The brain, cerebrospinal fluid (CSF), and blood are the three intracranial compartments that determine the size of the skull during infancy. Expansion of one compartment comes at the expense of another in order to maintain volume and pressure (see Chapter 4 ). The epidural, subdural, and subarachnoid spaces may expand with blood or CSF fluid and significantly affect cranial volume and the other intracranial compartments. Less important factors contributing to head size are the thickness of the skull bones and the rate of their fusion.
The intracranial content, the fusion of the sutures, and external forces on the skull determine its shape. Infants left supine all the time tend to develop flat occiputs. Premature infants resting on one side of the head all the time develop heads with large occipitofrontal diameter (dolichocephaly).
Measuring Head Siz e
Head circumference is determined by measuring the greatest occipitofrontal circumference. Influencing the accuracy of the measurement is the head shape and fluid in and beneath the scalp. Following a prolonged and difficult delivery, edema or blood may thicken the scalp and a cephalohematoma may be present as well. Fluid that infiltrates from a scalp infusion can markedly increase head circumference.
A round head has a larger intracranial volume than an oval head of equal circumference. A head with a relatively large occipitofrontal diameter has a larger volume than a head with a relatively large biparietal diameter.
Head circumference measurements are most informative when plotted over time (head growth). The head sizes of male and female infants are different, and one should not rely on head growth charts that provide median values for both genders. The rate of head growth in premature infants is considerably faster than in full-term newborns ( Figure 18-1 ). For this reason, the charting of head circumference is always by conceptional age and not by postnatal age.
Macrocephaly means a large head, larger than two standard deviations from the normal distribution. Thus, 2% of the “normal” population has macrocephaly. Investigation of such individuals may show an abnormality causing macrocephaly, but many are normal, often with a familial tendency for a large head. When asked to evaluate a large head in an otherwise normal child, first measure and plot the parents’ heads.
The causes of a large head include hydrocephalus (an excessive volume of CSF intracranially), megalencephaly (enlargement of the brain), thickening of the skull, and hemorrhage into the subdural or epidural spaces. Hydrocephalus is traditionally communicating (nonobstructive) or noncommunicating (obstructive), depending on whether CSF communicates or not between the ventricles and subarachnoid space ( Box 18-1 ). Hydrocephalus is the main cause of macrocephaly at birth in which intracranial pressure is increased.
Basilar impression (see Chapter 10 )
Choroid plexus papilloma ∗
∗ Denotes the most common conditions and the ones with disease modifying treatments(see Chapter 4 )
Posthemorrhagic (see Chapter 4 )
Aqueductal stenosis ∗
Chiari malformation (see Chapter 10 )
Mass lesions ∗
Tumors and neurocutaneous disorders
Vein of Galen malformation ∗
Other causes of increased intracranial CSF
Benign enlargement of subarachnoid space
The causes of megalencephaly are anatomical and metabolic. The anatomical disorders are primary megalencephaly and neurocutaneous disorders ( Box 18-2 ). Children with anatomical megalencephaly are often macrocephalic at birth but have normal intracranial pressure. Children with metabolic megalencephaly are usually normocephalic at birth and develop megalencephaly from cerebral edema during the neonatal period.
Megalencephaly with achondroplasia
Megalencephaly with gigantism (Sotos syndrome)
Megalencephaly with a neurological abnormality
Epidermal nevus syndrome
Hypomelanosis of Ito
Incontinentia pigmenti (see Chapter 1 )
Neurofibromatosis (see Chapter 5 )
Tuberous sclerosis (see Chapter 5 )
Alexander disease (see Chapter 5 )
Canavan disease (see Chapter 5 )
Galactosemia: transferase deficiency (see Chapter 5 )
Gangliosidosis (see Chapter 5 )
Globoid leukodystrophy (see Chapter 5 )
Glutaric aciduria type I (see Chapter 14 )
Maple syrup urine disease ∗
∗ Denotes the most common conditions and the ones with disease modifying treatments(see Chapter 1 )
Megalencephalic leukoencephalopathy with subcortical cysts
Metachromatic leukodystrophy (see Chapter 5 )
Mucopolysaccharidoses (see Chapter 5 )
Increased thickness of the skull bones does not cause macrocephaly at birth or in the newborn period. Macrocephaly develops during infancy. Box 18-3 lists the conditions associated with increased skull growth. The text does not contain a separate discussion. The discussion of intracranial hemorrhage in the newborn is in Chapter 1 , and intracranial hemorrhage in older children is in Chapter 2 .
