia, and papilledema. Headaches suggestive of increased ICP are those associated withnocturnal wakening; worse in the morning; with cough, micturition, defecation, or Valsalva maneuver; or progressivelyworsening. Infants who have an open fontanelle usually donot develop papilledema or abducens palsy. Specific signsof increased ICP in infants consist of a bulging fontanelle,suture diastasis, distended scalp veins, a persistent downward deviation of the eyes (sunsetting), and rapid growth ofhead circumference. Specific signs of increased ICP in theinfratentorial compartment (posterior fossa) include stiffneck and head tilt. Focal neurologic deficits reflect the siteof the lesion that is producing the increased ICP and mayinclude hemiparesis from supratentorial lesions, or ataxiaand cranial nerve palsies from infratentorial lesions.


Pediatrics_Nelson

Pediatrics_Nelson. deficits reflect the siteof the lesion that is producing the increased ICP and mayinclude hemiparesis from supratentorial lesions, or ataxiaand cranial nerve palsies from infratentorial lesions. Critically increased ICP may result in herniation syndromes, as discussed earlier. In addition, the Cushing triad of elevated blood pressure, bradycardia, and irregular respirations is a late sign of critically elevated ICP.


Pediatrics_Nelson

Pediatrics_Nelson. The clinical manifestations of hydrocephalus are caused byventricular distention and increased ICP. Dilation of the lateral ventricles stretches the corticopontocerebellar and corticospinalpathways, resulting in ataxia and spasticity that initially are mostmarked in the lower extremities because the leg fibers are closestto the ventricles. Distention of the third ventricle may compressthe hypothalamic regions and result in endocrine dysfunction.The optic nerves, chiasm, and tracts also are in proximity to theanterior third ventricle, and visual dysfunction results whenthese structures are compressed. Dilation of the cerebral aqueduct compresses the surrounding periaqueductal vertical gazecenter, causing downward deviation of the eyes. Manifestationsof increased ICP may evolve slowly when obstruction is not complete and there is time for transependymal absorption of CSF intothe veins, or rapidly when obstruction is abrupt and complete(subarachnoid hemorrhage) and compensation cannot


Pediatrics_Nelson

Pediatrics_Nelson. obstruction is not complete and there is time for transependymal absorption of CSF intothe veins, or rapidly when obstruction is abrupt and complete(subarachnoid hemorrhage) and compensation cannot occur.


Pediatrics_Nelson

Pediatrics_Nelson. The cause of increased ICP is determined by brain imaging with either head CT or brain MRI. CT is rapid, readilyavailable, and provides clear visualization of an acute hemorrhage or dilated ventricles. Mass lesions, hydrocephalus,and trauma are easily recognized. Diffuse brain swelling produced by hypoxic-ischemic injury, meningitis, encephalitis,metabolic abnormalities, or toxins may be better delineated by MRI. MRI is also superior to CT for visualizing the posterior fossa and cortical contusions. LP is the diagnostic testfor infection and for documentation of elevated ICP (essential for patients with idiopathic intracranial hypertension).However, LP is contraindicated in the setting of an intracranial mass lesion or clear hydrocephalus, because withdrawalof CSF can change pressures between the intracranial compartments and promote brainstem shifts and herniation.Idiopathic intracranial hypertension is diagnosed whendirect measurement of ICP with a manometer during LPreveals


Pediatrics_Nelson

Pediatrics_Nelson. between the intracranial compartments and promote brainstem shifts and herniation.Idiopathic intracranial hypertension is diagnosed whendirect measurement of ICP with a manometer during LPreveals elevated ICP in the absence of other CSF or imagingabnormalities.


Pediatrics_Nelson

Treatment of Elevated ICP

Pediatrics_Nelson. Treatment of Elevated ICP


Pediatrics_Nelson

Pediatrics_Nelson. The treatment of acute increased ICP should be carried out in an intensive care setting with continuous monitoring and vigilant attention to vital signs. The patient’s response to specific interventions must be carefully assessed. The head is placed at midline and the head of the bed elevated 30°. Immediate endotracheal intubation and hyperventilation (to a Paco2 not lower than 35 mm Hg) produces rapid, but transient, reduction in ICP by cerebral vasoconstriction, leading to decreased cerebral blood volume. Mannitol or 3% saline may be used acutely to produce an osmotic shift of fluid from the brain to the plasma. A ventricular catheter may be used to remove CSF and to monitor the ICP continuously. Pentobarbital-induced coma reduces pressure by severely suppressing cerebral metabolism and cerebral blood flow. Acetazolamide and furosemide may transiently decrease CSF production. Because acute interventions such as hyperventilation, osmotic therapies, and barbiturates can have negative


Pediatrics_Nelson

Pediatrics_Nelson. cerebral blood flow. Acetazolamide and furosemide may transiently decrease CSF production. Because acute interventions such as hyperventilation, osmotic therapies, and barbiturates can have negative impacts on systemic and cerebral perfusion and have only transient effects on ICP, they must be used judiciously.


Pediatrics_Nelson

Pediatrics_Nelson. The treatment of hydrocephalus may be medical or surgical, depending on the etiology. After subarachnoid hemorrhage or meningitis, the flow or absorption of CSF may be transiently impaired. In this circumstance, the use of medication that decreases CSF production, such as acetazolamide, may be beneficial. Surgical management consists of removing the obstructive lesion, placing a shunt, or both. A shunt consists of polyethylene tubing extending usually from a lateral ventricle to the peritoneal cavity (ventriculoperitoneal shunt). Shunts carry the hazards of infection or sudden occlusion with signs and symptoms of acute hydrocephalus.


Pediatrics_Nelson

Pediatrics_Nelson. Vasopressor drugs may be necessary to maintain adequate arterial pressure and cerebral perfusion pressure. Serum electrolytes and osmolarity should be monitored because of risk of the syndrome of inappropriate antidiuretic hormone or cerebral salt wasting. Maintaining normoglycemia may have a positive impact on outcomes. Other supportive measures include controlling agitation, fever, and seizures. All treatments for increased ICP are temporary measuresintended to prevent herniation until the underlying disease process either is treated or resolves spontaneously. Timely interventioncan reverse cerebral herniation. Complete neurologic recovery ispossible, but rare, after signs of transtentorial or foramen magnumherniation have begun. When these signs are complete, however,with bilaterally dilated, unreactive pupils, absent eye movements,and flaccid quadriplegia, recovery is no longer possible.


Pediatrics_Nelson

Pediatrics_Nelson. Children typically acquire developmental milestones in a variable but predictable sequence (Chapter 7). Rarely, children present with stagnation of development or frank loss of previouslyacquired skills. These neurodegenerative disorders encompassa large heterogenous group of diseases that result from specificgenetic and biochemical defects and varied unknown causes.Neurodegenerative disorders can present at any age. Clinical phenotypes also vary, but neurologic deterioration may bedemonstrated as loss of speech, vision, hearing, and intellectualor motor abilities—sometimes in concert with seizures, feedingdifficulties, and mental retardation. Progression may be slowover many years, or may lead to death in early childhood.


Pediatrics_Nelson

Pediatrics_Nelson. Degenerative diseases may affect gray matter (neuronal degenerative disorders), white matter (leukodystrophies),both gray and white matter, or specific, focal regions of the brain. Early seizures and intellectual impairment mark grey matter disorders, whereas upper motor neuron signs and progressive spasticity are the hallmarks of white matter disorders. Many neurodegenerative illnesses result from enzymatic disorders within subcellular organelles, including lysosomes, mitochondria, and peroxisomes (Table 185-1). Therefore, any Cognitive regression, hepatosplenomegaly, jaundice, seizures Test: acid sphingomyelinase (ASM) enzyme activity Hepatosplenomegaly, cytopenia, spasticity, hyperextension, extraocular palsies, trismus, difficulty swallowing Test: glucosylceramidase enzyme activity Infantile form—early feeding difficulties, global retardation, seizures, coarse facial features, hepatosplenomegaly, cherry red spot


Pediatrics_Nelson

Pediatrics_Nelson. Test: glucosylceramidase enzyme activity Infantile form—early feeding difficulties, global retardation, seizures, coarse facial features, hepatosplenomegaly, cherry red spot Juvenile form—incoordination, weakness, language regression; later, seizures, spasticity, blindness Test: GM1 ganglioside enzyme activity; GLB1 gene testing Tay-Sachs—progressive weakness, marked startle reaction, blindness, convulsions, spasticity, and cherry red spots Test: β-hexosaminidase A (HEX A) enzymatic activity Sandhoff disease—phenotype similar to Tay-Sachs Test: hexosaminidase A and B enzyme activity (both deficient) Irritability, hyperpyrexia, vomiting, seizures, hypertonia, blindness Test: galactocerebrosidase (GALC) enzyme activity Late infantile form—stiffening and ataxia of gait, spasticity, optic atrophy, intellectual deterioration, absent reflexes Juvenile and adult forms


Pediatrics_Nelson

Pediatrics_Nelson. Late infantile form—stiffening and ataxia of gait, spasticity, optic atrophy, intellectual deterioration, absent reflexes Juvenile and adult forms Test: 1. arylsulfatase A (ARSA) enzyme activity 2. If ARSA activity is <10% of controls, exclude ARSA pseudodeficiency with genetic testing of ARSA and/or abnormal urinary sulfatide excretion Visual loss, progressive dementia, seizures, motor deterioration Test: Diagnostic algorithm depends on age of symptom onset, and replies on stepwise testing for palmitoyl-protein thioesterase 1 (PPT1) and tripeptidyl-peptidase 1 (TPP-1) enzyme activity Academic difficulties, behavioral disturbances, hypoadrenalism, seizures, spasticity, ataxia, and swallowing difficulties. Spastic paraparesis, urinary incontinence, adrenal insufficiency Test: very long chain fatty acids Short stature, kyphoscoliosis, coarse facies, hepatosplenomegaly, cardiovascular abnormalities, and corneal clouding


