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Monocyte-to-Lymphocyte Ratio in Clot Analysis as a Marker of Cardioembolic Stroke Etiology
Jesús Juega1, Carlos Palacio-Garcia2, Maite Rodriguez3
1Stroke 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. jjuega@vhebron.net.
Insights
Flow cytometry analysis of intracranial clots identified the monocyte-to-lymphocyte ratio (MLr) as a key predictor for high-risk cardioembolic etiology (HRCE) in cryptogenic stroke (CS) patients. This finding offers a novel diagnostic marker for determining stroke causes.
Area of Science:
- Neurology
- Hematology
- Biomarker Discovery
Background:
- Cryptogenic stroke (CS) diagnosis remains challenging, often requiring differentiation between cardioembolic and other etiologies.
- Identifying high-risk cardioembolic etiology (HRCE) is crucial for targeted prevention strategies.
- Current diagnostic methods may not always definitively determine the stroke's origin.
Purpose of the Study:
- To identify novel biomarkers within intracranial clots for predicting high-risk cardioembolic etiology (HRCE) in patients with cryptogenic strokes (CS).
- To utilize flow cytometry (FC) analysis of clot components to distinguish HRCE from other stroke types, such as large arterial atherosclerosis (LAA).
Main Methods:
- A prospective single-center study analyzed clot composition using flow cytometry (FC) in patients with large vessel occlusion strokes.
- Key cellular components analyzed included granulocytes, monocytes, and lymphocytes, focusing on the monocyte-to-lymphocyte ratio (MLr).
- Machine learning models, specifically multilevel decision trees with random forest classifiers, were employed to identify predictors of HRCE.
Main Results:
- The monocyte percentage and MLr in clots independently predicted HRCE when compared to LAA strokes.
- In cryptogenic stroke patients, the MLr emerged as the most significant predictor of HRCE in decision tree analysis.
- An MLr cutoff of 1.59 demonstrated high sensitivity (91.23%) and moderate specificity (44%) for HRCE detection in CS patients.
Conclusions:
- Clot analysis via flow cytometry reveals elevated monocyte-to-lymphocyte ratio as an independent marker for cardioembolic etiology in cryptogenic strokes.
- The MLr shows significant potential as a diagnostic tool for identifying HRCE in CS patients.
- This research contributes to a more precise etiological diagnosis of stroke, guiding therapeutic decisions.
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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