Current Oncology Reports

, Volume 12, Issue 1, pp 50–59 | Cite as

Neurologic Complications of Cancer and its Treatment

  • Pierre Giglio
  • Mark R. Gilbert


The central nervous system (CNS) and peripheral nervous system (PNS) are very susceptible to cancer and its treatment. The most direct involvement of the nervous system manifests in the development of primary brain and spinal cord tumors. Many cancers exhibit a propensity toward spread to the CNS, and brain metastases are common problems seen in malignancies such as lung, breast, and melanoma. Such spread may involve the brain or spine parenchyma or the subarachnoid space. In the PNS, spread is usually through direct infiltration of nerve roots, plexi, or muscle by neighboring malignancies. In some cases, cancer has sudden, devastating effects on the nervous system: epidural spinal cord compression or cord transection from pathologic fractures of vertebra involved by cancer; increased intracranial pressure from intracranial mass lesion growth and edema; and uncontrolled seizure activity as a result of intracranial tumors (status epilepticus), which are neuro-oncologic emergencies. The best known indirect or remote effects of cancer on the nervous system are the neurologic paraneoplastic syndromes. Cancer can also result in a hypercoagulable state causing cerebrovascular complications. Treatment of cancer can have neurologic complications. The commonest of these complications are radiation-induced injury to the brain, spine, and peripheral nerves and chemotherapy-induced peripheral neuropathy. The suppressant effect of cancer and its treatment on the body’s immune system can result in infectious complications within the nervous system.


Cancer Nervous system complications Metastases 



No potential conflict of interest relevant to this article was reported.


Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    National Cancer Institute: Surveillance Epidemiology and End Results. Available at Accessed September 2009.
  2. 2.
    Clouston PD, DeAngelis LM, Posner JB: The spectrum of neurologic disease in patients with systemic cancer. Ann Neurol 1992, 31:268–273.CrossRefPubMedGoogle Scholar
  3. 3.
    Gavrilovic IT, Posner J: Brain metastases: epidemiology and pathophysiology. J Neuroncol 2005, 75:5–14.CrossRefGoogle Scholar
  4. 4.
    Tremont-Lukats IW, Bobustuc G, Lagos GK, et al.: Brain metastases from prostate carcinoma: The M.D. Anderson Cancer experience. Cancer 2003, 15:363–368.Google Scholar
  5. 5.
    Posner JB, Chernik NL: Intracranial metastases from systemic cancer. Adv Neurol 1978, 19:575–587.Google Scholar
  6. 6.
    Delattre JY, Krol G, Thaler HT, et al.: Distribution of brain metastases. Arch Neurol 1988, 45:741–744.PubMedGoogle Scholar
  7. 7.
    Borgelt B, Gelber R, Kramer S, et al.: The palliation of brain metastases: final results of the first two studies by the Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys 1980, 6:1–9.PubMedGoogle Scholar
  8. 8.
    Gaspar L, Scott C, Rotman M, et al.: Recursive partioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group brain metastases trials. Int J Radiat Oncol Biol Phys 1997, 37:745.PubMedGoogle Scholar
  9. 9.
    • Chang EL, Wefel JS, Hess KR, et al.: Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole brain irradiation: a randomized controlled trial. Lancet Oncol 2009, 10:1037–1044. In this very well-designed trial, the neurocognitive impairment from WBRT was so significant that the study was terminated prematurely.CrossRefPubMedGoogle Scholar
  10. 10.
    Posner JB, Chernik NL: Intracranial metastases from systemic cancer. Adv Neurol 1978, 19:579-592.PubMedGoogle Scholar
  11. 11.
    Wasserstrom WR, Glass JP, Posner JB: Diagnosis and treatment of leptomeningeal metastases from solid tumors: experience with 90 patients. Cancer 1982, 49:759–772.CrossRefPubMedGoogle Scholar
  12. 12.
    Kaplan JG, DeSouza TG, Farkash A, et al.: Leptomeningeal metastases: comparison of clinical features and laboratory data of solid tumors, lymphomas and leukemias. J Neurooncol 1990, 9:225–229.CrossRefPubMedGoogle Scholar
  13. 13.
    Little JR, Dale AJ, Okazaki H: Meningeal carcinomatosis. Clinical manifestations. Arch Neurol 1974, 30:138–143.Google Scholar
  14. 14.
    Ersboll J, Schultz HB, Thomsen BL, et al.: Meningeal involvement in non-Hodgkin’s lymphoma: symptoms, incidence, risk factors and treatment. Scand J Haematol 1985, 35:487–496.PubMedGoogle Scholar
  15. 15.
    Chamberlain MC: Carcinomatous meningitis. Arch Neurol 1997, 54:16–17.PubMedGoogle Scholar
  16. 16.
    • Chamberlain MC: Neoplastic meningitis. Oncologist 2008, 13:967–977. This article offers a recent comprehensive review on the subject of neoplastic meningitis. CrossRefPubMedGoogle Scholar
  17. 17.
    Rhodes CH, Glantz MJ, Glantz L, et al.: A comparison of polymerase chain reaction examination of cerebrospinal fluid and conventional cytology in the diagnosis of lymphomatous meningitis. Cancer 1996, 77:543–548.CrossRefPubMedGoogle Scholar
  18. 18.
    Chamberlain MC, Glantz M, Groves MD, Wilson WH: Diagnostic tools for neoplastic meningitis: detecting disease, identifying patient risk, and determining benefit of treatment. Semin Oncol 2009, 36:S35–S45.CrossRefPubMedGoogle Scholar
  19. 19.
    Chamberlain MC: Radioisotope CSF flow studies in leptomeningeal metastases. J Neurooncol 1998, 38:135–140.CrossRefPubMedGoogle Scholar
  20. 20.
    Glantz MJ, Hall WA, Cole BF, et al.: Diagnosis, management, and survival of patients with leptomeningeal cancer based on cerebrospinal fluid-flow status. Cancer 1995, 75:2919–2931.CrossRefPubMedGoogle Scholar
  21. 21.
    Chamberlain MC, Corey-Bloom J: Leptomeningeal metastases: 111indium-DTPA CSF flow studies. Neurology 1991, 41:1765–1769.PubMedGoogle Scholar
  22. 22.
    Chamberlain MC, Kormanik P, Jaeckle KA, et al. 111Indium-diethylenetriamine pentaacetic acid CSF flow studies predict distribution of intrathecally administered chemotherapy and outcome in patients with leptomeningeal metastases. Neurology 1999, 52:216–217.PubMedGoogle Scholar
  23. 23.
    Glantz MJ, LaFollette S, Jaeckle KA, et al.: Randomized trial of a slow-release versus a standard formulation of cytarabine for the intrathecal treatment of lymphomatous meningitis. J Clin Oncol 1999, 17:3110–3116.PubMedGoogle Scholar
  24. 24.
    Jaeckle KA, Batchelor T, O’Day SJ, et al.: An open trial of sustained-release cytarabine (DepoCyt) for the intrathecal treatment of solid tumor neoplastic meningitis. J Neurooncol 2002, 57:231–239.CrossRefPubMedGoogle Scholar
  25. 25.
    Tubian-Hulin M: Incidence, prevalence and distribution of bone metastases. Bone 1991, 12 (Suppl 1):9–10.CrossRefGoogle Scholar
  26. 26.
    Goetz CG: Direct metastatic disease. In Textbook of Clinical Neurology, edn 2. Philadelphia: WB Saunders; 2003:1042–1051.Google Scholar
  27. 27.
    Chamberlain MC, Kormanik PA: Epidural spinal cord compression: a single institution’s retrospective experience. Neuro Oncol 1999, 1:120–123.CrossRefPubMedGoogle Scholar
  28. 28.
    Jaeckle KA, Young DF, Foley KM: The natural history of lumbosacral plexopathy in cancer. Neurology 1985, 35:8–15.PubMedGoogle Scholar
  29. 29.
    Jaeckle KA: Nerve plexus metastases. Neurol Clin 1991, 9:857–866.PubMedGoogle Scholar
  30. 30.
