are caused by overproduction of CSF (from choroid plexus papilloma). Many causative factors that result in diminished CSF absorption are recognized, including maternal malnutrition, toxins, infections (bacterial, viral, cytomegalovirus, and toxoplasmosis), and other acquired conditions (e.g., intraventricular hemorrhage, bacterial infections, trauma, tumors). Congenital malformations of the CNS sometimes affect CSF circulation, causing ventricular enlargement and increased intracranial pressure. Arnold–Chiari malformations, agenesis of the corpus callosum, cerebellar hypoplasia, Dandy–Walker malformations, and other cortical malformations are associated with hydrocephalus.713,842 In addition, microscopic changes and parenchymal destruction are common in all patients with hydrocephalus. If left untreated, the progressive ventricular enlargement causes displacement and an eventual decrease in the number and caliber of the microvasculature, resulting in decreased blood flow to the periventricular white matter. With time, the tissue destruction leads to porencephalic cysts, which are frequently seen as diffuse white matter loss and periventricular encephalomalacia.232,713

Several terms pertaining to hydrocephalus warrant clarification. Normal-pressure hydrocephalus is a form of hydrocephalus in which signs of progressive hydrocephalus exist despite the fact that the CSF pressure is within the normal range. It is most commonly encountered as a sequela of meningitis or perinatal asphyxia. Intermittent spikes of high pressure may be responsible, requiring intracranial pressure monitoring. The term arrested hydrocephalus describes a disorder in which the hydrocephalus has spontaneously resolved although some residual clinical signs may persist (e.g., enlarged head size or enlarged ventricles). The term hydrocephalus ex vacuo is used to describe the situation in which enlarged ventricles result from periventricular white matter destructionratherthanactualhydrocephalus.Hydranencephaly refers to a situation in which most of the brain has been destroyed in utero and resorbed, being replaced by a CSF-filled sac. It should be emphasized that these mechanisms of ventricular dilation are not mutually exclusive. For example, long-standing hydrocephalus due to increased intracranial pressure eventually causes periventricular tissue damage and hemispheric atrophy. Conversely, hydranencephaly may become complicated by secondary impairment of CSF circulation, causing increased intracranial pressure.

Hydrocephalus due to CSF Overproduction

Hydrocephalus secondary to CSF overproduction occurs exclusively in choroid plexus papilloma, a rare neoplasm accounting for 2–4% of childhood intracranial tumors. Although overproduction of CSF alone can produce hydrocephalus, the presence of hydrocephalus in choroid plexus

papillomas may actually result from the complex interaction of CSF overproduction and partial restriction of CSF flow.725 Nearly half of these tumors occur in the first decade of life, with many occurring in infancy. These papillomas occur in infants, most frequently in the lateral ventricles, occasionally in the third and, rarely, in the fourth ventricle. This distribution pattern is reversed in older patients. These papillomas can produce huge amounts of CSF and present during infancy with macrocephaly and signs of intracranial hypertension. The tumors most commonly originate within the trigones of the lateral ventricles. Resection of the tumor is often curative for the hydrocephalus.

Noncommunicating Hydrocephalus

Noncommunicating hydrocephalus arises from a variety of lesions that cause blockage of CSF flow within the ventricular system at any level from the foramina of Monro to the foramina of Magendie and Luschka. Underlying disorders include tumors, aqueductal stenosis, aqueductal gliosis, arachnoid cysts, congenital anomalies, and isolated fourth ventricle. Tumors are the most common cause of this type of hydrocephalus.

Communicating Hydrocephalus

Communicating hydrocephalus results from extraventricular obstruction of CSF flow or reabsorption. After the CSF exits the ventricular system through the foramina of the fourth ventricle, it enters the cisterna magna and basilar cisterns and then flows into the subarachnoid space. CSF drainage may be impaired within the cisterns or when the arachnoid villi are obstructed. Continuous intracranial pressure recordings may provide potentially misleading diagnostic information in this form of hydrocephalus.272 Causative disorders include intraventricular hemorrhage, meningitis, CSF seeding of tumor, cerebral venous sinus thrombosis, and normal-pressure hydrocephalus.

