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Neuron-specific enolase is correlated with lesion topology, relative infarct volume and outcome of symptomatic NAIS
  1. Gemma Arca1,2,
  2. Juan Arnaez2,3,
  3. Thais Agut4,5,
  4. Christian Núñez4,6,
  5. Christian Stephan-Otto4,6,7,
  6. Anna Valls8,
  7. Alfredo García-Alix2,4,9
  1. 1 Department of Neonatology, Clinic Maternitat University Hospital, Barcelona, Spain
  2. 2 Fundación NeNe, Madrid, Spain
  3. 3 Department of Neonatology, Burgos University Hospital, Burgos, Spain
  4. 4 Institut de Recerca Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain
  5. 5 Department of Neonatology, Hospital Sant Joan de Déu, Barcelona, Spain
  6. 6 Parc Sanitari Sant Joan de Déu, Sant Boi de Llobregat, Barcelona, Spain
  7. 7 Centro de Investigación Biomédica en Red de Salud Mental, Madrid, Spain
  8. 8 Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain
  9. 9 Centro de Investigación Biomédica en Red de Enfermedades Raras, Madrid, Spain
  1. Correspondence to Dr Gemma Arca, Department of Neonatology, Hospital Clínic, Barcelona 08028, Spain; gemmarca{at}


Objective To correlate neuron-specific enolase (NSE) levels in cerebrospinal fluid (CSF) in neonate infants with symptomatic neonatal arterial ischaemic stroke (NAIS) with the arterial distribution of infarct, infarct volume and outcome.

Design Prospective observational multicentre cohort.

Setting Three paediatric university hospitals in Spain.

Subjects Thirty-eight neonates with more than 35 weeks’ gestational age between 2006 and 2016 were studied. They were diagnosed with NAIS by MRI. They underwent a lumbar puncture to measure CSF-NSE concentrations within 96 hours after the onset of symptoms. Sixty-seven neonates admitted with suspected infections served as controls. We used a classification based on the arterial distribution, and the lesions were segmented with ITK-Snap software to determine their volume. Neurodevelopment was assessed at 24 months using the Bayley-III, Gross Motor Function Classification System and Bimanual Fine Motor Function.

Results CSF-NSE levels were higher in patients with symptomatic NAIS when compared with controls. Neonates with multifocal NAIS and with NAIS located in middle cerebral artery (MCA)-M1 arterial territory showed higher CSF-NSE levels when compared with cases with MCA-M2-M3-M4 territories (p<0.001). A significant correlation was found between CSF-NSE and relative infarction volume (rs=0.597; p<0.001). CSF-NSE values were higher in those infants with symptomatic NAIS with adverse outcome compared with infants with good development (p=0.020). Infants with CSF-NSE values above 55 ng/mL had an OR of adverse outcome of 6.48 (95% CI 1.48 to 28.33).

Conclusions CSF-NSE is a potential early prognostic biomarker after an NAIS due to the relation between volume, topology and neurodevelopment at 2 years of age.

  • neonatal arterial ischaemic stroke
  • neuron-specific enolase
  • infarction volume

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  • Contributors The concept for the study came from AG-A. The data were collected by AG-A, JA and GA. The MR images were analysed by AG-A, GA and TA. Lesion segmentation and volume estimation were performed by CS-O and CN. Statistical analysis was conducted by JA. The manuscript was written by GA, JA and AG-A. All authors reviewed and approved the final manuscript.

  • Funding This study was supported by two grants (PI08/1366 and PI15/00846) from the Instituto de Salud Carlos III co-funded by FEDER.

  • Competing interests None declared.

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

  • Correction notice This paper has been amended since it was published Online First. The two boxes on the first page have been updated.

  • Patient consent for publication Obtained.