∗ Denotes the most common conditions and the ones with disease modifying treatments
Craniometaphyseal dysplasia of Pyle
The usual cause of communicating hydrocephalus is impaired absorption of CSF secondary to meningitis or subarachnoid hemorrhage. Meningeal malignancy, usually by leukemia or primary brain tumor, is a less common cause. Any of these processes may cause arachnoiditis or arachnoid infiltration and decrease reabsorption of CSF by the arachnoid villi. The excessive production of CSF by a choroid plexus papilloma rarely causes communicating hydrocephalus because the potential rate of CSF reabsorption far exceeds the productive capacity of the choroid plexus (see Chapter 4 ). Such tumors more commonly cause hydrocephalus by obstructing one or more ventricles.
Benign Enlargement of Subarachnoid Space
The terms used to describe benign enlargement of the subarachnoid space include external hydrocephalus, extraventricular hydrocephalus, benign subdural effusions, and benign extracerebral fluid collections. It is a relatively common cause of macrocephaly in infants, a fact not fully appreciated before the widespread use of computed tomography (CT) to investigate large head size. A genetic cause is likely in some cases, with the infant’s father often having a large head.
The condition occurs more commonly in males than females. A large head circumference is the only feature. An otherwise normal infant is brought to medical attention because serial head circumference measurements show an enlarging head size. The circumference is usually above the 90th percentile at birth, grows to exceed the 98th percentile, and then parallels the normal curve ( Figure 18-2 ). The anterior fontanelle is large but soft. Neurological findings are normal, but motor development is often slower. Head control is one of the earliest achievements in motor development for an infant. Macrocephalic infants take longer to control their heads and this delays other milestones such as sitting and standing; however, the ultimate development is normal in these children.
Cranial CT shows an enlarged frontal subarachnoid space, widening of the sylvian fissures and other sulci, and normal or minimally enlarged ventricular size ( Figure 18-3 ). Normal ventricular size distinguishes this condition from cerebral atrophy. In infants, the upper limit of normal size for the frontal subarachnoid space is 5.7 mm and for the sylvian fissure 7.6 mm. The CT scan often is read as brain atrophy as the brain looks smaller than the container; however, both the brain and the cranium are large.
Most affected infants develop normally and do not require ventricular shunts. Plot head circumference measurements monthly for 6 months after diagnosis to be certain that growth is paralleling the normal curve. Repeat CT is unnecessary unless head growth deviates from the normal curve, neurological examination is abnormal, or social and language development are slow.
Tumors that infiltrate the meninges and subarachnoid space impair the reabsorption of CSF and cause communicating hydrocephalus. Meningeal spread usually occurs from a known primary tumor site. Diffuse meningeal gliomatosis is the exception where the initial feature may be hydrocephalus.
Tumors that infiltrate the meninges are usually aggressive and cause rapid progression of symptoms. Headache and vomiting are the initial features and lethargy and personality change follow. Meningismus and papilledema are common features and may suggest bacterial meningitis. Multifocal neurological disturbances may be present.
Magnetic resonance imaging (MRI) shows dilatation of the entire ventricular system but not of the subarachnoid space, which may appear obliterated except for a layer of enhancement. The pressure of the CSF and its protein concentration are increased. The glucose concentration may be depressed or normal. Tumor cell identification in the CSF is rarely successful and meningeal biopsy is usually required for tissue diagnosis.