From the neuro-ophthalmologic standpoint, noncommunicating hydrocephalus is much more likely to cause impaired upgaze and the various features of the dorsal midbrain syndrome than the communicating variety, with most of these cases being due to developmental or acquired aqueductal stenosis.859 One recent study of motility disturbances found that children with hydrocephalus that was surgically treated before 1 year of age are more likely to present with strabismus, motility defects, or torticollis. The etiology of hydrocephalus, number of shunt revisions, and ventricular size had little correlation with motility disturbances.25

Common Causes of Hydrocephalus

in Children

In children, shunt malfunction, posterior fossa tumor, trauma, meningitis, and intracranial hemorrhage are frequent causes of acute hydrocephalus presentation.713,842 The common causes of hydrocephalus in the pediatric age group are summarized in Table 11.1 according to the age of onset.

Aqueductal Stenosis

Normally, the sylvian aqueduct in the newborn measures 3 mm in length and an average of 0.5 mm in cross section. The cerebral aqueduct is the most common site of ventricular obstruction of CSF flow, being the longest and narrowest passage. Complete obstruction of the aqueduct is referred to as atresia, incomplete obstruction as stenosis. In aqueductal stenosis, focal narrowing generally occurs either at the level of the superior colliculi or the intercollicular sulcus. Aqueductal stenosis occurs as a developmental abnormality or an acquired lesion due to obstruction of the sylvian aqueduct most often by tumor (e.g., tumors of the pineal gland or midbrain).696 When the aqueduct is obstructed after perinatal hemorrhage, meningitis, or other inflammatory disorder, the term aqueductal gliosis is sometimes used. The developmental variety of aqueductal stenosis accounts for approximately 20% of cases of hydrocephalus.

Less common causes of aqueductal stenosis or obstruction include systemic viral infections (e.g., mononucleosis,

Table 11.1  Common causes of hydrocephalus in the pediatric age group

Before age 2 years Aqueduct stenosis

Aqueductal gliosis (infection or hemorrhage) Chiari malformations (+/− myelomeningocele) Dandy–Walker malformation

Perinatal asphyxia, hemorrhage (premature infants) Intrauterine infection

Neonatal meningoencephalitis Congenital midline tumors Choroid plexus papilloma Vein of Galen malformation Congenital idiopathic

After age 2 years

Posterior fossa neoplasms

Aqueductal stenosis, gliosis, obstruction Chiari I malformation

Intracranial hemorrhage Intracranial infections Idiopathic

mumps),206,643 intracranial toxoplasmosis,935 basilar dolichoectasia,109 and mesencephalic venous malformations.646 Nontumoral aqueductal stenosis may occur in patients with NF1.338 A rare X-linked, genetic syndrome combines the features of aqueductal stenosis with hydrocephalus, macrocephaly, adducted thumbs, spasticity, mental retardation, and cerebral malformations (usually agenesis of corpus callosum) caused by a mutation of L1CAM.807 This condition is usually diagnosed at birth or prenatally by ultrasound and is usually lethal.806 A rarer form of aqueductal stenosis inherited as an autosomal recessive disorder has also been described.64

The onset of symptoms in both aqueductal stenosis and gliosis is usually insidious. Patients may become symptomatic at any age from birth to adulthood.745 Neuroimaging shows dilation of the lateral and third ventricles but a normalsized fourth ventricle.

Aqueductal stenosis is often accompanied by aqueductal forkingorbranchingoftheaqueductalchannel.Developmental aqueductal stenosis may be associated with fusion of the quadrigeminal bodies, fusion of the oculomotor nuclei, peaking of the tectum, and spina bifida cystica and occulta.

One rare cause of hydrocephalus due to obstruction of the sylvian aqueduct in children is an arteriovenous malformation involving the great vein of Galen (vein of Galen “aneurysm”) (Fig. 11.21).971 This malformation arises from a congenital connection between intracranial arteries (usually thalamoperforator, choroidal, and anterior cerebral arteries) and a vein in the region of the vein of Galen. This abnormal vascular communication produces aneurysmal dilatation of the short vein of Galen, located just behind the posterior wall of the third ventricle. The most common presenting symptom in children younger than 2 years of age is hydrocephalus. Neonates may present with congestive heart failure and loud intracranial bruits.