Pediatrics_Nelson

Pediatrics_Nelson. Short stature, kyphoscoliosis, coarse facies, hepatosplenomegaly, cardiovascular abnormalities, and corneal clouding Test: 1. lysosomal enzymes 2. urinary glycosaminoglycan excretion Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes Myoclonus, epilepsy, and ragged red fibers, dementia, hearing loss, optic nerve atrophy, ataxia, and loss of deep sensation Neuropathy, ataxia, and retinitis pigmentosa Tests: testing for mitochondrial disorders is complex and must be tailored to the individual clinical scenario; screening for blood and serum lactate and pyruvate is reasonable Hypotonia, feeding difficulties, respiratory irregularity, weakness of extraocular movements, and ataxia Test: depends on clinical phenotype Loss of purposeful hand movements and communication skills, social withdrawal, gait apraxia, seizures, spasticity, and kyphoscoliosis Test: MECP2 gene testing


Pediatrics_Nelson

Pediatrics_Nelson. Test: depends on clinical phenotype Loss of purposeful hand movements and communication skills, social withdrawal, gait apraxia, seizures, spasticity, and kyphoscoliosis Test: MECP2 gene testing Inborn error of copper metabolism resulting in signs of cerebellar and basal ganglia dysfunction


Pediatrics_Nelson

Pediatrics_Nelson. Test: MECP2 gene testing Inborn error of copper metabolism resulting in signs of cerebellar and basal ganglia dysfunction Test: serum ceruloplasmin levels, urinary copper excretion patient with a degenerative neurologic condition of unknown cause should have leukocytes or skin fibroblasts harvested for measurement of a standard battery of lysosomal, peroxisomal, and mitochondrial enzymes (Chapters 56, 57). Neuroimaging, usually with brain magnetic resonance imaging (MRI), is also typically warranted. The diagnosis of leukodystrophy usually can be made confidently on the basis of extensive cerebral white matter changes on MRI. Histologic and biochemical studies may be normal in gray matter encephalopathy, making the diagnosis much less secure. Acquired lesions (infectious, inflammatory, vascular, toxic) are difficult to exclude completely. Brain biopsy is not likely to be helpful.


Pediatrics_Nelson

Pediatrics_Nelson. The sphingolipidoses are characterized by intracellular storage of lipid substrates resulting from defective catabolism of the sphingolipids comprising cellular membranes. They are inherited in an autosomal recessive pattern. In most cases, there are several forms of these diseases, typically corresponding to the amount of residual activity in the relevant enzyme. The infantile forms are generally the most severe, usually presenting in the first or second year of life with rapid disease progression; affected individuals have virtually no normal enzyme activity. Juvenile and chronic forms are manifest somewhat later in childhood or even adulthood and have a less fulminant disease course because of some residual enzyme activity.


Pediatrics_Nelson

Pediatrics_Nelson. Classic Niemann-Pick disease is caused by a deficiency of sphingomyelinase and should be suspected in infants who exhibit the combination of hepatosplenomegaly, developmental delay, interstitial lung disease, and retinal cherry-red spots. The ganglion cells of the retina and macula are distended and appear as a large area of white surrounding a small red fovea that is not covered by ganglion cells. Cognitive regression, myoclonic seizures, hypotonia, and jaundice are also noted within the first year of life. Genetic testing for SMPD1 mutations is clinically available.


Pediatrics_Nelson

Pediatrics_Nelson. Although the most common form of Gaucher disease is an indolent illness of adults, there is a rapidly fatal infantile form featuring severe neurologic involvement caused by deficiency of the enzyme glucocerebrosidase. Glucoceramide accumulates in the liver, spleen, and bone marrow. The characteristic neurologic signs are opisthotonos (arching of the trunk), trismus (difficulty opening mouth), eye movement abnormalities, and bulbar signs including difficulty swallowing. Available @ StudentConsult.com Tay-Sachs disease (GM2 gangliosidosis) is caused by deficiency of hexosaminidase A and results in the accumulation of GM2 ganglioside in cerebral gray matter and cerebellum. Infants are typically normal except for a marked startle response until 6 months of age, when they develop listlessness, irritability, hyperacusis, intellectual retardation, and retinal cherry-red spots. Within months, blindness, convulsions, spasticity, and opisthotonos develop.


Pediatrics_Nelson

Pediatrics_Nelson. Metachromatic leukodystrophy (MLD) is a lipidosis causedby deficiency of arylsulfatase that results in demyelination ofthe central nervous system (CNS) and peripheral nervous system. Children with the late-infantile form present between 1and 2 years of age. After a period of normal development, progressive stiffening and ataxia of gait, spasticity, optic atrophy,intellectual deterioration, and absent reflexes occur. Diagnostictesting reveals increased cerebral spinal fluid protein (a sign ofCNS demyelination) and slowing of motor nerve conductionvelocity (a sign of peripheral demyelination). Older school-agechildren with the juvenile form of MLD may present with gradual onset of behavior difficulties and declining academic abilities, succeeded by gait difficulties, clumsiness, slurred speech,and sometimes seizures. Relentless progression is the rule.Bone marrow transplant is a treatment option, particularly if asibling is diagnosed with MLD before symptom onset.


Pediatrics_Nelson

Pediatrics_Nelson. Krabbe disease (globoid cell leukodystrophy) is caused by a deficiency of galactocerebrosidase. Individuals with the infantile form (85% to 90% of cases) appear to be normal during the first months of life. Symptoms begin by 6 months of age and include extreme irritability, hyperpyrexia, vomiting, seizures, hypertonia, and blindness. Demyelination of the CNS and peripheral nervous system results in upper and lower motor neuron signs. The neuronal ceroid lipofuscinoses are a group of inherited, neurodegenerative lysosomal storage disorders characterized by progressive vision loss, seizures, declining cognitive abilities, motordeterioration, and early death. Ten different types have been characterized, including infantile, late-infantile, and juvenile types.


Pediatrics_Nelson

Pediatrics_Nelson. The adrenoleukodystrophies (ALD) are a group of X-linked neurodegenerative disorders that are often associated with adrenocortical insufficiency. ALD is caused by accumulation of very long chain fatty acids in neuronal and adrenal tissue (Chapter 178) and is diagnosed by abnormal very long chain fatty acid testing. The most common leukodystrophy is classic X-linked adrenoleukodystrophy, caused by a mutation in the ABCD1 gene. Boys present between ages 5 and 15 years with academic difficulties, behavioral disturbances, and gait abnormalities, progressing to seizures, spasticity, ataxia, and swallowing difficulties. Brain MRI demonstrates a classic pattern of symmetric abnormal white matter signal in the parietal-occipital regions, with contrast enhancement at the anterior margin. Symptomatic adrenocortical insufficiency with fatigue, vomiting, and hypotension develops in 20% to 40% of patients with X-linked ALD. ALD should be considered in any male with primary adrenocortical


Pediatrics_Nelson

Pediatrics_Nelson. Symptomatic adrenocortical insufficiency with fatigue, vomiting, and hypotension develops in 20% to 40% of patients with X-linked ALD. ALD should be considered in any male with primary adrenocortical insufficiency, even in the absence of clear-cut neurological abnormalities. Adrenomyeloneuropathy, a chronic disorder of spinal cord and peripheral nerves, presents in the third decade of life. Female carriers of the ABCD1 mutation may also have symptoms similar to adrenomyeloneuropathy, beginning later in life (>35 years of age).


Pediatrics_Nelson

Pediatrics_Nelson. Mucopolysaccharidoses are caused by defective lysosomal hydrolases resulting in the accumulation of mucopolysaccharides within lysosomes (see Chapter 56). The clinical manifestations include coarse facies, short stature, kyphoscoliosis, hepatosplenomegaly, cardiovascular abnormalities, and corneal clouding. Neurologic involvement is seen in mucopolysaccharidosis types I (Hurler syndrome), II (Hunter syndrome),III (Sanfilippo syndrome), and VII (Sly syndrome). Children with Hurler syndrome, the most severe of these illnesses, appear normal during the first 6 months of life, then develop the characteristic skeletal and neurologic features. Intellectual disability, spasticity, deafness, and optic atrophy are progressive. Hydrocephalus frequently occurs because of obstruction to cerebrospinal fluid (CSF) flow by thickened leptomeninges.


Pediatrics_Nelson

Pediatrics_Nelson. Mitochondrial diseases represent a clinically heterogeneous group of disorders that fundamentally share a disturbance in oxidative phosphorylation (adenosine triphosphate synthesis) (Chapter 57). Abrupt symptoms are often manifest concurrent with periods of physiologic stress such as febrile illness or fasting. Specific genetic diagnoses are often difficult to identify because clinical features are pleotropic within individual defects and overlap between different defects, and because analysis of mitochondrial protein function is technically demanding. Specific syndromes include MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes); MERRF (myoclonus, epilepsy, and ragged red fibers) which can also manifest as combinations of dementia, sensorineural hearing loss, optic nerve atrophy, peripheral neuropathy, and occasionally cardiomyopathy with Wolff-Parkinson-White syndrome; and NARP (neuropathy, ataxia, and retinitis pigmentosa).


Pediatrics_Nelson

Pediatrics_Nelson. Rett syndrome is a neurodevelopmental disorder that classically affects girls. Typically, development appears normal during the first 6 to 18 months of life, followed by regression, loss of purposeful hand movements, loss of verbal communication skills, gait apraxia, and stereotypic repetitive hand movements that resemble washing, wringing, or clapping of the hands. Girls also develop acquired microcephaly. Episodic apnea and/or hyperpnea, peripheral vasomotor disturbances, growth retardation, abnormal muscle tone, and prolonged QTc interval often occur. The regression plateaus and stabilizes, but seizures, spasticity, and kyphoscoliosis develop. The etiology is a mutation on an X chromosome gene coding for methyl-CpG-binding protein 2 transcription factor. Boys with MECP2 mutations usually do not survive to delivery, but can present with severe neonatal encephalopathy, seizures, microcephaly, abnormal tone, and respiratory insufficiency.


