Obstructive hydrocephalus from posterior fossa tumor risk factors

Obstructive hydrocephalus from posterior fossa tumor risk factors

Saad et al. from the Emory University Hospital surveyed the CNS (Central Nervous System) Tumor Outcomes Registry at Emory (CTORE) for patients who underwent posterior fossa tumor surgery at 3 tertiary-care centers between 2006 and 2019. Demographic, radiographic, perioperative, and dispositional data were analyzed using univariate and multivariate models.

They included 617 patients undergoing PFT resection for intra-axial (57%) or extra-axial (43%) lesions. Gross total resection was achieved in 62% of resections. Approximately 13% of patients required permanent cerebrospinal fluid shunt. Only 31.5% of patients who required pre- or intraop external ventricular drain (EVD) placement needed permanent cerebrospinal fluid shunt. On logistic regression, Tumor size, transependymal edema, use of perioperative external ventricular drain, postoperative intraventricular hemorrhage (IVH), and surgical complications were predictors of permanent CSF diversion. Preoperative tumor size was the only independent predictor of postoperative shunting in patients with subtotal resection. In patients with intra-axial tumors, transependymal flow (P = .014), postoperative IVH (P = .001), surgical complications (P = .013), and extent of resection (P = .03) predicted need for shunting. In extra-axial tumors, surgical complications were the major predictor (P = .022).

The study demonstrates that the presence of preoperative hydrocephalus in patients with PFT does not necessarily entail the need for permanent CSF diversion. Saad et al. reported the major predictive factors for needing a permanent cerebrospinal fluid shunt for obstructive hydrocephalus 1).


Superior tumor extension (into the aqueduct) and failed total resection of tumor were identified as independent risk factors for postoperative hydrocephalus in patients with fourth ventricle tumor 2).


Cully and colleagues analyzed 117 patients and found the following factors to be associated with a higher incidence of postresection hydrocephalus (PRH): age <3 years, midline tumor location, subtotal resection, prolonged EVD requirement, cadaveric dural grafts, pseudomeningocele formation, and CSF infections 3).

Due-Tonnessen and Hleseth found that patients with medulloblastoma and ependymoma had much higher rates of postoperative shunt placement than astrocytomas 4). Kumar and colleagues in a study of 196 consecutive children found age <3 years, tumor histology of medulloblastoma/ependymoma and partial resections were associated with the increased chances of postresection hydrocephalus 5). A study noted that the only modifiable risk factor for the development of PRH was the presence of intraventricular blood in postoperative imaging 6).

Intraventricular blood can cause hydrocephalus either by the “snow globe effect” 7) or by other factors like impaired absorption of CSF by inflammation and fibrosis of the arachnoid granulations caused by blood degradation products 8).

Gopalakrishnan and colleagues noted the following risk factors for PRH: the need for CSF diversion in the pediatric population—children with symptomatology <3 months duration, severe hydrocephalus at presentation, tumor location in the midline, tumor histology, viz. medulloblastoma and ependymoma, use of intraoperative EVD, longer duration of EVD, postoperative meningitis, and pseudomeningocele 9). Similar findings were also reported by Bognar et al. who showed that the presence of EVD and the duration of EVD were associated with a significant increase in the incidence of postresection CSF diversion. In another recent study, Pitsika et al. 10) showed that patients who underwent EVD had a higher rate of postoperative VPS. They also noted a negative correlation between early EVD clamping and VPS indicating that clamping encourages the re-establishment of normal CSF flow when the obstructive tumor is removed 11). From 12).


