Neurologic Manifestations of Glioblastoma Multiforme

Neurologic Manifestations of Glioblastoma Multiforme

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Glioblastoma multiforme (GBM) is the most common and most aggressive of the primary brain tumors. The current World Health Organization (WHO) classification of primary brain tumors lists GBM as a grade IV astrocytoma. [1] Astrocytoma is one of 3 distinct types of gliomas in the brain, although mixed cell types occur as well. GBMs are highly malignant, infiltrate the brain extensively, and at times may become enormous before turning symptomatic. See the image below.


GBM is an anaplastic, highly cellular tumor with poorly differentiated, round, or pleomorphic cells, occasional multinucleated cells, nuclear atypia, and anaplasia. Under the modified WHO classification, GBM differs from anaplastic astrocytomas (AA) by the presence of necrosis under the microscope. Variants of the tumor include gliosarcoma, multifocal GBM, or gliomatosis cerebri (in which the entire brain may be infiltrated with tumor cells). These variants, however, do not alter the prognosis of the tumor. Multifocal metastasis of GBM, including far distant spinal drop metastasis in patients treated with antiangiogenic chemotherapy [2] , is extremely rare but is increasing. Two reasons for the metastasis are an antiangiogenic therapy – induced activation of glioma invasion [3] and the fact that patients are living longer. [4]

Among primary brain tumors, malignant astrocytomas are the most common in all age groups. (However, among all brain tumors, metastases are the most common.) GBMs are the most common primary brain tumors in adults, accounting for 12-15% of intracranial tumors and 50-60% of primary brain tumors. Several authors have reported a true increase in the incidence of brain tumors, especially among the elderly, and many have attributed the observed changes to developments in diagnostic imaging or changes in the classification system. [5]

International incidence of GBM is similar to that of the United States.

Morbidity is from the tumor location, progression, and pressure effects. The overall prognosis for GBM has changed little in the past 2 decades, despite major improvements in neuroimaging, neurosurgery, radiation treatment techniques, adjuvant chemotherapy, and supportive care. Few patients with GBM survive longer than 3 years and only a handful survive 5 years. Previously reported long-term survivors of GBM may be patients diagnosed with GBM who actually harbor low-grade glioma, pleomorphic xanthoastrocytoma, ganglioglioma, or other lesions. Occasional patients with a single necrotic, demyelinating plaque of multiple sclerosis also may be misdiagnosed with GBM, especially if only CT scans are obtained.

High-grade astrocytomas (HGAs) are slightly more common in whites than in blacks, Latinos, and Asians.

GBM is slightly more common in men than in women; the male-to-female ratio is 3:2.

While GBM occurs in all age groups, its incidence is increasing in elderly patients. A true increase in incidence of primary brain tumors exists, which cannot be explained by the aging population, better imaging techniques, or earlier detection at surgery.

Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007 Aug. 114 (2):97-109. [Medline].

Seiz M, Nolte I, Pechlivanis I, et al. Far-distant metastases along the CSF pathway of glioblastoma multiforme during continuous low-dose chemotherapy with temozolomide and celecoxib. Neurosurg Rev. 2010 Jul. 33(3):375-81; discussion 381. [Medline].

Tuettenberg J, Grobholz R, Seiz M, et al. Recurrence pattern in glioblastoma multiforme patients treated with anti-angiogenic chemotherapy. J Cancer Res Clin Oncol. 2009 Sep. 135(9):1239-44. [Medline].

Buhl R, Barth H, Hugo HH, Hutzelmann A, Mehdorn HM. Spinal drop metastases in recurrent glioblastoma multiforme. Acta Neurochir (Wein). 1998;. 140(10):1001-5.

Hess KR, Broglio KR, Bondy ML. Adult glioma incidence trends in the United States, 1977-2000. Cancer. 2004 Nov 15. 101(10):2293-9. [Medline].

Hardell L, Carlberg M, Soderqvist F, Mild KH, Morgan LL. Long-term use of cellular phones and brain tumours: increased risk associated with use for > or =10 years. Occup Environ Med. 2007 Sep. 64(9):626-32. [Medline].

Pichlmeier U, Bink A, Schackert G, Stummer W. ALA Glioma Study Group. Resection and survival in glioblastoma multiforme: an RTOG recursive partitioninganalysis of ALA study patients. Neuro-Oncol. Oct 2008. (6):1025-34.

Preusser M, de Ribaupierre S, Wohrer A, et al. Current concepts and management of glioblastoma. Ann Neurol. 2011 Jul. 70(1):9-21. [Medline].

Stupp R, Hegi ME, Mason WP, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009 May. 10(5):459-66. [Medline].

Hatanaka H. Analysis of clinical results of long surviving brain tumor patients who underwent Boron-neutron-capture therapy with mercapto undeca hydrocarborate. Proceedings of the Xth International Congress of Neurosurgery, Acapulco Mexico. 1993 Oct 17-22.

Westphal M, Hilt DC, Bortey E, et al. A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma. Neuro-oncol. 2003 Apr. 5(2):79-88. [Medline].

Darakchiev BJ, Albright RE, Breneman JC, Warnick RE. Safety and efficacy of permanent iodine-125 seed implants and carmustine wafers in patients with recurrent glioblastoma multiforme. J Neurosurg. 2008 Feb. 108(2):236-42. [Medline].

Hegi ME, Diserens AC, Gorlia T, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005 Mar 10. 352(10):997-1003. [Medline].

Iwamoto FM, Fine HA. Bevacizumab for malignant gliomas. Arch Neurol. 2010 Mar. 67(3):285-8. [Medline].

Perry JR, Belanger K, Mason WP, et al. Phase II trial of continuous dose-intense temozolomide in recurrent malignant glioma: RESCUE study. J Clin Oncol. 2010 Apr 20. 28(12):2051-7. [Medline].

Burkhardt JK, Riina H, Shin BJ, et al. Intra-arterial delivery of bevacizumab after blood-brain barrier disruption for the treatment of recurrent glioblastoma: progression-free survival and overall survival. World Neurosurg. 2012 Jan. 77(1):130-4. [Medline].

Rosati A, Tomassini A, Pollo B, Ambrosi C, Schwarz A, Padovani A. Epilepsy in cerebral glioma: timing of appearance and histological correlations. J Neurooncol. 2009 Jul. 93(3):395-400. [Medline].

Krex D, Klink B, Hartmann C, et al. Long-term survival with glioblastoma multiforme. Brain. 2007 Oct. 130(Pt 10):2596-606. [Medline].

Luther N, Cheung NK, Souliopoulos EP, et al. Interstitial infusion of glioma-targeted recombinant immunotoxin 8H9scFv-PE38. Mol Cancer Ther. 2010 Apr. 9(4):1039-46. [Medline].

Wang LF, Fokas E, Juricko J, et al. Increased expression of EphA7 correlates with adverse outcome in primary and recurrent glioblastoma multiforme patients. BMC Cancer. 2008 Mar 25. 8:79. [Medline]. [Full Text].

Liang Y, Bollen AW, Aldape KD, Gupta N. Nuclear FABP7 immunoreactivity is preferentially expressed in infiltrative glioma and is associated with poor prognosis in EGFR-overexpressing glioblastoma. BMC Cancer. 2006 Apr 19. 6:97. [Medline].

Wen PY, Fine HA, Black PM, et al. High-grade astrocytomas. Neurol Clin. 1995 Nov. 13(4):875-900. [Medline].

Wallner KE, Galicich JH, Krol G, et al. Patterns of failure following treatment for glioblastoma multiforme and anaplastic astrocytoma. Int J Radiat Oncol Biol Phys. 1989 Jun. 16(6):1405-9. [Medline].

Westermark B, Nister M. Molecular genetics of human glioma. Curr Opin Oncol. 1995 May. 7(3):220-5. [Medline].

Bruner JM. Neuropathology of malignant gliomas. Semin Oncol. 1994 Apr. 21(2):126-38. [Medline].

Burger PC, Vogel FS, Green SB, Strike TA. Glioblastoma multiforme and anaplastic astrocytoma. Pathologic criteria and prognostic implications. Cancer. 1985 Sep 1. 56(5):1106-11. [Medline].

Byrne TN. Imaging of gliomas. Semin Oncol. 1994 Apr. 21(2):162-71. [Medline].

Clarke J, Butowski N, Chang S. Recent advances in therapy for glioblastoma. Arch Neurol. 2010 Mar. 67(3):279-83. [Medline].

Colombo F, Barzon L, Franchin E, et al. Combined HSV-TK/IL-2 gene therapy in patients with recurrent glioblastoma multiforme: biological and clinical results. Cancer Gene Ther. 2005 Oct. 12(10):835-48. [Medline].

Davis ME, Stoiber AM. Glioblastoma multiforme: enhancing survival and quality of life. Clin J Oncol Nurs. 2011 Jun. 15(3):291-7. [Medline].

Eagan RT, Scott M. Evaluation of prognostic factors in chemotherapy of recurrent brain tumors. J Clin Oncol. 1983 Jan. 1(1):38-44. [Medline].

Gilbert MR, Loghin M. The Treatment of Malignant Gliomas. Curr Treat Options Neurol. 2005 Jul. 7(4):293-303. [Medline].

Green SB, Byar DP, Walker MD, et al. Comparisons of carmustine, procarbazine, and high-dose methylprednisolone as additions to surgery and radiotherapy for the treatment of malignant glioma. Cancer Treat Rep. 1983 Feb. 67(2):121-32. [Medline].

Grossman SA, Ye X, Chamberlain M, et al. Talampanel with standard radiation and temozolomide in patients with newly diagnosed glioblastoma: a multicenter phase II trial. J Clin Oncol. 2009 Sep 1. 27(25):4155-61. [Medline]. [Full Text].

Grossman SA, Ye X, Piantadosi S, et al. Survival of patients with newly diagnosed glioblastoma treated with radiation and temozolomide in research studies in the United States. Clin Cancer Res. 2010 Apr 15. 16(8):2443-9. [Medline]. [Full Text].

Kaye AH, Laws ER Jr. Brain Tumors: An Encyclopedic Approach. New York, NY: Churchill Livingtone; 1995. 449-77.

Kleihus P, Cavenee WK. Pathology and Genetics: Tumors of the Nervous System. Lyon, France: IARC Press; 2000. 56-64.

Lakka SS, Rajan M, Gondi C, et al. Adenovirus-mediated expression of antisense MMP-9 in glioma cells inhibits tumor growth and invasion. Oncogene. 2002 Nov 14. 21(52):8011-9. [Medline].

Leibel SA, Scott CB, Pajak TF. The management of malignant gliomas with radiation therapy: Therapeutic results and research strategies. Semin Radiat Oncol. 1991. 1:32-49.

Loeffler JS, Alexander E, Wen PY, et al. Results of stereotactic brachytherapy used in the initial management of patients with glioblastoma. J Natl Cancer Inst. 1990 Dec 19. 82(24):1918-21. [Medline].

Lu KV, Jong KA, Kim GY, et al. Differential induction of glioblastoma migration and growth by two forms of pleiotrophin. J Biol Chem. 2005 Jul 22. 280(29):26953-64. [Medline].

Macdonald DR. Adjuvant chemotherapy for brain tumor. Semin Radiat Oncol. 1991. 1:54-61.

Pallasch CP, Struss AK, Munnia A, et al. Autoantibodies against GLEA2 and PHF3 in glioblastoma: tumor-associated autoantibodies correlated with prolonged survival. Int J Cancer. 2005 Nov 10. 117(3):456-9. [Medline].

Rich JN, Hans C, Jones B, et al. Gene expression profiling and genetic markers in glioblastoma survival. Cancer Res. 2005 May 15. 65(10):4051-8. [Medline]. [Full Text].

Schold SC, Burger PC, Minna JD, et al. Primary Tumors of the Brain and Spinal Cord. Boston, Mass: Butterworth-Heinemann; 1997. 41-59.

Sipos EP, Brem H. New delivery systems for brain tumor therapy. Neurol Clin. 1995 Nov. 13(4):813-25. [Medline].

Stupp R, Mason WP. Concomitant and adjuvant temozolomide and radiotherapy for newly diagnosed glioblastoma multiforme. Conclusive results of randomized phase III trial by the EORTC brain and RT Groups and NCIC clinical trials group. American Society of Clinical Oncology. 2004. 23(1):

Valk PE, Budinger TF, Levin VA, et al. PET of malignant cerebral tumors after interstitial brachytherapy. Demonstration of metabolic activity and correlation with clinical outcome. J Neurosurg. 1988 Dec. 69(6):830-8. [Medline].

Vile R, Russell SJ. Gene transfer technologies for the gene therapy of cancer. Gene Ther. 1994 Mar. 1(2):88-98. [Medline].

ABM Salah Uddin, MD Private Practice, Norwood Neurology; Consulting Staff, Department of Neurology, St Vincent’s Hospital

ABM Salah Uddin, MD is a member of the following medical societies: American Academy of Neurology, American Epilepsy Society, American Medical Association

Disclosure: Nothing to disclose.

Tambi Jarmi, MD Resident Physician, Department of Internal Medicine, Carraway Methodist Medical Center

Tambi Jarmi, MD is a member of the following medical societies: American College of Physicians, American Medical Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Jorge C Kattah, MD Head, Associate Program Director, Professor, Department of Neurology, University of Illinois College of Medicine at Peoria

Jorge C Kattah, MD is a member of the following medical societies: American Academy of Neurology, American Neurological Association, New York Academy of Sciences

Disclosure: Nothing to disclose.

Stephen A Berman, MD, PhD, MBA Professor of Neurology, University of Central Florida College of Medicine

Stephen A Berman, MD, PhD, MBA is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, Phi Beta Kappa

Disclosure: Nothing to disclose.

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author Subramanian Hariharan, MD, to the development and writing of this article.

Neurologic Manifestations of Glioblastoma Multiforme

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