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Published in: Child's Nervous System 1/2021

01-01-2021 | Pathology | Original Article

Radiologic-pathologic evidence of brain injury: hypoperfusion in the Papez circuit results in poor neurodevelopmental outcomes in neonatal hypoxic ischemic encephalopathy

Authors: Qiang Zheng, Angela N. Viaene, Colbey W. Freeman, Misun Hwang

Published in: Child's Nervous System | Issue 1/2021

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Abstract

Purpose

To provide radiologic-pathologic correlation of brain injury in the Papez circuit in hypoxic-ischemic encephalopathy (HIE) neonates and correlate radiologic findings with long-term neurodevelopmental outcomes.

Methods

Twenty full-term HIE neonates were evaluated. Cerebral blood flow (CBF) values, obtained through pulsed arterial spin labeling (ASL) perfusion-weighted MRI, were compared by permutation test to identify brain regions with statistically significant perfusion changes between 14 HIE neonates without evidence of developmental delay by Bayley-III (mean age 8.2 ± 7.2 days) and 6 HIE neonates with evidence of developmental delay (mean age 13.1 ± 8.0 days). Four histopathologic studies on specimens were taken from post-mortem brains of another group of infants (mean age 10 ± 6.8 days) with HIE. The infants were not the same ones who had MRIs.

Results

Significantly decreased perfusion in Papez circuit was found in HIE neonates with developmental delay compared with HIE neonates without delay. Decreased ASL perfusion values were seen in Papez circuit structures of the fornix (p = 0.002), entorhinal cortex (p = 0.048), amygdala (p = 0.036), hippocampus (p = 0.033), and thalamus (p = 0.036). In autopsy specimens of neonates with HIE, anoxic (eosinophilic) neurons, reactive astrocytes, and white matter rarefaction were observed in these regions, providing pathology correlation to the imaging findings of HIE.