Choroid plexus cysts (CPCs) are a type of neuroepithelial cysts, benign lesions located more frequently in the supratentorial compartment. Symptomatic CPCs in the posterior fossa are extremely rare and can be associated with obstructive hydrocephalus

Predictive factors for postoperative hydrocephalus has been identified, including young age (< 3 years), severe symptomatic hydrocephalus at presentation, EVD placement before surgery, FOHR index > 0.46 and Evans index > 0.4, pseudomeningocelecerebrospinal fluid fistula, and infection. The use of a pre-resection cerebrospinal fluid shunt in case of signs and symptoms of hydrocephalus is mandatory, although it resolves in the majority of cases. As reported by several studies included in the present review, we suggest CSF shunt also in case of asymptomatic hydrocephalus, whereas it is not indicated without evidence of ventricular dilatation 13).


1)

Saad H, Bray DP, McMahon JT, Philbrick BD, Dawoud RA, Douglas JM, Adeagbo S, Yarmoska SK, Agam M, Chow J, Pradilla G, Olson JJ, Alawieh A, Hoang K. Permanent cerebrospinal fluid shunt in Adults With Posterior Fossa Tumors: Incidence and Predictors. Neurosurgery. 2021 Nov 18;89(6):987-996. doi: 10.1093/neuros/nyab341. PMID: 34561703; PMCID: PMC8600168.
2)

Chen T, Ren Y, Wang C, Huang B, Lan Z, Liu W, Ju Y, Hui X, Zhang Y. Risk factors for hydrocephalus following fourth ventricle tumor surgery: A retrospective analysis of 121 patients. PLoS One. 2020 Nov 17;15(11):e0241853. doi: 10.1371/journal.pone.0241853. PMID: 33201889; PMCID: PMC7671531.
3)

Cully DJ, Berger MS, Shaw D, Geyer R. An analysis of factors determing the need for ventriculoperitoneal shunts after posterior fossa tumor surgery in children. Neurosurgery 1994;34:402-8.
4) , 8)

Due-Tonnessen B, Helseth E. Management of hydrocephalus in children with posterior fossa tumors: Role of tumor surgery. Pediatr Neurosurg 2007;43:92-6
5)

Kumar V, Phipps K, Harkness W, Hayward RD. Ventriculoperitoneal shunt requirement in children with posterior fossa tumors: An 11-year audit. Br J Neurosurg 1996:10:467-70.
6)

Abraham A, Moorthy RK, Jeyaseelan L, Rajshekhar V. Postoperative intraventricular blood: A new modifiable risk factor for early postoperative symptomatic hydrocephalus in children with posterior fossa tumors. Childs Nerv Syst 2019;35;1137-46.
7)

Tamburrini G, Frassanito P, Bianchi F, Massimi L, Di Rocco C, Caldarelli M. Closure of endoscopic third ventriculostomy after surgery for posterior cranial fossa tumor: The “Snow Globe effect”. Br J Neurosurg 2015;29:386-9.
9)

Gopalakrishnan CV, Dhakoji A, Menon G, Nair S. Factors predicting the need for cerebrospinal fluid diversion following posterior cranial fossa tumor surgery in children. Pediatr Neurosurg 2012;48:93-101
10)

Pitsika M, Fletcher J, Coulter IC, Cowie CJA. A validation study of the modified Canadian preoperative prediction rule for hydrocephalus in children with posterior fossa tumors. J Neurosurg. doi: 10.3171/2021.1.PEDS20887.
11)

Bognar L, Borgulya G, Benke P, Madarassy G. Analysis of CSF shunting procedure requirement in children with posterior fossa tumors. Childs Nerv Syst 2003;19:332-6.
12)

Muthukumar N. Hydrocephalus Associated with Posterior Fossa Tumors: How to Manage Effectively? Neurol India. 2021 Nov-Dec;69(Supplement):S342-S349. doi: 10.4103/0028-3886.332260. PMID: 35102986.
13)

Anania P, Battaglini D, Balestrino A, D’Andrea A, Prior A, Ceraudo M, Rossi DC, Zona G, Fiaschi P. The role of external ventricular drainage for the management of posterior cranial fossa tumours: a systematic review. Neurosurg Rev. 2021 Jun;44(3):1243-1253. doi: 10.1007/s10143-020-01325-z. Epub 2020 Jun 3. PMID: 32494987.

Posterior Fossa A ependymoma

Posterior Fossa A ependymoma

Posterior fossa ependymoma comprise three distinct molecular variants, termed PF-EPN-A (PFA), PF-EPN-B (PFB), and PF-EPN-SE (subependymoma1).


While supratentorial ependymomas are characterized by recurrent oncogenic fusions, infratentorial ependymomas can be classified by their epigenetic signatures into two main groups, pediatric-type (PFA) and adult-type (PFB) ependymomas


Group A patients are younger, have laterally located tumors with a balanced genome, and are much more likely to exhibit recurrence, metastasis at recurrence, and death compared with Group B patients. Identification and optimization of immunohistochemical (IHC) markers for PF ependymoma subgroups allowed validation of findings on a third independent cohort, using a human ependymoma tissue microarray, and provides a tool for prospective prognostication and stratification of PF ependymoma patients 2).

H3K27me3 (me3) loss by immunohistochemistry (IHC) is a surrogate marker for PFA wherein its loss is attributed to overexpression of Cxorf67/EZH2 inhibitory protein (EZHIP), C17orf96, and ATRX loss. Nambirajan et al. aimed to subgroup posterior fossa ependymomas using me3 IHC and study correlations of the molecular subgroups with other histone-related proteins, 1q gain, Tenascin C, and outcome. IHC for me3, acetyl-H3K27, H3K27MATRXEZH2EZHIPC17orf96Tenascin C, and fluorescence in-situ hybridization for chromosome 1q25 locus were performed on an ambispective posterior fossa ependymomas cohort (2003-2019). H3K27M-mutant gliomas were included for comparison. Among 69 patients, PFA (me3 loss) constituted 64%. EZHIP overexpression and 1q gain were exclusive to PFA seen in 72% and 19%, respectively. Tenascin C was more frequently positive in PFA (p = 0.02). H3K27M expression and ATRX loss were noted in one case of PFA-EPN each. All H3K27M-mutant gliomas (n = 8) and PFA-EPN (n = 1) were EZHIP negative. C17orf96 and acetyl-H3K27 expression did not correlate with me3 loss. H3K27me3 is a robust surrogate for PF-EPN molecular subgrouping. EZHIP overexpression was exclusive to PFA EPNs and was characteristically absent in Diffuse midline glioma H3 K27M-mutants and the rare PFA harboring H3K27M mutations representing mutually exclusive pathways leading to me3 loss 3).

Ramaswamy and Taylor found that the strongest predictor of poor outcome in patients with posterior fossa ependymoma across the entire age spectrum was molecular subgroup PFA, which was reported in the paper entitled “Therapeutic impact of cytoreductive surgery and irradiation of posterior fossa ependymoma in the molecular era: a retrospective multicohort analysis” in the Journal of Clinical Oncology. Patients with incompletely resected PFA tumors had a very poor outcome despite receiving adjuvant radiation therapy, whereas a substantial proportion of patients with PFB tumors can be cured with surgery alone 4).


A total of 72 Posterior fossa ependymomas cases were identified, 89% of which were PFA. The 10-year progression-free survival rate for all patients with PFA was poor at 37.1% (95% confidence interval, 25.9%-53.1%). Analysis of consecutive 10-year epochs revealed significant improvements in progression-free survival and/or overall survival over time. This pertains to the increase in the rate of gross (macroscopic) total resection from 35% to 77% and the use of upfront radiotherapy increasing from 65% to 96% over the observed period and confirmed in a multivariable model. Using a mixed linear model, analysis of longitudinal neuropsychological outcomes restricted to patients with PFA who were treated with focal irradiation demonstrated significant continuous declines in the full-scale intelligence quotient over time with upfront conformal radiotherapy, even when correcting for hydrocephalus, number of surgeries, and age at diagnosis (-1.33 ± 0.42 points/year; P = .0042) 5).

Effective treatment is limited to surgical resection and focal radiotherapy.


1)

Cavalli FMG, Hübner JM, Sharma T, Luu B, Sill M, Zapotocky M, Mack SC, Witt H, Lin T, Shih DJH, Ho B, Santi M, Emery L, Hukin J, Dunham C, McLendon RE, Lipp ES, Gururangan S, Grossbach A, French P, Kros JM, van Veelen MC, Rao AAN, Giannini C, Leary S, Jung S, Faria CC, Mora J, Schüller U, Alonso MM, Chan JA, Klekner A, Chambless LB, Hwang EI, Massimino M, Eberhart CG, Karajannis MA, Lu B, Liau LM, Zollo M, Ferrucci V, Carlotti C, Tirapelli DPC, Tabori U, Bouffet E, Ryzhova M, Ellison DW, Merchant TE, Gilbert MR, Armstrong TS, Korshunov A, Pfister SM, Taylor MD, Aldape K, Pajtler KW, Kool M, Ramaswamy V. Heterogeneity within the PF-EPN-B ependymoma subgroup. Acta Neuropathol. 2018 Aug;136(2):227-237. doi: 10.1007/s00401-018-1888-x. Epub 2018 Jul 17. PMID: 30019219; PMCID: PMC6373486.
2)

Witt H, Mack SC, Ryzhova M, Bender S, Sill M, Isserlin R, Benner A, Hielscher T, Milde T, Remke M, Jones DT, Northcott PA, Garzia L, Bertrand KC, Wittmann A, Yao Y, Roberts SS, Massimi L, Van Meter T, Weiss WA, Gupta N, Grajkowska W, Lach B, Cho YJ, von Deimling A, Kulozik AE, Witt O, Bader GD, Hawkins CE, Tabori U, Guha A, Rutka JT, Lichter P, Korshunov A, Taylor MD, Pfister SM. Delineation of two clinically and molecularly distinct subgroups of posterior fossa ependymoma. Cancer Cell. 2011 Aug 16;20(2):143-57. doi: 10.1016/j.ccr.2011.07.007. PMID: 21840481; PMCID: PMC4154494.
3)

Nambirajan A, Sharma A, Rajeshwari M, Boorgula MT, Doddamani R, Garg A, Suri V, Sarkar C, Sharma MC. EZH2 inhibitory protein (EZHIP/Cxorf67) expression correlates strongly with H3K27me3 loss in posterior fossa ependymomas and is mutually exclusive with H3K27M mutations. Brain Tumor Pathol. 2020 Nov 1. doi: 10.1007/s10014-020-00385-9. Epub ahead of print. Erratum in: Brain Tumor Pathol. 2021 Jan 9;: PMID: 33130928.
4)

Ramaswamy V, Taylor MD. Treatment implications of posterior fossa ependymoma subgroups. Chin J Cancer. 2016 Nov 15;35(1):93. doi: 10.1186/s40880-016-0155-6. PMID: 27846874; PMCID: PMC5111181.
5)

Zapotocky M, Beera K, Adamski J, Laperierre N, Guger S, Janzen L, Lassaletta A, Figueiredo Nobre L, Bartels U, Tabori U, Hawkins C, Urbach S, Tsang DS, Dirks PB, Taylor MD, Bouffet E, Mabbott DJ, Ramaswamy V. Survival and functional outcomes of molecularly defined childhood posterior fossa ependymoma: Cure at a cost. Cancer. 2019 Jun 1;125(11):1867-1876. doi: 10.1002/cncr.31995. Epub 2019 Feb 15. PMID: 30768777; PMCID: PMC6508980.

May 2, Webinar Topic: Endoscopic Ant Fossa Meningioma Excision/ Intraventricular Tumor Management

IFNE/ WFNS Endoscopy Weekend Update 3
Topic: Endoscopic Ant Fossa Meningioma Excision/ Intraventricular Tumor Management

Time: May 2, 2020
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