Pediatrics_Nelson

Pediatrics_Nelson. Degenerative Diseases with Focal Manifestations Some neurodegenerative disorders have predilections to target specific regions or systems within the neuraxis, producing symptoms referable to the affected region. Wilson disease is a treatable degenerative condition thatexhibits signs of cerebellar and basal ganglia dysfunction. It is anautosomal recessive inborn error of copper metabolism. Serumceruloplasmin levels are low. Abnormal copper deposition isfound in the liver, producing cirrhosis; in the peripheral cornea, producing a characteristic green-brown (Kayser-Fleischer)ring; and in the CNS, producing neuronal degeneration andprotoplasmic astrocytosis. Neurologic symptoms characteristically begin in the early teenage years with dysarthria, dysphasia,drooling, fixed smile, tremor, dystonia, and emotional lability.MRI shows abnormalities of the basal ganglia. Treatment is witha copper-chelating agent, such as oral penicillamine. Available @ StudentConsult.com


Pediatrics_Nelson

Pediatrics_Nelson. Available @ StudentConsult.com Subacute necrotizing encephalomyelopathy, or Leigh disease, is a neuropathologically defined, degenerative inherited CNS disease primarily involving the periaqueductal region of the brainstem, caudate, and putamen. Symptoms usually begin before 2 years of age and consist of hypotonia, feeding difficulties, respiratory irregularity, weakness of extraocular movements, and ataxia. Blood and CSF lactate and pyruvate levels are elevated. Several alterations of mitochondrial function produce this clinical syndrome. Children with poorly controlled epilepsy may be continuously in either an ictal or a postictal state and may appearstuporous because of their epileptic encephalopathy. Antiepileptic drugs that are sedating or affect mood, memory,motivation, or attention may contribute to the lack or lossof developmental abilities and school failure. Use of highdoses or multiple anticonvulsants may compound thisproblem.


Pediatrics_Nelson

Pediatrics_Nelson. Chronic drug use or overuse (sedatives, tranquilizers, anticholinergics) can bring about progressive confusion, lethargy, and ataxia. Intoxications with heavy metals, such as lead, may cause chronic learning difficulties or may present acutely with irritability, listlessness, anorexia, and pallor, progressing to fulminant encephalopathy. Vitamin deficiency of thiamine, niacin, vitamin B12, and vitamin E can produce encephalopathy, peripheral neuropathy, and ataxia. Congenital and acquired hypothyroidism impairs cognition and retards developmental progress. Unrecognized congenital hypothyroidism produces irreversible damage if it is not treated immediately after birth (Chapter 175).


Pediatrics_Nelson

Pediatrics_Nelson. Structural brain diseases, such as hydrocephalus and slowly growing tumors, may mimic dementia. Certain indolent brain infections, such as rubeola (measles, causing subacute sclerosing panencephalitis), rubella (German measles), syphilis, and some fungal infections, cause neurologic deterioration over months and years. Congenital human immunodeficiency virus infection causes failure of normal development and regression of acquired skills. Psychiatric disorders, such as depression and severe psychosocial deprivation in infancy, can give rise to apathy andfailure to attain developmental milestones (Chapter 21). Children with autism spectrum disorder may go througha phase of developmental stagnation or disintegration atabout 12 to 18 months of age after a period of early normal milestones. Depression in older children can lead toblunting of affect, social withdrawal, and poor school performance, which raise the question of encephalopathy ordementia.


Pediatrics_Nelson

Pediatrics_Nelson. The skin, teeth, hair, nails, and brain are derived embryologically from ectoderm. Abnormalities of these surface structures may indicate abnormal brain development. Not all of the so-called neurocutaneous disorders have characteristic cutaneous lesions, however, and not all are of ectodermal origin. Neurofibromatosis (types 1 and 2), tuberous sclerosis, Sturge-Weber syndrome, von Hippel–Lindau disease, and ataxia-telangiectasia are the most common of the more than 40 neurocutaneous disorders.


Pediatrics_Nelson

Pediatrics_Nelson. Neurofibromatosis type 1 (NF1), also known as von Recklinghausen disease, is an autosomal-dominant disorder with an incidence of approximately 1 in 3000. It is caused by mutations of the NF1 gene, which codes for a tumor suppressor gene, neurofibromin. Neurofibromin is a major negative regulator of a key signal transduction pathway, the Ras pathway. Mutations results in increased downstream mitogenic signaling. Somatic mosaicism, in which an abnormality in one copy of the NF1 gene is present in some cells but not others, indicates a post-zygotic mutation and is called segmental neurofibromatosis. Available @ StudentConsult.com


Pediatrics_Nelson

Pediatrics_Nelson. Available @ StudentConsult.com The cardinal features of neurofibromatosis are café au lait spots, axillary or inguinal freckling, cutaneous neurofibromas, and iris hamartomas (Lisch nodules). Café au lait spotsare present in more than 90% of patients who have NF1 (Fig. 186-1). They typically appear in the first few years of life and increase in number and size over time. The presence of six or more café-au-lait spots larger than 5 mm in a prepubescent child suggests the diagnosis. Lisch nodules also increase in frequency with age and are present in more than 90% of adults who have NF1. FIGURE 186-1 Cafe au lait macules. (From Kliegman RE, Behrman RE, Jenson HB, editors: Nelson Textbook of Pediatrics, ed 19, Phila-delphia, 2007, Saunders, p 2680.)


Pediatrics_Nelson

Pediatrics_Nelson. FIGURE 186-1 Cafe au lait macules. (From Kliegman RE, Behrman RE, Jenson HB, editors: Nelson Textbook of Pediatrics, ed 19, Phila-delphia, 2007, Saunders, p 2680.) Neurofibromas are composed of various combinations of Schwann cells, fibroblasts, mast cells, and vascular elements. Dermal neurofibromas are nearly universal and consist of discrete, small, soft lesions that lie within the dermis and epidermis and move passively with the skin. They rarely cause any symptoms, but can cause significant cosmetic concerns. Neurofibromas may also be situated within viscera or along blood vessels and peripheral nerves. Plexiform neurofibromas are large, occasionally nodular, subcutaneous lesions that lie along the major peripheral nerve trunks. They often cause symptoms including pain, weakness, and invasion of adjacent viscera, bone, or spinal cord. Sarcomatous degeneration may occur. Surgical treatment may be attempted, but results are often unsatisfactory.


Pediatrics_Nelson

Pediatrics_Nelson. Common complications are learning disability, scoliosis, seizures, and cerebral vasculature abnormalities. Other tumors that occur in NF1 are optic nerve gliomas, astrocytomas of brain and spinal cord, and malignant peripheral nerve tumors. T2-weighted magnetic resonance images (MRI) reveal hyperintense lesions (hamartomas) in the optic tracts, internal capsule, thalamus, cerebellum, and brainstem that are common and distinctive for the disease. They are benign and disappear in adulthood. The average life expectancy of patients with NF1 may be reduced by 10 to 15 years. Malignancy is the most common cause of death. Genetic and psychological counseling are important components of care for this chronic disorder. Although it is an autosomal dominant disorder, spontaneous mutations account for 30% to 50% of cases.


Pediatrics_Nelson

Pediatrics_Nelson. Neurofibromatosis type 2 (NF2) is an autosomal-dominant disorder with an incidence of 1 in 25,000. Half the cases have no family history. The NF2 gene is a tumor suppressor gene, and disease results in neurologic, eye, and skin lesions. NF2 predisposes patients to multiple intracranial and spinal tumors, including bilateral acoustic schwannomas, schwannomas of other cranial and spinal nerves, meningiomas, and gliomas. Posterior capsular or cortical cataracts are common, and skin lesions include plaque-like lesions, subcutaneous nodules, and cutaneous schwannomas. Lisch nodules, cafe au lait spots, and axillary freckling are not features of NF2.


Pediatrics_Nelson

Pediatrics_Nelson. Tuberous sclerosis complex (TSC), an autosomal dominant disorder, is characterized by hamartomas in many organs, especially the brain, eyes, skin, kidneys, and heart. The incidence is 1 in 10,000 births. Two thirds of cases are sporadic and thought to represent new mutations. Germline mosaicism is uncommon, but explains how parents who apparently do not have the disease can have multiple children with tuberous sclerosis. Mutations affecting either of the presumed tumor suppressor genes, TSC1 or TSC2, cause tuberous sclerosis. The TSC1 and TSC2 genes encode distinct proteins, hamartin and tuberin, which are widely expressed in the brain and result in constitutive activation of the protein kinase mTOR (mammalian target of rapamycin), leading to the formation of numerous benign tumors (hamartomas).


Pediatrics_Nelson

Pediatrics_Nelson. TSC is an extremely heterogeneous disease with variable expression and a wide clinical spectrum varying from normal intelligence without seizures to severe mental retardation with refractory seizures, often within the same family. Tuberous sclerosis is one of the most common causes of infantile spasms. These children often develop intractable epilepsy, mental retardation, autism, and hyperactivity. Patients may have retinal lesions (retinal hamartomas, white depigmented patches) and brain lesions (cortical tubers, subependymal nodules, hydrocephalus). Tubers in the cerebral cortex are areas of dysplasia that, in combination with other microscopic areas of abnormal development, are responsible for the symptoms of mental retardation and epilepsy. Subependymal nodules are hamartomas that may mutate into a growth phase and become subependymal giant cell astrocytomas causing obstruction of cerebrospinal fluid outflow and resultant hydrocephalus.


Pediatrics_Nelson

Pediatrics_Nelson. Extracerebral manifestations include typical skin findings of hypomelanotic macules (ash leaf spots) which are easiest to visualize under a Wood ultraviolet lamp and are apparent in infancy. Facial angiofibromas (adenoma sebaceum) appear as small red nodules over the nose and cheeks that are sometimes confused with acne. Shagreen patches are elevated, rough plaques of skin with a predilection for the lumbar and gluteal regions that develop in late childhood or early adolescence. Cardiac rhabdomyomas are largest during prenatal life and infancy and are rarely symptomatic. Occasionally, they may cause arrhythmias or cardiac outflow obstruction. Renal angiomyolipomas may undergo malignant transformation and are the most common cause of death in adults with TSC. Interstitial pulmonary disease also affects adults with TSC (pulmonary lymphangioleiomyomatosis).


