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. 2025 Feb;97(3):1140-1146.
doi: 10.1038/s41390-024-03531-7. Epub 2024 Aug 27.

Perinatal arterial ischemic stroke diagnosed in infants receiving therapeutic hypothermia for hypoxic-ischemic encephalopathy

Fernando F Gonzalez  1 , Sarah E Monsell  2 , Marie-Coralie Cornet  3 , Hannah Glass  4 , Jessica Wisnowski  5 , Amit Mathur  6 , Robert McKinstry  7 , Yi Li  8 , Tai-Wei Wu  9 , Dennis E Mayock  10 , Patrick J Heagerty  2 , Sandra E Juul  10 , Yvonne W Wu  4
Affiliations

Perinatal arterial ischemic stroke diagnosed in infants receiving therapeutic hypothermia for hypoxic-ischemic encephalopathy

Fernando F Gonzalez et al. Pediatr Res. 2025 Feb.

Abstract

Background: Both perinatal arterial ischemic stroke (PAIS) and hypoxic-ischemic encephalopathy (HIE) can present with neonatal encephalopathy. We hypothesized that among infants undergoing therapeutic hypothermia, presence of PAIS is associated with a higher risk of seizures and a lower risk of persistent encephalopathy after rewarming.

Methods: We studied 473 infants with moderate or severe HIE enrolled in the HEAL Trial who received a brain MRI. We defined PAIS as focal ischemic infarct(s) within an arterial distribution, and HIE pattern of brain injury as central gray, peripheral watershed, or global injury. We compared the risk of seizures (clinically suspected or electrographic), and of an abnormal 5-day Sarnat exam, in infants with and without PAIS.

Results: PAIS was diagnosed in 21(4%) infants, most of whom (16/21, 76%) also had concurrent HIE pattern of brain injury. Infants with PAIS were more likely to have seizures (RR 2.4, CI 2.8-3.3) and persistent moderate or severe encephalopathy on 5-day Sarnat exam (RR 2.5, 95% CI 1.9-3.4).

Conclusion: Among infants undergoing therapeutic hypothermia, PAIS typically occurs with concurrent HIE pattern brain injury. The higher rate of encephalopathy after rewarming in infants with PAIS may be due to the frequent co-existence of PAIS and HIE patterns of injury.

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Conflict of interest statement

Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: The study protocol, site-specific informed consent forms, participant education and recruitment materials and all study modifications were approved by the local Institutional Review Board at each of the participating sites. Parents provided written permission for their child’s participation in the HEAL trial. Safety and progress reports were provided to the NIH-appointed data safety monitoring committee every 6 months.

Figures

Fig. 1
Fig. 1. Axial Apparent Diffusion Coefficient (ADC) maps of six patients with perinatal arterial ischemic stroke (PAIS).
a Infant with reduced diffusion (arrowheads) compatible with PAIS involving the entire right MCA territory. No background features of HIE were present. b Infant with left MCA territory focal reduced diffusion (arrowheads) compatible with embolic PAIS. Concomitant HIE pattern brain injury is also present, with reduced diffusion involving the thalami and cortical spinal tracts (white arrows). Additional mild reduced diffusion involving bilateral parietal occipital cortex and subcortical white matter (black arrows), as can be seen with a HIE peripheral watershed pattern of injury. c Infant with focal reduced diffusion in right MCA territory (arrowheads) compatible with PAIS and concordant peripheral HIE brain injury pattern (black arrows). d Infant with reduced diffusion in left caudate (arrowheads) compatible with PAIS and concordant central HIE pattern (white arrows, lateral putamen) and focal hemorrhage (gray arrow). e Infant with reduced diffusion in MCA territory, bilaterally, compatible with multiple PAIS. f Infant with multiple focal areas of reduced diffusivity in ACA and MCA territories, bilaterally, compatible with multiembolic PAIS.
See this image and copyright information in PMC

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