Alterations of Neurologic Function in Children

Neural tube defects (NTDs) are an arrest of the normal development of the brain and spinal cord during the first month of embryonic development. They occur in approximately 3000 pregnancies in the United States each year, although there are significant regional prevalence variations.3 Fetal death often occurs in the more severe forms, thereby reducing the actual prevalence of neural defects at birth.

The cause of NTDs is believed to be multifactorial (a combination of genes and environment). No single gene has been found to cause NTDs. Folic acid deficiency during preconception and early stages of pregnancy increases the risk for NTDs, and supplementation (400 mcg of folic acid per day) ensures adequate folate status. In 1996 the United States mandated folate fortification in many foods, and since that time NTDs have decreased by 20% to 30%. Guidelines are available for folic acid supplementation for women at high risk for NTDs.⁴ Other risk factors include a previous NTD pregnancy, maternal diabetes or obesity, use of anticonvulsant drugs (particularly valproic acid), and maternal hyperthermia.⁵ Defects of neural tube closure are divided into two categories: (1) anterior midline defects (ventral induction) and (2) posterior defects (dorsal induction). Anterior midline defects may cause brain and face abnormalities, with the most extreme form being cyclopia, in which the child has a single midline orbit and eye with a protruding nose-like proboscis above the orbit. Anencephaly (an, “without”; enkephalos, “brain”) and encephalocele are also anterior midline defects. Spina bifida (split spine) is the most common NTD. Vertebrae fail to close in spina bifida, and the defect includes meningocele, myelomeningocele, and spina bifida occulta. Disorders of embryonic neural development are summarized in Fig. 20.3.

Three timelines show disorders associated with specific stages of embryonic development. Top panel. The timeline shows three sections: gestation time (days), dorsal (posterior) induction (3 to 4 weeks), and ventral (anterior) induction (3 to 6 weeks). The data from the timeline are as follows. • 0 to 18 days. Development of three germ layers and formation of early neural plate. Disorders have no effect or death. • 18 days. Development of neural plate and groove. Disorders include anterior midline neural tube defects, cyclopia holoprosencephaly, and cleft lip and or palate. • 26 days. Closure of anterior neurospace. Disorder includes anencephaly. • 28 days. Closure of posterior neuropore. Disorders include posterior midline neural tube defects, myelomeningocele, encephalocele, cranium bifidum, and spina bifida occulta. • 32 days. Beginning of vascular circulation. Disorder includes microcephaly (primary; 30 to 175 days). • 42 days. Development of five cerebral vesicles, choroid plexus, and dorsal root ganglion. Middle panel. The timeline shows three sections: proliferation (2 to 4 months), migration (3 to 6 months), and organization (fifth fetal month to twenty-fourth postnatal month). The data from the timeline are as follows. • 56 days. Differentiation of cerebral cortex, meninges, ventricular foramina, and C S F circulation. Disorder includes true microcephaly. • 90 days. Corpus callosum development. • 150 days. Primary fissures of cerebral cortex; end of spinal cord at L 3 level. Disorders include abnormalities of the cerebral hemispheres and convolutions, and visual abnormalities. • 175 days. End of neuronal proliferation in cerebral cortex. • 7 to 9 months. Formation of secondary and tertiary sulci. The disorder includes destructive pathologic changes: microcephaly (secondary), intellectual disability, and seizure disorders. Bottom panel. The timeline shows two segments between myelination (6 months’ gestation to adulthood). The data from the timeline are as follows. • 6 months. Development of myelin wrapping. Disorders include Schilder disease, childhood multiple sclerosis, and leukodystrophies. • Adulthood.

Anencephaly is an anomaly in which the soft, bony component of the skull and part of the brain are missing. This disorder occurs in approximately 1 in 4600 births in the United States each year.6 These infants are stillborn or die within a few days after birth. The pathologic mechanism is unknown. Diagnosis is often made prenatally by using ultrasound or evaluating the maternal serum alpha fetoprotein (AFP).