Pediatrics_Nelson

Pediatrics_Nelson. Sturge-Weber syndrome is sporadic (not inherited) and characterized by abnormal blood vessels (angiomas) of the leptomeninges overlying the cerebral cortex in association with an ipsilateral facial port-wine stain involving the ophthalmic division of the trigeminal nerve (forehead and upper eyelid) and, often, glaucoma. The port-wine stain, also known as nevus flammeus, is due to an ectasia of superficial venules and may have a much more extensive and even bilateral distribution. Not all children with a facial port-wine stain have Sturge-Weber syndrome.


Pediatrics_Nelson

Pediatrics_Nelson. MRI with contrast demonstrates leptomeningeal angioma and white matter abnormalities thought to be due to chronic hypoxia and atrophy. Angiomas produce venous engorgement and, presumably, stasis within the involved areas, which are thought to result in hypoxia. Patients present with seizures, hemiparesis, stroke-like episodes, headaches, mental retardation, and learning disabilities. Seizures are the most common associated neurologic abnormality, occurring in 75% of patients, and develop because of ischemic injury to the brain. Many children with Sturge-Weber syndrome are intellectually normal, and seizures are well controlled with standard anticonvulsants. However, progressive ischemia of the underlying brain develops in some children with Sturge-Weber syndrome, resulting in hemiparesis, hemianopia, intractable focal seizures, and cognitive impairment. Hemispherectomy has been proposed for individuals with unilateral disease whose seizures are difficult to control. Intellectual and


Pediatrics_Nelson

Pediatrics_Nelson. hemianopia, intractable focal seizures, and cognitive impairment. Hemispherectomy has been proposed for individuals with unilateral disease whose seizures are difficult to control. Intellectual and motor outcome seems improved, compared with ongoing anticonvulsant drug treatment, but the surgical risks and sequelae of the procedure are considerable. Pulse dye laser surgery is the most promising therapeutic option for cosmetic management of the facial nevus flammeus. Expert ophthalmologic management of glaucoma is required. Endocrinology evaluations are also necessary, as these patients often have growth hormone deficiency and/or hypothyroidism.


Pediatrics_Nelson

Pediatrics_Nelson. Central nervous system malformations include disorders of spinal cord and neural tube formation, structure specification (neuronal migration, gray matter), brain growth and size, and skull growth and shape.


Pediatrics_Nelson

Pediatrics_Nelson. The precursor of the nervous system is the neural plate of the embryonic ectoderm, which develops at 18 days of gestation. The neural plate gives rise to the neural tube, which forms the brain and spinal cord, and neural crest cells, which form the peripheral nervous system, meninges, melanocytes, and adrenal medulla. The neural tube begins to form on day 22 of gestation. The rostral end forms the brain, and the caudal region forms the spinal cord. The lumen of the neural tube forms the ventricles of the brain and the central canal of the spinal cord. Most brain malformations are produced by a variety of injuries occurring during a vulnerable period of gestation. Precipitating factors include chromosomal, genetic, and metabolic abnormalities; infections (toxoplasmosis, rubella, cytomegalovirus, herpes); and exposure to irradiation, certain drugs, and maternal illness during pregnancy.


Pediatrics_Nelson

Pediatrics_Nelson. Defective closure of the caudal neural tube at the end of week 4 of gestation results in anomalies of the lumbar and sacral vertebrae or spinal cord called spina bifida. These anomalies range in severity from clinically insignificant defects of the L5 or S1 vertebral arches to major malformations, leaving the spinal cord uncovered by skin or bone on the infant’s back. The latter severe defect, called a myelomeningocele, results in flaccid paralysis and loss of sensation in the legs and incontinence of bowel and bladder, with the extent and degree of neurologic deficit dependent on the location of the myelomeningocele. In addition, affected children usually have an associated Chiari type II malformation (downward displacement of the cerebellar tonsils and medulla), resulting in hydrocephalus and weakness of face and swallowing. In a meningocele, the spinal canal and cystic meninges are exposed on the back, but the underlying spinal cord is anatomically and functionally intact. In spina


Pediatrics_Nelson

Pediatrics_Nelson. and weakness of face and swallowing. In a meningocele, the spinal canal and cystic meninges are exposed on the back, but the underlying spinal cord is anatomically and functionally intact. In spina bifida occulta, the skin of the back is apparently intact, but defects of the underlying bone or spinal canal are present. Meningoceles and spina bifida occulta may be associated with a lipoma, dermoid cyst, or tethering of the cord to a thick filum terminale. A dimple or tuft of hair may be present over the affected area. Patients may also have an associated dermoid sinus, an epithelial tract extending from the skin surface to the meninges; this increases the risk of meningitis. Patients with spina bifida occulta or meningocele may have weakness and numbness in the feet that can result in recurrent ulcerations, or difficulties controlling bowel or bladder function that may result in recurrent urinary tract infections, reflux nephropathy, and renal insufficiency. In diastematomyelia, a bone


Pediatrics_Nelson

Pediatrics_Nelson. ulcerations, or difficulties controlling bowel or bladder function that may result in recurrent urinary tract infections, reflux nephropathy, and renal insufficiency. In diastematomyelia, a bone spicule or fibrous band divides the spinal cord into two longitudinal sections. An associated lipoma that infiltrates the cord and tethers it to the vertebrae may be present. Symptoms include weakness and numbness of the feet and urinary incontinence.


Pediatrics_Nelson

Pediatrics_Nelson. Myelomeningocele in the fetus is suggested by an elevated alpha-fetoprotein in the mother’s blood and confirmed by ultrasound and high concentrations of alpha-fetoprotein and acetylcholinesterase in the amniotic fluid. After birth, screening ultrasound may be used with magnetic resonance imaging to confirm less dramatic underlying spinal abnormalities. Neonates with myelomeningocele must undergo operative closure of the open spinal defects (fetal or postnatal surgery) and often require treatment of hydrocephalus by placement of a ventriculoperitoneal shunt. Toddlers and children with lower spinal cord dysfunction require physical therapy, bracing of the lower extremities, and intermittent bladder catheterization. In the absence of associated brain anomalies, most survivors have normal intelligence, but learning problems and epilepsy are more common than in the general population.


Pediatrics_Nelson

Pediatrics_Nelson. Spina bifida can be prevented in many cases by folate administration to the pregnant mother. Because the defect occurs so early in gestation, all women of childbearing age are advised to take oral folic acid daily. Defective closure of the rostral neural tube produces anencephaly or encephaloceles. Neonates with anencephaly have a rudimentary brainstem or midbrain, but no cortex or cranium. This is rapidly fatal after delivery. Patients with encephalocele usually have a skull defect and exposure of meninges alone or meninges and brain. The recurrence risk in subsequent pregnancies for either cranial or spinal neural tube defects is 3% to 4%. Within a family, an anencephalic birth may be followed by the birth of a child affected with a lumbosacral myelomeningocele. The inheritance of neural tube defects is polygenic.


Pediatrics_Nelson

Pediatrics_Nelson. Agenesis of the corpus callosum may be partial or complete and may occur in an isolated fashion or in association with other anomalies of cellular migration. Dandy-Walker malformation is diagnosed on the basis of the classic triad: complete or partial agenesis of the cerebellar vermis, cystic dilation of the fourth ventricle, and enlarged posterior fossa. There may be associated hydrocephalus, absence of the corpus callosum, and neuronal migration abnormalities. Intelligence may be normal or impaired, depending on the degree of associated cerebral dysgenesis.


Pediatrics_Nelson

Pediatrics_Nelson. Holoprosencephaly represents varying degrees of failure of the forebrain (prosencephalon) to divide into two distinct cerebral hemispheres. Holoprosencephaly is often associated with midline facial defects (hypotelorism, cleft lip, cleft palate). This anomaly may be isolated or associated with a chromosomal or genetic disorder. The prognosis for infants with severe (alobar)holoprosencephaly is uniformly poor, but those with milder forms (semilobar, or lobar) may have less severe neurological outcomes. Children with trisomy 13 and trisomy 18 characteristically have varying degrees of holoprosencephaly.


Pediatrics_Nelson

Pediatrics_Nelson. Hydranencephaly is a condition in which the brain presumably develops normally, but then is destroyed by an intrauterine, probably vascular, insult. The result is virtual absence of the cerebrum with an intact skull. The thalamus, brainstem, and some occipital cortex are typically present. Children may have a normal external appearance at the time of birth, but do not achieve developmental milestones.


Pediatrics_Nelson

Pediatrics_Nelson. Macrocephaly represents a head circumference above the 97th percentile and may be the result of macrocrania (increased skull thickness), hydrocephalus (enlargement of the ventricles; see Chapter 184), or megalencephaly (enlargement of the brain). Diseases of bone metabolism or hypertrophy of the bone marrow cause macrocrania. Megalencephaly may be the result of a significant disorder of brain development or an accumulation of abnormal metabolic substances (Table 1871). Most often, however, macrocephaly is a familial trait of no clinical significance. If the child is developmentally normal but has macrocephaly, plotting the parents’ head circumference on a growth chart can provide reassurance and help to avoid unnecessary neurodiagnostic testing.


Pediatrics_Nelson

Pediatrics_Nelson. Microcephaly represents a head circumference below the 3rd percentile. Myriad syndromes and metabolic disorders are associated with microcephaly, some of which are hereditary (Table 187-2). In most instances, a small head circumference is a reflection of a small brain. Brain growth is rapid during the perinatal period, and any insult (infectious, metabolic, toxic, vascular) sustained during this period or during early infancy is likely to impair brain growth and result in microcephaly. Rarely, a small head is the result of premature closure of one or more skull sutures, called craniosynostosis. This diagnosis is readily made by the abnormal shape of the skull. As a rule, macrocephaly and microcephaly raise a concern about cognitive ability, but head circumference alone should never be used to establish a prognosis for intellectual development. Macrocrania (increased skull thickness) Achondroplasia Hypochondroplasia Fragile X syndrome Osteopetrosis Chronic, severe anemia


Pediatrics_Nelson

Pediatrics_Nelson. Macrocrania (increased skull thickness) Achondroplasia Hypochondroplasia Fragile X syndrome Osteopetrosis Chronic, severe anemia Hydrocephalus (enlargement of the ventricles; see Chapter 184) Masses Megalencephaly (enlargement of the brain) Embryologic disorder causing abnormal proliferation of brain Accumulation of abnormal metabolic substances Alexander disease Canavan disease Gangliosidoses Mucopolysaccharidoses Benign extracerebral collections of infancy Familial macrocephaly Disorders of Neuronal Migration Many malformations result from the failure of normal migration of neurons from the periventricular germinal matrix zone to the cortical surface at 1 to 5 months of gestation. Multiple malformations may exist in the same patient. Neurologic development with these anomalies varies and depends on the type and extent of the malformation.