Tumors

Tumors are the most common cause of noncommunicating hydrocephalus (obstruction of CSF flow within the ventricular system) in children. The sites of obstruction are most commonly those where the ventricular pathways are the narrowest: the foramina of Monro, the sylvian aqueduct, the fourth ventricle, and the foramina of Magendie and Luschka. The location and size of the tumor are significant determinants for the development of hydrocephalus; tumor size alone is less important. For example, large pontine gliomas are only infrequently associated with hydrocephalus, but tectal gliomas almost uniformly present with hydrocephalus. Tumors may also cause increased intracranial pressure by causing brain edema and swelling and by compression of the cerebral venous sinuses.

Intracranial Hemorrhage

Intraventricular hemorrhage arising from the subependymal germinal matrix, with subsequent rupture into the lateral ventricle, is the most common variety of intracranial hemorrhages and is characteristic of premature infants. This form of hemorrhage usually arises postnatally, less commonly perinatally and, rarely, prenatally.913,914 The subependymal germinal matrix, a cellular structure located immediately ventrolateral to the lateral ventricle, is a source of cerebral neuroblasts between 10 and 20 weeks of gestation, as well as glioblasts (progenitors of cerebral oligodendroglia and astrocytes) in the third trimester. The numerous thin-walled blood vessels within the germinal matrix are a ready source of bleeding. The most common site of bleeding is just posterior to the foramen of Monro. The blood spreads from one or both lateral ventricles into the third and fourth ventricles and the basal cisterns. It enters the cerebral and spinal subarachnoid space, where it may incite an obliterative arachnoiditis within the basal cisterns with obstruction of CSF flow. Impaired CSF dynamics may also occur at the level of the sylvian aqueduct and the arachnoid villi.

This form of intracranial hemorrhage is responsible for an increasing proportion of pediatric hydrocephalus as advances in neonatology enable us to salvage an increasing number of premature infants. Hydrocephalus is considered the main complication of intraventricular hemorrhage, with periventricular hemorrhagic infarction and germinal matrix destruction being additional common complications. The likelihood and rapidity of progression of hydrocephalus after intraventricular hemorrhage are directly related to the quantity of intraventricular blood.912 Large hemorrhages may lead to hydrocephalus within days, while smaller hemorrhages lead

to hydrocephalus over weeks. Acute obstructive hydrocephalus may arise from hematoma clogging the basal cisterns or the arachnoid villi. Later, an adhesive arachnoiditis develops that perpetuates the hydrocephalus long after the red blood cells break down. Another mechanism is organization of an intraventricular hematoma with reactive gliosis of the ventricular wall.

The pathogenesis of germinal matrix hemorrhage and subsequent intraventricular hemorrhage in premature children is multifactorial and related to intravascular, vascular, and extravascular factors.913 Intravascular factors pertain to control of blood flow and pressure within the germinal matrix and include fluctuations of cerebral blood flow, abrupt increases or decreases of flow, increased cerebral venous pressure and, in some infants, disturbances of platelet function.Vascular factors pertain to the microcirculation of the germinal matrix and include vulnerability of the matrix vessels to ischemic injury. Extravascular factors include the mesenchymal and glial support for the germinal matrix vessels and the local fibrinolytic activity in the germinal matrix.913,914

The imaging procedure of choice to detect intraventricular hemorrhage in a premature infant is real-time cranial ultrasound scanning. The severity of intraventricular hemorrhage may be graded by ultrasound criteria. Grade I denotes a germinal matrix hemorrhage with intraventricular hemorrhage involving less than 10% of the ventricular area on parasagittal views, grade II involves 10–50% of that area, grade III involves greater than 50% of that area, and grade IV is associated with intraparenchymal extension.914

Periventricular leukomalacia is a frequent accompaniment of intraventricular hemorrhage in premature infants but is not causally related to the intraventricular hemorrhage.

Its co-occurrence in the same patient may complicate the clinical picture when hydrocephalus also exists, because both processes are characterized by enlarged ventricular size

– in hydrocephalus, due to elevated CSF pressure, and in periventricular leukomalacia, due to hypoxic–ischemic injury to periventricular white matter.

In full-term infants, intracranial hemorrhage occurs most frequently after trauma. Intraventricular hemorrhage is less common in full-term infants than in premature infants, and the incidence of hydrocephalus due to this complication is therefore much less in the full-term infant. It may arise from extension of a hemorrhagic cerebral infarction or a thalamic hemorrhage, vascular malformation, tumor, trauma, residual germinal matrix, or a choroid plexus hemorrhage.

Intracranial Infections

Various infectious processes involving the intracranial compartment may result in hydrocephalus. Bacterial, viral, and fungal meningitis and various protozoan and parasitic infections of the brain may be associated with or followed by hydrocephalus. Brain abscesses occasionally cause hydrocephalus and/or homonymous hemianopia. Congenital infections of the CNS (congenital toxoplasmosis, cytomegalovirus, varicella, and herpes simplex virus) occasionally manifest with hydrocephalus.

The hydrocephalus may result from more than one mechanism in any given infection. For instance, neurocysticercosis (infestation of the brain by the larval form of Taenia solium) may cause hydrocephalus through obstruction of the CSF pathways with cysts, leptomeningitis, or the mass effect and associated edema of intraparenchymal cysts.958 Intracranial hydatid cysts due to Echinococcus granulosus infection often manifest with signs and symptoms of hydrocephalus in endemic areas.278 Granulomatous meningitis (e.g., tuberculous meningitis) is more likely to cause hydrocephalus than bacterial meningitis, which is more likely to cause it than viral meningitis. Meningitis causes hydrocephalus acutely through a combination of blockage of the CSF pathways with purulent exudates and involvement of the arachnoid granulations in the infectious process. Cerebral abscesses and cerebral venous sinus thrombosis may complicate meningitis and contribute to the production of hydrocephalus. Later, fibrosis and scarring of the subarachnoid space block CSF outflow. Clogging of the arachnoid granulations with debris may play a role. Subclinical virus infections may cause “noninflammatory” aqueductal stenosis and hydrocephalus. Rarely, neurosarcoidosis may underlie the manifestation of hydrocephalus in children.930

Two other infectious diseases of the CNS associated with hydrocephalus are particularly noteworthy; AIDS and Lyme

disease. Lyme disease, a multisystem disease caused by Borrelia burgdorferi, a tick-borne spirochete, commonly affects children.76 The disorder causes various ophthalmic manifestations, including cranial neuropathies, iridocyclitis, vitritis, pars planitis, orbital myositis, keratitis, episcleritis, conjunctivitis, and optic neuritis.29 The disease may manifest as a meningitis, a meningoencephalitis, or an isolated cranial neuropathy. In some patients, the disorder may resemble idiopathic intracranial hypertension.76 AIDS also occurs in children and can present with increased intracranial pressure because of various underlying lesions (lymphomas, infections), but these intracranial lesions tend to be rarer in children with AIDS than in adults.702

Chiari Malformations

Chiari malformations are characterized by herniation of the posterior fossa contents below the level of the foramen magnum. They are categorized into three types, and it is a common misconception that this classification is based on the degree of herniation.268 The different Chiari malformations do not represent different stages in the process of herniation; rather, they represent distinct malformations with different systemic associations. For example, the Chiari I malformation can be acquired, while Chiari II malformation is associated with myelomeningocele only, and Chiari III malformation is associated with encephaloceles, and Chiari IV is aplasia of the cerebellum. The treatment is generally directed at the posterior fossa pathology and includes decompression of the cervicomedullary junction, posterior decompressive procedures (e.g., opening of outlet foramina of the fourth ventricle, fourth ventricular shunting), and ventriculoperitoneal shunting.

Generally, the major presenting symptoms of the Chiari malformations are occipital headache (particularly with cough and other Valsalva maneuvers), pain, dissociative sensory loss, and weakness.434 The signs and symptoms of Chiari malformations are largely a result of impaction of the posterior fossa contents at the foramen magnum, abnormal CSF dynamics at the craniocervical junction, and the associated hydrocephalus and syringomyelia.

