Handbook of Pediatric Neurosurgery

and throm bosed berry aneurysm ( Table 31.1)
( Fig. 31.2).1,2,11,26
31.5 Surgical Considerations
Because surgical excision of intracranial lipomas
carries a significant risk, medical management of
potentially associated signs and symptoms should
be maximized before consideration of operative
intervention.30 Seizures associated with intracra-
nial lipomas typically respond to antiepileptic
drugs.15,24 Patients with hemifacial spasm with lip-
oma as the likely culprit should undergo medical
treatment including Botox before surgical
Table 31.1 Di erential diagnosis based on imaging findings
Imaging modality

Lipoma

Epidermoid

Dermoid

Hamartoma
MRI T1

Hyperintense

Slightly hyperintense
(white epidermoid)
to isointense
Hyperintense hetero-
genous
Isointense
MRI T2

Hypointense

Hypointense

Hypointense
heterogenous
Iso- to slightly
hyperintense
MRI FLAIR

Hyperintense

Hypointense

Hyperintense

Hyperintense
CT

Dark (low attenuation) Dark

Dark

Dark or isointense
HU

–50 to –100

Similar to CSF

–25 to –30
Contrast

Nonenhancing

Nonenhancing

Nonenhancing

Nonenhancing
Location

Midline, cisterns, CPA Cisterns

Sellar or parasellar,
frontonasal, posterior
fossa, midline vermis,
third or fourth
ventricle
Hypothalamus
Cortical in tuberous
sclerosis
Shape

Tubulonodular or cur-
vilinear
Well defined, lobu-
lated
Round, lobulated,
cystic
Variable
Calcifications

Yes, peripheral

Rarely

Yes

Yes
Abbreviations: CPA, cerebellopontine angle; CSF, cerebrospinal fluid; FLAIR, fluid-attenuated inversion recovery; HU,
Hounsfield unit; MRI, magnetic resonance imaging.
Fig. 31.2 (a) MRI of a lipoma in the posterior corpus callosum. (b) MRI of a lipoma in the anterior corpus callosum.
(c) MRI of a suprasellar lipoma. (d, e) MRI of a cerebellopontine angle lipoma. (f) MRI of a lipoma in the quadrigeminal
cistern. (g) CT image showing a typical sickle-shaped calcification.
Developmental and Congenital Cranial Disorders
258

intervention is considered.22,23 Lipomas associated
with balance disorders (vertigo and dizziness)
respond well to medical treatment.24 Hearing loss
or visual loss caused by compressive symptoms of
lipoma is not likely to improve with medical or
surgical treatment.6,11,24 Treatment with steroids
should be avoided as lipoma could potentially
grow in response to steroids, inducing hypertro-
phy of the fat tissue.31
Limited surgery can be considered after con-
servative management has failed and patient
continues to su er from disabling neurological
symptoms.
The management of asymptomatic incidentally
found lipomas should include close follow-up of
the patient and evaluation of a potential change in
tumor size. The surgical management depends on
the location of the lipoma. Total resection is usu-
ally quite di cult due to the deep location and
adhesive nature of the lesion. They tend to envelop
vessels and nerves and have attachments to
the underlying parenchyma via Virchow–Robin
spaces.9,32 Lipomas in cisternal locations causing
hydrocephalus are most often treated with shunts.
Endoscopic third ventriculostomy (ETV) is an op-
tion in selected cases but to our knowledge in the
literature there are no documented cases of treat-
ment of hydrocephalus caused by intracranial
lipoma with an ETV. Surgical management of CPA
lipomas should be reserved for patients with
intractable clinical symptoms due to tumor
overgrowth.24 Attempts at complete removal of
CPA lipomas may result in severe neurological
deficits; subtotal debulking of lipoma is often pre-
ferred.6,22,23,32
Electrophysiologic intraoperative
neuromonitoring can guide resection and help
prevent injury to adjacent structures.23
Corpus callosum: Complete removal of lipoma
from the corpus callosum should not be attempted
as the fatty tissue is vascularized and interspaced
with fibrous tissue that covers the pericallosal
arteries and its branches.1
31.6 Surgical Pearls
● Caution against total resection as incorporation
of neural and vascular structures makes risk of
complications high and is not necessary for
symptomatic relief.
● Use of intraoperative neuromonitoring may help
prevent injury to adjacent structures and give
information about when decompression in
adequate.
● Management of hydrocephalus with shunts or
for selected cases ETV.
● Seizures and vertiginous symptoms usually
successfully controlled with medical
management.
● Detection of intracranial lipomas is relevant
because of their frequent association with other
brain malformations.
31.7 Common Clinical
Questions
1. What is the most common location of
intracranial lipoma?
2. Do intracranial lipomas grow?
3. What are the operative indications for
intracranial lipomas?
31.8 Answers to Common
Clinical Questions
1. The most common location for intracranial
lipoma is corpus callosum. The anatomic
distribution of intracranial lipomas was
described by a retrospective review of 42
patients, identifying that 45% were
interhemispheric, 25% were in the
quadrigeminal cistern, 14% in the suprasellar/
interpeduncular cistern, 9% laterally in the CPA,
and only 5% more laterally in the sylvian
fissure.4
2. Intracranial lipomas are considered stable
lesions. These tumors have generally not been
shown to grow rapidly or undergo malignant
change.6,7
3. Intracranial lipomas should be managed
conservatively. Lipomas incorporate neural and
vascular structures, making surgical excision
risky. Limited surgery can be considered after
conservative management has failed and
patient continues to su er from disabling
neurological symptoms.
References
[1] Kazner E, Stochdorph O, Wende S, Grumme T. Intracranial
lipoma. Diagnostic and therapeutic considerations. J Neurosurg.
1980; 52(2):234–245
[2] Friedman RB, Segal R, Latchaw RE. Computerized tomographic
and magnetic resonance imaging of intracranial lipoma. Case
report. J Neurosurg. 1986; 65(3):407–410
[3] Baeesa SS, Higgins MJ, Ventureyra EC. Dorsal brain stem
lipomas: case report. Neurosurgery. 1996; 38(5):1031–1035
Intracranial Lipomas
259

[4] Truwit CL, Barkovich AJ. Pathogenesis of intracranial lipoma:
an MR study in 42 patients. AJNR Am J Neuroradiol. 1990; 11
(4):665–674
[5] Wolpert SM, Carter BL, Ferris EJ. Lipomas of the corpus
callosum. An angiographic analysis. Am J Roentgenol Radium
Ther Nucl Med. 1972; 115(1):92–99
[6] Jallo JI, Palumbo SJ, Buchheit WA. Cerebellopontine angle
lipoma: case report. Neurosurgery. 1994; 34(5):912–914,
discussion 914
[7] Pensak ML, Glasscock ME, III, Gulya AJ, Hays JW, Smith HP,
Dickens JR. Cerebellopontine angle lipomas. Arch Otolaryngol
Head Neck Surg. 1986; 112(1):99–101
[8] Kieslich M, Ehlers S, Bollinger M, Jacobi G. Midline
developmental anomalies with lipomas in the corpus
callosum region. J Child Neurol. 2000; 15(2):85–89
[9] Mattern WC, Blattner RE, Werth J, Shuman R, Bloch S,
Leibrock LG. Eighth nerve lipoma. Case report. J Neurosurg.
1980; 53(3):397–400
[10] Kurt G, Dogulu F, Kaymaz M, Emmez H, Onk A, Baykaner MK.
Hypothalamic lipoma adjacent to mamillary bodies. Childs
Nerv Syst. 2002; 18(12):732–734
[11] Giannini C, Reynolds C, Leavitt JA, et al. Choristoma of the
optic nerve: case report. Neurosurgery. 2002; 50(5):1125–
1128
[12] Beşkonakli E, Cayli SR, Ergün R, Okten AI. Lipoma of the
interpeduncular fossa: demonstration by CT and MRI.
Neurosurg Rev. 1998; 21(2–3):210–212
[13] Yildiz H, Hakyemez B, Koroglu M, Yesildag A, Baykal B.
Intracranial lipomas: importance of localization. Neuroradiology.
2006; 48(1):1–7
[14] Britt PM, Bindal AK, Balko MG, Yeh HS. Lipoma of the cerebral
cortex: case report. Acta Neurochir (Wien). 1993; 121(1–2):
88–92
[15] Saatci I, Aslan C, Renda Y, Besim A. Parietal lipoma associated
with cortical dysplasia and abnormal vasculature: case
report and review of the literature. AJNR Am J Neuroradiol.
2000; 21(9):1718–1721
[16] Savasta S, Chiapedi S, Perrini S, Tognato E, Corsano L, Chiara
A. Pai syndrome: a further report of a case with bifid nose,
lipoma, and agenesis of the corpus callosum. Childs Nerv
Syst. 2008; 24(6):773–776
[17] Karakas O, Karakas E, Boyacı FN, Celik B, Cullu N. Anterior
interhemispheric calcified
lipoma
together
with
subcutaneous lipoma and agenesis of corpus callosum: a rare
manifestation of midline craniofacial dysraphism. Jpn J
Radiol. 2013; 31(7):496–499
[18] Fitoz S, Atasoy C, Erden I, Akyar S. Intracranial lipoma with
extracranial extension through foramen ovale in a patient
with encephalocraniocutaneous lipomatosis syndrome.
Neuroradiology. 2002; 44(2):175–178
[19] Suri V, Sharma MC, Suri A, et al. Myelolipomatous change in
an interhemispheric lipoma associated with corpus callosum
agenesis: case report. Neurosurgery. 2008; 62(3):E745–,
discussion E745
[20] Yalcin S, Fragoyannis S. Intracranial lipoma. Case report. J
Neurosurg. 1966; 24(5):895–897
[21] Yilmaz N, Unal O, Kiymaz N, Yilmaz C, Etlik O. Intracranial
lipomas–a clinical study. Clin Neurol Neurosurg. 2006; 108
(4):363–368
[22] Inoue T, Maeyama R, Ogawa H. Hemifacial spasm resulting
from cerebellopontine angle lipoma: case report.
Neurosurgery. 1995; 36(4):846–850
[23] Barajas RF, Jr, Chi J, Guo L, Barbaro N. Microvascular
decompression in hemifacial spasm resulting from a
cerebellopontine angle lipoma: case report. Neurosurgery.
2008; 63(4):E815–E816, discussion E816
[24] Ono J, Ikeda T, Imai K, et al. Intracranial lipoma of the
quadrigeminal region associated with complex partial
seizures. Pediatr Radiol. 1998; 28(9):729–731
[25] Puget S, Garnett MR, Leclercq D, et al. Hypothalamic lipoma
associated with severe obesity. Report of 2 cases. J Neurosurg
Pediatr. 2009; 4(2):147–150
[26] Feldman RP, Marcovici A, LaSala PA. Intracranial lipoma of
the sylvian fissure. Case report and review of the literature. J
Neurosurg. 2001; 94(3):515–519
[27] Ichikawa T, Kumazaki T, Mizumura S, Kijima T, Motohashi S,
Gocho G. Intracranial lipomas: demonstration by computed
tomography and magnetic resonance imaging. J Nippon Med
Sch. 2000; 67(5):388–391
[28] Demaerel P, Van de Gaer P, Wilms G, Baert AL. Interhemispheric
lipoma with variable callosal dysgenesis: relationship between
embryology, morphology, and symptomatology. Eur Radiol.
1996; 6(6):904–909
[29] Given CA, Fields TM, Pittman T. Interhemispheric lipoma
connected to subcutaneous lipoma via lipomatous stalk.
Pediatr Radiol. 2005; 35(11):1110–1112
[30] Markou KD, Goudakos JK, Bellec O, et al. Lipochoristomas of the
cerebellopontine angle and internal acoustic meatus: a seven-
case review. Acta Neurochir (Wien). 2013; 155(3):449–454
[31] Haga HJ, Thomassen E, Johannesen A, Kråkenes J. Neural
compressive symptoms appearing during steroid treatment
in a patient with intracranial lipoma. Scand J Rheumatol.
1999; 28(3):184–186
[32] Zimmermann M, Kellermann S, Gerlach R, Seifert V.
Cerebellopontine angle lipoma: case report and review of the
literature. Acta Neurochir (Wien). 1999; 141(12):1347–1351
Developmental and Congenital Cranial Disorders
260

32 The Dandy–Walker Malformation: Disorders of
Cerebellar Development and Their Management
Greg Olavarria
32.1 Introduction: Incidence,
Genetics, and Evaluation
The Dandy–Walker malformation is an uncommon
congenital syndrom e associated with hydrocepha-
lus and other cerebral and systemic anomalies.
With a reported incidence of 1 in 25,000 to 35,000
live births, the malformation occurs early in intra-
uterine life (before the fourth week of gestation),
often a ecting multiple organ systems. Known eti-
ologies include in utero exposure to toxins, drugs,
or infectious agents, signaling pathway problems
attributed to ciliary dysfunction, and abnormal-
ities of chromosomes 3, 6, 9, 13, and 18.
The true Dandy-Walker malformation involves
either agenesis of the fourth ventricle outlet fora-
mina or lack of regression of fetal cystic structures,
producing an enlarged fourth ventricle and poste-
rior fossa displacing the tentorium and torcula
superiorly. The majority of patients have hydroce-
phalus, vermian, and cerebellar hypoplasia, and
the brainstem is often pushed anteriorly by the
cyst (Fig. 32.1 and Fig. 32.2). In most cases
(60–70%), but not all, the fourth ventricle cyst
communicates with the supratentorial ventricular
compartment through a patent aqueduct and this
has implications for management.1,2
Children usually present early in life with an
enlarging head circumference and signs of raised
intracranial pressure (secondary to hydrocepha-
lus). Hydrocephalus is present in the majority of
patients (60–80% of cases), and other central nerv-
ous system (CNS) anomalies can be observed, such
as callosal dysgenesis (in 32%), heterotopias, poly-
microgyria (5–10%), and encephaloceles (16%).3,4,5
A systemic workup should be initiated for associ-
ated cardiac and limb defects.
Magnetic resonance imaging (MRI) is the pre-
ferred imaging modality, and MR cine flow
sequences can be used to determine flow across
the aqueduct preoperatively. In the past, computed
tomography (CT) contrast ventriculography has
been used for this purpose.
32.2 Di erential Diagnosis
The true Dandy–Walker malformation must be
distinguished from other posterior fossa abnor-
malities such as varying degrees of vermian
hypoplasia and less severe posterior fossa cystic
collections (aka Dandy–Walker variant), persistent
Blake’s pouch, mega cisterna magna, and posterior
Fig. 32.1 True Dandy–Walker malformation with
hydrocephalus.
Fig. 32.2 The Dandy–Walker malformation with
hydrocephalus, note brainstem displacement.
261

fossa arachnoid cysts. The variant, better consid-
ered the “Dandy–Walker spectrum” of disorders,
may be seen with other CNS malformations (cal-
losal dysgenesis) but without accompanying
hydrocephalus (Fig. 32.3). On the other hand,
di use cerebellar hypoplasia is associated with
metabolic disorders, trisomies, teratogens, and
other in utero insults. A persistent Blake’s pouch,
an expansion of the embryonic posterior membra-
nous area, leads to an enlarged fourth ventricle
and posterior fossa. It can be associated with ver-
mian and cerebellar hypoplasia, and hydrocepha-
lus can occur if there is no communication with
the subarachnoid spaces.5 This entity should also
be included in the Dandy–Walker spectrum of
abnormalities (Fig. 32.4).
An enlarged cisterna magna does not compress
cerebellar structures, and the vermis and fourth
ventricle are normal. Hydrocephalus is absent,
because the enlarged cistern communicates with
the subarachnoid spaces.
Arachnoid cysts mimic the above entities, and
can compress structures, but those structures
themselves are not abnormal and the cyst itself
does not communicate with the fourth ventricle. It
is a separate entity from the subarachnoid space
around it, and can be distinguished on imaging
from the above cystic anomalies ( Fig. 32.5).
On imaging, the presence or absence of fourth
ventricle choroid plexus can be useful. In the true
Dandy–Walker malformation, it is absent, but in a
Blake’s pouch cyst, it is displaced superiorly in the
cyst wall. Though the true malformation is usually
evident (hydrocephalus is usually present), it is
nearly impossible to distinguish the various
Dandy–Walker spectrum disorders (the variant,
Blake’s pouch, and mega cisterna magna) from
each other radiographically.5,6
Fig. 32.3 The Dandy–Walker variant, with abnormal
vermis, dysplastic corpus callosum without
hydrocephalus.
Fig. 32.4 A Blake’s pouch cyst.
Fig. 32.5 Arachnoid cyst of the posterior fossa, note
normal structures present but displaced by the cyst.
Developmental and Congenital Cranial Disorders
262