Pediatrics_Nelson

Pediatrics_Nelson. Schizencephaly is characterized by clefts within the cerebral hemispheres that extend from the cortical surface to the ventricular cavity. Unilateral clefts can cause isolated congenital hemiparesis, whereas bilateral schizencephaly causes spastic quadriparesis and associated intellectual disability. Affected individuals are at high risk for focal epilepsy. A severe defect in cortical migration, lissencephaly results in a smooth brain without sulcation (agyria). The normal six-layered cortex does not develop. Affected children have difficult-to-control seizures and profound developmental retardation. This anomaly most commonly is part of a genetic disorder, which may be x-linked (DCX mutations) or caused by de novo autosomal dominant gene mutations (Lis-1 mutations). In pachygyria, the gyri are few in number and too


Pediatrics_Nelson

Pediatrics_Nelson. Lissencephaly Schizencephaly Pachygyria Micropolygyria Agenesis of the corpus callosum broad. In polymicrogyria, the gyri are too many and too small. Sometimes pachygyria and polymicrogyria affect an entire hemisphere, producing enlargement of that hemisphere and a clinical syndrome of severe, medically intractable seizures that begin in early infancy. Gray matter heterotopiasare abnormal islands within the central white matter of neurons that have never completed the migratory process. The authors thank Dr. James Dowling for his generous help in preparing Chapter 182 on weakness and hypotonia. Fenichel GM: Clinical Pediatric Neurology: a Signs and Symptoms Approach, ed 6, Philadelphia, 2009, Saunders Jacobs H, Gladstein J: Pediatric headache: a clinical review, Headache 52:333–339, 2012 Kliegman RM, Behrman RE, Jenson HB, et al: Nelson Textbook of Pediatrics, ed 19, Philadelphia, 2011, Saunders


Pediatrics_Nelson

Pediatrics_Nelson. Jacobs H, Gladstein J: Pediatric headache: a clinical review, Headache 52:333–339, 2012 Kliegman RM, Behrman RE, Jenson HB, et al: Nelson Textbook of Pediatrics, ed 19, Philadelphia, 2011, Saunders Mink JW, Zinner SH: Movement disorders II: chorea, dystonia, myoclonus and tremor, Pediatr Rev 31:287–295, 2010 Peredo DE, Hannibal MC: The floppy infant: evaluation of hypotonia, Pediatr Rev 30:e66–e76, 2009 Schunk JE, Schutzman SA: Pediatric head injury, Pediatr Rev 33:398–411, 2012 Zinner SH, Mink JW: Movement disorders I: tics and stereotypies, Pediatr Rev 31:223–233, 2010 Yvonne E. Chiu 25


Pediatrics_Nelson

Pediatrics_Nelson. Schunk JE, Schutzman SA: Pediatric head injury, Pediatr Rev 33:398–411, 2012 Zinner SH, Mink JW: Movement disorders I: tics and stereotypies, Pediatr Rev 31:223–233, 2010 Yvonne E. Chiu 25 Approximately one in three Americans of any age has at leastone recognizable skin disorder at any time. The most commoncutaneous diseases encountered in community settings aredermatophytosis, acne vulgaris, seborrheic dermatitis, atopicdermatitis (eczema), verrucae (warts), tumors, psoriasis, vitiligo, and infections such as herpes simplex and impetigo. Inchildren attending pediatric dermatology clinics, atopic dermatitis, impetigo, tinea capitis, acne vulgaris, verrucae vulgaris,and seborrheic dermatitis are the most common diagnoses.


Pediatrics_Nelson

Pediatrics_Nelson. The age of the patient, onset, duration, progression, associatedcutaneous symptoms (pain, pruritus), and associated systemicsigns or symptoms (fever, malaise, weight loss) are importantclues. Obtaining an accurate description of the original lesionimproves diagnostic accuracy. Over-the-counter remediesmay alter the appearance of a rash dramatically. Patients oftendo not consider a topical antibiotic or anti-itch medication astreatment. Thus it is important to probe deeply with relatedquestions in the history. Other important information includesa history of allergies, environmental exposure, travel history,previous treatment, affected contacts, and family history. A careful examination of the skin requires a visual and a tactile assessment. Examination of the skin over the entire body must be performed systematically. Mucous membranes, hair, nails, and teeth, all of ectodermal origin, also may be involved in cutaneous disorders and should be assessed. Available @ StudentConsult.com


Pediatrics_Nelson

Pediatrics_Nelson. Available @ StudentConsult.com A descriptive nomenclature of skin lesions helps with generating a differential diagnosis and also with communication between health care providers. Determination of the primary lesion and secondary change is the cornerstone of dermatologic diagnosis. A primary lesion is defined as the basic lesion that arises de novo and is most characteristic of the disease process (Table 188-1 and Fig. 188-1). Primary lesions are rarely seen on a patient at the time of presentation, as most lesions are altered by time or external factors such as Flat, nonpalpable lesion <1 cm in diameter Patch Similar to macule, but >1 cm in diameter Papule Elevated, solid lesion <1 cm in diameter Plaque Similar to papule, but >1 cm in diameter; has a flat and broad surface in contrast to a nodule Nodule Similar to papule, but >1 cm in diameter; has a rounded surface in contrast to a plaque


Pediatrics_Nelson

Pediatrics_Nelson. Plaque Similar to papule, but >1 cm in diameter; has a flat and broad surface in contrast to a nodule Nodule Similar to papule, but >1 cm in diameter; has a rounded surface in contrast to a plaque Tumor Similar to nodule, but implies a neoplastic growth rather than an inflammatory process Bulla Similar to vesicle, but >1 cm in diameter Pustule Pus-filled epidermal lesion, which may have an initial papular phase and often is surrounded by erythema Purpura Macule or papule resulting from extravasated blood into the skin; does not blanch with pressure Petechia Similar to purpura, but less than a few millimeters in diameter Ecchymosis Larger, hemorrhagic patch or plaque resulting from extravasated blood Wheal (hive) Pink, edematous papules and plaques that vary greatly in size and configuration; characterized by transient nature with individual lesions resolving within 24 hours Telangiectasia Collection of small superficial red blood vessels


Pediatrics_Nelson

Pediatrics_Nelson. Telangiectasia Collection of small superficial red blood vessels Milia Superficial, white, small epidermal keratin cysts Comedo Plug of keratin and sebum within the orifice of a hair follicle, which can be open (whitehead) or closed (blackhead); characteristic lesion of acne vulgaris Cyst Papule or nodule with an epidermal lining composed of fluid or solid material


Pediatrics_Nelson

Pediatrics_Nelson. Cyst Papule or nodule with an epidermal lining composed of fluid or solid material Figure 188-1 Morphology of primary skin lesions. A, Flat lesions. B, Palpable lesions. C, Fluid-filled lesions. D, Special primary lesions. (From Swartz MH: Textbook of Physical Diagnosis: History and Examination, Philadelphia, 1989, WB Saunders.) medication applied, secondary infection, or physical manipulation (e.g., scratching). A search for the primary lesion often proves worthwhile and focuses the differential diagnosis to a category of lesion that is specific for the underlying diagnosis. On occasion, two different types of primary lesions may be present. In most cases, secondary lesions are the residue, or result, of the effects of the primary lesion. They may be created by scratching or secondary infection and may be seen in the absence of a primary lesion (Table 188-2).


Pediatrics_Nelson

Pediatrics_Nelson. The color, texture, configuration, location, and distribution of the lesion should be recorded. A localized or grouped eruption may suggest a cutaneous infection, whereas widespread, symmetrical involvement of extensor surfaces may suggest a primary skin disorder, such as psoriasis. Herpesvirus lesions are usually grouped lesions. Annular lesions may suggest Lyme disease, syphilis, and fungal infections. Lesions on mucous membranes are usually short-lived, and lesions in thick-skinned areas, such as the palms and soles, may be particularly difficult to characterize. A thorough history and physical examination are usuallysufficient for diagnosis because of the visibility of the skin.Adjunctive tests at the time of examination include potassiumhydroxide (KOH) examination for fungi and dermatophytes,skin scrapings for scabies, cytologic examination (Tzancktest) for herpesvirus and varicella-zoster virus infection, andWood light examination for the yellowish gold fluorescence


Pediatrics_Nelson

Pediatrics_Nelson. Crust Dried collection of serum and cellular debris Erosion Shallow depression with loss of the superficial epidermis Ulcer Deeper depression with loss of the entire epidermis into dermis; heals with scarring Atrophy Thinning of epidermis (surface appears shiny and translucent) or dermis (skin is depressed) Scar Thickened, firm, and discolored collection of connective tissue that results from dermal damage; initially pink, but lightens with time Sclerosis Circumscribed or diffuse hardening of skin Lichenification Accentuated skin lines/markings that result from thickening of the epidermis Excoriation Superficial linear erosion that is caused by scratching Fissure Linear break within the skin surface that usually is painful of tinea versicolor. A skin biopsy may be performed to helpwith the diagnosis. The biopsy specimen can be accomplishedby either shave or punch biopsy, and both are simple, in-office procedures. Occasionally, laboratory or imaging studies are necessary.


Pediatrics_Nelson

Pediatrics_Nelson. Acne vulgaris (or acne) is a chronic inflammatory disorderthat affects areas with the greatest concentration of sebaceous glands, such as the face, chest, and back. The pathogenesis of acne is multifactorial. Gender, age, genetic factors,and environment are all major contributing factors. Stressmay trigger acne, possibly by affecting hormone levels.There is no evidence linking chocolate, candy, or fried foods to acne.


Pediatrics_Nelson

Pediatrics_Nelson. Acne is caused by chronic inflammation of the pilosebaceous unit (hair follicle with an associated sebaceous gland). The primary event in all acne lesions is the development of the micro-comedo, which results from the obstruction of the hair follicle with keratin, increased sebum production from sebaceous glands, and overgrowth of normal skin flora, leading to pilosebaceous occlusion and enlargement. Androgens are a potent stimulus of the sebaceous gland. The subsequent inflammatory component and pustule formation results from proliferation of Propionibacterium acnes, a commensal organism of the skin. The pathogenesis of acne thus involves three components: increased sebum production, hyperkeratosis, and bacterial proliferation. Effective treatment focuses on minimizing these factors.


Pediatrics_Nelson

Pediatrics_Nelson. Acne is the most common skin disorder in adolescents, occurring in 85% of teenagers. The incidence is similar in both sexes, although boys often are more severely affected. Acne may begin as early as 8 years of age and may continue into adulthood. Acne primarily affects areas with increased sebaceous glanddensity, such as the face, upper chest, and back. Superficialplugging of the pilosebaceous unit results in noninflammatorysmall (1to 2-mm) open (blackhead) and closed (whitehead) comedones. An open comedo is less likely to become inflammatory than a closed comedo. Rupture of a comedo into adjacent dermis and proliferation of P. acnes induce an inflammatory response and development of inflammatory papules and pustules. Larger, skin-colored or red cysts and nodulesrepresent deeper plugging and cystic acne. Increased and persistent inflammation, especially with rupture of a deep cyst,increases the risk of scarring.


Pediatrics_Nelson

Pediatrics_Nelson. The diagnosis of acne is usually not difficult because of the characteristic and chronic lesions. Laboratory studies and imaging studies are usually not necessary to diagnose acne. Screening tests may be necessary if there are signs of hyperandrogenism due to polycystic ovarian syndrome (irregular menses, hirsutism, insulin resistance) or an underlying androgen-secreting tumor (irregular menses, hirsutism, deepening voice, clitoromegaly). The mainstays of treatment of acne are topical keratolytic agents and topical antibiotics. Creams, lotions, gels, foams, and solutions are available. Gels and solutions are commonly used because acne skin is generally greasier and these agents tend to be drying, but they have the tendency to be irritating and may not be as well tolerated. Creams and lotions are better tolerated but may not be as effective.


Pediatrics_Nelson

Pediatrics_Nelson. The keratolytic agents (salicylic acid, azelaic acid, tretinoin, adapalene, tazarotene) produce superficial desquamation and, subsequently, relieve follicular obstruction. They are a mainstay of first-line therapy. The topical retinoids (tretinoin, adapalene, tazarotene) are based on the vitamin A molecule. They decrease keratin and sebum production and have some anti-inflammatory and antibacterial activity; thus they can be the most effective when used as monotherapy.


Pediatrics_Nelson

Pediatrics_Nelson. Topical antimicrobials (benzoyl peroxide, dapsone, sulfur-sulfacetamide) and topical antibiotics (erythromycin, clindamycin) are anti-inflammatory and inhibit P. acnes proliferation. Erythromycin efficacy has decreased as P. acnes has become increasingly resistant to this antibiotic; topical antibiotics should be combined with an antimicrobial such as benzoyl peroxide to prevent the development of resistance. Combination therapy of a topical keratolytic agent and a topical antimicrobial is more effective than either agent alone for inflammatory acne. Oral antibiotics (tetracycline, doxycycline, minocycline) are typically used for deeper cystic lesions but should always be used in combination with a topical regimen. Tetracyclines are the most effective antibiotics because of their significant anti-inflammatory activity. As with topical erythromycin, oral erythromycin is rarely used because of bacterial resistance.


Pediatrics_Nelson

Pediatrics_Nelson. For recalcitrant or severe nodulocystic acne, oral isotretinoinmay be instituted. Isotretinoin, an oral analog of vitamin A,normalizes follicular keratinization, reduces sebum production,and decreases 5α-dihydrotestosterone formation and androgen receptor–binding capacity. A course of isotretinoin (0.5 to1 mg/kg/day to reach a cumulative dose of 120 mg/kg) is theonly medication that can permanently alter the course of acne and induce a durable remission. Because of the high incidenceof adverse effects, it should be used only by physicians familiar with this medication. Isotretinoin therapy requires carefulpatient selection, pretreatment counseling, and monthly laboratory monitoring. It is teratogenic and must not be used immediately before or during pregnancy. Acne has significant and frequently devastating effects on an adolescent’s body image and self-esteem. There may be little correlation between severity and psychosocial impact. Scarring may result in permanent morbidity.


Pediatrics_Nelson

Pediatrics_Nelson. Classically, acne lasts 3 to 5 years, although some individuals may have disease for 15 to 20 years. Only early treatment with isotretinoin may alter the natural course of acne. Acne lesions often heal with temporary postinflammatory erythema and hyperpigmentation. Depending on the severity, chronicity, and depth of involvement, pitted, atrophic, or hypertrophic scars may develop. Cystic acne has the highest incidence of scarring because rupture of a deep cyst induces the greatest inflammation, though scarring may be caused by milder pustular or even comedonal acne.


Pediatrics_Nelson

Pediatrics_Nelson. Greasy hair and cosmetic preparations should be avoided becausethey exacerbate preexisting acne. There are no effective means forpreventing acne, and there is little evidence that diet is associated with acne. Repetitive cleansing with soap and water or useof astringents or abrasives removes only surface lipids. Their usemakes the skin appear less oily but does not prevent formation ofmicrocomedones and may paradoxically worsen acne. Atopic dermatitis is a chronic inflammatory disease with no known cure. It is associated with significant psychosocial morbidity and decreased health-related quality of life. For many affected individuals, atopic dermatitis is the skin manifestation of atopy accompanied by asthma and allergic rhinitis.


Pediatrics_Nelson

Pediatrics_Nelson. Atopic dermatitis manifests with a defective skin barrier,reduced innate immune responses, and exaggerated immuneresponses to allergens and microbes. Both genetic predisposition and environmental factors play a role in the development of atopic dermatitis. Genes associated with skin barrier dysfunction and inflammation have been linked with atopicdermatitis. Inflammatory mediators involved include predominantly T helper cells, with the TH2 pathway implicated early in acute lesions and a TH1 predominance found in chroniclesions. Langerhans cells, IgE, and eosinophils play a prominent role, as well as many other inflammatory mediators. Environmental and contact allergens, infections, irritants, extremesof temperature, sweat, and lack of humidity can exacerbate thecondition, as can scratching or rubbing. Triggers are somewhatvariable from individual to individual.


Pediatrics_Nelson

Pediatrics_Nelson. Atopic dermatitis is the most common skin disease in children,with an estimated prevalence of up to 20% of children. Only1% to 2% of adults manifest disease. In addition to genetic factors, an environmental influence contributes. Atopic dermatitisoccurs more frequently in urban areas and in higher socioeconomic classes. Prevalence is lower in areas where industrial pollution is less and where eosinophil-mediated infectionssuch as helminthic infections are endemic. Patients generally have a family history of atopy. Children with atopic dermatitis are predisposed to the development of allergy and allergic rhinitis, referred to as the atopic march. Asthma develops in up to half of children with atopic dermatitis, and allergic rhinitis even more frequently. Food allergies are commonly associated with atopic dermatitis.


Pediatrics_Nelson

Pediatrics_Nelson. Atopic dermatitis is a chronic, relapsing skin disease characterized by xerosis, pruritus, and characteristic skin findings. Thecondition generally improves with age and remits in adulthood,although some childhood cases will continue into adulthood. Characteristic lesions of atopic dermatitis are erythematous papules or plaques with ill-defined borders and overlying scale or hyperkeratosis. Lesions can be secondarily excoriated or have an overlying crust that is yellow or hemorrhagic. Weeping may be present in acute stages. Lichenification is found in older lesions. Formation of fissures is common in both acute and chronic lesions. Temporary hypoand hyperpigmentation can be seen after lesions resolve, but atopic dermatitis is not usually scarring unless secondary features become severe (e.g., infection or physical manipulation [scratching]).


Pediatrics_Nelson

Pediatrics_Nelson. Characteristic locations vary with the age of the patient. Infantile atopic dermatitis typically affects the face and extensor surfaces of the extremities and is often generalized. Childhood lesions predominate in flexural surfaces (antecubital and popliteal fossae), wrists, ankles, hands, and feet (Fig. 190-1).The adult phase occurs after puberty and manifests in the flexural areas including the neck, as well as predominant involvement on the face, dorsa of the hands, fingers and toes, and the upper arms and back. Secondary bacterial infection, most commonly with Staphylococcus aureus or less commonly with Streptococcus pyogenes, is frequently present. Patients are at increased riskfor infections with cutaneous viruses and can develop disseminated skin infections with viruses such as herpes simplexvirus (eczema herpeticum), varicella-zoster virus, smallpoxvirus (eczema vaccinatum), and molluscum contagiosum.Atopic skin is more susceptible to fungal infections as well.


Pediatrics_Nelson

Pediatrics_Nelson. Figure 190-1 Atopic dermatitis (arm). Signs of concomitant infection include acute worsening ofdisease in an otherwise well-controlled patient, resistance tostandard therapy, fever, and presence of pustules, fissures, orexudative or crusted lesions (Fig. 190-2). Eczema herpeticumand eczema vaccinatum can be life threatening if not treated. Diagnosis of atopic dermatitis is based on clinical signs and symptoms. Skin biopsy findings are generally characteristic but not exclusively diagnostic and can overlap with other skin conditions. Peripheral blood eosinophilia and elevated IgE levels can be found but are not specific. Skin prick testing or measurement of specific IgE antibody levels can detect sensitization to food and environmental allergens, although false-positive findings occur. The differential diagnosis of atopic dermatitis is extensive, but the history of a relapsing pruritic condition in the setting of atopy and skin lesions in a characteristic distribution is typical.


Pediatrics_Nelson

Pediatrics_Nelson. The differential diagnosis of atopic dermatitis is extensive, but the history of a relapsing pruritic condition in the setting of atopy and skin lesions in a characteristic distribution is typical. The lesions of seborrheic dermatitis have circumscribed and well-defined borders. The scale or hyperkeratosis is thicker,greasy, and yellowish. The distribution of seborrheic dermatitisis different from that of atopic dermatitis, typically involvingthe scalp, eyebrows, perinasal region, upper chest, and back.Occasionally the two conditions coexist. Psoriasis tends to localize on the elbows, knees, lower back, and scalp. The lesions of psoriasis on exposed surfaces are salmon color at the base with an overlying hyperkeratosis that is much thicker with silver coloration. They are generally very well demarcated, oval or round, thick plaques.


