Cerebrospinal fluid disturbances after 381 consecutive craniotomies for intracranial tumors in pediatric patients

Abstract

Object:
The aim of this study was to investigate the incidence of CSF disturbances before and after intracranial surgery for pediatric brain tumors in a large, contemporary, single-institution consecutive series.

Methods:
All pediatric patients (those < 18 years old), from a well-defined population of 3.0 million inhabitants, who underwent craniotomies for intracranial tumors at Oslo University Hospital in Rikshospitalet between 2000 and 2010 were included. The patients were identified from the authors' prospectively collected database. A thorough review of all medical charts was performed to validate all the database data.

Results:
Included in the study were 381 consecutive craniotomies, performed on 302 patients (50.1% male, 49.9% female). The mean age of the patients in the study was 8.63 years (range 0-17.98 years). The follow-up rate was 100%. Primary craniotomies were performed in 282 cases (74%), while 99 cases (26%) were secondary craniotomies. Tumors were located supratentorially in 249 cases (65.3%), in the posterior fossa in 105 (27.6%), and in the brainstem/diencephalon in 27 (7.1%). The surgical approach was supratentorial in 260 cases (68.2%) and infratentorial in 121 (31.8%). Preoperative hydrocephalus was found in 124 cases (32.5%), and 71 (86.6%) of 82 achieved complete cure with tumor resection only. New-onset postoperative hydrocephalus was observed in 9 (3.5%) of 257 cases. The rate of postoperative CSF leaks was 6.3%.

Conclusions:
Preoperative hydrocephalus was found in 32.5% of pediatric patients with brain tumors treated using craniotomies. Tumor resection alone cured preoperative hydrocephalus in 86.6% of cases and the incidence of new-onset hydrocephalus after craniotomy was only 3.5%.

Full text

J Neurosurg Pediatrics 14:604–614, 2014
604 J Neurosurg: Pediatrics / Volume 14 / December 2014
©AANS, 2014
IntracranIal brain tumors are the most common solid
tumors occurring in the pediatric population. Accord-
ing to the Central Brain Tumor Registry of the US,
approximately 2000 children and adolescents under the
age of 20 are diagnosed with primary CNS malignancies
each year in the US.8
First-line treatment for pediatric patients with intra-
cranial tumors is resection, with the goal of gross-total re-
section to obtain tissue diagnosis, relieve symptoms, and
increase survival. However, craniotomies do not come
without inherent risks, be they postoperative CSF leaks/
disturbances, hematomas, infections such as meningitis,
postoperative cerebral infarctions, neurological morbid-
ity, and even death.23 The objective of surgery is therefore
not only gross-total resection, but also avoidance of post-
operative complications.
There are few contemporary neurosurgical articles
studying the incidence of pre- and postoperative CSF
complications after craniotomies for brain tumors in chil-
dren. However, it is important to know an institution’s
complication rate, not only to have accurate information
about operative risk to give to patients and their guard-
ians, but also to compare results with other institutions
and to compare different treatment modalities to each
other. We therefore wanted to determine the rate of CSF
Cerebrospinal uid disturbances after 381 consecutive
craniotomies for intracranial tumors in pediatric patients
Clinical article
Sayied abdol Mohieb hoSainey, M.d.,1 benjaMin laSSen, M.d.,1
eirik helSeth, M.d., Ph.d.,2,3 and torStein r. Meling, M.d., Ph.d.1
1Department of Neurosurgery, Oslo University Hospital, Rikshospitalet; 2Faculty of Medicine, University of
Oslo; and 3Department of Neurosurgery, Oslo University Hospital, Ullevaal, Oslo, Norway
Object. The aim of this study was to investigate the incidence of CSF disturbances before and after intracranial
surgery for pediatric brain tumors in a large, contemporary, single-institution consecutive series.
Methods. All pediatric patients (those < 18 years old), from a well-dened population of 3.0 million inhabitants,
who underwent craniotomies for intracranial tumors at Oslo University Hospital in Rikshospitalet between 2000
and 2010 were included. The patients were identied from the authors’ prospectively collected database. A thorough
review of all medical charts was performed to validate all the database data.
Results. Included in the study were 381 consecutive craniotomies, performed on 302 patients (50.1% male,
49.9% female). The mean age of the patients in the study was 8.63 years (range 0–17.98 years). The follow-up rate
was 100%. Primary craniotomies were performed in 282 cases (74%), while 99 cases (26%) were secondary crani-
otomies. Tumors were located supratentorially in 249 cases (65.3%), in the posterior fossa in 105 (27.6%), and in the
brainstem/diencephalon in 27 (7.1%). The surgical approach was supratentorial in 260 cases (68.2%) and infratento-
rial in 121 (31.8%). Preoperative hydrocephalus was found in 124 cases (32.5%), and 71 (86.6%) of 82 achieved
complete cure with tumor resection only. New-onset postoperative hydrocephalus was observed in 9 (3.5%) of 257
cases. The rate of postoperative CSF leaks was 6.3%.
Conclusions. Preoperative hydrocephalus was found in 32.5% of pediatric patients with brain tumors treated
using craniotomies. Tumor resection alone cured preoperative hydrocephalus in 86.6% of cases and the incidence of
new-onset hydrocephalus after craniotomy was only 3.5%.
(http://thejns.org/doi/abs/10.3171/2014.8.PEDS13585)
key WordS • craniotomy • complications • intracranial tumor •
external ventricular drain • endoscopic third ventriculostomy • hydrocephalus •
surgical mortality • oncology
Abbreviations used in this paper: CI = confidence interval; DNET
= dysembryoplastic neuroepithelial tumor; ETV = endoscopic third
ventriculostomy; EVD = external ventricular drain; OR = odds
ratio; PNET = primitive neuroectodermal tumor; VP = ventriculo-
peritoneal.
This article contains some figures that are displayed in color
on line but in black-and-white in the print edition.

