Skip to main content

Cerebral Vasospasm

  • Chapter
  • First Online:
Introduction to Vascular Neurosurgery

Abstract

The arteries of the brain dynamically increase or decrease their caliber, in order to meet the moment to moment changing demands for oxygenated blood. This process is perturbed during trauma and/or subarachnoid hemorrhage (SAH), when cerebral arteries undergo active vasospasm to prevent extravasation. However, when vasospasm persists for too long, it can compromise tissue perfusion and lead to strokes. Over the past 50 years, the field has made major advances in understanding vasospasm, including recognizing its role in the pathogenesis of several neurological diseases. In this chapter, we summarize our mechanistic views of cerebral vasospasm in the context of SAH, where it has been primarily studied, as well as propose a management protocol for this complex disease process.

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

Access this chapter

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Gull W, others. Cases of aneurism of the cerebral vessels. Guys Hosp Rep. 1859;5:281–304.

    Google Scholar 

  2. Beadles CF. Aneurisms of the larger cerebral arteries. Brain. 1907;30(3):285–336.

    Article  Google Scholar 

  3. Robertson EG. Cerebral lesions due to intracranial aneurysms. Brain. 1949;72(2):150–85.

    Article  CAS  PubMed  Google Scholar 

  4. Fisher CM. Clinical syndromes in cerebral thrombosis, hypertensive hemorrhage, and ruptured saccular aneurysm. Neurosurgery. 1975;22(CN_suppl_1):117–47.

    Article  CAS  Google Scholar 

  5. Fisher C, Kistler J, Davis J. Relation of cerebral vasospasm to subarachnoid hemorrhage visualized by computerized tomographic scanning. Neurosurgery. 1980;6(1):1–9.

    Article  CAS  PubMed  Google Scholar 

  6. Saito I, et al. Vasospasm assessed by angiography and computerized tomography. J Neurosurg. 1979;51(4):466–75.

    Article  CAS  PubMed  Google Scholar 

  7. Ecker A, Riemenschneider PA. Arteriographic demonstration of spasm of the intracranial arteries with special reference to saccular arterial aneurisms. J Neurosurg. 1951;8(6):660–7.

    Article  CAS  PubMed  Google Scholar 

  8. Macdonald RL, Weir B. Cerebral vasospasm. Elsevier; San Diego, California. 2001.

    Google Scholar 

  9. Macdonald RLJNRN. Delayed neurological deterioration after subarachnoid haemorrhage. Nat Rev Neurol. 2014;10(1):44.

    Article  CAS  PubMed  Google Scholar 

  10. Takemae T, et al. Computed tomography of ruptured intracranial aneurysms in acute stage–relationship between vasospasm and high density on CT scan (author’s transl). No to shinkei= Brain and nerve. 1978;30(8):861–6.

    CAS  PubMed  Google Scholar 

  11. Reilly C, et al. Clot volume and clearance rate as independent predictors of vasospasm after aneurysmal subarachnoid hemorrhage. J Neurosurg. 2004;101(2):255–61.

    Article  PubMed  Google Scholar 

  12. KOIKE T, et al. Clinical analysis of cerebral vasospasm following subarachnoid hemorrhage—part 1 sequential changes of incidence and degree and its clinical significance—. Neurol Med Chir. 1979;19(8):793–800.

    Article  CAS  Google Scholar 

  13. Crowley RW, et al. Angiographic vasospasm is strongly correlated with cerebral infarction after subarachnoid hemorrhage. Stroke. 2011;42(4):919–23.

    Article  PubMed  Google Scholar 

  14. Ito H. A clinical study on vasospasm following subarachnoid hemorrhage using the ratio of inner diameters of cerebral arteries to the ganglionic portion of internal carotid artery (author’s transl). No to shinkei= Brain and nerve. 1978;30(7):795–804.

    CAS  PubMed  Google Scholar 

  15. Ochi RP, Vieco PT, Gross CE. CT angiography of cerebral vasospasm with conventional angiographic comparison. AJNR Am J Neuroradiol. 1997;18(2):265–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Takagi R, et al. Evaluation of three-dimensional CT angiography (3D-CTA) for the diagnosis of cerebral vasospasm. Nihon Igaku Hoshasen Gakkai Zasshi. 1997;57(1):64–6.

    CAS  PubMed  Google Scholar 

  17. Chaudhary SR, et al. Prospective evaluation of multidetector-row CT angiography for the diagnosis of vasospasm following subarachnoid hemorrhage: a comparison with digital subtraction angiography. Cerebrovasc Dis. 2008;25(1–2):144–50.

    Article  PubMed  Google Scholar 

  18. Aaslid R, Markwalder T-M, Nornes H. Noninvasive transcranial Doppler ultrasound recording of flow velocity in basal cerebral arteries. J Neurosurg. 1982;57(6):769–74.

    Article  CAS  PubMed  Google Scholar 

  19. Lindegaard K-F, et al. Cerebral vasospasm after subarachnoid haemorrhage investigated by means of transcranial Doppler ultrasound. Springer; Vienna, Austria. 1988.

    Google Scholar 

  20. Fahmy M, Smith R. Identification of presymptomatic cerebral vasospasm by transcranial Doppler sonography. 1992. Amer Heart Assoc 7272 Greenville Avenue, Dallas, TX 75231-4596.

    Google Scholar 

  21. Grosset D, et al. Prediction of symptomatic vasospasm after subarachnoid hemorrhage by rapidly increasing transcranial Doppler velocity and cerebral blood flow changes. Stroke. 1992;23(5):674–9.

    Article  CAS  PubMed  Google Scholar 

  22. Fontanella M, et al. Vasospasm after SAH due to aneurysm rupture of the anterior circle of Willis: value of TCD monitoring. Neurol Res. 2008;30(3):256–61.

    Article  PubMed  Google Scholar 

  23. Wintermark M, et al. Vasospasm after subarachnoid hemorrhage: utility of perfusion CT and CT angiography on diagnosis and management. Am J Neuroradiol. 2006;27(1):26–34.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Sozen T, et al. A clinical review of cerebral vasospasm and delayed ischaemia following aneurysm rupture. Acta Neurochir Suppl. 2011;110:5–6.

    Google Scholar 

  25. Fletcher TM, Taveras JM, Pool JL. Cerebral vasospasm in angiography for intracranial aneurysms: incidence and significance in one hundred consecutive angiograms. AMA Arch Neurol. 1959;1(1):38–47.

    Article  CAS  PubMed  Google Scholar 

  26. Dorsch N. Incidence, effects and treatment of ischemia following aneurysm rupture. In: Sano K, et al., editors. Cerebral vasospasm. Tokyo: University of Tokyo Press; 1990. p. 495–8.

    Google Scholar 

  27. Taneda M, et al. Angiographic demonstration of acute phase of intracranial arterial spasm following aneurysm rupture: case report. J Neurosurg. 1990;73(6):958–61.

    Article  CAS  PubMed  Google Scholar 

  28. Lovelock C, Rinkel G, Rothwell P. Time trends in outcome of subarachnoid hemorrhage: population-based study and systematic review. Neurology. 2010;74(19):1494–501.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Lanzino G, et al. Age and outcome after aneurysmal subarachnoid hemorrhage: why do older patients fare worse? J Neurosurg. 1996;85(3):410–8.

    Article  CAS  PubMed  Google Scholar 

  30. Rosenørn J, Eskesen V, Schmidt K. Clinical features and outcome in females and males with ruptured intracranial saccular aneurysms. Br J Neurosurg. 1993;7(3):287–90.

    Article  Google Scholar 

  31. Lasner TM, et al. Cigarette smoking—induced increase in the risk of symptomatic vasospasm after aneurysmal subarachnoid hemorrhage. J Neurosurg. 1997;87(3):381–4.

