Child's Nervous System

, Volume 35, Issue 2, pp 295–300 | Cite as

Age-associated hippocampal volume changes in childhood arterial ischemic stroke

  • Zak Ritchey
  • David M. Mirsky
  • David Weitzenkamp
  • Timothy J. Bernard
  • Paco S. Herson
  • Nicholas V. StenceEmail author
Original Paper



Recent evidence suggests that recovery from secondary neurodegeneration following arterial ischemic stroke (AIS) may be related to age at injury and site of occlusion. We conducted a study of hippocampal volume (HCV) in a cohort of pediatric patients with middle cerebral artery (MCA) territory AIS to determine whether HCV would be preserved in younger children as compared to older children.


This single-center, HIPAA-compliant retrospective study was approved by the institutional review board. The medical records of 149 children treated for AIS between 2000 and 2016 were reviewed for inclusion criteria: unilateral MCA territory AIS and availability of high-resolution T1-weighted MR imaging at both acute and chronic time periods. Manual segmentation was utilized to measure stroke-side HCV, contralateral HCV, hemispheric volumes, and stroke volume on each scan. To correct for variable brain size, HCV measurements were ratio normalized. Patients were divided into two age-at-stroke groups: younger (30 days–9 years old) and older (> 9–18 years old). Analysis was performed using Fisher’s test or Student’s t test.


The MR imaging of 19 children (9 younger, 10 older) was analyzed. At follow-up, the average stroke-side HCV increased by 10.9% in the younger group and decreased by 6.3% in the older group (P = 0.010); this between-group difference remained significant even when ratio normalized (P = 0.003). The total brain volume-adjusted acute stroke size between groups was not statistically different (P = 0.649).


In children with AIS, younger age is associated with the relative preservation of HCV, which could reflect differences in age-related plasticity.


Magnetic resonance imaging Arterial ischemic stroke Pediatric stroke Hippocampal volume 



This study was funded by the American Heart Association Predoctoral Fellowship to Z.R. (Award 15PRE25550151), the American Stroke Association/Bugher Foundation Stroke Collaborative Research Center (Grant 14BFSC17540000), and the Maternal and Child Health Bureau 340B Program at the Mountain States Hemophilia and Thrombosis Center.

Compliance with ethical standards

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Ethical approval

For this type of study, formal consent was not required.

Supplementary material

381_2018_4021_MOESM1_ESM.pdf (142 kb)
ESM 1 (PDF 141 kb)


  1. 1.
    Xie M, Yi C, Luo X, Xu S, Yu Z, Tang Y, Zhu W, Du Y, Jia L, Zhang Q, Dong Q, Zhu W, Zhang X, Bu B, Wang W (2011) Glial gap junctional communication involvement in hippocampal damage after middle cerebral artery occlusion. Ann Neurol 70(1):121–132. CrossRefGoogle Scholar
  2. 2.
    Tang X, Wang C, Xia L, Zhu W, Zhao L, Zhu W (2012) Volumetric MRI and 1H MRS study of hippocampus in unilateral MCAO patients: relationship between hippocampal secondary damage and cognitive disorder following stroke. Eur J Radiol 81(10):2788–2793. CrossRefGoogle Scholar
  3. 3.
    Max JE, Bruce M, Keatley E, Delis D (2010) Pediatric stroke: plasticity, vulnerability, and age of lesion onset. J Neuropsychiatry Clin Neurosci 22(1):30–39. CrossRefGoogle Scholar
  4. 4.
    Westmacott R, Askalan R, Macgregor D, Anderson P, Deveber G (2010) Cognitive outcome following unilateral arterial ischaemic stroke in childhood: effects of age at stroke and lesion location. Dev Med Child Neurol 52(4):386–393. CrossRefGoogle Scholar
  5. 5.
    Orfila JE, Grewal H, Bernard TJ, Macklin WB, Traystman RJ, Herson PS (2015) Neurophysiological responses of recovery in pediatric mice compared to adult mice with transient focal cerebral ischemia. [abstract]. Stroke 46:A19–A19Google Scholar
  6. 6.
    Bernard TJ, Manco-Johnson MJ, Lo W, MacKay MT, Ganesan V (2012) Towards a consensus-based classification of childhood arterial ischemic stroke. Stroke 43(2):371–377CrossRefGoogle Scholar
  7. 7.
    Boccardi M, Bocchetta M, Apostolova LG, Barnes J, Bartzokis G, Corbetta G, DeCarli C, deToledo-Morrell L, Firbank M, Ganzola R, Gerritsen L, Henneman W, Killiany RJ, Malykhin N, Pasqualetti P, Pruessner JC, Redolfi A, Robitaille N, Soininen H, Tolomeo D, Wang L, Watson C, Wolf H, Duvernoy H (2015) Duchesne S16, Jack CR Jr, Frisoni GB; EADC-ADNI working group on the harmonized protocol for manual hippocampal segmentation. Delphi definition of the EADC-ADNI harmonized protocol for hippocampal segmentation on magnetic resonance. Alzheimers Dement 11(2):126–138. CrossRefGoogle Scholar
  8. 8.
    Oppenheim C, Samson Y, Manai R, Lalam T, Vandamme X, Crozier S, Srour A, Cornu P, Dormont D, Rancurel G, Marsault C (2000) Prediction of malignant middle cerebral artery infarction by diffusion-weighted imaging. Stroke 31(9):2175–2181CrossRefGoogle Scholar
  9. 9.
    Uematsu A, Matsui M, Tanaka C, Takahashi T, Noguchi K, Suzuki M, Nishijo H (2012) Developmental trajectories of amygdala and hippocampus from infancy to early adulthood in healthy individuals. PLoS One 7(10):e46970. CrossRefGoogle Scholar
  10. 10.
    Hickey RW, Painter MJ (2006) Brain injury from cardiac arrest in children. Neurol Clin 24(1):147–158. CrossRefGoogle Scholar
  11. 11.
    Deng G, Yonchek J, Quillinan N, Strnad FA, Exo J, Herson PS, Traystman RJ (2014) A novel mouse model of pediatric cardiac arrest and cardiopulmonary resuscitation reveals age-dependent neuronal sensitivities to ischemic injury. J Neurosci Methods 222:34–41. CrossRefGoogle Scholar
  12. 12.
    Gold JJ, Trauner DA (2014) Hippocampal volume and memory performance in children with perinatal stroke. Pediatr Neurol 50(1):18–25. CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Internal MedicineUniversity of California IrvineOrangeUSA
  2. 2.Department of Radiology, Children’s Hospital ColoradoUniversity of Colorado DenverAuroraUSA
  3. 3.Department of Biostatistics and InformaticsColorado School of Public HealthAuroraUSA
  4. 4.Section of Child Neurology, Department of PediatricsUniversity of Colorado School of Medicine and Children’s Hospital ColoradoAuroraUSA
  5. 5.Department of AnesthesiologyUniversity of Colorado School of MedicineAuroraUSA

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