Systemic White Blood Cell Count as a Biomarker for Malignant Cerebral Edema in Large Vessel Ischemic MCA Stroke

Objectives: Large middle cerebral artery (MCA) strokes remain a major cause for mortality and morbidity all over the world, and therefore early identification of patients with the highest risk for malignant cerebral edema is crucial for early intervention. Neutrophils to lymphocytes ratio (NLR) and peripheral total white blood cell (WBC) count are inflammatory markers done routinely for all patients, and this study evaluated the use of NLR and elevated white blood cell count within the first 24 h of MCA ischemic stroke onset, with the absence of significant hemorrhagic transformation, to predict malignant cerebral edema.

Materials and methods: A total of 156 patients with large MCA strokes were included. We collected demographic, clinical, radiological data, and NLR and WBCs within the first 24 h from admission.We excluded patients who had any underlying infections diagnosed 7 days before or within 72 h after admission. We used a body temp of 38 C or more, abnormal CXR or abnormal urine analysis within the first 72 h to exclude patients with possible infections.We excluded immune-compromised patients and patients on steroid therapy. We compared the NLR and WBC count in patients who developed malignant cerebral edema versus the patients who did not. NLR > 3.5 and < 3.5 was used for comparison. We then conducted multivariate logistic regression models to explore the relationship between cerebral edema, WBCs and NLR count simultaneously.

Results: NLR, WBC, radiological involvement of more than 50% of MCA territory infarction on presentation, hyperdense MCA sign, and NIH stroke scale were all significantly higher in patients with malignant cerebral edema within the first 24 h. Using univariate logistic regression, NLR performs better than WBC when predicting the occurrence of malignant cerebral edema (AUC = 0.74 vs. 0.62). However, NIH stroke scale scores, and radiological involvement of more than 50% of MCA territory infarction on the first 24 h of presentation on CT scan both showed better discriminative performance for malignant cerebral edema than NLR (AUC = 0.84 and 0.76, respectively). When combined, NLR > 3.5 paired with the NIH stroke scale score had the best predictive performance (AUC = 0.87).

Conclusion: NLR > 3.5 can be used for early prognostication in patients with large vessel MCA ischemic strokes with no significant hemorrhagic transformation within the first 24 h regardless if they had reperfusion therapy or not. Combining NLR of > 3.5 in addition to high NIHSS provided the best predictive model in our study. Further studies are needed to further develop the best predictive model in diverse populations.