Intracranial ganglioglioma

Intracranial ganglioglioma

Children and young patients are usually affected, and no gender predominance is recognised. It accounts for around 2% (from 0.4-3.8%) of all primary intracranial tumors, and up to 10% of primary cerebral tumors in children.

Because of their rarity, large-scale, population-based studies focusing on epidemiology and outcomes are lacking.

Ganglioglioma is a benign slow-growing neoplasm that most frequently occurs at the supratentorial region. Nevertheless, there are occasional reports of ganglioglioma occurring in thebrainstem and spinal cord.

see Cerebellar ganglioglioma.

see Intraventricular ganglioglioma

see Optic pathway ganglioglioma.

see Multifocal intracranial ganglioglioma

Molecular pathogenesis, risk factors for malignant progression, and their frequent association with drug-resistant focal seizures remain poorly understood. This contrasts recent progress in understanding the molecular-genetic basis and targeted treatment options in diffuse gliomas. The Neuropathology Task Force of the International League against Epilepsy examined available literature to identify common obstacles in diagnosis and research of LEAT. Analysis of 10 published tumour series from epilepsy surgery pointed to poor interrater agreement for the histopathology diagnosis. The Task Force tested this hypothesis using a web-based microscopy agreement study. In a series of 30 LEAT, 25 raters from 18 countries agreed in only 40% of cases. Highest discordance in microscopic diagnosis occurred between GG and DNT variants, when oligodendroglial-like cell patterns prevail, or ganglion cells were difficult to discriminate from pre-existing neurons. Suggesting new terminology or major histopathological criteria did not satisfactorily increase the yield of histopathology agreement in 4 consecutive trials. To this end, the Task Force applied the WHO 2016 strategy of integrating phenotype analysis with molecular-genetic data obtained from panel sequencing and 450k methylation arrays. This strategy was helpful to distinguish DNT from GG variants in all cases. The Task Force recommends, therefore, to further develop diagnostic panels for the integration of phenotype-genotype analysis in order to reliably classify the spectrum of LEAT, carefully characterize clinically meaningful entities and make better use of published literature 1).

The most common presentation is with temporal lobe epilepsy, presumably due to the temporal lobes being a favoured location.

Imaging findings mirror the various patterns of growth which these tumours may demonstrate and thus their appearance is very variable. Partially cystic mass with an enhancing mural nodule is seen in ~45% of cases. They may also simply present as a solid mass expanding the overlying gyrus. An infiltrating mass is uncommon and may reflect higher grade.

Findings are of a mass which is often non-specific. General features include:

iso- or hypodense

frequently calcified ~35%

bony remodelling or thinning can indicate the slow growing nature of the tumour

enhancement is seen in approximately 50% of cases (involving the solid non-calcified component)

Reported MR signal characteristics include:

T1 Solid component isointense to hypointense.

T1 C+ (Gd) solid component variable contrast enhancement

T2 hyperintense solid component variable signal in the cystic component depending on the amount of proteinaceous material or the presence of blood products peritumoural FLAIR/T2 oedema is distinctly uncommon

T2* (GE/SWI) calcified areas (common) will show blooming signal loss

Main differential diagnosis is that of other cortical tumours, with helpful distinguishing features including:

Dysembryoplastic neuroepithelial tumors (DNET)

contrast enhancement uncommon ‘bubbly appearance’ common

Pleomorphic xanthoastrocytoma (PXA)

contrast enhancement prominent dural tail sign is often seen

Oligodendroglioma

calcifications common

Desmoplastic infantile astrocytoma and ganglioglioma

young children dural involvement prominent large often multiple lesions

If in the spinal cord consider:

astrocytoma

ependymoma

The aim of a study was to evaluate whether ganglioglioma (GGL), dysembryoplastic neuroepithelial tumour (DNET) and FCD (focal cortical dysplasia) are distinguishable through diffusion tensor imaging. Additionally, it was investigated whether the diffusion measures differed in the perilesional (pNAWM) and in the contralateral normal appearing white matter (cNAWM). Six GGLs, eight DNETs and seven FCDs were included in this study. Quantitative diffusion measures, that is, axial, radial and mean diffusivity and fractional anisotropy, were determined in the lesion identified on isotropic T2 or FLAIR-weighted images and in pNAWM and cNAWM, respectively. DNET differed from FCD in mean diffusivity, and GGL from FCD in radial diffusivity. Both types of glioneuronal tumours were different from pNAWM in fractional anisotropy and radial diffusivity. For identifying the tumour edges, threshold values for tumour-free tissue were investigated with receiver operating characteristic analyses: tumour could be separated from pNAWM at a threshold ≤ 0.32 (fractional anisotropy) or ≥ 0.56 (radial diffusivity) *10-3 mm2/s (area under the curve 0.995 and 0.990 respectively). While diffusion parameters of FCDs differed from cNAWM (radial diffusivity (*10-3 mm/s2): 0.74 ± 0.19 vs. 0.43 ± 0.05; corrected p-value < 0.001), the pNAWM could not be differentiated from the FCD 2).

