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October 10, 2023; 101 (15) Research Article

Association of Acute Infarct Topography With Development of Cerebral Palsy and Neurologic Impairment in Neonates With Stroke

View ORCID ProfileMark T. Mackay, View ORCID ProfileJian Chen, View ORCID ProfileJesse Shapiro, View ORCID ProfileManuela Pastore-Wapp, View ORCID ProfileNedelina Slavova, Sebastian Grunt, Belinda Stojanovski, Maja Steinlin, Richard J. Beare, View ORCID ProfileJoseph Yuan-Mou Yang
First published August 17, 2023, DOI: https://doi.org/10.1212/WNL.0000000000207705
Mark T. Mackay
From the Department of Neurology (M.T.M., B.S.), Royal Children's Hospital; Neuroscience Research (M.T.M., J.S., B.S., J.Y.-M.Y.), Murdoch Children's Research Institute; Florey Institute of Neurosciences and Mental Health (M.T.M.); Department of Paediatrics (M.T.M., J.Y.-M.Y.), University of Melbourne; Developmental Imaging (J.C., R.J.B., J.Y.-M.Y.); Brain and Mind (J.S.), Murdoch Children's Research Institute, Melbourne, Australia; Support Center for Advanced Neuroimaging (SCAN) (M.P.-W., N.S.), Institute of Diagnostic and Interventional Neuroradiology, University Hospital, Inselspital; Division of Neuropaediatrics, Development and Rehabilitation (S.G., M.S.), Department of Pediatrics, Inselspital Bern University Hospital, University of Bern, Switzerland; Peninsula Clinical School and National Centre for Healthy Ageing (R.J.B.), Monash University; Neuroscience Advanced Clinical Imaging Service (NACIS) (J.Y.-M.Y.), Department of Neurosurgery, Royal Children's Hospital, Melbourne, Australia; and ARTORG Center for Biomedical Engineering Research, Gerontechnology and Rehabilitation (M.P.-W.), University of Bern, Switzerland.
PhD
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Jian Chen
From the Department of Neurology (M.T.M., B.S.), Royal Children's Hospital; Neuroscience Research (M.T.M., J.S., B.S., J.Y.-M.Y.), Murdoch Children's Research Institute; Florey Institute of Neurosciences and Mental Health (M.T.M.); Department of Paediatrics (M.T.M., J.Y.-M.Y.), University of Melbourne; Developmental Imaging (J.C., R.J.B., J.Y.-M.Y.); Brain and Mind (J.S.), Murdoch Children's Research Institute, Melbourne, Australia; Support Center for Advanced Neuroimaging (SCAN) (M.P.-W., N.S.), Institute of Diagnostic and Interventional Neuroradiology, University Hospital, Inselspital; Division of Neuropaediatrics, Development and Rehabilitation (S.G., M.S.), Department of Pediatrics, Inselspital Bern University Hospital, University of Bern, Switzerland; Peninsula Clinical School and National Centre for Healthy Ageing (R.J.B.), Monash University; Neuroscience Advanced Clinical Imaging Service (NACIS) (J.Y.-M.Y.), Department of Neurosurgery, Royal Children's Hospital, Melbourne, Australia; and ARTORG Center for Biomedical Engineering Research, Gerontechnology and Rehabilitation (M.P.-W.), University of Bern, Switzerland.
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Jesse Shapiro
From the Department of Neurology (M.T.M., B.S.), Royal Children's Hospital; Neuroscience Research (M.T.M., J.S., B.S., J.Y.-M.Y.), Murdoch Children's Research Institute; Florey Institute of Neurosciences and Mental Health (M.T.M.); Department of Paediatrics (M.T.M., J.Y.-M.Y.), University of Melbourne; Developmental Imaging (J.C., R.J.B., J.Y.-M.Y.); Brain and Mind (J.S.), Murdoch Children's Research Institute, Melbourne, Australia; Support Center for Advanced Neuroimaging (SCAN) (M.P.-W., N.S.), Institute of Diagnostic and Interventional Neuroradiology, University Hospital, Inselspital; Division of Neuropaediatrics, Development and Rehabilitation (S.G., M.S.), Department of Pediatrics, Inselspital Bern University Hospital, University of Bern, Switzerland; Peninsula Clinical School and National Centre for Healthy Ageing (R.J.B.), Monash University; Neuroscience Advanced Clinical Imaging Service (NACIS) (J.Y.-M.Y.), Department of Neurosurgery, Royal Children's Hospital, Melbourne, Australia; and ARTORG Center for Biomedical Engineering Research, Gerontechnology and Rehabilitation (M.P.-W.), University of Bern, Switzerland.
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Manuela Pastore-Wapp
From the Department of Neurology (M.T.M., B.S.), Royal Children's Hospital; Neuroscience Research (M.T.M., J.S., B.S., J.Y.-M.Y.), Murdoch Children's Research Institute; Florey Institute of Neurosciences and Mental Health (M.T.M.); Department of Paediatrics (M.T.M., J.Y.-M.Y.), University of Melbourne; Developmental Imaging (J.C., R.J.B., J.Y.-M.Y.); Brain and Mind (J.S.), Murdoch Children's Research Institute, Melbourne, Australia; Support Center for Advanced Neuroimaging (SCAN) (M.P.-W., N.S.), Institute of Diagnostic and Interventional Neuroradiology, University Hospital, Inselspital; Division of Neuropaediatrics, Development and Rehabilitation (S.G., M.S.), Department of Pediatrics, Inselspital Bern University Hospital, University of Bern, Switzerland; Peninsula Clinical School and National Centre for Healthy Ageing (R.J.B.), Monash University; Neuroscience Advanced Clinical Imaging Service (NACIS) (J.Y.-M.Y.), Department of Neurosurgery, Royal Children's Hospital, Melbourne, Australia; and ARTORG Center for Biomedical Engineering Research, Gerontechnology and Rehabilitation (M.P.-W.), University of Bern, Switzerland.
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Nedelina Slavova
From the Department of Neurology (M.T.M., B.S.), Royal Children's Hospital; Neuroscience Research (M.T.M., J.S., B.S., J.Y.-M.Y.), Murdoch Children's Research Institute; Florey Institute of Neurosciences and Mental Health (M.T.M.); Department of Paediatrics (M.T.M., J.Y.-M.Y.), University of Melbourne; Developmental Imaging (J.C., R.J.B., J.Y.-M.Y.); Brain and Mind (J.S.), Murdoch Children's Research Institute, Melbourne, Australia; Support Center for Advanced Neuroimaging (SCAN) (M.P.-W., N.S.), Institute of Diagnostic and Interventional Neuroradiology, University Hospital, Inselspital; Division of Neuropaediatrics, Development and Rehabilitation (S.G., M.S.), Department of Pediatrics, Inselspital Bern University Hospital, University of Bern, Switzerland; Peninsula Clinical School and National Centre for Healthy Ageing (R.J.B.), Monash University; Neuroscience Advanced Clinical Imaging Service (NACIS) (J.Y.-M.Y.), Department of Neurosurgery, Royal Children's Hospital, Melbourne, Australia; and ARTORG Center for Biomedical Engineering Research, Gerontechnology and Rehabilitation (M.P.-W.), University of Bern, Switzerland.
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Sebastian Grunt
From the Department of Neurology (M.T.M., B.S.), Royal Children's Hospital; Neuroscience Research (M.T.M., J.S., B.S., J.Y.-M.Y.), Murdoch Children's Research Institute; Florey Institute of Neurosciences and Mental Health (M.T.M.); Department of Paediatrics (M.T.M., J.Y.-M.Y.), University of Melbourne; Developmental Imaging (J.C., R.J.B., J.Y.-M.Y.); Brain and Mind (J.S.), Murdoch Children's Research Institute, Melbourne, Australia; Support Center for Advanced Neuroimaging (SCAN) (M.P.-W., N.S.), Institute of Diagnostic and Interventional Neuroradiology, University Hospital, Inselspital; Division of Neuropaediatrics, Development and Rehabilitation (S.G., M.S.), Department of Pediatrics, Inselspital Bern University Hospital, University of Bern, Switzerland; Peninsula Clinical School and National Centre for Healthy Ageing (R.J.B.), Monash University; Neuroscience Advanced Clinical Imaging Service (NACIS) (J.Y.-M.Y.), Department of Neurosurgery, Royal Children's Hospital, Melbourne, Australia; and ARTORG Center for Biomedical Engineering Research, Gerontechnology and Rehabilitation (M.P.-W.), University of Bern, Switzerland.
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Belinda Stojanovski
From the Department of Neurology (M.T.M., B.S.), Royal Children's Hospital; Neuroscience Research (M.T.M., J.S., B.S., J.Y.-M.Y.), Murdoch Children's Research Institute; Florey Institute of Neurosciences and Mental Health (M.T.M.); Department of Paediatrics (M.T.M., J.Y.-M.Y.), University of Melbourne; Developmental Imaging (J.C., R.J.B., J.Y.-M.Y.); Brain and Mind (J.S.), Murdoch Children's Research Institute, Melbourne, Australia; Support Center for Advanced Neuroimaging (SCAN) (M.P.-W., N.S.), Institute of Diagnostic and Interventional Neuroradiology, University Hospital, Inselspital; Division of Neuropaediatrics, Development and Rehabilitation (S.G., M.S.), Department of Pediatrics, Inselspital Bern University Hospital, University of Bern, Switzerland; Peninsula Clinical School and National Centre for Healthy Ageing (R.J.B.), Monash University; Neuroscience Advanced Clinical Imaging Service (NACIS) (J.Y.-M.Y.), Department of Neurosurgery, Royal Children's Hospital, Melbourne, Australia; and ARTORG Center for Biomedical Engineering Research, Gerontechnology and Rehabilitation (M.P.-W.), University of Bern, Switzerland.
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Maja Steinlin
From the Department of Neurology (M.T.M., B.S.), Royal Children's Hospital; Neuroscience Research (M.T.M., J.S., B.S., J.Y.-M.Y.), Murdoch Children's Research Institute; Florey Institute of Neurosciences and Mental Health (M.T.M.); Department of Paediatrics (M.T.M., J.Y.-M.Y.), University of Melbourne; Developmental Imaging (J.C., R.J.B., J.Y.-M.Y.); Brain and Mind (J.S.), Murdoch Children's Research Institute, Melbourne, Australia; Support Center for Advanced Neuroimaging (SCAN) (M.P.-W., N.S.), Institute of Diagnostic and Interventional Neuroradiology, University Hospital, Inselspital; Division of Neuropaediatrics, Development and Rehabilitation (S.G., M.S.), Department of Pediatrics, Inselspital Bern University Hospital, University of Bern, Switzerland; Peninsula Clinical School and National Centre for Healthy Ageing (R.J.B.), Monash University; Neuroscience Advanced Clinical Imaging Service (NACIS) (J.Y.-M.Y.), Department of Neurosurgery, Royal Children's Hospital, Melbourne, Australia; and ARTORG Center for Biomedical Engineering Research, Gerontechnology and Rehabilitation (M.P.-W.), University of Bern, Switzerland.
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Richard J. Beare
From the Department of Neurology (M.T.M., B.S.), Royal Children's Hospital; Neuroscience Research (M.T.M., J.S., B.S., J.Y.-M.Y.), Murdoch Children's Research Institute; Florey Institute of Neurosciences and Mental Health (M.T.M.); Department of Paediatrics (M.T.M., J.Y.-M.Y.), University of Melbourne; Developmental Imaging (J.C., R.J.B., J.Y.-M.Y.); Brain and Mind (J.S.), Murdoch Children's Research Institute, Melbourne, Australia; Support Center for Advanced Neuroimaging (SCAN) (M.P.-W., N.S.), Institute of Diagnostic and Interventional Neuroradiology, University Hospital, Inselspital; Division of Neuropaediatrics, Development and Rehabilitation (S.G., M.S.), Department of Pediatrics, Inselspital Bern University Hospital, University of Bern, Switzerland; Peninsula Clinical School and National Centre for Healthy Ageing (R.J.B.), Monash University; Neuroscience Advanced Clinical Imaging Service (NACIS) (J.Y.-M.Y.), Department of Neurosurgery, Royal Children's Hospital, Melbourne, Australia; and ARTORG Center for Biomedical Engineering Research, Gerontechnology and Rehabilitation (M.P.-W.), University of Bern, Switzerland.
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Joseph Yuan-Mou Yang
From the Department of Neurology (M.T.M., B.S.), Royal Children's Hospital; Neuroscience Research (M.T.M., J.S., B.S., J.Y.-M.Y.), Murdoch Children's Research Institute; Florey Institute of Neurosciences and Mental Health (M.T.M.); Department of Paediatrics (M.T.M., J.Y.-M.Y.), University of Melbourne; Developmental Imaging (J.C., R.J.B., J.Y.-M.Y.); Brain and Mind (J.S.), Murdoch Children's Research Institute, Melbourne, Australia; Support Center for Advanced Neuroimaging (SCAN) (M.P.-W., N.S.), Institute of Diagnostic and Interventional Neuroradiology, University Hospital, Inselspital; Division of Neuropaediatrics, Development and Rehabilitation (S.G., M.S.), Department of Pediatrics, Inselspital Bern University Hospital, University of Bern, Switzerland; Peninsula Clinical School and National Centre for Healthy Ageing (R.J.B.), Monash University; Neuroscience Advanced Clinical Imaging Service (NACIS) (J.Y.-M.Y.), Department of Neurosurgery, Royal Children's Hospital, Melbourne, Australia; and ARTORG Center for Biomedical Engineering Research, Gerontechnology and Rehabilitation (M.P.-W.), University of Bern, Switzerland.
MBChB, PhD
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Association of Acute Infarct Topography With Development of Cerebral Palsy and Neurologic Impairment in Neonates With Stroke
Mark T. Mackay, Jian Chen, Jesse Shapiro, Manuela Pastore-Wapp, Nedelina Slavova, Sebastian Grunt, Belinda Stojanovski, Maja Steinlin, Richard J. Beare, Joseph Yuan-Mou Yang
Neurology Oct 2023, 101 (15) e1509-e1520; DOI: 10.1212/WNL.0000000000207705

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Abstract

Background and Objectives Research investigating neonatal arterial ischemic stroke (NAIS) outcomes have shown that combined cortical and basal ganglia infarction or involvement of the corticospinal tract predict cerebral palsy (CP). The research question was whether voxel-based lesion-symptom mapping (VLSM) on acute MRI can identify brain regions associated with CP and neurodevelopmental impairments in NAIS.

Methods Newborns were recruited from prospective Australian and Swiss pediatric stroke registries. CP diagnosis was based on clinical examination. Language and cognitive-behavioral impairments were assessed using the Pediatric Stroke Outcome Measure, dichotomized to good (0–0.5) or poor (≥1), at ≥18 months of age. Infarcts were manually segmented using diffusion-weighted imaging, registered to a neonatal-specific brain template. VLSM was conducted using MATLAB SPM12 toolbox. A general linear model was used to correlate lesion masks with motor, language, and cognitive-behavioral outcomes. Voxel-wise t-statistics were calculated, correcting for multiple comparisons using family-wise error (FWE) rate.

Results Eighty-five newborns met the inclusion criteria. Infarct lateralization was left hemisphere (62%), right (8%), and bilateral (30%). At a median age of 2.1 years (interquartile range 1.9–2.6), 33% developed CP and 42% had neurologic impairments. Fifty-four grey and white matter regions correlated with CP (t > 4.33; FWE < 0.05), including primary motor pathway regions, such as the precentral gyrus, and cerebral peduncle, and regions functionally connected to the primary motor pathway, such as the pallidum, and corpus callosum motor segment. No significant correlations were found for language or cognitive-behavioral outcomes.

Discussion CP after NAIS correlates with infarct regions directly involved in motor control and in functionally connected regions. Areas associated with language or cognitive-behavioral impairment are less clear.

Glossary

CP=
cerebral palsy;
CST=
corticospinal tract;
DWI=
diffusion-weighted imaging;
FWE=
family-wise error;
GM=
grey matter;
ICV=
intracranial volume;
IQR=
interquartile range;
NAIS=
neonatal arterial ischemic stroke;
PLIC=
posterior limb of the internal capsule;
PSOM=
Pediatric Stroke Outcome Measure;
RCHM=
Royal Children's Hospital Melbourne;
ROI=
regions of interest;
VLSM=
voxel-based lesion-symptom mapping;
WM=
white matter

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Submitted and externally peer reviewed. The handling editor was Associate Editor Courtney Wusthoff, MD, MS.

  • Editorial, page 641

  • Received January 20, 2023.
  • Accepted in final form June 9, 2023.
  • © 2023 American Academy of Neurology
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