Clinical Concepts of Brain Tumors

  • Carlotta Chiavazza
  • Federica Franchino
  • Roberta Rudà


Neurological symptoms and signs of brain tumors are not specifically tied to individual specific tumor types, but rather to location within the central nervous system (CNS). Tumor can damage neural tissue by infiltration or displace by compression, leading to focal symptoms. Direct invasion from a tumor typically occurs in gliomas, whereas meningiomas displace normal brain. The disruption of the blood–brain barrier by the tumor leads to vasogenic edema that is one of the main causes of neurological impairment: edema favors an increase of mass effect and thus a further compression of the surrounding brain [1].


  1. 1.
    Alentorn A, Hoang-Xuan K, Mikkelsen T. Presenting signs and symptoms in brain tumors. Handb Clin Neurol. 2016;134:19–26.PubMedGoogle Scholar
  2. 2.
    Posner JB, Saper CB, Schiff N, et al. Plum and Posner’s diagnosis of stupor and coma. Oxford: Oxford University Press; 2007.Google Scholar
  3. 3.
    Reddy GK, Bollam P, Caldito G, Willis B, Guthikonda B, Nanda A. Ventriculoperitoneal shunt complications in hydrocephalus patients with intracranial tumors: an analysis of relevant risk factors. J Neurooncol. 2011;103(2):333–42.PubMedGoogle Scholar
  4. 4.
    Malamud N. Psychiatric disorder with intracranial tumors of limbic system. Arch Neurol. 1967;17(2):113–23.PubMedGoogle Scholar
  5. 5.
    Weitzner MA. Psychosocial and neuropsychiatric aspects of patients with primary brain tumors. Cancer Invest. 1999;17(4):285–91.PubMedGoogle Scholar
  6. 6.
    Forsyth PA, Posner JB. Headaches in patients with brain tumors: a study of 111 patients. Neurology. 1993;43(9):1678–83.PubMedGoogle Scholar
  7. 7.
    Vázquez-Barquero A, Ibáñez FJ, Herrera S, Izquierdo JM, Berciano J, Pascual J. Isolated headache as the presenting clinical manifestation of intracranial tumors: a prospective study. Cephalalgia. 1994;14(4):270–2.PubMedGoogle Scholar
  8. 8.
    Schaefer PW, Miller JC, Singhal AB, Thrall JH, Lee SI. Headache: when is neurologic imaging indicated? J Am Coll Radiol. 2007;4(8):566–9.PubMedGoogle Scholar
  9. 9.
    Chen C, Yen DJ, Yiu CH, Shih YH, Yu HY, Su MS. Ictal vomiting in partial seizures of temporal lobe origin. Eur Neurol. 1999;42(4):235–9.PubMedGoogle Scholar
  10. 10.
    Biller J, Brazis PW, Masdeu JC. Localization in clinical neurology. Philadelphia: Wolters Kluwer Health; 2011.Google Scholar
  11. 11.
    Raelson C, Chiang G. Chiasmatic-hypothalamic masses in adults: a case series and review of the literature. J Neuroimaging. 2015;25(3):361–4.PubMedGoogle Scholar
  12. 12.
    Sathananthan M, Sathananthan A, Scheithauer BW, Giannini C, Meyer FB, Atkinson JL, Erickson D. Sellar meningiomas: an endocrinologic perspective. Pituitary. 2013;16(2):182–8.PubMedGoogle Scholar
  13. 13.
    Soffietti R, Ducati A, Rudà R. Brain metastases. Handb Clin Neurol. 2012;105:747–55.PubMedGoogle Scholar
  14. 14.
    Politsky JM. Brain tumor-related epilepsy: a current review of the etiologic basis and diagnostic and treatment approaches. Curr Neurol Neurosci Rep. 2017;17(9):70.PubMedGoogle Scholar
  15. 15.
    Banerjee PN, Filippi D, Allen Hauser W. The descriptive epidemiology of epilepsy-a review. Epilepsy Res. 2009;85(1):31–45.PubMedPubMedCentralGoogle Scholar
  16. 16.
    Rudà R, Bello L, Duffau H, Soffietti R. Seizures in low-grade gliomas: natural history, pathogenesis, and outcome after treatments. Neuro Oncol. 2012;14(Suppl 4):iv55–64.PubMedPubMedCentralGoogle Scholar
  17. 17.
    Shady JA, Black PM, Kupsky WJ, Tarbell NJ, Scott RM, Leong T, Holmes G. Seizures in children with supratentorial astroglial neoplasms. Pediatr Neurosurg. 1994;21(1):23–30.PubMedGoogle Scholar
  18. 18.
    Shamji MF, Fric-Shamji EC, Benoit BG. Brain tumors and epilepsy: pathophysiology of peritumoral changes. Neurosurg Rev. 2009;32(3):275–84. discussion 284–6.PubMedGoogle Scholar
  19. 19.
