Skip to main content

Applications of Transcranial Doppler Ultrasonography in Sickle Cell Disease, Stroke, and Critical Illness in Children

  • Chapter
  • First Online:
Neurovascular Sonography

Abstract

Transcranial Doppler (TCD) ultrasonography has an established clinical role in reducing a first ever stroke in children with sickle cell disease (SCD) by identifying those at high risk who benefit from blood transfusion. In this chapter, we will review the literature related to this topic. Beyond SCD, other potential roles for TCD in pediatrics include as a point of care ultrasound (POCUS) or as a neuromonitoring strategy in the pediatric intensive care unit (PICU). We will therefore also review the literature for the applications of TCD in critically ill children with traumatic brain injury (TBI), cerebral vasospasm, brain death, and those undergoing support with extracorporeal membrane oxygenation (ECMO). Based on the limited available evidence for these topics, TCD data in these populations should be treated as hypothesis-generating. TCD may serve as a precursor or adjunct to definitive imaging or invasive techniques. In order to put TCD into routine practice in the pediatric intensive care unit (PICU), collaboration and research is needed to determine the appropriate clinical indications and quantify the impact of use on clinical care and outcomes.

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

Access this chapter

eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 59.99
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. Adams R, McKie V, Nichols F, Carl E, Zhang DL, McKie K, et al. The use of transcranial ultrasonography to predict stroke in sickle cell disease. N Engl J Med. 1992;326(9):605–10.

    Article  CAS  PubMed  Google Scholar 

  2. Adams RJ, McKie VC, Hsu L, Files B, Vichinsky E, Pegelow C, et al. Prevention of a first stroke by transfusions in children with sickle cell anemia and abnormal results on transcranial doppler ultrasonography. N Engl J Med. 1998;339(1):5–11.

    Article  CAS  PubMed  Google Scholar 

  3. Adams RJ, McKie VC, Brambilla D, Carl E, Gallagher D, Nichols FT, et al. Stroke prevention trial in sickle cell anemia. Control Clin Trials. 1998;19(1):110–29.

    Article  CAS  PubMed  Google Scholar 

  4. Adams RJ, Brambilla DJ, Granger S, Gallagher D, Vichinsky E, Abboud MR, et al. Stroke and conversion to high risk in children screened with transcranial doppler ultrasound during the STOP study. Blood. 2004;103(10):3689–94.

    Article  CAS  PubMed  Google Scholar 

  5. Adams RJ, Brambilla D. Optimizing primary stroke prevention in sickle cell anemia trial I: discontinuing prophylactic transfusions used to prevent stroke in sickle cell disease. N Engl J Med. 2005;353(26):2769–78.

    Article  CAS  PubMed  Google Scholar 

  6. LaRovere KL, Tasker RC, Wainwright M, Reuter-Rice K, Appavu B, Miles D, et al. Transcranial doppler ultrasound during critical illness in children: survey of practices in pediatric neurocritical care centers. PCCM. 2020;21(1):67–74.

    Google Scholar 

  7. Tegeler CH, Crutchfield K, Katsnelson M, Kim J, Tang R, Passmore Griffin L, et al. Transcranial doppler velocities in a large, healthy population. J Neuroimaging. 2013;23(3):466–72.

    Article  PubMed  Google Scholar 

  8. O’Brien NF. Reference values for cerebral blood flow velocities in critically ill sedated children. Childs Nerv Syst. 2015;31(12):2269–76.

    Article  PubMed  Google Scholar 

  9. Bode H, Wais U. Age dependence of flow velocities in basal cerebral arteries. Arch Dis Child. 1988;63(6):606–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Quinn CT, Rogers ZR, Buchanan GR. Survival of children with sickle cell disease. Blood. 2004;103(11):4023–7.

    Article  CAS  PubMed  Google Scholar 

  11. Rothman SM, Fulling KH, Nelson JS. Sickle cell anemia and central nervous system infarction: a neuropathological study. Ann Neurol. 1986;20(6):684–90.

    Article  CAS  PubMed  Google Scholar 

  12. Kaul DK, Fabry ME, Nagel RL. Microvascular sites and characteristics of sickle cell adhesion to vascular endothelium in shear flow conditions: pathophysiological implications. Proc Natl Acad Sci U S A. 1989;86(9):3356–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Merkel KH, Ginsberg PL, Parker JC Jr, Post MJ. Cerebrovascular disease in sickle cell anemia: a clinical, pathological and radiological correlation. Stroke. 1978;9(1):45–52.

