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Dynamic magnetic resonance imaging findings in the early stages of neonatal hypoglycemic brain injury

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Abstract

Hypoglycemia is common among neonates and can cause neurological dysfunction. This study aimed to identify the specific time window to perform diffusion-weighted imaging (DWI) for detecting early brain injury in neonatal hypoglycemia and assess the clinical characteristics and neurological outcomes of different patterns of brain injury in neonatal hypoglycemia. We conducted a retrospective analysis of the changes in conventional magnetic resonance imaging (MRI) and DWI at different time points and clinical characteristics in 86 neonates with hypoglycemic brain injury. Among 139 DWI scans, 84 showed injury site hyperintensities within 7 days after hypoglycemia. Thirty-nine scans revealed low DWI and abnormal T1-/T2-weighted imaging signals within 11–23 days after onset, of which 21 showed DWI hyperintensities in the corpus callosum. Abnormal signals were undetected in the second scans of 13 infants within 9–20 days after onset. Vulnerable sites comprised the occipital lobe (98%), splenium of the corpus callosum (60%), and parietal lobe (30%). Compared with focal injury (n = 66), extensive injury (n = 20) had higher involvement of the internal capsule, basal ganglia, and thalamus (P < 0.05); higher incidence of recurrent convulsions, respiratory failure, and coma (P < 0.01); and a higher proportion of death and severe neurodevelopmental impairment (P < 0.05).

Conclusions: Neonatal hypoglycemic brain injury was most common in the occipital lobes. Severe clinical symptoms were significantly associated with extensive brain injury involving the internal capsule, basal ganglia, and thalamus, which could be attributed to hypoxia–ischemia and lead to a poor prognosis.

What is Known:

• There is no clear neurological safe threshold for hypoglycemia in neonates. Studies suggest that symptomatic hypoglycemia can be related to brain injury.

What is New:

• Severe clinical symptoms are significantly associated with extensive brain injury on MRI scans. Extensive brain injuries involving the internal capsule, basal ganglia, and thalamus, which could be due to associated hypoxia–ischemia and lead to a poor prognosis.

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Data availability

The original contributions generated for this study are included in the article/supplementary materials; further inquiries can be directed to the corresponding author.

Abbreviations

DWI:

Diffusion-weighted imaging

HIE:

Hypoxic–ischemic encephalopathy

MRI:

Magnetic resonance imaging

NDI:

Neurodevelopmental impairment

References

  1. Dani C, Corsini I (2020) Guidelines for management of neonatal hypoglycemia: are they actually applicable? JAMA Pediatr 174:638–639. https://doi.org/10.1001/jamapediatrics.2020.0632

    Article  PubMed  Google Scholar 

  2. McKinlay CJD, Alsweiler JM, Anstice NS, Burakevych N, Chakraborty A, Chase JG, Gamble GD, Harris DL, Jacobs RJ, Jiang Y, Paudel N, San Diego RJ, Thompson B, Wouldes TA, Harding JE (2017) Children With Hypoglycemia and Their Later Development (CHYLD) Study Team. Association of neonatal glycemia with neurodevelopmental outcomes at 4.5 Years. JAMA Pediatr 171:972–983. https://doi.org/10.1001/jamapediatrics.2017.1579

    Article  PubMed  PubMed Central  Google Scholar 

  3. Tin W (2014) Defining neonatal hypoglycaemia: a continuing debate. Semin Fetal Neonatal Med 19:27–32. https://doi.org/10.1016/j.siny.2013.09.003

    Article  PubMed  Google Scholar 

  4. Tam EW, Widjaja E, Blaser SI, Macgregor DL, Satodia P, Moore AM (2008) Occipital lobe injury and cortical visual outcomes after neonatal hypoglycemia. Pediatrics 122:507–512. https://doi.org/10.1542/peds.2007-2002

    Article  PubMed  Google Scholar 

  5. Filan PM, Inder TE, Cameron FJ, Kean MJ, Hunt RW (2006) Neonatal hypoglycemia and occipital cerebral injury. J Pediatr 148:552–555. https://doi.org/10.1016/j.jpeds.2005.11.015

    Article  PubMed  Google Scholar 

  6. Yalnizoglu D, Haliloglu G, Turanli G, Cila A, Topcu M (2007) Neurologic outcome in patients with MRI pattern of damage typical for neonatal hypoglycemia. Brain Dev 29:285–292. https://doi.org/10.1016/j.braindev.2006.09.011

    Article  PubMed  Google Scholar 

  7. Alkalay AL, Flores-Sarnat L, Sarnat HB, Moser FG, Simmons CF (2005) Brain imaging findings in neonatal hypoglycemia: case report and review of 23 cases. Clin Pediatr (Phila) 44:783–790. https://doi.org/10.1177/000992280504400906

