Venous and arterial TNF-R1 predicts outcome and complications in acute subarachnoid hemorrhage

  • Isabel FragataEmail author
  • Alejandro Bustamante
  • Anna Penalba
  • Patrícia Ferreira
  • Ana Paiva Nunes
  • Patrícia Canhão
  • Joan Montaner
Original Article



There is increasing evidence for the role of inflammation in clinical outcome after subarachnoid hemorrhage (SAH). Specifically, the TNF-alfa(α) pathway seems to be relevant after SAH. Although the TNF-α main receptor, TNF-R1 is associated with aneurysm growth and rupture, its relation to prognosis is unknown.

We sought to compare TNF-R1 levels in peripheral venous blood and arterial blood closer to the ruptured aneurysm to study the association of TNF-R1 blood levels with poor prognosis (modified Rankin Scale  > 2 at discharge, 3 and 6 months) and complications (hydrocephalus or delayed cerebral ischemia/DCI) following SAH.


We included consecutive SAH patients admitted in the first 72 h of symptoms. Blood samples were simultaneously collected from a peripheral vein and from the main parent artery of the aneurysm. Levels of TNF-R1 were measured using enzyme-linked immunosorbent assays.


We analyzed 58 patients. Arterial and venous levels of TNF-R1 were correlated (R = 0.706, p < 0.001). In multivariate regression analysis, venous TNF-R1 was an independent predictor of poor outcome at 6 months after adjusting by age and sex [odds ratio (OR) 11.63; 95% CI 2.09–64.7, p = 0.005] and after adjusting by Glasgow Coma Scale and Fisher scales (OR 8.74; 95% CI 1.45–52.7, p = 0.018). There was no association of TNF-R1 with DCI. A cut-off for arterial TNF-R1 of 1523.7 pg/mL had 75% sensitivity/66% specificity for the prediction of hydrocephalus.


Levels of venous TNF-R1 are associated with poor outcome in SAH. A specific association was found between levels of arterial TNF-R1 and hydrocephalus. These results are consistent with the role of TNF-α pathway in SAH and need to be validated in larger cohorts.


Subarachnoid hemorrhage TNF-R1 Prognosis Delayed cerebral ischemia Hydrocephalus 



We thank the Clinical Pathology Laboratory of Hospital São José, CHLC, for careful preparation of the blood samples.

Author’s Contribution

IF, AB, PC, JM contributed to project design; IF, AB, AP, PF, APN contributed to data collection; AB, IF performed data analysis; IF, AB, JM, PC contributed to Writing. All authors reviewed and approved the final manuscript.

Source of Support

Dr Fragata was supported by Sociedade Portuguesa de AVC/Tecnifar. Dr Bustamante is supported by a Juan Rodes research contract (JR16/00008) from Instituto de Salud Carlos III.

Compliance with Ethical Standards

Conflicts of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

Institutional review board approval was obtained for this study. Informed consent obtained from patient or legal representative.

Supplementary material

12028_2019_669_MOESM1_ESM.tiff (78.2 mb)
Figure 1 Flowchart depicting patients enrolled, included, and excluded in the study (TIFF 80095 kb)
12028_2019_669_MOESM2_ESM.docx (13 kb)
Supplementary material 2 (DOCX 13 kb)
12028_2019_669_MOESM3_ESM.docx (13 kb)
Supplementary material 3 (DOCX 13 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society 2019

Authors and Affiliations

  1. 1.Neuroradiology DepartmentCentro Hospitalar Lisboa CentralLisbonPortugal
  2. 2.Neurovascular Research LaboratoryVall d’Hebron Institute of Research (VHIR)BarcelonaSpain
  3. 3.Unidade Cérebro-VascularCentro Hospitalar Lisboa CentralLisbonPortugal
  4. 4.Neurology DepartmentCentro Hospitalar Lisboa NorteLisbonPortugal
  5. 5.Faculdade de Medicina, Instituto de Medicina MolecularUniversidade de LisboaLisbonPortugal
  6. 6.Institute de Biomedicine of SevilleIBiS/Hospital Universitario Virgen del Rocío/CSIC/University of SevilleSevilleSpain
  7. 7.Department of NeurologyHospital Universitario Virgen MacarenaSevilleSpain

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