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Neonatal arterial stroke location is associated with outcome at 2 years: a voxel-based lesion-symptom mapping study
  1. Christian Núñez1,2,
  2. Christian Stephan-Otto2,3,4,
  3. Gemma Arca5,6,
  4. Thais Agut2,6,7,
  5. Juan Arnaez6,8,
  6. Malaika Cordeiro9,
  7. Isabel Benavente-Fernández6,10,
  8. Nuria Boronat11,
  9. Simón Pedro Lubián-López6,10,
  10. Eva Valverde6,9,
  11. Montesclaros Hortigüela8,
  12. Alfredo García-Alix6
  1. 1 Departament de Psiquiatria, Institut d'Investigació Biomèdica-Sant Pau (IIB-Sant Pau), Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
  2. 2 Institut de Recerca Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain
  3. 3 Parc Sanitari Sant Joan de Déu, Sant Boi de Llobregat, Barcelona, Spain
  4. 4 Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
  5. 5 Departament de Neonatologia, Hospital Clínic, IDIBAPS, Barcelona, Spain
  6. 6 NeNe Foundation, Madrid, Spain
  7. 7 Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain
  8. 8 Departamento de Neonatología, Hospital Universitario de Burgos, Burgos, Spain
  9. 9 Departamento de Neonatología, Hospital Universitario La Paz, Madrid, Spain
  10. 10 Departamento de Neonatología, Hospital Puerta del Mar, Cádiz, Spain
  11. 11 Departamento de Neonatología, Hospital Universitario y Politécnico La Fe. Instituto de Investigación Sanitaria La Fe, Valencia, Spain
  1. Correspondence to Dr Alfredo García-Alix, NeNe Foundation, Madrid, Spain; alfredoalix{at}; Dr Christian Stephan-Otto, Institut de Recerca Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain; cstephanotto{at}


Objective In contrast to motor impairments, the association between lesion location and cognitive or language deficits in patients with neonatal arterial ischaemic stroke remains largely unknown. We conducted a voxel-based lesion-symptom mapping cross-sectional study aiming to reveal neonatal arterial stroke location correlates of language, motor and cognitive outcomes at 2 years of age.

Design Prospective observational multicentre study.

Setting Six paediatric university hospitals in Spain.

Participants We included 53 patients who had a neonatal arterial ischaemic stroke with neonatal MRI and who were followed up till 2 years of age.

Main outcome measures We analysed five dichotomous clinical variables: speech therapy (defined as the need for speech therapy as established by therapists), gross motor function impairment, and the language, motor and cognitive Bayley scales. All the analyses were controlled for total lesion volume.

Results We found that three of the clinical variables analysed significantly correlated with neonatal stroke location. Speech therapy was associated with lesions located mainly at the left supramarginal gyrus (p=0.007), gross motor function impairment correlated with lesions at the left external capsule (p=0.044) and cognitive impairment was associated with frontal lesions, particularly located at the left inferior and middle frontal gyri (p=0.012).

Conclusions The identification of these susceptible brain areas will allow for more precise prediction of neurological impairments on the basis of neonatal brain MRI.

  • neonatology
  • neurology

Data availability statement

All data used in this study are available upon reasonable request.

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Data availability statement

All data used in this study are available upon reasonable request.

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  • CN and CS-O are joint first authors.

  • Twitter @isabenaventef

  • Contributors CS and AG contributed to the conception and design of the study. CN, CS, and GA analysed the data. All authors contributed to drafting the manuscript and the figures.

  • Funding This work was supported by Grant PI15/00846 from the Instituto de Salud Carlos III co-funded by the European Regional Development Fund, and by a 'Beca Bombers' award from the Fundació Sant Joan de Déu.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.