Chiari I

The Chiari I is now considered to be the most common Chiari malformation and an underrecognised cause of headaches in children.5a This malformation is characterized by protrusion of the cerebellar tonsils below the level of the foramen magnum (Fig. 11.22). It may be observed in several clinically different settings: (1) Some infants develop herniation of the

Fig. 11.22  Chiari I malformation. MR image shows that cerebellar tonsils extend 1 cm below level of foramen magnum

cerebellar tonsils as a result of intrauterine hydrocephalus. These cases are usually diagnosed with hydrocephalus in infancy or early childhood. (2) Some patients may have craniocervical dysgenesis (e.g., Klippel–Feil anomaly). This group often has concurrent platybasia and cervical vertebral abnormalities and usually presents during childhood with headaches when straining and with cranial nerve palsies. (3) Some patients may have acquired deformities of the foramen magnum (e.g., basilar invagination). They are generally asymptomatic during childhood but present during adulthood, with symptoms and signs similar to group 2 above. (4) Some patients develop Chiari I as a result of lumbo-perito- neal shunting and may show resolution of the abnormalities after shunt removal. An abnormality of mesodermal development results in reduced posterior fossa volume with downward impaction of a normal sized cerebellum in most cases of Chiari I malformation.

In Chiari malformations, hydrocephalus generally results from lack of communication between the spinal subarachnoid space and the cranial subarachnoid space. The two subarachnoid compartments are separated by the impacted cerebellar tissue. Repetitive impaction of herniated cerebellar tissue with each beat of the heart creates a local increased intracranial pressure and a pressure wave in the spinal subarachnoid space and may lead to the development of syringo-

myelia. About 50% of patients with Chiari I malformation have concurrent syringomyelia. Symptoms of Chiari I may be intermittent and simulate those of multiple sclerosis.

The diagnosis of Chiari I malformation should be suspected in any patient with occipital headaches with cough strain or sneeze, vertigo, oscillopsia, ataxia, disequilibrium, or dysphagia, especially if these symptoms coexist with other more characteristic symptoms of the disorder, such as upper cervical pain or weakness.794 Compression of neural structures at the level of the medulla rarely produce systemic hypertension, which may resolve after surgical decompression.667 Skeletal abnormalities of the cervical spine, including basilar impression, atlanto-occipital fusion, atlanto-axial assimilation, and Klippel–Feil syndrome, are also associated with a high incidence of Chiari malformation.846

Neuro-ophthalmologic abnormalities reported in Chiari I malformation include the various disorders associated with increased intracranial pressure (if it coexists). An acquired downbeat nystagmus is the classical neuro-ophthalmologic finding associated with Chiari I malformation, but other types of nystagmus may occur (discussed later). It should be noted that some of the abnormalities associated with Chiari I malformation may be intermittent, causing a diagnostic quandary. Intermittent abnormalities include symptoms of increased intracranial pressure,915 oscillopsia, and downbeat nystagmus.961 A case of convergence nystagmus has been reported in which the nystagmus was provoked by a Valsalva maneuver with neck flexion or extension; the nystagmus diminished on deep inspiration.619 Precipitation of nystagmus through Valsalva maneuver or neck movements suggests an intermittent rise in intracranial pressure as the cause, as was documented by intraventricular monitoring in one patient.915 Although downbeat nystagmus is the most common cause of oscillopsia in this disorder, oscillopsia can also occur in the absence of nystagmus.344

The various eye movement disorders in Chiari I malformation largely result from cerebellar ectopia and lower brainstem distortion. Periodic alternating nystagmus, which also localizes a lesion to the level of the foramen magnum,42 has been reported. Interestingly, seesaw nystagmus (which usually localizes to the diencephalon or parasellar region)972 and convergence retraction nystagmus (which localizes to the pretectal area of the midbrain) have also been described. Another case with signs localizing to the midbrain was reported by Cogan,190 who described a patient in whom neck extension regularly induced spasm of the near reflex and an exacerbation of the downbeat nystagmus that lasted several seconds after the head was returned to the primary position. Another patient with a Chiari I malformation and spasm of the near reflex has since been reported.221 Gaze-evoked nystagmus6 and rebound nystagmus854 may occur. Other neuroophthalmologic disorders include Horner syndrome (due to associated spinal cord syringomyelia),852 comitant strabismus,