Neurooncology

Olfactory groove meningioma

Olfactory groove meningioma

Olfactory groove meningiomas (OGMs) are arachnoid cell neoplasms of the frontoethmoidal suture and lamina cribrosa, 1) and may involve any part of the area from the crista galli to the planum sphenoidale 2) 3) 4).

Epidemiology

Olfactory groove meningioma epidemiology

Classification

Olfactory groove meningioma classification

Clinical features

Olfactory groove meningioma clinical features

Diagnosis

Olfactory groove meningioma diagnosis.

Differential diagnosis

Tuberculum sellae meningioma

Planum sphenoidale meningioma

Treatment

Olfactory groove meningioma treatment.

Complications

Olfactory groove meningioma complications

Books

The Meningiomas Arising from the Olfactory Groove and Their Removal by the Aid of Electro-surgery By Harvey Cushing · 1927

Cushing H, Eisenhardt L (1938) The olfactory meningiomas with primary anosmia. In: Cushing H, Eisenhardt L (eds) Meningiomas: their classification, regional behavior, life history, and surgical results. Charles C Thomas, Springfield, pp 250–282

Ojemann RG (1991) Olfactory groove meningiomas. In: Al-Mefty O (ed) Meningiomas. Raven Press, New York, pp 383–393

Al-Mefty O (1993) Tuberculum sellae and olfactory groove meningioma. In: Sekhar LN, Janecka IP (eds) Surgery of cranial base tumors. Raven Press, New York, pp 507–519

Surgery of Skull Base Meningiomas: With a Chapter Madjid Samii, ‎Mario Ammirati · 2012

Meningiomas of the Skull Base Treatment Nuances in Contemporary Neurosurgery 2018

Videos

Olfactory groove meningioma videos.

Systematic Reviews

A systematic review was performed to identify studies that compared outcomes following EEA and TCA for OGMs. Data extracted from each study included gross total resection (GTR), the incidence of cerebrospinal fluid (CSF) leaks, and post-operative complications including anosmia. The results of the search yielded 5 studies that met the criteria for inclusion and analysis. All studies compared TCA (n = 922) with EEA (n = 141) outcomes for OGMs. Overall, the rate of gross total resection (GTR) was lower among the endoscopic group (70.9%) relative to the transcranial group (91.5%). The rate of postoperative CSF leak was 6.3% vs. 25.5% for the transcranial and endoscopic groups, respectively. Post-operative anosmia was higher for patients undergoing EEA (95.9%) compared with patients in the transcranial group (37.4%). In this analysis, EEA was associated with a lower rate of GTR and higher incidences of CSF leaks and post-operative anosmia. However, with increasing surgeon familiarity with the endoscopic anatomy and technique for managing ASB pathologies, a nuanced approach may be used to minimize patient morbidity and widen the spectrum of skull base surgery 5).

Electronic databases were searched from inception until December 2019 for studies delineating TCAs for OGM patients. Patient demographics, pre-operative symptoms, surgical outcomes, and complications were evaluated and analyzed with a meta-analysis of proportions. Results: A total of 27 observational case series comparing 554 unilateral vs. 451 bilateral TCA patients were eligible for review. The weighted pooled incidence of gross total resection is 94.6% (95% CI, 90.7-97.5%; I 2 = 59.0%; p = 0.001) for unilateral and 90.9% (95% CI, 85.6-95.4%; I 2 = 58.1%; p = 0.003) for bilateral cohorts. Similarly, the incidence of OGM recurrence is 2.6% (95% CI, 0.4-6.0%; I 2 = 53.1%; p = 0.012) and 4.7% (95% CI, 1.4-9.2%; I 2 = 55.3%; p = 0.006), respectively. Differences in oncologic outcomes were not found to be statistically significant (p = 0.21 and 0.35, respectively). Statistically significant differences in complication rates in bilateral vs. unilateral TCA cohorts include meningitis (1.0 vs. 0.0%; p = 0.022) and mortality (3.2 vs. 0.2%; p = 0.007). Conclusions: While both cohorts have similar oncologic outcomes, bilateral TCA patients exhibit higher postoperative complication rates. This may be explained by underlying tumor characteristics necessitating more radical resection but may also indicate increased morbidity with bilateral approaches. However, evidence from more controlled, comparative studies is warranted to further support these findings 6).

A PubMed search of the recent literature (2011-2016) was performed to examine outcomes following EEA and TCA for OGM. The extent of resection, visual outcome, postoperative complications, and recurrence rates were analyzed using percentages and proportions, the Fischer exact test, and the Student’s t-test using GraphPad PRISM 7.0Aa (San Diego, CA) software.

Results: There were 444 patients in the TCA group with a mean diameter of 4.61 (±1.17) cm and 101 patients in the EEA group with a mean diameter of 3.55 (± 0.58) cm (p = 0.0589). GTR was achieved in 90.9% (404/444) in the TCA group and 70.2% (71/101) in the EEA group (p < 0.0001). Of the patients with preoperative visual disturbances, 80.7% (21/26) of patients in the EEA cohort had an improvement in vision compared to 12.83%(29/226) in the TCA group (p < 0.0001). Olfaction was lost in 61% of TCA and in 100% of EEA patients. CSF leaks and meningitis occurred in 25.7% and 4.95% of EEA patients and 6.3% and 1.12% of TCA patients, respectively (p < 0.0001; p = 0.023).

The updated literature review demonstrates that despite more experience with endoscopic resection and skull base reconstruction, the literature still supports TCA over EEA with respect to the extent of resection and complications. EEA may be an option in selected cases where visual improvement is the main goal of surgery and postoperative anosmia is acceptable to the patient or in medium-sized tumors with existing preoperative anosmia. Nevertheless, based on our results, it seems more prudent at this time to use TCA for the majority of OGMs 7).

Case series

Olfactory groove meningioma case series

Case reports

Olfactory groove meningioma case reports.

1)

Guinto G. Olfactory Groove Meningiomaas. World Neurosurg. 2015 Jun;83(6):1046-7. doi: 10.1016/j.wneu.2014.12.044. Epub 2015 Jan 14. PMID: 25596435.
2)

Hentschel SJ, DeMonte F, Olfactory groove meningiomas. DeMonte F, McDermott MW, Al-Mefty O: Al-Mefty’s Meningiomas 2New York, Thieme, 2011. 196–205
3)

Nakamura M, Struck M, Roser F, Vorkapic P, Samii M: Olfactory groove meningiomas: clinical outcome and recurrence rates after tumor removal through the frontolateral and bifrontal approach. Neurosurgery 62:6 Suppl 31224–1232, 2008
4)

Pepper J, Hecht SL, Gebarski SS, Lin EM, Sullivan SE, Marentette LJ. Olfactory groove meningioma: discussion of clinical presentation and surgical outcomes following excision via the subcranial approach. Laryngoscope. 2011;121:2282–2289.
5)

Purohit A, Jha R, Khalafallah AM, Price C, Rowan NR, Mukherjee D. Endoscopic endonasal versus transcranial approach to resection of olfactory groove meningiomas: a systematic review. Neurosurg Rev. 2020 Dec;43(6):1465-1471. doi: 10.1007/s10143-019-01193-2. Epub 2019 Nov 10. PMID: 31709465.
6)

Feng AY, Wong S, Saluja S, Jin MC, Thai A, Pendharkar AV, Ho AL, Reddy P, Efron AD. Resection of Olfactory Groove Meningiomas Through Unilateral vs. Bilateral Approaches: A Systematic Review and Meta-Analysis. Front Oncol. 2020 Oct 22;10:560706. doi: 10.3389/fonc.2020.560706. PMID: 33194626; PMCID: PMC7642686.
7)

Shetty SR, Ruiz-Treviño AS, Omay SB, Almeida JP, Liang B, Chen YN, Singh H, Schwartz TH. Limitations of the endonasal endoscopic approach in treating olfactory groove meningiomas. A systematic review. Acta Neurochir (Wien). 2017 Oct;159(10):1875-1885. doi: 10.1007/s00701-017-3303-0. Epub 2017 Aug 22. PMID: 28831590.

Central nervous system tumor guidelines

Central nervous system tumor guidelines

NCCN Guidelines

The NCCN Guidelines for Central nervous system tumor focus on the management of the following adult CNS cancers: glioma (WHO grade 1, WHO grade 2-3 Oligodendroglioma IDH-mutant and 1p/19q-codeleted, WHO grade 2-4 Astrocytoma IDH-mutants, WHO grade 4 glioblastoma), intracranial and spinal ependymomas, medulloblastoma, limited and extensive brain metastases, leptomeningeal metastases, non-AIDS-related Primary central nervous system lymphomas, metastatic spine tumors, meningiomas, and primary spinal cord tumors. The information contained in the algorithms and principles of management sections in the NCCN Guidelines for CNS Cancers is designed to help clinicians navigate through the complex management of patients with CNS tumors. Several important principles guide surgical management and treatment with radiotherapy and systemic therapy for adults with brain tumors. The NCCN CNS Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel’s most recent recommendations regarding molecular profiling of gliomas 1)

AANS/CNS SECTION ON TUMORS

Evidence-based, clinical practice guidelines in the management of central nervous system tumors (CNS) continue to be developed and updated through the work of the Joint Section on Tumors of the Congress of Neurological Surgeons (CNS) and the American Association of Neurological Surgeons (AANS).

The guidelines are created using the most current and clinically relevant evidence using systematic methodologies, which classify available data and provide recommendations for clinical practice.

This update summarizes the Tumor Section Guidelines developed over the last five years for non-functioning pituitary adenomas, low-grade gliomas, vestibular schwannomas, and metastatic brain tumors 2).

National Cancer Institute

https://www.cancer.gov/types/brain/hp/adult-brain-treatment-pdq

European Society for Medical Oncology

https://www.esmo.org/guidelines/guidelines-by-topic/neuro-oncology

1)

Horbinski C, Nabors LB, Portnow J, Baehring J, Bhatia A, Bloch O, Brem S, Butowski N, Cannon DM, Chao S, Chheda MG, Fabiano AJ, Forsyth P, Gigilio P, Hattangadi-Gluth J, Holdhoff M, Junck L, Kaley T, Merrell R, Mrugala MM, Nagpal S, Nedzi LA, Nevel K, Nghiemphu PL, Parney I, Patel TR, Peters K, Puduvalli VK, Rockhill J, Rusthoven C, Shonka N, Swinnen LJ, Weiss S, Wen PY, Willmarth NE, Bergman MA, Darlow S. NCCN Guidelines® Insights: Central Nervous System Cancers, Version 2.2022. J Natl Compr Canc Netw. 2023 Jan;21(1):12-20. doi: 10.6004/jnccn.2023.0002. PMID: 36634606.
2)

Redjal N, Venteicher AS, Dang D, Sloan A, Kessler RA, Baron RR, Hadjipanayis CG, Chen CC, Ziu M, Olson JJ, Nahed BV. Guidelines in the management of CNS tumors. J Neurooncol. 2021 Feb;151(3):345-359. doi: 10.1007/s11060-020-03530-8. Epub 2021 Feb 21. PMID: 33611702.

Brain metastases

Brain metastases

see also Intracranial metastases.

Epidemiology

Brain Metastases Epidemiology.

Classification

Brain Metastases Classification.

Scales

Karnofsky Performance Score.

Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM).

Trials

Despite the frequency of brain metastases, prospective trials in this patient population are limited, and the criteria used to assess response and progression in the CNS are heterogeneous 1).

This heterogeneity largely stems from the recognition that existing criteria sets, such as RECIST 2) 3).

Genes involved

Whether brain metastases harbor distinct genetic alterations beyond those observed in primary tumors is unknown.

Brastianos et al. detected alterations associated with sensitivity to PI3K/AKT/mTOR, CDK, and HER2/EGFR inhibitors in the brain metastases. Genomic analysis of brain metastases provides an opportunity to identify potentially clinically informative alterations not detected in clinically sampled primary tumors, regional lymph nodes, or extracranial metastases 4).

COX2

HBEGF

ST6GALNAC5

HK2

FOXC1

HER2

VEGFA

LEF1

HOXB9

CDH2, KIFC1, and FALZ3

STAT3

αvβ3

HDAC3, JAG2, NUMB, APH1B, HES4, and PSEN1

Clinical Features

see Brain metastases Clinical Features.

Diagnosis

see Brain metastases diagnosis.

Differential diagnosis

see Brain metastases differential diagnosis.

Treatment

see Brain metastases treatment.

Outcome

Brain metastases outcome.

Recurrence

see Brain metastases recurrence.

Randomized controlled trials

There is a lack of prospective randomized studies. Based on retrospective case series, international guidelines recommend the harvesting (if required, stereotactically guided) of tissue for histological and molecular diagnosis in cases of unknown or possibly competing for underlying systemic malignant diseases, in cases of suspected tumor recurrence, and with regard to the evaluation of targeted therapies taking into account molecular heterogeneity of primary and secondary tumors. Surgical resection is particularly valuable for the treatment of up to three space-occupying cerebral metastases, especially to achieve clinical stabilization to allow further non-surgical treatment For cystic metastasis, a combination of stereotactic puncture and radiotherapy may be useful. Meningeal carcinomatosis can be treated with intrathecal medication via an intraventricular catheter system. Ventriculoperitoneal shunts represent an effective treatment option for patients with tumor-associated hydrocephalus.

Neurosurgical procedures are of central importance in the multimodal treatment of cerebral metastases. The indications for neurosurgical interventions will be refined in the light of more effective radiation techniques and systemic treatments with new targeted therapeutic approaches and immunotherapies on the horizon 5).

Case series

see Brain metastases case series.

Research

Zhu et al. reported a medium-throughput drug screening platform (METPlatform) based on organotypic cultures that allow evaluating inhibitors against metastases growing in situ. By applying this approach to the unmet clinical need of brain metastases, they identified several vulnerabilities. Among them, a blood-brain barrier permeable HSP90 inhibitor showed high potency against mouse and human brain metastases at clinically relevant stages of the disease, including a novel model of local relapse after neurosurgery. Furthermore, in situ proteomic analysis applied to metastases treated with the chaperone inhibitor uncovered a novel molecular program in brain metastases, which includes biomarkers of poor prognosis and actionable mechanisms of resistance. The work validates METPlatform as a potent resource for metastases research integrating drug screening and unbiased omics approaches that are compatible with human samples. Thus, this clinically relevant strategy is aimed to personalize the management of metastatic disease in the brain and elsewhere 6).