    Rudà R, Soffietti R. What is new in the management of epilepsy in gliomas? Curr Treat Options Neurol. 2015;17(6):351.PubMedGoogle Scholar
  20. 20.
    Wolf H, Roos D, Blumcke I, Pietsch T, Wiestler O. Perilesional neurochemical changes in focal epilepsies. Acta Neuropathol. 1996;91:376–84.PubMedGoogle Scholar
  21. 21.
    Kohling R, Senner V, Paulus W, Speckmann E. Epileptiform activity preferentially arises outside tumor invasion zone in glioma xeno-transplants. Neurobiol Dis. 2006;22:64–75.PubMedGoogle Scholar
  22. 22.
    Yuen T, Morokoff A, Bjorksten A, D’Abaco G, Paradiso L, Finch S, et al. Glutamate is associated with a higher risk of seizures in patients with gliomas. Neurology. 2012;79:883–9.PubMedGoogle Scholar
  23. 23.
    Glauser T, Ben-Menachem E, Bourgeois B, Cnaan A, Guerreiro C, Kälviäinen R, ILAE Subcommission on AED Guidelines, et al. Updated ILAE evidence review of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes. Epilepsia. 2013;54(3):551–63.PubMedGoogle Scholar
  24. 24.
    Kerrigan S, Grant R. Antiepileptic drugs for treating seizures in adults with brain tumours. Cochrane Database Syst Rev. 2011;8:CD008586.Google Scholar
  25. 25.
    Vecht CJ, Kerkhof M, Duran-Pena A. Seizure prognosis in brain tumors: new insights and evidence-based management. Oncologist. 2014;19:751–9.PubMedPubMedCentralGoogle Scholar
  26. 26.
    Kerkhof M, Dielemans JC, van Breemen MS, et al. Effect of valproic acid on seizure control and on survival in patients with glioblastoma multiforme. Neuro-Oncology. 2013;15:961–7.PubMedPubMedCentralGoogle Scholar
  27. 27.
    Rudà R, Pellerino A, Franchino F, Bertolotti C, Bruno F, Mo F, Migliore E, Ciccone G, Soffietti R. Lacosamide in patients with gliomas and uncontrolled seizures: results from an observational study. J Neuro-Oncol. 2018;136(1):105–14.Google Scholar
  28. 28.
    Lacy J, Saadati H, Yu JB. Complications of brain tumors and their treatment. Hematol Oncol Clin North Am. 2012;26(4):779–96.PubMedGoogle Scholar
  29. 29.
    Bourdillon P, Apra C, Guenot M, Duffau H. Similarity and differences in neuroplasticity mechanisms between brain gliomas and nonlesional epilepsy. Epilepsia. 2017;58(12):2038–47.PubMedGoogle Scholar
  30. 30.
    Duffau H. Brain mapping in tumors: intraoperative or extraoperative. Epilepsia. 2013;54(Suppl 9):79–83.PubMedGoogle Scholar
  31. 31.
    Duffau H. The challenge to remove diffuse low grade gliomas while preserving brain functions. Acta Neurochir. 2012;154:569–74.PubMedGoogle Scholar
  32. 32.
    Rudà R, Trevisan E, Soffietti R. Epilepsy and brain tumors. Curr Opin Oncol. 2010;22(6):611–20.PubMedGoogle Scholar
  33. 33.
    Roelcke U, Wyss MT, Nowosielski M, Rudà R, Roth P, Hofer S, Galldiks N, Crippa F, Weller M, Soffietti R. Amino acid positron emission tomography to monitor chemotherapy response and predict seizure control and progression-free survival in WHO grade II gliomas. Neuro Oncol. 2016;18(5):744–51.PubMedGoogle Scholar
  34. 34.
    Rudà R, Magliola U, Bertero L, Trevisan E, Bosa C, Mantovani C, Ricardi U, Castiglione A, Monagheddu C, Soffietti R. Seizure control following radiotherapy in patients with diffuse gliomas: a retrospective study. Neuro Oncol. 2013;15(12):1739–49.PubMedPubMedCentralGoogle Scholar
  35. 35.
    Avila EK, Chamberlain M, Schiff D, Reijneveld JC, Armstrong TS, Ruda R, Wen PY, Weller M, Koekkoek JA, Mittal S, Arakawa Y, Choucair A, Gonzalez-Martinez J, MacDonald DR, Nishikawa R, Shah A, Vecht CJ, Warren P, van den Bent MJ, DeAngelis LM. Seizure control as a new metric in assessing efficacy of tumor treatment in low-grade glioma trials. Neuro Oncol. 2017;19(1):12–21.PubMedGoogle Scholar
  36. 36.
    Mohile NA. Medical complications of brain tumors. Continuum (Minneap Minn). 2017;23(6, Neuro-oncology):1635–52.Google Scholar
  37. 37.
    Machein MR, Kullmer J, Fiebich BL, et al. Vascular endothelial growth factor expression, vascular volume, and, capillary permeability in human brain tumors. Neurosurgery. 1999;44(4):732Y740. discussion 740Y741.Google Scholar
  38. 38.
