CLINICAL ARTICLE - BRAIN TUMORS

True aqueductal tumors: a unique entity

Jonathan Roth & Kaisorn L. Chaichana & George Jallo &

GiuseppeMirone &Giuseppe Cinalli & Shlomi Constantini

Received: 29 August 2014 /Accepted: 21 October 2014# Springer-Verlag Wien 2014

AbstractBackground Pure aqueductal tumors (ATs) differ from pinealregion and tectal/tegmental tumors in that they are epicenteredwithin the aqueduct. Nevertheless, these tumors are rarelydescribed as a separate type of tumor, and are often groupedwith other lesions located in the same vicinity. The presentmulticenter study focuses on our experience treating patientswith pure ATs.Methods Data from three large tertiary centers was collectedretrospectively, including presenting symptoms, treatmentparadigm, surgical approaches, pathology, and outcome.Results Between 1999 and 2013, 16 patients with AT werediagnosed and treated at the three tertiary centers. Ages atpresentation ranged from 5.5 to 57 years. Thirteen patientspresented with hydrocephalus-related symptoms, and twowere identified incidentally. Thirteen patients underwent anendoscopic third ventriculostomy, and two of these underwenta simultaneous endoscopic biopsy (one grade II ependymoma,one non-specified low-grade glioma). Two others underwentshunt placement. Three patients underwent resection due totumor progression. Pathologies included glioblastomamultiforme, glioneural tumor, and ependymoma grade II. Allnon-resected tumors remained stable or grew only minimally.

Conclusions ATs are a rare entities that usually present withobstructive hydrocephalus. Treatment includes primarily ce-rebrospinal fluid drainage (preferably via an endoscopic thirdventriculostomy). Simultaneous endoscopic biopsy may bedone in selected cases. Tumor resection should be reservedfor growing tumors; the trans-fourth ventricular or trans-choroidal approaches are probably safer than other approachesused to reach the tectal region.

Keywords Aqueduct . Tumor . Hydrocephalus . Endoscopicthird ventriculostomy . Endoscopic biopsy

Introduction

True aqueductal tumors (ATs) are rare entities that have sel-dom been described. Most ATs are combined with other peri-aqueductal tumors including tectal, pineal, and/or posteriorthird ventricular tumors [4, 19, 30]. Similar to other “tectalregion” lesions, aqueductal tumors tend to occlude the aque-duct and cause obstructive hydrocephalus; however, there aresparse data on the pathological spectrum of these tumors andtheir natural history [12].

Prior publications have stated that ATs include astrocyto-mas, subependymomas, oligodendroglioma, ependymomas,and heterotopias [12, 22, 24, 25, 27, 30, 35, 36]. However,most pathological data are based on postmortem studies.Currently, there is no literature focusing on the diagnosticand treatment approaches to these tumors in the modern era,especially since the introduction of high-resolution magneticresonance imaging (MRI) and endoscopic techniques.

The objective of the current study was to report the expe-rience treating these rare tumors, focusing on anatomicalnuances, pathological findings, and treatment implications.

J. Roth (*) : S. ConstantiniDepartment of Pediatric Neurosurgery, Dana Children’s Hospital,Tel-Aviv Medical Center, Tel-Aviv University, 6 Weizman Street,Tel Aviv 64239, Israele-mail: jonaroth@gmail.com

K. L. Chaichana :G. JalloDepartment of Pediatric Neurosurgery, Johns Hopkins Children’sCenter, Baltimore, MD, USA

G. Mirone :G. CinalliDepartment of Pediatric Neurosurgery, Santobono-PausiliponChildren’s Hospital, Naples, Italy

Acta NeurochirDOI 10.1007/s00701-014-2264-9

Methods

Following institutional review board (IRB) approval, we com-pleted a retrospective, multicenter study. Patients with tumorsepicentered in the aqueduct of Sylvius were collected andanalyzed. Participating centers included Tel-Aviv MedicalCenter (Dana Children’s Hospital, DCH, Tel-Aviv, Israel),Johns Hopkins Medical Institute (Johns Hopkins Children’sCenter, JHCC, MD, USA), and Santobono-PausiliponChildren’s Hospital (SPCH, Naples, Italy).

Data since 2009 were collected retrospectively from thepatient registrar of the Department of Pediatric Neurosurgeryat DCH, since 1999 from the Department of PediatricNeurosurgery at JHCC, and since 2004 from SPCH. Theinformation collected included demographic, clinical, radio-logical, surgical, and outcome data.

All patients (both pediatric and adult) who had lesions withtheir epicenter within the aqueduct and suspected of being atumor (with a mass effect, not purely cystic, regardless ofcontrast enhancement) were included. Lesions were allowedto extend beyond the aqueduct (to the third or fourth ventri-cle); however, the main portion of the tumor had to be locatedwithin the aqueduct. To differentiate AT from other adjacentlocations, the tectum had to be non-expansive and with nosignal abnormality on axial and sagittal T2 sequences (asopposed to tectal gliomas), and the midbrain tegmentum hadto show no signal abnormality on axial and sagittal T2 (asopposed to an exophytic brainstem tumor).

Lesions where the epicenter could not be definitively lo-cated (such as large tectal/pineal/tegmental tumors) or lesionssuspected of being of infectious or vascular origin wereexcluded.

Statistics

Collected data were analyzed using an Excel database, calcu-lating average and standard deviation for the numerical data,and using descriptive measures for non-numerical data.

Results

Demographics

Between 1999 and 2013, 16 patients (9 female) were diag-nosed with true AT and treated at the three centers (8 at DCH,6 at JHCC, and 2 at SPCH). These included eight children(5.5–16 years old) and eight adults (19–57 years old). Twochildren had neurofibromatosis (NF type 1 and NF type 2).None of the other patients had any known genetic syndrome.

Presentation

The most common presenting symptoms were related to ele-vated intracranial pressure secondary to hydrocephalus (13 of16 patients), and included: headaches (9 patients), diplopia (7patients), gait disturbances (3), seizures (1), and nausea andvomiting (1). There were two incidental cases: one during NFtype 2 surveillanceMRI, and one following head injury and anacute epidural hematoma causing symptoms.

Signs at presentation included papilledema (seven pa-tients), gait instability (one), and visual decline (one, relatedto an optic pathway glioma [OPG] related to NF1). The otherseven patients were neurologically intact.

Radiological findings

All patients had evidence of ventriculomegaly, where threehad mild and the others moderate-severe ventricular enlarge-ment. Lesion sizes (superior-inferior) were 4–20 mm. Fifteenlesions were hyperintense and one isointense on T2. On T1,nine were hypointense and seven isointense. Three had patchyenhancement following gadolinium injection, while the re-maining 13 had no enhancement. Four had cystic components(of which two seemed to be tectal cysts disconnected from thetumor). The aqueductal tumor in the NF1 child was unrelatedto the OPG. Table 1 compares the radiographic characteristicsof the incidental, non-incidental, and growing lesions.Figures 1 and 2 illustrate examples of the lesions that wereincluded.

Primary treatment

Fifteen of 16 patients underwent a cerebrospinal fluid (CSF)-diversion procedure at presentation. Thirteen had an endo-scopic third ventriculostomy (ETV), where two underwentsimultaneous endoscopic biopsy of the tumor. All ETVs weredone using a rigid endoscope, and the biopsies were doneusing a flexible endoscope, entering through the same tract asfor the ETV. Two patients received a ventriculo-peritonealshunt (VPS), one due to an OPG and another due to a thick-ened third ventricular floor that precluded a safe ETV.Following CSF surgery, all symptoms resolved.

Pathological results of the biopsies were ependymomagrade II and non-specified low-grade glioma (LGG).

Follow-up

All 16 tumors were followed regardless of their primarypathology or treatment. Follow-up duration for the entiregroup ranged from 17.5 to 140 months (mean±standard de-viation, 50.5±37.4). Three patients underwent tumor resec-tion 15–19 months following presentation due to tumor pro-gression (illustrated in Figs. 3 and 4). Surgical approaches

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included trans-fourth ventricle (two) and parietal inter-hemispheric (one).

Follow-up of the 13 non-resected tumors was 17.5–140 months (55±40 months). One tumor displayed minimalgrowth and is still being followed, one tumor displayed min-imal shrinkage, and one tumor underwent cystic changes. Theremaining ten tumors were stable.

Pathological results and outcome of resected cases

Pathological results of the two endoscopic biopsies were oneependymoma (WHO grade II) and one non-specified low-grade glioma (Table 2). Pathological results of the threeresected tumors were one ependymoma (WHO grade II),one glioblastoma multiforme (GBM), and one glioneural

tumor (WHO grade I). One of the endoscopic biopsies (theependymoma grade II) was later resected and reclassified asthe glioneural tumor.

One resection patient (GBM) underwent additional oncolog-ical treatments, including both radiation and chemotherapy.

Surgical morbidity for the three patients that underwenttumor resection included permanent diplopia (GBM, trans-fourth ventricle approach), transient diplopia (ependymomaII, trans-fourth ventricle approach), and upper midbrain injury(glioneural tumor, parietal inter-hemispheric approach).

Follow-up of the resected cases was 28–42 months. TheGBM recurred and responded to additional oncological treat-ments. The remaining 2 two tumors (low-grade) did not recur.Glasgow outcome scale was 3 (GBM), 4 (glioneural tumor),and 5 (ependymoma).

Table 1 Radiological characteristics

Incidental (2 cases) Non-incidental (14 cases) Growing lesions (3 cases)

Primary size (mm) 4–13 4–20 4–16

Associated hydrocephalus 2/2 mod-sev 11/14 mod-sev, 3/14 mild 3/3 mod-sev

T1 2/2 iso 9/14 hypo, 5/14 iso 2/3 hypo, 1/3 iso

T1-gadolinium 2/2 no 3/14 patchy enh, 11/14 no 2/3 patchy enh

T2 1/2 iso, 1/2 hyper 14/14 hyper 3/3 hyper

Cystic component 0/2 3/14 0/3

Growing lesions 1/2 2/14 3/3

mod-sev moderate-severe, hypo hypointense, iso isointense, hyper hyperintense, enh enhancement

Fig. 1 Aqueductal tumors—sagittal view

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Fig. 2 Aqueductal tumors—axial view

Fig. 3 An 11-year-old boy with NF type 2 and aqueductal ependymoma. aAt presentation; b 7 months later, c 10 months later, and d 14 months later. eFollowing resection via trans-fourth ventricular approach

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Discussion

To our knowledge, this is the first series focusing on a selectgroup of true ATs that arise within the cerebral aqueduct withmodern imaging, follow-up, and a discussion of clinical andsurgical options.

Similar to tectal gliomas, most ATs present with the symp-toms of obstructive hydrocephalus [4, 12–14, 19, 22, 25, 35,36]. However, while tectal gliomas typically represent anindolent form of low-grade glial tumors infiltrating and “bal-looning” the tectum, ATconsist of a discrete aqueductal mass,representing a wider histo-pathological spectrum that includesboth low and high-grade pathologies.

Pathology

Aqueductal gliomas, once called “pencil gliomas”, typicallyarise from the periaqueductal region and occupy theaqueductal lumen [22, 25, 36]. Other aqueductal pathologiesinclude heterotopias [35], pilocytic astrocytomas [12, 13],s u b e p e n d ymoma s [ 1 2 ] , e p e n d ymoma s [ 3 2 ] ,ependymoblastomas [21], glioneuronal tumors (WHO I) [14,26], and medulloblastomas [21].

In the present series, most of the lesions remainedstable and were not sampled; however, three lesionsgrew and were resected. The pathologies identified in-cluded: ependymoma (grade II, associated with NF type2), glioneuronal tumor (grade I), and GBM. An addi-tional case was only biopsied (low-grade glioma,unspecified).

AT in the context of NF type 1, including pilocyticastrocytoma [13, 27] and fibrillary astrocytoma [25],have been described. In NF type 2, intracranialependymomas are rare, and have never been describedas an AT.

Fig. 4 A 31-year-old man with GBM. a,c At presentation (underwentonly an ETV); b, d 15 months later

Tab

le2

Operatedtumors,pathology,andoutcom

e

Age

atsurgery(years)

Pathologyper

endoscopicbiopsy

Pathologyperresection/

degree

ofresection

Adjuvanttreatments

Follow-upsinceprim

ary

diagnosis(m

onths)

Current

tumor

status

Clin

icalstatus

33Ependym

omaII

Glio

neuraltumor

(WHOI)/G

TR

28Noresidual

BilateralC

N3palsy,

neurocognitiv

edecline

27LGG

34Stable

Intact

11Ependym

omaII/G

TR

28Noresidual

Intact

31GBM

/GTR

Radiatio

n,chem

otherapy

42Noresidual

Diplopia

CNcranialn

erve,W

HOWorld

Health

Organization,GBM

glioblastomamultiforme

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Differential diagnosis

The differential diagnosis of AT includes other tumors in thesame region such as tectal gliomas and pineal tumors, as wellas non-neoplastic pathologies such as infections, vascularlesions, and blood clots, which may mimic neoplasms andcause aqueductal obstruction.

& Tectal gliomas are typically low-grade gliomas, causingtectal expansion and compression of the aqueduct, andoften extend to the pulvinar region. They are best diag-nosed on axial and sagittal MRI scans, are hyperintense onT2, iso-hypointense on T1, and usually do not enhance.AT, on the other hand, may include various pathologicalentities (including low- and high-grade lesions), and thusthe MRI signal may not be consistent; however, the le-sions are by definition located within the aqueduct, withthinning and out-bowing of the tectal plate (Figs. 1 and 2).Similarly, the midbrain tegmentum is not involved, though itmay be compressed. These neuroanatomical nuances are bestviewed on axial and sagittal T2 and non-contrast T1 se-quences. Despite these differences, the epicenter of the tumorcan be difficult to delineate even on MRI, and there is anoverlap between tegmental-aqueductal-periaqueductal-tectaltumors [15, 21, 37]. Realistically, some ATs are probablyincluded in “tectal glioma” series [4].

& Pineal tumors also display a variety of radiological fea-tures depending on pathology. They cause tectal andaqueductal compression, compressing these structuresfrom the superior–posterior aspect.

& In fec t ions loca t ed in the aqueduc t inc ludeneurocysticercosis, toxoplasmosis, hydatid cysts, and fun-gal infections such as cryptococcal meningitis [11, 31, 33,34]. These conditions are rare, often have a cystic appear-ance, and are usually accompanied by other radiologicalfindings (such as additional lesions) as well as a relevantpatient history.

& Vascular lesions may be located in the aqueduct and leadto obstructive hydrocephalus. These include cavernomas[12], venous angiomas [3, 12], and AVMs [10]. Theselesions usually display additional (and typical) radiologi-cal findings.

& Traumatic and spontaneous clots may also cause acuteaqueductal obstruction, and are usually easily differentiat-ed from tumors.

Treatment strategies

Based on this medium-sized series, it is only appropriate tosuggest potential treatment algorithms. Surgery for AT hasseveral goals:

1. Most important is controlling the hydrocephalus.2. Obtaining a tumor biopsy when feasible.3. Tumor resection, only when appropriate.

Most ATs present with obstructive hydrocephalus. Wetherefore recommend performing an ETV when possible, oralternatively a VPS as a second choice, as necessary.

With respect to dealing with the neoplasm and the onco-logical aspects, the literature on surgical treatment of AT islimited, as is our knowledge of the pathological spectrum,clinical progression, and outcome for these tumors. The cur-rently presented series demonstrates the pathological hetero-geneity, anatomical variation, and, therefore, different clinicalcourses observed over time. It is clear that treatment optionshave to be decided on an individual basis based on the vari-ables listed here.