    Brazis PW, Masdeu JC, Biller J: Cervical, brachial and lumbosacral plexuses. In Localization in Clinical Neurology. Edited by Brazis PW, Masdeu JC, Biller J. Philadelphia: Lippincott Williams & Wilkins; 2001:75–90.Google Scholar
  31. 31.
    Biasotto M: Numb chin syndrome as the presenting symptom in carcinomatous meningitis. Ann Oncol 2008, 19:599–601.CrossRefPubMedGoogle Scholar
  32. 32.
    Pourmand R: Lambert-eaton myasthenic syndrome. Front Neurol Neurosci 2009, 26:120–125.CrossRefGoogle Scholar
  33. 33.
    Dalmau J, Rosenfeld MR: Paraneoplastic syndromes of the CNS. Lancet Neurol 2008, 7:327–340. This article provides a very detailed comprehensive review on the subject with excellent discussion of pathophysiology. CrossRefPubMedGoogle Scholar
  34. 34.
    Dalmau J: Limbic encephalitis and variants related to neuronal cell membrane autoantigens. Rinsho Shinkeigaku 2008, 48:871–874.PubMedGoogle Scholar
  35. 35.
    Rosenfeld MR, Dalmau J: Paraneoplastic syndromes of the nervous system. In Cancer Neurology in Clinical Practice. Edited by Schiff D, Kesari S, Wen PY. New Jersey: Humana Press; 2008:237–255.Google Scholar
  36. 36.
    • Rogers LR: Management of stroke in cancer. Curr Oncol Rep2008, 10:72–77. This article provides an excellent recent review in an area of neuro-oncology that is lacking strong data, especially in terms of management recommendations.CrossRefPubMedGoogle Scholar
  37. 37.
    Graus F, Rogers LR, Posner JB: Cerebrovascular complications in patients with cancer. Medicine (Baltimore) 1985, 64:16–35.Google Scholar
  38. 38.
    Navi BB, Kawaguchi K, Hriljac I, et al.: Multifocal stroke from tumor emboli. Arch Neurol 2009, 66:1174–1175.CrossRefPubMedGoogle Scholar
  39. 39.
    Razier JJ, DeAngelis L: Cerebral sinus thrombosis diagnosed by MRI and MR venography in cancer patients. Neurology 2000, 54:1222–1226.Google Scholar
  40. 40.
    Giglio P, Gilbert MR: Cerebral radiation necrosis. Neurologist 2003, 9:180–188.Google Scholar
  41. 41.
    DeAngelis LM, Delattre YP, Posner JB: Radiation-induced dementia in patients cured of brain metastases. Neurology 1989, 39:789–796.PubMedGoogle Scholar
  42. 42.
    Chi D, Behin A, Delattre J-Y: Neurologic complications of radiation therapy. In Cancer Neurology in Clinical Practice. Edited by Schiff D, Kesari S, Wen PY. New Jersey: Humana Press; 2008:259–286.Google Scholar
  43. 43.
    Meyers CA, Weitzner MA, Valentine AD, et al.: Methylphenidate therapy improves cognition, mood, and function of brain tumor patients. J Clin Oncol 1998, 16:2522–2527.PubMedGoogle Scholar
  44. 44.
    Leung WM, Tsang NM, Chang FT, et al.: Lhermitte’s sign among nasopharyngeal cancer patients after radiotherapy. Head Neck 2005, 27:187–194.CrossRefPubMedGoogle Scholar
  45. 45.
    Uchida K, Nakajima H, Takamura T, et al.: Neurological improvement associated with resolution of irradiation-induced myelopathy: serial magnetic resonance imaging and positron emission tomography findings. J Neuroimaging 2009,19:274–276.CrossRefPubMedGoogle Scholar
  46. 46.
    Thyagarajan D, Cascino T, Harms G: Magnetic resonance imaging in brachial plexopathy of cancer. Neurology 1995, 45:421–427.PubMedGoogle Scholar
  47. 47.
    Wittenberg KH, AdkinsMC: MR imaging of nontraumatic brachial plexopathies: frequency and spectrum of findings. Radiographics 2000, 20:1023–1032.PubMedGoogle Scholar
  48. 48.
    • Bowen BC, Seidenwurm DJ: Plexopathy. AJNR 2008, 29:400–402. This article provides expert consensus guidelines for neuroimaging in plexopathy.PubMedGoogle Scholar
  49. 49.
    Bowen BC, Verma A, Brandon AH, et al.: Radiation-induced brachial plexopathy: MR and clinical findings. Am J Neuroradiol 1996, 17:1932–1936.PubMedGoogle Scholar
  50. 50.
    Wouter van Es H, Engelen AM, Witkamp TD, et al.: Radiation-induced brachial plexopathy: MR imaging. Skeletal Radiol 1997, 26:284–288.Google Scholar
  51. 51.
    Wolf S, Barton D, Kottschade L, et al.: Chemotherapy-induced peripheral neuropathy: prevention and treatment strategies. Eur J Cancer 2008, 44:1507–1515.CrossRefPubMedGoogle Scholar
  52. 52.
    • Schiff D, Wen PY, van den Bent MJ: Neurological adverse effects caused by cytotoxic and targeted therapies. Nat Rev Clin Oncol 2009, 6:596–603. This article provides a very recent review of neurotoxicity caused by targeted and newer therapies. CrossRefPubMedGoogle Scholar
  53. 53.
    Harati Y, Bosch EP: Disorders of peripheral nerves. In Neurology in Clinical Practice. Edited by Bradley WG, Daroff RB, Fenichel GM, Jankovic J. Philadelphia: Butterworth-Heinemann; 2008:2249–2356.Google Scholar
  54. 54.
    Siegal D, Keller A, Xu W, et al.: Central nervous system complications after allogeneic hematopoietic stem cell transplantation: incidence, manifestations, and clinical significance. Biol Blood Marrow Transplant 2007, 13:1369–1379.CrossRefPubMedGoogle Scholar
  55. 55.
    Chan KW, Mullen CA, Worth LL, et al.: Lorazepam for seizure prophylaxis during high-dose busulfan administration. Bone Marrow Transplant 2002, 29:963–965.CrossRefPubMedGoogle Scholar
  56. 56.
    Sioka C, Kyritsis AP: Central and peripheral nervous system toxicity of common chemotherapeutic agents. Cancer Chemother Pharmacol 2009, 63:761–767.CrossRefPubMedGoogle Scholar

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© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of NeurosciencesMedical University of South CarolinaCharlestonUSA
  2. 2.Department of Neuro-oncologyM. D. Anderson Cancer CenterHoustonUSA

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