    Article  CAS  PubMed  Google Scholar 

  14. Thust SC, Burke C, Siddiqui A. Neuroimaging findings in sickle cell disease. Br J Radiol. 2014;87(1040):20130699.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Stockman JA, Nigro MA, Mishkin MM, Oski FA. Occlusion of large cerebral vessels in sickle-cell anemia. NEJM. 1972;287(17):846–9.

    Article  CAS  PubMed  Google Scholar 

  16. Powars D, Wilson B, Imbus C, Pegelow C, Allen J. The natural history of stroke in sickle cell disease. Am J Med. 1978;65(3):461–71.

    Article  CAS  PubMed  Google Scholar 

  17. Russell MO, Goldberg HI, Hodson A, Kim HC, Halus J, Reivich M, et al. Effect of transfusion therapy on arteriographic abnormalities and on recurrence of stroke in sickle cell disease. Blood. 1984;63(1):162–9.

    Article  CAS  PubMed  Google Scholar 

  18. Brass LM, Pavlakis SG, DeVivo D, Piomelli S, Mohr JP. Transcranial doppler measurements of the middle cerebral artery. Effect of hematocrit. Stroke. 1988;19(12):1466–9.

    Article  CAS  PubMed  Google Scholar 

  19. Adams RJ, Nichols FT, Figueroa R, McKie V, Lott T. Transcranial doppler correlation with cerebral angiography in sickle cell disease. Stroke. 1992;23(8):1073–7.

    Article  CAS  PubMed  Google Scholar 

  20. Adams RJ, McKie VC, Carl EM, Nichols FT, Perry R, Brock K, et al. Long-term stroke risk in children with sickle cell disease screened with transcranial doppler. Ann Neurol. 1997;42(5):699–704.

    Article  CAS  PubMed  Google Scholar 

  21. Nichols FT, Jones AM, Adams RJ. Stroke prevention in sickle cell disease (STOP) study guidelines for transcranial doppler testing. J Neuroimaging. 2001;11(4):354–62.

    Article  CAS  PubMed  Google Scholar 

  22. Lee YS, Jung KH, Roh JK. Diagnosis of moyamoya disease with transcranial doppler sonography: correlation study with magnetic resonance angiography. J Neuroimaging. 2004;14(4):319–23.

    Article  PubMed  Google Scholar 

  23. Fullerton HJ, Elkind MS, Barkovich AJ, Glaser C, Glidden D, Hills NK, et al. The vascular effects of infection in pediatric stroke (VIPS) study. J Child Neurol. 2011;26(9):1101–10.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Wintermark M, Hills NK, deVeber GA, Barkovich AJ, Elkind MS, Sear K, et al. Arteriopathy diagnosis in childhood arterial ischemic stroke: results of the vascular effects of infection in pediatric stroke study. Stroke. 2014;45(12):3597–605.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Elkind MS, Hills NK, Glaser CA, Lo WD, Amlie-Lefond C, Dlamini N, et al. Herpesvirus infections and childhood arterial ischemic stroke: results of the VIPS study. Circulation. 2016;133(8):732–41.

    Article  PubMed  PubMed Central  Google Scholar 

  26. van Santbrink H, Schouten JW, Steyerberg EW, Avezaat CJ, Maas AI. Serial transcranial doppler measurements in traumatic brain injury with special focus on the early posttraumatic period. Acta Neurochir. 2002;144(11):1141–9.

    Article  PubMed  Google Scholar 

  27. Ract C, Le Moigno S, Bruder N, Vigue B. Transcranial doppler ultrasound goal-directed therapy for the early management of severe traumatic brain injury. Int Care Med. 2007;33(4):645–51.

    Article  Google Scholar 

  28. Trabold F, Meyer PG, Blanot S, Carli PA, Orliaguet GA. The prognostic value of transcranial doppler studies in children with moderate and severe head injury. Int Care Med. 2004;30(1):108–12.