1)

NU Lin, EQ Lee, H Aoyama, et al. Challenges relating to solid tumour brain metastases in clinical trials, part 1: patient population, response, and progression. A report from the RANO group Lancet Oncol, 14 (2013), pp. e396–e406
2)

EA Eisenhauer, P Therasse, J Bogaerts, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1) Eur J Cancer, 45 (2009), pp. 228–247
3)

P Therasse, SG Arbuck, EA Eisenhauer, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada J Natl Cancer Inst, 92 (2000), pp. 205–216
4)

Brastianos PK, Carter SL, Santagata S, Cahill DP, Taylor-Weiner A, Jones RT, Van Allen EM, Lawrence MS, Horowitz PM, Cibulskis K, Ligon KL, Tabernero J, Seoane J, Martinez-Saez E, Curry WT, Dunn IF, Paek SH, Park SH, McKenna A, Chevalier A, Rosenberg M, Barker FG 2nd, Gill CM, Van Hummelen P, Thorner AR, Johnson BE, Hoang MP, Choueiri TK, Signoretti S, Sougnez C, Rabin MS, Lin NU, Winer EP, Stemmer-Rachamimov A, Meyerson M, Garraway L, Gabriel S, Lander ES, Beroukhim R, Batchelor TT, Baselga J, Louis DN, Getz G, Hahn WC. Genomic Characterization of Brain Metastases Reveals Branched Evolution and Potential Therapeutic Targets. Cancer Discov. 2015 Sep 26. [Epub ahead of print] PubMed PMID: 26410082.
5)

Thon N, Karschnia P, Baumgarten LV, Niyazi M, Steinbach JP, Tonn JC. Neurosurgical Interventions for Cerebral Metastases of Solid Tumors. Dtsch Arztebl Int. 2023 Mar 10;(Forthcoming):arztebl.m2022.0410. doi: 10.3238/arztebl.m2022.0410. Epub ahead of print. PMID: 36650742.
6)

Zhu L, Retana D, García-Gómez P, Álvaro-Espinosa L, Priego N, Masmudi-Martín M, Yebra N, Miarka L, Hernández-Encinas E, Blanco-Aparicio C, Martínez S, Sobrino C, Ajenjo N, Artiga MJ, Ortega-Paino E, Torres-Ruiz R, Rodríguez-Perales S; RENACER, Soffietti R, Bertero L, Cassoni P, Weiss T, Muñoz J, Sepúlveda JM, González-León P, Jiménez-Roldán L, Moreno LM, Esteban O, Pérez-Núñez Á, Hernández-Laín A, Toldos O, Ruano Y, Alcázar L, Blasco G, Fernández-Alén J, Caleiras E, Lafarga M, Megías D, Graña-Castro O, Nör C, Taylor MD, Young LS, Varešlija D, Cosgrove N, Couch FJ, Cussó L, Desco M, Mouron S, Quintela-Fandino M, Weller M, Pastor J, Valiente M. A clinically compatible drug-screening platform based on organotypic cultures identifies vulnerabilities to prevent and treat brain metastasis. EMBO Mol Med. 2022 Feb 17:e14552. doi: 10.15252/emmm.202114552. Epub ahead of print. PMID: 35174975.

Cerebellar mutism

Cerebellar mutism

Cerebellar mutism (CM) was first described by Rekate et al. in 1985 following posterior fossa surgery in children 1) ;since then, it has increasingly been reported, mainly occurring as a postoperative complication.

Posterior fossa syndrome (PFS) and cerebellar mutism are often used interchangeably in the literature.

Epidemiology

Incidence of cerebellar mutism: 11–29% of children following surgery for cerebellar tumors 2) including cerebellar medulloblastoma (53%), posterior fossa ependymoma (33%) & cerebellar pilocytic astrocytoma (11%) 3).

Etiology

It has also been reported in both children and adults following several other cerebellar insults, including vascular events, infections, and trauma 4).

The uncertain etiology of PFS, myriad of cited risk factors and therapeutic challenges make this phenomenon an elusive entity.

Risk Factors

Cerebellar mutism risk factors

Posttraumatic cerebellar mutism

Cerebellar mutism is a rare occurrence following paediatric trauma 5) 6) 7) 8). , this phenomenon has rarely been reported following other insults, such as trauma, and its pathophysiology remains poorly understood.

A seven-year-old child who presented to the casualty department of Sultan Qaboos University Hospital in Muscat, Oman, in May 2013 with a traumatic right cerebellar contusion. The child presented with clinical features of cerebellar mutism but underwent a rapid and spontaneous recovery 9).

Pathophysiology

Cerebellar mutism Pathophysiology.

Pathogenesis

The pathogenic mechanism is likely due to the damage occurring to the proximal efferent cerebellar pathway, including the dentate nucleus, the superior cerebellar peduncle, and its decussation in the mesencephalic tegmentum 10).

Superior and inferior cerebellar peduncles and the superior part of the cerebellum were related to CMS, especially the right side 11).

Clinical features

This syndrome involves a variety of signs and symptoms including cerebellar mutism or speech disturbances, dysphagia, decreased motor movement, cranial nerve palsy and, emotional lability. These signs and symptoms develop from an average range of 24 to 107 hours after surgery and may take weeks to months to resolve.

Diagnosis

Multi-inflow time arterial spin-labeling shows promise as a noninvasive tool to evaluate cerebral perfusion in the setting of pediatric obstructive hydrocephalus and demonstrates increased CBF following the resolution of cerebellar mutism syndrome 12).

Differential diagnosis

The importance of olivary hypertrophic degeneration as a differential diagnosis in cerebellar mutism syndrome 13).

Prevention

Cerebellar mutism prevention.

Outcome

Early recognition of this syndrome could facilitate preventive and restorative patient care, prevent subsequent complications, decrease length of hospital stays, and promote patient and family understanding of and coping with the syndrome 14).

Case series

20 cases of PFS (8%), 12 males and 8 females. Age ranged from 1.5 to 13 years (mean = 6.5). Of the 20, 16 were medulloblastoma, 3 ependymoma and 1 astrocytoma. There was a 21 % incidence (16/76) of PFS in medulloblastoma of the posterior fossa. The incidence for ependymoma was 13% (3/24) and 1% (1/102) for astrocytoma. All 20 cases (100%) had brainstem involvement by the tumor. The most frequent postoperative findings included mutism, ataxia, 6th and 7th nerve palsies and hemiparesis. Mutism had a latency range of 1-7 days (mean = 1.7) and a duration of 6-365 days (mean = 69.2, median = 35). Although mutism resolved in all cases, the remaining neurologic complications which characterized our findings of PFS were rarely reversible. We describe potential risk factors for developing PFS after surgery with hopes of making neurosurgeons more aware of potential problems following the removal of lesions in this area. Early recognition of PFS would further promote patient and family understanding and coping with this síndrome 15)

19 children diagnosed with posterior fossa syndrome 16)

Case reports

Cerebellar mutism case reports.

1)

Rekate HL, Grubb RL, Aram DM, Hahn JF, Ratcheson RA. Muteness of cerebellar origin. Arch Neurol. 1985;42:697–8. doi: 10.1001/archneur.1985.04060070091023.
2)

Gudrunardottir T, Sehested A, Juhler M, et al. Cerebellar mutism: review of the literature. Childs Nerv Syst. 2011; 27:355–363
3)

Catsman-Berrevoets C E, Van Dongen HR, Mulder PG, et al. Tumour type and size are high risk factors for the syndrome of “cerebellar” mutism and subsequent dysarthria. J Neurol Neurosurg Psychiatry. 1999; 67:755–757
4)

Gudrunardottir T, Sehested A, Juhler M, Schmiegelow K. Cerebellar mutism: Review of the literature. Childs Nerv Syst. 2011;27:355–63. doi: 10.1007/s00381-010-1328-2.
5)

Erşahin Y, Mutluer S, Saydam S, Barçin E. Cerebellar mutism: Report of two unusual cases and review of the literature. Clin Neurol Neurosurg. 1997;99:130–4. doi: 10.1016/S0303-8467(97)80010-8.
6)

Fujisawa H, Yonaha H, Okumoto K, Uehara H, le T, Nagata Y, et al. Mutism after evacuation of acute subdural hematoma of the posterior fossa. Childs Nerv Syst. 2005;21:234–6. doi: 10.1007/s00381-004-0999-y.
7)

Koh S, Turkel SB, Baram TZ. Cerebellar mutism in children: Report of six cases and potential mechanisms. Pediatr Neurol. 1997;16:218–19. doi: 10.1016/S0887-8994(97)00018-0.
8)

Yokota H, Nakazawa S, Kobayashi S, Taniguchi Y, Yukihide T. [Clinical study of two cases of traumatic cerebellar injury] No Shinkei Geka. 1990;18:67–70.
9)

Kariyattil R, Rahim MI, Muthukuttiparambil U. Cerebellar mutism following closed head injury in a child. Sultan Qaboos Univ Med J. 2015 Feb;15(1):e133-5. Epub 2015 Jan 21. PubMed PMID: 25685374; PubMed Central PMCID: PMC4318595.
10)

Fabozzi F, Margoni S, Andreozzi B, Musci MS, Del Baldo G, Boccuto L, Mastronuzzi A, Carai A. Cerebellar mutism syndrome: From pathophysiology to rehabilitation. Front Cell Dev Biol. 2022 Dec 2;10:1082947. doi: 10.3389/fcell.2022.1082947. PMID: 36531947; PMCID: PMC9755514.
11)

Yang W, Li Y, Ying Z, Cai Y, Peng X, Sun H, Chen J, Zhu K, Hu G, Peng Y, Ge M. A presurgical voxel-wise predictive model for cerebellar mutism syndrome in children with posterior fossa tumors. Neuroimage Clin. 2022 Dec 13;37:103291. doi: 10.1016/j.nicl.2022.103291. Epub ahead of print. PMID: 36527996; PMCID: PMC9791171.
12)

Toescu SM, Hales PW, Cooper J, Dyson EW, Mankad K, Clayden JD, Aquilina K, Clark CA. Arterial Spin-Labeling Perfusion Metrics in Pediatric Posterior Fossa Tumor Surgery. AJNR Am J Neuroradiol. 2022 Oct;43(10):1508-1515. doi: 10.3174/ajnr.A7637. Epub 2022 Sep 22. PMID: 36137658; PMCID: PMC9575521.
13)

Ballestero M, de Oliveira RS. The importance of olivary hypertrophic degeneration as a differential diagnosis in cerebellar mutism syndrome. Childs Nerv Syst. 2022 Dec 21. doi: 10.1007/s00381-022-05815-x. Epub ahead of print. PMID: 36542117.
14) , 16)

Kirk EA, Howard VC, Scott CA. Description of posterior fossa syndrome in children after posterior fossa brain tumor surgery. J Pediatr Oncol Nurs. 1995 Oct;12(4):181-7. PubMed PMID: 7495523.
15)

Doxey D, Bruce D, Sklar F, Swift D, Shapiro K. Posterior fossa syndrome: identifiable risk factors and irreversible complications. Pediatr Neurosurg. 1999 Sep;31(3):131-6. PubMed PMID: 10708354.

Tranexamic acid for intracranial meningioma

Tranexamic acid for intracranial meningioma

Latest Pubmed Articles

Intracranial meningioma surgery is often complicated by significant blood loss requiring blood transfusion with its attendant risks. Although tranexamic acid is used to reduce perioperative blood loss, its blood conservation effect is uncertain in neurosurgery.

Systematic review and meta-analysis

Based upon Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), Wijaya et al. from the Universitas Pelita Harapan, Tangerang, Banten, Indonesia, Cedars-Sinai Medical Center, Los Angeles, CES University, El Poblado, Medellín, Antioquia, Colombia. collected fully published English literature on the administration of tranexamic acid for patients undergoing intracranial meningioma surgery using the keywords [“tranexamic acid” and “meningioma”] and its synonyms from Cochrane Central Register of Controlled Trials Database, the WHO International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov, and PubMed. The primary outcome of the current study was total blood loss. The secondary outcomes include individuals requiring blood transfusion, anesthesia duration, surgical duration, and complication rate. Each included study’s quality was assessed using the JADAD scale.

For qualitative and quantitative data synthesis, they included five RCTs (n = 321) with a mean age was 47.5 ± 11.9 years for the intervention group and 47.2 ± 11.9 years for the control group. The meta-analysis showed that the administration of TXA is associated with decreased total blood loss of standardized mean difference (SMD) of -1.40 (95% CI [-2.49, -0.31]), anesthetic time SMD -0.36 (95% CI [-0.63, -0.09]), and blood transfusion requirements RR 0.58 (95% CI [0.34, 0.99]).

The current study showed that TXA was associated with reduced intraoperative blood loss and intraoperative and postoperative blood transfusion. However, the studies are small. More RCT studies with a greater sample size are favorable 1).

Randomized controlled trials

Patients with supratentorial meningiomas and deemed suitable for surgical resection will be recruited in the trial. Patients will be randomized to receive either a single administration of 20 mg/kg TXA or a placebo of the same volume with a 1:1 allocation ratio after anesthesia induction. The primary endpoint is the cumulative incidence of early postoperative seizures within 7 days after craniotomy. Secondary outcomes include the incidence of non-seizure complications, changes in hemoglobin level from baseline, intraoperative blood loss, erythrocyte transfusion volume, Karnofsky Performance Status, all-cause mortality, length of stay, and total hospitalization cost.

Ethics and dissemination: This trial is registered at ClinicalTrial.gov and approved by the Chinese Ethics Committee of Registering Clinical Trials (ChiECRCT20200224). The findings will be disseminated in peer-reviewed journals and presented at national or international conferences relevant to the subject fields.

Trial registration number: NCT04595786 2).

conducted a prospective, randomized double-blind clinical study. The patient scheduled to undergo excision of intracranial meningioma were randomly assigned to receive intraoperatively either intravenous TXA or placebo. Patients in the TXA group received an intravenous bolus of 20 mg/kg over 20 min followed by an infusion of 1 mg/kg/h up to surgical wound closure. Efficacy was evaluated based on total blood loss and transfusion requirements. Postoperatively, thrombotic complications, convulsive seizure, and hematoma formation were noted.

Ninety-one patients were enrolled and randomized: 45 received TXA (TXA group) and 46 received placebo (group placebo). Total blood loss was significantly decreased in the TXA group compared to the placebo (283 ml vs. 576 ml; P < 0.001). Transfusion requirements were comparable in the two groups (P = 0.95). The incidence of thrombotic complications, convulsive seizure, and hematoma formation were similar in the two groups.

TXA significantly reduces intraoperative blood loss but did not significantly reduce transfusion requirements in adults undergoing resection of intracranial meningioma 3).

Case series

Thirty patients aged 18-65 years undergoing elective meningioma resection surgery were given either tranexamic acid or placebo (0.9% saline), tranexamic acid at a loading dose of 20 mg/kg, and infusion of 1 mg/kg/h during surgery. The intraoperative blood loss, coagulation profile, and the surgical field using the Likert scale were assessed.