Advances in the immunohistochemical detection of neuron-specific and neuronal-associated antigens have resulted in the discovery of neuronal elements in certain primary human brain tumors. The results have been not only to expand what neuropathologists commonly recognize as gangliogliomas, including the tumors now known as glioneurocytic tumor with neuropil rosettes and papillary ganglioneuroma, but also to expand the spectrum of tumor types to now include tumors such as central neurocytoma, dysembryoplastic neuroepithelial tumor, and desmoplastic infantile ganglioglioma.

Gangliogliomas are WHO grade I tumours most frequently found in the temporal lobes (70%) 3) 4) but do occur anywhere in the central nervous system.

In a minority of cases (5%) these tumours show aggressive behaviour and histopathologic features and are then called anaplastic gangliogliomas (WHO grade III) 5) 6)

At this stage, no criteria for WHO II gangliogliomas have been established 7).

Gangliogliomas, as their name suggests, are composed of two cell populations:

ganglion cells (large mature neuronal elements): ganglio- neoplastic glial element: -glioma primarily astrocytic, although oligodendroglial or pilocytic astroctytoma components are also enountered 9 The proportion of each component varies widely, and it is the grade of the glial component that determines biological behaviour.

Dedifferentiation into high-grade tumours does occasionally occur, and it is usually the glial component (into a GBM). Only rarely is it the neuronal component (into a neuroblastoma).

They are closely related to both gangliocytomas (which contain only the mature neural ganglion cellular component) and ganglioneurocytoma (which also have small mature neoplastic neurones).

Neuronal origin is demonstrated by positivity to neuronal markers:

Synaptophysin: positive

Neurofilament protein: positive

MAP2: positive

Chromogranin-A: positive (usually negative in normal neurones)

CD34: positive in 70-80%

The glial component may also show cytoplasmic positivity for GFAP.

Ganglioglioma and pleomorphic xanthoastrocytoma were the histologic types with the strongest association with CD34 positivity with an odds ratio of 9.2 and 10.4, respectively, compared with dysembryoplastic neuroepithelial tumors in Low-Grade Epilepsy-Associated Tumors 8).

BRAFV600 mutations are frequently found in several glioma subtypes, including pleomorphic xanthoastrocytoma (PXA) and ganglioglioma and much less commonly in glioblastoma.

Gross total resection is achieved in the majority of cases.

Is the largest retrospective study of adult low-grade GGs up to date. Younger age, female gender, temporal lobe location, and GTR indicated better survival. Adjuvant RT and/or chemotherapy should not be considered after whatever surgery in adult patients with low-grade GGs, unless the malignant transformation has been confirmed 9)

In the surgical treatment of temporal lobe epilepsy with mesial temporal lobe tumor, whether to remove the hippocampus aiming for a better seizure outcome in addition to removing the tumor is a dilemma. Two pediatric cases treated successfully with tumor removal alone are presented.

The first case was an 11-year-old girl with a ganglioglioma in the left uncus, and the second case was a 9-year-old girl with a pleomorphic xanthoastrocytoma in the left parahippocampal gyrus. In both cases, the hippocampus was not invaded, merely compressed by the tumor. Tumor removal was performed under intraoperative electrocorticography (ECoG) monitoring. After tumor removal, abnormal discharges remained at the hippocampus and adjacent temporal cortices, but further surgical interventions were not performed. The seizures disappeared completely in both cases.

When we must decide whether to remove the hippocampus, the side of the lesion, the severity and chronicity of the seizures, and the presence of invasion to the hippocampus are the factors that should be considered. Abnormal discharges on ECoG at the hippocampus or adjacent cortices are one of the factors related to epileptogenicity, but it is simply a result of interictal irritation, and it is not an absolute indication for additional surgical intervention 10).

Gangliogliomas and ganglioneuromas are slow growing benign tumors.

In the largest retrospective study of adult low-grade GGs till 2020. Younger age, female gender, temporal lobe location, and GTR indicated better survival. Adjuvant RT and/or chemotherapy should not be considered after whatever surgery in adult patients with low-grade GGs, unless the malignant transformation has been confirmed 11)

Local resection is the treatment of choice and determines prognosis. In the brain, where a reasonable resection margin can be achieved, the prognosis is good, with recurrence-free survival reported to be 97% at 7.5-year follow-up 12).

In contrast, in the spinal cord where complete resection is often not possible without devastating deficits, local recurrence is very common.

Although the majority of patients have an excellent prognosis, infants and patients with brainstem tumors have worse survival rates.

Intracranial ganglioglioma case series.

Ganglioglioma case reports.


1)

Blümcke I, Coras R, Wefers AK, Capper D, Aronica E, Becker A, Honavar M, Stone TJ, Jacques TS, Miyata H, Mühlebner A, Pimentel J, Söylemezoğlu F, Thom M. Challenges in the histopathological classification of ganglioglioma and DNT: microscopic agreement studies and a preliminary genotype-phenotype analysis. Neuropathol Appl Neurobiol. 2018 Oct 16. doi: 10.1111/nan.12522. [Epub ahead of print] Review. PubMed PMID: 30326153.
2)

Rau A, Kellner E, Foit NA, Lützen N, Heiland DH, Schulze-Bonhage A, Reisert M, Kiselev VG, Prinz M, Urbach H, Mader I. Discrimination of epileptogenic lesions and perilesional white matter using diffusion tensor magnetic resonance imaging. Neuroradiol J. 2018 Nov 21:1971400918813991. doi: 10.1177/1971400918813991. [Epub ahead of print] PubMed PMID: 30461353.
3)

Rumboldt Z, Castillo M, Huang B et-al. Brain Imaging with MRI and CT. Cambridge University Press. (2012) ISBN:1139576399.
4) , 6) , 7) , 12)

Louis DN, Ohgaki H, Wiestler OD, Cavenee WK “WHO Classification of Tumours of the Central Nervous System. 4th Edition Revised” ISBN: 9789283244929
5)

Song JY, Kim JH, Cho YH et-al. Treatment and outcomes for gangliogliomas: a single-center review of 16 patients. Brain Tumor Res Treat. 2014;2 (2): 49-55. doi:10.14791/btrt.2014.2.2.49
8)

Giulioni M, Marucci G, Cossu M, Tassi L, Bramerio M, Barba C, Buccoliero AM, Vornetti G, Zenesini C, Consales A, De Palma L, Villani F, Di Gennaro G, Vatti G, Zamponi N, Colicchio G, Marras CE. CD34 Expression in Low-Grade Epilepsy-Associated Tumors: Relationships with Clinicopathologic Features. World Neurosurg. 2018 Oct 9. pii: S1878-8750(18)32267-8. doi: 10.1016/j.wneu.2018.09.212. [Epub ahead of print] PubMed PMID: 30308344.
9) , 11)

Lin X, Huang R, Zhang P, Sun J, Dong G, Huang Y, Tian X. Low-grade gangliogliomas in adults: A population-based study. Cancer Med. 2020 Oct 27. doi: 10.1002/cam4.3577. Epub ahead of print. PMID: 33107220.
10)

Uda T, Kunihiro N, Nakajo K, Kuki I, Fukuoka M, Ohata K. Seizure freedom from temporal lobe epilepsy with mesial temporal lobe tumor by tumor removal alone without hippocampectomy despite remaining abnormal discharges on intraoperative electrocorticography: Report of two pediatric cases and reconsideration of the surgical strategy. Surg Neurol Int. 2018 Sep 10;9:181. doi: 10.4103/sni.sni_61_18. eCollection 2018. PubMed PMID: 30283714; PubMed Central PMCID: PMC6157038.

Very small intracranial aneurysm

Very small intracranial aneurysm

Very small intracranial aneurysm (VSIA) (< 3 mm).

Ruptured VSIA group has higher percentage of females and lower aspect ratio than ruptured non-VSIA group. Further studies regarding the characteristics of ruptured and unruptured VSIA patients is required for assistance in clinical decision related to treatment of VSIA group before the aneurysm sac rupture 1).

The most common site of rupture of very small aneurysm was the anterior communicating artery (ACoA). Rupture of small and very small aneurysms is unpredictable, and treatment may be considered in selected high-risk patients according to factors such as young age, ACoA location, and hypertension 2).

Treatment of very small unruptured intracranial aneurysms (VSUIAs, defined as ≤3 mm) can be indicated in selected circumstances. The feasibility and outcomes of endovascular therapy for VSUIAs have been recently published; however, the efficacy and complication rate of surgical clipping has not been reported in any large series to date.

In a study, 183 patients (128 women, mean age 51.3 years) were treated with 190 procedures for a total of 228 aneurysms. Most were anterior circulation aneurysms (n = 215). The majority were directly clipped (n = 222, 97.4%), with coagulation or wrapping in the remainder. After 1 reoperation for incomplete clipping, postoperative imaging of 225 aneurysms confirmed complete occlusion in 221 (98.2%), 1 neck remnant (0.44%), and 3 partial occlusions (1.3%). Mortality was 0%. Early postoperative neurological deficit developed in 12 patients (6.6%); posterior circulation location was a significant risk factor for early neurological deficit (P < .001). Middle cerebral artery aneurysms had the lowest rate of postoperative deficits at 1.5% (P = .023). After the initial 30-day perioperative period, all deficits related to treatment of posterior circulation aneurysms recovered; overall neurological morbidity decreased to 2.7% with no mortality.

VSUIA clipping is highly effective and is associated with a low morbidity rate. For VSUIAs selected for treatment, our data support surgical clipping as the modality of choice 3).


Aneurysms treated with a Pipeline Embolization Device in vessels less than 2.5 mm between June 2012 and August 2014 were included. They evaluated risk factors, family history of aneurysms, aneurysm characteristics, National Institute of Health Stroke Scale (NIHSS), and modified Rankin scale (mRS) on admission and angiography and clinical outcome at discharge, 6 months, and 1 year.

They included seven patients with a mean age of 65 years. The parent vessel size ranged from 1.5 to 2.3 mm; mean 1.9 mm. Location of the aneurysms was as follows: two aneurysms centered along the pericallosal artery (one left, one right), one on the right angular artery, one aneurysm at the anterior communicating artery (ACom), one at the ACom-right A2 anterior cerebral artery (ACA), one at the lenticulostriate artery, and one at the A1-A2 ACA artery. Aneurysms ranged from 1 to 12 mm in diameter. All aneurysms were treated with a single Pipeline™ Embolization Device (PED). No peri- or post-procedural complications or mortality occurred. The patients were discharged with no change in NIHSS or mRS score. Angiographic follow-up was available in six patients. Angiography showed complete aneurysm occlusion in all. NIHSS and mRS remained unchanged at follow-up.

The preliminary results show that flow diversion technology is an effective and safe therapy for aneurysms located on small cerebral arteries. Larger studies with long-term follow-up are needed to validate our promising results 4).


1)

Park GT, Kim JH, Jung YJ, Chang CH. Characteristics of patients with ruptured very small intracranial aneurysm sized less than 3 mm. J Cerebrovasc Endovasc Neurosurg. 2020 Oct 22. doi: 10.7461/jcen.2020.E2020.07.001. Epub ahead of print. PMID: 33086456.
2)

Lee GJ, Eom KS, Lee C, Kim DW, Kang SD. Rupture of Very Small Intracranial Aneurysms: Incidence and Clinical Characteristics. J Cerebrovasc Endovasc Neurosurg. 2015 Sep;17(3):217-22. doi: 10.7461/jcen.2015.17.3.217. Epub 2015 Sep 30. PubMed PMID: 26526401; PubMed Central PMCID: PMC4626345.
3)

Bruneau M, Amin-Hanjani S, Koroknay-Pal P, Bijlenga P, Jahromi BR, Lehto H, Kivisaari R, Schaller K, Charbel F, Khan S, Mélot C, Niemela M, Hernesniemi J. Surgical Clipping of Very Small Unruptured Intracranial Aneurysms: A Multicenter International Study. Neurosurgery. 2016 Jan;78(1):47-52. doi: 10.1227/NEU.0000000000000991. PubMed PMID: 26317673.
4)

Puri AS, Massari F, Asai T, Marosfoi M, Kan P, Hou SY, Howk M, Perras M, Brooks C, Clarencon F, Gounis MJ, Wakhloo AK. Safety, efficacy, and short-term follow-up of the use of Pipeline™ Embolization Device in small (<2.5mm) cerebral vessels for aneurysm treatment: single institution experience. Neuroradiology. 2015 Dec 23. [Epub ahead of print] PubMed PMID: 26700827.