Pediatrics_Nelson

Pediatrics_Nelson. Allergic contact dermatitis has a distribution limited to one area of the body corresponding to contact with the allergen.The lesions generally make bizarre, linear, square, or angulatedshapes corresponding to the source. Nickel dermatitis is common and results from contact sensitization to nickel in metals. It occurs in characteristic locations, such as the periumbilicalarea (where metal from pant buttons rub against skin); onthe ear lobule or neck (where earrings contact skin); circumferentially around the neck (necklaces); and under rings or wristbands. Patients with atopic dermatitis can have concomitant contact dermatitis as well. Figure 190-2 Atopic dermatitis with Staphylococcus superinfection.


Pediatrics_Nelson

Pediatrics_Nelson. Figure 190-2 Atopic dermatitis with Staphylococcus superinfection. Ideal therapy for atopic dermatitis includes three main components: frequent liberal use of bland emollients to restorethe skin barrier, avoidance of triggers of inflammation, and use of topical anti-inflammatory medication to affected areas of skin when needed. Control of pruritus and infection should be considered on an individual basis. If topicaltherapy and these measures are inadequate, systemic therapywith immunosuppressive agents or ultraviolet light therapy may be indicated.


Pediatrics_Nelson

Pediatrics_Nelson. A daily short bath with warm but not hot water is generally recommended, although this is controversial and there are some who advocate less frequent bathing. A moisturizing cream or ointment should be applied to the entire body immediately afterward to trap moisture. Application of topical medications is also most effective immediately after bathing. Additional information for patients and families can be found at the website of the National Eczema Association for Science and Education ( http://www.nationaleczema.org


Pediatrics_Nelson

Pediatrics_Nelson. Common triggers of inflammation in atopic dermatitis include rubbing or scratching, contact with saliva or foods that are acidic, soaps and detergents, fabric softeners, wool or other harsh materials, fragranced personal care products, sweat, highly chlorinated pools, low humidity, tobacco smoke, dust mites, animal dander, environmental pollens, and molds. Exposure to these triggers should be limited whenever possible. Infections that are unrelated to skin disease, such as an upper respiratory infection, can also exacerbate atopic dermatitis. Food allergy is commonly seen in patients with atopic dermatitis but typically presents with urticaria or anaphylaxis rather than exacerbation of the atopic dermatitis.


Pediatrics_Nelson

Pediatrics_Nelson. Topical corticosteroids are the mainstay of anti-inflammatory therapy for atopic dermatitis. Hundreds oftopical corticosteroids are available and are classified according to strength from I to VII. Class I is the highest potencyand class VII is the lowest potency. Potency varies accordingto the steroid molecule (active ingredient), and, for a giveningredient, strength can vary according to relative concentration and vehicle base. Enhanced penetration occurs in areasof natural occlusion (flexures such as axillae and groin), withexternal occlusion (diapers or bandages), in areas of openskin (excoriations), and with heat or hydration. Use of wetwraps with topical corticosteroid application takes advantageof this principle of heat and hydration for enhanced penetration for recalcitrant lesions. Class I and II steroids are typically avoided in young children or in areas of thinner skin orenhanced penetration.


Pediatrics_Nelson

Pediatrics_Nelson. Corticosteroids are available in different vehicles. In general, ointments are preferred because of their increased efficacy, occlusive nature, and tolerability. Creams may be slightly less effective for a given steroid ingredient but may be more cosmetically acceptable for older patients or in warmer climates. Lotions may have more preservatives that can cause irritation and are generally less potent. Sprays, foams, solutions, and gels can be especially useful for hair-bearing areas. Creams, lotions, sprays, solutions, and gels can be particularly irritating when applied to atopic skin and should generally be avoided on areas of open skin.


Pediatrics_Nelson

Pediatrics_Nelson. Topical corticosteroids should be used in conjunction with adequate skin care, such as avoiding triggers of inflammation and frequent application of emollients. Twice-daily application of corticosteroids is recommended. The goal is to limit the need for anti-inflammatory medications and thereby avoid potential for adverse effects. Local side effects such as skin atrophy, striae, acne, and hypopigmentation are related to corticosteroid potency, site of application, and duration of application. Systemic side effects of adrenal suppression or Cushing syndrome can result with application of a potent topical corticosteroid to large surface areas or occluded areas at risk of enhanced penetration.


Pediatrics_Nelson

Pediatrics_Nelson. Topical calcineurin inhibitors (also referred to as topicalimmune modulators) such as topical tacrolimus and pimecrolimus may be part of the treatment regimen for atopic dermatitis.These agents selectively inhibit T-cell proliferation by inhibitingcalcineurin and subsequent interleukin 2 production. There isno potential for skin atrophy; thus these agents are particularlyuseful for face or genital lesions. They are currently approvedfor intermittent therapy as second-line treatments for mild tomoderate atopic dermatitis. Long-term studies, combined withother modalities for treatment, are underway.


Pediatrics_Nelson

Pediatrics_Nelson. Sedating antihistamines (e.g., diphenhydramine, hydroxyzine)are useful adjunctive therapy, especially during flares. These may have only mild effect on pruritus but can improve the sleeplessness due to scratching during the night. A dose before bedtime is most effective, and additional daytime doses can be added on an individual basis when needed. Nonsedating antihistamines are of little benefit in controlling the pruritus of atopic dermatitis.


Pediatrics_Nelson

Pediatrics_Nelson. Short-term administration of systemic corticosteroids is rarely indicated for cases of severe disease and may be considered when adequate topical therapy failed or is being instituted.Systemic corticosteroid courses should be adequately taperedand used in conjunction with an appropriate atopic skin careregimen. Rebound flare of atopic dermatitis is common following withdrawal of corticosteroids and should be anticipated toavoid misinterpretation of the natural disease severity. Longterm and frequent repeated courses should be avoided to prevent adverse effects.


Pediatrics_Nelson

Pediatrics_Nelson. Ultraviolet light therapy (UVB, narrow band UVB, UVA, or UVA1) can be an option for moderate to severe cases in older children. Typically, light therapy is administered two to three times weekly until improvement is seen, and then is tapered or discontinued once the acute flare has resolved. More frequent use of light therapy in children is hindered by requirements for frequent office visits, ability to cooperate with standing in a light box while wearing protective goggles, and risk of long-term skin damage, including the potential for skin cancer development with excessive UV light exposure. Systemic cyclosporine (up to 5 mg/kg/day) can be effective therapy for atopic dermatitis in severe cases. It is used for periods of up to 1 year to gain control of severe disease and should be tapered once the atopic dermatitis is controlled. Available @ StudentConsult.com


Pediatrics_Nelson

Pediatrics_Nelson. Available @ StudentConsult.com An increased tendency toward bacterial, viral, and fungal skin infections is due to an impaired skin barrier and decrease in innate immune proteins in the skin as well as maladaptive secondary immune responses.


Pediatrics_Nelson

Pediatrics_Nelson. Secondary impetigo with S. aureus is the most common secondary skin infection found in atopic dermatitis. Group Astreptococcus infection is also common. Infection manifests with pustules, erythema, crusting, scabbing, flare of disease, orlack of response to adequate anti-inflammatory therapy. Localized lesions can be treated with topical mupirocin. Widespreadand generalized lesions require oral antibiotic therapy, most commonly with a first-generation cephalosporin, such as cephalexin. Methicillin-resistant S. aureus infection is increasinglycommon, and antibiotic therapy should be tailored based onlocal resistance rates and patient factors. Diagnosis of super-infection may be made clinically, but a superficial bacterialculture can confirm the diagnosis and provide antimicrobialsusceptibilities. Treatment should include a concomitant atopicskin care routine including the continued use of topical corticosteroids. Although secondary skin infection with S. aureus is common, progression


Pediatrics_Nelson

Pediatrics_Nelson. Treatment should include a concomitant atopicskin care routine including the continued use of topical corticosteroids. Although secondary skin infection with S. aureus is common, progression to cellulitis or septicemia is unusual.Rarely, intravenous antibiotics may nevertheless be required.Children with colonization and frequent infections may benefitfrom dilute bleach baths two to three times weekly; ¼ to ½ cupof household bleach is added to a half-full or full bathtub.


Pediatrics_Nelson

Pediatrics_Nelson. Eczema herpeticum (Kaposi’s varicelliform eruption) is oneof the potentially serious infectious complications in atopic dermatitis. After herpes simplex virus (HSV) infection, an eruption of multiple, pruritic, vesiculopustular lesions occurs in a disseminated pattern, both within plaques of atopic dermatitisand on normal-appearing skin. These characteristically ruptureand form crusted umbilicated papules and punched-out hemorrhagic erosions (Fig. 190-3). Irritability, anorexia, and fever canalso be seen. Systemic and central nervous system disease havebeen reported. Bacterial superinfection of eroded areas of the skin often occurs. Diagnosis can be made rapidly from a scrapingof the skin lesion stained with Giemsa or Wright’s stain (Tzanck test), though these are not highly sensitive. These stains allow microscopic visualization of the presence of multinucleatedgiant cells indicative of herpes simplex virus or varicella-zoster virus infection. Vesicle fluid can also be sent for


Pediatrics_Nelson

Pediatrics_Nelson. These stains allow microscopic visualization of the presence of multinucleatedgiant cells indicative of herpes simplex virus or varicella-zoster virus infection. Vesicle fluid can also be sent for polymerasechain reaction (PCR) detection of herpes simplex virus DNA, rapid direct fluorescent antibody testing, or viral culture. Laboratory confirmation of infection is important because similar clinical manifestations can occur with bacterial infections.


