Brainstem hypoxic–ischemic lesions on MRI in infants treated with therapeutic cooling: effects on the length of stay and mortality

Abstract

Objective

To test the hypothesis that brainstem hypoxic–ischemic injury on magnetic resonance imaging (MRI) would be independently associated with short-term outcomes in cooled asphyxiated infants.

Methods

A total of 90 consecutively cooled asphyxiated infants who survived to have brain MRI were reviewed. A neuroradiologist who was masked to outcomes evaluated MRI images for brainstem involvement. Outcomes were mortality and length of stay.

Results

Brainstem lesions were present on post-cooling brain MRI in 20 of the 90 infants (22%). Overall, four infants died before discharge, and all four had brainstem involvement. The infants with brainstem involvement had longer hospital stay (29 days, IQR 20–47 versus 16 days, IQR 10–26; P = 0.0001), compared to infants without brainstem lesions (n = 70); and upon multivariate analysis, brainstem involvement remained independently associated with prolonged hospital stay (β = 12.4, P = 0.001).

Conclusion

This study demonstrates the importance of recognizing brainstem injury for the prediction of short-term outcomes in cooled asphyxiated infants.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1: Brain MRI displaying brainstem involvement.

References

  1. 1.

    Leech RW, Alvord EC Jr. Anoxic ischemic encephalopathy in the human neonatal period: the significance of brain stem involvement. Arch Neurol. 1977;34:109–13.

    CAS  Article  Google Scholar 

  2. 2.

    Roland EH, Hill A, Norman MG, Flodmark O, MacNab AJ. Selective brainstem injury in an asphyxiated newborn. Ann Neurol. 1988;23:89–92.

    CAS  Article  Google Scholar 

  3. 3.

    Quattrocchi CC, Fariello G, Longo D. Brainstem tegmental lesions in neonates with hypoxic- ischemic encephalopathy: magnetic resonance diagnosis and clinical outcome. World J Radiol. 2016;8:117–23.

    Article  Google Scholar 

  4. 4.

    Logitharajah P, Rutherford MA, Cowan FM. Hypoxic-ischemic encephalopathy in preterm infants: antecedent factors, brain imaging, and outcome. Pediatr Res. 2009;66:222–9.

    Article  Google Scholar 

  5. 5.

    Martinez-Biarge M, Diez-Sebastian J, Kapellou O, Gindner D, Allsop JM, Rutherford MA, et al. Predicting motor outcome and death in term hypoxicischemic encephalopathy. Neurology. 2011;76:2055–61.

    CAS  Article  Google Scholar 

  6. 6.

    Martinez-Biarge M, Diez-Sebastian J, Wusthoff CJ, Lawrence S, Aloysius A, Rutherford MA, et al. Feeding and communication impairments in infants with central grey matter lesions following perinatal hypoxic-ischaemic injury. Eur J Paediatr Neurol. 2012;16:688–96.

    Article  Google Scholar 

  7. 7.

    Barkovich AJ, Westmark K, Partridge C, Sola A, Ferriero DM. Perinatal asphyxia: MR findings in the first 10 days. AJNR Am J Neuroradiol. 1995;16:427–38.

    CAS  PubMed  Google Scholar 

  8. 8.

    Myers RE. Two patterns of perinatal brain damage and their conditions of occurrence. Am J Obstet Gynecol. 1972;112:246–76.

    CAS  Article  Google Scholar 

  9. 9.

    Shankaran S, Laptook AR, Ehrenkranz RA, Tyson JE, McDonald SA, Donovan EF, et al. National Institute of Child Health and Human Development Neonatal Research Network. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med. 2005;353:1574–84.

    CAS  Article  Google Scholar 

  10. 10.

    Ambalavanan N, Carlo WA, Shankaran S, Bann CM, Emrich SL, Higgins RD, et al. National Institute of Child Health and Human Development Neonatal Research Network. Predicting outcomes of neonates diagnosed with hypoxemic–ischemic encephalopathy. Pediatrics. 2006;118:2084–93.

    Article  Google Scholar 

  11. 11.

    Barkovich AJ, Hajnal BL, Vigneron D, Sola A, Patridge JC, Allen F, et al. Prediction of neuromotor outcome in perinatal asphyxia: evaluation of MR scoring systems. Am J Neuroradiol. 1998;19:143–9.

    CAS  PubMed  Google Scholar 

  12. 12.

    Sarkar S, Donn SM, Bapuraj JR, Bhagat I, Barks JD. Distribution and severity of hypoxic–ischemic lesions on brain MRI following therapeutic cooling: selective head versus whole body cooling. Arch Dis Child Fetal Neonatol Ed. 2012;97:F335–9.

    Article  Google Scholar 

  13. 13.

    Sarkar S, Bhagat I, Bapuraj JR, Dechert RE, Donn SM. Does clinical status 1 week after therapeutic hypothermia predict brain MRI abnormalities? J Perinatol. 2013;33:538–42.

    CAS  Article  Google Scholar 

  14. 14.

    Gupta S, Bapuraj JR, Carlson G, Trumpower E, Dechert RE, Sarkar S. Predicting the need for home gavage or g-tube feeds in asphyxiated neonates treated with therapeutic hypothermia. J Perinatol. 2018;38:728–33.

    Article  Google Scholar 

  15. 15.

    Rutherford MA. The asphyxiated term infant. In: Rutherford M, editor. MRI of the neonatal brain. London: Saunders; 2002. p. 99–128.

  16. 16.

    Cowan F, Rutherford M, Groenendaal F, Eken P, Mercuri E, Bydder GM, et al. Origin and timing of brain lesions in term infants with neonatal encephalopathy. Lancet. 2003;361:736–42.

    Article  Google Scholar 

  17. 17.

    Miller SP, Ramaswamy V, Michelson D, Barkovich AJ, Holshouser B, Wycliffe N, et al. Patterns of brain injury in term neonatal encephalopathy. J Pediatr. 2005;146:453–60.

    Article  Google Scholar 

  18. 18.

    Shankaran S, McDonald SA, Laptook AR, Hintz SR, Barnes PD, Das A, et al. Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Neonatal magnetic resonance imaging pattern of brain injury as a biomarker of childhood outcomes following a trial of hypothermia for neonatal hypoxic-ischemic encephalopathy. J Pediatr. 2015;167:987–93.

    Article  Google Scholar 

  19. 19.

    Arca-Dı azG, Re TJ, Drottar M, Fortuno CR, De Macedo-Rodrigues K, Im K, et al. Can cerebellar and brainstem apparent diffusion coefficient (ADC) values predict neuromotor outcome in term neonates with hypoxic-ischemic encephalopathy (HIE) treatedwith hypothermia? PLoS ONE. 2017;12:e0178510.

    Article  Google Scholar 

  20. 20.

    Quattrocchi CC, Longo D, Delfino LN, Cilio MR, Piersigilli F, Capua MD, et al. Dorsal brain stem syndrome: MR imaging location of brain stem tegmental lesions in neonates with oral motor dysfunction. AJNR Am J Neuroradiol. 2010;31:1438–42.

  21. 21.

    Rutherford M, Ramenghi LA, Edwards AD, Brocklehurst P, Halliday H, Levene M, et al. Assessment of brain tissue injury after moderate hypothermia in neonates with hypoxic–ischaemic encephalopathy: a nested subset of a randomised control trial. Lancet Neurol. 2010;9:39–45.

    Article  Google Scholar 

  22. 22.

    Cheong JL, Coleman L, Hunt RW, Lee KJ, Doyle LW, Inder TE, et al. Prognostic utility of magnetic resonance imaging in neonatal hypoxic‒ischemic encephalopathy: substudy of a randomized trial. Arch Pediatr Adolesc Med. 2012;166:634–40.

    Article  Google Scholar 

  23. 23.

    Shankaran S, Barnes PD, Hintz SR, Laptook AR, Zaterka-Baxter KM, McDonald SA, et al. Brain injury following trial of hypothermia for neonatal hypoxic‒ischaemic encephalopathy. Arch Dis Child Fetal Neonatal Ed. 2012;97:F398–404.

    PubMed  PubMed Central  Google Scholar 

  24. 24.

    Gulati IK, Shubert TR, Sitaram S, Wei L, Jadcherla SR. Effects of birth asphyxia on the modulation of pharyngeal provocation-induced adaptive reflexes. Am J Physiol Gastrointest Liver Physiol. 2015;309:G662–9.

    CAS  Article  Google Scholar 

  25. 25.

    Massaro AN, Murthy K, Zaniletti I, Cook N, DiGeronimo R, Dizon M, et al. Short-term outcomes after perinatal hypoxic ischemic encephalopathy: a report from the Children’s Hospitals Neonatal Consortium HIE focus group. J Perinatol. 2015;35:290–6.

    CAS  Article  Google Scholar 

  26. 26.

    Takashima S, Becker LE. Relationship between abnormal respiratory control and perinatal brainstem and cerebellar infarctions. Pediatr Neurol. 1989;5:211–4.

    CAS  Article  Google Scholar 

  27. 27.

    Sarnat HB. Watershed infarcts in the fetal and neonatal brainstem. An aetiology of central hypoventilation, dysphagia, Mo¨bius syndrome and micrognathia. Eur J Pediatr Neurol. 2004;8:71–87.

    Article  Google Scholar 

  28. 28.

    Saito K. Reflections on the brainstem dysfunction in neurologically disabled children. Brain Dev. 2009;31:529–36.

    Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Contributions

Subrata Sarkar, MD, developed the study concept, design, and analysis. He also critically revised and approved the final paper. Siddhartha Sarkar collected the data and provided critical input into the analysis of the data. He wrote the first draft of the paper and received input from the authors below as part of the paper revision. Other co-investigators (Suneeti Gupta, MD; Jayapalli Bapuraj, MD; and Ronald E. Dechert, RRT) provided critical input into the design and analysis of the study. They also critically revised and approved the final paper.

Corresponding author

Correspondence to Subrata Sarkar.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Sarkar, S.S., Gupta, S., Bapuraj, J.R. et al. Brainstem hypoxic–ischemic lesions on MRI in infants treated with therapeutic cooling: effects on the length of stay and mortality. J Perinatol (2020). https://doi.org/10.1038/s41372-020-00873-y

Download citation

Search

Quick links