Neurologic Manifestations of Glioblastoma Multiforme Clinical Presentation

  • Author: ABM Salah Uddin, MD; Chief Editor: Stephen A Berman, MD, PhD, MBA   more...
 
Updated: Apr 19, 2010
 

History

Glioblastoma multiforme (GBM), like other brain tumors, produces symptoms by a combination of focal neurologic deficits from compression and infiltration of the surrounding brain, vascular compromise, and raised intracranial pressure. Presenting features include the following:

  • Headaches (30-50%)
    • Headaches are nonspecific and indistinguishable from tension headache.
    • As the tumor enlarges, it may have features of increased intracranial pressure.
  • Seizures (30-60%): Depending on the tumor location, seizures may be simple partial, complex partial, or generalized.
  • Focal neurologic deficits (40-60%): As some patients with GBM survive longer, an increasing number of patients experience cognitive problems, neurologic deficits resulting from radiation necrosis, communicating hydrocephalus, and occasionally cranial neuropathies and polyradiculopathies from leptomeningeal spread.
  • Mental status changes (20-40%): With the advent of MRI, GBMs are increasingly diagnosed at an earlier stage and with subtle personality changes.
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Physical

Physical findings depend on the location, size, and rate of growth of the tumor, as with any other CNS tumor. Tumors in less critical areas (eg, anterior frontal or temporal lobe) may present with subtle personality changes and memory problems. Similarly, motor weakness and sensory hemineglect are the hallmarks of tumors arising in the frontal or parietal lobes and thalamic regions. Sensory neglect is more prominent in right hemispheric lesions.

  • Seizures are a common presentation of small tumors in the frontoparietal regions (simple motor or sensory partial seizure) and temporal lobe (simple or complex partial seizure).
  • Occipital lobe tumors may present with visual field defects. Although these tumors are less frequent than tumors originating at other sites, patients generally are unaware of the slow onset of a cortically based hemianopsia.
  • Brainstem GBMs are rare in adults. However, they may present with bilateral crossed neurological deficits (eg, weakness on one side with contralateral cranial nerve palsy). Alternatively, they may present with rapidly progressive headache or altered consciousness.
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Causes

The etiology of GBM is unknown. However, at least 2 genetic pathways have been delineated in its development: de novo (primary) glioblastomas and secondary glioblastomas. De novo glioblastomas are most common. De novo GBM develops in older patients and demonstrates a high rate of epidermal growth factor receptor (EGFR) overexpression, phosphatase and tensin homologue deleted on chromosome 10 (PTEN) mutations, and p16INK4A deletions. In contrast, secondary GBM develops in younger patients and develops from a malignant transformation of a previously diagnosed low-grade tumor. TP53 and retinoblastoma gene (RB) mutations are more common in the development of secondary glioblastomas.

Several genetic disorders are associated with increased incidence of gliomas (eg, tuberous sclerosis, neurofibromatosis type 1 and type 2, Turcot syndrome, Li-Fraumeni syndrome). An association exists between ionizing radiation and astrocytomas. Children who receive low-dose intracranial radiation have a 2.6-fold increase in prevalence of astrocytomas, and prophylactic whole-brain radiation therapy in patients with acute lymphocytic leukemia increased the incidence of astrocytomas 22-fold.

Other suspected risk factors, such as electromagnetic radiation and cellular telephone use, are yet to be substantiated by large epidemiologic studies. However, researchers reviewed 16 published studies that looked at cell phone use and the risk of brain cancers and concluded that using cell phones for more than 10 years gives a consistent pattern of increased risk of at least 2 types of brain cancer such as acoustic neuroma and gliomas. The risk is significantly higher for the ipsilateral exposure (tumor on the same side of the brain as cell phone exposure).[5]

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Contributor Information and Disclosures
Author

ABM Salah Uddin, MD  Consulting Staff, Department of Internal Medicine, St Vincent's Hospital

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

Disclosure: Nothing to disclose.

Coauthor(s)

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 and American Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Amy A Pruitt, MD  Associate Professor of Neurology, University of Pennsylvania; Attending Neurologist, Hospital of the University of Pennsylvania

Amy A Pruitt, MD is a member of the following medical societies: American Academy of Neurology

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Senior Pharmacy Editor, eMedicine

Disclosure: eMedicine Salary Employment

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

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

Disclosure: Biogen Honoraria Consulting; Bayer Corporation Honoraria Consulting

Selim R Benbadis, MD  Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital

Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association

Disclosure: UCB Pharma Honoraria Speaking, consulting; Lundbeck Honoraria Speaking, consulting; Cyberonics Honoraria Speaking, consulting; Glaxo Smith Kline Honoraria Speaking, consulting; Pfizer Honoraria Speaking, consulting; Sleepmed/DigiTrace Honoraria Speaking, consulting

Chief Editor

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, and Phi Beta Kappa

Disclosure: Nothing to disclose.

References
  1. Seiz M, Nolte I, Pechlivanis I, Freyschlag CF, Schmieder K, Vajkoczy P, et al. Far-distant metastases along the CSF pathway of glioblastoma multiforme during continuous low-dose chemotherapy with temozolomide and celecoxib. Neurosurg Rev. Mar 2010;Epub.

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

  3. 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.

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

  5. Hardell L, Carlberg M, Söderqvist 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. Sep 2007;64(9):626-32. [Medline].

  6. 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.

  7. Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, 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. May 2009;10(5):459-66. [Medline].

  8. Hatanaka H. Analysis of clinical results of long surviving brain tumor patients who underwent Boron-neutron-capture therapy with mercapto undeca hydrocarborate. Acapulco Mexico: Abs; X international congress of Neurosurgery; 1993, pp199.

  9. 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. Apr 2003;5(2):79-88. [Medline].

  10. 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. Feb 2008;108(2):236-42. [Medline].

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

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

  13. Perry JR, Bélanger K, Mason WP, Fulton D, Kavan P, Easaw J, et al. Phase II Trial of Continuous Dose-Intense Temozolomide in Recurrent Malignant Glioma: RESCUE Study. J Clin Oncol. Mar 22 2010;[Medline].

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

  15. Krex D, Klink B, Hartmann C, von Deimling A, Pietsch T, Simon M, et al. Long-term survival with glioblastoma multiforme. Brain. Oct 2007;130:2596-606. [Medline].

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

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

  18. 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;6:97. [Medline].

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

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

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

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

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

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

  25. 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. Oct 2005;12(10):835-48. [Medline].

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

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

  28. 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. Feb 1983;67(2):121-32. [Medline].

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

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

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

  32. 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.

  33. 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. Dec 19 1990;82(24):1918-21. [Medline].

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

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

  36. 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. Nov 10 2005;117(3):456-9. [Medline].

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

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

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

  40. 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.

  41. 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. Dec 1988;69(6):830-8. [Medline].

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

  43. 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. Jun 1989;16(6):1405-9. [Medline].

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

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

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T1-weighted axial gadolinium-enhanced MRI demonstrates an enhancing tumor of the right frontal lobe. Image courtesy of George Jallo, MD.
T2-weighted image demonstrates notable edema and midline shift. This finding is consistent with a high grade or malignant tumor. Image courtesy of George Jallo, MD.
Histopathologic slide demonstrating a glioblastoma multiforme.
Magnetic resonance spectroscopy is representative of a glioblastoma multiforme.
 
 
 
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