Recent Articles on Endoscopic Third Ventriculostomy from

different journals... Chandra Mouli Devineni 9490328369

1.Long-Standing Overt Ventriculomegaly in Adults: A Systematic Review and Meta-Analysis of
Endoscopic Third Ventriculostomy Versus Ventriculoperitoneal Shunt as First-Line Treatment.
World Neurosurg. 2023 Jun;174:213-220.e2.
2.Concomitant, Single Burr Hole Endoscopic Third Ventriculostomy and Tumor Biopsy for
Pineal Lesions: Feasibility, Safety, and Benefits.
World Neurosurg. 2023 May;173:5-11.
3.Endoscopic third ventriculostomy versus ventriculoperitoneal shunt insertion for the
management of pediatric hydrocephalus in African centers - A systematic review and meta-
analysis.
Surg Neurol Int. 2022 Oct 14;13:467.
4.Failure of Endoscopic Third Ventriculostomy.
Cureus. 2022 May 19;14(5):e25136.
5.The Outcome of Surgical Intervention (Ventriculoperitoneal Shunt and Endoscopic Third
Ventriculostomy) in Patients With Hydrocephalus Secondary to Tuberculous Meningitis: A
Systematic Review.
Cureus. 2022 May 25;14(5):e25317.
6.Efficacy and safety of flexible versus rigid endoscopic third ventriculostomy in pediatric and
adult populations: a systematic review and meta-analysis.
Neurosurg Rev. 2022 Feb;45(1):199-216.
7.Endoscopic third ventriculostomy for hydrocephalus in a patient with achondroplasia: a
case report and literature review.
Childs Nerv Syst. 2021 Dec;37(12):3907-3911.
8.The Use of Endoscopic Third Ventriculostomy as Treatment for Idiopathic Intracranial
Hypertension: Case Report and a Review of Previously Reported Cases.
World Neurosurg. 2020 Sep;141:373-376.
9.Comparing the Efficiency of Two Treatment Methods of Hydrocephalus: Shunt Implantation
and Endoscopic Third Ventriculostomy.
Basic Clin Neurosci. 2019 May-Jun;10(3):185-198.
10.Role of Secondary Endoscopic Third Ventriculostomy in Children: Review of an
Institutional Experience.
Pediatr Neurosurg. 2019;54(3):188-195.
11.Endoscopic Third Ventriculostomy versus Ventriculoperitoneal Shunt in Patients with
Obstructive Hydrocephalus: Meta-Analysis of Randomized Controlled Trials.
World Neurosurg. 2019 Sep;129:334-340.
12.Safety and efficacy of Endoscopic Third Ventriculostomy in Diffuse Intrinsic Pontine Glioma
related hydrocephalus: a Systematic Review.
World Neurosurg. 2018 Dec 29:S1878-8750(18)32919-X.
Literature Review
Long-Standing Overt Ventriculomegaly in Adults: A Systematic Review and
Meta-Analysis of Endoscopic Third Ventriculostomy Versus Ventriculoperitoneal Shunt
as First-Line Treatment
Conor S. Gillespie1, Wen Yung Stephanie Fang2, Keng Siang Lee3,4, Abigail L. Clynch5,7, Ali M. Alam6,
Catherine J. McMahon7
Key words
- Adult hydrocephalus
- Endoscopic third ventriculostomy
- Long-standing overt ventriculomegaly in adults
- Ventriculoperitoneal shunt
Abbreviations and Acronyms
AS: Aqueduct stenosis
CI: Confidence interval
ETV: Endoscopic third ventriculostomy
LOVA: Long-standing overt ventriculomegaly in
adults
VPS: Ventriculoperitoneal shunt
From the 1Department of Clinical Neurosciences, University
of Cambridge, Cambridge; 2Department of Clinical
Neurosciences, St George’s, University of London, London;
3
Department of Neurosurgery, King’s College Hospital,
London; 4Department of Basic and Clinical Neurosciences,
Maurice Wohl Clinical Neuroscience Institute, Institute of
Psychiatry, Psychology and Neuroscience, King’s College
London, London; 5Institute of Systems, Molecular and
Integrative Biology, and 6Institute of Infection, Veterinary and
Ecological Science, University of Liverpool, Liverpool; and
7
Department of Neurosurgery, The Walton Centre NHS
Foundation Trust, Liverpool, United Kingdom
To whom correspondence should be addressed:
Conor S. Gillespie, M.Phil.
[E-mail: conorgillespie1@gmail.com]
Citation: World Neurosurg. (2023) 174:213-220.
https://doi.org/10.1016/j.wneu.2023.03.064
Journal homepage: www.journals.elsevier.com/world-
neurosurgery
Available online: www.sciencedirect.com
1878-8750/ª 2023 The Author(s). Published by Elsevier Inc.
This is an open access article under the CC BY license
(http://creativecommons.org/licenses/by/4.0/).
INTRODUCTION
Long-standing overt ventriculomegaly in
adults (LOVA) describes late-onset,
decompensated hydrocephalus in adults.
First described by Oi et al. in 2000,1 LOVA
encapsulates multiple forms of adult
hydrocephalus, including syndrome of
hydrocephalus in adults, chronic
ventriculomegaly, and aqueduct stenosis
(AS).2,3 A unique form of hydrocephalus,
LOVA is an emerging clinical problem,
which is increasing in incidence. LOVA
WORLD NEUROSURGERY 174: 213-220, JUNE 2023
- BACKGROUND: Long-standing overt ventriculomegaly in adults (LOVA) is a
heterogeneous term describing forms of adult hydrocephalus. LOVA incidence is
increasing, yet the optimal treatment strategy for symptomatic cases remains
unclear. We compared success rates and complication rates between endo-
scopic third ventriculostomy (ETV) and ventriculoperitoneal shunt (VPS) as first-
line treatment for LOVA.
- METHODS: A systematic review and meta-analysis was conducted in
accordance with PRISMA guidelines. Three databases were searched, and ar-
ticles published from 2000 to October 2022 were included (last search date
October 24, 2022). Success rates and complications of both ETV and VPS were
compared using random-effects models.
- RESULTS:
Of 895 articles identified, 22 studies were included in the analysis
(556 patients: 346 in ETV group, 210 in VPS group). Mean age was 44.8 years. The
most common presenting symptoms were gait disturbance (n [ 178), headache
(n [ 156), and cognitive decline (n [ 134). Combined success rates were 81.8%
(n [ 283/346) in the ETV group and 86.7% (n [ 182/210) in the VPS group (median
follow-up 41 months). There was no difference in success rates between ETV
and VPS groups (odds ratio 0.94, 95% confidence interval 0.86e1.03, I2 [ 0%).
Combined complication rates were 4.6% (n [ 16/346) in the ETV group and 27.1%
(n [ 57/210) in the VPS group. ETV had a lower rate of postoperative compli-
cations (odds ratio 0.22, 95% confidence interval 0.11e0.33, I2 [ 0%).
- CONCLUSIONS: Symptomatic LOVA can be successfully managed with sur-
gical intervention. ETV and VPS have similar success rates when used as first-
line treatment. VPS has a higher complication rate.
is being increasingly described and Treatment options include observation,
recognized as a distinct entity in the medical management with agents such as
literature.1,4-7 acetazolamide, and surgery.2,10 Surgery is
The natural history of LOVA is still un- thought to be the definitive management
clear.2 It is hypothesized to be linked to an for symptomatic LOVA, and procedures
initial insult that remains asymptomatic include endoscopic third ventriculostomy
until later decompensation from a (ETV) and ventriculoperitoneal shunt
triggering event such as a head injury.8 (VPS).4,11 Conflicting reports of efficacy
Symptoms often mirror other types of and outcomes have been reported in the
adult hydrocephalus and include literature, with advocates for both
headache, gait ataxia, urinary treatments.4,10 However, there has been
incontinence, visual changes, and little direct comparison between the 2
cognitive decline.9 Enlarged ventricles, procedures,5,12 and the optimal first-line
increased Evans index, sella destruction/ surgical treatment for LOVA remains un-
enlargement, and AS are often seen on clear. In this literature review, we aimed to
imaging.6 answer the following question: In patients
www.journals.elsevier.com/world-neurosurgery 213
 LITERATURE REVIEW
CONOR S. GILLESPIE ET AL. LOVA SYSTEMATIC REVIEW

with LOVA, what are the success rates and
complications of ETV compared with VPS?
MATERIALS AND METHODS
Search Strategy and Selection Criteria
We conducted a systematic review and
meta-analysis according to the PRISMA
(Preferred Reporting Items for Systematic
Reviews and Meta-Analyses) Guidelines.13
The review was registered a priori in
PROSPERO (CRDCRD42021277542). The
protocol was not modified.
We searched Medline, CINAHL Plus,
and Cochrane Database of Systematic Re-
views for full-text articles published in
English, from January 1, 2000, and
October 24, 2022 (search date October 24,
2022). Search terms used a combination of
the terms LOVA and hydrocephalus and
their associated synonyms. PICOS (Popu-
lation, Intervention, Comparator,
Outcome, Study Design) criteria were
used, and the specific inclusion criteria are
shown in Table 1. We included studies of
adults (
18 years old) that specifically
mentioned the term LOVA (or long-
standing overt ventriculomegaly in
adults) in the title or abstract. This was to
be as specific as possible for LOVA, as it is
known that different definitions are
applied to the condition, to allow for as
homogeneous a cohort as representative
of true LOVA as possible to compare
treatment modalities.1,6 We excluded
studies that reported adult hydrocephalus
or AS only. We excluded conference
abstracts, case reports, and studies
published before January 2000 (date of
publication of Oi et al.1 article and first
identified definition of LOVA used). For
studies that included LOVA as part of a
mixed series, we included studies only if
data were available to extract the number
of ETV and VPS procedures and the
success rates separately.
Two reviewers (C.S.G., W.Y.S.F.) inde-
pendently screened titles, abstracts, and
full texts to include articles. If reviewers
failed to reach consensus, a third author
(K.S.L.) was sought for clarification.
Data Extraction
Data extraction was completed by 2 au-
thors independently (C.S.G., W.Y.S.F.).
The following data were extracted from
included studies: year published, journal,
type of study (randomized controlled trial
or observational study), number of pa-
tients with LOVA, number of ETV pro-
cedures, and number of VPS procedures.
Presenting symptoms, Evans index, intra-
cranial pressure if reported, and mean/
median follow-up time were also recor-
ded. Primary outcomes included success
rates of ETV and VPS, success definition
employed by authors, and number of
complications. Complications were
further delineated by free text. The num-
ber of repeat ETV and repeat VPS pro-
cedures performed was also recorded in
addition to the success rates if available.
Quality Assessment
Quality assessment was completed by 2
reviewers independently (C.S.G.,
W.Y.S.F.). Retrospective studies were
classified according to the Newcastle-
Ottawa Scale,14 and randomized
controlled trials were assessed according
to the Cochrane Risk of Bias 2.0 tool.15

Table 1. PICOS (Population, Intervention, Comparator, Outcome, Study Design) Definitions

Inclusion Criteria ETV or VPS success was defined according
to the definitions used by study authors.
Review In patients with LOVA, what are the success rates and complications of ETV compared with
question VPS? This often related to clinical improvement
or stability of symptoms, radiological
Population Adults
18 years old with LOVA* improvement or stability after surgery, or
Intervention ETV not requiring further surgical intervention.
Comparator VPS
Statistical Analysis
Outcomes
Data were extracted via a Microsoft Excel
Primary ETV success rates (Microsoft Corp., Redmond, Washington,
ETV complication rate USA) spreadsheet, then exported to R
version 4.0 (R Foundation for Statistical
VPS success rate
Computing, Vienna, Austria) for analysis
VPS complication rate and generation of figures. Baseline de-
Secondary Repeat ETV success and complication rate mographics were summarized using
descriptive statistics. Symptom and pa-
Repeat VPS Success and complication rate
tient counts were summarized using mean
LOVA symptoms and SD or, if not normally distributed,
Number of studies with LOVA-specific data available median and interquartile range.16 For the
meta-analysis, we used a random-effects
Setting Studies taking place in any neurosurgical department or center
model for comparative estimates of bi-
Study design Phase 3 trials, prospective case series, and cohort studies with >1 adult patient nary outcomes (rates of ETV success or
Follow-up Any median or mean follow-up time reported complications) in accordance with pub-
lished guidelines.16 We generated forest
LOVA, long-standing overt ventriculomegaly in adults; ETV, endoscopic third ventriculostomy; VPS, ventriculoperitoneal
plots for studies that included both
shunt.
treatment types based on a random
*Studies published before January 2000 and nonspecific studies of adult hydrocephalus were excluded.
intercept model assessing binary

214 www.SCIENCEDIRECT.com WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2023.03.064

 LITERATURE REVIEW
CONOR S. GILLESPIE ET AL. LOVA SYSTEMATIC REVIEW

Figure 1. PRISMA (Preferred Reporting Items for Systematic inclusion in this review and meta-analysis. LOVA, long-standing
Reviews and Meta-Analyses) flow diagram of study selection for overt ventriculomegaly in adults.

WORLD NEUROSURGERY 174: 213-220, JUNE 2023 www.journals.elsevier.com/world-neurosurgery 215


CONOR S. GILLESPIE ET AL.
Table 2. Baseline Characteristics of
Included Studies
Characteristic
Total studies included
Published after 2010
Journal
Journal of Neurosurgery
World Neurosurgery
Acta Neurochirurgica
Neurosurgical Review
Other
Study details
Retrospective cohort
Median number of included
patients (IQR)
Total number of included
patients
Male:female ratio
Mean head circumference
(SD)
Presenting symptoms*
Gait ataxia
Headache
Cognitive decline
Urinary incontinence
Dementia
Psychiatric disturbance
Visual changes
Papilledema
Mean Evans index (SD)
Values are frequency (percentage) except where noted.
IQR, interquartile range.
*From a maximum of 349 patients with symptom data
available.
outcomes and odds ratios. Heterogeneity
was assessed using the I2 characteristic.
To consider the impact of studies that
reported only one treatment type in our
analysis (single arm), we carried out an
additional random-effects pooled propor-
tion analysis for each treatment type.
Publication bias was evaluated and pre-
sented as funnel plots. Rstudio Version
4.0.1 was used to perform meta-analysis
and create forest and funnel plots
216 www.SCIENCEDIRECT.com
(ggplot, tidyverse, metafor, metaprop, and
meta packages).
Value
RESULTS
22
Study Details
16 (72.7%) After removal of duplicates, 895 studies
were identified. After full-text assessment,
45 full-text studies were assessed for in-
3 (13.6%)
clusion. An additional 25 studies were
3 (13.6%) excluded. An additional 2 studies were
2 (9.1%) identified via hand searching, resulting in
22 studies being included (Figure 1). All
2 (9.1%)
studies were retrospective cohort studies.
12 (54.5%)
Baseline Study Characteristics
22 (100%) The baseline characteristics of included
studies are presented in Table 2. The most
24 (13e32)
common country of published studies was
the United Kingdom (27.3%, n ¼ 6). The
556 total number of patients included was
556 (ETV: 346; VPS: 210). The median
1.4:1 number of patients included per article
was 24.0 (interquartile range 13.0e32.0).
58.8 (1.5)
The presenting symptoms are listed in
Table 2. The most common reported
symptoms were gait ataxia (n ¼ 178),
178 (51.0%) headache (n ¼ 156), and cognitive
156 (44.7%) decline (n ¼ 134). The mean (SD) head
circumference was 58.8 (1.5) cm (range
134 (38.4%)
57.5e61.0 cm). The median follow-up af-
102 (29.2%)
ter surgery was 41.2 months (interquartile
68 (19.5%) range 36.0e57.0).
41 (11.7%)
Success Rates
41 (11.7%)
Success was defined as a clinical
9 (2.6%) improvement or reduction in symptoms in
17 articles and as a clinical improvement
0.46 (0.02)
and radiological improvement or stability
in 4 articles (Table 3). One article defined
success as not requiring surgical revision/
reoperation. The overall success rate for
surgery (both ETV and VPS) was 83.6%.
The success rate for ETV was 81.8%
(n ¼ 283/346), and the success rate for
VPS was 86.7% (n ¼ 182/210). The
complication rate was 4.6% for ETV (n ¼
16/346) and 27.1% for VPS (n ¼ 57/210)
(Table 3).
Comparison of Success Rates Between
ETV and VPS Groups
Ten studies compared success rates be-
tween ETV and VPS groups (n ¼ 292; ETV:
173 ETV; VPS: 119) and were therefore
included in the meta-analysis. There was
WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2023.03.064
LITERATURE REVIEW
LOVA SYSTEMATIC REVIEW
no difference in success rates between
ETV and VPS groups (odds ratio 0.94, 95%
confidence interval [CI] 0.86e1.03, I2 ¼
0%) (Figure 2). The funnel plot and linear
regression test of funnel plot asymmetry
did not show any significant publication
bias (P ¼ 0.5768) (Supplementary
Figure 1).
Complication Rate
Nine studies reported complication rates
for both ETV and shunt cohorts (n ¼ 292;
ETV: 172; VPS: 115). ETV had a signifi-
cantly lower complication rate than VPS
(relative risk 0.19, 95% CI 0.11e0.33, I2 ¼
0%) (Figure 3). The funnel plot did not
demonstrate any significant publication
bias (Supplemental Figure 2). The
complications in both groups are
summarized in Table 3.
ETV and VPS as Second-Line Treatments
Of the articles included, ETV was performed
for failed VPS in 10 cases (3 studies), and
VPS was performed for failed ETV in 25
cases (5 studies). The success rate of ETV
was 70% (n ¼ 7/10), and the success rate of
VPS was 56% (n ¼ 14/25).
Pooled Proportion Analysis including
Single-Arm Studies
The pooled proportion success rates
including single-arm studies was 83.7%
for ETV (19 studies, 95% CI 77.6e89.2,
I2 ¼ 24.9%) and 91.6% for VPS (13 studies,
95% CI 84.8e96.9, I2 ¼ 24.2%). The
pooled proportion complication rate was
2.7% for ETV (15 studies, 95% CI 0.3e6.7,
I2 ¼ 21.5%) and 33.2% for VPS (12 studies,
95% CI 15.4e53.2, I2 ¼ 82.1%).
Risk of Bias
The risk-of-bias assessment according to
the Newcastle-Ottawa Scale is shown in
Figure 4. The mean score (out of 9) for all
studies was 7.8, and 4 studies (18.2%)
were classified as high risk of bias. Eight
studies scored a 9 out of 9, 7 studies
scored 8 out of 9, and 3 studies scored 7
out of 9. Seven out of 9 questions had
100% agreement between 2 blinded
authors (C.S.G and W.Y.S.F), and the
remaining 2 were resolved with
consensus.
 LITERATURE REVIEW
CONOR S. GILLESPIE ET AL. LOVA SYSTEMATIC REVIEW

success used throughout. LOVA is an

Table 3. Success and Complications in Included Studies increasingly reported condition, with 22
Value studies included in this review. Given that
sizable patient cohorts are still lacking in
Success definition the literature, we pooled together all
Clinical improvement only 17 (77.3%) studies that treated LOVA to ascertain
differences in treatment methods.
Clinical and radiological improvement/stability 4 (18.2%)
Not requiring further surgery 1 (4.5%) Comparison with Literature
Follow-up, months Previous studies have attempted to estab-
lish both VPS and ETV as first-line treat-
Mean follow-up (SD) 29.7 (28.2)
ment for LOVA, with proponents of both
Median follow-up (IQR) 41.2 (36.0e57.0) VPS and ETV.7,17,18 Studies have
Success rates demonstrated both treatments to have a
success rate of 76%e83%.8,11,12 This is
ETV 283/346 (81.8%)
quantified in our analysis to 82% for ETV
VPS 184/210 (86.7%) and 87% for VPS, although the number
Complication rates of included VPS cases were lower than
ETV cases.
ETV 16 (4.6%)
Our study shows that VPS has a high
VPS 57 (27.1%) complication rate of 27.1%, which is in
keeping with the literature.9,19 This is
Complications ETV VPS
likely in part due to intrinsic risks of the
Subdural hematoma 0 (0.0%) 16 (7.6%) surgical procedure itself (e.g., infection,
shunt removal) as well as the inherently
Subdural hygroma 0 (0.0%) 4 (1.9%)
complex nature of patients with LOVA
Shunt blockage 0 (0.0%) 23 (11.0%) due to their changing cerebrospinal fluid
Shunt infection 0 (0.0%) 2 (1.0%) dynamics and intricate and preexisting
anatomical variations that respond
Wound infection 4 (1.2%) 1 (0.5%)
differently to intervention, which may
Cerebral abscess 1 (0.3%) 0 (0.0%) predispose to complications such as
Meningitis 1 (0.3%) 0 (0.0%) subdural hematomas and hygromas.3 The
Intracerebral hemorrhage/hematoma 4 (1.2%) 1 (0.5%)
reasons for this have been explored in
the literature and are theorized to be due
Postoperative seizures 3 (0.9%) 1 (0.5%) to these dynamics, cerebral atrophy that
DVT 1 (0.3%) 0 (0.0%) occurs with age, and head trauma
HAP 1 (0.3%) 0 (0.0%) changing intracranial pressure regulatory
processes.2,20 Complications in
CSF leak 1 (0.3%) 1 (0.5%) neurosurgery carry significant morbidity,
Abdominal sepsis 0 (0.0%) 1 (0.5%) and risk must be minimized whenever
Not reported 0 (0.0%) 2 (1.0%) possible.21 With both procedures having
a relatively similar success rate, the
Second-line treatment success
complication risk is important to
ETV 7/10 (70%) consider when deciding on surgical
VPS 14/25 (56%) management options in LOVA.12,20 Our
analyses illustrate that repeat surgery for
Values are frequency (percentage) except where noted. LOVA is also successful in 56%e70% of
IQR, interquartile range; ETV, endoscopic third ventriculostomy; VPS, ventriculoperitoneal shunt; DVT, deep vein thrombosis; cases.6,22 This reduced success rate is
HAP, hospital-acquired pneumonia; CSF, cerebrospinal fluid.
reflective of the complexity of the
condition, reiterating the importance of
minimizing complications in the primary
DISCUSSION procedures and 210 VPS procedures, we procedure.23,24
identified that ETV and VPS have similar
Summary of Findings success rates when used as first-line Clinical and Research Implications
To our knowledge, this systematic review treatment, with ETV having a signifi- Our results have several implications for
and meta-analysis is the first to directly cantly lower complication rate. Data were practice and research. The success rates
compare ETV and VPS as first-line treat- collected from retrospective cohort and complications of both procedures re-
ments for LOVA. By comparing 346 ETV studies, with differing definitions of ported in our results can be

WORLD NEUROSURGERY 174: 213-220, JUNE 2023 www.journals.elsevier.com/world-neurosurgery 217


CONOR S. GILLESPIE ET AL.
Figure 2. Forest plot comparing success rates of endoscopic third ventriculostomy and
ventriculoperitoneal shunt. ETV, endoscopic third ventriculostomy; VPS, ventriculoperitoneal shunt;
RR, relative risk; CI, confidence interval.
communicated to patients to allow
informed decisions to be made with
management of their condition.
Though we mentioned the relative risks
and benefits of VPS and ETV, our review
did not include any randomized studies,
trials, or prospective studies. These
studies are needed to definitively answer
the question of the optimal treatment
choice, as both selection and observer bias
may be prevalent, with many included
studies in the review illustrating only one
treatment type.10,25,26 Furthermore, the
reduced success rate of repeat treatments
infers that LOVA remains poorly
understood in its pathogenesis.
Preclinical studies of LOVA have not yet
been published, and such studies are key
to understanding the underlying
pathology and factors influencing its
recalcitrance to treatment. Whether
Figure 3. Forest plot comparing complication rates of endoscopic third ventriculostomy and
ventriculoperitoneal shunt. ETV, endoscopic third ventriculostomy; VPS, ventriculoperitoneal shunt;
RR, relative risk; CI, confidence interval.
218 www.SCIENCEDIRECT.com
LOVA is a distinct form of adult
hydrocephalus or not remains an area of
clinical uncertainty.27 Despite this review
indicating that ETV has a similar success
rate with reduced complications, this
may be due to anatomical variations, in
particular, the presence of AS.28 Some
authors argue that the presence of AS
indicates a good outcome with ETV6;
however, in cases of open aqueduct
LOVA, the pathogenesis and optimal
treatment are less clear.6,12 In these
patients, authors advocate VPS as first-
line treatment. The Japanese normal
pressure hydrocephalus guidelines classify
LOVA symptoms and include the presence
of radiological findings such as sella
destruction.29 This is an area of future
exploration, as these signs are not
encountered in all patients with LOVA,
and a clear clinical and radiological
WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2023.03.064
LITERATURE REVIEW
LOVA SYSTEMATIC REVIEW
picture will emerge as increasing
numbers of series of LOVA, with and
without AS, are reported.
Limitations
This study has several limitations. First, all
studies included were retrospective, pre-
cluding the higher forms of evidence.
Additionally, although 22 studies were
included in the review, only 10 studies
directly compared ETV and VPS, enabling
inclusion in the meta-analysis. Perhaps
most crucially, we did not include studies
that vaguely described LOVA, such as
those defining AS or simply adult hydro-
cephalus.30 This was done to ensure
homogeneity within the studies and
subsequent results—the low I2 value
obtained for both outcome measures
reflects this and suggests that while case
definition varies between included
studies (such as the inclusion of sella
destruction as an absolute criteria for
LOVA), our study inclusion criteria
reflect a homogeneous LOVA cohort.
Therefore, case attrition and lack of
representation from the available
literature are inevitable. In addition, we
believe that LOVA is a separate entity
from adult hydrocephalus, and as the
definition is still used infrequently, the
only way to ensure as homogeneous a
cohort as possible was to include articles
that mentioned LOVA specifically.
The median follow-up time was
approximately 3.5 years (41 months).
Therefore, this review may not reflect
long-term outcomes of both treatment
types beyond 4 years. In addition, the
number of both ETV and VPS procedures
as second-line treatments is likely too
small to make a sufficient judgment of
their efficacy in this setting—these
numbers will increase with long-term
follow-up, with a greater increase in VPS
use seen after ETV failure, although this is
based on the few studies that employed
this approach.5,12,31 Furthermore, there are
no current guidelines for how to manage
symptomatic LOVA; this may have
affected the indications for surgery in the
included studies, which may
subsequently influence the success and
complication rates, although the degree
to which this possible selection bias
influenced the results is unknown.29 Four
studies were also identified as being at
high risk of bias—mostly due to short or

CONOR S. GILLESPIE ET AL.
Figure 4. Risk of bias for included studies according to the Newcastle-Ottawa Scale.
incomplete follow-up or selective case in-
clusion criteria. We also excluded full-text
articles not available in English, restricting
paper eligibility. Finally, the overall num-
ber of patients (N ¼ 546) included in this
analysis is low, in part due to the inherent
rarity of the condition.
CONCLUSIONS
This is the first systematic review and
meta-analysis to our knowledge to directly
evaluate ETV and VPS as treatment
methods for LOVA. The success rates for
the 2 procedures are similar, but the
higher complication rate for VPS indicates
that ETV may be a safer, but similarly
efficacious treatment for LOVA. Random-
ized controlled trials to assess these
treatments further should be considered to
provide grade 1 evidence to answer this
important clinical question regarding
treatment of LOVA.
CRediT AUTHORSHIP CONTRIBUTION
STATEMENT
Conor S. Gillespie: Conceptualization,
Data curation, Formal analysis, Project
administration, Writing e original draft,
Writing e review editing. Wen Yung Ste-
phanie Fang: Data curation, Validation,
Formal analysis, Writing e review editing.
Keng Siang Lee: Writing e original draft,
WORLD NEUROSURGERY 174: 213-220, JUNE 2023
Writing e review editing, Visualization.
Abigail L. Clynch: Conceptualization,
Methodology, Project administration,
Writing e review editing. Ali M. Alam:
Writing e original draft, Writing e review
editing, Visualization. Catherine J.
McMahon: Conceptualization, Supervi-
sion, Writing e review editing.
REFERENCES
1. Oi S, Shimoda M, Shibata M, et al. Pathophysi-
ology of long-standing overt ventriculomegaly in
adults. J Neurosurg. 2000;92:933-940.
2. Craven CL, Ramkumar R, D’Antona L, et al.
Natural history of ventriculomegaly in adults: a
cluster analysis. J Neurosurg. 2019;132:741-748.
3. Cowan JA, McGirt MJ, Woodworth G, et al. The
syndrome of hydrocephalus in young and middle-
aged adults (SHYMA). Neurol Res. 2005;27:540-547.
4. Bianchi F, Ducoli G, Moriconi F, et al. Long-
standing overt ventriculomegaly in adults and
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treatment for the proper diagnosis. World Neuro-
surg. 2021;149:104-110.
5. Montemurro N, Indaimo A, Di Carlo DT, et al.
Surgical treatment of long-standing overt ven-
triculomegaly in adults (LOVA): a comparative
case series between ventriculoperitoneal shunt
(VPS) and endoscopic third ventriculostomy
(ETV). Int J Environ Res Public Health. 2022;19:1926.
6. Palandri G, Carretta A, La Corte E, et al. Long-
standing overt ventriculomegaly in adults (LOVA)
with patent aqueduct: surgical outcome and
etiopathogenesis of a possibly distinct form of
chronic hydrocephalus. Acta Neurochir. 2021;163:
3343-3352.
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7. Jenkinson MD, Hayhurst C, Al-Jumaily M, et al.
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J Neurosurg. 2009;110:861-866.
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Brenes A, et al. LOVA: the role of endoscopic
third ventriculostomy and a new proposal for
diagnostic criteria. Neurosurg Rev. 2017;40:605-611.
9. Kiefer M, Eymann R, Steudel WI, et al. Gravita-
tional shunt management of long-standing overt
ventriculomegaly in adult (LOVA) hydrocephalus.
J Clin Neurosci. 2005;12:21-26.
10. Ved R, Leach P, Patel C. Surgical treatment of
long-standing overt ventriculomegaly in adults
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tational shunts in longstanding overt ven-
triculomegaly in adults. Neurosurgery. 2005;57:
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12. Gillespie CS, Richardson GE, Mustafa MA, et al.
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PRISMA 2020 statement: an updated guideline for
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14. Stang A, Jonas S, Poole C. Case study in major
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15. Higgins JP, Altman DG, Gøtzsche PC, et al. The
Cochrane Collaboration’s tool for assessing risk of
bias in randomised trials. BMJ. 2011;343:d5928.
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ment of ‘decompensated’ longstanding overt
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219
Literature Review
Concomitant, Single Burr Hole Endoscopic Third Ventriculostomy and Tumor Biopsy for
Pineal Lesions: Feasibility, Safety, and Benefits
Augusto Leone1,2, Antonio Colamaria3, Nicola Pio Fochi4, Veronica Di Napoli4, Maria Blagia5, Matteo Sacco3,
Gerd Winkler1, Uwe Spetzger1, Wessam Almerayed6, Francesco Carbone1,4
Key words
- Endoscopic third ventriculostomy
- Hydrocephalus
- Pineal tumors
- Pineal lesions
- Single-entry approach
- Tumor biopsy
Abbreviations and Acronyms
CSF: Cerebrospinal fluid
ETV: Endoscopic third ventriculostomy
GCT: Germ cell tumor
IVH: Intraventricular hemorrhage
TB: Tumor biopsy
VPS: Ventriculoperitoneal shunt
From the 1Department of Neurosurgery, Städtisches Klinikum
Karlsruhe, Karlsruhe; 2Faculty of Human Medicine, Charité
Universitätsmedizin Berlin, Berlin, Germany; 3Division of
Neurosurgery, Policlinico “Riuniti”; 4Division of
Neurosurgery, University of Foggia, Foggia; 5Division of
Neurosurgery, “Giovanni XXIII” Hospital, Bari, Italy; and
6
Department of Neurology, Klinikum Mittelbaden Rastatt,
Rastatt, Germany
To whom correspondence should be addressed:
Nicola Pio Fochi, H.S.D.
[E-mail: fochinicola98@gmail.com]
Augusto Leone and Antonio Colamaria contributed equally to
this work and are considered coefirst authors.
Citation: World Neurosurg. (2023) 173:5-11.
https://doi.org/10.1016/j.wneu.2023.01.082
Journal homepage: www.journals.elsevier.com/world-
neurosurgery
Available online: www.sciencedirect.com
1878-8750/ª 2023 The Authors. Published by Elsevier Inc.
This is an open access article under the CC BY license
(http://creativecommons.org/licenses/by/4.0/).
INTRODUCTION
Pineal tumors account for 2.8%e11% and
0.4% of all primary brain tumors in the
pediatric and adult populations, respec-
tively.1 The most frequently encountered
group of malignancies in this region
comprises germ cell tumors (GCTs),
occurring primarily during childhood
and adolescence and exhibiting a
marked male predominance.2 These
tumors commonly show a rapid growth
pattern and can be further classified into
2 subgroups: (1) germinomas, which
most frequently manifest with signs of
WORLD NEUROSURGERY 173: 5-11, MAY 2023
Obtaining a prompt diagnosis, avoiding indwelling ventriculoperitoneal shunt,
and enhancing the predictive value of pathologic examinations are only some of
the advantages conferred by a simultaneous third ventriculostomy and tumor
biopsy in patients with pineal region tumors. The objective of this study was to
retrospectively search the literature on concomitant, single burr hole endo-
scopic third ventriculostomy (ETV) and tumor biopsy (TB) for pineal region tu-
mors and to analyze the feasibility, surgical safety, and benefits of these 2
combined procedures. Consequently, a comprehensive, systematic literature
search was performed in compliance with the updated PRISMA 2020 guidelines
within electronic databases MEDLINE/PubMed, EMBASE, PLOS, and Cochrane
Library. Statistical analysis was performed with IBM SPSS 28.0.1.1(14), using
Kendall’s and Spearman’s tests, with a P < 0.05 considered significant. A total of
25 studies were selected and included in this review, for a total of 368 patients
(mean age 20.6 years; range 1e86 years; SD 17.5). More than two-thirds of the
procedures were operated with a rigid endoscope and 27.6% were performed
with either a flexible endoscope, a combination of the 2, or not otherwise
specified. Germinoma represented the most frequent diagnosis (20.1%) followed
by astrocytoma (12.9%) and pineocytoma (9.9%). The single-entry approach
allowed a correct histologic diagnosis in 88.7% of the examined cases. Summing
up, concomitant ETV and TB represent a valuable option for the management of
non-communicating hydrocephalus and the initial assessment of pineal region
tumors. The histologic confirmation rate was 88.7% in the examined cohort, with
only 10% of the biopsies yielding inconclusive results.
non-communicating hydrocephalus, and among the general population and the
(2) non-germinomatous germ cell tumors, significant histologic and clinical
a highly diverse group that includes heterogeneity, surgical management
embryonal carcinoma, yolk sac tumors, options vary considerably among
choriocarcinoma, and teratomas.3-5 institutions, primarily reflecting the
Rarely, tumors originating directly from neurosurgeon’s own expertise and
pineocytes have been described, with experience.9,10 To improve patient
pineoblastoma representing the most outcomes and reduce the number of
aggressive histotype.6 surgeries required to manage these
Typical clinical manifestations second- tumors, several authors have proposed
ary to a pineal mass include headaches, performing ETV and tumor biopsy (TB)
cerebellar symptoms, and signs of during the same surgical procedure, with
obstructive hydrocephalus due to aqueduct recent evidence demonstrating the
stenosis. The non-communicating nature benefits of this approach.8,11 The
of such hydrocephalus has prompted many empirical advantages are indeed multiple:
surgeons to perform third ventricle floor (a) reduction of the time from the onset
fenestration into the interpeduncular of neurologic symptoms to treatment; (b)
cistern through an endoscopic third ven- when successful, ETV may avoid
triculostomy (ETV) for its management, indwelling ventriculoperitoneal shunting
also in emergency settings.1,7,8 However, in young patients; (c) detection of tumor
given the low incidence of pineal tumors biomarkers into cerebrospinal fluid
www.journals.elsevier.com/world-neurosurgery 5

AUGUSTO LEONE ET AL.
(CSF), enhancing the predictive value of
the pathologic diagnosis; and (d) because
most tumors located at the cerebral
aqueduct are encountered when small in
volume, pure endoscopic resection may
represent a feasible therapeutic
procedure.12 Moreover, in cases where
radiation therapy serves as the first line of
treatment (i.e., pure germinoma),
concomitant ETV and TB could directly
lead to tumor irradiation, consequently
avoiding a second surgery for histologic
confirmation.1
However, current evidence regarding the
role, safety, and feasibility of simultaneous
ETV and TB for pineal tumors is solely
based on sporadic case reports and series
with hitherto 1 qualitative single-centered
review published by Morgenstern et al.11
almost a decade ago, leaving uncertainty
regarding optimal patient selection for the
procedure and its factual benefits.11
Therefore, the aim of this study was to
examine and summarize the published
literature concerning the use of
concomitant ETV and TB in patients
presenting with signs of obstructive
hydrocephalus caused by pineal mass and
to identify when a single trajectory for the
2 procedures should be taken into
consideration (see Table 1).
METHODS
Search Strategy and Selection Criteria
A comprehensive, systematic search of the
literature was performed in compliance
Table 1. Pros and Cons of a Single-entry Trajectory
Pros
8
Reduced number of surgeries needed
Avoidance of shunt placement for non-
communicating hydrocephalus due to aqueduct
stenosis12
Reduced iatrogenic brain tissue damage1
Reduced intra and post-operative complications
and hospitalization times11
Reduced morbidity11,14
Simultaneous collection of CSF for tumor markers
investigation12
6 www.SCIENCEDIRECT.com
COMBINED ETV AND TB FOR PINEAL LESIONS
with the updated Preferred Reporting Items
for Systematic Reviews and Meta-Analyses
(PRISMA) 2020 guidelines, as shown in
Figure 1.19 Article inquiry was operated via
electronic databases MEDLINE/PubMed,
EMBASE, PLOS, and Cochrane Library for
articles reporting single-entry trajectory
approaches describing concomitant ETV
and pineal TB. Human studies in English,
Italian, German, and French languages
published between 1997 and May 2022 were
considered for inclusion. Primary search
terms included “endoscopy”, “pineal”,
“tumor”, and “hydrocephalus” in the article
titles and abstracts in various MeSH com-
binations. Inclusion criteria were: (1) case
reports or case series where at least 1 pa-
tient harboring a pineal lesion was treated
with concomitant ETV for obstructive hy-
drocephalus and TB and (2) availability of
sufficient patient-specific clinical, histo-
logic, and surgical information. Publica-
tions describing a double-timed ETV and
TB were excluded. A total of 198 records
were identified. The extracted citations
were then checked for duplicates and cita-
tions of the examined articles were also
screened for the purpose of this review.
Any irrelevant research, review articles,
meeting abstracts/summaries, editorials,
and studies with unavailable data con-
cerning postoperative neurologic outcomes
were excluded. A total of 125 were assessed
for eligibility and 100 were excluded for the
following reasons: non-suitable language
(n ¼ 28), wrong study design (n ¼ 21), not
relevant (n ¼ 30), wrong patient population
(n ¼ 15), and wrong intervention (n ¼ 6)
Cons
Intraoperative bleeding following tumor biopsy
increasing the risk of ETV failure13
Intraventricular hemorrhage obscuring field, thus
limiting ability to perform tumor biopsy14
Iatrogenic contusion of adjacent structures
during endoscopic manipulation15
Iatrogenic tumor cells dissemination and
intraspinal seeding [present results]
Intraoperative reduction of third ventricle size
following ETV limiting ability to perform biopsy16
Higher rate of inconclusive diagnosis17,18
WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2023.01.082
LITERATURE REVIEW
through an automated system (Covi-
dence).20 Finally, 25 publications were
included in the qualitative analysis.
Data Extraction
Two authors independently reviewed all
abstracts to identify articles that required
full-text review. Investigated abstracts
against predefined eligible criteria and all
included studies were discussed with a
third author. The following information
was obtained: first author’s name, coun-
try, publication year, number of patients,
clinical manifestations, type of endoscope,
histology, surgical treatment, complica-
tion rate, and outcomes (including median
overall survival, median progression-free
survival, hazard ratios, and 95% confi-
dence intervals, when available). Gathered
data were stored in a centralized database
(Microsoft Excel).
Data Analysis
Descriptive analysis of data was made us-
ing mean, median, percentages, and
maximum and minimum values. Contin-
uous variables were represented by mean
and range values, except in cases other-
wise specified. Correlation analysis be-
tween variables was obtained by means of
calculating the Spearman and Kendall
coefficient for non-Gaussian distributed
variables. Data were analyzed and pro-
cessed with SPSS version 24.0.1.1(14)
(IBM, Armonk, NY) and Microsoft Excel.
Statistical significance was considered for
P-value <0.05. Cohen’s D coefficient was
eventually calculated to investigate the
sample’s size effect. These results were
interpreted according to the expanded test
interpretation suggested by Sawilowski.21
The statistical analysis was performed by
2 independent reviewers (A.L. and N.P.F.).
RESULTS
Descriptive Statistics
After screening 198 articles retrieved from
databases, a total of 25 studies were
included in the present examination. Data
retrieved from 368 patients presenting a
mean age of 20.6 years (median 14 years,
range 1e86 years). The majority (57.8%) of
the patients were male, with only 3 patients
presenting with a bifocal lesion (pineal and
pituitary). Frequently represented neuro-
logic manifestations included headache

AUGUSTO LEONE ET AL.
Figure 1. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol
used for the present review.
(59.5% of the patients), diplopia (25.8%),
and blurred vision (10.6%). Of the total,
72.4% of the procedures were performed
through a rigid endoscope, 14.7% with a
flexible instrument, and only 12.9% with
either a combination of the 2 or otherwise
not specified in the article. When available,
information regarding postoperative com-
plications following concomitant ETV and
TB was collected, revealing that 55 patients
suffered from postoperative hemorrhage,
memory loss, diabetes insipidus and other
endocrine disorders, and meningitis.
However, the most represented complica-
tions were the persistence of hydrocephalus
(n ¼ 14), followed by alteration of the
consciousness (n ¼ 5) and metastatic
dissemination along the ETV tract (n ¼ 4).
In 3 cases, postoperative deficits were
WORLD NEUROSURGERY 173: 5-11, MAY 2023
COMBINED ETV AND TB FOR PINEAL LESIONS
permanent. At least 2 patients died as a
consequence of those complications
(intratumoral hemorrhage).
Concomitant ETV þ TB allowed a
conclusive histologic diagnosis in 88.7%
of the examined cases. Ten percent of the
biopsies were inconclusive and 1.3%
delivered an inaccurate diagnosis, as
proved by the following examination of
samples obtained during open surgery.
The most common diagnosis was repre-
sented by germinoma (20.1%) followed by
astrocytoma (12.9%) and pineocytoma
(9.9%). A total of 11.8% of the patients
underwent a second surgery for ven-
triculoperitoneal shunt (VPS) implantation
for persistent hydrocephalus at a mean
time of 12.6 months after the first
procedure.
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LITERATURE REVIEW
Inferential Statistics
Various parameters were investigated for
possible correlations with the “need for a
VPS”, intended as a failure of the ETV in
treating non-communicating hydrocephalus
(see Table 2). Sex and type of endoscope
were revealed not to be statistically
correlated with the failure of the technique
(P ¼ 0.769 and 0.196, respectively).
However, the median age of the patient
needing implantation of a VPS was 11
years, whereas patients who did not
require such intervention were generally
older (mean age 20.9 years). These
parameters suggested a strong correlation
(P ¼ 0.029, rs ¼ e0.204, sk ¼ e0.203).
Moreover, statistical analysis showed
Cohen’s D ¼ 1.484, which, according to
the expanded test interpretation suggested
by Sawilowski,21 is to be considered a “very
large” effect size, thus suggesting a
meaningful practical significance.
Clinical manifestations at presentation
were also investigated for possible correla-
tion with the ETV failure. Although diverse
parameters showed compelling differences
between the 2 cohorts, (e.g., “papilledema”:
36.4% of the patients in the VPS group, 23.2%
in the not-VPS group; “headache”: 81.8%
VPS, 59.6% not-VPS), only the symptom
“hemiparesis” demonstrated to be signifi-
cantly correlated with the eventual need for
VPS implantation. A total of 18.2% of the
enrolled patients who underwent a VPS sur-
gery suffered from the abovementioned
neurologic deficit, versus 2% of those who
did not need this measure (P ¼ 0.014, with
rs ¼ 0.264 and sk ¼ 0.264). In this case,
Cohen’s D was 0.181, suggesting a “small”
effect size, thus limiting the possible prac-
tical application of this correlation.
Finally, a possible correlation between
the final histologic diagnosis and failure in
obtaining a secure diagnosis with the
single-entry approach was investigated.
However, no statistical significance was
found (P ¼ 0.082).
Description of the Technique
Although surgical procedures varied slightly
among the reviewed studies, the most
commonly adopted approach consisted of a
single burr hole located on the midpupillary
line midway between the 2 generally used
entry points for simple ETV and endoscopic
biopsy of pineal lesions (i.e., coronal and
frontal-precoronal entry, respectively).8,37
Some authors sacrificed the massa
7
 LITERATURE REVIEW
AUGUSTO LEONE ET AL. COMBINED ETV AND TB FOR PINEAL LESIONS

Table 2. Overview of Patients’ Characteristics in Relation to the Type of Endoscope Used

Follow-
Patient Number of Biopsy Positivity Type of up,
Number Study Year Age, years Patients Rate Sex Endoscope months

1 Ellenbogen et al.22 1997 19 1 100% (1/1) M flexible 12

17
2 Ferrer et al. 1997 28.3 3 100% (3/3) 1M-2F flexible NA
3 Robinson et al.18 1997 15.7 3 100% (3/3) 2M-1F rigid NA
23
4 Gaab et al. 1998 46 1 100% (1/1) M rigid 34
24
5 Gangemi et al. 2001 36 5 100% (5/5) 3M-2F flexible 13,5
6 Pople et al.12 2001 33.7 17 100% (17/17) 11 M - 6 F NA 46,5
7 Haw et al.25 2001 14 1 100% (1/1) M rigid 29
8 Wong et al.26 2003 18 1 100% (1/1) M NA NA
9 Yamini et al.7 2004 8.5 6 66.7% (4/6) NA NA 30,5
27
10 O’Brien et al. 2006 37 42 76% (25/33), 9 NA 21 M - 21 F flexible 32
11 Endo et al.28 2007 31 1 100% (1/1) M flexible
12 Choi et al.29 2007 13 1 100% (1/1) F NA NA
13 Al-Tamimi et al.30 2008 9.9 8 62.5% (5/8) NA flexible NA
14 Ahn31 2010 11.3 20 65% (13/20) 16 M - 4 F flexible and rigid 156
8
15 Wong et al. 2011 13.5 21 95.2% (20/21) NA rigid 64
16 Morgenstern et al.11 2011 39.8 8 87.5% (7/8) 3M-5F rigid NA
17 Zhu et al.32 2012 24.4 8 100% (8/8) 7M-1F rigid 33
33
18 Ahmed et al. 2015 26 48 84.8% (39/46), 2 NA 32 M - 16 F rigid NA
19 Roth et al.16 2015 58 1 100% (1/1) F rigid NA
34
20 Abbassy et al. 2018 10.7 11 81.8% (9/11) 10 M - 1 F rigid 19
21 Samadian et al.15 2019 32 64 97% (62/64) 31 M - 33 F rigid NA
22 Attri et al.35 2020 28.7 34 78.8% (26/33), 1 NA 22 M - 12 F rigid 15,8
13
23 Liu et al. 2021 10.5 34 100% (34/34) 32 M - 2 F rigid 11,2
24 Schulz et al.1 2021 12.4 28 95.8% (23/24) 15 M - 13 F rigid 49
36
25 Cartmill et al. 2000 9 1 0% (0/1) F NA NA

intermedia to gain optimal direct
visualization of the pineal region during TB,
especially in small tumors, which was
usually performed after creating an opening
in the floor of the third ventricle.13 In
general, following the completion of ETV,
the rigid endoscope (30 lenses) was usually
rotated to gain a posterior direction of view
and obtain a variable number of tissue
samples depending on the tumor’s
radiologic and intraoperative appearance.
However, in cases where a rigid endoscope
(0 or 30 lenses) with the adjunct of a
flexible endoscope was utilized, the latter
was used to perform the biopsy while the
former was used to conduct anatomic
inspection of the pineal region and perform
ETV, therefore avoiding sacrificing
interposed structures.16 In most cases, CSF
collection was performed for biochemical
and cytologic examination during initial
ventricular cannulation and local bleeds
during the procedures were controlled
using irrigation and monopolar
cauterization.
DISCUSSION
Rationale for a Single-entry Approach
The heterogeneity of neurologic manifes-
tations and available treatment options for
the management of pineal tumors inevi-
tably reflect the neurosurgical conundrum
that these lesions represent.38 When
manifesting in children and adolescents,
pineal tumors are frequently associated
with cerebral aqueduct occlusion,
resulting in non-communicating hydro-
cephalus.8 In such cases, emergency CSF
diversion is often necessary.13 Therefore,
it is not seldom that these patients will
undergo 2 separate surgical procedures
with ETV or VPS implantation followed
by a second open transcranial or
endoscopic surgery to obtain pathologic
tissue samples or attempt tumor
resection, consequently exposing the
patient to multiple deferred operations.10
Additionally, it should be noted that the
choice between aggressive microsurgical

8 www.SCIENCEDIRECT.com WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2023.01.082


AUGUSTO LEONE ET AL.
cytoreductive surgery and minimally
invasive endoscopic sampling followed by
adjuvant therapy is determined mostly by
demographic, clinical, and radiologic
characteristics, which contribute to
predicting tumor type and therefore best
suitable management options. By way of
example, early radiation therapy in the
case of solitary pineal germinomas and
pineoblastomas alone or in combination
with chemotherapy leads to significant
improvement in overall survival,
progression-free survival, and lowers the
risk of recurrence without the need for
open surgery.24,39,40 In such cases, the
need for a rapid pathologic confirmation
is crucial and the ability to obtain tissue
samples during the management of
intracranial hypertension in patients
presenting to clinical observation with
non-communicating hydrocephalus
should be considered in order to signifi-
cantly reduce the time between admission
and diagnosis and to spare such usually
young patients a second invasive diag-
nostic procedure.
Comparison with Open Surgery
As a result of novel technological advance-
ments in the field of neuroendoscopy, con-
current ETV and tissue sampling for a pineal
region lesion are achievable with the use of
either a rigid endoscope providing a superior
quality of vision and a wider workspace or a
flexible instrument, avoiding excessive
stretching of interposed anatomic structures
including the interthalamic adhesion.16,24
When compared with transcranial open
biopsy, the endoscopic procedure presents
considerable advantages for both the
surgeon and the patient: firstly, the ability
to obtain multiple tissue specimens under
direct white-light visualization avoiding
damage to the surrounding structures,17
and, secondly, the reduction of the overall
risk of iatrogenic hemorrhages and
intraoperative complications secondary to a
transhemispheric access to this region,
lowering morbidity.11,22 On the other hand,
as previously described in case reports and
series, the main drawback associated with
endoscopic tissue sampling is the higher
rate of inconclusive diagnosis, despite no
direct correlation between surgical
approach and pathologic accuracy having
been proved, with higher rates of
inaccurate diagnosis being related with
WORLD NEUROSURGERY 173: 5-11, MAY 2023
COMBINED ETV AND TB FOR PINEAL LESIONS
tumor type rather than bioptic
technique.17,18
Complications of the Procedure
Although rarely encountered by experi-
enced endoscopic surgeons, major intra-
operative complications during
endoscopic pineal region biopsy may
include venous bleeding, intraventricular
hemorrhage (IVH), and iatrogenic
contusion of the fornix, with the latter
generally associated with rigid endoscope
adjustment, especially in patients pre-
senting a narrow foramen of Monro.13,15
On the other hand, more common
postoperative complications found in
the reviewed literature consisted of
transient neurologic deficits secondary
to IVH, non-infectious fever, intra-
tumoral hemorrhage, seizure, diabetes
insipidus, and meningitis. Nonetheless,
as shown in the Results section, no fatal
consequence has been reported during
endoscopic procedures, with only 1 case
of permanent memory impairment.14
Despite representing the most common
intraoperative complication, IVH should
only be considered a complication when
the procedure is interrupted. For
instance, irrigation and cauterization
may successfully control the bleeding.14
Conversely, whenever a severe IVH
occurs, before opting for conversion to
transcranial microsurgery, a range of
alternative procedures should be
considered, including a small cotton
pad,41 a combined irrigation-coagulation
suction cannula (the Nagasaka multi-
functional suction cannula; Fujita Medi-
cal Instruments, Tokyo, Japan),42 a
transparent sheath and a 10-cm-long
tube made of clear acrylic plastic,43 or the
adoption of the dry field technique.44
This technique, used by Oertel et al.45 in
their institution, has yielded
encouraging results for the management
of IVH during neuroendoscopic
procedures. For instance, during such
disastrous events, the suction of all the
CSF contained in the ventricular system
clears the vision of the surgical field and
favors clot formation through gravity
and air support.
Concerning whether ETV should pre-
cede tumor biopsy in the setting of a
single-entry approach procedure, several
authors suggest the management of hy-
drocephalus through ventriculostomy
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LITERATURE REVIEW
should be prioritized. However, the
increased risk of spreading tumor cells
through the cranial and spinal arachnoid
space should be considered, although this
possibility still represents a source of
debate.16 Moreover, the preference for
ventriculostomy as a standard first step
may also be supported by the increased
risk of tumor bleeding after the biopsy,
which could result in a technically
challenging ETV due to possible visual
obscuration. In conclusion, whenever
critical intracranial pressure is present,
obstructive hydrocephalus must be
managed first.
Limitations of the Study
Provided that the reported quantitative
analysis of clinical, radiologic, and path-
ologic factors has a potential role in
management plan individualization, the
results of this study are not devoid of
limitations.
Firstly, only patients undergoing
concomitant ETV and lesion biopsy
through a single entry endoscopic trajec-
tory were included for analysis, excluding
all patients receiving the same procedure
via a dual entry through a double burr
hole. This may constitute a selection bias
since the choice between the 2 approaches
is mostly driven by anatomic characteris-
tics of the third ventricle as well as tumor
dimension, dimensions of interthalamic
adhesion, and surgical goal, as previously
mentioned by Morgenstern et al.11
Therefore, considering uniquely “single
entry patients” may limit the
generalizability of the results regarding
the outcome and intraoperative surgical
complications given that such a
population may present with intrinsically
less aggressive lesions.
In addition, notwithstanding the in-
depth analysis and data extraction from
investigated publications that were oper-
ated, in some cases, it was not possible to
assess patient-specific values since these
were not reported in the original articles.
Therefore, the total number of values
included in the statistical examination
depended on the given analyzed parameter
(i.e., all patients were included for pa-
rameters such as age and sex evaluation
since these features were accessible in all
included publications, but not all articles
described the clinical manifestation at
presentation and were therefore excluded
9

AUGUSTO LEONE ET AL.
from the analysis of such parameter). The
maximum number of included patients
was 368 when assessing demographic pa-
rameters and type of endoscope (see
Table 2), 86 when assessing clinical
presentation at admission, 309 when
assessing the diagnostic rate of
endoscopic TB, 334 when assessing
pathological histotype of the tumor, and
22 when assessing the panel of serologic
and CSF markers in relation to a
confirmed diagnosis.
The absence of a patient-specific char-
acterization of anatomic elements,
including ventricular size, massa inter-
media dimension, and the relationship
between tumor and interthalamic adhe-
sion in the examined reports, did not
allow the inclusion of such valuable data
in the present analysis despite represent-
ing an essential factor when planning for
an endoscopic pineal region biopsy. The
selection of patients for this approach
should rely on individual features recog-
nized on head magnetic resonance imag-
ing and should only be complemented
with the data described in the present
article.
Lastly, the retrospective nature of the
study itself risks undermining the statis-
tical results obtained. Nonetheless, the
systematic nature of this review and the
different institutions and operators from
which the collected information was ob-
tained grant a reliable real-world, diverse,
generalizable set of data.
CONCLUSIONS
In the present study, a collection and
analysis of the published literature con-
cerning the single-entry approach for ETV
and TB are provided. A quantitative ex-
amination of multiple variables obtained
from clinical, surgical, and pathologic in-
formation suggests that this approach can
be safely considered in patients presenting
with pineal region tumors causing non-
communicating hydrocephalus. Nonethe-
less, further research regarding the ability
to predict low- and high-risk profiles for
such surgical techniques is foreseen.
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 www.surgicalneurologyint.com

Surgical Neurology International

Editor-in-Chief: Nancy E. Epstein, MD, Clinical Professor of Neurological Surgery, School of
Medicine, State U. of NY at Stony Brook.
SNI: Pediatric Neurosurgery Editor
 Frank Van Calenbergh, MD
 University Hospitals; Leuven, Belgium
Open Access

Review Article

Endoscopic third ventriculostomy versus

ventriculoperitoneal shunt insertion for the management
of pediatric hydrocephalus in African centers – A
systematic review and meta-analysis
Damilola Alexander Jesuyajolu1 , Abdulahi Zubair1, Armstrong Kpachi Nicholas2, Terngu Moti1, Osamagie Ehi Osarobomwen1,
Israel Anyahaebizi1, Charles Okeke1 , Samuel Olawale Davis1
Departments of 1Neurosurgery and 2Research, Surgery Interest Group of Africa, Abijo, Lagos, Nigeria.

E-mail: *Damilola Alexander Jesuyajolu - djesuyajolu@gmail.com; Abdulahi Zubair - zubairsantos@gmail.com;

Armstrong Kpachi Nicholas - armstrongnicho@gmail.com; Terngu Moti - motiterngu@gmail.com; Osamagie Ehi Osarobomwen - osaroosamagie@gmail.com;
Israel Anyahaebizi - tujay2in1@gmail.com; Charles Okeke - okekecharles66@yahoo.com; Samuel Olawale Davis - davissamuelola@gmail.com

*Corresponding author:
Damilola Alexander Jesuyajolu
Department of Neurosurgery,
Surgery Interest Group of
Africa, Abijo, Lagos, Nigeria.
djesuyajolu@gmail.com
Received : 17 August 2022
Accepted : 23 September 2022
Published : 14 October 2022
ABSTRACT
Background: Ventriculoperitoneal shunt (VPS) insertion and endoscopic third ventriculostomy (ETV) are
common surgical procedures used to treat pediatric hydrocephalus. There have been numerous studies comparing
ETV and VPS, but none from an African perspective. In this study, we sought to compare outcomes from African
neurosurgical centers and review the associated complications.
Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses were used in conducting
this study. PubMed, Google Scholar, and African Journal Online were searched. Data on treatment successes and
failures for ETV and VPS were pooled together and analyzed with a binary meta-analysis. A clinically successful
outcome was defined as no significant event or complication occurring after surgery and during follow-up (e.g.,
infection, failure, CSF leak, malfunction, and mortality). Seven studies fully satisfied the eligibility criteria and
were used in this review.
Results: There was no statistically significant difference between the outcomes of ETV and VPS (OR- 0.27; 95%
CI −0.39–0.94, P = 0.42). After reviewing the rates of complications of ETV and VPS from the identified studies,
four were recurrent. The infection rates of ETV versus VPS were 0.02% versus 0.1%. The mortality rates were
0.01% versus 0.05%. The reoperation rates were 0.05% versus 0.3%, while the rates of ETV failure and shunt
malfunction were 0.2% versus 0.2%.

DOI Conclusion: This study concludes that there is no significant difference between the outcomes of ETV and VPS
10.25259/SNI_747_2022 insertion.

Quick Response Code: Keywords: Endoscopy, Infection, Malfunction, Ventriculostomy

INTRODUCTION
There are not many neurosurgeons in Africa; it has the second highest neurosurgical workforce
deficit reported globally.[8] A recent estimate put the ratio of neurosurgeons in Africa to the

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to remix, transform, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.
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Surgical Neurology International • 2022 • 13(467) | 1

 Jesuyajolu, et al.: Endoscopic third ventriculostomy versus ventriculoperitoneal shunt insertion
population at one neurosurgeon to 4,000,000 people. This
means that neurosurgical services are unavailable to a large
number of people.[24] In addition, the innovations seen in
neurosurgery and the neurosciences are not commensurate
with the current practices in the developing world, especially in
Africa.[24] A lack of health-care funding, lack of neurosurgical
equipment, poor health-care planning, lack of resources, lack
of encouragement to establish local neurosurgery training,
and a lack of adequate local conditions or facilities to enable
neurosurgeons to practice properly are some of the factors
responsible for the paucity of neurosurgeons and neurosurgery
access in Africa.[9,16,18] This situation is worse with pediatric
neurosurgery as there are fewer than 15 fellowship-trained
pediatric neurosurgeons in Africa.[2]
Hydrocephalus is an enlargement of the ventricles
resulting from the inadequate passage or absorption of
cerebrospinal fluid (CSF).[17] The prevalence of infantile
hydrocephalus varies between one and 32/10,000 births.
Today, the population of African children that are <15 years is
>535.1 million, and there are about 100,000–200,000 new cases
of pediatric hydrocephalus each year in sub-Saharan Africa.[26]
Hydrocephalus can be classified in different ways: acquired
versus congenital, syndromic versus nonsyndromic,[19]
and communicating versus noncommunicating.[6] When
hydrocephalus occurs without an obvious extrinsic cause, it
is referred to as congenital. When it occurs as a complication
of another condition such as hemorrhage, infection, or
neoplasm, it is acquired or secondary.[22]
Ventriculoperitoneal shunt (VPS) insertion and endoscopic
third ventriculostomy (ETV) are common surgical
procedures used to treat pediatric hydrocephalus. In
emergency cases, however, external ventricular drainage can
be used as a lifesaving procedure while a definitive treatment
plan is arranged.[27] ETV involves the creation of a new CSF
pathway. This permits the third ventricle to communicate
with the CSF spaces surrounding the brain stem. It avoids
the risk of hardware infection, colonization, and malfunction
associated with shunts, especially useful in low-resource
settings.[25] ETV and choroid plexus cauterization (CPC), per
Benjamin Warf ’s reports, has been shown to have promising
results in Africa. As a result, this procedure has gained eager
attention and cautious support in the developed world.[7,13,25]
There have been numerous studies comparing ETV and
VPS, but none from an African perspective. In this study,
we sought to compare outcomes from African neurosurgical
centers and review the associated complications.
MATERIALS AND METHODS
The Preferred Reporting Items for Systematic Reviews and
Meta-Analyses (PRISMA guidelines) were used in conducting
this study. A guide that included the review question, search
strategy, eligibility criteria, and risk of bias assessment was
Surgical Neurology International • 2022 • 13(467) | 2
established before the commencement of this review. Papers
that compared ETV with VPS in the management of pediatric
hydrocephalus in African surgical centers were included
in this study. Studies that were not in the English language,
from non-African countries and studies that did not compare
ETV with VPS systems were excluded from the study.
Reviews, meta-analyses, abstracts, conference presentations,
commentaries, case reports, and letters to the editors were
excluded from the study. Studies that reported data on ETV or
VPS alone were excluded from the study. Studies that failed to
report disaggregated data on ETV and VPS were also excluded
from the study. To identify all eligible articles, a search was
conducted from inception to August 2022. PubMed, Google
Scholar, and African Journal Online were searched. During
the screening process, the references of similar review articles
were manually searched for studies that may have been missed
by our initial search. The search strategy was jointly devised
by the authors and is summarized in Table A1 in Appendix A.
The final search results were exported into Rayyan.ai where
duplicates were detected and removed after scrutiny.
To ensure consistency, two authors screened each article
twice. Where conflicts existed, they were resolved by the
third author. The search was broad and it aimed to identify
all papers with information on ETV and VPS. The titles and
abstracts were screened first, followed by a full-text screening.
We extracted the following data: the author, publication
year, country, study design, study arms, age, gender, cause
of the hydrocephalus, period of follow-up, CSF leak,
infection, mortality, reoperation, shunt malfunction, failure
of ETV, and successful outcomes. For this meta-analysis, a
clinically successful outcome was defined as no significant
event or complication occurring after surgery and during
follow-up (e.g., infection, failure, CSF leak, malfunction,
and mortality). Failure was defined as the occurrence of
a postoperative significant event (e.g., infection, failure,
CSF leak, malfunction, shunt erosion, and mortality). The
primary outcome was defined as the success or failure of
the procedure. Raw data on clinically successful outcomes
for ETV and VPS were pooled together and analyzed with a
binary meta-analysis. All studies were first analyzed together,
and then, all observational studies (6/7) were analyzed
together. Subgroup analysis based on the risk of bias was also
carried out. Tests of heterogeneity were also carried out with
the Egger’s test and a funnel plot. The meta-analysis feature
of IBM SPSS versus 28.0.1 was used. The analysis was carried
out with inverse variance, and a random effects meta-analysis
was used to account for the heterogeneity of studies. The level
of significance was set at 0.05 with a 95% confidence interval.
RESULTS
Seven hundred and fifty papers were excluded after the
titles and abstracts were screened, and 16 more studies
 Jesuyajolu, et al.: Endoscopic third ventriculostomy versus ventriculoperitoneal shunt insertion

were excluded after reading and assessing the full texts.
Nine studies were excluded because they did not report
the outcome of interest, two studies were excluded because
they did not report disaggregated data on ETV and VPS,
one study was excluded because the study was conducted
in a non-African country, while four studies were excluded
because the focus of their paper was on ETV alone. Seven
articles fully satisfied the eligibility criteria and were used in
this review and meta-analysis.[1,5,10-12,14,23] The PRISMA chart
is shown in Figure 1. The characteristics of the identified
studies are presented in Table 1. The list of excluded studies is
reported in the supplementary information.
The observational studies used in this review were evaluated
with the Newcastle Ottawa Scale evaluation to determine
the risk of bias. The studies are shown in Table 1. Four of
the studies scored 8, two scored 7, and one study scored 6.

Figure 1: Prisma flow chart

Table 1: Summary of studies.

Studies Country Nature of study Type of study Study arms Male (%) NOS score
Adebayo et al., 2021 [1]
Nigeria Prospective Cohort ETV‑CPC/VPS 60 7
Uche et al., 2017[23] Nigeria Prospective Cohort ETV/VPS 67 8
El‑Ghandour, 2011[10] Egypt Prospective Cohort ETV/VPS ND 8
Kulkarni et al., 2017[12] Uganda Prospective RCT ETV‑CPC/VPS 61 Low risk
Cairo et al., 2018[5] DRC Retrospective Cohort ETV‑CPC/VPS 48 6
Idowu et al., 2009[11] Nigeria Retrospective Cohort ETV/VPS 59 8
Laeke et al., 2017[14] Ethiopia Retrospective Cohort ETV/VPS 59 8
CPC: Choroid plexus cauterization, ETV: Endoscopic third ventriculostomy, VPS: Ventriculoperitoneal shunt insertion

Surgical Neurology International • 2022 • 13(467) | 3

 Jesuyajolu, et al.: Endoscopic third ventriculostomy versus ventriculoperitoneal shunt insertion

Five studies were of high quality while one study had a high
risk. There was one RCT among the selected studies. For that
study, we used the Cochrane tool. There was no statistically
significant difference between the outcomes of ETV and VPS
(OR- 0.27; 95% CI −0.39–0.94) P = 0.42) after analysis of the
seven studies. As there were six observational studies and
one RCT, we decided to exclude the RCT from the second
analysis and see if there would be any substantial difference.
After analysis, there was still no statistically significant
difference (OR- 0.47; 95% CI −0.25–1.19) P = 0.20); the forest
plot can be seen in the appendix as Figure A1 in Appendix A.
We went further to do a subgroup analysis by including
only high-quality observational studies (scores of 7–9 on
the NOS scale – low risk of bias studies), and still, there was
still no significant difference (OR−0.47; 95% CI −0.29 −1.24,
P = 0.23). The forest plot can be seen in the appendix as
Figure A2 in Appendix A. The initial I2 was 49%, indicating
moderate heterogeneity and the Q-statistic was 11.0, P = 0.088.
After the RCT was removed, however, the I2 was 41% while
the Q-statistic was 7.9, P = 0.159 indicating some degree of
homogeneity; the funnel plot of the observational studies
alone is shown in Figure A3 in Appendix A. Using only the
observational studies, we went ahead to test for bias using the
Egger’s test. The Egger’s test for a regression intercept gave
P = 0.852, indicating no evidence of possible bias. The data
showing the summary of clinically successful outcomes for
ETV versus VPS are summarized in Table 2. After reviewing
the rates of complications of ETV and VPS from the identified
studies, four were recurrent. The infection rates of ETV versus
VPS were 0.02% versus 0.1%. The mortality rates were 0.01%
versus 0.05%. The reoperation rates were 0.05% versus 0.3%,
while the rates of ETV failure and shunt malfunction were
0.2% versus 0.2%. The summary data of the complication and
their rates are shown in Tables 3 and 4. The forest plot of the
seven studies is shown in Figure 2.
DISCUSSION
Our study included 580 African children who had procedures
done in African centers. In this study, we sought to compare
the successful outcomes between ETV and VPS insertion
in the management of pediatric hydrocephalus. Although
this subject has been widely published in the literature, we
intended to compare these two from an African perspective
while paying attention to the findings and experiences from
neurosurgical centers across the continent. Interestingly, we
found no statistically significant difference in the outcomes.
Studies conducted in some African centers also found no
significant difference in outcomes between ETV–CPC and
ventriculoperitoneal shunting.[12] The rates of complications,
when pooled together, were also very low. The rates of CSF
leaks, infections, mortality, and failure/malfunction were all
below 1%. This is a very important finding and it has clinical

Table 2: Summary of clinically successful outcomes versus complications.

Studies Sample size Clinically ETV with Clinically successful VPS with
ETV/VPS successful ETVs complications VPS insertions complications
Adebayo et al., 2021[1] 23/22 14 9 13 9
Uche et al., 2017[23] 25/30 20 5 18 15
El‑Ghandour, 2011[10] 32/21 29 3 13 8
Kulkarni et al., 2017 [12] 51/49 33 18 37 12
Cairo et al., 2018[5] 3/113 3 0 91 22
Idowu et al., 2009[11] 29/36 25 4 31 5
Laeke et al., 2017[14] 24/77 10 14 38 39
ETV: Endoscopic third ventriculostomy, VPS: Ventriculoperitoneal shunt insertion

Table 3: Summary of complications and complication rates for ETV.

Studies
Adebayo et al., 2021 [1]
Uche et al., 2017[23]
El‑Ghandour, 2011[10]
Kulkarni et al., 2017[12]
Cairo et al., 2018[5]
Idowu et al., 2009[11]
Laeke et al., 2017[14]
ETV: Endoscopic third ventriculostomy
Sample size ETV Infection (ETV) Mortality (ETV) Reoperation (ETV) Failure (ETV)
23 0 0 ND 0
25 1 1 1 ND
32 0 0 2 2
51 2 1 ND 18
3 0 0 0 0
29 1 0 1 0
24 ND 0 ND 14

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 Jesuyajolu, et al.: Endoscopic third ventriculostomy versus ventriculoperitoneal shunt insertion

Table 4: Summary of complications and complication rates for VPS.

Studies Sample size VPS Infection VPS Mortality VPS Reoperation VPS Malfunction VPS
Adebayo et al., 2021 [1]
22 4 0 ND 5
Uche et al., 2017[23] 30 4 2 6 5
El‑Ghandour, 2011 [10] 21 2 1 8 8
Kulkarni et al., 2017[12] 49 2 1 ND 12
Cairo et al., 2018[5] 113 6 11 0 8
Idowu et al., 2009[11] 36 1 2 0 0
Laeke et al., 2017[14] 77 18 0 39 21
Total 348 37/348 (0.1%) 17/348 (0.05%) 53/200 (0.3%) 59/348 (0.2%)
VPS: Ventriculoperitoneal shunt insertion

Figure 2: Forest plot of studies.

implications when deciding on the right surgical modality
of management for a patient with pediatric hydrocephalus.
VPS devices are expensive for families in LMICs, and this
is one of the factors that have allowed for the development
and widespread use of the Chhabra shunt, which is
manufactured in India; the shunt device costs 90 USD.[7] The
malfunctioning of this shunt poses a great risk, especially in
the developing countries, where rapid emergency systems are
often deficient. This complication is responsible for a large
percentage of hydrocephalus-related deaths.[4,21] ETV is now
gaining popularity in the developing countries because of
the ability to leave the patient shunt-free and free of shunt-
related complications.
In our study, the failure rates were consistently lower with ETV
than they were with VPS. This finding is consistent with other
studies in the published literature.[3,10,15,20] This is likely due to
the nature of the procedure itself. While VPS involves the use
of a foreign body, which is prone to infection and blockage,
ETV does not. ETV has become more preferred to VPS
because of the lack of a need for foreign body insertion. The
failure rates of ETV and shunts have been reported to be very
high in low-resource settings and unwanted postoperative
surgical events have been said to occur more frequently
in LMICs than in high-income countries.[14] This study,
however, shows that the overall incidence of complications
is low and similar to what has been reported in developed
countries. In low-income countries, a VPS is often used as
the first choice for managing pediatric hydrocephalus,[14]
however, this poses a major challenge as a shunt malfunction
can quickly become a neurosurgical emergency and many of
these African countries have neither the infrastructure nor
workforce to ensure that these cases are managed swiftly.
Considering the similarity in outcomes between VPS and
ETV, where indicated, it may be beneficial to use ETV as the
first choice in managing pediatric hydrocephalus.
The amount of existing research on this subject is exhaustive
and many systematic reviews and meta-analyses have
provided evidence on this topic. This study, however, is the
first to look exclusively at the African literature, to generate
evidence that may guide local practices. Regardless, more
studies may need to be done on a geographic basis to
generate locally relevant guidelines and practices that will
improve patient care. Despite the comprehensive nature of
this study, we had some limitations. The small sample size
and the few African studies covered in this review make
generalization difficult. Because we included articles only in

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 Jesuyajolu, et al.: Endoscopic third ventriculostomy versus ventriculoperitoneal shunt insertion
the English language and searched three databases, we may
have missed potentially relevant papers from nonanglophone
countries. The heterogeneity of the studies in terms of how
the complications were defined makes it hard to generalize
the complications across the board.
CONCLUSION
This study concludes that there is no significant difference
between the outcomes of ETV and VP shunt insertion.
Considering the findings of this study, it would depend on
other factors such as cost, accessibility, the skill, experience,
and preference of the operating neurosurgeon when
determining a surgical modality for the management of
pediatric hydrocephalus. This paper contributes immensely
to the African pediatric neurosurgical front and adds
more evidence to local practices when managing pediatric
hydrocephalus.
Data availability
Data are available on reasonable request.
Ethical approval
Ethical approval was not needed for this paper.
Acknowledgments
We would like to acknowledge the Care for All foundation
for which D.J won a research grant award (CFA 3262-22).
Declaration of patient consent
Patient’s consent not required as there are no patients in this
study.
Financial support and sponsorship
Care for All Foundation Research Grant (CFA 3262-22).
Conflicts of interest
There are no conflicts of interest.
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Article
Received 04/05/2022
Review began 04/08/2022
Review ended 04/13/2022
Published 05/19/2022
© Copyright 2022
Lane et al. This is an open access article
distributed under the terms of the Creative
Commons Attribution License CC-BY 4.0.,
which permits unrestricted use, distribution,
and reproduction in any medium, provided
the original author and source are credited.
How to cite this article
Lane J, Akbari S A (May 19, 2022) Failure of Endoscopic Third Ventriculostomy. Cureus 14(5): e25136. DOI 10.7759/cureus.25136
DOI: 10.7759/cureus.25136
Failure of Endoscopic Third Ventriculostomy
Jessica Lane 1 , Syed Hassan A. Akbari 1
1. Department of Neurosurgery, Penn State Health Milton S. Hershey Medical Center, Hershey, USA
Corresponding author: Jessica Lane, jlane1@pennstatehealth.psu.edu
Abstract
Endoscopic third ventriculostomy (ETV) is an alternative to cerebrospinal fluid (CSF) shunting in the
treatment of hydrocephalus. Careful patient selection is critical as patient age, etiology of hydrocephalus,
and previous shunting have been shown to influence ETV success rates. Intraoperatively, patient anatomy
and medical stability may prevent or limit the completion of the ventriculostomy procedure, and findings
such as a patulous third ventricular floor or cisternal scarring may portend a lower chance of successful
hydrocephalus treatment. Patients in whom a ventriculostomy is completed may still experience continued
symptoms of hydrocephalus or CSF leak, representing an early ETV failure. In other patients, the ETV may
prove a durable treatment of hydrocephalus for several months or even years before recurrence of
hydrocephalus symptoms. The failure pattern for ETV is different than that of shunting, with a higher early
failure rate but improved long-term failure-free survival rates. The risk factors for failure, along with the
presentation and management of failure, deserve review.
Categories: Pediatrics, Neurosurgery
Keywords: adult hydrocephalus, hydrocephalus management, late etv failure, treatment failure, intraoperative
complications, pediatric hydrocephalus, endoscopic third ventriculostomy
Introduction And Background
Endoscopic third ventriculostomy (ETV) can be an effective and appealing treatment for hydrocephalus;
however, the procedure is not always successful. Varied success rates based on patient age, etiology of
hydrocephalus, and prior shunting highlight the importance of patient selection for ETV [1,2]. A number of
anatomic factors may also affect ETV success rates, including third ventricular size and shape, thickness and
position of the third ventricular floor, cisternal scarring and pulsation of the ventriculostomy edges with
cardiac cycle [3-5]. Operative complications that preclude the completion of the procedure may also lead to
an ETV failure, and these procedures are often converted to ventricular shunting within the same operation.
Perioperative failures occur in the same hospitalization as the procedure, often due to inadequate treatment
of the hydrocephalus or technical issues from the procedure. Late failures occur once the patient has been
discharged, sometimes after a period of months or years of clinical stability, and are generally due to closure
of the stoma or cisternal scarring. This review summarizes the etiology, presentation and treatment of ETV
failure based on timing of failure. Our aim is to summarize literature on the topic and provide a framework
for considering ETV failure for clinicians treating hydrocephalus.
Review
Intraoperative failure
Patient anatomy, medical instability, and operative complications may all contribute to the inability to
successfully complete an ETV. Patient selection is vital in maximizing the probability of a successful ETV. A
review of imaging can identify challenging anatomy preoperatively, allowing for an adjusted surgical plan or
the decision that a patient is not a good candidate for ETV. Thin cut sagittal MRI will demonstrate the shape
and position of the third ventricular floor and the underlying basilar artery. Basilar artery malformation is a
contraindication to the procedure. The presence of a short prepontine interval may make the procedure
more challenging, but with careful planning, a successful ETV may still be possible [6]. Preoperative
displacement or bowing of the third ventricular floor is a positive predictor of ETV success, with
postoperative imaging often showing a reduction in displacement [5,7]. An especially thickened or patulous
third ventricular floor may prove challenging operatively [8]. The size of the lateral and third ventricles, as
well as the intervening foramen of Monro, will affect the ease of the procedure. Slit ventricles or
stenotic/obstructed foramen of Monro will make endovascular navigation challenging and the chance of
intraoperative injury more likely. Patients with myelomeningocele often have ventricular abnormalities,
which can negatively impact the surgeon’s orientation and ability to perform the third ventriculostomy. A
review of 455 patients with hydrocephalus secondary to myelomeningocele found third ventricular
abnormalities in 41% of patients, with the most common being prominent massa intermedia, narrow tuber
cinereum, thickened or steep or vascular third ventricular floor, and interhypothalamic or mamillary
adhesions [9]. Patients with a history of hemorrhage or severe infection may also have distorted anatomy
that should be well studied with imaging before attempting an ETV.
While a close review of patient demographics and imaging preoperatively helps to select appropriate
 patients for ETV, endoscopic visualization may reveal an inhospitable corridor for ventriculostomy. In this
situation, the lamina terminalis may be inspected as an alternate point of fenestration if the endoscopic
trajectory and view allow. The visualization itself may be the limiting factor due to debris within the
cerebrospinal fluid, such as from tumor, infection, or hemorrhage, and cause the procedure to be aborted.
The surgeon may successfully create an opening in the floor of the third ventricle, only to struggle to
appropriately enlarge this due to thickening or scarring. She may also create a satisfactory ostomy only to
discover scarring or adhesions within the membrane of Lillequist that are unable to be lysed. Rates of
intraoperative failure can vary with the etiology of hydrocephalus, availability of preoperative imaging, and
experience of the surgical team. In a comparison of ETV in Uganda compared to pooled data from Canada,
Israel, and the UK, there was a 29% rate of intraoperative failure in the Ugandan cohort versus 2% in the
comparison cohort [10]. The authors note that the median Endoscopic Third Ventriculostomy Success Score
(ETVSS) was substantially lower in the Ugandan cohort and that the lack of preoperative MRI leads to
attempted ETV in patients with unfavorable anatomy who might not have been offered the procedure in
other settings. A single-center series of children and young adults in the United States noted a procedure
abandonment rate of 26%, with prior shunting leading to a greater likelihood of abandonment [8]. A large
meta-analysis including both adult and pediatric patients found an overall rate of procedure abandonment at
4.2% [11].

While performing the ETV, it may be possible to injure one of the smaller vessels in and around the
ventricular system. This may cloud the view and render an endoscopic approach impossible. Usually,
bleeding from these smaller vessels may be stopped with the use of gentle irrigation or tamponade from an
instrument or the endoscope itself. The more catastrophic possibility of a basilar artery injury will usually
result in the aborting of an ETV and the need for possible interventional procedures [12]. Basilar artery
rupture is rare and reported in 0.2% of ETVs, but rates of all intraoperative bleeding range from 0%-8.5%,
with less than 1% of ETV procedures being abandoned due to hemorrhage [13].

Cardiorespiratory concerns from the anesthesia team are, as with all surgery, a possible reason to abort a
planned procedure. In ETV specifically, bradycardia can be seen with the creation and enlargement of the
ventriculostomy or with the need to enlarge the ventricles with irrigation to allow for endoscopic navigation.
While this will often resolve with a pause in manipulation, continued bradycardia needs to be addressed.
Rates of bradycardia related to ventriculostomy have been cited between 6%-27%, and there are reported
asystolic events [14,15]. Symptoms of increased intracranial pressure, including bradycardia, can also be
seen when irrigation used for the procedure is not allowed to drain from the ventricles, which may be
addressed with open endoscope ports, aspiration of fluid through the working channels of the endoscope, or
withdrawal of the endoscope allowing fluid to drain through the sheath [16]. Unfortunately, herniation has
been reported in instances where irrigation was passed through an inadvertently closed endoscope system
[8,17].

When the decision is made to abort the procedure, a number of options remain. A ventricular shunt may be
placed within the same procedure. For this reason, many surgeons will position patients undergoing an ETV
as they would a ventriculoperitoneal shunt insertion in the event a shunt needs to be placed during the
operation. Alternatively, if the surgeon believes the ETV may yet be successful at a later date, an external
ventricular drain (EVD) or tapping reservoir may be left in place to temporize the patient until an ETV may
be reattempted. An EVD has the added benefit of being able to monitor intracranial pressures in the
perioperative phase. Some surgeons advocate leaving the drain clamped to monitor pressure, allowing for a
higher than normal threshold for opening the drain, with the hope that the added pressure might keep the
ostomy patent [18,19].

Perioperative failure
Failure of an ETV after its creation can occur because the ETV does not adequately treat the hydrocephalus
or because the new stoma ceases to function. In cases where the failure becomes evident immediately after
surgery, without a period of improvement, likely, the ETV was not sufficient to treat the hydrocephalus
during the index procedure [20]. CSF absorption may be poor, in which case patients would be expected to
present soon after ETV with continued signs and symptoms of elevated intracranial pressure while imaging
and repeat endoscopy would reveal an open stoma and flow of CSF [21]. Alternatively, the ETV may not
function due to membranes or adhesions beneath the floor of the third ventricle, which were missed and left
intact during the initial surgery [21]. Scarring of the prepontine cistern has been shown in multiple cohorts
to be a negative prognostic factor for ETV success [4,22,23].

The presentation of ETV failure in these situations will often reflect the signs and symptoms of initial
presentation, for example, a bulging fontanelle or Parinaud’s phenomenon in neonates. The continued
elevation of intracranial pressure in the setting of a new tract to the subgaleal surface may also cause a
cerebrospinal fluid leak through the incision should an ETV fail despite adequate technical closure.
Additionally, in those patients in whom a ventricular drainage catheter has been left in place, high output or
elevated intracranial pressure (ICP) readings may indicate failure. It is worth noting that many authors have
noted a period of adaptation a few days after ventriculostomy, during which intracranial pressures may be
transiently elevated [18,24]. This is often managed with some permissive hypertension in the absence of
symptomatology, as the additional pressure may theoretically help keep the ETV patent, or intermittent CSF

2022 Lane et al. Cureus 14(5): e25136. DOI 10.7759/cureus.25136 2 of 7

 removal for a few days before declaring ETV failure [19,25]. Should a drain need to be opened, it may be
prudent to attempt a delayed clamp trial before declaring true ETV failure and proceeding with shunt
placement.

In cases of perioperative ETV failure, imaging should be performed to rule out an operative complication, for
example, intraventricular hemorrhage obstructing the stoma [26]. Reduction in ventriculomegaly is not
always obvious in early postoperative imaging and should not be seen as requisite for a functional ETV [27].
While the appearance of a flow void on MRI and use of cine phase-contrast MRI is somewhat correlated with
ETV success, this is mostly studied at a later stage of follow-up, and the absence of these imaging findings
in the immediate postoperative setting is not diagnostic for ETV failure [16,27-29]. Repeat ventriculostomy
may be performed if there is concern for unfenestrated membranes, inadequately sized ventriculostomy, or
other treatable pathology. Alternately, a shunt may be placed. ETV failure or aborted ETV procedures have
not been shown to increase the risk of failure or infection in subsequently placed shunts [30].

Late ETV failure

Predicting the failure of an ETV after the acute operative/perioperative period has been subject to significant
study in the literature. Patient selection factors may influence the risk of ETV failure weeks to years after
surgery. Age appears to be a strong predictor of ETV success, with infants less than six months old having
the highest risk of failure, in some cases up to a five-fold increase in risk compared to older patients [1,31-
33]. It has been suggested that the milieu of growth factors in the CSF predisposes young infants to the
closure of the ventriculostomy [16,34]. Additionally, young infants are thought to have a lower capacity for
CSF absorption secondary to immature arachnoid granulations, which require a higher pressure gradient for
absorption [33,35]. The importance of the functional absorption of CSF from the subarachnoid space also
explains why etiology affects ETV success. Hydrocephalus caused by hemorrhage or infection, both of which
can cause dysfunction of the subarachnoid space, are less likely to be successfully treated with ETV
compared to hydrocephalus caused by aqueductal stenosis or tectal tumors. Similarly, patients with previous
shunting, which is thought to decrease absorptive capability, are more prone to ETV failure [16]. These risk
factors for failure may be related, as the etiologies for hydrocephalus differ in older and younger children,
and rates of previous shunting may be related to etiology. These three risk factors have been combined into
an Endoscopic Third Ventriculostomy Success Score (ETVSS, Table 1), which was designed to predict ETV
success at six months postoperatively, but has since been validated in multiple settings and for longer-term
outcomes [1,2,36-39]. In the ETVSS, the score represented the predicted percentage of successful cases. For
instance, a three-month-old child with postinfectious hydrocephalus and no previous shunt would have an
ETVSS of 20 and a 20% predicted success rate, compared to a 12-year-old with a tectal tumor and no
previous shunt with a predicted success rate of 90%.

Score = Age + Etiology + Previous shunt

0 <1 month Postinfectious Previous shunt

10 1 month to <6 months No previous shunt

20 Myelomeningocele, intraventricular hemorrhage, non-tectal brain tumor

30 6 months to 1 year Aqueductal stenosis, tectal tumor, other

40 1 year to <10 years

50 10 years or older

TABLE 1: ETV Success Score

The ETV Success Score, as described in Kulkarni et al., uses patient age, hydrocephalus etiology, and history of shunting to predict the likelihood of
successful ETV.

ETV Success Score, from Kulkarni et al. [1]

For excellent ETV candidates with ETVSS of 80 or above, the risk of ETV failure appears to be lower than the
risk of shunt failure from the beginning, becoming even more favorable with time. In patients with ETVSS 70
or below, the initial risk of ETV failure exceeds that of shunt failure in comparable patients but becomes
lower than shunt failure risk by 3-6 months postoperatively [40].

Even in the well-selected patient, ETVs may fail due to technical issues from the initial surgery. For example,
a smaller ETV may be more likely to scar, as is an ostomy that was created using monopolar cautery [41,42].
The charred edges of an ETV performed in this manner are more likely to cause scarring and ETV failure.
ETVs that are particularly bloody may undergo the same issues, as the blood clot can either plug the ostomy

2022 Lane et al. Cureus 14(5): e25136. DOI 10.7759/cureus.25136 3 of 7

 or promote inflammatory reactions that will promote scar formation [28,43]. Debris from tumors may also
cause closure of the ETV [26,44]. Stenting of the ventriculostomy has been reported in cases where the risk
of restenosis was felt to be high due to tumor or redundant tissue from the third ventricular floor (Figure 1)
[45,46].

FIGURE 1: Patulous floor of third ventricle with tumor infiltration.

An endoscopic image of a patulous third ventricular floor in the authors' patient undergoing ETV with a glial tumor.

Usually, if a patient initially tolerates an ETV and fails in a delayed fashion, this is due to the reclosure of the
stoma. The stoma itself may close or stenosis due to scarring or gliosis, causing the floor of the third
ventricle to appear intact either by ventriculoscopy or imaging. There can be a second membrane beneath
the floor of the third ventricle or redundancy of the membrane of Lilliquist that blocks the flow of CSF from
the third ventricle to the prepontine cistern, despite an open stoma. Arachnoid webbing may also develop
within the cistern, blocking absorption [20,21,47,48]. Evidence of stoma closure may be apparent on MRI
imaging, especially with flow-sensitive modalities [26-28,47]. In a mixed-age cohort, 14 symptomatic
patients underwent cine phase-contrast MRI before endoscopic re-exploration; the stoma obstruction was
confirmed in all 10 patients with no flow on MRI, and patency was confirmed in the remaining four with the
flow on their imaging [28]. In another series of 67 pediatric patients, surveillance cine phase-contrast MRI
identified stoma obstruction in five asymptomatic patients greater than a year after ETV and after multiple
earlier images demonstrated flow through the stoma [49]. However, there are series where the detection of
flow was not well associated with clinical outcomes, such as an American series of 89 patients where 23% of
patients with good clinical outcomes from ETV had no imaging evidence of flow through the stoma while
there was the appearance of flow in 58% of the clinical failures [3].

As these mechanisms of stoma closure require time, the expected clinical course would be a period of
improvement after the initial ETV followed by late presenting symptoms of ICP elevation [21]. When a
ventriculostomy fails due to closure of the stoma, a repeat ventriculostomy may be attempted. Success rates
for reopening a closed ETV vary greatly, 37%-78% in published series [20,47,48,50,51]. A long time from
initial surgery to failure is associated with the increased success of the repeat operation, with an interval
greater than six months associated with 90% success in one series [20]. Lack of subarachnoid adhesions is
associated with higher rates of success, but the effect of patient age at surgery is conflicting in the literature

2022 Lane et al. Cureus 14(5): e25136. DOI 10.7759/cureus.25136 4 of 7

 [20,50,51].

One of the benefits of ETV over shunting, especially in regions where resources are limited, is that the long-
term failure rate is low compared to shunts, despite a higher rate of failure in the early postoperative period.
In a propensity score-adjusted analysis, Kulkarni and colleagues demonstrate that while the early risk of
failure is at least 20% greater in ETV compared to shunting, after three months this relative risk decreases
steadily, and the risk of ETV failure at two years is half the risk of shunt failure [52]. While rare, very late
failure after ETV has been reported after years of clinical stability, and in some of these cases, the clinical
deterioration is rapid with very poor outcomes [53]. Patients should be counseled about this possibility and
the importance of urgent medical treatment in the setting of failure symptoms.

Conclusions
ETV can be a safe and effective treatment for hydrocephalus in well-selected patients. Nevertheless, several
risk factors make the procedure more difficult to successfully complete and more likely to fail over time.
While generally, the risk of ETV failure is the greatest in the perioperative and early postoperative period,
there are also cases of failure after years of clinical stability. Surgeons should assess a patient’s preoperative
risk factors based on history and imaging before attempting an ETV and should also use these and
intraoperative risk factors in planning follow-up and possible repeat procedures.

Additional Information
Disclosures
Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the
following: Payment/services info: All authors have declared that no financial support was received from
any organization for the submitted work. Financial relationships: All authors have declared that they have
no financial relationships at present or within the previous three years with any organizations that might
have an interest in the submitted work. Other relationships: All authors have declared that there are no
other relationships or activities that could appear to have influenced the submitted work.

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 Open Access Review
Article DOI: 10.7759/cureus.25317

The Outcome of Surgical Intervention

(Ventriculoperitoneal Shunt and Endoscopic
Review began 05/19/2022
Third Ventriculostomy) in Patients With
Review ended 05/23/2022
Published 05/25/2022 Hydrocephalus Secondary to Tuberculous
© Copyright 2022
Chalasani et al. This is an open access
Meningitis: A Systematic Review
article distributed under the terms of the
Roopa Chalasani 1 , Mastiyage R. Goonathilake 2 , Sara Waqar 1 , Sheeba George 1 , Wilford Jean-Baptiste 1 ,
Creative Commons Attribution License CC-
BY 4.0., which permits unrestricted use,
Amina Yusuf Ali 3 , Bithaiah Inyang 1 , Feeba Sam Koshy 1 , Kitty George 1 , Prakar Poudel 4, 1 , Lubna
distribution, and reproduction in any Mohammed 5
medium, provided the original author and
source are credited.
1. Research, California Institute of Behavioral Neurosciences and Psychology, Fairfield, USA 2. Pediatrics/Internal
Medicine, California Institute of Behavioral Neurosciences and Psychology, Fairfield, USA 3. Pediatrics, California
Institute of Behavioral Neurosciences and Psychology, Fairfield, USA 4. Internal Medicine, Chitwan Medical College of
Medical Science, Chitwan, NPL 5. Internal Medicine, California Institute of Behavioral Neurosciences and Psychology,
Fairfield, USA

Corresponding author: Roopa Chalasani, roopa.chalasani617@gmail.com

Abstract
The objective of this study is to analyze the outcome of the safety and efficiency of the surgical
interventions (ventriculoperitoneal shunt [VPS] and endoscopic third ventriculostomy [ETV]) in patients
with hydrocephalus due to tuberculous (TB) meningitis. A systematic literature search has been conducted
using PubMed, Google Scholar, PMC, and ScienceDirect databases from 2001 to 2022 April. A total of 16
studies have been included, irrespective of their design. These studies include patients diagnosed with
hydrocephalus secondary to TB meningitis (TBM) treated with VPS or ETV. A systematic review was
conducted to determine the efficiency of surgical procedures based on the outcomes and complications
associated with these procedures. A total of 2207 patients (aged one month to 68 years) have been included
in this study, out of which 1723 underwent VPS and 484 underwent ETV. The overall success rate in the VPS
group varied from 21.1% to 77.5%. The overall success rate in the ETV group ranged from 41.1% to 77%. The
overall complications rate in the VPS group varied from 10% to 43.8%, and the complications rate in the ETV
group varied from 3.8% to 22.5%. After ruling out the significant differences in the average percentages of
outcomes and complications followed by VPS and ETV, ETV is suggested in patients with chronic phases of
illness because the chances of ETV failure are high during the initial stage. The uncertainty of the ETV
gradually decreases over time. To attain favourable long-term outcomes with ETV in patients with TBM
hydrocephalus (TBMH), ETV should be performed after chemotherapy, anti-tubercular treatment, and
steroids. In addition, ETV is considered beneficial over VP shunt as associated long-term complications are
significantly less compared to VP shunt. In contrast, VP shunt is suggested as a modified Vellore grading
which shows a more favourable outcome in patients with acute illness than ETV.

Categories: Neurosurgery
Keywords: tuberculous meningitis, tb meningitis, hydrocephalus, ventriculoperitoneal shunt, endoscopic third
ventriculostomy

Introduction And Background

Tuberculous meningitis (TBM) is a bacterial infection of the central nervous system involving the meninges
of the brain and spinal cord. Mycobacterium tuberculosis is the causative organism of TBM. Hydrocephalus
is the most common complication of TB meningitis, affecting children more than adults [1]. It is almost
always present in patients who have had the disease for four to six weeks and occurs at an early stage of the
disease process [1]. The hydrocephalus in patients with tuberculous meningitis could be either the
communicating type or the obstructing type, the former being the more common [2]. The developmental
issue of the obstructive type of hydrocephalus in tuberculous meningitis is either due to blockage of the
fourth ventricle by thick exudates or leptomeningeal scarring [3]. The early stage of this communicating type
of hydrocephalus causes thick gelatinous exudates to block the subarachnoid spaces in the base of the brain
(more significant in the interpeduncular and ambient cistern). The later stage of the communicating type of
hydrocephalus causes the exudates, which leads to dense scarring of the subarachnoid spaces.
Communicating hydrocephalus may also result from an overproduction of CSF or secondary to reduced
absorption of CSF. Communicating hydrocephalus is seen more recurrently in patients with TBM [3].
According to body weight, the medical management of TBM hydrocephalus (TBMH; communicating type)
includes ATT (standard four-drug antitubercular therapy consisting of rifampicin, ethambutol, isoniazid,
and pyrazinamide), along with steroids (dexamethasone given if CT showed thick basal exudates and there
was evidence of infarcts) [2], and dehydrating agents acetazolamide, furosemide, and mannitol [1]. The
surgical management of TBMH includes endoscopic third ventriculostomy (ETV) and ventricular shunting

How to cite this article

Chalasani R, Goonathilake M R, Waqar S, et al. (May 25, 2022) The Outcome of Surgical Intervention (Ventriculoperitoneal Shunt and Endoscopic
Third Ventriculostomy) in Patients With Hydrocephalus Secondary to Tuberculous Meningitis: A Systematic Review. Cureus 14(5): e25317. DOI
10.7759/cureus.25317
 (VA, VP, VPL, LP), most commonly ventriculoperitoneal (VP) shunting, which has been the procedure of
choice so far [4]. Attempts to relieve pressure symptoms in infants with enlarged heads and adults with
papilloedema and high lumbar cerebrospinal fluid (CSF) include cerebellar decompression, lateral and third
ventriculostomy, and short-circuits between the ventricular system and subarachnoid space of the cerebral
hemispheres [5]. However, the best plan to relieve the communicating hydrocephalus is to persist with
intrathecal and systemic streptomycin [5]. High cerebrospinal fluid protein levels delay shunting.

Nevertheless, ventriculoperitoneal shunt (VPS) surgery complications in patients with TBMH are high, with
frequent shunt obstructions and shunt infections requiring repeated revisions [4]. Therefore, the clinical
grading system determines the patient's treatment strategy [3]. The most commonly used system is the
Vellore grading of TBMH (Table 1), proposed by Palur et al. [6]. Alongside, Table 2 briefly discusses modified
Vellore grading of patients with TBMH.

Grade Neurological status

Grade 1 Headache, vomiting, fever ± neck stiffness. No neurological deficit. Normal sensorium.

Grade 2 Neurological deficit present, normal sensorium.

Grade 3 Altered sensorium but easily arousable. Dense neurological deficit may or may not be present.

Grade 4 Deeply comatose, decerebrate or decorticate posturing.

TABLE 1: Vellore grading of tuberculous meningitis hydrocephalus patients.

Grade Neurological status GCS SCORE

Grade 1 Headache, vomiting, fever. No neurological deficit 15

Grade 2 Neurological deficit present 15

Grade 3 Neurological deficit may or may not be present 9-14

Grade 4 Neurological deficit may or may not be present 3-8

TABLE 2: Modified Vellore grading of TBMH.

TBMH: tuberculous meningitis hydrocephalus [7].

Review
Methodology
The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines 2020 were
followed in this systematic review [8], and the population, intervention, comparison, and outcome (PICO)
format was included in this study pattern.

The eligibility criteria of the studies in our survey can be found in Table 3.

2022 Chalasani et al. Cureus 14(5): e25317. DOI 10.7759/cureus.25317 2 of 14

 Inclusion criteria Exclusion criteria

Articles published in the English language with DOI number. Non-English publications.

Study age - 2001 January to 2022 April. Study age - before 2001 studies.

Study population - human infants, children, adolescents, and

Study population - animal study.
adults.

Eligible study - patients suffering from TBMH and those who Ineligible study - patients with alternative diagnosis to tubercular
underwent either VPS/ETV. meningitis, i.e., cryptococcal meningitis, pyogenic meningitis.

Study type - cohort studies (prospective and retrospective) Study type - literature reviews, case reports, case series, editorials,
randomised control trials, systematic reviews. incomplete peer reviews.

TABLE 3: The eligibility criteria of the studies included and excluded in our survey.
VPS: ventriculoperitoneal shunt, ETV: endoscopic third ventriculostomy.

Information sources, search strategy and data extraction process

A systematic literature search has been conducted using PubMed, Google Scholar, PMC, and ScienceDirect
databases using the relevant keywords and MeSH strategy mentioned below (Table 4). A total of 16 studies
have been included irrespective of their design and having been diagnosed with tuberculous meningitis and
treated with VPS surgery or endoscopic third ventriculostomy (ETV). Two researchers worked independently
to identify and extract the data. Quality assessment of each study is conducted using appropriate quality
appraisal tools (NOS - Newcastle Ottawa Assessment Scale for Prospective and Retrospective Cohort Studies
and Critical appraisal guide for Systematic Reviews (randomised studies) from April 21 to 30, 2022. After
removing all the duplicates manually and via Endnote, the author's inclusion and exclusion criteria were
used to evaluate the study. All the irrelevant studies have been omitted. The third author resolved the
differences of opinion between the first two authors. After a complete analysis, 16 articles have finally been
considered in this review.

The purpose of the study is to contemplate the outcome, safety, efficiency of surgeries (VPS and ETV), and
complications of patients who underwent either ventriculoperitoneal shunt or endoscopic third
ventriculostomy. The efficiency of procedures is based on the resolution of signs and symptoms and also on
Vellore grading of patients with TBMH.

The search strategy of different databases using relevant keywords and MeSH strategy is summarised in
Table 4.

2022 Chalasani et al. Cureus 14(5): e25317. DOI 10.7759/cureus.25317 3 of 14

 Databases Keywords MeSH strategy Filters applied

Humans, English,
Endoscopic third ventriculostomy OR ("Ventriculostomy/therapeutic use"
Endoscopic third child: birth-18 years,
[Majr] OR "Ventriculostomy/therapy"[Majr]) AND Ventriculoperitoneal shunt
ventriculostomy, child: 6-12 years,
OR ("Ventriculoperitoneal Shunt/statistics and numerical data"[Majr] OR
ventriculoperitoneal adolescent: 13-18
"Ventriculoperitoneal Shunt/therapeutic use"[Majr] AND
shunt, years, adult: 19+
PubMed ("Hydrocephalus/surgery"[Majr] OR "Hydrocephalus/therapy"[Majr]) AND TB
hydrocephalus, TB years, young adult:
meningitis OR ("Tuberculosis, Meningeal/cerebrospinal fluid"[Majr] OR
meningitis, 19-24 years, middle
"Tuberculosis, Meningeal/complications"[Majr] OR "Tuberculosis,
tuberculous aged: 45-64 years,
Meningeal/drug therapy"[Majr] OR "Tuberculosis, Meningeal/surgery"[Majr]
meningitis Study age - 2001
OR "Tuberculosis, Meningeal/therapy"[Majr])
Jan- 2022 April

Endoscopic third
ventriculostomy,
Google ventriculoperitoneal "Ventriculoperitoneal shunt" OR "endoscopic third ventriculostomy" AND
NONE
Scholar shunt, “tubercular meningitis" AND “hydrocephalus."
hydrocephalus, TB
meningitis

"Ventriculoperitoneal shunt" OR "endoscopic third ventriculostomy" AND

PMC Not used NONE
"TB meningitis" AND "hydrocephalus."

Endoscopic third
ventriculostomy,
Research articles,
ventriculoperitoneal "Ventriculoperitoneal shunt" OR "endoscopic third ventriculostomy" AND
ScienceDirect open access and
shunt, "TB meningitis" AND "hydrocephalus."
open archive
hydrocephalus, TB
meningitis

TABLE 4: Search strategy of different databases.

Results
Quality Assessment

Quality assessments of the reviews have been performed based on the guidelines mentioned below. In
addition, articles that met at least 70% of the criteria have been included.

We followed the guidelines of the Newcastle Ottawa Assessment Scale for prospective and retrospective
cohort studies: (1) Was the exposure and outcome of interest clearly explained? (2) Exposed people? (3) Non-
exposed people? (4) The outcome of interest not present at the start of the study (5) Were the people similar?
(6) Were the exposure and outcomes measured the same way? (7) Was the follow-up done correctly? (8) Was
the follow-up long enough and sufficient enough? (9) Was this study published in an indexed journal?
Outcome-based on: YES or NO.

The critical appraisals for systematic review are as follows: (1) Aim of the research; (2) Keyword explanation;
(3) MeSH strategy; (4) Did the authors describe all the databases they used to collect the data? (5) Inclusion
and exclusion criteria; (6) Did the authors check the quality (critical appraisal) of each study they included in
the article? How did they critically appraise it? (7) Is the article published in a reliable database? (8) Were
multiple authors involved in data extraction and quality appraisal? (9) Cochrane risk of bias assessment tool.
Outcome-based on: YES, PARTIAL YES, NO.

Risk of Bias

The risk of bias in the considered studies has been briefed in Table 5.

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 Study Detection bias, outcome Attrition bias, outcome Reporting bias, complications

Lampre-ht et al. [9] + + +

Husain et al. [10] + + +

Singh et al. [11] ? + ?

Jha et al. [12] + + ?

Figaji et al. [13] + + +

Sil and Chatterjee [14] + + +

Srikantha et al. [15] ? + ?

Chugh et al. [16] + + ?

Yadav et al. [17] + + +

Peng et al. [18] + + +

Savardekar et al. [19] + + +

Goyal et al. [20] + ? +

Kankane et al. [21] + + +

Rizvi et al. [22] + + +

Aranha et al. [4] + + +

Bhushan et al. [3] ? ? +

TABLE 5: Risk of bias.

+ = low risk bias, ? = not mentioned.

A summary of study selection using PRISMA flow diagram can be found in Figure 1.

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 FIGURE 1: PRISMA flow diagram.

Studies of patients with TBMH who underwent either VPS or ETV can be found in Table 6.

Year of
S.no Study Procedure (VPS/ETV) Patient details Outcome Complication Comment
publication

Total cases with TBMH – 65. The outcome in

Age – 4 to 131
shunted TBMH- Good-10(15.4%), moderate
months. VPS has a higher incidence
disability –26(40%), severe disability –
Communicating of complications in patients
15(23.1%) vegetative – 6(9.2%) dead – 8
-27 (41.5%), Shunted patients -32.3%. Shunt with TBMH rather than in
(12.3%). The outcome in the type of
non- infection – 9 (13.5%), shunt patients with non-tuberculous
Lamprecht hydrocephalus – good outcome and mortality
1 2001 VPS communicating obstruction – 9 (13.5%), over hydrocephalus shunt surgery.
et al. [9] in communicating type – 1 (3.7%) and 5
-38 (58.5%). shunting – 2 (3.1%). Wound However, they have indicated
(18.5%). Good outcomes and mortality in non-
Grade 2 – disruption -1 (1.5%). early VP shunt in patients
communicating type – 9 (23.7%) and 3 (7.9%).
29(44.6%), with non-communicating
The outcome in patients with GCS. 3-5 at the
Grade 3 – 36 hydrocephalus.
presentation (n=12) Good outcome – 0 Dead
(55.4%).
– 3 (25%).

Complication rate: 10%. CSF

Suggestion-ETV should be
leak: 2 cases responded to
regarded as the first surgical
ETV alone – 19, ETV intermittent lumbar drainage and
Age – 5 option in TBMH as the
+monroplasty – 2, ETV + The total number of TBMH cases – 28. oral acetazolamide (20–25 mg/kg
months – 68 outcome was satisfactory
Husain et septoplasty – 2, ETV with Outcome – Success rate – 68% (19/28), per day in divided doses for 2–3
2 2005 years. 15 (50%). Based on the clinical

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 al. [10] decompression/biopsy of acceptable – 18% (5/28), satisfactory – 50% weeks). Perioperative bleed: 1
males and 13 grade, ventriculoperitoneal
tuberculoma – 2, ETV with (14/28), unsatisfactory – 32% (9/28). case-controlled endoscopically
females. shunt surgery and EVD
abscess drainage-1. followed by EVD for five days,
should be reserved for
and the patient showed complete
patients with ETV failure.
recovery over two weeks.

They have suggested ETV

The total number of TBMH patients – 35. The
as an alternative way of
6 months – 32 overall success rate of ETV was 77%. Early
managing hydrocephalus and
years. Grade I recovery – 60% of patients. Delayed recovery
is worth trying before
– 6 patients, – 17% of patients. In a clinical recovery – the
Singh et al. subjecting the patients to VP
3 2005 ETV grade II – 7 outcome of success rate in patients with a thin
[11] shunt as they have observed
patients, grade transparent floor of the third ventricle is 87%,
fine results in patients with
III – 22 whereas it was 74% in patients with a thick or
both obstructed and
patients. granular floor. There was no significant
communicating
statistical difference.
hydrocephalus.

The presence of advanced

Age – 9 grade clinical grade, extra

months to 40 The total number of patients with TBMH -14. CNS TB, dense adhesions in
Jha et al.
4 2007 ETV years. 11 male Outcome – The success rate of patients who the prepontine cistern, and
[12]
and 3 female underwent ETV – 64.2% (9/14) cases. unidentifiable third ventricle

patients. floor anatomy leads to the

failure of ETV.

Complication rate -11.7% CSF

leak was present in 2 cases (In

one patient, the CSF leak led to

the later development of bacterial

The total number of patients with TBMH – 17.
Success rate: 41.1% (7/17). Failure rate:
29.4% (5/17). Five patients could not undergo
endoscopic third ventriculostomy due to
Figaji et al. ETV/fenestrations/endoscopic Age –
5 2007 abnormal anatomy. There were five
[13] biopsy <12years
fenestration procedures, three of which were
successful. Endoscopic biopsy of two
tuberculomas failed to yield a bacteriological
result.
meningitis, which was
Although ETV is technically
successfully treated). In one
possible in this situation, the
patient, brisk venous bleeding
patients must be adequately
was found. This was controlled
selected for the procedure to
with irrigation, but visibility was
ensure optimal treatment and
significantly obscured, and the
that the surgeon has
ETV could not be continued
experience with complex
safely. After five days, the
cases.
endoscopic procedure was

repeated. Visibility had by then

improved, ETV was performed,

and the hydrocephalus was

successfully treated.

They recommended that the

Total number of patients with TBMH – 32.
VP shunt will remain as the
Good outcome: 8 (25%) children, moderate
Age – 1 month only armamentarium in the
disability (cognition and ocular motility
Sil and to 12 years. Shunt infection: 5 (15.6%). Shunt arsenal of the neurosurgeon
disorders): 15 (46.9%) children, severe
6 Chatterjee 2008 VPS Grade II: 22 revisions due to blockade: 14 for treating this disease even
disability: 5 (15.6%) children, vegetative state:
et al. [14] (62.5%), Grade (43.8%) patients. if it gets replaced by a third
1 (3.2%) and death: 3 (9.3%) children. Patients
III: 12 (37.5%). ventriculostomy in the
in Palur grade II had comparatively better
treatment of other forms of
outcomes in each grade.
hydrocephalus.

The first management choice

for grade 4 patients with

hydrocephalus is VP shunt

implantation, ATT and

The total number of cases with TBMH – 95. steroids. VP shunt should be

Patients with the favourable short-term considered even in patients

outcome: 33% of cases (age older than three who do not show

years and duration of altered sensorium ≤3 improvement with an EVD.

days, GCS score > or equal to 12 at the time NOTE – Presence or

EVD ± VPS direct shunt -52
Srikantha Age – 1-55 of discharge were predictive of favourable absence of infarcts or basal
7 2009 patients. EVD followed by
et al. [15] years short-term outcome). Patients with the exudates, duration of
shunt – 43 patients.
favourable long-term outcome: 45% cases symptoms and GCS score at

(Glasgow Coma Scale score at presentation presentation did not correlate

was predictive of long-term outcome. GCS with short-term outcome.

scores of 7 or 8 at presentation had a Age, duration of symptoms or

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 favourable follow-up GOS score (4 or 5). altered sensorium, and

presence or absence of

infarcts or basal exudates did

not correlate with long-term

outcomes.

The total number of cases with TBMH – 26.

The overall success rate was 73.1%. The

Suggestion-ETV should be
outcome of ETV was observed to have a
Age – 7 considered the first surgical
Chugh et statistically significant correlation with the
8 2009 ETV months to 52 option for cerebrospinal fluid
al. [16] stage of illness and the presence of
years diversion in patients with TBM
intraoperative cisternal exudates. A better
with hydrocephalus.
outcome for ETV was observed in patients on

ATT for an extended period preoperatively.

ETV was safe and effective in

TBM hydrocephalus.

Significant causes of failure

to improve-complex

hydrocephalus and

associated cerebral infarcts.

Good results were observed

Total patients with blocked stoma
The total number of cases with in better grades. Results of
– 3 (5.1%) CSF leak = 6 patients
TBMH(Obstructive) – 59 cases. The overall ETV were better in patients
Yadav et Age - 6 months (10.1%) Total patients with
9 2011 ETV success rate, after ETV alone, was 58% (34 without cisternal exudates,
al. [17] – 76 years associated malnutrition- 31 (53%)
patients). After ETV plus lumboperitoneal good nutritional status, and
Total patients with complex
shunt: 80% (47 patients). thin and identifiable floor of
hydrocephalus – 13 (22%)
the third ventricle compared

to cases with cisternal

exudates, malnourished,

thick unidentifiable floor,

respectively, although the

difference was statistically

insignificant.

Shunt related complications –

Comment based on study
6/19 (31.57%), revisions required
demonstration - direct VP
following shunt block – 3/19
shunt placement could
(15.8%). Patients with
improve the outcome in
complications secondary to
Peng et al. 1 month – 14 Grade IV TBMH. The
10 2012 VPS ± EDV infections – 2/19 (10.5%)
[18] years response to EVD is not a
[including erosion of skin (n=1),
dependent indication for
pneumonia (n=2)] subdural
selecting the patients who
effusion and ventricular
would benefit from shunt
haemorrhage – 1/19 patients
surgery.
(5.3%).

Age – 4 Their viewpoint was that

Overall, 26 cases of TBMH. After 3 months: In Complication rate: 23.5% (6/26).
months – 11 direct VP shunt placement is
TBMH Grade III Good outcome: 71.4% Shunt blockage/malfunction – 2
Savardekar years. TBMH a riskless and successful
11 2013 VPS (15/21), mortality: 9.5% (2/21). In TBMH Grade patients, shunt infection – 2
et al. [19] Grade III: 21, option in poor-grade patients
IV good outcome: 20% (1/5). Overall good patients, intraventricular
TBMH Grade of TBMH, with a low
outcome: 61.5%, mortality: 60% (3/5). haemorrhage – 2 patients.
IV: 5. complication rate.

The total number of patients with TBMH is 48. Repositioning of shunt – 16.7%

The overall success rate in patients who (4 cases). The average

underwent VPS – 13(54.2%), mortality – 2 complication rate in the ETV

(One patient – Vellore grade 4, GCS – 6 and group is 16.75%. In the ETV

another patient – Vellore grade 3 died in the group, CSF leak was noted in The relative uncertainty of

postoperative period due to associated miliary seven cases (29.1%). Two ETV failure is higher than

tuberculosis. The overall success rate in patients developed meningitis that for shunt, but the

patients who underwent ETV – 41.7% (10 (8.33%), out of which one patient uncertainty becomes

cases). In ten cases (41.7%), a VP shunt was eventually died. Three patients progressively further down
Goyal et al. VPS and ETV each in 24 Age – <18
12 2014 done in the post-operative period for ETV had a bulge (12.5%) at the ETV with time. Therefore, if
[20] cases. years
failure. Two patients were lost in the follow-up site. Shunt-related complications patients pull through the early

period. Mortality – 2 cases. The first patient occurred in four (17%) patients high-risk period, they could

(Vellore grade 3) expired due to an associated and consisted of an obstruction at experience long-term survival

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 poor chest condition. In contrast, another the lower end of the shunt in advantages devoid of lifelong

patient was discharged in satisfactory three (13%) cases, leading to shunt-related complications.

condition, later reported to us for CSF leak revision, and one (4%) patient

and died due to fulminant meningitis. ETV had an infection at the shunt

failure was more in the young age group (<2 chamber site, leading to skin

years). excoriation and meningitis.

They suggested the direct

placement of the VP shunt in

Total number of cases with TBMH – 50, with
Age – 3 Grade 3 and 4 cases with
Kankane et grade 3 and 4. In grade 3 – outcome – 77.5%,
13 2016 VPS months-14 The complication rate was 10% TBMH without intervening in
al. [21] mortality – 0%. In grade 4-outcome – 30%,
years EVD, and the result was
mortality – 10%. Overall outcome – 68%.
good, with a low complication

rate.

The total number of cases with TBHM-1038.

Overall – 48.4% Good outcome (GOS 5 and

4), following ventriculoperitoneal shunt, was The outcome, following VPS,

observed in 58.26% of patients, 78.57% of depends on the clinical

patients in grade 1, 65.35% in grade 2 and severity of TBM. HIV-infected

Complications following VPS
67.9% in grade 3 achieved a good outcome patients have a worse
were 22.11% shunt blockage,
Imran Rizvi while only 31.51% in grade 4 could achieve a prognosis when compared
14 2017 VPS leading to shunting revision,
et al. [22] good outcome. On subgroup analysis, 61.08% with HIV uninfected patients.
which was the most common
of HIV-negative patients achieved a good Compared to children,
complication.
outcome as compared to only 25% of HIV- corresponding data is sparse

positive patients. There were 18.03% deaths in for adult patients with

the HIV-negative group as compared to tuberculous meningitis.

66.67% deaths in the HIV-positive group after

shunt surgery.

They found comparable ETV

results in communicating

hydrocephalus and

obstructive hydrocephalus. In

addition, they suggested that

In the ETV group, one case had it can be performed

Fifty-two paediatric patients with TBMH. The
a CSF leak which was resolved effectively in communicating
success rate in the ETV group was 65.4%
on conservative management hydrocephalus, high CSF cell
(17/26), and in the VP shunt group: 61.54%
Aranha et Age – with lumbar drainage. In the VPS counts, and protein levels,
15 2018 VPS or ETV each in 26 cases (16/26). The failure rate in the ETV group was
al. [4] <18years group, shunt-lower end despite an indistinct third
34.6% (9/26), and in the VP shunt group:
malfunction – 6, ventricular end ventricular floor anatomy. So,
38.4% (10/26). Two cases of mortality were
malfunction – 1, shunt tract ETV should be attempted as
observed in each group.
infection – 3. the first-choice CSF diversion

procedure in hydrocephalus

secondary to TBM, where

technical expertise and

experience with this

procedure are available.

In the acute phase of illness

The total number of cases with TBMH is 603. – VPS is preferred. In the

The overall success rate in patients who The complication rate is more in chronic phase of illness –
Bhushan et
16 2021 VPS or ETV underwent VPS was 51.8%. The overall VPS compared to ETV during the ETV is preferred. Reason –
al. [3]
success rate in patients who underwent ETV – chronic phase of illness. poor anatomy can lead to

68%. more complications with ETV

in the acute phase of illness.

TABLE 6: Studies of patients with TBMH who underwent either VPS or ETV.
TBMH: tuberculous meningitis hydrocephalus, VPS: ventriculoperitoneal shunt, ETV: endoscopic third ventriculostomy.

Outcomes

Results for the patients with TBMH who underwent ETV based on the outcomes of success rate and
complications can be found in Table 7.

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 Author year publication Number of patients (n) Age of the patients Follow-up period Good outcome% Complication%

Husain et al. [10] n=28 5 months - 68years 3 months to 2.5 years 68% 10%

Singh et al. [11] n=35 6 months - 32years 12 weeks 77%

Jha et al. [12] n=14 9 months - 40years 5 months 64.2%

Figaji et al. [13] n=17 <12 years 4–35 months 41.1% 11.7%

7 months - 52 years
Chugh et al. [16] n=26 1–15 months 73.1%

6 months - 76 years
Yadav et al. [17] n=59 7–54 months 58% 22.55%

Goyal et al. [20] n=24 <18years 6 months 41.7% 16.75%

Aranha et al. [4] n=26 <18years 5 months 65.4% 3.84%

Bhushan et al. [3] n=255 1 month - 68 years 68% 3.8% to 22.55%

TABLE 7: The outcome of TBMH patients who underwent ETV.

TBMH: tuberculous meningitis hydrocephalus, ETV: endoscopic third ventriculostomy.

Interpretation

The average follow-up period in the various studies mentioned above varied from one month to five years.
The average outcome success rate of the ETV procedure in the studies mentioned above is 61.8%. However,
the complication rate of the ETV procedure varied from 3.84% in the study of Aranha et al. to 16.75% in the
study of Goyal et al. [3,4,10,13,17,20]. The complication rate of ETV commonly includes CSF leak,
perioperative bleed, blocked stoma, the bulge at the ETV site, and meningitis.

Results for the patients with TBMH who underwent VPS based on the outcomes of success rate and
complications can be found in Table 8.

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 Author year Number of Age of the Follow-up
Good outcome Complications
publication patients (n) patients period

Lamprecht et al.
n=65 4–131 months 6 months 55.4% 32.3%
[9]

Sil and 1 month to 12

n=32 4–35 months 25% 43.8%
Chatterjee [14] years

Srikantha et al. Favourable short-term outcome: 33%; favourable

n=95 1–55 years 3–65 months
[15] long-term outcome: 45%

1 month to 14
Peng et al. [18] n=19 6–37 months 21.1% 31.57%
years

Savardekar et al. 4 months to

n=26 3 months 71.4% 23.5%
[19] 11 years

Goyal et al. [20] n=24 <18 years 54.2% 16.7%

Kankane et al. 3 months to

n=50 3 months In grade 3–77.5%; in grade 4–30% 10%
[21] 14 years

2 weeks to 6
Rizvi et al. [22] n=1038 <18 years 48.4% (GOS 5 and 4) 22.11%
years

Aranha et al. [4] n=26 <18 years 5 months 65.4% 38.4%

1 month to 68
Bhushan et al. [3] n=348 51.8% 10% to 43.8%
years

TABLE 8: The outcome of TBMH patients who underwent VPS.

TBMH: tuberculous meningitis hydrocephalus, VPS: ventriculoperitoneal shunt.

Interpretation

The average follow-up period in the various studies mentioned above varied from two weeks to six years.
The average outcome success rate of the VPS procedure in the studies mentioned above is 57.82%. GOS
(Glasgow Outcome Scale) and Vellore grading were outcome measures used by a few studies, and some
studies used either death or disabilities to determine the outcome. The overall complication rate of the VPS
procedure varied from 10% in the study by Kankane et al. to 43.8% in Sil and Chatterjee et al. [3,4,9,14,18-
22]. The common complications in VPS patients include shunt infections, shunt obstructions,
intraventricular haemorrhage, and multiple shunt revisions.

The preoperative and postoperative CT brain scans of a patient with TBMH who underwent VPS can be
found in Figures 2-4.

2022 Chalasani et al. Cureus 14(5): e25317. DOI 10.7759/cureus.25317 11 of 14

 FIGURE 2: Preoperative CT brain scan (contrast study, axial section) of
a patient showing tuberculomas in the left frontal region and right
cerebellum.

FIGURE 3: Preoperative CT brain contrast study (A - axial, B - coronal, C

- sagittal sections) of the same patient showing dilated bilateral lateral
and third ventricle with minimal periventricular seepage and
leptomeningeal enhancement.

FIGURE 4: Postoperative CT brain plane study (axial section) and CT

bone window of the same patient showing the burr hole defect in right
parietal bone, VP shunt in situ with its tip in the trigone of the lateral
ventricle.

Discussion

2022 Chalasani et al. Cureus 14(5): e25317. DOI 10.7759/cureus.25317 12 of 14

 Hydrocephalus is the most frequent complication of TBM and is profoundly more common in children than
in adults. Our study comprised 2207 patients with TBMH who underwent either VPS or ETV. Although
various studies determined the efficiency of the surgical intervention based on the clinical outcomes and
complications, the indications and timing of VPS and ETV were not steady across the studies. In our study
pattern, success rates of ETV in patients with TBMH varied widely from 41.1% to 77% [3,4,10-13,16,17,20].
The complication rate in ETV varied from 3.8% in the study of Aranha et al. [4] to 22.55% in Yadav et
al. [3,4,10,13,17,20]. The common complications in patients who have undergone ETV include CSF leak,
perioperative bleed, blocked stoma, bulge at the ETV site, and meningitis. The presence of advanced clinical-
grade, extra CNS TB, dense adhesions in the prepontine cistern, and unidentifiable third ventricle floor
anatomy leads to the failure of ETV [12]. Complex hydrocephalus and associated cerebral infarcts are
significant causes of failure to improve after ETV [17]. Results of ETV were better in patients without cistern
exudates, good nutritional status, and a thin and identifiable floor of the third ventricle. ETV should be
better avoided for acute hydrocephalus in patients with tuberculous meningitis and should be reserved for
those who have been on ATT for at least four weeks or those in the phase of chronic burnout and
hydrocephalus has developed late [1]. Some authors suggested ETV as worth trying before subjecting the
patients to VP shunt as it showed good results in both communicating and obstructing hydrocephalus [4,11].
Few studies regarded ETV as the first choice of management in patients with TBMH despite high CSF cell
counts, protein levels, and indistinct third ventricular floor anatomy [4]. On the other hand, a few studies
suggested ETV as the first management choice and considered VP shunt and EVD in patients with failed ETV
based on the clinical-grade [10]. Thus, there has been a lack of uniformity in the indications for performing
endoscopic third ventriculostomy (ETV). On the other hand, success rates of VPS in patients with TBMH
have varied widely from 21.1% to 77.5% [3,4,9,14,15,18-22]. The complication rate in VPS varied from 10% in
the study of Kankane et al. [21] to 43.8% in Sil and Chatterjee [3,4,9,14,18-22]. The common complications in
VPS patients include shunt infections, shunt obstructions, intraventricular haemorrhage, multiple shunt
revisions, abdominal CSF collections like pseudocyst, subdural hematomas, skin erosions, pneumonia, and
meningitis. One of the studies reported that shunt-related complications occurred in four patients and
consisted of an obstruction at the lower end of the shunt in three cases, leading to revision. One patient had
an infection at the shunt chamber site, leading to skin excoriation and meningitis [20]. A few studies
reported that 15.8% of patients expired in the second and fourth postoperative weeks, respectively; among
those who had undergone VPS placement, 21.1% of patients had a full recovery without sequelae, and the
other 63.2% of patients survived with various sequelae, including paralysis, impaired vision and hearing,
mental retardation, and epilepsy [18]. Rizvi et al. suggested that VPS outcome depends upon the clinical
severity of TBMH and holds an unpleasant prognosis in HIV-infected patients compared to HIV-uninfected
patients [22]. Srikantha et al. suggested a VP shunt as the first choice of management for grade 4 patients
with hydrocephalus and recommended it for patients who do not improve with an EVD [15]. A few studies
have suggested early VP shunt in patients with non-communicating hydrocephalus [9]. Prognostic factors to
rule out the outcome of shunt surgery include the age of the patient, duration of altered sensorium, CSF cell
count, and CSF protein levels. However, ETV has the theoretical ascendancy over VPS in enabling the CSF to
circulate through the previously inaccessible areas of the brain, which can generally absorb cerebrospinal
fluid. ETV also avoids lodging a foreign body in the form of a shunt, hence avoiding complexities like shunt
infection, blockage, and abdominal pseudocyst formation [1].

Limitations
The study scale of the ETV group is small compared to the VPS group, and the data extracted from an adult
population are inadequate to define any conclusion. In addition, there is a significant shortage of
information regarding the follow-up longevity, which might help determine the long-term outcomes and
complications of the VPS and ETV procedures and the timing of procedures in patients with TBMH. Finally,
apart from the former concerns, there is limited access to the data, and the methods of the studies could be
more specific in a better way.

Conclusions
After much interpretation, it is suggested that clinical grading of the patients is a basic and effective method
to determine the management of TBMH. Moreover, after ruling out the significant differences in the average
percentages of outcomes and complications followed by VPS and ETV, ETV is suggested in patients with
chronic illness because the chances of ETV failure are high during the initial phase. However, the uncertainty
of the ETV gradually descends over some time. Therefore, to attain favourable long-term outcomes with
ETV in patients with TBM, ETV should be performed after chemotherapy, ATT, and steroids. In addition, ETV
can be beneficial over VP shunt because it requires fewer incisions, associated long-term complications are
significantly less than VP shunt, and there are no implanted foreign bodies. In contrast, VP shunt is
suggested in the acute phase of illness as patients in modified Vellore grading show favourable outcomes
compared to ETV.

Additional Information
Disclosures
Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the
following: Payment/services info: All authors have declared that no financial support was received from

2022 Chalasani et al. Cureus 14(5): e25317. DOI 10.7759/cureus.25317 13 of 14

 any organization for the submitted work. Financial relationships: All authors have declared that they have
no financial relationships at present or within the previous three years with any organizations that might
have an interest in the submitted work. Other relationships: All authors have declared that there are no
other relationships or activities that could appear to have influenced the submitted work.

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Neurosurgical Review (2022) 45:199–216
https://doi.org/10.1007/s10143-021-01590-6

REVIEW

Efficacy and safety of flexible versus rigid endoscopic third

ventriculostomy in pediatric and adult populations: a systematic
review and meta‑analysis
Alessandro Boaro1,2 · Bhargavi Mahadik3 · Anthony Petrillo3 · Francesca Siddi1 · Sharmila Devi1,4 ·
Shreya Chawla1,4 · Abdullah M. Abunimer1 · Alberto Feletti2 · Alessandro Fiorindi5 · Pierluigi Longatti6 ·
Francesco Sala4 · Timothy R. Smith1 · Rania A. Mekary1,2

Received: 13 April 2021 / Revised: 13 May 2021 / Accepted: 14 June 2021 / Published online: 25 June 2021
© The Author(s) 2021

Abstract
Endoscopic third ventriculostomy (ETV) is a well-established surgical procedure for hydrocephalus treatment, but there is
sparse evidence on the optimal choice between flexible and rigid approaches. A meta-analysis was conducted to compare
efficacy and safety profiles of both techniques in pediatrics and adults. A comprehensive search was conducted on PubMED,
EMBASE, and Cochrane until 11/10/2019. Efficacy was evaluated comparing incidence of ETV failure, while safety was
defined by the incidence of perioperative complications, intraoperative bleedings, and deaths. Random-effects models were
used to pool the incidence. Out of 1365 studies, 46 case series were meta-analyzed, yielding 821 patients who underwent
flexible ETV and 2918 who underwent rigid ETV, with an age range of [5 days–87 years]. Although flexible ETV had a higher
incidence of failure in adults (flexible: 54%, 95%CI: 22–82% vs rigid: 20%, 95%CI: 22–82%) possibly due to confounding due
to etiology in adults treated with flexible, a smaller difference was seen in pediatrics (flexible: 36%, pediatric: 32%). Safety
profiles were acceptable for both techniques, with a certain degree of variability for complications (flexible 2%, rigid 18%)
and death (flexible 1%, rigid 3%) in pediatrics as well as complications (rigid 9%, flexible 13%), death (flexible 4%, rigid
6%) and intra-operative bleeding events (rigid 6%, flexible 8%) in adults. No clear superiority in efficacy could be depicted
between flexible and rigid ETV for hydrocephalus treatment. Safety profiles varied by age but were acceptable for both tech-
niques. Well-designed comparative studies are needed to assess the optimal endoscopic treatment option for hydrocephalus.

Keywords Flexible neuroendoscopy · Rigid neuroendoscopy · Endoscopic third ventriculostomy · Hydrocephalus ·

Efficacy · Complications

Introduction using different types of tools driven through the operative

Endoscopic third ventriculostomy (ETV) is a well-estab-
lished surgical procedure for the treatment of hydrocephalus.
It consists in the opening of the floor of the third ventricle
Timothy R Smith and Rania A Mekary are the co-senior authors
channel of an endoscope [18]. The first ever-reported ETV
was conducted by William J Mixter in 1923; he successfully
treated a case of non-communicating hydrocephalus using
an uretheroscope [18]. Ten years later, Tracy Putnam devel-
oped the “ventriculoscope,” the first endoscope specifically
designed to operate in cerebral ventricles. It included one

3
* Alessandro Boaro School of Pharmacy, Massachusetts College of Pharmacy
alessandro.boaro@univr.it and Health Sciences University, Boston, MA, USA
4
1 Faculty of Life Sciences and Medicine, King’s College
Computational Neurosciences Outcomes Center, Brigham
London, London, UK
and Women’s Hospital, Harvard Medical School, Boston,
5
MA, USA Department of Neurosurgery, University of Brescia, Brescia,
2 Italy
Institute of Neurosurgery, Department of Neurosciences,
6
Biomedicine and Movement Sciences, University of Verona, Department of Neurosurgery, University of Padova, Padova,
Verona, Italy Italy

13
Vol.:(0123456789)
200
optical glass rod and three grooves, one for the light source
and two for the diathermy electrodes [18]. The design and
the optic systems, as well as the available operative tools,
were then progressively refined. In the 1970s, the British
physicist Harold H Hopkins with his system of solid and
cemented glass rod lenses surrounded by fiberoptic bun-
dles, paved the way for both the modern rigid and flexible
endoscopy [18]. In 1973, Takanori Fukushima was the first
neurosurgeon to use a flexible endoscope to perform ven-
triculostomies with his refined “ventriculofiberscope” [18].
Rigid and flexible endoscopes are both currently used to
perform third ventriculostomy, and each type has distinct
advantages and drawbacks. Rigid endoscopes are more
commonly used compared with their flexible counterparts
because they generally produce higher quality images and
allow for easier passing of instruments [4]. Their use, how-
ever, can be restricted by the size of ventricles and made
difficult by the rigid linear nature of the rod lenses [4, 5,
16, 38]. Flexible endoscopes, on the other hand, have an
added degree of mobility to help overcome the nonlinear
ventricular anatomy. They have been used more frequently
in children given their narrower diameter, but they gener-
ally present images of lower quality and a limited set of
operative tools [4, 5, 22]. Interestingly, the published litera-
ture usually focuses on the nuances and outcomes of either
rigid or flexible endoscopy alone; only one paper compared
the two techniques in a comparative study design to assess
the optimal choice of treatment [57]. To our knowledge, no
meta-analysis has been conducted to compare efficacy and
safety of rigid endoscopy versus flexible endoscopy in ETV.
As the two approaches present both risks and benefits, we
decided to pool the available evidence and conduct a meta-
analysis to compare efficacy and safety of flexible and rigid
neuro-endoscopy in the performance of ETV in pediatric
and adult populations.
Materials and methods
Search strategy and study selection
A comprehensive electronic search was conducted on Pub-
MED, EMBASE, and Cochrane until November 10, 2019.
The search was filtered for English language articles. Com-
prehensive search results were obtained using relevant
MeSH terms, Emtree terms, and text words (Appendix
1). The duplicates were removed and data were exported
into Covidence software for screening [17]. All the articles
underwent two levels of screening (title/abstract and full-
text) by six reviewers (BM, AP, AB, FS, SD, AA). Dis-
crepancies were resolved by discussion or consulting senior
authors (AB, RM, FS). Reasons for rejection were listed in
accordance with the PRISMA checklist [26].
13
Neurosurgical Review (2022) 45:199–216
Inclusion and exclusion criteria
Articles were included in our study if: they had participants
suffering from hydrocephalus who underwent flexible endo-
scopic third ventriculostomy or rigid endoscopic third ven-
triculostomy; the study reported failure or reoperation rate
in the procedure; the study was an observational study, ran-
domized control trial, or case series of five or more patients
diagnosed with hydrocephalus. Articles were excluded from
our study if they were not in the English language or if they
did not report on patients’ outcome and follow-up.
Data extraction
Studies included after full text screening had their data
extracted by five authors (BM, AP, FS, SC, SD). Data were
extracted for study characteristics (author, publication year,
country of origin, study design and timing, and sample size),
patients’ characteristics (average age, age category -pedi-
atrics, adults-, type and etiology of hydrocephalus), and
intervention characteristics (type of intervention and type
of endoscope used). Efficacy or ETV failure was the primary
outcome and was defined as patients requiring reoperations
after ETV surgery which could either be a second ETV or
shunt placement. Safety was assessed as a secondary out-
come, evaluating incidence of complications including infec-
tion, intraventricular hemorrhage, neurological deficit, motor
aphasia, ependymitis, sepsis, and CSF leak, among others,
incidence of intra-operative bleeding (witnessed, controlled
and reported by the operating surgeon), and incidence of
death due to surgery. All the variables and outcomes were
recorded for adults, pediatrics, and mixed (both pediatrics
and adults) population. Number of events for failure and
safety outcomes were recorded for each intervention.
Data analysis
Incidence measures were analyzed for categorical outcomes
by using number of events and total sample size of outcome
measures. Pooled effect estimates of incidence measures
were analyzed by the random-effects model using the Der-
Simonian–Laird method [26]. Comprehensive meta-analysis
software (CMA) version 3 was used to perform the statistical
analyses. Unless otherwise specified, a two-sided p value
of < 0.05 was considered statistically significant.
Heterogeneity assessment and analysis
The presence of heterogeneity was assessed using
Cochrane Q statistic with a significance level of p < 0.10
[27]. Degree of heterogeneity among studies was
Neurosurgical Review (2022) 45:199–216
determined using the ­I2 value [27]. Degree of heteroge-
neity was reported to be low, medium, and high with I­ 2
values of 25, 50, and 75%, respectively [28]. All analyses
were stratified by age categories (pediatric, adult, mixed).
The p value comparing the subgroups was not derived as
these would be highly confounded due to the nature of the
included studies (non-comparative). An additional sensi-
tivity analysis was done by removing low quality studies
(< median score of 4) from all the analyses to assess the
robustness of the findings.
Risk of bias assessment
Publication bias was assessed by Begg’s [9] test and the
funnel plot was analyzed for visual determination of asym-
metry if the assessed outcomes had at least 10 studies [26].
If presence of publication bias was confirmed, the trim and
fill method was used to estimate the possible number of
missing studies, which were then imputed to recalculate
the new pooled effect estimate. As all the studies included
in the analysis were case series, the quality of the studies
was assessed by a questionnaire by Chan and Bhanush-
ali [14]. The questionnaire assessed all studies based on
whether their objective, protocol, inclusion and exclusion
criteria, time interval, and patient enrollment were well
defined and if the studies had a prospective collection of
outcome data and a high follow-up. Each category had
one point associated to it with the highest possible score
of 8. Studies with higher scores on the questionnaire were
assessed to be of better quality.
Fig. 1  Study selection process
of the identified articles
201
Results
Search results and characteristics
The electronic search yielded a total of 1365 studies [Pub-
Med (743), EMBASE (602) and Cochrane (20)]. Of all
imported studies, 1033 studies were screened and 46 case
series [1–3, 6–8, 10–13, 15, 18–21, 23–25, 29, 30, 33–35,
37, 39–60] were used for the final meta-analysis (Fig. 1).
The study timing for 39 studies was retrospective, while 7
studies were prospective. Patients in all age groups, from
neonatal to geriatric population, were captured in the stud-
ies. The age range of the patients was 5 days–89 years and
both naïve as well as previously shunted patients were
included in the analysis. Out of the 46 case series with 3739
patients, 12 studies included adult population [7, 11, 13,
24, 25, 34, 35, 39, 40, 49, 50], 14 studies included pediatric
population [1, 4, 7, 8, 12, 29, 33, 45, 46, 51, 58, 60], and 20
studies included patients from both groups [2, 10, 15, 19,
21, 23, 29, 30, 37, 41–44, 47, 52, 53, 55, 56, 59]. Regarding
flexible ETV, 10 studies [23, 34, 35, 41, 42, 48, 52, 53, 57,
58] reported outcomes with a total of 821 patients, of whom
38 were adults, 126 were pediatric, and 657 were a mixture
of adult and pediatric populations. For rigid ETV, 37 studies
[1–4, 6–8, 10–13, 15, 18–21, 24, 25, 29, 30, 33, 37, 39, 40,
43–47, 49–51, 54–57, 59, 60] reported outcomes for a total
of 2918 patients, of whom 1018 were adults, 747 were pedi-
atric, and 1153 patients were a mixture of adult and pediatric
populations. The types of hydrocephalus included were com-
municating hydrocephalus, non-communicating hydrocepha-
lus, and normal pressure hydrocephalus (Table 1).
13
 Table 1  Characteristics of studies included in the systematic review and meta-analysis
202

Author, Year Endoscope Study Design, Timing Hydrocephalus type Etiology (no. of Patient Population Age: Mean (range) unless other- Male, n (%) Study
(Rigid/Flex- patients) wise specified Qual-

13
ible) ity*

Abbassy et al., 2018 Rigid Case series, retrospec- Non-communicating Endodermal sinus Pediatric 11 years (1 year–17 years) 10 (90.9%) 3
[1] tive hydrocephalus tumor (1), Germi-
noma (2), Grade
II astrocytoma (1),
Mixed germ-cell
tumor (1), Pineo-
blastoma (3), Pilo-
cytic astrocytoma
(1), Grade II tectal
glioma (1), Pilocytic
astrocytoma (1)
Aranha et al., 2018 [3] Rigid Case series, prospec- Communicating Tuberculous meningi- Pediatric NR 15 (57.7%) 4
tive hydrocephalus tis (TBM) Hydro-
cephalus
Chiba et al., 2018 [15] Rigid Case series, retrospec- Non-communicating Aqueductal stenosis Adult and Pediatric 31.4 years (0.3 years–74 years) 17 (56.7%) 5
tive hydrocephalus (3), Cerebellar
tumor (2), Intraven-
tricular hemor-
rhage (3), Pineal
tumor (13), Fourth
ventricle tumor (2),
Brainstem tumor
(1), Tectal tumor
(3), Brain metas-
tasis (1), Isolated
fourth ventricle (1),
Bilateral thalamic
glioma (1)
Torres-Corzo et al., Flexible Case series, retrospec- Non-communicating NR Mixed 20.45 years 25 (52%) 4
2018 [52] tive hydrocephalus
Uche et al., 2018 [54] Rigid Case series, prospec- Non-communicating Aqueductal stenosis Pediatric 2.3 years (3 months–4.5 years) 37 (67%) 5
tive hydrocephalus (37), Dandy-Walker
malformation (7),
Arnold-Chiari
malformation (8),
Intraventricular cyst
loculations (3)
Wu et al., 2018 [59] Rigid Case series, retrospec- Non-communicating Chiari type I malfor- Adult and Pediatric 28.14 years (0.75 years–55 years) 4 (40%) 5
tive hydrocephalus mation (10)
Neurosurgical Review (2022) 45:199–216
 Table 1  (continued)
Author, Year Endoscope Study Design, Timing Hydrocephalus type Etiology (no. of Patient Population Age: Mean (range) unless other- Male, n (%) Study
(Rigid/Flex- patients) wise specified Qual-
ible) ity*

Sufianov et al., 2018 Rigid Case series, prospec- Non-communicating Aqueductal stenosis Pediatric NR 34 (53.1%) 4
[51] tive hydrocephalus (21), Post hemor-
rhagic hydrocepha-
lus (25), Post-infec-
tious hydrocephalus
(11), Dandy-Walker
malformation (4),
Neurosurgical Review (2022) 45:199–216

Myelomeningocele
(3)
Aref et al., 2017 [4] Rigid Case series, retrospec- Nr Normal pressure Adult 51.7 years 82 (62%) 4
tive hydrocephalus (40),
Obstructive tumor
(46), Aqueductal
stenosis (18),
Hemorrhage (3),
Unknown etiology
(19), Trauma (3),
Tuberculosis (1),
Cyst (7)
Oertel et al., 2017 Rigid Case series, retrospec- Non-communicating Benign aqueductal Adult and Pediatric NR 58 (51.3%) 2
[43] tive hydrocephalus stenosis (40), Tumor
(35), Infection/
hemorrhage (15),
Intracranial cysts
(13), Other (10)

13
203
 Table 1  (continued)
204

Author, Year Endoscope Study Design, Timing Hydrocephalus type Etiology (no. of Patient Population Age: Mean (range) unless other- Male, n (%) Study
(Rigid/Flex- patients) wise specified Qual-

13
ible) ity*

Wang et al., 2017 [57] Rigid Case series, retrospec- Nr Post-hemorrhagic Pediatric Median = 3.5 months 45 (52.9%) 5
tive hydrocephalus IQR = 1.2 months–5.7 months
(25), Aqueductal
stenosis (21),
Myelomeningocele
(23), Dandy-Walker
complex (6), Con-
genital idiopathic
hydrocephalus
(4), Postinfectious
hydrocephalus (6),
Other etiology (6)
Flexible Case series, retrospec- Nr Post-hemorrhagic Pediatric Median = 3.2 months 50 (54.9%) 5
tive hydrocephalus (44), IQR = 0.7 months—6.8 months
Aqueductal ste-
nosis(12), Mye-
lomeningocele(7),
Dandy-Walker mal-
formation (6), Con-
genital idiopathic
hydrocephalus
(6), Postinfectious
hydrocephalus (5),
Other etiology(5)
Rodriguez et al., 2017 Flexible Case series, retrospec- Nr Tumor (20), infectious Mixed (4 days–76 years) 76 (51%) 5
[58] tive or due to parasites
(75), Post-hemor-
rhagic (16), Congen-
ital (39)
Zhao et al., 2016 [60] Rigid Case series, retrospec- Non-communicating Posterior fossa tumor Pediatric (8 months–36 months) NR 4
tive hydrocephalus (24), or pineal tumor (9), Median = 21.6 months
communicating Idiopathic aqueduct
hydrocephalus (13) stenosis (15), Post-
meningitis (8), Post-
hemorrhagic (3)
Neurosurgical Review (2022) 45:199–216
 Table 1  (continued)
Author, Year Endoscope Study Design, Timing Hydrocephalus type Etiology (no. of Patient Population Age: Mean (range) unless other- Male, n (%) Study
(Rigid/Flex- patients) wise specified Qual-
ible) ity*

Grand et al., 2016 Rigid Case series, retrospec- Nr Aqueduct stenosis Adult 51 years (17 years–88 years) 128 (52.7%) 4
[24] tive (56), Intraventricular
hemorrhage (20),
Remote head trauma
(57), Post-craniot-
omy for posterior
fossa tumor (14),
Neurosurgical Review (2022) 45:199–216

Subarachnoid hem-
orrhage (23), Tumor
or cyst (42), Shunt
obstruction (23),
Other cause (8)
Kawsar et al., 2015 Rigid Case series, retrospec- Nr Aqueductal stenosis Mixed NR 224 (54.37%) 4
[30] tive (210), Posterior
fossa tumors (74),
Cysts (56), Previous
ventriculitis (49),
Shunt failure (8),
Posterior fossa
hemorrhage (6),
Hydrocephalus due
to Chiari malforma-
tion (6), Congenital
fourth ventricular
outflow obstruction
(2) Hydrocephalus
w/ empty sella
syndrome (1)
Niknejad et al., Rigid Case series, retrospec- Tri-ventricular Tumor (8), Giant basi- Adult 72.8 years (66 years–83 years) 11 (68.75%) 5
2015[39] tive hydrocephalus (14), lary tip aneurysm
communicating (1), Normal pressure
hydrocephalus (1), hydrocephalus (1),
quadri-ventricular idiopathic aque-
hydrocephalus (1) ductal stenosis (3),
post-hemorrhagic
(1), Tuberculous
meningitis (1),
Wegener granuloma
(1)
Obaid et al., 2015 [40] Rigid Case series, retrospec- Non-communicating Intraventricular hem- Adult 58 years (42 years–79 years) 9 (52.94%) 5
tive hydrocephalus orrhage

13
205
 Table 1  (continued)
206

Author, Year Endoscope Study Design, Timing Hydrocephalus type Etiology (no. of Patient Population Age: Mean (range) unless other- Male, n (%) Study
(Rigid/Flex- patients) wise specified Qual-

13
ible) ity*

Vulcu et al., 2015 [56] Rigid Case series, retrospec- Nr Benign aqueductal Mixed 35 years (8 days–77 years) 58 (51.3%) 4
tive stenosis (40), Tumor
(35), Infection/
hemorrhage (15),
Intracranial cysts
(13), Other (10)
Bisht et al., 2014 [10] Rigid Case series, retrospec- Non-communicating Congenital aqueductal Adult and Pediatric 7.45 years (1 month–52 years) 79 (77.45%) 6
tive hydrocephalus stenosis
Salvador et al., 2014 Rigid Case series, retrospec- Non-communicating Congenital malforma- Adult and Pediatric 22.1 years 98 (60%) 6
[47] tive hydrocephalus tions (74), Tumor
(52), Cysts (15),
Infection (12), Hem-
orrhage (11)
Stachura et al., 2014 Rigid Case series, retrospec- Non-communicating Primary aqueductal Adult 47 years (18 years–82 years) 55 (57.3%) 2
[50] tive hydrocephalus stenosis (24), Brain
tumor (61), Basilar
tip aneurysm (2),
Undetermined (9)
Ali et al., 2013 [2] Rigid Case series, retrospec- Non-communicating Posterior fossa tumor Mixed 15 years (6 months–60 years) 72 (46.45%) 5
tive hydrocephalus (83), Aqueductal
stenosis (37), Non
tectal tumor (8),
CP angle tumor
(7), Tectal tumor
(7), Posterior fossa
abscess (3), Poste-
rior fossa hematoma
(2)
Brusius & Cavalheiro, Rigid Case series, prospec- Non-communicating Blake pouch cyst (8) Pediatric 13.25 months (1 month– 5 (62.5%) 7
2013 [12] tive hydrocephalus 48 months)
Melot et al., 2013 [37] Rigid Case series, retrospec- Non-communicating Malformation (43), Adult and Pediatric NR NR 4
tive hydrocephalus Mass lesion (35),
Post-infectious (4)
Romeo et al., 2013 Rigid Case series, retrospec- Non-communicating Tectal plate gliomas Pediatric 11.6 years (4 years–18 years) 15 (68%) 3
[46] tive hydrocephalus
Neurosurgical Review (2022) 45:199–216
 Table 1  (continued)
Author, Year Endoscope Study Design, Timing Hydrocephalus type Etiology (no. of Patient Population Age: Mean (range) unless other- Male, n (%) Study
(Rigid/Flex- patients) wise specified Qual-
ible) ity*

Vogel et al., 2013 [55] Rigid Case series, retrospec- Non-communicating Aqueductal steno- Mixed 19.7 years (5 months–77 years) 46 (48%) 4
tive hydrocephalus sis (35), Non-
tectal tumor (23),
Tectal tumor (16),
Myelomeningocele
(9), Intracranial cyst
(6), Infection (3),
Neurosurgical Review (2022) 45:199–216

Chiari malformation
Type I (3)
Bouramas et al., 2012 Rigid Case series, retrospec- Non-communicating Aquetuctal stenosis Adult (43 years–89 years) 26 (48.14%) 5
[11] tive hydrocephalus (30), Post infection
(3), Cyst (5), Tumor
(15), Hemorrhage
(4)
Warf et al., 2012 [58] Flexible Case series, retrospec- Non-communicating Congenital aqueductal Pediatric NR 19 (54.28%) 4
tive hydrocephalus stenosis
Durnford et al., 2011 Rigid Case series, retrospec- Non-communicating Aqueductal steno- Mixed (0 years–19 years) 95 (57.2%) 4
[19] tive hydrocephalus sis (40), Non-
tectal tumor (39),
Intraventricular
Hemorrhage (23),
Tectal tumor (15),
Myelomeningocele
(5), Post-infectious
(7), Other (37)
Egger et al., 2010 [20] Rigid Case series, retrospec- Non-communicating Cyst (4), Tumor Pediatric Median = 3 years 4 months 6 (42.8%) 5
tive hydrocephalus (4), Chiari II
Malformation and
myelomeningocele
(3), Aqueductal
stenosis (3)
Ogiwara et al., 2010 Rigid Case series, retrospec- Non-communicating Congenital aque- Pediatric 87.7 days (5 days–158 days) 14 (60.8%) 4
[45] tive hydrocephalus duct stenosis (11),
Post-hemorrhagic
obstruction (6),
Myelomeningocele
(2), Post-meningitis
(2), Chiari I malfor-
mation (1), Dandy
walker variant (1)

13
207
 Table 1  (continued)
208

Author, Year Endoscope Study Design, Timing Hydrocephalus type Etiology (no. of Patient Population Age: Mean (range) unless other- Male, n (%) Study
(Rigid/Flex- patients) wise specified Qual-

13
ible) ity*

Torres-Corzo et al., Flexible Case series, retrospec- Non-communicating Neurocysticercosis Mixed (9 years–79 years) 42 (56%) 4
2010 [53] tive hydrocephalus (86)
Oertel et al., 2009 Rigid Case series, prospec- Non-communicating Cerebellar hem- Mixed 60.8 years (3 months–83 years) 15 (44%) 6
[44] tive hydrocephalus orrhage (17),
Thalamic hemor-
rhage (6), Intraven-
tricular hemorrhage
(5), basal ganglia
hemorrhage (3),
subarachnoid hem-
orrhage (2), pontine
hemorrhage (1)
Ersahin & Arslan, Rigid Case series, retrospec- Non-communicating Obstruction of fourth Mixed 14.8 years (2 months–77 years) 85 (54.8%) 5
2008 [21] tive hydrocephalus ventricular outlets,
Dandy-Walker Mal-
formation, Chiari
Malformation type I,
Chiari malformation
type II, Aqueductal
stenosis
Hailong et al., 2008 Rigid Case series, retrospec- Idiopathic normal Idiopathic normal- Adult 61.4 years 24 (75%) 3
[25] tive pressure (17), sec- pressure hydroceph-
ondary communicat- alus (17), Tuber-
ing hydrocephalus cular meningitis
(15) (1), Trauma (9),
Hypertensive intrac-
ranial hemorrhage
(4), Subarachnoid
hemorrhage (1)
Lipina et al., 2008 Rigid Case series, retrospec- Non-communicating Acqueductal stenosis Pediatric 105 days 8 (57.1%) 5
[33] tive hydrocephalus (5), Peri and
intraventricular
hemorrhage (8),
Hemorrhage and
Infection (1)
Idowu et al., 2008 Rigid Case series, prospec- Non-communicating Aqueductal stenosis Mixed (4 weeks to 48 years) 14 (56%) 4
[29] tive hydrocephalus (11), Dandy-Walker median = 6 months
malformation (9),
Myelomeningocele
(4), Pineal region
tumor(1)
Neurosurgical Review (2022) 45:199–216
 Table 1  (continued)
Author, Year Endoscope Study Design, Timing Hydrocephalus type Etiology (no. of Patient Population Age: Mean (range) unless other- Male, n (%) Study
(Rigid/Flex- patients) wise specified Qual-
ible) ity*

Baldauf et al., 2007 Rigid Case series, retrospec- Non-communicating Idiopathic aque- Pediatric 6.7 months 15 (71.4%) 3
[7] tive hydrocephalus ductal stenosis (8),
Other congenital
anomalies (4), Post-
hemorrhagic (3),
Tumor-related (3),
Shunt infection (2),
Neurosurgical Review (2022) 45:199–216

Shunt failure (1)

Baldauf et al., 2006 Rigid Case series, retrospec- Non-communicating cerebellar infarction Adult 62 years (25 years–85 years) 5 (55%) 4
[6] tive hydrocephalus
O’Brien et al., 2006 Flexible Case series, retrospec- Non-communicating NR Mixed 37 years (5 years–77 years) 21 (50%) 3
[41] tive hydrocephalus Median = 33
Baykan et al., 2005 Rigid Case series, retrospec- Non-communicating NR Pediatric (2 months—10 years) 120 (57.1%) 5
[8] tive hydrocephalus
O’Brien et al., 2005 Flexible Case series, retrospec- Non-communicating Spina bifida, aque- Mixed 27.78 (37 weeks–77 years) NR 4
[42] tive hydrocephalus ductal stenosis,
arachnoidi cysts,
primary infective
and haemorrhagic
origin
Flexible Case series, retrospec- Non-communicating Spina bifida, aque- Mixed 20.43 (9 months–69 years) NR 4
tive hydrocephalus ductal stenosis,
arachnoidi cysts,
primary infective
and haemorrhagic
origin (IVH)
Santamarta et al., Rigid Case series, retrospec- Non-communicating Primary aqueductal Adult Median = 53 IQR = 27–67 33 (50%) 5
2005 [49] tive hydrocephalus stenosis (27),
Tumoural (30), Non
tumoural (haemor-
rhage, cysts) (9)
Longatti et al., 2004 Flexible Case series, retrospec- Nr Primitive aqueductal Adult (35 years–82 years) 14 (58.3%) 5
[34] tive stenosis (3) second- Median = 59.5
ary CSF pathway
obstruction (11)
frontal cystic glio-
blastoma (1) normal
pressure hydroceph-
alus (6) previously
shunted (3)

13
209
 Table 1  (continued)
210

Author, Year Endoscope Study Design, Timing Hydrocephalus type Etiology (no. of Patient Population Age: Mean (range) unless other- Male, n (%) Study
(Rigid/Flex- patients) wise specified Qual-

13
ible) ity*

Longatti et al., 2004 Flexible Case series, retrospec- Normal pressure NR Adult (66 years–78 years) 8 (57.1%) 5
[35] tive hydrocephalus
Buxton et al., 2001 Rigid Case series, retrospec- Non communicating Third ventricular Adult 37.5 years (17 years–77 years) 38 (60.3%) 7
[13] tive until august hydrocephalus (44), tumor (22) Aque-
1994, post aug 1994 communicating duct stenosis (18),
prospective hydrocephalus (9) Third ventricular
arachnoid cyst (4)
Infection (4), SAH/
Post haemorrhagic
(2) Myelomenin-
gocoele (4), Other
(4) Hydrocephalus
cause (3)
Gangemi et al., 1999 Flexible Case series, retrospec- Triventricular hydro- Primary aqueductal Mixed 31 years (7 days–81 years) 72 (57.6%) 6
[23] tive cephalus (110), stenosis (77) mes-
tetraventricular encephalic tumors
hydrocephalus (15) (16), pineal region
tumors (9) posterior
fossa tumors (8)
blockage in the
posterior fossa
(11) subarachnoid
hemorrhage (3),
infection due to
Candida (1)
*
Study quality (Median 4, IQR 4–5) was assessed based on the quality assessment questionnaire for case series based on Chan and Bhandari
Neurosurgical Review (2022) 45:199–216
Neurosurgical Review (2022) 45:199–216
Efficacy (ETV failure) analysis
Flexible ETV showed a higher incidence of failure com-
pared with rigid ETV in adults (54% vs 20%) (Fig. 2),
while a smaller difference was found in pediatric patients
(36% flexible vs 32% rigid) (Fig. 3) and mixed age patients
(23% flexible vs 22% rigid) (Fig. 4) (Table 2).
Safety analysis (complications, bleeding, death)
Even though pooled results could not be compared with
a statistical p value, it was worth exploring the trends
resulting from our analysis. Flexible endoscopy presented
an overall lower incidence of complications in pediatric
(2 vs 18%) and mixed populations (8 vs 11%) but not in
adults (13 vs 9%) when compared with the rigid approach
(Table 3, Appendix 2). Flexible endoscopy presented an
overall trend towards lower incidence of intra-operative
bleeding in the mixed age category (4 vs 6%) but not in
the adult category (8 vs 6%) when compared with the rigid
approach. No studies conducted in pediatrics presented
data on intra-operative bleeding (Table 3, Appendix 3).
Flexible endoscopy reported lower incidence of death
related to surgery in each age group (pediatric 1 vs 3%,
adult 4 vs 6%, mixed 1.2 vs 1.7%) when compared with
the rigid approach (Table 3, Appendix 4).
Fig. 2  Forest plot for incidence of failure in adults stratified by endos-
copy type. For flexible ETV: incidence of failure = 54%; number
of studies = 2; P-heterogeneity = 0.001; ­I2 = 90.9%; for rigid ETV:
211
Quality score and bias assessment
The quality score for all studies ranged from 2 to 7 with
a median score of 4 (IQR 4–5) (Appendix 5) on the Chan
and Bhanushali questionnaire. Only 7 studies had a qual-
ity score < median [1,7,25,41,43,46,50,]. All studies had
a well-defined study objective and clinically relevant out-
comes. The majority of them had well-defined protocols and
high follow-up rates. A few studies did not report explicit
inclusion/exclusion criteria, time interval, and consecutive
patient enrollment. Only seven studies had prospective data
collection. Only the rigid endoscopy group with regard of
the incidence of failure had more than 10 studies in their
analysis for each of the adult and pediatric populations.
The funnel plot for the incidence of failure using the rigid
endoscopy did not show obvious signs of asymmetry in adult
population (Fig. 5a) or pediatric population (Fig. 5b), which
suggested the absence of publication bias. The Begg’s test
for each was not statistically significant, further confirm-
ing these findings (p value: 0.22 in adults; p value: 0.55 in
pediatrics).
Sensitivity analysis
All of the above analyses did not materially change when we
excluded studies with a quality score below the median level
(< 4) (Appendices 6 and 7).
incidence of failure: 20% number of studies = 16; P-heterogene-
ity = 0.002; ­I2 = 57.4%. Error bars represent the 95% CI. ETV: endo-
scopic third-ventriculostomy
13
212 Neurosurgical Review (2022) 45:199–216

Fig. 3  Forest plot for incidence of failure in pediatric population for rigid ETV: incidence of failure = 32%; number of studies = 19;
stratified by endoscopy type. For flexible ETV: incidence of fail- P-heterogeneity = 0.00; ­I2 = 85.2%. Error bars represent the 95% CI.
ure = 36%; number of studies = 2; P-heterogeneity = 0.14; ­I2 = 53.2%; ETV: endoscopic third-ventriculostomy

Fig. 4  Forest plot for incidence of failure in mixed population strati- ETV: incidence of failure = 22%; number of studies = 8; P-heteroge-
fied by endoscopy type. For flexible ETV: incidence of failure = 23%; neity = 0.01; ­I2 = 61%. Error bars represent the 95% CI. ETV: endo-
number of studies = 7; P-heterogeneity = 0.00; ­I2 = 86%; for rigid scopic third-ventriculostomy

Discussion adults. Safety profiles were mixed, while flexible endos-

copy showed fewer complications in pediatrics and lower
The results of this meta-analysis suggested the presence of death events in pediatrics and adults, rigid endoscopy
better efficacy of rigid endoscopy for ETV performance in showed fewer complications and bleeding events in adults.

13
Neurosurgical Review (2022) 45:199–216 213

Table 2  Pooled effect estimates for efficacy (failure)

Flexible ETV Rigid ETV

Outcome Population type; Pooled incidence (95% C.I.) I2 # of studies Pooled incidence (95% C.I.) I2 # of studies
value value
Failure Pediatric 36% (12%, 66%) 53.2% 2 32% (22%, 43%) 85.2% 19
Adult 54% (22%, 82%) 90.9% 2 20% (15%, 25%) 57.4% 16
Mixed 23% (16%, 31%) 86% 7 22% (16%, 27%) 61.6% 8

C.I.: Confidence interval

Table 3  Pooled effect estimates for safety outcomes of complications, bleeding, and death
Flexible ETV Rigid ETV

Outcome Population; Pooled incidence (95% C.I.) I2 # of studies Pooled incidence (95% C.I.) I2 # of studies
value value
Complications Pediatric 2% (0.1–34%) N.A 1 18% (7–41%) 90.8% 7
Adult 13% (3–40%) N.A 1 9% (5–13%) 55.9% 8
Mixed 8% (5–11%) 54% 5 11% (8–16%) 27.9% 4
Bleeding Adult 8% (2–27%) N.A 1 6% (4–10%) 0% 4
Mixed 4% (2–9%) 19.1% 5 6% (2–13%) 89.7% 4
Death Pediatric 1% (0.1–3%) 0% 2 3% (1–5%) 0% 12
Adult 4% (0.4–32%) 0% 2 6% (2–13%) 80.9% 10
Mixed 1.2% (0.6–2.7%) 0% 6 1.7% (1.1–2.8%) 0% 7

CI confidence interval, NA not applicable

Fig. 5  Funnel plots for incidence of failure in adult and pediatric confirmed these findings (adult p value 0.22, pediatric p value 0.55).
populations undergoing rigid ETV. No evident signs of asymmetry ETV: endoscopic third-ventriculostomy
are unveiled in adult (a) or pediatric (b) population. The Begg’s test

Regarding the efficacy profile, the results for the adult
group were limited by the availability of only two studies on
flexible endoscopy [34, 35]. It is particularly important to
notice that one of these two studies focused on patients suf-
fering from normal pressure hydrocephalus, which is known
to have overall better outcomes when treated with a shunt
[35], given the non-obstructive nature of the disease [36].
Therefore, the efficacy results were more suggestive of the
fact that ETV was able to provide actual benefit to patients
with hydrocephalus depending on its etiology, rather than
providing evidence of an overall superiority of flexible or
rigid approach over the other. The available literature has
in fact already shown that both etiology and age are crucial
factors to consider in the decision of treating hydrocephalus
through a shunt or ETV, particularly in the pediatric popula-
tion [31, 32].

13
214
In terms of safety, both flexible and rigid endoscopic
approaches turned out to be procedures with acceptable
peri-operative complication rates and very low occurrence
of intra-operative bleeding and death. With regard to peri-
operative complications, we could appreciate a trend towards
a lower rate in the use of flexible approach, particularly in
the pediatric population, but whether these comparisons
would reach statistical significance is yet to be confirmed in
future comparative studies. Flexible instruments are smaller
and tend to be more delicate, which could at least in part
explain our findings. With regard to intra-operative bleed-
ing, the results need to be interpreted cautiously. The risk of
bleeding depends also on the type of procedure performed
during the endoscopy: a patient who undergoes ETV alone
has a reduced risk of experience bleeding compared to a
patient who undergoes ETV along with the biopsy or partial
resection of a tumor or again the cauterization of the cho-
roid plexus, regardless the type of approach. Interestingly,
no pediatrics study reported occurrence of intra-operative
bleeding, even in the presence of choroid plexus cauteriza-
tion. Moreover, the ability of the flexible endoscope to reach
areas out of range for the rigid one, for example, the poste-
rior half of the third ventricle, allows the surgeon to perform
deeper maneuvers, hence exposing them to the related inher-
ent risks. Regardless the approach and age group, intraopera-
tive mortality was found to be a very rare event, confirming
both flexible and rigid endoscopy as safe techniques.
The ­I2 value for most groups was reported to be high. The
degree of heterogeneity could be explained by to the pres-
ence of other co-variates such as the type of hydrocephalus
(communicating, non-communicating, and normal pressure
hydrocephalus) and its etiology; however, we could not
assess their effect in the determination of the results due to
lack of data. Notably, study quality was not found to be a
source of heterogeneity as the results were not altered after
excluding the low-quality studies.
In the interpretation of the results of this study, a num-
ber of limitations needs to be taken into account. First, the
presence of reporting imbalance in the two techniques;
out of all the studies that were included in the final analy-
sis, only 10 studies reported data on flexible ETV, while
36 studies reported data on rigid ETV. The study design
consisted of case series and no other comparative studies.
Due to the lack of randomized control trials or compara-
tive (analytical) observational studies in the meta-analysis,
results need to be interpreted with caution due to pos-
sible confounding bias and other biases typically present
in case series. Hence, the p values comparing the pooled
point estimates between the 2 techniques were not derived.
A major challenge faced while conducting the study was
that only one study (Wang et.al) [57] had data for both
intervention arms directly compared in a propensity-score
matched cohort study, which were included as separate
13
Neurosurgical Review (2022) 45:199–216
groups in this analysis. The study included only pediatrics
and reported that rigid endoscopy had worse outcomes of
failure as compared with flexible endoscopy, which was
discordant with our findings. This begs the need for more
well-designed studies in pediatrics and adults in order to
accurately discern these differences. Notably, the type of
hydrocephalus and its etiology could not be taken into
account in the analysis due to lack of data, whereas in
clinical practice, these two factors are part of the deci-
sion-making process in the choice of treatment strategy.
Regardless, our aim was to evaluate efficacy and safety of
two approaches that are both endoscopic in nature, there-
fore specific considerations about indications for alterna-
tive treatments as, for example, shunt diversion, were out
the scope of this work.
Despite these limitations, our study had some strengths.
To our knowledge, this was the first meta-analysis per-
formed with the aim to evaluate efficacy and safety of
flexible vs rigid ETV for the treatment of hydrocepha-
lus. Another strength is the stratification of all safety and
efficacy outcomes by age category, while shedding light
on the available data in the entire neurosurgery literature
and suggesting steps needed for better designed studies to
address some uncertainties.
In conclusion, while our analysis could not depict a
clear superiority in terms of efficacy with regard to flex-
ible vs rigid endoscopy in the treatment of hydrocepha-
lus, our results suggested that both approaches presented
acceptable safety profiles, with some degree of variability
between age categories. Moving forward, well-designed
randomized controlled trials and comparative observa-
tional studies with larger sample sizes including patients
of different ages, types, and etiology of hydrocephalus are
needed in order to assess the optimal treatment options
between rigid ETV and flexible ETV for hydrocephalus
treatment.
Supplementary Information The online version contains supplemen-
tary material available at https://d​ oi.o​ rg/1​ 0.1​ 007/s​ 10143-0​ 21-0​ 1590-6.
Authors’ contribution AB was he proponent of the idea for this article
and contributed to manuscript draft and review. BM performed the
literature search and manuscript drafting; data analysis was performed
by BM and SC under the supervision of RAM. AP, FS, SD, AMA
contributed to paper screening and manuscript review. A Feletti, A
Fiorindi, PL, and FS contributed to critical revision of the manuscript.
TRS and RAM contributed to data analysis, critical revision, and super-
vision of the work.
Funding Open access funding provided by Università degli Studi di
Verona within the CRUI-CARE Agreement. No funding was received
to assist with the preparation of this manuscript.
Data availability Not applicable.
Code availability Not applicable.
Neurosurgical Review (2022) 45:199–216
Declarations
Ethics approval Not applicable.
Consent to participate Not applicable.
Consent for publication Not applicable.
Conflict of interest No conflict of interest or competing interests to
report related to this work.
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13
Child's Nervous System
https://doi.org/10.1007/s00381-021-05129-4

CASE REPORT

Endoscopic third ventriculostomy for hydrocephalus in a patient

with achondroplasia: a case report and literature review
Kenji Shoda 1 & Naoyuki Ohe 1 & Hideo Sasai 2 & Masafumi Miyai 3 & Hidenori Ohnishi 2 & Toru Iwama 1

Received: 27 January 2021 / Accepted: 11 March 2021

# The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021

Abstract
Hydrocephalus, a complication of achondroplasia, requires treatment when it is symptomatic. Hydrocephalus associated with
achondroplasia is often treated with ventriculoperitoneal shunting, and endoscopic third ventriculostomy (ETV) is rarely per-
formed in these patients. Here, we report the case of an 18-month-old boy with achondroplasia and progressive hydrocephalus
who underwent ETV. He had a family history of achondroplasia and was diagnosed with achondroplasia at birth. Magnetic
resonance imaging (MRI) at the age of 1 month showed no hydrocephalus. At the age of 15 months, he was admitted to our
hospital due to increased head circumference. He had developmental delays, and MRI showed hydrocephalus with ballooning of
the third ventricle. The ETV success score was 80 points; therefore, we performed ETV. Postoperatively, the progression of head
circumference increase was controlled. The ventricular size remained unchanged on MRI at 13 months after surgery. Recently, an
association between non-communicating hydrocephalus and achondroplasia has been reported. Depending on age and imaging
findings, ETV may be effective in some patients with achondroplasia with hydrocephalus.

Keywords Achondroplasia . Hydrocephalus . Endoscopic third ventriculostomy . Triventricular

Introduction treatment of hydrocephalus in achondroplasia. However, a

Achondroplasia is a disorder of chondrocyte function occur-
ring in approximately 1 in 20,000 live births [13]. Its charac-
teristic features are disproportionately short stature,
macrocephaly with frontal bossing, and midface hypoplasia
[4]. Hydrocephalus is a complication of achondroplasia, and
neurosurgical treatment is necessary if patients have neurolog-
ical symptoms or signs of raised intracranial pressure, such as
headache or papilledema. Ventriculoperitoneal (VP) shunting
is usually performed for treatment because the hydrocephalus
is of the communicating type [12]. Endoscopic third
ventriculostomy (ETV) is useful for non-communicating hy-
drocephalus and is generally not recommended for the
* Kenji Shoda
sho_ken@gifu-u.ac.jp
1
Department of Neurosurgery, Graduate School of Medicine, Gifu
University, 1-1 Yanagido, Gifu, Gifu 501-1194, Japan
2
Department of Pediatrics, Graduate School of Medicine, Gifu
University, Gifu, Japan
3
Department of Neurosurgery, Ogaki Tokusyukai Hospital,
Gifu, Japan
recent study suggested that non-communicating hydrocepha-
lus may occur in some cases of achondroplasia [1], and there
are reports of hydrocephalus in achondroplasia being treated
with ETV [3, 6, 15]. With advances in the device and tech-
nique, ETV is becoming less complicated, and its use is rap-
idly increasing [11]. Herein, we report the case of a patient in
whom ETV was performed to treat hydrocephalus associated
with achondroplasia.
Case description
The patient was an 18-month-old boy with a family history of
achondroplasia. He had short femoral length and large
biparietal diameter on fetal ultrasound, and was diagnosed
with achondroplasia at birth. Magnetic resonance imaging
(MRI) at the age of 1 month showed no foramen magnum
narrowing or increased ventricular size (Fig. 1a, b).
Subsequently, progressive enlargement of the head occurred,
and MRI at the age of 15 months showed stenosis of the
foramen magnum and marked hydrocephalus (Fig. 1c, d).
He could walk with support and did not have sleep apnea,
deglutition disorder, muscle weakness, or motor impairment.
 Childs Nerv Syst

Fig. 1 Axial and sagittal

magnetic resonance images. a and
b were obtained at 1 month,
showing no increased ventricular
size or foramen magnum
narrowing. c and d were obtained
at 15 months, showing dilatation
of the lateral and third ventricles
and foraminal stenosis

His head size was more than two standard deviations above
normal, and his developmental quotient score was 79, which
suggested developmental delay due to hydrocephalus. MRI
showed hydrocephalus with ballooning of the third ventricle
(triventricular). He had an Endoscopic Third Ventriculostomy
Success Score (ETVSS) [9] of 80. Therefore, ETV was per-
formed at 18 months of age (Fig. 2). Intraoperatively, the
intracranial pressure was elevated (13cm H2O). No complica-
tions related to the ETV procedure occurred, and decreased
ventricular size was seen on MRI at 1 month postoperatively
(Fig. 3a, b). At 10 months postoperatively, the patient’s de-
velopmental quotient score improved to 100. Ventricular size
was stabilized, and stoma patency was confirmed on MRI at
13 months postoperatively (Fig. 3c, d).
Discussion
Hydrocephalus is a common feature of achondroplasia, occur-
ring in 15–50% of cases [14]. It is generally left untreated in
cases without symptoms other than head enlargement and
ventriculomegaly. Hydrocephalus in achondroplasia is usual-
ly of the communicating type and is related to increased dural
venous sinus pressure, which impairs cerebrospinal fluid

Fig. 2 The intraoperation view of

the third ventricle floor. The
mammillary body was divided
into left and right. The tuber
cinereum was thin, and the basilar
artery could be seen through it.
The arrow heads indicate the
mammillary body, and the arrow
indicates the basilar artery
Childs Nerv Syst

Fig. 3 Axial and sagittal

magnetic resonance images. a and
b were obtained at 1 month after
endoscopic third ventriculostomy
(ETV) and show decreased ven-
tricular size. c and d were obtain-
ed at 13 months after ETV.
Ventricular size and stomal pa-
tency remain unchanged

(CSF) absorption [12, 16]; some cases are associated with
non-communicating hydrocephalus caused by stenosis of the
Sylvian aqueduct or obstruction of CSF outflow from the
fourth ventricle [1]. In cases of communicating hydrocepha-
lus, VP shunting is usually performed. However, it is associ-
ated with a high rate of shunt malfunction in children, (48% in
children at 5 years) [17]; King et al. reportedly performed 40
shunt revisions in 11 patients with achondroplasia [6].
There are few who reported that ETV was performed for
hydrocephalus with achondroplasia (Table 1). They had a
good clinical course and no recurrence. Swift et al. reported
improved symptoms and decreased ventricular size following
ETV in three patients who underwent foramen magnum de-
compression [15]. They suggested that non-communicating
hydrocephalus may be a good indication for ETV in these
patients. Etus et al. performed ETV in two patients with
achondroplasia who presented with headache due to hydro-
cephalus; the headache disappeared after ETV [3]. They sug-
gested that ETV is useful in patients with achondroplasia who
have triventricular hydrocephalus. Triventricular hydrocepha-
lus, which is frequently seen in patients with non-
communicating hydrocephalus, suggests the existence of a

Table 1 All report cases of endoscopic third ventriculostomy for hydrocephalus in patients with achondroplasia

Reference Age Follow- Symptoms ETVSS Recurrence History of shunt Triventricular

up hydrocephalus

[3] 14 yrs 24 mos Headache 90 No No Yes

12 yrs 7 mos Headache, decline in school success 90 No No Yes
[6] 8 yrs ND Headache 80 No No Yes
[15] 11 mos 84 mos Progressive ventricular enlargement 70 No No Yes
33 mos 96 mos Increasing ICP 70 No Yes Yes
12 yrs 60 mos Headache, decline in school success, increasing ICP 80 No Yes Yes
Our case 18 mos 13 mos Development disorder, increasing ICP 80 No No Yes

ETVSS Endoscopic Third Ventriculostomy Success Score, yrs years, mos months, ND not described, ICP intracranial pressure

pressure gradient between the third ventricle and prepontine
cistern and is a good indication for ETV [5]. Achondroplasia
is associated with triventricular rather than tetraventricular [2]
hydrocephalus; all the patients who underwent ETV in previ-
ous reports had triventricular hydrocephalus [3, 6, 15]. Etus
et al. reported that care should be taken, when performing
ETV, as the shape of the floor of the third ventricle changes
due to longstanding hydrocephalus [3].
Our case also presented with triventricular hydrocephalus
which may be related to foramen magnum stenosis. The
ETVSS of the patient was 80 points; this was considered a
good indication for ETV. Postoperatively, the ventricle size
decreased, and it seemed unchanged on routine MRI after 13
months. Similarly, in previous reports, symptoms improved
after ETV. Moreover, during the follow-up period, no recur-
rence was observed either in symptoms or on MRI findings.
For an ETVSS of 80 or higher, the success rate at 6 months
after surgery is reported to be 75.9% [8]. In addition, in chil-
dren over the age of 6 months, the success rates of ETV for
cerebral aqueduct stenosis are similar to those of VP shunting
[10]. Furthermore, age may have been a factor for the success
of this technique; the minimum age among all reported cases
was 11 months. In cases of achondroplasia, follow-up is only
recommended if the head circumference has increased [4, 7],
and it is expected that the age of intervention will be higher
than that in congenital hydrocephalus of other causes.
Therefore, depending on age and imaging findings, treatment
with ETV might be useful in patients with hydrocephalus and
achondroplasia. Although a few reports of successful treat-
ment of hydrocephalus following ETV in patients with achon-
droplasia exist, further studies are needed to prove the effec-
tiveness of the procedure.
Conclusion
We report a case of hydrocephalus in achondroplasia that was
successfully treated with ETV. Hydrocephalus in achondro-
plasia may be of the non-communicating type. ETV may be
useful in these patients, depending on age and imaging
findings.
Data availability The datasets used in the current study are available from
the corresponding author upon reasonable request.
Declarations
Ethics approval For this type of study, formal consent is not required.
Consent to participate Not applicable.
Consent for publication Not applicable.
Childs Nerv Syst
Conflict of interest The authors declare that they have no conflict of
interest.
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Poretti A (2015) Achondroplasia in children: correlation of
ventriculomegaly, size of foramen magnum and jugular foramina,
and emissary vein enlargement. Childs Nerv Syst 31:129–133.
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2. Erdinçler P, Dashti R, Kaynar MY, Canbaz B, Ciplak N, Kuday C
(1997) Hydrocephalus and chronically increased intracranial pres-
sure in achondroplasia. Childs Nerv Syst 13:345–348. https://doi.
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3. Etus V, Ceylan S (2005) The role of endoscopic third
ventriculostomy in the treatment of triventricular hydrocephalus
seen in children with achondroplasia. J Neurosurg 103(3 Suppl):
260–265. https://doi.org/10.3171/ped.2005.103.3.0260
4. Horton WA, Hall JG, Hecht JT (2007) Achondroplasia. Lancet
370:162–172. https://doi.org/10.1016/S0140-6736(07)61090-3
5. Kehler U, Regelsberger J, Gliemroth J, Westphal M (2006)
Outcome prediction of third ventriculostomy: a proposed hydro-
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https://doi.org/10.1055/s-2006-950382
6. King JAJ, Vachhrajani S, Drake JM, Rutka JT (2009)
Neurosurgical implications of achondroplasia. J Neurosurg
Pediatr 4:297–306. https://doi.org/10.3171/2009.3.PEDS08344
7. Kubota T, Adachi M, Kitaoka T, Hasegawa K, Ohata Y, Fujiwara
M, Michigami T, Mochizuki H, Ozono K (2020) Clinical practice
guidelines for achondroplasia. Clin Pediatr Endocrinol 29:25–42.
https://doi.org/10.1297/cpe.29.25
8. Kulkarni AV, Riva-Cambrin J, Holubkov R, Browd SR, Cochrane
DD, Drake JM, Limbrick DD, Rozzelle CJ, Simon TD, Tamber
MS, Wellons JC III, Whitehead WE, Kestle JRW, Hydrocephalus
Clinical Research Network, for the Hydrocephalus Clinical
Research Network (2016) Endoscopic third ventriculostomy in
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(2009) Endoscopic third ventriculostomy in the treatment of child-
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10. Kulkarni AV, Sgouros S, Constantini S, IIHS Investigators (2016)
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(1979) Achondroplasia and hypochondroplasia. Comments on fre-
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Journal Pre-proof

The Use of Endoscopic Third Ventriculostomy as Treatment for Idiopathic Intracranial

Hypertension: Case Report and a Review of Previously Reported Cases

Delano Trenchfield, Long Di, Ashish Shah, Devarsh Desai, Pavan Gudoor, Daniel G.
Eichberg, Evan M. Luther, Michael E. Ivan, Ricardo J. Komotar

PII: S1878-8750(20)31346-2
DOI: https://doi.org/10.1016/j.wneu.2020.06.088
Reference: WNEU 15307

To appear in: World Neurosurgery

Received Date: 24 April 2020

Accepted Date: 10 June 2020

Please cite this article as: Trenchfield D, Di L, Shah A, Desai D, Gudoor P, Eichberg DG, Luther EM,
Ivan ME, Komotar RJ, The Use of Endoscopic Third Ventriculostomy as Treatment for Idiopathic
Intracranial Hypertension: Case Report and a Review of Previously Reported Cases, World
Neurosurgery (2020), doi: https://doi.org/10.1016/j.wneu.2020.06.088.

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The Use of Endoscopic Third Ventriculostomy as Treatment for Idio

pathic Intracranial Hypertension: Case Report and a Review of Pre

viously Reported Cases

Delano Trenchfielda, Long Dib, Ashish Shahc, Devarsh Desaid, Pavan Gudoore,

Daniel G. Eichbergf, Evan M. Lutherg, Michael E. Ivanh, Ricardo J. Komotari

a
Medical Student, University of Miami School of Medicine (highest degree B.S.)
b
Medical Student, University of Miami School of Medicine (highest degree B.S)
c
Department of Neurological Surgery, University of Miami (MD)
d
Undergraduate student, University of Miami
e
Undergraduate student, University of Miami
f
Department of Neurological Surgery, University of Miami (MD)
g
Department of Neurological Surgery, University of Miami (MD)
h
Department of Neurological Surgery, University of Miami (MD)

Affiliation Address:1600 NW 10th Avenue, Miami, FL, USA, 33136.

Corresponding Author: Delano Trenchfield (drt19@med.miami.edu, 8681 Lakeside Bend,

Parkland, FL, 33076.

Key Words:

1. Endoscopic third ventriculostomy

2. Idiopathic intracranial hypertension

3. Lumboperitoneal shunt

4. Ventriculoperitoneal shunt

5. Treatment

Short Title: Treating IIH with ETV

The Use of Endoscopic Third Ventriculostomy as Treatment for Idio

pathic Intracranial Hypertension: Case Report and a Review of Pre

viously Reported Cases

Key Words:

1. Endoscopic third ventriculostomy

2. Idiopathic intracranial hypertension

3. Lumboperitoneal shunt

4. Ventriculoperitoneal shunt

5. Treatment

______________________________________________________________________________

Abstract

Background: Idiopathic intracranial hypertension (IIH), or pseudotumor cerebri (PTC), is a

rare disorder marked by the increase of CSF pressure that may cause severe headaches,

papilledema, vision loss, and more. IIH is typically treated with shunts, but shunts are prone to

malfunction and infection, resulting in many patients experiencing recurrent headaches post-

treatment.

Case Description: We present the case of a 41-year-old woman with IIH who exhibited a

history of severe headaches and seizures with documented elevated intracranial pressure (OP:

250 mm H2O). After the failure of several medical treatments, the patient was offered surgery for

symptomatic relief. Given their ventricular anatomy and preference, the patient’s IIH was treated

with endoscopic third ventriculostomy (ETV) rather than the conventional shunt.

1
 Trenchfield

Conclusion: Reported resolution of the patient’s headaches and improved quality of life

following the procedure indicated that ETV can be used to treat IIH if ventricles are not

completely slit-like. Additionally, we detail a review of all previously reported cases in which

ETV was used for the treatment of IIH.

Introduction

Idiopathic intracranial hypertension (IIH) is a rare disorder characterized by an increase in

CSF pressure due to an unknown etiology, most often presenting in obese females.1 Headaches,

papilledema, and visual loss are typical markers of IIH, but other symptoms including

photophobia, nausea, pulsatile tinnitus, visual field defects, and diplopia may be present as well.
2-4
This condition is most commonly diagnosed using the modern Dandy criteria which requires

1) the absence of impaired consciousness and neurological abnormalities (excluding abducens

nerve palsies) 2) a CSF opening pressure of >250 mm H2O following lumbar puncture in adults

and >280 mm in children 3) normal CSF composition 4) the lack of etiology for increased ICP

upon imaging review. 1,2,4 A diagnosis may also be made without the presence of papilledema if

imaging reveals further findings that align with IIH such as an empty sella or transverse sinus

stenosis.2 Presurgical treatment for IIH includes acetazolamide and lifestyle modifications, and,

if unsuccessful, surgical interventions such as optic nerve sheath fenestration,

ventriculoperitoneal or lumboperitoneal shunts, sinus stenting, and bariatric surgery are

performed5. Endoscopic third ventriculostomy (ETV) is another procedure often used to alleviate

increased ICP in the presence of obstructive hydrocephalus that doesn’t involve implantation of a

shunt tubing or valve.6 ETV obviates the need for shunt placement and maintenance, offering

several advantages such as the need for fewer incisions and lower long-term complication rate.7

2
 Trenchfield

We present the case of a patient with IIH treated with ETV that experienced significant

symptomatic relief and quality of life improvement.

Case Description

A 41-year-old female experiencing severe headaches arrived at our clinic following a

seizure-like episode that resulted in the loss of consciousness. She suffered from persistent

headaches despite a normal physical examination, and as a result, she underwent 3 lumbar

punctures. Each confirmed elevated ICP (>250 mm H2O) with transient relief of symptoms. Over

the ensuing years, she was given extended release Diamox 500 mg twice daily, but symptoms

recurred necessitating a neurosurgical referral. The patient didn’t have papilledema and denied

any vision loss or other focal neurological deficits. MRI/MR Venography did not demonstrate

any significant radiological abnormalities (patent venous sinuses, no structural abnormality). A

clinical diagnosis of IIH was made and the patient was advised of potential options including an

endoscopic third ventriculostomy and a ventriculoperitoneal shunt for treatment-refractory IIH.

Given that the ventricles were not slit-like, ETV was recommended due to the significant long-

term morbidity associated with ventriculoperitoneal shunts. Following patient consent, an ETV

was performed with no peri-operative complications. Of note, the foramen of Munro was noted

too small intraoperatively, which necessitated a foraminoplasty with balloon assistance to

facilitate the ETV. This was successfully performed without damaging the fornix. The patient

was discharged on post-operative day 1. At a two-week follow-up, the patient was doing well

postoperatively with the resolution of her headaches. At a four-month follow-up, the patient

continued to experience a dramatic improvement in preoperative symptoms.

Discussion

3
 Trenchfield

Idiopathic intracranial hypertension (IIH), or pseudotumor cerebri (PTC), is a rare disorder

that causes elevated intracranial pressures of unknown etiology.1 IIH only affects 1 out of

100,000 individuals annually.3 However, the incidence rate for obese of childbearing age

significantly increases to 19 per 100,000 in North America.8 It primarily affects obese women as

approximately 90% of those diagnosed with IIH are female and 94% are obese.1

Classically, the triad of symptoms representative of IIH includes daily severe headaches,

papilledema, and vision loss.4 Other possible symptoms are photophobia, nausea, pulsatile

tinnitus, visual field defects, diplopia, photopsia, retrobulbar pain, and abducens nerve palsy.2,3

Papilledema is usually considered the defining symptom of IIH, and can result in severe

morbidity if left untreated.3 10% to 25% of patients develop visual loss secondary to chronic

papilledema due to damage done to the optic disk.3,7 Although headaches are the most reported

symptom, visual loss remains the most feared complication.2 Our patient complained of

persistent headaches with no visual loss.

Although the modern Dandy criteria is the most commonly used method to diagnose IIH,

diagnosis can also be made without the presence of papilledema if other signs of IIH, such as an

empty sella, transverse venous sinus stenosis, cerebellar tonsillar descent, slit-like ventricles,

flattening of the posterior aspect of the globe, distention of the subarachnoid perioptic space, or

protrusion of the optic nerve papillae into the vitreous, are present.2,9

The exact cause of IIH is unknown, but there have been several proposed mechanisms

attempting to explain its occurrence, such as CSF hypersecretion. However, in patients with

excess CSF production, there is often development of ventriculomegaly and hydrocephalus,

whereas normal or decreased ventricular size is seen in IIH.7 Malabsorption of CSF due to a

decreased gradient between CSF and venous pressures is also a common etiology. This is evident

4
 Trenchfield

in obese individuals whose intra-abdominal pressures are elevated, which is transmitted via

venous vessels to the spine, resulting in increased intracranial pressure and decreased venous

return from the brain.2,4 Cerebral venous stenosis, particularly in the bilateral or dominant

transverse sinuses, is an imaging finding seen in most patients. It is possible that stenoses cause

decreased venous outflow, which also slows CSF reabsorption. However, several case studies

have shown improvement in patency of stenoses with CSF drainage suggesting that stenoses

develop as a result of increased intracranial pressure as opposed to being an underlying cause.4

Another mechanism grounded on obesity focuses on the link between obesity and increased

levels of cytokines and interleukins, suggesting an inflammatory component.4 In a study

analyzing the concentrations of 14 cytokines, IIH was found to be associated with elevated levels

of IL-17 and IL-2 in the CSF.5 In addition, chronic inflammation associated with obesity can

lead to a pro-thrombotic state leading to the development of IIH.8

Loss of 5 to 10 percent of total body weight usually alleviates symptoms of IIH.4 The major

drawbacks of this method of lifestyle modification are weight loss being too much of a long-term

solution when acute symptoms such as vision loss are also present, and difficulty maintaining

weight loss long-term if this method is employed.8 Hence, bariatric surgery is an excellent

alternative to achieve alleviation.9 Bariatric surgery in IIH patients may lead to the resolution of

papilledema and a return to normal CSF pressures.5 It may also be appropriate for obese patients

who continue to experience symptoms of IIH after medical or surgical treatment.9

Acetazolamide (Diamox) has been the traditional primary medical treatment route for IIH.4

It inhibits CSF production through inhibition of cerebral carbonic anhydrase and serves as a mild

diuretic.5 It has been shown to reduce CSF production by up to 50 percent and has been highly

effective for treating mild visual loss and severe papilledema.5 However, its effects on treating

5
 Trenchfield

headaches are not well known so headache medications such as topiramate are usually

administered if headaches persists.5,8 Acetazolamide yielded unsuccessful results in eliminating

our patient’s headaches.

Optic nerve sheath fenestrations (ONSF), having replaced subtemporal decompression, is

usually performed when the patient reports visual loss with papilledema and medical treatment

has failed.4 Several slits are made in the dura and arachnoid mater posterior to the globe to drain

CSF and decrease optic nerve edema.5 In the right setting, ONSF may lead to improvements in

visual fields and visual acuity.5 Even if performed in a single eye, the contralateral eye could

have improvements in the degree of papilledema.3 ONSF has also shown to improve headaches

in 50 percent of patients, although its effect on ICP has not been well-established.3,5 A drawback

of ONSF is that the results are not durable; at one-year and three-year follow-ups, ONSF has

failure rates of 34% and 45%, respectively.3 Patients may even need repeat surgery.1

Complications include hemorrhage, ophthalmoplegia, infection, diplopia, and loss of vision from

central retinal artery occlusion or neuropathy.3,5

CSF diversion with a ventriculoperitoneal (VPS) or lumboperitoneal (LPS) shunt is usually

performed when the main symptom is headache but it also stabilizes papilledema, vision loss,

and diplopia.1,5 Both types of shunt use a one-way valve to control CSF flow, but VPS leads to

fewer revisions, decreased shunt migration, and shorter hospital stays.1,3 Shunts also provide

visual stability in 90% of patients.3 Headache improves in almost all patients after shunting, but

50 percent of patients end up experiencing recurrent severe headaches within 3 years.4 Shunts are

associated with several complications, including infection, CSF leakage, abdominal or back pain,

and malfunction requiring revision.3

6
 Trenchfield

Venous stenting is a very effective and low complication procedure used to treat occlusion of

the cerebral venous sinuses.5 Up to 93% of patients diagnosed with IIH have stenosis within the

dural venous sinus system.10 Venous stenting results in significant improvements of headaches,

papilledema, pulsatile tinnitus, and decreased pressure gradients.8,10 Possible complications of

the procedure include ipsilateral headache, intracranial hemorrhage, proximal stent stenosis, in-

stent thrombosis, and stent migration.1 Before and after stenting, patients are typically

maintained on ant-platelet therapy to prevent stent thrombosis.

Endoscopic third ventriculostomy (ETV) has the advantage of providing physiological

cerebrospinal fluid diversion without the need for shunt placement, thereby reducing the risk of

subsequent infection and malfunction.10 It is used mainly to treat obstructive hydrocephalus by

creating an opening in the floor of the third ventricle (tuber cinereum) using an endoscope to

permit CSF drainage into the basal cisterns and bypass the obstruction. Traditionally, ETV has

been utilized in cases of hydrocephalus secondary to congenital aqueductal stenosis, obstructive

tumors/masses, cerebellar infarcts, and multiloculated hydrocephalus. However, over the last

decade, indications for ETV have been expanded to include traditional communicating

hydrocephalus (preterm hemorrhagic hydrocephalus of childhood, normal pressure

hydrocephalus, and post-infectious hydrocephalus).11 In IIH cases, ETV is able to redirect CSF

to naïve subarachnoid spaces which may be able to absorb CSF since traditional mechanisms of

CSF absorption in the lateral ventricles may be impaired. Small ventricles and difficult

ventricular floor anatomy are two important factors that can affect the difficulty and outcome of

the procedure, but overall, the success rate of ETV has been increasing with decreasing

morbidity and mortality.12

7
 Trenchfield

To our knowledge, our case represents one of the first successful attempts to treat classic IIH

with an ETV. In our review of the literature, we were able to find one case where ETV was used

to treat IIH as the last option. A 16-year-old girl, diagnosed with IIH at 12, underwent 26 lumbar

punctures, 9 LP shunts, bilateral subtemporal decompressions, VP shunts with 8 revisions, a

foramen magnum decompression, and 2 cisterna magnum–peritoneal shunts. Procedures

continued to fail so ETV was performed as an alternative but, unfortunately, the ETV failed

within 24 hours as she began leaking CSF from the site of her previous foramen magnum

decompression.12 However, this case may not be an accurate representation of the efficacy of

ETV for IIH given the extensive surgical history of this patient. Excessive CSF leakage from her

many prior drainage procedures most likely contributed to treatment failure. ETV was pursued in

our patient as the primary surgical option with great success and quality of life improvement. We

believe, following imaging evaluation in anatomically suitable patients, ETV may be pursued as

a less invasive procedure to facilitate CSF outflow/redirection and decrease risk of long-term

shunt-associated morbidity.

Conclusion

The most common surgical treatment for IIH is CSF diversion using a shunt, and it is usually

performed when headaches are the main complaint.1 However, shunts are prone to infection and

malfunction.12 ETV offers immediate relief of headaches like shunts do, but the chance of

infection is significantly less after ETV than after a shunt. The concern of a future

malfunctioning shunt or revision is also avoided entirely. As the indications for ETV continue to

expand beyond obstructive hydrocephalus, our case highlights its ability to successfully and

effectively treat IIH if the ventricles are not completely slit-like.

8
Basic and Clinical
May, June 2019, Volume 10, Number 3

Review Paper: Comparing the Efficiency of Two Treatment

Methods of Hydrocephalus: Shunt Implantation and
Endoscopic Third Ventriculostomy
Seifollah Gholampour1* , Mehrnoush Bahmani1 , Azadeh Shariati1

1. Department of Biomedical Engineering, Faculty of Electrical & Computer Engineering, Tehran North Branch, Islamic Azad University, Tehran, Iran.

Use your device to scan

and read the article online
Citation Gholampour, S., Bahmani, M., & Shariati, A. (2019). Comparing the Efficiency of Two Treatment Methods of Hy-
drocephalus: Shunt Implantation and Endoscopic Third Ventriculostomy. Basic and Clinical Neuroscience, 10(3), 185-198. http://
dx.doi.org/10.32598/bcn.9.10.285
: http://dx.doi.org/10.32598/bcn.9.10.285

AB STRACT

Introduction: Hydrocephalus is one of the most common diseases in children, and its treatment
requires brain operation. However, the pathophysiology of the disease is very complicated and
Article info:
still unknown.
Received: 17 May 2018
First Revision: 28 Jun 2018 Methods: Endoscopic Third Ventriculostomy (ETV) and Ventriculoperitoneal Shunt (VPS)
implantation are among the common treatments of hydrocephalus. In this study, Cerebrospinal
Accepted: 26 Aug 2018
Fluid (CSF) hydrodynamic parameters and efficiency of the treatment methods were compared
Available Online: 01 May 2019
with numerical simulation and clinical follow-up of the treated patients.
Results: Studies have shown that in patients under 19 years of age suffering from hydrocephalus
related to a Posterior Fossa Brain Tumor (PFBT), the cumulative failure rate was 21% and
29% in ETV and VPS operation, respectively. At first, the ETV survival curve shows a sharp
decrease and after two months it gets fixed while VPS curve makes a gradual decrease and
reaches to a level lower than ETV curve after 5.7 months. Post-operative complications in
ETV and VPS methods are 17% and 31%, respectively. In infants younger than 12 months
with hydrocephalus due to congenital Aqueduct Stenosis (AS), and also in the elderly patients
suffering from Normal Pressure Hydrocephalus (NPH), ETV is a better treatment option.
Computer simulations show that the maximum CSF pressure is the most reliable hydrodynamic
Keywords: index for the evaluation of the treatment efficacy in these patients. After treatment by ETV and
Cerebrospinal Fluid, shunt methods, CSF pressure decreases about 9 and 5.3 times, respectively and 2.5 years after
Intracranial Pressure, shunt implantation, this number returns to normal range.
Intracranial compliance, Conclusion: In infants with hydrocephalus, initial treatment by ETV was more reasonable
Survival curve, Reynolds than implanting the shunt. In adult with hydrocephalus, the initial failure in ETV occurred
number, CSF velocity sooner compared to shunt therapy; however, ETV was more efficient.

* Corresponding Author:
Seifollah Gholampour, PhD.
Address: Department of Biomedical Engineering, Faculty of Electrical & Computer Engineering, Tehran North Branch, Islamic Azad University,
Tehran, Iran.
Tel: +98 (21) 77009836-42
E-mail: s.gholampour@iau-tnb.ac.ir

185
 Basic and Clinical
May, June 2019, Volume 10, Number 3

Highlights

● Although in adult hydrocephalus, the effectiveness of shunt implantation is better in the short term, Endoscopic
Third Ventriculostomy (ETV) is a more appropriate option in the long term.

● Cerbrospinal Fluid (CSF) volume and more importantly CSF pressure are the most effective hydrodynamic param-
eters in evaluating the treatment methods of hydrocephalus.

● After treatment by the ETV and shunt methods, CSF pressure decreases about 9 and 5.3 times, respectively.

● ETV is a potentially safer option for hydrocephalus in patients with osteoporosis.

Plain Language Summary

The imbalance between CSF production and absorption or CSF path obstruction results in hydrocephalus. It is one
of the most common diseases in children. Endoscopic Third Ventriculostomy (ETV) and Ventriculoperitoneal Shunt
(VPS) implantation are among the common treatment methods of hydrocephalus. However, the pathophysiology of
the disease is still unknown. ETV is a better treatment option in infants younger than 12 months with hydrocephalus
due to congenital Aqueduct Stenosis (AS) and also elderly patients suffering from Normal Pressure Hydrocephalus
(NPH). In adult hydrocephalus, the long-term effectiveness of ETV is better. Volume and especially pressure were
the most effective parameters in evaluating the treatment methods of hydrocephalus. After treatment by the ETV and
shunt methods, CSF pressure decreases about 9 and 5.3 times, respectively and 2.5 years after shunt implantation, this
number returns to the normal range.

1. Introduction through perineural space; while some part of it will be

H
ydrocephalus is one of the most common
diseases in children (Karimy et al., 2016;
Muir, Wang, & Warf, 2016). In devel-
oped countries, congenital hydrocephalus
prevalence is 0.5-1 per 1000 live-born in-
fants. Whereas, the prevalence of acquired hydrocepha-
lus is 3 to 5 per 1000 live-born infants (Wiswell, Tuttle,
Northam, & Simonds, 1990; Chi, Fullerton, & Gupta,
2005; Munch et al., 2012; Tully & Dobyns, 2014). The
prevalence of idiopathic Normal Pressure Hydrocepha-
lus (iNPH) has been reported to be 1.8 to 2.2, respective-
ly per 100000 and 1000000 people (Gallia, Rigamonti,
& Williams, 2006).
To properly understand the hydrocephalus, it is neces-
sary to initially discuss the production and absorption
of Cerebrospinal Fluid (CSF) and its pathway. CSF is
mainly produced by choroid plexus in the lateral, third
and fourth ventricles (Wise & Schlosser, 2007;‌Brinker,
Stopa, Morrison, & Klinge, 2014). Ependymal cells and
capillaries also play minor roles in the secretion of CSF
(Kagerbauer et al., 2013). Through arachnoid granula-
tions, CSF will be drained into venous sinuses and then
to the lymphatic system via Virchow-Robin spaces.
Next, it will be mostly drained into craniospinal nerves
drained into the spinal cord (Brinker et al., 2014; Ducros
& Biousse, 2015).
CSF circulates within cerebral ventricles (laterals, the
third and fourth ventricles and aqueducts) and cere-
brospinal Subarachnoid Space (SAS) (Sakka, Coll, &
Chazal, 2011). In general, CSF volume is about 160 mL
that 25% of this volume is circulating within ventricles
and 75% in spinal and subarachnoid cortical spaces
(Bateman, Stevens, & Stimpson, 2009). The Mean±SD
production rate of CSF is equal to 0.34±0.13 mL/min;
the average CSF absorption rate in the spinal cord is
0.17 mL/min (Edsbagge, Tisell, Jacobsson, & Wikkelso,
2004). It should be mentioned that under normal physi-
ological condition, CSF circulation has fixed inflow and
pulsing (Davis & Cushing 1925;‌ Taketomo & Saito,
1965; Milhorat, 1975).
The most important hydrodynamic parameter indicat-
ing the incidence of hydrocephalus is the CSF pressure
(Gholampour, Fatouraee, Seddighi, & Yazdani, 2014;
Fatouraee, Gholampour, & Seddighi, 2015; Hajirayat,
Gholampour, Seddighi, & Fatouraee, 2016; Gholampour,
Hajirayat, Erfanian, Zali, Shakouri, 2017; Gholampour,
Fatouraee, Seddighi, & Seddighi, 2017a; Gholampour,

186 Gholampour, S., et al. Comparing the Efficiency of Two Treatment Methods of Hydrocephalus. BCN, 10(3), 185-198.
Basic and Clinical
Fatouraee, Seddighi, & Seddighi, 2017b; Gholampour,
2018; Gholampour & Taher, 2018).
Intracranial Pressure (ICP) refers to the numerical val-
ues of CSF pressure in upper convexity of the brain in
SAS. It should be noted that ICP wave differs from the
Arterial Blood Pressure (ABP) wave (Schmidt et al.,
2018). ICP values in normal infants younger than one
year, children, and adults are respectively 3-4 mm Hg,
11 mm Hg, and 10-15 mm Hg (Ekstedt, 1978; Malm,
Jacobsson, Birgander, & Eklund, 2011; Sakka et al.,
2011; Lawley et al., 2015). Biological fluid flow such
as CSF for healthy subjects and also hydrocephalus pa-
tients have been described through Navier-Stokes and
Arbitrary Lagrangian-Eulerian (ALE) equations (Ma,
Liu, Zu, & Tang, 2012; Gholampour et al., 2017a), using
Computational Fluid Dynamics (CFD) solution methods
and Fluid-Structure Interaction (FSI) simulation.
Many CSF circulation parameters such as CSF flow veloc-
ity and flow rate diagrams for patients with hydrocephalus
and healthy subjects are measured via Cine phase contrast
Magnetic Resonance Imaging (Cine PC-MRI). Meanwhile,
these equipment are more useful to understand the patients’
pathophysiology (Linninger et al., 2007; Akutsu et al.,
2018). ICP may be measured by an invasive method, ICP
monitoring, and or by noninvasive computer simulations as
CFD and FSI (Eide, Holm, & Sorteberg, 2012; Gholam-
pour et al., 2014; Fatouraee et al., 2015).
2. Hydrocephalus
The imbalance between production and absorption of
CSF or obstruction of CSF flow path results in hydro-
cephalus. This causes ventricular dilatation and increas-
es ICP (Langner et al., 2017). It is almost one century
ago that Dandy performed the first empirical studies on
hydrocephalus (Greitz, 2004).
2.1. Various types of hydrocephalus
Dandy and Blackfan categorized hydrocephalus in
three groups of Non-Communicating Hydrocephalus
(NCH), Communicating Hydrocephalus (CH), and Nor-
mal Pressure Hydrocephalus (NPH) (Dandy & Blackfan,
1914; Eide & Pripp, 2016). There are numerous defini-
tions for these three groups. However, the most common
definitions for these groups are as follows:
2.1.1. Communicating hydrocephalus
CSF circulation path in Subarachnoid Space is ob-
structed, whereas CSF is still circulating between brain
Gholampour, S., et al. Comparing the Efficiency of Two Treatment Methods of Hydrocephalus. BCN, 10(3), 185-198.
May, June 2019, Volume 10, Number 3
ventricles (Hakim, & Adams, 1965; Tasiou, Brotis,
Esposito, & Paterakis, 2016). Communicating Hydro-
cephalus (CH) results from obstruction in basic cisterns
level or arachnoid villi. It is also called extra-ventricular
obstructive hydrocephalus (Rekate, 2009).
2.1.2. Non-Communicating Hydrocephalus
An obstruction or abnormality exists in CSF flow with-
in the ventricular system. Usually, the Sylvius aqueduct,
a connection between the third and fourth ventricles of
the brain, is blocked, resulting in obstruction of CSF
flow through ventricles (Sæhle & Eide, 2015; Eide &
Pripp, 2016). NCH is mostly called obstructive hydro-
cephalus and is described as intraventricular CSF flow
obstruction (Maller & Gray, 2016).
2.1.3. Normal pressure hydrocephalus
It is a chronic disorder resulted from interrupted CSF
absorption or flow (Kang et al., 2018), when CSF vol-
ume increases in the lateral, third and fourth ventricles,
with no considerable increase in ICP. The pathophysiol-
ogy is still unknown (Bateman, 2000).
In another classification based on hydrodynamics, hy-
drocephalus is divided into two main types of acute and
chronic. Conventionally, acute hydrocephalus is caused
by intraventricular obstruction. Chronic hydrocephalus
creates arterial pulsations and increase of capillary pul-
sations, because of reduction of intracranial compliance
(ΔV/ΔP) (Greitz, 2004). Acute hydrocephalus is diag-
nosed via compression of venous outflow by dilated ca-
pacitance arteries. Chronic hydrocephalus is diagnosed
through compression of capacitance vessels and reduc-
tion of compliance (Greitz, 2004). In the acute phase,
ICP reduction is related to fluid draining from obstructed
ventricles. In the chronic phase, intracranial compliance
increase is related to the increase of capacitance vessels
flow (Greitz, 2004).
Dandy-Walker Syndrome (DWS) is also a type of
congenital anomaly with a lack of formation of cerebel-
lar vermis or it being small, cystic fourth ventricle, and
large posterior fossa as its symptoms. The term Chiari
Malformation (CM) alludes to the caudal displacement
of the cerebellar tonsils through the foramen magnum.
DWS and CM may occur with or without hydrocephalus
(Khoshnevisan, Sistani Allah Abadi, & Abdollahzadeh,
2012; Gholampour, 2018).
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May, June 2019, Volume 10, Number 3
2.2. Hydrocephalus diagnosis and treatment methods
Hydrocephalus is mainly diagnosed clinically (Tasiou
et al., 2016). However, Computed Tomography (CT) and
Magnetic Resonance Imaging (MRI) play an important role
in the diagnosis of hydrocephalus (Maller & Gray, 2016).
Shunt implantation, ETV, and posterior fossa decompres-
sion are the prevalent methods for the treatment of hydro-
cephalus. In those cases accompanied by DWS or CM,
these three methods could also be used for treatment (Gre-
itz, 2004; Gholampour & Taher, 2018). The effectiveness
of hydrocephalus treatment method also depends on the
causes of the disease (Khoshnevisan et al., 2012).
2.2.1. Shunt implantation
Shunt implantation treatment is an invasive method of
treatment. A lateral perforation will be created in the brain
and a catheter will be placed in one of the lateral ventricles
(Thompson, 2017). Additional CSF will be drained under
the skin through the catheter to the peritoneal cavity, pleural
cavity, lung, or right atrium of the heart (Wallace, McCona-
thy, Menias, Bhalla, Wippold, 2014; Thompson, 2017). In
Figure 1. ICP ranges in different types of shunt
A. Five pressure ranges in the model; B and C. Strata, pressure range in lying back and standing positions; D. Pressure range
in CSF-flow control model
188 Gholampour, S., et al. Comparing the Efficiency of Two Treatment Methods of Hydrocephalus. BCN, 10(3), 185-198.
Basic and Clinical
general, shunt implantation is the first choice of treatment
for those suffering from NPH (Kang et al., 2018). It should
be mentioned that one of the shunt malfunction factors may
be brain compliance reduction (Fukuhara, Luciano, Brant,
& Klauscie, 2001).
All shunts drain CSF from ventricle; however, their
outputs are different. For example, if CSF is drained into
the peritoneum, it is called ventriculo-peritoneal shunt
(VPS) (Thompson, 2017); and if it is drained into the
lung, it is called Ventriculo-Pleural Shunt (VPL). If CSF
is drained into the atrium, it is called Ventriculo-Atrial
(VA) shunt (Wallace et al., 2014). The most common
concerns about hydrocephalus treatment are related to
shunt implantation, while it has limited controlling op-
tions. In this regard, “smart shunt” may improve con-
nection, feedback and telemetry controls. In this type of
shunt, the physician may be informed of the patient’s sta-
tus and performance of shunt through a smartphone or a
sensor-based controller. Figure 1 shows the adjustment
pressure and flow rate range for the shunts.
Basic and Clinical
Figure 2. Brain in three states
A. Healthy; B. Under shunt therapy; and C. Under ETV treatment
2.2.2. Endoscopic Third Ventriculostomy
It is a minimally invasive method via the application
of rigid and flexible endoscopy. In ETV method, the
third ventricle floor is perforated to create a connection
between ventricles and cisterns in SAS; which in turn
results in ICP decrease (Harris, & McAllister, 2011;
Spennato et al., 2011). The method is more useful in
treating obstructive hydrocephalus or idiopathic hydro-
cephalus (Hakim & Adams, 1965; Fukushima, 1978;
Tasiou et al., 2016). ETV or implanting a shunt in the
patients suffering from chronic hydrocephalus do not
mainly aim at absorbing CSF but to increase intracra-
nial compliance (Greitz, 2004).
Figure 2 shows the brain in the three following situa-
tions: healthy status, treatment with a shunt, and treat-
ment with ETV. ETV primarily aims at improving in-
tracranial compliance status, through cerebral pulsation
restoration and normalization of CSF flow (Fountas,
Kapsalaki, Paterakis, Lee, Hadjigeorgiou, 2012; Tasiou
et al., 2016). It should be noted that ETV is effective
in patients suffering from Aqueduct Stenosis (AS) and
is not much effective in patients with non-obstructive
hydrocephalus (Bargalló et al., 2005).
2.2.3. Posterior fossa decompression
In many cases, CM disorders are also accompanied
by hydrocephalus. In many types of CM, physical dam-
ages in craniocervical junction disrupt CSF circulation
in the fourth ventricle. In this case, posterior fossa de-
compression may be a good treatment option. The ba-
sic mechanism is to increase intracranial compliance,
through posterior fossa decompression (Greitz, 2004;
Eide & Pripp, 2016). The common challenges con-
fronted with the “smart shunt” are humidity elimina-
tion and lack of recalibration after implantation (Lutz,
Venkataraman, & Browd, 2013).
Gholampour, S., et al. Comparing the Efficiency of Two Treatment Methods of Hydrocephalus. BCN, 10(3), 185-198.
May, June 2019, Volume 10, Number 3
3. Comparing the effectiveness of VPS and ETV
Some in vivo and in vitro models have been proposed
for simulation and or comparing VPS and ETV treat-
ment methods. There have been fewer instances of com-
plications such as malfunction or infection in ETV com-
pared to shunt implantation; however, ETV is usually
accompanied with hemorrhage and thalamus damage
(Fountas et al., 2012; Tasiou et al., 2016). Also, studies
have shown that ETV has relatively higher success and
lower complications rate in iNPH patients. Minimally
invasive ETV method is mainly effective in AS patients.
However, there are several reports indicating that ETV
has been effective, leading to improvement of ventricle
size (Akutsu et al., 2018). It seems that ETV is a po-
tentially safer option for hydrocephalus in patients with
osteoporosis because the infection risk would be lower
than that in shunt implantation. Shunt infection is one of
the causes of death of patients with osteoporosis.
As VPS should also be removed, there are some points
to be taken into consideration. Fukuhara et al. (2001)
studied the effects of removing VPS on oxygen and brain
compliance of the patients with chronic obstructive hy-
drocephalus. In their model, the changes in physiologi-
cal parameters were evaluated in three untreated, shunt
implanted, and shunt-removed phases and then brain
compliance curve was measured in all phases.
In their study, adult dogs were used and 13 weeks after
the operation, MRI was performed on dogs. The lateral
and third ventricle size in addition to ICP in hydrocepha-
lus dogs and the healthy group were compared. The
results showed that, after shunt implantation in chronic
obstructive hydrocephalus, the ventricle size and ICP
decreased while O2 saturation and brain compliance in-
creased and improvement was seen in response to hyper-
ventilation in brain tissue (Figure 3).
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May, June 2019, Volume 10, Number 3
Figure 3. Comparison the ventricular volume and brain compliance
a. Changes in the ventricle size before implanting shunt, when it is implanted, and after shunt removal; and b. Changes in brain
compliance in low pressure before and after shunt removal.
Hyperventilation significantly reduced ICP and O2
saturation levels. It significantly reduced tissue O2 satu-
ration, when the shunt was implanted (Fukuhara et al.,
2001). The ventricle size in hydrocephalus patients also
increased gradually and shunt implantation prevented
this increase in size (Figure 3 a). Shunt removal rein-
creased the ventricle size.
3.1. Infant hydrocephalus
Regarding the prevalence of hydrocephalus in infants,
evaluating the effectiveness of ETV and VPS in treating
these patients is very important. However, there are dif-
ferent views on the effectiveness of these two treatment
methods in infants.
Chowdhury et al. (2017) followed up for 4 years treat-
ment of 1-2 years children suffering from AS-related
hydrocephalus. The results showed that ETV treatment
compared to shunt implantation is more appropriate for
this group. Also, ETV has been proved to be a better op-
Figure 4. Results of survival curves measured by Kaplan-Meier method
a) Comparison the results of survival curve for patients that treated with VPS and ETV; b) Comparison the proportion without
repeat intervention in patients that treated with VPS and ETV
190 Gholampour, S., et al. Comparing the Efficiency of Two Treatment Methods of Hydrocephalus. BCN, 10(3), 185-198.
Basic and Clinical
tion to treat congenital AS resulting in secondary NCH.
Compared to post-hemorrhagic patients or post-infective
hydrocephalus group, ETV had a better outcome in the
aforementioned group.
The results of Kulkarni et al. (2016) research on hydro-
cephalus infants showed that initial treatment through
ETV was more reasonable than using shunts. The reason
is that, in infants younger than 6 months, the failure rate
is higher when treated with a shunt (Figure 4 a). In infants
with hydrocephalus, depending on the type of treatment
used either Endoscopic Third Ventriculostomy with Cho-
roid Plexus Cauterization (ETV/CPC) or VPS treatment,
various changes may occur in the craniometrics.
The results showed that in infants followed up 6 months
after hydrocephalus treatment by ETV/CPC method,
ventricle size remained unchanged, which is one of the
success indexes in the treatment method (Dewan et al.,
2018). Uche et al. Research showed that the mortality
rate of those treated with ETV was lower than that of
Basic and Clinical
May, June 2019, Volume 10, Number 3

Figure 5. Comparison CSF velocity and vortex in samples

a-c. Shows the vortex in the inferior section of the third ventricle of a patient with NCH before shunting; d-f. Shows the vortex
in the inferior section of the third ventricle of a normal subject; b, e. Shows the vortex during the fill period; and c, f. Shows it
during the flush period (Gholampour, 2018).

the VPS. Therefore, ETV is the first treatment option
for children with Non-Communicating Non-Tumor Hy-
drocephalus (NCNTH), except in cases of severe mac-
rocephaly (Uche, Okorie, Iloabachie, Amuta, & Uche,
2018). Li, Gui, and Zhang (2017) research showed that
the failure rate and success rate of ETV and shunt im-
plantation were similar one year after the treatment.
3.2. Pediatric hydrocephalus
In the following, we compare the effectiveness of these
two methods of treating pediatric hydrocephalus. Limbrick
et al. compared the pediatric hydrocephalus of 3-8 years old
patients, in terms of treatment with shunt and ETV (Lim-
brick et al., 2014). General results of previous research
showed that both methods were appropriate options to treat
pediatric hydrocephalus patients (Limbrick, Baird, Klimo,
Riva-Cambrin, Flannery, 2014; Tasiou et al., 2016).
3.3. Adult hydrocephalus
In adult hydrocephalus, the effectiveness of both ETV
and VPS methods is of great importance. Dewan et al.
studied the patients under 19 years suffering from hy-
drocephalus and Posterior Fossa Brain Tumor (PFBT),
who were under treatment with VPS and ETV methods.
Based on their results, the initial failure has occurred in
ETV sooner than in shunt therapy. After 3 months, the
failure rate in ETV has become lower than the shunt
implantation. This shows the more lasting advantage of
survival curves in ETV method (Dewan, Lim, Shannon,
& Wellons, 2017).
After removing PFBT, the failure time in both ETV and
VPS methods were computed, and survival curves were
drawn via the Kaplan-Meier method. In medicine, the sur-
vival curve obtained through the Kaplan-Meier method is
mostly used to measure the fraction of subjects living for a
certain amount of time after treatment. In fact, the Kaplan-

Gholampour, S., et al. Comparing the Efficiency of Two Treatment Methods of Hydrocephalus. BCN, 10(3), 185-198. 191
 Basic and Clinical
May, June 2019, Volume 10, Number 3

(A) (B)
4 Severe+ETV
Severe
Mild+ETV 1080
Ventricular displacement [mm]

Mild
3 Open

CSF Pressure [Pa]

1040
2

1000 Severe+ETV
1 Severe
Mild+ETV
Mild
Open
0 960
4 6 8 10 4 6 8 10
Skull radius [cm] Skull radius [cm]

Figure 6. Changes in ventricular displacement and CSF pressure

a. Ventricular displacement; and b. CSF pressure in open aqueductal modes, as well as in mild and severe AS cases (with and
without ETV consideration) (Vardakis, Tully, & Ventikos, 2013).

Meier survival curve is an observed function to estimate the shunt implantation and ETV have been simulated via
survival function (Lacny et al.; Kaplan, & Meier, 1958). computer. However, in none of these studies, a simul-
taneous and comprehensive comparison has been per-
In Figure 4 b, 5.7 months shows the first time VPS sur- formed on the hydrodynamic parameters changes in the
vival curve has reached to lower level than that of ETV two treatment methods (Gholampour, Soleimani, Zalii,
method. Then, the obtained data were compared by the & Seddighi, 2016a; Hajirayat, Gholampour, Sharifi, &
Wilcoxon rank-sum and the Chi-square tests. The re- Bizari, 2017; Khademi, Mohammadi, Gholampour, &
sults showed that failure in ETV occurred sooner than Fatouraee, 2016; Gholampour et al., 2016b; Gholam-
VPS method; however, ETV treatment was more lasting pour, Fatouraee, Naderi, & Bagheri, 2019). Thus, we
(about 12-29 months) (Figure 4 b, red rectangle). Thus, made such comparison separately in the continuation of
both ETV and VPS experience failure occurred, but as this study. To evaluate the changes in CSF hydrodynam-
time passes VPS failure rate gets lower than that of ETV. ics, CSF flow conditions were simulated in healthy and
Of course, these results were different from the results of patient charts (Figure 5).
the Kulkarni study (Figure 4 a), which was different for
pediatric hydrocephalus after the 12th month. Reynolds number is the index to determine the fluid
laminar or turbulent flow (Hajirayat et al., 2016; Ghol-
3.4. Elder hydrocephalus ampour et al., 2017). In healthy subjects, Reynolds num-
ber is about 311 whereas, the mean number in AS pa-
Effectiveness of the two methods on the elderly people tients is 409. After shunt operation, the value reduced to
is also significant. However, a limited number of stud- 329, indicating the parameter improvement after the op-
ies have been performed on this issue, including the one eration (Gholampour et al., 2017a; Gholampour, 2018).
by Kang et al. (2018). Their results on 1 to 12 months
follow-up of NPH patients (average age of 70) showed In all conditions, either before or after the treatment
that ETV was more effective. Also, Tasiou et al. (2016) of patients and also in healthy subjects, the number of
studied ETV treatment on iNPH patients. Reynolds remained within the laminar range. Gholam-
pour studied and compared CSF hydrodynamics via FSI
4. Comparing changes of CSF hydrodynam- simulation in NCH patients before shunt implantation
ics in ETV and VPS and 2.5 years after implantation (Gholampour, 2018).
Then, the results were compared with FSI simulation
Many studies compared CSF hydrodynamic param- in a healthy subject. According to the results, the mean
eters in hydrocephalus patients and healthy subjects ICP domain in NCH patients were 5.3 and 2 times higher
(Gholampour et al., 2014; Gholampour et al., 2017b; than those of healthy subjects, respectively (Gholam-
Gholampour, 2018). In some studies, brain compliance pour et al., 2017a).
has also been examined in patients (Eide & Pripp, 2016;
Gholampour, 2018). Meanwhile, in some other studies,

192 Gholampour, S., et al. Comparing the Efficiency of Two Treatment Methods of Hydrocephalus. BCN, 10(3), 185-198.
Basic and Clinical
CSF pressure in NCH patients due to AS was about 5.3
times higher than that of a healthy subject. Despite the
fact that after shunt implantation, CSF pressure and vol-
ume decreased significantly (pressure almost returned to
the normal range of healthy subjects), the volume did
not return to normal condition (with a considerable dif-
ference to the healthy subject) even 2.5 years after
shunt implantation (Gholampour, 2018). In the research,
compliance increase curve was studied 2.5 years after
patients’ treatment. Fukuhara’s research also confirmed
these results (Figure 3 b).
Reynolds number and phase difference between pres-
sure and flow curves increased after outbreak of hydro-
cephalus; however, the two parameters did not demon-
strate considerable decrease after shunt implantation.
CSF volume and especially pressure were the most re-
liable parameters in evaluating the treatment methods
of hydrocephalus because this parameter more than any
other parameter gets closer to normal range (Gholam-
pour et al., 2017a; Gholampour et al., 2017b; Gholam-
pour, 2018).
Farnoush et al. (2016) studied CSF flow velocity
simulation in AS and imposed pressure in the third
ventricle, with and without ETV. After ETV operation,
CSF flow velocity peak in Sylvius aqueduct and peak
positive pressure decreased 5 and 9 times, respectively.
This pressure drop was more than pressure drop and
velocity reported in Gholampour research on the treat-
ment by shunt implantation (Gholampour et al., 2017a;
Gholampour, 2018).
ETV changes the time characteristics of CSF pressure
waveform. After ETV operation, CSF velocity peak in
Sylvius aqueduct and pressure peak reduced 2.5 and 3
times, respectively. This number is less than the simi-
lar numbers obtained from Gholampour research which
suggests that shunt implantation effectiveness gets better
over time. Pressure and velocity reduction in this model
has been less than those of shunt implantation results in
Gholampour research (Gholampour et al., 2017a).
Effectiveness of changes of hydrodynamic parameters
of flow, including velocity and Wall Shear Stress (WSS)
has been studied by Vardakis et al. during ETV treatment
in open aqueductal modes as well as in mild and severe
AS (Figure 6) (Vardakis et al., 2013). The results showed
that maximum CSF flow velocity is about 15.6 cm/s in
the healthy subjects, 45.4 cm/s in AS-related mild ob-
struction, and about 72.8 cm/s in a severe case of AS-
related obstruction. Using ETV reduced AS velocity up
Gholampour, S., et al. Comparing the Efficiency of Two Treatment Methods of Hydrocephalus. BCN, 10(3), 185-198.
May, June 2019, Volume 10, Number 3
to 16-17 cm/s. ETV effectiveness depends on AS level in
the CSF circulation path (Farnoush et al., 2016).
5. Discussion
There are various methods of treating obstructive hy-
drocephalus, including shunt planting, ETV, and posterior
fossa decompression. ETV is an alternative method of ob-
structive hydrocephalus treatment and effective treatment
for CH patients. Of course, both ETV and shunt implan-
tation methods improve brain compliance. Also, in infants
younger than 12 months with congenital AS-related hydro-
cephalus, ETV is considered to be a better option. However,
the method is less effective in patients with non-obstructive
hydrocephalus.
All in all, there are many controversies about the effi-
ciency of ETV and shunts in infants diagnosed with hy-
drocephalus. In patients younger than 19 years with PFBT-
related hydrocephalus, failure occurs earlier with ETV
method, compared to shunt implantation. However, after
a long period of time, ETV-related complications are less
than VPS-related complications. VPS is the most common
method of iNPH treatment. Of course, a paucity of research
has been done in relation to a higher level of ETV effective-
ness in iNPH. However, results have shown that for the el-
derly subjects suffering from iNPH, ETV is a more effective
method of treatment. Also, it is an acceptable alternative of
occlusive hydrocephalus operation. Also, ETV is superior
to shunt implantation in NCH patients and its effectiveness
depends on AS level in CSF circulation path.
Computer simulations in which reduction of hydrodynam-
ic parameters are compared separately for ETV and shunt-
ing implantation have shown higher effectiveness of ETV
in the model with aqueductal stenosis hydrocephalus com-
pared to shunt operation. However, in the model without
aqueductal stenosis hydrocephalus, ETV was less effective
than shunt implantation method. Also, the improvement of
Reynolds number has been observed in AS patients after
shunt operation. However, in all conditions, either before
or after the treatment of patients and in healthy subjects, the
Reynolds number remains within the laminar range.
Such parameters as the patient’s age, cause of hydroceph-
alus, and history of hydrocephalus operation are considered
as important factors in the selection of appropriate treat-
ment method (ETV or VPS) . The assessment of CSF hy-
drodynamics showed that volume and especially pressure
were the most reliable parameters in evaluating the treat-
ment methods of hydrocephalus because this parameter has
become close to normal range more than other parameters.
193

May, June 2019, Volume 10, Number 3
After ETV operation, CSF flow velocity peak in Sylvi-
us aqueduct and peak positive pressure decreased 5 and
9 times, respectively. This pressure drop is higher than
the pressure drop and velocity is seen after treatment
by shunt implantation. Moreover, ETV changes time
characteristics of CSF pressure waveform. After ETV
operation, CSF flow velocity peak in Sylvius aqueduct
and pressure peak reduce 2.5 and 3 times, respectively.
The research results on infants with hydrocephalus
showed that initial treatment by ETV is more reasonable
than implanting the shunt. The results also showed that
both ETV and shunt implantation are appropriate options
to treat pediatric hydrocephalus. In adult hydrocepha-
lus, the initial failure in ETV occurs sooner compared
to shunt therapy. However, ETV has been better dur-
ing efficacy time. ETV is a potentially safer option for
hydrocephalus in patients with osteoporosis. Computer
simulation of hydrocephalus before and after shunt im-
plantation and ETV treatments were showed that maxi-
mum CSF pressure is the most relevant and suitable hy-
drodynamic index in the analysis of these patients.
Ethical Considerations
Compliance with ethical guidelines
There was no ethical considerations to be considered
in this research.
Funding
This research did not receive any specific grant from
funding agencies in the public, commercial, or not-for-
profit sectors.
Authors' contributions
Conceptualization: Seifollah Gholampour; Methodol-
ogy: Seifollah Gholampour, Mehrnoush Bahmani; Inves-
tigation: Seifollah Gholampour, Mehrnoush Bahmani,
Azadeh Shariati; Validation: Seifollah Gholampour;
Writing-original draft: Seifollah Gholampour, Meh-
rnoush Bahmani, Azadeh Shariati; Writing-review &
editing: Seifollah Gholampour, Mehrnoush Bahmani;
Supervision: Seifollah Gholampour; and Visualization:
Mehrnoush Bahmani.
Conflict of interest
The authors declared no conflict of interest.
194 Gholampour, S., et al. Comparing the Efficiency of Two Treatment Methods of Hydrocephalus. BCN, 10(3), 185-198.
Basic and Clinical
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 Original Paper
Pediatr Neurosurg
DOI: 10.1159/000500641
Role of Secondary Endoscopic Third
Ventriculostomy in Children: Review of
an Institutional Experience
Salman Shaikh Chandrashekhar Eknath  Deopujari Vikram Karmarkar
Kapil Muley Chandan Mohanty
Department of Neurosurgery, Bombay Hospital Institute of Medical Science, Mumbai, India
Keywords
Endoscopic third ventriculostomy · Hydrocephalus ·
Pediatric patients · Secondary endoscopic third
ventriculostomy · Shunt independence
Abstract
Background: Endoscopic third ventriculostomy (ETV) has
become a standard and safe procedure for obstructive hy-
drocephalus. ETV can also play an important role in children
presenting with shunt malfunction with an added advan-
tage of shunt independence. Secondary ETV can be defined
as either a redo endoscopic ventriculostomy done after pri-
mary ETV stoma closure or that done in cases presenting
with shunt malfunction. Objective: The aim of our study was
to evaluate the role of secondary ETV in the pediatric age
group patients. Methods: This is a retrospective analysis of
36 children (<18 years) who underwent ETV after shunt mal-
function and 4 children with ETV done after previous ETV
stoma closure from 2004 until 2018. In all patients, the ob-
structive pattern suggesting aqueduct outflow obstruction
was observed on MRI. Patients were followed up for a mean
period of 4.25 years. Results: ETV was considered successful
© 2019 S. Karger AG, Basel
E-Mail karger@karger.com
www.karger.com/pne
Received: February 25, 2019
Accepted after revision: April 27, 2019
Published online: June 3, 2019
if the patient avoided a shunt insertion later on in their life.
Considering this definition, a success rate of 72% was ob-
served with secondary ETV for shunt malfunction whereas a
success rate of 75% was observed after primary ETV failure
without any major side effects in any of the patients. Conclu-
sion: ETV can be considered a primary treatment modality in
children with shunt malfunction and has a good success rate
in cases presenting with closure of previously performed ETV
stoma. © 2019 S. Karger AG, Basel
Introduction
Endoscopic third ventriculostomy (ETV) is consid-
ered as a standard and safe method for primary treatment
of obstructive hydrocephalus [1, 2]. However, some pa-
tients with obstructive hydrocephalus are being treated
by ventriculoperitoneal (V-P) drainage of cerebrospinal
fluid (CSF) via shunt implantation even today in India
and other developing countries, the most common rea-
son for this being a high prevalence of postinfective or
posthemorrhagic hydrocephalus or hydrocephalus asso-
130.159.21.97 - 6/12/2019 2:45:21 AM
Chandrashekhar Eknath Deopujari
Bombay Hospital Institute of Medical Science
University of Strathclyde
Room No. 114, 1st Floor
MRC Building, 12, New Marine Lines, Mumbai 400020 (India)
Downloaded by:
E-Mail d.chandrashekhar11 @ gmail.com

a b
c d
Fig. 1. a T2W axial MRI of an 18-year-old girl with tubercular
meningitis and hydrocephalus. b Axial FLAIR images showing ex-
udates, hydrocephalus with parietal end of the ventriculoperito-
neal shunt seen which had malfunctioned. c Intraoperative image
of the floor of the third ventricle with basilar artery seen through
ciated with spina bifida. Unavailability of a neuroendo-
scope, absence of high-definition MRI, and a lack of spe-
cialist neurosurgeons in remote areas contributes to this
predicament. Moreover, the risk of shunt malfunction is
relatively high. In children, the shunt failure rate has been
found to be 31.3% for the 1st year and 4.5% per year there-
after [3]. Thus, the majority of shunted patients require
revision after 12 years. In such cases, the role of secondary
ETV needs to be evaluated. Secondary ETV may be con-
sidered as either a redo endoscopic ventriculostomy for
treatment of a failed ETV due to stoma closure or that
done in cases presenting with shunt malfunction.
Materials and Methods
A retrospective analysis of 40 children who underwent ETV
after either shunt malfunction (n = 36) or due to failure of previous
ETV (n = 4) was performed from 2004 until 2018. Patients up to
18 years of age and previously shunted patients presenting with
shunt malfunction were included in the study and patients more
than 19 years of age were excluded from this series. In all patients,
the obstruction in aqueduct or outflow parts of the fourth ventricle
was observed in an MRI CSF flow study. Standard ETV procedure
was performed through the right frontal pre-coronal burr hole
with a rigid neuroendoscope. The anatomy of the third ventricular
floor was defined in all cases except 2 children where intraopera-
tive neuronavigation was utilized as an adjunct. The third ventric-
ular floor was punctured with a monopolar probe (without cur-
rent) and the ventriculostomy stoma was further dilated with the
help of Fogarty’s balloon catheter inflating with 0.2 ml of saline.
2 Pediatr Neurosurg
DOI: 10.1159/000500641
Color version available online
e
the thin membrane. d Perforation of the first and second mem-
brane followed by dilatation of the third ventriculostomy with
Fogarty’s catheter. e Postoperative CT scan showing resolution of
the hydrocephalus with the ventricular end of the shunt seen (left
behind in situ).
Warm Ringer’s lactate solution with added sodium bicarbonate
was used as an irrigation fluid. An external ventricular device
(Ommaya reservoir) was kept in all cases at the end of the proce-
dure to enable emergency CSF tapping.
The previous shunt tube along with the ventricular catheter
were removed whenever possible at the end of the procedure. Post-
operatively, all patients were kept in the neurointensive care unit
for 1 day for monitoring metabolic parameters or raised intracra-
nial pressure due to sudden acute hydrocephalus, which is known
to occur after ETV failure. Serum electrolytes were checked on
postoperative evening to rule out any imbalance. Patients were
then shifted to the ward on the next day after mobilization and
were discharged at the earliest. Earlier, the patency of the third
ventriculostomy track used to be assessed by CT contrast ventric-
ulography study. This was then replaced by MRI CSF dynamic
flow study done 3 months after the procedure. However, CT con-
trast ventriculography plays a role in the assessment of immediate
or early ETV failures even today. The reservoir was removed after
confirming the patency of ventriculostomy on follow-up MRI after
6–9 months. Parameters assessed were age, sex, etiology of hydro-
cephalus, time interval between primary procedure and secondary
ETV, complications, ETV success score, whether redo ETV or
shunt was performed in cases with secondary ETV failure, and
follow-up duration.
Results
The study group consisted of 40 children (32 male and
8 female) aged less than 18 years including 36 patients
with shunt malfunction and 4 patients with post-ETV
failure. The age ranged from 3 months to 18 years with a
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University of Strathclyde
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 Color version available online
a

b c d

Fig. 2. a MRI of the brain, T2-weighted axial and sagittal images of tion of the floor of the third ventricle after dilatation with Fogarty’s
an 18-year-old boy who had undergone 16 shunt revisions in the catheter. d CSF flow void seen in the prepontine space confirming
past along with ETV 2 years previously. b Scarred closure of the flow through the perforated track.
third ventricular floor stoma with fibrous adhesion. c Re-perfora-

mean age of 109.55 months (9.13 years) at the time of Table 1. Etiology of shunt malfunction (n = 36)
ETV. The shunt malfunctioned primarily due to infection
Shunt malfunction etiology
in our case series closely followed by ventricular end
blockage (Table 1). None of the patients developed any Infection, n 15
major electrolyte imbalance postoperatively. 16 out of the Ventricular end blockage, n 11
40 patients required CSF drainage at least twice by lumbar Peritoneal end issue (i.e., malabsorption,
puncture postoperatively. These patients were either very loculation, peritoneal extrusion, etc.), n 8
Shunt migration, n 1
young (i.e., less than 3 years) or had a pathology other
Shunt tube (silicone) allergy, n 1
than aqueduct stenosis, which led us to expect meningeal
malabsorption in them. The average stay in hospital was
5.5 days. The mean duration of follow-up was 50.95
months (4.25 years) ranging from 4 months to 14 years. years after shunt procedure with hydrocephalus (Fig. 1).
The malfunctioning shunt was removed in 30 out of Secondary ETV was performed ensuring that the mem-
the 36 patients. Ventricular end was left behind in 6 cases branes of the floor of the third ventricle were perforated
due to the tip being adhered to the choroid plexus. One and adequately dilated. CSF flow was confirmed on post-
such case was that of an 18-year-old girl who had a his- operative MRI. The girl has been on follow-up for the last
tory of childhood tubercular meningitis and presented 16 2 years.
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Role of Secondary ETV in Children Pediatr Neurosurg 3

DOI: 10.1159/000500641
University of Strathclyde
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 Color version available online
a b c d e

Fig. 3. a ETV performed in a 9-year-old boy with Dandy-Walker dilatation with Fogarty’s catheter. d Visualization of the entry into
malformation who presented with shunt malfunction. b Primary aqueduct of Sylvius. e Aqueductoplasty performed in the same sit-
stoma closure due to fibrous adhesions seen during secondary ting as secondary ETV (ETV Plus).
ETV procedure. c Re-perforated floor of the third ventricle after

Color version available online

ETVSS vs. shunt-free duration correlation
6 *Shunt-free duration score
5 No shunt/shunt after >2 years/redo ETV
Shunt-free duration score

5 4 Shunt after >18 months

3 Shunt after >12 months
4
2 Shunt after >6 months
3 1 Shunt within 6 months

0
0 10 20 30 40 50 60 70 80 90
ETVSS

Correlation coefficient, r
0.51

Fig. 4. Correlation coefficient score of 0.51 between ETVSS and shunt-free duration. Correlation coefficient r measures the strength and
direction of a linear relationship between two variables on a scatterplot. The value of r is always between +1 and –1. A +0.50 score de-
notes a moderate uphill (positive) relationship.

Amongst the 4 patients with primary ETV failure, 1
patient presented with hydrocephalus on follow-up with
no CSF flow from ETV track 2 years after his ETV proce-
dure (Fig. 2). He had a history of shunt malfunction due
to silicone allergy and was further treated with repeat
ETV. He has been under close follow-up for the last 2
years and 7 months. This patient has been considered in
both the shunt malfunction and ETV failure group. In all
4 patients, the previous stoma was blocked due to fibrous
bands. A 9-year-old boy with Dandy-Walker syndrome
presented with hydrocephalus due to blockage of the ven-
tricular catheter, which was inserted 7 years ago. After
having undergone ETV, the stoma closed after 8 months
due to fibrous adhesions. He underwent redo perforation
of the floor of the third ventricle along with aqueducto-
plasty (ETV Plus) since he had a concomitant trapped 4th
ventricle. He has been asymptomatic for a year now
(Fig. 3).
The predicted mean ETV success score was 71 for
post-shunt failure and 77 for post-primary ETV failure.
ETV was considered successful if the patient avoided a
shunt insertion later on in his/her life. Considering this
definition, a 72% success rate was seen with secondary
ETV for shunt malfunction (26/36), while a 75% success
rate (3/4) was seen in secondary ETV for primary ETV
failure. The findings over time in both groups matched
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4 Pediatr Neurosurg Shaikh/Deopujari/Karmarkar/Muley/

DOI: 10.1159/000500641 Mohanty
University of Strathclyde
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 Color version available online
Shunt within 2 years after ETV

ETVSS 80 70 60 50 40 TOTAL
Yes 1 2 1 1 1 6
No 9 11 2 1 0 23
100% 10 13 3 2 1 29

ETVSS vs shunt within 2 years of ETV

100 ■ Series 1
90 ■ Series 2

Shunt within 2 years of ETV, %

80
70
60
50
40
30
Fig. 5. Number of patients with 2 years of 20
follow-up after secondary ETV or shunt 10
inserted after ETV (whichever is earlier) 0
along with their corresponding ETVSS. 80 70 60 50 40
Blue denotes those who required a shunt
ETVSS
and orange denotes those who did not re-
quire a shunt on follow-up.

Color version available online

% of patients (out of 23) who did not require shunt within 2 years

ETVSS 80 70 60 50 40
% subjects 39.1 47.8 8.7 4.3 0

% of patients who did not require shunt within 2 years of ETV

60

50

40

30

20

10

0
Fig. 6. Percentage of patients out of the 23
80 70 60 50 40
who did not require shunt within 2 years
with their corresponding ETVSS.

with the predicted endoscopic third ventriculostomy Statistical Analysis

success score (ETVSS). The follow-up period required
was much longer than for a primary procedure, as fail-
ures were seen even 2 years following secondary ETV.
There were no major complications such as vascular in-
jury, meningitis or deaths due to late ETV failure in this
series.
There were 29 children with more than 2 years of fol-
low-up duration. This group was analyzed further to em-
phasize the need for longer follow-up and to achieve sta-
tistical significance. A correlation coefficient score of 0.51
was noted between ETVSS and shunt-free duration which
denotes a moderately positive linear relationship between
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Role of Secondary ETV in Children Pediatr Neurosurg 5

DOI: 10.1159/000500641
University of Strathclyde
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Table 2. Study of associative risk of age less than 18 months with
ETV failure: analysis of children with follow-up of at least 2 years
or shunt done (whichever was earlier)
Age ETV failure, n
yes no
Less or equal to 18 months 4 2
More than 18 months 7 16
Relative risk, 2.2; odds ratio, 4.6.
the two (Fig. 4). 23 out of 29 children in this group did
not require a shunt within 2 years of secondary ETV
(Fig. 5). Close to 87% of these children had ETVSS of 70
or more (Fig. 6). A strong association was found between
children aged less than or equal to 18 months and risk of
ETV failure (odds ratio 4.6) (Table 2).
Discussion
V-P shunt remains the most commonly used method
for treating hydrocephalus even today irrespective of
the etiology, type of hydrocephalus, and previous pro-
cedure performed. This is mainly due to unavailability
of a neuroendoscope, a high-defined MRI facility and
specialist neurosurgeons in remote parts of the world.
Though ETV is being used primarily in congenital aq-
ueduct stenosis and other cases of obstructive hydro-
cephalus, its role in other conditions is still being de-
bated even in the developed nations. Shunt is associated
with its own various complications, one of which is
shunt malfunction. We have therefore studied the role
of ETV in cases presenting with shunt malfunction or
primary ETV failure (secondary ETV) irrespective of
the primary etiology.
Vincent Darwin L’Espinasse, a Chicago urologist, who
used a cystoscope to fulgurate the choroid plexus in 2 in-
fants with hydrocephalus, performed the first neuroen-
doscopic procedure in 1910. Using an urethroscope, Wil-
liam J. Mixter in 1923 performed the first successful ETV
in a 9-month-old patient with hydrocephalus. However,
neuroendoscopic procedures were not widely adopted
during the first half of the 20th century. With improved
neuroendoscopic techniques and endoscopic optics, the
use of endoscope was revisited for hydrocephalus treat-
ment again, making it an efficient and safe procedure.
The role of ETV in other conditions like normal pressure
6 Pediatr Neurosurg
DOI: 10.1159/000500641
hydrocephalus in adults has been described in the litera-
ture [4–6].
Radiological correlation of a successful ETV is denot-
ed either by the presence of a CSF flow void in the aque-
duct on a sagittal image [7] or by quantitative CSF flow
on a phase-contrast MRI study [8].
Today, ETV is the first choice for treatment of obstruc-
tive hydrocephalus [2]. Advantages of ETV over V-P
drainage include restoration of physiological CSF circula-
tion, absence of foreign material (shunt independence)
and lower incidence of late complications [2, 9]. The orig-
inal assumption that after a few years with working V-P
drainage, the lowering of CSF reabsorption capacity oc-
curs has not yet been confirmed in the literature.
One of the earliest reported series of secondary ETV in
a mixed age group is by Cinalli et al. [10] who studied 30
patients from 1974 to 1996. A successful outcome was re-
ported in 23 patients while the failures manifested within
10 days of the procedure. Siomin et al. [11] reported a se-
ries of 20 patients (children and adults) in 2001 who un-
derwent repeat ETV with a success rate of 65%. Some im-
portant intraoperative findings noted by them during
secondary ETV were occlusion of the primary orifice by
scar, virginal floor of the third ventricle, pinhole ventric-
ulostomy, incompletely penetrated membrane, and blood
clot occluding the orifice. O’Brien et al. [12] studied 63
patients of mixed age group who underwent secondary
ETV and found it to be less of an origin-specific proce-
dure as compared to 170 patients of primary ETV. Wood-
worth et al. [13] pointed out that there was a 2.5 times
greater risk of ETV failure in patients with previous V-P
drainage. Hader et al. [14] in their study of 45 pediatric
patients found an increased risk of intraoperative and
postoperative ETV complications, namely 31% in pa-
tients with previous V-P drainage. These findings led to
a further reluctance amongst neurosurgeons to perform
a secondary ETV. However, with advances in endoscope,
illumination and optics along with an increase in simula-
tion training exercises [15], ETV has now emerged as a
safe and effective option in such cases.
Bilginer et al. [16] studied 45 pediatric cases of second-
ary ETV and reported a success rate of close to 80%, which
is comparable to the success rate of primary ETV.
ETV success rates reported in the literature in previ-
ously shunted patients of a mixed age group range from
60 to 93% [4, 17–23] (Table 3). With regards to the exist-
ing shunt, there are various schools of thought as to how
to best deal with it with no method yet considered to be
superior to the other. Shunt removal may not always be
possible due to adherence of the ventricular tip to the
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 Table 3. Review of the literature

Series Author Year Patients Age Secondary ETV Major

No. group success rate, % complications

1 Cinalli et al. [10] 1998 30 Mixed 76.7 NA

2 Siomin et al. [11] 2001 20 Mixed 65 1%
3 O’Brein et al. [12] 2005 63 Mixed 70 NA
4 Woodworth et al. [13] 2007 19 Adults 25 NA
5 Hader et al. [14] 2008 45 Pediatric 80 31%
6 Bilginer et al. [16] 2009 45 Pediatric 80 NA
7 Jenkinson et al. [17] 2009 61 Mixed 67 5.8%
8 Marton et al. [25] 2010 22 Pediatric 64 NA
9 Melikian et al. [18] 2010 60 Mixed 72 5% of patients
10 Baldauf et al. [19] 2010 30 Mixed 60 6.7%
11 Lee et al. [4] 2011 19 Mixed 68.4 None
12 Mahapatra et al. [20] 2011 32 Mixed 93.2 None
12 Neils et al. [21] 2013 20 Mixed 70 None
13 Hellwig et al. [22] 2013 8 Mixed 87.5 12.5%
15 Zhao et al. [26] 2016 37 Pediatric 60 NA
16 Chan et al. [23] 2018 31 Mixed 65.35 NA
17 Duru et al. [27] 2018 51 Pediatric 69.7 NA
18 Deopujari et al. (present study) 2019 40 Pediatric 73.5 None

brain matter. Neils et al. [21] mention that shunt ligation
provides a slightly higher success rate for ETV as com-
pared to the malfunctioned shunt being left behind in
situ. Shunt infection need not be considered a contrain-
dication for ETV even though the success rate might be
slightly lower in such cases [24]. Secondary ETV success
rates in pediatric case series reported in the literature
range from 60 to 80% [14, 16, 25–27] which matches with
the success rate of 73.5% in our case series. Marton et al.
[25] studied 22 children in 2010 who underwent ETV for
shunt malfunction and found no significant correlation
between ETV failure and patient age or etiology of hydro-
cephalus. Zhao et al. [26] found a history of preterm birth
and age <6 months at initial shunt insertion to be a nega-
tive predictor of success while Duru et al. [27] reported
etiology other than isolated aqueductal stenosis to be a
negative predictor of success for secondary ETV. Second-
ary ETV has been found to be effective in close to 100%
of cases of following hemorrhagic hydrocephalus as
against 61% of cases with primary ETV. This may be due
to maturation of the arachnoid villi with time [28]. The
CSF dynamics have been proven to change to a shunt-
independent state within a week of ETV which is not the
case with intraventricular pressure that reduces gradually
over time [29].
Even though more than 95% of ETV failures are evi-
dent within 1 month of the procedure [12], our series had
3 patients presenting with stoma closure as late as 2 years
after secondary ETV. This necessitates the need for a lon-
ger follow-up in such cases.
Conclusion
Based on the literature and our results, it would be rea-
sonable to offer all patients with malfunctioning shunts
and a favorable anatomy the opportunity for shunt inde-
pendence irrespective of the original cause of hydroceph-
alus. Secondary ETV is an effective, safe and justifiable
treatment option for obstructive hydrocephalus due to
either shunt malfunction or failure of primary ETV. ETV
implementation in such cases carries a strong possibility
of further shunt independence or at the least pushes fur-
ther the need for subsequent intervention [30]. Due to the
possibility of late ETV stoma closure, long-term follow-
up of these patients is essential.
Acknowledgement
The authors would like to acknowledge the contribution of Dr.
Kanharam Patel towards statistical analysis of this series.
130.159.21.97 - 6/12/2019 2:45:21 AM

Role of Secondary ETV in Children Pediatr Neurosurg 7

DOI: 10.1159/000500641
University of Strathclyde
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 Statement of Ethics
The authors declare that written informed consent has been
taken from all the patients for this retrospective study.
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Shaikh/Deopujari/Karmarkar/Muley/
Mohanty
University of Strathclyde
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Literature Review
Endoscopic Third Ventriculostomy versus Ventriculoperitoneal Shunt in Patients with
Obstructive Hydrocephalus: Meta-Analysis of Randomized Controlled Trials
Liang Lu, Hongwu Chen, Shaotao Weng, Yimin Xu
Key words
- Endoscopic third ventriculostomy
- Obstructive hydrocephalus
- Ventriculoperitoneal shunt
Abbreviations and Acronyms
CI: 95% Confidence interval
CSF: Cerebrospinal fluid
ETV: Endoscopic third ventriculostomy
OR: Odds ratio
RR: Risk ratio
SF: Cerebrospinal fluid
VPS: Ventriculoperitoneal shunt
Department of Neurosurgery, The First Affiliated Hospital of
Shantou University Medical College, Shantou, Guangdong,
PR China
To whom correspondence should be addressed:
Yimin Xu, M.D., Ph.D.
[E-mail: xuym777@163.com]
Citation: World Neurosurg. (2019) 129:334-340.
https://doi.org/10.1016/j.wneu.2019.04.255
Journal homepage: www.journals.elsevier.com/world-
neurosurgery
Available online: www.sciencedirect.com
1878-8750/$ - see front matter ª 2019 Published by Elsevier
Inc.
INTRODUCTION
Hydrocephalus can occur at any age but is
most common in infants and adults aged
60 and older. This health condition is
characterized by excessive accumulation of
cerebrospinal fluid (CSF), leading to ven-
tricular dilatation and increased intracra-
nial pressure, and may be accompanied by
secondary brain parenchymal atrophy.
Ventriculoperitoneal shunt (VPS) remains
the classical treatment for hydrocephalus
due to its relatively high safety features.
Other modes such as ventricle atrial shunt
and lateral ventricleecisterna magna
shunt have rarely been used.1,2
Recently, endoscopic third ven-
triculostomy (ETV) was deemed to be
indispensable for treating obstructive
hydrocephalus, on account of minimal
complications because it avoids foreign-
body associated infections. First reported
by Mixter in 1923 for hydrocephalus,3 the use
of ETV in routine practice before the 1990s
334 www.SCIENCEDIRECT.com
- OBJECTIVE: Endoscopic third ventriculostomy (ETV) and ventriculoperitoneal
shunt (VPS) are 2 surgical methods used for the treatment of obstructive hy-
drocephalus. However, the efficacy and safety of these 2 procedures are un-
known. Therefore we conducted a meta-analysis to compare the safety and
efficiency of ETV and VPS in patients with obstructive hydrocephalus.
- METHODS: In January 2019, a comprehensive search strategy of 3 electronic
databases was initiated. A systematic search from database inception to
December 30, 2018, on clinical outcome, safety, and efficiency of ETV and VPS in
the treatment of obstructive hydrocephalus was conducted. The following
electronic databases were searched: PubMed, Embase, and Cochrane Library for
related randomized controlled trials (RCTs). Main outcomes included post-
operative hematoma, postoperative infection, postoperative cerebrospinal fluid
leakage, blockage rate, and mortality.
- RESULTS: Of the 546 studies identified, 4 RCTs involving 250 patients met our
inclusion criteria. The pooled results show that ETV was associated with lower
incidence of postoperative infection (risk ratio [RR] 0.09, 95% confidence interval
[CI]: 0.02e0.32, P [ 0.0002); postoperative hematoma (RR 0.26, 95% CI: 0.08e0.88,
P [ 0.03); and blockage rate (RR 0.28, 95% CI: 0.13e0.60, P [ 0.001) compared
with VPS. Compared with VPS, ETV had no significant effect on incidence rate of
postoperative cerebrospinal fluid leakage (RR 2.00, 95% CI: 0.30e13.16, P [ 0.47)
and mortality rates (RR 0.19, 95% CI: 0.03e1.09, P [ 0.06), but there have been no
deaths in patients treated with ETV.
- CONCLUSIONS: On the basis of the meta-analysis of RCTs evaluating ETV and
VPS, the incidence of complications and mortality was higher with the VPS
procedure, and therefore greater benefits can be achieved using ETV.
was rather limited due to the lack of meta-analysis of all randomized controlled
effective endoscopic and relevant surgical trials (RCTs) to compare clinical outcomes,
instruments, leading to poor relief from major complications, and mortality of these
hydrocephalus and high mortality rates.4 2 techniques in patients with obstructive
However, rapid advances in neuroimaging, hydrocephalus. It is expected that this study
the endoscopic manufacturing process, will provide guidance for future studies in
operation instruments, and a stereotaxic the treatment of hydrocephalus.
neuronavigation system in recent
years have led to widespread use of
MATERIALS AND METHODS
endoscopy for various procedures including
obstructive hydrocephalus.5,6 Several The methodology adopted in this study is
studies have examined the efficiency and in accordance with Preferred Reporting
safety of VPS and ETV for the treatment of Items for Systematic Reviews and Meta-
obstructive hydrocephalus. Nevertheless, it Analysis guidelines.7
remains unclear as to which of these 2 is
more beneficial to patients because Search Strategy
both methods have advantages and A comprehensive search strategy was
disadvantages. Therefore we conducted a developed wherein 3 electronic databases
WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2019.04.255
 LITERATURE REVIEW
LIANG LU ET AL. ETV VS. VPS FOR OBSTRUCTIVE HYDROCEPHALUS

were conducted to identify eligible studies in

the EndNote software program.

Study Selection Criteria

Figure 1. Flow chart of search and study selection. In total, 546 records were
identified from 3 databases. After screening, 4 randomized controlled trials
that fulfilled all the eligibility criteria remained.
were searched. Searches were from database
inception to December 30, 2018. The
following electronic databases were
searched: PubMed, Embase, and the
Cochrane Library. Search terms included
medical subject headings [MeSH]/EMTREE
terms and/or text words): 1) for patients,
“Obstructive Hydrocephalus”[MeSH]; and
2) for intervention, “Ventriculoperitoneal
Shunt” [MeSH] and “Third Ven-
triculostomy”[MeSH]. Manual searches of
reference lists from all the relevant studies
Studies were selected for inclusion in the
meta-analyses of the clinical effectiveness
of the 2 procedures—VPS and ETV—
through predefined and explicit criteria.
The full literature search results were
independently screened by 2 investigators
(L.L. and H.C.) to identify all citations that
possibly met the inclusion criteria, fol-
lowed by independent extraction of data
and quality assessment.
All English-language articles of RCTs
comparing the efficacy and safety of ETV
or VPS for patients with obstructive hy-
drocephalus were selected for the meta-
analysis. Our inclusion criteria were as
follows: 1) studies with randomized
controlled design; 2) all included patients
had obstructive hydrocephalus; and 3)
patients received ETV or VPS. Exclusion
criteria were as follows: 1) preclinical
study; 2) case reports, letters, review arti-
cles, and any other stylistic feature that
cannot provide complete information for
trials; 3) not all patients suffered from
obstructive hydrocephalus; 4) not ran-
domized clinical trial; 5) noneEnglish
language publications; and 6) studies
with the same patient cohorts as in pre-
vious trials. For articles with relevant ab-
stracts, the full-text versions were

Table 1. Characteristics of Included Studies

Intervention Outcomes Measured
Number of Number of
Study Patients Age (years) Males (%) Follow-up
Study Design ETV/VPS ETV/VPS* ETV/VPS Operation Duration Clinical Outcomes Complication

Kamikawa RCT 44/44 4.47
0.73/4.48
23 (52.3)/25 ETV/VPS 24 Months Revision rates, major Bleeding, infection,
et al., 200110 0.86 (56.8) complications blockage, damage to brain
tissue
El-Ghandour, RCT 32/21 6.5
2.1/7.2
2.6 18 (56.3)/12 ETV/VPS 27.4/25 Improvement of symptoms, Bleeding, infection,
201111 (57.1) months postoperative CT, major blockage, CSF leakage
complications, procedure
failure, death
Navaei, et al., RCT 22/27 3.91
3.34/3.60
13 (59.1)/19 ETV/VPS 36 months Major complications, Bleeding, infection, raised
201812 2.95 (months) (70.4) procedure failure, death, intracranial pressure
estimated survival
Rahman, RCT 30/30 18.29
19.74/17.24 NR ETV/VPS 30 days Improvement of symptoms, Bleeding, infection,
et al., 201813
18.56 major complications, blockage, CSF leakage,
procedure failure, death pseudomeningocele

ETV, endoscopic third ventriculostomy; VPS, ventriculoperitoneal shunt; RCT, randomized controlled trial; CT, computed tomography; CSF, cerebrospinal fluid; NR, not reported.
*Age was reported as mean
standard deviation in all of the studies.

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 LITERATURE REVIEW
LIANG LU ET AL. ETV VS. VPS FOR OBSTRUCTIVE HYDROCEPHALUS

ratio (RR) or odds ratio (OR) with a 95%

El-Ghandour, N. M.2011
confidence interval (CI) for dichotomous
Rahman, M. M.2018 variables to reflect event probabilities.

Kamikawa, S.2001
Navaei, A. A.2018
Heterogeneity was assessed by I2 and c2
test metric. A fixed-effect model was
applied when I2 < 50%; otherwise, a
random-effects model was used.9

Random sequence generation (selection bias)

+

RESULTS
Allocation concealment (selection bias)
+

Study Selection
Blinding of participants and personnel (performance bias) A total of 546 publications were identified
+

through our initial database search. After

Blinding of outcome assessment (detection bias)
+

screening the titles, abstracts, and key-

Incomplete outcome data (attrition bias) words and removal of duplicates, 532 ar-
+

ticles were excluded according to our

Selective reporting (reporting bias)
+

prescribed criteria. Fourteen studies were

Other bias considered for the perusal of full text, and
+

4 RCTs10-13 were included for a detailed

Figure 2. Risk of bias summary. assessment. The Preferred Reporting
Items for Systematic Reviews and Meta-
Analysis flow diagram of the publication
obtained and assessed independently on Washington, USA). Surgical success was selection is presented in Figure 1.
the basis of criteria mentioned previously. defined as partial or complete relief of
symptoms or need for no further surgery. Study Characteristics
Table 1 summarizes the main
Data Extraction characteristics of the included studies.10-13
Two reviewers independently extracted the Quality Assessment In total, 250 patients (ETV group: 128; VPS
relevant information according to a pre- The Cochrane Collaboration tool was used group: 122) were included. The mean or
pared form that included authors, publi- to assess the risk of biases8—selection median age of patients ranged from 3.6
cation years, study design, number of bias (random sequence generation and months to 16.3 years. Of the 4 RCTs
patients per group (intervention and con- allocation concealment), performance, included, information on patients’ sex was
trol groups), participants’ age and sex, detection, attrition, reporting bias, and missing in 1,13 while the remaining 3
surgical procedures, follow-up duration, others. Two reviewers (L.L. and H.C.) studies were predominantly male (57.9%).
number of successful cases, mortality, and independently assessed the quality of the Three studies11-13 provided a specific
complications. We focused on the number included RCTs. Any disagreement was number of successful operations and the
of postoperative complications such as resolved by discussion and consultation total number of complications except for
infection, hematoma, CSF leakage, and in order to avoid errors in the process. the study by Kamikawa in 2001.10 The
blockage, referring to stoma malformation deaths of 6 patients, all of whom received
in the ETV group or shunt blockage in the Statistical Analysis VPS, were noted in all studies. Adverse
VPS group after operation. Data extracted All statistical analysis was conducted by effects were recorded: 28 patients with
were distilled into an Excel database Rev-Man software (version 5.3). Results blockage in 3 RCTs10,11,13 (ETV group: 6;
(Microsoft Excel; Microsoft, Redmond, from the RCTs were presented as the risk VPS group: 22); 4 patients with CSF

ETV VPS Risk Ratio Risk Ratio

Study or Subgroup Events Total Events Total Weight M-H, Fixed, 95% CI M-H, Fixed, 95% CI
El-Ghandour, N. M.2011 0 32 2 21 10.8% 0.13 [0.01, 2.65]
Kamikawa, S.2001 0 44 14 44 52.2% 0.03 [0.00, 0.56]
Navaei, A. A.2018 0 22 2 27 8.1% 0.24 [0.01, 4.82]
Rahman, M. M.2018 1 30 8 30 28.8% 0.13 [0.02, 0.94]

Total (95% CI) 128 122 100.0% 0.09 [0.02, 0.32]

Total events 1 26
Heterogeneity: Chi² = 1.07, df = 3 (P = 0.78); I² = 0%
0.01 0.1 1 10 100
Test for overall effect: Z = 3.73 (P = 0.0002)
Favours [ETV] Favours [VPS]

Figure 3. Forest plot of postoperative infection rates for shunt for treating obstructive hydrocephalus.
endoscopic third ventriculostomy and ventriculoperitoneal

336 www.SCIENCEDIRECT.com WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2019.04.255

 LITERATURE REVIEW
LIANG LU ET AL. ETV VS. VPS FOR OBSTRUCTIVE HYDROCEPHALUS

ETV VPS Risk Ratio Risk Ratio

Study or Subgroup Events Total Events Total Weight M-H, Fixed, 95% CI M-H, Fixed, 95% CI
El-Ghandour, N. M.2011 2 32 3 21 30.5% 0.44 [0.08, 2.40]
Kamikawa, S.2001 0 44 3 44 29.5% 0.14 [0.01, 2.69]
Navaei, A. A.2018 0 22 2 27 19.0% 0.24 [0.01, 4.82]
Rahman, M. M.2018 0 30 2 30 21.0% 0.20 [0.01, 4.00]

Total (95% CI) 128 122 100.0% 0.26 [0.08, 0.88]

Total events 2 10
Heterogeneity: Chi² = 0.54, df = 3 (P = 0.91); I² = 0%
0.01 0.1 1 10 100
Test for overall effect: Z = 2.17 (P = 0.03)
Favours [ETV] Favours [VPS]

Figure 4. Forest plot of postoperative hematoma rates for shunt for treating obstructive hydrocephalus.
endoscopic third ventriculostomy and ventriculoperitoneal

leakage in 2 RCTs11,13 (ETV group: 3; VPS
group: 1); 12 patients (ETV group: 2; VPS
group: 10) with postoperative hematoma;
and 27 patients (ETV group: 1; VPS group:
26) with postoperative infection.
Quality Assessment
Assessment of bias risk for included
studies was conducted according to the
Cochrane Handbook for Systematic Re-
views of Intervention (version 5.0.2):
Criteria for judging the risk of bias in the
“risk of bias” assessment tool. Randomi-
zation methods were described in all 4
RCTs. Because it was impossible to blind
key study personnel and participants
because patients had to provide written
informed consent before surgery, we
judged that blinding is unlikely to influ-
ence the outcome. One of the RCTs13 was
of high quality with a low risk of biases in
all domains, while it was unclear in the
remaining 310-12 because these RCTs
lacked information on random sequence
generation and allocation concealment.
Reporting bias was of high risk in
Kamikawa10 without results from
successful cases. Quality assessments for
the eligible studies are shown in Figure 2.
Postoperative Infection
Studies10-13 that reported dates of post-
operative infection were included in the
analysis. In the ETV group, only 1 patient
with postoperative infection was re-
ported13 and those in the VPS group
numbered 26 and included ventriculitis
and peritonitis. The pooled data showed
significantly lower postoperative infection
rates in the ETV group than VPS group
(RR 0.09, 95% CI: 0.02e0.32, P ¼
0.0002) without heterogeneity (I2 ¼ 0%,
P ¼ 0.78) (Figure 3).
Postoperative Hematoma
All RCTs reported data on postoperative
hematoma,10-13 and the incidence of
postoperative hematoma was 1.6% in the
ETV group and 8.2% in the VPS group,
without heterogeneity in the studies (I2 ¼
0%, P ¼ 0.91). Postoperative hematoma
incidence rates were significantly lower in
the ETV group than in the VPS group (RR
0.26, 95% CI: 0.08e0.88, P ¼ 0.03)
(Figure 4).
Blockage Rate
Three10,11,13 of the included RCTs provided
data on the blockage. There were 22 cases
of shunt blockage in the VPS group and 6
cases with stoma malformation in the ETV
group, with a significant difference be-
tween the 2 groups (RR 0.28, 95% CI:
0.13e0.60, P ¼ 0.001) and a moderate-
level heterogeneity (I2 ¼ 44%, P ¼ 0.17)
(Figure 5).
Postoperative Cerebrospinal Fluid
Leakage
Two studies11,13 reported data on post-
operative CSF leakage for the 2 groups,
and 4 of 113 cases were identified. Three of
the 4 were treated by ETV and 1 by VPS.
The pooled results showed that CSF
leakage was not significantly different be-
tween groups (RR 2.00, 95% CI: 0.30e
13.16, P ¼ 0.47) without heterogeneity
(I2 ¼ 0%, P ¼ 1.00) (Figure 6).
Mortality
All 4 RCTs reported data on mortality,10-13
but only VPS groups had associated mor-
tality. When mortality data were pooled,
there was no significant difference for
overall mortality between ETV and VPS
treatment in patients with obstructive hy-
drocephalus (RR 0.19, 95% CI: 0.03e1.09,
P ¼ 0.06) without heterogeneity (I2 ¼ 0%;
P ¼ 0.96) (Figure 7).

ETV VPS Risk Ratio Risk Ratio

Study or Subgroup Events Total Events Total Weight M-H, Fixed, 95% CI M-H, Fixed, 95% CI
El-Ghandour, N. M.2011 0 32 6 21 32.1% 0.05 [0.00, 0.87]
Kamikawa, S.2001 0 44 4 44 18.5% 0.11 [0.01, 2.00]
Rahman, M. M.2018 6 30 12 30 49.4% 0.50 [0.22, 1.16]

Total (95% CI) 106 95 100.0% 0.28 [0.13, 0.60]

Total events 6 22
Heterogeneity: Chi² = 3.56, df = 2 (P = 0.17); I² = 44%
0.01 0.1 1 10 100
Test for overall effect: Z = 3.29 (P = 0.001)
Favours [ETV] Favours [VPS]

Figure 5. Forest plot of blockage rates for endoscopic third ventriculostomy and ventriculoperitoneal shunt for treating obstructive
hydrocephalus.

WORLD NEUROSURGERY 129: 334-340, SEPTEMBER 2019 www.journals.elsevier.com/world-neurosurgery 337

 LITERATURE REVIEW
LIANG LU ET AL. ETV VS. VPS FOR OBSTRUCTIVE HYDROCEPHALUS

E TV VPS R i s k R a ti o R i s k R a ti o
Study or Subgroup Events Total Events Total Weight M-H, Fixed, 95% CI M-H, Fixed, 95% CI
Rahman, M. M.2018 2 30 1 30 62.5% 2.00 [0.19, 20.90]
El-Ghandour, N. M.2011 1 32 0 21 37.5% 2.00 [0.09, 46.90]

Total (95% CI) 62 51 100.0% 2.00 [0.30, 13.16]

Total events 3 1
Heterogeneity: Chi² = 0.00, df = 1 (P = 1.00); I² = 0%
0.01 0.1 1 10 100
Test for overall effect: Z = 0.72 (P = 0.47)
Favours [ETV] Favours [VPS]

Figure 6. Forest plot of postoperative cerebrospinal fluid ventriculoperitoneal shunt for treating obstructive
leakage rates for endoscopic third ventriculostomy and hydrocephalus.

Postoperative Success
Three studies11-13 provided a specific
number of successful surgeries (118 of 162
patients), but not the study by Kami-
kawa.10 The rate of success was 72.84%,
which was close (75%) to the study by
Kamikawa.10 The pooled data showed
that there was no significant difference
in the rate of success between ETV and
VPS (RR 1.30, 95% CI: 0.72e2.37, P ¼
0.38). However, the chi-squared test
showed that the studies had a consider-
able degree of heterogeneity (I2 ¼ 87%;
P ¼ 0.0006) (Figure 8).
DISCUSSION
Hydrocephalus is due to the accumulation
of an excessive amount of CSF within the
cerebral ventricles and/or subarachnoid
space leading to their dilation. The
disturbance of CSF formation, flow, or
absorption on account of obstacles,
congenital or acquired, leads to an in-
crease in overall CSF volume in the central
nervous system. As well, premature com-
plications such as intraventricular hemor-
rhage and diseases such as tumors,
meningitis, traumatic head injury, or
subarachnoid hemorrhage can also block
CSF circulation.14,15 With recent advances
in endoscopy, ETV has become an indis-
pensable tool for obtaining relief from
obstructive hydrocephalus. Nevertheless,
comparisons between ETV and VPS in the
domains of symptom improvement and
postoperative complication are lacking.
Although a previous comparative analysis
was observational in nature, we report for
the first time a meta-analysis of all ETV-
and VPS-related RCT studies. The overall
aim of the meta-analysis was to enable
physicians with guidance for future
studies in treatment for hydrocephalus
and to investigate the safety and efficiency
of ETV and VPS in patients with obstruc-
tive hydrocephalus. Although current
RCTs do not recommend ETV vs. VPS, our
meta-analysis showed that ETV could
effectively reduce the incidence of com-
plications and mortality compared with
VPS.
Despite its frequent use in the treatment
for hydrocephalus, VPS has a higher
complication rate than ETV. There were 26
cases of infection in the VPS group
compared with 1 in the ETV group in all 4
RCTs, which was significantly different.
Strikingly, 6 patients died after VPS sur-
gery, 5 from shunt infection and severe
sepsis, while there was no mortality after
ETV. Few plausible explanations for this
difference are the larger surgical area of
VPS compared with that of ETV, as well as
the use of implantation materials in VPS,
which presents a higher risk of bacterial
infection. In addition, the patients’ own
immune status and surgical process may
have an impact on postoperative infec-
tion.16 Thus postoperative infection is the
most important fatal complication of
surgery in patients with obstructive
hydrocephalus.
Both shunt blockage and stoma mal-
formation obstruct CSF drainage, and our
pooled data showed significantly lower
blockage rates in the ETV group than in
the VPS group. As the most common
complication, shunt blockage can easily
lead to the failure of VPS, and severe cases
require shunt replacement twice or even
more. The lack of detailed information has
impeded further analysis into the reason
for shunt blockage in our study; however,
literature reports on the causes of
blockage cite 1) the number of cells with
high protein content in CSF enables the
deposit of sediment easily; 2) intraven-
tricular choroid plexus cell injury can
cause the accumulation of cell debris in
the shunt tube, resulting in obstructions;
and 3) the greater omentum of pseudocyst
surrounding the peritoneal end.17,18

E TV VPS R i s k R a ti o R i s k R a ti o
Study or Subgroup Events Total Events Total Weight M-H, Fixed, 95% CI M-H, Fixed, 95% CI
El-Ghandour, N. M.2011 0 32 1 21 23.8% 0.22 [0.01, 5.21]
Kamikawa, S.2001 0 44 0 44 Not estimable
Navaei, A. A.2018 0 22 2 27 29.8% 0.24 [0.01, 4.82]
Rahman, M. M.2018 0 30 3 30 46.3% 0.14 [0.01, 2.65]

Total (95% CI) 128 122 100.0% 0.19 [0.03, 1.09]

Total events 0 6
Heterogeneity: Chi² = 0.07, df = 2 (P = 0.96); I² = 0%
0.01 0.1 1 10 100
Test for overall effect: Z = 1.86 (P = 0.06)
Favours [ETV] Favours [VPS]

Figure 7. Forest plot of mortality rates for endoscopic third ventriculostomy and ventriculoperitoneal shunt for treating obstructive
hydrocephalus.

338 www.SCIENCEDIRECT.com WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2019.04.255


LIANG LU ET AL.
Study or Subgroup
El-Ghandour, N. M.2011
Navaei, A. A.2018
Rahman, M. M.2018
Total (95% CI)
Total events
Heterogeneity: Tau² = 0.24; Chi² = 15.26, df = 2 (P = 0.0005); I² = 87%
Test for overall effect: Z = 0.88 (P = 0.38)
Figure 8. Forest plot of postoperative success rates for endoscopic third ventriculostomy and ventriculoperitoneal shunt for
treating obstructive hydrocephalus.
Postoperative hematoma is a rare and
serious complication, which can lead to
neurologic dysfunction. The incidence of
postoperative hematoma in the current
study is 8.2%, which is higher than the
1.08% incidence reported by Zhou and Liu 5
years ago.19 Postoperative hematoma
includes intraventricular hematoma,
subdural hematoma, and epidural
hematoma, of which the former 2 are
common. Intraventricular hemorrhage is
often caused by multiple catheterization or
venous injury.20 Subdural hematoma and
epidural hematoma are caused by excessive
drainage. In our study, there were 5 cases
of intraventricular hematoma, 3 cases of
subdural hematoma, and 2 cases of
epidural hematoma in the VPS group. In
comparison, a study by El-Ghandour
showed 2 patients with intraventricular he-
matoma.11 Our study confirmed that ETV
could significantly reduce the risk of
postoperative hematoma compared with
the VPS group.
Further, we found 4 cases of post-
operative CSF leakage that stopped spon-
taneously without treatment. Others
including the study by Kamikawa10 showed
many other complications, such as bowel
perforation (2 cases), skull deformity (7
cases), and slitlike ventricle (24 cases) in
the VPS group, but not in the ETV group.
A study by Rahman13 reported on 1 case
with excessive drainage. All these results
suggest that ETV outperformed VPS in its
ability to reduce the incidence of
complications.
Our study is not without a few limita-
tions: 1) the small number of RCTs
included in our meta-analysis can
compromise the generalizability of the re-
sults; 2) information on the specific causes
of hydrocephalus was not available, and
WORLD NEUROSURGERY 129: 334-340, SEPTEMBER 2019
ETV VS. VPS FOR OBSTRUCTIVE HYDROCEPHALUS
E TV VPS R i s k R a ti o
Events Total Events Total Weight M-H, Random, 95% CI
29 32 13 21 34.0% 1.46 [1.03, 2.08]
15 22 24 27 34.8% 0.77 [0.56, 1.05]
25 30 12 30 31.2% 2.08 [1.31, 3.32]
84 78 100.0% 1.30 [0.72, 2.37]
69 49
0.01
Favours [ETV] Favours [VPS]
treatment effects between ETV and VPS
according to specific causes were not
calculated; 3) information on the quality of
long-term survival and prognosis was
insufficient; and 4) age may affect the
outcome of these 2 methods; however, data
on the age of patients with hydrocephalus
was lacking. Despite these limitations, the
results of our meta-analysis are rigorous
and can be used to guide future research.
CONCLUSION
On the basis of the meta-analysis of RCTs
evaluating ETV and VPS, the incidence of
complications and mortality was higher
with the VPS procedure and therefore
greater benefits can be achieved using
ETV. These data should be confirmed in
large-scale high-quality RCTs in the
future.
REFERENCES
1. Kousi M, Katsanis N. The genetic basis of hy-
drocephalus. Annu Rev Neurosci. 2016;39:409-435.
2. Kalani MY, Turner JD, Nakaji P. Treatment of
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3. Mixter W. Ventriculoscopy and puncture of the
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6. Cage TA, Auguste KI, Wrensch M, et al. Self-re-
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vention in patients with idiopathic normal
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R i s k R a ti o
M-H, Random, 95% CI
0.1 1 10 100
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PRISMA statement for reporting systematic re-
views and meta-analyses of studies that evaluate
health care interventions: explanation and elabo-
ration. J Clin Epidemiol. 2009;62:e1-e34.
8. Higgins JPT, Altman DG, Gotzsche PC, et al. The
Cochrane Collaboration’s tool for assessing risk of
bias in randomised trials. BMJ. 2011;343:d5928.
9. Higgins JP, Thompson SG, Deeks JJ, et al.
Measuring inconsistency in meta-analyses. BMJ.
2003;327:557-560.
10. Kamikawa S, Inui A, Kobayashi N, et al. Endo-
scopic treatment of hydrocephalus in children: a
controlled study using newly developed Yamadori-
type ventriculoscopes. Minim Invasive Neurosurg.
2001;44:25-30.
11. El-Ghandour NM. Endoscopic third ven-
triculostomy versus ventriculoperitoneal shunt in
the treatment of obstructive hydrocephalus due to
posterior fossa tumors in children. Childs Nerv Syst.
2011;27:117-126.
12. Navaei AA, Hanaei S, Habibi Z, et al. Controlled
trial to compare therapeutic efficacy of endoscopic
third ventriculostomy plus choroid plexus cauter-
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with obstructive hydrocephalus. Asian J Neurosurg.
2018;13:1042-1047.
13. Rahman MM, Salam MA, Uddin K, et al. Early
surgical outcome of endoscopic third ven-
triculostomy in the management of obstructive
hydrocephalus: a randomized control trial. Asian J
Neurosurg. 2018;13:1001-1004.
14. Rekate HL. A contemporary definition and clas-
sification of hydrocephalus. Semin Pediatr Neurol.
2009;16:9-15.
15. Jiang L, Gao G, Zhou Y. Endoscopic third ven-
triculostomy and ventriculoperitoneal shunt for
patients with noncommunicating hydrocephalus.
Medicine. 2018;97:e12139.
16. Simon TD, Butler J, Whitlock KB, et al. Risk fac-
tors for first cerebrospinal fluid shunt infection:
findings from a multi-center prospective cohort
study. J Pediatr. 2014;164:1462-1468.
17. Reddy GK, Bollam P, Caldito G. Long-term out-
comes of ventriculoperitoneal shunt surgery in
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2013;81:404-410.
339
Literature Review
Safety and Efficacy of Endoscopic Third Ventriculostomy in Diffuse Intrinsic Pontine
Glioma Related Hydrocephalus: A Systematic Review
Lelio Guida1, Frank-Emmanuel Roux2, Maura Massimino3, Carlo E. Marras4, Erik Sganzerla1, Carlo Giussani1
Key words
- Diffuse intrinsic pontine glioma
- Endoscopic third ventriculostomy
- Hydrocephalus
- Torkildsen shunt
- Ventriculocisternal shunt
- Ventriculoperitoneal shunt
Abbreviations and Acronyms
DIPG: Diffuse intrinsic pontine gliomas
ETV: Endoscopic third ventriculostomy
VPS: Ventriculoperitoneal shunt
From the 1Department of Neurosurgery, Università degli studi
di Milano Bicocca, School of Medicine, Ospedale San
Gerardo, Monza, Italy; 2Pôle Neuroscience (Neurochirurgie),
Centre Hospitalo-Universitaire de Toulouse, Université de
Toulouse, UPS, Toulouse, France; 3Department of Pediatric
Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori,
Milan, Italy; and 4Department of Neurosurgery, Bambino
Gesù Children’s Hospital IRCCS, Rome, Italy
To whom correspondence should be addressed:
Carlo Giussani, M.D.
[E-mail: carlo.giussani@unimib.it]
Citation: World Neurosurg. (2019) 124:29-35.
https://doi.org/10.1016/j.wneu.2018.12.096
Journal homepage: www.journals.elsevier.com/world-
neurosurgery
Available online: www.sciencedirect.com
1878-8750/$ - see front matter ª 2018 Elsevier Inc. All
rights reserved.
INTRODUCTION
Brainstem tumors are a group of heteroge-
neous neoplasms arising in the midbrain,
pons, medulla, and upper cervical spine. In
past years, several radiologic classification
systems based on either computed tomog-
raphy or magnetic resonance imaging have
been proposed, with the most commonly
used being the one proposed by Choux et al.1
that uses both computed tomography and
magnetic resonance images to group
brainstem tumors into 4 types. Type I
brainstem tumors include diffuse gliomas,
which arise from the pons (diffuse intrinsic
pontine gliomas [DIPG]), that are the most
commonly encountered entity representing
58%e75% of brainstem tumors.2 In the
last decade, interesting findings regarding
genetic expression in pediatric glioma3,4
WORLD NEUROSURGERY 124: 29-35, APRIL 2019
- OBJECTIVE: Diffuse intrinsic pontine glioma (DIPG) related hydrocephalus
occurs as the result of tumor growth and sylvian aqueduct obstruction. There is
no consensus about the best surgical option; thus, a review has been performed
to clarify the rate of success, complications, and possible issues of endoscopic
third ventriculostomy (ETV) in comparison to other available techniques.
- METHODS: This systematic review followed the Preferred Reporting Items for
Systematic Reviews and Meta-Analyses (PRISMA) statement, and was regis-
tered with the International Prospective Register of Systematic Reviews
(PROSPERO) (registration number CRD42018089001). MEDLINE, Web of Knowl-
edge, and EMBASE were searched for published series in which ETV was
performed to treat hydrocephalus in DIPG patients.
- RESULTS: Six studies were included. Two further cases from our experience
were added for a total amount of 55 patients treated through either ETV, ven-
triculoperitoneal shunt (VPS), or ventriculocisternal shunt according to Tor-
kildsen. Eighty-six percent of patients who underwent ETV experienced clinical
improvement after surgery (P value 0.03). Torkildsen shunt placement was
associated with a 50% failure rate. Two patients implanted with VPS developed
symptoms of shunt malfunction and increased ventricular sizes (10%). The Fisher
exact test was applied to compare efficacy of VPS and ETV with no statistical
difference between the 2 groups (P value 0.17). Patients who underwent ETV did
not experience major complications, and no procedural termination was
observed.
- CONCLUSIONS: ETV is an effective and safe treatment option, associated
with a low complication rate and a high success rate. Evidences from this re-
view suggest considering ETV as the first-line treatment of hydrocephalus in
DIPG patients.
have brought about the development of development of hydrocephalus ranges from
molecular-based subcategorization of these 22%e89%6,7 according to the case series,
tumors according to the presence of specific and it is said to occur in the terminal
genetic mutations in genes encoding the stages of the pathology.8 This significantly
Histone H3 and BRAF proteins.4 The natural worsens the patient’s quality of life; thus,
history of patients affected by DIPG is eventually requiring a treatment strategy
similar to that of glioblastoma multiforme, that may rapidly relieve related symptoms
constituting the primary cause of brain and decrease the incidence of associated
tumorerelated deaths in children.5 The complications. Moreover, a recent study by
median survival time for these patients Massimino et al.9 has indirectly correlated
remains at <12 months after initial the onset of hydrocephalus with a more
diagnosis, despite radiation therapy and favorable prognosis (longer overall survival
further adjuvant treatments.5 in 4 patients developing hydrocephalus).
Hydrocephalus occurs as the result of The proposed mechanism is that the
tumor growth and would be mainly owing obstructive hydrocephalus would be
to sylvian aqueduct obstruction. The associated with larger dimensions of the
www.journals.elsevier.com/world-neurosurgery 29

LELIO GUIDA ET AL.
Figure 1. PRISMA 2009 flow diagram for systematic review. modified from Moher et al., 2009.15
tumor and consequently less aggressive
behavior.9
Endoscopic third ventriculostomy
(ETV) is a minimally invasive technique,
associated with high rates of success in
cases of hydrocephalus owing to
obstruction of the sylvian aqueduct both
in cases of malformative and tumoral
etiologies.10,11 Apart from ethical con-
siderations raised by some authors
regarding the indication to treat hydro-
cephalus in a poor prognosis condition
such as DIPG,6 there is no unanimous
consensus regarding the best way to
manage hydrocephalus in DIPG in the
literature. Some authors advocate the
use of ETV,7,12-14 whereas others prefer
ventriculoperitoneal shunts (VPS) or
ventriculocisternal shunts according to
Torkildsen.6 Because of the presence of
such opposite positions, a systematic
review of the literature has been
performed to clarify the rate of success,
complications, and predictable
anatomosurgical issues associated with
the different surgical strategies.
30 www.SCIENCEDIRECT.com
MATERIALS AND METHODS
In conducting this systematic review, the
Preferred Reporting Items for Systematic
Reviews and Meta-Analyses (PRISMA)
statement was followed.15 This statement,
mainly elaborated by Liberati et al.,16 is an
evolution of the older Quality of Reporting
of Meta-Analyses (QUOROM) statement
published in 1999.17 Study design was
registered with the International
Prospective Register of Systematic Reviews
(PROSPERO) (registration number
CRD42018089001).
MEDLINE, EMBASE, and Web of Science
were consulted between January and March
2018 using combinations of key words,
MeSH terms, and lexical variants regarding
“endoscopic third ventriculostomy in
brainstem tumors” ((endoscopic third ven-
triculostomy) OR (ventriculo peritoneal shunt) OR
(Torkildsen shunt) OR (ventriculo cisternal shunt))
AND hydrocephalus AND ((brainstem glioma) OR
(diffuse pontine intrinsic glioma)). Only articles
written in English were selected. Study titles,
abstracts, and full-texts were then screened
according to the following Patients,
WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2018.12.096
LITERATURE REVIEW
ETV IN DIPG-RELATED HYDROCEPHALUS
Interventions, Control, Outocome, Study
design criteria:

Patients: Patients affected by Type I
brainstem tumors and suffering from
symptomatic chronic or acute hydro-
cephalus that required surgical
treatment.

Intervention: Endoscopic fenestration of
the third ventricle floor through a pre-
coronal burr hole using an indifferently
flexible or rigid endoscope.

Control: Treatment of hydrocephalus
through the placement of a VPS or a ven-
triculocisternal shunt according to Tor-
kildsen. This latter technique, described
by Torkildsen in 1939, involves the diver-
sion of cerebrospinal fluid from the oc-
cipital horn of the lateral ventricle to the
cisterna magna.18 In previous years, with
the introduction of ventriculoperitoneal
and ventriculoatrial shunts, this
procedure has been regarded as obsolete
in contemporary neurosurgery. However,
it has been recently revaluated and used
in cases of infeasibility of ETV for narrow
interpeduncular space or infiltration of
the third ventricle floor.19

Outcome: There is still much debate
regarding the appropriate definition of
outcome in patients who underwent
ETV. As previously discussed by other
authors, primary outcome was defined
as the resolution of hydrocephalus while
avoiding a second surgery for a VPS
implant.11,20 At the same time, compli-
cations that occurred were documented
and recorded.

Study design: Case series and case reports
were eligible for inclusion if radiologic
or pathological diagnosis, procedure
outcome, and associated complication
were explained.
Articles potentially eligible for inclusion
were read and their references were inde-
pendently screened by 2 reviewers (L.G. and
C.G.) in search of other potentially useful
studies. Search strategy is summarized in
Figure 1. Statistical analysis was performed
using Microsoft Excel (Microsoft Corp.,
Redmond, Washington, USA).
In addition to the cases collected in the
literature, we retrospectively analyzed our
database of patients affected by diffuse
intrinsic pontine glioma and treated
WORLD NEUROSURGERY 124: 29-35, APRIL 2019

LELIO GUIDA ET AL.

Table 1. Details and Summary of Findings From Studies Included in the Systematic Review
Number of Median Age
Author and Year Procedures Success Complication Mean of Patients Time of Onset Overall
of Publication Institution Type of Study Accomplished Outcome (%) Rate (%) Follow-Up (Years) of Hydrocephalus Survival

Amano et al., 20027 Kyushu University, Case series ETV ¼ 9 ETV 9/9 (100%) ETV 0/9 (0%) N/A 6 5.1  3.3 11.8  6.5 months
Fukuoka, Japan VPS ¼ 7 VPS 7/7 (100%) VPS 0/7 (0%) (mean  SD) (mean  SD)
Ray et al., 200514 Johns Hopkins Case series ETV ¼ 14 ETV 11/14 (79%) ETV 0/14 (0%) 24.6 months 9.8 N/A N/A
Hospital, Baltimore,
Maryland, USA
Klimo and Goumnerova 200612 Harvard Medical Case series ETV ¼ 9 ETV 8/9 (89%) ETV 0/9 (0%) N/A 5.8 N/A 2.7 months (median)
School, Boston,
Massachusetts,
USA
Roujeau et al., 20116 Hôpital Necker Case series ETV ¼ 2 ETV 1/2 (50%) ETV 0/2 (0%) 263 days 6.7 3.2 months (median) 8.8 months (median)
Enfants VPS ¼ 9 VPS 9/9 (100%) VPS 0/9 (0%)
Malades, Paris,
France
Kobayashi and Ogiwara, 201613 National Center for Case series ETV ¼ 6 ETV 6/6 (100%) ETV 0/6 (0%) 9 months 7 N/A N/A
Child Health and
www.journals.elsevier.com/world-neurosurgery

Development,
Okura, Japan
Raja and Adada, 200721 Arkansas Children Case report ETV ¼ 1 ETV 1/1 100% ETV 0/1 (0%) N/A 15 N/A N/A
Hospital, University
of Arkansas for
Medical Sciences,

ETV IN DIPG-RELATED HYDROCEPHALUS

Little Rock,
Arkansas, USA
Our series San Gerardo Personal ETV ¼ 2 ETV 2/2 (100%) ETV 0/2 (100%) 11 months 5 3.5 months (median) 10  7.3
Hospital, University experience (mean  SD)
of Milan Bicocca,
Monza, Italy

ETV, endoscopic third ventriculostomy; VPS, ventriculoperitoneal shunt; N/A, not available.

LITERATURE REVIEW
31
 LITERATURE REVIEW
LELIO GUIDA ET AL. ETV IN DIPG-RELATED HYDROCEPHALUS

32 www.SCIENCEDIRECT.com WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2018.12.096


LELIO GUIDA ET AL.
through ETV from 2004e2018 at San
Gerardo Hospital, Monza, Italy. As per
hospital policy, all patients included in
the database had signed a formal consent
allowing the use of intraoperative
and radiologic images, which were
anonymized.
RESULTS
Six studies were identified to be eligible
for qualitative and quantitative anal-
ysis,6,7,12-14,21 including 5 retrospective
observational case series and a case report.
No randomized trials nor case-control
studies were found in the literature
regarding this subject. The Cochrane
Collaboration risk of bias tool was used to
minimize risk of bias. In addition to the
previously mentioned studies, 2 further
cases from our experience were added to
the series (Table 1).
A total of 55 patients were identified as
having symptomatic obstructive hydro-
cephalus treated through either ETV (37
patients, 67%), VPS (16 patients, 29%), or
ventriculocisternal shunt according to
Torkildsen (2 patients, 4%), with a mean
age  SD of 6.7 years  4 years (range 2e
15 years), 48% men and 52% women.
Mean follow-up time was available for just
2 studies, and was 5.6 months  7.8
months. Mean time of hydrocephalus
onset from tumor diagnosis was reported
in 2 studies and was 5.25 months  0.2
months. End points were homogeneous
and included both clinical (resolution of
symptoms) and radiologic (decrease in
ventricular dimensions) evidence of hy-
drocephalus resolution. In patients who
underwent ETV, the need for placing a
VPS system was interpreted as treatment
failure. In patients treated trough VPS,
shunt malfunction was considered a
treatment failure because it exposed the
patient to further surgery.
In all the studies, the choice of
implanting a VPS instead of performing an
ETV was guided by surgeon experience,
without any objective radiologic criteria in
Figure 2. T2-weighted magnetic resonance images of a 2-year-old patient suffering from diffuse intrinsic pontine gliomas, who
presented with signs and symptoms of hydrocephalus and underwent endoscopic third ventriculostomy. Preoperative images
show the tumoral mass dramatically reducing the prepontine interval (A and B), the increase of ventricular diameters (C), and the
evidence of temporal horns (D). (E and F) Four-month postoperative magnetic resonance images. The images document the
slight but persistent and clinically successful reduction of ventricular diameters and temporal horns.
WORLD NEUROSURGERY 124: 29-35, APRIL 2019
relation to the expected reduction of the
interpeduncular cisternal space.
To the degree that classification system
is concerned, there was no homogeneity
in the definition of radiologic or patho-
logical nature of lesions, with some au-
thors referring to DIPG6,12,13,21 and others
using the generic term “brainstem tu-
mors.”7,14 Despite this nonspecific defini-
tion, the latter studies were included into
the systematic review because authors
describing diffuse brainstem tumors had
excluded focal and exophytic forms of tu-
mors, as tectal plate gliomas, that have a
different clinical course and prognosis. A
biopsy was performed in cases of unusual
radiologic presentation (6 cases, 11% of
the series).
Regarding success rate, 30 of 35 patients
(86%) who underwent ETV experienced a
persistent clinical improvement after sur-
gery (P value 0.03). Ventriculocisternal
shunt placement was associated with a
50% failure rate. Two patients with VPS
implants experienced symptoms of shunt
malfunction and increased ventricular
sizes (10%), neither showing intra-
operative possible causes of system mal-
function. The Fisher exact test was applied
to compare the efficacy of ETV and VPS in
the treatment of hydrocephalus related to
diffuse brainstem tumors, with no statis-
tical relevant difference found between the
2 groups (P value 0.17).
In terms of surgical complications, pa-
tients who underwent ETV did not expe-
rience major complications, but minor
bleedings were resolved with continuous
irrigation during surgery.14 All ETV were
successfully accomplished, with no
procedural terminations. Of the 2 cases
of ventriculocisternal shunt implantation,
1 patient needed the placement of a VPS
and the other died of infection.7
DISCUSSION
The onset of hydrocephalus establishes an
impending problem complicating the
clinical course of patients affected by
www.journals.elsevier.com/world-neurosurgery
LITERATURE REVIEW
ETV IN DIPG-RELATED HYDROCEPHALUS
DIPG.6,7 This topic is poorly discussed in
the literature and the small case series
available often show contradictory results.
Moreover, considering the poor prognosis
connected to this pathology and inevitable
death owing to tumor infiltration of vital
centers located in the brainstem, ethical
perplexities might arise regarding the
choice of treating hydrocephalus in these
patients.6 Despite the limited number of
patients reported in the literature, the
results of the present systematic review
support an interventional behavior and
suggest that the treatment of
hydrocephalus may represent more than
a palliative choice or a compassionate
procedure. First, we must consider the
high rate of success in the relief of the
hydrocephalus-related symptoms (nausea
and vomiting, headache and lethargy).
Amano et al.7 compared the Karnofsky
Performance Scale score before and after
the resolution of hydrocephalus,
demonstrating a statistically significant
improvement in treated patients.7
Second, in contrast to the concept that
hydrocephalus occurs in the final stages of
pathology, the present review reveals that
the mean time from the diagnosis of DIPG
is 5.25 months  0.2 months—in the
middle of expected patient survival time.
Another argument supporting the
treatment of hydrocephalus would be the
improvement of overall survival when
patients undergo surgery, but further
studies will be needed to univocally
clarify this aspect. A statistical relevant
increase in mean life expectancy has been
reported by Amano et al.,7 (6.3  4.3 vs.
14.1  6.1) but it contrasts with that
reported by Roujeau et al.6 Possible
explanations are the small number of
patients collected and a selection bias
in the study of Amano et al., in which
the group of patients not treated
consisted mainly of children in poor
general condition.
Another issue to mention is anatomic
and functional feasibility of ETV in the
patients affected by DIPG. Almost
33

LELIO GUIDA ET AL.
invariably, tumor mass infiltrating the
pons reduces the volume of inter-
peduncular and prepontine cisterns avail-
able to perform a cisternostomy.22
Moreover, the midbrain tends to extend
above the tentorium, thus, distorting the
third ventricle floor anatomy7 and
eventually discouraging even expert
neuroendoscopists from attempting an
ETV.
Despite these technical difficulties, it has
been clearly established in the literature that
a narrow prepontine interval does not
impact the feasibility of the procedure.23 In
the present series, no intraprocedural
terminations have been registered and
interpeduncular cistern have been
described as almost constantly patent, at
least in its upper part. Kobayashi and
Ogiwara13 describe a case of almost
complete obliteration of the cistern with
cerebrospinal fluid filling a narrow
subarachnoid space at 1 side, and managed
through a ventriculostomy located in the
lateral part of the third ventricle floor.13 In
such cases of complete obliterations, the
ventriculostomy would be alternatively
achieved through the fenestration of the
lamina terminalis, in which efficacy and
feasibility of endoscopic fenestration of
lamina terminalis has been recently
reviewed by our group.24 This aspect
underlines the essential importance of
preoperative planning, which may
influence surgical strategy.
The high rate of success of ETV in these
patients (87%) would be mainly owing to
the obstructive nature of hydrocephalus.
This is believed to be the dominant mech-
anism in DIPG patients except for the cases
of leptomeningeal dissemination, a condi-
tion reported to occur in 4%e50% of
patients with pontine glioma.25-27 In these
cases, there would be an incompetence of
the mechanisms of cerebrospinal fluid
absorption in the subarachnoid spaces, and
ETV would be less effective.
An important result demonstrated in the
present systematic review is that of non-
superiority of VPS to ETV. These data allow
us to disprove previously published works
that advocated ETV as a procedure at high
risk, and suggested VPS as the best way to
treat hydrocephalus in DIPG patients.6
A further interesting consideration
highlighted by the present review is the
management of patients with DIPG
complicated by hydrocephalus at the
34 www.SCIENCEDIRECT.com
time of diagnosis in which a stereotactic
biopsy is planned. The choice of per-
forming a biopsy in these tumors has
raised several ethical perplexities.28
However, the improving knowledge
regarding the genetic substrate of
DIPG, and the development of mini
invasive bioptic techniques,29 have led
some centers to more interventional
attituded. In this series, all patients but
1 underwent biopsy before the onset of
hydrocephalus. In 1 case, DIPG was
diagnosed at the occurrence of signs
and symptoms of hydrocephalus,13 the
tumor mass expanded into the
prepontine cistern and the biopsy was
endoscopically performed after
cisternostomy. No cases of stereotactic
biopsy in children with DIPG-related
hydrocephalus have been reported in
the present review. The eventual man-
agement of these latter cases requires a
technical consideration. While perform-
ing a stereotactic biopsy, the Nashold
needle should never cross ventricles
because of the high risk of tumoral cells
seeding through the cerebrospinal fluid.
In cases of ventricular enlargement, this
would lead to needle trajectory with an
angle of >25 , with consequent
improved risk for posterior cerebral
artery injury. In this scenario, the treat-
ment of hydrocephalus should always
precede the biopsy.
Finally, we would like to discuss
possible complications associated with
different treatment strategies. ETV is
considered a safe technique in which
complication rate is low and mainly
includes the difficultly to control hemor-
rhages and limited injuries of the dien-
cephalic neural structures.30 Late sudden
deterioration, which may concur to
patient death, is extremely rare and has
an incidence of <0.1%.30 Although
anatomic distortions related to tumor
infiltration, with the third ventricle floor
lifted up and the basilar artery pushed
against the clivus, no complications were
registered in the cases collected. This
may be explained by a technical
consideration; in the common practice,
at the time of lateral ventricular puncture
with cerebrospinal fluid drainage,
surgeons experience a relief of the
hydrostatic pressure on the third
ventricle floor with its consequent
detachment from the cisternal
WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2018.12.096
LITERATURE REVIEW
ETV IN DIPG-RELATED HYDROCEPHALUS
neurovascular structures (Figure 2). To
the degree that ventriculocisternal shunt
placement is concerned, a severe
infection lead to the death of a child in
which this device was positioned. No
patient who underwent VPS placement
developed infections or abdominal
complications. In conducting this
systematic review, 3 case reports about
tumoral dissemination of DIPG through
the distal catheter of VPS in the
abdominal cavity were observed.31-33 The
development of extraneural metastases
from pediatric brain tumor in a derived
patient is a significant clinical problem
because it may result in ascites with
consequential worsening of patient
quality of life. However, it is a rare
complication that has been demonstrated
to occur in <0.5% in autoptic studied.34
Because of evident publication bias,
these cases were not included in the
present analysis.
The exiguity of literature regarding this
topic does not allow us to draw definitive
conclusions regarding the best way to treat
hydrocephalus in DIPG patients. However,
considering the efficacy, the feasibility, and
the equal effectiveness of ETV to VPS, we do
suggest ETV as the first-line treatment of
hydrocephalus in these patients. Among
different surgical options, third ven-
triculostomy is a demonstrated less invasive
procedure than VPS placement and carries a
lower risk of infection in the pediatric
population.35 In oncologic patients with
such poor prognosis who frequently
undergo radiation and eventually
chemotherapy avoiding the placement of a
silicon prothesis may further decrease the
infection rate.
CONCLUSIONS
Hydrocephalus complicates the natural
history of patients suffering from DIPG in
the early stages after diagnosis. Treatment
is associated with rapid and satisfying
relief of signs and symptoms. Further
studies will be needed to clarify the impact
of hydrocephalus and its effect on life
expectancy of these patients. ETV is an
effective and safe treatment option,
notwithstanding anatomic alterations
induced by tumor development. This
technique is associated with a low rate of
complications and a high success rate.
Despite the lack of large case series about
this subject, evidence from this systematic

LELIO GUIDA ET AL.
review suggest treating DIPG-related
hydrocephalus primarily through ETV,
after a careful preoperative planning based
on radiologic studies verifying its
feasibility.
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Conflict of interest statement: The authors declare that the
article content was composed in the absence of any
commercial or financial relationships that could be construed
as a potential conflict of interest.
Received 5 September 2018; accepted 11 December 2018
Citation: World Neurosurg. (2019) 124:29-35.
https://doi.org/10.1016/j.wneu.2018.12.096
Journal homepage: www.journals.elsevier.com/world-
neurosurgery
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