Idiopathic intracranial hypertension surgery

Idiopathic intracranial hypertension surgery

Systematic reviews

Prospective studies on the surgical options for Idiopathic intracranial hypertension (IIH) are scant and no evidence-based guidelines for the surgical management of medically refractory IIH have been established. A search in Cochrane LibraryMEDLINE and EMBASE from 1 January 1985 to 19 April 2019 for controlled or observational studies on the surgical treatment of IIH (defined in accordance with the modified Dandy or the modified Friedman criteria) in adults yielded 109 admissible studies. Venous sinus stenting (VSS) improved papilledemavisual fields and headaches in 87.1%, 72.7%, and 72.1% of the patients respectively, with a 2.3% severe complication rate and 11.3% failure rate. Cerebrospinal fluid diversion techniques diminished papilledema, visual field deterioration, and headaches in 78.9%, 66.8%, and 69.8% of the cases and are associated with a 9.4 severe complication rate and a 43.4% failure rate. Optic nerve sheath fenestration ameliorated papilledema, visual field defects and headaches in 90.5, 65.2%, and 49.3% of patients. The severe complication rate was 2.2% and the failure rate was 9.4%. This is currently the largest systematic review for the available operative modalities for IIH. VSS provided the best results in headache resolution and visual outcomes, with low failure rates and a very favorable complication profile. In light of this, Venous sinus stenting ought to be regarded as the first-line surgical modality for the treatment of medically refractory IIH 1).

Indications

Idiopathic intracranial hypertension patients may require surgical management when maximal medical treatment has failed.

Controversy still exists about which is the preferred initial surgical treatment for IIH. Emerging procedures include venous sinus stenting in cases with venous sinus stenosis, and bariatric surgery for weight loss. Cranial (suboccipital or subtemporal) decompression was a more popular surgical procedure in the past, but can still have a role in selected cases with impaired cerebrospinal flow dynamics (e.g. Chiari malformation) or after multiple failed conventional surgical procedures 2).

Venous sinus stenting ought to be regarded as the first-line surgical modality for the treatment of medically refractory IIH 3).

The election will likely be based on local expertise until well designed, multicentered clinical trials clarify which intervention best suits a particular patient 4).

The visual outcomes of these procedures are favorable, though they tend to be associated with a high rate of complication and failure. Recent trials suggest that venous sinus stenting offers both comparable rates of efficacy – with improved papilledema in 97% of patients, resolved headache in 83%, and improved visual acuity in 78% – and improved safety and reliability relative to older surgical techniques.

Patients whose sight is threatened by medically refractory IIH must often consider invasive procedures to control their disease. Venous sinus stenting may offer equal efficacy and lower failure and complication rates than traditional surgical approaches such as optic nerve sheath fenestration and cerebrospinal fluid diversion.

Several surgical treatment modalities, including lumboperitoneal shunt or ventriculoperitoneal shunt surgery, subtemporal decompression, endovascular venous sinus stenting, optic nerve decompression (OND), were used in the management of idiopathic intracranial hypertension (IIH). Each surgical technique has different advantages and disadvantages. Endoscopic OND is rarely used in the management of IIH. There are only forteen reported cases 5).

Techniques

Cerebrospinal fluid diversion procedures

The most commonly performed surgical treatments for IIH are cerebrospinal fluid diversion procedures (e.g. ventriculo- and lumboperitoneal shunts).

Lumboperitoneal shunt

see Lumboperitoneal shunt for idiopathic intracranial hypertension

Ventriculoperitoneal shunt

see Ventriculoperitoneal shunt for pseudotumor cerebri

Transverse sinus stenting

see Transverse sinus stenting for idiopathic intracranial hypertension.

Optic nerve sheath fenestration

see Optic nerve sheath fenestration.

Subtemporal decompression

see Subtemporal decompression.

References

1) , 3)

Kalyvas A, Neromyliotis E, Koutsarnakis C, Komaitis S, Drosos E, Skandalakis GP, Pantazi M, Gobin YP, Stranjalis G, Patsalides A. A systematic review of surgical treatments of idiopathic intracranial hypertension (IIH). Neurosurg Rev. 2020 Apr 25. doi: 10.1007/s10143-020-01288-1. [Epub ahead of print] Review. PubMed PMID: 32335853.
2)

Spitze A, Malik A, Lee AG. Surgical and endovascular interventions in idiopathic intracranial hypertension. Curr Opin Neurol. 2014 Feb;27(1):69-74. doi: 10.1097/WCO.0000000000000049. PubMed PMID: 24296639.
4)

Uretsky S. Surgical interventions for idiopathic intracranial hypertension. Curr Opin Ophthalmol. 2009 Nov;20(6):451-5. doi: 10.1097/ICU.0b013e3283313c1c. Review. PubMed PMID: 19687737.
5)

Sencer A, Akcakaya MO, Basaran B, Yorukoglu AG, Aydoseli A, Aras Y, Sencan F, Satana B, Aslan I, Unal OF, Izgi N, Canbolat A. Unilateral endoscopic optic nerve decompression for idiopathic intracranial hypertension: a series of 10 patients. World Neurosurg. 2014 Nov;82(5):745-50. doi: 10.1016/j.wneu.2014.03.045. Epub 2014 Apr 2. PubMed PMID: 24704940.
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