The editors and current author would like to thank and acknowledge the significant contribution of the previous author of this chapter from the 2004 first edition, Dr. Andrée M. Bouterie. This current second edition chapter is a revision and update of the original author’s work.
A 12 week old female infant presents to the emergency department with progressive vomiting, lethargy, and difficulty feeding over the past two days. Her mother reports that the infant has been increasingly irritable in the last week, and does not appear to be herself. She has been less interactive, and her cry has become more high-pitched and weak. She has not been breastfeeding well. Additionally, her mother is concerned because she thinks her infant's head has grown, and the "soft spot" on her head appears fuller. She thinks that the infant has felt "warm", but she has not measured the temperature with a thermometer. The infant has had fewer wet diapers and no bowel movements today. She reports that the infant was born on time and that there were no prenatal or perinatal complications. The infant was released after a 48 hour stay in the regular newborn nursery, and had follow-up initially with her pediatrician about 1 week after discharge. She has had no further follow-up. From the previous medical records it is confirmed that the infant was born at term. There was poor prenatal care, but the labor and delivery were unremarkable. Mother's prenatal labs were normal. The infant weighed 2900 grams at birth (25th percentile), measured 47.8 cm in length (10th to 25th percentile), and had a head circumference of 34 cm (25th percentile).
Exam: VS: T 36.5 C, P 165, R 45, BP 98/65. Weight 4.20 kg (5th percentile), length 57 cm (10th to 25th percentile), HC 42.6 cm (95th percentile). In general, this is a lethargic infant with a weak, high-pitched cry. Her head is oddly shaped and looks like an inverted pear. Her scalp veins are prominent, and the anterior fontanelle is tense and bulging. Eyes show pupils which are equal and round, but are sluggishly reactive to light. Red reflex is present bilaterally. Extraoccular movements (EOM) are clearly dysconjugate. She has a downward gaze. There is mild tachypnea with slight intercostal retractions. Lung fields are clear to auscultation bilaterally. Her heart examination reveals tachycardia with a regular rhythm and a grade 2/6 systolic ejection murmur at the left sternal border. Capillary refill is 2 seconds. Her spine is straight without protrusions or apparent defects. Her upper extremities show good tone and full range of motion with slightly brisk reflexes. Her lower extremities show increased tone with brisk reflexes bilaterally. There is 4+ clonus bilaterally. On neurologic examination, there is a poor suck. The startle response is minimally present. The grasp and glabellar reflexes are present. No parachute reflex can be elicited. The Moro is present.
Imaging studies demonstrate hydrocephalus and aqueductal stenosis. A ventriculoperitoneal shunt procedure is performed by a neurosurgeon. Following surgery, the patient's anterior fontanelle is concave and the head circumference has decreased.
Hydrocephalus is defined as the abnormal accumulation of cerebrospinal fluid (CSF) within the central nervous system (CNS), due to a disruption in its formation, flow, or absorption (1). This definition excludes such conditions as benign intracranial hypertension, in which there is no increase in CSF volume, as well as cerebral atrophy and focal destructive lesions, which lead to a passive accumulation of CSF secondary to an increase in available space (sometimes referred to as hydrocephalus ex vacuo) (1).
Most CSF is produced by the choroid plexus located within the four ventricles of the brain, with 20% produced by transependymal movement of fluid from brain parenchyma to ventricular system. CSF flows through the ventricular system from the lateral ventricles to the third ventricle by way of the intraventricular foramina of Monro, then to the fourth ventricle through the cerebral aqueduct, and out the fourth ventricle through the foramina of Luschka and Magendie to circulate throughout the subarachnoid space (2). Conventional knowledge holds that CSF is reabsorbed into the venous system entirely through the arachnoid granulations of the subarachnoid space, although recent evidence has called this into question. Proposed alternative sites of reabsorption include olfactory nerves, the cribriform plate, nasal lymphatics, and across brain tissue itself (1). These alternative pathways appear to play a greater role in fluid dynamics in patients younger than one year of age, in whom arachnoid granulations are not yet fully developed (3,4).
An increase in volume of CSF can be due to a disruption in its formation, flow, or absorption. However, the rate of absorption is capable of increasing in response to an increase in CSF pressure, and therefore increased production of CSF will rarely result in hydrocephalus as absorption can increase accordingly (5). The exception to this is the case of a choroid plexus papilloma, a benign tumor usually located in the antrum of the lateral ventricle that can cause hydrocephalus by overproduction of CSF so substantial that it is capable of exceeding absorptive capabilities (2,5). Excluding this exception, hydrocephalus can then be classified as either communicating or non-communicating. Communicating hydrocephalus involves a disruption in absorption of CSF from the subarachnoid space to the venous circulation, whereas non-communicating hydrocephalus involves a disruption in flow of CSF from the ventricles to the subarachnoid space (1). "Communicating" therefore refers to whether the increase in CSF volume is spread throughout the CNS or is confined to the ventricles. Some authors refer to communicating hydrocephalus as "absorptive" hydrocephalus and non-communicating hydrocephalus as "obstructive" hydrocephalus, but this classification is problematic given that almost all hydrocephalus involves obstruction at one point or another, be it within the ventricles or at the level of the arachnoid granulations.
The differential diagnosis of hydrocephalus is extensive. Hydrocephalus can be classified by etiology as either congenital or acquired. Congenital hydrocephalus is present at birth, while acquired hydrocephalus occurs after development of the brain and ventricles has occurred. Congenital hydrocephalus accounts for approximately 55% of cases of pediatric hydrocephalus (1), and occurs in approximately 1/1000 births (5). It is most often a result of structural abnormalities as seen in Dandy-Walker malformation, holoprosencephaly, myelomeningocele and Chiari malformations, aqueductal stenosis, arachnoid cysts, vein of Galen malformation, or rarely congenital neoplasms. It is also more rarely caused by hemorrhage or infection during fetal growth and development. Congenital hydrocephalus can be further divided into syndromic or non-syndromic, with syndromic hydrocephalus referring to any hydrocephalus due to a genetic anomaly (6). The associated syndromes are numerous, and include X-linked hydrocephalus, chromosomal defects, Walker-Warburg syndrome, achondroplasia, and various lysosomal storage diseases (1,6). Acquired hydrocephalus is most often due to neoplasm, hemorrhage, or infection, but can also be caused by acquired aqueductal stenosis or cerebral venous or sinus thrombosis. Up to 15% of cases of hydrocephalus are idiopathic (2). The more common causes of hydrocephalus will be discussed below.
Dandy-Walker malformation (DWM) is a complex consisting of hypoplasia or agenesis of the cerebellar vermis, cystic enlargement of the fourth ventricle, and elevation of the roof of the posterior fossa (7). DWM occurs in 1/25,000 births and is more common in girls than boys (2). Hydrocephalus is observed in 80% of cases of DWM (7). Usually not present at birth, it tends to develop within the first 3 months of life (7) and its pathogenesis is still poorly understood. In addition to the usual findings of hydrocephalus, patients with DWM often have a prominent bulging occiput (8).
Chiari malformations involve inferior displacement of the cerebellum and brainstem. In type I, the cerebellar tonsils extend into the foramen magnum. In type II, a myelomeningocele causes the cerebellar vermis and tonsils, medulla, and pons to herniate through the foramen magnum into the spinal canal and compress the fourth ventricle. While both type I and type II malformations are associated with hydrocephalus, it is much more common in type II, occurring in 80% to 90% of patients with myelomeningocele (1). In half of these cases, hydrocephalus is evident at birth (1).
Aqueductal stenosis is an important cause of hydrocephalus that can be either congenital or acquired, accounting for 10% of cases of pediatric hydrocephalus altogether (2). Aqueductal stenosis causes non-communicating hydrocephalus by obstructing flow of CSF through the cerebral aqueduct with subsequent enlargement of the lateral and third ventricles. Congenital aqueductal stenosis encompasses not only narrowing of the cerebral aqueduct but also "forking" of the aqueduct, with formation of small aqueductal branches, and formation of an aqueductal septum. It is seen in Bicker-Adams syndrome, an X-linked hydrocephalus that accounts for 7% of cases of hydrocephalus in males, in which aqueductal stenosis is accompanied by severe mental retardation and flexion-adduction abnormalities of the thumbs (2). Acquired aqueductal stenosis is most often due to neoplasm, infection with secondary gliosis, or germinal matrix hemorrhage (2,5).
Intraventricular hemorrhage (IVH) primarily occurs in preterm infants, and is due to a combination of factors including impaired autoregulation of cerebral blood flow, hypotension and low cardiac output, fragile and immature vasculature, metabolic abnormalities including hypoglycemia and hypernatremia, and impaired immune responses (9). IVH occurs in 40% of preterm infants weighing less than 1500g at birth, and generally occurs within the first 24 hours of life (2). When hydrocephalus occurs as a consequence of IVH, it is referred to as post-hemorrhagic hydrocephalus (PHH), and is thought to be due to impaired CSF absorption due to fibrosis and gliosis following hemorrhage (9), although rarely it may be due to obstruction of the aqueduct from blood or blood products (2). Nonprogressive ventricular dilatation is apparent in 25% of patients with IVH, and progressive PHH occurs in an additional 25% (9). In preterm infants in whom PHH develops with evidence of raised intracranial pressure (ICP), management is aimed at delaying permanent shunt placement, as earlier placement has been associated with poorer prognosis in these patients. Repeat lumbar punctures up to once per day are the initial intervention, followed by temporary CSF diversion through the use of a ventricular reservoir or ventriculosubgaleal shunt should elevated ICP persist. Only 15% of patients with IVH will require permanent CSF diversion (9).
Infectious causes of hydrocephalus include meningitis, encephalitis, congenital syphilis, CMV, toxoplasmosis, and mumps (1). Bacterial meningitis more commonly causes hydrocephalus than viral meningitis. Hydrocephalus is usually communicating, and pathogenesis is thought to be due to arachnoidal fibrosis (2). Non-communicating hydrocephalus can also occur due to acquired aqueductal stenosis.
The clinical manifestations of hydrocephalus depend primarily on whether it is compensated or uncompensated, i.e., whether or not an increase in CSF volume has translated into an increase in intracranial pressure (ICP). ICP is the sum of pressures exerted by the brain parenchyma, the CSF, and the vascular system. The Monro-Kellie doctrine states that due to the fixed volume of the cranium, an increase in volume of any one of these components will lead to an increase in ICP unless it is accompanied by an equivalent decrease in the volume of one of the other components. A gradual increase in CSF volume allows compression of brain parenchyma to maintain a normal ICP, and patients will less likely present with characteristic signs and symptoms of increased ICP. Infants and young children with non-fused cranial bones also have the additional capability of spreading apart the cranial bones to achieve an increase in cranial volume (5). The clinical features of hydrocephalus thus depend not only on the rate at which CSF volume increases but also upon the age of the child.
In children over 2 years of age, cranial sutures are generally closed and with the acute onset of hydrocephalus, the child will likely present with signs and symptoms of increased ICP including nausea, vomiting, headache, drowsiness, gait changes, papilledema with associated blurred vision, and impaired upward or lateral gaze (1). Cushing's classic triad of hypertension with widened pulse pressure, bradycardia, and irregular respirations is a late finding of increased ICP in children, and when it occurs is associated with high rates of mortality (19). More indolent but progressive hydrocephalus may manifest with learning problems, reduced intellectual function, and delayed neurological development (1). Abnormal hypothalamic functions including abnormalities in growth, obesity, delayed puberty, and diabetes insipidus can occur secondary to either increased ICP or dilatation of the third ventricle (1).