Encephalocele refers to a herniation or protrusion of the brain and meninges through a defect in the skull, resulting in a sac-like structure. The incidence is approximately 1 in 10,500 live births in the United States each year.⁷ Encephalocele treatment involves surgical closure of the skull opening. The complexity of the surgery depends on the location and content of the defect. Often several surgeries may be needed with variable long-term neurologic sequelae.

Meningocele is a sac-like cyst of meninges filled with spinal fluid and is a mild form of spina bifida (Fig. 20.4). It develops during the first 4 weeks of pregnancy when the neural tube fails to close completely and is the rarest type of spina bifida. The cystic dilation of meninges protrudes through the vertebral defect but does not involve the spinal cord or nerve roots and may produce no neurologic deficit or symptoms. Meningoceles occur most commonly in the lumbar spine.

Closeup A shows an infant on the side with a large herniation, the size of the infant’s head, at the base of the head. Two pairs of accompanying illustrations show lateral and cross-sectional views of the spine. One pair shows meningocele and the other pair shows myelomeningocele. Closeup B shows an infant lying on its stomach with the legs curled toward to the abdomen. There is a large herniation on the lower back. Two pairs of accompanying illustrations show lateral and cross-sectional views of a normal spine and a spine affected by spina bifidia. Some of the vertebrae are missing in the spine with spina bifida.

Myelomeningocele (meningomyelocele; spina bifida cystica) is a hernial protrusion of a sac-like cyst (containing meninges, spinal fluid, and a portion of the spinal cord with its nerves) through a defect in the posterior arch of a vertebra. It is most commonly located as a sac on the lumbar and lumbosacral regions, the last regions of the neural tube to close. Myelomeningocele is one of the most common and severe developmental anomalies of the nervous system, with an incidence of approximately 1 per 4000 live births.8 It accounts for 75% of all spina bifida cases.

Meningocele and myelomeningoceles are evident at birth as a pronounced skin defect on the infant's back (see Fig. 20.4). The bony prominences of the unfused neural arches can be palpated at the lateral border of the defect. The defect usually is covered by a transparent membrane that may have neural tissue attached to its inner surface. This membrane may be intact at birth or may leak cerebrospinal fluid (CSF), thereby increasing the risks of infection and neuronal damage. The spinal cord and nerve roots are malformed below the level of the lesion, resulting in loss of motor, sensory, reflex, and autonomic functions. A brief neurologic examination concentrating on motor function in the legs, reflexes, and sphincter tone is usually sufficient to determine the level above which spinal cord and nerve root function is preserved (Table 20.2). This is useful to predict if the child will ambulate, require bladder catheterization, or be at high risk for developing scoliosis (see Chapter 45).

Hydrocephalus occurs in 85% of infants with myelomeningocele.⁹ Seizures also occur in 30% of those with myelomeningoceles. Visual and perceptual problems, including ocular palsies, astigmatism, and visuoperceptual deficits, are common. Motor and sensory functions below the level of the lesions are altered. These problems should not worsen as the child grows. If a neurologic decline is identified in a child with spina bifida, the cause needs to be investigated.

Myelomeningoceles are almost always associated with the Chiari II malformation.⁹ This is a complex malformation of the brainstem and cerebellum in which the cerebellar tonsils are displaced downward through the foramen magnum and into the cervical spinal canal. The upper medulla and lower pons are elongated and thin, and the medulla is also displaced downward and sometimes has a “kink” (Fig. 20.5). The Chiari II malformation is associated with hydrocephalus from pressure that blocks the flow of CSF. The Chiari II malformation is also associated with syringomyelia, an abnormality resulting from CSF migrating into the center of the spinal cord forming a pocket or cyst (syrinx) that can expand and cause pressure on the spinal cord, resulting in bowel, bladder, sensory, and motor dysfunction. The incidence of Chiari II malformation is reduced in those children operated on in utero for myelomeningocele.

Illustration A is a left lateral view of the brain with the following parts labeled: cerebellum, cerebral tonsils, fourth ventricle, pons, and medulla. Illustration B is a left lateral view of the base of the brain with the following parts labeled: tentorium, fourth ventricle, pons, downward displacement of cerebellar tonsils through foramen magnum, area of compression, and medulla.

