Advertisement
Clinical paper| Volume 182, 109634, January 2023

Download started.

Ok

Limbic pathway vulnerability associates with neurologic outcome in children after cardiac arrest

      Abstract

      Aim

      To analyze whether brain connectivity sequences including diffusion tensor imaging (DTI) and resting state functional magnetic resonance imaging (rsfMRI) identify vulnerable brain regions and networks associated with neurologic outcome after pediatric cardiac arrest.

      Methods

      Children aged 2 d-17 y with cardiac arrest were enrolled in one of 2 parent studies at a single center. Clinically indicated brain MRI with DTI and rsfMRI and performed within 2 weeks after arrest were analyzed. Tract-wise fractional anisotropy (FA) and axial, radial, and mean diffusivity assessed DTI, and functional connectivity strength (FCS) assessed rsfMRI between outcome groups. Unfavorable neurologic outcome was defined as Pediatric Cerebral Performance Category score 4–6 or change > 1 between 6 months after arrest vs baseline.

      Results

      Among children with DTI (n = 28), 57% had unfavorable outcome. Mean, radial, axial diffusivity and FA of varying direction of magnitude in the limbic tracts, including the right cingulum parolfactory, left cingulum parahippocampal, corpus callosum forceps major, and corpus callosum forceps minor tracts, were associated with unfavorable neurologic outcome (p < 0.05). Among children with rsfMRI (n = 12), 67% had unfavorable outcome. Decreased FCS in the ventromedial and dorsolateral prefrontal cortex, insula, precentral gyrus, anterior cingulate, and inferior parietal lobule were correlated regionally with unfavorable neurologic outcome (p < 0.05 Family-Wise Error corrected).