The patients in the tranexamic group had significantly decreased intraoperative blood loss compared to the placebo group (616.42 ± 393.42 ml vs. 1150.02 ± 416.1 ml) (P = 0.02). The quality of the surgical field was better in the tranexamic group (median score 4 vs. 2 on Likert Scale) (P < 0.001). Patients in the tranexamic group had an improved coagulation profile and decreased blood transfusion requirement (p=0.016). The blood collected in the closed suction drain in 24 h postsurgery was less in the tranexamic acid group compared to the placebo group (84.7 ± 50.4 ml vs. 127.6 ± 62.2 ml) (P = 0.047).

Tranexamic acid bolus followed by infusion reduces perioperative blood loss by 46.43% and blood transfusion requirement with improved surgical field and coagulation profile in patients undergoing intracranial meningioma resection surgery 4).

In the Department of Neurosurgery, All India Institute of Medical Sciences (AIIMS), New Delhi, India, Sixty adults undergoing elective craniotomy for meningioma excision were randomized to receive either tranexamic acid or placebo, initiated prior to skin incision. Patients in the tranexamic acid group received an intravenous bolus of 20mg/kg over 20min followed by an infusion of 1mg/kg/h till the conclusion of surgery. Intraoperative blood loss, transfusion requirements, and estimating surgical hemostasis using a 5-grade scale were noted. Postoperatively, the extent of tumor excision on CT scan and complications were observed. Demographics, tumor characteristics, amount of fluid infusion, and duration of surgery and anesthesia were comparable between the two groups. The amount of blood loss was significantly less in the tranexamic acid group compared to the placebo (830mlvs 1124ml; p=0.03). The transfusion requirement was less in the tranexamic acid group (p>0.05). The patients in the tranexamic acid group fared better on a 5-grade surgical hemostasis scale with more patients showing good hemostasis (p=0.007). There were no significant differences between the groups regarding the extent of tumor removal, perioperative complications, hospital stay, or neurologic outcome. To conclude, the administration of tranexamic acid significantly reduced blood loss in patients undergoing excision of meningioma. Fewer patients in the tranexamic acid group received blood transfusions. Surgical field hemostasis was better achieved in patients who received tranexamic acid 5).

Case reports

A man in his 40s with a history of coronary artery disease previously treated with a drug-eluting stent presented for elective craniotomy and resection of an asymptomatic but enlarging meningioma. During his craniotomy, he received desmopressin and tranexamic acid for surgical bleeding. Postoperatively, the patient developed chest pain and was found to have an ST-elevation myocardial infarction (MI). Because of the patient’s recent neurosurgery, standard post-MI care was contraindicated and he was managed symptomatically in the intensive care unit. The echocardiogram on a postoperative day 1 demonstrated no regional wall motion abnormalities and an ejection fraction of 60%. His presentation was consistent with the thrombosis of his diagonal stent. He was transferred out of the intensive care unit on postoperative day 1 and discharged home on postoperative day 3 6).

Raghavendra et al. report the intraoperative use of tranexamic acid to secure complete hemostasis as a rescue measure in intracranial meningioma resection in uncontrollable bleeding 7).

Three of 13 patients with intracranial meningiomas showed the pre-and postoperative elevation of tissue-type plasminogen activator (t-PA) related fibrinolytic activity in euglobulin fractions (EFA). During the operation, two of these three patients showed a significant elevation of the level of fibrinogen degradation products and oozing in the operating field. However, oozing was not observed in the third patient who had been given tranexamic acid preoperatively. Fibrin autography revealed that a broad lytic band of mol wt 50-60 kDa, probably free t-PA, appeared in the plasma obtained from two of the three patients after the operation when EFA elevated significantly. In all patients studied, the t-PA antigen levels were normal preoperatively but increased both during and after the operation, and correlated mainly with the intensities of a lytic band of mol wt 110 kDa, probably t-PA complexed with its major inhibitor (PAI-1). These results suggest that excessive fibrinolysis can induce local hemorrhagic diathesis during operation and may be related to t-PA function in plasma 8).

1)

Wijaya JH, July J, Quintero-Consuegra M, Chadid DP. A systematic review and meta-analysis of the effects of tranexamic acid in surgical procedure for intracranial meningioma. J Neurooncol. 2023 Jan 12. doi: 10.1007/s11060-023-04237-2. Epub ahead of print. PMID: 36633801.
2)

Li S, Yan X, Li R, Zhang X, Ma T, Zeng M, Dong J, Wang J, Liu X, Peng Y. Safety of intravenous tranexamic acid in patients undergoing supratentorial meningiomas resection: protocol for a randomized, parallel-group, placebo control, non-inferiority trial. BMJ Open. 2022 Feb 2;12(2):e052095. doi: 10.1136/bmjopen-2021-052095. PMID: 35110315; PMCID: PMC8811564.
3)

Rebai L, Mahfoudhi N, Fitouhi N, Daghmouri MA, Bahri K. Intraoperative tranexamic acid use in patients undergoing excision of intracranial meningioma: Randomized, placebo-controlled trial. Surg Neurol Int. 2021 Jun 14;12:289. doi: 10.25259/SNI_177_2021. PMID: 34221620; PMCID: PMC8247750.
4)

Ravi GK, Panda N, Ahluwalia J, Chauhan R, Singla N, Mahajan S. Effect of tranexamic acid on blood loss, coagulation profile, and quality of the surgical field in intracranial meningioma resection: A prospective randomized, double-blind, placebo-controlled study. Surg Neurol Int. 2021 Jun 7;12:272. doi: 10.25259/SNI_296_2021. PMID: 34221603; PMCID: PMC8247710.
5)

Hooda B, Chouhan RS, Rath GP, Bithal PK, Suri A, Lamsal R. Effect of tranexamic acid on intraoperative blood loss and transfusion requirements in patients undergoing excision of intracranial meningioma. J Clin Neurosci. 2017 Mar 7. pii: S0967-5868(16)31491-6. doi: 10.1016/j.jocn.2017.02.053. [Epub ahead of print] PubMed PMID: 28283245.
6)

Westfall KM, Ramcharan RN, Anderson HL 3rd. Myocardial infarction after craniotomy for asymptomatic meningioma. BMJ Case Rep. 2022 Dec 29;15(12):e252256. doi: 10.1136/bcr-2022-252256. PMID: 36581354; PMCID: PMC9806024.
7)

Raghavendra H, Varsha KS, Reddy MA, Kumar SS, Sunanda G, Nagarjuna T, Latha S. Rescue Measure in Giant Intracranial Meningioma Resection by Tranexamic Acid. J Neurosci Rural Pract. 2017 Aug;8(Suppl 1):S127-S129. doi: 10.4103/jnrp.jnrp_198_17. PMID: 28936089; PMCID: PMC5602238.
8)

Tsuda H, Oka K, Noutsuka Y, Sueishi K. Tissue-type plasminogen activator in patients with intracranial meningiomas. Thromb Haemost. 1988 Dec 22;60(3):508-13. PMID: 3149049.

Radiation necrosis diagnosis

Radiation necrosis diagnosis

Latest Pubmed Related Articles

Unfortunately, symptomatic radiation necrosis is notoriously hard to diagnose and manage. The features of RN overlap considerably with tumor recurrence and misdiagnosing RN as tumor recurrence may lead to deleterious treatment which may cause detrimental effects on the patient 1)

Differentiating radiation necrosis from tumor progression on standard magnetic resonance imaging (MRI) is often difficult and advanced imaging techniques may be needed to make an accurate diagnosis.

Mayo et al. performed a literature review addressing the radiographic modalities used in the diagnosis of radiation necrosis.

Differentiating radiation necrosis from tumor progression remains a diagnostic challenge and advanced imaging modalities are often required to make a definitive diagnosis. If diagnostic uncertainty remains following conventional imaging, a multi-modality diagnostic approach with perfusion MRI, magnetic resonance spectroscopy (MRS), positron emission tomography (PET), single photon emission spectroscopy (SPECT), and radiomics may be used to improve diagnosis.

Several imaging modalities exist to aid in the diagnosis of radiation necrosis. Future studies developing advanced imaging techniques are needed 2).

Mangesius et al. provide the experience of a tertiary tumor center with this important issue in neurooncology and provide an institutional pathway for dealing with this problem 3).

Differential diagnosis

Radiation necrosis differential diagnosis.

1)

Vellayappan B, Tan CL, Yong C, Khor LK, Koh WY, Yeo TT, Detsky J, Lo S, Sahgal A. Diagnosis and Management of Radiation Necrosis in Patients With Brain Metastases. Front Oncol. 2018 Sep 28;8:395. doi: 10.3389/fonc.2018.00395. PMID: 30324090; PMCID: PMC6172328.
2)

Mayo ZS, Halima A, Broughman JR, Smile TD, Tom MC, Murphy ES, Suh JH, Lo SS, Barnett GH, Wu G, Johnson S, Chao ST. Radiation necrosis or tumor progression? A review of the radiographic modalities used in the diagnosis of cerebral radiation necrosis. J Neurooncol. 2023 Jan 12. doi: 10.1007/s11060-022-04225-y. Epub ahead of print. PMID: 36633800.
3)

Mangesius J, Mangesius S, Demetz M, Uprimny C, Di Santo G, Galijasevic M, Minasch D, Gizewski ER, Ganswindt U, Virgolini I, Thomé C, Freyschlag CF, Kerschbaumer J. A Multi-Disciplinary Approach to Diagnosis and Treatment of Radionecrosis in Malignant Gliomas and Cerebral Metastases. Cancers (Basel). 2022 Dec 19;14(24):6264. doi: 10.3390/cancers14246264. PMID: 36551750; PMCID: PMC9777318.

1p/19q co-deletion

1p/19q co-deletion

Latest Pubmed Related Articles

1p19q codeletion stands for the combined loss of the short arm chromosome 1 (i.e. 1p) and the long arm of chromosome 19 (i.e. 19q) and is recognized as a genetic marker predictive of therapeutic response to both chemotherapy and combined chemoradiotherapy and overall longer survival in patients with diffuse gliomas, especially those with oligodendroglial components

IDH positive + 1p/19q co-deletion = oligodendroglioma = better prognosis

IDH positive + no 1p/19q co-deletion = astrocytoma 1)

Indications

Latest Pubmed Related Articles

Currently, classification of neoplasms, especially regarding gliomas, is established on molecular mutations in isocitrate dehydrogenase (IDH) genes and the presence of 1p/19q co-deletion 2)

1p/19q co-deletion should be tested whenever oligodendroglial features are present or if oligodendroglioma is suspected on other grounds. This is tested using FISH (fluorescence in situ hybridization) or PCR. It is often sent out, results typically take 3–7 days. Cost for FISH is on the order of $200 U.S., PCR is $300–500 U.S

Oligodendrocyte transcriptional factor-2 (Olig2) is an essential marker for oligodendrocytes expression. Olig2 marker cannot be used as an alternative diagnostic method for 1p 19q co-deletion to distinguish oligodendrogliomas from other glial neoplasms. Although some glial tumors showed diffuse Olig2 expression, 1p19q co-deletion testing is the best diagnostic method 3).

Oligodendroglioma 1p/19q co-deletion

Oligodendroglioma 1p/19q co-deletion.

Anaplastic astrocytoma without 1p/19q co-deletion

Anaplastic astrocytoma without 1p/19q co-deletion.

Extraventricular neurocytoma

1p/19q co-deletion has not been reported in central neurocytoma, but it can be seen in extraventricular neurocytoma.

1)

https://radiopaedia.org/articles/1p19q-codeletion#:~:text=1p19q%20codeletion%20stands%20for%20the,in%20patients%20with%20diffuse%20gliomas%2C
2)

Casili G, Paterniti I, Campolo M, Esposito E, Cuzzocrea S. The Role of Neuro-Inflammation and Innate Immunity in Pathophysiology of Brain and Spinal Cord Tumors. Adv Exp Med Biol. 2023;1394:41-49. doi: 10.1007/978-3-031-14732-6_3. PMID: 36587380.
3)

Kurdi M, Alkhatabi H, Butt N, Albayjani H, Aljhdali H, Mohamed F, Alsinani T, Baeesa S, Almuhaini E, Al-Ghafari A, Hakamy S, Faizo E, Bahakeem B. Can oligodendrocyte transcriptional factor-2 (Olig2) be used as an alternative for 1p/19q co-deletions to distinguish oligodendrogliomas from other glial neoplasms? Folia Neuropathol. 2021;59(4):350-358. doi: 10.5114/fn.2021.112562. PMID: 35114775.

Trigone ventricular meningioma

Trigone ventricular meningioma

Trigone meningioma is a intraventricular meningioma in a deep-seated location surrounded by intact neural tissue, near to vital ventricular structures, and deeply vascularized.

Intraventricular intracranial meningiomas as a rule arise in the trigone.

Diagnosis

Thirty patients with trigone meningiomas were enrolled in this retrospective study. Conventional MRI was performed in all patients; SWI (17 cases), dynamic contrast-enhanced PWI (10 cases), and dynamic susceptibility contrast PWI (6 cases) were performed. Demographics, conventional MRI features, SWI- and PWI-derived parameters were compared between different grades of trigone meningiomas.

On conventional MRI, the irregularity of tumor shape (ρ = 0.497, P = 0.005) and the extent of peritumoral edema (ρ = 0.187, P = 0.022) might help distinguish low-grade and high-grade trigone meningiomas. On multiparametric functional MRI, rTTPmax (1.17 ± 0.06 vs 1.30 ± 0.05, P = 0.048), Kep, Ve, and iAUC demonstrated their potentiality to predict World Health Organization grades I, II, and III trigone meningiomas.

Conventional MRI combined with dynamic susceptibility contrast and dynamic contrast-enhanced can help predict the World Health Organization grade of trigone meningiomas 1).

Treatment

Trigone ventricular meningioma treatment.

Case series

Trigone ventricular meningioma case series.

Case reports

Trigone ventricular meningioma case reports.

Trigone Meningioma General University Hospital of Alicante Cases

A 65-year-old female refers to a speech disorder (slowed speech and stuttering) for months of evolution, the reason for which an MRI study was performed. Refers to impaired reading (blurred vision of some letters) associated.