Infants and young children less than 18 months of age are less likely to present with signs of increased ICP, as their cranial sutures are generally not yet fused allowing enlargement of the skull. More subtle signs of increased ICP are possible, particularly with a rapid accumulation of CSF, and may include drowsiness, irritability, poor feeding, and vomiting (1). Failure to thrive, delayed development, apneic spells, bradycardia, divergent strabismus, upward gaze palsy, persistence of early infantile reflexes, and spasticity of the lower extremities may also be evident (1,8). The "setting sun sign" is an early indicator of hydrocephalus, in which there is a forced downward deviation of both eyes leading to disappearance of a portion of the iris below the lower eyelid (10). The characteristic abnormality seen in infants is an increase in head circumference, or macrocephaly. Macrocephaly is rarely present at birth, and usually develops gradually. Accompanying signs include distended scalp veins that become particularly dilated when the child cries, thin and shiny scalp skin, splaying of cranial sutures, and a large, tense, non-pulsatile anterior fontanel (1,8). Advanced hydrocephalus can lead to craniofacial disproportion where the face appears small relative to the cranium, accompanied by low-set ears and eyes (1,8).
Imaging techniques are becoming increasingly helpful in the diagnosis of hydrocephalus, particularly in the fetal period. Fetal hydrocephalus can be identified in utero using ultrasonography or MRI to detect ventricular enlargement at as early as 8 weeks gestation. Diagnosis of hydrocephalus in a neonate requires identification of ventricular enlargement as well as an abnormal rate of skull growth, defined as head circumference greater than 2 standard deviations above the mean based on body weight or length, accelerated growth crossing centile curves, or continued head growth of more than 1.25 cm per week (1). The differential diagnosis of macrocephaly includes chronic subdural hematoma, expanding porencephalic cyst, hydrencephaly, mass lesions, or megalencephaly (increase in the brain parenchyma itself).
In infants with an open anterior fontanelle, cranial ultrasound can be used to quickly and easily identify ventricular enlargement. Although CT is sometimes used, MRI is the imaging modality of choice for identifying ventricular enlargement in older children and evaluating the underlying cause of hydrocephalus. Dilation of the ventricles proximal to the obstruction is characteristic of non-communicating hydrocephalus, whereas dilation of the entire ventricular system with enlargement of the subarachnoid space is seen in communicating hydrocephalus (11).
Treatment options depend on the child’s age, symptomatology, and underlying cause of the hydrocephalus. Rapid onset of hydrocephalus with evidence of increased ICP is an emergency and requires urgent management. Post-hemorrhagic and post-meningitic hydrocephalus can be treated with lumbar puncture in this situation. Infants may be treated with ventricular tap. Other options include external ventricular drainage and placement of a ventriculoperitoneal (VP) shunt (1).
Shunting procedures are the mainstay of treatment of hydrocephalus, allowing decompression of the ventricular system. A VP shunt is placed between the lateral ventricle and the peritoneal cavity, which is preferential because the peritoneum can accommodate a greater catheter length and obviate the need for shunt replacement as the child grows. Alternative sites of drainage include the pleural cavity and the right atrium, the latter of which is known as a vascular shunt and is accomplished by way of the jugular vein and superior vena cava. Shunts allow unidirectional flow of CSF due to a valve system with a preset pressure requirement for flow (1).
Complications of VP shunting include infection, peritonitis, CSF ascites, inguinal hernia, intra-abdominal cysts, intracranial granulomas, gastrointestinal obstruction, migration of shunt within peritoneal cavity, headache, and perforation of abdominal viscera (1). Infection occurs in up to 10% of patients (12), and usually occurs in the first two months after shunt placement (1). Headaches may be due to "slit ventricle syndrome", a condition in which severe headaches are accompanied by normally sized or small ventricles in a patient with a shunt (1). Craniosynostosis may also occur in infants in whom a shunt is placed, as decompression of the ventricles may interfere with cranial vault growth and lead to premature fusion of sutures in this population (13). Rates of shunt failure are high, with up to 40% failing in the first year after placement (1), and a subsequent 10% each year thereafter (14). Signs of shunt failure (also known as shunt obstruction) include bulging fontanelle, fluid collection along the shunt, depressed level of consciousness, irritability, abdominal pain, nausea and vomiting, abnormal shunt pump test, accelerated head growth, and headache (15). Brain imaging is routine performed to assess VP shunt function. CT scanning is rapid, brief, and more available, but there is some harm from the radiation exposure. MRI scanning is slow, is less easily obtained, and requires sedation. Some centers are using rapid MRI protocols specifically to assess VP shunt function in which few scans are obtained using faster sequencing methods to shorten the MRI imaging time and avoid the need for sedation. Common reasons for failure include obstruction, infection, mechanical failure, overdrainage, loculated ventricles, and abdominal complications (1).
Endoscopic third ventriculostomy (ETV) is another treatment option, in which an opening is created in the floor of the third ventricle to allow passage of CSF directly into the basal cisterns for subsequent absorption by arachnoid villi. Unlike VP shunt placement, which may be used to treat both communicating and non-communicating hydrocephalus, ETV is useful only in cases of non-communicating hydrocephalus. Additionally, given the poor development of arachnoid villi in young infants, failure rates are high in this population and therefore many experts do not recommend ETV in patients younger than 1 year of age (4,14). The major advantages of ETV are avoidance of foreign body implantation and the establishment of a physiological CSF circulation (16), which can prevent many complications associated with VP shunt placement. Incidence of infection is also lower with ETV compared to VP shunting, and the infections that do occur tend to have a more benign course (16). ETV failure has been found to occur in 10% to 20% of patients with aqueductal stenosis and up to 50% of patients in whom the procedure is performed for other indications (14). Other complications include rare permanent neurologic complications including hemiparesis, gaze palsy, memory disorders, and altered sensorium, intraoperative hemorrhage, permanent diabetes insipidus, weight gain, and precocious puberty (14).
Not all patients with hydrocephalus require surgical decompression of the ventricular system. In patients with hydrocephalus due to an accessible mass, resection of the mass may suffice to resolve the hydrocephalus and shunt placement or ventriculostomy may prove unnecessary. Mild and slowly progressive hydrocephalus may be initially treated with medical management (mannitol, acetazolamide, or furosemide) or observation alone. Observation is also reasonable in the rare case of chronic, non-progressive hydrocephalus with normal CSF pressure; however these patients must be watched carefully for signs of neurologic impairment (1).
Mortality rates and developmental outcomes of congenital hydrocephalus vary greatly and are dependent upon the underlying etiology. Hydrocephalus due to arachnoid cysts, atresia of Monro, corpus callosum agenesis, and fetal intracranial hemorrhage are associated with good outcomes (normal development or mild retardation), while hydrocephalus due to holoprosencephaly, encephalocele, fetal virus infection, or syndromic hydrocephalus more commonly leads to poor outcomes (severe retardation or death) (6). Similarly, neurologic sequelae in patients with pediatric hydrocephalus are largely related to the underlying etiology rather than the hydrocephalus itself. Adult morbidity is due to, in descending order of frequency, cognitive impairment, motor impairment, epilepsy, behavior disturbance, endocrine disorders, vision loss, pain, and breathing problems (17). In addition, the vast majority of patients with VP shunts will require at least one shunt revision, and this risk continues into adulthood although the frequency of shunt malfunctions does decrease as patient’s age. Only very rarely will a shunted patient ever achieve shunt independence (17).
Most patients treated for hydrocephalus will now reach adult age; however, data on lifelong functional and social outcomes are lacking. Ideally, patients should be followed throughout their lifetimes with careful attention paid to psychosocial, educational, and vocational needs (18).
1. True/False: CSF overproduction is a common cause of hydrocephalus.
2. What are some signs and symptoms of increased ICP in a young child?
3. What is the difference between hydrocephalus, megalencephaly, and macrocephaly?
4. What would be the purpose of routine cranial ultrasound screening in very low birth weight infants?
5. True/False: The diagnosis of hydrocephalus in a neonate is made on the basis of increased ventricular size alone.
6. What is the "setting sun" sign?
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2. Cohen AR. Ch. 40 - Disorders in head size and shape. In: Martin: Fanaroff and Martin's neonatal-perinatal medicine. 9th ed. Mosby; 2010.
3. Symss NP, Oi S. Theories of cerebrospinal fluid dynamics and hydrocephalus: historical trend. J Neurosurg Pediatrics. 2013;11:170-177.
4. Oi S, Di Rocco C. Proposal of "evolution theory in cerebrospinal fluid dynamics" and minor pathway hydrocephalus in developing immature brain. Childs Nerv Syst 2006;22(7):662-669.
5. Fenichel G. Ch 4 – Increased intracranial pressure. In: Clinical pediatric neurology. 6th ed. Saunders; 2009.
6. Yamasaki M, Nonaka M, Bamba Y, Teramoto C, Ban C, Pooh R. Diagnosis, treatment, and long-term outcomes of fetal hydrocephalus. Seminars in fetal and neonatal medicine 2012;17:330-335.
7. Spennato P, Mirone G, Nastro A, Buonocore MC, Ruggiero C, Trischitta V, Aliberti F, Cinalli G. Hydrocephalus in Dandy-Walker malformation. Childs Nerv Syst 2011;27:1665-1681.
8. Varma R, Williams SD, Wesse HB. Ch 15 – Neurology. In: Zitelli and Davis' Atlas of Pediatric Physical Diagnosis. 6th ed. Saunders; 2012.
9. Robinson S. Neonatal posthemorrhagic hydrocephalus from prematurity: pathophysiology and current treatment concepts. J Neurosurg Pediatrics. 2012;9:242-258.
10. Boragina M, Cohen E. An infant with the "setting-sun" eye phenomenon. CMAJ 2006;175(8):878.
11. Bouterie AM. Chapter XVIII.9. Hydrocephalus. In: Yamamoto L, Inaba A, Okamoto J, Patrinos M, Yamashiroya V (eds). Case Based Pediatrics for Medical Students and Residents. Honolulu; 2004.
12. Drake JM. The surgical management of pediatric hydrocephalus. Neurosurgery 2008;62(2):633-640.
13. Doorenbosch X, Molloy CJ, David DJ, Santoreneos S, Anderson PJ. Management of cranial deformity following ventricular shunting. Child’s Nervous System 2009;25:871-874.
14. Moorthy RK, Rajshekhar V. Endoscopic third ventriculostomy for hydrocephalus: A review of indications, outcomes, and complications. Neurology India 2011;59(6):848-853.
15. Piatt JH. Clinical diagnosis of ventriculoperitoneal shunt failure among children with hydrocephalus. Pediatr Emerg Care 2008;24(4):201-210.
16. Di Rocco C, Massimi L, Tamburrini G. Shunts vs endoscopic third ventriculostomy in infants: are there different types and/or rates of complications? Childs Nerv Syst 2006;22:1573-1589.
17. Vinchon M, Baroncini M, Delestret I. Adult outcome of pediatric hydrocephalus. Childs Nerv System 2012;28:847-854.
18. McDonagh JE, Viner RM. Lost in transition? Between paediatric and adult services. BMJ 2006;332:435-436.
19. Tsze DS, Steele DW. Neurosurgical Emergencies, Nontraumatic. In: Fleisher GR, Ludwig S. Textbook of Pediatric Emergency Medicine. 6th edition. Lippincott Williams & Wilkins; 2010.
Answers to questions
1. False. Choroid plexus papilloma is the only cause of hydrocephalus due to overproduction of CSF. In addition, even in the case of choroid plexus papilloma, most cases of hydrocephalus are actually due to obstruction of the fourth ventricle.
2. Nausea, vomiting, headache, drowsiness, gait changes, papilledema with associated blurred vision, and impaired upward or lateral gaze.
3. Hydrocephalus is an increased volume of CSF within the CNS. Megalencephaly is an increase in the amount of brain parenchyma. Macrocephaly is an abnormally large head circumference (greater than 2 standard deviations above the mean) and may be a consequence of hydrocephalus, megalencephaly, or various other causes.
4. When present, intraventricular bleeding in the very low birth weight infant usually occurs within the first 24 hours of life. Because up to 50% of these events will occur without immediate clinical symptomology, it is recommended that routine screening be performed between days 4 to 7 of life.
5. False. The diagnosis of hydrocephalus in a neonate requires confirmation of increased rate of skull growth in addition to evidence of ventricular enlargement.
6. The setting-sun sign is a forced downward deviation of both eyes leading to disappearance of a portion of the iris below the lower eyelid. It is a sensitive sign of increased ICP, and is likely due to compression of periaqueductal structures. This sign appears in 40% of children with hydrocephalus and 13% of patients with VP shunt failure.