    Article  Google Scholar 

  29. Chaiwat O, Sharma D, Udomphorn Y, Armstead WM, Vavilala MS. Cerebral hemodynamic predictors of poor 6-month Glasgow outcome score in severe pediatric traumatic brain injury. J Neurotrauma. 2009;26(5):657–63.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Visocchi M, Chiaretti A, Genovese O, Di Rocco F. Haemodynamic patterns in children with posttraumatic diffuse brain swelling. A preliminary study in 6 cases with neuroradiological features consistent with diffuse axonal injury. Acta Neurochir. 2007;149(4):347–56.

    Article  CAS  PubMed  Google Scholar 

  31. O’Brien NF, Maa T, Moore-Clingenpeel M, Rosenberg N, Yeates KO. Relationships between cerebral flow velocities and neurodevelopmental outcomes in children with moderate to severe traumatic brain injury. Childs Nerv Syst. 2018;34(4):663–72.

    Article  PubMed  Google Scholar 

  32. Kochanek PM, Tasker RC, Carney N, Totten AM, Adelson PD, Selden NR, et al. Guidelines for the management of pediatric severe traumatic brain injury, third edition: update of the brain trauma foundation guidelines. PCCM. 2019;20(3S Suppl 1):S1–S82.

    Google Scholar 

  33. Kochanek PM, Tasker RC, Carney N, Totten AM, Adelson PD, Selden NR, et al. Guidelines for the management of pediatric severe traumatic brain injury, third edition: update of the brain trauma foundation guidelines, executive summary. Neurosurgery. 2019;84(6):1169–78.

    Article  PubMed  Google Scholar 

  34. Alkhoury F, Kyriakides TC. Intracranial pressure monitoring in children with severe traumatic brain injury: National Trauma Data Bank-Based Review of outcomes. JAMA Surg. 2014, Jun;149(6):544–8.

    Article  PubMed  Google Scholar 

  35. Alali AS, Gomez D, Sathya C, Burd RS, Mainprize TG, Moulton R, et al. Intracranial pressure monitoring among children with severe traumatic brain injury. J Neurosurg Pediatr. 2015;16(5):523–32.

    Article  PubMed  Google Scholar 

  36. Morris KP, Forsyth RJ, Parslow RC, Tasker RC, Hawley CA, Group UKPTBIS, Paediatric Intensive Care Society Study G. Intracranial pressure complicating severe traumatic brain injury in children: monitoring and management. Int Care Med. 2006;32(10):1606–12.

    Article  Google Scholar 

  37. Bennett TD, Riva-Cambrin J, Keenan HT, Korgenski EK, Bratton SL. Variation in intracranial pressure monitoring and outcomes in pediatric traumatic brain injury. Arch Pediatr Adolesc Med. 2012;166(7):641–7.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Dixon RR, Nocera M, Zolotor AJ, Keenan HT. Intracranial pressure monitoring in infants and young children with traumatic brain injury. PCCM. 2016;17(11):1064–72.

    Google Scholar 

  39. Van Cleve W, Kernic MA, Ellenbogen RG, Wang J, Zatzick DF, Bell MJ, et al. National variability in intracranial pressure monitoring and craniotomy for children with moderate to severe traumatic brain injury. Neurosurgery. 2013;73(5):746–52.

    Article  PubMed  Google Scholar 

  40. Figaji AA, Zwane E, Fieggen AG, Siesjo P, Peter JC. Transcranial doppler pulsatility index is not a reliable indicator of intracranial pressure in children with severe traumatic brain injury. Surg Neurol. 2009;72(4):389–94.

    Article  PubMed  Google Scholar 

  41. Melo JR, Di Rocco F, Blanot S, Cuttaree H, Sainte-Rose C, Oliveira-Filho J, et al. Transcranial doppler can predict intracranial hypertension in children with severe traumatic brain injuries. Childs Nerv Syst. 2011;27(6):979–84.

    Article  PubMed  Google Scholar 

  42. O’Brien NF, Maa T, Reuter-Rice K. Noninvasive screening for intracranial hypertension in children with acute, severe traumatic brain injury. J Neurosurg Pediatr. 2015;16(4):420–5.

    Article  PubMed  Google Scholar 

  43. Fanelli A, Vonberg FW, LaRovere KL, Walsh BK, Smith ER, Robinson S, et al. Fully automated, real-time, calibration-free, continuous noninvasive estimation of intracranial pressure in children. J Neurosurg Pediatr. 2019;24(5):509–19.