    Article  CAS  PubMed  Google Scholar 

  32. Weir BK, et al. Cigarette smoking as a cause of aneurysmal subarachnoid hemorrhage and risk for vasospasm: a report of the Cooperative Aneurysm Study. J Neurosurg. 1998;89(3):405–11.

    Article  CAS  PubMed  Google Scholar 

  33. de Rooij NK, et al. Delayed cerebral ischemia after subarachnoid hemorrhage: a systematic review of clinical, laboratory, and radiological predictors. Stroke. 2013;44(1):43–54.

    Article  PubMed  Google Scholar 

  34. Pool JL, Jacobson S, Fletcher TA. Cerebral vasospasm-clinical and experimental evidence. J Am Med Assoc. 1958;167(13):1599–601.

    Article  CAS  PubMed  Google Scholar 

  35. Rothenberg SF, Corday E. Etiology of the transient cerebral stroke. J Am Med Assoc. 1957;164(18):2005–8.

    Article  CAS  PubMed  Google Scholar 

  36. Hakim S, Fisher CM. A new technique for the microscopic examination of cerebral vessels in vivo. J Neurosurg. 1957;14(4):405–12.

    Article  CAS  PubMed  Google Scholar 

  37. Gurdjian ES, et al. Cinephotomicrography of the pial circulation; a study of factors influencing vascular caliber; preliminary report. AMA Arch Neurol Psychiatry. 1958;80(4):418–35.

    Article  CAS  PubMed  Google Scholar 

  38. Echlin FA. Vasospasm and focal cerebral ischemia: an experimental study. Arch Neurol Psychiatr. 1942;47(1):77–96.

    Article  Google Scholar 

  39. Hara H, Nosko M, Weir B. Cerebral perivascular nerves in subarachnoid hemorrhage: a histochemical and immunohistochemical study. J Neurosurg. 1986;65(4):531–9.

    Article  CAS  PubMed  Google Scholar 

  40. Uemura Y, et al. Changes of vasoactive intestinal polypeptide-like immunoreactivity in cerebrovascular nerve fibers after subarachnoid hemorrhage: an experimental study in the dog. Neurosci Lett. 1986;71(2):137–41.

    Article  CAS  PubMed  Google Scholar 

  41. Bevan JA, Bevan RD, Frazee JG. Functional arterial changes in chronic cerebrovasospasm in monkeys: an in vitro assessment of the contribution to arterial narrowing. Stroke. 1987;18(2):472–81.

    Article  CAS  PubMed  Google Scholar 

  42. MIYAOKA M, et al. Etiology and treatment of prolonged vasospasm—experimental and clinical studies—. Neurol Med Chir. 1976;16(2):103–14.

    Google Scholar 

  43. Alpers BJ, Forster FM. The reparative processes in subarachnoid hemorrhage. J Neuropathol Exp Neurol. 1945;4(3):262–8.

    Article  Google Scholar 

  44. Hammes EM. Reaction of the meninges to blood. Arch Neurol Psychiatr. 1944;52(6):505–14.

    Article  Google Scholar 

  45. Kajikawa H, et al. Cerebral vasospasm and hemoglobins—clinical and experimental studies. Neurol Med Chir. 1979;19(1):61–71.

    Article  CAS  Google Scholar 

  46. German JW, et al. Systemic complement depletion inhibits experimental cerebral vasospasm. Neurosurgery. 1996;39(1):141–6.

    Article  CAS  PubMed  Google Scholar 

  47. Chaichana KL, et al. Haptoglobin 2-2 genotype determines chronic vasospasm after experimental subarachnoid hemorrhage. Stroke. 2007;38(12):3266–71.

    Article  CAS  PubMed  Google Scholar 

  48. Borsody M, et al. Haptoglobin and the development of cerebral artery vasospasm after subarachnoid hemorrhage. Neurology. 2006;66(5):634–40.

    Article  CAS  PubMed  Google Scholar 

  49. Jackson IJ. Aseptic hemogenic meningitis: an experimental study of aseptic meningeal reactions due to blood and its breakdown products. Arch Neurol Psychiatr. 1949;62(5):572–89.

