The peripheral immune response in hyperglycemic stroke

Objectives: Hyperglycemia is common in acute ischemic stroke patients and is associated with poor clinical outcome. However, aggressive reduction of post-stroke hyperglycemia did not improve clinical outcome, suggesting that other mechanisms are playing a detrimental role in hyperglycemic stroke. We hypothesize that the acute post-stroke immune response is altered in the hyperglycemic state leading to higher mortality and morbidity. The objective of this study was to characterize temporal changes in circulating immune cells after stroke and their association with clinical outcomes in hyperglycemic compared to euglycemic patients. Patients and methods: This retrospective study included 97 (58 % euglycemic, 42 % hyperglycemic) patients presenting within 12 h of symptom onset of stroke. Blood neutrophil, monocyte and lymphocyte concentrations were measured sequentially for 96 h post stroke. Primary clinical outcome was the difference in the NIH stroke scale at admission compared to discharge. Secondary outcome measures included discharge disposition and the modified Rankin Scale (mRS) at 90 days. Results: Circulating neutrophils were significantly higher in hyperglycemic than in euglycemic patients within the first 48 h post stroke, while lymphocyte counts trended to be lower. Hyperglycemic patients had higher mortality rates, less favorable discharge disposition and worse neurological function at 90 days. In both groups, the neutrophil to lymphocytes ratio ((NLR) remained strongly associated with neurological function at discharge within the first 24 h (p < 0.001), and remained significant in hyperglycemic patients up to 48 h (p < 0.001). Multivariate regression analysis showed no confounding by other factors and a significant correlation with differences in NIHSS score (CI; 9.287 to-1.46, p = 0.0077**) and NLR (CL; 0.6058-6.901, p = 0.0203*) in hyperglycemic patients. Conclusions: Our data suggests that circulating immune cells play an important role in mediating poor clinical outcome in hyperglycemic patients following stroke. The NLR is a strong predictor of neurological outcomes in hyperglycemic patients. Thus, the modulation of immune cells may be a viable therapeutic approach to improve outcomes for this high risk group.