Tumor biopsy

In selected cases—such as large or enhancing tumors, andthose extending into the third ventricle—it may be feasibleand advisable to perform an endoscopic biopsy simultaneous-ly with the ETV. Knowing the pathology at this initial stage ofthe disease may be very helpful in designing a rational treat-ment strategy for the individual patient. According to a re-cently published series of 293 endoscopic biopsies fromventricular/paraventricular tumors [6], 90 % of biopsies werediagnostic. Of 78 patients who underwent subsequent opensurgery, only 11 % had a significant mismatch between theendoscopic and open biopsies; with all mismatches showing alow-grade finding on the endoscopic specimen and a higher-grade finding with the open biopsy.

Since the endoscopic approach to the third ventricle islimited by the foramen of Monro, working at the aqueductalregion requires modification of the standard ETV procedure.Similar discussions in the context of pineal region tumorsappear frequently in the neuroendoscopic literature. Threeoptions are described: working with two entry burr holes fortwo separate trajectories [5, 16, 18]; working with a single“compromised” burr hole for both the ETVand the biopsy [7,16, 28]; and using a flexible endoscope [17, 20, 23]. Foraqueductal tumor, located at the posterior-inferior part of thethird ventricle, and often below the level of the floor of thethird ventricle, we recommend working with a single entryport as for an ETVusing a rigid endoscope, which has superiorvisual quality compared to the flexible endoscope, and thenperforming the biopsy using a flexible endoscope, which hasbetter maneuverability compared to the rigid endoscope. Thelimitations of this approach are the need for an additionalendoscope, and the small biopsy samples obtained with theflexible endoscope. An alternative is to use the flexible endo-scope to perform both the biopsy and the ETV [19]. Theshortcoming of the flexible endoscope is its small lumen,

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which restricts the forceps size and subsequent biopsy size.One of the two biopsies in the current series produced resultsthat differed from the final pathological result of the operatedcase (ependymoma II [biopsy] versus glioneural tumor [sur-gery]). Currently, there is controversy in the literature regard-ing the accuracy of endoscopic biopsies performed using aflexible versus a rigid endoscope. The flexible endoscopicbiopsy forceps are smaller than those of the rigid systems,affecting the size of the biopsy specimen. Thus, several au-thors have postulated that specimens obtained with the flexi-ble endoscope are more susceptible to sampling error [1, 7].On the other hand, others have not demonstrated any reducedrate of diagnostic accuracy using the flexible endoscopes [2, 9,17, 20]. Thus, to reduce the chance of sampling error, espe-cially when performing small biopsies with flexible endo-scopes, we recommend obtaining several pathological speci-mens whenever possible.

Surgical resection

The pathological results obtained from endoscopic biopsiesmust be used with caution. When the pathology indicates ahigh-grade tumor, it can serve as the basis for a decision tooperate, or alternatively, treat with radiation and/or chemo-therapy. On the other hand, when the pathology indicates alow-grade tumor (including ependymoma grade II), a moreconservative approach of careful follow-up with surveillanceimaging may be indicated. One of the advantages of thisapproach is that both patients and surgeons may more readilyaccept the potential morbidity associated with resection at thisregion, when it is indicated. Even mild diplopia and certainlyupper-gaze palsy may dramatically affect the quality of life ofa patient, especially in adults. We therefore prefer, under suchcircumstances, to reserve surgical resection for those withdocumented tumor growth and/or development of symptoms.These treatment strategies, including surgical and medicalalternatives, must be discussed openly with the patients andtheir families.

There are several options for surgical resection of AT,depending primarily on anatomical variables such as theirheight within the aqueduct and the size of the ventricles.Isolated case reports of endoscopic resection of AT exist [8,26, 29, 32]; however, endoscopic resection is limited byseveral factors. For example, use of endoscopes for tumorresection necessitates rigid endoscopes with larger workingchannels as well as an endoscopic ultrasonic aspirator [26].While use of flexible endoscopes for removal of third ventric-ular or aqueductal tumors has been described [8], the extent ofremoval is often only partial due to technical limitations.Using endoscopic suction for resection may have limitedefficacy, especially when the tumors are vascular or not ame-nable to suction. Regardless of the endoscopic type, whenapproaching the tumor, the long axis of the tumor is not in line

with the approach trajectory, and thus resection is limited andmore difficult.

Open approaches to the pineal/tectal region include thesupracerebellar infratentorial, occipital transtentorial, and theparietal inter-hemispheric transsplenial approaches. All theseapproaches provide access to the tectum, but with limitedexposure to the aqueduct. In addition, splitting the tectum inthe midline injures the crossing fibers of the trochlear nerve atthe level of the inferior culliculi and the posterior commissurejust above the tectum. Thus, we do not recommend theseapproaches for aqueductal tumors. Rather, we suggest usingeither a trans-fourth ventricular approach (approaching thetumor from below), or a trans-choroidal approach (ap-proaching the tumor from above, through the third ventricle),depending on specific anatomical considerations.

The trans-fourth ventricular approach requires maximumhead flexion, and bilateral release of the tela-velar bands.Then, both tonsils as well as the vermis may be elevated andheld with self-retaining retractors, enabling a tight but suffi-cient corridor to the lower opening of the aqueduct. It isimportant to protect the fourth ventricle floor with cottonoids.Once the lower end of the tumor is exposed, careful dissectionand piecemeal tumor resection is performed. A trans-fourthventricle approach is preferred if the lesion does not bulgeupward, if the tumor is located closer to the lower end of theaqueduct, or if the tumor extends below the aqueduct.

The trans-choroidal approach from the lateral and thirdventricles is preferred when the tumor bulges towards thethird ventricle, or when it is located closer to the upper endof the aqueduct. Technically, the tumor is removed in a similarfashion in both approaches.

It is important to clarify if there is a true border between thetumor and the ependyma of the aqueduct (such as inependymomas), or if the tumor infiltrates into the surroundingperiaqueductal region (such as in diffuse astrocytomas).Infiltrative tumors should probably be subtotally removed toavoid tectal and tegmental injury. Ultrasonic aspirators mayhave a limited role in tumor removal, as the working space isnarrow.

Limitations

The main limitation of this study is its retrospective nature, aswell as the fact that all three participating departments treatmostly pediatric patients. Thus, there is a bias towards pedi-atric inclusion. Another major limitation is the anatomicaloverlap of ATs with other neighboring tumors, such as tectalgliomas. It is very likely that the actual prevalence of ATs ishigher than that noted in this study, since some ATs haveprobably been misclassified as tectal gliomas due to a trueoverlap between both pathologies as well as the lack ofawareness of the AT entity. Additionally, this relatively smallseries, although the largest to date on this entity, prevails true

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conclusions regarding the natural history of ATs, and generalrecommendations regarding their treatment. We hope that thispaper will encourage other groups to help define the uniquefeatures of AT in the future.

Conclusions

ATs are a rare entity that present mostly with obstructivehydrocephalus. Treatment includes primarily CSF diversionprocedures (preferably an ETV). Simultaneous endoscopicbiopsy may be done in selected cases, such as for large orenhancing tumors; we recommend using a flexible endoscopefor this task. Tumor resection should be reserved for growingtumors; the trans-fourth or trans-choroidal approaches areprobably safer than other approaches used to reach the tectalregion.

Acknowledgments We thank Lyonell Kone, B.S. for his assistancecollecting data, Mrs. Sigal Friedman for graphic editing, and Mrs. AdinaSherer for text editing.

Conflict of interest All authors certify that they have no affiliationswith or involvement in any organization or entity with any financialinterest (such as honoraria; educational grants; participation in speakers’bureaus; membership, employment, consultancies, stock ownership, orother equity interest; and expert testimony or patent-licensing arrange-ments), or non-financial interest (such as personal or professional rela-tionships, affiliations, knowledge or beliefs) in the subject matter ormaterials discussed in this manuscript.

References

1. Ahn ES, Goumnerova L (2010) Endoscopic biopsy of brain tumorsin children: diagnostic success and utility in guiding treatment strat-egies. J Neurosurg Pediatr 5:255–262

2. Al-Tamimi YZ, Bhargava D, Surash S, Ramirez RE, Novegno F,Crimmins DW, Tyagi AK, Chumas PD (2008) Endoscopic biopsyduring third ventriculostomy in paediatric pineal region tumours.Childs Nerv Syst 24:1323–1326

3. Bannur U, Korah I, Chandy MJ (2002) Midbrain venous angiomawith obstructive hydrocephalus. Neurol India 50:207–209

4. Bowers DC, Georgiades C, Aronson LJ, Carson BS, Weingart JD,Wharam MD, Melhem ER, Burger PC, Cohen KJ (2000) Tectalgliomas: natural history of an indolent lesion in pediatric patients.Pediatr Neurosurg 32:24–29

5. Chibbaro S, Di Rocco F, Makiese O, Reiss A, Poczos P, Mirone G,Servadei F, George B, Crafa P, Polivka M, Romano A (2012)Neuroendoscopic management of posterior third ventricle and pinealregion tumors: technique, limitation, and possible complicationavoidance. Neurosurg Rev 35:331–338, Discussion 338–340

6. Constantini S, Mohanty A, Zymberg S, Cavalheiro S, Mallucci C,Hellwig D, Ersahin Y, Mori H, Mascari C, Val JA, Wagner W,Kulkarni AV, Sgouros S, Oi S (2013) Safety and diagnostic accuracyof neuroendoscopic biopsies: an international multicenter study. JNeurosurg Pediatr 11:704–709

7. Depreitere B, Dasi N, Rutka J, Dirks P, Drake J (2007) Endoscopicbiopsy for intraventricular tumors in children. J Neurosurg 106:340–346

8. Feletti A, Marton E, Fiorindi A, Longatti P (2013) Neuroendoscopicaspiration of tumors in the posterior third ventricle and aqueductlumen: a technical update. Acta Neurochir (Wein) 155:1467–1473

9. Gangemi M, Maiuri F, Colella G, Buonamassa S (2001) Endoscopicsurgery for pineal region tumors. Minim Invasive Neurosurg 44:70–73

10. Geibprasert S, Pereira V, Krings T, Jiarakongmun P, Lasjaunias P,Pongpech S (2009) Hydrocephalus in unruptured brain arteriovenousmalformations: pathomechanical considerations, therapeutic implica-tions, and clinical course. J Neurosurg 110:500–507

11. Gokalp HZ, Erdogan A (1988) Hydatid cyst of the aqueduct ofSylvius: case report. Clin Neurol Neurosurg 90:83–85

12. Ho KL (1982) Tumors of the cerebral aqueduct. Cancer 49:154–16213. Hosoda K, Kanazawa Y, Tanaka J, Tamaki N, Matsumoto S (1986)

Neurofibromatosis presenting with aqueductal stenosis due to a tu-mor of the aqueduct: case report. Neurosurgery 19:1035–1037

14. Marcorelles P, Fallet-Bianco C, Oury JF, van Wallenghem E, ParentP, Labadie G, Lagarde N, Laquerriere A (2005) Fetal aqueductalglioneuronal hamartoma: a clinicopathological and physiopatholog-ical study of three cases. Clin Neuropathol 24:155–162

15. May PL, Blaser SI, Hoffman HJ, Humphreys RP, Harwood-Nash DC(1991) Benign intrinsic tectal “tumors” in children. J Neurosurg 74:867–871

16. Morgenstern PF, Souweidane MM (2013) Pineal region tumors:simultaneous endoscopic third ventriculostomy and tumor biopsy.World Neurosurg 79(S18):e19–13

17. O’Brien DF, Hayhurst C, Pizer B, Mallucci CL (2006) Outcomes inpatients undergoing single-trajectory endoscopic thirdventriculostomy and endoscopic biopsy for midline tumors present-ing with obstructive hydrocephalus. J Neurosurg 105:219–226

18. Oi S, ShibataM, Tominaga J, Honda Y, ShinodaM, Takei F, TsuganeR, Matsuzawa K, Sato O (2000) Efficacy of neuroendoscopic proce-dures inminimally invasive preferential management of pineal regiontumors: a prospective study. J Neurosurg 93:245–253

19. Oka K, Kin Y, Go Y, Ueno Y, Hirakawa K, Tomonaga M, Inoue T,Yoshioka S (1999) Neuroendoscopic approach to tectal tumors: aconsecutive series. J Neurosurg 91:964–970

20. Oppido PA, Fiorindi A, Benvenuti L, Cattani F, Cipri S, Gangemi M,Godano U, Longatti P, Mascari C, Morace E, Tosatto L (2011)Neuroendoscopic biopsy of ventricular tumors: a multicentric expe-rience. Neurosurg Focus 30:E2

21. Pendl G, Vorkapic P, Koniyama M (1990) Microsurgery of midbrainlesions. Neurosurgery 26:641–648

22. Pool JL (1968) Gliomas in the region of the brain stem. J Neurosurg29:164–167

23. Pople IK, Athanasiou TC, Sandeman DR, Coakham HB (2001) Therole of endoscopic biopsy and third ventriculostomy in the manage-ment of pineal region tumours. Br J Neurosurg 15:305–311

24. Rilliet B, Reverdin A, Haenggeli CA, Pizzolato GP, Berney J (1990)Tumors of aqueduct of Sylvius. Presentation of 5 cases and review ofthe literature. Neurochirurgie 36:336–346

25. Sanford RA, Bebin J, Smith RW (1982) Pencil gliomas of theaqueduct of Sylvius: report of two cases. J Neurosurg 57:690–696

26. Selvanathan SK, Kumar R, Goodden J, Tyagi A, Chumas P (2013)Evolving instrumentation for endoscopic tumour removal of CNStumours. Acta Neurochir (Wein) 155:135–138

27. Sola J, Arcas I, Martinez-Lage JF, Martinez Perez M, Esteban JA,Poza M (1987) Astrocytoma of the cerebral aqueduct. Childs NervSyst 3:294–296

28. Song JH, Kong DS, Shin HJ (2010) Feasibility of neuroendoscopicbiopsy of pediatric brain tumors. Childs Nerv Syst 26:1593–1598

29. Souweidane MM, Luther N (2006) Endoscopic resection of solidintraventricular brain tumors. J Neurosurg 105:271–278

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30. Steinbok P, BoydMC (1987) Periaqueductal tumor as a cause of late-onset aqueductal stenosis. Childs Nerv Syst 3:170–174

31. Takei H, Goodman JC, Powell SZ (2007) Cerebral phaeohyphomycosiscaused by ladophialophora bantiana and Fonsecaeamonophora: report ofthree cases. Clin Neuropathol 26:21–27

32. Terasaki M, Uchikado H, Takeuchi Y, Shigemori M (2005)Minimally invasive management of ependymoma of the aqueductof Sylvius: therapeutic considerations and management. MinimInvasive Neurosurg 48:322–324

33. van Landeghem FK, Stiller B, Lehmann TN, Sarioglu N, Sander B,Lange PE, Stoltenburg-Didinger G (2000) Aqueductal stenosis andhydrocephalus in an infant due to aspergillus infection. ClinNeuropathol 19:26–29

34. van Toorn R, Rabie H (2005) Pseudocystic cryptococcalmeningitis complicated by transient periaqueductal obstruc-tion in a child with HIV infection. Eur J Paediatr Neurol 9:81–84

35. Vuia O (1975) Stenosis of the aqueduct of Sylvius by aheterotopic island of grey matter. Neurochirurgia (Stuttg) 18:109–112

36. Wagle VG, Hall A, Voytek T, Silberstein H, Uphoff DF (1990)Aqueductal (pencil) glioma presenting as neurogenic pulmonaryedema: a case report. Surg Neurol 34:435–438

37. Yeh DD, Warnick RE, Ernst RJ (2002) Management strategy foradult patients with dorsal midbrain gliomas. Neurosurgery 50:735–738, Discussion 738–740

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