    Article  CAS  Google Scholar 

  50. Tourtellotte WW, et al. Spontaneous subarachnoid hemorrhage: factors affecting the rate of clearing of the cerebrospinal fluid. Neurology. 1964;14(4):301.

    Article  CAS  PubMed  Google Scholar 

  51. Pradilla G, et al. Inflammation and cerebral vasospasm after subarachnoid hemorrhage. Neurosurg Clin N Am. 2010;21(2):365–79.

    Article  PubMed  Google Scholar 

  52. Vorkapic P, Bevan JA, Bevan RD. Longitudinal in vivo and in vitro time-course study of chronic cerebrovasospasm in the rabbit basilar artery. Neurosurg Rev. 1991;14(3):215–9.

    Article  CAS  PubMed  Google Scholar 

  53. Pluta RM, et al. Cerebral vasospasm following subarachnoid hemorrhage: time for a new world of thought. Neurol Res. 2009;31(2):151–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Suzuki H, et al. Endothelin immunoreactivity in cerebrospinal fluid of patients with subarachnoid haemorrhage. Ann Med. 1990;22(4):233–6.

    Article  CAS  PubMed  Google Scholar 

  55. Ehrenreich H, et al. Long term monitoring of immunoreactive endothelin-1 and endothelin-3 in ventricular cerebrospinal fluid, plasma, and 24-h urine of patients with subarachnoid hemorrhage. Res Exp Med. 1992;192(1):257–68.

    Article  CAS  Google Scholar 

  56. Suzuki M, et al. Increased levels of nitrite/nitrate in the cerebrospinal fluid of patients with subarachnoid hemorrhage. Neurosurg Rev. 1999;22(2):96–8.

    Article  CAS  PubMed  Google Scholar 

  57. Kaura V, Bonner S. Subarachnoid haemorrhage: early clinical indicators and biomarkers. Trends Anaesth Crit Care. 2012;2(1):42–7.

    Article  Google Scholar 

  58. Lad SP, et al. Proteomic biomarker discovery in cerebrospinal fluid for cerebral vasospasm following subarachnoid hemorrhage. J Stroke Cerebrovasc Dis. 2012;21(1):30–41.

    Article  PubMed  Google Scholar 

  59. Fishman J, Ryan G, Karnovsky M. Endothelial regeneration in the rat carotid artery and the significance of endothelial denudation in the pathogenesis of myointimal thickening. Lab Invest. 1975;32(3):339–51.

    CAS  PubMed  Google Scholar 

  60. Burns ER, Spaet TH, Stemerman MB. Response of the arterial wall to endothelial removal: an autoradiographic study. Proc Soc Exp Biol Med. 1978;159(3):473–7.

    Article  CAS  PubMed  Google Scholar 

  61. Kin H, et al. The pathological study of so-called vasospasm. Neurol Med Chir. 1976;16(2):115–25.

    Article  CAS  Google Scholar 

  62. Dreier JP. The role of spreading depression, spreading depolarization and spreading ischemia in neurological disease. Nat Med. 2011;17(4):439–47.

    Article  CAS  PubMed  Google Scholar 

  63. Sabri M, et al. Mechanisms of microthrombi formation after experimental subarachnoid hemorrhage. Neuroscience. 2012;224:26–37.

    Article  CAS  PubMed  Google Scholar 

  64. Stoltenburg-Didinger G, Schwarz K. Brain lesions secondary to subarachnoid hemorrhage due to ruptured aneurysms. In: Cervós-Navarro J, Ferszt R, editors. Stroke and microcirculation. New York: Raven Press; 1987. pp. 471–80.

    Google Scholar 

  65. Stein SC, et al. Thromboembolism and delayed cerebral ischemia after subarachnoid hemorrhage: an autopsy study. Neurosurgery. 2006;59(4):781–8.

    Article  PubMed  Google Scholar 

  66. Mayberg MR. Cerebral vasospasm. Neurosurg Clin N Am. 1998;9(3):615–27.

    Article  CAS  PubMed  Google Scholar 

  67. Hinson HE, Sheth KN. Manifestations of the hyperadrenergic state after acute brain injury. Curr Opin Crit Care. 2012;18(2):139–45.

    Article  PubMed  Google Scholar 

  68. Tam AK, et al. Impact of systemic inflammatory response syndrome on vasospasm, cerebral infarction, and outcome after subarachnoid hemorrhage: exploratory analysis of CONSCIOUS-1 database. Neurocrit Care. 2010;13(2):182–9.

    Article  PubMed  Google Scholar 

  69. Diringer MN, et al. Critical care management of patients following aneurysmal subarachnoid hemorrhage: recommendations from the Neurocritical Care Society’s Multidisciplinary Consensus Conference. Neurocrit Care. 2011;15(2):211–40.

    Article  PubMed  Google Scholar 

  70. Heros RC, Zervas NT, Varsos V. Cerebral vasospasm after subarachnoid hemorrhage: an update. Ann Neurol. 1983;14(6):599–608.

    Article  CAS  PubMed  Google Scholar 

  71. Kosnik EJ, Hunt WE. Postoperative hypertension in the management of patients with intracranial arterial aneurysms. J Neurosurg. 1976;45(2):148–54.

    Article  CAS  PubMed  Google Scholar 

  72. Connolly ES 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(6):1711–37.

    Article  PubMed  Google Scholar 

  73. Hasan D, et al. Effect of fluid intake and antihypertensive treatment on cerebral ischemia after subarachnoid hemorrhage. Stroke. 1989;20(11):1511–5.

    Article  CAS  PubMed  Google Scholar 

  74. Treggiari MM, others. Hemodynamic management of subarachnoid hemorrhage. Neurocrit Care. 2011;15(2):329.

    Article  PubMed  Google Scholar 

  75. Kassell NF, et al. Treatment of ischemic deficits from vasospasm with intravascular volume expansion and induced arterial hypertension. Neurosurgery. 1982;11(3):337–43.

    Article  CAS  PubMed  Google Scholar 

  76. Pritz MB, et al. Treatment of patients with neurological deficits associated with cerebral vasospasm by intravascular volume expansion. Neurosurgery. 1978;3(3):364–8.

    CAS  PubMed  Google Scholar 

  77. Giannotta S, McGillicuddy J, Kindt G. Diagnosis and treatment of postoperative cerebral vasospasm. Surg Neurol. 1977;8(4):286–90.

    CAS  PubMed  Google Scholar 

  78. Le Roux PD, others. Anemia and transfusion after subarachnoid hemorrhage. Neurocrit Care. 2011;15(2):342.

    Article  PubMed  Google Scholar 

  79. Dhar R, et al. Comparison of induced hypertension, fluid bolus, and blood transfusion to augment cerebral oxygen delivery after subarachnoid hemorrhage. J Neurosurg. 2012;116(3):648–56.

    Article  PubMed  Google Scholar 

  80. McKhann GM II, Le Roux PD. Perioperative and intensive care unit care of patients with aneurysmal subarachnoid hemorrhage. Neurosurg Clin N Am. 1998;9(3):595–613.

    Article  PubMed  Google Scholar 

  81. Etminan N, et al. Effect of pharmaceutical treatment on vasospasm, delayed cerebral ischemia, and clinical outcome in patients with aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis. J Cereb Blood Flow Metab. 2011;31(6):1443–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Langley MS, Sorkin EM. Nimodipine. Drugs. 1989;37(5):669–99.

    Article  CAS  PubMed  Google Scholar 

  83. Allen GS, et al. Cerebral arterial spasm–a controlled trial of nimodipine in patients with subarachnoid hemorrhage. N Engl J Med. 1983;308(11):619–24.

    Article  CAS  PubMed  Google Scholar 

  84. Mees SD, et al. Calcium antagonists for aneurysmal subarachnoid haemorrhage. Cochrane Database Syst Rev. 2007;(3):CD000277.