Conclusion

The Papez circuit is susceptible to hypoxic-ischemic injury in neonates as demonstrated by perfusion-weighted imaging and histopathology. This sheds new light onto a possible non-familial mechanism of neuropsychiatric disease evolution initiated in the infant period and raises the potential for early identification of at-risk children.
Literature
1.
go back to reference Papez JW (1937) A proposed machanism for emotion. Arch Neurol Psychiatr 38:725–743CrossRef Papez JW (1937) A proposed machanism for emotion. Arch Neurol Psychiatr 38:725–743CrossRef
2.
go back to reference MacLean PD (1949) Psychosomatic disease and the "visceral brain": recent developments bearing on the Papez theory of emotion. Psychosom Med 11:338–353CrossRef MacLean PD (1949) Psychosomatic disease and the "visceral brain": recent developments bearing on the Papez theory of emotion. Psychosom Med 11:338–353CrossRef
3.
go back to reference Shah A, Jhawar SS, Goel A (2012) Analysis of the anatomy of the Papez circuit and adjoining limic system by fiber dissection techniques. J Clin Neurosci 19:289–298CrossRef Shah A, Jhawar SS, Goel A (2012) Analysis of the anatomy of the Papez circuit and adjoining limic system by fiber dissection techniques. J Clin Neurosci 19:289–298CrossRef
4.
go back to reference Concha L, Gross DW, Beaulieu C (2005) Diffusion tensor tractography of the limbic system. AJNR Am J Neuroradiol 26:2267–2274PubMed Concha L, Gross DW, Beaulieu C (2005) Diffusion tensor tractography of the limbic system. AJNR Am J Neuroradiol 26:2267–2274PubMed
5.
go back to reference Choi SH, Kim YB, Paek SH, Cho ZH (2019) Papez circuit observed by in vivo human brain with 7.0T MRI super-resolution track density imaging and track tracing. Front Neuroanat 18:13–17 Choi SH, Kim YB, Paek SH, Cho ZH (2019) Papez circuit observed by in vivo human brain with 7.0T MRI super-resolution track density imaging and track tracing. Front Neuroanat 18:13–17
6.
go back to reference Torrico TJ, Abdijadid S (2019) Neuroanatomy, limbic system. StatPearls Torrico TJ, Abdijadid S (2019) Neuroanatomy, limbic system. StatPearls
7.
go back to reference Roxo MR, Franceschini PR, Zubaran C, Kleber FD, Sander JW (2011) The limbic system conception and its historical evolution. Sci World J 11:2428–2441CrossRef Roxo MR, Franceschini PR, Zubaran C, Kleber FD, Sander JW (2011) The limbic system conception and its historical evolution. Sci World J 11:2428–2441CrossRef
8.
go back to reference Bubb EJ, Kinnavane L, Aggleton JP (2017) Hippocampal-diencephalic-cingulate networks for memory and emotion: an anatomical guide. Brain Neurosci Adv 1:2398212817723443CrossRef Bubb EJ, Kinnavane L, Aggleton JP (2017) Hippocampal-diencephalic-cingulate networks for memory and emotion: an anatomical guide. Brain Neurosci Adv 1:2398212817723443CrossRef
9.
go back to reference Yang DS, Kwon HG, Jang SH (2016) Injury of the thalamocingulate tract in the Papez circuit in patients with mild traumatic brain injury. Am J Phys Med Rehabil 95:e34–e38CrossRef Yang DS, Kwon HG, Jang SH (2016) Injury of the thalamocingulate tract in the Papez circuit in patients with mild traumatic brain injury. Am J Phys Med Rehabil 95:e34–e38CrossRef
10.
go back to reference Jang SH, Kwon HG (2018) Injury of the Papez circuit in a patient with traumatic spinal cord injury and concomitant mild traumatic brain injury. Neural Regen Res 13:161–162CrossRef Jang SH, Kwon HG (2018) Injury of the Papez circuit in a patient with traumatic spinal cord injury and concomitant mild traumatic brain injury. Neural Regen Res 13:161–162CrossRef
11.
go back to reference Escobar I, Xu J, Jackson CW, Perez-Pinzon MA (2019) Altered neural networks in the Papez circuit: implications for cognitive dysfunction after cerebral ischemia. J Alzheimers Dis 67:425–446CrossRef Escobar I, Xu J, Jackson CW, Perez-Pinzon MA (2019) Altered neural networks in the Papez circuit: implications for cognitive dysfunction after cerebral ischemia. J Alzheimers Dis 67:425–446CrossRef
12.