    Article  Google Scholar 

  8. Banker BQ (1967) The neuropathological effects of anoxia and hypoglycemia in the newborn. Dev Med Child Neurol 9:544–550. https://doi.org/10.1111/j.1469-8749.1967.tb02323.x

    Article  PubMed  CAS  Google Scholar 

  9. Burns CM, Rutherford MA, Boardman JP, Cowan FM (2008) Patterns of cerebral injury and neurodevelopmental outcomes after symptomatic neonatal hypoglycemia. Pediatrics 122:65–74. https://doi.org/10.1542/peds.2007-2822

    Article  PubMed  Google Scholar 

  10. Inder T (2008) How low can I go? The impact of hypoglycemia on the immature brain. Pediatrics 122:440–441. https://doi.org/10.1542/peds.2008-1417

    Article  PubMed  Google Scholar 

  11. Parmentier CEJ, de Vries LS, van der Aa NE, Eijsermans MJC, Harteman JC, Lequin MH, Swanenburg de Veye HFN, Koopman-Esseboom C, Groenendaal F (2022) Hypoglycemia in infants with hypoxic-ischemic encephalopathy is associated with additional brain injury and worse neurodevelopmental outcome. J Pediatr 245:30-38.e1. https://doi.org/10.1016/j.jpeds.2022.01.051

    Article  PubMed  Google Scholar 

  12. Boardman JP, Hawdon JM (2015) Hypoglycaemia and hypoxic-ischaemic encephalopathy. Dev Med Child Neurol 57(Suppl 3):29–33. https://doi.org/10.1111/dmcn.12729

    Article  PubMed  Google Scholar 

  13. Wong DS, Poskitt KJ, Chau V, Miller SP, Roland E, Hill A, Tam EW (2013) Brain injury patterns in hypoglycemia in neonatal encephalopathy. AJNR Am J Neuroradiol 34:1456–1461. https://doi.org/10.3174/ajnr.A3423

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. De Angelis LC, Brigati G, Polleri G, Malova M, Parodi A, Minghetti D, Rossi A, Massirio P, Traggiai C, Maghnie M, Ramenghi LA (2021) Neonatal hypoglycemia and brain vulnerability. Front Endocrinol (Lausanne) 12:634305. https://doi.org/10.3389/fendo.2021.634305

    Article  Google Scholar 

  15. Bayley N (1993) Manual for the Bayley scales of infant development, 2nd edn. Psychological Corporation, San Antonio, TX

    Google Scholar 

  16. Onder H (2016) Reversible diffusion restriction in the splenium of the corpus callosum due to severe hypoglycemia: a case report and literature review. J Neuroradiol 43:419–421. https://doi.org/10.1016/j.neurad.2016.05.005

    Article  PubMed  Google Scholar 

  17. Maruya J, Endoh H, Watanabe H, Motoyama H, Abe H (2007) Rapid improvement of diffusion-weighted imaging abnormalities after glucose infusion in hypoglycaemic coma. J Neurol Neurosurg Psychiatry 78:102–103. https://doi.org/10.1136/jnnp.2006.096776

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Landais A (2015) Reversible splenium diffusion weighted MRI changes associated with hypoglycemia. J Diabetes Complications 29:607–610. https://doi.org/10.1016/j.jdiacomp.2015.02.012

    Article  PubMed  Google Scholar 

  19. Kim JH, Koh SB (2007) Extensive white matter injury in hypoglycemic coma. Neurology 68:1074. https://doi.org/10.1212/01.wnl.0000258546.83251.36

    Article  PubMed  Google Scholar 

  20. Righini A, Doneda C, Parazzini C, Arrigoni F, Matta U, Triulzi F (2010) Diffusion tensor imaging of early changes in corpus callosum after acute cerebral hemisphere lesions in newborns. Neuroradiology 52:1025–1035. https://doi.org/10.1007/s00234-010-0745-y

    Article  PubMed  Google Scholar 

  21. Epelman M, Daneman A, Halliday W, Whyte H, Blaser SI (2012) Abnormal corpus callosum in neonates after hypoxic-ischemic injury. Pediatr Radiol 42:321–330. https://doi.org/10.1007/s00247-011-2238-5

    Article  PubMed  Google Scholar 

  22. Wagenaar N, Chau V, Groenendaal F, Kersbergen KJ, Poskitt KJ, Grunau RE, Synnes A, Duerden EG, de Vries LS, Miller SP, Benders MJNL (2017) Clinical risk factors for punctate white matter lesions on early magnetic resonance imaging in preterm newborns. J Pediatr 182:34-40.e1. https://doi.org/10.1016/j.jpeds.2016.11.073

