Skip to main content

Cerebrovascular Complications in Patients with Cancer

  • Chapter
  • First Online:
Central Nervous System Metastases
  • 638 Accesses

Abstract

The hypercoagulable state associated with cancer, known since the descriptions of Trousseau in the nineteenth century, has become a well-recognized cause of venous thromboembolism. It has only more recently become apparent that cancer increases the risk of arterial thromboembolism as well. In patients with cancer, cerebrovascular disease is the second leading cause of lesions of the central nervous system (CNS), only behind metastases (Graus F, Rogers LR, Posner, JB, Medicine 64:16–35, 1985). The most frequent cause of cerebrovascular disease in this population is stroke, both ischemic and hemorrhagic; this chapter will focus primarily on these entities. While patients with cancer remain at risk for conventional mechanisms of cerebrovascular disease, cancer patients have unique risk factors including complications of coagulation disorders, direct tumor effects, toxicity of cancer treatment, and increased risk of infection in the setting of immunosuppression. These features make this population distinct from the general population and should be considered carefully during their evaluation and care.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Graus F, Rogers LR, Posner JB. Cerebrovascular complications in patients with cancer. Medicine. 1985;64:16–35.

    Article  CAS  PubMed  Google Scholar 

  2. Noone AM, Howlader N, Krapcho M, Miller D, Brest A, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA, editors. SEER cancer statistics review, 1975–2015. Bethesda: National Cancer Institute; 2018.. https://seer.cancer.gov/csr/1975_2015/. Based on November 2017 SEER data submission, posted to the SEER web site, April 2018

    Google Scholar 

  3. Zoller B, Ji J, Sundquist J, Sundquist K. Risk of haemorrhagic and ischaemic stroke in patients with cancer: a nationwide follow-up study from Sweden. Eur J Cancer. 2012;48:1875–83.

    Article  PubMed  Google Scholar 

  4. Navi BB, Reiner AS, Kamel H, et al. Association between incident cancer and subsequent stroke. Ann Neurol. 2015;77:291–300.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Navi BB, Reiner AS, Kamel H, et al. Risk of arterial thromboembolism in patients with cancer. J Am Coll Cardiol. 2017;70:926–38.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Sanossian N, Djabiras C, Mack WJ, Ovbiagele B. Trends in cancer diagnoses among inpatients hospitalized with stroke. J Stroke Cerebrovasc Dis. 2013;22:1146–50.

    Article  PubMed  Google Scholar 

  7. Uemura J, Kimura K, Sibazaki K, Inoue T, Iguchi Y, Yamashita S. Acute stroke patients have occult malignancy more often than expected. Eur Neurol. 2010;64:140–4.

    Article  PubMed  Google Scholar 

  8. Cocho D, Gendre J, Boltes A, et al. Predictors of occult cancer in acute ischemic stroke patients. J Stroke Cerebrovasc Dis. 2015;24:1324–8.

    Article  PubMed  Google Scholar 

  9. Selvik HA, Thomassen L, Bjerkreim AT, Naess H. Cancer-associated stroke: the Bergen NORSTROKE Study. Cerebrovasc Dis Extra. 2015;5:107–13.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Cestari DM, Weine DM, Panageas KS, Segal AZ, DeAngelis LM. Stroke in patients with cancer: incidence and etiology. Neurology. 2004;62:2025–30.

    Article  CAS  PubMed  Google Scholar 

  11. Zhang YY, Chan DK, Cordato D, Shen Q, Sheng AZ. Stroke risk factor, pattern and outcome in patients with cancer. Acta Neurol Scand. 2006;114:378–83.

    Article  PubMed  Google Scholar 

  12. Zhang YY, Cordato D, Shen Q, Sheng AZ, Hung WT, Chan DK. Risk factor, pattern, etiology and outcome in ischemic stroke patients with cancer: a nested case-control study. Cerebrovasc Dis. 2007;23:181–7.

    Article  CAS  PubMed  Google Scholar 

  13. Navi BB, Singer S, Merkler AE, et al. Cryptogenic subtype predicts reduced survival among cancer patients with ischemic stroke. Stroke. 2014;45:2292–7.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Jang H, Lee JJ, Lee MJ, et al. Comparison of enoxaparin and warfarin for secondary prevention of cancer-associated stroke. J Oncol. 2015;2015:502089.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Schwarzbach CJ, Schaefer A, Ebert A, et al. Stroke and cancer: the importance of cancer-associated hypercoagulation as a possible stroke etiology. Stroke. 2012;43:3029–34.

    Article  PubMed  Google Scholar 

  16. Tapia-Vieyra JV, Delgado-Coello B, Mas-Oliva J. Atherosclerosis and cancer; a resemblance with far-reaching implications. Arch Med Res. 2017;48:12–26.

