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Monocyte-to-Lymphocyte Ratio in Clot Analysis as a Marker of Cardioembolic Stroke Etiology

Translational Stroke Research (2021)Cite this article

Abstract

The aim of the study was to find markers of high-risk cardioembolic etiology (HRCE) in patients with cryptogenic strokes (CS) through the analysis of intracranial clot by flow cytometry (FC). A prospective single-center study was designed including patients with large vessel occlusion strokes. The percentage of granulocytes, monocytes, lymphocytes, and monocyte-to-lymphocyte ratio (MLr) were analyzed in clots extracted after endovascular treatment (EVT) and in peripheral blood. Large arterial atherosclerosis (LAA) strokes and high-risk cardioembolic (HRCE) strokes were matched by demographics and acute reperfusion treatment data to obtain FC predictors for HRCE. Multilevel decision tree with boosting random forest classifiers was performed with each feature importance for HRCE diagnosis among CS. We tested the validity of the best FC predictor in a cohort of CS that underwent extensive diagnostic workup. Among 211 patients, 178 cases underwent per-protocol workup. The percentage of monocytes (OR 1.06, 95% CI 1.01–1.11) and MLr (OR 1.83, 95% CI 1.12–2.98) independently predicted HRCE diagnosis when LAA clots (n = 28) were matched with HRCE clots (n = 28). Among CS (n = 82), MLr was the feature with the highest weighted importance in the multilevel decision tree as a predictor for HRCE. MLr cutoff point of 1.59 yield sensitivity of 91.23%, specificity of 44%, positive predictive value of 78.79%, and negative predictive value of 68.75 for HRCE diagnosis among CS. MLr ≥ 1.6 in clot analysis predicted HRCE diagnosis (OR, 6.63, 95% CI 1.85–23.71) in a multivariate model adjusted for age. Clot analysis by FC revealed high levels of monocyte-to-lymphocyte ratio as an independent marker of cardioembolic etiology in cryptogenic strokes.

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source of stroke: high-risk cardioembolic strokes (HRCE) in patients with major cardiac disease that require anticoagulation treatment like atrial fibrillation A(F) or other major cardiac sources; large arterial atherosclerosis (LAA) strokes; and other infrequent determined source in cases of etiologies like symptomatic arterial dissections. Strokes of unknown etiology that completed the diagnostic workup were categorized as cryptogenic strokes and were divided according to MFC analysis of the clot in patients with high MLr (> 1.6) and patients with low MLr (< 1.6). Completion of diagnostic workup was performed in each group looking for HRCE origin: echocardiographic studies, continuous cardiac Holter monitoring up to 60 days, and diagnosis of AF obtained in medical records until 1 year of follow-up

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Availability of Data and Material

The data that support the findings of this study are available on request from the corresponding author.

Code Availability

Not applicable.

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Acknowledgements

All the members of the stroke units are thanked for their support in the study and Cristina Granes is thanked for conducting the statistical analysis.

Funding

This work was supported by “Project 355/C/2017, Fundació La Marató de TV3 in Strokes and traumatic spinal cord and brain injury, 2017 call of projects”. J.J. was supported by a Rio Hortega contract CM18/00253 from The Instituto de Salud Carlos III (Institute of Health Carlos III, Spain).

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Authors and Affiliations

  1. Stroke Unit, Department of Neurology, Medicine Department, Vall d’Hebron Research Institute, Valld’Hebron University Hospital, Autonomous University of Barcelona, Passeig de la Vall d’Hebron, 119-129, 08035, Barcelona, Spain

    Jesús Juega, Maite Rodriguez, Matias Deck, David Rodriguez-Luna, Manuel Requena, Álvaro García-Tornel, Noelia Rodriguez-Villatoro, Marta Rubiera, Sandra Boned, Marian Muchada, Marc Ribo, Estela Sanjuan, José Álvarez-Sabin, Carlos A. Molina & Jorge Pagola

  2. Hematology Department, Vall d’Hebron University Hospital, Vall d’Hebron Hospital Campus, Barcelona, Spain

    Carlos Palacio-Garcia, Laura Gallur, Maria Sanchez & Sara Gonzalez-Rubio

  3. Department of Neuroradiology, Valld’Hebron University Hospital, Barcelona, Spain

    Carlos Pinana, David Hernandez, Pilar Coscojuela, Humberto Diaz & Alejandro Tomasello

  4. Stroke Unit, Department of Neurology, Germans Trias I Pujol University Hospital, Badalona, Spain

    Maria Hernandez-Perez & Laura Dorado

  5. Stroke Unit Department of Neurology, Bellvitge University Hospital, Hospitalet de Llobregat, Spain

    Helena Quesada, Pere Cardona & Carolina De-La-Torre

  6. Department of Pathology Vall d, Hebron University Hospital, Barcelona, Spain

    Jessica Camacho & Santiago Ramon-y-Cajal

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  1. Jesús Juega
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  30. Carlos A. Molina
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on behalf of the ITACAT study group

Corresponding author

Correspondence to Jesús Juega.

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The study was approved by the Ethical Committee in line with the last Helsinki.

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Written informed consent was obtained from all participants.

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Juega, J., Palacio-Garcia, C., Rodriguez, M. et al. Monocyte-to-Lymphocyte Ratio in Clot Analysis as a Marker of Cardioembolic Stroke Etiology. Transl. Stroke Res. (2021). https://doi.org/10.1007/s12975-021-00946-w

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  • DOI: https://doi.org/10.1007/s12975-021-00946-w

Keywords

  • Stroke
  • Flow cytometry
  • Diagnosis
  • Thrombectomy
  • Intracranial embolism
  • Embolic stroke