    Gerstner ER, Duda DG, di Tomaso E, et al. VEGF inhibitors in the treatment of cerebral edema in patients with brain cancer. Nat Rev Clin Oncol. 2009;6(4):229Y236.Google Scholar
  39. 39.
    Schiff D. Pneumocystis pneumonia in brain tumor patients: risk factors and clinical features. J Neurooncol. 1996;27(3):235Y240.Google Scholar
  40. 40.
    Leuthardt EC, Wippold FJ 2nd, Oswood MC, Rich KM. Diffusion-weighted MR imaging in the preoperative assessment of brain abscesses. Surg Neurol. 2002;58(6):395–402.PubMedGoogle Scholar
  41. 41.
    Streiff MB, Ye X, Kickler TS, et al. A prospective multicenter study of venous thromboembolism in patients with newly-diagnosed high-grade glioma: hazard rate and risk factors. J Neurooncol. 2015;124(2):299–305.PubMedPubMedCentralGoogle Scholar
  42. 42.
    Alshehri N, Cote DJ, Hulou MM, et al. Venous thromboembolism prophylaxis in brain tumor patients undergoing craniotomy: a meta-analysis. J Neurooncol. 2016;130(3):561–70.PubMedGoogle Scholar
  43. 43.
    Gerber DE, Grossman SA, Streiff MB. Management of venous thromboembolism in patients with primary and metastatic brain tumors. J Clin Oncol. 2006;24(8):1310–8.PubMedGoogle Scholar
  44. 44.
    Lee AY, Levine MN, Baker RI, et al. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med. 2003;349(2):146–53.PubMedGoogle Scholar
  45. 45.
    Levin JM, Schiff D, Loeffler JS, et al. Complications of therapy for venous thromboembolic disease in patients with brain tumors. Neurology. 1993;43(6):1111–4.PubMedGoogle Scholar
  46. 46.
    Gilbert MR, Dignam JJ, Armstrong TS, et al. A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med. 2014;370(8):699–708.PubMedPubMedCentralGoogle Scholar
  47. 47.
    Kreisl TN, Toothaker T, Karimi S, DeAngelis LM. Ischemic stroke in patients with primary brain tumors. Neurology. 2008;70(24):2314–20.PubMedGoogle Scholar
  48. 48.
    Roongpiboonsopit D, Kuijf HJ, Charidimou A, et al. Evolution of cerebral microbleeds after cranial irradiation in medulloblastoma patients. Neurology. 2017;88(8):789–96.PubMedPubMedCentralGoogle Scholar
  49. 49.
    Roddy E, Sear K, Felton E, et al. Presence of cerebral microbleeds is associated with worse executive function in pediatric brain tumor survivors. Neuro Oncol. 2016;18(11):1548–58.PubMedPubMedCentralGoogle Scholar
  50. 50.
    McGirt MJ, Chaichana KL, Gathinji M, et al. Persistent outpatient hyperglycemia is independently associated with decreased survival after primary resection of malignant brain astrocytomas. Neurosurgery. 2008;63(2):286–91.PubMedGoogle Scholar
  51. 51.
    Sathyapalan T, Dixit S. Radiotherapy-induced hypopituitarism: a review. Expert Rev Anticancer Ther. 2012;12(5):669–83.PubMedGoogle Scholar
  52. 52.
    Pietilä S, Mäkipernaa A, Koivisto AM, Lenko HL. Growth impairment and gonadal axis abnormalities are common in survivors of paediatric brain tumours. Acta Paediatr. 2017;106(10):1684–93.PubMedGoogle Scholar
  53. 53.
    Rooney AG, Carson A, Grant R. Depression in cerebral glioma patients: a systematic review of observational studies. J Natl Cancer Inst. 2011;103(1):61–76.PubMedGoogle Scholar
  54. 54.
    Douw L, Klein M, Fagel SS, et al. Cognitive and radiological effects of radiotherapy in patients with low-grade glioma: long-term follow-up. Lancet Neurol. 2009;8(9):810–8.PubMedGoogle Scholar
  55. 55.
    Kaiser J, Bledowski C, Dietrich J. Neural correlates of chemotherapy-related cognitive impairment. Cortex. 2014;54:33–50.PubMedGoogle Scholar
  56. 56.
    Young JS, Chmura SJ, Wainwright DA, Yamini B, Peters KB, Lukas RV. Management of glioblastoma in elderly patients. J Neurol Sci. 2017;380:250–5.PubMedGoogle Scholar
  57. 57.
    de Moraes FY, Laperriere N. Glioblastoma in the elderly: initial management. Chin Clin Oncol. 2017;6(4):39.PubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Carlotta Chiavazza
    • 1
  • Federica Franchino
    • 1
  • Roberta Rudà
    • 1
  1. 1.Department of Neuro-OncologyUniversity and City of Health and Science HospitalTurinItaly

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