    Article  CAS  PubMed  Google Scholar 

  17. Conen D, Wong JA, Sandhu RK, et al. Risk of malignant cancer among women with new-onset atrial fibrillation. JAMA Cardiol. 2016;1:389–96.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Guzzetti S, Costantino G, Vernocchi A, Sada S, Fundaro C. First diagnosis of colorectal or breast cancer and prevalence of atrial fibrillation. Intern Emerg Med. 2008;3:227–31.

    Article  PubMed  Google Scholar 

  19. Kim SG, Hong JM, Kim HY, et al. Ischemic stroke in cancer patients with and without conventional mechanisms: a multicenter study in Korea. Stroke. 2010;41:798–801.

    Article  PubMed  Google Scholar 

  20. Merkler AE, Navi BB, Singer S, et al. Diagnostic yield of echocardiography in cancer patients with ischemic stroke. J Neuro-Oncol. 2015;123:115–21.

    Article  CAS  Google Scholar 

  21. Dutta T, Karas MG, Segal AZ, Kizer JR. Yield of transesophageal echocardiography for nonbacterial thrombotic endocarditis and other cardiac sources of embolism in cancer patients with cerebral ischemia. Am J Cardiol. 2006;97:894–8.

    Article  PubMed  Google Scholar 

  22. Lefkovitz NW, Roessmann U, Kori SH. Major cerebral infarction from tumor embolus. Stroke. 1986;17:555–7.

    Article  CAS  PubMed  Google Scholar 

  23. Behrendt CE, Ruiz RB. Cerebral ischemic events in patients with advanced lung or prostate cancer. Neuroepidemiology. 2005;24:230–6.

    Article  PubMed  Google Scholar 

  24. Navi BB, Kawaguchi K, Hriljac I, Lavi E, DeAngelis LM, Jamieson DG. Multifocal stroke from tumor emboli. Arch Neurol. 2009;66:1174–5.

    Article  PubMed  Google Scholar 

  25. Prandoni P, Falanga A, Piccioli A. Cancer and venous thromboembolism. Lancet Oncol. 2005;6:401–10.

    Article  PubMed  Google Scholar 

  26. Bick RL. Cancer-associated thrombosis. N Engl J Med. 2003;349:109–11.

    Article  CAS  PubMed  Google Scholar 

  27. Rogers LR. Cerebrovascular complications in patients with cancer. Semin Neurol. 2010;30:311–9.

    Article  PubMed  Google Scholar 

  28. Li SH, Chen WH, Tang Y, et al. Incidence of ischemic stroke post-chemotherapy: a retrospective review of 10,963 patients. Clin Neurol Neurosurg. 2006;108:150–6.

    Article  PubMed  Google Scholar 

  29. Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2018;49:e46–e110.

    Article  PubMed  Google Scholar 

  30. Masrur S, Abdullah AR, Smith EE, et al. Risk of thrombolytic therapy for acute ischemic stroke in patients with current malignancy. J Stroke Cerebrovasc Dis. 2011;20:124–30.

    Article  PubMed  Google Scholar 

  31. Murthy SB, Karanth S, Shah S, et al. Thrombolysis for acute ischemic stroke in patients with cancer: a population study. Stroke. 2013;44:3573–6.

    Article  CAS  PubMed  Google Scholar 

  32. Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. N Engl J Med. 1995;333:1581–7.

    Article  Google Scholar 

  33. Etgen T, Steinich I, Gsottschneider L. Thrombolysis for ischemic stroke in patients with brain tumors. J Stroke Cerebrovasc Dis. 2014;23:361–6.

    Article  PubMed  Google Scholar 

  34. Murthy SB, Moradiya Y, Shah S, Shastri A, Bershad EM, Suarez JI. In-hospital outcomes of thrombolysis for acute ischemic stroke in patients with primary brain tumors. J Clin Neurosci. 2015;22:474–8.

    Article  PubMed  Google Scholar 

  35. Merkler AE, Marcus JR, Gupta A, et al. Endovascular therapy for acute stroke in patients with cancer. Neurohospitalist. 2014;4:133–5.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Navi BB, Iadecola C. Ischemic stroke in cancer patients: a review of an underappreciated pathology. Ann Neurol. 2018;83:873–83.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Lee AYY, 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;349:146–53.

    Article  CAS  PubMed  Google Scholar 

  38. Raskob GE, van Es N, Verhamme P, et al. Edoxaban for the treatment of cancer-associated venous thromboembolism. N Engl J Med. 2018;378:615–24.