    Article  PubMed  Google Scholar 

  23. Kelly CJ, Arulkumaran S, Tristão Pereira C, Cordero-Grande L, Hughes EJ, Teixeira RPAG, Steinweg JK, Victor S, Pushparajah K, Hajnal JV, Simpson J, Edwards AD, Rutherford MA, Counsell SJ (2019) Neuroimaging findings in newborns with congenital heart disease prior to surgery: an observational study. Arch Dis Child 104:1042–1048. https://doi.org/10.1136/archdischild-2018-314822

    Article  PubMed  Google Scholar 

  24. de Courten-Myers GM, Xi G, Hwang JH, Dunn RS, Mills AS, Holland SK, Wagner KR, Myers RE (2000) Hypoglycemic brain injury: potentiation from respiratory depression and injury aggravation from hyperglycemic treatment overshoots. J Cereb Blood Flow Metab 20:82–92. https://doi.org/10.1097/00004647-200001000-00012

    Article  PubMed  Google Scholar 

  25. Auer RN, Siesjö BK (1993) Hypoglycaemia: brain neurochemistry and neuropathology. Baillieres Clin Endocrinol Metab 7:611–625. https://doi.org/10.1016/s0950-351x(05)80210-1

    Article  PubMed  CAS  Google Scholar 

  26. Kim DE, Park SH, Kim SK, Nam HW, Lee YS, Chung JK, Roh JK (2000) Hypoglycemia-induced cerebellar dysfunction and quantitative positron emission tomography study. Neurology 55:418–422. https://doi.org/10.1212/wnl.55.3.418

    Article  PubMed  CAS  Google Scholar 

  27. Johkura K, Nakae Y, Kudo Y, Yoshida TN, Kuroiwa Y (2012) Early diffusion MR imaging findings and short-term outcome in comatose patients with hypoglycemia. AJNR Am J Neuroradiol 33:904–909. https://doi.org/10.3174/ajnr.A2903

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Yoneda Y, Yamamoto S (2005) Cerebral cortical laminar necrosis on diffusion-weighted MRI in hypoglycaemic encephalopathy. Diabet Med 22:1098–1100. https://doi.org/10.1111/j.1464-5491.2005.01568.x

    Article  PubMed  CAS  Google Scholar 

  29. Thompson-Branch A, Havranek T (2017) Neonatal hypoglycemia. Pediatr Rev 38:147–157. https://doi.org/10.1542/pir.2016-0063

    Article  PubMed  Google Scholar 

  30. Thornton PS, Stanley CA, De Leon DD, Harris D, Haymond MW, Hussain K, Levitsky LL, Murad MH, Rozance PJ, Simmons RA, Sperling MA, Weinstein DA, White NH, Wolfsdorf JI (2015) Pediatric Endocrine Society. Recommendations from the pediatric endocrine society for evaluation and management of persistent hypoglycemia in neonates, infants, and children. J Pediatr 167:238–245. https://doi.org/10.1016/j.jpeds.2015.03.057

    Article  PubMed  Google Scholar 

  31. Stanley CA, Rozance PJ, Thornton PS, De Leon DD, Harris D, Haymond MW, Hussain K, Levitsky LL, Murad MH, Simmons RA, Sperling MA, Weinstein DA, White NH, Wolfsdorf JI (2015) Re-evaluating “transitional neonatal hypoglycemia”: mechanism and implications for management. J Pediatr 166:1520–5.e1. https://doi.org/10.1016/j.jpeds.2015.02.045

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We want to appreciate the radiologists of the Shengjing Hospital for their support and help in reassessing the head magnetic resonance imaging scans.

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Authors and Affiliations

  1. Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China

    Yi Zhang, Dan Chen, Yalian Ji, Wenting Yu & Jian Mao

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  1. Yi Zhang
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  2. Dan Chen
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  4. Wenting Yu
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Contributions

Yi Zhang and Jian Mao contributed to the study conception and design. Yi Zhang, Dan Chen, Yalian Ji, and Wenting Yu performed the material preparation, data collection, and analysis. Yi Zhang wrote the first draft of the manuscript, and all authors read and approved the final manuscript.

Corresponding author

Correspondence to Jian Mao.

Ethics declarations

Ethics approval

This study was performed in line with the principles of the Declaration of Helsinki. The study design was approved by the ethics committee of Shengjing Hospital (approval no: 2020PS609K).

Consent to participate

The need for informed consent was waived because of the study’s retrospective nature. Parental consent was obtained for the magnetic resonance imaging examinations.

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Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Communicated by Daniele De Luca

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Zhang, Y., Chen, D., Ji, Y. et al. Dynamic magnetic resonance imaging findings in the early stages of neonatal hypoglycemic brain injury. Eur J Pediatr 181, 4167–4174 (2022). https://doi.org/10.1007/s00431-022-04637-y

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  • DOI: https://doi.org/10.1007/s00431-022-04637-y

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