Other types of Chiari malformations are not associated with spina bifida. In type I Chiari malformation the cerebellar tonsils protrude into the foramen magnum and the brainstem is not involved. Type I Chiari is the most common of all Chiari malformations and may be asymptomatic or symptomatic (e.g., neck pain, dizziness, difficulty with gait and swallowing), sometimes requiring neurosurgical intervention. In type III, the brainstem or cerebellum extends into a high cervical myelomeningocele and can cause serious neurologic defects. Type IV is characterized by lack of cerebellar development (cerebellar hypoplasia).

Most cases of meningocele and myelomeningocele are diagnosed prenatally by a combination of maternal serologic testing (AFP) and prenatal ultrasound. In these cases, the fetus is usually delivered by elective cesarean section to minimize trauma during labor. Surgical repair is critical and can be performed by in utero fetal surgery or during the first 72 hours of life.10 It is possible for a defect to occur without any visible exposure of meninges or neural tissue, and the term spina bifida occulta is then used. The defect is common and occurs to some degree in 10% to 25% of infants. Spina bifida occulta usually causes no neurologic dysfunction because the spinal cord and spinal nerves are normal. A sacral dimple on examination of a newborn infant can be associated with spina bifida occulta and should be further evaluated. Any midline skin abnormality such as a hairy tuft, hemangioma type lesion, or unusual dimple may indicate underlying spinal pathology and should be evaluated. Tethered cord syndrome may develop after surgical correction for myelomeningocele. The cord becomes abnormally attached or tethered in the lumbar cistern as a result of scar tissue as the cord ascends in the vertebral canal with growth.¹¹ Although radiographically almost all persons affected by myelomeningocele will appear to be tethered, only those with symptoms or new neurologic decline warrant further investigation, and prompt neurosurgical release of the tethering is appropriate. Special attention should be given to children whose myelomeningocele was corrected in utero, because their risks of spinal cord retethering is increased (see Emerging Science Box: In Utero Myelomeningocele Surgery).

Skull malformations range from minor, insignificant defects to major defects that are incompatible with life. Craniosynostosis (craniostenosis) is the premature closure of one or more of the cranial sutures (sagittal, coronal, lambdoid, metopic) during the first 18 to 20 months of the infant's life. The incidence of craniosynostosis is approximately 1 per 2500 live births.12 Males are affected twice as often as females. Fusion of a cranial suture prevents growth of the skull perpendicular to the suture line, resulting in an asymmetric shape of the skull. The general term plagiocephaly, meaning “misshapen skull,” is used to describe deformities that result from craniosynostosis or from asymmetric head posture (positional). When a single coronal suture fuses prematurely, the head is flattened on that side in front. When the sagittal suture fuses prematurely, the head is elongated in the anteroposterior direction (known as scaphocephaly). Single suture craniosynostosis requires early surgical intervention because it is not just a cosmetic issue. When multiple sutures fuse prematurely, surgical intervention is necessary. Brain growth may be restricted, and surgical repair may prevent neurologic dysfunction (Fig. 20.6). Syndromic craniosynostosis involves deformities in other systems (i.e., the heart, limbs, and CNS).

Six pairs of illustrations of skulls show normal and abnormal head configurations. Each pair shows the right lateral view and the anterior view of the skull. Top left, normal skull. The sagittal suture is identified in the lateral view. The coronal suture is identified in the anterior view. Top right, brachycephaly. The sagittal suture in the lateral view is shrunken. The coronal suture in the anterior view is almost non-existent. The head is unusually large. Middle left, microcephaly and craniostenosis. The skulls are smaller than normal. The sagittal suture in the lateral view is shrunken. The coronal suture in the anterior view is minimal. Middle right, oxycephaly or acrocephaly. The sagittal suture in the lateral view and the coronal suture are almost non-existent. The head is almost twice as long as normal. Bottom left, scaphocephaly or dolichocephaly. The skulls are larger and narrower. The sagittal suture and the coronal suture are minimal. Bottom right, plagiocephaly. The skulls are misshapen. The left and the right side are disproportional. The sagittal suture is present. The coronal suture is only partially present.