J Neurosurg: Pediatrics / Volume 14 / December 2014
CSF disturbances in pediatric brain tumors
605
disturbances in our patients by reviewing our prospective-
ly collected database on craniotomies performed between
2000 and 2010 on those patients less than 18 years old.
Methods
Study Population
The dened pediatric neurosurgical catchment area
for Oslo University Hospital-Rikshospitalet is the south-
west, south, and eastern health region of Norway, consist-
ing of 0.7 million inhabitants under the age of 18. The
hospitals’ data protection ofcials approved the study.
Our prospectively collected database was used to
identify all patients less than 18 years old who underwent
a craniotomy for an intracranial tumor in the period of
2000–2010 at Oslo University Hospital-Rikshospitalet.
Patients who underwent stereotactic or endoscopic bi-
opsy were not included. A total of 413 craniotomies were
identied, but because 32 patients with preexisting ven-
tricular shunts were excluded from this study, the cohort
consisted of 381 craniotomies.
Data Collection
The following patient data were recorded: age, sex,
primary or secondary (repeated) resection, main tumor
location (supratentorial, infratentorial, or brainstem/dien-
cephalon), specic tumor location, histology, surgical ap-
proach (supratentorial or infratentorial, and whether the re-
section was transventricular/intraventricular or not), preop-
erative hydrocephalus, choice of treatment of preoperative
hydrocephalus, presence of postoperative hydrocephalus,
treatment mode of postoperative hydrocephalus, time of
postcraniotomy shunt placement, surgical intervention for
a postcraniotomy CSF leak, meningitis, and lastly, tumor
resection radicality.
Specic tumor locations were cerebrum, cerebellum,
brainstem/diencephalon, intraventricular, pituitary gland,
cranial nerve, cranium, and meninges. Furthermore, they
were classied according to histology as: glioma of WHO
Grades I–IV, primitive neuroectodermal tumor (PNET),
dysembryoplastic neuroepithelial tumors (DNET), ger-
minoma, ependymoma, craniopharyngioma, plexus tu-
mor, other benign tumor, and other malignant tumor. For
odds ratio (OR) analysis, WHO Grade I was used as the
reference category unless otherwise stated.
Primary craniotomy was dened as the rst crani-
otomy in a specic location, while all subsequent crani-
otomies in the same location were dened as secondary.
Thus, 1 patient could have more than 1 primary crani-
otomy, if undergoing an operation in more than 1 loca-
tion. The degree of resection was evaluated by reviewing
all the postoperative MR images: complete resection was
dened as no visible residual tumor, subtotal resection
was dened as less than 10% residual tumor, and partial
resection as anything less than 90% resection. The se-
nior author (T.R.M.) thereafter carefully reviewed all the
charts and MR images to validate the database.
Preoperative hydrocephalus was dened as ventricu-
lomegaly and the presence of symptoms and/or signs of
raised intracranial pressure. Regarding the treatment mo-
dality of preoperative hydrocephalus, we divided the pa-
tients into 3 groups: 1) external ventricular drain (EVD),
2) preoperative endoscopic third ventriculostomy (ETV),
or 3) tumor resection only. The timing of postcraniotomy
shunt placement was dichotomized into early (within 30
days after craniotomy) and late (within 3 months after
craniotomy).
All CSF leaks and pseudomeningoceles requiring
surgical intervention were recorded according to the
highest level of treatment required to resolve the leak,
according to the following scale: compression bandages,
direct aspiration of subcutaneous CSF collection, sec-
ondary skin sutures, multiple lumbar punctures, lumbar
drainage, EVD, ETV, operative closure of stula, and per-
manent CSF diversion.23
Surgical mortality was dened as death within 30
days of surgery. Vital status (dead or alive) and time of
death were obtained from the Norwegian Population
Registry (Folkeregisteret) on June 10, 2011. The cause of
death was identied in cases of surgical mortality.
Statistical Analysis
Analysis of overall survival was conducted using
Kaplan-Meier curves, measuring survival from time of
surgery until death. Univariate and multivariate logistic
regression was used to determine the impact of different
independent variables on CSF disturbances. Analysis of
variances was used for continuous variables. A p value <
0.05 was considered statistically signicant. The statisti-
cal software program JMP (version 9, SAS Institute Inc.)
was used for all statistical analyses.
Results
Patient Population
There were 381 consecutive craniotomies performed
on 302 patients included in this study. The mean patient
age at the time of surgery was 8.63 years (range 0–17.98
years); the youngest patient underwent craniotomy the
day after birth. One hundred ninety-one craniotomies
were performed on male patients and 190 craniotomies
on female patients, yielding a male-to-female ratio of 1:1.
The median follow-up duration was 38.7 months (range
0.1–136.3 months, mean 49.1 months) and the follow-up
rate was 100% (Table 1).
Tumor Location
Main tumor location was supratentorial in 249 cas-
es (65.3%), in the posterior fossa (infratentorial) in 105
(27.6%), and in the brainstem/diencephalon in 27 (7.1%;
Table 2). With respect to specic tumor location, 130
(34.1%) were located in the cerebrum, 49 (12.9%) in the
cerebellum, 27 (7.1%) in the brainstem/diencephalon,
118 (31.0%) intraventricularly, 20 (5.3%) in the pituitary
gland, 23 (6.0%) in cranial nerves, 10 (2.6%) in the cra-
nium, and 4 (1.0%) in the meninges (Table 1).
Surgery
Of the 381 craniotomies, 282 cases (74.0%) were
primary while 99 (26.0%) were secondary craniotomies.

S. A. M. Hosainey et al.
606 J Neurosurg: Pediatrics / Volume 14 / December 2014
Complete resection was achieved in 184 cases (48.3%),
subtotal resection in 177 (46.5%) cases, and in 20 cases
(5.2%) a partial resection/biopsy was performed. A su-
pratentorial approach was used in 260 cases (68.2%) and
an infratentorial surgical approach in 121 cases (31.8%;
Table 2). In 127 craniotomies (33.3%), the approach en-
tered the ventricular system.
Preoperative Hydrocephalus
Incidence and Treatment. There were 124 cases
(32.5%) with preoperative hydrocephalus (Fig. 1, Table 2).
Of these 124 cases, 8 (6.5%) underwent ETV prior to cra-
niotomy, 33 (26.6%) received an EVD either prior to (n =
9) or simultaneously with tumor resection (n = 24), while
82 patients (66.1%) underwent tumor resection alone (Fig.
1). One patient had a ventriculoperitoneal (VP) shunt in-
serted at the same time as this patient underwent a cra-
niotomy.
Risk Factors. In the univariate analysis, risk fac-
tors for preoperative hydrocephalus included: younger
age (OR 1.1, 95% condence interval [CI] 1.1–1.2; p <
0.001); primary craniotomy (OR 3.9, 95% CI 2.1–7.2; p <
0.001); main tumor location infratentorial (OR 8.1, 95%
CI 4.9–13.6; p < 0.001); specic tumor location in brain-
stem/diencephalon (OR 4.5, 95% CI 1.7–11.7; p < 0.01),
intraventricular (OR 8.5, 95% CI 4.5–16.7; p < 0.001), and
in cerebellum (OR 11.1, 95% CI 5.2–25.0; p < 0.001); and
histology (p < 0.001; Table 3, Fig. 2).
Using multivariate analysis, the risk factors for pre-
operative hydrocephalus included younger age (OR 1.1,
95% CI 1.0–1.2; p < 0.05), primary craniotomy (OR 3.9,
95% CI 2.0–8.2; p < 0.001), main tumor location infraten-
torial (OR 3.3, 95% CI 1.9–5.8; p < 0.001), and histology
(p < 0.01; Table 3).
Persisting Postoperative Hydrocephalus
Incidence and Treatment. Of the 124 cases with
preoperative hydrocephalus, 24 (19.4%) had persisting
postoperative hydrocephalus. Of these 24 patients, 20 re-
quired early VP shunt placement and 4 required late VP
shunt placement (Fig. 3).
Risk Factors. Only meningitis was associated with
increased risk of postoperative hydrocephalus in both uni-
variate and multivariate analysis, (OR 7.0, 95% CI 1.1–55.7,
p < 0.05; and OR 9.5, 95% CI 1.3–85.8, p < 0.05, respec-
tively). Age, sex, primary/secondary resection, main tumor
location, specic tumor location, histology, and surgical
approach were not statistically signicant.
New-Onset Postoperative Hydrocephalus
Incidence and Treatment. Of the 257 patients without
hydrocephalus preoperatively, a total of 9 patients (3.5%)
developed hydrocephalus after surgery, of whom 7 were
boys. Five patients required early VP shunt placement
and 4 required late VP shunt placement.
Risk Factors. In univariate analysis, male sex (OR 4.0,
95% CI 1.5–11.2; p < 0.01), main tumor location infraten-
torial (OR 6.2, 95% CI 1.4–27.4; p < 0.05), and infratento-
rial surgical approach (OR 5.6, 95% CI 1.4–23.6; p < 0.05)
were signicantly associated with increased risk of devel-
oping new-onset postoperative hydrocephalus. Age, prima-
ry/secondary resection, specic tumor location, histology,
and meningitis did not reach any signicance.
In the multivariate analysis, only infratentorial tumor
TABLE 1: Patient characteristics
Variable Value (%)
no. of cases 381 (100)
sex
M 191 (50.1)
F 190 (49.9)
age (yrs)
<1 33 (8.7)
1–3 46 (12.1)
3–10 147 (38.6)
10–18 155 (40.7)
type of surgery
primary 282 (74.0)
secondary 99 (26.0)
craniotomy
total resection 184 (48.3)
subtotal resection 177 (46.5)
biopsy 20 (5.2)
main tumor location
supratentorial 249 (65.3)
infratentorial 10 5 (27.6)
brainstem/diencephalon 27 (7.1)
specic tumor location
cerebrum 130 (34.1)
cerebellum 49 (12.9)
brainstem/diencephalon 27 (7.1)
intraventricular 118 (31.0)
pituitary gland 20 (5.3)
cranial nerve 23 (6.0)
cranium 10 (2.6)
meninges 4 (1.0)
main histology
WHO Grade I 115 (30.2)
WHO Grade II 19 (5.0)
WHO Grade III 15 (3.9)
WHO Grade IV 17 (4.5)
PNET 59 (15.5)
DNET 19 (5.0)
germinoma 10 (2.6)
ependymoma 35 (9.2)
craniopharyngioma 15 (3.9)
plexus tumors 21 (5.5)
other benign tumors 51 (13.4)
other malignant tumors 5 (1.3)

J Neurosurg: Pediatrics / Volume 14 / December 2014
CSF disturbances in pediatric brain tumors
607
location (OR 5.1, 95% CI 1.3–21.3; p < 0.05) was signi-
cantly associated with developing new-onset postoperative
hydrocephalus. Age, sex, specic tumor location, surgical
approach, and meningitis were not signicantly associated
with developing new-onset postoperative hydrocephalus.
Overall Incidence of Postoperative Hydrocephalus
Incidence and Treatment. A total of 33 (8.7%) of
381 patients had hydrocephalus after surgery (Fig. 3). Of
these 381 patients, 24 (6.3%) had persistent postopera-
tive hydrocephalus, of whom 20 required early VP shunt
placement and 4 required late VP shunt placement. Nine
patients (2.4%) had new-onset postoperative hydrocepha-
lus, of whom 5 required early VP shunt placement and 4
required late VP shunt placement (Fig. 3).
Risk Factors. The risk factors in the univariate analy-
sis included younger age (OR 1.1, 95% CI 1.0–1.2; p <
0.01), main tumor location infratentorial (OR 2.2, 95%
CI 1.0–4.8; p < 0.05), PNET histology (OR 2.4, 95% CI
1.0–5.8; p < 0.05), infratentorial surgical approach (OR
2.2, 95% CI 1.1–4.5; p < 0.05), untreated preoperative hy-
drocephalus (OR 6.6, 95% CI 3.0–14.7; p < 0.001), and
meningitis (OR 11.5, 95% CI 2.2–59.5; p < 0.01).
In the multivariate analysis, younger age (OR 1.1,
95% CI 1.0–1.2; p < 0.05), untreated preoperative hy-
drocephalus (OR 4.8, 95% CI 2.2–11.6; p < 0.001), and
meningitis (OR 7.7, 95% CI 1.3–47.4; p < 0.05) were sig-
nicantly associated with an increased risk of developing
postoperative hydrocephalus.
CSF Leaks
Incidence and Treatment. There were 24 patients
with postoperative CSF leaks (6.3%). Of these 24 pa-
tients, 2 were successfully treated with compression ban-
dages, 2 with secondary skin sutures, 5 by lumbar punc-
tures, 4 required postoperative EVD placement, and 2 pa-
tients underwent endoscopic fenestration. Only 9 patients
(2.4%) required postoperative VP shunt placement, of
whom 7 were treated early whereas 2 were treated within
3 months postoperatively.
Risk Factors. In univariate analysis, the following
factors were signicantly associated with an increased
risk of postoperative CSF leak: younger age (OR 1.2, 95%
CI 1.1–1.3; p < 0.001), main tumor location infratentorial
(OR 3.8, 95% CI 1.6–9.4; p < 0.01), infratentorial surgical
approach (OR 3.3, 95% CI 1.4–7.6; p < 0.01) and existing
preoperative hydrocephalus (OR 4.6, 95% CI 1.9–11.1; p
< 0.01).
TABLE 2: Craniotomy characteristics*
Primary Craniotomies (n = 282, 74.0%) Secondary Craniotomies (n = 99, 26.0%)
Tumor Cerebri No Preop
Hydrocephalus Preop Hydrocephalus No Preop
Hydrocephalus Preop Hydrocephalus
supratentorial (n = 249, 65.3%) 140 (49.7%) 40 (14.2%) 62 (62.6%) 8 (8.1%)
infratentorial (n = 105, 27.6%) 19 (6.7%) 63 (22.3%) 17 (17.2%) 6 (6.1%)
brainstem/diencephalon (n = 27, 7.1%) 13 (4.6%) 7 (2.5%) 6 (6.0%) 0 (0.0%)
* One patient had a brainstem tumor extending superiorly, resulting in it being located both in the brainstem and supratentorially.
Fig. 1. Flow chart showing the diagnosis and treatment of preoperative hydrocephalus (HC). *One patient included in this
group had VP shunt insertion simultaneously with craniotomy. pt = patient.

S. A. M. Hosainey et al.
608 J Neurosurg: Pediatrics / Volume 14 / December 2014
In multivariate analysis, only younger age (OR 1.2,
95% CI 1.1–1.3; p < 0.01), main tumor location infraten-
torial (OR 3.0, 95% CI 1.2–7.9; p < 0.05), and new-onset
postoperative hydrocephalus (OR 5.6, 95% CI 2.1–14.8; p
< 0.01) were signicantly associated with postoperative
CSF leaks. Sex, primary/secondary resection, specic
tumor location, histology, and surgical approach did not
reach signicance.
Meningitis
Incidence and Treatment. Six patients developed
post operative meningitis (1.6%), in 2 cases secondary to
CSF leaks. These patients were treated successfully with
intravenous antibiotics and suffered no long-term effects.
Untreated preoperative hydrocephalus was present in 5 of
these 6 patients, 3 of whom needed ventricular shunting
due to postoperative hydrocephalus (2 at an early stage
and 1 at a late stage).
Risk Factors. In univariate analysis, intraventricular
approach (OR 10.4, 95% CI 1.2–89.7; p < 0.01), untreated
preoperative hydrocephalus (OR 5.3, 95% CI 1.0–29.3; p
< 0.05), CSF leak (OR 8.0, 95% CI 1.4–46.2; p < 0.05),
and new onset postoperative hydrocephalus (OR 11.5,
95% CI 2.2–59.5; p < 0.01) were signicant risk factors
for developing postoperative meningitis.
In multivariate analysis, CSF leakage (OR 10.2, 95%
CI 1.2–70.5; p < 0.05) and new-onset postoperative hy-
drocephalus (OR 13.6, 95% CI 2.2–87.7; p < 0.05) were
signicantly associated with postoperative meningitis.
Age, sex, primary versus secondary resection, and pre-
operative hydrocephalus were not signicantly associated
with a risk of developing postoperative meningitis.
Surgical Mortality
There were 2 deaths within 30 days after surgery,
giving a surgical mortality rate of 0.5%. The rst patient
died 3 days postcraniotomy after a resection of a large
PNET in the temporoparietal region. The second patient
died 30 days after primary surgery due to a massive ce-
rebral infarction secondary to central venous thrombosis.
The patient had undergone a primary subtotal resection
of a pilocytic astrocytoma in the brainstem.
TABLE 3: Risk factors for developing untreated preoperative hydrocephalus using univariate and multivariate
regression analysis*
Univariate Analysis Multivariate Analysis
Variable OR 95% CI OR 95% CI
age (continuous variable) 1.1† 1.1–1.2 1.1‡ 1.0–1.2
sex
M 1
F 0.8 0.5–1.2 0.9 0.5–1.5
primary craniotomy 3.9† 2.1–7.2 3.9† 2.0–8.2
secondary craniotomy 1
main tumor location
supratentorial 1
infratentorial 8.1† 4.6–13.6 3.3† 1.9–5.8
brainstem/diencephalon 1.5 0.6–3.8 1.4 0.5–3.5
histology
WHO Grade I 1 1
WHO Grade II 0.4 0.1–1.2 0.8 0.2–2.5
WHO Grade III 0.2‡ 0–0.9 0.7 0.1–3.1
WHO Grade IV 0.5 0.1–1.4 1.3 0.3–4.5
PNET 3.2† 1.6–6.2 2.3§ 1.1– 4.9
DNET (5.1 × 10-8)† NC, 0.2 (1.9 × 10-8)§ NC, 0.4
germinoma 0.4 0.1–1.6 0.8 0.1–3.5
ependymoma 0.8 0.3–1.7 0.6 0.3–2.1
craniopharyngioma 0.2‡ 0.1–0.9 0.5 0.1–2.3
plexus tumor 1.4 0.5–3.5 1.5 0.5–4.2
other benign tumor 0.1† 0–0.2 0.1§ 0–0.4
other malignant tumors (5.1 × 10-8)‡ NC, 0.7 (1.8 × 10-8)NC, 7.1
* NC = zero or less than zero, and thus not able to be calculated.
† p < 0.001.
‡ p < 0.05.
§ p < 0.01.

J Neurosurg: Pediatrics / Volume 14 / December 2014
CSF disturbances in pediatric brain tumors
609
Discussion
Complication studies are of importance to the prac-
ticing neurosurgeons as they can lead to an increased
awareness of complications and possibly thereby lead to
improved patient care. Traditionally, most studies on peri-
operative complications in surgery for pediatric brain tu-
mors have focused on the posterior fossa. Although most
complications regarding CSF circulation and dynamics
may be related to disturbance of CSF ow in the posterior
fossa territory, it is important to also include supraten-
torial tumors as they account for up to two-thirds of all
pediatric tumors.23,29,31 Unfortunately, there are few pub-
lished case series on CSF disturbances that include both
infra- and supratentorial tumors.
Preoperative Hydrocephalus and Its Treatment
In this study of 381 consecutive craniotomies for
supra- and infratentorial pediatric brain tumors, 32.5%
presented with preoperative hydrocephalus. Numer-
ous series have reported rates of hydrocephalus prior to
surgery ranging from 69% up to 92%, although most of
these studies concerned tumors in the posterior fossa re-
gion.2,4,9,19,25,34
We found that younger patient age and infratento-
rial tumor location were the two most important risk fac-
tors for preoperative hydrocephalus (Table 3), which is
in accordance with results from previous studies.34 With
respect to patient age, this might partially be explained
by an immaturity of the arachnoid granulations (pacchio-
nian bodies) for CSF reabsorption in the young, as they
only reach functionality in the late infantile period.37
With respect to tumor histology, PNETs were signi-
cantly associated with a higher risk of preoperative hy-
drocephalus compared with WHO Grade I tumors (Table
3). This is in accordance with the published literature, al-
though the main focus of these studies has been restricted
to tumors located in the posterior fossa and less attention
Fig. 2. Graph of the results of the univariate analysis of risk factors for preoperative hydrocephalus. “Yes and No” refers to the
presence or absence of hydrocephalus, respectively.

S. A. M. Hosainey et al.
610 J Neurosurg: Pediatrics / Volume 14 / December 2014
has been given to the precise signicance of tumor histo-
pathology.17,18
Of our 124 cases with preoperative hydrocephalus, 82
were treated using tumor resection only, and 11 of these
patients went on to require shunt surgery for hydrocepha-
lus, yielding a cure rate of 86.6% (Fig. 1). Other series
report persistent hydrocephalus postoperatively in ap-
proximately 10%–30% of cases, even though these stud-
ies reect the rates of posterior fossa tumors only.3,25,33,35
Our results are on the lower end of this scale, in part pos-
sibly due to our inclusion of both supra- and infratentorial
tumors.
In our study, only 1 patient early in the series received
a VP shunt concomitant with tumor craniotomy (0.3%).
In a recent study by Wong et al.,39 the authors demon-
strated a trend toward less shunting prior to, or simultane-
ously with, craniotomy, from 17.6% in the early 1970s to
2.7% in the period 2001–2008. Precraniotomy shunting
has been largely abandoned and replaced by preoperative
ETV or EVD as effective modalities for CSF diversion in
more contemporary series.1,9,15,16,25,33,36,39
Feng et al.11 concluded in their series of 58 patients
(including both children and adults) that ETV prior to sur-
gery is a most effective treatment for cases of preoperative
obstructive hydrocephalus caused by aqueductal stenosis
and space-occupying lesions. In the same study, shunt in-
dependence after ETV was achieved in 82% of patients
with tumor-related obstructive hydrocephalus. In a Swiss
series by de Ribaupierre et al.6 with 48 pediatric patients
(0–18 years old), 24 had preoperative ETV because of ob-
structive hydrocephalus. Of these, 8 patients experienced
failure of the ETV, of whom 5 eventually needed a VP
shunt. In a study by Houdemont et al.,19 22 (38.6%) of
57 patients with preoperative hydrocephalus had an ETV
before surgery, and none of these patients needed post-
operative shunt placement. Sainte-Rose et al.33 reported
in their series of 196 pediatric patients that only 3 (6.4%)
of 47 patients with preoperative hydrocephalus treated by
ETV needed postoperative shunting, compared with 16
(19.5%) of 82 patients without preoperative ETV. Other
series have reported similar high ETV success rates,2,32,33
although these series involved pediatric patients with pos-
terior fossa tumors. In our study, 8 (6.5%) of 124 cases
underwent ETV prior to craniotomy for relief of preoper-
ative hydrocephalus, none of whom went on to require an
early VP shunt after craniotomy (Fig. 1). In addition, our
study demonstrates a similar high success rate of ETV
in both supra- and infratentorial tumors, albeit in a very
limited number of patients. Previous studies have con-
icting recommendations as to routine preoperative ETV,
with some authors recommending it as a rst choice for
obstructive hydrocephalus caused by tumors,10,33 whereas
others discourage it.3,12 Nonetheless, we believe that care-
ful patient selection for ETV prior to surgery may have a
great impact on postoperative outcome.
Placement of an EVD to treat preoperative hydro-
cephalus is commonly used in neurosurgical practice and
numerous studies have shown its effectiveness with re-
spect to postoperative outcome.4,26,36 Most often the EVD
is inserted simultaneously during tumor resection and the
EVD is subsequently weaned after surgery. If this fails,
placement of a permanent VP shunt is performed.7 In our
study, 33 (26.6%) of 124 cases received an EVD to treat
preoperative hydrocephalus, 24 of which were incidental
to the craniotomy (Fig. 1).
The success rate of the EVD (63.6%) was less than
Fig. 3. Flow chart showing the diagnosis and treatment of postoperative hydrocephalus.

J Neurosurg: Pediatrics / Volume 14 / December 2014
CSF disturbances in pediatric brain tumors
611
that of preoperative ETV (87.5%) or craniotomy alone
(86.6%), because 12 of 33 patients subsequently received
VP shunts because of persistent hydrocephalus postop-
eratively, either early (10 patients) or within the rst 3
months after the craniotomy (2 patients; Fig. 1).
Bognár et al.3 reported that 41% of patients with pre-
operative (13 of 27), intraoperative (2 of 27), and post-
operative (12 of 27) EVD placement underwent postop-
erative shunt placement in their series of 180 pediatric
patients with posterior fossa tumors. Similarly, Culley et
al.4 reported a shunt insertion rate of 33% in children who
received an EVD either preoperatively (18/81) or at the
time of surgery (63/81) in a series of 117 pediatric pa-
tients. Our study of both supratentorial and infratentorial
tumors showed a postoperative shunt placement rate of
36.4%, which is within the same range of the aforemen-
tioned studies. Possible explanations for the lower success
rate of perioperative EVD insertion compared with pre-
operative ETV or tumor resection alone might include a
negative selection bias and an increased risk of infections
and complications related to the drainage of CSF, which
have been shown by numerous studies in the past.3,4,26,33
In the aforementioned study by Bognár et al.,3 28
(15.6%) of 180 patients received a shunt postoperative-
ly, 6.7% within the rst 6 weeks postoperatively, and
8.9% between 2 and 83 months after surgery. Further-
more, 15.3% of children who showed hydrocephalus on
their admission CT scan underwent postoperative shunt
placement, producing a shunt-free treatment success rate
of 84.7%. In another similar study by Fritsch et al.,12 46
(88.5%) of 52 patients did not require permanent CSF di-
version (neither VP shunt placement nor EVD/ETV). We
report a similar high postoperative shunt-free success rate
of 86.6% after tumor resection only (Fig. 1).
New-Onset Postoperative Hydrocephalus
Of the 257 patients with no preoperative hydrocepha-
lus, only 9 patients (3.5%) developed new-onset hydro-
cephalus postoperatively. In the same study mentioned
earlier by Bognár et al.,3 7 (16%) of 43 patients without
preoperative hydrocephalus developed shunt-dependent
hydrocephalus postoperatively. Santos de Oliveira et al.
reported in their retrospective study of 64 patients that
2 (40%) of 5 patients without preoperative hydrocepha-
lus developed new-onset postoperative hydrocephalus,
both of whom received shunts.34 In the study by Culley
et al.,4 3.1% of patients had new-onset postoperative hy-
drocephalus requiring shunting. Similarly, Morelli et al.25
reported new-onset postoperative hydrocephalus in 4.3%.
Most studies have not identied signicant risk fac-
tors associated with new-onset postoperative hydrocepha-
lus. In our study, male sex, main tumor location infraten-
torial, and infratentorial surgical approach were signi-
cantly associated with an increased risk of developing
new-onset postoperative hydrocephalus. Interestingly, in
comparison with the risk factors for postoperative hydro-
cephalus in the overall analysis, younger age did not reach
statistical signicance in the univariate analysis (OR
3.9, p < 0.065). Seven of the 9 patients with new-onset
postoperative hydrocephalus were boys, suggesting that
younger boys have a particularly high risk of developing
new-onset postoperative hydrocephalus. This result is in
accordance with the study of Lassen et al.,23 who reported
that boys have a higher risk of postoperative CSF leakage,
a well-known risk factor.
Overall Postoperative Hydrocephalus
In our study, a total of 33 patients had postoperative
hydrocephalus, of whom 24 (6.3%) had persistent postop-
erative hydrocephalus and 9 (2.4%) had new-onset post-
operative hydrocephalus (Fig. 3). Younger age (OR 1.1),
preoperative hydrocephalus (OR 4.8), and meningitis (OR
7.7) were highly associated with a risk of postoperative
hydrocephalus. In a study by Riva-Cambrin et al.30 in 343
pediatric patients with posterior fossa tumors, younger
patient age and degree of hydrocephalus preoperatively
were signicant predictors of postoperative hydrocepha-
lus. Culley et al.4 and Papo et al.26 also found that younger
children had a higher incidence of postoperative shunt
placement, presumably because of postoperative hydro-
cephalus. In contrast to our study, Culley et al.4 did not
nd preoperative hydrocephalus to be a signicant risk
factor for predicting the need for postoperative shunt
placement. However, in our study, young age and untreat-
ed preoperative hydrocephalus were also signicantly
associated with developing postoperative CSF leaks, in
accordance with results from previous studies by Lassen
et al.23 and Bognár et al.,3 which further strengthen the as-
sociation between young age and untreated preoperative
hydrocephalus as risk factors for developing postopera-
tive hydrocephalus.
The univariate analysis in our study showed that pa-
tients with PNETs (OR 2.4) have an increased risk of de-
veloping postoperative hydrocephalus. Past studies have
reported signicant correlations between postoperative
shunting due to persisting postoperative hydrocephalus
and patients with medulloblastomas.3,14,22,25,30 Medulloblas-
tomas occur mostly infratentorially in the posterior fossa
and can obstruct CSF pathways. Another factor that may
explain the possibility of developing hydrocephalus post-
operatively is their potential for metastasis intracranially
before the tumor is surgically removed. Both PNETs and
infratentorial tumor location were signicantly associated
with postoperative hydrocephalus overall in the univariate
analysis of our study, but in the multivariate analysis they
did not reach signicance. For persisting postoperative hy-
drocephalus, only meningitis was a signicant risk factor
in both univariate and multivariate analysis.
With regard to shunt treatment of postoperative hy-
drocephalus, 20 patients required early VP shunt place-
ment while 4 required late VP shunt placement in our
study (Fig. 3). In a recent study of craniotomies in 641
pediatric patients, von Lehe et al.38 reported that 27.0%
of craniotomies for tumor cases required shunts or ETV
due to permanent hydrocephalus, more often performed
in younger children (p < 0.05). Other risk factors for per-
manent hydrocephalus included low preoperative Kar-
nofsky Performance Scale scores, infratentorial surgery
(40.4% vs 2.6% for supratentorial surgeries), intraaxial
or subdural surgery, and emergency surgery. Other pa-
tient series have postoperative hydrocephalus rates rang-
ing from 10% to 35%,3,4,12,22,25,33 although these series are

S. A. M. Hosainey et al.
612 J Neurosurg: Pediatrics / Volume 14 / December 2014
restricted to posterior fossa tumors. The overall rate of
postoperative hydrocephalus with subsequent VP shunt
placement in our study is relatively low, even though we
included all patients regardless of tumor location and
state of preoperative hydrocephalus. The literature states
that approximately 30% are in need of permanent shunt
placement due to postoperative hydrocephalus, but these
rates reect posterior fossa tumors.7,24,30 In the aforemen-
tioned study by Wong et al.,39 their rate of postoperative
ventricular shunting was 31.1% in the period from 2001
to 2008, yielding a success rate with postoperative shunt
independence of 68.9%, whereas in our series the success
rate is higher than 80% in the past decade.
CSF Leakage and Meningitis
Our postoperative CSF leak rate was 6.3%. This rath-
er high rate of CSF leaks might partially be explained by
how leakage was dened; we have included all identied
leaks, including hygromas and leakage of CSF uid along
EVD lines, and not only those requiring operative treat-
ment. Most of the aforementioned series have not speci-
ed the term “CSF leakage.” Nevertheless, our rate is in
the midrange of previously published series, in which
2.0%–10.3% of children undergoing craniotomies devel-
op CSF leakage according to Lassen et al.23
In the aforementioned study by Houdemont et al.,19
which included 117 pediatric and adolescent patients (age
range 0.3–21.4 years), 1.7% of cases were complicated by
meningitis. Lassen et al.23 reported a postoperative men-
ingitis rate of 1.8%. Our rate of postoperative meningitis
was 1.6% compared with other reported series.1,3,13
As previous studies have shown, CSF leaks are
closely related to postoperative infections and prolonged
hospital stay.5,20,21 For instance, Houdemont et al.19 re-
ported that infected patients stayed 4 times longer in the
pediatric intensive care unit than those without infection.
Furthermore, nancial costs and hospital stays increase
considerably with CSF leaks and it is of importance to
be aware of cost-effectiveness regarding CSF complica-
tions. In a prospective study by Piek et al.27 performed in
545 patients with a variety of different intracranial proce-
dures, costs per case nearly doubled because of complica-
tions regarding postoperative CSF leakage.
With CSF infections contributing greatly to increased
morbidity and even mortality, it is important to select pa-
tients carefully to undergo perioperative EVD placement.
In such settings, we therefore recommend antibiotic-
impregnated EVD catheters rather than standard EVD
catheters due to their safety prole, although other fac-
tors such as the duration of EVD placement must also be
taken into account. However, in a recent study by Pople et
al.,28 the use of antibiotic-impregnated EVD catheters did
not signicantly reduce the risk of EVD infection com-
pared with standard EVD catheters.
Strengths of the Study
The strengths of this study lie in its setting, design,
and follow-up. The data were restricted to 1 health cen-
ter only (Rikshospitalet), thereby reducing the possible
confounding effect of differences in access to health care
services between health centers. Thus, we have avoided
the selection bias inherently present in large multicenter
studies, as there is only 1 neurosurgical unit performing
these surgeries within a geographically well-dened area.
Our series includes both supratentorial and infratentorial
tumors, thereby reecting the panorama of brain tumors
observed in a pediatric neurosurgical practice. Further-
more, the study includes both primary and secondary cra-
niotomies, also reecting a common clinical setting. Our
study design is a retrospective analysis of a prospectively
registered database. As the study includes all cranioto-
mies performed for a histologically veriable brain tumor
within the study period, there is no selection bias. With
respect to data quality, we only used easily veriable end
points. In addition, every single complication registered
in the database was veried by a thorough retrospective
chart review by 2 independent reviewers (S.A.M.H. and
T.R.M.). Lastly, we obtained a 100% follow-up rate. To
the best of our knowledge, our study is the largest study
with regard to postoperative CSF disturbances after cra-
niotomies for pediatric brain tumors.
Limitations of the Study
The rst limitation of the study is the retrospective
analysis of patient outcome with respect to CSF leaks and
meningitis, as these data were not systematically regis-
tered in the database and were identied by chart reviews.
Second, although this is a large series, the total number of
patients may still be so low that a statistical Type II error
(i.e., failure to identify a true prognostic factor) may occur
when performing the multivariate analyses. Third, most
contemporary patient series conducted in pediatric brain
tumors in the neurosurgical literature comprise tumors lo-
cated in the posterior fossa territory, which makes them
challenging for direct comparisons to our study. Lastly, the
statistical analyses may have been affected unfavorably by
including patients who underwent multiple craniotomies.
Conclusions
Preoperative hydrocephalus was found in 32.5% of
pediatric patients with brain tumors treated using crani-
otomies. Tumor resection alone cured preoperative hy-
drocephalus in 86.6% of cases, and the incidence of new-
onset hydrocephalus after craniotomy was only 3.5%. In
general, complication rates are low with regard to periop-
erative CSF disturbances. Further studies are needed for
better understanding and alleviation of these complica-
tions. The authors’ data could be used as a benchmark for
future studies.
Acknowledgments
We thank Elisabeth Elgesem and Hanne Vebenstad for excel-
lent secretarial assistance, and David Scheie, M.D., for neuropathol-
ogy services.
Disclosure
The authors report no conflict of interest concerning the mate-
rials or methods used in this study or the findings specified in this
paper.

J Neurosurg: Pediatrics / Volume 14 / December 2014
CSF disturbances in pediatric brain tumors
613
Author contributions to the study and manuscript preparation
include the following. Conception and design: Meling, Lassen,
Helseth. Acquisition of data: Meling, Hosainey, Lassen. Analysis
and interpretation of data: all authors. Drafting the article: Meling,
Hosainey, Lassen. Critically revising the article: Meling, Helseth.
Reviewed submitted version of manuscript: all authors. Approved
the final version of the manuscript on behalf of all authors: Meling.
Statistical analysis: Meling. Administrative/technical/material sup-
port: Meling. Study supervision: Meling, Helseth.
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Accepted August 22, 2014.
Please include this information when citing this paper: published
online October 17, 2014; DOI: 10.3171/2014.8.PEDS13585.
Address correspondence to: Torstein R. Meling, M.D., Ph.D.,
De partment of Neurosurgery, Oslo University Hospital, Rikshospi-
talet, N-0027 Oslo, Norway. email: torsteinrmeling@mailcity.com.