go back to reference Hisle-Gorman E, Susi A, Stokes T, Gorman G, Erdie-Lalena C, Nylund CM (2018) Prenatal, perinatal, and neonatal risk factors of autism spectrum disorder. Pediatr Res 84:190–198CrossRef Hisle-Gorman E, Susi A, Stokes T, Gorman G, Erdie-Lalena C, Nylund CM (2018) Prenatal, perinatal, and neonatal risk factors of autism spectrum disorder. Pediatr Res 84:190–198CrossRef
13.
go back to reference Badawi N, Dixon G, Felix JF, Keogh JM, Petterson B, Stanley FJ, Kurinczuk JJ (2006) Autism following a history of newborn encephalopathy: more than a coincidence? Dev Med Child Neurol 48:85–89CrossRef Badawi N, Dixon G, Felix JF, Keogh JM, Petterson B, Stanley FJ, Kurinczuk JJ (2006) Autism following a history of newborn encephalopathy: more than a coincidence? Dev Med Child Neurol 48:85–89CrossRef
14.
go back to reference Zornberg GL, Buka SL, Tsuang MT (2000) Hypoxic-ischemia-related fetal/neonatal complications and risk of schizophrenia and other nonaffective psychoses: a 19-year longitudinal study. Am J Psychiatry 157:196–202CrossRef Zornberg GL, Buka SL, Tsuang MT (2000) Hypoxic-ischemia-related fetal/neonatal complications and risk of schizophrenia and other nonaffective psychoses: a 19-year longitudinal study. Am J Psychiatry 157:196–202CrossRef
15.
go back to reference Zhao F, Yang J, Cui R (2017) Effect of hypoxic injury in mood disorder. Neural Plast 2017:1–10 Zhao F, Yang J, Cui R (2017) Effect of hypoxic injury in mood disorder. Neural Plast 2017:1–10
16.
go back to reference Haukvik UK, McNeil T, Lange EH, Melle I, Dale AM, Andreassen OA, Agartz I (2014) Pre- and perinatal hypoxia associated with hippocampus/amygdala volume in bipolar disorder. Psychol Med 44:975–985CrossRef Haukvik UK, McNeil T, Lange EH, Melle I, Dale AM, Andreassen OA, Agartz I (2014) Pre- and perinatal hypoxia associated with hippocampus/amygdala volume in bipolar disorder. Psychol Med 44:975–985CrossRef
17.
go back to reference Bayley N (2006) Bayley scales of infant and toddler development, third edn. Harcourt Assessment, Inc, San Antonio Bayley N (2006) Bayley scales of infant and toddler development, third edn. Harcourt Assessment, Inc, San Antonio
18.
go back to reference Alsop DC, Detre JA, Golay X, Gunther M, Hendrikse J, Hernandez-Garcia L, Lu H, Maclntosh BJ, Parkes LM, Smits M, van Osch MJ, Wang DJ, Wong EC, Zaharchuk G (2015) Recommended implementation of arterial spin labeled perfusion MRI for clinical applications: a consensus of the ISMRM perfusion study group and the European consortium for ASL in dementia. Magn Reson Med 73:102–116CrossRef Alsop DC, Detre JA, Golay X, Gunther M, Hendrikse J, Hernandez-Garcia L, Lu H, Maclntosh BJ, Parkes LM, Smits M, van Osch MJ, Wang DJ, Wong EC, Zaharchuk G (2015) Recommended implementation of arterial spin labeled perfusion MRI for clinical applications: a consensus of the ISMRM perfusion study group and the European consortium for ASL in dementia. Magn Reson Med 73:102–116CrossRef
19.
go back to reference Wang Z, Aguirre GK, Rao H, Wang J, Fernandez-Seara MA, Childress AR, Detre JA (2008) Empirical optimization of ASL data analysis using an ASL data processing toolbox: ASLtbx. Magn Reson Imaging 26:261–269CrossRef Wang Z, Aguirre GK, Rao H, Wang J, Fernandez-Seara MA, Childress AR, Detre JA (2008) Empirical optimization of ASL data analysis using an ASL data processing toolbox: ASLtbx. Magn Reson Imaging 26:261–269CrossRef
20.
go back to reference Herscovitch P, Raichle ME (1985) What is the correct value for the brain blood partition coefficient for water. J Cereb Blood Flow Metab 5:65–69CrossRef Herscovitch P, Raichle ME (1985) What is the correct value for the brain blood partition coefficient for water. J Cereb Blood Flow Metab 5:65–69CrossRef
21.
go back to reference Liu P, Chalak LF, Krishnamurthy LC, Mir I, Peng SL, Huang H, Lu H (2016) T1 and T2 values of human neonatal blood at 3 tesla: dependence on hematocrit, oxygenation, and temperature. Magn Reson Med 75:1730–1735CrossRef Liu P, Chalak LF, Krishnamurthy LC, Mir I, Peng SL, Huang H, Lu H (2016) T1 and T2 values of human neonatal blood at 3 tesla: dependence on hematocrit, oxygenation, and temperature. Magn Reson Med 75:1730–1735CrossRef
22.
go back to reference Cavusoglu M, Pfeuffer J, Ugurbil K, Uludag K (2009) Comparison of pulsed arterial spin labeling encoding schemes and absolute perfusion quantification. Magn Reson Imaging 27:1039–1045CrossRef Cavusoglu M, Pfeuffer J, Ugurbil K, Uludag K (2009) Comparison of pulsed arterial spin labeling encoding schemes and absolute perfusion quantification. Magn Reson Imaging 27:1039–1045CrossRef
23.
go back to reference Counsell SJ, Kennea NL, Herlihy AH, Allsop JM, Harrison MC, Cowan FM, Hajnal JV, Edwards B, Edwards AD, Rutherford MA (2003) T2 relaxation values in the developing preterm brain. AJNR Am J Neuroradiol 24:1654–1660PubMed Counsell SJ, Kennea NL, Herlihy AH, Allsop JM, Harrison MC, Cowan FM, Hajnal JV, Edwards B, Edwards AD, Rutherford MA (2003) T2 relaxation values in the developing preterm brain. AJNR Am J Neuroradiol 24:1654–1660PubMed
24.
go back to reference Feng L, Li H, Oishi K, Mishra Y, Song L, Peng Q, Ouyang M, Wang J, Slinger M, Jeon T, Lee L, Heyne R, Chalak L, Peng Y, Liu S, Huang H (2019) Age-specific gray and white matter DTI atlas for human brain at 33, 36 and 39 postmenstrual weeks. Neuroimage 185:685–698CrossRef Feng L, Li H, Oishi K, Mishra Y, Song L, Peng Q, Ouyang M, Wang J, Slinger M, Jeon T, Lee L, Heyne R, Chalak L, Peng Y, Liu S, Huang H (2019) Age-specific gray and white matter DTI atlas for human brain at 33, 36 and 39 postmenstrual weeks. Neuroimage 185:685–698CrossRef
25.
go back to reference Kurinzcuk JJ, White-Koning M, Badawi N (2010) Epidemiology of neonatal encephalopathy and hypoxic-ischaemic encephalopathy. Early Hum Dev 86:329–338CrossRef Kurinzcuk JJ, White-Koning M, Badawi N (2010) Epidemiology of neonatal encephalopathy and hypoxic-ischaemic encephalopathy. Early Hum Dev 86:329–338CrossRef
26.
go back to reference Miller SP, Ramaswarmy V, Michelson D, Barkovich AJ, Holshouser B, Wycliffe N, Glidden DV, Deming D, Partridge JC, Wu YW, Ashwal S, Ferriero DM (2005) Patterns of brain injury in term neonatal encephalopathy. J Pediatr 146:453–460CrossRef Miller SP, Ramaswarmy V, Michelson D, Barkovich AJ, Holshouser B, Wycliffe N, Glidden DV, Deming D, Partridge JC, Wu YW, Ashwal S, Ferriero DM (2005) Patterns of brain injury in term neonatal encephalopathy. J Pediatr 146:453–460CrossRef
27.
go back to reference Catani M, Dell'acqua F, de Schotten MT (2013) A revised limbic system model for memory, emotion and behaviour. Neurosci Biobehav Rev 37:1724–1737CrossRef Catani M, Dell'acqua F, de Schotten MT (2013) A revised limbic system model for memory, emotion and behaviour. Neurosci Biobehav Rev 37:1724–1737CrossRef
28.
go back to reference Tortora D, Mattei PA, Navarra R, Panara V, Salomone R, Rossi A, Detre JA, Caulo M (2017) Prematurity and brain perfusion: arterial spin labeling MRI. Neuroimage Clin 15:401–407CrossRef Tortora D, Mattei PA, Navarra R, Panara V, Salomone R, Rossi A, Detre JA, Caulo M (2017) Prematurity and brain perfusion: arterial spin labeling MRI. Neuroimage Clin 15:401–407CrossRef
29.
go back to reference Massaro AN, Jeromin A, Kadom N, Vezina G, Hayes RL, Wang KK, Streeter J, Johnston MV (2013) Serum biomarkers of MRI brain injury in neonatal hypoxic ischemic encephalopathy treated with whole-body hypothermia: a pilot study. Pediatr Crit Care Med 14:310–317CrossRef Massaro AN, Jeromin A, Kadom N, Vezina G, Hayes RL, Wang KK, Streeter J, Johnston MV (2013) Serum biomarkers of MRI brain injury in neonatal hypoxic ischemic encephalopathy treated with whole-body hypothermia: a pilot study. Pediatr Crit Care Med 14:310–317CrossRef
30.
go back to reference Delcour M, Russier M, Amin M, Baud O, Paban V, Barbe MF, Coq JO (2012) Impact of prenatal ischemia on behavior, cognitive abilities and neuroanatomy in adult rats with white matter damage. Behav Brain Res 232:233–244CrossRef Delcour M, Russier M, Amin M, Baud O, Paban V, Barbe MF, Coq JO (2012) Impact of prenatal ischemia on behavior, cognitive abilities and neuroanatomy in adult rats with white matter damage. Behav Brain Res 232:233–244CrossRef
31.
go back to reference Schmahmann JD, Sherman JC (1998) The cerebellar cognitive affective syndrome. Brain 121:561–579CrossRef Schmahmann JD, Sherman JC (1998) The cerebellar cognitive affective syndrome. Brain 121:561–579CrossRef
32.
go back to reference Bhatia KD, Henderson LA, Hsu E, Yim M (2018) Reduced integrity of the uncinate fasciculus and cingulum in depression: a stem-by-stem analysis. J Affect Disord 235:220–228CrossRef Bhatia KD, Henderson LA, Hsu E, Yim M (2018) Reduced integrity of the uncinate fasciculus and cingulum in depression: a stem-by-stem analysis. J Affect Disord 235:220–228CrossRef
33.
go back to reference Whitford TJ, Lee SW, Oh JS, Rd L-G, Savadjiev P, Alvarado JL, Westin CF, Niznikiewicz M, Nestor PG, McCarley RW, Kubicki M, Shenton ME (2014) Localized abnormalities in the cingulum bundle in patients with schizophrenia: a diffusion tensor tractography study. Neuroimage Clin 5:93–99CrossRef Whitford TJ, Lee SW, Oh JS, Rd L-G, Savadjiev P, Alvarado JL, Westin CF, Niznikiewicz M, Nestor PG, McCarley RW, Kubicki M, Shenton ME (2014) Localized abnormalities in the cingulum bundle in patients with schizophrenia: a diffusion tensor tractography study. Neuroimage Clin 5:93–99CrossRef
34.
go back to reference Catheline G, Periot O, Amirault M, Braun M, Dartigues JF, Auriacombe S, Allard M (2010) Distinctive alterations of the cingulum bundle during aging and Alzheimer's disease. Neurobiol Aging 31:1582–1592CrossRef Catheline G, Periot O, Amirault M, Braun M, Dartigues JF, Auriacombe S, Allard M (2010) Distinctive alterations of the cingulum bundle during aging and Alzheimer's disease. Neurobiol Aging 31:1582–1592CrossRef
35.
go back to reference Northington FJ, Chavez-Valdez R, Martin LJ (2011) Neuronal cell death in neonatal hypoxia-ischemia. Ann Neurol 69:743–758CrossRef Northington FJ, Chavez-Valdez R, Martin LJ (2011) Neuronal cell death in neonatal hypoxia-ischemia. Ann Neurol 69:743–758CrossRef
36.
go back to reference Greer DM (2006) Mechanisms of injury in hypoxic-ischemic encephalopathy: implications to therapy. Semin Neurol 26:373–379CrossRef Greer DM (2006) Mechanisms of injury in hypoxic-ischemic encephalopathy: implications to therapy. Semin Neurol 26:373–379CrossRef
37.
go back to reference Chen Y, Swanson RA (2003) Astrocytes and brain injury. J Cereb Blood Flow Metab 23:137–149CrossRef Chen Y, Swanson RA (2003) Astrocytes and brain injury. J Cereb Blood Flow Metab 23:137–149CrossRef
38.
go back to reference Zhang F, Liu C, Qian L, Hou H, Guo Z (2016) Diffusion tensor imaging of white matter injury caused by prematurity-induced hypoxic-ischemic brain damage. Med Sci Monit 22:2167–2174CrossRef Zhang F, Liu C, Qian L, Hou H, Guo Z (2016) Diffusion tensor imaging of white matter injury caused by prematurity-induced hypoxic-ischemic brain damage. Med Sci Monit 22:2167–2174CrossRef
39.
go back to reference Nakajima W, Ishida A, Lange MS, Gabrielson KL, Wilson MA, Martin LJ, Blue ME, Johnston MV (2000) Apoptosis has a prolonged role in the neurodegeneration after hypoxic ischemia in the newborn rat. J Neurosci 20:7994–8004CrossRef Nakajima W, Ishida A, Lange MS, Gabrielson KL, Wilson MA, Martin LJ, Blue ME, Johnston MV (2000) Apoptosis has a prolonged role in the neurodegeneration after hypoxic ischemia in the newborn rat. J Neurosci 20:7994–8004CrossRef
40.
go back to reference Ambrosio ALD, Pinsky DJ, Connolly ES (2001) The role of the complement cascade in ischemia/reperfusion injury: implications for neuroprotection. Mol Med 7:367–382CrossRef Ambrosio ALD, Pinsky DJ, Connolly ES (2001) The role of the complement cascade in ischemia/reperfusion injury: implications for neuroprotection. Mol Med 7:367–382CrossRef
41.
go back to reference Bubb EJ, Metzler-Baddeley C, Aggleton JP (2018) The cingulum bundle: anatomy, function, and dysfunction. Neurosci Biobehav Rev 104:104–127CrossRef Bubb EJ, Metzler-Baddeley C, Aggleton JP (2018) The cingulum bundle: anatomy, function, and dysfunction. Neurosci Biobehav Rev 104:104–127CrossRef
Metadata
Title
Radiologic-pathologic evidence of brain injury: hypoperfusion in the Papez circuit results in poor neurodevelopmental outcomes in neonatal hypoxic ischemic encephalopathy
Authors
Qiang Zheng
Angela N. Viaene
Colbey W. Freeman
Misun Hwang
Publication date
01-01-2021
Publisher
Springer Berlin Heidelberg
Published in
Child's Nervous System / Issue 1/2021
Print ISSN: 0256-7040
Electronic ISSN: 1433-0350
DOI
https://doi.org/10.1007/s00381-020-04795-0

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