Pediatrics_Nelson

Pediatrics_Nelson. Figure 190-3 Eczema herpeticum (hand). The psychosocial impact of atopic dermatitis can be significant. There is often disfigurement, lack of sleep from pruritus resulting in irritability and fatigue, and limitations on participation in sports. Significant time, as well as financial strain, is involved in caring for a child with atopic dermatitis. Thus, management should address these potential issues and provide adequate anticipatory guidance. Atopic dermatitis frequently remits during childhood and is much less common after puberty. The condition is generally most severe and widespread in infancy and early childhood. Relapse of disease in adults can occur and commonly manifests as face or hand dermatitis. Frequently, adults have generalized dry skin and are aware that their skin is sensitive to many over-the-counter preparations. Patients with atopic dermatitis can also develop asthma and allergic rhinitis. Asthma is more commonly associated with more severe skin disease.


Pediatrics_Nelson

Pediatrics_Nelson. Individual flares of atopic dermatitis can be prevented by avoiding triggers of inflammation and can be lessened with frequent emollient application. Some evidence suggests that breastfeeding for at least 4 months prevents or delays the occurrence of atopic dermatitis in early childhood. For infants with a parent or sibling with atopic disease and who are not exclusively breastfed for 4 to 6 months, there is modest evidence that the onset of atopic dermatitis may be delayed or prevented by the use of extensively hydrolyzed casein-based formulas. There is insufficient evidence that soy-based formulas, delaying the introduction of complementary foods beyond 4 to 6 months of age, or other dietary intervention prevents the development of atopic disease. There is no convincing evidence that women who avoid peanuts or other foods during pregnancy or while breastfeeding lower their child’s risk of allergies.


Pediatrics_Nelson

Pediatrics_Nelson. Inflammation in the top layers of the skin, caused by direct contact with a substance, is divided into two subtypes: irritant contact dermatitis and allergic contact dermatitis. Irritant contact dermatitis is observed after the skin surface is exposed to an irritating chemical or substance. Allergic contact dermatitis is a cell-mediated immune reaction, also called typeIV or delayed-type hypersensitivity. The antigens, or haptens,involved in allergic contact dermatitis readily penetrate theepidermis and are bound by Langerhans cells, the antigen-presenting cells of the skin. The hapten is presented to T lymphocytes, and an immune cascade follows. Contact dermatitismay occur in any age, and girls are more frequently affectedthan boys.


Pediatrics_Nelson

Pediatrics_Nelson. Irritant contact dermatitis is characterized by ill-defined, scaly, pink or red patches and plaques (Fig. 191-1). The eruption is localized to skin surfaces that are exposed to the irritant. Irritant contact dermatitis is observed frequently on the dorsal surfaces of the hands in patients, often from repeated hand washing or exposure to irritating chemicals. Diaper dermatitis is a common problem in infants and most commonly is a form of irritant contact dermatitis. The dermatitis is caused by irritation from urine and feces, typically affecting the perianal region and the buttocks while sparing the protected groin folds and other occluded areas. Secondary infection by Candida albicans or bacterial pathogens may complicate diaper dermatitis as well.


Pediatrics_Nelson

Pediatrics_Nelson. Allergic contact dermatitis may be acute (such as Rhus dermatitis) or chronic (such as nickel dermatitis). Acute lesionsare bright pink, pruritic patches, often in linear or sharplymarginated bizarre configurations. Within the patches areclear vesicles and bullae (Fig. 191-2). Signs and symptomsof the disease may be delayed for 7 to 14 days after exposureif the patient has not been sensitized previously. On reexposure, symptoms begin within hours and are usually moresevere. The eruption may persist for weeks. Chronic lesionsare pink, scaly, pruritic plaques, often mimicking atopic dermatitis. Even intermittent exposure can result in a persistentdermatitis. The diagnosis is established by clinical presentation andhistory of exposure to a recognized irritant or allergen.Skin-prick testing and serum IgE levels are not helpful indetermining the cause of allergic contact dermatitis. Patchtesting may be used to determine the allergen causing thereaction in difficult cases.


Pediatrics_Nelson

Pediatrics_Nelson. Figure 191-1 Irritant diaper dermatitis. Figure 191-2 Allergic contact dermatitis to tincture of benzoin. The distribution and appearance of the dermatitis and a detailed exposure history are the most useful diagnostic tools. Involvement of the lower legs and distal arms suggests exposure to plants of the Rhus species (poison ivy or poison oak), especially when linear configurations of lesions are present. Dermatitis of the ears (earrings), wrist (bracelet or watch), or periumbilical region (belt buckle or pant buttons) suggests a metal allergy to nickel. Distribution on the dorsal surfaces of the feet indicates a shoe allergy, usually to dyes, rubber, or leather. Topical antibiotics (neomycin) and fragrances (soaps, perfumes, cosmetics) are frequent causes of allergic contact dermatitis.


Pediatrics_Nelson

Pediatrics_Nelson. Diaper rashes caused by Candida are quite common. Irritant contact dermatitis primarily affects the prominent, exposed surfaces, whereas Candida primarily affects intertriginous areas. The two are frequently present simultaneously, as secondary Candida infection may complicate irritant dermatitis. Psoriasis, seborrheic dermatitis, and Langerhans cell histiocytosis can present with an erythematous rash in the diaperarea. Referral to a dermatologist should be considered for anychild with severe rash or with diaper rash that does not respondto conventional therapy. Topical corticosteroids are effective in treatment of allergic and irritant contact dermatitis. High-potency corticosteroids, and even short courses of oral corticosteroids, may be necessary for severe reactions of allergic contact dermatitis. Oral antihistamines may be required to control itching.


Pediatrics_Nelson

Pediatrics_Nelson. Treatment of candidal diaper dermatitis consists of topical nystatin or topical azole antifungals. Low-potency topical corticosteroids are frequently used in addition to topical anti-fungal therapy to treat the irritant component of the diaper dermatitis when present concomitantly. In addition to superinfection of diaper dermatitis by C. albicans, bacterial superinfection may complicate any form of contactdermatitis. This is especially common if the skin barrier is nolonger intact because of blistering or scratching. Every effort should be made to identify the trigger of allergic or irritant contact dermatitis. With allergic contact dermatitis, reexposure often leads to increasingly severe reactions.


Pediatrics_Nelson

Pediatrics_Nelson. Every effort should be made to identify the trigger of allergic or irritant contact dermatitis. With allergic contact dermatitis, reexposure often leads to increasingly severe reactions. Seborrheic dermatitis is a common, chronic inflammatory disease that has different clinical presentations at different ages. Seborrheic dermatitis classically presents in infants as cradle cap or dermatitis in the intertriginous areas of the axillae, groin, antecubital and popliteal fossae, and umbilicus. It is seen in adolescents as dandruff. The pathogenesis of seborrheic dermatitis is unclear, but it is theorized that there is an abnormal inflammatory response to commensal Malassezia species in sebum-rich areas. Areas prone to seborrheic dermatitis include the scalp, eyebrows, eyelids, nasolabial folds, external auditory canals, and posterior auricular folds.


Pediatrics_Nelson

Pediatrics_Nelson. Seborrheic dermatitis in infants begins during the first month and persists during the first year of life. It is also called cradle cap because of the thick, greasy and waxy, yellow-white scaling and crusting of the scalp (Fig. 192-1). It is usually prominent on the vertex of the scalp, but it may be diffuse. Greasy, scaly, erythematous, nonpruritic patches and plaques may extend to the face and posterior auricular folds, sometimes involving the entire body. Diaper and intertriginous areas can have sharply demarcated, shiny, erythematous patches with yellow, greasy, or waxy-appearing scale. Hypopigmentation may persist after the inflammation has faded. The eruption is usually asymptomatic, which helps differentiate it from infantile atopic dermatitis, which is pruritic.


Pediatrics_Nelson

Pediatrics_Nelson. Classic seborrheic dermatitis during adolescence is typically localized to the scalp. The mild form is commonly known as dandruff, a fine, white, dry scaling of the scalp with minor itching. Additional findings of seborrheic dermatitis vary from diffuse, brawny scaling to focal areas of thick, oily, yellow crusts with underlying erythema. The external auditory canals, eyebrows, eyelids, and intertriginous areas may be involved as well. Pruritus may be minimal or severe. Figure 192-1 Seborrheic dermatitis (cradle cap). Laboratory studies and imaging studies are not necessary todiagnose seborrheic dermatitis. Fungal cultures and potassiumhydroxide studies may be necessary to help differentiate seborrheic dermatitis of the scalp from tinea capitis (see Chapter 98).


Pediatrics_Nelson

Pediatrics_Nelson. Seborrheic dermatitis in an infant may be difficult to differentiate from atopic dermatitis, and in fact, some cases may represent an overlap. In a teenager, seborrheic dermatitis of the scalpand psoriasis of the scalp may have very similar clinical findings; it may be very difficult to differentiate the two disorders,especially if there are no other cutaneous findings to provideadditional clues. Intractable, severe, generalized seborrheicdermatitis suggests Langerhans cell histiocytosis. Intractableseborrheic dermatitis, accompanied by chronic diarrhea andfailure to thrive, suggests Leiner disease or acquired immunodeficiency syndrome (AIDS).


Pediatrics_Nelson

Pediatrics_Nelson. Seborrheic dermatitis of the scalp is usually asymptomatic andgenerally does not require treatment. Minor amounts of scalecan be removed easily by frequent shampooing. For infantswith cradle cap, oil (such as mineral oil or olive oil) may begently massaged into the scalp and left on for a few minutesbefore gently brushing out the scale and shampooing. Dailyshampooing with ketoconazole, zinc pyrithione, selenium sulfide, or salicylic acid shampoos can treat scalp scale. Seborrheicdermatitis with inflamed lesions responds rapidly to treatmentwith low-potency steroids two times daily. The response to treatment is usually rapid. Secondary bacterial infection can occur but is uncommon. Intractable disease and other complications warrant further evaluation for other etiologies. Cradle cap is self-limited and resolves during the first year of life. Seborrheic dermatitis does not cause permanent hair loss.


Pediatrics_Nelson

Pediatrics_Nelson. Cradle cap is self-limited and resolves during the first year of life. Seborrheic dermatitis does not cause permanent hair loss. For teenagers, continued use of an antiseborrheic shampoo is often required for control of dandruff. Frequent shampooing, especially with early signs of seborrheic dermatitis, may help prevent progression.