    Article  CAS  PubMed  Google Scholar 

  39. Agnelli G, Becattini C, Bauersachs R, et al. Apixaban versus dalteparin for the treatment of acute venous thromboembolism in patients with cancer: the Caravaggio Study. Thromb Haemost. 2018;118:1668–78.

    Article  PubMed  Google Scholar 

  40. Seok JM, Kim SG, Kim JW, et al. Coagulopathy and embolic signal in cancer patients with ischemic stroke. Ann Neurol. 2010;68:213–9.

    PubMed  Google Scholar 

  41. Lee MJ, Chung JW, Ahn MJ, et al. Hypercoagulability and mortality of patients with stroke and active cancer: the OASIS-CANCER Study. J Stroke. 2017;19:77–87.

    Article  PubMed  Google Scholar 

  42. Kamphuisen PW, Beyer-Westendorf J. Bleeding complications during anticoagulant treatment in patients with cancer. Thromb Res. 2014;133:S49–55.

    Article  CAS  PubMed  Google Scholar 

  43. Navi BB, Marshall RS, Bobrow D, et al. Enoxaparin vs aspirin in patients with cancer and ischemic stroke: the TEACH Pilot Randomized Clinical Trial. JAMA Neurol. 2018;75:379–81.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Li N. Platelets in cancer metastasis: to help the “villain” to do evil. Int J Cancer. 2016;138:2078–87.

    Article  CAS  PubMed  Google Scholar 

  45. Navi BB, Singer S, Merkler AE, et al. Recurrent thromboembolic events after ischemic stroke in patients with cancer. Neurology. 2014;83:26–33.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Kim JM, Jung KH, Park KH, Lee ST, Chu K, Roh JK. Clinical manifestation of cancer related stroke: retrospective case-control study. J Neuro-Oncol. 2013;111:295–301.

    Article  Google Scholar 

  47. Kneihsl M, Enzinger C, Wunsch G, et al. Poor short-term outcome in patients with ischaemic stroke and active cancer. J Neurol. 2016;263:150–6.

    Article  CAS  PubMed  Google Scholar 

  48. Shin YW, Lee ST, Jung KH, et al. Predictors of survival for patients with cancer after cryptogenic stroke. J Neuro-Oncol. 2016;128:277–84.

    Article  CAS  Google Scholar 

  49. Kondziolka D, Bernstein M, Resch L, et al. Significance of hemorrhage into brain tumors: clinicopathological study. J Neurosurg. 1987;67:852–7.

    Article  CAS  PubMed  Google Scholar 

  50. Lieu AS, Hwang SL, Howng SL, Chai CY. Brain tumors with hemorrhage. J Formos Med Assoc. 1999;98:365–7.

    CAS  PubMed  Google Scholar 

  51. Schrader B, Barth H, Lang EW, et al. Spontaneous intracranial haematomas caused by neoplasms. Acta Neurochir. 2000;142:979–85.

    Article  CAS  PubMed  Google Scholar 

  52. Navi BB, Reichman JS, Berlin D, et al. Intracerebral and subarachnoid hemorrhage in patients with cancer. Neurology. 2010;74:494–501.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Reichman J, Singer S, Navi B, et al. Subdural hematoma in patients with cancer. Neurosurgery. 2012;71:74–9.

    Article  PubMed  Google Scholar 

  54. Schouten LJ, Rutten J, Huveneers HAM, Twijnstra A. Incidence of brain metastases in a cohort of patients with carcinoma of the breast, colon, kidney, and lung and melanoma. Cancer. 2002;94:2698–705.

    Article  PubMed  Google Scholar 

  55. Barnholtz-Sloan JS, Sloan AE, Davis FG, Vigneau FD, Lai P, Sawaya RE. Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System. J Clin Oncol. 2004;22:2865–72.

    Article  PubMed  Google Scholar 

  56. Kaya B, Cicek O, Erdi F, et al. Intratumoral hemorrhage-related differences in the expression of vascular endothelial growth factor, basic fibroblast growth factor and thioredoxin reductase 1 in human glioblastoma. Mol Clin Oncol. 2016;5:343–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Liwnicz BH, Wu SZ, Tew JM Jr. The relationship between the capillary structure and hemorrhage in gliomas. J Neurosurg. 1987;66:536–41.

    Article  CAS  PubMed  Google Scholar 

  58. Rogers LR. Cerebrovascular complications in cancer patients. Neurol Clin N Am. 2003;21:167–92.

    Article  Google Scholar 

  59. Velander AJ, DeAngelis LM, Navi BB. Intracranial hemorrhage in patients with cancer. Curr Atheroscler Rep. 2012;14:373–81.