Reduced proliferation or accelerated apoptosis (programmed cell death) of brain cells causes congenital microcephaly (microencephaly—small brain). Increased proliferation of brain cells causes megalencephaly (macrencephaly—abnormally large brain). Both disorders are rare. Diagnosis is made by clinical history, family history, and brain imaging.13,14

Microcephaly (small head) is associated with a defect in brain growth as a whole (see Fig. 20.6). Cranial size is significantly below average for the infant's age, gender, race, and gestation. The small size of the skull reflects a small brain (microencephaly), which is caused by reduced proliferation or accelerated apoptosis. True (primary) microcephaly is usually caused by an autosomal recessive genetic or chromosomal defect. Secondary (acquired) microcephaly is associated with various causes, such as intrauterine infection (including emergence of the Zika virus)¹⁵; trauma; metabolic disorders; maternal anorexia experienced during the third trimester of pregnancy; in utero exposure to alcohol, toxins, or certain medications; and the presence of other genetic syndromes. Children with microcephaly are usually developmentally delayed. Microcephaly can be familial and, if so, can be associated with normal development.

Cortical dysplasias (malformations) are defects in brain development and related to failure of embryonic neurons to migrate to the right places in the brain. These disorders may range from a small area of abnormal tissue to an entire brain that is smooth and without the normal configuration of gyri and sulci, known as lissencephaly (Fig. 20.7), or a brain that has too many small gyri (folds), known as polymicrogyria. There is a specific genetic defect for some of these disorders; others are multifactorial or acquired (e.g., intrauterine trauma or infection). Cortical dysplasias increase the risk for seizures that are difficult to control and cause developmental delay and motor dysfunction. Genetic testing assesses risk in other family members and guides therapy.^16,17 Congenital hydrocephalus is present at birth and characterized by increased CSF pressure and enlargement of the ventricles. The overall incidence of hydrocephalus is approximately 1 to 2 per 1000 live births.¹⁸ Hydrocephalus may be caused by blockage within the ventricular system where the CSF flows, an imbalance in the production of CSF, or a reduced reabsorption of CSF. The increased pressure within the ventricular system dilates the ventricles and pushes and compresses the brain tissue against the skull cavity (Fig. 20.8A and B). When hydrocephalus develops before fusion of the cranial sutures, the skull can expand to accommodate this additional space-occupying volume and preserve neuronal function (Types of hydrocephalus are discussed in Chapter 17).

Illustration A shows the right lateral view of a child’s head and a superior view of the brain, both with nonhydrocephalus. Illustration B shows the right lateral view of a child’s head and a superior view of the brain, both with hydrocephalus. The structures in the hydrocephalus are different from those in the nonhydrocephalus in the following ways. • Lateral ventricle covers most of the brain. • Third ventricle is almost twice as large. • Aqueduct of Sylvius is thinner. • Fourth ventricle is about thrice as large. • Foramen of Luschka is bigger. • Cisternal magna is bigger. • Foramen of Magendie is shorter. • Compression of brain tissue with ischemia and necrosis. Closeup C shows the right lateral profile of an infant with hydrocephalus. The infant’s head is abnormally large. Closeup D shows the front profile of an infant with hydrocephalus. The infant’s head is abnormally large.

Congenital hydrocephalus may cause fetal death in utero, or the increased head circumference may require cesarean delivery of the infant. Symptoms depend directly on the cause and rate of hydrocephalus development. When there is separation of the cranial sutures, a resonant note sounds when the skull is tapped, a manifestation called the Macewen sign, or “cracked pot” sign. The eyes may assume a staring expression, unable to look upwards, with sclera visible above the cornea, called sunsetting (see Fig. 20.8D). Treatment outcomes are variable. Cognitive impairment in children with hydrocephalus is often related to associated brain malformations or episodes of shunt failure or infection. Approximately 40% to 65% of children with uncomplicated congenital hydrocephalus complete schooling and are employed when treated successfully with shunting or endoscopic third ventriculostomy with or without choroid plexus cauterization.^19–21

The Dandy-Walker malformation (DWM) is a congenital defect of the cerebellum characterized by a large posterior fossacyst that communicates with the fourth ventricle, cerebellar hypoplasia, and macrocephaly. DWM is commonly associated with hydrocephalus. Other causes of obstructions within the ventricular system that can result in hydrocephalus include brain tumors, cysts, trauma, arteriovenous malformations, blood clots, infections, and the Chiari malformations (Emerging Science Box: Gene Therapy for Pediatric Neurologic Conditions).

Static or nonprogressive encephalopathy describes a neurologic condition caused by a fixed lesion without active and ongoing disease. Causes include brain malformations or brain injury that may occur during gestation or birth or at any time during childhood. The degree of neurologic impairment is directly related to the extent of the injury or malformation and the stage of development at the time of injury. Anoxia, trauma, and infections are the most common causes of injury to the nervous system in the perinatal period. Infections, metabolic disturbances (acquired or genetic), trauma, toxins, and vascular disease may injure the nervous system in the postnatal period.22

Cerebral palsy is a disorder of movement, muscle tone, or posture that is caused by injury or abnormal development in the immature brain, before, during, or after birth up to 1 year of age. Cerebral palsy is one of the most common crippling disorders of childhood, affecting nearly 764,000 children in the United States alone. Although the exact incidence is unknown, studies suggest that the prevalence is approximately 1 in 345 children in the United States.²³

Risk factors include prenatal or perinatal cerebral hypoxia, hemorrhage, infection, genetic abnormalities, or low birth weight (Table 20.4). Cerebral palsy can be classified on the basis of neurologic signs and motor symptoms, with the major types being spasticity, dystonia, ataxia, or a combination of these symptoms (mixed). Diplegia, hemiplegia, or tetraplegia may be present.

Pyramidal/spastic cerebral palsy is the most common. It results from damage to corticospinal pathways (upper motor neurons) and is associated with increased muscle tone, persistent primitive reflexes, hyperactive deep tendon reflexes, clonus, rigidity of the extremities, scoliosis, and contractures. Extrapyramidal/nonspastic cerebral palsy is less common and is caused by damage to cells in the basal ganglia or cerebellum and includes two subtypes: dystonic and ataxic. Dystonic (dyskinetic) cerebral palsy is associated with injury to the basal ganglia with extreme difficulty in fine motor coordination and purposeful movements. Movements are stiff, uncontrolled, and abrupt. Ataxic cerebral palsy is caused by damage to the cerebellum, with alterations in coordination and movement. There is a broad-based gait in an attempt to maintain balance, and tremor is common with intentional movements. A child may have symptoms of each of these cerebral palsy types, which leads to a mixed disorder.²⁴

Children with cerebral palsy often have associated neurologic disorders, such as seizures and intellectual impairment ranging from mild to severe. Other complications include visual impairment, communication disorders, respiratory problems, bowel and bladder problems, and orthopedic disabilities, such as hip pain or dislocation, balance problems, or hand dysfunction.²⁵

Drug-induced encephalopathies must always be considered a possibility in the child with unexplained neurologic changes. Such encephalopathies may result from accidental ingestion, therapeutic overdose, intentional overdose, or ingestion of environmental toxins. There were 37.7/1000 children younger than 6 years of age with poison exposures in 2018. Approximately 44.2% of all poison exposures occurred in children younger than 6 years of age, with the highest incidence being 1- and 2-year-old children. The most commonly ingested poisons in children younger than 6 years are cosmetics and personal care products, cleaning substances, and over-the-counter analgesics and other medications (Table 20.5).²⁸

Lead poisoning results in high blood levels of lead. If lead poisoning is untreated, lead encephalopathy results and is responsible for serious and irreversible neurologic damage. Those at greatest risk are children ages 2 to 3 years and children prone to the practice of pica—the habitual, purposeful, and compulsive ingestion of nonfood substances, such as clay, soil, and paint chips or paint dust. Lead intoxication also may occur from chronic exposure to lead in cosmetics, inhalation of gasoline vapors, and ingestion of airborne lead.²⁹ Fetal neurotoxicity occurs with maternal lead exposure, particularly during the first trimester.³⁰ Details related to lead intoxication are described in Chapter 2. Refer to Fig. 20.10 for a summary of toxic lead effects.

A flowchart tracks a systemic effects of increased lead absorption in children. The flowchart shows four systems. The hematologic system is as follows. Impaired update and utilization of iron and prevention of formation of hemoglobin leads to anemia. Anemia leads to accumulation of intermediate metabolites, which in turn results in either of the following: • Erythrocyte, protoporphyrin. • Urinary, increased coproporphyrin, increased delta-aminolaevulinic acid. The renal system undergoes the following changes. • Damages cells of proximal rental tubule and loop of Henle. • Glycosuria, phosphaturia, aminoaciduria, and ketonuria. • Urinary, increased coproporphyrin, increased delta-aminolaevulinic acid. The skeletal system undergoes the following changes. • Accumulated as tertiary lead phosphate and calcium. • Interferes with growth of metaphysis in long bones. • Decreased growth rate. The neurologic system undergoes the following changes. • Inhibits sulfhydryl enzymes. • Increases membrane permeability. • Increased intracranial pressure (I C P) and cerebral edema. • Tissue ischemia. • Irreversible necrosis and tissue atrophy. • Behavior changes, intellectual disability, convulsions, coma, and death. Increased release from storage occurs with illness, acidosis, and detoxification leads to accumulation of intermediate metabolites.

Perinatal stroke is defined as stroke occurring from 28 weeks’ gestation to 28 days postnatal.35 Perinatal arterial ischemic stroke is estimated at 1 in 4000 live births and is a leading cause of perinatal brain injury, cerebral palsy, and lifelong disability. Although a cause for perinatal stroke is usually not found, clotting abnormalities may make the child prone to further vascular events. Up to 80% are ischemic with the remainder secondary to hemorrhage or cerebral sinovenous thrombosis (CSVT).

Childhood stroke occurs in 1.3 to 1.6 per 100,000 children per year and may be divided into two categories: ischemic and hemorrhagic.35,36 According to the Center for Disease Control and Prevention, cerebrovascular disease (stroke) is one of the 10 leading causes of death in children and adolescents from 1 to 24 years of age. Ischemic (occlusive) stroke in children may result from embolism, Cerebral sinovenous thrombosis (CSVT), or congenital or iatrogenic narrowing of vessels, leading to decreased flow of blood and oxygen to areas of the brain. Although rare, it is more common than hemorrhagic stroke. Children with arterial ischemic stroke do not have the typical adult risk factors of atherosclerosis and hypertension. Many children with acute ischemic stroke have no identifiable risk factors.³⁵ Arteriopathies, cardiac anomalies, sickle cell disease, infections, head and neck disorders, systemic conditions, and prothrombic states are the common disorders associated with arterial ischemic stroke.³⁵

Hemorrhagic stroke is most commonly caused by bleeding from congenital cerebral arteriovenous malformations and is rare in children younger than 19 years. Intraventricular hemorrhage associated with premature birth is related to immature blood vessels and unstable blood pressure. There is a high risk of developing posthemorrhagic hydrocephalus in very low birth weight (<1000 g) preterm infants with increased risk of developmental disabilities.³⁷

The clinical presentation of stroke varies according to the vessels involved and the age of the individual. Symptoms include hemiplegia, weakness, seizures, headaches, high fever, nuchal rigidity, hemianopia, sensory changes, facial palsy, and temporary aphasia. Obtaining a thorough history of evolving symptoms and risk factors is important for diagnosis. Laboratory studies may be indicated. Neuroimaging studies assist in determining the extent of the disease. Surgery is an option for treatment, and anticoagulants and antithrombotics may be used in selected cases.

Moyamoya disease is a rare, chronic, progressive vascular stenosis of the circle of Willis of unknown etiology. There is obstruction of arterial flow to the brain and the development of small basal arterial collateral vessels that vascularize the hypoperfused brain distal to the occluded vessels.³⁸ Moyamoya means a puff of smoke in Japanese and represents the appearance of these small vessels on cerebral angiography. The disease is most common in East Asia and is associated with genetic factors, particularly those associated with vascular growth factors. These children often present with transient ischemic attacks (TIAs) because the new vessels fail to provide adequate perfusions.³⁹ Diagnosis is made by cerebral angiography, and the most effective treatment is surgical revascularization.

Brain tumors are the most common solid tumor, are the second most common primary neoplasm in children (after leukemia), and can be benign or malignant.45,53 They are the leading cause of cancer-related death in children, and the 5-year survival is approximately 74%, varying significantly by tumor type. Primary brain tumors arise from brain tissue and do not metastasize outside the brain. The cause of brain tumors is unknown, although genetic, environmental, and immune factors have been investigated. Exposure to radiation therapy has been the only environmental factor consistently related to the development of brain tumors.^46,53

Brain tumors can arise from any CNS cell, and tumors are classified by cell type and molecular markers. The most common tumors are embryonal tumors, including medulloblastoma, atypical medulloblastoma, atypical teratoid rhabdoid tumors, CNS primitive neuroectodermal tumors, and high-grade gliomas, including glioblastomas, diffuse pontine gliomas, and other malignant astrocytomas. Other tumor types are less common, including low-grade astrocytomas (especially pilocytic astrocytomas), neuronal and mixed neuronal-glial tumors, and ependymal tumors (ependymomas). Brain tumors in children are often located in the posterior fossa (Fig. 20.11). The types and characteristics of the more common childhood brain tumors are summarized in Table 20.6.

An illustration of the left lateral view of a child’s brain identifies the location of brain tumors. The data from the illustration are as follows. Craniopharyngiomas. • Located adjacent to the Sella turcica (structure containing the pituitary gland), often considered to lie supratentorial. • Considered to have benign properties but is life threatening because of its location near vital structures. Optic nerve gliomas. • Most often a low-grade astrocytoma. Cerebral tumors (supratentorial). • Astrocytomas invade surrounding structures but grow slowly. • Ependymomas arise from lining tissue of lateral ventricle. Brain stem gliomas. • Arise from pons or medulla. • Slow growing. • May involve cranial nerves V to X. Medulloblastomas (infratentorial). • Arise from cerebellum. • Can invade fourth ventricle, subarachnoid space, and cerebrospinal fluid pathways. • Fast growing. • Arise from embryonic cerebellum. Infratentorial ependymomas. • Arise from lining tissue of fourth ventricle. Cerebellar Astrocytomas. • Slow growing. • Grading system 1 to 4 with 1 and 2 less malignant than 3 and 4.

Signs and symptoms of brain tumors in children vary from generalized and vague to localized and related specifically to an anatomic area. Signs of elevated ICP may occur, including headache, vomiting, lethargy, and irritability. If a young child complains of repeated and worsening headache, a thorough investigation should take place because headache is an uncommon complaint in young children. Headache caused by elevated ICP usually is worse in the morning and gradually improves during the day, when the child is upright and venous drainage is enhanced. The frequency of headache and other symptoms increases as the tumor grows. Irritability or possible apathy and increased somnolence also may result. Like headache, vomiting occurs more commonly in the morning. Often it is not preceded by nausea and may become projectile, differing from a gastrointestinal disturbance in that the child may be ready to eat immediately after vomiting. Persistent headaches with vomiting in a child should be evaluated promptly. Other signs and symptoms include increased head circumference with bulging fontanelles in the child younger than 2 years, cranial nerve palsies, and papilledema (Box 20.1).

Localized findings relate to the degree of disturbance in physiologic functioning in the area where the tumor is located. The majority of pediatric brain tumors involve the cerebellum, brain stem, and fourth ventricle affecting all pediatric age groups. Children with infratentorial tumors (posterior fossa) exhibit localized signs of impaired coordination and balance, including ataxia, gait difficulties, truncal ataxia, and loss of balance. Supratentorial tumors of the cerebral hemispheres are more common in children younger than 3 years of age.46 Most pediatric brain tumors require surgical resection. Aggressive radiation and chemotherapy are required for high-grade tumors, although radiation therapy is rarely offered to children younger than 4 years of age, due to significant long-term side effects. Advances are being made in areas of immunotherapy and targeted molecular therapy (see Emerging Science Box: The New Evolving Classification System for Pediatric Brain Tumors).⁴⁷