Brain MRI:

In the left hemisphere, a rounded tumor of 28 mm in greater diameter is located inside the lateral ventricle. It is a tumor slightly hypointense on T1, slightly hyperintense on Flair, and practically isointense on T2. The lesion uptakes contrast intense and relatively uniform way. The posterior horn of the ventricle appears dilated and there is a modification of the signal intensity of the adjacent tissue. However, the midline does not appear displaced. the ventricle right lateral and third ventricles are dilated

General anesthesia. Right lateral decubitus position with Mayfield skull clamp. Incision and craniotomy location with craniometric points (intraparietal point). Left parietal craniotomy with the high-speed motor. U-shaped dural opening with a sagittal sinus base. The postcentral sulcus and intraparietal sulcus are visualized in the cortex. Location of the atrium and tumor with intraoperative ultrasound. Approach through the intraparietal sulcus in its lower portion until the ventricle was opened and a pinkish-colored tumor with a rubbery consistency visible, macroscopically compatible with meningioma. Dissection of the edges at the intraventricular level, separating the choroid plexus and coagulating and sectioning several nutrient arteries. Tumor dissection with CUSA until leaving a small fragment that is dissected from the medial wall of the ventricle and excised. Macroscopically complete resection. Careful hemostasis and abundant washing. Dural closure is almost hermetic and sealed with Tachosil. Bone replacement with titanium trephine plates and plugs. Cutaneous closure by planes. Stapled skin. The sample is sent to pathology.

1)

Yang X, Xiao Z, Xing Z, Lin X, Wang F, Cao D. Grading Trigone Meningiomas Using Conventional Magnetic Resonance Imaging With Susceptibility-Weighted Imaging and Perfusion-Weighted Imaging. J Comput Assist Tomogr. 2022 Jan-Feb 01;46(1):103-109. doi: 10.1097/RCT.0000000000001256. PMID: 35027521.

Cerebellar pilocytic astrocytoma

Cerebellar pilocytic astrocytoma

Latest news

Key concepts

● Often cystic, half of these have a mural nodule.

● Usually presents during the second decade of life (ages 10–20 yrs).

● A subtype of pilocytic astrocytoma. Formerly referred to by the nonspecific and confusing term cystic cerebellar astrocytoma.

Epidemiology

Cerebellar pilocytic astrocytoma epidemiology.

Classification

Children

see Cerebellar pilocytic astrocytoma in children.

Adult

Cerebellar pilocytic astrocytomas in adults should be treated with macroscopic complete surgical resection whenever possible. If this is achieved, long-term survival rates are excellent, whereas subtotal resection carries a high risk of tumor recurrence. Ki67 is less important prognostically than the extent of initial resection 1).

Clinical features

In the posterior fossa tumors, there is predominantly a mass effect with signs of raised intracranial pressure, especially when hydrocephalus is present. Bulbar palsy or cerebellar syndrome may also be present.

Diagnosis

Cerebellar pilocytic astrocytoma diagnosis.

Differential diagnosis

Cerebellar pilocytic astrocytoma differential diagnosis.

Treatment

see Cerebellar pilocytic astrocytoma treatment.

Outcome

Nine percent of the children in a study underwent repeated surgery due to progressive tumor recurrence, and 15% were treated for persistent hydrocephalus 2).

The long-term functional outcome of low-grade cerebellar astrocytoma is generally favourable, in the absence of post-operative complications and brainstem involvement. No major impact of neurological deficits, cognitive functions and emotional disorders on academic achievement and independent functioning was observed 3).

The good long-term outcomes suggest that it may be appropriate to do incomplete resection rather than risk additional neurological deficit 4).

There is controversy about whether patients with tumor remaining after surgery should receive radiation therapy. It is also unclear whether only patients with incomplete resection require follow-up and for how long 5).

Complications

Acute hemorrhagic presentation in pilocytic astrocytomas (PAs) has become increasingly recognized. This type of presentation poses a clinically emergent situation in those hemorrhages arising in PAs of the cerebellum, the most frequent site, because of the limited capacity of the posterior fossa to compensate for mass effect, predisposing to rapid neurological deterioration.

Complete resection

Complete resection of cerebellar astrocytoma is an important prognostic factor, indicating a more favorable prognosis than subtotal resection. This was also the conclusion of a much larger study by Villarejo et al. who reviewed 203 cases of low-grade cerebellar astrocytoma 6).

Loh et al., documented that patients with subtotal removal of cerebellar astrocytoma can have arrested tumor growth or spontaneous tumor regression during long-term follow-up. Following partial resection of pediatric cerebellar astrocytoma, they recommend that the patients be followed up a “wait and see” approach with surveillance using MRI. They found that several tumors treated with radiotherapy after surgery had malignant transformation and do not recommend adjuvant radiation treatment for children with cerebellar astrocytoma who have subtotal resection. More research is needed on the prognosis of patients with subtotal resection of cerebellar astrocytoma 7).

Pilomyxoid features and anaplasia

A subset may behave in a more aggressive fashion and clinically progress despite the use of conventional treatments. Histologic features associated with a more aggressive course include the presence of monomorphous pilomyxoid features (ie, pilomyxoid variant) and anaplasia in the form of brisk mitotic activity with or without necrosis 8).

Case series

Cerebellar pilocytic astrocytoma case series.

Case reports

Cerebellar pilocytic astrocytoma case reports.

References

1) 

Wade A, Hayhurst C, Amato-Watkins A, Lammie A, Leach P. Cerebellar pilocytic astrocytoma in adults: a management paradigm for a rare tumour. Acta Neurochir (Wien). 2013 Aug;155(8):1431-5. doi: 10.1007/s00701-013-1790-1. Epub 2013 Jun 22. PubMed PMID: 23793962.

2) 

Due-Tønnessen BJ, Lundar T, Egge A, Scheie D. Neurosurgical treatment of low-grade cerebellar astrocytoma in children and adolescents: a single consecutive institutional series of 100 patients. J Neurosurg Pediatr. 2013 Mar;11(3):245-9. doi: 10.3171/2012.11.PEDS12265. Epub 2012 Dec 14. PubMed PMID: 23240848.

3) 

Ait Khelifa-Gallois N, Laroussinie F, Puget S, Sainte-Rose C, Dellatolas G. Long-term functional outcome of patients with cerebellar pilocytic astrocytoma surgically treated in childhood. Brain Inj. 2014 Nov 10:1-8. [Epub ahead of print] PubMed PMID: 25383654.

4) 

Steinbok P, Mangat JS, Kerr JM, Sargent M, Suryaningtyas W, Singhal A, Cochrane D. Neurological morbidity of surgical resection of pediatric cerebellar astrocytomas. Childs Nerv Syst. 2013 Aug;29(8):1269-75. doi: 10.1007/s00381-013-2171-z. Epub 2013 May 29. PubMed PMID: 23715810.

5) 

Dirven CM, Mooij JJ, Molenaar WM. Cerebellar pilocytic astrocytoma: a treatment protocol based upon analysis of 73 cases and a review of the literature. Childs Nerv Syst. 1997;13:17–23. doi: 10.1007/s003810050033.

6) 

Villarejo F, Diego JMB, Riva AG. Prognosis of cerebellar astrocytoma in children. Childs Nerv Syst. 2008;24:203–210. doi: 10.1007/s00381-007-0449-8.

7) 

Loh JK, Lieu AS, Chai CY, Hwang SL, Kwan AL, Wang CJ, Howng SL. Arrested growth and spontaneous tumor regression of partially resected low-grade cerebellar astrocytomas in children. Childs Nerv Syst. 2013 Nov;29(11):2051-5. doi: 10.1007/s00381-013-2113-9. Epub 2013 May 1. PubMed PMID: 23632690; PubMed Central PMCID: PMC3825417.

8) 

Rodriguez FJ, Scheithauer BW, Burger PC, Jenkins S, Giannini C. Anaplasia in pilocytic astrocytoma predicts aggressive behavior. Am J Surg Pathol. 2010;34(2):147–160.