32.3 Management and
Outcomes
Surgical treatment is indicated for large sympto-
matic cysts causing compression of the brainstem
or hydrocephalus. Shunting the posterior fossa
cyst, shunting the ventricles, shunting both, and/
or endoscopic techniques are viable options tail-
ored to each individual case. Controversy exists
regarding best initial intervention, with the main
goal of decompressing the cyst and reducing focal
pressure. Management strategy depends on com-
munication between the supratentorial ventricles
and the posterior fossa cyst. Postshunting stenosis
of the aqueduct and failure of the posterior fossa
cyst to resolve has been described with lateral ven-
tricular shunts, leading some authors to recom-
mend cyst shunting primarily or connecting the
two via a connector as the initial procedure.1,3,7
Advocates of ventricular shunting as initial inter-
vention cite numerous complications associated
with posterior fossa shunts.7 Endoscopy has been
attempted, with third ventriculostomy procedures
as sole treatment and/or combined with endos-
copy-assisted stent placement. Third ventriculos-
tomy can be tried if the aqueduct is open, although
success rates in infants are less than with older
patients.8,9,10
Direct fenestration of the cyst,
though mostly of historical interest, is still prac-
ticed by some, especially in patients presenting
later in life.7 A flexible approach should be taken,
as the child’s shunting needs may change over
time.
The prognosis of children with Dandy–Walker
malformation is largely dependent on other cere-
bral and systemic anomalies. At least half the chil-
dren with the severe form of malformation have
neurocognitive delays.11 Complications associated
with shunt surgery are also a factor, that is,
infection, malfunction, and numerous surgical
procedures, that can impact a child’s intellectual
functioning.
References
[1] Yüceer N, Mertol T, Arda N. Surgical treatment of 13 pediatric
patients with Dandy–Walker syndrome. Pediatr Neurosurg.
2007; 43(5):358–363
[2] Detwiler PW, Porter RW, Rekate HL. Hydrocephalus clinical
features and management: Dandy–Walker malformation and
two compartment hydrocephalus. In: Choux M, ed. Pediatric
Neurosurgery. Churchill Livingstone; 1999
[3] Hirsch JF, Pierre-Kahn A, Renier D, Sainte-Rose C, Hoppe-
Hirsch E. The Dandy–Walker malformation. A review of 40
cases. J Neurosurg. 1984; 61(3):515–522
[4] Hart MN, Malamud N, Ellis WG. The Dandy–Walker
syndrome. A clinicopathological study based on 28 cases.
Neurology. 1972; 22(8):771–780
[5] Barkovich AJ. Congenital malformations of the brain and
skull. In: Barkovich AJ, ed. Pediatric Neuroimaging.
Philadelphia, PA: Lippincott, Williams and Wilkins; 2005:
291–439
[6] Wilkinson CC, Winston KR. Congenital arachnoid cysts and
the Dandy–Walker complex. In: Albright, Pollack, Adelson,
eds. Principles and Practice of Pediatric Neurosurgery. New
York, NY: Thieme; 2008
[7] Kumar R, Jain MK, Chhabra DK. Dandy–Walker syndrome:
di erent modalities of treatment and outcome in 42 cases.
Childs Nerv Syst. 2001; 17(6):348–352
[8] Garg A, Suri A, Chandra PS, Kumar R, Sharma BS, Mahapatra
AK. Endoscopic third ventriculostomy: 5 years’ experience at
the All India Institute of Medical Sciences. Pediatr Neurosurg.
2009; 45(1):1–5
[9] Faggin R, Bernardo A, Stieg P, Perilongo G, d’Avella D.
Hydrocephalus in infants less than six months of age:
e ectiveness of endoscopic third ventriculostomy. Eur J
Pediatr Surg. 2009; 19(4):216–219
[10] Mohanty A. Endoscopic third ventriculostomy with
cystoventricular stent placement in the management of
Dandy–Walker malformation: technical case report of three
patients. Neurosurgery. 2003; 53(5):1223–1228, discussion
1228–1229
[11] Bindal AK, Storrs BB, McLone DG. Management of the
Dandy–Walker syndrome. Pediatr Neurosurg. 1990–1991; 16
(3):163–169
The Dandy–Walker Malformation: Disorders of Cerebellar Development and Their Management
263

33 Craniosynostosis
Christopher D. Kelly, Martin H. Sailer, Raphael Guzman
33.1 Introduction
Craniosynostosis is the premature ossification of
the cranial sutures. Various nomenclatures are
used, with craniostenosis and craniosynostosis
often considered to be synonymous. Craniosynos-
tosis can occur primarily as idiopathic craniosy-
nostosis, may be syndromic or arise secondarily.
By suture closure, a skull deformity arises. In addi-
tion to the deformity, the brain growth can be
a ected and intracranial pressure may increase,
resulting in corresponding complications.1 Even if
there is no problem with intracranial pressure, the
deformity may lead to psychosocial problems.2
Surgery is therefore recommended, the optimum
time of which is dependent on the a ected suture
and the surgical technique used. Surgical correc-
tion of craniosynostosis is not a new concept,
but it was associated with a high morbidity and
was very controversial in its early days. Almost
simultaneously two surgeons reported their
first experiences. In 1890, Odilon Lannelongue
described the first incision of a suture, and in 1892
Lane described a technique for synostectomy.3 The
modern and successful treatment of cranial
deformities and craniosynostosis was founded and
decisively shaped by Tessier.4
In the following, we will discuss the various
deformities, surgical techniques, and the expected
results of treatment.
33.2 Classification
Craniosynostoses can be classified along several
dimensions, which are now used in clinical assess-
ment. Depending on the number of a ected
sutures, they may be described as “simple” or “iso-
lated” if only one suture closes prematurely, or
“complex” if more than one suture is a ected.5 Pri-
mary craniosynostosis describes the idiopathic
premature closure of one or more cranial sutures
without detectable genetic changes. Secondary
craniosynostoses result from a number of patholo-
gies and are often just an expression of the pri-
mary disease. Another possible classification is
into syndromic or nonsyndromic types. The pro-
portion of nonsyndromic is approximately 80 to
85%, with 15 to 20% correspondingly classified as
syndromic.6 In the latter, more than 100 known
syndromes are associated with craniosynostosis,
the most important of which are listed in
Table 33.1.
The phenotypic classification describes either
the head shape or the underlying prematurely
closed suture. The most frequently used terms are
scaphocephaly in sagittal synostosis, brachyce-
phaly with coronal synostosis, trigonocephaly in
frontal (aka metopic) suture synostosis, and pla-
giocephaly in lambdoid synostosis (Fig. 33.1).
33.3 Epidemiology
The incidence of craniosynostosis is estimated at 1
to 1.6 in 1,000 live births.7 In England, it is esti-
mated at 0.4:1,000, in Israel at 0.6:1,000,8 and in
France and in Holland at 0.47:1,000 and
0.64:1,000, respectively.9 Similarly, the birth prev-
alence in a large U.S. cohort was estimated at
0.43:1,000.10
The frequency of each craniosynostosis is shown
in Table 33.2. In most craniosynostoses, only one
suture is a ected, and in 5 to 15% of cases two or
more sutures are closed prematurely.11 Most cra-
niosynostoses occur sporadically, with familial
cases estimated to account for 7 to 14%,7 which are
mostly inherited in an autosomal dominant
fashion. If one parent and one child are a ected,
the risk for craniosynostosis in the next child is
Table 33.1 Classification
Primary

Nonsyndromal
(80–85%)
Syndromal
(15–20%)
Apert’s, Crouzon’s,
Pfeiffer’s, Saethre–
Chotzen
Secondary

Metabolic

Rickets, hyperthyr-
oidism, hypophos-
phatemia
Hematological Polycythemia vera,
sickle cell disease,
thalassemia
Pharmacological Valproate, phenytoin,
retinoids, methotrex-
ate
Structural

Microcephaly, shunt
overdrainage
264

estimated to be 50%. If both parents are asympto-
matic and two children are a ected, the risk for
the third child is estimated to be 25%.12 Di erent
family members may have involvement of di er-
ent sutures.
33.4 Etiology and Genetic
Factors
The etiology of craniosynostosis is unknown. How-
ever, some factors are known which may coincide
with the occurrence of craniosynostosis. Multiple
teratogens, hematological, and metabolic disorders
have been associated with the early suture closure.
Also, maternal cigarette smoking during preg-
nancy leads to an increased risk of a single suture
craniosynostosis.13 Therefore, an accurate preg-
nancy and birth history is important. Specifically,
intrauterine exposure to medicines, products of
tobacco smoking, and drugs should be consid-
ered.13,14,15,16 Further, intrauterine constriction in
twin pregnancy,7 abnormal position in the pelvis,
amniotic bands, or oligohydramnios have been
postulated as etiological factors17 (Table 33.1).
Also, family history is important so that familial
cases are not overlooked. Because of progress in
molecular genetics, genetic mutations and interac-
tions that are associated with premature suture
closure have also been discovered. The physiology
Fig. 33.1 3D computed tomography (CT) images of the typical bony changes in craniosynostosis.
Table 33.2 Epidemiology
Suture

Frequency

Male/female ratio

Familial
Sagittal

1/5,000

2–3:1 M:F

2–6%
Coronal

1/11,000

1:1–2 M:F

7–14%
Metopic

1/15,000

3:1 M:F

2–6%
Lambdoid

1/200,000

1:1–2 M:F

N/A
Craniosynostosis
265

of cranial suture growth and closure depends on a
complex balance between the proliferation of mes-
enchymal stem cells within the cranial suture me-
senchyme and their di erentiation into osteoblasts
at the osteogenic front18 (Fig. 33.2). Most syn-
dromic craniosynostoses are caused by mutations
in the genes that code for fibroblast growth factor
receptors (FGFR1, FGFR2, and FGFR3) or the tran-
scription factors Twist1, Runx2, and Msx2.19,20,21
These mutations are the cause of approximately
20% of all craniosynostoses (Table 33.3).
33.4.1 Clinical Disease and
Radiological Investigation
The suspected diagnosis of craniosynostosis is pri-
marily based on the presence of typical features on
clinical examination, described in detail later. The
deformity may be visible at birth, but often
becomes apparent only within the first month of
life. Persistent deformity 2 to 3 months after
birth should be investigated. In children with
syndromes, which can result in a secondary
craniosynostosis, long-term follow-up should be
performed.22
The clinical examination must
include a detailed neurological assessment to rule
out associated pathologies. It is important to
obtain a measurement of head circumference in
order to exclude a microcephaly, which could indi-
cate a secondary suture closure with underdevel-
opment of the cerebrum.
The diagnosis of craniosynostosis is primarily
made clinically and confirmed by computed
tomography (CT). If there is no clinical suspicion of
a synostosis or the typical picture of positional
plagiocephaly is observed, then CT is not indicated,
in order to minimize radiation exposure. Therefore,
medical assessment by a specialist with experience
with this disease is important. In a clinically sus-
pected craniosynostosis, further evaluation by cra-
nial CT is indicated. This allows the determination
of the prematurely closed suture and shows the
characteristics of the deformity, including cranial
contour and possible presence of thickening or ridg-
ing at the synostosis. Examples are shown in
Fig. 33.1. The CT also serves to exclude other mal-
formations23 and may demonstrate hydrocephalus
or indirect signs of increased intracranial pressure,
the so-called thumb printing or beaten copper
appearance of the tabula interna (Fig. 33.3).
Fig. 33.2 Graphical illustration of the genes involved in craniosynostosis and their interactions. FGFR1, fibroblast growth
factor receptor 1; FGFs, fibroblast growth factors.
Developmental and Congenital Cranial Disorders
266

Table 33.3 Genetic factors
Gene

Mutation found in
syndrome/
symptom
Genetic alteration
Pathophysiological mechanism/
gene function
Reference
FGFR1

Crouzon’s, Pfeiffer’s,
Apert’s, Beare–Stevenson,
Jackson–Weiss
Gain-of-function

Activated
FGF-signaling
5
FGFR2

Crouzon’s, Pfeiffer’s,
Jackson–Weiss
Gain-of-function

Activated
FGF-signaling
5
FGFR2c

Crouzon’s, Apert’s

Gain-of-function

Enhanced affinity for FGF7 and
FGF10
5
FGFR3

Crouzon’s, Muenke’s

Gain-of-function

Activated
FGF-signaling
5
Twist1

Saethre–Chotzen

Loss-of-function

Twist1 normal function:
downregulation of Runx2
5,24
Msx2

Boston-type
craniosynostosis
Gain-of-function

Promotes preosteoblast
differentiation
25,26
Runx2/ Cbfa1

Pancraniosynostosis

Gain-of-function

Causes overossification. Runx2
deficient mice: complete bone
loss
27
GliA

Greig’s cephalopolysyn-
dactyly with craniosy-
nostosis
Unknown

Activated
Gli3-signaling
28
NELL-1

Unilateral
craniosynostosis
Gain-of-function

Unknown

29
FBN2,
IGF2BP3,
TINAGL1
Altered transcription in
nonsyndromic
craniosynostosis
FBN2, IGF2BP3:
gain-of-function.
TINAGL1:
loss-of-function
In combination are associated
with increased Runx2
expression
30
Abbreviation: FGFR, fibroblast growth factor receptor.
Fig. 33.3 Signs of a latent increased intracranial pressure. (a) 3D CTshows thinning of some sites of the inner surface of
the skull (“thumb printing” or “beaten copper” appearance). Various pathologies with increased intracranial pressure
can lead to this picture. (b) Example of a resected sagittal suture with some translucent patches. (c) Example of a
resected coronal suture with “thumb printing” of the tabula interna.
Craniosynostosis
267

33.5 Craniosynostoses and
Their Treatment
33.5.1 Sagittal Craniosynostosis
The sagittal suture craniosynostosis, with an inci-
dence of 1/5,000, is the most common craniosy-
nostosis. The isolated premature ossification of the
sagittal suture is found in 50 to 60% of craniosy-
nostoses.7 There are two to three times more boys
than girls a ected.31 Because of the ossification of
the sagittal suture, cranial growth is restricted in
width, and there is a compensatory growth in
length. This creates the head shape of scaphoce-
phaly (boat-shaped skull), which is characterized
by a narrow and elongated head with prominent
occiput. The term dolichocephaly (elongated skull)
describes the long head with a high forehead. In
severe cases, there is a bifrontal prominent fore-
head (bifrontal bossing). In the clinical examina-
tion, suture ridging is apparent by palpation
(Fig. 33.4).
33.5.2 Coronal Craniosynostosis
With an incidence of 1/11,000, coronal craniosynos-
tosis is the second most common craniosynostosis.7
It accounts for approximately 20% of craniosynosto-
ses. The ratio of girls to boys is 2:1.32 The coronal
synostosis may occur unilaterally or bilaterally. In
the bilateral premature ossification of the coronal
suture, the increased growth in cranial width and
height is seen. This resulting brachycephaly (short
skull) is characterized by a short head with a high
forehead. Because of the bicoronal ossification, the
anterior cranial fossa is shortened, resulting in shal-
low orbits with retracted orbital roof, which may be
associated with hypertelorism, exophthalmos, and
strabismus. Bicoronal synostoses are significantly
more frequently familial than the unicoronal synos-
toses.32 In the unilateral coronal synostosis (anterior
plagiocephaly), an ipsilateral growth in width occurs,
such that the ipsilateral forehead appears high and
flat with a compensatory prominence of the con-
tralateral forehead. Because of the restriction of the
Fig. 33.4 Example of a child with
sagittal craniosynostosis showing the
typical head shape of scaphocephaly.
(a) Characteristic long head shape with
prominent occiput. (b) Example of an
excised sagittal suture. (c) Preopera-
tive image. (d) Two-year postoperative
image.
Developmental and Congenital Cranial Disorders
268

frontal growth on the side of the synostosis, there
occurs an ipsilateral elongation of the sphenoid wing
and the lower face, as well as elevation of the ipsilat-
eral orbit, the classic image of the harlequin eye
(Fig. 33.5).
33.5.3 Metopic Craniosynostosis
The metopic craniosynostosis is the closure of the
frontal suture (aka metopic suture). It occurs with
an incidence of 1/15,000 live births, and is three
times more common in boys than girls. The pre-
mature closure of the frontal suture results in a
limitation of growth in width of the anterior cra-
nial fossa and bilateral constriction of the frontal
lobes. The phenotypic manifestation is a trigonoce-
phaly, namely a triangular-shaped forehead
(Fig. 33.6). The reduction of grow th in width
often leads to hypotelorism and flattening of
lateral orbital roofs. It is important to distinguish
benign frontal suture prominence from a true
metopic craniosynostosis. The frontal suture can
ossify physiologically between 6 and 12 months,
which may result in a so-called benign metopic
ridge. Since in these cases the base of the skull
develops normally, there is no hypotelorism and
no limitation of the anterior cranial fossa. Benign
metopic ridging per se does not require treatment,
but can be treated surgically for cosmetic reasons
(Fig. 33.6).
33.5.4 Lambdoid Craniosynostosis
The lambdoid suture is located between the occi-
pital bone and the parietal bone. Lambdoid suture
craniosynostosis is rare and manifests with an
incidence of 1/200,000,7 which is approximately
5% of all cases of craniosynostosis. When lambdoid
craniosynostosis is unilateral, it results in ipsilat-
eral posterior plagiocephaly. The one-sided flat
back of the head ipsilateral to synostosis must be
distinguished from postural plagiocephaly. In pos-
tural plagiocephaly, due to one-sided supine head
posture preference, the ipsilateral ear shifts
forward in relation to the contralateral ear and the
ipsilateral forehead is prominent. In lambdoid cra-
niosynostosis, there is a growth restriction of the
lateral skull base so that the ipsilateral ear as well
as the ipsilateral forehead is shifted to the rear in
relation to the contralateral side ( Fig. 33.7 and
Fig. 33.8). Thus, the head viewed from above
resembles a parallelogram in postural plagioce-
phaly and a trapezoid in unilateral lambdoid
craniosynostosis.
Fig. 33.5 Example of a child with
unilateral coronal craniosynostosis on
the right. (a) Characteristic harlequin
eye on the ipsilateral right side with
ipsilaterally strongly elevated lateral
sphenoid wing. (b) Example of a fused
coronal suture in the area of the lateral
sphenoid wing. (c) Characteristic as-
pect of the anterior plagiocephaly with
a right-sided coronal suture craniosy-
nostosis with flattening of the ipsi-
lateral forehead, lack of orbital roof
protection on the right, and deviation
of the nose to the opposite side.
(d) Three-year postoperative control.
Craniosynostosis
269

Fig. 33.6 Example of a child with metopic craniosynostosis. (a) Characteristic prominent frontal suture with triangular
forehead shape and hypotelorism. (b) 3D CT of a metopic craniosynostosis. (c) Six-month postoperative control.
Fig. 33.7 Example of a child with
lambdoid suture craniosynostosis.
(a–b) 3D CT with characteristic poste-
rior plagiocephaly due to early closure
of the right lambdoid suture.
(c) Noteworthy is the involvement of
the entire skull base. (d) Patient
positioning and skin incision for
bilateral correction of posterior
plagiocephaly.
Developmental and Congenital Cranial Disorders
270

33.6 Surgical Treatment
33.6.1 Indication
Two main factors justify the indication to surgery.
The first is correction of the skull deformity to pre-
vent psychosocial disadvantages,33 and the second
is prevention of a potential increase in intracranial
pressure.34 Studies have demonstrated that up to
30% of children even with only single-suture cra-
niosynostosis can present with an increased intra-
cranial pressure.35,36,37,38,39 Several studies were
aimed to examine the neurocognitive develop-
ment in children with single-suture craniosynos-
tosis. Especially, reading and/or spelling learning
disabilities were found in the long term in children
with craniosynostosis compared to children with-
out craniosynostosis.40 It is debated whether an
early operation can reduce the development of
these deficits.41
33.6.2 Time of Treatment
The optimal time for surgical treatment of cranio-
synostosis is controversial. While older children
better tolerate the surgery hemodynamically, the
correction of the deformity and bone regeneration
is better in younger children. Older children (>6
months) tolerate the significant blood loss better
than younger children. However, in children older
than 12 months, the operation may take longer due
to the more extensive bone reconstruction neces-
sary to cover bone defects, which in turn is associ-
ated with increased blood loss.42 Most surgeons pre-
fer to operate on children with craniosynostosis
between 3 and 12 months. We tend to perform sur-
gery for sagittal suture synostosis between 4 and 6
months of age and all others (coronal, metopic, and
lambdoid) between 6 and 12 months.42 It is also
postulated that cognitive development is better if
the child is operated before 12 months of age.43
Timing is also dependent on the method of opera-
tion. The newer endoscopic procedures especially
with sagittal craniosynostosis are performed
between the ages of 1 and 4 months.44,45
33.6.3 Surgery
Numerous surgical techniques and nuances are
described in the literature. The general principle is
to allow free growth of the skull by opening or
removing the closed suture. In the sagittal suture
craniosynostosis, a so-called strip craniectomy is
performed where the closed sagittal suture is
removed ( Fig. 33.3b and Fig. 33.4b). Important
for the preparation and planning of an operation is
the presence of an open anterior or posterior fon-
tanelle. These are exposed at the beginning of the
operation and the sagittal synostectomy, extend-
ing from the anterior fontanelle (junction of the
sagittal, coronal, and frontal suture) to the poste-
rior fontanelle (interface of the lambdoid and sag-
ittal suture), is performed. Subsequently, to correct
the long and narrow head shape in scaphocephaly,
lateral osteotomies are performed in the area of
the parietal and frontal bone. This allows the
biparietal diameter to increase and a wider head
shape to develop. To reduce the elongated head
shape, which is often associated with a pointed
occipital bone, a remodeling of the occipital bone
is carried out by multiple osteotomies. Usually, a
fixation with resorbable plates or sutures is not
necessary in the correction of sagittal synostosis.
In older children (>12 months), after the period of
rapid head growth, fixation may be necessary to
maintain the corrected head shape. In younger
Fig. 33.8 Schematic illustration of
head shape and ear positions in
postural plagiocephaly (parallelogram,
ipsilateral ear shifted forward) and
unilateral posterior plagiocephaly in
lambdoid suture craniosynostosis (tra-
pezoid, ipsilateral ear shifted to the
rear).
Craniosynostosis
271

children, the modeling essentially takes places due
to the physiological rapid head growth.
In metopic and coronal craniosynostosis, a
fronto-orbital advancement is performed in most
centers42 (Fig. 33.9). For that purpose, a bifrontal
craniotomy is first performed with particular care
to protect the superior sagittal sinus. Countless
variations exist concerning the posterior and lat-
eral extent of the craniotomy. This is then followed
by the en bloc removal of the superior and lateral
margins of the orbit. Osteotomies at the orbital
roof, nasoethmoidal, and lateral in the area of
sphenoid wing must be made to remove the so-
called orbital bandeau (Fig. 33.9b). Both bones,
the frontal bone and the “orbital bandeau,” are then
reattached in an advanced position (Fig. 33.9b)
using resorbable plates and screws. This is done by
placing the lateral orbital margins in a normal
advanced position and thus correcting the entry
angle of the orbit. The deformity of the forehead,
which is either trigonocephalic or brachycephalic, is
corrected by remodeling of the frontal bone.
In lambdoid suture synostosis, an occipital cra-
niotomy is performed with correction of the poste-
rior plagiocephaly (Fig. 33.7). Again, there are
countless variations with unilateral or bilateral
correction, exchange of the a ected occipital
squama with the una ected, and rotations of the
bone plates.
In the endoscopic techniques, the correction is
carried out primarily through small incisions in
the region of the closed suture. Under endoscopic
view, a subperiosteal preparation of the suture is
performed followed by a synostectomy. The chil-
dren then undergo helmet therapy for modeling of
the head shape for 7 to 12 months, as is done for
positional plagiocephaly. The average hospital stay
is 3 to 5 days for the open technique and 1 to
2 days for the endoscopic method.
The most critical point and therefore also the
most frequently cited complication is blood loss
requiring transfusion. Meticulous hemostasis at
each step of the operation is essential. Especially in
the more complex fronto-orbital advancement
surgery for coronal and metopic synostosis, the
blood loss is significant. With a standard technique
and an experienced team, the blood loss can be
limited to a mean of 120 mL.42 However, blood loss
of about 250 mL, which corresponds to one-third
to one-fourth of the total blood volume of the
child, is often mentioned in the literature.45 The
amount of blood loss correlates with the operation
time and the age of the patient.42,45 Other surgical
risks include intraoperative air embolism, which,
however, can be well controlled with modern
anesthesia, good patient positioning, and standard
surgical techniques. Another avoidable complica-
tion with modern anesthesia is prevention of
hypothermia. The risk of infection is reduced by
prophylactic perioperative antibiotics.
33.6.4 Outcome
The mortality rate is now below 1% and the
morbidity rate around 5%. Morbidity is especially
due to infections, which are reported to be
between 1 and 10%.42,46 The risk is increased in re-
operations or corrections of complex syndromes.
The same applies to the risk of dural injury with
cerebrospinal fluid fistula, also occurring espe-
cially in reoperations. Postoperative hyperthermia
on day 2 to 3 is often observed but rarely associ-
ated with infection.46,47
A satisfactory correction in craniosynostosis sur-
gery depends on multiple factors. An important
factor is the age at correction. The head growth
after correction of craniosynostosis is not di erent
from the normal growth and a significant remod-
eling thereby takes place after the operation. Gen-
erally, a correction is recommended within the
first year of life.28 Corrections after the first year of
life are more complex because the natural remod-
eling is limited and the capacity to grow bone is
reduced. Especially in the correction of trigonoce-
phaly and coronal craniosynostosis, the timing
seems to be important. The highest relapse rates
were shown for first operations before 6 months
of age and after 12 months of age,49 whereas the
operations with the best outcomes were with
patients aged between 6 and 12 months.50 It is
expected that after the first operation a satisfac-
tory correction of the deformity can be reached in
over 90% of patients.42,47
33.7 Conclusion
The treatment of craniosynostosis in the first year
of life is essential to obtain good surgical results.
Also, surgery is indicated to prevent a potential
increase in intracranial pressure, which can occur
in up to 30% of a ected children. Craniosynostosis
cannot be treated conservatively. The treatment
should take place in a center with a specialized
and experienced team of surgeons, anesthetists,
and intensive care physicians.
Developmental and Congenital Cranial Disorders
272

33.8 Common Clinical
Questions
1. What is craniosynostosis and how are
craniosynostoses classified?
2. What are the most common genetic causes of
syndromic craniosynostoses?
3. How is craniosynostosis diagnosed, and what is
“thumb printing” or “beaten copper”
appearance?
Fig. 33.9 (a-e) Illustration of the operating technique for (a) Fronto-orbital advancement with bifrontal craniotomy and
removal of the orbital bandeau. (b, c) After the remodeling, the reconstruction with resorbable plates and screws is
performed. (Reproduced with permission from Guzman et al.42)
Craniosynostosis
273

4. What is the indication for surgery?
33.9 Answers to Common
Clinical Questions
1. Craniosynostosis is the premature closure of
one or more cranial sutures. Craniosynostoses
can be classified as “simple” or “isolated” versus
“complex,” primary versus secondary,
syndromic versus nonsyndromic ( Table 33.1),
or by phenotypic classification ( Fig. 33.1)
based on head shape or the underlying
prematurely closed suture (since skull growth is
restricted in the direction perpendicular to the
prematurely closed suture).
2. See Table 33.3 and Fig. 33.2. Most
syndromic craniosynostoses are caused by
mutations in the genes that code for fibroblast
growth factor receptors (FGFR1, FGFR2, and
FGFR3 or the transcription factors Twist1,
Runx2, and Msx2.
3. The suspicion of craniosynostosis is based on
clinical evaluation. Typical sign is skull
deformity persisting 2 to 3 months after birth
and first occurring at birth or within the first
month of life. Clinical evaluation includes a
detailed neurological assessment to rule out
associated pathologies, measurement of head
circumference in order to exclude a
microcephaly, and the exclusion of positional
plagiocephaly by head shape and ear position
(Fig. 33.8). In a clinically suspected
craniosynostosis, further evaluation by cranial
CT is indicated. This will demonstrate the
prematurely closed suture or sutures and the
characteristics of the deformity with the cranial
contour and/or ridging at the synostosis
(Fig. 33.1). “Thumb printing” and “beaten
copper” describe the radiological evidence of
increased intracranial pressure and are evident
from the appearance of the tabula interna on
skull CTor X-ray (Fig. 33.3).
4. Two factors justify surgery: first, the correction
of the skull deformity to prevent psychosocial
disadvantages and, secondly, the prevention of a
potential increase in intracranial pressure.
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[43] Arnaud E, Meneses P, Lajeunie E, Thorne JA, Marchac D,
Renier D. Postoperative mental and morphological outcome
for nonsyndromic brachycephaly. Plast Reconstr Surg. 2002;
110(1):6–12, discussion 13
[44] Jimenez DF, Barone CM. Early treatment of anterior calvarial
craniosynostosis using endoscopic-assisted minimally invasive
techniques. Childs Nerv Syst. 2007; 23(12):1411–1419
[45] Seruya M, Oh AK, Rogers GF, et al. Factors related to blood
loss during fronto-orbital advancement. J Craniofac Surg.
2012; 23(2):358–362
[46] Esparza J, Hinojosa J. Complications in the surgical treatment
of craniosynostosis and craniofacial syndromes: apropos of
306 transcranial procedures. Childs Nerv Syst. 2008; 24(12):
1421–1430
[47] Esparza J, Hinojosa J, García-Recuero I, Romance A, Pascual B,
Martínez de Aragón A. Surgical treatment of isolated and
syndromic craniosynostosis. Results and complications in
283 consecutive cases. Neurocirugia (Astur). 2008; 19(6):
509–529
[48] Marchac D, Renier D. Craniosynostosis. World J Surg. 1989;
13(4):358–365
[49] Selber JC, Brooks C, Kurichi JE, Temmen T, Sonnad SS,
Whitaker LA. Long-term results following fronto-orbital
reconstruction in nonsyndromic unicoronal synostosis. Plast
Reconstr Surg. 2008; 121(5):251–260
[50] Foster KA, Frim DM, McKinnon M. Recurrence of synostosis
following surgical repair of craniosynostosis. Plast Reconstr
Surg. 2008; 121(3):70–76
Craniosynostosis
275

34 Management of Craniofacial Syndromes
Miguel A. Medina III, Gerhard S. Mundinger, Amir H. Dorafshar
34.1 Introduction
Roughly 15% of patients with craniosynostosis
present with an underlying syndromic condition.
The presence of associated syndromic anomalies,
coupled with the rarity of these disorders and the
relatively increased severity of synostosis, makes
surgical management of patients with most
syndromic craniosynostosis, such as Apert’s and
Pfei er’s syndrome, more challenging and
nuanced when compared to patients with nonsyn-
dromic synostosis. In contrast, many patients with
unilateral coronal synostosis may have underlying
identifiable mutations, as in Muenke’s syndrome,
that confer relatively mild phenotypes and o er
targets for early pharmacological intervention. The
craniofacial surgeon may be the first person to
thoroughly examine a child with craniofacial
anomalies and must endeavor to identify associ-
ated abnormalities and anomalies that may be
present. By definition, syndromes are a pattern of
anomalies that occur across noncontiguous
embryological sites; however, they are pathogeni-
cally related.1
34.2 Embryology/Development
The developing skull and face is derived from three
tissue lines: the membranous neurocranium, the
cartilaginous neurocranium, and the visceral
splanchnocranium. Facial development occurs
between 3 and 8 weeks of gestation. Screening
ultrasound can reliably identify craniofacial abnor-
malities between 14 and 28 weeks.2
34.2.1 Calvarial Skeletal
Ossification
The fetal calvarium (membranous neurocranium)
ossifies through intramembranous ossification
(bone develops directly from mesenchymal pre-
cursor). The dura and the periosteum together
provide osteogenic signals for the growing calva-
rium; however, unlike the periosteum, the dura
loses its osteogenic potential in late infancy/early
childhood.3 The cranial base is composed of carti-
laginous neurocranium and ossifies through
endochondral ossification. These tissues are first
cartilaginous structures before undergoing pro-
gressive replacement by bone. In the infant cranio-
facial skeleton, the margins of the cranial base
form synchondroses allowing continued growth.
Restriction of growth at these interfaces result in
many types of midfacial chondrodysplasias. The
cranial vault in particular grows in response to
brain growth. These bones grow in a perpendicular
fashion to their sutures. The cranial base responds
with cartilaginous growth followed by ossification
creating a malleable base that responds to calvarial
growth.
Herniation of the cerebellar tonsils occurs in a
significant percentage of children with syndromic
craniosynostosis, and is thought to be an acquired
anomaly resulting from downward pressure on
the cerebellar tonsils due to relatively decreased
intracranial volume. By increasing intracranial vol-
ume, anterior vault decompression has proven
e ective in correcting tonsilar herniation in
asymptomatic patients, though herniation may
recur over time.4 Posterior vault remodeling with
suboccipital decompression is recommended for
symptomatic patients with cerebellar tonsillar her-
niation and for patients with syndromic Chiari
malformations.5
Additionally, in children with
bicoronal craniosynostosis, turribrachycephaly,
and evidence of elevated intracranial pressure
(ICP), posterior expansion becomes the surgical
priority. This may be achieved through a single
operation or through distraction.
34.2.2 Facial Skeletal Ossification
The facial skeleton is derived from the visceral
splanchnocranium. The midfacial skeleton and
mandible both undergo intramembranous ossifi-
cation. Final facial skeletal grow th is not achieved
until late adolescence/early adulthood.
34.2.3 Facial Clefting
Orofacial clefting may result in cranial base defects,
encephaloceles, and hypertelorism. The most com-
monly accepted classification scheme for facial
276

clefting was described by Tessier ( Fig. 34.1).
Clefts 10 to 14 are most likely to require a com-
bined neurosurgical and plastic surgical approach.
34.3 Genetics
34.3.1 Syndromic
● FGFR: Mutations of genes in the fibroblast
growth factor receptor (FGFR) family account for
the majority of known mutations in syndromic
craniosynostosis. These mutations are generally
activating, which accounts for observed
autosomal dominant transmission patterns of all
craniofacial syndromes caused by FGFR
mutations.6 FGFR1, FGFR2, and FGFR3 signaling
modulates osteoblast activity in both
endochondral and intramembranous bone
ossification.7 These receptors contain three
major immunoglobulinlike regions with variable
binding a nity for 22 known FGF ligands.6
Activation and homodimerization of receptors
facilitate downstream signaling via the MAP/ERK
and PI3K/AKTsignaling cascades.8 Mutations in
FGFR genes account for Apert’s, Cruzon’s,
Pfei er’s, and Muenke’s syndromes, among
others.9
● MSX: A gain-of-function mutation in the muscle
segment homeobox 2 (MSX2) accounts for
Boston-type craniosynostosis,10 which has been
identified in one cohort in the Boston, MA,
area.6 Expression and suture involvement is
variable, accounting for variable phenotypes,
from fronto-orbital recession to cloverleaf skull
deformities.9
● TWIST1: Over 100 mutations of the helix-loop-
helix transcription factor TWIST1, accounting for
Saethre–Chotzen syndrome, have been
identified.7 Mutations include nucleotide
substitutions (missense and nonsense),
deletions, insertions, duplications, and complex
rearrangements. These loss-of-function
mutations result in haploinsu ciency, and
cluster at the DNA binding and dimerization
domains of the protein.
34.3.2 Associated Disorders/
Anomalies
It would be beyond the scope of this chapter to
provide an exhaustive list of associated anomalies
in children with syndromic craniofacial disorders.
However, it is important to note the other dysmor-
phisms are common in the extremities (syndactyly
is especially common). Additionally, cardiac defects
such as patent ductus arteriosus (PDA), conotruncal
defects, and atrial septal defects (ASDs) are common
with frontonasal dysplasias. Other overlooked
a ected areas in syndromic children are genitouri-
nary dysmorphologies and vertebral anomalies.1 It
is also worth noting many children will fall into the
unnamed syndrome category where syndromic
pathology is present but has yet to fall into a well-
described pathogenic/genetic mechanism.
34.3.3 Craniofacial Syndromes
As over 180 syndromes involve craniosynostosis11
or craniofacial dysplasia, only the most common
Fig. 34.1 Tessier classification. (Re-
produced with permission from
Anatomical classification of facial,
cranio-facial and latero-facial clefts. J
Maxillofac Surg. 1976.)
Management of Craniofacial Syndromes
277

and well characterized will be discussed here.
There is significant overlap between Apert’s and
Crouzon’s syndrome (this at one time were
thought to be the same entity), while Muenke’s,
Pfei er’s, and Sathre–Chotzen syndromes are sim-
ilar with distinctions in associated anomalies and
facial dysmorphology patterns.
Apert’s Syndrome
Apert’s syndrome (1 in 60,000–90,000 births) is
characterized by turribrachycephaly, forehead ret-
rusion, midface retrusion, exorbitism, beaked nose,
lateral canthal dystopia, downward slanting palpe-
bral fissures, trapezoidal upper lip, eyebrows with
a break in continuity,12 and open mouth breath-
ing.7 Cleft palate and hearing loss due to fused
ossicles may also be present. Central to the clinical
diagnosis is complex symmetric acrocephalosyn-
dactyly of the hands and feet. Radiohumeral fusion
is variably present. Malformations of the central
nervous system are numerous, and include hydro-
cephalus, ventriculomegaly, megalencephaly, gyral
malformations, and defects in the corpus callosum,
septum pellucidum, hippocampus, and cerebral
cortex.13
Skeletal pathology includes bilateral
coronal synostosis. Initially, there may be a wide
calvarial defect from the posterior fontanel to the
glabella, but this typically closes over time.
Patients have variable degrees of neurodevelop-
mental delay. Two mutations, FGFR2 S252 W and
P253 R, account for 71 and 26% of cases, respec-
tively.11 Inheritance is autosomal dominant. Ma-
nagement of children with Apert’s syndrome is
complex, including surgical correction of craniosy-
nostosis, cleft palate, and midface hypoplasia.
Treatment typically includes a combination of cal-
varial vault remodeling, monobloc advancement
with distraction,14 Le Fort III15 osteotomies, facial
bipartition,16
and/or midface distraction,17
depending on the severity and location of vault
and midface deformities.18,19
Crouzon’s Syndrome
Crouzon’s patients (1 in 65,000 births) typically
demonstrate hypertelorism, divergent strabismus,
midface hypoplasia, proptosis, relative mandibular
prognathism, and a beaked nose.7 Optic atrophy,
found in approximately 20% of Crouzon’s patients,
and the lack of hand and foot syndactyly, distin-
guishes this syndrome from Apert’s syndrome.12
Craniosynostosis is typically bicoronal, with occa-
sional early pansynostosis.7
Crouzon’s patients
appear to have the highest incidence of cerebellar
tonsilar (non-Chiari) herniation, with up to 71% of
patients a ected in some series.4 There are no
associated limb features, and intelligence is nor-
mal. Features of the disorder are frequently seen in
relatives. Crouzon’s is typically caused by FGFR2
mutations. Crouzon’s syndrome with acanthosis
nigricans of the axilla and groin (<5% of cases) is
caused by the FGFR3 (A391E) mutation.7 Goals of
surgery are aimed at correction of turricephaly,
and include bifrontal advancement with anterior
vault remodeling between 6 months and 2 years of
age.9,19 In particular, most institutions now ini-
tially perform posterior vault expansion, followed
by anterior vault remodeling, then in later child-
hood address facial deformity through monobloc
advancement or Le Fort III advancement.
Pfei er’s Syndrome
Phenotypic presentation of Pfei er’s syndrome (1
in 100,000 births) is variable: patients typically
have turribrachycephaly, hypertelorism, strabis-
mus, choanal stenosis, midface hypoplasia, short,
broad thumbs and toes, auditory canal atresia, air-
way obstruction, variable brachydactyly, and varia-
ble craniosynostoses.7 Anomalies of the thumbs
and toes can aid in clinically distinguishing
Pfei er’s syndrome from Crouzon’s syndrome. The
posterior skull may develop a “swiss cheese”
appearance due to increased intracranial pressure
in the setting of multisuture synostosis.20 Central
nervous system anomalies are common, and
acquired Chiari malformations may be present in
as many at 50% of cases.21 Generally, bicoronal cra-
niosynostosis is present, with multiple other
sutures variably involved.19,20 Pfei er’s syndrome
has been divided into three subtypes based on cal-
varial and midface severity as follows7: type 1:
mildest and most common clinical presentation,
and with least intellectual impairment; type 2:
more severe, with cloverleaf skull, severe propto-
sis, medially deviated toes and thumbs, hydroce-
phalus, seizures, and intellectual disability; type 3:
similar to type 2, but without cloverleaf skull, yet
more severe mental disability and nonsynostotic
anomalies. Greater than 95% of patients with this
syndrome have FGFR2 mutations.11 The remainder
have FGFR1 mutations. Inheritance is autosomal
dominant. Goals of craniofacial surgery include cor-
rection of proptosis, reduction of ICP, correction of
airway obstruction, and anterior cranial vault
remodeling.19 Choice of surgical procedure is based
on presenting symptoms and morphology, with
Developmental and Congenital Cranial Disorders
278

probable benefits to earlier surgery in types 2 and 3
patients, and posterior decompression with symp-
tomatic Chiari malformations in patients greater
than 1 year of age.20 As with Apert’s patients, surgi-
cal management is complex and highly tailored to
patient needs, with debate regarding timing and
indications for specific procedures.9,19,20
Saethre–Chotzen Syndrome
Saethre–Chotzen syndrome (1 in 25,000–50,000
births) is characterized by a low-set hairline, devi-
ated nose with beaked appearance, prominent
chin, ptosis, and small ears with a prominent hori-
zontal Cruz. Syndactyly of the index and long fin-
gers is variably present. Less common features
include cleft palate, maxillary hypoplasia, and
hearing loss. Intelligence is typically normal, but
may be abnormal with complete TWIST1 deletion.
Phenotypic presentation may be mild and mimic
nonsyndromic coronal synostosis. Patients typi-
cally have unicoronal or bicoronal synostosis, but
may have metopic and sagittal synostosis as well.
The majority of Saethre–Chotzen cases (40–80%)
are caused by variable TWIST1 mutations, includ-
ing substitutions, deletions, and rearrangements.11
Inheritance is autosomal dominant. Goals of sur-
gery include correction of facial asymmetry in uni-
coronal synostosis, reduction of ICP, and correction
of midfacial hypoplasia.22 Cleft palate repair typi-
cally follows cranial vault remodeling.
Muenke’s Syndrome
Similar to Saethre–Chotzen, patients with Muenke’s
syndrome (1 in 30,000 births) display great clinical
variability, and may have only mild unicoronal syn-
ostosis.9 Phenotypes range from mild anterior pla-
giocephaly to brachycephaly, to cloverleaf skull
deformity from multisuture synostosis.7 Craniosy-
nostosis is typically uni- or bicoronal. Patients may
also have midface hypoplasia and ocular hypertelor-
ism, though this is less common. Associated
findings may include Klippel–Feil cervical anomaly,
brachydactyly, and carpal bone fusion. Intelligence
is usually normal. Muenke’s syndrome is caused by
a single FGFR3 mutation (P250R).11 Inheritance is
autosomal dominant. Variable expression accounts
for the wide range of clinical findings, and this mu-
tation may account for 20% of coronal synostosis
cases. All patients with uni- or bicoronal synostosis
should therefore be screened for this mutation,9
and screening of patients with unclassified brachy-
cephaly may result in increased diagnoses of this
syndrome.23 Goals of surgery include correction of
facial asymmetry, correction of turribrachycephaly
in bicoronal synostosis, and reduction of ICP.9,24
Carpenter’s Syndrome
Carpenter’s syndrome (1 in 1,000,000 births) is
characterized by any combination of multiple
suture craniosynostosis in association with poly-
dactyl, syndactyly, obesity, hypogenitalism, and
congenital heart disease.9 The degree of develop-
mental delay is variable.11 Loss-of-function RAB23
mutations disrupting vesicular transport protein
cascades and sonic hedgehog signaling are thought
to account for this syndrome.11 Inheritance is
autosomal recessive. Given the variable pheno-
typic presentation of this disorder, corrective sur-
gery is dependent on suture involvement and
deformation severity, and generally involves cor-
rection of anterior fossa underdevelopment.25
Craniofrontonasal Dysplasia
Patients with craniofrontonasal dysplasia (1 in
100,000–120,000 births) demonstrate brachycephaly
or plagiocephaly due to coronal synostosis, hyperte-
lorism (frequently asymmetric), cleft lip–cleft palate,
limb abnormalities, frizzy curled hair, and longitudi-
nal ridging and splitting of nails.9,26 Mutations of the
EFNB1 gene on Xq12, encoding a transmembrane
protein, are responsible.11 Transmission is X-linked,
females are more severely a ected than males, and
severity increases with increased parental age.9 Sur-
gical correction typically includes staged four-wall
orbital box osteotomies or facial bipartition (depend-
ing on degree of bimaxillary cant and occlusal plane
deformities).19,26
Cranial Clefts
These are clefts of the superolateral orbit and
extend through the frontal bone and/or the cranial
base. They are usually associated with lower orofa-
cial clefting as described by Tessier. Clefts 10 to 14
may result in hypertelorism and/or encephaloceles
are repaired with respect to closure of the ence-
phalocele and correction of the hypertelorism.
These clefts tend to be rare and can in many cases
be associated with severe central nervous system
(CNS) anomalies and poor life expectancy.
34.4 Surgical Approaches
The standard craniofacial approaches are the
fronto-orbital advancement (FOA), the monobloc/
Management of Craniofacial Syndromes
279

Le Fort III advancement, facial bipartition, and
orbital box osteotomies. These operations and
variations of them form the basic foundation for
correction of all craniofacial dysplasias.
● Indications: Elevated ICP, exorbitism/corneal
exposure, normalization of craniofacial
morphology, and airway obstruction.
● Typical timing and staging of procedures:
– 6–8 months: Posterior vault remodeling if
required (elevated ICP, severe
turribrachycephaly).
– 7–12 months: FOA, with calvarial remodeling
for associated craniosynostosis deformities.
– 7–10 years of age: Midfacial advancement and
correction of orbital dystopias with treatment
options including onobloc advancement,
extracranial Le Fort III advancement, facial
bipartition, or orbital box osteotomies,
depending on type and degree of deformity.
Midfacial correction is greatly individualized to
each patient’s particular dysmorphology.
– 15–18 years of age: Orthognathic surgery for
correction of final occlusion at skeletal
maturity.
34.4.1 Fronto-Orbital
Advancement
Indications/Procedure
The most common intracranial craniofacial proce-
dure is the FOA. A common feature among many
craniofacial dysmorphologies is a retrusive frontal
bar. In addition, the osteotomies for the FOA form
the foundation for all other craniofacial advance-
ment procedures. In particular, it is critical to
understand the cranio-orbital relationship in
major craniofacial malformations; the majority of
these disorders will exhibit some degree of hyper-
or hypotelorbitism, vertical dystopia, or frank
exorbitism.27 The degree of frontal bar retrusion is
measured from the anthropometric points orbitale
superius (os) to apex corneae (ACOR). Os is the
anterior most soft tissue projection of the superior
orbital rim and ACOR is the anterior most corneal
projection. Normal os to ACOR is 8 to 10 mm
dependent on age.27 Indications for FOA are dic-
tated by degree of orbital retrusion, in severe cra-
niofacial cases os-ACOR is often a negative value
demonstrating exorbitism. FOA is also indicated as
part of secondary correction of frontal craniosy-
nostotic plagiocephaly resulting in distortion of
the frontal bar and upper midfacial symmetry.28
Patients with severe exorbitism, corneal exposure,
elevated ICP, or changes in vision require earlier
operations. Those patients requiring nonfunctional
advancement can be delayed till the child is older.
The approach to an FOA forms the basis for
all other intracranial craniofacial operations
(Fig. 34.2Fig. 34.3).
● A standard oral endotracheal intubation is
perform ed. After induction of anesthesia, a
Foley catheter is placed, in a central venous
line, and in an arterial line. Additionally, it is
standard at our institution to place a
precordial Doppler probe to m onitor for air
em bolus.
● The child is prepped and draped in the supine
position, the head is placed in a padded
horseshoe Mayfield; typically, the head is shaved
or a coronal strip is shaved. The scalp is injected
with a dilute epinephrine solution with or
without dilute topical anesthetic (similar to
tumescent solution). The eyes are protected with
Fig. 34.2 Before and after fronto-orbital advancement in patient with multisuture synostosis. (a) Pre-operative lateral
image demonstrating severe frontal bar retrusion secondary to coronal synostosis. (b) Intraoperative frontal bar and
frontal bone unit after recontouring. (c) Postoperative result after advancement.
Developmental and Congenital Cranial Disorders
280

tarsorrhaphy sutures. Either a straight line or a
z-type incision is used for the frontal bone
exposure. In males it is best to place the incision
as far posterior as possible to avoid visibility
with male pattern baldness.
● After the scalp incision, the exposure is carried
down through the pericranium. The pericranium
is carried attached to the scalp flap, thereby
preserving pericranium for pericranial flaps if
necessary. The temporalis muscle is raised in
a subperiosteal plane attached to anterior skin
flap.
● Throughout the exposure m anagem ent of
blood loss is essential, and every attempt
m ade to control skin edge bleeding with
bipolar cautery and the use of bone wax or
other comm ercial hemostatic agents for
control of bony blood loss. In addition, active
comm unication between the operating
surgeon and the anesthesia sta m ust be
m aintained with regard to resuscitation. The
two points of maximum blood loss are the
elevation of the scalp flaps and the elevation
of the bony flaps. During this period,
hemodynamic end points m ust be actively
m onitored and warm colloid resuscitation
through a large-bore intravenous (IV)
catheter is perform ed. At our institution,
these children are resuscitated with packed
red cells and fresh frozen plasm a in either
1:1 or 2:1 ratios with m inimal use of
crystalloid. Once the craniotom ies are
complete, the blood tends to be m inim al for
the rem ainder of the case and blood
products should be used judiciously from this
point dictated by objective end points: urine
output, central venous pressure, hemoglobin
trend, base deficit, etc.
● The dissection must be carried in a subperiosteal
plane to expose the nasal radix, the superior and
lateral orbit and orbital rims. Often a 2-mm
osteotome is often required to free the superior
orbital neurovascular bundle from its ostia.
● This exposure forms the basis for all subsequent
craniofacial procedures.
● After exposure for the upper midface and frontal
bone, markings are made for the advancement
and removal of the frontal bone and frontal bar.
The burr hole sites are placed with care to avoid
the sagittal sinus.
● Once the frontal bone has been removed, the
osteotomies for the FOA may be performed.
Typically, the frontal lobe is retracted and the
temporal lobe is dissected free from the dural
attachments to the middle cranial fossa in
preparation for the osteotomies (inadvertent
injury to the temporal lobe is possible during the
lateral releasing osteotomies if attention is not
paid to the middle cranial fossa). First a medial
to lateral osteotomy is made in the anterior
cranial fossa into the superior orbit. These
osteotomies are made, using a reciprocating saw
or a side cutting drill bit, across the superior
orbit and laterally along the temporal bone.
Once the lateral orbital wall is encountered, the
osteotomy is deepened into the temporal fossa
and carried out to the distal temporal bar (as
marked). Care is taken to protect the temporal
lobe with a retractor in the middle temporal
fossa during the lateral most osteotomy, as the
saw can inadvertently enter the middle cranial
fossa with a long temporal bone extension. Next,
attention is turned to completion of the lateral
orbital rim osteotomy with connection to the
superior orbital osteotomy completely the lateral
dissociation of the frontal bar from the
Fig. 34.3 (a,b) Fronto-orbital
advancement.
Management of Craniofacial Syndromes
281

calvarium. Lastly, in order to release the frontal
bar, a central osteotomy through the frontal
bone above the cribiform plate is made, superior
to the nasofrontal suture.
● After advancement and contouring of the frontal
bone and frontal bar, they are rigidly fixated
with absorbable plates and screws ( Fig. 34.3).
Common complications include frontal bar relapse,
cerebrospinal fluid (CSF) leak secondary to dural
tears, and residual cosmetic deformity.
34.4.2 Le Fort III/Monobloc
Advancement
Indications/Procedure
Syndromic patients often su er from midfacial
dysplasia or hypoplasia. In particular, children with
Apert’s, Crouzon’s, and Pfei er’s14,16,17,18,19
syn-
dromes may present with severe exorbitism exa-
cerbated by underdeveloped midfacial structures.
Thus, advancement of the supraorbital bar alone
would not correct the exorbitism because of con-
current maxillary hypoplasia that is best addressed
in unison.15 In these children, a monobloc advance-
ment allows correction of the frontal bone and can
help treat the bicoronal synostosis, frontal bar
position, inferior orbit, and maxillary position. In
patients that do not require early correction (i.e.,
they are able to protect their globes, and do not
have evidence of optic nerve strain) of the superior
orbit and inferior orbit, midfacial advancement
may be delayed into mid childhood (7–10 years of
age) (Fig. 34.4). Additionally, a less well identi-
fied but emerging indication for midfacial advance-
ment in these children is obstructive sleep apnea
and tracheostomy dependence in severe cases.
● Initial preparation and exposure is performed as
with FOA procedures. The endotracheal tube
may be orally placed and is often secured to the
mandible with a circumandibular wire or wired
to the central mandibular incisors for older
children (teeth should be wired in pairs to
prevent accidental extraction via the wire).
● After exposure for FOA, the lateral extent is
carried down to the zygomatic arches and
complete exposure of the lateral orbital rim and
inferior orbital rim is obtained. A second
transconjuctival incision may be utilized to assist
in the orbital floor exposure and inferior orbital
rim exposure (this is surgeon and center
specific). The orbit must be circumferentially
freed in a subperiosteal plane.
● Additionally, the lower midface is also exposed
using an upper gingivobuccal incision in order to
free the lower midfacial periosteal attachments
if necessary. This exposure in particular is used
for an intraoral pterygomaxillary osteotomy. Or,
if a gingivobuccal incision is not required, a
posterior upper sulcal incision may be made for
the intraoral pterygomaxillary disimpaction.
This osteotomy may also be made through a
superior temporal approach without intraoral
incisions (these decisions are often case and
surgeon specific).
● A frontal bone craniotomy is performed as with
an FOA; however, in a monobloc advancement,
the frontal bar is left attached to the midface.
The same osteotomies are performed initially to
free the superior orbital roof and lateral wall;
however, the nasofrontal buttress is left intact
preserving the frontal bar as an attached unit of
the midface. The midline osteotomy is instead
perpendicular to the FOA approach and placed in
the anterior most cribriform plate through the
Fig. 34.4 Patient with Apert’s syndrome with midfacial retrusion. (a) Preoperative appearance. (b) Postoperative results
after extracranial Le Fort III midfacial advancement. (c) Illustration of Le Fort III advancement.
Developmental and Congenital Cranial Disorders
282

cranial base into the primitive nasoethmoid
sinuses.
● Next, the orbital osteotomies are continued
through the medial wall and orbital floor
connecting to the lateral wall osteotomies
performed earlier. Additionally, separate
anterior zygomatic arch osteotomies are also
performed. Once the orbits and the cranial base
have been separated and the zygomatic arches
have been cut, the face is only held to the
calvarium via the pterygomaxillary buttress. This
osteotomy is typically addressed intraorally with
a curved osteotome but may also be approached
through the temporal exposure. Care must be
taken not to injury the internal maxillary artery.
Injuries to this vessel may cause life-threatening
hemorrhage and frequently require
endovascular embolization for control.
● Monobloc advancements are typically used with
distraction osteogenesis and placement of
distractors. In cases where advancement of less
than 10 to 15 mm may be performed a single
stage with rigid fixation. In these cases,
placement of pericranial flaps in the cranial base
is critical to preventing CSF leaks and
nasocranial communications with a risk of
secondary meningitis (Fig. 34.5).15,29,30
Complications include relapse, CSF leak, epidural
abscess, meningitis, malocclusion, and endotra-
cheal tube dislodgement/injury.
34.4.3 Facial Bipartition and Box
Osteotomies
Indications/Procedure
Hypertelorism or orbital dystopia is common in
patients with craniofacial anomalies. In these cases,
the facial skeleton must be split either into halves
or into separate orbital segments. Normal adult
intercanthal distance is less than 35 mm, measured
from medial canthus to medial canthus. For most
cases this measurement provides the approximate
degree of hypertelorism, but true measurement for
repair can be derived from measurement of the
bony dacryon–dacryon on imaging. The bony
dacryon is a cephalometric point defined as the
junction of the maxillary, lacrimal, and frontal bone.
Normal distances are 25 to 30 mm. For symmetric
hypertelorism with a narrow palate, the face may
be addressed as a split monobloc advancement
with removal of the portions of the central frontal
bone, nasal skeleton, and maxilla.29 This constitutes
a facial bipartition (Fig. 34.6). If the maxilla does
not require widening and the child’s occlusion is
una ected, box osteotomies are performed leaving
the maxilla unchanged (Fig. 34.6). These proce-
dures are usually deferred until approximately 5 to
7 years of age because the tooth roots of the perma-
nent dentition before this reside at or just below
the inferior orbital rim.
● Surgical approach and preparation is the same as
with monobloc advancement.
● Once dissection is complete, a portion of the
central face is removed corresponding to the
degree of hypertelorism and necessary palatal
widening. The frontonasoethmoidal resection is
planned by degree of widening (or degree of
bimaxillary cant) seen clinically and on imaging.
– Most significantly the decision whether to
proceed with a facial bipartition versus a box
osteotomy is decided by evaluation of the
maxilla. If the maxilla is widened or canted, a
facial bipartition is performed. If the maxilla is
normal, then only box osteotomies are
necessary. In facial bipartition, the maxilla is
cut in the midline and realigned. For box
osteotomies, a Le Fort I level cut is made to
free the orbits from their attachment to the
maxilla.
● This resection leaves the potential for a
central facial dead space and oronasal
comm unication w ith the m eninges and thus
Fig. 34.5 (a, b) Monobloc
advancement.
Management of Craniofacial Syndromes
283

the anterior cranial base should be lined with
a pericranial flap.29,30
● Preoperative imaging may play a critical role in
these cases, as often encephaloceles and other
sphenoethmoidal abnormalities are present. The
location and types of abnormalities will a ect
placement of cranial base osteotomies and
repair.
● Box osteotomies follow a similar approach but
allow for preservation of the maxillary occlusion
and can be used to address both vertical and
horizontal asymmetries. Instead of a central
maxillary osteotomy, the box osteotomies are
carried out along the upper maxilla just inferior
to the infraorbital nerve out laterally to the
zygomas (in a Le Fort I fashion) and connected to
the lateral orbital osteotomies allowing the
anterior orbit to be positioned as a single unit
(Fig. 34.7).
Complications are typically the same as for mono-
bloc advancement.
Postoperative Care
Every e ort is made to extubate children at the
conclusion of the procedure. In the pediatric inten-
sive care unit (ICU), blood gases and chemistries
are rechecked and the level of resuscitation eval-
uated. In addition, it is critical to limit excessive
crystalloid resuscitation; if additional volume is
necessary, an additional unit of blood is often
given. The use of warm colloid resuscitation pre-
vents postoperative third spacing, coagulopathies,
and development of significant craniofacial edema.
Typically, a drain is left under the scalp flaps and
removed once it is draining less than 20 to 30 mL
per day. The patient is observed overnight in
the pediatric ICU and hourly neuro checks are
Fig. 34.6 (a, b) Facial bipartition and four-wall box osteotomies.
Developmental and Congenital Cranial Disorders
284

performed during this period. For patients with an
intraoral incision, a liquid diet is started, those
without oral incisions are typically advanced as
tolerated. On postoperative day 1, patients are
usually transferred to the floor and are discharged
on average on postoperative day 3 to 5 from the
hospital. The dressings are removed on the first
postoperative day and antibiotic ointment is then
used once daily on the incision for approximately
1 week.
34.5 Summary
Craniofacial syndromes present complex anoma-
lies of the craniofacial skeleton requiring a com-
bined plastic and neurosurgical approach for
repair. Many syndromes have readily identifiable
clinical phenotypes that determine indications for
surgery, and the genetic underpinnings of these
syndromes are increasingly well characterized.
The understanding of the timing of repair and the
surgical indications are critical to successfully
addressing craniofacial dysmorphologies. Typical
first repair addresses the calvarium and supra-
orbital bar (after posterior distraction in cases
with turribrachycephaly). The timing of repair is
usually between 6 and 10 months of age but may
be sooner in cases of elevated ICPs or severe exor-
bitism with the threat of corneal exposure. Midfa-
cial dysmorphologies and orbital dystopias are
addressed in midchildhood because of the poten-
tial risk to facial growth. Thus, age of repair is typi-
cally reserved until 7 to 10 years of age. Final
orthognathic procedures, which do not require a
combined intracranial approach, are addressed
when final facial skeletal maturity has been
achieved (15–18 years old). Computer-aided design
and preoperative modeling provide a window into
the future of craniofacial surgery with preplanned
operations based on objective cephalometric data
and preoperative 3D CT imaging to guide in pre-
cise placement of osteotomies and degree of
advancement. It is also crucial in the evaluation of
syndromic children to assess for other anomalies
and genetic counseling and analysis will be impor-
tant factors in future understanding of the root
causes of these syndromes.
34.6 Common Clinical
Questions
1. When can significant craniofacial anomalies be
diagnosed with prenatal ultrasound?
Fig. 34.7 Hypertelorism correction for
severe orbital hypertelorism with
frontal bone clefting. (a) Preoperative
image demonstrating severe hyper-
telorism. (b) Intraoperative image of
frontal bone and supraorbital bar
markings prior to osteotomies of box
orbital segments. (c) Intraoperative
advancement and medialization of box
orbital segments with central fixation.
(d) Postoperative result demonstrating
significant improvement in orbital
hypertelorism and frontal bone
contour.
Management of Craniofacial Syndromes
285

2. What are the major operative indications for
craniofacial dysmorphologies?
3. When should craniofacial dysplasias be
addressed, what are indications for urgent
intervention?
4. How should craniofacial operations be staged
for repair?
34.7 Answers to Common
Clinical Questions
1. Typically, major craniofacial anomalies may be
diagnosed by the 16- to 18-week ultrasound.
2. Major indications for operation are evidence of
elevated ICP, corneal exposure for severe
exorbitism, and significant facial deformity.
3. Urgent intervention is dictated by elevated ICP
leading often to early (4–6 month posterior
vault expansion), and FOA for severe exorbitism
with threatened corneal exposure, temporizing
tarsorrhaphy sutures may be placed for corneal
protection. Additionally, tracheostomies may be
necessary.
4. Syndromic craniofacial operations are staged by
order of urgency and skeletal age of the child.
They start with early posterior vault expansion.
Next, the frontal bone and superior orbit are
addressed, followed by midfacial procedures
once the child is older, and orthognathic
surgery and final rhinoplasty at completion of
skeletal growth.
● Typical timing and staging of procedures:
– 6–8 months: Posterior vault remodeling if
required (elevated ICP, severe
turribrachycephaly).
– 7–12 months: FOAwith calvarial
remodeling for associated craniosynostosis
deformities.
– 7–10 years of age: Midfacial advancement
and correction of orbital dystopias with
utilization of monobloc advancement,
extracranial Le Fort III advancement, facial
bipartition, or orbital box osteotomies,
depending on type and degree of deformity.
Midfacial correction is greatly
individualized to each patient’s particular
dysmorphology.
– 15–18 years of age: Orthognathic surgery
for correction of final occlusion at skeletal
maturity. Rhinoplasty can also be
performed at this stage depending on
surgical indication.
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Management of Craniofacial Syndromes
287

35 Germinal Matrix Hemorrhage in Premature Infants
Moise Danielpour, Lindsey Ross
35.1 Introduction
Despite advances in prenatal care and sophisti-
cated postnatal monitoring, the incidence of
major neurodevelopmental deficits in very-low-
birth-weight infants remains unacceptably high.1
National outcomes data show that almost one-
fourth of these children su er major neurological
deficits, with nearly one-fifth requiring some form
of special education at school age.2 Germinal
matrix hemorrhage (GMH) is the most common
diagnosed brain lesion in preterm infants and is
often seen in the sickest and most premature.
GMH with intraventricular extension and the
resultant complication, of posthemorrhagic hydro-
cephalus of prematurity (PHH), is one of the most
dreaded myriad of diseases that plague the prema-
ture infant. Despite numerous prevention and
intervention trials, GMH occurs in up to 20% of
preterm infants less than 1,500 g birth weight and
is the predominant cause of neurodevelopmental
disability in these infants.3,4,5
35.2 Pathophysiology of
Germinal Matrix
The germinal matrix and the ventricular germinal
zones are the sites of neuronal and glial prolifera-
tion from immature radial glia. The majority of the
developing cortical neurons complete generation
by 25 weeks’ gestational age. During the late sec-
ond and early third trimester, the germinal matrix
gives rise to cortical neuronal and glial cell precur-
sors, which involute and migrate toward the
caudothalamic groove. By 32 weeks’ gestation, the
cellular component of cerebral cortex has nearly
completely populated the appropriate layers. Dur-
ing this time there is an abundance of cortical axo-
nal and dendritic activity with exponential
increase in synaptic contacts. Thus, GMH, which
most commonly occurs prior to 32 weeks of gesta-
tion, can have dramatic e ects on cortical develop-
ment and ultimately cognitive maturity.
More specifically, during the late second and
early third trimesters, the microvasculature of the
brain undergoes dramatic expansion to meet met-
abolic needs of the germinal matrix and cortex.6
The capillary beds of the germinal matrix are com-
posed of large and irregular vessels that are not
yet identifiable as arterioles, venules, or capillaries.
Additionally, there are luminal areas, which are
significantly larger than the cortical vessels and
these areas lack the traditional components of the
blood–brain barrier, and may be more susceptible
to disruption.7
Animal studies have demonstrated that autoregu-
lation of cerebral blood flow matures with increas-
ing gestation. During the late second and early third
trimester, cerebral autoregulation is ine cient. This
leaves the region susceptible to fluctuations of sys-
temic blood pressure and cerebral blood flow. The
germinal matrix and periventricular white matter
are watershed zones at high risk for hypotensive
injury. Because the germinal matrix is a metabol-
ically active area, it tends to be exceptionally sensi-
tive to hypoperfusion and hypotension. All these
factors lead to extreme susceptibility to infarction
and/or hemorrhage in the premature infant.
Pathogenesis of perinatal factors and comorbid-
ities associated with an increased risk of hemor-
rhage.
35.2.1 Comorbidities
● Postnatal hypoxia because of any cause including
respiratory distress syndrome, pneumothorax,
anemia, or sepsis.
● Hypercapnia maximally dilates the thin-walled
vasculature. If this is followed by increases in
volume or perfusion of the tissue, this can result
in hemorrhage.
● Increased venous pressure (i.e., positive pressure
ventilation, stimulation, endotracheal
suctioning) can result in hemorrhage.
● Dehydration followed by rapid resuscitation with
hyperosmolar fluids encourages osmotic flow of
fluids out of the tissue and into the vascular
space resulting in rapid changes in transmural
pressure and vascular rupture.
35.2.2 Risk Factors
● Weight less than or equal to 1,500 g.5,8,9
● Early gestational age (EGA) (<28 weeks).
● Increased cerebral perfusion pressure (CPP),
decreased tissue oxygenation or hypoxia, and
increased cerebral blood flow.
– Asphyxia or hypercapnia
– Rapid volume expansion
288

– Seizures
– Pneumothorax
– Cyanotic heart disease
– Mechanical positive pressure ventilation
anemia
– Decreased blood glucose on arterial
catheterization
– Blood pressure fluctuations
– Acidosis
– Chorioamnionitis
– Coagulopathies, maternal aspirin use
– Extracorporeal membrane oxygenation
(ECMO)
– Maternal cocaine abuse
– General anesthesia for cesarean section
● Failure to give antenatal steroids 48 hours prior
to preterm delivery.
● Low Apgar’s scores at 1 minute (<4) or 5 minutes
(<8).
35.3 Epidemiology
35.3.1 Incidence
GMH is thought to a ect 15 to 20% of infants with
birth weights less than 1,500 g.10 Nevertheless,
many preterm patients are asymptomatic following
GMH and may not be detected if routine surveil-
lance is not instituted. In 1978, Papile utilized com-
puted tomography (CT) to find that GMH occurred
in 43% of extremely low-birth-weight infants with a
mortality of 55% compared to mortality rate of 23%
for premature infants without GMH.11 Ultrasonog-
raphy is the study of choice for detection of GMH in
premature infants with a sensitivity of 90%.12
35.3.2 Timing
GMH has a bimodal distribution with 50% of hemor-
rhages occurring within 12 hours of birth and 45%
of hemorrhages occurring by postnatal days 3 to 4.
GMH may develop after day 4 in approximately 5%
of these infants. Progression is documented in up to
20% of patients, which most frequently occurs
within the first week of the initial hemorrhage.13
35.4 Etiology of Posthemorrhagic
Ventricular Dilation
Following are the three main etiologies:
1. Communicating hydrocephalus from GMH with
ventricular extension, which results in scarring
of cerebrospinal fluid (CSF) flow pathways,
impeding CSF circulation, and decreasing CSF
reabsorption by the arachnoid granulations.
Transforming growth factor-β and other
cytokines, which are released into the CSF
following GMH, appear to stimulate
extracellular matrix protein deposition,
impeding the process of CSF absorption.
2. ex vacuo hydrocephalus from encephalomalacia
and periventricular leukomalacia. GMH
destroys repository stem cells in the germinal
matrix, resulting in decreased number of
neurons and myelinated oligodendrocytes.
Late-onset obstructive hydrocephalus may occur
following CSF diversion procedure in a patient
with communicating hydrocephalus, leading to an
isolation of the fourth ventricle. This phenomenon
has mostly been documented as a late finding in
patients with intraventricular hemorrhage (IVH)
of prematurity following a fluid diversion proce-
dure such as placement of a ventriculoperitoneal
shunt, where the infant appears to develop secon-
dary aqueductal stenosis.
35.4.1 Etiology of
Postperiventricular
Hemorrhagic Infarction
● Ventricular hemorrhage evolves to compress and
occlude the terminal veins, which serve to drain
the internal cerebral veins into the vein of Galen.
This leads to subsequent venous infarct and
secondary hemorrhage.4,14
35.5 Clinical Presentation
It follows one of three following patterns4:
1. Catastrophic—Rapid neurological demise
requiring aggressive neurosurgical intervention.
Rare; carries a dismal prognosis.
2. Salutatory—Evolution over hours to days in
stepwise fashion associated with decreased
activity, abnormal eye movements, respiratory
discordance, and hypotonia.
3. Clinically silent—Which may present as slight
decrease in hematocrit and may be diagnosed
via cranial ultrasound.
35.5.1 Grading System
The most commonly used grading system is based
on CT or ultrasound. There is a direct correlation
Germinal Matrix Hemorrhage in Premature Infants
289

between the Papile grading system, gestational
age, and neurological outcome (Table 35.1).11
The incidence of grade IV germinal matrix hem-
orrhage is inversely proportional to gestational
age, that is, 30% of GMH patients are grade IVat 22
weeks and only 3% are grade IV at 28 weeks.15
Among the severely premature infants (24–26
weeks’ gestational age), 32% will have a grade III
(Fig. 35.1) and 19% will have grade IV, as com-
pared to the premature infants at 31 to 32 weeks’
gestational age, where 11% will have a grade II and
5% will su er from a grade IV ( Fig. 35.2).15
35.6 Diagnosis
Routine head circumference measurements and
examination of the anterior fontanel should be
part of the daily examination performed on the
premature infant. However, when there is a suspi-
cion of possible germinal matrix injury, the diag-
nosis is best made via bedside cranial ultrasound.
35.6.1 Ultrasound
Cranial ultrasound is the standard diagnostic tool
used for diagnosis and follow-up of premature
infants with GMH. The accuracy is approximately
88% (91% sensitivity, 85% specificity).
The main advantages of using cranial ultraso-
nography (CUS) are as follows:
● CUS is performed at the bedside, obviating the
need to transport a fragile infant.
Fig. 35.1 Neonatal cranial ultrasound series exhibiting a left-sided grade III premature intraventricular hemorrhage.
Table 35.1 Papile grading system
Grade Extent of hemorrhage
I

Restricted to germinal matrix
II

Intraventricular hemorrhage without ventricular
dilation
III

Intraventricular with ventricular dilation
IV

IVH with parenchymal involvement
Abbreviation: IVH, intraventricular hemorrhage.
Developmental and Congenital Cranial Disorders
290

● It is noninvasive test.
● Sedation is not required as occasional
movements are well tolerated.
● There is no exposure to ionizing radiation.
● CUS demonstrates the size and location of
hemorrhage, size of the ventricles, and thickness
of the cortical mantle.
● CUS can be followed serially with relative ease.
The main disadvantage of using cranial ultrasound
is poor visualization of the posterior fossa.
Determining severity of hydrocephalus in the
preterm infant is objectified by calculation and
knowledge of the following:
● Levene’s ventricular index—Midline falx to lateral
anterior horn in coronal view at foramen of
Monro. Normal ventricular index +4 mm is used
as criteria for surgical intervention.14,16
– Normal 27-week EGAventricular index at 97th
percentile =14 mm +4 mm =18 mm would
meet criteria for intervention.
● Anterior horn width (AHW) may be an even more
e ective way to measure early ventricular
expansion. Normal AHW in a neonate is less
than 3 mm and a greater than 6 mm is grossly
abnormal.16
35.6.2 Computed Tomography
It may be helpful in complex cases where anatomy
is di cult to characterize, or there is need for bet-
ter visualization of the contents of the posterior
fossa. Use is limited given associated risks of radia-
tion in the brain of a premature infant.
35.6.3 Magnetic Resonance
Imaging
It is uncommonly used secondary to poor visual-
ization of acute hemorrhage. This is reserved for
cases where there is a need for detailed imaging of
the brain such as in patients with aqueductal
stenosis or isolated fourth ventricle. This modality
often requires sedation and significant time away
from the neonatal intensive care unit. Use of ultra-
fast imaging and MRI compatible incubators
have increased the utility of MRI scans in these
patients.
Fig. 35.2 CT scan serial images of the neonatal brain exhibiting a right-sided grade IV premature intraventricular
hemorrhage.
Germinal Matrix Hemorrhage in Premature Infants
291

35.7 Pathology Associated
with IVHp
Cystic periventricular leukomalacia with IVH grade
III is often misdiagnosed as grade IV GMH.
Although, they may share similar pathophysiologi-
cal features, they are separate processes with likely
di erent etiologies.17 Often cerebellar hemorrhage
can coexist with GMH as well. However, this is dif-
ficult to diagnose on magnetic resonance imaging
(MRI) (10%) and even more di cult via ultrasound
(~2%).18 The presence of cerebellar hemorrhage
also increases the risks of neurological complica-
tions by fivefold.18
35.8 Treatment
The goal of treatment is to optimize cerebral per-
fusion pressures without excessive elevation of
cerebral blood flow, while carefully maintaining
mean arterial pressures, normalizing Pco2, and
reducing ventriculomegaly. With recent evidence
of the possible detrimental e ects of blood break-
down products, as a consequence of methemoglo-
bin-inducing expression of proinflammatory
cytokines, there are ongoing discussions of the role
of early ventricular drainage to reduce secondary
injury.19
35.8.1 Ventriculomegaly
● Transient ventriculomegaly (may occur in the
first few days of life, often not associated with
raised intracranial pressure).
● Progressive ventriculomegaly occurs in 20 to 50%
of cases as a result of decreased CSF reabsorption
or obstruction of CSF flow versus hydrocephalus
ex vacuo due to loss of brain tissue. If associated
with increasing head circumference or
physiological changes, it will require
intervention.
35.8.2 Lumbar Puncture
Lumbar punctures can be e ective at controlling
the deleterious e ects of posthemorrhagic hydro-
cephalus, but does not appear to reduce the fre-
quency of long-term permanent shunting. Serial
lumbar punctures in neonates can be cumbersome
and di cult to perform, and have a variable suc-
cess rate. As a result, they are usually used as a
short-term temporizing or diagnostic measure.
About 25% of patients with GMH with PHH will
have progressive ventriculomegaly. In 60% of these
progressive patients, early temporization will lead
to arrest of ventriculomegaly over several days to
weeks.20,21
35.8.3 Ventricular Puncture
Multiple ventricular punctures can result in poor
outcome and carry an increased risk of complica-
tions.20 Ventricular punctures should be reserved
for a neonate in extremis, as an initial temporizing
event, or for diagnostic purposes.
35.8.4 External Ventricular Drain
Use of an external ventricular drain (EVD) is lim-
ited by technical di culty secondary to small
ventricular size, mobility of neonatal skin, and
susceptibility to dislodging. Additionally, most
neonates will require an extended period of drain-
age, which carry an unacceptably high risk for
infection. Although theoretical advantages include
decreased risk of overdrainage and subsequent for-
mation of subdural hygromas, ability to monitor
intracranial pressure, and continuous removal of
CSF protein and blood products, evidence suggests
that the increased risk of infection from CSF drain-
age catheters are an independent predictor of poor
neurodevelopment and this risk far outweighs the
benefits attained from use of external drains.21
35.8.5 Medical Therapy
Antenatal betamethasone (a corticosteroid) reduces
the incidence of IVH in preterm infants.22 Medical
CSF diversion through acetazolamide and/or furose-
mide has not shown to decrease need for perma-
nent shunting and has been shown to increase the
incidence of neurological morbidity.23 Intraventricu-
lar fibrinolytic therapy results in an increased risk
of rehemorrhage and death.24 Nevertheless, studies
show that patients who survive the perinatal period
have improved neurological function on long-term
follow-up.20 Fibrinolytic therapy is currently not
used as standard therapy and in fact may be asso-
ciated with mild motor delays at 1 year of age.21,23
35.8.6 Surgical Therapy
About 34% of IVHp infants less than 1,500 g require
CSF drainage after failed medical management. In
infants with grade III and IV IVH greater than 70%
will develop progressive ventriculomegaly and 32
Developmental and Congenital Cranial Disorders
292

to 47% of these patients will ultim ately require
a shunt.25
Following are two surgical techniques for tem-
porary CSF diversion/removal:
● Ventriculosubgaleal (VSG) shunt.
● Ventricular reservoir.
35.9 There is no Data to Prove
Superiority of Either VSG Shunt
or Reservoir Placement
Subcutaneous reservoir placement was first used
for treatment of IVHp by McComb and colleagues
in 1983 and originally had a 20% mortality rate,
10% infection rate, and was associated with an ulti-
mate need for permanent CSF diversion of 75% of
neonates with progressive ventriculomegaly.26 The
quantity of CSF that is removed is adjusted to
opening pressure. In our practice, we limit number
of CSF taps to three times per day to minimize the
risk of secondary infections. Historically, infection
has been the most common complication,
although the infection rates have decreased dra-
matically. Other complications include skin
necrosis, CSF fistula, or development of subdural
hygromas.
VSG shunting involves placement of reservoir
with a piece of shunt tubing attached to the reser-
voir outlet, which allows for redirection of CSF to
subgaleal pocket where it collects and slowly reab-
sorbed. This allows for continuous CSF diversion,
with a theoretically decreased risk of developing
increased fluctuations in intracranial pressure and
size of the cerebral ventricles. There does not
appear to be any appreciable di erence in the inci-
dence of shunt placement or complications when
compared to a CSF reservoir. Additionally, this
technique allows for real-time observation in
variance of CSF resorption overtime. One is able
to easily ascertain if the patient is improving
resorption capacity. Nevertheless, this also appears
to be associated with a greater amount of parental
anxiety as the pouch is a dysmorphic feature
(Table 35.2).
35.9.1 Neuroendoscopy
The use of endoscopy in GMH with PHH is limited
but may allow for dilution of hemosiderin prod-
ucts and in special cases allows for single clot
removal and relief of obstructive hydrocephalus.
Gudegast et al published a series of seven patients
with complex hydrocephalus defined by recurrent
infections and subsequent multiple shunt revi-
sions that showed neuroendoscopy to be essential
in clean up and communication of isolated com-
partments.27
35.9.2 Endoscopic Technique for
Placement of a VSG Shunt,
Ventricular Irrigation, and
Aqueductoplasty
Technique for placement of CSF reservoirs and VSG
shunts has been reported previously.28 Since 2004,
we have employed the endoscopic method for
placement of the majority of our VSG shunts and
ventricular reservoirs, and ventriculoperitoneal
shunts (VPSs) in children with progressive ventri-
culomegaly following IVHp. This has allowed us
both visualization of the cerebral aqueduct and
decreased incidence of poorly placed ventricular
catheters.
35.9.3 Postoperative
Patients are monitored daily by examining the
anterior fontanel, vital signs, incidence of apnea
and bradycardia, and accumulation of CSF in the
subgaleal pocket when applicable. Weekly head
ultrasounds can be used to monitor ventricular
size.
35.9.4 Complications of VSG
Shunt
● Readhesion of subgaleal pocket especially with
lying on ipsilateral hemisphere. This can also be
a sign of resolution of hydrocephalus.
● Increase in occipital frontal diameter of cranium.
Risk decreases with immobilization and cranial
padding.
Table 35.2 Benefits of VSG versus SQ reservoir
placement
Benefits

VSG SQ reservoir
Less CSF aspiration

+

−
Permanent decompression

+

−
Less electrolyte and fluid shifts +

−
Conserves cerebral pressure

+

−
Dynamic observation

+

−
Abbreviations: CSF, cerebrospinal fluid; SQ, subcutane-
ous; VSG, ventriculosubgaleal.
Germinal Matrix Hemorrhage in Premature Infants
293

● CSF leakage at attachment of reservoir to catheter;
CSF leak from incision site occurred 4.7 to 32% of
the time in the Koksal series and has a 0 to 10%
risk of ventriculitis or meningiti.28 We have not
experienced any cases of CSF leaks in our patients,
or an increased risk of infection.
35.9.5 Tapping for CSF Removal
Removal of CSF via a reservoir or by lumbar punc-
ture plays an important role in not only relieving
intracranial pressure, but also decreasing the
proinflammatory byproducts of IVH. Nevertheless,
there is little evidence showing that frequent
tapping reduces the risk of shunt dependence,
morbidity, or mortality. In fact, repeated taps are
associated with an increased risk of central
nervous system infection.20,29 CSF tapping is per-
formed on an as needed basis to prevent progres-
sive ventriculomegaly. The frequency and quantity
should vary based on evidence of intracranial
pressure commonly measured through daily head
circumference, fontanel characteristics and physio-
logical changes, and direct measurements during
the removal of spinal fluid. In patients where
larger volumes of CSF have to be removed on a
daily basis, there may be a need for replacement in
the form of IV or PO isotonic fluids, especially in
children who weigh less than 1 kg.
35.9.6 Permanent Shunting
Delayed insertion of permanent shunting in this
population can result in decreased incidence of
early VPS revisions. Permanent CSF diversion is
required in 32 to 85% of patients following IVH of
prematurity.28,30
Most pediatric neurosurgeons
also advocate waiting until an infant is greater
than 2.5 kg and CSF protein is less than 1.5 g/L
before placing a permanent shunt as this has also
been shown to decrease surgical complications.29
CSF removal through tapping is thought to remove
hemosiderin blood products, thereby decreasing
risk of obstructive hydrocephalus. Additionally,
with delayed shunting, the infant is able to mature,
gain weight, and improve immunity and skin
integrity, which will improve overall ability to
recover from surgical procedures.29
Approxi-
mately, 45% of infants who receive VPS insertion
before 1 year of age require revision within 9
months.31
Endoscopic third ventriculostomy (ETV) is used
to treat patients with an obstructive component of
hydrocephalus, which may be currently under-
diagnosed in the GMH population. The role of ETV
in GMH with PHH remains controversial. ETV pro-
vides high success rates (77%) for patient with
pure aqueductal stenosis.32 However, due to the
complexity of IVHp and large component of com-
municating hydrocephalus multicenter trials have
shown a poor success rate for IVHp patients under-
going ETV.33 Theoretically, there is less risk of
infection and a very low subsequent shunt place-
ment rate.32 ETV can be successful for a small and
select group of patients following IVH of prema-
turity.34
35.10 Prognosis
Neurological complications of GMH include cere-
bral palsy, seizures, and cognitive delay. Multicen-
ter studies have shown that premature neonates
with IVH of prematurity have poorer neurofunc-
tional outcomes at 5-year follow-up regardless of
surgical management.35 Often resolution of hydro-
cephalus is associated with normal cerebral cortex
functioning and is often a good prognostic indica-
tor.30
Positive prognostic indicators of GMH
include antenatal corticosteroid treatment, cesar-
ean delivery, and prophylactic intravenous
indomethacin treatment3637,38. Several studies
including a recent meta-analysis exhibited few
very poor prognostic indicators including presence
of chorioamnionitis, which increased the risk of
cerebral palsy by 140%.39
Term-equivalent MRI scan of the brain appears
to be the most e ective imaging modality available
at this time to provide a relative indication of long-
term neurological prognosis.14 This is primarily
determined through measurement of summation of
white matter thinning, delayed gyral maturation,
and gray or white matter signal abnormalities.14
However, MRI continues to be very poor predictor
of cognitive outcomes.
35.11 Conclusions
Neurosurgeons have a unique perspective with
respect to care of patients with IVH of prematur-
ity; this is not simply a disease of the premature
infant, but a lifelong disease with perpetual oppor-
tunities for complications including shunt depend-
ency, repeat surgeries, and neurodevelopmental
sequelae.
One of the most promising studies include the
use of biologics to ameliorate the delayed e ects of
IVH on brain development. One recent study
Developmental and Congenital Cranial Disorders
294

utilized intraventricular administration of a tumor
necrosis factor-α (TNF-α inhibitor in a rabbit pup
model. This was associated with decreased peri-
ventricular cell death, gliosis, and neuronal degen-
eration.40 Additionally, promising research in the
use of stem cells retrieved from umbilical cord
blood at birth, which may di erentiate to pluripo-
tent neuronal stem cells in vitro, may have a role
in the treatment of these infants. Studies thus far
have shown that stem cells assist in anti-inflam-
mation and restoring normal milieu, rather than
replacement of injured cells.41 Although such stem
cell therapies may not ultimately replace the cells
lost, but they may reduce the secondary injury to
the remaining healthy neural tissue.42
Germinal matrix hemorrhage with subsequent
posthemorrhagic hydrocephalus is the most com-
mon disease process the pediatric neurosurgeon
will encounter among the preterm neonatal popu-
lation. Although the incidence has continued to
decline with technological advancements in
perinatal care and improved understanding of
molecular and cellular pathophysiology, there may
be significant new therapies looming in the
horizon for these infants.
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Developmental and Congenital Cranial Disorders
296

36 Surgical Management of Hydrocephalus
Martina Messing-Jünger
36.1 Introduction
Hydrocephalus is a complex multifactorial disor-
der and can be congenital or acquired. The most
important prognostic factors are age of onset and
etiology.1,2 The earlier a developing brain is con-
fronted with problems leading to hydrocephalus,
the greater will be the negative impact. Whenever
a hydrocephalic disorder is associated with other
brain malformations, there is an increased risk of
neurodevelopmental problems. Besides these pre-
existing facts, the treatment of a hydrocephalic
child and potential complications are additional
risk factors for the long-term course. Adequate
treatment indication, thorough surgery, and fol-
low-up concepts play an important role in order to
provide the best neurological and developmental
outcome.
36.2 Surgical Indications
According to the child’s age and the given pathol-
ogy, the treatment of choice can either be shunt
implantation or endoscopic third ventriculostomy
(ETV). In some cases, endoscopic-assisted shunt
surgery might be appropriate as well. A posthe-
morrhagic hydrocephalus in a preterm infant most
often requires a temporary reservoir or other
drainage device before a definite shunt implanta-
tion is indicated. Not all cases of childhood hydro-
cephalus need to be treated surgically at the time
of diagnosis. Besides meticulous clinical investiga-
tions, invasive intracranial pressure (ICP) measure-
ments can be helpful. It is recommended, for
example, in low-pressure entities, to record the
pressure overnight. This can be realized by using a
simple ventriculostomy, which is connected to a
pressure monitoring system or by a telemetric
probe.
36.2.1 Imaging
In order to precisely define a potential indication
for endoscopic surgery, magnetic resonance imag-
ing (MRI), preferably with high-resolution T2
sequences (CISS or TRUFI) in all three dimensions,
is mandatory. For simple shunting, ultrasound or
computed tomography (CT) scans are su cient.
Because of the increased risk of acquired cancers
after CT scans in childhood, this imaging method
should only be reserved for emergency cases.3,4
36.2.2 ETV versus Shunting
Numerous publications exist regarding ETV indica-
tions,5,6,7 probably the most practicable and eval-
uated one is the ETV success score (ETVSS). This
score describes the patient’s age, hydrocephalus
etiology, and the fact whether a previous shunt
surgery was performed or not.8 Young age and a
previous shunt are related to a low success rate.
Postinfectious etiology also bears a high failure
rate, whereas nontectal brain tumor, myelomenin-
gocele, and history of intraventricular hemorrhage
(IVH) have a medium risk. Aqueductal stenosis
and tectal tumors as well as other typical occlusive
three-ventricular entities are good risk indications
for ETV.
There is still an ongoing discussion regarding
long-term outcome of low-pressure ventriculome-
galy in children, for example, after ETV, since
normalization of the ventricular width is a rare
exception in these cases.7
The immediate surgical risk for both methods—
shunting and ETV—is considerably low in skilled
hands. The mortality rate for the shunting proce-
dure is less than 0.1%, for ETV up to 1%. During
long-term follow-up, the shunt mortality rate
raises substantially due to late fatal shunt failure.
Also, the overall complication rate is higher in
shunted patients and can be expected to be greater
than 40%, although exact figures are missing. The
most important failures are obstruction and infec-
tion. Children younger than 12 to 18 months of
age have the highest complication rates, although
in this age group also the highest failure rate of
ETV is found and indications are less frequent. The
overall complication rate of ETV is 6 to 20%. Infec-
tion rate after ETV is 1 to 5% and 1 to 20% after
shunting. Infections after ETV are less severe. Gen-
erally, the major advantages of ETV are avoidance
of foreign body implantation and a more physio-
logical cerebrospinal fluid (CSF) circulation. But
still, most of all hydrocephalus cases require
shunting, either primarily or secondarily after ETV,
due to the nature of the disease.5,9,10,11,12,13,14,15
297

Box 36.1 Shunting protocol with
important rules
● Shunt surgery, if possible, no.1 on schedule
● Experienced surgeon at the table
● Doors of operating room closed
● As few sta as possible
● Thorough and repeated skin disinfection by
surgeon
● Antiseptic hair washing (in theater)
● Keeping hardware in sterile inner packing as
long as possible
● After unwrapping, hardware flushing and
keeping in fluid
● Don’t touch hardware with sharp instruments
or fingers (if avoidable)
● Use of antimicrobial sutures
For both types of procedures, it could be proven
that a specifically experienced surgeon and a
standardized protocol are able to significantly
reduce immediate and long-term complication
rates.16,17 Therefore, it is one of the most important
surgical rules in pediatric neurosurgery that
shunting and endoscopic procedures are no sur-
geries for beginners! (Box 36.1).
36.3 Shunt Implantation
36.3.1 Preparations
In elective shunt cases, preparations start already
on admission. Systemic infection should be ruled
out clinically and by assessing specific blood
parameters (C-reactive protein [CRP], white blood
cell [WBC]). Head and hair as well as the whole
body are washed with an antiseptic solution prior
to transportation to the operating room. Preopera-
tive antibiotic prophylaxis and potentially neces-
sary antiepileptic drugs are administered at least
30 minutes before starting surgery. The second-ge-
neration cephalosporin cefuroxime is recom-
mended (30 mg/kg body weight), since it is passing
the blood–brain barrier and has a wider gram-ne-
gative spectrum compared to first-generation
cephalosporins.
Shunt operations should be on the first position
of the operation list.17
Anesthesia introduction is conducted in a sepa-
rate room and the intubated child will be trans-
ported into the operating room after preparation of
all surgical tables and coverage of the instruments.
The child is positioned on a heating mattress. The
final positioning using adequate positioning materi-
als such as horseshoe headrest, silicone pads, and
padding bandages is realized by the surgeon. Talk-
ing and air movements leading to particle turbulen-
ces should be avoided when silicone implants are
used. Therefore, the number of individuals inside
the operation room should be restricted.
It is necessary to stretch the patient’s neck in
order to avoid skin folds and to facilitate tunneling
during the catheter implantation. The hairy head
and the whole surgical field are prewashed with
alcoholic disinfectant. Then the hair is combed and
divided in the area of planned incisions. If neces-
sary, a small hairy area is shaved as late as possible
and adjacent hair clipped away. After surgical hand
disinfection using an alcoholic solution, the sur-
geon performs the surgical skin disinfection,
which covers usually the entire hairy head and the
exposed half of the neck, anterior part of the chest,
and the abdomen. If the child has bright skin and
hair, the use of an undyed solution is recom-
mended.
After a second surgical hand disinfection, the
surgeon is dressed and places the surgical drapes,
using impregnated incision drapes for the skin and
hairy scalp as well as adhesive drapes to cover the
body outside the surgical field.
36.3.2 Shunt Surgery
In virgin cases or new shunt insertions, the proce-
dure starts with skin incisions for the burr hole
and the peritoneal opening. Two standard burr
hole sites do exist: a frontal precoronal one (Koch-
er’s point) and a parieto-occipital one (Frazier’s
point). The choice depends on the ventricular
shape and the surgeon’s preference ( Fig. 36.1
andFig. 36.2).
Positioning and draping must allow palpation of
important landmarks (tip of the nose, ipsilateral
eye, and ear) through the entire surgical proce-
dure. The sagittal midline is preferably marked by
a drape along its margin.
The abdominal incision can be made in one of
the quadrants or directly at the umbilicus. The
patient’s conditions must be carefully considered
before the incision is planned. If the umbilicus is
deep and irregularly shaped, adequate disinfection
may be a problem. Former abdominal interven-
tions or diseases need to be explored in advance
and abdominal ultrasound is recommended. The
less a ected quadrant is chosen. Some neurosur-
geons prefer the left abdominal half in infants due
Developmental and Congenital Cranial Disorders
298

to a regular large liver in this age group. Does the
child have a laparotomy history abdominal cathe-
ter insertion together with an experienced pedia-
tric surgeon and with endoscopic assistance can
be an option.
The first step is the opening of the peritoneal
cavity, which is performed via an incision as small
as possible depending on the thickness of the
abdominal wall. The single layers will be opened
according to their grain directions. The perito-
neum itself can be punctured bluntly (trocar) or by
a small incision just allowing to insert the catheter.
If the catheter is not easily gliding into the cavity,
or in cases of expected adhesions, a wider opening
is mandatory in order to visualize or digitally
explore the peritoneal cavity. In order to avoid
Fig. 36.1 (a–d) Frontal burr hole and
puncture of the lateral ventricle.
Fig. 36.2 (a, b) Occipital burr hole and
puncture of the lateral ventricle.
Surgical Management of Hydrocephalus
299

early reoperation due to insu cient catheter
length, as much catheter length as possible should
be put into the cavity.
The next step is to perform a burr hole. In young
infants, this is easily done by using a dissector or a
knife as a drill. The periosteum is not detached
from the skull in order to avoid ingrowth of the
shunt components into the bone.
All shunt components have been kept in the
sterile inner packaging on the instrumentation
table. Now the catheters and the valve are
unwrapped and put into Ringer’s solution in order
to avoid particle contamination from air. Flushing
is recommended according to the manufacturer’s
prescription.
The next step is the tunneling of the peripheral
catheter, which may already been connected to the
valve and a possible pumping or flushing chamber.
It is recommended to implant such a flushing re-
servoir, whenever possible. It helps to identify cer-
tain shunt malfunctions and allows aspiration of
CSF.
If necessary, small skin incisions are made in the
episternal, subclavian, or retroauricular region to
allow staged tunneling. During the whole tunnel-
ing maneuver, the silicone components are not
touched by the surgeon’s gloves. Instead, blunt
instruments or wet gauze pads are used. All open
silicone parts are immediately covered with wet
pads. It is also recommended to use iodine swabs,
for example, when silicone tubes are in contact
with skin edges.
At the end, the dura is opened using a knife or a
small bipolar forceps, and the brain surface is coa-
gulated. The central catheter with a guidewire and
a rectangular deviation positioned at the planned
intradural catheter length is inserted into the ven-
tricle.
It is important that the central catheter is situ-
ated deeply enough inside the ventricle, and does
not interfere with the choroid plexus in order to
avoid plexus ingrowth and early obstruction.
Ideally a parieto-occipital central catheter is placed
with the tip in the frontal horn. In this case, the
catheter is aimed toward the ipsilateral pupil and
bluntly forwarded inside the ventricle until about
10 cm of length is inside the dura (Fig. 36.2). In
order to place a frontal catheter exactly, the dura is
penetrated perpendicular aiming at the inner can-
tus of the ipsilateral eye ( Fig. 36.1). The median
depth is 5 cm, depending on the size of the head.
After 3 to 4 cm, a change in resistance indicates
ependymal penetration, and in normal or
increased intraventricular pressure, CSF flow is
observed at the open catheter end. If no spontane-
ous CSF flow occurs, the catheter end is hold down
in order to produce a negative pressure. If there is
still no visible flow, aspiration or flushing is not
recommended. Another trial or better, the use of a
navigation tool should be considered.
It is recommended to use navigation, like ultra-
sound devices or standard neuro-navigation sys-
tems for adequate central catheter placement, for
example, in narrow ventricles.
Now, all components will be connected and put
in place. It is advisable to perform a pocket
between the epicranium and the periosteum for
valve body and flushing chamber. In infants, all
components may easily pass through the soft tis-
sue layers. All connector points will be secured
with non-resorbable ligatures. The knots are
placed towards the skull in order to avoid skin ero-
sions. Generally, the shunt hardware should not be
placed underneath a skin incision and no connec-
tors or additional valves are allowed below the
level of the skull. This prevents rupture or discon-
nection of the shunt catheter, reactive scar forma-
tion, and pain.
Finally, the skin is closed in a two-layer fashion.
Intracutaneous stitches are allowed and in chil-
dren with a thin skin layer, additional liquid band-
age with or without steri-strip augmentation is
recommended.
36.3.3 Postoperative Follow-up
Postoperative clinical monitoring includes electro-
cardiogram (ECG) and oxygen saturation during
sleep, and when the child is without surveillance,
regular neurological and abdominal checks and
daily wound inspections. A final CRP is taken
before discharge.
In young children, the wound healing process,
for example, in silicone implantations, should be
controlled 2 weeks before exposure to water and
physical stress is allowed.
All children will be provided with a shunt pass
and parents are informed regarding an appropriate
follow-up program.
Postoperative imaging depends on the intraope-
rative course and the specific patient condition. In
general, ultrasound of the brain in an infant is easy
to obtain and is recommended as soon as possible.
Abdominal ultrasound is able to detect the posi-
tion of the peripheral catheter and free intraperi-
toneal fluid as sign of a functioning shunt. Early
MRI or CT scans are indicated after complicated
surgery or in older children when they are
Developmental and Congenital Cranial Disorders
300

symptomatic for shunt malfunction. Otherwise, it
is recommended to perform sectional imaging
after 3 months, when the expected drainage e ect
is visible. These scans will serve as baseline pic-
tures for future follow-up.
36.3.4 Variations of Shunt Surgery
Variations of this shunting procedure are frequent
and depending on the patient’s condition.
Whenever multiple compartments need to be
drained, first a possible indication for endoscopic
fenestration must be considered ( Fig. 36.3). It is
essential to keep the number of hardware compo-
nents as low as possible, since each of them may
cause complications. If it is unavoidable to put
more than one central catheter, it is generally rec-
ommended to connect those in front of the valve,
otherwise di erential ICP can cause problems. One
exception from this rule is an intended di erential
pressure, for example, when a subdural hygroma
is drained together with a ventricular hydrocepha-
lus. In secondary shunt procedures, often only sin-
gle components are revised. Because of the fact
that in secondary shunt procedures not all steps
are clear in advance, a general informed consent
for an entire shunt procedure should be obtained.
36.3.5 Ventriculoatrial Shunt
Ventriculoatrial shunting is becoming rare. A dis-
advantage of atrial shunting is the relatively high
peripheral revision rate in young children in order
to keep the catheter tip in the atrium.13 However,
some children with a complicated abdominal his-
tory may benefit from such a procedure. The
peripheral catheter is placed into the right atrium.
Venous access is performed on the ipsilateral side
of the central catheter by open venisection of the
facial vein or one of the jugular veins. A special
atrial catheter with a tapered pliant tip facilitates
the intravenous insertion and intra-atrial catheter
movement. The tip position must be checked
intraoperatively by fluoroscopy. In order to avoid
thrombotic ingrowth of the catheter tip, the intra-
atrial position is mandatory. There the catheter tip
is in constant moving. ECG monitoring is impor-
tant during surgery to indicate that there is no
persistent arrhythmia. Like in central venous line
insertion, it is important to ensure that no air is
getting into the venous system. Increase of positive
end-expiratory pressure (PEEP), flushing and aspi-
ration of the catheter, and clamp occlusion are
necessary steps.
In small infants and after a prolonged intensive
medical treatment, access to peripheral or even
central veins can be a major problem. In these
cases, instead of open venesection regular central
venous puncture and insertion of the peripheral
catheter via Seldinger’s technique is recom-
mended. Postoperative imaging should include
chest X-ray to verify atrial catheter position.
36.3.6 General Considerations
Further alternatives are peripheral catheter place-
ment into the gallbladder, the ureter, and the
pleural space. Disadvantages are the necessity of a
special surgical expertise and a limited resorption
capacity of the pleural space.
A broad variety of shunt devices and additional
valve systems is on the market. So far, there is no
proof that one of the devices is superior.18 Over-
drainage and slit-ventricle complications are well-
known late sequelae mostly occurring years after
primary shunting. It is assumed that standard dif-
ferential pressure valves do not properly address
the phenomenon of overdrainage in upright
position. Therefore, special valve components like
Fig. 36.3 Cystic posthemorrhagic hydrocephalus with
two central catheters in place prior to endoscopic
fenestration.
Surgical Management of Hydrocephalus
301

antisiphoning or antigravity devices are in use. In
order to prevent shunt infections, the use of anti-
biotic-impregnated systems (AIS) is recom-
mended. There is growing evidence that these
materials are preventive against shunt infections.
Whether this justifies a general usage is not yet
proven statistically.19,20,21,22 There is some evi-
dence that antimicrobial sutures are also able to
reduce wound and shunt infections.16
36.4 Endoscopic Third
Ventriculostomy
ETV is an easy and elegant way to reestablish
intracranial CSF circulation. It was originally
invented to cure a typical occlusive three-ventricu-
lar hydrocephalus. However, more indications
have been proven of being successfully addressed
by this method.
It is essential to perform a brain MRI with T2-
weighted images in all three dimensions, for
example, a midsagittal slice, for evaluation of the
inner CSF spaces and basal cisterns, and potential
variations of brain structures and vessels. Nor-
mally, access is planned through the nondominant
hemisphere. In cases with a small foramen of
Monro, the contralateral side should be preferred.
Although the procedure itself is not di cult,
potential damage can result to brain structures
and adjacent vessels leading to devastating
complications. Therefore, conduction of a highly
standardized procedure with a four-handed well-
trained surgical sta is mandatory.
Anesthesia introduction is realized in a separate
room. Parallel to this, the instrumentation tables
and necessary settings (positioning of endoscopy
tower, endoscopy, and flushing system) are
arranged and checked according to a strict proto-
col. Only when all components are checked of
being fully functioning, the surgical procedure
itself can start. The patient’s head is positioned in
a straight, slightly inclined fashion on a horseshoe
headrest and securely fixed or in a Mayfield clamp.
General hygienic and disinfection rules as well as
draping are comparable to the shunt-implantation
process. Again, landmarks like nose and ears as
well as the sagittal midline must be identifiable
after draping. A straight or curved skin incision
just in front of the nondominant coronal suture in
the middle of the median third of the suture is per-
formed and the periosteum is cut and shove o . A
burr hole wide enough to let the endoscope trocar
easily pass through is placed just underneath. After
cutting the dura and coagulating the brain surface,
the obturated trocar of the endoscope (or a peel-
away sheath in case of using a small endoscope) is
gently moved forward the same direction as punc-
turing the lateral ventricle in shunt surgery. After
approximately 4 cm, the resistance changes and
the ventricle is entered. After removal of all obtu-
rators, first the endoscope (0-degree optic) is
inserted. Then the flushing line is attached. From
now on, the whole team is watching the monitor
pictures for intraventricular control. The endo-
scope/trocar can be steered freehand or using a
supporting arm. Ideally, the tip of the endoscope
directly points at the ipsilateral foramen of Monro.
All landmarks will be identified. The choroid
plexus is diving into the third ventricle, laterally
the superior thalamostriate vein (terminal vein) is
running over the thalamus and medially the septal
vein points into the direction of the foramen
(Fig. 36.4). The endoscope is gently forwarded
through the foramen. After this step, the fornix
cannot be visualized any longer and must be kept
in mind in order to avoid lesions. The floor of the
third ventricle should be thinned out showing a
grayish color and resembles a triangle. The tip of
the basilar artery and the posterior cerebral
arteries can be surmised just in front of the mam-
millary bodies at the base of the triangle. At the tip
tiny vessels create a red dot and most often the
infundibular recess can be identified. Ventrally the
Fig. 36.4 Endoscopic view on the foramen of Monro
(*), the choroid plexus (↑), on the lateral aspect the
superior thalamostriate vein (↑↑), and medially the
septal vein (↑↑↑).
Developmental and Congenital Cranial Disorders
302

clivus becomes visible ( Fig. 36.5). In a markedly
enlarged ventricle the third cranial nerves can be
identified as well as white linear structures. Only
in the middle of the membranous floor the open-
ing is safe. It is important to use only blunt instru-
ments without force and to avoid coagulation in
order to create an opening of the sometimes
resistant membrane. Otherwise, cisternal struc-
tures can be injured. Once the opening is per-
formed, a 3-French Fogarty catheter, which is
slowly inflated only at the level of the floor, is used
as a bougie. An eventual bleeding is controlled best
by flushing and compressing with the Fogarty
catheter itself. During the whole procedure, gentle
flushing is possible. It is important to keep the out-
flow (suction) channel open. This helps to keep an
optimum pressure and filling inside the ventricles.
Ringer’s solution is less pyrogenic compared to
physiological NaCl solution and should have body
temperature.
For a few minutes, the intraventricular site is
watched without flushing to detect minor bleed-
ings. In case of no bleeding, the whole system will
be removed under vision in order to detect hidden
bleedings above the tip of the endoscope. The
access is plugged with a piece of Gelfoam. The dura
is closed and the periosteum can be sutured as
well before the two-layer wound closure is per-
formed. Some colleagues prefer to put a reservoir
or a ventriculostomy inside the ventricle in order
to control ICP during the first postoperative days.
We only consider these means in complicated
cases due to the related risks, for example, infec-
tion and secondary wound healing disorders.
Postoperative monitoring is comparable to
shunt surgery. Postoperative MRI should always
include a midsagittal T2 sequence. A patent third
ventriculostomy will be identified by a typical
flow void through the floor into the prepontine
cistern at the site of the fenestration.
36.4.1 Surgical Pearls
● Shunt surgery and ETVare supposed to be easy
procedures. However, because of a significant
intraoperative risk for ETVand high
postoperative complication rates for shunting,
only specifically skilled and experienced
surgeons should perform this kind of surgeries.
● It is recommended to implement a standardized
shunting protocol, since this has been proven to
decrease shunt infection rates.
● In normal ventricular configurations,
transfrontal puncture of the lateral ventricle is
safe, when a precoronal, 2 to 2.5 cm parasagittal
burr hole is performed and the direction of the
puncture is perpendicular aiming at the inner
cantus of the ipsilateral eye and the ipsilateral
tragus.
● A long-persisting open exposure of the CSF
system during surgery bears a high infection
risk, therefore, placing the central catheter
should be the last part of the surgery.
● Multiple punctures of the ventricle should be
avoided.
● All kinds of connectors or inline components
below the insertion of the nuchal muscles
should be avoided in order to prevent rupture
and scar formation.
● A flushing or pumping reservoir helps to identify
potential complications during the further
course.
● In order to prevent the child from early
peripheral shunt revision, insertion of the entire
catheter length is recommended.
36.5 Common Clinical
Questions
1. Which patients will most likely benefit from
ETV?
2. Which kind of diagnostic is mandatory to define
ETV indication?
Fig. 36.5 Endoscopic view on the floor of the third
ventricle: mammillary bodies (**), basilar tip (↑),
infundibular recess (↑↑).
Surgical Management of Hydrocephalus
303

3. What are the most common complications after
shunt surgery and which kind of patients are
mostly a ected?
4. What are the most important aspects regarding
ventriculoatrial shunt placement?
36.6 Answers to Common
Clinical Questions
1. The highest benefit from ETV will have
hydrocephalus patients who are older than 1
year of age, su ering from a typical occlusive
three-ventricular hydrocephalus, and never had
a shunt before. The lowest success rate is to be
expected in postinfectious hydrocephalus in
very young infants, for example, when there
was already a shunt in place.
2. Prior to any endoscopic procedure, MRI, for
example, T2 with midsagittal projection and at
least axial and/or coronal series are mandatory.
Best demonstration of cystic components and
membranes are provided by special T2
sequences like CISS or TRUFI.
3. The most common shunt complications do not
occur intraoperatively but during follow-up.
Obstruction and infection are by far the most
common problems. Preterm infants with a
history of posthemorrhagic hydrocephalus
and myelomeningocele patients are mostly
a ected.
4. The most important points in ventriculoatrial
shunting are the placement of the peripheral tip
inside the right atrium in order to assure a
constant movement and avoidance of air inside
the venous system.
References
[1] Rashid QT, Salat MS, Enam K, et al. Time trends and age-
related etiologies of pediatric hydrocephalus: results of a
groupwise analysis in a clinical cohort. Childs Nerv Syst.
2012; 28(2):221–227
[2] Serlo W, Fernell E, Heikkinen E, Anderson H, von Wendt L.
Functions and complications of shunts in di erent etiologies
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[3] Pearce MS, Salotti JA, Little MP, et al. Radiation exposure from
CT scans in childhood and subsequent risk of leukaemia and
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[4] Mathews JD, Forsythe AV, Brady Z, et al. Cancer risk in
680,000 people exposed to computed tomography scans in
childhood or adolescence: data linkage study of 11 million
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[5] Di Rocco C, Massimi L, Tamburrini G. Shunts vs endoscopic
third ventriculostomy in infants: are there di erent types
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[6] Kulkarni AV, Drake JM, Kestle JR, Mallucci CL, Sgouros S,
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Pediatr. 2010; 6(4):310–315
[7] Kulkarni AV, Hui S, Shams I, Donnelly R. Quality of life in
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[8] Kulkarni AV, Riva-Cambrin J, Browd SR. Use of the ETV
Success Score to explain the variation in reported endoscopic
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[9] Durnford AJ, Kirkham FJ, Mathad N, Sparrow OC. Endoscopic
third ventriculostomy in the treatm ent of childhood
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[11] Paulsen AH, Lundar T, Lindegaard KF. Twenty-year outcome
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37 Treatment of Hydrocephalus in the
Developing World
Rodrigo Mercado, Jesus A. Villagómez, Luis A. Arredondo
37.1 Introduction
Hydrocephalus is a common clinical problem in
pediatric neurosurgical practice in the developing
countries. It is defined as a condition wherein the
excess of cerebrospinal fluid (CSF) within the ven-
tricular system and cisterns of the brain leads to
increased intracranial pressure (ICP).1 Hydroce-
phalus a ects 1 to 2% of the general population.2 It
occurs due to subnormal reabsorption or overpro-
duction of CSF. The etiologies can be described as
either congenital or acquired.
37.1.1 Congenital
● Associated with myelomeningocele (MMC) with
or without Chiari malformation. The
hydrocephalus associated with MMC in
developing countries represents the more
common specific congenital etiology in
children3; 11 to 16% of congenital hydrocephalus
cases are associated with MMC. It is just second
to infectious diseases in general infant
populations and often associated with
aqueductal stenosis.4 Only one out six infants
with MMC presents signs of ICP at birth and
hydrocephalus is more commonly noticed at 2 to
3 weeks of age.5
● Perinatal germinal matrix hemorrhage.
Intraventricular hemorrhages require definitive
ventricular shunts in 15 to 35% of the cases.6,7
● Primary aqueductal stenosis.
● Chiari I. Chiari is associated with hydrocephalus
in 14% of cases.8 In patients with hydrocephalus,
shunting is indicated prior to foramen magnum
decompression.
● Dandy–Walker malformation.
37.2 Acquired
● Infectious: Infectious diseases are the most
common specific etiology of hydrocephalus in
infants.4 It is not only observed as an acute
complication of bacterial meningitis, but also
associated with chronic granulomatous
arachnoiditis observed in parasitic,
mycobacterial, and fungal infections.
– Postacute bacterial meningitis.
– Tuberculosis. Signs of increased ICP are
described in more than 70% of children with
central nervous system (CNS) complications of
tuberculosis. Hydrocephalus is a common
radiological feature. Close to 17% of patients
with tuberculosis (TB) and CNS involvement
displayed this finding.9
– Cysticercosis.
● Posthemorrhagic.
● Secondary to masses: Noncommunicating
hydrocephalus secondary to obstruction of CSF
flow inside or from outside the ventricle walls.
– Neoplastic or no neoplastic
○ Posterior fossa lesions compressing or
occupying the fourth ventricle.
○ Tumors occupying the third ventricle and
obstructing the cerebral aqueduct arising
either from the sellar or the pineal region.
○ Diencephalic lesions compressing or
obstructing either the foramen of Monro or
the third ventricle walls.
○ Overproducer CSF tumors such as the
choroid plexus papilloma and choroid plexus
carcinoma.
● Postoperative.
● Associated with spinal tumors.
● Constitutional ventriculomegaly.
37.3 Treatment
In spite of the growing experience with endo-
scopic procedures in many developing countries,
ventricular shunts remain as the main treatment
option in hydrocephalus, in particular, in pediatric
populations.10 Nulzen and Spitz introduced the
use of internalized CSF derivative in the 50s. Most
of the devices pose three components: ventricular
catheter, valve, and peritoneal catheter. The com-
ponents are made of Sylastic, impregnated with a
radiopaque material for radiographic localization.
Either the location of the distal catheter or their
hydrodynamic features can be used to classify
shunts. Based on the location of the distal catheter,
the ventriculoperitoneal (VP) shunt is the most
widely used. It can be completed via two main
approaches, the frontal precoronal and the poste-
rior parietal. It uses the abdominal cavity as the
recipient of the CSF, and it is contraindicated when
305

there is an acute abdominal condition such as peri-
tonitis, or the presence of adhesions or ine ective
absorption secondary to prior abdominal sur-
geries. The ventriculoatrial (VA) shunt sends the
CSF flow to the cardiac atrium through the internal
jugular vein. It is indicated when the patient is not
eligible for an abdominal derivative location. The
rest of the probable locations are less common and
are considered only when the VP and VA shunts
are not defined as a therapeutic option: the distal
catheter can be located at the subgaleal space,
pleura, bladder, or biliary tract.11
Based on the mechanism of hydrodynamics, the
valve can be described as:
Di erential pressure valve (PS Medical Standard
Valve, Medtronic). This is the most widely used
valve. They work with a fixed opening pressure,
which means that the valve will let the CSF flow
out of the valve when the pressure di erence
drops below a predetermined pressure thresh-
old.11 They are available in three di erent opening
pressures: low, medium, and high (Table 37.1).
The main disadvantage is the variation in CSF flow
with position changes, and the probable need of
repetitive revisions.
Flow-controlling shunts (Delta Valves, Med-
tronic; Orbits Sigma Valve). The progressive nar-
rowing of the outflow orifice controls the flow of
CSF, which increases in turn the pressure needed
to increase the CSF flow.12
Adjustable valves. They permit the adjustment
of valve opening pressures with an external
controller.13 There are four types of adjustable
valves (Table 37.2). They are considered the ideal
shunting devices for their capacity to adjust to dif-
ferent CSF pressure requirements and control drain-
age-related complications. Their main disadvantages
in developing countries are the elevated cost and
the poor distribution of specialized centers for peri-
odic revisions and pressure adjustments.
37.4 Surgical Indications and
Contraindications
Ventricular shunts are indicated in cases of
obstructive hydrocephalus such as in intraventric-
ular or posterior fossa tumor cases, Chiari I malfor-
mation, and stenosis of the cerebral aqueduct, in
particular, when an endoscopic third ventriculos-
tomy (ETV) has failed, is contraindicated, or is not
immediately available. It is also indicated in most
cases of communicating hydrocephalus when the
blood cell count and/or protein content of the CSF
are not elevated. This concept is controversial in
cases of chronic granulomatous meningitis due to
neurocysticercosis or meningeal tuberculosis, con-
ditions in which the elevations of both, white cells
and protein content, are common CSF features.
An ongoing CNS infection is an absolute contra-
indication. Any infectious condition with no evi-
dence of pharmacological control and persistent
fever will increase the risk of a CNS infection facili-
tated by the opening of the blood–brain barrier or
contamination of the components of the shunting
device. The peritoneal approach is absolutely
Table 37.1 Main features of set pressure valves
Low pressure

Medium pressure

High pressure
Dot code



Closing pressure range

5–50 mm H2O

51–110 mm H2O

110–180 mm H2O
Flow pressure

50–75 mm
H2O
50–140 mm H2O

110–220 mm H2O
Opening pressure

5

10

15 cm H2O
Table 37.2 Features of programmable valves
Codman–Hakim

Strata

Sophysa

Miethke ProGAV
Opening pressure
(mm H2O)
30–200

15–170

30–200

30–200
Antisiphon device

Yes

No

No

Gravitational unit
MRI compatibility

Yes

Yes

Yes

Yes
Abbreviation: MRI, magnetic resonance imaging.
Developmental and Congenital Cranial Disorders
306