      Conclusion

      Decreased multimodal connectivity measures of paralimbic tracts were associated with unfavorable neurologic outcome after pediatric cardiac arrest. Longitudinal analysis correlating brain connectivity sequences with long term neuropsychological outcomes to identify the impact of pediatric cardiac arrest in vulnerable brain networks over time appears warranted.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Resuscitation
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Holmberg M.J.
        • Ross C.E.
        • Fitzmaurice G.M.
        • et al.
        Annual incidence of adult and pediatric in-hospital cardiac arrest in the United States.
        Circul Cardiovas Qual Outcomes. 2019; 12: e005580
        • Atkins D.L.
        • Everson-Stewart S.
        • Sears G.K.
        • Daya M.
        • Osmond M.H.
        • Warden C.R.
        • et al.
        Epidemiology and outcomes from out-of-hospital cardiac arrest in children: the Resuscitation Outcomes Consortium Epistry-Cardiac Arrest.
        Circulation. 2009; 119: 1484-1491
        • Holmberg M.J.
        • Wiberg S.
        • Ross C.E.
        • et al.
        Trends in survival after pediatric in-hospital cardiac arrest in the United States.
        Circulation. 2019; 140: 1398-1408
        • Fink E.L.
        • Prince D.K.
        • Kaltman J.R.
        • et al.
        Unchanged pediatric out-of-hospital cardiac arrest incidence and survival rates with regional variation in North America.
        Resuscitation. 2016; 107: 121-128
        • Slomine B.S.
        • Silverstein F.S.
        • Christensen J.R.
        • Page K.
        • Holubkov R.
        • Dean J.M.
        • Moler F.W.
        Neuropsychological outcomes of children 1 year after pediatric cardiac arrest: secondary analysis of 2 randomized clinical trials.
        JAMA Neurol. 2018; 75: 1502-1510
        • Smith A.E.
        • Friess S.H.
        Neurological prognostication in children after cardiac arrest.
        Pediatr Neurol. 2020; 108: 13-22
        • Topjian A.A.
        • de Caen A.
        • Wainwright M.S.
        • et al.
        Pediatric Post-cardiac arrest care: A scientific statement from the American heart association.
        Circulation. 2019; 140: e194-e233
        • Geocadin R.G.
        • Callaway C.W.
        • Fink E.L.
        • et al.
        Standards for studies of neurological prognostication in comatose survivors of cardiac arrest: A Scientific statement from the American Heart Association.
        Circulation. 2019; 140: e517-e542
        • Koenig M.A.
        • Holt J.L.
        • Ernst T.
        • et al.
        MRI default mode network connectivity is associated with functional outcome after cardiopulmonary arrest.
        Neurocrit Care. 2014; 20: 348-357
        • Kirschen M.P.
        • Licht D.J.
        • Faerber J.
        • et al.
        Association of MRI brain injury with outcome after pediatric out-of-hospital cardiac arrest.
        Neurology. 2021; 96: e719-e731
        • Fink E.L.
        • Panigrahy A.
        • Clark R.S.B.
        • et al.
        Regional variations in brain MRI and correlation with outcome after pediatric cardiac arrest.
        Poster presentation at the American Society for Neuroradiology 48th Annual Meeting, Boston, MA. 2010
        • Basser P.J.
        • Pierpaoli C.
        Microstructural and physiological features of tissues elucidated by quantitative-diffusion-tensor MRI.
        J Magn Reson B. 1996; 111: 209-219
        • Sair H.I.
        • Hannawi Y.
        • Li S.
        • et al.
        Early functional connectome integrity and 1-year recovery in comatose survivors of cardiac arrest.
        Radiology. 2018; 287: 247-255
        • Velly L.
        • Perlbarg V.
        • Boulier T.
        • et al.
        Use of brain diffusion tensor imaging for the prediction of long-term neurological outcomes in patients after cardiac arrest: a multicentre, international, prospective, observational, cohort study.
        The Lancet Neurology. 2018; 17: 317-326
        • Gerdes J.S.
        • Walther E.U.
        • Jaganjac S.
        • Makrigeorgi-Butera M.
        • Meuth S.G.
        • Deppe M.
        Early detection of widespread progressive brain injury after cardiac arrest: a single case DTI and post-mortem histology study.
        PLoS ONE. 2014; 9: e92103
        • Bodien Y.G.
        • Chatelle C.
        • Edlow B.L.
        Functional networks in disorders of consciousness.
        Semin Neurol. 2017; 37: 485-502
        • Greicius M.D.
        • Supekar K.
        • Menon V.
        • Dougherty R.F.
        Resting-state functional connectivity reflects structural connectivity in the default mode network.
        Cereb Cortex. 2009; 19: 72-78
        • Piantino J.A.
        • Ruzas C.M.
        • Press C.A.
        • et al.
        Use of magnetic resonance imaging in neuroprognostication after pediatric cardiac arrest: Survey of current practices.
        Pediatr Neurol. 2022;
        • Fink E.L.
        • Berger R.P.
        • Clark R.S.
        • et al.
        Serum biomarkers of brain injury to classify outcome after pediatric cardiac arrest*.
        Crit Care Med. 2014; 42: 664-674
        • Fiser D.H.
        Assessing the outcome of pediatric intensive care.
        J Pediatr. 1992; 121: 68-74
        • Jenkinson M.
        • Beckmann C.F.
        • Behrens T.E.
        • Woolrich M.W.
        • Smith S.M.
        FSL.
        Neuroimage. 2012; 62: 782-790
        • Silva S.
        • de Pasquale F.
        • Vuillaume C.
        • et al.
        Disruption of posteromedial large-scale neural communication predicts recovery from coma.
        Neurology. 2015; 85: 2036-2044
        • Rolls E.T.
        • Huang C.C.
        • Lin C.P.
        • Feng J.
        • Joliot M.
        Automated anatomical labelling atlas 3.
        Neuroimage. 2020; 206: 116189
        • Topjian A.A.
        • Scholefield B.R.
        • Pinto N.P.
        • et al.
        P-COSCA (Pediatric core outcome set for cardiac arrest) in children: An advisory statement from the international liaison committee on resuscitation.
        Resuscitation. 2021; 162: 351-364
        • Fink E.L.
        • Panigrahy A.
        • Clark R.S.
        • et al.
        Regional brain injury on conventional and diffusion weighted MRI is associated with outcome after pediatric cardiac arrest.
        Neurocrit Care. 2013; 19: 31-40
        • Fink E.L.
        • Wisnowski J.
        • Clark R.
        • et al.
        Brain MR imaging and spectroscopy for outcome prognostication after pediatric cardiac arrest.
        Resuscitation. 2020; 157: 185-194
        • Manchester L.C.
        • Lee V.
        • Schmithorst V.
        • Kochanek P.M.
        • Panigrahy A.
        • Fink E.L.
        Global and regional derangements of cerebral blood flow and diffusion magnetic resonance imaging after pediatric cardiac arrest.
        J Pediatr. 2016; 169 (28-35 e1)
        • Velly L.
        • Perlbarg V.
        • Boulier T.
        • et al.
        Use of brain diffusion tensor imaging for the prediction of long-term neurological outcomes in patients after cardiac arrest: a multicentre, international, prospective, observational, cohort study.
        Lancet Neurol. 2018; 17: 317-326
        • Soares J.M.
        • Marques P.
        • Alves V.
        • Sousa N.
        A hitchhiker's guide to diffusion tensor imaging.
        Front Neurosci. 2013; 7: 31
        • Lee J.K.
        • Liu D.
        • Jiang D.
        • et al.
        Fractional anisotropy from diffusion tensor imaging correlates with acute astrocyte and myelin swelling in neonatal swine models of excitotoxic and hypoxic-ischemic brain injury.
        J Comp Neurol. 2021; 529: 2750-2770
        • Song S.K.
        • Sun S.W.
        • Ramsbottom M.J.
        • Chang C.
        • Russell J.
        • Cross A.H.
        Dysmyelination revealed through MRI as increased radial (but unchanged axial) diffusion of water.
        Neuroimage. 2002; 17: 1429-1436
        • Song S.K.
        • Sun S.W.
        • Ju W.K.
        • Lin S.J.
        • Cross A.H.
        • Neufeld A.H.
        Diffusion tensor imaging detects and differentiates axon and myelin degeneration in mouse optic nerve after retinal ischemia.
        Neuroimage. 2003; 20: 1714-1722
        • Song S.K.
        • Yoshino J.
        • Le T.Q.
        • et al.
        Demyelination increases radial diffusivity in corpus callosum of mouse brain.
        Neuroimage. 2005; 26: 132-140
        • Chalela J.A.
        • Wolf R.L.
        • Maldjian J.A.
        • Kasner S.E.
        MRI identification of early white matter injury in anoxic-ischemic encephalopathy.
        Neurology. 2001; 56: 481-485
        • Takahashi S.
        • Higano S.
        • Ishii K.
        • et al.
        Hypoxic brain damage: cortical laminar necrosis and delayed changes in white matter at sequential MR imaging.
        Radiology. 1993; 189: 449-456
        • Rajmohan V.
        • Mohandas E.
        The limbic system.
        Indian J Psychiatry. 2007; 49: 132-139
        • Hetherington H.
        • Bandak A.
        • Ling G.
        • Bandak F.
        Advances in imaging explosive blast mild traumatic brain injury.
        Handbook Clin Neurol. 2015; 127: 309-318
        • Ameis S.H.
        • Fan J.
        • Rockel C.
        • Soorya L.
        • Wang A.T.
        • Anagnostou E.
        Altered cingulum bundle microstructure in autism spectrum disorder.
        Acta Neuropsychiatrica. 2013; 25: 275-282
        • Uchida M.
        • Hung Y.
        • Green A.
        • et al.
        Association between frontal cortico-limbic white-matter microstructure and risk for pediatric depression.
        Psychiatry Res Neuroimaging. 2021; 318: 111396
        • Lee H.J.
        • Kwon H.
        • Kim J.I.
        • et al.
        The cingulum in very preterm infants relates to language and social-emotional impairment at 2 years of term-equivalent age.
        Neuroimage Clin. 2021; 29: 102528
        • Hung Y.
        • Uchida M.
        • Gaillard S.L.
        • et al.
        Cingulum-Callosal white-matter microstructure associated with emotional dysregulation in children: A diffusion tensor imaging study.
        Neuroimage Clin. 2020; 27: 102266
        • Keser Z.
        • Hasan K.M.
        • Mwangi B.
        • et al.
        Limbic pathway correlates of cognitive impairment in multiple sclerosis.
        J Neuroimaging. 2017; 27: 37-42
        • Sydnor V.J.
        • Bouix S.
        • Pasternak O.
        • et al.
        Mild traumatic brain injury impacts associations between limbic system microstructure and post-traumatic stress disorder symptomatology.
        Neuroimage Clin. 2020; 26: 102190
        • Enciso-Olivera C.O.
        • Ordóñez-Rubiano E.G.
        • Casanova-Libreros R.
        • et al.
        Structural and functional connectivity of the ascending arousal network for prediction of outcome in patients with acute disorders of consciousness.
        Sci Rep. 2021; 11: 22952
        • Parra-Morales A.M.
        • Rudas J.
        • Vargas J.A.
        • et al.
        Structural and functional connectivity of ascending reticular activating system in a patient with impaired consciousness after a cardiac arrest: A case report.
        Medicine (Baltimore). 2019; 98: e15620
        • Lv H.
        • Wang Z.
        • Tong E.
        • et al.
        Resting-state functional MRI: everything that nonexperts have always wanted to know.
        AJNR Am J Neuroradiol. 2018; 39: 1390-1399
        • Power J.D.
        • Cohen A.L.
        • Nelson S.M.
        • et al.
        Functional network organization of the human brain.
        Neuron. 2011; 72: 665-678
        • Biswal B.
        • Yetkin F.Z.
        • Haughton V.M.
        • Hyde J.S.
        Functional connectivity in the motor cortex of resting human brain using echo-planar MRI.
        Magn Reson Med. 1995; 34: 537-541
        • Wagner F.
        • Hänggi M.
        • Weck A.
        • et al.
        Outcome prediction with resting-state functional connectivity after cardiac arrest.
        Sci Rep. 2020; 10: 11695
        • Peran P.
        • Malagurski B.
        • Nemmi F.
        • et al.
        Functional and structural integrity of frontoparietal connectivity in traumatic and anoxic coma.
        in: Crit Care Med. 48. 2020: e639-e646
        • Edlow B.L.
        • Barra M.E.
        • Zhou D.W.
        • et al.
        Personalized connectome mapping to guide targeted therapy and promote recovery of consciousness in the intensive care unit.
        Neurocrit Care. 2020; 33: 364-375
        • Wang S.
        • Gan S.
        • Yang X.
        • et al.
        Decoupling of structural and functional connectivity in hubs and cognitive impairment after mild traumatic brain injury.
        Brain Connect. 2021; 11: 745-758
        • Kirsch M.
        • Guldenmund P.
        • Ali Bahri M.
        • et al.
        Sedation of patients with disorders of consciousness during neuroimaging: effects on resting state functional brain connectivity.
        Anesth Analg. 2017; 124: 588-598
        • Fink E.L.
        • Maddux A.B.
        • Pinto N.
        • et al.
        A core outcome set for pediatric critical care.
        Crit Care Med. 2020; 48: 1819-1828
        • Jarvis J.M.
        • Fayed N.
        • Fink E.L.
        • Choong K.
        • Khetani M.A.
        Caregiver dissatisfaction with their child's participation in home activities after pediatric critical illness.
        BMC Pediatr. 2020; 20: 415
        • Carlson H.L.
        • Laliberté C.
        • Brooks B.L.
        • et al.
        Reliability and variability of diffusion tensor imaging (DTI) tractography in pediatric epilepsy.
        Epilepsy Behav. 2014; 37: 116-122
        • Concha L.
        • Gross D.W.
        • Beaulieu C.
        Diffusion tensor tractography of the limbic system.
        AJNR Am J Neuroradiol. 2005; 26: 2267-2274
        • Yeh F.C.
        Shape analysis of the human association pathways.
        Neuroimage. 2020; 223: 117329
        • Power J.D.
        • Mitra A.
        • Laumann T.O.
        • Snyder A.Z.
        • Schlaggar B.L.
        • Petersen S.E.
        Methods to detect, characterize, and remove motion artifact in resting state fMRI.
        Neuroimage. 2014; 84: 320-341