Ventricular shunt relieves symptoms of increased intracranial pressure. Radiation therapy and chemotherapy provide palliation and extend life in some cases, but the outcome is generally poor.
Complete obstruction of the flow of CSF from the ventricles to the subarachnoid space causes increased pressure and dilation of all ventricles proximal to the obstruction. The incidence of congenital hydrocephalus is 1 in 1500 live births. The best estimate is that 40 % of the cases of congenital hydrocephalus have a genetic basis. X-linked hydrocephalus accounts for 5–15 % of all cases. The responsible gene is at Xq28 encoding for L1CAM. Other environmental factors that may lead to congenital hydrocephalus are exposure to radiation, alcohol or infections in utero ( ).
Noncommunicating hydrocephalus is the most common form of hydrocephalus in fetuses. Aqueductal stenosis is the usual cause of congenital hydrocephalus in the absence of other associated cerebral malformations. Aqueductal stenosis is less common during infancy but its frequency increases during childhood. Mass lesions are the most common cause of aqueductal obstruction during childhood. Children with congenital hydrocephalus who have seizures usually have other cerebral malformations. Such children have a higher incidence of cognitive impairment.
Congenital Aqueductal Stenosis
At birth, the mean length of the cerebral aqueduct is 12.8 mm and its smallest cross-sectional diameter is usually 0.5 mm. The small lumen of the cerebral aqueduct, in relation to its length, makes it especially vulnerable to internal compromise from infection and hemorrhage, and to external compression by tumors and venous malformations. Congenital atresia or stenosis of the cerebral aqueduct can occur as a solitary malformation or can occur as part of a spectrum of abnormalities associated with the L1 syndrome described below.
Hydrocephalus is present at birth. Head circumference ranges from 40–50 cm and may cause cephalopelvic disproportion and poor progress of labor requiring cesarean section. The forehead is bowed, the scalp veins dilated, the skull sutures widely separated, and the fontanelles large and tense. These signs exaggerate when the child cries but also are present in the quiet state. The eyes are deviated downward so that the sclera shows above the iris ( setting-sun sign ), and abducens palsies may be present.
Intrauterine sonography is diagnostic after 20 weeks when the ventricles expand. Sonograms performed earlier are misleading. When macrocephaly is present in the fetus, amniotic fluid assay of α-fetoprotein is useful for the detection of neural tube defects (see Chapter 12 ). Chromosomal analysis provides further information concerning the integrity of the fetal nervous system to develop a management plan.
CT readily provides the postpartum diagnosis of aqueductal stenosis. Marked enlargement of the lateral ventricle, the third ventricle, and the cephalic end of the cerebral aqueduct is easily visualized. The remainder of the cerebral aqueduct and the fourth ventricle cannot be seen ( Figure 18-4 ).
Congenital hydrocephalus caused by aqueductal stenosis is severe, does not respond to medical therapy directed at decreasing the volume of CSF, and progresses to a stage that harms the brain. Diversion of the CSF from the ventricular system to an extracranial site is the only effective method of management.
The management of fetal hydrocephalus depends on the presence of other malformations. Three-quarters of affected fetuses have other abnormalities, usually spina bifida.
Ventriculoperitoneal shunt is the procedure of choice for newborns and small infants with aqueductal stenosis. It is easier to revise and is better tolerated than ventriculoatrial shunt. Mechanical obstruction and infection are the most common complications of shunt placement in infancy (see Chapter 4 ).
The relief of hydrocephalus increases the potential for normal development, even when the cerebral mantle appears very thin preoperatively, but does not necessarily result in a normal child. The growth of intelligence is often uneven, with better development of verbal skills than of nonverbal skills. Associated anomalies may cause motor deficits and seizures.
X-Linked Hydrocephalus (L1 Syndrome)
The L1 syndrome encompasses HSAS syndrome (X-linked hydrocephalus with stenosis of the aqueduct of Sylvius), MASA syndrome (mental retardation, aphasia, spastic paraplegia, and adducted thumbs), X-linked complicated hereditary spastic paraplegia type 1, and X-linked complicated corpus callosum agenesis ( ).
Hydrocephalus, cognitive impairment, spasticity of the legs, and adducted thumbs are characteristic features in affected males. The spectrum of severity is wide depending on the nature of the mutation. Mental retardation ranges from mild to severe, and the gait abnormality from shuffling gait to spastic paraplegia. Adducted thumbs are characteristic of several phenotypes.
Molecular genetic testing is commercially available.
Most affected infants require early ventriculoperitoneal shunt placement.
The Dandy-Walker malformation consists of a ballooning of the posterior half of the fourth ventricle, often associated with failure of the foramen of Magendie to open, aplasia of the posterior cerebellar vermis, heterotopia of the inferior olivary nuclei, pachygyria of the cerebral cortex, and other cerebral and sometimes visceral anomalies. Hydrocephalus may not be present at birth but develops during childhood or later. The size of the lateral ventricles does not correlate with the size of the cyst in the fourth ventricle. Other malformations are present in two-thirds of children. The most common associated malformation is agenesis of the corpus callosum. Other malformations are heterotopia, abnormal gyrus formation, dysraphic states, aqueductal stenosis, and congenital tumors.
The responsible gene is on chromosome 3, but the mode of inheritance is uncertain ( ).
Diagnosis at birth occurs in only a quarter of affected newborns and in three-quarters by 1 year of age. Macrocephaly is the usual initial feature. Bulging of the skull, when present, is more prominent in the occipital than in the frontal region. The speed of head growth is considerably slower than with aqueductal stenosis. Compression of posterior fossa structures leads to neurological dysfunction, including apneic spells, nystagmus, truncal ataxia, cranial nerve palsies, and hyperreflexia in the legs.
Macrocephaly or ataxia is the indication for CT or MRI. Both studies show cystic dilatation of the posterior fossa and partial or complete agenesis of the cerebellar vermis ( Figure 18-5 ). MRI is more useful because it also identifies other cerebral abnormalities such as heterotopia. Incomplete vermian agenesis may be difficult to differentiate from an enlarged cisterna magna. The Dandy-Walker malformation is part of the spectrum of anomalies associated with trisomy 9 and with mutations on the X chromosome.
Decompression of the cyst alone provides immediate relief of symptoms; however, hydrocephalus recurs and ventricular shunting is required in two–thirds of affected children. Shunting of the lateral ventricle alone provides immediate relief of hydrocephalus but fails to relieve brainstem compression. The procedure of choice is a dural shunt of both the lateral ventricle and the posterior fossa cyst.
Even after successful shunt placement, many children have transitory episodes of lethargy, personality change, and vomiting that falsely suggest shunt failure. The mechanism of such episodes, which may prove fatal, is unknown.
Klippel-Feil syndrome is a malformation of the craniocervical skeleton that may be associated with the Chiari malformation and with basilar impression. It involves the congenital fusion of at least two cervical vertebrae. The incidence is about 1 in 40000–42000 live births. Obstruction of the flow of CSF from the fourth ventricle to the subarachnoid space causes hydrocephalus. Several different entities comprise the syndrome. One or more are recessive, one is dominant, and some may have no genetic basis. There are three types of Klippel-Feil syndrome: type I is the single fusion of two cervical vertebrae; type II is the fusion of multiple non-contiguous cervical vertebrae; and type III is the fusion of multiple contiguous cervical vertebrae. Scoliosis occurs in about 50 % of the cases and occurs more often with involvement of the lower cervical vertebrae, with multiple fusions, and with hemivertebrae ( ).
The essential features of the Klippel-Feil syndrome are a low posterior hairline, a short neck, and limitation of neck movement. Head asymmetry, facial asymmetry, scoliosis, and mirror movements of the hands are common. Unilateral or bilateral failure of downward migration of the scapula ( Sprengel deformity ) is present in 25–35 % of patients. Malformations of the genitourinary system and deafness are associated features. The deafness may be of the sensorineural, conductive, or mixed type. Hydrocephalus affects the fourth ventricle first and then the lateral ventricles. The resulting symptoms are those of posterior fossa compression: ataxia, apnea, and cranial nerve dysfunction.
Radiographs of the spine reveal the characteristic fusion and malformations of vertebrae. MRI may show an associated Chiari malformation and dilatation of the ventricles.
Children with unstable cervical vertebrae require cervical fusion to prevent myelopathy. Those with symptoms of obstructive hydrocephalus require a ventriculoperitoneal shunt to relieve pressure in the posterior fossa.
Congenital Brain Tumors
Congenital brain tumors and congenital brain malformations are both disorders of cellular proliferation. A noxious agent active during early embryogenesis might stimulate either or both abnormalities. The relative oncogenicity or teratogenicity depends on the virulence of the agent, the timing of the insult, the duration of exposure, and the genetic background and health of the fetus. The most common tumors of infancy are astrocytoma, medulloblastoma, teratoma, and choroid plexus papilloma.
Congenital tumors are more often supratentorial than infratentorial and more often in the midline than situated laterally. Newborns with hemispheric gliomas and teratomas may develop hydrocephalus in utero or in the first days or weeks postpartum. The point of obstruction is usually at the cerebral aqueduct (see Chapter 4 ). Choroid plexus papillomas are usually located in one lateral ventricle and become symptomatic during infancy rather than in the perinatal period. They produce hydrocephalus either by obstruction of the foramen of Monro or less likely by excessive production of CSF (see Chapter 4 ). Medulloblastomas are located in the posterior fossa and obstruct the fourth ventricle and cerebral aqueduct (see Chapter 10 ).
The clinical features of all congenital tumors are those of increasing intracranial pressure: enlarging head size, separation of the sutures, lethargy, irritability, difficult feeding, and vomiting. Seizures are unusual. Because of its posterior fossa location, medulloblastoma also produces nystagmus, downward deviation of the eyes, opisthotonus, and apnea.
CT or MRI, performed to investigate hydrocephalus, readily visualizes all congenital tumors. Intrauterine sonography identifies some tumors.
Vein of Galen Malformation
Arteriovenous malformations of the cerebral circulation may become symptomatic during infancy and childhood (see Chapter 4 , Chapter 10 ), but the malformation associated with congenital hydrocephalus is the vein of Galen malformation. Vein of Galen vascular malformations are not aneurysms and do not involve the vein of Galen. Instead, the normal vein of Galen does not develop and the median prosencephalic vein of Markowsky persists, dilates, and drains to the superior sagittal sinus. Multiple arteriovenous fistulas are associated.
Eighty percent of newborns with vein of Galen malformations are male. The usual initial feature is either high-output cardiac failure or an enlarging head size. Hemorrhage almost never occurs early in the course. A cranial bruit is invariably present. Some affected children experience unexplained persistent hypoglycemia.
Large midline arteriovenous malformations produce a hemodynamic stress in the newborn because of the large quantities of blood shunted from the arterial to the venous system. The heart enlarges in an effort to keep up with the demands of the shunt, but high-output cardiac failure ensues. Affected newborns often come first to the attention of a pediatric cardiologist because of the suspicion of congenital heart disease. Then, the initial diagnosis of an intracranial malformation is during cardiac catheterization.
When the hemodynamic stress is not severe and cardiac compensation is possible, the initial symptoms are in infancy or early childhood. In such a case, obstructive hydrocephalus results from compression of the tegmentum and aqueduct. Symptoms usually begin before age 5 and always before age 10. The lateral ventricles enlarge, causing headache, lethargy, and vomiting. In infants, the head enlarges and the fontanelle feels full.
Contrast-enhanced CT ( Figure 18-6 ) or MRI readily visualizes the vein of Galen malformation. The lateral and third ventricles dilate behind the compressed cerebral aqueduct. Radiographs of the chest in newborns with high-output cardiac failure show an enlarged heart with a normal shape.