Glioblastoma

Glioblastoma

J.Sales-Llopis

Neurosurgery Service, Alicante University General Hospital, Alicante Institute for Health and Biomedical Research (ISABIAL – FISABIO Foundation), Alicante, Spain.

Definition

While glioblastoma was historically classified as isocitrate dehydrogenase (IDH)-wildtype and IDH-mutant groups, the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT-NOW) and the World Health Organization Classification of Tumors of the Central Nervous System 2021 clearly updated the nomenclature to reflect glioblastoma to be compatible with wildtype IDH status only. Therefore, glioblastoma is now defined as “a diffuse, astrocytic glioma that is IDH-wildtype and H3-wildtype and has one or more of the following histological or genetic features: microvascular proliferation, necrosis, TERT promoter mutation, Epidermal growth factor receptor gene amplification, +7/-10 chromosome copy-number changes (CNS WHO grade 4) 1).

History

see Glioblastoma History.

Epidemiology

see Glioblastoma epidemiology.

Prior malignancies in patients harboring glioblastoma

Patients who develop Glioblastoma following a prior malignancy constitute ~8% of patients with Glioblastoma. Despite significant molecular differences these two cohorts appear to have a similar overall prognosis and clinical course. Thus, whether or not a patient harbors a malignancy prior to diagnosis of Glioblastoma should not exclude him or her from aggressive treatment or for consideration of novel investigational therapies 2).

Classification

see Glioblastoma classification.

Molecular pathways in the development of glioblastoma

Genome-wide profiling studies have shown remarkable genomic diversity among glioblastomas.

Molecular studies have helped identify at least 3 different pathways in the development of glioblastomas.

● 1st pathway: dysregulation of growth factor signaling through amplification and mutational activation of receptor tyrosine kinase (RTK) genes. RTKs are transmembrane proteins that act as receptors for an epidermal growth factor (EGF), vascular endothelial growth factor (VEGF) & platelet-derived growth factor (PDGF). They can also act as receptors for cytokines, hormones, and other signaling pathways

● 2nd pathway: activation of the Phosphoinositide 3 kinase (PI3K)/AKT/mTOR, which is an intracellular signaling pathway that is essential in regulating cell survival

● 3rd pathway: inactivation of the p53 and retinoblastoma (Rb) tumor suppressor pathways

Risk factors

Glioblastomas are intrinsic brain tumors thought to originate from a neuroglial stem or progenitor cells. More than 90% of glioblastomas are isocitrate dehydrogenase (IDH)-wildtype tumors. Incidence increases with age, males are more often affected. Beyond rare instances of genetic predisposition and irradiation exposure, there are no known glioblastoma risk factors.

Biomarkers

Glioblastoma biomarker.

Pathogenesis

see Glioblastoma pathogenesis

Microcirculation patterns

Vessels with different microcirculation patterns are required for glioblastoma (Glioblastoma) growth. However, details of the microcirculation patterns in Glioblastoma remain unclear.

Mei et al. examined the microcirculation patterns of Glioblastoma and analyzed their roles in patient prognosis together with two well-known GMB prognosis factors (O6 -methylguanine DNA methyltransferase [MGMT] promoter methylation status and isocitrate dehydrogenase [IDH] mutations).

Eighty Glioblastoma clinical specimens were collected from patients diagnosed between January 2000 and December 2012. The microcirculation patterns, including endothelium-dependent vessels (EDVs), extracellular matrix-dependent vessels (ECMDVs), Glioblastoma cell-derived vessels (GDVs), and mosaic vessels (MVs), were evaluated by immunohistochemistry (IHC) and immunofluorescence (IF) staining in both Glioblastoma clinical specimens and xenograft tissues. Vascular density assessments and three-dimensional reconstruction were performed. MGMT promoter methylation status was determined by methylation-specific PCR, and IDH1/2 mutations were detected by Sanger sequencing. The relationship between the microcirculation patterns and the patient prognosis was analyzed by the Kaplan-Meier method.

All 4 microcirculation patterns were observed in both Glioblastoma clinical specimens and xenograft tissues. EDVs was detected in all tissue samples, while the other three patterns were observed in a small number of tissue samples (ECMDVs in 27.5%, GDVs in 43.8%, and MVs in 52.5% tissue samples). GDV-positive patients had a median survival of 9.56 months versus 13.60 months for GDV-negative patients (P = 0.015). In MGMT promoter-methylated cohort, GDV-positive patients had a median survival of 6.76 months versus 14.23 months for GDV-negative patients (P = 0.022).

GDVs might be a negative predictor for the survival of Glioblastoma patients, even in those with MGMT promoter methylation 3).

Pathology

Glioblastoma Pathology.

Genetics

see Glioblastoma Genetics.

Growth

see Glioblastoma growth.

Radioresistance

Glioblastoma Radioresistance

Clinical Features

It generally presents with epilepsy, cognitive decline, headache, dysphasia, or progressive hemiparesis. 4).

Seizures as the presenting symptom of glioblastoma predicted longer survival in adults younger than 60 years. The IDH1 R132H mutation and p53 overexpression (>40%) were associated with seizures at presentation. Seizures showed no relationship with the tumor size or proliferation parameters 5).

Diagnosis

see Glioblastoma diagnosis.

Differential diagnosis

Glioblastoma Differential Diagnosis

Scores

SHORT score.

Treatment

see Glioblastoma treatment.

Outcome

see Glioblastoma outcome

Diet

see Ketogenic Diet in glioblastoma

Complications

see Glioblastoma complications.

Case series

see Glioblastoma case series.

Case reports

Glioblastoma case reports

1)

Chen J, Han P, Dahiya S. Glioblastoma: Changing concepts in the WHO CNS5 classification. Indian J Pathol Microbiol. 2022 May;65(Supplement):S24-S32. doi: 10.4103/ijpm.ijpm_1109_21. PMID: 35562131.
2)

Zacharia BE, DiStefano N, Mader MM, Chohan MO, Ogilvie S, Brennan C, Gutin P, Tabar V. Prior malignancies in patients harboring glioblastoma: an institutional case-study of 2164 patients. J Neurooncol. 2017 May 27. doi: 10.1007/s11060-017-2512-y. [Epub ahead of print] Review. PubMed PMID: 28551847.
3)

Mei X, Chen YS, Zhang QP, Chen FR, Xi SY, Long YK, Zhang J, Cai HP, Ke C, Wang J, Chen ZP. Association between glioblastoma cell-derived vessels and poor prognosis of the patients. Cancer Commun (Lond). 2020 May 2. doi: 10.1002/cac2.12026. [Epub ahead of print] PubMed PMID: 32359215.
4)

Thomas DGT,Graham DI, McKeran RO,Thomas DGT. The clinical study of gliomas. In: Brain tumours: scientific basis, clinical investigation and current therapy. In: Thomas DGT, Graham DI eds. London: Butterworths, 1980:194–230.
5)

Toledo M, Sarria-Estrada S, Quintana M, Maldonado X, Martinez-Ricarte F, Rodon J, Auger C, Aizpurua M, Salas-Puig J, Santamarina E, Martinez-Saez E. Epileptic features and survival in glioblastomas presenting with seizures. Epilepsy Res. 2016 Dec 26;130:1-6. doi: 10.1016/j.eplepsyres.2016.12.013. [Epub ahead of print] PubMed PMID: 28073027.