    Article  Google Scholar 

  44. O’Brien NF, Lovett ME, Chung M, Maa T. Non-invasive estimation of cerebral perfusion pressure using transcranial doppler ultrasonography in children with severe traumatic brain injury. Childs Nerv Syst. 2020;36(9):2063–71.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Rao VK, Haridas A, Nguyen TT, Lulla R, Wainwright MS, Goldstein JL. Symptomatic cerebral vasospasm following resection of a medulloblastoma in a child. Neurocrit Care. 2013;18(1):84–8.

    Article  PubMed  Google Scholar 

  46. Pendharkar AV, Guzman R, Dodd R, Cornfield D, Edwards MS. Successful treatment of severe cerebral vasospasm following hemorrhage of an arteriovenous malformation. Case report. J Neurosurg Pediatr. 2009;4(3):266–9.

    Article  PubMed  Google Scholar 

  47. O’Brien NF, Reuter-Rice KE, Khanna S, Peterson BM, Quinto KB. Vasospasm in children with traumatic brain injury. Int Care Med. 2010;36(4):680–7.

    Article  Google Scholar 

  48. O’Brien NF, Maa T, Yeates KO. The epidemiology of vasospasm in children with moderate-to-severe traumatic brain injury. CCM. 2014;43(3):674–85.

    Google Scholar 

  49. Philip S, Chaiwat O, Udomphorn Y, Moore A, Zimmerman JJ, Armstead W, et al. Variation in cerebral blood flow velocity with cerebral perfusion pressure >40 mm Hg in 42 children with severe traumatic brain injury. CCM. 2009;37(11):2973–8.

    Google Scholar 

  50. O’Brien NF, Mutatshi Taty T, Moore-Clingenpeel M, Bodi Mabiala J, Mbaka Pongo J, Ambitapio Musungufu D, et al. Transcranial doppler ultrasonography provides insights into neurovascular changes in children with cerebral malaria. Pediatrics. 2018;203(116–24):e113.

    Google Scholar 

  51. Garg K, Singh PK, Sharma BS, Chandra PS, Suri A, Singh M, et al. Pediatric intracranial aneurysms--our experience and review of literature. Childs Nerv Syst. 2014;30(5):873–83.

    Article  PubMed  Google Scholar 

  52. Moftakhar P, Cooke DL, Fullerton HJ, Ko NU, Amans MR, Narvid JA, et al. Extent of collateralization predicting symptomatic cerebral vasospasm among pediatric patients: correlations among angiography, transcranial doppler ultrasonography, and clinical findings. J Neurosurg Pediatr. 2015;15(3):282–90.

    Article  PubMed  Google Scholar 

  53. Udomphorn Y, Armstead WM, Vavilala MS. Cerebral blood flow and autoregulation after pediatric traumatic brain injury. Pediatr Neurol. 2008;38(4):225–34.

    Article  PubMed  PubMed Central  Google Scholar 

  54. O’Brien NF, Buttram SDW, Maa T, Lovett ME, Reuter-Rice K, LaRovere KL. Cerebrovascular physiology during pediatric extracorporeal membrane oxygenation: a multicenter study using transcranial doppler ultrasonography. PCCM. 2019;20(2):178–86.

    Google Scholar 

  55. Rilinger JF, Smith CM, deRegnier RAO, Goldstein JL, Mills MG, Reynolds M, et al. Transcranial doppler identification of neurologic injury during pediatric extracorporeal membrane oxygenation therapy. J Stroke Cerebrovasc Dis. 2017;26(10):2336–45.

    Article  PubMed  Google Scholar 

  56. Thiagarajan RR, Barbaro RP, Rycus PT, McMullan DM, Conrad SA, Fortenberry JD, et al. Extracorporeal life support organization registry international report 2016. ASAIO. 2017;63(1):60–7.

    Article  Google Scholar 

  57. Bembea MM, Felling RJ, Caprarola SD, Ng DK, Tekes A, Boyle K, et al. Neurologic outcomes in a two-center cohort of neonatal and pediatric patients supported on extracorporeal membrane oxygenation. ASAIO. 2020;66(1):79–88.

    Article  Google Scholar 

  58. Barrett CS, Bratton SL, Salvin JW, Laussen PC, Rycus PT, Thiagarajan RR. Neurological injury after extracorporeal membrane oxygenation use to aid pediatric cardiopulmonary resuscitation. PCCM. 2009;10(4):445–51.

    Google Scholar 

  59. Waitzer E, Riley SP, Perreault T, Shevell MI. Neurologic outcome at school entry for newborns treated with extracorporeal membrane oxygenation for noncardiac indications. J Child Neurol. 2009;24(7):801–6.

    Article  PubMed  Google Scholar 

  60. Schiller RM, Madderom MJ, Reuser JJ, Steiner K, Gischler SJ, Tibboel D, et al. Neuropsychological follow-up after neonatal ECMO. Pediatrics. 2016;138(5):e20161313.

    Article  PubMed  Google Scholar 

  61. Bembea MM, Felling R, Anton B, Salorio CF, Johnston MV. Neuromonitoring during extracorporeal membrane oxygenation: a systematic review of the literature. PCCM. 2015;16(6):558–64.

    Google Scholar 

  62. Kwon HM, Park JH, Kim JM, Yoon BW. Mild left ventricular dysfunction is associated with thrombogenicity in cardioembolic stroke. Eur Neurol. 2006;56(4):217–21.

    Article  PubMed  Google Scholar 

  63. Yang Y, Grosset DG, Li Q, Lees KR. Identification of echocardiographic “smoke” in a bench model with transcranial doppler ultrasound. Stroke. 2000;31(4):907–14.

    Article  CAS  PubMed  Google Scholar 

  64. Asinger RW, Koehler J, Pearce LA, Zabalgoitia M, Blackshear JL, Fenster PE, et al. Pathophysiologic correlates of thromboembolism in nonvalvular atrial fibrillation: II. Dense spontaneous echocardiographic contrast (The Stroke Prevention in Atrial Fibrillation [SPAF-III] study). J A Soc Echocardiogr. 1999;12(12):1088–96.

    Article  CAS  Google Scholar 

  65. Ringelstein EB, Droste DW, Babikian VL, Evans DH, Grosset DG, Kaps M, et al. Consensus on microembolus detection by TCD. International consensus group on microembolus detection. Stroke. 1998;29(3):725–9.

    Article  CAS  PubMed  Google Scholar 

  66. Imaduddin SM, LaRovere KL, Kussman BD, Heldt T. A time-frequency approach for cerebral embolic load monitoring. IEEE Trans Biomed Eng. 2019;67(4):1007–18.

    Article  PubMed  Google Scholar 

  67. LaRovere KL, Kapur K, McElhinney DB, Razumovsky A, Kussman BD. Cerebral high-intensity transient signals during pediatric cardiac catheterization: a pilot study using transcranial doppler ultrasonography. J Neuroimaging. 2017;27(4):381–7.

    Article  PubMed  Google Scholar 

  68. Sanker P, Roth B, Frowein RA, Firsching R. Cerebral reperfusion in brain death of a newborn. Case report. Neurosurg Rev. 1992;15(4):315–7.

    CAS  PubMed  Google Scholar 

  69. Glasier CM, Seibert JJ, Chadduck WM, Williamson SL, Leithiser RE Jr. Brain death in infants: evaluation with doppler US. Radiology. 1989;172(2):377–80.

    Article  CAS  PubMed  Google Scholar 

  70. Bode H, Sauer M, Pringsheim W. Diagnosis of brain death by transcranial doppler sonography. Arch Dis Child. 1988;63(12):1474–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. World malaria report 2018. Geneva: World Health Organization; 2018.

    Google Scholar 

  72. Okiro EA, Al-Taiar A, Reyburn H, Idro R, Berkley JA, Snow RW. Age patterns of severe paediatric malaria and their relationship to plasmodium falciparum transmission intensity. Malar J. 2009;8(4):1–11.

    Google Scholar 

  73. Taylor TE. Caring for children with cerebral malaria: insights gleaned from 20 years on a research ward in Malawi. Trans R Soc Trop Med Hyg. 2009;103(Suppl 1):S6–10.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Nicole F. O’Brien .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2022 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

LaRovere, K.L., O’Brien, N.F. (2022). Applications of Transcranial Doppler Ultrasonography in Sickle Cell Disease, Stroke, and Critical Illness in Children. In: Ziai, W.C., Cornwell, C.L. (eds) Neurovascular Sonography . Springer, Cham. https://doi.org/10.1007/978-3-030-96893-9_19

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-96893-9_19

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-96892-2

  • Online ISBN: 978-3-030-96893-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics