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Cite this article: Sacko O, Sol JC, Niaré M, Schmidt E, Brenner A, et al. (2017) Outcome Analysis of Hydrocephalus Associated with Cerebellopontine Angle Tumors Managed by Endoscopic Third Ventriculostomy. JSM Brain Sci 2(2): 1012.

*Corresponding authorOumar Sacko, Department of Neurosurgery, Centre hospitalo-universitaire de Toulouse, 31059 Toulouse, France, Tel: 33-561775605 Fax: 33-561 77 76 78; Email:

Submitted: 01 April 2017

Accepted: 11 May 2017

Published: 12 May 2017

Copyright© 2017 Sacko et al.

ISSN: 2573-1289

OPEN ACCESS

Keywords•Cerebellopontine angle tumor•Endoscopic third ventriculostomy•Hydrocephalus•Shunt

Research Article

Outcome Analysis of Hydrocephalus Associated with Cerebellopontine Angle Tumors Managed by Endoscopic Third VentriculostomyOumar Sacko1,2*, Jean-Christophe Sol1,2, Mahamadou Niaré1,2, Eric Schmidt1,2, Adam Brenner3,4, Virakpagna Chhun2,6, Guillaume Penchet5, and Franck-Emmanuel Roux1,2

1Department of Neurosurgery, Centre hospitalo-universitaire de Toulouse, France2Université Paul-Sabatier, France3Harrison Medical Center, USA4Western University of Health Sciences, USA5Department of Neurosurgery, Centre hospitalo-universitaire de Bordeaux, France6University of Health Sciences, Calmette Hospital, Cambodia

Abstract

Background: After the treatment of cerebellopontine angle (CPA) tumors, there is a risk of worsening an existing hydrocephalus (HCP) or developing a new hydrocephalus. Both types of HCP have been usually managed by an external ventricular drain or shunt; however, both of these remedies can have their own set of complications.

Objective: The authors undertook a work to determine if the risk of developing hydrocephalus after tumor treatment, and shunt-related complications could be avoided by performing an endoscopic third ventriculostomy (ETV).

Methods: We compared two groups of patients who underwent CSF diversion (prior to tumor treatment) for CPA-related hydrocephalus: 20 subjects in whom a VP shunt was performed and 25 patients in whom an ETV was performed for symptomatic hydrocephalus at two neurosurgical centers.

Results: The median follow-up period was 67 months (22-166 months) and the overall ETV/shunt success rate was 64% and 45%, respectively (Gehan-Breslow survival p=1,000). After CSF diversion, 6 patients were treated by FSRT and 39 were operated on. Among the 20 patients with a shunt, 55% experienced at least one shunt complication and 15% had multiple complications. The overall complication rate was 0% in the ETV group and 55% in the shunt group (Gehan-Breslow Statistic = 3,947, p=0,047). After tumor removal, in both groups, no patient experienced a CSF leak or pseudomeningocele.

Conclusions: ETV is simple to perform, has a low morbidity rate, and is a safe treatment option for hydrocephalus related to CPA tumors. It can avoid shunting and its complications.

ABBREVIATIONSCPA: Cerebellopontine Angle; CSF: Cerebrospinal Fluid; ETV:

Endoscopic Third Ventriculostomy; EVD: External Ventricular Drainage; FSRT: Fractionated Stereotactic Radiotherapy; VP: Ventriculo-Peritoneal; VPS: Ventriculo-Peritoneal Shunting; VS: Vestibular Schwannomas

INTRODUCTIONIn cerebellopontine angle (CPA) tumors, hydrocephalus

occurs in 18 to 42% of patients before treatment [1-4] from 4% to 14% after radiosurgery [5], and in up to 12% of the cases after fractionated stereotactic radiotherapy (FSRT) [3,6]. Partial or total resection of CPA tumors does not result in complete

resolution of hydrocephalus in up to 22% in cases [2,4,7]. The hydrocephalus (HCP) could be caused by various factors, compression of the fourth ventricle or alteration of cerebrospinal fluid (CSF) flow dynamics [8,9]. Furthermore, surgery in patients with untreated hydrocephalus may be more difficult and have higher complication rates with adverse outcomes [2,4,7]. Therefore, initial CPA related hydrocephalus was managed by the placement of a ventriculoperitoneal (VP) shunt prior to surgery or by the placement of an external ventricular drainage (EVD), either before or at the time of surgery [7,10].

Because of the possible complications of a VP shunt or an external ventricular drainage (EVD), the ideal situation remains a shunt free patient. In the past, endoscopic third

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ventriculocysternostomy (ETV) had been accepted as the procedure of choice for the treatment of obstructive hydrocephalus [11-13]. While controversial, recent reports also claim its usefulness for treating communicating types of hydrocephalus [13-19].

Although hydrocephalus is a recognized and treatable complication of CPA tumors, published data about its management by ETV is quite limited. To our knowledge, only one study has been devoted to the success rate of ETV in CPA tumors [20]. Since 1999, our group has adopted ETV as a routine procedure to treat hydrocephalus [21]. The purpose of this paper is to evaluate the effectiveness of ETV in the management of hydrocephalus associated with CPA tumors and to determine whether the risk of developing hydrocephalus after tumor treatment and shunt-related complications could be avoided by this procedure.

MATERIALS AND METHODSThis is a two-center retrospective study approved by the

Toulouse University Hospital’s independent ethics committee. Between July 1999 and December 2014, 825 ETVs were performed in 801 patients with hydrocephalus at two French neurosurgical centers: Toulouse and Bordeaux University Hospitals. Fifty-five patients presented CPA-related hydrocephalus and 45 of them had any form of CSF diversion before tumor management. These 45 cases underwent either ETV (n= 25) or VP shunting (n= 20) prior to tumor treatment. Both groups were comparable in age, histology, tumor’s size and location (Table 1). Prior to CSF diversion, there was no treatment on CPA tumors (radiosurgery, fractionated stereotactic radiotherapy or surgery). Information recorded included age, gender, MRI (tumors’ size, Evans ratio, 4th ventricle effacement), histology, new shunt insertions, and surgical complications. The Evans index is the ratio of the maximum width of the frontal horns to the maximum diameter of the inner table of the skull at the same level. The Shunt/ETV success was defined as clinical improvement and no more CSF diversion strategy after initial procedure, the failure was defined as any subsequent surgical procedure for CSF diversion and the surgical complication as unwanted side effect of diversion

strategies. The complications of the shunt led to their failure. Occurrences of tiny hemorrhages from the free edge of the ETV stoma and mild hemorrhages from ependymal veins were not considered to be complications. The follow-up was measured as either time to shunt/ETV failure or the last follow-up visit.

Endoscopic technique

The technique used was based on the procedural description of Roux et al. [22]. Perforation of the floor was made just behind the clivus, halfway between the infundibulum and the mammillary bodies in the midline followed by dilatation with a balloon catheter. The procedure was considered successful if both the clivus and the basilar artery could be clearly visualized, as described by Cinally [11], Drake [12] and Sacko et al. [21].

VP shunt placement was performed routinely (right side) using a programmable valve SOPHYSA SM8A (Sophysa, USA Inc, n = 13) and CODMAN HAKIM (DePuy, USA, n = 7).

Statistical analysis

Data were analyzed using the Sigma Stat® 4.0 software package (Systat Inc., Point Richmond, CA 94804-2028, USA). Categorical data were analyzed by the chi-square; t-test; normality (Shapiro-Wilk); Mann-Whitney Rank Sum or Fisher’s exact test if the expected frequencies were small. Significance was assigned as p < 0.05. The Gehan-Breslow statistic was used for the survival curves and a Multiple Logistic Regression (Pearson, Likelihood Ratio and Homer-Lemeshow tests) was applied to establish the relationship between various risk factors and ETV/shunt success or failure.

RESULTS

Patients characteristics

There were 7 males and 13 females in the shunt group with a median age of 59.5 (range 42-88). The ETV group included 10 males and 15 females, median age 55.5 (range 24 - 82). The median follow-up period was 67 months (range 22-166 months). All patients presented with symptomatic hydrocephalus and

Table 1: Demographic variable in 45 patients with CPA tumor and hydrocephalus.

ETV group, n=25 Shunt group, n=20 P

Median age, years 55.5 (24-82) 59.5 (42-88) 0.614

Mean age, years 56.8±5 58.3±8 0.614

Male/Female 10/15 7/13 0.731

HCP acute/chronic type 4/21 4/16 0.727

Evan’s ratio 0.36 (0.34-0.39) 0.35 (0.33-0.39) 0.712

Mean tumor size, cm 4 (1.8-6.3) 4.3 (2.8-5.9) 0.108

Tumor grade III/IV 7/14 6/12 1.000

Tumor removal 21 18 0.556

Meningioma/schwannoma 3/18 3/15 0.837

Radiotherapy without surgery 4* 2* 0.556P value from Chi square, Mann-Whitney Rank Sum and Fisher Exact testETV: endoscopic third ventriculostomyHCP: hydrocephalus*There was no histology for the 6 patients who had fractionated radiotherapy

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Table 2: CSF diversion outcome in 45 patients with hydrocephalus in CPA tumor.

ETV GROUP, n=25 SHUNT GROUP, n=20

Infection 0 3Overall procedure complications 0 11

Redo surgery for failure 9 11Tumor removal complicationsCSF leakage 0 0

Pseudomeningocele 0 0

Minor hematoma 1 1

Facial nerve palsy 38% (8/21) 39% (7/18)CSF: cerebro-spinal fluidCPA: cerebello-pontine angleETV: endoscopic third ventriculostomy

Table 3: Summary of previous reports, CSF leak after tumor removal in pre-operative hydrocephalus.

Treated HCP No treated HCP (%)

Briggs et al., [8] NA 36

Atlas et al., [23] NA 11.6

Pirouzmand et al., [2] NA 21

Tanaka et al., [4] 0 29Hayhurst et al., [20] (ETV) 0 NA

Present series (ETV) 0 NAHCP: hydrocephalus CSF : cerebro-spinal fluidNA : not available

Table 4: Correlation between the ETV failure and prognostic factors, details of the Logistic Regression Equation.

Independent variable P value Odds ratio Conf.

(low-upper)Constant .322 .0001 8 - 4366

Complication .997 .000001 0- (+inf)

Age .266 1.20 .8 - 1.68

Tumor size .237 .24 .02 - 2.52

Right/left .499 1.92 .3 - 12.8

Gender .260 3.48 .4 - 304th ventricle effacement .137 .13 .01 - 1.9

Histology .542 1.54 .4 - 6.2p value from Pearson statistic, Likelihood Ratio and Homer-Lemeshow testsConf.: confidence interval

Table 5: Correlation between the shunt failure and prognostic factors, details of the Logistic Regression Test.Independentvariable P value Odds ratio Conf.

(low-upper)Constant .364 .0005 5 - 5931

Age .576 1 0.9 - 1.2

Tumor size .485 2.49 .2 - 32

Right/left .690 1.69 .12 - 22

Gender .833 .726 .003 - 144th ventricle effacement .853 1.27 .1 - 15

Histology .555 1.71 .28 - 10p value from Pearson statistic, Likelihood Ratio and Homer-Lemeshow testsConf: confidence interval

radiological evidence of ventricular enlargement with a mean Evans ratio of 0.36 and 0.35 in ETV and shunt groups, respectively. There was a communicating type of HCP in 21 patients (ETV group) versus 16 cases in the shunt group. The mean tumor size was 4 cm (range 1.8-6.3 cm), and 4.3 (2.8-5.9 cm) in the ETV and shunt groups, respectively. After CSF diversion, 6 patients were treated by FSRT (without histology) and 39 were operated on with translabyrinthine (n = 32) and retrosigmoid (n = 7) approaches. The tumors were resected totally or near totally in 81%. In both groups, the CPA tumors consisted of 6 meningiomas and 33 vestibular schwannomas. (Table 1) lists the characteristics of the 45 patients included in this study. The complication and failure rates are detailed in (Table 2, Figure 1,2).

Shunt group

Among the 20 patients with a shunt, 55% (n=11) experienced at least one shunt complication and 15% (n=3) had multiple complications. The cumulative VP shunt complication rate was 5% (n=1) in the 1st month and 35% (n= 7) at 5 years. The complications of the shunt led to their failure. Thus, the causes of these 11 shunt failures were obstruction (n=8) and meningitis (n=3). These 3 infections were cured by appropriate antibiotic treatment; 54% (n=6/11) of the shunt failures occurred in the 1st year.

ETV group

There were no complications related to ETV surgery. The mean time between ETV and tumor treatment was 34 days (2-40 days). The overall ETV success rate (shunt free and no hydrocephalus symptoms) in this series was 64% (16 shunt free patients). In these 16 successful cases, ventricular size as measured by the Evans ratio remained unchanged at 1 year in 5 cases (31 %), and decreased in the others. The multiple logistic regression analysis (Table 4) did not show any significant correlation between various risk factors and ETV outcome (p = 0.322). After ETV, 67% (6 out of 9) of the failures occurred within the first month. In 3 patients who had FSRT, the ETV failed respectively 2, 7, and 15 months after treatment. The overall ETV success rate in patients younger than 50 years of age was 75% (6/8), compared with 59% (10/17) in patients ≥ 50 (p = 0.661). All the 9 patients with ETV failure required shunt placement. Four of them re-failed during a mean f o l lo w up period of 22 months (range 5 – 86 months). These 4 patients had multiple shunt procedures.

The Gehan-Breslow statistic found a significant difference between the ETV/Shunt complication survival curves (Gehan-Breslow Statistic = 3,947 and p=0,047), in the other hand there was no difference in the failure rates (p=1,000; 95%CI = 75-140 and 51-120 for ETV and shunt groups, respectively (Figures

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1,2). A multiple logistic regression model found no correlation between the different prognostic variables and the Shunt/ETV failure rate (Tables 4,5).

After tumor removal, no patient experienced a CSF leak or pseudomeningocele. There was no surgical mortality although some surgical complications were noted such as facial nerve palsy or minor intracranial hematoma after CPA tumor removal.

DISCUSSIONSome patients with CPA tumors develop hydrocephalus,

either at presentation or following tumor management even if they did not have any clinico-radiological sign of hydrocephalus before tumor treatment. Managements for CPA-tumors-related hydrocephalus include tumor removal without hydrocephalus treatment; shunting before tumor resection; tumor excision with external ventricular drainage; pretreatment with steroids and some authors have proposed CSF diversion procedures only for those who have postoperative progressive hydrocephalus [2,23]. Becker et al., stated that patients with symptomatic hydrocephalus should have an EVD a few days before tumor removal, which should be left in place until a few days after surgery [10]. The same procedure can be used for patients with asymptomatic HCP or with symptoms associated with adult onset chronic hydrocephalus [10].

Whatever the etiology of hydrocephalus or even the patients’ age, VP shunt failures are common with a significant morbidity. In the Tuli et al., series [24], over the 10-year period, there were 1183 shunt failures (all HCP etiologies) in 839 patients (141%).

The ratio of first shunt insertion to subsequent surgical revision was 1-2.5, thus the failure rate by 1 year after shunting was 25-40%. In the same patients, the number of redo surgeries for shunt failure varied from 6 to 30 [24]. Long-term study suggest that 81% of all VP patients required at least one revision with a mean revision number of 4.5 (range 0-26) [25]. In the present cohort and in the Wu et al., study [26], the cumulative shunt complication rate at 5 years was 35% and 32%, respectively.

Neurosurgeons are constantly working to reduce the number of shunt complications. One of the best ways of managing these complications is avoiding shunting [25]. Thus, since the middle of the 1990’s, ETV has become the standard treatment procedure for many cases of hydrocephalus. The ease of this procedure in trained hands, its high success and low complication rates have permitted the continuous review and expansion of indications for ETV, even in communicating hydrocephalus [2,17,27].

The pathogenesis of hydrocephalus in CPA tumors

The pathophysiology of hydrocephalus with CPA tumors is complex and not well understood. Hydrocephalus could be caused by compression of the fourth ventricle [8], the sloughing of protein from the tumor secondary to increased vascular permeability, or plugging of the arachnoid granulations resulting in malabsorption [28]. Alteration of CSF flow dynamics in the basilar cisterns [29], seeding of tumor cells, recurrent tumor bleeding producing meningeal adhesions [1], arachnoiditis [7], or a high fibrinogen concentration in the CSF [1] have also been described in the development of hydrocephalus in CPA tumors. Obstructive hydrocephalus, due to partial or complete occlusion

Failure survival analysis

Time, month

0 20 40 60 80 100 120 140 160 180

Sur

viva

l

0,0

0,2

0,4

0,6

0,8

1,0ETV Group

Shunt Group

ETV group

Shunt group

Figure 1 Graph showing the Kaplan-Meier survival of ETV/Shunt failure rate, the Gehan-Breslow statistic did not show a significant difference between the curves (p=1,000) (95%CI 75-140 and 51-120 for ETV and shunt, respectively).

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of the CSF pathway, may persist after tumor removal because of synechiae. In our series, only 8 patients (4 in both group) had radiologically complete obstruction of the aqueduct and/or the 4th ventricle. The occurrence of hydrocephalus in tumors less than 3 cm could result from insufficient CSF resorption, secondary to elevated CSF protein levels and/or arachnoid scarring [3,9], both resulting from the tumor. Overall, obstructive and communicating HCP may coexist [1,4]; CSF resorption troubles could be more important than an obstructive mechanical factor [1]. As had those of another series [2,9] most of our patients had symptoms similar to those observed in chronic adult hydrocephalus. Furthermore, in the Pirouzmand et al. [2], cohort the symptoms in 92% of the patients were mostly chronic and mild, consistent with normal pressure HCP. One could hypothesize on these data, the main cause of hydrocephalus in CPA tumors could be related to CSF troubles of resorption.

Different risk factors seem correlated with hydrocephalus development or persistence after tumor treatment: large tumor size, irregular tumor surface, and severe preoperative hydrocephalus [3,7]. Germanov et al., found that the surface of the tumor was the sole tumor characteristic which significantly correlated with HCP resolution; hydrocephalus resolved without additional treatment in 85.7% of vestibular schwannomas with a smooth surface [7]. In the other study [3], partial effacement of the fourth ventricle before treatment was the principal independent predictor of developing HCP with a risk of 28%. Finally, another author found, using a multiple logistic regression analysis, that only the CSF protein concentration was predictive for the

development of HCP [1]. In our cohort, there was no statistical difference between diversion procedures’ outcome and neither 4th ventricle effacement nor other prognostic factors (Table 4,5). A single statistical difference was found in the procedures’ complication rates (Figure 2).

ETV prognosis

Because CPA tumors surgery in patients with untreated hydrocephalus have higher complication rates or may lead to a worse outcome [2,4,7], some surgeons prefer initial hydrocephalus treatment by an EVD or even placement of a VP shunt prior to surgery [7]. In the Briggs [8] and Atlas et al., studies [23], as shown in Table (3), CSF leaks were encountered respectively in 36% and 11.6% of the patients in whom the hydrocephalus was not managed before tumor treatment. Pirouzmand et al., reported a rate of 17% for postoperative pseudomeningoceles and 21% for CSF leaks in patients who had untreated hydrocephalus [2]. In the same series, 39% of patients with preoperative hydrocephalus, who had tumor resection without shunt placement, presented with symptoms of persistent hydrocephalus [2]. In the Tanaka et al., cohort [4], CSF leakage was encountered in 0% of the patients with hydrocephalus who had a shunt, and in 29.2% of the patients with untreated hydrocephalus at the time of tumor resection.

The results of these series may encourage hydrocephalus treatment before CPA tumors treatment. Moreover, Hayhurst et al., noted neither CSF leakage nor pseudomeningocele formation in a series of 11 patients with CPA tumors and hydrocephalus

Complications survival analysis

Time, months

0 20 40 60 80 100 120 140 160 180

Sur

viva

l

0,0

0,2

0,4

0,6

0,8

1,0

ETV group

Shunt group

Figure 2 Graph showing the Kaplan-Meier survival of ETV/Shunt complication rate, demonstrating a significant difference between survival curves (Gehan-Breslow Statistic = 3,947 and p=0,047).

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treated by ETV prior to surgery [20]. In the present study, after tumor removal, there was no CSF leakage or pseudomeningocele in both groups. Although still controversial, ETV could also be effective in some cases of presumed communicating hydrocephalus [13,14,18], especially with CPA tumors [30]. Moreover, as shown in our and other [31,32] series, ETV can be used in cases of communicating hydrocephalus with some success.

We believe that initial management should be directed toward treatment of hydrocephalus before tumor excision, and primary ETV can avoid the need for perioperative CSF external drainage and shunting. In this retrospective study, CSF protein levels and MRI-based CSF sequences before and after ETV were not obtained for most of the patients. We used, as did Drake et al. [12], a fairly strict and patient oriented definition for ETV success, a positive outcome was defined as the improvement of clinical symptoms and no further CSF diversion procedures. The overall 64% success rate in our cohort is very similar to the sole previously reported successful rates of ETV in CPA tumors [20]. Nevertheless, this result could be related to the resection of the space-occupying lesions performed after ETV and not directly to ETV itself. Then, the success rate of ETV itself could be overestimated. In our practice, the number of VP shunts used for treating hydrocephalus in CPA tumors over the last 10 years decreased by four times in favor of the ETV.

CONCLUSIONSOverall, we believe that ETV could be used as the first line

of hydrocephalus management in CPA tumors. ETV is simple to perform, has a low morbidity rate, and is a safe treatment option for hydrocephalus related to CPA tumors. It can avoid shunting and its complications.

ACKNOWLEDGEMENTSThe authors thank the « Association pour la Recherche sur les

Tumeurs Cérébrales, ARTC » (Association for Research on Brain Tumors) for their support to neuro-oncology patients, medicine residents and our research on brain tumors.

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