    Google Scholar 

  85. Vergouwen MD, et al. Microthrombosis after aneurysmal subarachnoid hemorrhage: an additional explanation for delayed cerebral ischemia. J Cereb Blood Flow Metab. 2008;28(11):1761–70.

    Article  PubMed  Google Scholar 

  86. Macdonald RL, et al. Clazosentan to overcome neurological ischemia and infarction occurring after subarachnoid hemorrhage (CONSCIOUS-1) randomized, double-blind, placebo-controlled phase 2 dose-finding trial. Stroke. 2008;39(11):3015–21.

    Article  CAS  PubMed  Google Scholar 

  87. Macdonald RL, et al. Clazosentan, an endothelin receptor antagonist, in patients with aneurysmal subarachnoid haemorrhage undergoing surgical clipping: a randomised, double-blind, placebo-controlled phase 3 trial (CONSCIOUS-2). Lancet Neurol. 2011;10(7):618–25.

    Article  CAS  PubMed  Google Scholar 

  88. Macdonald RL, et al. Randomized trial of clazosentan in patients with aneurysmal subarachnoid hemorrhage undergoing endovascular coiling. Stroke. 2012;43(6):1463–9.

    Article  CAS  PubMed  Google Scholar 

  89. Vergouwen MD, Algra A, Rinkel GJ. Endothelin receptor antagonists for aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis update. Stroke. 2012;43(10):2671–6.

    Article  CAS  PubMed  Google Scholar 

  90. Satoh S-I, et al. Amelioration of endothelial damage/dysfunction is a possible mechanism for the neuroprotective effects of Rho-kinase inhibitors against ischemic brain damage. Brain Res Bull. 2010;81(1):191–5.

    Article  CAS  PubMed  Google Scholar 

  91. Liu GJ, et al. Systematic assessment and meta-analysis of the efficacy and safety of fasudil in the treatment of cerebral vasospasm in patients with subarachnoid hemorrhage. Eur J Clin Pharmacol. 2012;68(2):131–9.

    Article  CAS  PubMed  Google Scholar 

  92. Tiebosch IA, et al. Effect of interferon-β on neuroinflammation, brain injury and neurological outcome after experimental subarachnoid hemorrhage. Neurocrit Care. 2013;18(1):96–105.

    Article  CAS  PubMed  Google Scholar 

  93. Feigin VL, et al. Corticosteroids for aneurysmal subarachnoid haemorrhage and primary intracerebral haemorrhage. Cochrane Database Syst Rev. 2005;(3):CD004583.

    Google Scholar 

  94. Zubkov YN, Nikiforov B, Shustin V. Balloon catheter technique for dilatation of constricted cerebral arteries after aneurysmal SAH. Acta Neurochir. 1984;70(1):65–79.

    Article  CAS  PubMed  Google Scholar 

  95. Zwienenberg-Lee M, et al. Effect of prophylactic transluminal balloon angioplasty on cerebral vasospasm and outcome in patients with Fisher grade III subarachnoid hemorrhage: results of a phase II multicenter, randomized, clinical trial. Stroke. 2008;39(6):1759–65.

    Article  PubMed  Google Scholar 

  96. DeWitt CR, Waksman JC. Pharmacology, pathophysiology and management of calcium channel blocker and β-blocker toxicity. Toxicol Rev. 2004;23(4):223–38.

    Article  CAS  PubMed  Google Scholar 

  97. Jabbarli R, et al. Endovascular treatment of cerebral vasospasm after subarachnoid hemorrhage: more is more. Neurology. 2019;93(5):e458–66.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Aman B. Patel .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2022 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Muñoz, W., Stapleton, C.J., Patel, A.B. (2022). Cerebral Vasospasm. In: Mascitelli, J.R., Binning, M.J. (eds) Introduction to Vascular Neurosurgery. Springer, Cham. https://doi.org/10.1007/978-3-030-88196-2_9

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-88196-2_9

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-88195-5

  • Online ISBN: 978-3-030-88196-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics