Rudolph's Pediatrics, 22nd Ed.

CHAPTER 553. Hydrocephalus and Pseudotumor Cerebri

Nicole J. Ullrich

HYDROCEPHALUS

Hydrocephalus is a condition in which there is an accumulation of cerebrospinal fluid (CSF) within the ventricles, leading to increased intracranial pressure. Hydrocephalus may be caused by increased production, decreased absorption, or obstruction to flow of CSF. By contrast, ventricular dilatation due to loss of brain tissue or atrophy is not considered to be hydrocephalus.

CEREBROSPINAL FLUID DYNAMICS

Typically, cerebrospinal fluid (CSF) is produced at a volume of 20 mL/hour, or more than 500 mL per day, in the adult. Total CSF volume in infants is approximately 50 mL, as compared to approximately 150 mL in normal adults. Cerebrospinal fluid is produced by active secretion and diffusion predominantly in the choroid plexus, located in the lateral ventricles and the roof of the fourth ventricle. Cerebrospinal fluid passes from the lateral ventricles into the paired foramina of Monro to reach the third ventricle and then along the cerebral aqueduct into the fourth ventricle. Once in the fourth ventricle, CSF flows through the midline foramen of Magendie or laterally through the paired foramina of Luschka into focally enlarged areas of subarachnoid space known as the basal cisterns, which connect the spinal and intracranial subarachnoid spaces (Fig. 553-1). Cerebrospinal fluid is in continual flow around the brain and spinal cord and within the ventricles in a cephalad direction. Production of CSF is regulated by the enzyme carbonic anhydrase, and reabsorption occurs within the arachnoid villi in the meninges into the venous channels of the sagittal sinus. Smaller amounts of CSF absorption also occurs across the ependymal lining of the ventricles. Typically, there is a delicate balance between CSF production and reabsorption; hydrocephalus results when that balance is disrupted. However, CSF production rarely fluctuates in normal circumstances and even in the face of rising intracranial pressure, unless extremely elevated pressures are reached.

POTENTIAL ETIOLOGIES

Hydrocephalus is generally classified as communicating, obstructive, and external, depending on the underlying etiology.1 Communicating hydrocephalus refers to a situation in which cerebrospinal fluid (CSF) flows freely into the subarachnoid space, but the total volume of CSF is increased secondary to either impaired reabsorption or overproduction. Impaired reuptake of CSF may result from blood within the ventricular system (as occurs with subarachnoid hemorrhage) increased protein content (resulting from meningitis) or an increased cell content from malignant cells such as leukemia. Some tumors, such as choroid plexus tumors, may increase CSF production thereby contributing to hydrocephalus (Fig. 553-2).2

Obstructive, or noncommunicating hydrocephalus, results from obstruction to the outflow of CSF. Aqueductal stenosis is the most frequent cause, accounting for about 20% of cases, with an incidence of 0.5 to 1 per 1000 births.3Anatomically, the cerebral aqueduct is vulnerable to external compression because of its long, narrow tract connecting the third and fourth ventricles. Stenosis may be congenital, often associated with spina bifida, or may result from inflammatory or neoplastic processes. The Chiari malformation describes a condition in which the inferior poles of the cerebellum protrude caudally into the foramen magnum, resulting in compression of the medulla (Fig. 553-3). These malformations, either alone or in combination with other congenital abnormalities, account for 40% of cases of hydrocephalus.4,5

Any decrease in cerebral venous drainage (and resultant increase in cerebral venous pressure), as seen with cerebral or jugular vein thromboses, can result in increased intracranial pressure (ICP) and hydrocephalus. In addition, superior mediastinal obstruction compromising superior vena cava flow has been reported as a cause of increased ICP.6,7

FIGURE 553-1. Schematic diagram of a sagittal section of the brain with arrows that trace the flow of cerebrospinal fluid. Cerebrospinal fluid flows out of the ventricular system through the fourth ventricle outlets into the basal cisterns, and then through the tentorium over the cerebral hemispheres toward the arachnoid granulations in the superior sagittal sinus. There is bidirectional flow of CSF in the spinal canal. A, lateral ventricle; B, subarachnoid space; C, cerebellum; D, foramen of Magendie; E, aqueduct of Sylvius; F, third ventricle; G, foramen of Monro.

Benign enlargement of the subarachnoid space, otherwise referred to as benign extra-axial fluid, external hydrocephalus, idiopathic external hydrocephalus, or extraventricular hydrocephalus, is relatively common, occurring in approximately 16% of infants.8,9 Head circumference typically increases to greater than the 90th percentile and then parallels the normal curve. The head growth velocity then slows to normal by the age of 6 months. Typically these children experience normal development and have normal neurologic examination; nonetheless, their development should be monitored closely.10 This benign increase in the size of the subarachnoid space should be contrasted with the extra-axial fluid collections that are observed in children who spent extensive periods of time in the neonatal intensive care unit or on extracorporeal membrane oxygenation. In these circumstances, the increased head size and fluid collections may be associated with adverse neurologic sequelae and/or poor developmental outcomes.11

CLINICAL SIGNS AND SYMPTOMS

The clinical signs and symptoms of hydrocephalus are nonspecific and independent of underlying etiology. In young children, the most obvious sign of hydrocephalus is a rapid increase in head size, often accompanied by a bulging, enlarged anterior fontanel, conspicuous scalp veins, and/or frontal bossing.3 Other symptoms may include irritability, increased sleepiness, vomiting, seizures, and downward eye deviation—the “setting sun sign”—in which the sclerae are visible above the iris.12 In older children, symptoms of hydrocephalus reflect the increased intracranial pressure and include headaches, nausea, vomiting, and, occasionally, changes in vision with double vision and/or blurry vision. Headaches that are the result of increased intracranial pressure often occur early in the morning and may be associated with nausea and vomiting. Prolonged increases in intracranial pressure (ICP) may be accompanied by changes on ophthalmological examination, such as papilledema, as well as changes in balance or walking and increased sleepiness. Physical examination may also demonstrate palsies of the third or sixth cranial nerves.

EVALUATION AND MANAGEMENT OF HYDROCEPHALUS: CEREBROSPINAL FLUID DIVERSION

Evaluation for hydrocephalus includes imaging studies to assess the ventricular size and to assess for signs of anatomical obstruction, the presence of mass lesions, or signs of impending herniation. In young infants, ultrasonography is the preferred imaging modality, because it is portable and avoids ionizing radiation. In older children, computerized tomography (CT) or magnetic resonance imaging (MRI) should be performed.13 In addition, direct ophthalmoscopy is useful to evaluate for signs of papilledema, reflecting increased intracranial pressure (Fig. 553-4).12

FIGURE 553-2. Hydrocephalus resulting from a choroid plexus papilloma in a 3-month-old boy, resulting in enlargement of the left lateral ventricle and midline shift. Tumors are thought to arise from the choroid plexus and tumor cells secrete cerebrospinal fluid, leading to an increased amount of fluid and, eventually, to hydrocephalus.

The goal of therapy is to relieve the increased intracranial pressure, restore flow of cerebrospinal fluid (CSF), and prevent irreversible neurologic deterioration. This can be achieved by several approaches. Often, mechanical shunts are placed as soon as the hydrocephalus is recognized in order to drain excess accumulation of CSF. Although this does not address the cause of the hydrocephalus, it does effectively treat the symptoms and stops progression of the ventricular dilatation and minimizes neurologic deterioration. Shunt placement involves placement of a plastic catheter directly into the ventricle, typically on the right. The catheter can be connected to a one-way valve system to better regulate pressure; alternatively, a reservoir can be placed to administer chemotherapy. The catheter is tunneled under the skin and the distal end of the system is then connected and placed into the right atrium of the heart (ventriculoatrial shunt) or into the peritoneal cavity (ventriculoperitoneal shunt). This allows a bypass of the site of obstruction, either mechanical or functional, into a site where the fluid can be reabsorbed into the systemic circulation. Externalized shunt devices, also referred to as external ventricular drains (EVDs) are often placed in the setting of acute hydrocephalus for pressure monitoring and temporary CSF diversion. They may also be placed during management of a shunt infection.

FIGURE 553-3. Sagittal magnetic resonance image of a patient with neurofibromatosis type 1 and a Chiari I malformation, in which the cerebellar tonsils protrude through the foramen magnum into the spinal canal (arrow). This may cause secondary aqueductal stenosis and hydrocephalus, requiring surgical decompression.

Endoscopic third ventriculostomy (ETV) is a procedure in which a perforation is placed in the floor of the third ventricle, creating a direct connection to the subarachnoid space and thus bypassing the obstruction.14,15 This procedure has been used for the initial treatment of select cases of obstructive hydrocephalus and as an alternative to shunt revision. ETV may avoid the issues related to foreign body implantation and establishes a more “physiologic” cerebrospinal fluid circulation, thus avoiding the need for future shunt-related complications and/or the need for revisions.16 The overall success of ETV depends on the age of the patient and the etiology of the hydrocephalus; shunt failure and/or webbing along the ventriculostomy site may occur, leading to secondary obstruction and the need for a repeat procedure.14,17 Medical therapy, such as diuretics and serial lumbar punctures, can be used as a temporizing measure if the underlying etiology is thought to be transient and the child is stable clinically (see section below on treatment of pseudotumor cerebri).18,19 For further management of hydrocephalus in the preterm and newborn infant, see Chapter 52.

SHUNT MALFUNCTIONS

Complications of shunts implanted for hydrocephalus typically result from mechanical malfunction of the shunt or to infection.20 Mechanical failure is more likely during the first year after shunt placement, and primarily results from obstruction at the ventricular site, due to broken tubing or migration of all or a portion of the shunt.

Shunt infection is often caused by skin flora, such as staphylococcus epidermidis, followed less frequently by infections with Staphylococcus aureus, enteric bacteria, and Streptococcus species.20 This may occur at the time of surgery or in the postoperative period due to breakdown of the overlying skin. The incidence of shunt infection is highest during the month after initial placement and in patients requiring multiple revisions, and ranges from 5% to 15%.21 Infection must be considered in any child with a mechanical shunt who develops a persistent fever. Shunt infections can present with few or no symptoms; in some cases, symptoms develop only when subsequent obstruction occurs, leading to increased intracranial pressure. Ventriculoperitoneal shunts may also present with symptoms of peritonitis, including fever, abdominal pain, and anorexia. Ventriculoatrial infections can also present with fever and bacteremia. Diagnostic evaluation includes plain radiographs of the skull, neck, chest, and abdomen (shunt series) to look for mechanical breaks, kinks, and disconnections in the shunt, and a cranial computed tomography (CT) scan to evaluate for signs of increased ventricular size, blood culture and cerebrospinal fluid (CSF) analysis, preferably through direct aspiration of the shunt. Antibiotic therapy is guided by the results of the CSF analysis. In most cases, the shunt must then be removed; if the underlying hydrocephalus remains an issue, another drainage procedure would be indicated with replacement of the shunt once the CSF is sterile.

PSEUDOTUMOR CEREBRI/IDIOPATHIC INTRACRANIAL HYPERTENSION

Pseudotumor cerebri, also known as idiopathic or benign intracranial hypertension (IIH), is a syndrome of increased intracerebral pressure in the absence of change in ventricular size, with normal cerebrospinal fluid (CSF) fluid analysis and normal neuroimaging.

EPIDEMIOLOGY/POPULATIONS AT RISK

The incidence of idiopathic or benign intracranial hypertension (IIH) is 0.9 per 100,000 persons in the general population, including children; the risk is thought to be higher in adolescents compared to children, and in women ages 20 to 44 years, who are more then 20% above ideal body weight.22 In one meta-analysis of studies evaluating IIH in childhood, there was an even gender distribution in children less than 12 years; however, in children 12 to 17 years, more than 70% were female, and the rates of obesity were significantly higher.23 Idiopathic or benign intracranial hypertension has been associated with numerous underlying secondary comorbidities, including endocrine, rheumatologic, and immunologic conditions.24 In addition, medications such as corticosteroids, nitrofurantoin, and vitamin A derivatives have been associated with secondary IIH. Some of these are well supported, whereas others are cited in case reports. Up to 84% of prepubertal children have an identifiable cause of the IIH.

PATHOPHYSIOLOGY

The pathophysiology of IIH remains poorly defined. Based on the current understanding of cerebrospinal fluid (CSF) flow, proposed contributors may include CSF overproduction or underabsorption, cerebral edema, or vascular congestion resulting in elevated cerebral venous pressure and resistance to the outflow of CSF.25

CLINICAL FEATURES

Presenting symptoms vary with age of onset, yet are similar to those associated with hydrocephalus and typically include headache and changes in vision. As noted above, headaches that occur in the setting of increased intracranial pressure (ICP) are often worse at night and may lead to nighttime awakenings. Valsalva maneuvers, during coughing or defecation, may worsen the headache. Some patients experience blurry or double vision, as with hydrocephalus, in addition to pulsatile tinnitus. Ataxia, torticollis, paresthesias, facial numbness or pain, and dizziness have also been described.

By definition, the neurologic examination is typically normal, although there may be falsely localizing palsy of the abducens or facial nerves. Patients with IIH should be referred to an ophthalmologist for full acuity and visual field testing, including the perimetry. Papilledema, characterized by optic disc edema with elevation of the optic nerve head, blurring of the disc margin, loss of venous pulsations, and venous congestion, is almost always noted in adults, but may be inconsistent in children and adolescents (Fig. 553-4). Papilledema is typically not observed in infants, because the increased intracranial pressure (ICP) is at least in part relieved by the splitting of the sutures and bulging of the fontanel. Loss of vision may either occur before the definitive diagnosis has been made, or may occur after several years. Typical changes in visual field include enlargement of the physiologic blind spot and presence of scotomas and other abnormalities.26 One study demonstrated visual field changes in 85% of prepubertal children at time of presentation.27 Visual acuity testing and detailed visual field evaluation is necessary at baseline and after initiation of treatment to evaluate for progressive optic atrophy.

FIGURE 553-4. This view of the optic disc demonstrates papilledema, or swelling of the optic nerve, resulting in optic disc edema as a result of increased intracranial pressure. Papilledema is almost always bilateral and can occur in hours to weeks.

DIAGNOSIS

The diagnosis of idiopathic or benign intracranial hypertension (IIH) is made by demonstration of cerebrospinal fluid (CSF) pressure greater than 25 cm H2O, a normal CSF composition, and the exclusion of any structural, anatomical or vascular lesions that might otherwise result in increased intracranial pressure. By definition, no other cause of increased intracranial pressure (ICP) should be identified. The diagnosis requires a thorough medication history to determine possible drug exposures and recent weight gain that might represent risk factors.

Neuroimaging studies should be performed in any person who presents with headache and papilledema to exclude the presence of an underlying mass lesion or hydrocephalus. Although computerized tomography (CT) scan is often the first imaging modality utilized in many children, magnetic resonance imaging (MRI) is preferable.13 Up to 70% of persons with IIH are found to have an empty sella on neuroimaging; this is thought to result from the longstanding effects of pulsatile high-pressure CSF that leads to downward herniation of the arachnocele through a defect in the sella.28 In addition, flattening of the posterior sclera is commonly observed in up to 80% of patients, without other associated ocular abnormalities such as enhancement of the prelaminar optic nerve, tortuosity of the orbital optic nerve, or distension of the perioptic subarachnoid space.29 Evaluation of the venous sinus system using magnetic resonance venography is important to exclude cerebral venous thrombosis, which can mimic IIH in children and adults.

Lumbar puncture is performed after imaging studies confirm the lack of space-occupying lesion. Ideally, opening pressure of CSF is measured with the patient lying relaxed with both legs extended in the lateral decubitus position. The pressure is then measured and CSF sent for analysis of cell count, glucose, protein, cytology, and infectious studies. When the opening pressure is elevated, CSF should be removed until the closing pressure approximates normal levels.

TREATMENT

The goal for therapy of idiopathic or benign intracranial hypertension (IIH) is to treat the symptoms such as headaches and to prevent deterioration of vision and subsequent permanent visual impairment. Treatment should be coordinated between a neurologist and an ophthalmologist with regular evaluations to assess for progressive vision loss.30

In patients for whom a precipitating factor or contributor has been identified, withdrawal of that agent or treatment of the underlying condition may itself lead to resolution of the symptoms. For example, weight loss may lead to recovery of papilledema and improvement in visual fields. Thus, supervised weight loss may be the first line treatment for overweight children with IIH.31

As noted above, the production of CSF is controlled in large part by the enzyme carbonic anhydrase. The diuretic agents acetazolamide and furosemide decrease CSF production by inhibition of choroid plexus carbonic anhydrase; acetazolamide is much more potent in terms of specific inhibition of choroid plexus carbonic anhydrase, however, and is recommended for the first line medical therapy.32,33Possible side effects include gastrointestinal upset, extremity tingling, anorexia, and drowsiness. Furosemide is less potent when given alone, but has been used as an adjunct to acetazolamide. Steroids may also be effective, but are not recommended for long-term use because of potential side effects, which include elevation of intracranial pressure (ICP).

Repeated lumbar punctures have been used as a temporizing measure. However, the long-term efficacy is probably poor, because CSF is replenished within several hours after the intervention. Patients who experience progressive optic atrophy or visual field deterioration despite maximal medical therapy may benefit from optic nerve fenestration to relieve the papilledema.34,35 The procedure involves creating a window, or fenestration, into the optic nerve sheath just proximal to the globe. Unilateral fenestration ultimately leads to improvement bilaterally in many patients as well as reduction in severity of headache. Efficacy has been shown primarily in adults, with stabilization or improvement in vision in up to 85% to 100% of patients and concomitant improvement of visual function. Experience in children is more limited but results are thought to be comparable. Although this does not relieve the increased ICP, it may spare vision.

Surgery, such as placement of lumboperitoneal or ventriculoperitoneal shunt, is reserved for children in whom visual function is severely compromised and/or continues to deteriorate despite maximal medical management.36