    Article  PubMed  Google Scholar 

  60. Gordon MS, Margolin K, Talpaz M, et al. Phase I safety and pharmacokinetic study of recombinant human anti-vascular endothelial growth factor in patients with advanced cancer. J Clin Oncol. 2001;19:843–50.

    Article  CAS  PubMed  Google Scholar 

  61. Khasraw M, Holodny A, Goldlust SA, DeAngelis LM. Intracranial hemorrhage in patients with cancer treated with bevacizumab: the Memorial Sloan-Kettering experience. Ann Oncol. 2012;23:458–63.

    Article  CAS  PubMed  Google Scholar 

  62. Weinstock MJ, Uhlmann EJ, Zwicker JI. Intracranial hemorrhage in cancer patients treated with anticoagulation. Thromb Res. 2016;140:S60–5.

    Article  CAS  PubMed  Google Scholar 

  63. Kamel H, Navi BB, Hemphill JC 3rd. A rule to identify patients who require magnetic resonance imaging after intracerebral hemorrhage. Neurocrit Care. 2013;18:59–63.

    Article  PubMed  Google Scholar 

  64. Atlas SW, Grossman RI, Gomori JM, et al. Hemorrhagic intracranial malignant neoplasms: spin-echo MR imaging. Neuroradiology. 1987;164:71–7.

    CAS  Google Scholar 

  65. Tung GA, Julius BD, Rogg JM. MRI of intracerebral hematoma: value of vasogenic edema ratio for predicting the cause. Neuroradiology. 2003;45:357–62.

    Article  CAS  PubMed  Google Scholar 

  66. Hemphill JC 3rd, Greenberg SM, Anderson CS, et al. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2015;46:2032–60.

    Article  PubMed  Google Scholar 

  67. Connolly ES Jr, Rabinstein AA, Carhuapoma JR, et al. Guidelines for the management of aneurysmal subarachnoid hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2012;43:1711–37.

    Article  PubMed  Google Scholar 

  68. Patchell RA, Tibbs PA, Walsh JW, et al. A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med. 1990;322:494–500.

    Article  CAS  PubMed  Google Scholar 

  69. Licata B, Turazzi S. Bleeding cerebral neoplasms with symptomatic hematoma. J Neurosurg Sci. 2003;47:201–10.

    CAS  PubMed  Google Scholar 

  70. Omofoye OA, Barnett R, Lau W, Trembath D, Jordan JD, Sasaki-Adams DM. Neoplastic cerebral aneurysm from metastatic nonsmall cell lung carcinoma: case report and literature review. Neurosurgery. 2018;83:E221–5.

    Article  PubMed  Google Scholar 

  71. Choucair AK, Silver P, Levin VA. Risk of intracranial hemorrhage in glioma patients receiving anticoagulant therapy for venous thromboembolism. J Neurosurg. 1987;66:357–8.

    Article  CAS  PubMed  Google Scholar 

  72. Yust-Katz S, Mandel JJ, Wu J, et al. Venous thromboembolism (VTE) and glioblastoma. J Neuro-Oncol. 2015;124:87–94.

    Article  CAS  Google Scholar 

  73. Schiff D, DeAngelis LM. Therapy of venous thromboembolism in patients with brain metastases. Cancer. 1994;73:493–8.

    Article  CAS  PubMed  Google Scholar 

  74. Donato J, Campigotto F, Uhlmann EJ, et al. Intracranial hemorrhage in patients with brain metastases treated with therapeutic enoxaparin: a matched cohort study. Blood. 2015;126:494–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Silvis SM, Hiltunen S, Lindgren E, et al. Cancer and risk of cerebral venous thrombosis: a case-control study. J Thromb Haemost. 2018;16:90–5.

    Article  CAS  PubMed  Google Scholar 

  76. Raizer JJ, DeAngelis LM. Cerebral sinus thrombosis diagnosed by MRI and MR venography in cancer patients. Neurology. 2000;54:1222–6.

    Article  CAS  PubMed  Google Scholar 

  77. Grisold W, Oberndorfer S, Struhal W. Stroke and cancer: a review. Acta Neurol Scand. 2009;119:1–16.

    Article  CAS  PubMed  Google Scholar 

  78. Saposnik G, Barinagarrementeria F, Brown RD Jr, et al. Diagnosis and management of cerebral venous thrombosis: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2011;42:1158–92.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Alan Z. Segal .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Burch, J.E., Segal, A.Z. (2020). Cerebrovascular Complications in Patients with Cancer. In: Ramakrishna, R., Magge, R., Baaj, A., Knisely, J. (eds) Central Nervous System Metastases. Springer, Cham. https://doi.org/10.1007/978-3-030-42958-4_10

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-42958-4_10

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-42957-7

  • Online ISBN: 978-3-030-42958-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics